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Biomedical subjects

S Levine

Publications and source records attributed to S Levine.

At least 523 records · Page 29Linked to original sources

Polypeptides of respiratory syncytial virus.

Radiolabeled respiratory syncytial virus was purified from medium that had been harvested from infected HeLa cell monolayers before it contained much cellular debris. After isopycnic centrifugation in linear gradients prepared with sucrose dissolved in Hanks balanced salt solution, almost all the infectivity and most of the radioactivity were recovered in a single band with density from 1.16 to 1.23 g/cm3 and a peak at 1.2 g/cm3. Analysis by polyacrylamide gel electrophoresis resolved the purified virus into seven polypeptides of approximate molecular weights 20,000 to 80,000, of which the two largest and the smallest proved to by glycoproteins.

Glycoproteins↗

Role of tissue hypermetabolism in stimulation of ventilation by dinitrophenol.

Several authors have hypothesized that tissue hypermetabolism accounts for increases in ventilation (VE) elicited by 2,4-dinitrophenol. However, some data in the literature indicate that stimulation of VE by isomers of dinitrophenol is unrelated to tissue metabolic rate. To test this latter concept, we compared three different isomers of dinitrophenol (i.e., 2,4-dinitrophenol (2,4-DNP), 2,5-dinitrophenol (2,5,-DNP), 2,6-dinitrophenol (2,6-DNP) with respect to stimulation of VE and with respect to stimulation of oxygen consumption (VO2). In all experiments, 3-4 mg/kg of one dinitrophenol isomer was administered to chloralose anesthetized dogs by intra-arterial infusion. 2,4-DNP elicited large increments in both VE and VO2, 2,6-DNP elicited moderate increments in both VE and VO2, whereas 2,5-DNP elicited small increments in both VE and VO2. These observations demonstrate a correlation between ventilatory and metabolic changes affected by isomers of dinitrophenol. Accordingly, these results are consistent with the hypothesis that ventilatory stimulation by congeners of dinitrophenol is related to tissue hypermetabolism.

Animals↗

Suppression of the hyperacute form of experimental allergic encephalomyelitis by drugs.

Numerous drugs were tested for ability to suppress the hyperacute form of experimental allergic encephalomyelitis (EAE). This very severe disease produced clinical signs after 7-9 days which progressed rapidly to paralysis and death. Treatment during the first five days of the incubation period with cycloleucine, cyclophosphamide EN3638, 6-mercaptopurine, methotrexate and procarbazine produced important delays in onset. Corticosteroids, nonsteroidal antiinflammatory drugs, antilymphocyte serum, asparaginase, gold, cytarabine and tilorone, all previously reported to suppress ordinary EAE, had moderate, little or no effect in hyperacute EAE. Proteacted treatment was of no avail with some of these drugs, but it revealed the remarkable suppressive effect of EN3638, equal to cyclophosphamide. Hyperacute EAE was a rapid and economical screening test for immunosuppressive drugs, and a highly discriminating tool for comparison of potent agents.

Acute Disease↗

Experimental allergic encephalomyelitis in the Lewis rat: farther delineation of active sites in guinea pig and bovine myelin basic proteins.

Highly encephalitogenic peptide (37-88), derived from the guinea pig myelin basic protein by peptic digestion, was treated chemically to destroy its tyrosyl and histidyl residues and enzymatically to remove its C-terminal sequence Val-His-Phe. Neither of the modifications resulted in loss of activity in Lewis rats. The enccephalitogenic region within peptide (37-88) was located by examination of derivative peptides obtained by selective proteolytic cleavage. The results showed that peptide (61-88), like peptide (43-88), was fully active at the level of 0.02 nmole whereas peptides (72-88) and (72-84) were fully active at levels of 0.5 and 2.5 nmole, respectively. In contrast, peptides (43-71) and (75-88) were completely inactive. These results demonstrated that the undecapeptide Gln-Lys-Ser-Gln-Arg-Ser-Gln-Asp-Glu-Asn-Pro (residues 72-84), although not as encephalitogenic as peptides (43-88) or (61-88), does contain the elements essential for the induction of disease. At the levels tested (10.8 and 2.2 nmole) only peptides (43-88) and (61-88) were capable of inhibiting the induciton of disease by passively transferred lymph node cells; this inhibition, however, was less than that achieved by the intact guinea pig basic protein. Further studies on the encephalitogenicity of the bovine basic protein in Lewis rats demonstrated that the active site in the C-terminal half of this protein is present in its entirety within residues 89 to 115.

Amino Acid Sequence↗

Interaction between ethyl methylene blue and cyanide-induced increases in blood lactate.

Previous workers have reported that ethyl methylene blue (EMB) diminishes cyanide-induced increases in blood lactate (CIL); the present study investigates the mechanism underlying this interaction. Accordingly, sodium cyanide (1.2 mg./Kg.) was infused into the abdominal aorta of anesthetized, spontaneously breathing dogs. Following cyanide infusion, arterial lactate concentration increased 5.4 +/- 1.1 mmol./L. and arterial PCO2 decreased 22 +/- 3 mm. Hg. A second group of dogs was pretreated with EMB (8 to 15 mg./Kg.); this dose of EMB elicited twofold increments in oxygen consumption and induced the formation in vivo of methemoglobin (0.8 +/- 0.1 gm./100 ml.). Following cyanide infusion, the increase in lactate in EMB animals was only 0.6 +/- 0.2 mmol./L.; the decrease in arterial PCO2 was limited to 5 +/- 1 mm. Hg. In order to clarify the relationship between cyanide-induced hypocapnia and CIL, cyanide was infused into a third group of dogs that were maintained isocapneic via mechanical ventilation; despite constancy of arterial PCO2, lactate increased 6.0 +/- 0.7 mmol./L. To determine the effect of EMB-induced tissue hypermetabolism on CIL, twofold increments in oxygen consumption were produced in a fourth group of dogs by pretreatment with sodium salicylate. Following cyanide infusion, salicylate-pretreated animals increased lactate 7.2 +/- 1.2 mmol./L. In order to assess the relationship between EMB-induced methemoglobinemia and the decrease in CIL, similar concentrations of methemoglobin were produced in two subsequent groups of dogs by two different techniques (i.e., by aniline pretreatment or by infusion of methemoglobinemic blood that had been prepared in vitro by addition of sodium nitrite). CIL in these animals was again markedly diminished (i.e., increments of only 0.6 +/- 0.3 mmol./L.) It is concluded that EMB diminishes CIL by a mechanism other than elimination of cyanide-induced hypocapnia or induction of tissue hypermetabolism. The results suggest that methemoglobin formation may completely account for the ability of EMB to effect a decrement in CIL.

Aniline Compounds↗

De novo Kaposi's sarcoma in renal transplantation. Case report and brief review.

This report describes a de novo development of Kaposi's sarcoma in a Puerto-Rician man 9 months after a cadaveric renal transplant. Progression of the disease was observed despite local irradiation, while the patient remained immunosuppressed with prednisone and azathioprine. This was accompanied by depressed immunologic tests. Discontinuation of azathioprine and addition of chemotherapy (bleomycin and vincristine), while continuing prednisone to maintain functional survival of renal allograft, has led in this patient to regression of extensive cutaneous and suspected pulmonary Kaposi's sarcoma lesions. The possible importance of a depressed immunosurveillance mechanism and activation of latent oncogenic virus by the presence of an allograft in the de novo appearance of Kaposi's sarcoma in transplant recipients is briefly discussed.

Antibody Formation↗

Pituitary--adrenal responsiveness of rat mothers to noxious stimuli and stimuli produced by pups.

Studies on the response of female rats to various stresses during the course of lactation showed a marked reduction in pituitary-adrenal activity. Maximum suppression coincided with the period of maximum lactation, about 14 days after parturition. Both pituitary corticotropin and the release of corticosterone were significantly reduced. Females showing maternal behaviour but not lactating did not exhibit this buffering of the stress response. Another aspect of pituitary-adrenal activity has been studied in lactating female rats. Females, although they have a buffered stress response, responded differently, in terms of pituitary-adrenal activity, to stimuli emitted by the pups: pups which are exposed to noxious stimuli elicit a much greater pituitary-adrenal response in lactating females than do pups which are merely handled. Separation from the pups does not elicit a pituitary-adrenal response. This difference in response is modified if the infants are malnourished and is not observed in virgin animals that are not lactating.

Adrenocorticotropic Hormone↗

Influence of maternal malnutrition on pituitary-adrenal responsiveness to offspring.

Maternal pituitary-adrenal responsiveness to noxious and pup-produced stimuli was investigated in rat mothers fed low protein or control diets. While low protein (LP) mothers did not differ from control (C) dams in basal secretion of corticosterone or in their response to ether or novelty stress, the LP mother's response to pups which had been either handled (H) or shocked (S) differed from controls. This responsiveness to pups depended on both the mother's and pup's nutritional condition. While control pups elicited a differential pattern of pituitary-adrenal response which depended on pup treatment (H/S) from both C and LP mothers, malnourished pups were not capable of eliciting this differential pattern from either type of dam. Overall, malnourished pups elicited less responsiveness. In addition, low protein mothers displayed a decreasing responsiveness toward malnourished pups as lactation proceeded. Thus, this physiological evidence confirms behavioral observations indicating that both the mother's and pup's nutritional condition play a role in determining mother-infant relationships.

Animals↗

Plasma corticosterone levels as an index of the strength of illness induced taste aversions.

Data are presented which demonstrate the task generality of pituitary-adrenal changes that accompany avoidance conditioning. In two experiments a conditioned aversion to milk was established by pairing it with lithium chloride (LiCl). In Experiment 1 conditioned pituitary-adrenal activation occurred when, in a conflict situation, animals reexperienced milk that had earlier been paired with LiCl. The relationship between the strength of aversion and corticosterone levels was such that animals showing the greatest avoidance showed the largest elevations in plasma corticosterone. In Experiment 2 this behavior/steroid relationship was manipulated. Dexamethasone (DEX) pretreatment on the day of conditioning was used to attenuate the conditioned aversion. Compared to saline (SAL) controls when reexposed to milk, DEX animals showed an attenuated aversion (i.e., drank more) and a smaller conditioned response (i.e., less adrenocortical activity). The reduction of conditioned elevation in corticosterone was not due to any residual effects of DEX at the time of testing (Experiment 3). Plasma levels of corticosterone represent an index for assessing the strength of illness induced conditioned taste aversions.

Animals↗

Nutritional variables and their effect on the development of ultrasonic vocalizations in rat pups.

Measures of ultrasonic vocalizations were made on alternate days during the first and second weeks postpartum in rat pups reared by mothers fed either control (23%) or low protein (8%) diets. Compared to those reared by control mothers, pups reared by low protein mothers emitted significantly fewer ultrasonic vocalizations. The hypothesis that malnutrition might shift the age at which peak rate of vocalizations were emitted was not confirmed.

Animals↗