Search PubMed⌕ Search

Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 253 records · Page 14Linked to original sources
PubMed1992

The stability of neuropsychological test performance in a group of parenteral drug users.

The stability of neuropsychological performance in a sample of drug abusers was investigated for a wide range of neuropsychological tests, using a test-retest paradigm with 16 parenteral drug users. The battery administered included tests of general intellectual function, abstract reasoning, verbal memory, language, attention, visuospatial ability, set switching, speeded performance, and manipulative dexterity. Stability coefficients were of a moderate to high magnitude for most of the tests and were comparable to coefficients found in other studies of non-drug-users. Two exceptions, however, were the Selective Reminding Test and the Perdue Pegboard. Possible reasons for instability with these two tests are discussed. It is concluded that neuropsychological investigations of drug abusers can yield consistent and reliable data, although further studies should employ alternative and/or supplementary measures of verbal memory and motor function.

Adult↗
PubMed1992

Radiation-induced generation of chlorine derivatives in N2O-saturated phosphate buffered saline: toxic effects on Escherichia coli cells.

The radiolysis of aqueous chloride solutions has been investigated using pulse and steady-state methods. We have found a correlation between the yields of Cl2- and HOCl formed in pulse-irradiated N2O-saturated solutions. The yields increased with the increasing concentrations of Cl- and phosphate. Phosphate enhanced the yield of Cl2- in neutral solutions because of a proton transfer from H2PO4- to HOCl- with a rate constant of (2.6 +/- 0.5) x 10(8) M-1s-1. HOCl could not be detected in pulse-irradiated He or air-saturated, phosphate-buffered saline (PBS) solutions or in gamma-irradiated N2O, He, or air-saturated PBS solutions. The results are discussed in light of previously suggested mechanisms for the formation and decay of Cl2-. Pulse-irradiated N2O-saturated PBS solutions have a lethal effect on Escherichia coli cells, which is proportional to the amount of HOCl in the solutions. Gamma-irradiation of cells in N2O-saturated PBS solution also raises the radiosensitivity of the cells, although HOCl does not accumulate in this system. The effects of the radiation-induced toxic products on E. coli cells are similar to the effects of NaOCl. The cell membrane is probably the site of physiological injury induced by the radiation products.

Adenosine Triphosphate↗
PubMed1992

Spontaneous and inducible ventricular arrhythmias in a canine model of chronic heart failure: relation to haemodynamics and sympathoadrenergic activation.

The relationship between the incidence, frequency and complexity of spontaneous ventricular arrhythmias and the extent of haemodynamic compromise and sympathoadrenergic hyperactivity was evaluated in a canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. Ambulatory ECG Holter monitoring recorded during chronic heart failure in 18 dogs revealed spontaneous ventricular arrhythmias ranging from single ventricular premature beats (VPBs) to non-sustained episodes of ventricular tachycardia (VT). Single VPBs were present in 94% of dogs, couplets in 67%, triplets in 28% and spontaneous episodes of non-sustained VT in 33%. Dogs with > 28 VPBs.h-1 (n = 9) had a markedly higher plasma norepinephrine (PNE) concentration (1001 +/- 185 vs 561 +/- 31 pg.ml-1) (P < 0.03), and a higher pulmonary artery wedge pressure (PAWP) (18 +/- 2 vs 12 +/- 1 mmHg) (P < 0.03) than dogs with < or = 28 VPBs.h-1 (n = 9). Dogs that developed spontaneous episodes of VT also had significantly higher PNE levels (1119 +/- 247 pg.ml-1) compared to dogs that did not develop VT (612 +/- 64 pg.ml-1) (P < 0.02). Programmed ventricular stimulation performed in seven of 18 dogs resulted in the development of sustained monomorphic VT in three and ventricular fibrillation in three dogs each (43%, 43%). Dogs with inducible sustained monomorphic VT had a significantly higher number of ambient arrhythmias and higher PAWP compared to dogs that did not develop sustained VT. The observed complexity, frequency and incidence of spontaneous and inducible ventricular arrhythmias in this canine model are similar to those described in patients with chronic heart failure.

Animals↗
PubMed1992

Left ventricular shape changes during the course of evolving heart failure.

The temporal relationship between left ventricular (LV) shape changes and the development of LV dysfunction, dilation, and sympathoadrenergic hyperactivity was examined in 10 dogs with chronic heart failure produced by multiple sequential intracoronary microembolizations. LV shape was quantitated from serial ventriculograms based on the ratio of the major to minor axis at end systole and end diastole. Measurements were made at baseline (before embolizations) and were repeated at 2, 8, and 16 wk after the last embolization. A significant increase of LV sphericity was present at 2 wk, with only minimal changes occurring thereafter. Despite the tendency for LV shape changes to plateau between 2 and 16 wk, LV ejection fraction continued to decline (31 +/- 1 vs. 20 +/- 2%; P less than 0.001), and LV end-diastolic volume continued to increase (86 +/- 6 vs. 103 +/- 9 ml; P less than 0.01) as did plasma norepinephrine concentration (456 +/- 30 vs. 868 +/- 172 pg/ml; P less than 0.02). These data indicate that in the course of evolving heart failure, LV shape abnormalities precede the development of profound LV dysfunction, dilation, and overt activation of the sympathetic nervous system.

Adrenal Glands↗
PubMed1992

Left atrial contribution to ventricular filling during the course of evolving heart failure.

BACKGROUND: Abnormal left ventricular (LV) filling has been observed in patients with heart failure and is characterized by marked heterogeneity of mitral inflow velocity. In the present study, the contribution of the left atrium to LV filling was examined in eight dogs during the course of evolving heart failure. METHODS AND RESULTS: Heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Pulsed Doppler echocardiography was used to measure mitral inflow velocity at baseline, before embolization, and at 3, 8, 15, 23, and 33 weeks after initiation of microembolization. The early rapid LV filling (Ei) and late left atrial filling (Ai) components were quantitated based on the time-velocity integral of the early and late mitral inflow velocity waveforms, respectively. Ei decreased progressively from 7.6 +/- 1.5 cm at baseline to 4.0 +/- 0.4 cm at 33 weeks (p less than 0.01). In contrast, Ai initially increased from 1.8 +/- 0.9 cm at baseline to 2.7 +/- 0.4 cm at 3 weeks (p less than 0.01) and subsequently decreased gradually to below baseline values reaching 0.8 +/- 0.4 cm at 33 weeks (p less than 0.01). These temporal changes of Ei and Ai were accompanied by a gradual reduction of LV ejection fraction (56 +/- 5% versus 22 +/- 2%) (p less than 0.01) (baseline versus 33 weeks) and by a gradual increase of LV end-diastolic wall stress (24 +/- 7 versus 92 +/- 8 g/cm2) (p less than 0.01), left atrial dimension (2.4 +/- 0.2 cm to 3.3 +/- 0.3 cm) (p less than 0.01), and left atrial fractional shortening (22 +/- 3% versus 15 +/- 2%) (p less than 0.01). CONCLUSIONS: The initial rise in left atrium contribution to LV filling may represent a compensatory response to the diminution of the rapid early component of LV filling. With further progression of LV dysfunction, the left atrium contribution to LV filling gradually decreased. This reduction may be mediated by increased workload imposed on the left atrial myocardium due to increased LV diastolic wall stress, which, over time, may have lead to intrinsic left atrium dysfunction.

Animals↗
PubMed1992

Expression of hepatic insulin-like growth factor-I and insulin-like growth factor-binding protein-1 genes is transcriptionally regulated in streptozotocin-diabetic rats.

Insulin-like growth factor-I (IGF-I) and IGF-binding protein-1 (BP-1) are critical cell regulators, with regulation and action in endocrine, paracrine, and autocrine modes. Although IGF-I and BP-1 are thought to be modulated mainly at the level of synthesis, underlying molecular mechanisms are poorly understood. To examine regulation by insulin, we used run-on assays to measure IGF-I and BP-1 gene transcription rates in nuclei isolated from the livers of normal and diabetic rats. Streptozotocin (STZ)-treated rats exhibited 20-25% weight loss, a 2.5- to 3-fold increase in serum glucose, and a 50-60% fall in circulating IGF-I levels (all P less than 0.001). Diabetic animals also had a 45% reduction in hepatic IGF-I mRNA and over 400% increases in BP-1 mRNA (both P less than 0.005); all parameters were restored toward normal after treatment with insulin. Metabolically responsive IGF-I gene transcription was evaluated effectively with a 3.2-kilobase BglII/EcoRI genomic probe located down-stream from all initiation sites in exon 1, while BP-1 gene transcription was studied with a cDNA probe. Animals treated with 144 mg/kg STZ exhibited 50-97% decreases in IGF-I gene transcription (P less than 0.05), while insulin treatment raised IGF-I gene transcription to control levels (P less than 0.02). IGF-I gene transcription appeared to be more sensitive to metabolic status than IGF-I mRNA levels, resulting in a modest correlation between transcription rates and mRNA levels (r = 0.68; P less than 0.001). In contrast, changes in BP-1 mRNA and gene transcription appeared to be exquisitely sensitive to metabolic status.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Nutrition and somatomedin XXIX. Molecular regulation of IGFBP-1 in hepatocyte primary culture.

The insulinlike growth factors (IGFs) circulate in association with insulinlike growth factor binding proteins (IGFBPs) that modulate IGF action, but mechanisms of IGFBP regulation are poorly understood. We investigated the regulation of IGFBPs in primary cultures of rat hepatocytes, measuring the appearance of export proteins by ligand blotting after separation via SDS/PAGE, and evaluating mRNA with cDNA probes. Northern blotting studies revealed that IGFBP-1 was expressed at high levels in cultured hepatocytes, in which sustained release of both insulinlike growth factor I and albumin marks preservation of differentiated status. In contrast, transcripts of IGFBP-3 and IGFBP-2 were not detected. Release of IGFBP-1 was unaffected by exposure to glucose (20-500 mg/dl) or to provision of amino acids (0.25-6.25 times normal rat arterial plasma levels). Hormonal studies revealed little effect of glucagon, inhibition by insulin, stimulation by dexamethasone, and blunting of dexamethasone effects by added insulin. Adding dexamethasone provided progressive stimulation: 5-, 11-, and 26-fold at 10(-9), 10(-8), and 10(-7) M, all P less than 0.01; increases in IGFBP-1 protein (ligand blot) and IGFBP-1 mRNA (Northern blot) were highly correlated (r = 0.62, P less than 0.001). In contrast, adding insulin resulted in progressive suppression of both IGFBP-1 protein and IGFBP-1 mRNA, 43% at 10(-10) M, 74% at 10(-9) M, and 83% (maximal) at 10(-8) M; ED50 of approximately 10(-10) M is within the physiological range of insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Religious and ethnic self-identification in the United States 1989-90: a case study of the Jewish population.

"In 1989-90, a three-stage national survey was conducted [in the United States]...to identify those households in which the respondents did not report their religion as Jewish but which contained any persons (including the respondent) who 'considered' themselves Jewish, who were raised Jewish, or who had a Jewish parent.... This paper evaluates the extent to which the...different forms of Jewish attachment produce sub-populations with varying socio-demographic characteristics and the degree to which inclusion or exclusion of particular sub-groups affects the overall size and composition of the aggregate Jewish population." This paper was originally presented at the 1991 Annual Meeting of the Population Association of America.

Americas↗
PubMed1991

Insulin-like growth factor binding protein 3 accumulates to high levels in culture medium of senescent and quiescent human fibroblasts.

Insulin-like growth factor binding protein 3 (IGFBP-3) mRNA levels were consistently higher in both senescent normal human diploid fibroblasts (HDFs) at late passage (old cells) and prematurely senescent HDFs from a subject with Werner syndrome (WS) during serum depletion and repletion of growth medium and during proliferation from sparse to high-density inhibited cultures, compared to normal early-passage (young) HDFs. However, IGFBP-3 protein accumulated to higher levels in conditioned medium of old cells than in medium of WS and young cells, in that order, under the same conditions. Insulin-like growth factor I (IGF-I) was not detected in naive medium or in any of the media conditioned by these three cell types, whereas IGF-II was detectable in serum-repleted medium and remained relatively constant. Thus, molar ratios of IGFBP-3/IGF-II were consistently higher in old and WS cells and increased substantially as all three cell types became quiescent, due to either serum depletion or high cell density. These data are consistent with either an adaptive or a causal role for IGFBP-3 protein in the senescent and quiescent growth arrest of HDFs.

Carrier Proteins↗
PubMed1991

Effectiveness of imazodan for treatment of chronic congestive heart failure. The Imazodan Research Group.

A 12-week, multicenter, double-blind, randomized, placebo-controlled trial of imazodan, a type III phosphodiesterase inhibitor, was conducted in 147 patients with congestive heart failure to determine clinical efficacy and safety. Patients were randomized to placebo or 2, 5 or 10 mg of imazodan administered twice daily. Patients were maintained on their standard therapy including diuretics, digoxin and an angiotensin-converting enzyme inhibitor. The mean ejection fraction was 23 +/- 10%. Exercise time increased from baseline in all 4 groups. There was no significant difference observed between the placebo group and any of the treated groups with regard to exercise time, ejection fraction, frequency of ventricular premature complexes or ventricular tachycardia. When analyzed by intent to treat, the placebo mortality was 7% (3 of 44) and the imazodan mortality was 8% (8 of 103) (p = not significant). This study failed to demonstrate that imazodan provided any benefit in exercise performance when compared with placebo.

Administration, Oral↗
PubMed1991

Extraction and nutritional/hormonal regulation of tissue insulin-like growth factor 1 activity.

Studies of insulin-like growth factor 1 (IGF-1) mRNA translation products suggest synthesis as a high Mr precursor, larger than circulating forms. To search for a precursor, we characterized IGF-1 immunoreactivity and IGF bioactivity in extracts from the liver and other body tissues. Sequential extraction with neutral followed by acid buffer was superior to extraction with acid/ethanol or acid alone in yield of immunoreactivity and specific activity. Extracts of normal rat liver exhibited both immuno- and bioactivity parallel to that of recombinant IGF-1 and serum IGFs over a 25-fold concentration range. Based on immunoreactivity, the liver of a 134-g rat appears to contain 1.2 micrograms of IGF-1 equivalents, 50% of the 2.45 micrograms in the circulation. Diaphragm, spleen, and kidney contained no significant IGF bioactivity and 8, 17, and 32% of the IGF-1 immunoreactivity of normal liver, respectively. Although serum IGFs were found at 7.5 kDa after size exclusion chromatography at pH 3, hepatic extracts contained a predominant peak of immuno- and bioactivity of apparent molecular mass of 30-35 kDa; both sizes were present in liver perfusates. Both immunoaffinity chromatography followed by Western blotting and IGF-binding protein affinity chromatography followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two predominant species, at 18-19 and 12 kDa. The 18-19-kDa species is consistent with the apparent size of the glycosylated propeptide encoded by IGF-1A mRNA, while the 12-kDa species may be nonglycosylated propeptide. Extract activity was pituitary-dependent; the livers of hypophysectomized rats contained 15.4 and 48.8% of normal immuno- and bioactivity, respectively. During fasting and refeeding of rats, fluctuations in hepatic extract IGF-1 immunoreactivity generally paralleled changes in serum IGF-1 (r = 0.93, p less than 0.001). These studies demonstrate that the liver contains a pituitary- and nutrition-dependent, high Mr form of IGF-1 with immunological and biological properties similar to circulating IGF-1. Processing of this 18-19-kDa molecule through a 12-kDa intermediate may contribute IGF-1 to the circulation.

Animals↗
PubMed1991

Multidisciplinary baseline assessment of homosexual men with and without human immunodeficiency virus infection. III. Neurologic and neuropsychological findings.

We explored the possibility that neurologic and neuropsychological changes constitute the earliest detectable manifestations of human immunodeficiency virus (HIV) infection. Without knowledge of HIV status, we assessed neurologic signs and symptoms and administered a battery of neuropsychological tests to 208 homosexual men, of whom 84 were HIV negative, 49 were HIV positive and asymptomatic, 29 were mildly symptomatic, and 46 had significant medical symptoms but not the acquired immunodeficiency syndrome. There was no difference between the HIV-negative and HIV-positive men in the frequency of neurologic signs or of defective or borderline performance on any neuropsychological test. However, HIV-positive men performed slightly but significantly worse than HIV-negative men on tests of verbal memory, executive function, and language. Similar results were obtained when comparisons were limited to HIV-positive medically asymptomatic and HIV-negative men. There was no degradation of neurologic status or neuropsychological performance across stages of HIV severity, but neurologic and neuropsychological summary scores correlated with CD4/CD8 ratios in the HIV-positive group. Ratings of neurologic signs and symptoms correlated with neuropsychological summary scores in the HIV-positive group only. Cognitive complaints were more frequent in the HIV-positive men; they correlated with actual test performance in the HIV-positive but not HIV-negative men. The constellation of subjective and objective neuropsychological and neurologic findings suggests the possibility of a definable syndrome associated with HIV infection in asymptomatic individuals.

Adolescent↗
PubMed1991

Altered visceral yolk sac function produced by a low-molecular-weight somatomedin inhibitor.

A fraction from diabetic rat serum containing a low-molecular-weight (800-1000) somatomedin inhibitor (SI) alters growth and development in both neurulation and early limb bud staged mouse embryos in vitro. Previous studies suggested that an accumulation of serum proteins and morphological changes of the visceral yolk sac (VYS) were produced following exposure to the SI in early limb bud staged conceptuses. The morphological changes, characterized by the presence of large endosomes in the endodermal cells, suggested that the SI altered histiotrophic nutrition, whereby proteins are pinocytosed by the endodermal VYS cells and degraded to constituent amino acids. Therefore, the effects of the SI on pinocytosis and protein degradation by the VYS were evaluated using the whole embryo culture system. Results showed that the SI reduced fluid phase pinocytosis as determined by the uptake of [U-14C]sucrose, but that accumulation of [3H]leucine-labeled hemoglobin ([3H]Hb) by the VYS was greater following exposure to the SI than in controls. In contrast, the accumulation of 3H-labeled amino acids in the embryo (produced from the degradation of [3H]Hb by the VYS) was reduced by the SI. The extent of amino acid reduction in embryonic accumulation is dependent upon the concentration of SI in the culture medium and correlates with the incidence of malformations produced by the SI, i.e., high rates of malformations occur with large reductions in embryonic 3H-labeled amino acid accumulation. The apparent paradox of high [3H]Hb accumulation in the presence of decreased pinocytosis appears to be the result of altered processing of the [3H]Hb in the endodermal cells. The altered processing decreases the "elimination" of the proteins from the VYS and results in the decrease in 3H-labeled amino acid present in the embryo proper. Therefore, the SI appears to alter two processes of VYS histiotrophic function. (1) decreased pinocytosis and (2) altered protein processing, ultimately resulting in a decreased availability of substrates for the embryo. During the early stages of embryogenesis in the human, the trophoblast cells of the placenta are responsible for the transport of nutrients from the maternal to embryonic systems. Since these cells show high phagocytic and pinocytotic activities, the SI may also disrupt these processes in the chorioallantoic placenta and contribute to diabetes-induced embryopathies.

Animals↗