Showing papers by "Icahn School of Medicine at Mount Sinai published in 1978"

Extreme myopia produced by modest change in early visual experience.

Abstract: Chicks whose vision was restricted to the frontal visual field became extremely myopic (mean, -10 diopters; maximum, -24 diopters) and had eyes of increased axial length. Animals restricted to lateral field vision did not differ from normal animals. Monocular deprivation of form vision also produced myopia and eye enlargement and, in addition, produced increased anterior chamber depth.

Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950

Abstract: Comparison of the oligonucleotide maps of the RNAs of current human influenza (H1N1) virus isolates shows these strains to be much more closely related to viruses isolated in 1950 than to strains which circulated before or after that period.

Measurements of Visual Evoked Potentials in Parkinson's Disease

Abstract: Visual evoked potentials elicited by reversing grating patterns were recorded in 35 patients with Parkinson's disease and in 26 controls. The average latency of evoked potentials in patients with Parkinson's disease exceeded by two standard deviations the average of the age-matched control group of other neurological patients. Over two-thirds of all patients with Parkinson's disease had abnormal latency. In these patients latency did not correlate with age. In 5 patients the latency became less prolonged on levodopa therapy, suggesting that catecholaminergic pathways have either indirect or direct effects on the generation of visual evoked potentials. Extrapyramidal connections of the visual cortex, as well as retinal dopaminergic neurons, require further study in Parkinson's disease.

Cancer in Crohn's disease after diversionary surgery: A report of seven carcinomas occurring in excluded bowel

Abstract: The incidence of bowel cancer was studied in 132 patients who had undergone bypass surgery for Crohn's disease and who had been admitted to The Mount Sinai Hospital between 1960 and 1976. Seven patients (5.3 per cent) developed cancer (4 of 63 with ileocolitis and 3 of 69 with ileitis). All seven cancers appeared in excluded loops, four in small bowel and three in colon. Six of the cancers occurred at sites of previous active inflammatory disease and one in a relatively normal “skipped” area of cecum. Four were associated with fistulas: two with enterovesical; one with enterocutaneous; and one with both. In only one case was a tumor mass palpable. All seven patients in this series underwent operation and all showed metastatic spread to liver, lymph nodes, or adjacent organs. All patients died within two years of the diagnostic laparotomy. The mean latent period between onset of disease and appearance of cancer was twenty-seven years, and between bypass surgery and appearance of cancer thirteen years. Four of the seven cancers occurred relatively early, within four years of the bypass procedure, but all seven cases had one feature in common—a long duration of Crohn's disease prior to the development of cancer, ranging from seventeen to forty-four years. The diagnosis of cancer in excluded bowel was difficult to make and impossible to confirm prior to laparotomy. Among the large bowel cancers, a preoperative diagnosis was established, by sigmoidoscopy, in only one case. Cancer in a bypassed loop should be suspected in any case of Crohn's disease of long duration when a late recrudescence of symptoms occurs, especially when the symptoms are associated with the new appearance of fistula or mass.

Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls

Abstract: Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers ("null" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities.

Opiate-like and abstinence-like effects of intracerebral histamine administration in rats.

Abstract: HISTAMINE is generally thought to act as a neurotransmitter in the central nervous system (see, for example, ref. 1). Electrophysiological2 and biochemical3 studies have indicated that both H1- and H2-receptors are present in the brain. Functionally, histamine has been implicated in central mechanisms of thirst4 and thermoregulation5. A role for brain histamine in tolerance and physical dependence to morphine has also been suggested6,7. We describe here studies in which we microinjected histamine into various regions of the rat brain and observed analgesia and catalepsy from periaqueductal sites and effects resembling symptoms of morphine withdrawal from sites in the hippocampus.

Fasting decreases triiodothyronine receptor capacity

Abstract: Fasting decreases the ratio of hepatic nuclear to serum triiodothyronine (T3) by diminishing the binding capacity of nuclear T3 receptors. In combination with the lower serum T3 concentration caused by fasting, the decrease in receptor content results in a marked decrease in nuclear T3-receptor complexes. The changes in T3 receptor content and circulating T3 in fasted animals appear to be independent synergistic adaptations for caloric conservation in the fasted state. Unlike changes in hormonal level, the modification of nuclear receptor content provides a mechanism that may protect cells with a low caloric reserve independently of the metabolic status of the whole animal.

Phospholipase A and the mechanism of action of aldosterone.

Abstract: ALDOSTERONE stimulates Na transport across the renal tubule and this effect is also seen in ‘model’ epithelia such as amphibian urinary bladder, skin and colon1–3. This hormone is thought to act by inducing the formation of proteins through nuclear transcription4. Their nature and actions are unknown but it has been suggested that one such protein may act like a ‘permease’ and increase the permeability of the apical side of the epithelial cells or they could stimulate the activity of the Na transport pump. Goodman et al.5, have suggested that “some key enzyme” which increases the turnover of fatty acids may be involved and this could be phospholipase. We report here the identification of phospholipase A in toad bladder and frog skin epithelial cells and in their incubation media. Mepacrine, an inhibitor of phospholipase A, blocked the response to aldosterone on Na transport.

The generation of hydroxyl radicals in biologic systems: toxicological aspects.

Abstract: — The formation of hydroxyl radicals in vitro was studied through their reaction with 2-keto-4-thiomethylbutyric acid to form ethylene gas. The autoxidation reaction of 6-aminodopamine served as a model source of hydroxyl radicals. Ethylene production was suppressed by catalase and by superoxide dismutase, indicating that both hydrogen peroxide and superoxide were involved in the reaction. Hydroxyl radical scavengers (thiourea > benzoate > ethanol) suppressed ethylene production in good agreement with their respective rate constants for reaction with hydroxyl radicals. Urea served as a negative control. Several substituted thiourea derivatives also suppressed ethylene production to a similar degree as thiourea itself. Biologic studies centered on several cytotoxic agents whose mechanisms of action are thought to involve hydroxyl radicals. These agents included alloxan, which destroys the beta cells of the pancreas, and 6-hydroxy- and 6-aminodopamine, which destroy sympathetic nerves. Damage to tissues in vivo was blocked to varying degrees by pretreatment of animals with hydroxyl radical scavengers such as ethanol or the thiourea derivatives. In addition, hydroxyl radical scavengers blocked the action of 5,7-dihydroxytryptamine, a neurotoxin whose effects on noradrenaline neurons were previously shown to be blocked by inhibitors of monoamine oxidase. The data indicate that these cell toxins produce their damaging actions on specific target cells through the intracellular generation of hydroxyl radicals.

beta-Endorphin is not detectable in plasma from normal human subjects.

Abstract: beta-Endorphin is not detectable in plasma from normal human subjects when measured under baseline conditions or after the subjects have received vasopressin, an agent that elevates beta-lipotropin and adrenocorticotropic hormone (ACTH). Significant amounts of beta-endorphin are present in plasma of patients with endocrine disorders associated with increased ACTH and beta-lipotropin production. Highly purified, natural beta-lipotropin is not peripherally converted to beta-endorphin in vivo in normal subjects.

Overview of present day treatment of Parkinson's disease.

Abstract: In the light of present day knowledge, augmenting striatal dopaminergic activity is the most effective means for controlling the symptoms of parkinsonism. This is best accomplished by the administration of levodopa with a peripheral decarboxylase inhibitor. However, limitations in its benefits develop after long-term administration in a substantial number of patients. In an attempt to overcome these a number of pharmacological agents acting on striatal dopaminergic mechanisms have undergone clinical trial. Of those tried Deprenyl, an MAO-B inhibitor, given with levodopa and carbidopa has shown the most promise. Preliminary results in 35 patients indicate that it is useful in diminishing the incidence of “on-off” phenomena—one of the most limiting reactions to levodopa—as well as enabling some patients to recoup their loss of therapeutic benefits. Though far from resolving all of the therapeutic difficulties encountered with prolonged use of levodopa, it appears to be a valuable adjunctive agent for the long-term problem patient.

beta-Lipotropin in brain: localization in hypothalamic neurons by immunoperoxidase technique.

Abstract: β-Lipotropin (β-LPH) has been localized in hypothalamus and pituitary of sheep and ox by the immunoperoxidase technique. In both species β-LPH was found in perikarya of arcuate neurons as well as in cells of the anterior and intermediate lobes of the pituitary. A large number of immunoreactive axons were found in the arcuate region; some appeared to innervate other neurons and others projected to portal capillaries. Stained fiber segments were also scattered throughout the hypothalamus. The presence of β-LPH in hypothalamic neurons supports the possibility that brain β-LPH may be a precursor for opiate-like or other peptides which may be involved in neuromodulation or neurohormonal activities.

Teratogenic action of a bis(dichloroacetyl)diamine on rats: Patterns of malformations produced in high incidence at time‐limited periods of development

Abstract: Win 18,446, a bis(dichloroacetyl)diamine, is a drug that was previously shown to suppress spermatogenesis and to be an effective oral abortifacient in rats. The present study shows that the drug is capable of producing characteristic congenital malformations in high incidence, by a single treatment, and with high survival of fetuses to day 21. Gestation day 11 is the most sensitive time. The teratologies obtained after various schedules of treatment include malformations of the snout (100%), septal heart defects (100%) diaphragmatic hernias (100%), cryptorchism (100%), cervical pockets (100%) and absent or small irregular thymus (92%). Some of these data, namely of the heart, face and thymus, cluster in patterns that indicate that the action of the drug is upon a time-resistricted developmental process. These periods of sensitivity are subsiding or have ended before primordia of these structures appear, but they coincide with the proliferation and migration of those mesenchyme cells that will eventually form or contribute to the structures affected. It is postulated that the drug acts on these mesenchyme cells, or on the extracellular matrix that provides the necessary framework for their dispersal.

Asbestos‐associated disease in United States shipyards

Abstract: During the past 15 years the important disease potential of asbestos exposure has been clarified. The principal hazards have been demonstrated to be cancer of a num ber of sites, and asbestosis. Among asbes tos workers, approximately 20 percent of all deaths are due to lung cancer, six per cent or seven percent to pleural and/or peritoneal mesothelioma, and there is an excess found in several other categories (e.g., cancer of the esophagus, stomach, colon-rectum, oropharynx, larynx, kid ney). Table I provides an analysis of causes of death among 17,800 asbestos insula tion workers in the United States and Canada followed prospectively from January 1, 1967 to January 1, 1977. Risk of asbestos-associated disease has also been observed in workers in other trades where asbestos exposure occurs —¿

The effects of alcoholic liver disease and alcohol ingestion on sex hormone levels.

Abstract: This study showed that alcohol significantly decreases plasma testosterone levels, with changes noted as early as the first day of alcohol use (loss of pulsatile secretion). This effect is due, in part, to a direct testicular action since it occurred without LH suppression and in the presence of elevated LH levels. More chronic use of alcohol resulted in a suppression of LH. Thus, alcohol use in nonalcoholic men is associated with an effect both at the testicular and hypothalamic-pituitary levels.

Concentration dependence of ethanol metabolism in vivo in rats and man.

Abstract: The metabolism of ethanol to acetaldehyde has been widely considered to be almost independent of concentration (i.e., “pseudolinear”) except when blood ethanol was near the Km (0.5–1.0 m/M) of alcohol dehydrogenase (ADH). On the contrary, we report the concentration dependency of ethanol metabolism, in rats and man, at blood ethanol levels several fold the Km of ADH. After intravenous loading, blood ethanol disappearance in 10 rats at blood levels between 38 and 17 m/M ethanol exceeded that between 17 and 4 m/M (14.09 ± 1.38 versus 8.80 ± 0.86 mmoles/liter blood water/hr ± SEM;p < 0.001). Similarly, in 12 men, blood ethanol disappeared faster at 30–17 m/M ethanol compared to 17–4 m/M (5.96 ± 0.33 versus 4.96 7plusmn; 0.28 mmole/liter blood water/hr ± SEM; p < 0.001). When ethanol was maintained at either the 30–60 m/M or 3–19 m/M ethanol range in the blood of 14 fasted rats by constant intravenous infusion, ethanol oxidation was 25% greater at the higher concentration (9.08 ± 0.50 versus 7.23 ± 0.41 mmole/liter blood water/hr ± SEM;p < 0.02). Faster ethanol oxidation at high ethanol concentration could be due to the presence of the microsomal ethanol-oxidizing system (MEOS), which would only be fully engaged, because of its Km (8.5 m/M), at ethanol levels exceeding those necessary to saturate ADH. The concentration dependency of ethanol metabolism casts doubt on the validity of the common medicolegal practice of calculating prior blood ethanol levels by linear extrapolation of subsequent ones, on the false assumption that metabolism is unaffected by concentration.

Preparation, Purification, and Stability of High Specific Activity 125I-Labeled Thyronines

Abstract: A modified chloramine-T method is described for the preparation of several radioiodothyronines by an exchange reaction, which results in low specific activity preparations, or by an addition reaction, which yields radioiodothyronines with specific activities up to 7 mCi/microgram. Purification by paper chromatography is shown to be more convenient than by LH-20 chromatography and provides better resolution among the various thyronines. Radioiodothyronines with only a single iodine atom in the outer (3,5,3'-triiodothyronine and 3,3'-diiodothyronine) are stable for several months when stored in organic solvents. The least stable radioiodothyronines are those with two 125I atoms in the outer ring (3,3',5'-triiodothyronine (rT3) produced from 3-iodothyronine and thyroxine (T4) from 3,5-diiodothyronine). The stability of rT3 and T4 stored in human plasma at 4 C is much greater than when stored in buffer at the same pH. The use of high specific activity [125I]rT3 has permitted the development of a radioimmunoassay with a sensitivity of 1 pg rT3/ml incubation volume.

Variation of properties of chrysotile asbestos subjected to milling.

Abstract: Mechanical milling is commonly used to produce short chrysotile asbestos for experimental purposes. Such manipulation also decreases fiber crystallinity, alters Si-O and Mg-O interlayer bonding, induces coordination changes in the brucite layer, diminishes the ability of fiber to reduce specific free radicals and physisorb organic molecules, and decreases hemolytic potency and antagonist sorption capabilities. The degree of alteration is related to the time of milling. Results of biological experimentation with these materials must be interpreted with caution. Interaction mechanisms in the biological setting are suggested for chrysotile fiber.

AMINO ACID METABOLISM IN GLIAL CELLS: HOMEOSTATIC REGULATION OF INTRA‐ and EXTRACELLULAR MILIEU BY C‐6 GLIOMA CELLS

Abstract: — The amino acid and carbohydrate metabolism of confluent cultures of C-6 glioma cells has been investigated. It was observed that the presence of glutamine in the incubation fluid was essential to maintain high glutamine levels in the cells during a 2 h incubation. When cells were incubated in a cerebrospinal fluid-like medium glutamate, glutamine, aspartate and γ-aminobutyrate (GABA) levels were comparable to those occurring in whole forebrain of adult rat in vivo. Glucose uptake was high, approx 1 μmol/mg protein/2 h, 50% of which was accounted for by lactate production. Of the remaining glucose uptake a substantial proportion was unaccounted for by known oxygen-coupled citric acid cycle flux, or glycogen or amino acid synthesis. Interestingly, the cells released into the medium significant amounts of the neuroinhibitory amino acids, GABA and glycine, and rapidly cleared the medium of the neuroexcitatory amino acids glutamate and aspartate. Metabolism of [2-14C]glucose and [3H]acetate by the cells indicated rapid labelling of the glutamate and aspartate pools of the cells by glucose in 1 h, but the relative specific activities of glutamine and GABA were much lower. The metabolism of tracer concentrations of [3H]acetate to glutamate by the cells indicated greater dilution of this isotope compared to that of labelled glucose. However, the ratio of 3H to 14C radioactivity in glutamate and other amino acids was similar to that in the mixture of glucose and acetate added to the medium. Therefore, some active route of acetate metabolism which communicates metabolically with the route of glucose metabolism to glutamate appears to exist in the cells. Significant acetate activation and fatty acid turnover would explain the present results. Some of the amino acid labelling patterns observed in these studies are not consistent with these glial-like cells behaving as models for the small compartment of amino acid metabolism in brain. Enzyme measurements corroborated the metabolic studies. Glutamate decarboxylase activity was 3–10% of the level found in whole brain. GABA transaminase was also low compared to brain as was glutamine synthetase. Glutamate dehydrogenase was present at levels equal to or higher than those of whole brain.

Differential chemotherapeutic susceptibility of human T-lymphocytes and B-lymphocytes in culture.

Abstract: After previous work from this laboratory revealed that asparaginase was 800-2,000 times more inhibitory against human T-lymphocytes in culture than against B-lymphocytes, a similar further study of 13 chemotherapeutic and immunosuppressive agents was done. Cytosine arabinoside and 5-fluorouracil also had differential inhibitory activities on human T- and B-cells in culture. On the basis of the dose producing 50% inhibition of viable cell growth on day 5, cytosine arabinoside had 45-80 times more inhibitory activity against T-cells than against B-cells. In contrast to asparaginase and cytosine arabinoside, 5-fluorouracil had 10-20 times more inhibitory activity against B-cells. The rest of the chemotherapeutic and immunosupressive agents tested had minor or no differential activity. These findings indicated that T-cell response to asparaginase and cytosine arabinoside and B-cell response to 5-fluorouracil may be exploitable for the differential immunosuppressive effects presumed to be active in vivo. In addition, such differential responses may predict differential tumor cell behavior against these chemotherapeutic agents by T- and B-cell neoplasms in vivo.