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Biomedical subjects

D Goldblatt

Publications and source records attributed to D Goldblatt.

At least 145 records · Page 8Linked to original sources
PubMed1980

Antigenicity of histones in various chromatins.

Antisera specific to purified histone fractions are used to assess the antigenicity of the histones present in chromatin derived from various sources. The results indicate that the antigenicity of the histones present in chromatin is markedly diminished as compared to the antigenicity of the histones free in solution. The antigenicity of histones in chromatins derived from three different tissues of the rat is very similar. The antigenicity of the histones present in chromatin derived from calf thymus is higher than that of the histones present in rat thymus. It is concluded that the major reason for diminished antigenicity of histones in chromatin is that the histones are complexed in the nucleosome conformation and that the antigenic determinants residing in histones in various chromatins are exposed to similar degrees.

Animals↗
PubMed1980

Muscle insulin resistance in myotonic dystrophy: effect of supraphysiologic insulinization.

In myotonic dystrophy, there is resistance of forearm muscle to physiologic concentrations of insulin. To determine whether this resistance is due to a shift in the dose-response curve resulting from decreased numbers of insulin receptors, we measured the effects of supraphysiologic insulinization (200 mu U per kilogram per minute) on the uptake of glucose by forearm muscle in three patients with myotonic dystrophy and five denervated patients with comparable wasting. Although insulin levels were higher in patients with myotonic dystrophy than in controls, peak glucose uptake remained significantly lower in myotonic dystrophy patients. The findings are consistent with a postinsulin receptor defect of muscle and with altered membrane function in myotonic dystrophy.

Adult↗
PubMed1979

Computerized tomography in acute hemorrhagic leukoencephalopathy: a case report.

Computerized tomography in a case of acute hemorrhagic leukoencephalopathy showed extensive bilateral white matter damage, which resolved almost completely. The patient's near-complete recovery from the disease is followed by serial CT scans, suggesting that initial bilateral demyelinization is followed by slow remyelinization rather than disappearance of edema. CT scanning proves to be useful in the diagnosis and follow-up of white matter diseases.

Acute Disease↗
PubMed1978

Double-blind evaluation of deanol in tardive dyskinesia.

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

Adult↗
PubMed1978

Huntington's disease: treatment with muscimol, a GABA-mimetic drug.

Muscimol, a gamma-aminobutyric acid (GABA) analogue that exerts potent and specific agonist effects on GABA receptors, was administered orally to 10 patients with Huntington's disease. In this double-blind study, muscimol treatment did not result in improvement in these patients' motor or cognitive functions. However, muscimol administration did ameliorate chorea in the most severely hyperkinetic patient, and it was associated with the appearance of dystonic features, electroencephalographic changes, and behavioral alterations in some patients. These latter observations support a functional relationship between GABA-ergic activity and the genesis of both systonia and EEG abnormalities in humans. The therapeutic failure of muscimol indicates that the GABA disturbances in Huntington's disease does not alone account for the clinical features of this disorder.

Activities of Daily Living↗
PubMed1978

A micromethod for preparation of human macrophage cultures for the study of lymphocyte-macrophage interaction in immune interferon production and blastogenesis.

A new economical and reproducible micromethod for the preparation of human macrophage cultures in wells of a microtiter plate is described. The technique has been employed for the study of events which occur in the interaction of lymphocytes with macrophages in PHA-stimulated immune interferon production and blastogenesis. By comparison with the current Leighton tube macroculture systems, the microculture technique yielded a 7-fold increase in the number of macrophage cultures and a 5-fold increase in the number of T lymphocyte macrophage cultures from a given volume of blood. The replicability from sample to sample with regard to 3H-thymidine incorporation and amount of interferon produced is better in the microculture system than in the Leighton tube system. Such a microculture technique will thus provide a system whereby ready analysis of monocyte-macrophage function and interaction with lymphocytes in numerous disease states can now be realized.

Cell Adhesion↗
PubMed1978

Decreased insulin sensitivity of forearm muscle in myotonic dystrophy.

Previous studies of patients with myotonic dystrophy have demonstrated hyperinsulinism after glucose loading. This hyperinsulinism has been attributed by some investigators to tissue insulin resistance. We have directly studied insulin sensitivity of forearm muscle in patients having such hyperinsulinism. The effect of an intrabrachial arterial insulin infusion (100 mu U/kg per min) on glucose uptake was determined in six cases of myotonic dystrophy, six normal subjects, and in seven disease control subjects with myotonia or wasting from other disorders. There was no significant difference in insulin tolerance comparing myotonic dystrophy patients to the normal and disease control groups. Glucose tolerance and basal insulin levels were normal in the myotonic dystrophy patients, but hyperinsulinism occurred after glucose ingestion. After 25 min of intra-arterial insulin, the mean peak muscle glucose uptake in myotonic dystrophy was 2.54 +/- 0.54 mu mol/min per 100 ml forearm compared to 5.24 +/- 0.86 mu mol/min per 100 ml for disease controls (P is less than 0.05). Myotonic dystrophy patients showed a peak glucose uptake increment of only 2.6 +/- 0.2-fold over basal contrasted with the disease control value of 6.5 +/- 1.0-fold (P is less than 0.02) and the normal control value of 8.8 +/- 1.1-fold (P is less than 0.01). Thus, there was an absolute as well as a relative decrease in muscle insulin sensitivity in myotonic dystrophy patients compared to both control groups. The peak increments in arterio-superficial venous glucose concentration differences after insulin infusion were not significantly different comparing myotonic dystrophy and control groups. These data suggest that in myotonic dystrophy, there is insulin insensitivity of skeletal muscle.

Adult↗
PubMed1977

Molecular homogeneity of the histone content of HeLa chromatin subunits.

Interaction of affinity chromatographically purified antihistone H3 and antihistone H4 with isolated HeLa core particles, followed by separation of unreacted and reacted particles by sedimentation, demonstrates that every core particle contains these histones. Taken together with our previous data indicating the presence of H2B in every nucleosome (Simpson, R. T., and Bustin, M. (1976), Biochemistry 15, 4305), these data lead to the conclusion that each core particle contains two each of the four smaller histones. In contrast to the lack of interference in binding of more than one molecule of antibody to a single species of histone to the core particle, steric hindrance exists when attempts are made to bind both anti-H3 and anti-H4 to core particles.

Antibodies↗
PubMed1977

Slow eye movements, with absent saccades, in a patient with hereditary ataxia.

Saccadic and smooth eye movements are controlled by separate mechanisms within the nervous system. We describe a patient with familial ataxia, considered to be a form of olivopontocerebellar degeneration, who is incapable of generating reflex or voluntary saccades. She can, however, move her eyes smoothly to the normal limits of lateral gaze, even when her head is prevented from moving. Latency before onset of movement is prolonged, and the velocity of movement is abnormally slow. We postulate that the degenerative process may have affected selectively those cells of the ventral paramedian pontine tegmentum responsible for the generation of saccades; and the the prolonged latency from presentation of a visual stimulus to the onset of movement is related to an inability to generate burst discharges needed to overcome the viscoelastic properties of the orbital tissues.

Adult↗
PubMed1977

Isolation and partial characterization of plasma membranes bearing human fetal-associated antigens.

A rabbit antiserum to first-trimester human fetal tissue had greater reactivity in complement fixation and saturation binding assays with fetal tissues than with both a pool of normal adult lung, liver, and kidney and pools of the individual organs. This anti-fetal membrane reactivity was only partially inhibited by carcinoembryonic antigen. The serum still reacted strongly with human fetal and tumor cells after rendering it specific for plasma membrane components by adsorption to and elution from intact human fetal tissue culture cells. This plasma membrane-specific serum was then used to monitor the purification of the fetal membrane-associated antigens. The fetal antigens copurified with the putative plasma membrane enzymatic markers 5'-nucleotidase and Mg2+-adenosinetriphosphatase through differential and density gradient centrifugation. Insulin-binding activity only partially copurified with the antigenic activity. Little antigenic activity was found in nuclear and mitochondrial fractions. The isolation protocol gives fetal plasma membrane-associated antigens in approximately 50% yield with moderate purification. The sera and isolation procedures described should have general utility for the detection of human oncofetal antigens.

Adenosine Triphosphatases↗
PubMed1976

Chromatin structure visualization by immunoelectron microscopy.

Antibodies elicited in rabbits by chromatin and by purified histone H2B have been used to study the structure of chromatin by immunoelectron microscopy. Chromatin spread on grids reveals a structure of closely packed spherical particles with an average diameter of 104 A, arranged either in clusters or in linear arrays of beads, some of which have a supercoil-like arrangement. No DNA strings connecting the beads could be observed. Upon antibody binding, the diameter of the particles increases up to 300 A. This size is compatible with a model where one layer of gamma globulin molecules 110 A long encircles a sphere of chromatin 100 A in diameter. The presence of rabbit gamma globulins on the enlarged beads has been verified by the addition of ferritin-labeled goat anti-rabbit gamma globulins. Anti-chromatin sera which react with nonhistone proteins but not with free histones or DNA react with more than 95% of the beads; this suggests that most of the beads contain nonhistone proteins. Since the number of nonhistone proteins is large, it is improbable that each sphere contains a full complement of these proteins. We therefore suggest that the various chromatin spheres contain different types of nonhistone proteins. About 90% of the chromatin spheres reacted with antibodies to histone H2B, suggesting the most of the chromatin beads contain this type of histone.

Antigen-Antibody Reactions↗
PubMed1976

Hybridization kinetics of ribonucleic acid and deoxyribonucleic acid from antigen-stimulated mouse spleen cells.

In an attempt to explore the mechanism by which antigenic stimulation alters gene expression in lymphoid cells in vivo, three different hybridization techniques have been used to compare the complexity of the genome of lymphoid cells from normal and from immune BALB/c mice. RNA/DNA hybridization experiments at a DNA excess of 1000 demonstrated that normal RNA and immune RNA hybridized identically with DNA extracted from mouse spleen cells before and after immunization and with liver DNA. These findings indicate that DNA sequences complementary to immune RNA or to normal RNA are represented in a number of copies not significantly different in the genome of normal lymphoid cells and in that of immune lymphoid cells. Hybridizations of normal and of immune RNA with normal and immune pulse-labeled DNA, done at RNA excess, detected no differences between these two DNA. However, significant differences were observed in the percentage of DNA hybridized with normal and immune RNA; 3 to 4% of the DNA hybridized with normal RNA and 8 to 9% with immune RNA. This indicates that more DNA sequences are transcribed 48 hr after immunization than before immunization. The RNA exhaustion rates caused by normal and immune DNA were found to be identical, indicating that antigenic stimulation did not induce major changes in the number of DNA base sequences complementary to the RNA tested. However, when normal and immune pulse-labeled RNA were compared by exhaustion with DNA, the immune pulse-labeled RNA obtained 48 hr after immunization displayed a slower exhaustion rate than normal RNA or RNA extracted 72 hr after immunization. These results suggest the temporary synthesis, at a higher frequency, of certain RNA sepcies 48 hr after immunization, as compared to the RNA synthesis in normal, nonimmune cells, or that occurring 72 hr after immunization. Thus, the three experimental approaches used lead to the conclusion that antigenic stimulation does not induce major gene amplification; it does, however, change the transcription rate of certain RNA species.

Animals↗
PubMed1975

Exposure of histone antigenic determinants in chromatin.

The exposure of antigenic determinants of histones present in "native" chromatin was studied by: (1) testing their ability to elicit anti-histone antibodies and (2) measuring their ability to interact with anti-histone sera. To this end, antisera specific to purified histone fractions and to purified rat liver chromatin were elicited in rabbits. The anti-chromatin sera did not react with pure histone fractions and pure histone fractions F2b, F3, F2a1, and F2a2 failed to inhibit the complement fixation resulting from the binding of anti-chromatin to chromatin. These results suggest that in native chromatin, determinants in these histones are not immunogenic. Histone F1, however, inhibited the reaction between chromatin and anti-chromatin. Antisera elicited by histone fractions reacted weakly with "native" chromatin. The maximal complement fixations (obtained with 5-10 mug of chromatin DNA) were as follows: 60% with anti-F2b, 20% with anti-F1 and anti-F3, and less than 5% with either anti-F2a1 or anti-F2a2. Studies of the interaction between anti-histone antibodies and chromatin in which chromatin was used as an immunoadsorbent indicated that antibodies against different histones were adsorbed to a different degree by the same amount of chromatin. Differences in the immunoadsorbing capacity between sonicated and nonsonicated chromatin were found. Quantitative adsorbtion studies revealed that in the "native" chromatin structure, antigenic determinants of F1 and F2b were more available to interact with homologous antibody than those of F3 and F2a1 and that determinants in F2a2 were the least available. It could be calculated that the "equivalent antigenicity" of the histones in chromatin was 9.6% for F1, 3.2% for F2b, and 0.90% for F3 and F2a1. Upon sonication these values did not change for F1 but increased two-, three-, and fourfold for F2b, F3, and F2a1, respectively. Digestion of chromatin with trypsin totally abolished the ability of chromatin to adsorb anti-histone antibodies.

Animals↗