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Biomedical subjects

R Levy

Publications and source records attributed to R Levy.

At least 685 records · Page 38Linked to original sources

Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma.

We have studied the clinical effects of a murine monoclonal anti-human T-cell antibody in seven patients with T-cell lymphoma. Four to 17 treatments with anti-Leu-1 were given to each patient over periods of 14-75 days. Doses of antibody ranged from 250 micrograms to 100 mg. Antibody treatments usually caused a rapid fall in circulating T cells, with return to baseline levels within 24-48 hr. The optimum dose appeared to vary for each patient. Clearance of circulating tumor cells correlated with the amount of antibody bound to cells. Other than dyspnea in one patient, no serious toxicity was noted. Five patients had definite tumor responses, but these were of short duration (1.5-4 mo). Four patients developed anti-mouse immunoglobulin (Ig) antibodies, and in three patients, this was responsible for tumor escape from therapy. Although 95% of the host anti-mouse Ig response was directed against mouse Ig constant region determinants, a small but significant component was found to be antiidiotype.

Adult↗

Down regulation of enkephalin (delta) receptors. Demonstration in membrane-bound and solubilized receptors.

The pentapeptide leucine enkephalin induced down-regulation of enkephalin receptors in neuroblastoma-glioma NG108-15 hybrid cells in a reversible fashion, whereas the stable enkephalin analogue D-Ala2-Met-enkephalinamide (AMEA), and the potent opiate alkaloid, etorphine, had a prolonged effect. The opiate alkaloid, morphine, which has low affinity to delta-type enkephalin receptors of these cells did not induce down-regulation, whereas AMEA decreased the binding of both opiate agonists and antagonists but had no effect on the binding of the alpha 2-adrenergic ligand, [3H]yohimbine. From several experiments that were designed to remove the tightly bound AMEA, and from experiments with solubilized receptor we ruled out the possibility that the decreased binding capacity of enkephalin-treated cells reflects only receptor masking. The study suggests that down-regulation of enkephalin receptors that may also occur in vivo can account for some of the abnormal physiological responses of subjects treated chromically with opiates. However, since opiates from the morphine type can induce opiate tolerance in vivo, but not down-regulation of enkephalin receptors in the cultured cells, we suggest that down-regulation of delta-type opiate receptors may not be prerequisite for the development of the physiological tolerance/dependence on these alkaloids.

Alkaloids↗

[Horton's disease: retrospective study of 33 cases and review of the literature].

Temporal arteritis is still often overlooked in 1982 as shown by the diagnostic delay reported in a retrospective review of 33 patients and in the series previously published in the medical literature. Clinical features to be especially kept in mind are the occasional nature of temporal signs, the pathognomonic value of jaw claudication and the existence of signs which may constitute a premonitory syndrome of blindness. The frequent rise in alkaline phosphatase levels is often misleading. In patients over 65 with an unexplained inflammatory syndrome, biopsy of both temporal arteries should be promptly performed, prior to the unpleasant and costly investigations designed to detect an occult carcinoma. Corticosteroids are still the best treatment of giant cell arteritis but the optimal initial dosage remains unknown as no data from randomized trials are available. Symptomatic relapses have been reported up to 10 years (5 years for ocular symptoms) after onset of the disease. Because of this protracted course, which makes adequate follow-up difficult to ensure, recovery rates from different series are at variance. The main side-effects of maintenance corticosteroid therapy in these elderly patients are osteoporosis, which warrants systematic countermeasures, and probably an increased rate of atheromatosis.

Adrenal Cortex Hormones↗

A genetic approach to reveal the action of the opiate receptor in selected neuroblastoma-glioma cells. Interaction with alpha-adrenoceptors, calmodulin and Ca2+-ATPase.

Three clones of neuroblastoma-glioma cells that contain low amounts of calmodulin were selected from the NG108-15 cells after several treatments with high concentrations of chlorpromazine. Purified membranes of the three clones had decreased numbers of both alpha-adrenergic and opiate receptors, monitored with [3H]yohimbine and [3H,D-Ala2]methionine encephalinamide, respectively. No changes were observed in the affinity of these radioactive ligands to the receptors of the selected cells as compared to the parent cells. Addition of bovine brain calmodulin did not affect the binding of [3H,D-Ala2]methionine encephalinamide to the membranes of the selected cells and they had the same number of acetylcholine receptors, determined with 1-quinuclidinyl-[phenyl-4-3H]-benzilate, as the parent NG108-15 cells. The basal ATPase activity in the membranes of the selected cells was 35-50% of the parent cells, with a decreased V value and no significant change in the affinity constant Ka to ATP. Addition of Ca2+ to the purified membranes increased the V of the ATPase in the selected as well as the parent cells but the V of the selected cells remained lower than that of the parent cells. Ca2+ had no effect on the Ka to ATP in either cell type. The Ca2+-dependent ATPase activity of both the parent and the selected cells was also calmodulin-dependent dependent since it was blocked in vitro by chlorpromazine. The co-regulation of opiate and adrenergic receptors and their interaction with calmodulin and Ca2+-ATPase is discussed in view of recent observations indicating biochemical and physiological association between opiates, Ca2+ and adrenergic compounds.

Animals↗

A rapid and sensitive ELISA for serum ferritin employing a fluorogenic substrate.

A fluorescent enzyme-linked immunosorbent assay is described for the rapid measurement of serum ferritin. Increased sensitivity was achieved by using 4-methyl-umbelliferyl-beta-D-galactopyranoside as the substrate for beta-galactosidase coupled to the purified antiferritin antibody. Further enhancement of the specific antigen-antibody reaction was attained by the addition of 4% polyethylene glycol 6000 to the antiferritin-beta-galactosidase conjugate. The procedure is performed in microELISA plates. These modifications of the method permit the measurement of serum ferritin at concentrations ranging from 0.25 to 50 microgram/liter with a coefficient of variation of 8% or less. The entire procedure is performed at ambient temperature and is completed within one working day. The cost of the assay is less than 10% of the immunoradiometric assay for serum ferritin.

Animals↗

The erythrocyte membrane in essential hypertension. Modified temperature-dependence of Li+ efflux.

The rate of ouabain-resistant Li+-efflux was studied in erythrocytes of normal controls and of patients with essential hypertension. Despite variability in rate, erythrocytes from normotensive persons revealed a uniform pattern of temperature dependence of the efflux, with two slopes (K = 9.4 and 19.1 kcal/mol, respectively) and a transition at about 25 degrees C. Erythrocytes from the patients showed both a higher rate of Li+ efflux and significant changes in the temperature response, with essentially a single slope (Ka = 14 kcal/mol). The data indicate localized changes in the membrane organization of hypertensive erythrocytes, involving lipid-protein interaction.

Acetylcholinesterase↗

Cellular response in humans following vaccination with Gripax influenza virus.

Cellular response of peripheral blood lymphocytes to influenza antigens was measured in a group of young nurse-student volunteers (17-24 years old), following vaccination with a formol-inactivated trivalent influenza vaccine (Gripax). Cord blood lymphocytes (controls) did not react with any of the antigens. This excluded the possibility of any nonspecific mitogenicity of viral antigens. Viability of the cells was indicated by their responsiveness to phytohemagglutinin (PHA). Prior to immunization antigenic recognition to circulating strains (A/England (H3N2) and B/Hong Kong) was found in about 44% of the vaccinees; recognition of the recent strain A/USSR (H1N1) was found in only 10.5%. Following vaccination, approximately 80% of the subjects exhibited cellular response to all three vaccine strains. This includes the negative subjects, who showed an approximate 70% rate of conversion. There was no correlation between the antibody state and cellular response prior to and following vaccination as gathered from matched data of each participant.

Adolescent↗

T-lymphocyte subsets in follicular lymphomas compared with those in non-neoplastic lymph nodes and tonsils.

Using monoclonal antibodies on frozen sections, the authors define the anatomic localization of T-lymphocyte subsets in follicular lymphomas as well as in nonneoplastic lymph nodes and tonsils. The percentage of Leu-1+ T cells in the follicles of follicular lymphomas (20 per cent) was virtually identical to that seen in the follicles of nonneoplastic lymph nodes or tonsils (22 per cent). There were 50 per cent T cells in the interfollicular regions of follicular lymphomas and 75 per cent in the paracortical regions of the nonneoplastic specimens. In neoplastic follicles the number of Leu-3a+ cells was 67 per cent of the number of Leu-1+ cells, whereas, virtually the entire T-cell population in the nonneoplastic follicles expressed the Leu-3a antigen. These T cells of helper phenotype may facilitate the neoplastic process or an immune response against it or may be bystanders to the B-cell proliferation. Hum Pathol 13:618-625, 1982

Antibodies, Monoclonal↗

Multiple HLA-DR antigens: detection with monoclonal antibodies and translation in vitro.

L203 and L227 are mouse monoclonal antibodies specific for human HLA-DR antigens. Their reactivity with multiple, structurally different, HLA-DR antigens was examined by using radioiodinated human lymphoblastoid cells and cell lines, heterozygous or homozygous at the HLA-D locus. Antibody L203 precipitates DR antigens composed of 34,000 Mr heavy chains (alpha), and 28,000-29,000 Mr light chains (beta). Antibody L227 recognizes two other species of DR antigens. Their heavy chains have similar molecular weights of 34,000 but their light chains are different, one (beta) being 28,000-29,000 Mr and the other (beta') 23,000-25,000 Mr. Whereas L203 is directed against a combinatorial determinant generated by both DR chains, L227 is able to recognize each of the two light chains alone and reprecipitate them after their separate elution from sodium dodecyl sulfate gels. Poly(A)-containing mRNA was isolated from Raji cells and translated in vitro by microinjection in Xenopus oocytes. The oocytes translated and fully assembled all the DR molecules recognized by L203 and L227 antibodies.

Animals↗

A re-evaluation of an automated tailored test of concept learning with elderly psychiatric patients.

Aspects of a revised version of the Picture Matching Test were evaluated in a sample of 33 elderly psychiatric patients. The new version of the test shared many defects of the older form, e.g. an uneven increase in levels of difficulty and a low ceiling. The derived speed of response measure was more closely related to the way in which the system responded to a subject's errors than to any of the other more direct measures of a subject's performance. Furthermore, there was no evidence to suggest that the method of controlling for practice effects, as suggested by the test's distributors, would be effective.

Aged↗

99mTc-HIDA cholescintigraphy in Dubin-Johnson and Rotor syndromes.

99mTc-HIDA cholescintigraphy was performed in 6 patients with Dubin-Johnson syndrome and 1 patient with Rotor syndrome. In the patients with Dubin-Johnson syndrome, the cholescintigrams had a characteristic pattern of delayed visualization or nonvisualization of the gallbladder and bile ducts in the presence of intense, homogeneous, and prolonged visualization of the liver. In the patient with Rotor syndrome, the hepatobiliary system was not visualized at all. It is concluded that 99mTc-HIDA cholescintigraphy may be helpful in the diagnosis of Dubin-Johnson syndrome and Rotor syndrome and in the differential diagnosis between these two conditions.

Diagnosis, Differential↗

Prediction of outcome in senile dementia--a computed tomography study.

Forty patients suffering from senile dementia who had been subjected to detailed clinical and psychological assessment and computed tomography (CT) were followed up for a mean period of 28.78 months. All but one were traced. The deceased (27) were compared with the survivors (12). All males had died at follow-up. The mean age was not statistically significant, but the survivors differed significantly from the deceased in having performed better on a number of clinical and psychological tests, particularly those involving speech functions and constructional ability. Measures of ventricular size and cortical atrophy were not of predictive value, but a new technique of measuring radiological density showed that this was significantly lower in the right parietal region in the original CT scans of those who subsequently died. The study confirms that clinical involvement of the parietal lobes is an indication of poor prognosis and reports the first radiological support for this view. It also suggests that a more directly quantitative approach to computed tomography may yield results which are more useful than those obtained from visual reconstructions.

Aged↗

Fluctuations of free choline levels in plasma of Alzheimer patients receiving lecithin: preliminary observations.

Plasmas of 12 patients currently taking part in a double-blind trial of lecithin in senile or presenile dementia of Alzheimer type were analysed for plasma choline levels at fixed intervals during lecithin treatment. The values were not maintained at a constant level and showed a decline after one or two months of treatment, often followed by a subsequent rise. Possible explanations for this observation are given, and its significance to the treatment of dementia discussed.

Aged↗