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Biomedical subjects

M Geller

Publications and source records attributed to M Geller.

At least 55 records · Page 3Linked to original sources
PubMed1986

Brief survey of scope and limitations of quantum and statistical mechanical methods.

An attempt is made to delineate the scope and limitations, and future perspectives, of the theoretical methods being applied increasingly to various aspects of drug design and associated problems. The two methods of approach, quantum mechanics and statistical physics (Monte Carlo, Molecular Dynamics), are used to evaluate such properties as electron density distribution, structure and conformation, intermolecular interactions, etc. for isolated molecules and their autoassociates, and for interactions with the environment (e.g., solvent, receptor molecules). The validity of such calculations, dependent on factors such as geometrical optimalization, correlation energy and differing approximations of the form of the wave function, is illustrated in the case of enol-keto tautomerism of nitrogen heterocycles, relevant to the biological (including chemotherapeutic) activities of some nucleoside analogues. Intermolecular interactions, including the role of solvent, are assessed for purine and pyrimidines. The scope of the Molecular Dynamics methods is exemplified by its application to the mode of action of lysozyme.

Drug Compounding↗
PubMed1984

Primary culture of isolated adipocytes. A new model to study insulin receptor regulation and insulin action.

The mechanism by which insulin regulates cell surface insulin receptors was examined in primary cultured rat adipocytes. When cells were incubated in insulin-free medium, specific 125I-insulin binding progressively increased over 3-4 days followed by a plateau of binding. Insulin prevented up-regulation at low doses (1 ng/ml), while higher doses (5-25 ng/ml) resulted in a net loss of surface receptors. A lag period of 4-6 h preceded insulin-induced changes in receptor number, and such a lag was seen prior to the inhibitory effect of insulin on the insertion of nascent receptors into the plasma membrane. Regulation of surface receptors continued after the removal of insulin, consistent with the idea that insulin generates a signal which can sustain receptor regulation in the absence of ligand. Thus, a 1-h insulin pulse (100 ng/ml) was sufficient to block up-regulation, whereas longer exposure times (4-12 h) produced a net loss of surface receptors. When cells were exposed to insulin for a fixed time (5 h), subsequent receptor loss was insulin dose-dependent. Thus, the net number of cell surface insulin receptors is determined by both insulin concentration and the duration of insulin exposure. Time course studies after a 12-h insulin pulse revealed a progressive loss of surface receptors for up to 36 h. At later times receptor number returned toward control values, thus demonstrating that triggering of receptor regulation is reversible. To determine whether insulin-induced down-regulation was mediated by receptor loss, or by receptor translocation to an intracellular site, we measured receptor distribution (cell surface and intracellular pools) in control and 72-h insulin-treated adipocytes. These data revealed that down-regulation was mediated by a net loss of receptors rather than by receptor redistribution. An early biological response of adipocytes to insulin is rapid endocytosis of insulin-receptor complexes, and we found that insulin plays an important role in regulating this endocytotic uptake rate. Thus, compared to freshly isolated cells, adipocytes cultured for 72 h in insulin-free medium had an enhanced ability to internalize both insulin and insulin receptors, whereas cells chronically treated with insulin endocytosed insulin-receptor complexes at a much slower rate. These data are interpreted as an insulin-mediated change in one of the cellular responses of adipocytes to the biological action of insulin.

Adipose Tissue↗
PubMed1984

Brainstem auditory evoked responses in the newborn lamb. Studies during postnatal development and acute hypoxia.

Brainstem auditory evoked responses (BAER) have been studied in several species and have provided a neurophysiologic 'window' into brainstem function. We have pursued further studies in the newborn lamb and adult sheep. BAER amplitude increased as the stimulus intensity increased from 45 to 95 dB and as the click frequency decreased from 88.8 to 22.2 Hz. BAER latency increased as both the stimulus intensity decreased and the click frequency increased. Developmental studies were performed between the 2nd and 35th day of life in the newborn lamb. No significant change in either latency, amplitude, or wave morphology was noted in contrast to other species where developmental changes are prominent. This was due to both the prenatal maturation of the lamb's brain and to the relatively short interval of the postnatal studies. We also studied the effect of prolonged severe hypoxia and acidosis on the BAER in the newborn lamb and found no significant change in either the amplitude or latency of the response.

Acidosis↗
PubMed1981

Short-term efficacy trial and twenty-four-month follow-up of flunisolide nasal spray in the treatment of perennial rhinitis.

Seventy-eight patients with perennial rhinitis underwent a double-blind, placebo-controlled. 12-wk trial with flunisolide nasal spray, a new potent topical steroid. Eighteen of these patients were followed in an open study and evaluated at intervals for side effects and dosage of spray used. Baseline and plasma cortisol concentrations were performed before and at the end of the 12-wk, double-blind period. Adrenocorticotropic hormone (ACTH) stimulation testing was performed on six patients after 1 yr of flunisolide therapy at 300 micrograms/day or less. Flunisolide was found to be safe and effective over a short period. Over a 2-yr follow-up there were no serious side effects or evidence of adrenal suppression. Ten patients with perennial rhinitis continue to obtain subjective benefit after 2 yr of therapy with flunisolide nasal spray.

Administration, Intranasal↗
PubMed1981

Skin test sensitivity to Acacia pollen in Brazil.

A total of 36 patients with asthma and/or rhinitis were evaluated for the presence of allergy skin sensitivity to Acacia pollen in Brazil (eastern and southern regions). Only four patients showed mild intradermal skin test reactions to Acacia pollen extract (1,000 PNU/ml). Despite being largely distributed in those regions, Acacia pollen is not an important allergen involved in the pathogenesis of respiratory atopy in Brazil.

Adolescent↗
PubMed1980

Studies on Alternaria allergens. III. Isolation of a mafor allergenic fraction (ALT-I).

The allergens present in crude Alternaria alternata extract were fractionated by sequential ammonium sulfate precipitation, DEAE cellulose ion-exchange chromatography, preparative flat-bed electrofocusing, and Sephadex G-100 gel filtration. The carbohydrate-rich fraction isolated (Alt-I) was heterogeneous by polyacrylamide gel disc electrophoresis and by thin-layer electrofocusing. By preparative polyacrylamide gel electrophoresis the Alt-I fraction could be further separated into at least five subfractions, all of which contained similar allergenic activity. Significant elevations in IgE antibody to Alt-I were found in 21

Allergens↗
PubMed1980

HLA antigen frequencies and natural history in Alternaria-sensitive and perennial nonallergic asthmatics.

The frequency of HLA-A, -B, and -C loci antigens in random populations of Alternaria-sensitive (N = 100) and perennial nonallergic asthmatics (N = 87) were compared with age- (+/- 5 yr) and sex-matched controls from the same geographic region. There was no association between HLA antigens as measured by frequency analyses and Alternaria-sensitive or perennial nonallergic asthma. Moreover there was no association between HLA antigens and the age of onset of asthma, associated allergic disorders, various environmental factors provoking asthma, total serum IgE levels, and Alternaria-specific IgE antibody.

Adult↗
PubMed1980

Serum IgE levels in toxoplasmosis.

Elevated levels of serum IgE are found in many helminthic parasitic diseases. The authors have previously demonstrated that giardiasis, amoebiasis and Chagas' disease were not associated with hyperimmunoglobulinaemia E. To determine the influence of toxoplasma gondii on IgE levels of clinically symptomatic patients, a controlled study was performed. There was no difference found between the serum IgE values from Brazilian patients with toxoplasmosis and those from matched healthy Brazilian controls. This again confirms that protozoan parasitic infections do not increase serum IgE levels.

Amebiasis↗
PubMed1978

Absence of inhibitory effect of leprosy sera upon normal E rosetting.

Inhibitory serum factors in certain infectious diseases (leprosy, tuberculosis, histoplasmosis) and malignant conditions (Hodgkin's disease, primary intracranial neoplasms) are said to be partially responsible for decreased cell-mediated immunity (CMI) and consequent anergy. The immunologic derangement in leprosy is not yet completely understood. In order to determine the effect of sera from patients with leprosy upon the rosetting capacity of normal T. lymphocytes, sera from untreated lepromatous (L) and tuberculoid (T) patients were studied. Control sera were obtained from normal volunteers and from patients with other dermatologic conditions (contact dermatitis and leg ulcer). The data indicated that test sera did not inhibit either spontaneous E rosette formation or active rosetting of normal lymphocytes.

Adolescent↗
PubMed1978

Serum IgE levels in giardiasis.

Raised levels of serum immunoglobulin E are found in many parasitic diseases. In order to determine the influence of Giardia lamblia on IgE levels of clinically symptomatic patients, a controlled study was performed. There was no difference between the serum IgE values from Brazilian patients with giardiasis and those from normal Brazilian controls, although in both groups there were many individuals with values higher than the normal range reported from the northern hemisphere.

Adolescent↗
PubMed1978

HLA antigen frequencies in allergic bronchopulmonary aspergillosis.

The frequency of HLA antigens in twenty-two Caucasian patients with allergic broncho-pulmonary aspergillosis (ABPA) and sixty-nine unrelated Caucasian controls was determined. The results indicated that there was no increased frequency of a specific HLA antigen in patients with ABPA. Moreover, studies in thirteen families of ABPA patients also demonstrated that, within families, there was no consistent association between a specific haplotype and asthma, allergies or hay fever.

Adolescent↗
PubMed1978

Serum IgE levels in Chagas' disease.

Elevated levels of serum immunoglobulin E are found in many parasitic diseases caused by helminths. We have previously demonstrated that giardiasis was not associated with hyperimmunoglobulinaemia E. In order to determine the influence of Trypanosoma cruzi on IgE levels of clinically symptomatic patients, a controlled study was performed. There was no difference between the serum IgE values from Brazilian patients with Chagas' disease and those from matched healthy Brazilian controls. We suggest that protozoan parasitic infections do not increase serum IgE levels.

Adult↗