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Biomedical subjects

E Kaplan

Publications and source records attributed to E Kaplan.

At least 109 records · Page 6Linked to original sources

A fluorescence technique to distinguish attached from ingested erythrocytes and zymosan particles in phagocytosing macrophages.

While investigating the role of [Ca2+]i in Fc receptor-mediated phagocytosis, we found that clamping the [Ca2+]i to low levels by a variety of methods often led to increased plasma membrane permeability, rendering the hypotonic lysis method for calculating the phagocytosis index unreliable. To overcome this difficulty we developed a method for calculating the phagocytosis index of IgG-coated RBC that does not depend on hypotonic lysis. It depends on the ability of ingested RBC to create dark-appearing phagocytic vacuoles when the cytoplasm of murine macrophages is stained with acridine orange. Uningested or partially ingested RBC do not change the appearance of the otherwise uniformly stained cytoplasm of the macrophages. Since this method does not rely on hypotonic lysis to distinguish attached from ingested RBC, it can be used in situations when macrophages are unusually sensitive to hypotonic treatment (e.g. after clamping the macrophage [Ca2+]i to low levels). It can also be applied to the study of phagocytosis of particles that are not susceptible to hypotonic lysis (e.g., zymosan).

Acridine Orange↗

Fine structure of receptive-field centers of X and Y cells of the cat.

We investigated the fine structure of receptive field centers of X and Y cells of the retina and lateral geniculate nucleus of the cat using sinusoidal grating stimuli of high spatial frequency. By measuring orientation tuning and spatial-frequency tuning at multiple orientations, the two-dimensional sensitivity distribution was examined. We found that receptive-field centers typically have multiple sensitivity peaks that can be modeled as several spatially offset subunits. A subunit structure was found in both X and Y cells, with an average number of subunits per receptive-field center of approximately 2.9 in X cells and approximately 4.6 in Y cells. In X cells these subunits may correspond to individual cone bipolar inputs. In Y cells, the subunits may reflect the structure of the dendritic tree. The observation of the subunit structure of the receptive-field center, in conjunction with manipulation of the retinal wiring through pharmacological intervention, may provide a new tool for probing the circuitry of the retina.

Animals↗

Visual hierarchical analysis of Block Design configural errors.

Patients have been frequently observed to violate the overall configuration on the WAIS-R Block Design subtest. The significance of these configural errors was investigated with hierarchical patterns consisting of large "global" shapes made from smaller "local" shapes. Subjects were administered two similarity judgment tasks in which they were asked to decide which of two hierarchically structured comparison figures most resembled a standard figure. Results indicated that subjects who made configural errors on Block Design were less likely than a matched sample who did not make configural errors to select the comparison figure that resembled the standard figure at the global level. Furthermore, the present findings were obtained from subjects without known right-hemisphere lesions, suggesting that the correlation between Block Design errors and global/local performance is applicable to a broad range of patient and non-patient populations. The data are consistent with the view that errors on Block Design may reflect differences in the perceptual encoding of global/local features.

Adult↗

Medical and judicial perceptions of the risks associated with use of antipsychotic medication.

To determine whether occupational perspective influences the decision to prescribe antipsychotic medications, we presented a group of psychiatrists and judges with a hypothetical case involving a potentially psychotic patient. The subjects were asked what probability of drug-induced tardive dyskinesia they would accept in order to prevent psychotic decompensation. The subjects were then asked to estimate the actual probability that tardive dyskinesia would occur if the patient received antipsychotic medications. From the responses to these questions we inferred their treatment decisions. Although the psychiatrists and judges agreed on an acceptable level of risk, they differed significantly in their estimates of the actual risk involved and, by inference, their decisions concerning treatment. Our findings have several implications for adjudication of cases involving treatment decisions and the right to refuse treatment.

Antipsychotic Agents↗

Host-parasite interaction in the pathogenesis of rheumatic fever.

Recent investigation has delineated some of the bacterial and host factors that may play a role in the pathogenesis of rheumatic fever. Continuing studies support the role of antibodies to crossreactive antigens in human tissues and the group A streptococcal cell in inducing tissue damage associated with this disease. Several specific epitopes have now been defined that are common to the crossreactive antigens. Data from recent outbreaks of rheumatic fever in the USA suggest that mucoid group A streptococcal strains, belonging to serotypes M1, M3, M5, M6 and M18 may have accounted for these outbreaks. While these strains are thought to be rheumatogenic, the exact characteristic(s) that renders them so is yet to be determined.

Host-Parasite Interactions↗

Guidelines for neuropsychological research in multiple sclerosis.

Acquisition of scientific information regarding the neuropsychological aspects of multiple sclerosis has been hampered by studies using small, inadequately described patient and control samples and a wide array of cognitive test procedures that hinder multicenter data pooling. Based on a review of key issues of clinical need and experimental interest, research guidelines are proposed for investigations in this burgeoning research area. The guidelines include suggestions for sampling methods, population characterization, and control groups as well as a recommended core battery of neuropsychological tests for use in this population. It is hoped that these guidelines will advance knowledge about the neuropsychology of multiple sclerosis by helping to promote sound experimental design, facilitate cross-study comparison, and encourage multicenter collaborative efforts.

Cognition Disorders↗

A prospective, multicenter study of patients' refusal of antipsychotic medication.

Refusal of treatment with antipsychotic medication was studied prospectively in a sample of 1434 psychiatric patients admitted to four acute inpatient units in state-operated mental health facilities in Massachusetts during a 6-month period. Compared with a control group of patients who accepted prescribed antipsychotic treatment, the 103 patients who refused were older, of a higher social class, and less likely to have been prescribed antiparkinsonian medications. On admission, prior to refusal of medication, patients who refused were found to have significantly higher Brief Psychiatric Rating Scale scores than compliant patients and more negative attitudes regarding their hospitalization and past, present, and future treatment. Treatment refusal had negative effects on the hospital milieu and on the patient; refusers were more likely to require seclusion or restraint and had longer hospitalizations than treatment acceptors. Most refusal episodes ended with voluntary acceptance of treatment. In 23% of cases medications were discontinued. Only 18% of the sample reached formal, judicial review, and in every case that did, involuntary treatment was ordered. The policy implications of these findings are discussed.

Adult↗

Light adaptation in the primate retina: analysis of changes in gain and dynamics of monkey retinal ganglion cells.

The responses of monkey retinal ganglion cells to sinusoidal stimuli of various temporal frequencies were measured and analyzed at a number of mean light levels. Temporal modulation tuning functions (TMTFs) were measured at each mean level by varying the drift rate of a sine-wave grating of fixed spatial frequency and contrast. The changes seen in ganglion cell temporal responses with changes in adaptation state were similar to those observed in human subjects and in turtle horizontal cells and cones tested with sinusoidally flickering stimuli; "Weber's Law" behavior was seen at low temporal frequencies but not at higher temporal frequencies. Temporal responses were analyzed in two ways: (1) at each light level, the TMTFs were fit by a model consisting of a cascade of low- and high-pass filters; (2) the family of TMTFs collected over a range of light levels for a given cell was fit by a linear negative feedback model in which the gain of the feedback was proportional to the mean light level. Analysis (1) revealed that the temporal responses of one class of monkey ganglion cells (M cells) were more phasic at both photopic and mesopic light levels than the responses of P ganglion cells. In analysis (2), the linear negative feedback model accounted reasonably well for changes in gain and dynamics seen in three P cells and one M cell. From the feedback model, it was possible to estimate the light level at which the dark-adapted gain of the cone pathways in the primate retina fell by a factor of two. This value was two to three orders of magnitude lower than the value estimated from recordings of isolated monkey cones. Thus, while a model which includes a single stage of negative feedback can account for the changes in gain and dynamics associated with light adaptation in the photopic and mesopic ranges of vision, the underlying physical mechanisms are unknown and may involve elements in the primate retina other than the cone.

Adaptation, Ocular↗

Memory impairment in multiple sclerosis.

We compared the performance of 50 multiple sclerosis (MS) patients and 35 normal controls on a variety of memory tasks to determine the nature and severity of memory deficits in the MS patients and the proportion of patients affected. We also determined the relationship between memory and other cognitive functions, demographic factors, disease characteristics, depression, and psychoactive medication. We found significant differences between patients and controls on almost all memory tests. Patterns of learning, effects of interference, and improvement with cuing were similar for both groups. Thirty percent of patients showed severe memory impairment, 30% were moderately impaired, and 40% were mildly or not impaired. Memory dysfunction was related to impairment of other cognitive functions, lower socioeconomic status, chronic progressive type of MS, and use of antianxiety medication, but not to severity of disability, duration of MS symptoms or depression.

Adult↗

Circadian rhythms in Limulus photoreceptors. II. Quantum bumps.

The light response of the lateral eye of the horseshoe crab, Limulus polyphemus, increases at night, while the frequency of spontaneous discrete fluctuations of its photoreceptor membrane potential (quantum bumps) decreases. These changes are controlled by a circadian clock in the brain, which transmits activity to the eye via efferent optic nerve fibers (Barlow, R. B., S. J. Bolanski, and M. L Brachman. 1977. Science. 197:86-89). Here we report the results of experiments in which we recorded from single Limulus photoreceptors in vivo for several days and studied in detail changes in their physiological and membrane properties. We found that: (a) The shape of (voltage) quantum bumps changes with the time of day. At night, spontaneous bumps and bumps evoked by dim light are prolonged. The return of the membrane potential to its resting level is delayed, but the rise time of the bump is unaffected. On average, the area under a bump is 2.4 times greater at night than during the day. (b) The rate of spontaneous bumps decreases at night by roughly a factor of 3, but their amplitude distribution remains unchanged. (c) The resting potential and resistance of the photoreceptor membrane do not change with the time of day. (d) the relationship between injected current and impulse rate of the second order neuron, the eccentric cell, also remains unchanged with the time of day. Thus the efferent input from the brain to the retina modulates some of the membrane properties of photoreceptor cells. Our findings suggest that the efferent input acts on ionic channels in the membrane to increase the sensitivity of the photoreceptor to light.

Animals↗

The circadian rhythm of the N-terminus and C-terminus of the atrial natriuretic factor prohormone.

Circadian variation in the circulating concentrations of the N-terminal and C-terminal portions of the atrial natriuretic factor prohormone (pro ANF) was evaluated in 8 men, ages 41-47, who have been followed for 19 years with respect to circadian variation in physiological variables including blood pressure and clinical chemistries. The N-terminus of the ANF prohormone contains two peptides consisting of amino acids 1-30 and 31-67 while the C-terminus contains 1 peptide (amino acids 99-126) of this 126 amino acid prohormone which lower blood pressure and have natriuretic properties. To determine if either the N-terminus and/or the C-terminus of the prohormone have a circadian variation in their circulating plasma concentrations these 8 men had blood samples obtained for radiommunoassay every 3 hr during a 24-hr period. Three radiommunoassays which immunologically recognize (1) the whole N-terminus (i.e. amino acids 1-98), (2) the midportion of the N-terminus (amino acids 31-67) and (3) the C-terminus (amino acids 99-126) of the ANF prohormone were utilized. The whole N-terminus, the midportion of the N-terminus which circulates after being proteolytically cleaved from the rest of the N-terminus, and the C-terminus each had a peak circulating concentration between 0400 and 0700 which were significantly (P less than 0.001) higher than their concentrations at any other time throughout the 24-hr period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Extended ex vivo preservation of the heart and lungs. Effects of acellular oxygen-carrying perfusates and indomethacin on the autoperfused working heart-lung preparation.

The autoperfused working heart-lung preparation has been proposed as a method for long-term heart-lung preservation. We investigated the effects of acellular oxygen-carrying perfusates (study 1) and the effect of donor pretreatment with indomethacin (study 2) on the working ex vivo heart-lung block. In study 1 perfusion with stroma-fee hemoglobin resulted in significantly reduced survival (118 +/- 46 minutes) compared with autologous blood (561 +/- 125 minutes, p less than 0.05) or perfluorocarbon (438 +/- 114 minutes, p less than 0.05). Decrease in survival with stroma-free hemoglobin perfusate is associated with a marked decrease in left ventricular performance and a significant increase in pulmonary vascular resistance. Perfusion with autologous blood is associated with a significant increase in pulmonary vascular resistance after 240 minutes of explantation, which is significantly delayed by perfusion with perfluorocarbon. Perfusion for 6 hours with blood pretreated with indomethacin (study 2) resulted in a decrease in the concentration of prostacyclin and thromboxane A2 metabolites but an increase in the prostaglandin/thromboxane A2 metabolite ratio. This is associated with abrogation of the increase in pulmonary vascular resistance (12,787 +/- 1682 dynes/sec/cm-5, T = 0; 13,134 +/- 2654 dynes/sec/cm-5, T = 360 minutes) observed in preparations perfused with autologous blood (13,194 +/- 1942 dynes/sec/cm-5, T = 0; 24,768 +/- 3325 dynes/sec/cm-5, T = 360 minutes, p less than 0.05). We conclude that alteration of the cellular and humoral components of autologous blood may prove advantageous for increasing the utility of the autoperfused working heart-lung preparation as a preservation technique.

Animals↗

Severe group A streptococcal infections associated with a toxic shock-like syndrome and scarlet fever toxin A.

There is concern that group A streptococci, which have caused less serious infections in developed countries in recent decades, may be acquiring greater virulence. We describe 20 patients from the Rocky Mountain region who had group A streptococcal infections from 1986 to 1988 that were remarkable for the severity of local tissue destruction and life-threatening systemic toxicity. Among the 20 patients (median age, 36), necrotizing fasciitis with or without myositis was the most common soft-tissue infection (55 percent). Nineteen patients (95 percent) had shock, 16 (80 percent) had renal impairment, and 11 (55 percent) had acute respiratory distress syndrome. The mortality rate was 30 percent. All patients but 1 had positive tissue cultures for Streptococcus pyogenes; 12 had positive blood cultures. Most of the patients had no underlying disease; 2 used intravenous drugs. Strains of group A beta-hemolytic streptococci isolated from 10 patients were not of a single M or T type; however, 8 of the 10 strains produced pyrogenic exotoxin A (scarlet fever toxin A, a classic erythrogenic toxin), which has rarely been observed in recent years. From our study of this cluster of severe streptococcal infections with a toxic shock-like syndrome, we conclude that in our region, more virulent group A streptococci have reappeared that produce the pyrogenic toxin A associated with scarlet fever.

Adult↗

Interleukin-1 and the response to injury.

Traumatic injury is the leading cause of morbidity and mortality in Americans less than 45 years old. People surviving the initial insult undergo metabolic, hemodynamic and immunologic changes which contribute to both early and late complications. Though necessary for normal immunologic response and for wound healing, pathologic alterations of IL-1 synthesis, degradation, and binding to receptors on both a local and systemic level could lead to these changes. Manipulation of IL-1-mediated effects might be of therapeutic utility in the management of trauma in the future.

Animals↗

Effects of atrial cardioplegia on the ischemic right ventricle after acute coronary artery occlusion and reperfusion.

Right atrial cardioplegia has been advocated as a simple method of delivering retrograde cardioplegia. Passive distention of the right heart inherent with right atrial cardioplegia has been shown to impair right ventricular function in a canine model of global ischemia. This study was designed to compare right ventricular performance after right atrial cardioplegia administered intermittently (n = 5) and continuously (n = 5) with coronary sinus retrograde cardioplegia (n = 5) and aortic root cardioplegia (n = 8) in a canine model of acute right ventricular ischemia and reperfusion. Right ventricular performance was assessed using the load-independent relationship of end-systolic pressure versus dimension (myocardial fiber length). Right ventricular performance was well preserved after reperfusion in those dogs protected with intermittent right atrial cardioplegia (95% of control). Results with continuous right atrial cardioplegia (66% of control) and coronary sinus retrograde cardioplegia (40% of control) demonstrated diminished postreperfusion right ventricular performance. Right ventricular performance in the group protected with aortic root cardioplegia was significantly impaired after reperfusion when compared with all retrograde groups (34% of control, p less than 0.05). In this model, postreperfusion right ventricular performance was preserved in the right atrial cardioplegia groups despite passive ventricular distention. All methods of retrograde cardioplegia resulted in superior preservation of right ventricular performance when compared with standard aortic root cardioplegia.

Animals↗