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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 361 records · Page 20Linked to original sources
PubMed1988

Potential role of somatomedin inhibitors in the production of diabetic embryopathies.

Mouse conceptuses at the 18-21-somite stage were grown for 2-24 h in vitro in the presence of a serum fraction (Mr = 800-1,080 daltons) possessing somatomedin-inhibitory activity (SI) isolated from diabetic rats. Following an 8-h exposure to the SI, DNA and incorporation of 3H-thymidine were reduced in the embryos while 12 h was required to observe a reduction in total protein and RNA. At the 24-h time point, the neurectoderm was thinner than in controls, and autoradiograms of this region showed a substantial decrease in grain density with 3H-thymidine, but not 3H-leucine or -uridine. Effects of the visceral yolk sac (VYS) preceded those on the embryo. The cytoplasm of the VYS endoderm cells from conceptuses exposed to the SI contained many vacuoles by 4 h, which were larger by 24 h. Total protein was greater than in controls from 4 h onward, although 3H-leucine incorporation, which had increased after 2 h of SI exposure, returned to control levels by 8 h. As seen by SDS-polyacrylamide gel electrophoresis, VYSs from conceptuses exposed to the SI for 4 or 24 h were enriched (compared to control VYSs) in four protein bands also present in the culture medium (primarily rat serum), suggesting that protein degradation and/or transfer of amino acids and peptides to the embryo was inhibited in these VYSs. Such a conclusion was supported by a quantitative decrease in proteins and amino acids in the exocoelomic fluid of conceptuses exposed to the SI for 24 h. The altered processing of proteins may therefore represent a primary cause of the SI-induced embryonic abnormalities.

Abnormalities, Drug-Induced↗
PubMed1988

Somatomedin inhibitors from human serum produce abnormalities in mouse embryos in culture.

Two human serum fractions, one from normal individuals (Mr 1,150-1,310 daltons) and the other (Mr 800-1,100 daltons) from patients suffering with uremia (renal failure, azotemia), were added to the medium used to grow embryos in whole-embryo culture (WEC) beginning at the 3-5 (day 9) or 18-21 (day 10) somite stage. Both of these fractions possessed somatomedin (insulin-like growth factor) inhibitory activity. Day 9 embryos exposed to either of the serum fractions for 24 hr exhibited incomplete rotation and neural tube closure defects and were smaller than control embryos (decreased total protein content). Developmental abnormalities induced in day 10 embryos following 24 hr in culture included a marked decrease in expansion of the brain regions, hypoplasia of the first two branchial arches, and decreased amounts of total protein compared to controls. The visceral yolk sacs (VYSs) of somatomedin inhibitor (SI)-exposed conceptuses were opaque, and those from day 10 conceptuses contained significantly more protein than controls. Morphologically, the VYS endoderm cells from SI-exposed embryos contained a much higher density of "vacuoles" than controls. These results mimic those produced by exposure of conceptuses to an SI of Mr800-1,100 obtained from the serum of diabetic rats and suggest that similar substances and mechanisms are involved.

Animals↗
PubMed1988

Risk identification at the time of admission to coronary care unit in patients with suspected myocardial infarction.

The in-hospital clinical course was evaluated in 2,162 consecutive patients admitted with a diagnosis of suspected myocardial infarction. Of these, 1609 patients were considered to be in the high-risk group, based on the presence of 16 clinical criteria present at the time of admission. The remaining 553 patients were classified as low risk. The overall rate of complications in the coronary care unit was greater in the high-risk group, 64%, compared to 26% in the low-risk group (p less than 0.001). Similarly life-threatening events (occurrence or recurrence of ventricular fibrillation, sustained ventricular tachycardia, complete heart block, asystole, or cardiogenic shock) were more common in the high risk-group compared to the low-risk group, 11% and 0.9%, respectively (p less than 0.001). The high-risk group required significantly more interventions, such as electrical cardioversion, temporary pacing, pulmonary artery catheterization, and intraaortic balloon counterpulsation, compared to the low-risk group (20% vs 2%, respectively; p less than 0.001). Myocardial infarction was confirmed in 892 patients in the high-risk group (55%) compared to 90 (16%) in the low-risk group (p less than 0.001). The coronary care unit mortality rate was greater in the high-risk group compared to the low-risk group (8.2% vs 0.4%, respectively; p less than 0.0002). It is concluded that based on readily available clinical criteria at the time of admission, a subgroup of patients at low risk for developing life-threatening complications requiring coronary care unit interventions can be identified and admitted directly to an intermediate-care unit.

Coronary Care Units↗
PubMed1988

Altered plasma dexamethasone and cortisol suppressibility in patients with panic disorders.

Some abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis in patients with panic disorders were recently reported. The possibility that the disposition of dexamethasone, which has been reported to influence the Dexamethasone Suppression Test (DST), might be altered in this subgroup of patients has not, as yet, been reported. We report that 4:00 PM dexamethasone plasma concentrations following a 1-mg oral DST were significantly (p less than 0.01) lower in 23 patients with panic disorders (0.49 +/- 0.44 ng/ml) compared to 52 normal control subjects (1.09 +/- 0.64 ng/ml). This is in addition to the significantly higher (p less than 0.05) 4:00 PM postdexamethasone cortisol values per nanogram per milliliter of dexamethasone in the panic disorder patients compared to normal controls (17.7 +/- 29.6 versus 5.0 +/- 11.2 micrograms/dl). The mean percent suppression of cortisol from baseline in panic disorder was normal despite one-half the dexamethasone concentrations in these subjects. The cortisol suppression versus dexamethasone concentration curve was also shifted lower (greater fraction of cortisol suppression) and to the left (toward lower dexamethasone concentrations). These results further suggest that the HPA system is indeed altered in panic disorders, but in a manner that is not readily apparent from the DST alone.

Adult↗
PubMed1988

Cortisol suppression per nanogram per milliliter of plasma dexamethasone in depressive and normal subjects.

It has been suggested that dexamethasone pharmacokinetics may affect cortisol suppression during the Dexamethasone Suppression Test (DST). In depressed patients the cortisol response has been shown to negatively correlate with dexamethasone plasma concentrations, which also influence the sensitivity and specificity of the DST. These findings have been interpreted as weakening the utility of the DST. However, the analysis of pre- and post-1 mg DST cortisol concentrations corrected for plasma dexamethasone concentrations suggest that compared with normals (n = 52), patients with major depressive disorder (MDD) as a group (n = 71) had less suppressibility of cortisol to the same plasma dexamethasone concentrations. Moreover, when the MDD patients were evaluated based on DST status, the suppressors had cortisol/dexamethasone ratios (micrograms/dl of cortisol per ng/ml of plasma dexamethasone) similar to the normal controls, whereas the nonsuppressors had ratios that were significantly higher. These data suggest that DST non-suppression, as well as sensitivity and specificity of the DST in depression, is not only attributable to altered dexamethasone disposition, but indeed, there is a genuine reduced sensitivity of cortisol to dexamethasone that still points to an abnormality of the delayed feedback mechanism of the hypothalamic-pituitary-adrenal system in some depressed patients.

Adult↗
PubMed1988

Effects of soy protein and casein in low cholesterol diets on plasma lipoproteins in normolipidemic subjects.

Dietary plant proteins may lower plasma cholesterol and LDL concentrations in hypercholesterolemic patients when substituted for animal proteins, particularly in diets with low cholesterol and saturated fat content. Plant protein diets appear, however, to be without effect on plasma lipoprotein levels in normal subjects. In the present study, we have examined whether the origin of the dietary protein, i.e. plant (soy) or animal (casein), affects the plasma lipoproteins in normolipidemic subjects when these proteins are presented as components of diets low in cholesterol and saturated fat. The study followed a crossover design. Five men and 5 women consumed liquid formula diets containing 20% of calories as casein or soy protein, 28% as fat (mainly monounsaturated), and 52% as carbohydrate; the intake of cholesterol was less than 100 mg per day. The two dietary periods, each of 1 month duration, were separated by an interim period of 1 month on self-chosen food. Following an initial 30% reduction of cholesterol and LDL plasma levels on both diets, the concentrations of each of the major lipoprotein classes (VLDL, IDL, LDL, HDL2 and HDL3) were similar during the two experimental dietary periods. Body weights were essentially constant. Dietary soy protein and casein could not be distinguished in their effects on the plasma concentrations and chemical composition of the major lipoprotein classes in normolipidemic subjects.

Adult↗
PubMed1988

Nutrition and somatomedin. XVI: Somatomedins and somatomedin inhibitors in fasted and refed rats.

Nutritional deprivation is associated with poor growth and decreased levels of net circulating somatomedin activity, as measured by bioassay. Since somatomedin activity reflects the contributions both of somatomedins (which stimulate cartilage) and of somatomedin inhibitors (which antagonize the ability of the somatomedins to stimulate cartilage), we asked if changes in net somatomedin activity could involve progressive underlying alterations in levels of both somatomedins and somatomedin inhibitors. Groups of rats were killed during three days of fasting and 24 hours of refeeding. Fasting was associated with a rise in serum beta-hydroxybutyrate from 1.6 to 12.6 mmol/L after one day, followed by a decline to 4 mmol/L at three days. Somatomedins (low-MW) were separated from somatomedin inhibitors (high-MW) by gel permeation chromatography at acid pH on Sephadex G-50 and TSK-2000 HPLC. Somatomedins fell 35% after one day of fasting, and decreased to 59% below control levels after three days (P less than .05). Somatomedins did not change with six hours of refeeding, but then rose rapidly, reaching control levels after 24 hours. Somatomedins were correlated with change in weight (r = .41, P less than .05), but not with glucose or beta-hydroxybutyrate. Inhibitors rose to 195% above control-levels after one day of fasting, and continued to rise to 375% above control after three days (P less than .01). In contrast to the delayed change in somatomedins with refeeding, there was an abrupt fall in inhibitors (41% below three-day fasted levels after six hours), returning to control levels after 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1988

Formation and degradation of 1-(ethyl)-1-(2-hydroxyethyl) aziridinium chloride in aqueous media--a comparative NMR study.

The formation and decomposition of 1-(ethyl)-1-(2-hydroxyethyl) aziridinium chloride in aqueous media (10 mM solutions) was studied by NMR spectroscopy. Compared to 1-diethyl aziridinium chloride which lacks the hydroxyl group, the degradation of the title compound at 37 degrees C and pH = 7.4 is about 10 times faster. However, liquid nitrogen frozen solutions of both aziridinium salts are stable for long periods of time (1-6 months).

Aziridines↗
PubMed1988

Role of the aziridinium moiety in the in vivo cholinotoxicity of ethylcholine aziridinium ion (AF64A).

To assess the role of the aziridinium moiety for the cholinotoxicity of ethylcholine aziridinium ion (AF64A) we compared in vitro and in vivo effects of AF64A with those of various precursors as well as decomposition products of AF64A. In vitro, AF64A was the most effective irreversible inhibitor of high-affinity choline transport (HAChT) in hippocampal synaptosomes. The uncyclized precursor acetylethylcholine mustard and the acetylated form of AF64A were about 3 times less potent. Their potency, however, was reduced considerably when hydrolysis of the choline esters was prevented by physostigmine. Destruction of the aziridinium ring either by high pH (alcohol formation) or by thiosulfate (formation of Bunte salt) resulted in a loss of biological activity. This was also the case for the in vivo cholinotoxicity, as assessed by the decline in hippocampal concentration of acetylcholine (ACh) 7 days after intracerebroventricular (i.c.v.) infusion. The most pronounced reduction in ACh content was achieved after i.c.v. infusion of AF64A, whereas the precursor and the acetylated analog of AF64A induced a significant, but smaller reduction in the ACh content. These data indicate that the aziridinium ring of AF64A is essential for both the inhibition of HAChT in vitro and the cholinotoxicity in vivo. However, cyclization of the precursor compound as well as hydrolysis of acetylated AF64A also occur in tissue, leading to a partial activity of these compounds.

Animals↗
PubMed1988

A critical reevaluation of some assay methods for superoxide dismutase activity.

We have compared the direct method of pulse radiolysis to the indirect methods of cytochrome c and nitroblue tetrazolium for assaying the superoxide dismutase activity of a compound. We have shown that with pulse radiolysis, where high concentrations of O2- are generated, the "turnover" rate constant, kcat, can be determined directly, while with the indirect methods, where relatively low steady state concentrations of O2- are formed, the value of kcat determined by these methods, can be orders of magnitude lower than that determined directly. The main reason for the lower values obtained with the indirect methods is due to the fast reoxidation of the reduced compound by molecular oxygen. Additional problems which arise with the use of indirect methods for determining superoxide dismutase catalytic activity are discussed.

Copper↗
PubMed1988

Hospitalization stress in children: sensitizer and repressor coping styles.

To examine the effects of individual sensitizer/repressor coping styles on responses to hospital procedures, 56 children (mean age = 6.5 years) were observed during hospitalization for minor surgery. Although the sensitizer children, as classified by their mothers, did not differ from the repressor children on baseline measures including hospital preparation, they were more talkative, expressive, and active during hospital play observations. During blood tests and preoperative injections, the sensitizers, compared with the repressors, were reported by their mothers to observe the procedures, to seek additional information about the procedures, and to show more protest behaviors. Finally, the sensitizer children required fewer hours of intensive care.

Adaptation, Psychological↗
PubMed1988

Contamination of perfused donor kidneys by starch from surgical gloves.

Starch induces a variety of inflammatory reactions in humans and may contaminate surgical procedures from surgical gloves. Using polarized microscopy and electron microscopy, the authors observed starch particles in renal perfusate and in glomeruli of perfused donor kidneys. Group 1 consisted of 10 unusable kidneys handled with standard concern of glove sterility. Eight other kidneys (Group 2) were perfused with particular attention toward avoidance of starch contamination. The gloves were rinsed five times, and the cuffs were not dipped into the perfusate. Two kidneys (Group 3), deemed unsuitable for transplantation, were perfused for 24 hours with perfusate swished with unwashed sterile gloves. Group 4 consisted of five transplant biopsies performed within one week after transplantation. Perfusates alone were also circulated through the Waters Perfusion Machine continuously for 24, 72, and 188 hours with and without the use of gloves. The number of birefringent crosses were counted in each of 25 glomeruli per specimen. Group 1 displayed a mean of 1.8 birefringent crosses per glomerulus; Group 2, 0; Group 3, 5.3; and Group 4, 4.4. Groups 1 and 3 also exhibited birefringent crosses in peripheral renal vessels. Perfusate alone, handled without gloves, showed no birefringent crosses; by contrast, perfusate handled with gloves showed numerous birefringent crosses. The authors conclude that starch from surgical gloves can enter the perfusate and lodge in glomeruli and other sites of donor kidneys. Rinsing gloves five times and avoiding contact of the perfusate with the glove cuff effectively eliminates the contamination.

Birefringence↗
PubMed1988

Predictive value of ventricular arrhythmias in resuscitated out-of-hospital cardiac arrest victims.

Twenty-four hour ambulatory electrocardiograms recorded in 103 survivors of out-of-hospital cardiac arrest were analyzed to find those characteristics of the ventricular premature complex (VPC) which provide the best combination of sensitivity, specificity, and predictive accuracy for subsequent mortality. VPC characteristics were grouped as: (1) frequent (greater than or equal to 25 h-1), (2)bigeminal, (3) multiform, (4) early coupled, (5) pairing, (6) repetitive greater than or equal to 2, (7) repetitive greater than or equal to 3, (8) repetitive greater than or equal to 6, (9) the combination of frequent and repetitive, or (10) complex defined as any multiform, early, bigeminal or repetitive VPC. In an average follow-up period of 43 months, 42 deaths occurred, 17 of which were classified as sudden. Each characteristic was a significant predictor for all causes of subsequent death except early coupled VPCs and repetitive VPCs greater than 6. None of the characteristics reached significance as predictors for sudden death. The number of repetitive VPCs when stratified to none, greater than or equal to 2 and greater than or equal to 3 successive VPCs correlated with mortality in an incremental fashion. The combination of frequent VPCs and repetitive VPCs provided the best combination of sensitivity, specificity and predictive accuracy for death from all causes within five years.

Arrhythmias, Cardiac↗
PubMed1988

Infants of depressed mothers show "depressed" behavior even with nondepressed adults.

To determine whether the "depressed" behavior (e.g., less positive affect and lower activity level) of infants noted during interactions with their "depressed" mothers generalizes to their interactions with nondepressed adults, 74 3-6-month-old infants of "depressed" and nondepressed mothers were videotaped in face-to-face interactions with their mothers and with nondepressed female strangers. "Depressed" mothers and their infants received lower ratings on all behaviors than nondepressed mothers and infants. Although the infants of "depressed" versus nondepressed mothers also received lower ratings with the stranger adult, very few differences were noted between those infants' ratings when interacting with their mother versus the stranger, suggesting that their "depressed" style of interacting is not specific to their interactions with depressed mothers but generalizes to their interactions with nondepressed adults as early as 3 months of age.

Adolescent↗