PubMed Health⌕ Search

Biomedical subjects

M Barnett

Publications and source records attributed to M Barnett.

At least 37 records · Page 2Linked to original sources
PubMed1995

The molecular biology of temperature-dependent sex determination.

Many reptiles do not have heteromorphic sex chromosomes and for these species sex is determined during embryogenesis by the temperature of egg incubation rather than at conception. The phenomenon of temperature-dependent sex determination (TSD) was discovered almost thirty years ago, but few advances have been made towards the elucidation of its mechanism. In the past few years substantial progress has been made in the understanding of the molecular basis of XY chromosomal (genetic) sex determination (GSD) through the discovery of SRY. It is now possible to start comparing TSD with GSD. TSD is found in some evolutionarily ancient vertebrates and has been postulated to be the ancestral process from which GSD has evolved. If this is true then the two mechanisms may share a common molecular basis. This paper details the current knowledge of TSD, our progress on the investigation of the involvement of SRY-type proteins, and finally presents some of the problems that need to be resolved to gain an understanding of the molecular basis of TSD.

Alligators and Crocodiles↗
PubMed1995

Basal glucose turnover in Psammomys obesus. An animal model of type 2 (non-insulin-dependent) diabetes mellitus.

The aim of this study was to examine whole-body glucose turnover and glucose uptake into individual tissues in Psammomys obesus. The animals were classified according to the level of circulating glucose and insulin in the fed state: group A was normoglycaemic and normoinsulinaemic (glucose < 8.0 mmol/l), insulin < 150 mU/l), group B was normoglycaemic and hyperinsulinaemic (glucose < 8.0 mmol/l, insulin > or = 150 mU/l), and group C was hyperglycaemic and hyperinsulinaemic (glucose > or = 8.0 mmol/l, insulin 150 mU/l). The animals were deprived of food for 6 h, after which they were anaesthetized and cannulated, using the jugular vein for infusions and the carotid artery for blood sampling. Whole-body glucose turnover was measured using a primed-continuous infusion of 6-[3H]-glucose and saline to quantitatively assess hepatic glucose production (HGP), glucose disposal (Rd), and the metabolic clearance rate of glucose (MCR). Following the 2-h infusion period, the glucose metabolic index (Rg') of individual tissues was measured using a fixed-dose bolus of 2-deoxy-[14C] glucose. Under the steady-state conditions of the experiment, HGP was assumed to be equal to Rd, and both variables were found to be significantly correlated to the fasting glucose concentration (r=0.534, P<0.05, n=19). On the other hand, MCR was found to be inversely correlated to the fasting plasma glucose concentration (r=0.670 P < 0.01, n=19). When the animals were divided into three groups as described above, HGP in group C animals was significantly elevated compared with group A (20.8 +/- 2.6 vs 12.7 +/- 0.6 mg.kg-1.min-1; P < 0.05), and MCR showed a tendency to be lower in group C than group A, although the difference was not statistically significant. HGP and MCR were not significantly different between groups A and B. Measurement of the glucose metabolic index in individual tissues showed that group C animals had significantly higher Rg' values in muscles and adipose tissues compared with those in group A (P < 0.05). In addition, Rg' in group B white gastrocnemius and soleus were significantly higher than in group A despite similar rates of HGP and levels of glycaemia. These findings suggest that an early increase in skeletal muscle glucose uptake and hyperinsulinaemia can be demonstrated in group B Psammomysobesus before significant hyperglycaemia.

Adipose Tissue↗
PubMed1994

Autologous transplants for chronic myelogenous leukaemia: results from eight transplant groups.

Chronic myelogenous leukaemia (CML) can be cured by donor marrow transplant. Unfortunately, suitably HLA-matched related or unrelated donors are not available for the majority of patients. Transplant of stem cells derived from a patient's own marrow or peripheral blood (autologous transplant) avoids the need for an HLA-matched donor, is associated with a less complicated and shorter hospital course than donor transplantation, and has been successful in the treatment of other haematological malignancies. We report results of autologous transplants in 200 patients with CML at eight marrow transplant centres over seven years. This is the first multicentre analysis of autologous transplants for CML and reports on the largest number of patients studied to date. We show that autologous transplants provide a plateau in the survival curve not observed in conventional treatments. Autologous transplants are associated with a high engraftment rate, low mortality, and prompt return of both younger and older patients to normal activity levels. Our results suggest that autologous transplants provide an alternative to conventional treatment in the care of patients not eligible for donor transplant.

Adolescent↗
PubMed1994

A cross-sectional and short-term longitudinal characterisation of NIDDM in Psammomys obesus.

The present study was undertaken to examine the cross-sectional and short-term longitudinal changes in glucose and insulin concentrations as well as measure the enzymatic activity of PEPCK and glycogen synthase in our Psammomys obesus colony. In the cross-sectional study, blood samples were taken from one group of animals at 19 weeks of age (n = 37) in the fed state and following a 4-h fast. In a separate group of 19-week-old animals (n = 69), samples were taken 1 h following an OGTT (1 g/kg body weight) in Psammomys subjected to a 16-h fast. In the longitudinal study, blood samples were taken from one group of animals in the fed state at 7, 11, 15 and 19 weeks of age. All of the cross-sectional data have described the classic inverted U-shaped curve (Starling's curve of the pancreas) in the relationship between glucose and insulin levels. This trend was also reflected by Psammomys subjected to the OGTT; a mild impairment in glucose tolerance was associated with an increase in the insulin response and a further impairment in glucose tolerance was associated with a reduction in the insulin response. Similar results were obtained following a 4-h fast. The short-term longitudinal glucose and insulin data revealed that of the 37 animals examined over the 12-week period, 16 progressed along the inverted U-shaped curve described by the cross-sectional data. Of the other animals, 8 remained unchanged, 7 were unclassifiable and 6 hyperglycaemic Psammomys developed normoglycaemia at the expense of elevated insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effect of restricting energy intake on diabetes in Psammomys obesus.

The aim of this paper was to determine whether restricting energy intake would reduce the elevated levels of glucose, insulin, cholesterol and triglyceride in diabetic Psammomys obesus (sand rat). Between 11 and 12 weeks of age Psammomys obesus were divided into three groups based on blood glucose and plasma insulin levels in the fed ad libitum state; group 1 was normoglycemic (4.4 +/- 0.3 mM) and normoinsulinemic (0.46 +/- 0.04 ng/ml), group 2 was normoglycemic (5.0 +/- 0.3 mM) and hyperinsulinemic (3.58 +/- 0.62 ng/ml) and group 3 was hyperglycemic (11.2 +/- 1.2 mM) and hyperinsulinemic (6.23 +/- 0.73 ng/ml). Energy intake was restricted to 67% of normal for 2 weeks before ad libitum feeding was resumed for a further 2 weeks. Animals in group 3 developed the most abnormalities when compared to group 1 including increased levels of food intake (16.3 +/- 0.5 vs 14.2 +/- 0.5 g/day, P < 0.05), body weight (192 +/- 5 vs 162 +/- 4 g, P < 0.05), triglycerides (1.5 +/- 0.2 vs 0.96 +/- 0.08 mM, P < 0.05), and cholesterol (2.8 +/- 0.2 vs 2.1 +/- 0.1 mM, P < 0.05). In group 3, food restriction was effective in reducing glucose levels (but not insulin) both during and following the restriction period respectively (11.2 +/- 1.2 vs 4.6 +/- 0.5, and 5.9 +/- 1.3, mM, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The prevention of accelerated cardiac allograft rejection in sensitized recipients after treatment with brequinar sodium.

Brequinar sodium (BQR) is a novel immunosuppressive agent that is highly effective in preventing B lymphocyte-mediated antibody production. We have examined the effects of BQR treatment in sensitized recipients on graft survival, donor-specific antibody responses (IgM and IgG), and the appearance of immunopathological lesions present in the grafts. LEW rat recipients were sensitized with single ACI skin graft on day 7 and received heterotopic ACI cardiac grafts on day 0. The recipients rejected the cardiac grafts in an accelerated fashion at day 2.5 post-transplantation, compared to day 7.0 in unsensitized recipients. The animals were treated with low (3 mg/kg/day) or high (12 mg/kg/3x weekly) doses of BQR during skin graft sensitization and/or after challenge with ACI heart allografts. All groups treated with BQR showed significant prolongation of graft survival in the sensitized recipients. The best survival was observed following high-dose BQR therapy during both sensitization and effector phases (median survival time = 40.0 days, P << 0.001). Daily treatment with BQR (3 mg/kg/day) prevented IgM (but not IgG) antibody responses. Treatment with higher doses of BQR (12 mg/kg/3x weekly) before and after skin graft sensitization was effective in preventing both IgM and IgG production. In general, BQR treatment resulted in effective suppression of anti-donor antibody responses, stable graft function, and a reduction in the severity of the acute vascular lesions in the graft. The effectiveness of BQR in preventing accelerated graft rejection when used at 12 mg/kg/3x weekly was comparable to that seen with treatment of sensitized animals with CsA at 15 mg/kg/day for 30 days. Daily treatment with cyclophosphamide at 5 or 15 mg/kg/day was ineffective for preventing graft rejection in sensitized recipients. These results indicated that BQR may provide an important addition to treatment protocols designed to prevent transplantation rejection in presensitized patients. BQR has the ability to significantly inhibit host cellular and humoral immune responses to the donor graft and this facet of the immunosuppressive activity of the drug may be responsible for preventing this aggressive form of rejection.

Animals↗
PubMed1993

The biology of normal and neoplastic stem cells in CML.

Chronic myeloid leukemia (CML) has long served as a prototype malignancy for basic as well as clinical studies aimed at developing curative cancer treatment protocols. Well established features of chronic phase CML are its origin in a pluripotent stem cell, a now well defined molecular genetic basis involving the creation of a BCR-ABL fusion gene and evidence of resultant abnormalities in the mechanisms that normally control primitive hemopoietic cell proliferation. We have recently shown how the long-term marrow culture system can be adapted to quantitate and characterize a very primitive cell type in normal blood and marrow samples, as well as their normal and leukemic counterparts in patients with CML. This system has also been used to dissect mechanisms of normal progenitor regulation and to identify specific anomalies affecting leukemic (CML) progenitors. Our studies show that cells detected by their ability to initiate long-term cultures (LTC) of leukemic cells (i.e., CML LTC-initiating cells or LTC-IC) are differently distributed between marrow and blood by comparison to LTC-IC in normal individuals and, although functionally similar in terms of the number and differentiation types of clonogenic cells they produce, CML LTC-IC exhibit defective self-maintenance. Phenotypically these primitive leukemic cells are heterogeneous; the majority display features of activated/proliferating cells but a significant proportion do not. We have also documented heterogeneity in primitive CML cell responses to two factors that specifically and reversibly arrest the cycling of primitive normal hemopoietic cells; i.e., TGF-beta and MIP-1 alpha, to which CML cells are normally responsive and abnormally unresponsive, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cells↗
PubMed1992

A prospective study of transmission by transfusion of HTLV-I and risk factors associated with seroconversion.

To evaluate the risk of transfusion-related transmission of HTLV-I in Jamaica, a prospective study was initiated, prior to availability of a licensed HTLV-I serological screening assay. This information would prove useful in formulating strategies for blood-donor screening. We followed 118 pre-transfusion HTLV-I-negative transfusion recipients at monthly intervals post-transfusion for 1 year. Laboratory and questionnaire data were obtained at each visit to evaluate the clinical and immunological status of recipients. Cumulative incidence of HTLV-I seroconversion was estimated and risk-factor data associated with seroconversion among 66 HTLV-I-exposed transfusion recipients were analyzed. Seroconversion occurred in 24/54 (44%) of recipients of HTLV-I-positive cellular blood components, 0/12 recipients of positive non-cellular donor units and 0/52 recipients of HTLV-I-negative donor units. Significant risk factors associated with recipient seroconversion were receipt of a seropositive cellular blood component stored for less than one week [odds ratio (OR) = 6.34, 95% confidence interval (CI) = 1.83 to 21.92], male sex (OR = 4.79, 95% CI = 1.15 to 20.0) or use of immuno-suppressive therapy at time of transfusion (OR = 12.20, 95% CI = 0.95 to 156). Risk of blood-borne infection per person per year in Jamaica was estimated to be 0.009%. Our results confirm that blood transfusion carries a significant risk of HTLV-I transmission and that screening of donor blood effectively prevents HTLV-I seroconversion. Recipients at greatest risk for seroconversion were those who required multiple transfusions or who were receiving immunosuppressive therapy at the time of transfusion. These patients should be given priority in receiving selectively screened blood components, if universal blood-donor screening for HTLV-I is not possible.

Blood Donors↗
PubMed1992

The longitudinal effect of inhibiting fatty acid oxidation in diabetic rats fed a high fat diet.

This study was designed to examine the time-course of response to inhibition of fatty acid (FA) oxidation in rats rendered mildly diabetic with streptozotocin and fed a high fat diet (50% of energy derived from fat). Etomoxir, a specific carnitine palmitoyltransferase (CPT-1) inhibitor, was administered subcutaneously (12.5 mg/kg) to inhibit long chain fatty acid oxidation. Diabetic and non-diabetic control rats were maintained on the high fat diet. Following an overnight fast, glucose, free fatty acid (FFA) and triglyceride (TG) concentrations were determined after three days, one week and four weeks of treatment. The effect of Etomoxir treatment in reducing fasting glucose concentrations was not evident until after one week, while fasting FFA and TG concentrations were already reduced after three days treatment. All of these changes were maintained over the four week period (P less than 0.001), resulting in reduced levels of fasting plasma glucose (17.6 +/- 2.4 vs 22.3 +/- 1.9 mmol/l), fasting plasma TG (0.32 +/- 0.07 vs 0.98 +/- 0.14 mmol/l) and fasting serum FFA (1.52 +/- 0.26 vs 3.51 +/- 0.69 mEq/l). In addition, the improvements in glucose and lipid levels were accompanied by restored rates of growth towards that of non-diabetic control rats. These results suggest that the short term inhibition of FA oxidation improves fasting glucose, FFA and TG concentrations in diabetic rats fed a high fat diet.

Animals↗
PubMed1991

Outcome of treatment of first relapse of Hodgkin's disease after primary chemotherapy: identification of risk factors from the British Columbia experience 1970 to 1988.

The outcome of treatment for a first relapse of Hodgkin's disease after primary chemotherapy was analyzed in 80 patients. They were divided into four groups: group 1 (n = 24) had initially been treated with three cycles of (mechlorethamine, vincristine, prednisone, and procarbazine [MOPP]) and wide-field irradiation therapy; group 2 (n = 25) had six cycles of MOPP; group 3 (n = 15) and group 4 (n = 16) both initially received MOPP/ABVD (MOPP plus doxorubicin, bleomycin, vinblastine, and dacarbazine) or MOPP/ABV hybrid, but group 3 received conventional salvage regimens whereas group 4 was treated with high-dose chemotherapy and autologous bone marrow transplantation as salvage therapy (n = 16). Freedom from second failure (FF2F) was used as the major endpoint. Actuarial FF2F for all patients was 38% after a median follow-up of 75 months for patients who were alive. Risk factor analysis was performed on the 71 patients who had been treated with curative intent. The presence or absence of any one of three risk factors had a strong negative impact on outcome: stage IV disease at primary diagnosis, B symptoms at relapse, or a time from primary treatment to relapse of less than 1 year. Actuarial FF2F at 5 years was 17% in the group of patients with one or more of these three factors present (n = 49). If none of these factors was present, FF2F was 82% (n = 22) (P less than .001). Even high-dose chemotherapy and autologous bone marrow transplantation were not able to overcome the negative impact of one or more risk factors (FF2F = 19%, n = 12). The outcome of salvage treatments depends most on the presence or absence of these three risk factors and less on the type of salvage treatment. Patients with none of these risk factors present have an excellent outcome if they are treated with non-cross-resistant chemotherapy, or radiotherapy, or both. Novel approaches are needed for patients with one or more of these factors present. Reports on salvage treatments for Hodgkin's disease in first relapse after primary chemotherapy should include data on the proportion of patients having stage IV disease at diagnosis, B symptoms at relapse, and a time from primary treatment to relapse of less than 1 year.

Adolescent↗
PubMed1991

Detection of early human T-cell lymphotropic virus type I antibody patterns during seroconversion among transfusion recipients.

From a cohort of human T-cell lymphotropic virus type I (HTLV-I) exposed transfusion recipients (N = 71) enrolled in the Jamaican Transfusion Study, 11 were selected for detailed laboratory evaluation. All recipients were followed at monthly intervals for 6 months and then bimonthly up to 1 year for evidence of HTLV-I seroconversion. Without regard to results on screening assays, pretransfusion and posttransfusion samples were tested with two licensed HTLV-1 whole-virus screening enzyme immunoassays (EIAs), recombinant EIAs for antibody against tax (p40x) and p21e envelope, standard whole virus Western blot (WB), WB enhanced with recombinant p21e, and radioimmunoprecipitation assay (RIPA). In the early period posttransfusion, antibody to gag core protein was predominant with anti-p24 generally appearing before anti-p19. Recombinant anti-p21e envelope protein, in EIA and WB format, was frequently the earliest envelope reactivity detected, while anti-gp46 in WB and anti-gp61/68 in RIPA system appeared later. Anti-tax antibodies appeared later in the time course of seroconversion. The whole-virus EIAs were less sensitive than the confirmatory assays. The combination of WB and RIPA or WB enhanced with recombinant p21e appeared equally effective in confirming samples as positive by the Public Health Service two gene group confirmatory algorithm. However, specificity of this assay approach could not be addressed in this study.

Adolescent↗