Showing papers by "Icahn School of Medicine at Mount Sinai published in 1984"
TL;DR: In baboons fed alcohol, the progression of hepatic fibrosis is associated with transformation of lipocytes to transitional cells characterized by a depletion of lipid droplets and a hypertrophy of the rough endoplasmic reticulum; these transitional cells may play a role in promoting hepatic Fibrosis in alcoholic liver injury.
301 citations
TL;DR: Results do not support the view that subgroups of patients have predominantly either negative or positive symptoms, and there was a positive correlation of positive and negative symptoms within the paranoid and undifferentiated subtypes.
Abstract: Negative and positive symptoms were determined for 46 drug-free patients who met Research Diagnostic Criteria (RDC) and/or Feighner criteria for schizophrenia. A modified version of the Scale for the Assessment of Negative Symptoms (SANS) was completed for each patient based on items from the Schedule for Affective Disorders and Schizophrenia (SADS) and other scales. Positive symptoms were scored from the SADS as well as from the following four diagnostic systems: RDC, Schneider's first-rank symptoms, the 12-point Flexible system, and Langfeldt's criteria for poor prognosis schizophrenia. For all patients, there was no correlation of negative symptoms and positive symptoms defined by any diagnostic system. Within the paranoid and undifferentiated subtypes, there was a positive correlation of positive and negative symptoms. Patients moving from stable to exacerbated states had an increase in both positive and negative symptoms, and patients with a poor history of treatment response had both more positive and more negative symptoms than responsive patients in a stable state. These results do not support the view that subgroups of patients have predominantly either negative or positive symptoms.
289 citations
TL;DR: Ulastructural studies using the immunoferritin technique showed collagen VI along thin filaments or in amorphous regions of aortic media or placenta but not in association with thick, cross-striated collagen fibrils or elastin, supporting previous suggestions that collagen VI is a constituent of microfibrillar structures of the body.
Abstract: Collagen VI was solubilized with pepsin from human placenta and used for preparing rabbit antisera. Major antigenic determinants were located in the central region of the antigen including triple-helical and globular structures. Antisera prepared against a constituent-chain showed preferential reactions with unfolded structures. Antibodies were purified by affinity chromatography and failed to cross-react with other collagen types I-V and with fibronectin. These antibodies demonstrated intracellular and extracellular collagen VI in fibroblast and smooth muscle cell cultures. Immunoblotting identified a disulfide-bonded constituent chain about twice as large as those of the pepsin fragments in both cell cultures and tissue extracts. Rotary shadowing electron microscopy indicated that the increase in mass is due to larger globular domains present at both ends of collagen VI monomers. Indirect immunofluorescence demonstrated a wide occurrence of collagen VI in connective tissue particularly of large vessels, kidney, skin, liver and muscle. Collagen VI is apparently not a typical constituent of cartilage or of basement membranes. Ultrastructural studies using the immunoferritin technique showed collagen VI along thin filaments or in amorphous regions of aortic media or placenta but not in association with thick, cross-striated collagen fibrils or elastin. This supports previous suggestions that collagen VI is a constituent of microfibrillar structures of the body.
285 citations
TL;DR: The results suggest that the central serotonergic system is less responsive in depressed patients than controls, and fenfluramine, a serotonin releasing agent, was administered to 18 depressed patients and 10 controls.
243 citations
TL;DR: It is suggested that apolipoproteins A-1 and A-2 in supersaturated human gallbladder bile could inhibit the rate of formation of solid cholesterol crystals and thus help to prevent spontaneous cholesterol gallstone formation in humans.
Abstract: Apolipoproteins A-1 and A-2 were purified from human plasma. At concentrations present in human bile these proteins prolonged the nucleation time of cholesterol monohydrate crystals when added to model systems of supersaturated bile. In contrast, apolipoprotein C-3 and other serum proteins did not have this effect. Also, when human gallbladder bile was fractionated by gel filtration chromatography, apolipoproteins A-1 and A-2 were among the proteins present in a fraction of bile enriched in potent inhibitors of cholesterol crystal nucleation. These findings suggest that apolipoproteins A-1 and A-2 in supersaturated human gallbladder bile could inhibit the rate of formation of solid cholesterol crystals and thus help to prevent spontaneous cholesterol gallstone formation in humans.
187 citations
TL;DR: Transplantation of normal fetal preoptic area tissue into the third ventricle of adult female hypogonadal mice revealed GnRH-containing neurons in the grafts and Gn RH-containing processes extending to the lateral median eminence of the host brains.
Abstract: Adult female hypogonadal mice, in whom hypogonadism is secondary to a genetic deficiency in hypothalamic gonadotropin-releasing hormone (GnRH), are infertile. Mating, pregnancy, and delivery of healthy litters were achieved after transplantation of normal fetal preoptic area tissue, a major site of GnRH-containing cell bodies, into the third ventricle of adult female hypogonadal mice. Immunocytochemistry revealed GnRH-containing neurons in the grafts and GnRH-containing processes extending to the lateral median eminence of the host brains.
184 citations
TL;DR: GDH‐deficient patients were encountered with predominantly extrapyramidal manifestations (atypical Parkinson's disease), cerebellar dysfunction with peripheral neuropathy, or anterior horn cell signs, suggesting that a pleomorphic phenotypic expression of the enzymatic deficiency may occur.
Abstract: Glutamate dehydrogenase (GDH) activity was measured in leukocytes from 88 patients with various types of degenerative neurological disorders affecting primarily the cerebellum and/or the basal ganglia, and 26 healthy control subjects. Twelve patients with slowly progressive multiple-system atrophic disorders were found to have a partial deficiency of this enzyme (52% of control level). The majority of these patients evidenced a constellation of neurological findings consistent with the diagnosis of olivopontocerebellar atrophy, although others were atypical in their neurological manifestations. Thus, GDH-deficient patients were encountered with predominantly extrapyramidal manifestations (atypical Parkinson's disease), cerebellar dysfunction with peripheral neuropathy, or anterior horn cell signs, suggesting that a pleomorphic phenotypic expression of the enzymatic deficiency may occur. Seven cases of GDH deficiency were familial and 5 were sporadic. The former patient group consisted of siblings of either sex, but no parents or offspring were affected. The genetic pattern of the disorder is compatible with autosomal recessive inheritance. Patients with dominantly inherited olivopontocerebellar atrophy or other types of cerebellar or basal ganglia degenerative neurological disorders showed normal GDH activity. Leukocyte GDH was fractionated into "particulate-heat labile" and "soluble-heat stable" components. In the patients the decrease in activity was limited to the "particulate-heat labile" component. A genetic mutation of a GDH "isoenzyme" may occur in some patients with multiple-system degeneration.
182 citations
TL;DR: In this paper, a 13-year-old girl with the severe form of the Maroteaux-Lamy syndrome (mucopolysaccharidosis Type VI, arylsulfatase B deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched sister who had normal aryLSB activity.
Abstract: A 13-year-old girl with the severe form of the Maroteaux-Lamy syndrome (mucopolysaccharidosis Type VI, arylsulfatase B deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched sister who had normal arylsulfatase B activity. Full engraftment has been present for 24 months. The following biochemical and clinical changes have occurred: arylsulfatase B activity in peripheral lymphocytes and granulocytes increased to normal levels, and the activity in serial liver-biopsy specimens increased from about 3 per cent of the mean normal level 43 days after transplantation to about 16 per cent at 600 days. Urinary excretion of acid mucopolysaccharide decreased. Ultrastructural evidence of accumulated dermatan sulfate was no longer detectable in bone-marrow cells; in peripheral-blood lymphocytes, granulocytes, or platelets; or in Ito cells of liver. Twenty-four months after engraftment, hepatosplenomegaly was substantially decreased and cardiopulmonary function was normal. Visual acuity and joint mobility were also improved. The patient returned to school and continued to perform well in academic studies. Thus, bone-marrow transplantation provided a source of enzymatically normal cells, which have altered the metabolic and clinical course of the disease.
182 citations
TL;DR: It is suggested that the kidney accumulates platinum in part by transport or specific binding to the base transport system in the kidney and biotransforms it intracellularly.
180 citations
TL;DR: In this paper, a northern blot analysis of total RNA and polyadenylated RNA isolated from adult rat testes showed that a proopiomelanocortin (POMC)-like messenger RNA molecule is present in these extracts.
Abstract: Northern blot analysis of total RNA and polyadenylated RNA isolated from adult rat testes showed that a proopiomelanocortin (POMC)-like messenger RNA molecule is present in these extracts. The testicular POMC messenger RNA is comparable in length to amygdala and midbrain POMC messenger RNA and appears to be at least 200 nucleotides shorter than POMC messenger RNA found in the hypothalamus and anterior and intermediate lobes of the pituitary gland. Hybridization in situ showed that POMC messenger RNA is located in Leydig cells, which are the only testicular cells that contain immunostainable POMC-derived peptides. These results suggest that local synthesis of POMC occurs in the testis.
172 citations
TL;DR: It is suggested that an abnormal response to protein loading in renal disease may herald the fall in the baseline glomerular filtration rate and the rise in plasma creatinine level.
Journal Article•
TL;DR: This study demonstrates the homologous nature of the female paraurethral glands and the prostate and supports speculations about functional similarity.
Abstract: Homology between female paraurethral glands and the prostate has often been suggested. A means was developed that would lend histochemical support to this hypothesis. Female urethra from autopsy and surgical material was serially sectioned and studied in 19 patients ranging in age from newborn to 86 years. Paraurethral glands were identified in 18 of these. The tissue was stained with antibodies to prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAcPh) using the peroxidase-antiperoxidase method. Of those cases in which paraurethral glands were seen, 83% were positive for PSA and 67% for PSAcPh. Intensity of staining was semi-quantitatively evaluated. In addition, intraluminal secretions and urethral columnar epithelium showed positive enzyme and antigen staining. There was no discernible variation of glandular development or pattern of staining with patient age. This study demonstrates the homologous nature of the female paraurethral glands and the prostate and supports speculations about functional similarity.
TL;DR: In a system reconstituted with NADPH-cytochrome P-450 reductase, NADPH, and phospholipid, purified cytochromes P- 450f and b were discovered to promote conversion of retinoic Acid to polar metabolites, including 4-hydroxy-retinoic acid.
TL;DR: The affected dog was the offspring of a father-daughter mating and had a large head, a shortened maxilla, and corneal granularities, and most joints were extremely lax, easily subluxated, with joint capsules that were swollen and fluctuant.
Abstract: Summary: This report describes a third mucopolysaccharidosis in animals: canine mucopolysaccharidosis VII. The affected dog was the offspring of a father-daughter mating. Weakness in the rear legs was evident at 8 weeks of age and became progressively worse. He had a large head, a shortened maxilla, and corneal granularities. Most joints were extremely lax, easily subluxated, with joint capsules that were swollen and fluctuant. The dog was alert and had apparently normal pain perception. At 13 months of age, there was radiographic evidence of extensive skeletal disease including bilateral femoral head luxation, abnormalities in the shape and density of the carpal and tarsal bones, radiolucent lesions of the epiphyseal regions of most long bones, and cervical vertebral dysplasia and platyspondylia. The electrophoretic pattern of precipitated glycosaminoglycans indicated a predominance of chondroitin sulfate. The animal died suddenly from gastric dilatation. There was generalized hepatomegaly, thickening of the atrioventricular heart valves, and generalized polyarthropathy. Vacuolated cytoplasm was observed in hepatocytes, keratocytes, fibroblasts, chondrocytes and cells of the synovial membrane, retinal pigment epithelium, and cardiac valves. Neurons had cytoplasmic vacuoles. Electron microscopy demonstrated membrane-bound cytoplasmic inclusions in polymorphonuclear leukocytes, hepatocytes, synovium, heart valves and spleen. The activities of 12 lysosomal hydrolases were determined in liver from the affected and control dogs: β-glucuronidase (EC 3.2.1.31), β-hexosaminidases A and B (EC 3.2.1.30), α-hexosaminidase (EC 3.2.1.-), α-L-iduronidase (EC 3.2.1.76), α-galactosidase A (EC 3.2.1.22), β-galactosidase (EC 3.2.1.23), arylsulfatases A and B (EC 3.1.6.1), acid α-mannosidase (EC 3.2.1.24), acid β-mannosidase (EC 3.2.1.25), and N-acetyl-D-galactosamine-6-sulfate sulfatase (EC 3.1.6.-). The activity of β-glucuronidase was reduced to less than 2% of the normal mean value of normal controls.
TL;DR: Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of Hla-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies.
Abstract: An increased prevalence of Type 1 (insulin-dependent) diabetes has been reported in patients with congenital rubella Rubella virus multiplies in the pancreas, and we have hypothesized that studies of children with congenital rubella would be of great importance in following the development of Type 1 diabetes in a defined, susceptible population Two hundred and forty-one children with congenital rubella (mean age 174±03 years; 65% black and hispanic) have been evaluated, 30 of whom already have diabetes and 17 of whom have borderline glucose tolerance In these latter two groups, HLA-DR3 is significantly increased and HLA-DR2 significantly decreased Pancreatic islet cell cytotoxic surface antibodies are found in 20% of the total congenital rubella population, including in more than 50% in the time period before they develop diabetes and are not related to any specific HLA type In addition, anti-microsomal and anti-thyroglobulin antibodies are found in 34% of this population The data demonstrate that Type 1 diabetes developing in congenital rubella patients has the genetic and immunological features of classical Type 1 diabetes, namely the presence of HLA-DR3, the absence of HLA-DR2, islet cell surface antibodies before decompensation and an increased prevalence of anti-thyroid antibodies Patients with non-diabetic congenital rubella represent an easily identifiable group in whom other immunological factors associated with Type 1 diabetes can be elucidated and possibly modified
TL;DR: To study the effects of ethanol (and its oxidation product acetaldehyde and associated metabolite lactate) on myofibroblast collagen synthesis, the cell cultures were incubated for 24 h in a medium containing either 50 mM ethanol, 200 μM acetaldehyde, or 5 mM lactate.
TL;DR: It is suggested that a 4-wk course of adenine arabinoside monophosphate therapy does not induce an increased rate of long-term remissions in chronic type B hepatitis.
TL;DR: The electrocardiogram obtained in the first few hours of AMI is reliable in localizing the LAD as the infarct-related artery and in the absence of true posterior or lateral wall changes, an inferior wall AMI was highly specific and predictive of right coronary artery narrowing.
Abstract: One hundred fifty-two patients underwent cardiac catheterization and coronary arteriography within 6.3 ± 6.0 hours from the onset of acute myocardial infarction (AMI). All had standard 12-lead electrocardiograms recorded within 1 hour of cardiac catheterization. The electrocardiographic abnormalities present were correlated with the infarctrelated artery as determined by coronary arteriography. ST-segment elevation was the most common finding in patients with the left anterior descending (LAD) or right coronary artery as the infarct-related artery. ST-segment depression was the most common abnormality in patients with the left circumflex (LC), artery as the infarct-related artery. A classic pattern of anteroseptal AMI was seen in 93% of all patients with the LAD as the infarct-related artery. A classic pattern of inferior AMI was seen in 53% of patients with right or LC narrowing taken as 1 group. The pattern of true posterior and isolated lateral wall AMI in the absence of classic changes in the inferior leads was highly specific and predictive of LC narrowing. In contrast, the pattern of an inferior wall AMI, in the absence of true posterior or lateral wall changes, was highly specific and predictive of right coronary artery narrowing. Fifty-six percent of patients with LC artery as the infarct-related artery presented with non-classic electrocardiographic abnormalities. The electrocardiographic patterns in patients with subtotal occlusions were similar to those of patients with total occlusions. Thus, the electrocardiogram obtained in the first few hours of AMI is reliable in localizing the LAD as the infarct-related artery. Certain patterns are specific but not sensitive in localizing the right coronary artery as opposed to the LC artery as the infarct-related artery. Presentation with signs and symptoms of AMI and a nonclassic electrocardiogram is suggestive of LC narrowing.
TL;DR: The results indicate that the ability of iron to promote hydroxyl radical production and the role that superoxide plays as a reductant of iron depends on the nature of the system as well as the chelating agent employed.
TL;DR: The localization and relative number of serotonergic (5HT) cell bodies in the brainstem of the cat were studied through the use of a specific immunocytochemical technique to find regions in addition to the classical raphe nuclei.
TL;DR: The author provides an excellent overview of the three major pathways for the metabolism of ethanol, and the toxic effects of hydrogen and acetaldehyde are explored in detail.
TL;DR: This work suggests that foods which are more satiating reduce intake by decreasing desire to eat, not by accelerating the onset of meal termination, and suggests that the differential satiating efficiencies are related to differences in nutrient dispersion, orosensory cues, or temperature.
TL;DR: It is concluded that hepatic mitochondria in baboons are altered by chronic ethanol consumption; it is noteworthy that these changes are fully developed already at the fatty liver stage, and that morphological alteration appears to reflect the damage of mitochondrial membranes rather than an adaptive hypertrophy.
TL;DR: The results indicate that Na+-, K+-ATPase activity and the presence of HCO3- are required for active ion transport in this preparation, and the biphasic effect of ouabain on the electrical parameters cannot be explained by a toxic effect but rather as a selective inhibition of the Na++, K+ and HCO4-pump.
TL;DR: The present findings indicate that prostatic acid phosphatase may function in vivo as a phosphotyrosyl-protein phosphatased, and exhibits high specificity towards phosphoseryl-proteins and phosphothreonyl- Proteins examined.
Abstract: Using [32P]P-Tyr-IgG and [32P]P-Tyr-casein phosphorylated by pp60v-src as substrates, studies on the phosphotyrosyl-protein phosphatase activity in human prostate gland indicate that it is associated with prostatic acid phosphatase. Evidence to support this conclusion include the following: (a) these two enzymatic activities co-purify to apparent homogeneity; (b) they co-migrated on polyacrylamide gel electrophoresis, ion-exchange and gel filtration chromatographies; (c) the exhibit identical thermostability; and (d) the phosphotyrosyl-protein phosphatase activity is sensitive to inhibition by p-nitrophenyl phosphate and by several classical inhibitors of prostatic acid phosphatase including l(+)-tartrate, molybdate, vanadate and NaF. The purified enzyme exhibits high specificity towards phosphotyrosyl-proteins with little activity towards several phosphoseryl-proteins and phosphothreonyl-proteins examined. The present findings indicate that prostatic acid phosphatase may function in vivo as a phosphotyrosyl-protein phosphatase.
TL;DR: It appears that alterations in the phospholipid composition of the mitochondrial membranes are responsible, at least in part, for the depression of cytochrome oxidase activity produced by chronic ethanol consumption.
TL;DR: The pyrogallol method was not significantly affected by large excesses of glutathione and appears to be a superior method for tissue extracts likely to be rich in glutathion.
TL;DR: Sensitization to cocaine- and d-amphetamine-induced rotation was studied in male and female rats and sensitivity returned to normal within 14 days.
TL;DR: The serotonergic innervation of the rat thalamus was studied with an indirect immunocytochemical technique using an antiserum raised against a serotonin‐hemocyanin conjugate in animals pretreated with L‐tryptophan and a monoamine oxidase (MAO) inhibitor.
Abstract: The serotonergic innervation of the rat thalamus was studied with an indirect immunocytochemical technique using an antiserum raised against a serotonin-hemocyanin conjugate in animals pretreated with L-tryptophan and a monoamine oxidase (MAO) inhibitor. When pretreatment was not used there was a decrease in the number of immunoreactive fibers observed in the thalamic region. Innervation was greatest in nucleus ventralis corporis geniculati lateralis, and in the following midline nuclei: nucleus periventricularis, nucleus rhomboideus, and nucleus reuniens. Also well labeled were nucleus anterior ventralis, the intralaminar nuclei, and nucleus lateralis dorsalis. Moderate innervation was found in nucleus reticularis, nucleus anterior dorsalis, nucleus ventralis medialis, nucleus lateralis pars posterior, the posterior complex, and in nucleus dorsalis corporis geniculati lateralis. Very few serotonergic fibers were observed in nucleus paratenialis, nucleus gelatinosus, nucleus anterior medialis, nucleus medialis dorsalis, nucleus ventralis, nucleus ventralis pars dorsomedialis, or in nucleus corporis geniculati medialis. Serotonin immunoreactivity was also noted in a number of fiber bundles in the thalamic region. These include the fasciculus retroflexus, the fasciculus mamillothalamicus, the stria medullaris, and the stria terminalis. These results differ from those of previous descriptions of the serotonergic innervation of thalamic nuclei most notably in the midline nuclei and in the posterior complex. In this study the midline nuclei, nucleus rhomboideus, and nucleus reuniens were more densely innervated than had been described, and in the posterior complex a moderate, rather than sparse, innervation was observed. The more densely innervated nuclei of the anterior and lateral nuclear groups, nucleus lateralis dorsalis and nucleus anterior ventralis, also contained a greater number of labeled fibers than had been indicated.