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Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 145 records · Page 8Linked to original sources

Association of amino acid sequences in the HLA-DQB1 first domain with antitopoisomerase I autoantibody response in scleroderma (progressive systemic sclerosis).

Previous studies in Caucasians with progressive systemic sclerosis (PSS) have suggested associations of antitopoisomerase I (antitopo I) autoantibodies with either serologically defined HLA-DR2 or DR5. To better define class II HLA associations with the antitopo I response, 161 PSS patients (132 Caucasians and 29 American blacks) were studied for antitopo I autoantibodies by immunodiffusion and immunoblotting, and their HLA-DRB1, DRB3, DQA1, and DQB1 alleles were determined by restriction fragment length polymorphic analysis and DNA oligotyping. Among Caucasians with antitopo I, HLA-DR5(DRB1*1101-*1104), DRB3*0202 and DQw3 (DQw7,8,9) were significantly increased in frequency. In American blacks, however, only HLA-DQB1*0301(DQw7) was significantly increased. The presence of HLA-DQB1*0301(DQw7) and other HLA-DQB1 alleles bearing the uncharged polar amino acid residue tyrosine at position 30 of the outermost domain was found in all antitopo I-positive Caucasian PSS patients compared with 66% of antitopo I-negative PSS patients (pc = 0.007) and 70% of normal controls (pc = 0.008), as well as all antitopo I-positive black patients. The association with HLA-DQB1 was independent of HLA-DR5(DRB1*1101-*1104) or any other HLA-DRB1, DRB3, or DQA1 alleles. Alternative or additional candidate epitopes for this autoimmune response include alanine at position 38 and threonine at position 77 of these same DQB1 alleles. These data suggest that genetic predisposition to the antitopo I response in PSS is associated most closely with the HLA-DQB1 locus.

Alleles↗

Arginine-vasotocin (AVT)--a pineal hormone in mammals.

Covering more than 30 years of studying the pineal peptide hormones physiology, this study largely discusses the main personal research as well as international literature indirectly or directly supporting the idea that the nonapeptide hormone arginine-vasotocin (AVT) is a pineal hormone in mammals. After a short review of the problem, the data are structured in two chapters: one including all the indirect arguments, i.e. those results demonstrating that the ly synthetic exogenous AVT mimics all the effects attributed to the pineal gland itself or to its releasing hormone the indole melatonin, or are contrary to those reported after pinealectomy, and a second chapter that includes all the data directly demonstrating that AVT is contained, synthetized and released from the pineal gland of mammals. Special emphasis was placed on the personal results regarding the AVT effects, the mechanisms of action, the release and interference with some of the basic functions of the brain such as sleep, behaviour, attention or maturation.

Animals↗

The paradoxical sleep-cerebral maturation relationship.

Cerebral maturation (CM) is a complex genetically determined process which consists of four stages (neuritogenesis, synaptogenesis, elimination of the abnormal synapses and myelinization), all modulated or fine-tuned by endo- or exogenous factors, among which the paradoxical sleep (PS) is the most important. In the present review it is stated by direct and indirect evidence that PS is the only state of vigilance compatible with such a modulation of the CM. Many results from literature as well as our data give strong support in demonstrating that PS is involved in all four stages of the CM. In the light of the two hypotheses concerning the role of the PS in CM (the ontogenetic and the specific behaviour one), the results and data presented here support the idea that these are not reciprocally exclusive and suggest some real biochemical mechanisms by which PS could achieve its maturational role.

Animals↗

[Familial hypobetalipoproteinemia with steatorrhea and malabsorption].

In a family in which the father was the mother's uncle, 3 of the 7 children were affected by a syndrome of malabsorption with various clinical symptoms. Diarrhea appeared in 2 of the children at birth, and in the third child at six months. The diarrhea led to failure-to-thrive, muscular wasting and abdominal swelling. However, the children improved spontaneously over the years. During childhood all 3 had manifest steatorrhea. Serum cholesterol was between 39 and 100 mg/dl, while triglycerides were normal to high. Reevaluation during the past year revealed areflexia, deficiency of vitamins A and E and of apoproteins A and B, and prolonged PT time in 2 of the children. Electron and light microscopy of small intestinal biopsies revealed vacuoles in the enterocytes. Electrophysiological tests revealed major disturbances in sensory conduction and brain-stem function. These cases differ from those described in the literature. Although in hypobetalipoproteinemia, 1 of the parents would be expected to be heterozygous and have low serum levels of APO B, in this family the parents had normal levels. Their children had low levels of serum APO A, while in patients with hypobetalipoproteinemia the levels are normal. There is a report of a case of deficiencies of both apolipoproteins, but the patient was asymptomatic, had chylomicronemia after a prolonged fast, and lower cholesterol levels than our patients. 8 other cases of apolipoprotein deficiency have been reported with biochemical characteristics similar to those of our patients, but with retention of chylomicrons in the small intestine.

Apoproteins↗

Electrocardiographic subset analysis of diltiazem administration on long-term outcome after acute myocardial infarction. The Multicenter Diltiazem Post-Infarction Trial Research Group.

The effect of diltiazem on long-term outcome after acute myocardial infarction (AMI) was assessed in 2,377 patients enrolled in the Multicenter Diltiazem Post-Infarction Trial and subsequently followed for 25 +/- 8 months. The study population included 855 patients (36%) with at least 1 prior AMI before the index infarction and 1,522 patients (64%) with a first AMI, of whom 409 (27%) had a first non-Q-wave AMI, 664 (44%) a first inferior Q-wave AMI, and 449 (30%) a first anterior Q-wave AMI. This post hoc analysis revealed that, among patients with first non-Q-wave and first inferior Q-wave AMI, there were fewer cardiac events during follow-up in the diltiazem than in the placebo group, and that the reverse was true for patients with first anterior Q-wave AMI or prior infarction. The diltiazem:placebo Cox hazard ratio (95% confidence limits) for the trial primary end point (cardiac death or nonfatal reinfarction, whichever occurred first) was: first non-Q-wave AMI-0.48 (0.26, 0.89); first inferior Q-wave AMI-0.66 (0.40, 1.09); first anterior Q-wave AMI-0.82 (0.51, 1.31); and prior AMI-1.11 (0.85, 1.44). Use of cardiac death alone as an end point gave an even more sharply focused treatment difference: first non-Q-wave AMI-0.46 (0.18, 1.21); first inferior Q-wave AMI-0.53 (0.27, 1.06); first anterior Q-wave AMI-1.28 (0.68, 2.40); prior infarction-1.26 (0.90, 1.77). Further analysis revealed that these differences in the effect of diltiazem in large part reflected the different status of the 4 electrocardiographically defined subsets in terms of left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Diltiazem↗

Symptom schemata in chronic respiratory patients.

In view of evidence that illness prognoses and adaptive functioning may be influenced by the accuracy of people's knowledge about their physical symptoms, the present study extended these findings to the chronic care population. It was hypothesized that individuals hold beliefs and develop theories about their physical symptoms and that the accuracy of these beliefs is predictive of the individuals' general level of adaptive functioning. A modified version of an instrument designed to measure the accuracy of illness schemata was employed with a sample of 31 chronic respiratory patients. Accuracy rating correlated positively and significantly with ratings of adaptive functioning, whereas no relationship was observed between adaptive functioning and severity of the patients' medical condition. Well-informed patients functioned at a higher level physically, psychologically, and socially than less-informed patients. These findings point to the importance of patient education for prognosis. Possible mediating factors are discussed.

Adult↗

Metabolic fate of chylomicrons obtained from rats maintained on diets varying in fatty acid composition.

The importance of the fatty acid component in the metabolism of chylomicrons was demonstrated by feeding diets varying in fatty acid composition which resulted in chylomicrons of different sizes. On a diet rich in polyunsaturated fatty acids (PUFA) from safflower oil, chylomicrons of diameter 1853 +/- 192 A were harvested from the mesenteric lymph, whereas on coconut oil and medium-chain triglyceride diets the chylomicron size was 1403 +/- 83 and 604 +/- 40 A, respectively. When the isolated chylomicrons were injected into recipient rats maintained on a regular diet, their half-life (t1/2) decreased from 5.4 +/- 0.4 to 1.8 +/- 0.3 min with the increase in particle size. No significant difference in the apolipoprotein profile of chylomicrons of various sizes was noted, indicating that alterations of chylomicron removal are not related to apolipoprotein composition. Rats maintained on PUFA diets showed a marked increase in their adipose tissue lipoprotein lipase activity. The fast removal of large chylomicrons and increased tissue lipoprotein lipase activity, together with suppression of hepatic lipogenesis on this diet, apparently explains the low plasma triglyceride level in rats maintained on diets rich in PUFAs.

Animals↗

Perioperative renal function in patients undergoing orthotopic liver transplantation. A randomized trial of the effects of verapamil.

Patients who undergo orthotopic liver transplantation often experience a significant drop in GFR postoperatively. Postulated mechanisms include intraoperative hemodynamic changes, suboptimal renal perfusion during the anhepatic stage, and cyclosporine administration. We undertook a prospective double-blind study to investigate these factors, as well as to determine the protective effects of verapamil on perioperative renal function. Twenty-five patients with normal renal function undergoing OLT received either placebo (n = 13) or verapamil (n = 12) intraoperatively and for six weeks post-OLT. No CsA was administered until after reperfusion of the graft liver, and venovenous bypass (VVB) was utilized in all cases. Patients completing six weeks of the study experienced 61% and 48% decreases in GFR within the placebo and verapamil groups respectively. A significant decrease in GFR occurred in the placebo group between one and six weeks post-OLT, and a significant drop in GFR occurred in the verapamil group by one week post-OLT. Differences between the groups were not significant, however. Systemic, renal, and hepatic hemodynamics were similar at all times between groups, and renal hemodynamics and urine output were unchanged during VVB. We conclude that (1) perioperative factors do not contribute to renal dysfunction post-OLT when VVB is used; (2) VVB preserves renal hemodynamics during the anhepatic phase; (3) CsA is the most likely causative agent for post-OLT renal dysfunction; and (4) intraoperative verapamil serves no protective role, as administered in this study.

Double-Blind Method↗

Simultaneous color constancy: paper with diverse Munsell values.

Arend and Reeves [J. Opt. Soc. Am. A 3, 1743 (1986)] described measurements of color constancy in computer simulations of arrays of colored papers of equal Munsell value under 4000-, 6500-, and 10,000-K daylight illuminants. We report an extension of those experiments to chromatic arrays spanning a wide range of Munsell values. The computer-simulated scene included a standard array of Munsell papers under 6500-K illumination and a test array, an identical array of the same papers under 4000 or 10,000 K. Observers adjusted a patch in the test array in order to match the corresponding patch in the standard array by one of two criteria. They either matched hue and saturation or they made surface-color matches, in which the test patch was made to "look as if it were cut from the same pice of paper as the standard patch." The test and the standard patches were surrounded by a single color (annulus display) or by many colors (Mondrian display). The data agreed with those of our previous equal-value experiment. The paper matches were often approximately color constant. The hue-saturation matches were in the correct direction for constancy but were always closer to a chromaticity match (no constancy) than to the chromaticity required for hue-saturation constancy.

Adaptation, Ocular↗

Effect of luminance on suprathreshold contrast perception.

Perceived contrast was measured under natural viewing conditions with the use of contrast-matching and magnitude-estimation paradigms and found to be independent of luminance over a range of luminances from 37.5 down to 8 cd/m2. However, this contrast constancy broke down when the dimmer target was below 8 cd/m2. The perceived contrast of the dimmer target then fell below that expected from contrast constancy. The extended range of contrast constancy previously reported [J. Physiol. 252, 627 (1975); Vision Res. 16, 1419 (1976)] has been thought to imply neural mechanisms with unlimited constancy, but these researchers permitted differential adaptation to the brighter and dimmer targets, which were seen haploscopically (by different eyes). As our natural-viewing procedure ensured that both bright and dim targets were presented to retinal areas in a roughly constant state of adaptation, our failure to find extended contrast constancy implies an important limitation on the neural processing of contrast.

Adaptation, Ocular↗

A rare complement component C4 restriction fragment length polymorphism in two families with systemic lupus erythematosus.

C4 null alleles with or without C4A,21-OHA gene deletions are associated with systemic lupus erythematosus (SLE) in various populations. We describe a new, rare C4 restriction fragment length polymorphism (RFLP), a Taq I 3.5 kb fragment, in 2 patients with SLE and their families. This RFLP is not associated with one particular major histocompatibility complex (MHC) haplotype and has not been reported in patients with SLE, patients with congenital adrenal insufficiency, or in healthy individuals.

Adult↗

Effect of clonidine on gallbladder contraction and small bowel transit time in insulin-treated diabetics.

Cholelithiasis is more prevalent in diabetics than in nondiabetics. Gallbladder dysmotility is supposed to be one of the causative factors. Reduced alpha-adrenergic tone has been demonstrated in the enterocytes of diabetic rats, and its correction by clonidine might explain the beneficial effect that the drug has on diabetic diarrhea. We therefore surmised that diabetic cholecystoparesis could also be due to alpha-adrenergic alterations. To test this hypothesis, we studied gallbladder contractions by real time ultrasonography, and small bowel transit time by lactulose hydrogen breath test, in 13 insulin-requiring diabetics before and after administration of the alpha-adrenergic stimulant clonidine (0.3 mg orally). That plasma levels were sufficient was evidenced indirectly by a fall in blood pressure. Clonidine significantly improved the rate of emptying (0.0193 +/- 0.00057/min vs. 0.0318 +/- 0.0027/min; p less than 0.005), but not the fasting and residual gallbladder volumes. Small bowel transit time was significantly prolonged after clonidine (169 +/- 17 min vs. 208 +/- 17; p less than 0.05). These results suggest that 1) reduced alpha-adrenergic tone corrected by clonidine may be present in the diabetic gallbladder, and 2) clonidine's antidiarrheal effect might be explained, at least in part, by a prolongation of the small bowel transit time.

Adult↗

Fish oil treatment of hyperlipidemia in children and adolescents receiving renal replacement therapy.

The effect of 8 weeks of daily oral fish oil supplementation in a dose of 3 to 8 g/d on serum lipid levels was studied in 16 patients, 7 to 8 years of age, who had end-stage renal disease and were receiving renal replacement therapy. Fasting serum cholesterol (CHOL), triglyceride (TG) levels, and lipoprotein profiles were measured before therapy, 8 weeks after fish oil supplementation, and 4 weeks after its cessation. During 8 weeks of treatment the mean serum CHOL level did not change. The mean serum TG level, however, decreased significantly (P less than .01) from 236 +/- 31 mg/dL to 171 +/- 21 mg/dL (27.5%). Four weeks after treatment was stopped, the mean serum TG level returned to a value not significantly different from the pretreatment level (208 +/- 30 mg/dL). In a subgroup of 11 excessively hyperlipidemic patients, with serum CHOL and TG levels greater than or equal to 50% of the 90th percentile for age and sex, the mean serum TG level decreased even more (30.8%), from 286 +/- 35 mg/dL to 198 +/- 24 mg/dL (P less than .01), and the mean CHOL/high-density lipoprotein CHOL ratio decreased from 8.4 +/- 1.2 to 7.4 +/- 1.3 (P less than .05). Blood pressure and platelet counts remained stable during the entire study period. Side effects of the treatment were minimal. These results show that dietary fish oil supplementation reduces serum TG levels in young patients receiving renal replacement therapy and improves their "atherogenic" serum lipoprotein profile.

Adolescent↗

Effect of fenoldopam in dogs with spontaneous renal insufficiency.

Fenoldopam administration orally or i.v. resulted in significant increases in paraaminohippuric acid (PAH) clearance in both four control dogs and four dogs with chronic renal failure. Oral fenoldopam resulted in significant plasma levels of fenoldopam sulfate metabolites. One metabolite, fenoldopam-8-sulfate, a potential inhibitor of organic anion transport, did not depress renal cortical slice accumulation of PAH. The data therefore indicate that in dogs with chronic renal failure, PAH clearance after fenoldopam administration is a reliable measure of renal plasma flow, and fenoldopam can result in an increase in renal plasma flow.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗