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Biomedical subjects

B Goldstein

Publications and source records attributed to B Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1996

SPECT of Brain and Vertigo - A Case Report.

Vertigo has been identified as a complaint associated with the symptom of tinnitus; as well as a specific clinical type of tinnitus i.e., vestibular tinnitus. Classically, the clinical diagnosis of Ménière's Disease includes a quadrad of complaints, highlighted by episodic vertigo, ear blockage, a gradual progressive sensorineural hearing loss, and an associated complaint of a "low frequency tinnitus". Diagnostic and etiologic difficulties for Ménière's Disease have resulted in multiple diagnostic entities, e.g., Ménière's Syndrome, Cochlear Ménière's Disease; Vestibular Ménière's Disease, etc. Single Photon Emission Computed Tomography (SPECT) imaging of brain is a technique which has been reported to improve the diagnostic accuracy of patients with the symptom of tinnitus; and has now been applied for recurrent persistent vertigo. A case report, diagnosed classically as Ménière's Disease, is presented to demonstrate the increased diagnostic accuracy provided by SPECT of brain for the chief complaint of vertigo. SPECT revealed significant perfusion asymmetries in brain. The medical significance of the SPECT findings and its application for both diagnosis and treatment are presented.

Journal Article↗
PubMed1996

Tinnitus - Hyperacusis and the Loudness Discomfort Level Test - A Preliminary Report.

This paper is a preliminary report from the Tinnitus Center, HSCB-SUNY, of hyperacusis in a patient population who request consultation for tinnitus of the severe disabling type. Forty-two consecutive patients seen from January to August 1995 were reviewed for this preliminary report. There is a positive correlation between tinnitus and hyperacusis as well as a positive correlation between hyperacusis and the loudness discomfort level test (LDL). Hyperacusis is an increased sensitivity to sound that occurs with/without a hearing loss in individuals with tinnitus of the severe disabling type. The present method of assessment for hyperacusis includes pure tone audiometry, LDL's, Feldmann Masking Curves and the Metz test for recruitment. A classification system exists for hearing loss and a similar system is suggested for hyperacusis.

Journal Article↗
PubMed1996

A Final Common Pathway for Tinnitus - Implications for Treatment.

A final common pathway for tinnitus is hypothesized to exist for all patients with tinnitus. Its function is the transition of the sensory to the affect component of the symptom of tinnitus. Single Photon Emission Computerized Tomography (SPECT) with the radio isotope TC99-HMPAO has identified side to side perfusion asymmetries highlighted by that of the amygdala - hippocampal complex. It is hypothesized that a fundamental function of the amygdala - hippocampal structures is the establishment of a paradoxical auditory memory for tinnitus i.e., an aberrant auditory signal. It is a result of alteration in normal auditory masking; and found in all tinnitus patients. Underlying mechanisms are hypothesized to exist and to be highlighted by a diminution of inhibition mediated by gamma aminobutyric acid (GABA) due to disconnection from excitatory (glutamate) inputs. Blockage of GABA mediated inhibition results in Tinnitogenesis, a epileptiform auditory phenomenon. Significant neurochemistry implications for treatment are suggested by the Final Common Pathway for Tinnitus. The overall hypothesis of a final common pathway for tinnitus; and the clinical implications for treatment are presented.

Journal Article↗
PubMed1996

Synthesis and antimicrobial activities of 4-purpuromycin derivatives.

Purpuromycin (1) is a natural antibiotic with a broad spectrum of activity encompassing bacteria, fungi and protozoa. A new series of derivatives of 1 was prepared by the modification or replacement of the C-4 hydroxyl group. The physico-chemical characteristics and the in vitro antimicrobial activity of these new semisynthetic purpuromycin derivatives are reported. Attachment of a variety of bulky groups to the C-4 hydroxyl group as well as acylation or mesylation of 1 gave derivatives with significantly reduced antifungal activity, while the antimicrobial activity of these derivatives against Gram-positive and Gram-negative bacteria was only slightly decreased. All compounds were inactive against Escherichia coli. The C-4 epimers showed different in vitro activity as compared with those having the natural configuration, particularly against fungi.

Anti-Bacterial Agents↗
PubMed1995

Simultaneous cross-linking by two nontriggering bivalent ligands causes synergistic signaling of IgE Fc epsilon RI complexes.

We have used two bivalent ligands that bind IgE to study the relationship between the aggregation of receptors with high affinity for IgE (Fc epsilon RI) and the responses (receptor immobilization, Ca2+ influx, and degranulation) of rat basophilic leukemia (RBL-2H3) cells. One of these is a symmetric bivalent ligand, N,N'-bis[[epsilon-[(2,4-dinitrophenyl)amino]caproyl]-L-tyrosyl]-L- cystine ((DCT)2-cys), which binds specifically to the combining sites of a mAb anti-DNP IgE and efficiently cross-links cell surface IgE, but does not trigger significant degranulation or increases in intracellular Ca2+. Several lines of evidence, including lateral mobility measurements, indicate that this ligand preferentially forms stable cyclic complexes containing two (DCT)2-cys and two IgE. The second ligand is a mAb anti-IgE, B1E3, which causes lateral mobility changes consistent with dimerized IgE-Fc epsilon RI and also does not trigger increases in intracellular Ca2+ or degranulation. The two ligands together trigger robust responses. In the presence of B1E3, (DCT)2-cys causes immobilization of IgE-Fc epsilon RI in a broad concentration range; in a more narrow concentration range, it is a potent stimulant of changes in both degranulation and Ca2+. We have compared the dose-response curves for cellular activation to simulated IgE aggregation curves, i.e., curves that predict the equilibrium IgE aggregate size distribution as a function of the (DCT)2-cys concentration. Our results indicate that maximal cellular activation occurs at a much higher (DCT)2-cys concentration than maximal IgE aggregation. When IgE aggregation is maximal, almost all aggregated IgE is in cyclic dimers. Thus, cyclic dimers appear to be functionally ineffective, even after they have been cross-linked by B1E3. Aggregated IgE-Fc epsilon RI that is effective in stimulating a cellular response may have particular structural or dynamic properties that allow critical interactions for initiating the signaling cascade.

Animals↗
PubMed1995

Kinetics of tyrosine phosphorylation when IgE dimers bind to FC epsilon receptors on rat basophilic leukemia cells.

Previously, we demonstrated that aggregates of the high affinity receptor for IgE (Fc epsilon RI), formed by the binding of chemically cross-linked oligomers of IgE, continue to signal early and late cellular responses long after the formation of new aggregates is blocked. In the present work, we explore quantitatively the relationship between aggregation of the receptors and one of the earliest biochemical changes this initiates. We compare the time course of aggregate formation, inferred from studies of the binding of dimers of IgE, and the time course of phosphorylation of tyrosines on receptor subunits when the receptors are aggregated. A simple model does not fit the data. It appears that aggregates formed late in the response are less effective signaling units than those formed initially. We propose new explanations for the persistence of the response and the unusual kinetics.

Animals↗
PubMed1995

Solution assembly of a soluble, heteromeric, high affinity interleukin-2 receptor complex.

In this study, we report the use of coiled-coil (leucine zipper) molecular recognition for the solution assembly of stable, high affinity, heteromeric interleukin-2 receptor complexes. Co-expression of interleukin-2 receptor alpha and beta extracellular domains (ectodomains), each fused to seven coiled-coil heptad repeats, resulted in the formation of heteromeric complexes that bound interleukin-2 in a cooperative fashion and with much higher affinity than similar homomeric complexes. The dissociation constants for these solution complexes are within the range of values reported for the comparable cell surface "pseudo high affinity" interleukin-2 receptor. Ligand-induced cross-linking of homomeric or heteromeric receptor subunits is the common signal transmission mechanism employed by hematopoietin receptors. Individual receptor ectodomains, however, often do not bind ligand with measurable affinity. This is the first study to demonstrate the feasibility of coiled-coil mediated preassembly of cytokine receptor complexes.

Allosteric Regulation↗
PubMed1995

The kinetics of bivalent ligand-bivalent receptor aggregation: ring formation and the breakdown of the equivalent site approximation.

When bivalent ligands capable of bridging binding sites on two different receptors interact with bivalent receptors, aggregates form. The aggregates can be of two types: chains (open structures containing n receptors, n-1 doubly bound ligands and 0, 1, or 2 singly bound ligands) and rings (closed structures containing n receptors and n doubly bound ligands). Both types of aggregates have been detected experimentally. In general, to determine the time dependence of the concentration of any particular aggregate requires solving an infinite set of coupled ordinary differential equations (ODEs). Perelson and DeLisi [19] showed that great simplification results if all receptor binding sites are equivalent, i.e., the binding properties of a site on a receptor are independent of the size of the aggregate the receptor is in. If only chains form, the problem reduces to solving two coupled ODEs for the concentrations of singly and doubly bound ligands. From the solutions to these ODEs, the time dependence of the entire aggregate size distribution can be determined. We show that the equivalent site approximation as formulated by Perelson and DeLisi [19] is incompatible with ring formation. We then present a modified equivalent site approximation that is useful if chains of any size can form but rings above a certain size (k) cannot. We show how to reduce the resulting infinite set of coupled ODEs to a closed system of at most 4k + 2 ODEs for the ligand concentrations, the ring concentrations, and the concentrations of all chains up to size k. Although we can only predict the kinetics of aggregate formation for aggregates of size k or less, at equilibrium the modified equivalent site approximation yields the complete aggregate size distribution.

Animals↗
PubMed1995

Approximating the effects of diffusion on reversible reactions at the cell surface: ligand-receptor kinetics.

We consider the problem of determining the time dependence of the bound ligand concentration for the reversible binding of a diffusing monovalent ligand to receptors uniformly distributed over the surface of a spherical cell. We start by formulating a boundary value problem that captures the essential physics of this situation. We then introduce a systematic approximation scheme based on the method of weighted residuals. By this means we convert the initial boundary value problem into a simpler problem that requires solving only a small number of ordinary differential equations. We show how, at the lowest order of approximation, the method can be used to obtain modified chemical rate equations where, in place of fundamental rate constants, effective rate coefficients appear. These rate coefficients are functions of the ligand diffusion coefficient, the cell radius, the receptor density and other variables. We compare exact and approximate solutions and discuss under what conditions the approximate equations can be used. We also apply the method of weighted residuals to obtain approximate descriptions of the binding kinetics when (1) there are two different cell surface receptor populations that bind the ligand and (2) the cell secretes a ligand that can bind back to receptors on the cell (autocrine binding).

Biophysical Phenomena↗
PubMed1995

Cell contacts orient some cell division axes in the Caenorhabditis elegans embryo.

Cells of the early Caenorhabditis elegans embryo divide in an invariant pattern. Here I show that the division axes of some early cells (EMS and E) are controlled by specific cell-cell contacts (EMS-P2 or E-P3 contact). Altering the orientation of contact between these cells alters the axis along which the mitotic spindle is established, and hence the orientation of cell division. Contact-dependent mitotic spindle orientation appears to work by establishing a site of the type described by Hyman and White (1987. J. Cell Biol. 105:2123-2135) in the cortex of the responding cell: one centrosome moves toward the site of cell-cell contact during centrosome rotation in both intact embryos and reoriented cell pairs. The effect is especially apparent when two donor cells are placed on one side of the responding cell: both centrosomes are "captured," pulling the nucleus to one side of the cell. No centrosome rotation occurs in the absence of cell-cell contact, nor in nocodazole-treated cell pairs. The results suggest that some of the cortical sites described by Hyman and White are established cell autonomously (in P1, P2, and P3), and some are established by cell-cell contact (in EMS and E). Additional evidence presented here suggests that in the EMS cell, contact-dependent spindle orientation ensures a cleavage plane that will partition developmental information, received by induction, to one of EMS's daughter cells.

Animals↗
PubMed1995

Autonomic modulation of heart rate variability during endotoxin shock in rabbits.

OBJECTIVE: Gram-negative septic shock is associated with severe hypotension and autonomic cardiovascular dysfunction. We hypothesized that in an anesthetized rabbit model of endotoxin shock, autonomic modulation of cardiac activity, as measured by power spectral analysis of heart rate (HR) variability, would be decreased compared with the anesthetized control rabbits. DESIGN: Experimental, comparative study. SETTING: Laboratory of a university hospital. SUBJECTS: Fourteen adult male New Zealand white rabbits (2.7 to 3.1 kg body weight) were studied under anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied the absolute and temporal changes in HR power spectra and plasma catecholamine concentrations in eight experimental and six control New Zealand white rabbits during Escherichia coli endotoxin-induced shock. HR, respirations, arterial blood pressure (BP), HR power spectra, and plasma catecholamine concentrations were measured at 5- to 10-min intervals for 60 mins in control rabbits or until the mean arterial pressure (MAP) decreased by > or = 20 mm Hg in experimental rabbits. There were no differences in basal HR, respiratory rate, BP, HR power spectra, or catecholamine concentrations between groups. After endotoxin administration, MAP decreased (82 +/- 7 vs. 62 +/- 5 mm Hg; p < .05) as did log low-frequency HR power (-2.14 +/- 2.46 vs. -2.20 +/- 2.48 beats/min2; p < .05). Low-frequency HR power and MAP remained unchanged in control animals. Log high-frequency HR power decreased in control and experimental rabbits (-1.02 +/- 1.34 vs. -1.69 +/- 2.12 [control], p < .05; -1.53 +/- 2.19 vs. -2.19 +/- 2.85 beats/min2 [experimental], p < .05). While there was an inverse relationship between low- and high-frequency HR power and MAP, the direction of change was opposite in six of six rabbits in the control group and in six of eight rabbits in the experimental group. Plasma catecholamine concentrations did not change during the experiment in either group. CONCLUSIONS: Sympathetic modulation of cardiac activity decreased, while the sympathomedullary response remained unchanged during endotoxin shock. We speculate that a concomitant decrease in low-frequency HR power as MAP decreases may prove to be an early marker for impending shock.

Animals↗
PubMed1995

An analysis of the response to gut induction in the C. elegans embryo.

Establishment of the gut founder cell (E) in C. elegans involves an interaction between the P2 and the EMS cell at the four cell stage. Here I show that the fate of only one daughter of EMS, the E cell, is affected by this induction. In the absence of the P2-EMS interaction, both E and its sister cell, MS, produce pharyngeal muscle cells and body wall muscle cells, much as MS normally does. By cell manipulations and inhibitor studies, I show first that EMS loses the competence to respond before it divides even once, but P2 presents an inducing signal for at least three cell cycles. Second, induction on one side of the EMS cell usually blocks the other side from responding to a second P2-derived signal. Third, microfilaments and microtubules may be required near the time of the interaction for subsequent gut differentiation. Lastly, cell manipulations in pie-1 mutant embryos, in which the P2 cell is transformed to an EMS-like fate and produces a gut cell lineage, revealed that gut fate is segregated to one of P2's daughters cell-autonomously. The results contrast with previous results from similar experiments on the response to other inductions, and suggest that this induction may generate cell diversity by a different mechanism.

Actin Cytoskeleton↗
PubMed1995

SPECT Imaging of Brain and Tinnitus-Neurotologic/Neurologic Implications.

Single Photon Emission Computed Tomography (SPECT) of brain with technetium-99m hexamethyl propyleneamine oxine (Tc-HMPAO) is an imaging technique which has been introduced for the identification of abnormalities of regional cerebral blood flow (rCBF) in patients with a central type of subjective idiopathic tinnitus, which was characterized as severe and disabling. These patients demonstrate a negative clinical history, physical examination does not evidence central nervous system disease, and CT/MRI studies of brain were negative. Two typical cases are presented which demonstrate significant regional abnormalities in cerebral perfusion bilateral of temporal, frontal, parietal and hippocampal amygdala regions when compared with normative Tc-HMPAO SPECT of brain data. Neurotologic and neurologic implications are suggested which include cerebrovascular disease, neurodegenerative disorder and dementia, and neuropsychiatric mood disorder. SPECT results of brain demonstrate for the first time the in vivo significance of the organicity of brain for a central type of tinnitus.

Journal Article↗
PubMed1994

Spared descending pathways mediate locomotor recovery after subtotal spinal cord injury.

The location of pathways responsible for locomotor recovery after incomplete spinal cord injury has been studied in adult rats. Animals were allowed to recover from subtotal mid-thoracic cord section which spared left lateral and ventral funiculus fibers. Subsequent lumbar commissurotomy or left thoracic cord hemisection abolished the locomotor recovery. Spared descending fibers passing through the initial incomplete cord lesion appear to mediate locomotor recovery.

Animals↗
PubMed1994

Dynamics of signal transduction after aggregation of cell-surface receptors: studies on the type I receptor for IgE.

Many ligands stimulate cellular responses by aggregating the cell-surface receptors to which they are bound. We investigated several mechanistic questions related to aggregation of receptors by using the high-affinity receptor for IgE (Fc epsilon RI) on mast cells as a model system. We briefly exposed cells to covalently cross-linked oligomers of IgE and then added excess monomeric IgE to prevent further aggregation. Early events were examined by monitoring the phosphorylation of protein tyrosines; later events were examined by monitoring secretion. We found that aggregated receptors continue to signal both late and early events in the absence of formation of new aggregates. Additional experiments suggested that the clustered receptors undergo a dynamic process of phosphorylation and dephosphorylation. Our findings suggest that for these and related receptors that function by aggregation, the persistence of signal transduction is directly related to the intrinsic affinity of the ligand for the individual receptor.

Animals↗
PubMed1994

Heart rate power spectrum analysis of autonomic dysfunction in adolescents with anorexia nervosa.

We studied autonomic modulation of heart rate in 8 females with anorexia nervosa (AN) using power spectral analysis (PSA) of heart rate variability in the supine and standing positions at baseline and after 2 weeks of intensive nutritional rehabilitation, and compared findings with healthy female control subjects. The results indicate that there is a decrease in sympathetic modulation of heart rate, evident by a deficit of low frequency (0.01-0.15 Hz) heart rate power in the supine position in AN compared with control subjects. In addition, parasympathetic modulation of heart rate failed to decrease with standing. A trend toward improvement in autonomic control of heart rate in adolescents with AN occurs in the supine position relatively early in weight rehabilitation. PSA is a sensitive, quantitative, and noninvasive means of determining autonomic control of heart rate and could be a useful tool in monitoring the health of patients with AN.

Adolescent↗
PubMed1994

M/RMS: an EMG method for quantifying upper motoneuron and functional weakness.

A new method for quantifying upper motoneuron (UMN) weakness using standard EMG equipment is presented and compared to the twitch occlusion method. Control subjects and patients with stroke, spinal cord injury (SCI), and peripheral nerve injury (PNI) were evaluated. Force, EMG, and twitch force from nerve electrical stimulation were recorded during isometric contractions of the biceps and triceps. Ratios of the elicited CMAP amplitude (M)/voluntary-root-mean-square EMG activity (RMS) and of the voluntary contraction twitch force (Ti)/the resting twitch force (Tmax) were the two measures of UMN weakness studied. Both ratios are linearly correlated with force for controls, log M/RMS (r = 0.96) and Ti/Tmax (r = 0.86). Log M/RMS ratio was abnormally high (> mean + 2 SD; i.e., > 1.09) for weak muscles affected by stroke and incomplete SCI, but was normal in muscles weakened by PNI. An elevated M/RMS ratio, may aid in quantification of deficient supraspinal activation from UMN or functional weakness.

Adult↗