identifier: March, Sandra B. <https://research.library.mun.ca/view/creator_az/March=3ASandra_B=2E=3A=3A.html>   (1982) The antibacterial activity of trimethoprim-sulfamethoxazole in urine.  Masters thesis, Memorial University of Newfoundland.

abstract: Cotrimoxazole (TMP-SMX) is a premixed combination of the antimicrobial agents, trimethoprim (TMP) and sulfamethoxazole (SMX), in a fixed ratio.  The drug has been used for the treatment of urinary tract and other infections for more than 10 years but its efficacy and the nature of its antibacterial activity have remained controversial.  The present work was undertaken in an effort to clarify some of the issues which have been raised. -- The antibacterial properties of the drug and its components were assessed in several in vitro systems.  Synergy between TMP and SMX, one of the main arguments supporting the use of the fixed combination, was examined by drug diffusion in agar, checkerboard titration, and time-kill curves against a standard Escherichia coli strain (ATCC 25922) and against a variety of bacterial pathogens isolated from patients with urinary tract infection.  Minimal inhibitory concentrations for 100 clinical isolates were established by agar dilution and the parameters by which synergy is defined were evaluated.  Time-kill curves, constructed from growth in drug-supplemented broth and urine, and in urine from cotrimoxazole-treated patients, were used to assess the kinetics of antibacterial activity of TMP-SMX and its components against pathogens commonly associated with urinary tract infections. -- The results reported here indicate that TMP is the more active agent in the mixture and in many instances inhibition is afforded by the TMP component alone.  In vitro synergy could be demonstrated when the test organism was sensitive to each of the components but the synergistic effect was clear only at drug levels significantly lower than those achievable in urine following usual drug dosage.  Time-kill curves demonstrate the bactericidal nature of TMP-SMX activity but results with TMP alone were not markedly different.  Bactericidal effects could not be detected for SMX. -- Bioassay of urine samples from cotrimoxazole-treated patients showed that TMP was the major active constituent.  Only low levels of biologically active SMX were detected by assay against a TMP-resistant strain of Proteus mirabilis.  The minor contribution of SMX to total antibacterial activity in urine specimens from these patients was confirmed by the addition of para-aminobenzoic acid (PABA), a known antagonist of sulfonamides. -- The data presented do not support the efficacy of the fixed ratio combination in management of urinary tract infections.


identifier: Sheppard, S. L. (Sarah Lyn) <https://research.library.mun.ca/view/creator_az/Sheppard=3AS=2E_L=2E_=28Sarah_Lyn=29=3A=3A.html>   (1980) The attachment of encephalomyocarditis virus to Krebs II ascites tumour cells.  Masters thesis, Memorial University of Newfoundland.

type: Thesis NonPeerReviewed

format: application/pdf application/pdf

abstract: Attachment, the first stage of viral infection, was investigated using Encephalomyocarditis (EMC) virus and Krebs II ascites tumour cells (Krebs cells).  The initial stage of the research was concerned with the Krebs cell surface, which was found to consist of a plasma membrane and a glycocalyx.  Plasma membranes from Krebs cells, the purity of which was determined by marker enzyme assays, electron microscopy and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), contained about 20 coomassie blue staining components (proteins) and one periodic acid Schiff’s (PAS) staining component (glycoprotein) of apparent molecular weight 225,000 daltons as revealed by SDS-PAGE.  Three of the major proteins were labeled when Krebs plasma membranes were iodinated but the glycoprotein component was not labeled.  SDS-PAGE of the glycocalyx was shown to influence cell surface activities since it partially blocked the iodination of whole cells and the action of neuraminidase on the cell surface. -- The Krebs cell receptor for EMC virus was not found to be a glycocalyx component because attachment, growth and haemagglutination of EMC virus were unaffected by the presence or absence of the glycocalyx.  EMC virus attached equally well to whole Krebs cells, isolated plasma membranes and human erythrocytes.  Neuraminidase or trypsin treatment of Krebs cells or plasma membranes reduced EMC virus attachment and infectivity suggesting that the virus was attaching to a sialoglycoprotein component. -- Glycoprotein preparations from Krebs cells and plasma membranes examined by SDS-PAGE contained a single PAS positive component of apparent molecular weight 215,000 daltons which is very similar to that of the membrane PAS component.  These preparations inhibited virus attachment, infectivity and haemagglutination and inhibition was reduced by treating the preparations with trypsin or neuraminidase.  It is, therefore, probable that EMC virus attaches to the sialoglycoprotein component of the Krebs plasma membrane.


identifier: Dickson, Maureen Anne <https://research.library.mun.ca/view/creator_az/Dickson=3AMaureen_Anne=3A=3A.html>   (1978) The behavioural, psychological and social characteristics of Newfoundland children with bleeding disorders.  Masters thesis, Memorial University of Newfoundland.

abstract: This study tested the hypotheses that children with hemophilia differ from other children behaviourally, psychologically and socially, and that differences within the population of children with hemophilia are related to factors within the home, to factors within the child, and to the medical treatment. -- The total population of children under seventeen years of age, diagnosed as having hemophilia, and living in Newfoundland, Canada, was assessed, and compared with a sample of children with spina bifida, and a sample of children without chronic physical handicap which were also assessed. -- The assessment for each child consisted of: -- 1.  Standardized psychiatric interview with the child.  This incorporated tests of selected neurological features. -- 2.  Intelligence and reading achievement testing for the school-age children. -- 3.  Standardized parental assessment interview. -- 4.  Questionnaire completed by teachers. -- 5.  Interviews with physicians involved in the child's treatment. -- 6.  Review of medical records. -- The three groups of children were compared for rates of psychiatric disorder, as determined by the parental and child interviews, and the teachers' questionnaire.  Comparison of the three groups was also carried out for all individual items from the parental and child interviews, and the teachers’ questionnaire.  The results of these comparisons were questionable due to difficulties obtaining adequately large control groups.  Those difficulties were examined in detail. -- The rates of psychiatric disorder, the intelligence and achievement scores did not differ for the three groups of children studied.  Children without chronic physical handicap had a significantly higher range of peer contacts than those of the other two groups.  The children with hemophilia were hospitalized more frequently than the children in the other groups, but the activity of the three groups did not differ. -- Within the population of children with hemophilia, comparisons of all individual items were made between the group with psychiatric disorder, and the group without psychiatric disorder.  The two groups of children with hemophilia did not differ in intelligence, reading achievement scores or any individual item of recent behaviour and emotional state.  The families of the two groups of children differed in several respects.  Limited information provided by physicians and hospital records precluded complete statistical analysis of medical care data.


identifier: Sutherland, Peter Michael <https://research.library.mun.ca/view/creator_az/Sutherland=3APeter_Michael=3A=3A.html>   (1987) Production of human-mouse somatic cell hybrids and characterization for carcinoembryonic antigen expression.  Masters thesis, Memorial University of Newfoundland.

abstract: Carcinoembryonic antigen (CEA), a human tumor-associated marker for many epithelial tumors, has been well characterized immunologically and structurally but its biological function(s) remains a mystery.  The objectives of this investigation were to produce interspecific somatic cell hybrids between human colorectal, CEA expressing/secreting, cancer cell lines (LS174T, SKC01 and HT29) and mouse cell lines (NS1 SP2/0, RAG, PG19 and STO) and to characterize the resultant hybrids  for CEA expression/secretion with the longer term goal of assigning the CEA gene(s) to a particular chromosome. -- Fusions were performed using a polyethylene glycol (PEG) suspension technique and hybrids were isolated by hypoxanthine-aminopterin-thymidine/ouabain double selection and characterized for CEA expression/secretion in specific CEA immunoassays.  Forty-eight fusions were performed (43, monolayer-suspension; 5, monolayer-monolayer) producing 344 hybrid colonies of the following types (SKCO1xRAG, SKCO1xSTO, HT29xRAG, HT29xSTO and HT29xNS1).  Chromosomal analysis by Giemsa differential staining confirmed that these fusion products were definite hybrids containing human and mouse chromosomes.--- This study has demonstrated (1) the successful production of human-mouse somatic cell hybrids, (2) that fusion of monolayer-monolayer cell lines resulted in a greater yield of hybrids and (3) that none of the hybrids obtained showed high levels of CEA expression/secretion, probably because the RAG and STO cell lines were nonpermissive fusion partners.


identifier: Thompson, Peter Maurice <https://research.library.mun.ca/view/creator_az/Thompson=3APeter_Maurice=3A=3A.html>   (1987) Serotonin participation in the suppression of focal epileptiform activity by noxious stimulation.  Masters thesis, Memorial University of Newfoundland.

abstract: Noxious stimulation acting, at least in part, by a serotonergic mechanism suppresses penicillin-induced focal epileptiform activity in the rat (Neuman, 1986b). In the present study the site of serotonin's action and the serotonin receptor subtype involved in the process were investigated. The working hypothesis was that an increase in  the cortical concentration of serotonin arising from the rostral raphe nuclei mediated the suppression of focal epileptiform activity by noxious stimulation. -- The systemic administration of agents known to inhibit raphe unit activity including serotonin agonists 8-0H-2-(di-n-propylamine) tetralin. 2-methoxyphenylpiperazine and trifluoromethylpiperazine as well as blockers of serotonin uptake, imipramine and fluoxetine, prevented the suppression  of focal epileptiform activity by noxious stimulation. Analgesia at the spinal cord level was not thought to be a factor in this blockade, but rather the drugs were considered to act by inhibiting dorsal raphe neurons. -- The  pressure ejection of serotonin and 8-0H-2-(di-n-propylamine) tetralin into the dorsal raphe also blocked the suppression of focal epileptiform activity by noxious stimulation, despite a several minute delay between pressure ejection of drug and response. Available histology confirmed that the majority of responsive sites were located in the dorsal raphe, while the majority of non-responsive sites were located outside the dorsal raphe region. While the involvement of the dorsal raphe was clearly established in this study, the degree of this involvement could not be determined. -- Studies at the cortical level involving the pressure ejection of 1) the serotonin precursor L-5-hydroxytryptophan in rats pretreated with p-chlorophenylalanine, and 2) the serotonin releaser p-chloroamphetamine, provided some evidence that serotonin at the cortical level was essential to the suppression of focal  epileptiform activity by noxious stimulation. However, similar studies with serotonin or fenfluramine failed to show any effect. -- Serotonin antagonists with affinity for 5-HT, but not 5-HT₂ and 5-HT₁C, but not 5-HT₃ receptors, blocked the suppression of focal epileptiform activity by noxious stimulation. Based on the available data it appears that 5-HT mediates the suppression of focal epileptiform activity by noxious stimulation by an action at 5-HT₂ and/or  5-HT₁C receptors. -- Key Words -- Focal Epileptiform Activity; Serotonin; Noxious Stimulation; Dorsal Raphe; Cerebral Cortex.


identifier: Pang, Stephen Ching-ng <https://research.library.mun.ca/view/creator_az/Pang=3AStephen_Ching-ng=3A=3A.html>   (1980) The correlation of medial composition of the abdominal aorta and renal artery with blood pressure in the developing, spontaneously-hypertensive rat (SHR).  Masters thesis, Memorial University of Newfoundland.

abstract: The elevation of arterial blood pressure in the spontaneously hypertensive rat (SHR) has been postulated to be the result of increased vascular resistance and that such an augmentation of vascular resistance may be due, at least in part, to changes of the vessel wall.  The present study is designed to examine this hypothesis. -- Animals from each strain of SHR, WAR and WKY were sacrificed at 2, 4, 5, 6, 7, 8, 12 and 18 weeks of age.  Blood pressures from each group were obtained by intra-arterial cannulation.  The volume fractions of SMC, collagen and elastin in the media of the abdominal aorta and of the left renal artery of 2, 4, 8, 12 and 18 weeks old animals were estimated by stereological analysis at the EM level.  The estimated values of these components in the SHR were compared with those obtained from the WAR and the WKY controls. -- The systolic blood pressure in the SHR rose to a significant level from 5 weeks and further increased to a hypertensive level by 18 weeks of age, as compared with the controls.  As revealed by stereological analysis of the medial composition of the abdominal aorta and the left renal artery of the SHR, no significant difference was observed when comparing these parameters with those of the controls. -- The results of the present study indicate that the medial components of the arteries studied were not significantly different among the three strains of rat, up to 18 weeks of age, while the systolic blood pressure of the SHR was elevated significantly from 5 weeks of age. -- The elevation of arterial blood pressure during the development of the SHR therefore appears not to be the result of morphological changes in the media of the abdominal aorta and the renal artery.


identifier: Drover, Mary Sheila Lewis <https://research.library.mun.ca/view/creator_az/Drover=3AMary_Sheila_Lewis=3A=3A.html>   (1986) Study of a monoclonal antibody to human B cells.  Masters thesis, Memorial University of Newfoundland.

abstract: The purpose of this work was to characterize and determine the specificity of a mouse monoclonal antibody (NFLD.M1) which was derived from a fusion between SP2/0-Ag14 and spleen cells from a Balb/c mouse that had been hyperimmunized with B-cells from a chronic lymphatic leukemic patient.  Cloning was done by limiting dilution and positive clones were selected by screening on a panel of viable cells using the cellular enzyme-linked immunosorbent assay (CELISA).  This assay was shown to be more specific and sensitive than an ELISA that used glutaraldehyde-fixed cells. -- Two sources of the antibody (purified IgG1 from ascites fluid and supernatant from overgrown cultures) appeared to be identical in their serological pattern on several B-cell lines.  Specificity testing using the CELISA and several different cell types revealed that NFLD.M1 recognized some B-cells, but failed to react with any of the T-cells tested.  A Frequency Distribution plot of the data showed that NFLD.M1 reacted with the cells in a bimodal fashion compared to the normal distribution observed with the monomorphic monoclonal antibody, NEI anti-Ia.  Furthermore when NFLD.M1 antibody was expressed as a percent of the NEI anti-Ia it was found that all the DR4 positive cells produced values greater than 50% whereas DR4 negative cells gave values less than 30%.  Using 30% as a cutoff point a correlation analysis was done on the CELISA results for 42 cell lines.  The r value obtained for DR4 and NFLD.M1 was 1 with a p value of 2 x 10⁻¹⁰.  In addition significant r values were obtained for DRw53 and DQw3 which are in linkage disequilibrium with DR4. -- One-dimensional electrophoresis of the immunoprecipitated molecules from a DR4 cell produced a banding pattern that was compatible with that of the alpha and beta subunits of DR.


identifier: Casson, Alan Graham <https://research.library.mun.ca/view/creator_az/Casson=3AAlan_Graham=3A=3A.html>   (1985) Targeted chemotherapy : evaluation of monoclonal anti-CEA antibody drug conjugate efficacy.  Masters thesis, Memorial University of Newfoundland.

abstract: Targeted chemotherapy, a potentially clinically relevant method of increasing the selective delivery of cytotoxic agents to tumor cell populations has been evaluated. -- The model used in these studies comprised a target, the tumor associated carcinoembryonic antigen, which is expressed by a wide range of human solid tumors, and conjugates of vindesine, a potent vinca alkaloid, covalently linked to a specific monoclonal anti-CEA antibody. -- Characterisation of human tumor cell lines by immunocytochemistry and radiobinding assays established a range of CEA expression enabling selected cell lines to be used for the assessment of conjugate efficacy in vitro, and to be grown as xenografts in nude mice enabling a relevant pre-clinical model to be developed.  The effect of conjugate treatment upon the growth of xenografts with a range of CEA expression was then assessed. -- These studies demonstrated the efficacy and selectivity of immunochemotherapy both in vitro and in vivo using this model, confirming theoretical predictions.  In addition, prolonged survival of mice treated with conjugate and reduced toxicity of conjugated compared to free drug was demonstrated in one experimental protocol. -- Further investigations and the clinical potential of this approach are discussed.


identifier: York, Laura Jean <https://research.library.mun.ca/view/creator_az/York=3ALaura_Jean=3A=3A.html>   (1981) The genetics of the sixth and seventh complement components in man.  Masters thesis, Memorial University of Newfoundland.

abstract: The purpose of this thesis was to study the human complement components C6 and C7, in Newfoundland and to pursue the genetics of these proteins within the limits of the material obtained and the time allowed. -- Approximately 2400 sera from three Newfoundland populations were allotyped by the method of isoelectric focusing in polyacrylamide gel followed by specific hemolytic overlay.  The frequencies of the common alleles were calculated for two of these populations.  The West Coast community had frequencies of C6*a (0.6321) and C6*B (0.3670) and the Newfoundland families plus random individuals in a group had C6*A (0.6947) and C6*B (0.2980.  These frequencies are similar to those found in other populations.  The C6 alleles observed in the three populations were inherited in a manner consistent with a single autosomal locus and there was no evidence to suggest selection against the inheritance of the rare alleles.  Examination for linkage of C6 with HLA reiterated the negative results of previous studies.  An attempt to link the C6 and SOD (superoxide dismutase) loci in a West Coast family having a rare SOD variant was made but the data were uninformative. -- The homozygous C7*1 pattern was by far the most commonly observed, occurring in more than 99% of the samples allotyped.  The novel observation and investigation of an artifact associated with prolonged serum storage of the C7*1 protein such that it is modified and mimics the migration of the C7*3 protein during isoelectric focusing is described.  Genuine C7*3 alleles were also observed, two in heterozygote form, C7 3-1, and one which was due to either C7*3 homozygosity or C7 3-0.  Data suggesting the C7*2 allele is of Chinese origin are presented. -- ADDENDUM -- Since the final writing of this thesis, nine unrelated local Chinese people have been bled and their serum typed for C7.  Of the nine, three were heterozygous for C7*2.  This supports the suggestion that this allele is of Chinese origin and appears with a frequency of approximately 17%.  Further studies are currently in progress to accumulate family data for linkage efforts. -- SECOND ADDENDUM -- Following evaluation of this thesis, it has been pointed out that the term “allele” has been used here, as it sometimes is in published literature on C6 & C7, in an imprecise manner.  The DNA sequence coding for a polymorphic polypeptide is, strictly speaking the allele, whilst the polymorphic poly-peptide or protein should be referred to as the gene product.  The thesis should be read with this reservation in mind.


identifier: Ryan, Mary Catherine <https://research.library.mun.ca/view/creator_az/Ryan=3AMary_Catherine=3A=3A.html>   (1983) The prevalence of symptomatic chronic bronchitis in two iron ore processing plants.  Masters thesis, Memorial University of Newfoundland.

abstract: This research was undertaken to study the prevalence of symptomatic chronic bronchitis in a group of mining and mill workers to determine if there was an association between symptomatic chronic bronchitis and  tobacco smoking, length of dust exposure or age, individually or synergistically. -- Analyses were done by two statistical methods.  First, bivariate analysis done by cross tabulations using Chi-square as a test of significance gave the following results.  -- (a) There was a significant association between tobacco smoking and symptomatic chronic-bronchitis.  This association held when controlled by age and length of dust exposure. -- (b) Age was not significantly associated to symptomatic chronic bronchitis. -- (c) Length of dust exposure was not significantly associated to symptomatic chronic bronchitis. -- Second, a log-linear analysis was used to test different models for associations among the variables.  The results confirmed the association between symptomatic chronic bronchitis and smoking, and showed that there were some interactive effects between the independent variables, smoking, age and length of exposure which may be explained by the correlation between age and length of exposure and by some differences in smoking habits by age.


identifier: Deganus-Amorin, Sylvia <https://research.library.mun.ca/view/creator_az/Deganus-Amorin=3ASylvia=3A=3A.html>   (1992) A prospective study of early puerperal morbidity in Kumasi, Ghana.  Masters thesis, Memorial University of Newfoundland.

abstract: The objectives of this study were to; (1) describe the incidences and determinants of early puerperal morbidities in women in Kumasi; and (2) provide information for use in improving the postpartum health care of these women. -- A cohort of 472 women from home, who had vaginal deliveries at the Komfo Anokye hospital in Kumasi, Ghana, were recruited and followed up during their early puerperal period.  Morbidity was assessed through interview, physical examination and haemoglobin investigation.  An overall 81% follow-up rate was obtained.  Forty-eight percent of subjects scheduled for follow-up failed to attend the special clinic and had to be traced to their homes. -- The subjects were mostly from low socioeconomic levels.  Their mean age and parity was 25.4 years and 2.8 deliveries respectively.  While three-quarters of them (78.4%) had at least one identifiable pregnancy or labour risk factor (nearly 40% were anaemic at labour) they had relatively uneventful deliveries. -- Nine out of every ten women seen postpartum reported at least one health complaint.  The most frequent symptoms were fever (28%), abdominal pain (64%), perineal soreness (31%) and dysuria (26%).  Nearly 60% of the study women self-treated with potent medications ranging from analgesics to antibiotics. -- On assessment, 66.6% of the women discharged home routinely after delivery, were found to have at least one puerperal health complication requiring medical attention.  In 46% of subjects morbidity was severe enough to warrant medical attention within 72 hours or less.  The incidences of puerperal upper and lower genital tract infection in the study sample were 180 and 151 per 1000 deliveries respectively.  Postpartum anaemia occurred in 35.1% of women.  The incidences of postpartum hypertension, acute urinary tract infection, and mastitis were 88.2, 52.2 and 13.1 per 1000 respectively. -- The findings in this study suggest that high rates of puerperal complications occur in women in Kumasi who are discharged home in a "satisfactory" health condition within a few hours after delivery.  Postpartum health care services should address this need.  It is recommended that: (1) a routine early postpartum clinic be organised for all women discharged home within hours after delivery; (2) women receive health education about the hazards of self-medication, and (3) further attention be paid to identifying the determinants of the specific morbidities.


identifier: Desousa, Jacques Real Barroso <https://research.library.mun.ca/view/creator_az/Desousa=3AJacques_Real_Barroso=3A=3A.html>   (1993) Investigation of woodchuck hepatitis virus-cell interactions.  Masters thesis, Memorial University of Newfoundland.

abstract: Hepatitis B virus (HBV) is a highly hepatotropic DNA virus, which causes several life threatening liver diseases.  These diseases are a major public health problem of worldwide proportions.  Initial binding of HBV to host cells is poorly understood.  However, virus attachment is an event of utmost importance because it determines viral species specificity and cell tropism and, in consequence, viral pathogenicity.  Among hepadnaviruses, the woodchuck hepatitis virus (WHV) displays the highest degree of molecular and biological similarity to HBV.  Pending the availability of applicable cell cultures, a woodchuck model of hepatitis B offers a valuable in vivo system for the study of hepadnaviral attachment. -- The aim of this thesis was to recognize the properties of WHV binding to the host cell surface.  The studies revealed that the WHV envelope (WHsAg) binds to woodchuck hepatocyte plasma membranes (HPMs) with kinetics that suggest specific ligand-receptor interaction.  Further, they also demonstrated that a 330-kD HPM molecule is involved in the virus attachment.  Plasma membranes isolated from woodchuck splenocytes and kidney cells also bound WHsAg, however, to a lesser extent, when compared to HPMs.  These non-hepatic membranes exhibited a similar 330-kD WHV binding molecule.  Results obtained through virus and lectin affinity chromatography and enzymatic digestions revealed that the binding of the WHV envelope displayed by the 330-kD molecule is mediated both by N-linked polymannose and O-linked heparan sulphate, but not by the protein core which links these carbohydrates.  This suggests that the 330-kD receptor is a proteoglycan and that its virus binding site is constituted both by heparan sulphate and by polymannose.  Preincubation of the WHV envelope with an exogenous glycosaminoglycan, heparin, inhibited the binding of WHV envelope to the 330-kD receptor, as well as to host intact HPMs.  This suggests that the WHV attachment may be blocked by heparin-like substances in vivo. -- The nature of the WHV envelope interaction with host cells was further investigated when a peptide homologous to the N-terminal sequence of the virus envelope preS1 protein, predicted to be exposed at the virion surface, was synthesized and used to test its specificity towards species, cells and subcellular organelles.  The peptide demonstrated specific binding to an intracellular component exclusively expressed in woodchuck hepatocytes and lymphoid cells, suggesting that an intracellular receptor molecule(s) may play a role in determining virus tropism.


identifier: Gyapong, Tony Emmanuel <https://research.library.mun.ca/view/creator_az/Gyapong=3ATony_Emmanuel=3A=3A.html>   (1986) 3α-Hydroxysteroid dehydrogenase activity in the cytosolic fractions of human placenta, kidney and liver.  Masters thesis, Memorial University of Newfoundland.

abstract: Although the major metabolites of 3-ketosteroids voided in human urine are 3α-hydroxysteroids or their derivatives, there has been very little published work on the purification and characterization of the human 3α-hydroxysteroid dehydrogenases which must be involved in their genesis. -- The presence of the 3α-hydroxysteroid dehydrogenases in human liver, kidney and placenta has been demonstated by incubation of extracts of these tissues with 17α-methyl-5α-androstane-3α,17β-diol which was converted to the 3-ketone.  This was identified by thin layer chromatography and by high performance liquid chromatography and by further characterization after sodium borohydride reduction of the 3-ketone to the 3β-alcohol. -- The NAD-dependent liver cytosol enzyme activity found in the 40-60% ammonium sulphate precipitate has been partially purified using ion-exchange and gel filtration chromatography.  The 3α-HSD activity appears to reside in a number of isozymes separable by carboxymethyl-cellulose chromatography one is tentatively identified as being a human liver ADH, β1β1 which was shown by iso-electric focussing to have a pI between 9 and 10.  4-Methyl pyrazole was found to inhibit the ethanol dehydrogenase activity but not the 3α-HSD activity of these isozymes. -- A two-fold ratio of 3α- : 3β-HSD activity was observed in the human kidney cytosol but the activity in the microsomal fraction was entirely due to 3β-HSD with only a trace of 3α-HSD activity.  The 3α-HSD activity found in the cytosolic fraction of the human placenta was very unstable.


identifier: Cheng, Linong <https://research.library.mun.ca/view/creator_az/Cheng=3ALinong=3A=3A.html>   (1990) An examination of the measurement of mean circulatory filling pressure in the anaesthetized rat.  Masters thesis, Memorial University of Newfoundland.

abstract: The measurement of mean circulatory filling pressure (MCFP) is widely used in research, yet the basic assumption of equal pressures throughout the body during MCFP measurement has not been adequately tested. Therefore, this study examined whether there is pressure equilibrium between tributary veins and the central vena cava during the MCFP manoeuvre. The time course needed for pressure equilibrium was also examined. Pressures in the iliac artery, the hepatic portal vein (HPVP), the renal vein (RVP) and the inferior vena cava (IVCP) were determined at 4-second intervals over a 20-second period of circulatory arrest, produced by inflating a right atrial balloon, under the conditions of normal blood volume (NBV), 10% blood volume depletion (-10% BV) and 10% blood volume expansion (+10% BV)  in urethane-anaesthetized rats. HPVP was found to be higher than IVCP during the full period of arrest at -10% BV and during the first 16 seconds of arrest at +10% BV. At NBV, HPVP was significantly higher than IVCP only at the 4th second of the arrest. RVP was virtually equal to IVCP in the  three volume states. At the 8th second of the arrest in -10%  BV , HPVP was 6.2 ± 0.8 mmHg and IVCP was 3.4 ± 0.2 mmHg; in  +10% BV, HPVP was 7.7 ± 0.5 mmHg and IVCP was 6.2 mmHg ± 0.4  mmHg, differences between HPVP and IVCP being significant (p < 0.01 for each of the comparisons). To test if this pressure disequilibrium resulted from reflex vasoconstriction, the MCFP manoeuvre was carried out following ganglionic blockade with hexamethonium and atropine. HPVP was found still to be significantly higher than IVCP for 12 seconds in both -10% and +10% BV conditions. It is concluded that during conditions of rapid blood volume alterations, HPVP is significantly higher than IVCP during the MCFP manoeuvre; physical transhepatic resistance at zero inflow appears to play a role in the constitution of this pressure disequilibrium. -- Keywords: mean circulatory filling pressure (MCFP) -- hepatic portal venous pressure -- blood volume alteration -- ganglionic blockade -- anaesthetized rats.


identifier: Yang, Xiaolong <https://research.library.mun.ca/view/creator_az/Yang=3AXiaolong=3A=3A.html>   (1995) An in vitro study of oncogenesis of primary cervical cells by human papillomavirus 16 and cigarette smoke condensate.  Masters thesis, Memorial University of Newfoundland.

abstract:
Previous epidemiological studies indicated that cigarette smoking females are at increased risk of developing cervical  cancer. However, because of the confounding variables of these studies, and since other studies have given conflicting results, convincing evidence is lacking. Furthermore, the molecular role of cofactors, such as hormones, in the multistage carcinogenic process is still unclear. -- To examine the role of human papillomavirus (HPV) and cigarette smoking in the carcinogenesis of cervical cancer, I studied two HPV16 immortalized endocervical cell lines previously established in this lab, HEN-16 and HEN-16-2. Both lines were treated with cigarette smoke condensate (CSC) at 75, 100, 125 μg/ml. After 6-12 months' treatment with CSC, 10⁷ cells of treated and untreated immortalized cells with equal passages were injected into female nude mice. Four to six weeks later, only CSC-treated cells but not CSC-untreated immortalized cells formed palpable tumors, which were subsequently used to derive tumor cell lines, HEN-16T and HEN-16-2T. -- Further characterization of the immortalized cell lines and CSC-transformed cell lines indicated that the CSC-treated
tumorigenic cells a) displayed distinct morphologies in monolayer and organotypic (raft) cultures; b) proliferated faster in DMEM, a medium containing physiological calcium levels; c) showed in vitro anchorage-independency; d) contained and expressed similar levels of HPV16; e) expressed similar levels of some cellular genes associated with enhanced malignancy, c-myc, H-ras, p53, WAF1, GADD45, GADD153, and fibronectin, compared with immortalized cells. However, f) HEN-16T and HEN-16-2T expressed higher levels of  B-myb and PCNA; and g) obtained enhanced resistance to growth inhibition by tansforming growth factor-β1 (TGF-β1) and retinoic acid (RA) . On the other hand, the two immortalized cell lines displayed higher levels of p53, B-myb, PCNA and lower levels of Wafl and fibronectin, compared  with primary endocervical cells. -- In addition, two novel cDNAs, designated PA4 and PA9, which were specifically expressed at higher levels in immortalized cells and primary  endocervical cells, respectively, were identified and cloned  using differential display assays. Further characterization of these two novel cDNAs will be very helpful for us to fully understand the molecular pathogenesis of cervical cancer. -- In summary, this study provided the first in vitro evidence that cigarette smoke can enhance the risk of developing cervical cancer in HPV-infected patients. Furthermore, the in vitro system will be very useful to investigate the mechanism of multistep carcinogenesis of cervical cancer.


identifier: Khare, Suvarnalatha <https://research.library.mun.ca/view/creator_az/Khare=3ASuvarnalatha=3A=3A.html>   (1995) Analysis of the role of glucocorticoid response elements (GREs) of human papillomavirus type 16 through consensus mutations of GREs.  Masters thesis, Memorial University of Newfoundland.

abstract: The association of certain papillomaviruses with cancer of the uterine cervix has been established unequivocally by previous studies. In addition, steroid hormones, especially glucocorticoids and progesterone, have been implicated as an  important cofactor in the oncogenesis. In this study, the role of glucocorticoid hormones in human papillomavirus type  16 (HPV16) expression and in the immortalization of cervical  cells by HPV16 was analyzed. -- To demonstrate the direct effect of the hormones on expression, the three glucocorticoid response elements (GREs) in the HPV16 regulatory region were mutated to the consensus GRE (cGRE) sequence, GGTACA(N)₃TGTTCT. The effect of these mutations on  expression was assayed using the chloramphenicol acetyl transferase (CAT) reporter gene, which was placed under the control of the HPV16 enhancer with the cGREs, in pBLCAT2 vector. Activity of the CAT from these constructs was assayed in the HeLa cervical carcinoma cells. The CAT assays  revealed that both single cGRE and triple cGRE mutations enhanced the expression of the reporter gene in the presence  of glucocorticoid dexamethasone (dex). Similar results were obtained in the CAT assays when these constructs were transfected into primary baby rat kidney (BRK) epithelial cells. -- To examine the molecular involvement of the GREs in the enhanced in vivo CAT activities from cGRE constructs,  assays for DNA-protein interaction were performed in vitro using 22 base pair oligomers, representing the wild type GREs or cGREs at nucleotide (nt) 7385 and nt 7474, and HeLa whole cell protein extracts. Binding with the 22-mer representing the nt 7474 cGRE sequence in the mobility shift  assays was more, in comparison with the wild type GRE 22-mer. A moderate difference between the binding ability of nt  7385 GRE and the cGRE 22-mers was evident. The results of UV  crosslinking indicated that a HeLa cell protein of approximately 96 kDa, the size of the native glucocorticoid receptor (GR), interacted with the different GRE 22-mers. Southwestern blot assays using these 22-mers also suggested the interaction of the cGRE sequences with a protein, possibly the GR, which is known to be present in HeLa extracts. -- The HeLa cervical cell-pBLCAT2 system was an efficient and quantitative model for dex-induced expression,  possibly mediated by GR. To advance to a homologous promoter  and the natural target of HPV infection, whole HPV16 constructs and primary cultures of ectocervical cells were chosen. The effect of the cGRE mutations on the expression of E6 and E7 viral oncogenes in these cells was analyzed by the sensitive in situ hybridization assays. Strong hybridization signal for the E6-E7 oncogenes was displayed in the presence of dex, when the RNA from the cells transfected with the HPV16 genome construct containing cGREs, was analyzed. Next, these ectocervical cells, which are the appropriate cell type and the natural target of steroid hormone action, were chosen for stable transfection of the whole HPV16 genome construct with triple cGREs. An immortalized population of cells, designated HEC-16cGRE, was  established. These cells were morphologically distinct from the parental ectocervical cells. Analysis of the high molecular weight DNA in HEC-16cGRE cells by Southern blot indicated the presence of HPV16 DNA in an integrated form. The integrated HPV16 DNA was transcriptionally active, as shown by Northern blot assays which showed 4.5 and 2.3 kb transcripts, that contain mostly E6-E7. Interestingly, the viral RNA levels were about 2-fold higher in HEC-16cGRE than  in HEC-16, which contains HPV16 with wild type GREs. These cells were not tumorigenic, as shown by soft agar assays and  injection into nude mice. Further, the HPV16 genome construct with triple cGREs exhibited greater transformation  of BRK cells with activated ras oncogene than the wild type HPV16 genome. -- In conclusion, these results demonstrated an increase in expression and transformation from triple cGRE constructs. The enhanced expression was correlated with  the specific protein-binding to the GREs. The HEC-16cGRE cells generated from HPV16 with cGRE mutations could be a valuable tool to test the models proposed earlier for HPV and hormone-mediated oncogenesis.


identifier: Foley, Robert N. <https://research.library.mun.ca/view/creator_az/Foley=3ARobert_N=2E=3A=3A.html>   (1996) Cardiac complications of end-stage renal disease : identification of risk factors and design of clinical trials.  Masters thesis, Memorial University of Newfoundland.

abstract: This thesis has no abstract


identifier: Chen, Gang <https://research.library.mun.ca/view/creator_az/Chen=3AGang=3A=3A.html>   (1993) cDNA cloning and analysis of a flg variant fibroblast growth factor receptor from Xenopus laevis.  Masters thesis, Memorial University of Newfoundland.

abstract: 1. A cDNA library was constructed with mRNA isolated from stage 8 Xenopus embryos. -- 2. A full length cDNA clone encoding a FGFR-1/flg gene was isolated by screening this cDNA library. It is designated XFGFR-A3. -- 3. The XFGFR-A3 clone was sequenced by dideoxynucleotide chain termination method on both strands with synthetic oligonucleotides. It is 3863 bp in length and is predicted to encode an 810 aa protein. -- 4. The XFGFR-A3 clone contains two dipeptide deletions, Val⁴²³⁻ Thr⁴²⁴ and Pro⁴⁴¹Ser⁴⁴², which are different  from the published XFGFR-1 sequence ( Figure 8 ) . The Pro⁴⁴¹Ser⁴⁴² deletion has been described previously, however, this is the first report of the Val⁴²³⁻Thr⁴²⁴ deletion in Xenopus. Both dipeptide deletions result in the removal of consensus phosphorylation sites for Protein Kinase C ( PKC )  which may have consequences on intracellular signal transduction and the regulation of embryonic development. -- 5. RT-PCR results showed that XFGFR-A3 was expressed at all stages of Xenopus embryonic development. -- 6. The RNase protection experiment showed that XFGFR-A3 is a minor form of the XFGFR-1 in all stages of Xenopus embryonic development. Like the wild type XFGFR-1, XFGFR-A3 is also uniformly expressed throughout Xenopus development. -- 7. The XFGFR-A3 genomic DNA sequence covering the VT deletion region was sequenced. The VT deletion is located at an exon/intron boundary and comparison with the cDNA sequence suggests that the XFGFR-A3 variant arises from the use of an  alternate 5'splice donor site. -- 8. Expression vectors containing an insert covering the VT deletion region fused to the cDNA encoding GST were constructed by using XFGFR-A2 and XFGFR-A3. A PKC assay using the purified fusion proteins  products showed that Thr⁴²⁴ of XFGFR-A2 can be phosphorylated by PKC in vitro.


identifier: Wang, Dong <https://research.library.mun.ca/view/creator_az/Wang=3ADong=3A=3A.html>   (1990) Cerebral ischemia, spatial memory and locomotor activity.  Masters thesis, Memorial University of Newfoundland.

abstract: Stroke is among one of the leading neurological disorders in  clinics. The purpose of this study was to investigate the functional deficits of the experimental "stroke" animal. In order to get a better understanding of the real mechanisms behind these deficits, a systematic observation of the behavioural and pathological changes associated with cerebral ischemia was carried out in three experiments in Mongolian gerbils. -- In Experiment 1, an animal model using  delayed, repetitive cerebral ischemia was used to determine the behavioural and neuropathological changes following multi-episodes of cerebral ischemia. -- In Experiment 2, animals were pre-exposed to the test environment before ischemia and an attempt was made to determine whether the post-ischemic hyperactivity resulted from a simple change in  motor function or a deficit in spatial mapping ability. -- In Experiment 3, the neuropathological and locomotor activity changes resulting from different carotid artery occlusion durations (5,10 and 15 minutes) were investigated.  An attempt was made to determine whether the graded ischemia  resulting from the different ischemic durations resulted in graded increases in locomotor activity. -- From these three experiments it is concluded that the basis for the increased  locomotor activity following an episode of cerebral ischemia  is an alteration of spatial learning ability.


identifier: Devireddy, Laxminarayana R. <https://research.library.mun.ca/view/creator_az/Devireddy=3ALaxminarayana_R=2E=3A=3A.html>   (1996) Characterization of a cDNA encoding a novel transcription factor regulating expression of human neurotropic JC virus.  Masters thesis, Memorial University of Newfoundland.

abstract: JC virus (JCV) is a ubiquitous human neurotropic polyomavirus and is the etiological agent of the human demyelinating disease, progressive multifocal leukoencephalopathy (PML). Clinically, PML is found when immunodeficiency is caused by neoplasia,chronic disease, the  immunosuppressive chemotherapy used for organ transplantation and, more recently, AIDS. JCV is closely related to two other polyomaviruses, BKV and SV40. Unlike BKV and SV40, JCV has a narrow tissue-tropism to glial cells. Several lines of evidence were used to attribute the JCV neurotropism to the viral regulatory region, which is organized as two 98 bp repeats. -- Previous studies from our  laboratory demonstrated glial cell-specific expression of JCV in differentiating P19 embryonal carcinoma cells. The specificity was shown to be conferred by the NF-1 motifs present in the JCV regulatory region (Nakshatri et al., 1990a; Kumar et al., 1993). A cDNA encoding a factor that binds to the JCV NF-1 motif was cloned from a P19 glial cell  cDNA library (Kumar, 1994). -- The objective for this thesis  was to characterize this cDNA to understand its role in the expression and lifecycle of JCV. First, the cDNA sequence was determined. The analysis of the sequence of the cDNA revealed a significant homology both at protein and nucleic acid levels to a recently characterized factor interacting with Bc1-2 proto-oncogene protein called BAG-1. However, the  cDNA isolated in our laboratory has a different 3'-end (nt 710-973). Therefore the cDNA was named bag-2. The 3'-end of the cDNA appeared to be alternatively spliced, because the point of divergence of the cDNA sequence from that of bag-1 was a consensus splice site. -- The bag-2 cDNA encoded a major 30 kDa protein, as determined by in vitro translation.  The in vitro-translated BAG-2 protein was bound specifically  to the JCV NF-1 II/III oligonucleotide and to the JCV enhancer, as determined by mobility shift and Southwestern blot assays. Further, the transfected bag-2 cDNA specifically transactivated JCV early (JCVE) and late (JCVL)  promoters in non-glial HeLa cells and the transactivation required the integrity of the JCV NF-1 motifs. The recombinant BAG-2 produced in bacteria stimulated JCVE transcription in vitro by 3-fold, further suggesting that BAG-2 controls transcription. Interestingly, overexpression of BAG-2 in P19 glial cells inhibited the activated, but not  the basal, level of transcription of both JCVE and JCVL in a  dose dependent manner. However, such an inhibitory effect was not observed in U87 MG human glioblastoma cells. These results are reminiscent of the squelching observed for eukaryotic transcription factors. The bag-1 and 2 mRNAs were  expressed in mouse embryonal carcinoma and human cervical cells but not in U87 MG cells. However, the BAG-2 specific C-terminus was expressed only in P19 cells. -- Deletion analysis of BAG-2 revealed that the C-terminus (a.a 195-229)  was essential for transactivation, while the central α-helical region was important for DNA-binding. Though, the BAG-2 C-terminus was observed in P19 UD, glial and muscle cells, only in P19 glial cells was BAG-2 translocated into the nucleus. This was further confirmed by Southwestern blot  analysis with nuclear extracts from these cells. -- The BAG-1 is important for modulating cell death. Since BAG-2 showed  a significant homology to BAG-1, I tested the effect of BAG-2 on p53 promoter to delineate its possible role in apoptosis. The BAG-2 negatively regulated the mouse p53 promoter, as revealed by CAT assays. Thus, the BAG-2 might protect virus-infected cells from p53-induced apoptosis by decreasing the expression levels of p53. A model was proposed to explain the latency of JCV outside the central nervous system (CNS) and JCV glial cell-specific expression in CNS. In the model, BAG-2 is a novel transcription factor that modulates the expression of JCV differentially in glial  and non-glial cells. In the former it activates the expression of JCV as a transcription factor in the nucleus, explaining the neurotropism of JCV. In the latter it inhibits the apoptosis induced by p53 thus, allowing the virus to persist for prolonged time.


identifier: Le Gal, Yves Marcel <https://research.library.mun.ca/view/creator_az/Le_Gal=3AYves_Marcel=3A=3A.html>   (1973) Large volume hemodilution perfusion in newborn pigs : its effect on plasma volume, plasma proteins, and plasma electrolytes.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: Simultaneous evaluations of plasma volume, plasma protein and plasma electrolyte changes in response to large volume hemodilution perfusion in newborn pigs were made. These data  are needed for the application of the technique of extracorporeal circulation using large volume hemodilution in the neonate. -- Seven days old pigs were used in this study. Two groups of 15 animals underwent arteriovenous perfusion with the chest closed, at normothermia, and without an oxygenator in the system, perfusion was continued  until complete mixing of the blood and priming fluid was accomplished. The extracorporeal circuit was primed in group  I with a buffered Ringer-lactate solution, and in group II with a buffered solution of 2% Rheomacrodex in Ringer-lactate. Priming solutions were individually tailored to result in a (mixed blood and prime) hematocrit of 22%. The volume of the diluted blood in the circuit after perfusion, was identical to the volume of the priming fluid. A third group consisting of littermates of the above animals was subjected to the same surgical procedures but without perfusion. -- Hematocrit, plasma volume, total plasma proteins and electrophoretic patterns of proteins, osmolarity, and the major plasma electrolytes were measured immediately before and after perfusion, then every 8 hours over a period of 24 hours. Mean arterial blood pressure, heart rate and rectal temperature were monitored at the same  time. -- In both groups the hematocrit values came very close to the desired target of 22%. The hematocrit in group I showed a further drop until 16 hours following perfusion, whereas, that of group II rose steadily. -- Immediately after perfusion the deficit in plasma volume was more pronounced in group I suggesting an internal loss from the intravascular space, since there was no corresponding reduction in body weight. The replenishment of plasma volumes followed an exponential curve and was faster in group I. The restoration of plasma proteins in both experimental groups was also exponential and was faster in group II. -- Osmotic equilibrium was reached at the end of perfusion. There was a steady rise in osmolarity during the following 24 hours. Sodium and chloride followed the osmolarity pattern. -- Newborn pigs can cope with a large volume hemodilution resulting in a hematocrit of 22%. Their ability to counteract plasma volume and plasma proteins losses is well developed so that restoration is accomplished  in about 24 hours. The restoration of plasma volume occurs faster than the restoration of plasma proteins, but when Rheomacrodex is present the reverse is the case. -- The reappearance rate of proteins is about identical to the disappearance rate of Rheomacrodex. This substance binds water selectively, therefore it has a stabilizing effect on plasma volume shifts but not on plasma osmolarity. Two percent Rheomacrodex in Ringer-lactate enhances protein restoration considerably.


identifier: Hobeika, Christine M. <https://research.library.mun.ca/view/creator_az/Hobeika=3AChristine_M=2E=3A=3A.html>   (1997) Knowledge, behaviours, perceived barriers and facilitators in university women regarding heart health.  Masters thesis, Memorial University of Newfoundland.

abstract: Cardiovascular disease (CVD) is the number one cause of mortality in Canada. A number of risk factors for CVD have been identified. Some of these risk factors are modifiable, such as smoking and use of oral contraceptives; others are unmodifiable, such as family history. Often the modifiable risk factors are acquired early in life. Females have unique  risk factors and shared risk factors act differently in men and women. -- The objectives of this study were to determine: (1) level of heart health knowledge in university  females 17-25 years, (2) level of awareness of how daily behaviours may impact on the etiology of CVD, (3) level of concern regarding CVD, (4) presence of risk factors, (5) practices with respect to heart health behaviour and (6) factors viewed as barriers/facilitators to the practice of heart health. -- A cross-sectional descriptive study using a  self-completed questionnaire was applied to females attending Memorial University of Newfoundland. A randomized one-stage cluster sample was employed. The study sample consisted of 463 university females ages 17-25. -- Eighty-seven percent of respondents believe present behaviours may impact future health; 85% believe CVD can be prevented; and 68% stated they were concerned about CVD and its risk factors. -- Knowledge, incidence of risk factors and present  health practices were compared with the Newfoundland Heart Health Study (1990). In general, the overall knowledge level  and present health practices were higher in this study population than in the NHHS subjects, while the prevalence of risk factors was lower in this study population compared to the NHHS subjects. -- Recommendations for the development  of appropriate and relevant health promotion programming for  the target population were developed.


identifier: Thangavelu, Maya <https://research.library.mun.ca/view/creator_az/Thangavelu=3AMaya=3A=3A.html>   (1987) Effect of paracentric inversion on Meiosis and reproduction.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: Paracentric inversions are intrachromosomal rearrangements that involve inversion of a segment on one arm of a chromosome. Unlike other rearrangements, the frequency of paracentric inversions and that of their recombinants is low  in the normal human population as well as in clinically defined ones. The effect of heterozygosity for each of a variety of paracentric inversions (varying in the length of the inverted segment and location relative to the centromere), on some aspects of meiosis and reproduction, in  male and female mice, were investigated to determine the existence of mechanisms which may explain this observation. -- In male mice, heterozygosity for paracentric inversions involving large segments, was associated with meiotic disturbance, measured by a decrease in the proportion of haploid secondary spermatocytes and an increase in that of heteroploid secondary spermatocytes. This disturbance appears to be associated with dicentric recombinants. Studies suggest that loop formation during the pachytene stage of spermatogenesis has a role in preventing crossover and consequently recombinant formation. Association between size of the inverted segment and meiotic disturbance was not  evident in female heterozygotes. -- Despite meiotic disturbance in male heterozygotes, litter size, a measure of  postnatal phenotypic expression of chromosomal rearrangement, is not affected, suggesting pre-gametic selection. Pre-gametic selection and consequent reduction or  absence of phenotypic expression in male heterozygotes may result in underascertainment of paracentric inversion. On the contrary, despite lack of significant meiotic disturbance, reduction in litter size is observed in females  heterozygous for some inversions. These observations in females suggest post-gametic and possibly post fertilization  selection. Differences between males and females in the stage at which selection operates may account for differences in the efficiency of selection in the two sexes.  This may explain why the mother, rather than the father, is the carrier of paracentric inversion in most instances of recombinants reported in humans. -- The observations made in  this study, suggest that a variety of unique factors may be responsible for the low frequency of balanced paracentric inversions and their recombinants in humans. They are: cytogenetic limitations in the identification of the inversion, meiotic mechanisms that suppress recombinant formation, efficient pre-gametic selection in male heterozygotes and failure of the resulting gametic loss to affect reproductive fitness in male heterozygotes.


identifier: Hamed, Azza <https://research.library.mun.ca/view/creator_az/Hamed=3AAzza=3A=3A.html>   (1990) Effect of zinc deficiency on cadmium-induced immunopathology.  Masters thesis, Memorial University of Newfoundland.

abstract: The heavy metal cadmium is a widely distributed naturally occurring toxic element. Zinc and cadmium have striking physical and chemical similarities. The fact that they compete with each other for the same metallothionein makes their biological interactions very likely. In this study the  effect of zinc deficiency on potentiating the pathologic effects of cadmium on the immune system and the kidneys were  studied. Four week old C57BL6 male mice were fed zinc deficient diet (Zn 1 ppm) for 4 weeks, then cadmium 50 ppm was added to the drinking water, and after 3 weeks they were  fed a regular chow diet. Animals were sacrificed at 0, 3 and  6 weeks after cessation of treatment. In other groups, 50 ppm zinc was added to the regular chow diet. -- The number of IgM and IgG antibody forming cells in the spleen was significantly lower after treatment with zinc-deficient diet  compared to nontreated controls. Concurrent administration of cadmium antagonised that reduction. Proliferative response of spleen cells to the T cell-mitogen, phytohaemagglutinin decreased after treatment with zinc-deficient diet and cadmium administration tended to increase  it. The number of CD4+ and CD8+ cells was decreased after treatment with zinc-deficient diet and a further reduction was observed after concurrent cadmium administration. Natural killer cell activity in the spleen decreased after treatment with zinc deficient diet. Concurrent cadmium administration caused more suppression. -- Simultaneous Treatment with zinc deficient diet and cadmium did not alter  spleen, thymus and kidney weights and lymphocyte count. However, lymphocyte count in blood collected from the right atrium of the heart was significantly decreased in animals treated with zinc-deficient diet. -- On electron microscopic  examination, kidneys of cadmium-treated mice showed ultrastructural alterations in the proximal tubular epithelial cells. However, animals treated with low zinc diets showed cellular degeneration mainly in the cortical area of the thymus. Zinc concentrations in the kidney tended  to decrease after treatment with zinc-deficient diet. Cadmium concentrations increased after treatment with zinc-deficient diet and further increase observed after concurrent cadmium administration. -- INDEXING KEY WORDS: Cadmium; Zinc; Cellular Immunity.


identifier: Dawe, Doreen Elizabeth Noble <https://research.library.mun.ca/view/creator_az/Dawe=3ADoreen_Elizabeth_Noble=3A=3A.html>   (1991) Effects of acute exercise on neuropsychological performance in an elderly population.  Masters thesis, Memorial University of Newfoundland.

abstract: The effects of a single 15-minute bout (i.e. acute) of nonstrenuous exercise on three neuropsychologic tests were evaluated using a randomized pre-post experimental design. Two tests measured memory recall performance; the modified Set test and the Word Fluency test. The third was a test of psychomotor performance; the Symbol Digit test. Twenty nursing home residents (aged 76-93 years) were assigned randomly to an exercise or passive intervention condition, with the tests administered pre-intervention, immediately post-intervention, and again after a 30-minute delay. Significant results were obtained on the modified Set test, which is a word fluency test with semantic cues. The scores at both post-tests were significantly elevated over the pretest score in the exercise group (p <.01), whereas the control group scores did not differ significantly across times of measurement. The magnitude of exercise-induced gain  (i.e., approximately 20% over the pretest level) was such that the effects of acute exercise are indicated to have meaningfully facilitated semantic recall in nursing home residents. Demographic studies indicate that the 75 and over  age group will show the greatest growth rate within the senior population thus increasing the demand for institutionalized care. The findings of this study indicate that aspects of memory can be improved using exercise which can be readily incorporated into daily nursing home care; this may help maintain the independence of this frail group.


identifier: Balram, B. Christofer M. <https://research.library.mun.ca/view/creator_az/Balram=3AB=2E_Christofer_M=2E=3A=3A.html>   (1982) Coronary heart disease risk factors in Newfoundland children.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: A cross-sectional epidemiological study was carried out to investigate the distribution of coronary heart disease (CHD)  risk factors in children aged 8-10 and 14-16 years living in  two regions of Newfoundland characterised by high and low CHD mortality rates among adults. The age-adjusted CHD mortality rates for males and females in the high mortality region (HMR) were 298 and 131 per 100,000 respectively, compared to 198 and 85 per 100,000 population for males and females respectively in the low mortality region (LMR). Participants attended schools, randomly chosen from two communities in each region. -- Height, weight, systolic and diastolic blood pressures were measured in Phase I. Also, an EKG was recorded and a questionnaire administered. -- In the HMR, 275 (87%) children aged 8-10 and 383 (89%) aged 14-16 years responded positively. In the LMR, 255 (94%) children aged 8-10 and 259 (89%) children aged 14-16 years participated. -- Ten-hour fasting blood samples were taken in Phase II. Participants in the first phase were eligible to give blood. Sera were analysed for total and HDL cholesterol, triglyceride, uric acid and glucose. In the HMR, 242 (88%) children aged 8-10 and 350 (91%) aged 14-16 years participated, compared to 240 (94%) children aged 8-10 and 201 (78%) aged 14-16 years from the LMR. -- The following significant results were considered to be of epidemiological importance: -- 1. Boys and girls, aged 8-10 and 14-16 years, in the HMR had significantly higher mean systolic and diastolic blood pressures than those in the LMR. -- 2. Body mass index (weight/height²) was significantly greater for boys and girls aged 14-16 years in  the HMR than in the LMR. This risk factor was a strong discriminant between this age group in the two mortality regions. -- 3. The prevalence of elevated levels of systolic   blood pressure was significantly higher for boys and girls aged 8-10 years and for boys aged 14-16 in the HMR. -- 4. Boys and girls aged 14-16 years in the HMR had a significantly higher prevalence of elevated diastolic blood pressure. -- 5. The total number of boys aged 14-16 years with one and clusters of two and three primary CHD risk factors simultaneously was significantly higher in the HMR. -- 6. The prevalence of Type IV hyperprebetalipoproteinemia was significantly higher in children living in the HMR. -- The risk of developing premature CHD in adulthood appears to  be higher for chi1dren in the HMR. A primary prevention CHD program should, therefore, be started in this region. This program should employ health education as a means of improving nutrition, weight control, physical activity and preventing the onset of smoking. The effectiveness of this program, in reducing risk factor levels in a young population, should be evaluated.


identifier: Mandeville, Robert Parnell <https://research.library.mun.ca/view/creator_az/Mandeville=3ARobert_Parnell=3A=3A.html>   (1978) Lymphocytes and rheumatoid arthritis.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

title: Lymphocytes and rheumatoid arthritis

abstract: This thesis describes research into the immunological aspects of Rheumatoid Arthritis. The work uses as its model the immune-mediated reactions between graft and host which have been investigated intensively by immunologists in animals. The only natural situation in which these reactions  might be precipitated are those that arise during pregnancy when the immune systems of mother and offspring are in close  contiguity. Accordingly pregnancy is the focal point with concentration upon aetiological agents that might interact with the genetic make-up of mother and child to give rise to  the disease manifestation of Rheumatoid Arthritis in the later life of the offspring. -- In order to see if specific immunological sensitivity or tolerance could be passed from mother to offspring experiments were performed on rats in which the skin sensitizing agent Dinitrochlorobenzene was put on females prior to mating and the offspring were tested  for hypersensitivity using a popliteal lymph node weight assay. Within the limits of this assay there was no detectable effect of maternal priming on the reaction of the  offspring to this antigen. However, there was a pronounced effect of maternal priming on the spleen weights of the offspring in spite of the removal of the antigen in the skin  slough by the time of conception. The spleen weights had been determined crudely to detect immunological runting in the offspring but retrospective analysis revealed that in all experiments in which this protocol was followed the spleen effect was significant in spite of the standard error  introduced by the assay. -- Five Juvenile Rheumatoid Arthritis families were investigated using the mixed leucocyte culture reactions to detect genetically determined  factors that might predispose to maternal-offspring immune interaction. Two and possibly three of the probands were homozygotes at the HLA-D locus and in two of the families there was some evidence of genotypic or phenotypic inter-ference not related to the HLA region of chromosome six. These results are discussed in the light of the initial model and some possible immunological mechanisms outlined in  an appendix.


identifier: Kasinadhuni, Satyanarayana <https://research.library.mun.ca/view/creator_az/Kasinadhuni=3ASatyanarayana=3A=3A.html>   (1994) Enhancer activity of human papillomavirus type 11 in mouse embryonal carcinoma cells.  Masters thesis, Memorial University of Newfoundland.

abstract:
The activity of minimal constitutive enhancer (MCE (nucleotides 7657-7870) of human papillomavirus 11 was studied in undifferentiated and retinoic acid-differentiated  P19 mouse embryonal carcinoma cells. The enhancer was active  in RA-differentiated cells but not in undifferentiated cells. The in vivo activity was correlated with in vitro DNA-protein interactions by DNaseI protection assay. Four protected regions (I-IV) were detected with RA-differentiated nuclear extracts,, while protection was observed with undifferentiated nuclear extracts for the regions III and IV. To further study the functional importance of the protected regions, deletion mutant enhancers were tested for their in vivo activity. Mutant enhancers were active like wild type in RA-differentiated but not in undifferentiated cells. Deletion of protected region I and a 9 base pair sequence of the imperfect NF1 palindrome of protected region II of HPV11 MCE displayed activity close to that of wild type MCE. This suggests that the major constitutive enhancer activity is exhibited by the  minimal sequences of MCE (nucleotide 7785-7870) in P19 RA-differentiated cells. The mutant enhancer (nucleotide 7811-7870) which lost both protected regions I and II showed only  50% of the wild type activity. This indicates that sequences  displaying major constitutive activity of HPV11 MCE are
present in the protected region II, although functional synergism appears to be important for full activity of the enhancer. The role of entire protected region II by itself including the 9 base pair sequence which was deleted in the minimal enhancer sequences, was examined for its in vivo activity. The protected region II alone showed substantial in vivo activity in RA-differentiated cells which was 90-fold higher than the residual activity observed for undifferentiated cells. The in vivo activity of protected region II in RA-differentiated-dependent manner was correlated with in vitro DNA-protein interactions. The protected region II showed an extra DNA-protein complex with  RA-differentiated nuclear extracts in the gel retardation assay. The formation of this complex was competed by the imperfect NF1 palindromic sequences but not by the NF1 half-site sequence of protected region II. This suggests that certain factor(s) in RA-differentiated cells specifically binds the imperfect NF1 palindrome. The DNA-protein interaction was specific for HPV11 imperfect NF1 palindrome as the complex formation was not abolished either by polyoma  JC virus perfect NF1 palindrome or its mutant sequence. This  suggests the existence of family of NF1 proteins in P19 RA-differentiated cells that show different binding specificities for the NF1 binding sequences of imperfect and  perfect palindromic nature. As the extra RA-differentiated DNA-protein complex was specific for the imperfect NF1 palindrome, UV cross-linking was performed to determine the number of proteins interacting with it. At least six proteins were found to interact with the imperfect NF1 palindrome and three of them were specific for RA-differentiated nuclear extracts. The exact nature and binding sites of these three proteins for the functional importance of protected region II in RA-differentiated cells  require further investigation.


identifier: Rahman, Anisur <https://research.library.mun.ca/view/creator_az/Rahman=3AAnisur=3A=3A.html>   (1986) Factors influencing the intestinal absorption and metabolism of polynuclear aromatic hydrocarbons.  Masters thesis, Memorial University of Newfoundland.

abstract: In this study various factors governing the intestinal absorption and metabolism of polynuclear aromatic hydrocarbons (PAHs) were examined. -- In the first part, the effects of gastrointestinal hormones and post-resection intestinal adaptive hypertrophy on xenobiotic-metabolizing enzymes, benzo(a)pyrene hydroxylase (BPH) and UDP-glucuronyl  transferase (UDP-GT) were observed. Fasted rats were injected with either saline, 250 μg/kg pentagastrin, 20 μg/kg cholecystokinin-octapeptide (CCK-OP) or 75 units/kg secretin daily for three days and killed on the fourth day. Microsomal preparations were made from the intestinal mucosa  and used in the enzyme assays. Pentagastrin produced a 236% increase in BPH activity in colonic mucosa but the rest of the intestinal segments remained unaffected. CCK and secretin did not cause any change in BPH activity in the intestine. UDP-GT activity in all parts of the rat intestine  was unaffected by the hormonal treatment. It is concluded that under the present experimental situation only pentagastrin has a significant effect on BPH activity in the  colon. -- Fasted rats were killed 4 weeks after a 70-cm resection of proximal intestine. Remaining ileal segments were thickened and increased in diameter. The mean villous height in the remnant ileum was l77% and 130% greater than the villous height in the control ileum and jejunum, respectively. The total protein content in the remnant ileum  also increased. UDP-GT activity per mg of protein showed a statistically significant drop in the remnant ileal mucosa but the BPH activity remained unchanged. It is proposed that  the presumably less mature hyperplastic cells have diminished UDP-GT activity. The unchanged BPH activity remains unexplained. -- In the second half of this study, factors influencing the bioavailability of PAHs from the intestinal content were observed. -- Rats with biliary and duodenal fistulae were administered radiolabelled hydrocarbons - 2,6-dimethylnaphthalene, phenanthrene, 7,12-dimethylbenzanthracene, anthracene and benzo(a)pyrene - dissolved in corn oil only or corn oil with exogenous bile. Subsequent 24-hour biliary and urinary excretion of radiolabel was monitored to assess the efficiency of absorption with and without bile. The following values for absorption without bile (as a % of absorption with bile) were obtained : 2,6-DMN-91.6%, phenanthrene-96.7%, anthracene-70.8%, 7,12-DMBA-43.4% and BP-22.9%. The values for anthracene, 7,12-DMBA and BP were significantly less than 100% but the values for 2,6-DMN and phenanthrene were not. Since the water solubility of the structural isomers phenanthrene and anthracene are 1.29 mg/L and 0.073 mg/L respectively, it is proposed here that for these PAHs, a water solubility of approximately less than 1 mg/L, makes the presence of duodenal bile a prerequisite for efficient absorption. -- In continuation of the studies with the PAHs,  it was established in the last part of this study that the bioavailability of 2,6-DMN from the intestinal content was not affected by the nature of the dietary vehicle (lipid or non-lipid vehicle) and concomitant fat digestion and absorption. Also, the biliary metabolites of 2,6-DMN undergo  an efficient enterohepatic circulation. -- [KEYWORDS]: Anthracene; Benzo(a)pyrene(BP); Benzo(a)pyrene Hydroxylase (BPH); Cholecystokinin; 7,12-Dimethylbenzanthracene (DMBA); 2,6-Dimethylnaphthalene (DMN); Intestinal resection and PAHs  metabolism; Pentagastrin; Phenanthrene; Polynuclear Aromatic  Hydrocarbons (PAHs); Secretin; UDP-Glucuronyl transferase (UDP-GT)


identifier: Kotsopoulos, Sotirios <https://research.library.mun.ca/view/creator_az/Kotsopoulos=3ASotirios=3A=3A.html>   (1983) Extralinguistic speech characteristics of children with conduct and anxiety disorder.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: The purpose of this study was to investigate in child psychiatric patients the associations between reflection-cognitive planning and temporal extralinguistic measures, and between anxiety and speech breath measures. It was postulated that patients with conduct disorder will be significantly less reflective while those with anxiety disorder will be significantly more anxious. Eighteen children were selected to participate in the study; nine fulfilled the criteria of conduct and nine those of anxiety disorder of the tri-axial classification scheme. Independent  measures were also taken on the Behaviour Problem Checklist (Peterson-Quay), Junior Eysenck Personality Inventory and Matching Familiar Figures Test. In the experiment, which was  carried out during the routine psychiatric assessment, the subjects were requested to respond to verbal tasks (counting, picture description, story telling). -- As predicted, disturbance of conduct was associated with short initial hesitation (delay) measures. This was shown both in the comparison between the conduct and anxiety disorder groups and in the correlation between conduct characteristics and initial hesitation. The average length of pauses was not found to vary with any of the independent measures. There was a significant negative association between frequency of pauses and 'Extraversion' on the picture description task. The initial hesitation and pausing  variables were independent of each other. As predicted also, anxiety across subjects was associated with increased breath  rate and lower output of speech per breath. The conduct and anxiety disorder groups were not distinguished from each other on speech breath measures; independent measures of anxiety showed also that children with conduct disorder were  as anxious as those with anxiety disorder. -- It is suggested that the initial hesitation variables are measures  of reflection and cognitive planning. Children with disturb-ance of conduct reflect little when responding to a verbal task; likewise they probably reflect little in planning their actions. Short reflection is a cognitive characteristic associated with disturbance of conduct while anxiety is an emotion not specific to anxiety disorders. It is concluded that extralinguistic measures may be useful in the diagnosis and management (cognitive behaviour therapies)  of child psychiatric disorders.


identifier: McWilliam, Tina Marie <https://research.library.mun.ca/view/creator_az/McWilliam=3ATina_Marie=3A=3A.html>   (1990) Effect of deuterium oxide (D2,O) on vascular smooth muscle.  Masters thesis, Memorial University of Newfoundland.

abstract: The influence of deuterium oxide (D₂O) on aortic vascular smooth muscle was investigated. The effect on receptor- and voltage-operated calcium channels was studied with the use of phenylephrine and potassium chloride respectively. D₂O depressed the phenylephrine induced contraction response in a dose dependent manner with 50% inhibition of maximum contraction observed with 60% D₂O. The effect of 60% D₂O on phenylephrine induced contraction was reversible and not dependent on an intact endothelium. Sixty percent D₂O also reduced potassium chloride induced contractions by 50% indicating an effect on voltage operated calcium channels. Studies with Bay K 8644, an L-type calcium channel activator, and calcium free buffer studies, confirm an effect on utilization of extracellular calcium sources. Inhibition of sucrose induced contraction and acetylcholine and isoprenaline induced relaxation with 60% D₂O suggest an effect on intracellular calcium mobilization or on the contractile elements themselves. D₂O also affected both the pD₂' for nifedipine and the pA₂ for prazosin. Collectively, these data indicate that D₂O acts at multiple sites. -- In vivo studies indicate that chronic oral administration of 25% D₂O for 12 days reduces the blood pressure of spontaneously hypertensive (SHR) and normotensive (WKY) rats. However, the lowering of blood pressure did not result  in a corresponding change in vascular smooth muscle contractility induced with phenylephrine and potassium chloride. These results support previous evidence that a reduction in blood pressure after hypertension has developed  does not reduce vascular reactivity changes. A further acute  study revealed that desensitization results from chronic exposure to D₂O such that 60% D₂O produces a significant depression of contraction only in aortic rings obtained from  SHR and WKY rats which had not been chronically treated with  twenty-five percent D₂O. -- KEY WORDS: Aorta; Calcium channels; Contraction; Deuterium oxide; Hypertension; In vitro; In vivo; Relaxation; Reversibility; Vascular smooth muscle


identifier: Sreenivasan, Uma <https://research.library.mun.ca/view/creator_az/Sreenivasan=3AUma=3A=3A.html>   (1981) A study of effeminate behaviour in boys.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

title: A study of effeminate behaviour in boys

abstract: Effeminacy is an attribute of gender, meaning thereby, that certain characteristics are present in boys or men which are  considered to be appropriate for girls or women. The existence of such an entity in this context has been recorded in myth and legend; ancient and modern, history. -- In this research, an attempt was made to assess the prevalence of effeminacy in a consecutive series of boys aged 6-12 years who were routine referrals to a child psychiatry clinic. Effeminacy was not the reason for referral in any of the boys. -- Effeminacy was measured as a quantitative variable by assigning weighted scores to a number of items obtained from the literature and from discussions with established researchers in this field. Of one hundred boys assessed, 15 per cent scored high, 39 per cent moderate and 46 per cent low on Effeminacy. -- A number of factors were shown to be related significantly to the presence of high scores on Effeminacy. Other factors also suggested in the literature to be important, were looked for, but did not relate significantly.


identifier: Jin, Yi-Ming <https://research.library.mun.ca/view/creator_az/Jin=3AYi-Ming=3A=3A.html>   (1993) Identification and characterization of a novel class of receptor for encephalomyocarditis virus on human cells.  Masters thesis, Memorial University of Newfoundland.

abstract: Encephalomyocarditis (EMC) virus belongs to the genus cardiovirus of the picornavirus family. The virus is important in the etiological study of several virus-induced human diseases. However, little is known about EMC virus attachment to nucleated cells. In this thesis, the results on the characterization of the biochemical nature of EMC virus receptors on two human nucleated cell lines, K562 and HeLa cells, are presented. The study showed that EMC virus bound specifically to both cell types. The number of receptor sites on HeLa cells was in the range of 1.6 x 10⁵ per cell and the dissociation constant for virus binding was  1.1 nM. These results are consistent with previously determined values for the binding of EMC virus to K562 cells. After trypsin digestion of K562 and HeLa cells, regeneration of virus binding activity was inhibited by cycloheximide treatment, suggesting that recovery of the EMC  virus-specific receptor is dependent upon intracellular protein synthesis. Further, digestion with proteases and neuraminidase, as well as lectin treatment of intact cells, cell membrane preparations and detergent-solubilized cell membranes, demonstrated that receptors for the virus on both  K562 and HeLa cells are sialoglycoproteins. Affinity chromatography employing EMC virus columns isolated 70-kD receptor proteins from K562 and HeLa cells. Virus overlay protein assay revealed that EMC virus specifically recognized only the 70-kD proteins in both the purified receptor preparations and in detergent solubilized cell membranes, suggesting that virus attachment to K562 and HeLa  cells could be exclusively mediated by the identified receptor molecules. Using the chromatofocusing technique, it  was found that the receptor on K562 cells is likely more sialylated than that on HeLa cells. Finally, Western blot analysis using anti-glycophorin A antibody revealed that the  antibody does not recognize the EMC virus 70-kD receptor on K562 or HeLa cells (the latter does not express glycophorin A). This indicates that the identified receptor proteins may  not be glycophorin A, but they represent novel, not yet described EMC virus receptor molecules.


identifier: Richler, Avrum <https://research.library.mun.ca/view/creator_az/Richler=3AAvrum=3A=3A.html>   (1979) A study of ocular refraction in western Newfoundland.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: Myopia is a debilitating condition that, in extreme cases, can cause blindness. For over 100 years, investigators have argued its etiology, with the hereditary and environmental schools polarized to the extreme. It was felt that a study of a population which had been exposed to two types of near work environments and which was fairly stable in composition  would further elucidate the relative influences of these factors on refraction. -- The population of three communities in Western Newfoundland was studied. These communities had been relatively isolated until about 1956, and had not had formal compulsory education until 1948. Subjects were examined optometrically and psychologically to  investigate previously reported associations of ocular refraction with near work, personality and body build. Familial resemblances for refraction and near work were also  examined. -- The study took place as part of a larger health  survey undertaken by the Faculty of Medicine at Memorial University of Newfoundland. Nine hundred and seventy-one subjects, or 80% of the target population were examined. -- This study addressed directly refraction, near work, education, heredity, personality and body build, to investigate previously reported associations of these variables. A literature review is presented for each of these reported associations, followed by results of the investigation. -- The findings were that females were more myopic than males and achieved myopia earlier than the males  in this population. Those under 30 years of age had more negative mean refraction than those over 30. Those who started school in 1948 were 30 years of age at the time of the study (1974). Those who did substantial near work at work or at leisure had more negative refractions. Near work showed substantial correlation with refraction after adjustment for other influencing variables, at all ages. The  parallel fit of mean near work, in hours, to mean refraction  by five year age intervals over essentially the entire life span was striking. -- The number of persons in this population with uncorrected refractive errors was very high compared to the United States population. This represents a serious public health problem. -- It was found that the correlation of first degree relatives for refraction was on the order of .20 to .25, and could have been inflated by familial similarities in near work patterns. -- Contrary to previous claims, no association was found for refraction and  personality or body build.


identifier: Laher, Ismail <https://research.library.mun.ca/view/creator_az/Laher=3AIsmail=3A=3A.html>   (1983) A study of the relationship between the chemical sensitivity of smooth muscle and the blood pressure of genetically hypertensive rats.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: An increased neuronal uptake and postsynaptic sensitivity to  noradrenaline in arterial smooth muscle from spontaneously hypertensive rats (SHR) has been reported by numerous laboratories. Also reported are changes in vascular reactivity of perfused arterial beds, and a deficiency in homeostasis of intracellular calcium (Ca²⁺) in some tissues  of SHR. The work presented here studied these changes in SHR and related animals to determine their relationship to the blood pressure. Also, these changes were studied in another model of genetic hypertension, the Dahl model of salt-sensitive (DS) hypertensive and salt-resistant (DR) normotensive rats. -- Increased neuronal uptake of noradrenaline in arterial smooth muscle (tail artery) was present from 6-8 week onward in SHR related animals. This became more pronounced at the later age groups studies (12-16 week and > 52 week old). In venous (portal vein) and non-vascular (anococcygeus) smooth muscle increased neural uptake of noradrenaline was present in only the very old SHR-related animals. Postsynaptic sensitivity to noradrenaline was increased only in tail arteries from very old SHR. The increased uptake 1 and enhanced postsynaptic sensitivity to noradrenaline were not present in DS and DR rats; in fact there was a trend for reduced uptake 1 activity in tissues from the DS hypertensive rat. -- While perfused mesenteric beds isolated from 12-16 week SHR had a greater reactivity and contractility to noradrenaline, no such changes were observed in mesenteric beds from DS and DR  using either noradrenaline, phenylephrine or serotonin as the agonist. The results using papaverine-induced relaxations of DS and DR aortae also suggested no aberrations in sequestration of Ca²⁺ in the Dahl rat. -- The  response to La³⁺, thought to reflect a more mobile pool of Ca²⁺ in the SHR, correlated with blood pressure in SHR-related animals when the results were expressed as a percentage of the maximal noradrenaline response, but was not correlated when expressed as mg tension per mg tissue weight. This was due to a negative correlation between blood pressure and the maximal response to noradrenaline in these animals. -- The results reported in this study suggested that alterations in pharmacological and mechanical properties of vascular smooth muscle observed in SHR were probably unique to that model of genetic hypertension.


identifier: Skirving, Paul Douglas <https://research.library.mun.ca/view/creator_az/Skirving=3APaul_Douglas=3A=3A.html>   (1983) Inactivation of ES and SS isozymes of horse liver alcohol dehydrogenase by 2R, 4S-2, 4-CYCLO-5[alpha]-Androstane-3[alpha], 17[beta]-Diol, a cyclopropyl steroid.  Masters thesis, Memorial University of Newfoundland.

abstract: This thesis has no abstract


identifier: Warrington, Richard John <https://research.library.mun.ca/view/creator_az/Warrington=3ARichard_John=3A=3A.html>   (1973) Inflammatory and other factors produced when sensitised lymphocytes are stimulated with antigen.  Doctoral (PhD) thesis, Memorial University of Newfoundland.

abstract: The tuberculin reaction is thought to be a specific immune response by sensitised lymphocytes to the antigen. It is characterised histologically by infiltration with mononuclear leukocytes. -- In experiments described in this thesis, mononuclear leukocytes from peripheral blood of tuberculin-sensitive guinea-pigs, and consisting of greater than 90% small lymphocytes, were stimulated in vitro in serum-free medium with the tuberculin antigen, PPD, for 3 days. The concentrated cell-free supernatants from these cultures produced an inflammatory reaction when injected intradermally into unimmunized guinea-pigs. Supernatants from cultures without antigen did not produce an inflammatory response. The reaction was characterised by erythema and induration reaching a peak at 4-6 hours with perivascular infiltration of polymorphonuclear and mononuclear leukocytes. The supernatants possessing inflammatory activity contained a factor inhibiting the migration of peritoneal macrophages from unimmunized guinea-pigs. -- In experiments in man, it was demonstrated that peripheral blood leukocytes, consisting of 10% lymphocytes and 90% polymorphs from tuberculin-sensitive donors, were inhibited in their movements by the presence of PPD. This inhibition, which did not occur in cells from tuberculin-negative donors, was blocked by 1 uM actinomycin D. In supernatants from PPD-stimulated serum-containing cultures of mononuclear cells from individuals sensitive to tuberculin, there occurred a factor capable of inhibiting the movement of polymorphs. This factor was not produced by cells from tuberculin-negative donors and was not demonstrable in the absence of serum. However, serum-free cultures of peripheral blood mononuclear cells from tuberculin-positive donors when stimulated with PPD released  a soluble factor producing erythema and induration when injected intradermally into unimmunized guinea-pigs. This reaction, characterized by an infiltration of mononuclear cells and polymorphs, was maximal at 4-6 hours. There appeared to be a correlation between antigen-specific release of this inflammatory factor and the ability of supernatants to enhance migration of polymorphs.


identifier: Darlow, John Michael <https://research.library.mun.ca/view/creator_az/Darlow=3AJohn_Michael=3A=3A.html>   (1991) Immunochemical and biochemical investigation of serum cholinesterase in hyperlipidaemia.  Masters thesis, Memorial University of Newfoundland.

abstract: Serum cholinesterase is an enzyme similar to acetylcholinesterase but of unknown function. Activity varies widely between individuals and numerous variants are known. Numerous studies have related the activity of serum cholinesterase to serum lipid concentrations but it is not known whether the enzyme plays a part in lipoprotein metabolism nor, if it does, whether this is related to its catalytic activity or to some other feature of the protein. It was therefore decided to compare the relationships of its  concentration and activity to the concentrations of serum lipids and lipoproteins. -- Cholinesterase was purified from  human serum, and antiserum was raised in a rabbit. The antiserum was used to measure the concentration of the enzyme by radial immunodiffusion in sera from 117 blood donors and 282 patients for whom serum lipid profiles had been requested. -- In the donor group the correlation between activity and concentration of the enzyme was 0.95 and there was little difference between the correlations of the two measures of cholinesterase with lipids. In the patient group the correlation between serum cholinesterase activity and concentration was only 0.88 and all the lipid indices correlated better with the concentration of cholinesterase than with activity. This was probably because  of variable loss of activity during transport and storage, and because of enzyme inhibition by drugs. -- For further analysis the patients were preferred because they had fasted  before blood sampling and had a greater range of lipid concentrations. Correlations with cholinesterase concentration were in the order 'total LDL' (LDL + VLDL) > VLDL > triacylglycerols > cholesterol. The correlation coefficients were similar, 0.51 with 'total LDL' as against 0.41 with cholesterol, but the shapes of the plots were markedly different. The plot of cholinesterase against cholesterol showed very weak relationship. The plot against triacylglycerols showed a well-defined triangular shape. At lower triacylglycerol concentrations a wide range of cholinesterase concentrations was found but with high triacylglycerol concentrations the enzyme concentration was always high. The possible nature of the relationship is discussed. -- In the preparatory stages, impurities occurring in affinity-purified cholinesterase were investigated by western blotting; and in concentration measurement, reproducible variation in precipitin ring patterns between individuals was observed. -- Key words: Serum cholinesterase concentration; serum lipids; immunological variation of serum cholinesterase.


identifier: Clarke, Cordell Godfrey <https://research.library.mun.ca/view/creator_az/Clarke=3ACordell_Godfrey=3A=3A.html>   (1995) Activation of locus coeruleus and concurrent observation of perforant path evoked potential, single unit activity and EEG in the dentate gyrus of the rat.  Masters thesis, Memorial University of Newfoundland.

abstract: Glutamate ejection in the vicinity of locus coeruleus (LC) in urethane anesthetized rats was used to selectively activate norepinephrine (NE) release from LC fibers. Extracellular units, 0.1 Hz perforant path-evoked potentials  (PP-EP), and hippocampal EEG were concurrently monitored in the dentate gyrus. In all experiments, LC activation induced  potentiation of the PP-EP. Significant potentiation of the PP-EP was not seen until an average of 20 s. after glutamate  ejection. Significant changes in spontaneous neuronal activity occurred both immediately and with a delay following LC activation. Subgranular layer, nonbursting neurons with narrow action potentials were immediately excited by NE for an average duration of 26.6 s. Distal subgranular layer, nonbursting neurons with wider action potentials were inhibited by LC activation for an average duration of 88 s. Bursting hilar neurons showed a delayed suppression, beginning an average of 10 s. after the flag and lasting for an average of 276 s. Finally, a group of three cells were unaffected. Theta was present before and after the ejection in the majority of experiments (11) and increases in theta frequency were seen in 3 animals. A loss of theta occurred within an average of 36 s. after the ejection in 8 experiments and lasted an average of 6 min. -- Based on the electrophysiological and anatomical results, a model is suggested in which there are three different interneuron types which are affected differently by LC-NE (excitiation, inhibition, and unaffected) and contribute to modulating excitation and inhibition in the system. Bursting  cells are either unaffected or show prolonged reduced activity similar to the period of LC suppression. -- It seems that conditions are set up by LC-NE release which contribute to the promotion of an increased coupling between  PP input and granule cell output which would increase DG circuit throughput.