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Biomedical subjects

B Goldstein

Publications and source records attributed to B Goldstein.

At least 145 records · Page 8Linked to original sources
PubMed1990

Supercarbia in children: clinical course and outcome.

Supercarbia (PCO2 greater than or equal to 150 torr) may result in a number of pathophysiologic conditions in experimental models and in humans. We report the clinical course and outcome after supercarbia secondary to hypoventilation in five children. Supercarbia resulted from severe airway obstruction in four children and central hypoventilation in one. Maximal PCO2 values ranged from 155 to 269 torr (mean 206). The time course to development of maximal PCO2 was between 35 min and 2 days. The pH ranged between 6.76 and 7.10 (mean 6.86). No patient was severely hypoxemic (PaO2 less than or equal to 55 torr) during the supercarbia period. Despite very high levels of PCO2 and low pH, the only pathophysiologic change found was temporary depression of neurologic function manifested by stupor or coma. Long-term follow-up of these patients has shown no serious adverse neurologic or developmental effects.

Airway Obstruction↗
PubMed1990

Emergency intraosseous infusion in severely burned children.

Severely burned patients require rapid administration of large volumes of isotonic fluids. Obtaining adequate intravenous (IV) access in children with greater than 70% total body surface area burns may be difficult, time-consuming, and sometimes impossible. This report describes the use of intraosseous infusion technique as a life-saving means of establishing IV access in two severely burned children.

Bone and Bones↗
PubMed1990

Acne fulminans.

The pathogenesis of acne fulminans remains obscure despite extensive investigations discussed in this review, but evidence points toward an immune mediated phenomenon (eg, hypergammaglobulinemia, depressed complement, circulating immune complexes, hematuria, lytic bone lesions, or inflammatory myositis). Whether acne fulminans begins as an autoimmune process de novo, or whether the process is somehow triggered by minimal inflammation in susceptible individuals remains to be elucidated. Acne fulminans is a rare, disfiguring, and disabling disease. It is associated with many problems, including abnormalities revealed in the laboratory or on roentgenogram. We have reviewed past and present therapies. In conclusion, we emphasize the importance of early diagnosis and treatment to decrease the significant morbidity of acne fulminans.

Acne Vulgaris↗
PubMed1990

Combined immunodeficiency associated with xeroderma pigmentosum.

We report a 15-month-old boy with xeroderma pigmentosum, a history of repeated infections, and immune deficiency who developed a fatal pneumonia with parainfluenza type 1. Immunologic evaluation revealed a severe combined immunodeficiency with hypoglobulinemia, C3 deficiency, anergic response to skin testing, and an abnormal lymphocytic response to mitogens. We suggest that patients with xeroderma pigmentosum be evaluated carefully for immune deficiencies, should repeated infections occur.

Agammaglobulinemia↗
PubMed1989

Stannosis. A report of 2 cases.

Stannosis is a condition in which tin-oxide is deposited in lung tissue after inhalation. Tin-oxide is radiologically visible although there is no tissue reaction to its presence. Two examples of the condition are described. It is of value to recognise the condition and so avoid unnecessary invasive diagnostic procedures.

Humans↗
PubMed1989

Competition between solution and cell surface receptors for ligand. Dissociation of hapten bound to surface antibody in the presence of solution antibody.

We present a joint theoretical and experimental study on the effects of competition for ligand between receptors in solution and receptors on cell surfaces. We focus on the following experiment. After ligand and cell surface receptors equilibrate, solution receptors are introduced, and the dissociation of surface bound ligand is monitored. We derive theoretical expressions for the dissociation rate and compare with experiment. In a standard dissociation experiment (no solution receptors present) dissociation may be slowed by rebinding, i.e., at high receptor densities a ligand that dissociates from one receptor may rebind to other receptors before separating from the cell. Our theory predicts that rebinding will be prevented when S much greater than N2Kon/(16 pi 2D a4), where S is the free receptor site concentration in solution, N the number of free surface receptor sites per cell, Kon the forward rate constant for ligand-receptor binding in solution, D the diffusion coefficient of the ligand, and a the cell radius. The predicted concentration of solution receptors needed to prevent rebinding is proportional to the square of the cell surface receptor density. The experimental system used in these studies consists of a monovalent ligand, 2,4-dinitrophenyl (DNP)-aminocaproyl-L-tyrosine (DCT), that reversibly binds to a monoclonal anti-DNP immunoglobulin E (IgE). This IgE is both a solution receptor and, when anchored to its high affinity Fc epsilon receptor on rat basophilic leukemia (RBL) cells, a surface receptor. For RBL cells with 6 x 10(5) binding sites per cell, our theory predicts that to prevent DCT rebinding to cell surface IgE during dissociation requires S much greater than 2,400 nM. We show that for S = 200-1,700 nM, the dissociation rate of DCT from surface IgE is substantially slower than from solution IgE where no rebinding occurs. Other predictions are also tested and shown to be consistent with experiment.

Animals↗
PubMed1988

The distribution of cell surface proteins on spreading cells. Comparison of theory with experiment.

Bretscher (1983) has shown that on uniformly spread giant HeLa cells, the receptors for low density lipoprotein (LDL) and transferrin are concentrated toward the periphery of the cells. To explain these nonuniform distributions, he proposed that on giant HeLa cells, recycling receptors return to the cell surface at the cell's leading edge. Since the distribution of coated pits on these cells is uniform, Bretscher and Thomson (1983) proposed that there is a bulk membrane flow toward the cell centers. Here we present a mathematical model that allows us to predict the distribution of cell surface proteins on a thin circular cell, when exocytosis occurs at the cell periphery and endocytosis occurs uniformly over the cell surface. We show that on such a cell, a bulk membrane flow will be generated, whose average velocity is zero at the cell center and increases linearly with the distance from the cell center. Our model predicts that proteins that aggregate in coated pits will have concentrations that are maximal at the cell periphery. We fit our theory to the data of Bretscher and Thomson (1983) on the distribution of ferritin receptors for the following cases: the receptors move by diffusion alone; they move by bulk membrane flow alone; they move by a combination of diffusion and bulk membrane flow. From our fits we show that tau m greater than 3.5 tau p, where tau m and tau p are the lifetimes of the membrane and the ferritin receptor on the cell surface, and that tau pD less than 6.9 X 10(-7) cm2, where D is the ferritin receptor diffusion coefficient. Surprisingly, we obtain the best fits to the data when we neglect membrane flow. Our model predicts that for proteins that are excluded from coated pits, the protein concentration will be Gaussian, being maximal at the cell center and decreasing with the distance from the cell center. If on giant HeLa cells a protein with such a distribution could be found, it would strongly support Bretcher's proposal that there is an inward membrane flow.

Cell Membrane↗
PubMed1988

Effect of membrane flow on the capture of receptors by coated pits. Theoretical results.

Coated pits trap cell surface receptors and mediate their internalization. Once internalized, many receptors recycle back to the cell surface. When recycled receptors are inserted into the plasma membrane, they move until they are again trapped in coated pits. The mechanisms for moving receptors from their insertion sites to coated pits are unknown. Unaided diffusion as the transport mechanism is consistent with the observed kinetics of receptor recycling. Another candidate for the transport mechanism is convection. For receptors that recycle to random positions on the cell surface, or to restricted regions about coated pits, we assess the importance of convective flow in the transport of receptors to coated pits. First we consider local flows set up by the formation of coated pits and their transformation into coated vesicles. As coated pits form and round into coated vesicles, surrounding membrane is drawn inward, creating flows directed toward the coated pit centers. We show that unless the lifetime of a coated pit is very short, 10 s or less, such local flows have a negligible effect on the time it takes receptors to reach coated pits. We also show that they are unlikely to be the mechanism that keeps receptors that have reached coated pits trapped within coated pits until they are internalized. Finally we calculate the mean time tau for a diffusing receptor to reach a coated pit in the presence of membrane flow that is constant in magnitude and direction, as may occur on moving cells. We show that for typical membrane flow velocities, tau can be reduced significantly from its value in the absence of flow. For example, a velocity v = 2.8 micron/min cuts the mean transport time in half.

Biophysical Phenomena↗
PubMed1987

Pathological findings in mine workers: I. Description of the PATHAUT database.

A computerized system for recording the results of structured, numerically coded autopsy reports on various types of mine workers has been in operation at the National Centre for Occupational Health in Johannesburg since 1975. Historical developments, particularly those associated with compensation for occupational disease, have resulted in very high autopsy rates, especially among whites. Since its inception, the pathology automation (PATHAUT) system has accumulated the results of more than 33,000 autopsies. The data set is described in the hope of stimulating interest in the possible uses of the data and encouraging collaborative research. Some characteristics of the database with potential research implications are discussed. These include differing age and work patterns for blacks and whites and geographic factors with potential influence on whether a body or only the cardiorespiratory organs are sent for examination.

Autopsy↗
PubMed1987

Pathological findings in mine workers: II. Quality of the PATHAUT data.

To assess the feasibility of using the pathology automation system (PATHAUT) for research, the quality of the data was explored by examining who comes to autopsy, the quality of the autopsy material, interobserver variability, and repeatability of diagnoses. The data indicated that autopsy rates in the gold mining industry, especially for whites, are high and that even among blacks, gold miners are represented in proportions exceeding the relative size of the working population. Because of the perception of the autopsy service as a means of obtaining compensation, miners with occupational diseases fully compensated in life are probably underrepresented. The autopsy material submitted for full autopsy is generally better preserved than cardiorespiratory organs that are sent for examination. The gold mining industry has a high proportion of full autopsies as does the Iron and Steel Corporation of South Africa. Full autopsies are more commonly performed on older deceased miners. This was true for both blacks and whites. The allocation of material to pathologists for full autopsies and examinations of the cardiorespiratory organs were clearly not random, and this may affect comparisons among pathologists. Active tuberculosis, silicosis, and emphysema prevalences appeared fairly comparable across pathologists; however, there was wide variability in the prevalence of bronchiolitis as determined by the pathologists. Agreement between the diagnoses on PATHAUT and reclassifications by single pathologists was very good for the severity of emphysema and the histological type of bronchogenic carcinoma.

Autopsy↗
PubMed1987

Some investigations into the nature and cause of massive fibrosis (MF) in the lungs of South African gold, coal, and asbestos mine workers.

Samples from fibrotic lung lesions greater than 1 cm in diameter macroscopically (by definition, massive fibrosis; MF) were taken from the lungs of 9 randomly selected post-mortem cases of mine workers all showing a background of a pneumoconiosis. These samples were studied histologically, biochemically, and by X-ray diffraction and electron microscopy. As controls for the biochemical and X-ray diffraction investigations, nonfibrosed lung tissue was taken from the same specimens. The findings suggest that the higher quartz content may be the primary cause responsible for the MF formation in this series of cases, while other factors such as tuberculosis may play a part according to some relevant literature on MF. Although an area of MF appears macroscopically to be a solid lesion, on microscopy this is not the case and the lesion is composed of dense and sparse collagen bundles and cellular elements.

Aged↗
PubMed1987

The effect of co-operativity on the equilibrium binding of symmetric bivalent ligands to antibodies: theoretical results with application to histamine release from basophils.

A theory for the co-operative binding of bivalent ligands to cell surface or solution antibody is presented. The theory treats both negative co-operativity, where the binding of a ligand to one site on an antibody makes it more difficult to bind to the second site, and positive co-operativity, where the binding of a ligand to one site on an antibody makes it easier to bind to the second site. Candidates for bivalent ligands exhibiting negative co-operativity (caused probably by steric hindrance) are certain anti-immunoglobulin antibodies. We show how to calculate the amount of ligand bound, the fraction of antibody in cross-links (i.e. in ligand-antibody aggregates) and the fraction of antibody in any size ligand-antibody aggregate. With sample calculations it is demonstrated that there can be major differences in the binding and cross-linking properties of co-operative and non-co-operative bivalent ligands. We discuss how the theory can be used to analyze experiments where human basophils or rat basophilic leukemia cells are exposed to bivalent ligands that bind co-operatively to immunoglobulin E.

Animals↗
PubMed1987

The effect of receptor density on the forward rate constant for binding of ligands to cell surface receptors.

For monovalent ligands interacting with cell surface receptors we have directly observed the functional dependence of the forward rate constant on the number of receptors per cell (N). The experimental system we studied consisted of monovalent ligand, 2,4-dinitrophenyl (DNP)-aminocaproyl-L-tyrosine (DCT), binding to bivalent, monoclonal anti-DNP immunoglobulin E (IgE) anchored to its high affinity receptor on rat basophilic leukemia (RBL) cells. To measure the fractional occupation of antibody combining sites by DNP we employed a recently developed fluorescence technique (Erickson, J., Kane, B. Goldstein, D. Holowka, and B. Baird, 1986, Mol. Immunol., 72:769-781). Our results are well fitted by the equation (Berg and Purcell, 1977, Biophys. J., 20:193-219) konc = 4 pi DaN kappa on/[4 pi Da + N kappa on] where konc is the forward rate constant for binding to the cell, D is the diffusion constant of the ligand, a is the radius of the cell, and kappa on is the intrinsic forward rate constant describing a single IgE combining site-DNP interaction. If D is fixed at 10(-5) cm2/s, the best fit of accumulated data predicts an average cell radius of approximately 4 microns and kappa on of approximately 1.8 x 10(-13) cm3/s [1.1 x 10(8)(M . s)-1]; both in excellent agreement with RBL cell size and the single-site forward rate constant for the binding of DCT to IgE in solution, respectively. We believe this is the first report of experimental evidence that directly illustrates the effect of surface density in determining the rates of binding for small molecules to membrane receptors.

Animals↗
PubMed1987

Electrical high-frequency audiometry. Preliminary medical audiologic experience.

This paper reports our clinical experiences with the electrical high frequency audiometer (EHFA)-Tonndorf, used in conjunction with conventional audiologic site of lesion testing. The EHFA is routinely used in the site of lesion hearing evaluation battery. We are reporting on the first 100 subjects, aged 6-85 years, seen in otologic/neurotologic consultation for complaint(s) of hearing loss, tinnitus, vertigo, ear blockage alone and/or in combination from 1983 to 1985. The significance of the data obtained suggests that: (1) Patient responses with EHFA are influenced by age, degree of hearing loss, degree of ear disease, site of lesion and disease, noise exposure and ototoxicity. (2) The degree of hearing loss as well as symmetry (asymmetry) of the loss affect the EHFA responses. (3) Responses to EHFA can be correlated with subject group classification. Five groups were well defined based upon degree and symmetry (asymmetry) of the hearing loss. (4) Electrical high-frequency audiograms (EHFAs) can be classified into five different patterns of response. (5) EHFA should be part of a site-of-lesion audiometry test battery.

Adolescent↗