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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 289 records · Page 16Linked to original sources

Inhibition of immune precipitation in rheumatic disease. A clinical and laboratory study.

Antigen-antibody complexes formed in the presence of serum do not precipitate. This complement-dependent function is impaired in approximately half of all patients with seropositive rheumatoid arthritis (RA) but not in patients with other chronic inflammatory arthropathies. As patients with seropositive RA have normal or elevated serum complement levels, this findings suggests that an inhibitor is present in the serum of these patients. Although degree of impairment of solubilization is correlated with rheumatoid factor (RF) titre, decreases in RF titre in patients receiving gold therapy were not always accompanied by improvement of the solubilization process. Thus we can conclude that impaired solubilization is related to, but may be distinct form, RF. Impaired solubilization was associated with the presence of subcutaneous nodules, but not with other systemic features of RA. Thus this phenomenon may be of pathogenetic importance.

Antigen-Antibody Complex↗

Stereoselectivity of isozyme C of glutathione S-transferase toward arene and azaarene oxides.

Three of the isozymes of glutathione S-transferase (EC 2.5.1.18) from rat liver (isozymes A, B, and C) catalyze the addition of glutathione to phenanthrene 9, 10-oxide with varying degrees of efficiency and stereoselectivity. Isozyme C is 2-fold and 35-fold more efficient toward this substrate than are isozymes A and B, respectively, and gives a 20 to 1 ratio of the two possible diastereomeric products. The stereoselectivities of isozymes A (approximately 1 to 1) and B (3 to 1) are considerably lower. The major product diastereomer from isozyme C is deduced to have the 9S, 10S absolute configuration by circular dichroism spectroscopy, implying attack of glutathione on the oxirane carbon on R absolute configuration. Isozyme C shows little kinetic discrimination between other K-region arene oxides such as pyrene 4,5-oxide and the enantiomers of benz[a]anthracene 5,6-oxide and benzo[a]pyrene 4,5-oxide. However, the stereoselectivity toward all the substrates is conserved with predominant (greater than 95%) attack at the oxirane carbon of R absolute configuration to give the S,S product. The stereoselectivity of isozyme C is very sensitive to the introduction and location of nitrogen substitution in the phenyl rings of phenanthrene 9,10-oxide. As a result isozyme C shows little or no stereoselectivity toward 4,5-diaza- and 4-azaphenanthrene 9,10-oxide. In contrast, 1-azaphenanthrene 9,10-oxide is attacked preferentially at the R carbon of the oxirane. The results suggest that hydrophobic interactions between the enzyme surface and the substrate distal to the oxirane ring are important in determining the stereoselectivity of the enzyme toward arene oxides.

Animals↗

Dexamethasone suppression, protirelin stimulation, and insulin infusion in subtypes of recovered depressive patients.

Twenty-eight patients (10 bipolar, 13 depressive spectrum disease, and 5 familial pure depressive), recovered from depression for an average of 1 year, underwent a series of basal and provocative endocrine tests. No significant differences were found among depressive subtypes in thyrotropin, cortisol, or growth hormone measurements either before or after provocative testing with the exception of growth hormone response to insulin-induced hypoglycemia. Patients with depressive spectrum disease showed a significantly different growth hormone response to insulin-induced hypoglycemia than patients with bipolar disorder, a finding which suggests differences in alpha-adrenergic receptor sensitivity between these groups.

Adult↗

Calcium and phosphorus utilisation in chickens fed on diets high in N-alkane-grown yeast.

Interactions between calcium (Ca) and phosphorus (P) were studied in young chickens fed on diets high in n-alkane-grown yeast and in chicks fed on control soya-fishmeal diets for 14 d. Additions of inorganic Ca to diets containing 300 g yeast/kg caused increases in body-weight gain, gain:food ratio and bone mineralisation up to a total dietary concentration of 13.9 g Ca/kg. At all additions of Ca, bone mineralisation was inferior in yeast-fed chicks compared with control chicks. Supplementation of high Ca diets (16.8 g Ca/kg) with inorganic P led to further improvements in body-weight gain, food intake and food utilisation of chicks fed on high-yeast diets. Bone mineralisation also improved but was always inferior in the yeast-fed chicks compared with control chicks. It was concluded that Ca and P supplementation was necessary in high-yeast diets due to low dietary Ca concentrations and low availability.

Alkanes↗

Gold levels produced by treatment with auranofin and sodium aurothiomalate.

Sixty-three patients with rheumatoid arthritis were randomly divided into 3 groups, and treated with either sodium aurothiomalate (Myocrisin), auranofin, or placebo. Gold levels in whole blood, plasma, and haemolysate were measured serially along with clinical and laboratory parameters of efficacy. Auranofin produced a higher ratio of haemolysate to plasma gold than Myocrisin, and it appears that the affinity of the red cell for gold is reduced during therapy with auranofin. Gold levels did not correlate with changes in the pain score, erythrocyte sedimentation rate, and C-reactive protein, nor with the development of toxicity. In the Myocrisin group the haemolysate gold level achieved was dependent on the number of cigarettes smoked. In the auranofin group there was no such correlation, but the haemolysate gold level was higher for smokers than non-smokers. The likely action of gold is discussed.

Adult↗

Diabetes, a hypercoagulable state? Hemostatic variables in newly diagnosed type 2 diabetic patients.

37 type 2 diabetic patients with no clinical evidence of retinopathy or vascular disease were studied at diagnosis and following control of hyperglycaemia for evidence of abnormalities of coagulation, fibrinolysis and platelet behaviour. 38% showed hyperactive platelets, demonstrating either in vitro hyperaggregability, circulating platelet aggregates, or raised plasma beta-thromboglobulin levels. 36% showed abnormally raised factor VIII coagulant activity (FVIIIc) levels, though this was mainly in female patients. The mean level of FVIIIc decreased with treatment. Anti-thrombin III (AT-III) levels were decreased, and 33% of the patients had levels less than 80%. In this group AT-III increased following treatment. No abnormalities of fibrinolysis were demonstrated. These findings support the concept that diabetes can be associated with a hypercoagulable state, which is not necessarily dependent on the presence of overt vascular disease, or correlated with the degree of chronic hyperglycaemia (HbA1c levels).

Adenosine Diphosphate↗

Development of selected neurological skills.

The development of several selected neurological skills in 592 children, ages 3 to 6 years 11 months, were studied. The sequence in the development of these skills included the ability to point up and down, to keep the arms extended, pointing back, to open and close a safety pin, pointing front, figure identification, single finger identification, and right-left concept developing shortly after the others. Clinical implications of these findings have not been evaluated in this study.

Brain Damage, Chronic↗

Attenuated pressure natriuresis in hypertensive rats.

We studied the isolated blood-free perfused nonclipped kidneys from the 2-kidney Goldblatt hypertensive rat model (GHR) to evaluate intrinsic excretory responses to changes in perfusion pressure. We examined kidneys from 10 control rats (in vivo systolic BP 110 +/- 3.6 mm Hg), from 9 rats with nonmalignant hypertension (HBP) (in vivo systolic BP 158 +/- 6.5 mm Hg), and from 5 rats with malignant HBP (in vivo systolic BP 183 +/- 6.4 mm Hg). We found that at all levels of perfusion pressure, the renal vascular resistances were significantly higher and glomerular filtration rate (GFR) lower in kidneys from hypertensive rats than in kidneys from control rats. Kidneys from hypertensive rats had lower urinary excretion of sodium (UNaV) and urine flow than kidneys from control rats at all levels of pressure above 100 mm Hg. The most striking differences in all functional parameters were noted in kidneys from rats with malignant HBP. Kidneys from both hypertensive and control rats failed to show changes in vascular resistance in response to Saralasin. We conclude that the nonclipped kidney in GHR exhibits a blunted natriuresis in response to elevated perfusion pressure which occurs in the absence of angiotensin II (AII) and renin substrate. This diminished pressure natriuresis may be caused partly by the lower GFR and by reduced pressure transmission due to greater renal vascular resistance and thus may be partially responsible for the maintenance of the hypertensive state.

Animals↗