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Biomedical subjects

Peter Thomas

Publications and source records attributed to Peter Thomas.

At least 91 records · Page 5Linked to original sources
PubMed2003

Role of arachidonic acid and protein kinase C during maturation-inducing hormone-dependent meiotic resumption and ovulation in ovarian follicles of Atlantic croaker.

The roles of arachidonic acid (AA) and protein kinase C (PKC) during in vitro maturation-inducing hormone (MIH)-dependent meiotic resumption (maturation) and ovulation were studied in ovarian follicles of Atlantic croaker (Micropogonias undulatus). The requirement for cyclooxygenase (COX) metabolites of AA was examined using a nonspecific COX inhibitor, indomethacin (IM), as well as two COX products, prostaglandin (PG) F(2alpha) and PGE(2), whereas the role of lipoxygenase (LOX) was investigated using a specific LOX inhibitor, nordihydroguaiaretic acid (NDGA). The involvement of PKC was examined using phorbol 12-myristate 13-acetate (PMA), a PKC activator, as well as GF109203X (GF), a specific inhibitor of PKC and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), nonspecific inhibitor of protein kinases. Genomic mechanisms were examined with the transcription-inhibitor actinomycin D (ActD) and the functionality of heterologous (oocyte-granulosa) gap junctions (GJ) with a dye transfer assay. The AA (100 microM) and PGF(2alpha) (5 microM) did not induce maturation, and NDGA (10 microM) did not affect MIH-dependent maturation. However, IM (100 microM) partially inhibited MIH-dependent maturation. Conversely, AA and both PGs induced, and IM and NDGA inhibited, MIH-dependent ovulation in matured follicles. The PMA (1 microg/ml) did not induce maturation but caused ovulation in matured follicles, whereas PKC inhibitors (GF, 5 microM; H7, 50 microM) did not affect MIH-dependent maturation but inhibited MIH- and PMA-dependent ovulation. The PMA-dependent ovulation was inhibited by IM but not by NDGA. In addition, ActD (5 microM) blocked MIH-dependent, but not PMA-dependent, ovulation, and PGF(2alpha) restored MIH-dependent ovulation in ActD-blocked follicles. The AA and PGs did not induce, and GF did not inhibit, MIH-dependent heterologous GJ uncoupling. In conclusion, AA and PKC mediate MIH-dependent ovulation but not meiotic resumption or heterologous GJ uncoupling in croaker follicles, but a permissive role of COX products of AA during maturation is possible. A novel model of MIH-dependent ovulation is proposed in which 1). LOX and COX metabolites of AA are both required for ovulation, but at upstream and downstream sites of the pathway, respectively, relative to PKC, and 2). PKC is downstream of genomic activation.

Aging↗
PubMed2003

Breathlessness clinics within specialist palliative care settings can improve the quality of life and functional capacity of patients with lung cancer.

This paper is a development on recent research that proved the value of non-pharmacological techniques and strategies in the management of breathlessness in lung cancer. It evaluates the intervention in a specialist palliative care setting using an outpatient clinic at Lewis-Manning House. Referrals were made by the patients' physician or specialist nurse. Patients (n = 30) were assessed and treated by the senior physiotherapist in charge of the clinic over three sessions. A number of outcomes were measured at various stages of the patients' treatment. The results have confirmed and strengthened the previous published results. Highly significant improvements in patients' breathlessness, functional capacity, activity levels and distress levels have been shown. For example, the percentage of patients experiencing breathlessness several times or more per day was reduced from 73% to 27% four weeks later. In addition, this project has been able to demonstrate significant improvements in quality of life and high levels of satisfaction with the interventions. Qualitative data enhanced the findings of objective measurements.

Aged↗
PubMed2003

Fatal influenza A virus infection in a child vaccinated against influenza.

We report a fatal infection with influenza A virus in a 13-year-old child who had been vaccinated against influenza. Influenza A virus RNA was detected by PCR in lungs, bronchi and myocardium. A penicillin-sensitive strain of Staphylococcus aureus was also isolated from her bronchi. This case indicates that a primary viral pneumonia with influenza A virus complicated by a bacterial superinfection with S. aureus can run a fatal course even in a vaccinated child.

Adolescent↗
PubMed2002

Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease.

Selective skewing of autoreactive interferon-gamma (IFN-gamma)-producing T helper cells (Th1) toward an interleukin-4 (IL-4)-producing (Th2) phenotype can in experimental animals alleviate autoimmune disease without inducing general immunosuppression. In a prospective dose escalation study, we assessed treatment with human IL-4 (rhuIL-4) in 20 patients with severe psoriasis. The therapy was well tolerated, and within six weeks all patients showed decreased clinical scores and 15 improved more than 68%. Stable reduction of clinical scores was significantly better at 0.2-0.5 microg rhuIL-4 than at < or =0.1 microg rhuIL-4 (P = 0.009). In psoriatic lesions, treatment with 0.2-0.5 microg/kg rhuIL-4 reduced the concentrations of IL-8 and IL-19, two cytokines directly involved in psoriasis; the number of chemokine receptor CCR5+ Th1 cells; and the IFN-gamma/IL-4 ratio. In the circulation, 0.2-0.5 microg/kg rhuIL-4 increased the number of IL-4+CD4+ T cells two- to three-fold. Thus, IL-4 therapy can induce Th2 differentiation in human CD4+ T cells and has promise as a potential treatment for psoriasis, a prototypic Th1-associated autoimmune disease.

Adolescent↗
PubMed2002

Regulation of androgen receptors in Atlantic croaker brains by testosterone and estradiol.

A nuclear androgen receptor (AR1), distinctly different from the mammalian AR, has previously been identified in the brain of the Atlantic croaker, Micropogonias undulatus. Interestingly, brain AR1 levels were higher in gonadally recrudesced than in regressed fish. Therefore, the possible involvement of gonadal steroids in the regulation of brain AR1 levels was investigated in the present study. Saturation analysis of [3H]testosterone binding showed that brain AR1 levels were significantly reduced (2-3-fold) in either the nuclear or cytosolic fractions of both males and females three weeks after gonadectomy. Implantation of gonadectomized females with testosterone or estradiol-17beta one week prior to sampling resulted in physiological plasma steroid concentrations and restored brain AR1 levels to 60-105% of those in intact or sham-operated fish. These results suggest that gonadal factors, including both androgens and estrogens, are involved in the physiological regulation of brain androgen receptors in a teleost species during the reproductive cycle.

Animals↗
PubMed2002

A comparison of antagonist-precipitated withdrawal under anesthesia to standard inpatient withdrawal as a precursor to maintenance naltrexone treatment in heroin users: outcomes at 6 and 12 months.

To compare two methods of heroin withdrawal, 51 heroin users were randomised to undergo a 1 day precipitated withdrawal procedure using naloxone under anaesthetic. About 50 participants were randomised to receive the current standard inpatient withdrawal treatment using clonidine plus symptomatic medication. Following withdrawal, both groups were offered 9 months of naltrexone treatment and supportive counselling. Outcome measures were: commencement of naltrexone, retention in treatment and heroin use at 6 and 12 months. Significantly more of the precipitated withdrawal group completed withdrawal, commenced naltrexone and stayed in treatment for the first 3 months. Overall, there was a significant reduction in both self-reported heroin use and morphine concentration in hair over the 12 month study period, with participants in the precipitated withdrawal group showing significantly lower morphine concentration at 6 months. Being younger and having a lower level of dependence were predictors of abstinence at 6 and 12 months. The advantage of precipitated withdrawal under anesthesia did not persist beyond 3 months with respect to retention in naltrexone treatment or beyond 6 months with respect to heroin use. Long-term follow-up is crucial in assessing the effects of treatment interventions for heroin dependence.

Adrenergic alpha-Agonists↗
PubMed2002

Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes.

Induction of NF-kappaB-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease (ALD). Curcumin, a phenolic antioxidant, inhibits the activation of NF-kappaB. We determined whether treatment with curcumin would prevent experimental ALD and elucidated the underlying mechanism. Four groups of rats (6 rats/group) were treated by intragastric infusion for 4 wk. One group received fish oil plus ethanol (FE); a second group received fish oil plus dextrose (FD). The third and fourth groups received FE or FD supplemented with 75 mg. kg(-1). day(-1) of curcumin. Liver samples were analyzed for histopathology, lipid peroxidation, NF-kappaB binding, TNF-alpha, IL-12, monocyte chemotactic protein-1, macrophage inflammatory protein-2, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitrotyrosine. Rats fed FE developed fatty liver, necrosis, and inflammation, which was accompanied by activation of NF-kappaB and the induction of cytokines, chemokines, COX-2, iNOS, and nitrotyrosine formation. Treatment with curcumin prevented both the pathological and biochemical changes induced by alcohol. Because endotoxin and the Kupffer cell are implicated in the pathogenesis of ALD, we investigated whether curcumin suppressed the stimulatory effects of endotoxin in isolated Kupffer cells. Curcumin blocked endotoxin-mediated activation of NF-kappaB and suppressed the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. Thus curcumin prevents experimental ALD, in part by suppressing induction of NF-kappaB-dependent genes.

Alanine Transaminase↗
PubMed2002

A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status.

This study describes the natural history of atopic and wheezy disorders from birth to adult life in a cohort at risk of atopy. One hundred subjects born in Poole, England, were selected at birth in 1976 on the basis that at least one parent was atopic. Subjects were examined annually in the preschool years, and at the ages of 11 and 22 yr. Skin prick tests and total serum immunoglobulin E (IgE) were performed at each visit, and at 11 and 22 yr, bronchial hyperresponsiveness (BHR) to inhaled histamine was measured. Sixty-three subjects remained on follow-up at 22 yr. The annual prevalence of both wheeze and atopy increased with age. Twenty-five percent of adults showed both wheeze and BHR (asthma). Remission of wheeze was common in subjects younger than 5 yr of age and likely if wheezing occurred on less than two occasions, but wheeze at 11 yr was likely to persist. Sixty percent of the adult subjects with asthma developed sensitivity to common allergens by the age of 2 yr and were showing BHR by mid-childhood. Sensitization to dietary allergens occurred in infancy and waned after early childhood but predicted the early sensitization to inhalant allergens. In conclusion, adults with asthma can begin wheezing at any age but tend to sensitize early and have abnormal airway characteristics by the age of 11 yr.

Adolescent↗
PubMed2002

Effects of the maturation-inducing steroid on LH secretion and the GnRH system at different stages of the gonadal cycle in Atlantic croaker.

The effects of treatment with the maturation-inducing steroid 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) on luteinizing hormone-releasing hormone analog (LHRHa)-induced LH secretion were examined during several phases of the gonadal cycle in Atlantic croaker, Micropogonias undulatus. 20beta-S (1 and 5 microg/g of body wt) was administered by intraperitoneal (ip) injection, 24 h prior to injection with LHRHa (10-50 ng/g of body wt) and fish were bled 1 h after LHRHa injection. Treatment with both doses of 20beta-S resulted in plasma concentrations of the steroid within the normal physiological range for this species during final oocyte maturation and ovulation. The 20beta-S treatments altered the LH response to LHRHa throughout the reproductive cycle in both sexes, but the direction and magnitude of the response varied. 20beta-S treatment decreased the LH response to LHRHa in fish with recrudescing and fully recrudesced gonads and in females with regressed gonads. On the other hand, 20beta-S treatment significantly increased the LH response to LHRHa in males with regressing or regressed gonads. 20beta-S treatment also altered preoptic anterior hypothalamic (POAH) and pituitary seabream gonadotropin-releasing hormone (sbGnRH) contents, and the patterns of these changes were similar to those observed in LH secretion. The finding that moderate increases in plasma 20beta-S concentrations, similar to those occurring during final oocyte maturation, significantly inhibit the LH response to LHRHa at the end of the reproductive cycle suggests that this action of 20beta-S is of physiological importance during the periovulatory period. Moreover, the fact that concurrent changes occur in POAH and pituitary sbGnRH contents suggests that the actions of 20beta-S on LH secretion are at least partly mediated via the GnRH system.

Animals↗
PubMed2002

Progestin membrane receptors involved in the meiotic maturation of teleost oocytes: a review with some new findings.

The endocrine control of oocyte maturation in fish has proven to be a valuable model for investigating rapid, nongenomic steroid actions at the cell surface. Considerable progress has been made over the last decade in identifying and characterizing progestin membrane receptors mediating these actions in fish, in understanding the hormonal regulation and physiological roles of these receptors in oocyte maturation, in elucidating the signal transduction pathways they activate, and in determining their nature. Recent advances on these topics are briefly reviewed. New data demonstrating the involvement of pertussis toxin-sensitive inhibitory G-proteins in induction of oocyte maturation by the maturation-inducing steroid (MIS) in teleosts is also presented. In addition, the cloning strategy to isolate the MIS receptor gene from spotted seatrout ovaries and the characteristics of a novel gene and protein discovered by this approach are discussed. Current evidence suggests this G-protein-coupled receptor-like protein is the long sought after MIS receptor mediating meiotic maturation of teleost oocytes.

Animals↗
PubMed2002

Expression profiling and interferon-beta regulation of liver metastases in colorectal cancer cells.

Liver metastasis is the major cause of death among colorectal cancer patients. Many gene products have been associated with the colon cancer cells' ability to metastasize to the liver, including carcinoembryonic antigen (CEA) and mucins. In this study we examined changes in expression of 384 genes in a model of human colorectal cancer metastasis in nude mice. Using DNA microarrays, we compared expression between MIP-101 cells, a poorly metastatic human colon cancer cell line, with an interferon-beta (IFN-beta) resistant subline of MIP-101 (beta-MIP) that is metastatic to the liver. Treatment of beta-MIP cells with increasing concentrations of IFN-beta caused a reversion to the non-metastatic phenotype. The array data showed down-regulation of genes involved in apoptosis in beta-MIP cells and their return to the MIP-101 pattern upon IFN-beta treatment. Cluster analysis also showed involvement of genes belonging to cell cycle, angiogenesis and invasion pathways. Selected genes were chosen to validate the microarray data by semi-quantitative RT-PCR. Association between gene expression pattern and metastatic phenotype was verified by intra-splenic injection in nude mice. The number of genes examined in this study was small, but carefully selected. Significant changes associated with cell growth and survival were observed, which gave the metastatic cells an advantage to grow in the liver. This information may help identifying new markers for colorectal cancer prognosis as well as aid the development of new therapeutic approaches.

Animals↗
PubMed2002

Enhancing reliability in portfolio assessment: discussions between assessors.

This paper reports the reliability in assessments of a series of portfolios assembled by a cohort of participants attending a course for prospective general practice trainers. Initial individual assessments are compared with open discussion between random pairs of assessors to produce paired composite scores, and analysed using kappa statistics. Overall reliability of a global pass/refer judgement improved from a kappa of 0.26 (fair) using individual assessment, to 0.5 (moderate) with paired discussants.

Cohort Studies↗
PubMed2001

Enhancing reliability in portfolio assessment: 'shaping' the portfolio.

This paper reports a follow-on project that assessed a series of portfolios assembled by a cohort of participants attending a course for prospective general practice trainers. In an attempt to enhance reliability, a framework for defining and addressing problems using a reflective practice model was offered to participants. The reliability of the judgements made by a panel of assessors about individual 'components', together with an overall global judgement about performance were studied. The reliability of individual assessors' judgements (i.e. their consistency) was moderate, but inter-rater reliability did not reach a level that could support making a safe summative judgement. Despite offering a possible structure for demonstrating reflective processes, the levels of reliability reached were similar to the earlier work and other subjective assessments generally, and perhaps reflected individuality of personal agendas of both the assessed and the assessors, and variations in portfolio structure and content; even agreement among the assessors about evidence of the framework being used was poor. Suggestions for approaches in the future are made. The conclusion remains that while portfolios might be valuable as resources for learning, as assessment tools they should be treated as problematic.

Journal Article↗
PubMedDate not supplied

Vitamin E co-treatment reduces Aroclor 1254-induced impairment of reproductive neuroendocrine function in Atlantic croaker.

We have shown previously that exposure of Atlantic croaker to a PCB mixture (Aroclor 1254) results in impaired reproductive neuroendocrine function. In addition, we have identified hypothalamic tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin (5-hydroxytryptamine) synthesis, as a target of PCB neuroendocrine toxicity. In order to further elucidate the mechanisms of PCB neurotoxicity, the present study investigated whether PCB-induced decrease in hypothalamic TPH activity resulted from degradation of the enzyme protein. Fish were exposed to Aroclor 1254 in the diet (0.1 mg/100 g body weight (BW)/day) for 30 days. The PCB exposure elicited a significant decrease in hypothalamic TPH protein content, which could be at least partially responsible for the reduced TPH activity. To test whether a similar PCB exposure could cause oxidative damage in croaker hypothalamic tissues, we examined the formation of malondialdehyde (MDA) protein adducts as a marker of lipid peroxidation (LPO). The same dose of PCB increased the MDA-protein adduct formation in the hypothalamus. In a separate experiment, the role of vitamin E, an antioxidant, to prevent or decrease the effect of PCB on hypothalamic TPH activity and gonadal growth was examined. The vitamin E co-treatments (1 and 10 mg/100 g BW/day) with PCB significantly reduced the effects of PCB on TPH activity and gonadal growth. These results suggest possible involvement of oxidative processes in PCB neurotoxicity.

Animals↗
PubMedDate not supplied

Modeling vitellogenesis in female fish exposed to environmental stressors: predicting the effects of endocrine disturbance due to exposure to a PCB mixture and cadmium.

A wide variety of chemical and physical environmental stressors have been shown to alter the reproductive processes in fish by interfering with endocrine function. Most endocrine indicators or biomarkers are static measures from dynamic hormonally-mediated processes, and often do not directly relate to reproductive endpoints of ecological significance. Adequate production of the yolk precursor protein, vitellogenin, is critical for the survival and normal development of the sensitive egg and yolk-sac larval fish life stages. We developed a model that simulates vitellogenesis in a mature female sciaenid fish. The model simulates the major biochemical reactions over a 6-month period from the secretion of gonadotropin (GtH) into the blood to the production of vitellogenin. We simulated the effects of two endocrine disrupting chemicals (EDCs) that have different actions on vitellogenin production: a PCB mixture and cadmium. Predicted changes in steroid concentrations and cumulative vitellogenin production compared favorably with changes reported in laboratory experiments. Simulations illustrate the potential utility of our model for interpreting reproductive endocrine biomarkers measured in fish collected from degraded environments.

Animals↗
PubMedDate not supplied

Comparative immunotoxicity evaluation of amphotericin B and ABELCET, an amphotericin B lipid complex (ABLC).

ABELCET, an amphotericin B lipid complex formulation (ABLC) and an aqueous, non-lipid-containing formulation with sodium deoxycholate (AmBd), were evaluated for their potential to induce immunotoxicity in B6C3F1 female mice. ABLC was administered intravenously at doses of 1, 3, and 10 mg/kg daily for 28 days, while AmBd at 1 mg/kg was administered by the same route and duration. The effect of ABLC and AmBd on clinical signs, body weight, and spleen weight was determined. Peritoneal macrophage function was measured by phagocytosis of 51Cr-labeled chicken red blood cells and generation of hydrogen peroxide during respiratory burst. The ability of natural killer cells to lyse radiolabeled tumor target cells was evaluated in a short-term chromium-release assay. The ability of splenic T and B cells to undergo blastogenesis and of splenic T cells to recognize alloantigens present on foreign cells was assessed in a splenic lymphocyte assay and the ability of mice to generate antibody-forming cells following immunization with sheep red blood cells was measured. Neither ABLC nor AmBd affected the metabolic or functional activity of murine phagocytic cells. These agents also did not cause any biologically significant or dose-related changes in B- or T-cell responses to mitogens, T-cell responses to allogeneic cells in the mixed lymphocyte culture assay, or natural killer cell function. The ability to generate a primary antibody response to a T cell-dependent antigen was also unimpaired. Based on the results of this study, it was concluded that neither ABLC at dose up to 10 mg/kg nor AmBd at dose up to 1.0 mg/kg produce biologically significant immunologic changes in B6C3F1 mice.

Amphotericin B↗
PubMedDate not supplied

A study of the effectiveness of professional development groups.

In 1995 Nursing Times published my study (Thomas, 1995) on the effectiveness of staff support groups within community nursing settings. This work has continued to develop over the past seven years and this article looks at the development of the model within acute mental health wards and discusses a recent evaluation of the groups by its members. It is encouraging to find that these groups continue to be found valuable by the participants. The rationale behind the name change from staff support groups to professional development groups reflects the concept of staff using the groups to reflect on their roles and take responsibility for their professional development rather than the concept of support groups, which may indicate passivity.

Attitude of Health Personnel↗