Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 271 records · Page 15Linked to original sources

PubMed1991

Low-dose dobutamine in patients with acute myocardial infarction identifies viable but not contractile myocardium and predicts the magnitude of improvement in wall motion abnormalities in response to coronary revascularization.

To assess the effects of coronary revascularization on viable but noncontractile myocardium, we examined 21 patients with a documented anterior acute myocardial infarction who had a significant improvement in wall motion abnormality evaluated by two-dimensional echocardiography in the infarct-related artery in response to low-dose dobutamine infusion. All patients had a significant residual stenosis in the infarct-related artery. In response to low-dose dobutamine, there was a marked improvement in contractility in the infarct-related area segments and this was reflected by a decrease in echocardiographic score index from 1.5 +/- 0.15 to 1.09 +/- 0.08 (p = 0.0001). Of these 21 patients, 13 underwent successful revascularization: 10 had percutaneous transluminal coronary angioplasty (PTCA) and three had coronary artery bypass grafts (CABG) (group I). Eight patients received medical therapy only (group II). At 40 +/- 15 days of follow-up, both groups had improvement in their segmental wall motion abnormalities. However, the improvement in group I was greater than that in group II, 1.1 +/- 0.13 and 1.35 +/- 0.1, respectively (p = 0.0002). We conclude that: (1) low-dose dobutamine infusion may identify viable but noncontractile myocardium in patients with acute myocardial infarction and (2) in these patients revascularization causes a greater improvement in left ventricular function over time when compared with a nonrevascularized group.

Aged↗

PubMed1991

Natural history of the first non-Q wave myocardial infarction in the placebo arm of the Beta-Blocker Heart Attack Trial.

Despite extensive investigation, the prognostic significance of the first non-Q wave acute myocardial infarction (AMI), when compared with Q wave AMI, remains controversial. The placebo arm of the Beta-Blocker Heart Attack Trial (BHAT) provides a unique opportunity to compare the long-term cardiac events in patients suffering from their first and uncomplicated Q wave or non-Q wave AMI. Of a total 3837 patients enrolled in the BHAT, 3375 were classifiable in terms of appearance or absence of Q waves during the prerandomization period. Of these, 1444 patients with their first AMI were randomized to placebo. Of these, 1186 experienced a Q wave AMI; the remaining 258 suffered a non-Q wave AMI. At 36 months of follow-up, the mortality was 8.4% in the Q wave AMI group and 7.4% in the non-Q wave AMI group. Sudden death was 5.4% in the Q wave AMI group and 4.7% in the non-Q wave AMI group. The reinfarction rate was 5.5% in the Q wave AMI patients and 7.4% in the non-Q wave AMI patients. More patients developed angina (44.6%) in the non-Q wave AMI group compared with 35.2% in the Q wave AMI group. Despite similar long-term cardiac event rates within the two groups, the 1-year mortality rate for patients with Q wave AMI appeared higher than in the non-Q wave AMI group, 5.2% versus 3.1%, respectively. In contrast, the rate of reinfarction appeared higher at the 12-month follow-up period in the non-Q wave AMI group, 4.7% versus 3.4%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)c

Double-Blind Method↗

PubMed1991

The genetic fate of molecularly cloned simian immunodeficiency virus in experimentally infected macaques.

We have examined genetic variation of the simian immunodeficiency virus (SIV) in four macaques inoculated with virions derived from molecular clones of proviral DNA. Our data demonstrated that the SIV genome is capable of rapid and extensive genetic variation. This variation was especially large in the env gene, where nucleotide substitution frequencies were as high as 10(-1)/site/year. In some env clones, a high G to A transition rate was observed that accounted for up to 79% of the observed nucleotide substitutions. Moreover, in env clones with a high G to A transition rate, multiple in-frame stop codons were generated exclusively at tryptophan codons. Another interesting observation was the lack of variation in the region analogous to the V3 loop in the HIV-1 Env protein. Considered together, these data have important implications for studies of pathogenesis and vaccine development in the SIV model system.

Amino Acid Sequence↗

PubMed1991

Medical therapy after acute myocardial infarction.

Several therapeutic agents have been tested for secondary prevention after acute myocardial infarction. Each patient presents a clinical challenge and gives the physician an opportunity to use the tests and therapy most likely to benefit the clinical course. The presence of other associated medical conditions, the type of myocardial infarction, the presence or absence of accompanying ischemia, left ventricular dysfunction, intracardiac thrombus, or ventricular arrhythmias dictate the choices that are to be made. It is apparent from this review that no single class of agents can be considered a cure, although beta-adrenergic blocking agents come the closest to this role. Analysis of these drugs helps individualize drug therapy and provides a physiologic probe to understanding the pathophysiologic processes that characterize the period after myocardial infarction. To address the impact of developing technology and drug availability on the practice and cost of medical care, the American College of Cardiology and the American Heart Association have developed guidelines for the management of patients with myocardial infarction. The clinical trial remains the best test for the assessment of therapeutic choices and can also expand our knowledge of the natural history of the disease process. Nevertheless, the issue of appropriate therapy is ever-changing, affected by the explosion of new technology and the continued investigation into the pathophysiology of coronary artery disease.

Adrenergic beta-Antagonists↗

PubMed1991

Cerebral blood flow and metabolism in aging and dementia.

There are structural, perfusive, and metabolic changes that occur in normal aging and in dementia. In Alzheimer's disease (AD), changes in blood flow and metabolism occur primarily in the parietal and temporal cortices. These changes are distinct from those seen in normal aging. These alterations correspond to known neuronal changes that occur in AD and are consonant with changes that are seen in cognitive function. Characteristic patterns are also emerging in other forms of dementia such as Pick's disease, multi-infarct dementia, and primary progressive aphasia. Finally, there is some preliminary evidence that functional neuroimaging procedures may be useful in both the diagnosis and treatment strategies of dementia.

Aging↗

PubMed1991

Diverse gene sequences are overexpressed in werner syndrome fibroblasts undergoing premature replicative senescence.

Genes that play a role in the senescent arrest of cellular replication are likely to be overexpressed in human diploid fibroblasts (HDF) derived from subjects with Werner syndrome (WS) because these cells have a severely curtailed replicative life span. To identify some of these genes, a cDNA library was constructed from WS HDF after they had been serum depleted and repleted (5 days in medium containing 1% serum followed by 24 h in medium containing 20% serum). Differential screening of 7,500 colonies revealed 102 clones that hybridized preferentially with [32P]cDNA derived from RNA of WS cells compared with [32P]cDNA derived from normal HDF. Cross-hybridization and partial DNA sequence determination identified 18 independent gene sequences, 9 of them known and 9 unknown. The known genes included alpha 1(I) procollagen, alpha 2(I) procollagen, fibronectin, ferritin heavy chain, insulinlike growth factor-binding protein-3 (IGFBP-3), osteonectin, human tissue plasminogen activator inhibitor type I, thrombospondin, and alpha B-crystallin. The nine unknown clones included two novel gene sequences and seven additional sequences that contained both novel segments and the Alu class of repetitive short interspersed nuclear elements; five of these seven Alu+ clones also contained the long interpersed nuclear element I (KpnI) family of repetitive elements. Northern (RNA) analysis, using the 18 sequences as probes, showed higher levels of these mRNAs in WS HDF than in normal HDF. Five selected mRNAs studied in greater detail [alpha 1(I) procollagen, fibronectin, insulinlike growth factor-binding protein-3, WS3-10, and WS9-14] showed higher mRNA levels in both WS and late-passage normal HDF than in early-passage normal HDF at various intervals following serum depletion/repletion and after subculture and growth from sparse to high-density confluent arrest. These results indicate that senescence of both WS and normal HDF is accompanied by overexpression of similar sets of diverse genes which may play a role in the senescent arrest of cellular replication and in the genesis of WS, normal biological aging, and attendant diseases.

Base Sequence↗

PubMed1991

A canine model of chronic heart failure produced by multiple sequential coronary microembolizations.

A canine model of chronic heart failure was produced by multiple sequential intracoronary embolizations with microspheres. Twenty closed-chest dogs underwent three to nine intracoronary embolizations performed 1-3 wk apart. Embolizations were discontinued when left ventricular (LV) ejection fraction was less than 35%. LV ejection fraction was 64 +/- 2% at baseline and decreased to 21 +/- 1% at 3 mo after the last embolization (P less than 0.001). During the same period, LV end-diastolic pressure increased from 6 +/- 1 to 22 +/- 3 mmHg (P less than 0.001); LV end-diastolic volume increased from 64 +/- 3 to 101 +/- 6 6 ml (P less than 0.001), and cardiac output decreased from 2.9 +/- 0.2 to 2.3 +/- 0.1 l/min (P less than 0.01). These changes were accompanied by significant increases of pulmonary artery wedge pressure and systemic vascular resistance. Plasma norepinephrine increased from 332 +/- 17 pg/ml at baseline to 791 +/- 131 pg/ml at 3 mo after the last embolization (P less than 0.01); plasma levels of atrial natriuretic factor increased from 12.7 +/- 10.0 to 28.8 +/- 8.6 pmol/l (P less than 0.01), whereas plasma renin activity remained unchanged. Gross and microscopic postmortem examination showed patchy myocardial fibrosis and LV hypertrophy. We conclude that multiple intracoronary embolizations with microspheres, separated in time, can lead to chronic heart failure in dogs. The preparation is stable and reproducible and manifests many of the sequelae of heart failure that result from loss of contractile myocardium.

Animals↗

PubMed1991

Imipramine receptor binding and serotonin uptake in platelets of women with premenstrual changes.

Gonadal hormones are believed to be involved in the pathophysiology of premenstrual changes (PMC) possibly through their interaction with neurotransmitter systems in the brain. The serotonergic system, an important central modulator of mood and behavior which is involved in the pathophysiology of affective disorders has been suggested to play a role in the genesis of dysphoric PMC. Blood platelet serotonin (5-HT) uptake and imipramine (IMI) binding have been shown to share similarities with serotonergic mechanisms in the brain thus enabling the study of serotonergic mechanisms. In this study, we report on platelet 5-HT uptake and IMI receptor binding which were simultaneously studied in women with PMC. Subjects with PMC showed a large interindividual variability with no consistent typical pattern or change during the late symptomatic as compared to the early nonsymptomatic luteal phase. Their IMI receptor binding, however, was lower compared to controls already during the early luteal phase before they developed symptoms and was similar during the symptomatic phase. This might suggest a preexistent vulnerability to the development of dysphoric PMC that might be related to impaired gonadal hormone modulation of the serotonergic system.

Adult↗

PubMed1991

Psychological factors related to prehospital delay during acute myocardial infarction.

BACKGROUND: Prior studies have had difficulty identifying factors that significantly explain patients' delay in responding to symptoms of acute myocardial infarction (AMI). METHODS AND RESULTS: We therefore examined factors affecting the time between symptom onset and hospital arrival for 103 AMI patients admitted to a Detroit metropolitan hospital between October 1989 and January 1990. Variables evaluated included demographic and medical history factors, psychological characteristics of somatic and emotional awareness, and type A behavior. The mean prehospital delay time was 9.0 +/- 10.8 hours (median, 5.0 hours; range, 0.25-62.0 hours). Delay time was not significantly associated with demographic or medical history categories or with type A behavior. Of study variables that can be identified prior to evolution of an AMI, somatic and emotional awareness were the only factors significantly predictive of delay time. Patients who were more capable of identifying inner experiences of emotions and/or bodily sensations sought treatment significantly earlier than patients with low emotional or somatic awareness (low emotional awareness median delay, 12.8 hours; high emotional awareness median delay, 3.8 hours; low somatic awareness median delay, 7 hours; high somatic awareness median delay, 4 hours). CONCLUSIONS: Variations in sensitivity to bodily sensations and emotions appear to play an important role in treatment seeking and thus potentially in treatment outcome for AMI patients. Assessment of these characteristics in patients with coronary risk factors could allow early identification of persons at risk of excessive delay in responding to symptoms of AMI.

Attitude to Health↗

PubMed1991

Immune functions during treatment of growth hormone-deficient children with biosynthetic human growth hormone.

Immune functions, including cell surface markers, interleukin-2 receptor levels and responses of lymphocytes to mitogenic stimulation were evaluated in seven growth hormone deficient children ages 4-15 years, during treatment with biosynthetically derived human growth hormone. Treatment resulted in a decrease in % B cells and in % T total cells and also decreases in most individual patients' mitogen responses and interleukin-2 receptor levels. Most of the changes noted were transient and similar to those previously demonstrated during pituitary-derived human growth hormone treatment. Although not resulting in overt clinical manifestations in our patients, we think that potential interactions between growth hormone and immune functions need to be considered by physicians treating children with growth hormone.

Adolescent↗

PubMed1991

Nutrition and somatomedin. XXII: Molecular regulation of insulin-like growth factor-I during fasting and refeeding in rats.

The liver is thought to be the locus of nutritional/hormonal regulation of circulating insulin-like growth factor-I (IGF-I). To probe the basis of nutritional regulation, we examined changes in serum IGF-I, hepatic content of extractable IGF-I immunoreactivity (a high Mr putative precursor) and hepatic IGF-I mRNA during fasting and refeeding in rats. Preliminary studies revealed that the hepatic level of IGF-I mRNA was consistently reduced only after food was withheld for 3 days, so the effects of refeeding were subsequently examined in such animals. After 3 days of fasting, animals lost 30% of their initial weight; weight regain was apparent within 3 h of refeeding ad libitum and, after 48 h, weight was comparable to initial fed levels. Fasting reduced levels of serum and extractable hepatic IGF-I to 19 and 26% of control (fed) values respectively (both P less than 0.005 vs control). There was no change in levels of serum IGF-I over the first 3 h of refeeding, but IGF-I rose above fasted levels at both 9 and 48 h (both P less than 0.005). Extractable hepatic IGF-I rose more slowly and was still below fasted levels after 9 h of refeeding, and modestly, but not significantly, greater than fasted levels after 48 h. The ratio of serum to hepatic IGF-I was decreased compared with control after 3 days of fasting, but increased after 3 and 9 h of refeeding (P less than 0.02 at 9 h). Northern blot analysis of total hepatic RNA revealed four species of IGF-I mRNA 0.8-1.1, 2.0, 4.0 and 7.5 kb in size. Each mRNA species fell to 15-28% of control levels after 3 days of fasting (all P less than 0.001). There was a prompt increase in each transcript after 3 h of refeeding, and all values were significantly (P less than 0.05) greater than fasted levels at 9 h but, at 48 h, most species were still below control levels. Levels of mRNA for the cytoskeletal proteins beta-actin and cyclophilin also fell with fasting, but were restored more rapidly than IGF-I mRNA, to or above control levels after 3 h of refeeding. The observation that IGF-I expression was decreased at 3 h when beta-actin and cyclophilin were normalized suggests specificity of regulation. Despite the temporal incongruity between IGF-I mRNA and serum and hepatic IGF-I, there were highly significant correlations (all P less than 0.002) between each pair of parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Actins↗

PubMed1991

Nutrition and somatomedin. XXIII. Molecular regulation of IGF-I by amino acid availability in cultured hepatocytes.

The poor growth associated with protein-calorie malnutrition occurs despite circulating growth hormone levels that are normal or elevated and is thought to be mediated partly by blunted generation of insulinlike growth factor I (IGF-I) in the liver. To explore underlying mechanisms, we asked whether altered availability of amino acids could regulate hepatic IGF-I release independent of the contributions of regulatory hormones. Normal rat hepatocytes were isolated by collagenase digestion and maintained in serum-free medium with fixed concentrations of insulin and dexamethasone. Levels of immunoassayable albumin and IGF-I accumulation in daily changes of medium were sustained for 3-5 days, and all studies were performed within this period. Cellular viability and content of DNA were unaffected by deprivation of the essential amino acids lysine or tryptophan and the nonessential amino acids cysteine and/or cystine. However, deletion of tryptophan or lysine from the culture medium led to 63 and 76% declines in IGF-I release, respectively (both P less than 0.001 vs. complete medium), although omission of cysteine or cysteine plus cystine produced no significant change. Over 5 days of culture, release of albumin was maintained in complete medium, but omission of tryptophan depressed albumin release over days 2-5 (P less than 0.001). In complete medium, IGF-I release rose for 3 days and then declined. In tryptophan-deficient medium, IGF-I levels were comparable to control values after 24 h but did not rise at 48 h and then fell rapidly after 72 h in culture, with values significantly below levels in complete medium (all P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1991

Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes.

Although decreased levels of circulating insulinlike growth factor I (IGF-I) and hepatic IGF-I mRNA in diabetic animal models support a role for insulin in IGF-I regulation, it has been difficult to study the effects of insulin in vitro. Few immortal cell lines exhibit hormone-responsive production of IGF-I, and studies of cultured hepatocytes have often been inconclusive because conventional methods may not reproduce the IGF-I transcripts recognized in vivo. We have modified the hepatocyte isolation and RNA extraction procedures to circumvent this problem, resulting in transcripts of 1, 2, and 7.5 kb. With increasing insulin from 10(-10) to 10(-6) M, dexamethasone from 10(-10) to 10(-7) M, and amino acids from 1 to 10 x rat arterial levels, IGF-I release rose by 226, 257, and 447%, respectively (P less than 0.05), with correlated changes in IGF-I mRNA (r = 0.75, P less than 0.005). In the presence of 5 x amino acids and 10(-7) M dexamethasone, insulin-stimulated IGF-I release was dose dependent, increasing 183% at 10(-6) M (P less than 0.01). Across a broad range of amino acid concentrations (0.25-6.25 x), insulin provided consistent stimulation of both IGF-I mRNA content and release of IGF-I. Cells cultured for 2 days at 10(-10) M insulin and then 2 days at 10(-6) M insulin released 66% more IGF-I than cells cultured 4 days at 10(-10) M insulin (P less than 0.01). Hepatocyte IGF-I release was correlated strongly with content of IGF-I mRNA, both sum of transcripts (r = 0.76, P less than 0.001) and individual transcripts. Insulin appears to regulate IGF-I release at the mRNA level in hepatocyte primary culture. This system should be a useful tool for further studies of molecular mechanisms of IGF-I regulation.

Amino Acids↗

PubMed1991

Nutrition and somatomedin. XXV. Regulation of insulinlike growth factor binding protein 1 in primary cultures of normal rat hepatocytes.

Although mRNAs encoding insulinlike growth factor (IGF) binding proteins (BPs) are present in adult rat liver and IGF BP-1 circulates at elevated levels in diabetic animals, there is little knowledge of the metabolic regulation of IGF BPs in normal tissues. We examined the release of IGF BPs by adult rat hepatocytes maintained in primary culture. When cultured for 2 days in the absence of added insulin, hepatocytes released a BP identified as BP-1 on the basis of approximately 30,000-Mr on ligand blotting and reactivity with antiserum to human BP-1 in immunoblotting and immunoprecipitation studies. Release of BP-1 was sensitive to insulin with suppression of 24 +/- 4, 73 +/- 5, and 64 +/- 14% at 10(-10), 10(-8), and 10(-6) M insulin, respectively; ED50 was approximately 1.7 x 10(-9) M, which is within the physiological range. Suppression by insulin was reversible and began within 3 h. Because normal hepatocytes in primary culture exhibit insulin-responsive release of both BP-1 and IGF-1, this system may be an ideal model for studies of molecular mechanisms of metabolic regulation.

Animals↗

PubMed1991

Nutrition and somatomedin. XXVII. Total and free IGF-I and IGF binding proteins in rats with streptozocin-induced diabetes.

Impaired growth in diabetic humans occurs despite increased growth hormone and normal insulinlike growth factor I (IGF-I). Because IGF-I circulates complexed to binding proteins (BPs), we asked whether diabetes-related changes in IGF BPs could be associated with alterations in free unbound IGF-I--presumably the active form. Rats were given streptozocin (STZ) in increasing doses to produce graded severity of diabetes. IGF BP-1 and BP-3 were measured by ligand blotting, total IGF-I was determined by radioimmunoassay after separation from BPs by isocratic high-performance liquid chromatography (HPLC) at pH 3.9, and free IGF-I was estimated operationally as immunoreactivity with molecular weight equal to native IGF-I after HPLC at pH 7. Animals given 36 mg/kg STZ exhibited a glucose level of 9.74 mM and impaired weight gain, with little alteration in IGF BPs or total or free IGF-I. In contrast, animals given 72 mg/kg STZ (glucose level 24.64 mM and weight loss) had insignificant changes in total IGF-I and BP-3 but a 300% increase in BP-1 and a 50% fall in free IGF-I (both P less than 0.005). With 144 and 288 mg/kg STZ, animals had further metabolic decompensation and weight loss, with progressive fall in BP-3 and rise in BP-1; total and free IGF-I fell to 10-20% of control (both P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Comparison between different assays for superoxide dismutase-like activity.

The direct and indirect methods for assaying the superoxide dismutase activity of a compound are compared. With the use of a direct method, the mechanism of the catalysis of O2- dismutation by the tested compound can be determined, while with the indirect method it cannot, and this may lead to misinterpretation of the results. Assuming that the catalysis occurs via the 'ping-pong' mechanism, both the direct and indirect methods are limited to the determination of values of kcat greater than 10(5) M-1 s-1 and kcat greater than 3 x 10(6) M-1 s-1, respectively. Moreover, many side reactions may occur with the indirect method which may interfere with the measurements. Nevertheless, the indirect method approximates better the in vivo conditions than the direct method, and a tested compound that has high SOD activity using a direct method and low SOD activity using an indirect method, will most probably be a poor SOD mimic in vivo.

Catalysis↗

PubMed1991

The relative efficiency of radicals in radiation damage to deoxyribose.

The radiation damage to Deoxyribose was studied with a view to identify the damaging species. Our results indicate that H, eaq-, CO2- do not cause any appreciable damage in the absence of metal compounds and .OH is the sole damaging entity. Iron compounds sensitize very little O2- damage and CO2- damage could not be sensitized. In N2-saturated solutions metal compounds increase the damage by converting eaq- into deleterious .OH.

Copper↗

PubMed1991

Requirements for SOD mimics operating in vitro to work also in vivo.

When an efficient SOD mimic operating in vitro is introduced into cells, the following requirements are needed in order that this compound will catalyze O2- dismutation efficiently: it should be non toxic, stable, has a long metabolic half life, does not form ternary complexes with the cell components, its reduced form reacts slowly with molecular oxygen, should be able to cross cell membranes and also to reach lipophilic or hydrophobic regions. Thus, it seems that finding an efficient compound that has high SOD-like activity in vivo will not be easily achieved.

Catalysis↗