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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 541 records · Page 30Linked to original sources
PubMed1989

The DNA binding site of the Xenopus transcription factor IIIA has a non-B-form structure.

On the basis of nuclease digestion studies we proposed that the DNA binding site of transcription factor IIIA (TFIIIA) may have an overall structure with A-type rather than B-type characteristics. This proposal was substantiated by the crystal structure of a part of the TFIIIA binding site. Recently, however, it has been reported that the binding site for TFIIIA is B-form in solution, thus implying that the conformation present in crystals is not the structure in solution. We have carried out a study using comparative circular dichroism (CD) spectroscopy of a number of double stranded deoxyoligonucleotides of different sequence, and known crystal structure. The correlation we have found between CD characteristics and certain structural parameters indicates that the solution and crystal structures of the TFIIIA binding site are closely related. This structure may be classed as an intermediate type, between A-form and B-form DNA.

Animals↗
PubMed1989

Pathogenesis of low dose streptozotocin induced diabetes in mice: requirement for alpha 1-adrenoceptor activation and vasoactive amine release.

Pancreatic islet inflammation and subsequent diabetes was induced by multiple low doses of streptozotocin in male C57 Bl/6J mice. The development of hyperglycaemia was almost completely prevented by treating the animals with the alpha 1-adrenoceptor antagonist prazosin (20 mg.kg-1.day-1) as well as by the vasoactive amine antagonists methysergide (50 mg.kg-1.day-1), disodium cromoglycate (100 mg.kg-1.day-1), pizotifen (5 mg.kg-1.day-1) or cyproheptadine (20 mg.kg-1.day-1). Treatment with vasoactive amine antagonists largely inhibited infiltration of pancreatic islets by L3T4+-lymphocytes and to a lesser extent by Lyt2+-cells. The infiltration of macrophages was not affected except after pizotifen treatment. These results indicate that alpha 1-adrenoceptor activation is required for disease development and that vasoactive amine release is a prerequisite for lymphocytic insulitis but not for macrophage infiltration of islets.

Animals↗
PubMed1989

Correlation of plasma lipid fractions with colorimetrically determined glycated hemoglobin in a nondiabetic population.

To evaluate the incidence of protein glycation (measured as glycated hemoglobin) on plasma lipid levels in a free-living population, a colorimetric method has been used to detect 5-hydroxymethylforfural (HMF) released from glycated hemoglobin (GHb) and enzymatic methods have been used to evaluate total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glycemia, and total plasma triacylglycerides. These results have been used to calculate low-density lipoprotein-(LDL) cholesterol levels with the Friedewald formula. Results show that a positive correlation exists in men, but not in premenopausal women, between GHb and fasting glycemia (P less than 10(-14], GHb and total plasma cholesterol (P less than .001), GHb and LDL cholesterol (P less than .0001), and GHb with the atherogenic index total/HDL cholesterol (P less than .0001), whereas a negative correlation was shown between GHb and HDL cholesterol (P less than .05). Fasting glycemia does not correlate with cholesterol lipoprotein fractions, but correlates well with total triacylglycerides. These correlations are significant when they are adjusted by age and body mass index. It has also been observed that the positive correlation between glycation of hemoglobin and total cholesterol occurs constantly at all glycohemoglobin levels, and affects all cholesterol fractions analyzed. This suggests an increased atherogenicity with increasing glycohemoglobin levels. Comparisons between groups with high and low GHb levels show variations in the order of 6.5% of total cholesterol levels and a major proportion in the different cholesterol fractions. The higher-range "glycated" populations show total cholesterol, LDL cholesterol and HDL cholesterol values significantly different from the lower-range "glycated" population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Double blind study on the efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute alcohol withdrawal syndrome.

1. Efficacy and safety of tetrabamate and chlordiazepoxide in the treatment of the acute or Primary Alcohol Withdrawal Syndrome (PAWS) were assessed during a randomized double blind clinical trial, carried out on sixty male alcoholic in-patients. 2. The two drugs were administered four times a day in double dummy conditions, according to a fixed-flexible decreasing dosage schedule (six days basic regimen). 3. Drug efficacy was measured daily throughout the study period using a battery of standard instruments for collecting quantitative clinical, behavioral, psychopathological and laboratory data. Side effects were daily recorded. 4. Tetrabamate was found to be as efficient as chlordiazepoxide in reducing the intensity of the PAWS, improving sleep and vital signs rapidly and alleviating anxiety progressively. 5. Tetrabamate was found particularly beneficial for severe tremor. Psychomotor and mood scores consistently favored tetrabamate, suggesting psychoanaleptic properties of this compound (increased diurnal vigilance). 6. Side effects were minimal with tetrabamate and generally of weak intensity with chlordiazepoxide. 7. The results of this study indicate that tetrabamate may represent a new alternative drug of choice for the therapy of the acute alcohol withdrawal syndrome.

Adult↗
PubMed1989

Evidence that matching for HLA antigens significantly increases transplant survival in 1001 renal transplants performed in the northwest region of England.

In the 20-year period from March 1968 to March 1988, 860 patients received 1001 renal transplants in the Northwestern Regional Renal Transplant Unit at Manchester Royal Infirmary. Through a continuing policy of avoiding mismatches for HLA antigens and lymphocytotoxic antibody crossmatching, transplant survival rates were found to correlate with the degree of HLA-A and B antigen mismatching from 1968 to 1978 and with HLA-B and DR antigen mismatching from 1979 to 1988. Mismatching for HLA-B and DR antigens was also found to correlate with transplant survival in highly sensitized patients and in patients transplanted since 1981, the "cyclosporine era." Recipients who were HLA-DR1 positive were found to have the highest graft survival compared to recipients negative for this antigen. In contrast, HLA-DR3 positive recipients had the poorest outcome. Transplants from HLA-DRw6 positive donors showed higher transplant survival rates than donor kidneys positive for any other HLA-DR antigen. A correlation of transplant survival with HLA-B and DR mismatching was seen whether kidneys were collected within our region or received through the UK Transplant Service. We conclude that avoidance of mismatching for HLA-B and DR antigens confers high transplant survival rates (91.1% at 5 years for 0 HLA-B and DR mismatches), and in order to achieve this rate for most recipients exchange of donor kidneys between transplant centers will be essential.

Adolescent↗
PubMed1989

Recombinant vaccinia virus expressing the herpes simplex virus type 1 glycoprotein C protects mice against herpes simplex virus challenge.

The gene encoding the herpes simplex virus type 1 (HSV-1) glycoprotein C (gC) was isolated and cloned into a vaccinia virus insertion vector, and the resulting vaccinia-gC vector was used to construct a recombinant vaccinia virus that expressed gC (VVgC5). Infection of cells with VVgC5 resulted in cell surface expression of authentic HSV-1 gC. HSV-1 gC-specific neutralizing antibodies were produced in VVgC5-immunized mice, and lymphocytes exhibited an HSV-1-specific proliferation response in vitro following infection. More importantly, VVgC5-immunized mice were resistant to subsequent lethal HSV-1 challenge.

Animals↗
PubMed1989

Evaluation of antiviral immunity using vaccinia virus recombinants expressing cloned genes for herpes simplex virus type 1 glycoproteins.

Immunization of mice with vaccinia virus recombinants expressing the glycoproteins B or D of herpes simplex virus type 1 (HSV-1) induced humoral antibody as well as multiple aspects of HSV-1-specific T lymphocyte-mediated responses. However, vaccinated mice were not completely resistant to HSV-1 challenge and were unable to eliminate an epithelial infection rapidly. Evidence is presented which indicates that immunization with either vaccinia virus recombinant, while inducing the necessary protective populations of CD4+ T lymphocytes, fails to induce the complementing CD8+ cytotoxic T lymphocytes necessary for high levels of protection against a primary HSV-1 infection. These findings are discussed with relevance to the future development of anti-HSV vaccines.

Animals↗
PubMed1989

Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology.

Herpetic stromal keratitis (SK), a frequent cause of visual impairment, is considered to represent an immune-mediated inflammatory response to persistent herpes simplex virus virions or subcomponents within the corneal stroma. The experimental disease in mice involves the essential participation of T lymphocytes, but the role of T-lymphocyte subsets in either mediating or controlling the disease is uncertain. In this report, rat monoclonal antibodies were used to selectively deplete mice in vivo of CD4+ (helper-inducer) and CD8+ (cytotoxic-suppressor) T-cell populations and the effect on herpetic SK was evaluated. As measured by flow cytometry, mice treated with anti-CD4 monoclonal antibody (GK 1.5) were greater than 95% depleted of CD4+ T lymphocytes and mice treated with anti-CD8 monoclonal antibody (2.43) were 90% depleted of CD8+ T lymphocytes. Depleted and nonspecific mouse ascites-treated control mice were infected topically on the corneas with herpes simplex virus type 1, and the induction of various immune parameters during the acute infection was evaluated. CD4+-depleted mice failed to produce either a significant antiviral antibody or delayed-type hypersensitivity response but were capable of producing normal cytotoxic T-lymphocyte responses. In contrast, CD8+-depleted mice produced antiviral antibody and delayed-type hypersensitivity responses comparable with those in control animals, but cytotoxic T-lymphocyte responses were markedly reduced. Clinical observations of the corneas revealed that SK in CD4+-depleted mice was significantly reduced, whereas in CD8+-depleted mice SK developed more rapidly, was more severe, and involved a greater percentage of mice. These observations implicate the CD4+ T-lymphocyte subset as the principal mediators of SK and CD8+ T lymphocytes as possible regulators that control the severity of SK.

Animals↗
PubMed1989

Impaired renal tubular function in chronic alcoholics.

Despite the well known effects of chronic alcohol abuse on the gastrointestinal, cardiovascular, nervous and endocrine systems, little information is available on its effect on renal function. To assess renal function we measured urinary excretion of albumin, alpha 1 microglobulin and retinol binding protein in 30 chronic alcoholic patients. Our data shows that 40% of chronic alcoholic patients have impaired renal tubular function.

Adult↗
PubMed1989

Clinical, biochemical, and neuropathologic findings following transplantation of adrenal medulla to the caudate nucleus for treatment of Parkinson's disease.

We transplanted autologous adrenal medullary tissue into the caudate nucleus of 3 patients with advanced Parkinson's disease. The 1st patient, a 59-year-old man with parkinsonian symptoms for 15 years, had mild improvement in his motor functioning after the operation. However, his postoperative course was characterized by prolonged drowsiness and complex visual hallucinations. The patient died suddenly 8 months after the transplant, and an autopsy revealed coronary atherosclerosis. Examination of the graft site showed necrotic adrenal medullary tissue surrounded by inflammatory cells. The 2nd patient, a 50-year-old man with a 21-year history of parkinsonian symptoms, improved the most after the procedure. The 3rd patient, a 43-year-old man with 12 years of parkinsonian symptoms, had mild improvement in his motor functioning. CSF homovanillic acid increased postoperatively in the 3 patients, but then returned to preoperative levels in all except the 2nd patient. The anatomic, neurochemical, and physiologic basis for the modest clinical improvement shown in these patients is not yet understood.

Activities of Daily Living↗
PubMed1989

Kidney transplantation in the northwest region of England--experience of 1,132 transplants in 21 years.

1. In more than 1,100 kidney transplants performed at a single center in 21 years a conservative approach to immunosuppressive therapy and HLA antigen matching has ensured high survival rates after both short- and long-term follow-up. 2. Retransplantation has been carried out in 16.6% of patients with transplant survival rates not differing significantly from those in first transplant recipients. 3. Living-related donor transplants accounted for only 7.9% of cases since 1982 and transplant survival was no different from HLA-A,B,DR-identical cadaver donor transplants. 4. Pretransplant blood transfusions were given to over 98% of recipients since 1982 and transplant survival in such CsA-treated patients was 10% higher than in the few nontransfused recipients. 5. By adopting a meticulous policy of pretransplant cytotoxic antibody screening and HLA antibody definition followed by careful pretransplant crossmatching using all available patient sera, accelerated transplant rejection has largely been avoided. 6. Monitoring of posttransplant recipient sera has shown that the appearance of cytotoxic antibodies leads to transplant failure and these antibodies are usually directed against HLA antigens mismatched between donor and recipient. 7. Matching for HLA antigens has a striking positive effect on transplant survival with more than 30% difference between the no mismatch and no match groups. Positive HLA matching effects on transplant survival were found in retransplants, highly sensitized recipients, male and female recipients, all ABO blood groups, and after long-term (20 years) follow-up.

Adolescent↗