PubMed Health⌕ Search

Biomedical subjects

R Goldstein

Publications and source records attributed to R Goldstein.

At least 19 recordsLinked to original sources
PubMed1992

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 2. Synthesis and biological activity of 8-(benzenesulfonamido)-7-(3-pyridinyl)octaonic acid and related compounds.

A series of arylsulfonamide alkanoic acids substituted with a 3-pyridinyl group along the aliphatic chain were synthesized and tested in vitro for their ability to antagonize thromboxane A2 (TxA2) receptors and inhibit thromboxane synthase. These compounds were found to potently inhibit the U 46619-induced aggregation of human platelets and to also inhibit TxA2 biosynthesis in a human microsomal platelet preparation. However, some members of the series, notably compound 21, were found to display agonist activity on the rabbit aorta TxA2 receptor. This unwanted agonist activity appeared to be related to the presence of a substituent beta to the arylsulfonamido group.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Thromboxane receptor antagonism combined with thromboxane synthase inhibition. 3. Pyridinylalkyl-substituted 8-[(arylsulfonyl)amino]octanoic acids.

A series of 8-[(arylsulfonyl)amino]octanoic acids substituted with a pyridinylalkyl group along the chain were synthesized and tested in vitro for their ability to both antagonize the binding of thromboxane A2 to its receptors and to inhibit the thromboxane synthase enzyme. This series of compounds were found to inhibit the U 46619-induced aggregation of human platelets and the U 46619-induced contraction of dog saphenous vein. The compounds also inhibited TxA2 biosynthesis in a human microsomal platelet preparation. The relative position of the pyridinylalkyl and arylsulfonamide groups had significant effects on the thromboxane receptor antagonist (TxRA) activity and thromboxane synthase inhibitor (TxSI) activity. Compounds with the pyridine ring at the 7- or 8-position of the octanoic acid side chain were weakly active as TxSI but behaved as potent TxRA at the platelet receptor for TxA2. However, these compounds were agonists at the vascular receptor. Substitution of the pyridinylalkyl group at the 2- or 3-position resulted in compounds with potent TxSI activity and weak TxRA activity. The activity profile of the compounds with the pyridinylalkyl substitution at the 4-, 5-, or 6-position was very desirable. Compound 22 with a pyridinylpropyl substituent at the 4-position was found to display extremely potent TxRA and TxSI properties.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Racial differences in the frequencies of scleroderma-related autoantibodies.

OBJECTIVE: To determine demographic differences in scleroderma-related autoantibodies. METHODS: One hundred fifty-six patients with systemic sclerosis were prospectively examined for anticentromere antibodies (ACA), anti-topoisomerase I (anti-topo I, or Scl-70), antinucleolar, and anti-U1 RNP autoantibodies. RESULTS: ACA was found in 36% of Caucasians and 4% of American blacks (P = 0.002, odds ratio [OR] 15). Anti-topo I was found in 37% of American blacks, compared with 17% of Caucasians (P = 0.04, OR 3). No significant differences in the frequencies of antinucleolar and anti-U1 RNP autoantibodies were found. CONCLUSION: These data suggest important demographic differences in scleroderma-associated autoantibodies.

Autoantibodies↗
PubMed1992

The effect of desogestrel for hormone replacement therapy on the blood lipid profiles of postmenopausal women.

OBJECTIVE: To determine the effect of a hormone replacement protocol containing conjugated equine estrogens and desogestrel (which has a highly selective progestogenic and low androgenic effect) as the progestogen, on the plasma lipid profile, as compared with two other hormone replacement treatments (HRT). METHOD: Eighty-nine healthy postmenopausal women were divided prospectively into four groups. A control group of 24 women did not receive HRT. Twenty-nine women received conjugated equine estrogen and medroxyprogesterone, and 13 women received a protocol containing estradiol, estriol and norethisterone acetate. Fasting blood lipid was taken at the end of each third cycle. The cumulative therapeutic response was calculated in each group as compared with initial values and between groups. Significance was analyzed by t-tests. RESULTS: A protocol containing desogestrel significantly decreased low-density lipoprotein cholesterol (27%; P < 0.05) and increased high-density lipoprotein cholesterol (HDL-C) by 30% (P < 0.05%) after 9 months. The ratio of total cholesterol to HDL-C also decreased significantly (44%; P < 0.05). CONCLUSION: The most beneficial effect on plasma lipid profile was obtained with an HRT protocol containing desogestrel as the progesterone.

Cholesterol↗
PubMed1992

Effect of task difficulty and interstimulus interval on blink parameters.

The effects of task difficulty and interstimulus interval (ISI) on blink rate, blink latency and blink duration, were studied in a modified Sternberg memory task in which either two or six characters were to be memorized. Stimuli were presented in ISI blocks at either 5.3 or 9.3 s (SOAs of 6 or 10 s). While blink rate and blink duration declined prior to each stimulus, the difficulty of the expected task (the length of the memory set) did not affect the rate of decline or the final prestimulus level. Concerning ISI, blink rate declined more rapidly during shorter ISIs but the final prestimulus level, as was the case with task difficulty, was unaffected by the ISI duration. Presentation of the 6-character memory set produced a marked immediate inhibition of blinking. The data suggest that the encoding of visual stimuli is more akin to processes invoked in preparation for input than to ensuing processing stages since both encoding as well as preparation are accompanied by inhibition of blinking.

Adolescent↗
PubMed1992

Auditory distortion products measured with averaged auditory evoked potentials.

The purpose of this investigation was to describe the properties of averaged auditory evoked potential distortion products (AEP-DPs) in guinea pigs. This study provided a step toward developing a clinical index of nonlinear processing of auditory signals and supplied a baseline for studies evaluating the effect of cochlear damage on AEP-DPs. The amplitude of the AEP-DPs was evaluated as a function of f2/f1 ratio (1.12-1.52) and primary frequency (500 Hz-2000 Hz). The amplitude of the AEP cubic difference tone (AEP-CDT) increased with increasing f2/f1 ratio for the 500-Hz f1 primary and remained constant for the 800-Hz and 1700-Hz f1 primaries. The AEP-CDT generated by the 1100-Hz and 1400-Hz f1 primaries was maximum for the middle f2/f1 ratios (1.22, 1.32, and 1.42). The AEP-CDT could not be distinguished from the noise floor for the 2000-Hz f1 primary. The AEP difference tone (AEP-DT) was larger and more frequently identified than the AEP-CDT. The amplitude of the AEP-DT decreased with an increase in f2/f1 ratio. The decrease was more pronounced for low-frequency f1 primaries than for high-frequency f1 primaries.

Acoustic Stimulation↗
PubMed1992

Studies of the HLA class II alleles involved in human responses to ragweed allergens Ambrosia artemisiifolia V (Ra5S) and Ambrosia trifida V (Ra5G)

Previous studies have associated skin test sensitivity and specific IgE response to Ambrosia artemisiifolia V (Amb a V) with HLA-DR2, and to Ambrosia trifida V (Amb t V) with HLA-DRw52 haplotypes in atopic individuals. Using HLA class II typing by restriction fragment length polymorphism (RFLP) analysis with DRB, DQB and DQA DNA probes to define the HLA-D alleles, we have demonstrated the association of the DQw6 in 16 out of 16 (100%) Amb a V-responsive individuals, compared to 3 out of 18 (17%) ragweed-sensitive but Amb a V-nonresponsive individuals (p = 5.7 x 10(-6), RR greater than 75). We suggest that the DQw6 association with Amb a V sensitivity may be a reflection of an association with the DQA*0102 allele. This suggests an association of a particular HLA class II allele with an immune response to a well-characterized antigen (Amb a V). The HLA-DRw52 haplotypes in the Amb t V-sensitive individuals are not of one particular subtype. The HLA-DRw52 association with Amb t V sensitivity may reside in homologous DRB1 alleles linked on HLA-DRw52-bearing haplotypes.

Alleles↗
PubMed1992

Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis (scleroderma).

HLA class II alleles (detected by DNA typing) were determined in 116 Caucasians with systemic sclerosis positive and negative for anticentromere autoantibodies (ACA). Significantly increased frequencies of HLA-DR5(DRw11) (P = 0.009) and the Dw13(DRB1*0403, *0407) subtypes of DR4 (probability corrected, Pc = 0.005) were seen in ACA positive patients, and HLA-DR1 and DRw8 were also increased. These findings appeared to reflect linkage disequilibrium of DR5(DRw11) and many DR4(Dw13) haplotypes with HLA-DQw7 and DR1 with DQw5. In fact, the presence of a DQB1 allele having a polar glycine or tyrosine at position 26 of the DQB1 first domain versus a hydrophobic leucine accounted for 100% of ACA positive Caucasian systemic sclerosis patients compared to 69% of the ACA negative SS patients (P = 0.0008) and 71% of Caucasian controls (P = 0.0003) as well as all 7 ACA patients of non-Caucasian background. Furthermore, the genotype frequency of DQB1 alleles lacking leucine at position 26 was 73% in ACA positive SS patients, compared to 42% of ACA negative patients (P = 1.2 x 10(-5)) and 38% of controls (P = 5.8 x 10(-7)). These data, then, suggest that the second hypervariable region of the HLA-DQB1 chain may form the candidate epitope associated with the ACA response.

Alleles↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

[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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗