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Biomedical subjects

M G Thomas

Publications and source records attributed to M G Thomas.

At least 91 records · Page 5Linked to original sources

Regulatory roles of high-density and low-density lipoproteins in cellular proliferation and secretion of progesterone and insulin-like growth factor I by enriched cultures of bovine small and large luteal cells.

We tested the hypotheses that bovine high-density (HDL) and low-density (LDL) lipoproteins differentially influence cellular proliferation and progesterone and IGF-I production by bovine small and large luteal cells. Unit gravity sedimentation was used to produce enriched cultures of small (> 95% pure) and large (75 to 90% pure) luteal cells from corpora lutea (CL) on d 4 and 10 of the estrous cycle. Addition of LDL, HDL, or both resulted in the maintenance of higher (P < .05) numbers of 3beta-hydroxysteroid dehydrogenase (HSD)-positive small and large cells in culture and produced a marked proliferation of 3beta-HSD-negative small luteal cells compared to control medium. Low-density lipoprotein and HDL each stimulated greater (P < .01) progesterone secretion in enriched large cell cultures on both days of the cycle, and by small luteal cells on d 10, compared to the control. Together, LDL and HDL maximized this response. Lipoproteins markedly stimulated (P < .01) the secretion of IGF-I by bovine large luteal cells, and secretion was greater (P < .05) by cells from d 10 CL compared to d 4 CL. Results suggest that the actions of lipoproteins in bovine luteal cells extend beyond their widely recognized roles in steroidogenesis and include remarkable effects on cellular proliferation and IGF-I secretion. Type of lipoprotein (LDL vs HDL) did not have differential effects on any of the variables measured.

3-Hydroxysteroid Dehydrogenases↗

Methscopolamine bromide blocks hypothalamic-stimulated release of growth hormone in ewes.

Twenty-five nonlactating ewes were used to test the hypothesis that methscopolamine bromide (MB) blocks secretion of growth hormone (GH) by affecting hypothalamic rather than pituitary mechanisms. Ewes were randomly assigned to receive a s.c. injection of 96 mg of MB or 2 mL of saline at min = 0. Saline-treated ewes were assigned to receive a subsequent (at +60 min) i.v. injection of 10 microg of growth hormone-releasing hormone (GHRH) to test pituitary responsiveness or .3 mg of clonidine to test hypothalamic responsiveness. Methscopolamine bromide-treated ewes were assigned to receive a subsequent (at +60 min) i.v. injection of 10 microg of GHRH, .3 mg of clonidine, or 2 mL of saline. Jugular blood samples were collected at 10-min intervals from -120 min to +240 min, and serum concentrations of GH were quantified with a RIA. No difference was detected in serum concentrations of GH with respect to MB vs saline treatment (P = .20). Concentrations of GH increased in saline-pretreated ewes following injections of clonidine or GHRH (P < .01). Treatment of ewes with MB, however, limited the ability of clonidine-induced mechanisms to increase concentrations of GH, but did not affect pituitary responsiveness to GHRH (P < .01). These data support the hypothesis that MB inhibits hypothalamic and not pituitary mediated mechanisms that regulate the secretion of GH.

Adrenergic alpha-Agonists↗

Dietary fats varying in their fatty acid composition differentially influence follicular growth in cows fed isoenergetic diets.

The working hypothesis was that dietary fats differing in fatty acid composition would differentially influence ovarian follicular growth. Cows (n = 27) were fed isoenergetic, isonitrogenous, and isofibrous diets containing no added fat (control; CT, n = 7) or diets supplemented with fats containing primarily saturated (SAT, n = 7), polyunsaturated (PU, n = 7), or highly polyunsaturated (HPU, n = 6) fatty acids. Coincident changes in serum lipid metabolites, insulin, and GH and the concentration of IGF-I in large and medium-sized follicles also were examined. Body weights and body condition scores remained similar for all groups throughout the study. Polyunsaturated fat increased (diet x day, P = .06) the number of medium-sized follicles on d 5 through 9 of a synchronized estrous cycle within 3 wk of onset of feeding and maximized (P < .001) this to a fourfold difference at ovariectomy after 7 wk. Fats with predominantly SAT and HPU tended (P < .10) to produce these effects after 7 wk. All fat-supplemented diets increased serum concentrations of total cholesterol (P < .05), GH (P < .05), and follicular fluid IGF-I in large follicles (P < .065) compared to CT but differentially influenced serum concentrations of insulin. Polyunsaturated fat stimulated a marked increase (P < .001) in serum insulin relative to controls within 3 wk, whereas SAT and HPU increased (P < .05) serum insulin only after 6 to 7 wk. We conclude that consumption of PU fatty acids stimulates a greater rate of ovarian follicular growth in cattle compared to CT, AT, and HPU. Future research should investigate the potential role of insulin in mediating PU effects on follicular growth.

Animal Nutritional Physiological Phenomena↗

Meningitis complicating spinal surgery.

STUDY DESIGN: A retrospective review of all cases of bacterial meningitis after spinal surgery. OBJECTIVES: To identify the usual clinical and laboratory features, and to determine the frequency of this complication. SUMMARY OF BACKGROUND DATA: Meningitis has been recognized as a rare complication of spinal surgery, but no series of cases has been reported previously, and there are no published estimates of its frequency. METHODS: A retrospective review of the medical records of all cases of bacterial meningitis after spinal surgery in Auckland over a 3-year period was done. RESULTS: Four cases were identified after 2180 operations, an incidence of 0.18%. All four patients survived. CONCLUSIONS: This is a rare complication from which a good outcome is possible with early diagnosis and prompt management.

Adult↗

Metabolic hormone secretion and FSH-induced superovulatory responses of beef heifers fed dietary fat supplements containing predominantly saturated or polyunsaturated fatty acids.

Ovulatory responses following FSH treatment were examined in beef heifers fed dietary fat supplements expected to produce differential effects on serum insulin concentrations and follicular recruitment patterns. Twenty-one heifers (n = 7/group) exhibiting regular estrous cycles were assigned randomly to either a control diet or to 1 of 2 fat-supplemented diets consisting of soybean oil (polyunsaturated fatty acids) or animal tallow (saturated fatty acids). The diets were formulated to be isoenergetic and isonitrogenous, and were fed until ovariectomy between experimental Days 35 and 45. Experimental Day 1 was defined for each heifer as the first day all of the treatment diet was consumed. After 20 d of diet consumption, estrous cycles were synchronized with prostaglandin F(2alpha) (PGF(2alpha)), and ovarian follicle populations were monitored via transrectal ultrasound for 4 d. Four days after estrus, the dominant follicle was aspirated and heifers were treated with FSH-P to induce superovulation. Ovulation rate was determined at ovariectomy 5 d after the superovulatory estrus (experimental Days 35 to 45). Both soybean oil and animal tallow diets increased (P < 0.05) the number of medium-sized follicles and increased (P < 0.02) serum concentrations of GH relative to the control diet. The soybean oil diet also increased (P < 0.001) serum concentrations of insulin on Days 14, 28, and 5 d after the superovulatory estrus. However, the number of ovulations following FSH treatment did not differ due to diet. Procedures employed in the current study were ineffective in recruiting the increased number of medium-sized follicles into the superovulatory pool.

Journal Article↗

Hepatitis B virus variants with core gene deletions in the evolution of chronic hepatitis B infection.

BACKGROUND & AIMS: Genomic variants of the hepatitis B virus (HBV) with core gene deletions have been identified in patients with chronic active hepatitis B, but the significance of these mutations in the course of chronic HBV infection remains unknown. The aim of this study was to longitudinally analyze the changes of HBV core gene deletion variants under the enhanced immune pressure of interferon alfa treatment and hepatitis B e antigen (HBeAg) to antibody to hepatitis B e antigen (anti-HBe) seroconversion. METHODS: HBV precore/core gene was amplified in 358 serum samples from 67 chronic HBV carriers (all HBeAg-positive) followed up for a period of 2-11 years. The core gene deletions were analyzed by gel electrophoresis, cloning, and DNA sequencing. RESULTS: HBV mutants with core gene deletions (37-250 base pairs) were detected in patients with long-standing HBV replication and ongoing hepatic inflammation, always together with the wild-type strain. They were associated with a significantly lower level of viremia and a high rate of seroconversion to anti-HBe. Core gene deletion mutants were preferentially eliminated after seroconversion, in contrast to the accumulation of HBV strains with a precore stop codon. CONCLUSIONS: These data indicate that HBV variants with core gene deletions may inhibit HBV replication, do not persist in preference of the wild-type HBV under enhanced immune pressure, and do not confer resistance to interferon alfa treatment.

Adult↗

Tc-99m stannous colloid-labeled leukocyte scintigraphy in the evaluation of the painful arthroplasty.

The aim of this study was to evaluate the utility of scintigraphy using leukocytes labeled with Tc-99m stannous colloid in the assessment of painful arthroplasties. The results of three-phase bone scintigraphy and imaging with Tc-99m-labeled leukocytes in 40 patients with painful joint prostheses, requiring the exclusion of infection are reported. Results were compared with microbiologic culture and/or long-term clinical review. Bone scintigraphy had a sensitivity of 100%, a specificity of 64%, and a diagnostic accuracy of 73% in detecting prosthetic infection. Tc-99m-labeled leukocytes yielded a sensitivity of 70%, a specificity of 100%, and a diagnostic accuracy of 93%. Leukocyte scintigraphy improves the specificity of bone scintigraphy in the assessment of the painful prosthetic joint. A positive study is highly suggestive of infection and warrants appropriate treatment.

Adult↗

Efficient retroviral infection of mammalian cells is blocked by inhibition of poly(ADP-ribose) polymerase activity.

Integration of proviral DNA into the host cell genome is a characteristic feature of the retroviral life cycle. This process involves coordinate DNA strand break formation and rejoining reactions. The full details of the integration process are not yet fully understood. However, the endonuclease and DNA strand-joining activities of the virus-encoded integrase protein (IN) are thought to act in concert with other, as-yet-unidentified, endogenous nuclear components which are involved in the DNA repair process. The nuclear enzyme poly(ADP-ribose) polymerase (PARP), which is dependent on DNA strand breaks for its activity, is involved in the efficient repair of DNA strand breaks, and maintenance of genomic integrity, in nucleated eukaryotic cells. In the present work, we examine the possible involvement of PARP in the retroviral life cycle and demonstrate that inhibition of PARP activity, by any one of three independent mechanisms, blocks the infection of mammalian cells by recombinant retroviral vectors. This requirement for PARP activity appears to be restricted to processes involved in the integration of provirus into the host cell DNA. PARP inhibition does not affect viral entry into the host cell, reverse transcription of the viral RNA genome, postintegration synthesis of viral gene products, synthesis of the viral RNA genome, or the generation of infective virions. Therefore, efficient retroviral infection of mammalian cells is blocked by inhibition or PARP activity.

3T3 Cells↗

Imported malaria in Auckland in 1993.

AIM: To determine the number of people with malaria in Auckland in 1993 and determine species, sources, exposure history, use of chemoprophylaxis, outcome and geographic attack rates. METHODS: We prospectively obtained the numbers of people with laboratory diagnosed malaria from all haematology departments in Auckland and then contacted the patients and their doctors to elicit further details. RESULTS: Forty three people, 30 men and 13 women, had malaria. Twenty eight were New Zealanders, 10 migrants, three temporary visitors and two not determined. Thirty two had P vivax infection, 11 P falciparum: none had complications. The highest attack rate was in travellers to the Solomon Islands. Eighty two per cent took prophylaxis. CONCLUSIONS: Malaria is an uncommon diagnosis in Auckland. Most patients took prophylaxis. The disease is undernotified. No one died of malaria in 1993 in Auckland.

Adolescent↗

Genomic variations in the hepatitis B core gene: a possible factor influencing response to interferon alfa treatment.

BACKGROUND/AIMS: Interferon treatment causes a sustained loss of virus replication only in a proportion of patients with chronic hepatitis B. This study investigated whether genomic variations in the precore/core gene of hepatitis B virus affect the response to interferon alfa. METHODS: The precore/core region was sequenced in 46 serum samples obtained before, during, and after interferon treatment of 12 patients. RESULTS: In 23 samples from 7 responders (group A), there were 24 missense mutations, whereas in 23 samples from 5 patients who did not respond or relapsed after treatment (group B), there were 141 missense mutations (P < 0.001). All group B patients had cirrhosis, but only 2 of 7 patients in group A had cirrhosis (P = 0.026). Substitutions in amino acids 21-27 of the core protein, known to diminish HLA-A2-restricted cytotoxic T-cell function, were found in all nonresponders but in none of the responders. No significant changes occurred in the precore/core region in responders after seroconversion to antibody to hepatitis B e antigen, but multiple variations persisted in group B during treatment and new mutations appeared with the relapse of hepatitis. CONCLUSIONS: Specific mutations in the core protein that can interfere with T-cell function occur frequently in patients with advanced chronic hepatitis B and may affect the response to interferon.

Adult↗

Disclosure of trauma and immune response to a hepatitis B vaccination program.

This study investigated whether emotional expression of traumatic experiences influenced the immune response to a hepatitis B vaccination program. Forty medical students who tested negative for hepatitis B antibodies were randomly assigned to write about personal traumatic events or control topics during 4 consecutive daily sessions. The day after completion of the writing, participants were given their first hepatitis B vaccination, with booster injections at 1 and 4 months after the writing. Blood was collected before each vaccination and at a 6-month follow-up. Compared with the control group, participants in the emotional expression group showed significantly higher antibody levels against hepatitis B at the 4 and 6-month follow-up periods. Other immune changes evident immediately after writing were significantly lower numbers of circulating T helper lymphocytes and basophils in the treatment group. The finding that a writing intervention influences immune response provides further support for a link between emotional disclosure and health.

Adaptation, Psychological↗

Steroidogenic activity, insulin-like growth factor-I production, and proliferation of granulosa and theca cells obtained from dominant preovulatory and nonovulatory follicles during the bovine estrous cycle: effects of low-density and high-density lipoproteins.

The role of high- and low-density lipoproteins (HDL and LDL) in regulating steroidogenic activity, cellular viability and proliferation, and insulin-like growth factor-I (IGF-I) production was examined in granulosa and theca cells from dominant preovulatory (DO) and nonovulatory (DNO) bovine follicles. Follicles were obtained from pluriparous nonlactating beef cows at ovariectomy 24 h after administration of a luteolytic dose of prostaglandin F2 alpha (DO) or during the first follicular wave on Days 5-8 of the estrous cycle (DNO). Lipoprotein effects on hormone production (ng/1.5 x 10(5) viable cells) and cell viability were studied in serum-free, defined medium containing LH and FSH (granulosa) or LH only (theca). During late stages (96-144 h) of culture, HDL in the presence of gonadotropins increased (p < 0.001) the production of progesterone by granulosa and theca cells and the production of IGF-I by granulosa cells. LDL did not stimulate granulosa or thecal progesterone synthesis and attenuated HDL-stimulated progesterone production by both cell types. Gonadotropin stimulation of terminal synthetic pathways was either attenuated (granulosa estradiol production) by addition of lipoproteins or maximally stimulated (theca cell androstenedione production) by a combination of LDL and HDL. Both lipoproteins increased (p < 0.05) granulosa cell viability in both follicle types, and a marked proliferation (p < 0.001) of steroidogenically inactive theca cells was observed from DO but not DNO follicles. Proliferation potential appeared to be switched off during the late stages of maturation of DNO follicles and switched on after induced luteal regression and rescue of DO follicles.

Animals↗