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Biomedical subjects

M Rubinstein

Publications and source records attributed to M Rubinstein.

At least 199 records · Page 11Linked to original sources
PubMed1986

The interferon receptors.

Early studies on the mode of action of interferons have indicated that a receptor system on the cell surface is involved in its action. The first direct evidence to a high-affinity binding site was found only after pure interferon was available. Two different receptors, one specific for interferons-alpha and beta, and the other for interferon-gamma were recognized. A correlation between affinity to the receptor and specific activity was established. Cross-linked complexes of labeled interferons with their receptors were visualized on gel electrophoresis and even partially purified. Internalization of interferons after binding to the receptor was reported. The role of gangliosides as helpers of interferon binding was recently investigated. Fragments of interferons which still retained binding capacity were described and helped in elucidating the binding site on the interferon molecule.

Animals↗
PubMed1986

The interferon-gamma receptor in human monocytes is different from the one in nonhematopoietic cells.

The receptor for interferon-gamma (IFN-gamma) on peripheral blood monocytes was characterized and was compared with that of human WISH cells. 125I-IFN-gamma was specifically bound to both cells; however, different binding characteristics were obtained. In the case of monocytes, Scatchard analysis gave an upward concave dependency curve, indicating either multiple binding sites or a negative cooperativity among the binding sites. In contrast, a linear Scatchard plot was obtained for the binding in WISH cells. Competition studies gave even more striking differences. Acid-treated IFN-gamma (95% inactivated) effectively competed with 125I-IFN-gamma for binding to the receptor on WISH cells, but not on monocytes. The significance of these differences was evaluated by analyzing the various biological activities of IFN-gamma in these two cell types. IFN-gamma was found to induce an antiviral state in WISH cells, but not in monocytes. Acid-treated IFN-gamma was found to be almost as active as IFN-gamma itself in inducing HLA-DR in WISH cells, but was almost completely inactive as an HLA-DR inducer in monocytes. It is proposed that these variations in biological activity stem from the presence of different receptors for IFN-gamma in monocytes and in WISH cells. Moreover it is suggested that the immunoregulatory functions of IFN-gamma in monocytes are related to the presence of a distinct IFN-gamma receptor in these cells.

Amnion↗
PubMed1986

Posterior stabilized knee arthroplasty. Six years' experience.

The posterior stabilized knee arthroplasty, a descendent of the cruciate sacrificing total condylar design, is a cruciate-substituting prosthesis that achieves motion previously attainable only by cruciate-retaining knee arthroplasties. Its clinical success has not been associated with complications directly attributable to the design.

Adult↗
PubMed1985

Amphetamine response and relapse risk after depot neuroleptic discontinuation.

Twenty-five schizophrenic outpatient subjects in a depot neuroleptic discontinuation study received an amphetamine challenge approximately 6 weeks after their last dose. Only five of these showed greater than three-point increases in positive symptoms on the BPRS, and all five relapsed within 30 days of the challenge. The 20 with less than three-point increases in positive symptoms showed extremely variable stability, relapsing from 20- greater than 600 days after the challenge. Thus, increase in positive symptoms after amphetamine may identify a group at risk for rapid relapse after neuroleptic discontinuation, but lack of such a response gives little prognostic information.

Adult↗
PubMed1985

The fate of [125I]-labeled human leukocyte-derived alpha interferon in the rat.

In order to follow the catabolic fate of interferon in the body, [125I]-labeled human alpha interferon was infused into rats. Interferon activity and TCA-precipitable radioactivity in the blood reached a steady state after 60 min of infusion, while TCA-soluble radioactivity continued to increase during the entire infusion period. A massive accumulation of both active interferon and degradation products of interferon were found in the kidney at the end of the infusion. Most of the interferon activity was found in the mitochondrial-lysosomal fraction, while most of the interferon degradation products were found in the supernatant fraction. Ligation of the kidney's blood vessels resulted in a large increase of interferon activity in the blood. Only a small increase was found in other organs, with no increase at all in radioactive degradation products. Our results suggest the kidney to be the main site of interferon catabolism. Low molecular weight degradation products are excreted from the kidney into the blood and are at least partially secreted in the urine and also taken up by other organs.

Animals↗
PubMed1985

Basic metabolic rate in emotional stress: its potential influence on cochlear function.

Using a model previously described, prolonged emotional stress was induced in guinea pigs. Under this condition, arterial blood gases, blood glucose level, PO2 and PCO2 in the expired air, and the heat irradiated by the animals were measured and compared to those of the anesthetized guinea pigs. From the present study, two important findings should be mentioned. First, the metabolic rate of the animals under stress was 30% higher than in the anesthetized group. Second, the arterial PO2 level of the animals under stress was significantly lower than that in the anesthetized ones. Evaluating the noxious effect of severe and/or prolonged emotional stress, one should not neglect the increased oxygen demand resulting from the high metabolic rate of the subject. This factor, together with the decreased arterial blood PO2 level, reinforce the hypoxic effects on the cochlear function, caused by the vasoconstriction of the labyrinthine vessels.

Action Potentials↗
PubMed1985

Problems in interpretation of brainstem-evoked response audiometry results.

This report describes 6 cases - 3 adults and 3 children - in which no response could be obtained during the brainstem-evoked response audiometry (ABR) examination. This, in spite of the fact that maximal click intensity was used during the test, and despite the patients' nearly normal hearing sensitivity. All of the cases presented a slight degree of neurological deficiency, which could explain the faulty synchronization of the biological response to clicks. Attention is drawn to the fact that lack of response in ABR in cases with central nervous system involvement is not necessarily proof of severe hearing loss, and could supply important diagnostic cues.

Adult↗
PubMed1985

Minimal time interval in auditory temporal resolution.

Human auditory temporal resolution was measured. Normal-hearing adults in 3 age groups (I: mn age: 24 yrs, N:55; II: mn age: 44.5 yrs, N: 25; III: mn age: 66.4 yrs, N:18) were required to indicate in which of 2 successive noise bursts of relatively low frequency (concentrated from .1-.5 kc/s) a brief temporal gap was inserted. The noise was created by passing a 100-c/s square wave through an electronic switch with virtually instantaneous rise-fall time and through a clinical audiometer to the associated earphone. The level was set at about the loudness of each S's HTL at .25 kc/s. The minimum detectable time interval (delta t) varied lawfully and significantly (p less than .001) with burst duration and with age. For all ages delta t was approximately equal to 3 msec when the burst duration was longest (85 msec), but at the shortest duration (10 msec) it rose to 17.6, 22.2, and 29.9 msec for Grps I-III, respectively. The interaction between age and duration was also significant (p less than .001). It was suggested that establishment of delta t by this or a similar procedure could offer an important parameter for evaluation of auditory function.

Adult↗
PubMed1984

Influence of catecholamines on perilymph Po2.

In a previous study, a special rheological model of intra-arterial perfusion was used to examine the existence and effectiveness of vasomotor control of the cochlear vessels in guinea pigs. Catecholamines were injected intra-arterially into this animal model and the changes induced in the cochlear action potentials were examined. In this investigation, we used the same animal model and technique to measure the perilymph Po2 after perfusion of the cochlea with catecholamines. In addition, the effect of drainage of the CSF before infusion was examined. The results indicated that opening the labyrinth allows the escape of CSF through the patent cochlear duct. This may modify the concentration of the substance under study in the perilymph and cause inaccuracies in the data obtained.

Animals↗
PubMed1984

Isolation of two discrete human interferon-gamma (immune) subtypes by high-performance liquid chromatography.

A rapid procedure for isolation of two biologically active human interferon-gamma subtypes was developed. Crude interferon-gamma produced in a serum-free culture of peripheral blood mononuclear cells by mitogen stimulation was concentrated and partially purified by chromatography on controlled-pore glass. Following desalting and concentration by ultrafiltration, a step of cation-exchange high-performance liquid chromatography was performed. A linear NaCl gradient (0.01-0.4 M) at pH 7 was employed and four peaks of biological activity eluting at 0.17, 0.20, 0.26 (major peak), and 0.3 M were obtained. The major peak of biological activity coincided with two protein peaks. Analysis of one fraction from the major activity peak by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a protein band having an apparent molecular weight of 26,000, while an adjacent fraction of the same activity peak contained a protein band corresponding to a molecular weight of 21,000. The specific activity of both subtypes was 7-10 X 10(6) units/mg.

Chromatography, High Pressure Liquid↗
PubMed1984

Efficient constitutive production of human fibroblast interferon by hamster cells transformed with the IFN-beta 1 gene fused to an SV40 early promoter.

The coding sequence of the human interferon (IFN)-beta 1 gene, fused 60 bp downstream from the RNA start site of the SV40 early gene, was transfected into dihydrofolate reductase (DHFR)-deficient Chinese hamster ovary (CHO) cells together with a selectable DHFR gene. Most transformants continuously secreted IFN-beta 1 into the medium. Induction did not stimulate expression of the fused SV40-IFN-beta 1 gene. The role of the SV40 promoter was verified by transforming cells with the unmodified human IFN-beta 1 gene, or by the IFN-beta 1 coding region fused to another poly(rI):(rC)-inducible gene. In these cases, the transformants showed strictly inducible (not constitutive) IFN secretion. By selection for methotrexate resistance, CHO clones with a 10-20-fold amplification of the SV40-IFN-beta 1 DNA were obtained. Such clones constitutively produce up to 350,000 units IFN/ml per 10(6) cells/24 hr, i.e., over 10 times more than fully induced human fibroblasts. In continuous culture with daily changes of medium, accumulation of IFN-beta 1 is constant at a rate of 300,000 molecules per cell/hr. Batches of up to 16 mg of IFN-beta 1 produced by the transformed CHO cells were purified to homogeneity by affinity chromatography on monoclonal antibodies. This IFN appears identical in size, activity, and immunospecificity to the native human IFN-beta 1 glycoprotein.

Animals↗
PubMed1984

Type I and Type II interferon receptors.

Binding site competition studies of 125I-interferon (IFN)-gamma were performed with homogeneous preparations of IFNs alpha 2, beta, and gamma. It was found that only IFN-gamma could compete for the specific binding site of 125I-IFN-gamma in both WISH and FS11 cells. Thus, a clear distinction between the receptor of IFN- alpha and beta on one hand, and the receptor of IFN-gamma on the other hand, was obtained. This result is unambiguous because all IFN preparations which were used were purified to homogeneity by specific monoclonal antibody immunoaffinity chromatography. We propose to assign the names "Type I" for the receptor of IFN-alpha and IFN-beta, and "Type II" for the specific receptor of IFN-gamma.

Binding, Competitive↗
PubMed1984

Effects of graded insulin therapy on cardiac function in diabetic rats.

To determine the effects of graded insulin therapy on cardiac function and biochemistry, rats were made diabetic by streptozotocin (50 mg/kg) and subsequently treated with either 3 U of insulin per day (D3) or 5 U/day (D5) and compared with untreated diabetic rats (D phi) and a nondiabetic control group (C). Blood glucose, water consumption, and heart and body weights in D3 and D5 showed dose-dependent responses between those of D phi and C. Cardiac function was studied at similar heart rates and similar left atrial and aortic pressures in an isolated working heart apparatus. Hearts from D phi showed significant decreases in end-diastolic pressure, peak left ventricular systolic pressure, and positive dP/dt, whereas these values in D3 and D5 were similar to those in C. The isovolumic relaxation period was significantly longer in the D phi group, intermediate between D phi and C in D3, and the same in D5 and C. Ca2+-ATPase activity of myosin and actin-activated Mg2+-ATPase activity was depressed in D phi, partially corrected in D3, and completely corrected in D5. Myosin isoenzyme distribution displayed a shift from the predominant V1 pattern observed in C to a predominant V3 pattern in D phi. Treatment with 3 U of insulin per day partially corrected the isoenzyme abnormality, and treatment with 5 U/day restored the isoenzyme distribution to normal. These results indicate that gross cardiac contractile function can be normalized with insulin dosages that are not sufficient to correct hyperglycemia, polydipsia, or body and heart weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗