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B Goldstein

Publications and source records attributed to B Goldstein.

At least 181 records · Page 10Linked to original sources
PubMed1982

Kinetic analysis of histamine release due to covalently linked IgE dimers.

We present a kinetic model of histamine release from human basophils due to covalently linked IgE dimers. Comparison of theory with experiment shows that the model gives a good description of histamine release by IgE dimers and allows a number of the parameters of the model to be determined. Comparison with previous models of release by conventional antigens indicates that despite their covalent structure, IgE dimers are subject to the same laws governing inactivation as are antigen produced crosslinks. In addition, the kinetic equation which relates the rate of histamine release to the number of crosslinked Fc epsilon receptors per cell is the same for crosslinks formed by IgE dimers as for antigen induced crosslinks. Quantitative fitting of histamine release data also yields a value for the rate constant for crosslink formation by IgE dimer on the cell surface (rx approximately 5 x 10(-10) cm2/sec). This rate constant is remarkably high and indicates that the reaction is diffusion controlled.

Basophils↗
PubMed1982

Studies on the mechanism of the enhancement of the antihypertensive activity of captopril by a diuretic in spontaneously hypertensive rats.

Captopril (30 mg/kg/day orally for two days) in spontaneously hypertensive rats (SHR) inhibited serum angiotensin converting enzyme (ACE) activity 92.3%; increased plasma renin activity (PRA) 18-fold and reduced mean arterial blood pressure (MABP) 19 mm Hg. Hydrochlorothiazide (HCTZ) (100 mg/kg-day 1; 10 mg/kg-day 2, orally) increased PRA 3-fold but did not affect serum ACE or MABP. HCTZ plus captopril inhibited serum ACE 95.2%; increased PRA 38-fold and reduced MABP 47.5 mm Hg. Captopril or HCTZ plus captopril did not alter the responses of isolated aortic strips to norepinephrine (NE), serotonin, angiotensin II (AII) or isoproterenol. Pressor responses of conscious SHR to AII and NE were unaltered by captopril or HCTZ plus captopril although the bradykinin-induced depressor responses were significantly but equally potentiated. These results suggest that the potentiating effect of HCTZ is due to some mechanism that shifts the animal's blood pressure maintenance system to a renin-dependent state and is not due to changes in vascular reactivity.

Angiotensin II↗
PubMed1982

The epidemiology of indoor nitrogen dioxide in the U.K.

The results of three studies on the effect of gas cooking on the lung function of children are reported. The studies which have been carried out in England and Scotland with children aged 6-11, 6-7 and 5-6 years, respectively, show that there is only a weak association between indoor levels of NO2 and respiratory illness. Nevertheless, the consistency of the difference in the rate of respiratory diseases in children from homes with electric and gas cookers suggest there is some hazard to the use of unflued gas appliances which may warrant further epidemiological investigation.

Child↗
PubMed1981

Analysis of coated pit recycling on human fibroblasts.

The recycling to the cell surface of previously internalized coated pits has been proposed as a likely mechanism for the rapid regeneration of coated pits on human fibroblast surfaces at 37 degrees C (1). We present a general mathematical model of coated pit recycling for the case when the coat cycles as a single unit, and use it to analyze certain time and temperature dependent data obtained by Anderson et al. (1) and Vermeer et al. (2). We show how recycling can account for these data and how this type of data can be used to distinguish between different possible recycling mechanisms. We show that these data are inconsistent with a two compartment model where coat material simply shuttles back and forth between coated pits and short-lived coated vesicles. From these data we estimate for human fibroblasts at 37 degrees C: that the time for a coated pit to be replenished through recycling after it is lost through internalization is greater than 3.5 min; and that at any moment 53% or less of the cell's clathrin that is involved in coated pit recycling is on the cell surface.

Cell Membrane↗
PubMed1981

Interactions of low density lipoprotein receptors with coated pits on human fibroblasts: estimate of the forward rate constant and comparison with the diffusion limit.

We present a theoretical study of the interaction of low density lipoprotein (LDL) receptors with coated pits. From published experiments we estimate that the forward rate constant, k+, for the binding of a LDL receptor to a coated pit on a human fibroblast at 37 degrees C is greater than or equal to 3 X 10(-10) cm2/sec, and the mean time an LDL receptor spends on the cell surface before being captured by a coated pit, tc, is less than or equal to 1.8 min. If, when an LDL receptor enters, it remains within the coated pit until the coated pit pinches off to form a coated vesicle, then k+ = 3 X 10(-10) cm2/sec and tc = 1.8 min. We derive expressions for the diffusion limit of k+ and tc when particles (LDL receptors) diffuse in two dimensions until they hit and are absorbed by circular absorbers (coated pits) that have finite lifetimes. The absorbers appear and disappear at equal rates so that their concentration remains constant. We use these expressions to show that a diffusion limit of k+ = 3 X 10(-10) cm2/ sec would be obtained if D, the diffusion coefficient for an LDL receptor on a human fibroblast at 37 degrees C equaled 3.3 X 10(-11) cm2/sec. Because this value is in agreement with the experimentally determined value for D, we conclude that random insertion of LDL receptors into the plasma membrane, followed by pure diffusional motion of LDL receptors on the cell surface until they are irreversibly absorbed in coated pits, is consistent with experiment.

Cell Membrane↗
PubMed1981

Qualitative characteristics of histamine release from human basophils by covalently cross-linked IgE.

We have studied the effects of permanent oligomers of human IgE produced using the cross-linking reagent, dimethyl suberimidate, on histamine release from human basophils. IgE dimers were found to be sufficient stimuli for both release and desensitization of these cells; monomeric IgE had no effect. Histamine release was augmented by deuterium oxide (D2O) in the medium, but D2O was not an absolute requirement to observe release. Desensitization by the dimeric IgE was specific in that the response to anti-IgE was not affected by preincubation of the leukocytes with the IgE dimer under suboptimal releasing conditions. IgE trimers and higher oligomers of IgE also caused both release and desensitization. IgE trimers were 3- to 4-fold more effective than IgE dimers with regard to the amount required for 50% histamine release. Dilution studies with monomeric IgE suggested that the difference was due to the presence of more "active" dimers in the trimeric IgE fractions. We conclude that dimeric IgE, by juxtaposing 2 receptors on the basophil membrane, is the "unit signal" for both release and desensitization of these cells.

Animals↗
PubMed1981

Tinnitus classification: medical audiologic assessment.

Medical-audiologic assessment for tinnitus classification is essentially an attempt to objectivize the subjective complaint. An attempt is made to classify the symptom by a pattern of test results including: 1. Audiologic test findings; 2. Vestibular test findings; 3. Tinnitus description, by frequency spectrum and intensity level; 4. Residual inhibition, both its presence or absence, and its duration; 5. Masking-curve data and typing of homolateral and contralateral curves of narrow band and pure tone where applicable. The collection of these data is necessary to establish etiology in terms of the medical site of the lesion, audiological site, and tinnitus site. The audiologist and the otologist must work together to establish the proper diagnosis and develop the most effective treatment for the patient who presents tinnitus as the chief complaint.

Female↗
PubMed1980

Theory of equilibrium binding of a bivalent ligand to cell surface antibody: the effect of antibody heterogeneity on cross-linking.

We investigate the equilibrium binding of symmetric bivalent ligands to a heterogeneous population of symmetric bivalent cell surface receptors. The receptors are heterogeneous in their binding affinities (equilibrium binding constants) for the ligand. For any distribution of receptor binding affinities we show how to calculate the total concentration of receptors that are cross-linked by the ligand, i.e., the concentration of cell surface aggregates composed of two or more receptors, as well as the concentration of any given aggregate. We show that certain qualitative properties of cross-linking which hold for homogeneous antibody populations fail to hold in the heterogeneous case. We use our results to interpret certain in vitro experiments in which synthetic bivalent haptens are used to trigger histamine release from basophils which have on their surface antibody specific for the hapten.

Animals↗
PubMed1980

Optimal strategies in immunology III. The IgM-IgG switch.

During a primary immune response generally two classes of antibody are produced, immunoglobulin M (IgM) and immunoglobulin G (IgG). It is currently thought that some lymphocytes which initially produce IgM switch to the production of IgG with the same specificity for antigen. During a secondary immune response IgG is the predominant antibody made throughout the response. In this paper we address the question of why such apparently complicated modes of response should have been adapted by evolution. We construct mathematical models of the immune response to growing antigens which incorporate complement dependent cell lysis. By comparing the times required to eliminate antigen we show that under certain conditions it is advantageous for an animal to switch some of its lymphocytes from IgM to IgG production during a primary response, but yet to secrete only IgG during a secondary response. The sensitivity of such a conclusion to parameter variations is studied and the biological basis and implications of our models are fully discussed.

Animals↗
PubMed1980

Familial mitochondrial myopathy with cataract.

A 62-year-old female had severe progressive ophthalmoplegia associated with facial, pharyngeal and limb muscle involvement. When 40, she had undergone surgery for bilateral cataract present for about 20 years. Biopsies of skeletal muscles indicated myopathy; histochemistry and electron microscopy gave evidence of abnormal mitochondria in type I fibres. Bilateral cataract needing surgical treatment at 32 was the prominent symptom in her daughter, then with only mild facial weakness. Despite absence of ophthalmoplegia, similar pathological changes were observed in an inferior oblique muscle. The child of the former, a 10-year-old clinically healthy boy, had been surgically treated for a bilateral cataract at the age of 3. As indicated by a review of literature, cataract is not an exceptional occurrence in this particular type of ocular myopathy and therefore should be included within its multisystem associations. The same HLA haplotype (A2-B21) was found in the three patients.

Adult↗
PubMed1980

A model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils.

We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.

Basophils↗
PubMed1979

Scleral buckles and rotation of the ciliary body.

Angle closure glaucoma is a well-known complication of scleral buckling and it is of particular interest when it occurs in eyes with previously normal angles. Forward rotation of the ciliary body about the scleral spur has been postulated as one possible mechanism for such angle closure. Large buckles were used in macaque rhesus monkeys and histopathologic examination indicated rotation of the ciliary body about the scleral spur as the cause of angle closure. Pupillary block was not present and large choroidal detachments were not needed to produce the observed closure. The exaggerated buckles used do not allow these monkeys to serve as a clinical model and great caution is stressed in making clinical extrapolations.

Animals↗
PubMed1979

Two malignant pleural mesotheliomas with unusual histological features.

Morphologically, mesotheliomas may be composed of epithelial and/or sarcomatous elements with various patterns, such as tubular, papillary, tubulopapillary, and diffuse epithelial or mixtures of these. Two cases are descirbed in which, in addition to typical mesothelioma, there was cartilage with foci of calcification and ossificated with the mesothelioma, which suggested that they formed an integral part of the tumour. One of the cases also showed a cuff of cartilage and bone round blood vessels and bronchioles in the lung parenchyma. The patholgenesis could be explained if the mesothelial cell is considered to be totipotent and able to give rise to epithelial and connective tissue elements. Other theories that must be considered are: that there are two separate neoplasms; that there is a circulating substance, perhaps induced by the mesothelioma, which stimulated the cartilage and bone formation; and that the cartilage and bone were due to a previous or associated infection such as tuberculosis. Calcification is also common in asbestotic pleural plaques.

Adult↗