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S Goldman

Publications and source records attributed to S Goldman.

At least 19 recordsLinked to original sources
PubMed1992

A repressor region in the human beta-myosin heavy chain gene that has a partial position dependency.

Expression of the human beta-myosin heavy chain (beta MHC) gene was studied by transient assay in culture and in situ by direct injection of plasmids into adult rat hearts. In this report we describe a unique repressor region located -326/-309 (5'-TTGGTGGTCGTGGTCAGT-3') of the human beta MHC gene that is conserved among the rat, rabbit, and human beta MHC genes. This sequence conferred repression onto heterologous promoters when the sequence was located 5' but not 3' to the promoters. This partial positional dependency suggests that the factor may act by limiting the binding of enhancers, located more proximally, to their DNA binding sites.

Animals↗
PubMed1992

Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators.

BACKGROUND: Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, longterm therapy with the angiotensin-converting--enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. We investigated whether captopril could reduce morbidity and mortality in patients with left ventricular dysfunction after a myocardial infarction. METHODS: Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive doubleblind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an average of 42 months. RESULTS: Mortality from all causes was significantly reduced in the captopril group (228 deaths, or 20 percent) as compared with the placebo group (275 deaths, or 25 percent); the reduction in risk was 19 percent (95 percent confidence interval, 3 to 32 percent; P = 0.019). In addition, the incidence of both fatal and nonfatal major cardiovascular events was consistently reduced in the captopril group. The reduction in risk was 21 percent (95 percent confidence interval, 5 to 35 percent; P = 0.014) for death from cardiovascular causes, 37 percent (95 percent confidence interval, 20 to 50 percent; P less than 0.001) for the development of severe heart failure, 22 percent (95 percent confidence interval, 4 to 37 percent; P = 0.019) for congestive heart failure requiring hospitalization, and 25 percent (95 percent confidence interval, 5 to 40 percent; P = 0.015) for recurrent myocardial infarction. CONCLUSIONS: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction.

Adult↗
PubMed1992

Ontogeny of cholecystokinin receptors in the human striatum.

The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the human striatum at midgestation, birth and adulthood. In the adult, cholecystokinin receptors are inhomogeneously distributed with patches of reduced labeling. In the caudate nucleus but not in the putamen these patches match the striosomal organization as revealed by acetylcholinesterase staining. At midgestation, patches of high density of cholecystokinin receptors are in register with the dopamine D1 receptor-enriched striosomes. At birth, this striosomal organization has already evolved into the adult pattern of higher matrix level in contrast to the striosomal pattern of acetylcholinesterase staining.

Acetylcholinesterase↗
PubMed1992

Induction chemotherapy with carboplatin and 5-fluorouracil in combination with radiotherapy in loco-regionally advanced epidermoid carcinoma of the anus--preliminary results.

During the last decade conservative treatment of anal carcinoma based on radiotherapy has gained popularity. Radiotherapy is often combined with concurrent chemotherapy although no firm evidence exists that such combinations are more effective than radiotherapy alone. Treatment results with respect to anal sphincter function are generally better for small tumors. In an effort to improve the treatment results for locally advanced epidermoid anal carcinoma, a selection of patients with such tumors has been treated with induction chemotherapy comprising two or three courses of a combination of carboplatin 300-350 mg/m2 i.v. and 5-fluorouracil 1,000 mg/(m2 x d) x 5 d prior to radiotherapy. Six female patients aged 37 to 74 have completed the regimen. All had complete tumor regressions at conclusion of radiotherapy. No recurrence has yet occurred but the follow-up period is still short (8-21 months). No interruption of chemotherapy due to toxic side effects was necessary and no severe toxicity registered. Further study is needed to evaluate the efficacy and toxicity of the regimen, but these early findings are promising.

Adult↗
PubMed1992

Perianal Paget's disease: report of five cases.

Paget's disease of the anus is a rare perianal disorder. The condition is often associated with underlying invasive carcinoma. The prognosis is poor when rectal adenocarcinoma is present. Five own cases of perianal Paget's disease are presented. In two of our cases an underlying adenocarcinoma was found in the anorectum. Adenocarcinoma is sweat gland ducts was found in one case. One patient developed an adenocarcinoma in the anorectal junction four years after the Paget diagnose. In only one of our cases no underlying adenocarcinoma was found.

Adenocarcinoma↗
PubMed1992

Interval cancer and survival in a randomized breast cancer screening trial in Stockholm.

The aim of the present study was to analyse the survival rate in a group of breast cancers detected in the intervals between screening examinations in relation to clinically detected cancers in a non-screened population. All interval and control cancers were recruited from a randomized controlled mammography screening trial in Stockholm. The overall survival up to eight years of observation was higher in 191 patients with interval cancers than in 142 control cancers (p = 0.01). There were no significant differences between the two groups with regard to tumor size, stage distribution, or mean age, though the interval group did have a larger proportion of younger women. The similarity was confirmed by multiple regression analysis. The overall survival stage by stage was consistently higher in interval cancers. The survival rate in the true interval cancers was similar to that for those found in retrospect to have been detectable or traceable at the time of screening. No correlation was found between the length of the interval and the survival of patients with interval cancers. These results contradict the hypothesis that a high growth rate is associated with a poorer prognosis and that interval cancers are a more aggressive form of breast neoplasia.

Adult↗
PubMed1992

Immunocytochemical analysis of receptors for estrogen and progesterone in fine needle aspirates from anal epidermoid carcinoma.

Fifteen patients with anal epidermoid carcinoma were examined with percutaneous or transanorectal fine needle aspiration (FNA) cytology. Aspirates from all patients allowed cytologic verification of the diagnosis. Estrogen receptor (ER) and progesterone receptor (PgR) were analyzed using an immunohistochemical technique well adapted for steroid receptor analysis in hormone-dependent carcinomas. Neither ER nor PgR could be detected in any of the aspirates. This finding is somewhat unexpected since there is a strong female predominance in this tumor type. However, our findings do not negate that sex steroid hormones may indirectly play a role in the tumorigenesis of anal epidermoid carcinoma.

Adult↗
PubMed1992

Effects of beta-adrenergic blockade on papillary muscle function and the beta-adrenergic receptor system in noninfarcted myocardium in compensated ischemic left ventricular dysfunction.

BACKGROUND: beta-Adrenergic receptor blockade has been reported to improve hemodynamics and beta-adrenergic receptor-adenylate cyclase function in idiopathic dilated cardiomyopathy. The purpose of this study was to determine the effects of beta-adrenergic receptor blockade on the beta-adrenergic receptor system and myocardial function in a model of compensated ischemic heart failure. METHODS AND RESULTS: We examined the effects of propranolol treatment on the beta-adrenergic receptor-adenylate cyclase system and isolated papillary muscle isometric function in noninfarcted left ventricular myocardium in rats after coronary artery ligation. In untreated rats with large myocardial infarction (MI), developed tension (DT) (3.0 +/- 0.7 versus 5.1 +/- 1.1 g/mm2), peak rate of tension rise (+dT/dt) (40.3 +/- 9.5 versus 71.2 +/- 12.0 g/mm2/sec), and peak rate of tension fall (-dT/dt) (24.4 +/- 5.0 versus 38.2 +/- 6.0 g/mm2/sec) were decreased (p < 0.05). In addition, DT, +dT/dt, and -dT/dt of untreated MI rats demonstrated an impaired response to isoproterenol stimulation compared with controls. beta-Adrenergic receptor density (Bmax) measured by [125I]iodocyanopindolol (ICYP) binding was decreased 23% after infarction (9.3 +/- 0.6 versus 12.0 +/- 1.8 fmol/mg protein [prot]) (p < 0.05); however, the dissociation constant (Kd) for ICYP was not changed (24.1 +/- 5.7 versus 33.2 +/- 12.1 pM). Adenylate cyclase activity in the presence of 10(-2) M MgCl2 was reduced (p < 0.05) in MI rats (30.3 +/- 10.8 versus 45.9 +/- 12.5 pmol cAMP/min/mg prot). Maximal isoproterenol (52.5 +/- 7.3 versus 79.9 +/- 10.0 pmol cAMP/min/mg prot), guanyl-5'-imidodiphosphate (GppNHp) (95 +/- 8 versus 141 +/- 25 pmol cAMP/min/mg prot) and forskolin (503 +/- 76 versus 753 +/- 157 pmol cAMP/min/mg prot) stimulation of adenylate cyclase was also decreased (p < 0.05). In addition, manganese-stimulated adenylate cyclase activity was depressed (p < 0.05) in MI rats compared with controls (23.5 +/- 2.8 versus 52.1 +/- 9.0 pmol cAMP/min/mg prot). Chronic propranolol treatment in MI rats improved DT (4.1 +/- 0.9 versus 3.0 +/- 0.7 g/mm2) and +dT/dt (54.4 +/- 11.3 versus 40.5 +/- 9.5 g/mm2/sec) (p < 0.05); however, isoproterenol-stimulated isometric function remained impaired. Propranolol treatment normalized Bmax (11.9 +/- 1.7 versus 9.3 +/- 0.6 fmol/mg prot) (p < 0.05), whereas adenylate cyclase activity remained depressed. CONCLUSIONS: After large MI in rats, there is impaired papillary muscle function with decreased beta-adrenergic receptors and adenylate cyclase activity in the noninfarcted myocardium. Propranolol treatment improved basal isometric muscle function and beta-adrenergic receptor density in rats after myocardial infarction but did not improve adenylate cyclase activity or isoproterenol-stimulated muscle function. These data suggest that there is a primary defect in adenylate cyclase function that persists despite upregulation of receptors with propranolol treatment.

Adenylyl Cyclases↗
PubMed1992

Arterial mechanics in spontaneously hypertensive rats. Mechanical properties, hydraulic conductivity, and two-phase (solid/fluid) finite element models.

To characterize the interaction between mechanical and fluid transport properties in hypertension, we measured in vivo elastic material constants and hydraulic conductivity in intact segments of carotid arteries in normal and spontaneously hypertensive rats (SHR). With the use of a finite element model, the arterial wall was modeled as a large-deformation, two-phase (solid/fluid) medium, which accounts for the existence and motion of the tissue fluid. Measurements of internal diameter and transmural pressures were obtained during continuous increases in pressure from 0 to 200 mm Hg. Strain and stress components were calculated based on a pseudostrain exponential energy density function. To measure the hydraulic conductivity, segments of the carotid artery were isolated, filled with a 4% oxygenated albumin-Tyrode's solution, and connected to a capillary tube. The movement of the meniscus of the capillary tube represented the fluid filtration across the artery. To study the influence of transmural pressure on hydraulic conductivity, measurement of fluid filtration across the arterial wall was obtained at transmural pressures of 50 and 100 mm Hg. The material constants in the SHR (n = 9) were higher (p less than 0.05 for all variables) than in normal rats (n = 10): c = 1,343 +/- 96 versus 1,158 +/- 65 mm Hg, b1 = 1.84 +/- 0.24 versus 1.22 +/- 0.22, b2 = 0.769 +/- 0.114 versus 0.616 +/- 0.11, b3 = 0.017 +/- 0.005 versus 0.0065 +/- 0.002, b4 = 0.206 +/- 0.04 versus 0.083 +/- 0.03, b5 = 0.0594 +/- 0.007 versus 0.0217 +/- 0.006, and b6 = 0.22 +/- 0.09 versus 0.123 +/- 0.02, respectively. The hydraulic conductivity of the total wall, calculated from the filtration data, was lower (p less than 0.05) at both 50 and 100 mm Hg in the SHR (n = 6) compared with normal rats (n = 7): 1.12 +/- 0.31 x 10(-8) and 0.72 +/- 0.23 x 10(-8) versus 1.95 +/- 0.53 x 10(-8) and 1.35 +/- 0.47 x 10(-8) cm/(sec.mm Hg), respectively. The intergroup comparisons between 50 and 100 mm Hg in both SHR and normal rats were also different (p less than 0.05). The finite element model was used to predict tissue fluid pressure distribution, tissue fluid velocity distribution, and total Cauchy stress gradients developed in the arterial wall during fluid pressurization in both species.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Positron emission tomography-guided stereotactic brain biopsy.

We describe a technique that allows target definition for stereotactic brain biopsy using coordinates calculated on stereotactic positron emission tomographic (PET) images. In this study, PET images were obtained using [18F]-labeled fluorodeoxyglucose, a marker for glucose metabolism. The difference between PET-calculated and actual stereotactic coordinates of simulated targets is within PET spatial resolution. Combined computed tomography- and PET-guided stereotactic biopsies were performed in 11 patients with brain tumors. In this report, we describe two representative patients who underwent stereotactic brain biopsy using the present technique. Because of the complementary role of PET and computed tomography, their integration in multimodality planning might optimize the target selection for stereotactic brain biopsies.

Astrocytoma↗
PubMed1992

Captopril and ANP: changes in renal hemodynamics, glomerular-ANP receptors and guanylate cyclase activity in rats with heart failure.

To define the renal effects of atrial natriuretic peptide (ANP) in heart failure, we studied rats with heart failure after coronary artery ligation. The rats received either captopril (2 milligrams drinking water) or placebo for 4 weeks. Glomerular filtration rate, renal plasma flow, filtration fraction, urine volume, urinary sodium excretion and the percent fractional excretion of sodium were measured before and after an infusion of ANP (0.3 microgram/kg/min). To determine whether changes in ANP receptor binding and responsiveness occur in heart failure and after captopril treatment, we performed radioreceptor binding studies and measured guanylate cyclase activity. Atrial natriuretic peptide in sham-operated rats decreased mean arterial pressure from 118 +/- 5 to 95 +/- 5 mm Hg (P less than .001), increased urine volume from 0.06 +/- 0.02 to 0.16 +/- 0.05 ml/min/kg (P less than .05), urinary sodium excretion, 14.2 +/- 3.1 to 41.4 +/- 8.9 mu eq/min/kg (P less than .02), filtration fraction from 0.30 +/- 0.03 to 0.40 +/- 0.4 (P less than .05), and the percent fractional excretion of sodium from 0.84 +/- 0.19 to 2.85 +/- 0.61 (P less than .02). Atrial natriuretic peptide in untreated rats with heart failure produced no significant systemic or renal hemodynamic effects. In rats with heart failure treated with captopril, ANP decreased mean arterial pressure from 93 +/- 4 to 86 +/- 4 mm Hg (P less than .05) and increased hematocrit from 50 +/- 2 to 52 +/- 1 (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Observations, legends, and conjectures concerning restricted T-cell receptor usage and autoimmune disease.

It has become clear over the past few years that a variety of experimental autoimmune conditions are mediated by T cells bearing a highly restricted subset of antigen receptors. This restricted TcR usage raises important questions concerning not only the recognition of autoantigens, but also the pathogenic mechanisms underlying many models of autoimmunity. Furthermore, the extension of these findings in certain cases to human disease has raised the possibility of specific therapeutic immune intervention. In this review, we examine the available data on restricted T-cell receptor usage in autoimmune disorders and explore the interpretations and the theoretical and practical implications of these findings.

Autoimmune Diseases↗
PubMed1992

Cardiac effects of 3,5-diiodothyropropionic acid, a thyroid hormone analog with inotropic selectivity.

Thyroid hormone exerts a strong positive inotropic action on the heart and induces alpha-myosin heavy chain (MHC) gene expression. 3,5-Diiodothyropropionic acid (DITPA), a carboxylic acid analog with low metabolic activity, was observed to induce alpha-MHC mRNA in heart cell culture with EC50 approximately 5 x 10(-7) M. To determine if the compound has positive inotropic actions, the effects of DITPA and L-thyroxine on heart rate, left ventricular pressures, left ventricular dP/dt, myosin isoenzymes and hepatic alpha-glycerolphosphate dehydrogenase activity were compared in hypothyroid rats. Binding affinities of DITPA and triiodothyronine for bacterially expressed alpha-1 and beta-1 thyroid hormone receptors (TRs) also were determined. Over the dosage range of 150 to 1500 micrograms/100 g, DITPA produced increases in left ventricular dP/dt comparable to those obtained with L-thyroxine at dosages of 1.5 to 15 micrograms/100 g, but with significantly less tachycardia. The increase in alpha-MHC mRNA was about the same with both compounds whereas alpha-MHC protein content and GPDH activity increased less with DITPA. These differences could not be explained by preferential binding of DITPA to TR subtypes. Because heart rate is a major determinant of myocardial oxygen consumption, DITPA is able to achieve increased cardiac performance at lower myocardial oxygen costs.

Animals↗
PubMed1992

Baroreflex control of heart rate in rats with heart failure after myocardial infarction: effects of captopril.

Activation of the renin-angiotensin and sympathetic nervous systems in heart failure may result in altered baroreflex control of heart rate. To determine the specific effects of treatment with captopril on baroreceptor dysfunction in heart failure, baroreflex control of heart rate was measured in conscious rats with heart failure 6 weeks after ligation of the left coronary artery. Plasma norepinephrine was measured as a reflection of sympathetic nervous system activity. After bolus injections of phenylephrine (2-50 micrograms/kg) and nitroprusside (2-50 micrograms/kg), the arterial baroreflex was analyzed by fitting percentage of mean arterial pressure changes and heart rate changes to a logistic regression function. There were no differences in baroreflex function between normal and sham-operated rats. Plasma norepinephrine was increased (P < .05) in the heart-failure rats and did not change with captopril treatment. In untreated rats, heart failure increased (P < .05) the centering point by 900%, threshold by 243% and saturation by 89%, whereas decreasing (P < .05) the operational point by 73%. There was a decrease (P < .05) in the nitroprusside-related gain and an increase (P < .05) in phenylephrine-related gain, but the overall baroreflex gain was not changed. In heart-failure rats, captopril increased (P < .05) threshold, saturation and centering point and decreased (P < .05) operational point and nitroprusside- and phenylephrine-related gain abnormalities. The increase in operational point and decreases in threshold, saturation, centering point and phenylephrine-related gain were the results of a specific interactive effect of captopril in heart failure (P = .0033, .0176, .0509, .0217 and .0567, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of captopril on contractility after myocardial infarction: experimental observations.

After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗