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Showing papers by "Icahn School of Medicine at Mount Sinai published in 1982"


Journal ArticleDOI
TL;DR: Variations of the liquid diet formulation are compared and three standardized basic formulas are being proposed for the rat, suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of liver changes characterized by a fatty liver.
Abstract: The technique of feeding ethanol as part of a totally liquid diet was invented two decades ago and its successful application for the intervening period is reviewed. This technique results in much higher ethanol intake than with conventional procedures. As a consequence, various complications observed in alcoholics were reproduced in animal models, including fatty liver, hyperlipemia, various metabolic and endocrine disorders, tolerance to ethanol and other drugs, physical dependence and withdrawal, the fetal alcohol syndrome and, in the baboon, liver fibrosis and cirrhosis. Variations of the liquid diet formulation are compared and three standardized basic formulas are being proposed for the rat: (1) a regular diet, comparable to the diet previously referred to as the "Lieber-DeCarli Formula" and suitable for most experimental applications, particularly those intended to mimic the clinical situation in which the various effects of alcohol occur in the setting of liver changes characterized by a fatty liver; (2) a low fat diet comparable in all respects to the preceding diet but with a lower fat content, intended to minimize the hepatic changes; and (3) a high protein formula particularly useful in those circumstances in which an oversupply of dietary protein might be recommended (i.e., pregnancy and lactation).

676 citations


Journal ArticleDOI
TL;DR: There were several similarities between the human data and those previously reported in rats, demonstrating that studies in the rat may reveal mechanisms and functions of brain asymmetry that are relevant to man.

325 citations


Journal ArticleDOI
TL;DR: It is estimated that approximately 8,200 asbestos-related cancer deaths are now occurring annually, which will rise to about 9,700 annually by the year 2000 and will remain substantial for another three decades.
Abstract: Estimates have been made of the numbers of cancers that are projected to result from past exposures to asbestos in a number of occupations and industries. From 1940 through 1979, 27,500,000 individuals had potential asbestos exposure at work. Of these, 18,800,000 had exposure in excess of that equivalent to two months employment in primary manufacturing or as an insulator (greater than 2-3 f-yr/ml). 21,000,000 of the 27,500,000 and 14,100,000 of the 18,800,000 are estimated to have been alive on January 1, 1980. It is further estimated that approximately 8,200 asbestos-related cancer deaths are now occurring annually. This will rise to about 9,700 annually by the year 2000. Thereafter, the mortality rate from past exposure will decrease, but still remain substantial for another three decades.

261 citations


Journal ArticleDOI
09 Apr 1982-Science
TL;DR: In patients with recessive, adult-onset olivopontocerebellar degeneration associated with a partial deficiency of glutamate dehydrogenase, the concentration of glutamate in plasma was significantly higher than that in controls and plasma alpha-ketoglutarate was significantly lower.
Abstract: In patients with recessive, adult-onset olivopontocerebellar degeneration associated with a partial deficiency of glutamate dehydrogenase, the concentration of glutamate in plasma was significantly higher than that in controls. Plasma alpha-ketoglutarate was significantly lower. Oral administration of monosodium glutamate resulted in excessive accumulation of this amino acid in plasma and lack of increase in the ratio of plasma lactate to pyruvate in the glutamate dehydrogenase-deficient patients. Decreased glutamate catabolism may result in an excess of glutamate in the nervous system and cause neuronal degeneration.

234 citations


Journal ArticleDOI
TL;DR: It was concluded that while tenography was a significant diagnostic adjuvant, the diagnosis and decision for surgical intervention must be based primarily upon the clinical findings.
Abstract: Ten patients with spontaneous rupture of the tibialis posterior tendon were evaluated in regards to clinical and roentgenographic diagnostic criteria, tenographic findings, conservative treatment, and surgical repair. It was concluded that while tenography was a significant diagnostic adjuvant, the diagnosis and decision for surgical intervention must be based primarily upon the clinical findings. Previously described surgical repairs either gave less than optimum results or were impossible to achieve due to the extent of tendon damage. A new surgical technique, consisting of a side to side anastamosis of both the normal proximal and distal portions of the tibialis posterior tendon to the adjacent flexor digitorum longus tendon, proved a simple procedure and gave consistently excellent results.

216 citations


Journal ArticleDOI
TL;DR: This is the first report of the satiety effect of CCK-8 in obese humans and it suggests that the therapeutic potential of CCk-8 for the treatment of obesity deserves investigation.

209 citations


Journal ArticleDOI
TL;DR: In conclusion, hydralazine fails to produce consistent hemodynamic and clinical benefits in patients with primary and secondary pulmonary hypertension, and it frequently causes serious adverse reactions.
Abstract: Thirteen consecutive patients with primary and secondary pulmonary hypertension who had normal left ventricular function were treated with hydralazine in an effort to reduce pulmonary vascular resistance and clinical symptoms. Despite marked decreases in systemic vascular resistance (40 per cent; P less than 0.001), hydralazine produced only moderate decreases in pulmonary arteriolar resistance (21 per cent), without improving stroke volume or pulmonary-artery pressure. Instead, mean arterial pressure fell markedly (17.5 mm Hg, P less than 0.01) in association with a reflex increase in heart rate (11 beats per minute, P less than 0.01). Four patients became symptomatically hypotensive within 24 hours of the initiation of treatment; two of these four required pressors for circulatory support, and one died. Progressive renal insufficiency developed in one patient, and a symptomatic decrease in systemic arterial oxygen saturation occurred in another; both changes were reversed upon discontinuation of the drug. In conclusion, hydralazine fails to produce consistent hemodynamic and clinical benefits in patients with primary and secondary pulmonary hypertension, and it frequently causes serious adverse reactions.

204 citations


Journal ArticleDOI
19 Mar 1982-Science
TL;DR: Influenza is caused by highly variable RNA viruses belonging to the orthomyxovirus group, capable of constantly changing the genes coding for their surface proteins as well as for their nonsurface proteins.
Abstract: Influenza is caused by highly variable RNA viruses belonging to the orthomyxovirus group. These viruses are capable of constantly changing the genes coding for their surface proteins as well as for their nonsurface proteins. The mechanisms responsible for these changes in type A influenza viruses include recombination (reassortment) of genes among strains, deletions and insertions in genes, and, frequently, point mutations. In addition, old strains may reappear in the population. Influenza viruses of types B and C appear to vary to a lesser degree. The mechanisms responsible for changes in these viruses are not well characterized.

199 citations


Journal ArticleDOI
TL;DR: A degree of plasticity in the opiate receptor system is indicated that may correlate with specific functional pathways in the brain following chronic administration of naltrexone.

194 citations


Journal ArticleDOI
TL;DR: An inherited disorder of connective tissue, with cutaneous, ophthalmologic, and systemic manifestations, with an estimated prevalence of one in 160,000 people.
Abstract: PSEUDOXANTHOMA elasticum is an inherited disorder of connective tissue, with cutaneous, ophthalmologic, and systemic manifestations. The disease has an estimated prevalence of one in 160,000.1 Vari...

159 citations


Journal ArticleDOI
TL;DR: Abnormal delay in visual evoked potential (VEP) could be normalized in 9 of 14 previously untreated parkinsonian patients under the influence of levodopa/carbidopa therapy and in 6 of 11 previously untreated schizophrenic patients the VEP latency became abnormal following therapy with agents known to cause dopaminergic blockade.
Abstract: Abnormal delay in visual evoked potential (VEP) could be normalized in 9 of 14 previously untreated parkinsonian patients under the influence of levodopa/carbidopa therapy. In 6 of 11 previously untreated schizophrenic patients the VEP latency became abnormal following therapy with agents known to cause dopaminergic blockade. Besides defects in retrobulbar conduction secondary to demyelination, synaptic dysfunction due to neurotransmitter deficiency or receptor blockade must also be considered as a mechanism underlying VEP delays in humans.

Journal ArticleDOI
TL;DR: Golgi preparations reveal that the most frequent type of pallidal neuron (principal cell), which has been recognized in all previous reports, is large (20–50 (Am)), fusiform, with dendrites up to 700 μm long.
Abstract: Golgi preparations reveal that the most frequent type of pallidal neuron (principal cell), which has been recognized in all previous reports, is large (20-50 microns), fusiform, with dendrites up to 700 microns long. Large neurons of globular shape are less frequently impregnated. The morphology of dendrites varies considerably within the same neuron. Some exhibit numerous spines and protrusions and are seen to terminate in elaborate arborizations. A small interneuron (12 microns), with relatively short dendrites, up to 150 microns, and a short sparsely branching axon is observed less frequently. At least two types of afferent axons are present. A small-diameter fiber from the neostriatum enters the pallidum in bundles and gives rise to numerous thin branching processes with varicosities about 1 micron in size. The axon collaterals are oriented orthogonal to the main axon and parallel to the dendrites of principal cells. A large-caliber fiber with clusters of 2-3 microns swellings can also be seen in close proximity to large pallidal dendrites. Ultrastructurally, principal cell dendrites (trunks, spines, and protrusions) are totally covered by synapsing axon terminals. In contrast, some small dentrites, presumed to belong to interneurons, form very few synapses. At least six categories of profiles containing vesicles are observed. One group has cytologic features of dendrites and participates in serial and triadic synapses with other profiles in the pallidal neuropil. Results suggest that the synaptic organization of the globus pallidus may be viewed as a repetitive, geometric arrangement of striatal and other afferent axons ensheathing and synapsing with the dendrites of principal cells. This pattern is interrupted by the presence of presynaptic dendrites, probably belonging to interneurons, which participate in complex synaptic arrangements.

Journal ArticleDOI
TL;DR: Findings suggest that a metabolite of vitamin A rather than vitamin A itself may have been responsible for the potentiation ofitamin A toxicity by ethanol, and implications for the routine treatment of alcoholics with vitamin A and the monitoring for possible signs of toxicity are discussed.

Journal ArticleDOI
TL;DR: PCB congeners with chlorines in both 4-positions of the biphenyl ring were the major components in plasma and adipose tissue and had higher adipose-plasma partition than those with unsubstituted 3,4-pos positions, regardless of the degree of chlorination.

Journal ArticleDOI
01 Sep 1982-Appetite
TL;DR: It is suggested that the quadratic equation could be useful for characterizing factors that lead to changes in the rate of eating during the course of a meal and that such changes might have diagnositic value in assessing eating disorders.

Journal ArticleDOI
TL;DR: Data suggest that clinician competence to a certain extent is modeled by the discourse analysis, and a model of listener interaction with text was pursued whereby constituent statements of discourse are organized on interpretation into hierarchal structures according to their mutual presupposition relationships.

Journal ArticleDOI
TL;DR: The findings suggest that the development of cirrhosis is coincident with, or favored by a failure of hepatic collagen degradative enzymes to keep pace with liver protein synthesis.

Journal ArticleDOI
01 Dec 1982-Diabetes
TL;DR: The HLA antigens of 173 patients with the congenital rubella syndrome are reported, and data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mel-litus are necessary for the development of glucose intolerance in CR patients.
Abstract: The HLA antigens of 173 patients with the congenital rubella syndrome (CR) are reported. Twenty-one of these patients are also clinically diabetic, and among them the frequencies of the HLA antigens DR2 and DR3 are significantly lower and higher, respectively, than in CR patients without diabetes or in controls. These data suggest that the genes that control susceptibility to type I or insulin-dependent diabetes mel-litus are necessary for the development of glucose intolerance in CR patients.

Journal ArticleDOI
25 Jun 1982-Science
TL;DR: The disassociation between these cerebrospinal fluid and plasma patterns and values suggests that the secretory activity of neurons that release estrogen-stimulated neurophysin and oxytocin into the cerebroSpinal fluid is controlled by mechanisms different from those that control their release into the plasma.
Abstract: The concentrations of oxytocin, arginine vasopressin, and estrogen stimulated neurophysin in cerebrospinal fluid of monkeys showed a daily fluctuation with high concentrations occurring during the light period. The patterns of oxytocin and estrogen-stimulated neurophysin in the cerebrospinal fluid were not observed in the plasma nor were they altered after the administration of a dose of estradiol that increased concentrations of estrogen-stimulated neurophysin in plasma. The disassociation between these cerebrospinal fluid and plasma patterns and values suggests that the secretory activity of neurons that release estrogen-stimulated neurophysin and oxytocin into the cerebrospinal fluid is controlled by mechanisms different from those that control their release into the plasma.

Journal ArticleDOI
TL;DR: The idea that each paratope recognizes an idiotope obviously requires that 'conventional' antigenic determinants, expressed on molecules other than immunoglobulins and designated as epitopes, must cross-react with idiotopes.

Journal ArticleDOI
TL;DR: Seven patients with medically unresponsive attacks of angle-closure glaucoma were successfully treated with the argon laser, making laser treatment preferable to and safer than intraocular iridectomy in such cases.

Journal ArticleDOI
TL;DR: In isolated rat hepatocytes, the ethanol-induced redox shift was markedly exaggerated by oxygen tensions similar to those found in centrolobular zones, a change which may contribute to the exacerbation of the damage in the perivenular area of the hepatic lobule.
Abstract: Chronic alcohol administration to baboons results in perivenular lesions in the liver. To study possible mechanisms, the effect of ethanol on splanchnic oxygen consumption was measured. Acute ethanol administration increased splanchnic oxygen consumption in the control baboons, but the consequences of this effect on oxygenation of the perivenular zones were offset by a concomitant rise in blood flow, resulting in unchanged hepatic venous oxygen tensions. In alcohol-fed baboons, splanchnic oxygen consumption was not increased, either in the withdrawal state or after ethanol infusion. To study the magnitude of the shift in redox state induced by ethanol in the perivenular zones, we compared the effects of ethanol on the lactate/pyruvate ratio in hepatic venous blood (an approximation of that in perivenular hepatocytes) with the ratio in total liver. Prior to ethanol infusion, the lactate and pyruvate were the same in liver and in hepatic venous blood. By contrast, in all baboons, ethanol produced a much greater rise in the lactate/pyruvate ratio and decreased pyruvate more in hepatic venous blood than in total liver. Moreover, in isolated rat hepatocytes, the ethanol-induced redox shift was markedly exaggerated by oxygen tensions similar to those found in centrolobular zones. This suggests that the normally low oxygen tensions existing in perivenular zones exaggerate the ethanol-induced redox shift, a change which may contribute to the exacerbation of the damage in the perivenular area of the hepatic lobule.

Journal ArticleDOI
TL;DR: The data suggest that the intracellular levels of 5–10 methylene tetrahydrofolate necessary for the pharmacologic interaction of FdUMP with thymidylate synthetase may be a limiting factor under certain conditions and that it is possible to overcome this metabolic limitation with exogenous reduced folate or by the addition of oxidizing agents which may increase intrACEllular levels.

Journal ArticleDOI
TL;DR: In summary, immunostainable beta-EP has been identified in Leydig cells of five species and Stainable material is also present in the epithelium of other portions of the male reproductive tract and in steroid-secreting cells of the ovary and the adrenal.
Abstract: Previous studies from this laboratory have demonstrated immunostainable beta-endorphin-like material (beta-EP) in Leydig cells and epithelia of the epididymis, seminal vesicle and vas deferens of the rat. These observations would be strengthened if it could be demonstrated that they were not a peculiarity of the rat. Accordingly, we now present immunocytochemical evidence for the presence of beta-EP in the Leydig cells of mouse, hamster, guinea pig and rabbit. No immunoreactive material was identified in Sertoli, myoid, endothelial or germ cells of any of the species examined. Immunostainable beta-EP was also demonstrated in the epididymides of mouse, guinea pig, rabbit, and rat, but not hamster. Immunostainable material was also present in the epithelia of the vas deferens and seminal vesicles of mouse and rat, the only two species thus far examined. Since beta-EP was present in Leydig cells, we wondered whether this peptide could be identified in other steroid-producing tissues. When rat ovaries and adrenals were reacted with anti-beta endorphin, staining was demonstrated in corpus luteum and adrenal cortex. No staining was observed in the adrenal medulla or other portions of the ovary. In order to determine whether the beta-EP detected in the testis and epididymis was derived from a pituitary source, animals were hypophysectomized and tissues examined 2 weeks later. Both the Leydig cells and the epididymal epithelium remained immunostainable. In summary, immunostainable beta-EP has been identified in Leydig cells of five species. Stainable material is also present in the epithelium of other portions of the male reproductive tract and in steroid-secreting cells of the ovary and the adrenal. Such beta-EP may have a paracrine function in the testis and other portions of the male reproductive tract.

Journal ArticleDOI
TL;DR: The prediction that Contingency (particularly with High FAS) would elicit greater physiologic and behavioral hyperresponsiveness in A's than B's received some support in the data for RT speed and plasma NE.
Abstract: Cardiovascular, plasma catecholamine, and behavioral effects of control over aversive events were studied in 87 Type A and B male adults. Subjects performed a choice reaction time (RT) task during which they received loud noise bursts and/or electric shocks on designated trials. About half of the cases were told they could avoid noise and shock by attaining a predetermined criterion of RT speed (Contingency). The remaining half were instructed that noxious stimulation would be delivered randomly, irrespective of their performance (No Contingency). Half of the cases in each treatment were exposed to high frequency of aversive stimulation (High FAS), whereas the remaining half received low frequency of such stimulation (Low FAS). Within Contingency, High and Low FAS were designed to signify failure and success, respectively. Aversive stimulation in No Contingency was gratuitous and, therefore, did not convey information about performance. Relative to No Contingency, the Contingency treatment induced greater increases in RT speed, systolic and diastolic blood pressure, and plasma epinephrine. Differential FAS did not potentiate these differences. It also was found that the Type A subjects had higher systolic blood pressure and heart rate responses than Type B's. The prediction that Contingency (particularly with High FAS) would elicit greater physiologic and behavioral hyperresponsiveness in A's than B's received some support in the data for RT speed and plasma NE. Findings were discussed in terms of sympathetic activation of hemodynamic changes under conditions of active coping. Consideration was given to the role of the sympathetic nervous system and Type A behavior in cardiovascular disease.

Journal ArticleDOI
30 Apr 1982-Science
TL;DR: Several different kinds of asbestos minerals in addition to erionite have now been found in environmental samples taken from the villages where these diseases occur.
Abstract: Pleural mesothelioma, lung cancer, pleural calcification and fibrosis, and interstitial parenchymal fibrosis have been observed among inhabitants of several villages in south-central Turkey. Earlier reports have stated that environmental and lung tissue samples from this area contained the fibrous zeolite mineral erionite, and this mineral has generally been assumed to be the agent responsible for these endemic pathological conditions in the absence of asbestos outcroppings and usage. Several different kinds of asbestos minerals in addition to erionite have now been found in environmental samples taken from the villages where these diseases occur. The lung tissues of mesothelioma patients from these villages contain both fibrous zeolites and asbestos minerals.

Journal ArticleDOI
16 Apr 1982-Science
TL;DR: Endogenous phospholipase A2 activity of brain synaptic vesicles was Ca2+ -dependent and was increased by prostaglandin F2 alpha, calmodulin, adenosine 3', 5' -monophosphate, andAdenosine triphosphate; and light-scattering measurements demonstrated that stimulation of the enzyme's activity correlated with the induction of vesicle-vesicle aggregation.
Abstract: Endogenous phospholipase A2 activity of brain synaptic vesicles was Ca2+ -dependent and was increased by prostaglandin F2 alpha, calmodulin, adenosine 3', 5' -monophosphate, and adenosine triphosphate, whereas the activity was inhibited by prostaglandin E2 in the absence or presence of calmodulin. Light-scattering measurements demonstrated that stimulation of the enzyme's activity correlated with the induction of vesicle-vesicle aggregation. The effects of these compounds on endogenous synaptic vesicle phospholipase A2 activity may imply a common end point of their purported neuromodulatory actions, and indicate that synaptic vesicle phospholipase A2 may play a central role in presynaptic neurotransmission.

Journal ArticleDOI
TL;DR: The HRP axonal transport method revealed that regeneration of the severed nerve resulted in an alteration of the somatotopic organization of the hypoglossal nucleus and a random growth of the axons into branches of the nerve in all the rats irrespective of the treatment.

Journal ArticleDOI
TL;DR: Flash and pattern visual evoked potentials to two temporal frequencies of stimulation were studied in nineteen rats and dopamine blockade was followed by administration of apomorphine, a dopamine agonist, VEP delays could be partially reversed.
Abstract: Flash and pattern visual evoked potentials (VEPs) to two temporal frequencies of stimulation were studied in nineteen rats. The effect of a tyrosine hydroxylase inhibitor and of a dopamine receptor blocker on the VEP was explored in ten animals. Significant latency change occurred following injection of either drug, while only the hydroxylase inhibitor reduced the VEP amplitude. These changes were not caused by the anesthesia used in these experiments, although the same anesthetics in higher doses did depress VEP amplitudes. When dopamine blockade was followed by administration of apomorphine, a dopamine agonist, VEP delays could be partially reversed. Besides conduction defects of myelinated axons, synaptic malfunction may also cause delays in sensory evoked potentials.

Journal ArticleDOI
TL;DR: The correlation of plasma concentration of the more highly chlorinated PCBs, which had been used in the past, with total duration of employment suggested accumulation over time, and males had higher concentrations of PCBs than females.
Abstract: In an effort to assess exposure among workers engaged in capacitors manufacture, PCB concentration was determined in plasma (290) and adipose tissue (61). In general, males had higher concentrations of PCBs than females. The correlation of plasma concentration (1-546 ppb) of the more highly chlorinated PCBs, which had been used in past, with total duration of employment suggested accumulation over time. The gc-ec pattern of these PCB peaks was, in most cases, characteristic of exposure to a PCB mixture with 54% chlorine. The less highly chlorinated PCBs, di-, tri-, and tetrachlorobiphenyls, were the source of current exposure, and were observed in concentrations of 6-2530 ppb in plasma. Higher exposure occurred among persons with direct contact with PCBs in jobs such as capacitor filling. Adipose tissue concentrations, for both the more highly chlorinated PCBs (1-165 ppm) and lower chlorinated PCBs (0.6-414 ppm), were proportional to those in plasma.