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Biomedical subjects

J Kaplan

Publications and source records attributed to J Kaplan.

At least 379 records · Page 21Linked to original sources

Recognition of nucleophile-treated alpha 2-macroglobulin by the alveolar macrophage alpha-macroglobulin . protease complex receptor.

Rabbit alveolar macrophages exhibit high affinity surface receptors which recognize alpha 2-macroglobulin . protease complexes but not native alpha 2- macroglobulin. Binding of alpha 2-macroglobulin . protease complexes to surface receptors is independent of the protease used to form the complex. In this communication, we demonstrate that treatment of human alpha 2-macroglobulin with nucleophilic agents (methyl amine, ammonium salts) converts native alpha 2-macroglobulin into a form recognized by the surface receptor for alpha 2-macroglobulin protease complexes. Analysis of the concentration dependency of ligand binding revealed that the surface receptor did not distinguish between nucleophile-treated alpha 2-macroglobulin and alpha 2-macroglobulin . protease complexes. These results are consistent with the hypothesis that proteases or nucleophilic agents effect the hydrolysis of an internal thiol-ester bond (Tack, B. F., Harrison, R. A., Janatova, J., Thomas, M. L., and Prahl, J. W. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 5764-5768), leading to an alteration in alpha 2-macroglobulin conformation. The altered conformation results in recognition of the alpha 2-macroglobulin by surface receptors.

Ammonium Chloride↗

Kindling in developing rats: variability of afterdischarge thresholds with age.

In the kindling model, the occurrence of afterdischarges is necessary for the development of seizures. In this study, the afterdischarge thresholds of the amygdala were determined in rats of 4 different age groups, beginning with 15-day-old suckling rats. Afterdischarges were triggered in 75% of the suckling rats and in all of the rats in the older age groups. The afterdischarge thresholds varied with age, being highest in the suckling group, lowest in the 35-day-old group and intermediate in the older groups. This variability of the thresholds did not correlate with the alterations in the catecholamine levels in the amygdala that occur during maturation. The failure of 25% of suckling rats to develop afterdischarges may explain why some suckling rats do not kindle.

Aging↗

Polypeptide-binding membrane receptors: analysis and classification.

Polypeptide receptors on mammalian plasma membranes can be categorized on the basis of function. The binding of ligand by class I receptors results in changes in cell metabolism or behavior. Hormone-receptor interactions typify this group. The binding of ligand by class II receptors in ligand internalization. Although changes in cellular activity may result from metabolism of the internalized ligand, the interaction between ligand and class II receptor does not itself lead to alterations in cell behavior. Class II receptors include those for low-density lipoproteins and for alpha-macroglobulin-protease complexes. Although receptors within each category are chemically disparate, they show striking similarities in behavior. Analysis of the behavioral patterns of receptors in each category reveals insights into receptor physiology and allows for a prospective analysis of receptor characteristics.

Animals↗

Analysis of the effect of amines on inhibition of receptor-mediated and fluid-phase pinocytosis in rabbit alveolar macrophages.

Incubation of rabbit alveolar macrophages in vitro with methyl amine led to a time- and concentration-dependent inhibition of uptake of alpha macroglobulin-125I-trypsin complexes (alpha M-125I-T). Upon addition of methyl amine (50 mM) to cells prelabeled with alpha M-125I-T there was a rapid inhibition of lysosomal catabolism of internalized ligand. In the absence of ligand, incubation of cells with 50 mM methyl amine led to a 40-70% decrease in surface-receptor number. The methyl amine-induced decrease in surface-receptor number only occurred in metabolically active cells since cells incubated at 0 degrees C, or treated with N-ethyl maleimide and incubated at 37 degrees C, did not show the effect. Incubation of cells at 37 degrees C with methyl amine also effected a 40-70% decrease in fluid-phase pinocytosis. Although there was a decline in surface-receptor number, the remaining population of receptors were capable of mediating (at least) one round of ligand internalization. However, further ligand uptake was prevented. Data demonstrate that although receptors were present on cell surfaces, they were incapable of mediating ligand internalization. Incubation of macrophages with chloroquine at 37 degrees C for 60 min also led to a disappearance of receptors, and a concomitant reduction in fluid-phase pinocytosis.

Animals↗

Response of collateral channels to histamine: lack of vagal effect.

A new technique using a monodispersed aerosol of histamine delivered to sublobar bronchi through a flexible fiber-optic bronchoscope was used to study the role of the vagus nerve and the effect of anesthesia in the response of collateral channels to exogenous histamine. Studies were performed in paralyzed dogs anesthetized with pentobarbital sodium or alpha-chloralose. Challenges with histamine aerosol were delivered to separate bronchi in each animal before and after bilateral cervical vagotomy. Resistance through collateral channels increased in a reproducible manner following histamine challenge. Vagotomy resulted in no significant change in base-line resistance through collateral channels. The response of collateral channels to exogenous histamine aerosol was not significantly affected by vagotomy or the type of anesthesia used. We conclude that vagal reflexes do not play a significant role in the response of collateral channels to exogenous histamine.

Airway Resistance↗

Abnormal inspiratory flow-volume curves in patients with sleep-disordered breathing.

Although flow-volume curves are valuable in detecting extrathoracic airway obstruction, their role in testing patients with sleep-disordered breathing is undefined. To determine whether patients with sleep-disordered breathing have abnormal flow-volume curves consistent with variable extrathoracic obstruction, 60 subjects referred with suspected sleep disorders prospectively underwent spirometry and assessment of flow-volume curves. These tests were interpreted independent of the outcome of polysomnography. Fourteen of 35 subjects (40%) with sleep-disordered breathing had abnormal flow-volume curves consistent with variable extrathoracic airway obstruction, and 2 of 25 (8%) with no breathing disorder had extrathoracic obstruction (p less than 0.02). The presence of extrathoracic airway obstruction in subjects with mixed or obstructive sleep apnea did not correlate with age, the presence of snoring, excessive daytime hypersomnolence, obesity, or the severity of sleep apnea. Abnormal flow-volume curves were found more frequently in women who had no obvious structural upper airway abnormality. Because of the high specificity (92%) of the flow-volume curve, the finding of extrathoracic obstruction in patients with a history consistent with sleep-disordered breathing substantially increases the likelihood that sleep apnea is present.

Adult↗

In vivo damage of rat lungs by oxygen metabolites.

The intrapulmonary instillation into rat lung of enzymes that generate oxygen metabolites results in acute lung injury. The injection of xanthine oxidase and xanthine produces acute lung injury that, in the presence of superoxide dismutase, but not in the presence of catalase, can be significantly diminished, suggesting that O2- has the capacity to injure the lung. Instillation of a generator of H2O2, namely glucose oxidase, will, in sufficient quantities, produce acute injury that is not neutrophil-dependent. When either a low dose of glucose oxidase alone or lactoperoxidase alone is employed, little lung injury occurs. However, instilling the combination of the two enzymes produces severe, acute injury that can be blocked in a dose-dependent manner by catalase, but not by superoxide dismutase. Purified human leukocytic myeloperoxidase, but not horseradish peroxidase, will substitute for lactoperoxidase in the model of lung injury. The lung damaging effects of these enzymes cannot be attributed to the presence of contaminating proteases. Acute lung injury produced by the instillation of glucose oxidase and lactoperioxidase progresses to interstitial fibrosis. These studies represent a direct application of generators of oxygen metabolites to the in vivo induction of lung injury. The data suggest that rat lung is susceptible to injury by a variety of oxygen metabolites, including O2-, H2O2 and its lactoperoxidase or myeloperoxidase-produced derivatives. The studies also indicate that lung injury produced by oxygen metabolites can result in interstitial pulmonary fibrosis.

Animals↗

Fluphenazine decanoate and tardive dyskinesia: a possible association.

The authors examined the charts of 22 outpatients who had received intramuscular fluphenazine decanoate and oral fluphenazine hydrochloride to assess the incidence of tardive dyskinesia. The severity of tardive dyskinesia was assessed with the Abnormal Involuntary Movement Scale (AIMS). Both the total dose and average daily dose of fluphenazine decanoate correlated significantly with high AIMS scores. There were also significant correlations of AIMS scores with total dose of antiparkinsonian medication and total dose of other neuroleptics. Total dose of antiparkinsonian medication correlated with total dose of fluphenazine decanoate. The authors discuss the clinical and physiological implications of these correlations.

Adult↗

The Cleveland NIAAA prospective alcohol-in-pregnancy study: the first year.

Data from 2,913 antepartum gravidas screened for alcohol problems during the first year of a large prospective study designed to relate antenatal drinking behavior to infant outcome have been analyzed. The Michigan Alcoholism Screening Test (MAST) appears to separate two populations of pregnant patients. Differences between positive and negative MAST responders indicate variables, such as ethnicity, previous pregnancies, nutrition and cigarette smoking, which will require control when infant outcome data are evaluated. Positive MAST responders were found to be more likely to drink alcohol, to drink greater volumes and to drink more frequently than matched negative responders. They obtained a smaller proportion of their alcohol intake from wine and were more likely to drink a combination of beer, wine and/or liquor than the negative responders. The positive responders significantly decreased their alcohol intake as pregnancy progressed, while negative responders did not, suggesting the possibility that abstinence oriented therapy may be helpful. Problems with quantitating alcohol intake by humans and strategies for separating chronic and acute alcohol effects are discussed.

Adult↗

Snake venom antibodies in Ecuadorian Indians.

Serum samples from 223 Waorani Indians, a tribe in eastern Ecuador, were investigated by enzyme-linked immunosorbent assay for antibodies to snake venom. Seventy-eight per cent were positive, confirming the highest incidence and mortality from snake bite poisoning yet recorded in the world. Most samples were positive for more than one venom antibody. Antibodies were found to venoms of Bothrops viper in 60% of positive cases, of Micrurus coral snake in 21%, and of the bushmaster, Lachesis muta, in 18%. Further studies are needed to determine whether high venom-antibody levels afford protection against further snake envenoming.

Adolescent↗

Acute myelofibrosis terminating in an acute lymphoblastic leukemia: a case report.

A patient with acute myelofibrosis developed acute leukemia during the course of her disease. Light microscopic examination showed that the cells were lymphoblasts. The presence of terminal deoxynucleotidyl transferase and T- and B-lymphocyte markers suggested that the malignancy was of immature lymphoid cell origin. Terminal leukemic transformation in some cases of acute myelofibrosis may be of a lymphoid nature and, thus, less toxic chemotherapy could be used with a better prognosis.

Antigens, Surface↗