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Biomedical subjects

D Schachter

Publications and source records attributed to D Schachter.

At least 19 recordsLinked to original sources

Child psychiatry and early intervention: I. The aggregate burden of suffering.

This paper discusses the need to estimate the costs of an illness to properly allocate intervention resources for the various psychiatric disorders of childhood. Disorders that require the most community resources should be given the highest priority for early intervention programs. Factors to consider for estimating disorders which are most costly are discussed here: the incidence of the disorder, its severity, whether it is episodic or stable, and its impact on the individual family and the community. These factors contribute to the aggregate burden of suffering caused by a disorder.

Adolescent

Child psychiatry and early intervention: II. The internalizing disorders.

This paper uses the concepts introduced in the paper Child Psychiatry and Early Intervention: I. The Aggregate Burden of Suffering to review the internalizing disorders of childhood. This review surveys the internalizing disorders from the point of view of early intervention, for their prevalence, course, risk, early indicators, associated impairment, and responses to intervention. In general, the internalizing disorders have little effect on the community. When coupled with other disorders such as conduct disorder, or when dealing with suicide, the community's concern for these disorders increases and allocation of resources to target populations who are at risk becomes an important public health goal.

Anxiety Disorders

Child psychiatry and early intervention: IV. The externalizing disorders.

This paper is the last in a series of four using the concept of the aggregate burden of suffering to review the major psychiatric disorders of childhood. This paper reviews the externalizing disorders of childhood to prioritize early intervention programs. The paper discusses the prevalence, course, risk and early indicators, associated impairments, and responses to intervention. The externalizing disorders affect the individual, family and community and are thought to result in the greatest aggregate burden of suffering of all the childhood mental disorders. Early intervention is advocated and will likely need to be intense and long term for this group of children. The need for research into efficient and effective programs is emphasized.

Adolescent

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

Functional interactions of lipids and proteins in rat intestinal microvillus membranes.

Interactions of lipids and proteins in isolated rat intestinal microvillus membranes were examined by studying the temperature dependence of enzyme activities and of D-glucose transport in relation to the membrane lipid thermotropic transition observed by fluorescence polarization (26 +/- 2 degrees C) and differential scanning calorimetry (23--39 degrees C). Two groups of activities were defined. Enzymes of the first group, comprising lactase, maltase, sucrase, leucine aminopeptidase, and gamma-glutamyl transpeptidase, all yielded a single slope on the Arrhenius plot in the range 10--40 degrees C and did not appear to experience functionally the effects of the lipid thermotropic transition. Each activity of the second group, comprising calcium- and magnesium-dependent adenosine triphosphatases, p-nitrophenylphosphatase, and D-glucose transport, showed a change in the slope of the Arrhenius plot in the range 25--30 degrees C, corresponding to the lower region of the lipid transition. The terms "extrinsic" and "intrinsic" activities could be applied to these groups. Delipidation of the particulate p-nitrophenylphosphatase removed the discontinuity in the Arrhenius plot. Subsequent relipidation with a variety of lipids restored a break point, but the temperature corresponded to the original discontinuity (25--29 degrees C) rather than to the phase transition temperature of the exogenous lipid added.

4-Nitrophenylphosphatase

Modulation of erythrocyte membrane proteins by membrane cholesterol and lipid fluidity.

Human erythrocyte membranes were enriched or depleted of cholesterol and effects on membrane proteins assessed with a membrane-impermeant sulfhydryl reagent, [35S]glutathione-maleimide. Reaction of the probe with intact cells quantifies exofacial sulfhydryl groups and reaction with leaky ghost membranes permits quantification of endofacial sulfhydryl groups. The mean endofacial sulfhydryl titer of cholesterol-enriched membranes exceeded that of cholesterol-depleted membrane by approximately 45 nmol/mg of protein or 64%. The corresponding exofacial titer of cholesterol-enriched cells was less than that of cholesterol-depleted cells by approximately 0.4 nmol/mg of protein, or 14%. Labeled membranes were examined by autoradiography of sodium dodecyl sulfate-polyacrylamide gel electropherograms to determine the labeling patterns of individual protein bands. Cholesterol enrichment enhanced the surface labeling of Coomassie brilliant blue stained bands 1,2,3, and 5, decreased the labeling of band 6, and did not change significantly that of band 4. The results demonstrate that changes in membrane cholesterol which influence lipid fluidity can alter the surface labeling of both intrinsic and extrinsic membrane proteins.

Cholesterol

Fluorescence polarization studies of rat intestinal microvillus membranes.

Rat intestinal microvillus membranes and lipid extracts prepared from them have been studied by fluorescence polarization with three lipid-soluble fluorophores: diphenylhexatriene, retinol, and anthroyl-stearate. The degree of fluorescence polarization of diphenylhexatriene, which provides an index of the "microviscosity" of the lipid regions of the membrane, is exceptionally high in microvillus membranes, the highest yet reported in normal biological membranes. Both the membrane proteins and lipids were found to contribute to the high values. With each of the three probes the polarization values are higher in ileal microvillus membranes as compared to membranes from proximal intestinal segments. Temperature-dependence studies of the fluorescence polarization of diphenylhexatriene and anthroylstearate demonstrate a phase transition in microvillus membranes and in liposomes prepared from their lipid extracts at approximately 26+/-2 degrees C. Ambient pH influences markedly the diphenylhexatriene fluorescence polarization in microvillus membranes but has little effect on that of human erythrocyte ghost membranes. The "microviscosity" of jejunal microvillus membranes is maximal at pH 6.5-7.0 and decreases as much as 50% at pH 3.0, an effect which depends largely upon the membrane proteins. Addition of calcium ions to suspensions of microvillus membranes increases the fluorescence polarization of retinol and anthroyl-stearate, but not that of diphenyl-hexatriene. This confirms the localization of the last compound to the hydrophobic interior of the membrane, relatively distant from the hydrophilic head groups of the polar lipids. Microvillus membrane proteins solubilized with Triton X-100 give relatively high fluorescence polarization and intensity values with retinol, suggesting the presence of binding proteins which could play a role in the normal absorptive mechanism for the vitamin.

Animals

Impermeant maleimides. Oriented probes of erythrocyte membrane proteins.

Maleimides impermeant to human erythrocyte membranes have been synthesized and applied to studies of the sulfhydryl groups of the membrane. Reaction of radioactive dextran-maleimide and glutathione-maleimide with either intact erythrocytes or ghosts yields sulfhydryl titers for the outer (exofacial) and inner (endofacial) surfaces, respectively, of 1.5 to 1.7 and 27 to 28 amol/cell. Corresponding values for sulfhydryl groups within the membrane interior, as estimated with radioactive N-ethylmaleimide, are 16 to 22 amol/cell. After exofacial labeling of intact cells with [35S]glutathione-maleimide, autoradiography of sodium dodecyl sulfate-polyacrylamide gels demonstrates four bands (alpha, beta, gamma, and delta) containing, respectively, 13%, 63%, 11%, and 13% of the radioactivity. The major beta-band corresponds in position to polypeptides of molecular weight 40,000 to 70,000 and to Coomassie brilliant blue-stained Band 5. Selective extraction demonstrates that the major Band 5 protein is not identical with the labeled beta-band polypeptides. Following endofacial labeling of ghosts with [35S]glutathione-maleimide, autoradiography reveals radioactivity in all of the major Coomassie brilliant blue bands. The impermeant maleimides described are also applicable to studies of discrete functional proteins of the erythrocyte membrane, including the hexose transport mechanism and the major Rho antigenic site.

Blood Protein Electrophoresis

Impermeant maleimides. Identification of an exofacial component of the human erythrocyte hexose transport mechanism.

The facilitated diffusion of D-glucose across human erythrocyte membranes requires an exofacial (outer surface) sulfhydryl group which can be alkylated by the impermeant reagents glutathione-maleimide and dextran-maleimide. The irreversible inhibition produced by these reagents is asymmetric; inhibition of glucose efflux considerably exceeds that of influx when transport is assayed in the absence of glucose on the opposite side of the membrane. Both D-glucose and cytochalasin B protect the exofacial transport site from alkylation by the impermeant maleimides. This masking effect provides the basis for a two-step procedure for differential labeling of the outer transport site with radioactive glutathione-maleimide. The method labels clearly and consistently a component of the membrane proteins which migrates in sodium dodecyl sulfate-polyacrylamide gels between Coomassie brilliant blue-stained Bands 4.2 and 5, corresponding to an apparent molecular weight of 65,000 to 70,000. Transport studies after inhibition with N-ethylmaleimide suggest that the hexose mechanism also requires a second sulfhydryl group which is not accessible at the cell surface.

Binding Sites

Active transport of iron to mucosal surface of rat jejunum.

Estimations of steady-state fluxes of divalent Fe across rat intestinal segments in vitro provide evidence for two active transport mechanisms. Segments of the distal small intestine transport the mineral against electrochemical potential gradients from the serosal to the mucosal surface. Active transport in the reverse direction was confirmed with segments of proximal duodenum. The distal mechanism is dependent on cellular metabolism and is markedly decreased by metabolic inhibitors or in the absence of a metabolizable hexose. Cycloheximide, which inhibits protein biosynthesis, also blocks the active transport. Perfusion of jejunal and duodenal intestinal loops in situ in anesthetized rats provides evidence that endogenous Fe can be transferred to the lumen by a process otherthan shedding of mucosal cells. It is suggested that such transfer may occur via the active transport mechanism.

Animals

Vitamin D-dependent, particulate calcium-binding activity and intestinal calcium transport.

A vitamin D-dependent calcium-binding activity of relatively high molecular weight has been identified in the particulate fraction of rat small intestinal mucosa. The Ca-binding activity is sedimented at 140,000 X g after treatment of the mucosal particulate fraction with Triton X-114. Intestinal brush-border suspensions can also be used as starting material. The Ca-binding component is inactivated by heat and repeated freeze-thawing and consists of one or more protein complexes in the range of 0.5-1.0 million mol wt as indicated by gel filtration. The Ca-binding activity correlates positively with known features of the intestinal Ca transport mechanism, as demonstrated by studies of the distribution in the small intestine and the effects of vitamin D, dietary Ca, cycloheximide treatment, and rat age. It is suggested that the component might function in the transit of Ca across the brush-border surface to the cytosol of intestinal mucosal cells.

Adenosine Triphosphatases