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Biomedical subjects

M A Watson

Publications and source records attributed to M A Watson.

114 records · Page 7Linked to original sources

Endogenous cell-mediated immunity, blood transfusion, and outcome of renal transplantation.

The cell-mediated immunity (CMI) of a group of patients on regular dialysis was measured by a quantitative dinitrochlorobenzene (DNCB) skin test, the reaction being graded 0--15. The score in these patients varied widely, although the mean was much lower than that occurring in a group of 15 healthy subjects. 55 cadaveric renal allografts were subsequently done in 51 of these patients, and graft survival was assessed at 6 months. The 39 patients with weak DNCB skin reactions had a much higher graft survival (71%) than did the 12 with strong reaction (15%) (p less than 0.01). The weak DNCB reactors also had more pre-transplant blood transfusions. The findings suggest that the CMI of the recipient as measured by the DNCB test has an important influence on subsequent graft survival. This influence may partly be related to pre-transplant blood transfusion.

Adolescent↗

Calretinin and calbindin-D28K in male rats during postnatal development.

Calcium-binding proteins play potentially important roles in neurogenesis and neuroprotective mechanism(s). Some evidence exists that brain calbindin-D28K (CALB) is regulated by androgens. In the present study, calretinin (CALRET) and CALB patterns were determined by Western analysis in the medial basal hypothalamus (MBH) from male rats along with assaying plasma testosterone levels during postnatal development. Testosterone levels were very low in 7-, 10-, and 30-day-old animals (approximately 0.5 ng/mL), increased in a stair-step fashion to peak levels at 90 days (approximately 3.8 ng/mL), then declined with increasing age to very low levels at 300 days of age (approximately 0.3 ng/mL). At 7 and 10 days, MBH CALRET and CALB levels were low; however, at Day 30 a significant twofold increased was observed. Thereafter, in 60-, 120-, 180-, and 300-day-old animals MBH CALRET and CALB levels were, in general, comparable to 30-day-old values. These findings suggest that there is not a clear correspondence between the androgen status in male rats and the calcium-binding proteins (CALRET & CALB) expressed in the MBH. Therefore, it appears that brain CALRET and CALB are regulated in a developmental fashion with significant increases in expression occurring around the 4th postnatal week.

Aging↗

Cardiac and vascular abnormalities in renal transplant patients: differential effects of cyclosporin and azathioprine.

Renal transplant patients die prematurely of cardiovascular disease and LV hypertrophy is now recognised as an important adverse prognostic indicator. This study investigated the factors implicated in the development of echocardiographic abnormalities (including LV hypertrophy) and the possible differential effects of treatment with cyclosporin and azathioprine. A cross-sectional study was undertaken in 46 patients randomly assigned to immunosuppressant treatment with either cyclosporin or azathioprine at 1 year post-transplantation: patients were studied not less than 5 years after assignment to cyclosporin (CyA) - or azathioprine (Aza)-based treatment regimens. Although clinic blood pressure control was not different in the two treatment groups, 24 hour ambulatory BP (ABP), particularly night-time BP, was significantly higher in the CyA group. There was a trend for both left ventricular hypertrophy (61 vs. 43%) and carotid wall thickening (43 vs. 26%) to be more common in the CyA group though this failed to achieve statistical significance. Left ventricular mass was determined by ABP, rather than clinic BP, and was also associated with increased QT dispersion. Multivariate analysis identified that 24 hour ambulatory systolic blood pressure (ASBP) and time on renal replacement therapy (RRT) were the major determinants of LV mass. Thus, despite the absence of differences in clinic BP measurements, CyA treatment was associated with higher rates of cardiovascular functional and structural abnormalities. This small scale study has identified cardiovascular functional and structural abnormalities in renal transplant patients, particularly in those receiving CyA-based immunosuppressive therapy. However, rather than reflecting a direct effect of CyA they are related to increased 24 ABP (but not clinic BP). These data suggest that ABP should be used to monitor and target antihypertensive therapy in this high risk patient group. Moreover, the future use of non-calcineurin inhibitor immunosuppressant therapy may have benefits on blood pressure control and LV mass.

Adult↗

Low dose pulse methotrexate therapy in rheumatoid arthritis.

Thirty-two patients with definite or classical rheumatoid arthritis were treated with low dose pulse methotrexate (MTX). A therapeutic response was shown in 2/3 of the patients by statistically significant joint changes and improved global response. Greater than one-half of those who improved demonstrated a drop in sedimentation rate. Eight patients discontinued treatment because of inefficacy and 2 because of gastrointestinal distress. One patient died of neoplasm. Five liver biopsies performed in patients with abnormal liver enzymes demonstrated no MTX related changes. We conclude that MTX may be an effective alternative to other more toxic immunosuppressive regimens and should undergo future evaluation.

Adult↗

p53 and K-ras in radon-associated lung adenocarcinoma.

Mutations in the p53 tumor suppressor gene and the K-ras proto-oncogene are common genetic defects in lung cancer. Analysis of the patterns of damage in these genes may provide important insights into the mechanisms by which environmental mutagens initiate cancer. Previously, our laboratory found that a rare p53 codon 249 mutation (AGG(ARG) to ATG(MET) transversion) was present in 31% of a series of 52 large and squamous cell lung cancers from uranium miners, suggesting that this mutation might be a marker for radon exposure. In the current study, we analyzed 23 lung adenocarcinomas from the same cohort of highly exposed uranium miners. These tumors failed to show the codon 249 transversion, but 9 (39%) of 23 contained 1 or more mutations within hotspots in the K-ras gene. The results suggest that there is a histological tissue-type specificity for the codon 249 mutation; although this mutation was common in squamous and large cell tumors from very highly exposed uranium miners, it is rare in adenocarcinomas from the same cohort of miners.

Adenocarcinoma↗