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Biomedical subjects

D Schachter

Publications and source records attributed to D Schachter.

At least 37 records · Page 2Linked to original sources

Child psychiatry and early intervention: III. The developmental disorders.

This paper is the third in a series of four using the concepts introduced in the paper Child Psychiatry and Early Intervention: I. The Aggregate Burden of Suffering. This paper reviews the developmental disorders of childhood to set priorities for early intervention programs. This review discusses the prevalence, course, risk, early indicators, associated impairments, and responses to intervention. The specific developmental disorders, especially learning disabilities, have a significant impact on community resources. Since the developmental disorders are easily recognized among preschool children, early intervention is feasible. However, successful interventions have yet to be demonstrated. Priority should be given to the development of effective interventions. There is a great need for research studies on the effects and effectiveness of early intervention with these individuals.

Adolescent↗

Immunoglobulin and renal abnormalities in Dahl genetically hypertensive rat.

The Dahl salt-sensitive rat (DS) is a model of genetically determined arterial hypertension exacerbated by dietary salt. We report two additional abnormalities of DS rats, which are both genetically determined and enhanced by salt: 1) immunoglobulin disorders and 2) renal dysfunctions. These abnormalities precede and are not the result of the arterial hypertension. In young, prehypertensive DS rats the plasma and tissue concentrations of immunoglobulin (Ig) G, but not of IgM or IgA, are decreased compared with those of the salt-resistant strain (DR). A high-salt diet (8.0% NaCl) decreases the plasma and tissue IgG levels of DS but not of DR rats. Reduction of IgG in the DS strain results from both decreased synthesis and increased urinary excretion. Renal dysfunction in young, prehypertensive DS animals is manifested by increased excretion of high molecular weight proteins, including albumin, IgG, IgA, and IgM. The high-salt diet increases the urinary excretion of these proteins within 1-2 days, and the effect is much greater in DS compared with DR rats. The urinary excretion of IgG is selectively increased relative to immunoglobulin light chains, IgA and IgM in DS compared with DR animals. The present studies provide new markers characteristic of the DS phenotype and pose the issue of possible genetic or functional interrelationships among the salt-sensitive hypertension, immunoglobulin disorders, and renal dysfunctions.

Albuminuria↗

Informed consent and tardive dyskinesia.

To determine whether a formalized informing process transmitted knowledge concerning the risks and benefits of neuroleptic medication, particularly the risk of tardive dyskinesia, to stable schizophrenic outpatients, the authors administered a multiple-choice questionnaire to 21 patients who were read a standardized information form and 27 patients who were not. The mean scores for the informed patients were significantly higher, and the differences between the two groups remained significant at 6-month follow-up. The information process had no adverse effects on frequency of psychiatric admission, noncompliance with medication, or the need for increased antipsychotic medication.

Adult↗

Tricyclic maintenance therapy in unipolar depression.

The risk of recurrence of depression must be balanced against the problems and risks of maintenance therapy. The goal of maintenance therapy is to prevent new episodes of depression. A review of the literature reveals that the existing data does not provide sufficient evidence to demonstrate the usefulness of tricyclic maintenance therapy. Nonetheless, it would be premature to conclude that this type of treatment is not useful. Further studies of maintenance therapy are indicated and should include a continuation period of at least 16 weeks during which patients are symptom free (that is, Global Assessment Scale 71 or more). In the interim, each patient should be evaluated individually to determine the optimum duration of treatment.

Antidepressive Agents, Tricyclic↗

Lithium and memory: a long-term follow-up study.

This study examined the effects of long-term lithium therapy on memory functions in 18 patients suffering from bipolar affective disorder. Patients were retested on the Wechsler Memory Scale, Benton Visual Retention Test, and Zung Self-Rating Depression Scale 6 years after initial testing. Mean memory test scores remained remarkably stable over the 6-year interval with only one of the 10 memory subtests showing a statistically, but not clinically, significant decrease. The sample was split at the median duration of lithium therapy into a long- and shorter term group (with means of 12.9 and 5.2 years, respectively). There were no significant differences between these groups on any of the memory tests when controlled for age and initial memory scores. Negative correlations between several memory test scores and the duration of lithium treatment could in part be explained by the effects of age. Patients' subjective complaints of impaired memory functioning, rated on a visual analogue scale, correlated with the level of depression at the second testing as well as with three memory test scores measuring immediate and short-term visual recall. The results are discussed in view of the demographic and clinical characteristics of the sample and are compared with previous research findings.

Adult↗

Tissue distribution and vitamin D dependence of IMCAL in the rat.

Integral membrane calcium-binding protein (IMCAL) is a vitamin D-dependent integral membrane protein that binds calcium with relatively high affinity (J. Biol. Chem. 225: 10834-10840, 1980). Specific immunoassays for IMCAL utilizing rabbit polyclonal and mouse monoclonal antibodies were developed and applied to studies of its tissue distribution and regulation by vitamin D3 and dietary calcium in the rat. The results indicate that vitamin D-dependent, cross-reactive protein is present in small intestinal mucosa, cecal mucosa, bone, kidney, brain, testis, heart, lung, spleen, and skin. Rats maintained on a low- (0.02%) compared with & high- (2.0%) calcium diet had significantly higher content of IMCAL in duodenal mucosa, cecal mucosa, bone, kidney, brain, testis, and heart. Treatment of rats on the high-calcium diet with 1,25-dihydroxyvitamin D3 increased the IMCAL content of the duodenal mucosa, cecal mucosa, and kidney. The widespread tissue distribution of vitamin D-dependent IMCAL, its close correlation in intestinal mucosa with the calcium transport mechanism, and its occurrence in isolated preparations of enterocyte plasma membranes (microvillus and basolateral membranes) suggest that the protein is involved in the regulation of calcium flux in a number of cell types.

Animals↗

Increased rigidity of red blood cell membrane in young spontaneously hypertensive rats.

The micropipette test was used to study the effects of age on the elasticity of red blood cell (RBC) membrane in spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY), ranging from 3 to 23 weeks of age. The development of hypertension in the SHR started at 3 weeks and was fully established at 7 to 8 weeks. In the developmental phase of hypertension (3-5 weeks), the SHR showed a significant increase in RBC membrane elastic modulus (i.e., a decrease in RBC membrane deformability) when compared with the age-matched normotensive control rats (WKY). After the establishment of hypertension (7-8 weeks), however, the deformability of the RBC membrane of SHR improved and became comparable to that of the WKY. These results indicate that abnormal erythrocyte membrane elasticity is an early event in SHR and that adaptive recovery occurs when hypertension is fully developed.

Aging↗

Some biophysical properties of the erythrocyte membrane in Duchenne muscular dystrophy.

Inasmuch as prior authors have suggested a 'generalized membrane defect' in patients with Duchenne muscular dystrophy, this study was undertaken to examine some biophysical properties of the erythrocytes in affected individuals. Using the micropipette technique we investigated the rheological properties of erythrocytes from 11 Duchenne muscular dystrophy patients (boys 3-14 years old) and 5 carriers (mothers 20-42 years old). The mean elastic modulus and membrane viscosity of the patient's erythrocytes were not significantly different from those of a group of 8 unaffected age-matched boys. The carrier group did not differ significantly from the adult control group in any of the rheological parameters. A significant increase in the number of stomatocytes was observed in the patient group, and a similar trend (not statistically significant) was observed in the carrier group. The membrane lipid fluidity of erythrocytes from patients, carriers, and normal controls was assessed with three different probes by fluorescence depolarization, and no significant differences were found. Our results indicate that there is a progressive elevation of the membrane elastic modulus with increasing age of the patients: the younger patients have a lower elastic modulus than their age-matched controls, while the older patients have a higher elastic modulus than their age-matched controls.

Adolescent↗

Decreased content of integral membrane calcium-binding protein (IMCAL) in tissues of the spontaneously hypertensive rat.

Prior studies report that plasma membranes of the spontaneously hypertensive rat (Okamoto-Aoki strain) bind less calcium than do the corresponding preparations from Wistar Kyoto controls. The possibility that the differences result from a decrease in the content of integral membrane calcium-binding protein (IMCAL) was explored by the application of immunoassays with polyclonal antisera and a mouse monoclonal antibody. IMCAL binds calcium with relatively high affinity, and its content in many rat tissues is regulated by vitamin D and the level of dietary calcium. Immunoassays of tissue IMCAL demonstrate significant reductions in content in the erythrocyte ghost, intestinal mucosa, kidney, heart, testis, and liver of the spontaneously hypertensive rat as compared to the control strains. The decreases are observed both at 4-5 weeks of age, before the onset of severe hypertension and at 8-9 weeks in the presence of severe hypertension. Moreover, the magnitude of the decrease in erythrocyte IMCAL can account for much of the decrease in the calcium-binding capacity of erythrocyte membranes reported by others. The results are especially significant because an abnormality in the membrane binding of calcium and in the regulation of cytosolic calcium ion concentration could underlie the pathogenesis of the hypertension.

Animals↗

Sulfhydryl substituents of the human erythrocyte hexose transport mechanism.

Sulfhydryl substituents of the hexose transport mechanism of human erythrocyte membranes were studied with membrane-impermeant and -permeant maleimide derivatives. Three sulfhydryl classes have been identified on the basis of their reactivity toward the reagents and their effects on the transport mechanism. Type I sulfhydryl is located at the outer (exofacial) surface of the membrane and bound covalently on treatment of intact cells with the membrane-impermeant glutathione-maleimide. This sulfhydryl is required for the transport, and it is protected from alkylation, i.e., its reactivity toward maleimides is decreased by the presence of D-glucose or cytochalasin B. Type II sulfhydryl is also required for the transport, but it differs from type I in that D-glucose (but not cytochalasin B) increases the reactivity toward maleimides. Further, it is located at the endofacial surface of the membrane, since reaction with glutathione-maleimide occurs only in leaky ghosts and not in intact cells. Alkylation by glutathione-maleimide of type I and type II sulfhydryls increases the half-saturation for the binding of D-glucose to erythrocyte membranes. In contrast, inactivation of type III sulfhydryls by N-ethylmaleimide or dipyridyl disulfide decreases the half-saturation concentration for the binding of D-glucose and other transported hexoses to the membranes; nontransported sugars are not affected similarly. Type III sulfhydryl is not inactivated by the polar reagent glutathione-maleimide and is probably located in a nonpolar domain of the transport mechanism. Inactivation of either type I or II sulfhydryls decreases or eliminates the flux asymmetry of the hexose transport mechanism.

Biological Transport↗

A role for catecholamines in the pathogenesis of neuroleptic malignant syndrome.

The authors present a case report in which an agitated response to antidepressants preceded the neuroleptic malignant syndrome (NMS). In a review of 64 cases of NMS in the literature, they found that 80% were described as agitated prior to the development of the syndrome. Polypharmacy was common. A review of the literature on theories of pathogenesis involving sympathetic amines other than dopamine is presented to explain this phenomena. It is suggested that these toxic reactions to medication can be interpreted as resulting from a relative NE/DA excess, in which antidepressants increase the numerator, while neuroleptics functionally decrease the denominator. It is recommended that where an agitated response to antidepressants is observed, neuroleptics should be used only with considerable caution.

Akathisia, Drug-Induced↗

Macrophage phagocytosis and membrane fluidity in mice: the effect of age and dietary protein.

Male C57BL/6NNia mice were used to investigate the effects of age and dietary protein intake on Fc and C3b receptor-mediated phagocytosis and on membrane fluidity. Six-month-old (adult) and 24-month-old (aged) mice were fed a 6% or 25% protein diet for 3, 5, or 6 weeks at which time thioglycollate elicited peritoneal macrophages were isolated. Both binding of IgG-coated sheep red blood cells to the macrophages and ingestion via the Fc-receptor were identical in all 4 groups after 3 and 6 weeks of feeding but were decreased at 5 weeks in the aged animals fed 6% protein. Phagocytosis via the C3b receptor was not depressed in either age group fed the low protein diet; it was, however, augmented significantly in the aged animals fed the 25% protein diet for 5 and 6 weeks. Membrane fluidity of the plasma membrane outer hemileaflet was monitored with an impermeant fluorescent probe. No changes were observed between adult and aged mice maintained up to 6 weeks on the diets.

Aging↗

Effects of benzyl alcohol on erythrocyte shape, membrane hemileaflet fluidity and membrane viscoelasticity.

The effects of benzyl alcohol on cell shape, hemileaflet lipid fluidity and membrane rheology of human red blood cells were studied. Membrane fluidity was assessed by determining the fluorescence anisotropy of permeant probes (1,6-diphenyl-1,3,5-hexatriene,12-(9-anthroyloxy)stearate, 2-(9-anthroyloxy)stearate) and a new impermeant probe (N-stachyosylsuccinic acid dihydrazide-2-(9-anthroyloxy)stearate). Measurements made on intact red blood cells reflected primarily the outer leaflet fluidity while measurements made on red blood cells ghosts reflected the fluidity of both leaflets. Membrane viscoelasticity was determined by micropipette aspiration. Treatment of intact red blood cells with benzyl alcohol up to 50 mM caused progressive stomatocytic shape change but no change in membrane viscoelasticity, 1,6-diphenyl-1,3,5-hexatriene anisotropy or stachyosyldihydrazide-2(9-anthroyloxy)stearate correlation time; similar treatment of leaky ghosts yielded decreases in 1,6-diphenyl-1,3,5-hexatriene anisotropy and stachyosyldihydrazide-2(9-anthroyloxy)stearate correlation time. With benzyl alcohol above 50-60 mM, intact red blood cells became echinocytic, and decreases in 1,6-diphenyl-1,3,5-hexatriene anisotropy and stachyosyldihydrazide-2(9-anthroyloxy)stearate correlation time occurred in both intact cells and ghosts; there was no change in membrane viscoelasticity. These results indicate that benzyl alcohol up to 50 mM affects primarily the inner leaflet of the red blood cell membrane and that higher concentrations affect both leaflets. These increases in membrane fluidity are not associated with changes in membrane viscoelasticity. This study illustrates the use of fluorescence techniques to monitor specifically the lipid fluidity of each hemileaflet of the erythrocyte membrane.

Benzyl Alcohol↗

Variations in dietary triacylglycerol saturation alter the lipid composition and fluidity of rat intestinal plasma membranes.

Rats were maintained on nutritionally complete diets enriched in unsaturated (corn oil) or saturated (butter fat) triacylglycerols. After 6 weeks, significant differences in the lipid composition and fluidity of a number of intestinal membranes were observed. The corn oil diet (enriched mainly in linoleic acid) increased the overall unsaturation of the acyl chains and enhanced the lipid fluidity, as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene, of enterocyte microvillus and basolateral membranes and of colonocyte basolateral membranes. Concomitantly, the cholesterol content and the cholesterol/phospholipid molar ratio were increased in the microvillus but not in the basolateral membranes. The increased cholesterol in ileal microvillus membranes can result from enhanced cellular biosynthesis, since ileal slices from rats fed the unsaturated diet incorporated [14C]octanoate more rapidly into digitonin-precipitable sterol. Increased fluidity of the enterocyte microvillus and basolateral membranes, respectively, enhanced the enzyme specific activities of p-nitrophenylphosphatase and (Na+ + K+)-dependent adenosine triphosphatase. The results indicate that the lipid composition, fluidity and enzyme activities of intestinal plasma membranes can be altered by dietary means. Moreover, rat enterocytes possess regulatory mechanisms which modulate the cholesterol content of the microvillus membranes so as to mitigate changes in lipid fluidity.

Animals↗

Calcium alters the acyl chain composition and lipid fluidity of rat hepatocyte plasma membranes in vitro.

Calcium ion decreases the lipid fluidity of isolated rat hepatocyte plasma membranes by modulating the activity of membrane enzymes which alter the lipid composition. To explore the mechanism of the effect of the cation, eight fluorophores were used to assess lipid fluidity via estimations of either steady-state fluorescence polarization or excimer fluorescence intensity. The results demonstrate that the reduction in fluidity occurs in the hydrophobic interior of the bilayer and that both the dynamic and static (lipid order) components of fluidity are affected by treatment with calcium. Analysis of the membrane lipids demonstrates that calcium treatment decreases the arachidonic acid content of the polar lipid fraction and, thereby, reduces the double-bond index of the fatty acids. This change in composition, which is expected to reduce the lipid fluidity, may result from activation by calcium of the endogenous hepatocyte plasma membrane phospholipase A2.

Animals↗

Lipid fluidity and composition of intestinal microvillus membranes isolated from rats of different ages.

The lipid composition and fluidity of microvillus (luminal) membranes isolated from the small intestines of Fisher 344 rats aged 6, 17, and 117 weeks were compared. Lipid fluidity, as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene, was significantly greater in rats aged 6 weeks as compared to 17 or 117 weeks. A lipid thermotropic transition was observed at 17.5 +/- 1.3 degrees C in the membranes of the youngest group, approx. 5-6 degrees C lower than that of the older animals. The differences in lipid composition which account for the higher fluidity of the youngest preparations include a decreased cholesterol/phospholipid molar ratio in both the proximal and distal halves of the small intestine and, in the proximal half alone, increases in the lipid/protein ratio and double bond index. The foregoing reduction in cholesterol/phospholipid ratio derives mainly from a higher content of total phospholipid, and the increment in double bond index results from an increase in arachidonic acid residues. The results demonstrate an age-dependent decrease in fluidity of intestinal microvillus membranes in the early post-weaning period in the rat. This pattern was unlike that of the microvillus membrane p-nitrophenylphosphatase, whose specific activity declined progressively in the older age groups.

Aging↗

Lipid composition and fluidity of rat enterocyte basolateral membranes. Regional differences.

The lipid composition and fluidity of basolateral membranes prepared from the mucosa of the proximal, middle and distal thirds of the rat small intestine were determined. Fluidity, as assessed by the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene and a series of anthroyloxy fatty acid derivatives, is decreased in the distal third as compared to the proximal segments. This pattern is similar to that described previously for microvillus membranes. The decrease in fluidity of the distal as compared to the proximal membranes results from an increase in cholesterol content, cholesterol/phospholipid molar ratio and degree of saturation of the fatty acid residues. In the middle and distal thirds of the gut, the degree of saturation of the fatty acid residues is higher in microvillus as compared to basolateral membranes, accounting in part for the characteristically lower fluidity of the luminal membranes. The specific activity of the basolateral membrane (Na+ + K+)-dependent adenosine triphosphatase is significantly lower in the distal as compared to the proximal and middle thirds of the intestinal mucosa. Studies of the binding of [3H]ouabain indicate that this pattern results from fewer enzyme sites in the distal membranes.

Animals↗