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Biomedical subjects

C S Brown

Publications and source records attributed to C S Brown.

At least 109 records · Page 6Linked to original sources

Monopalmitoylphosphatidylcholine incorporation into human erythrocyte ghost membranes causes protein and lipid immobilization and cholesterol depletion.

The effects of lysophosphatidylcholine (lysoPC) on human erythrocyte (RBC) ghost morphology, transmembrane protein and lipid lateral mobilities, and membrane lipid composition were studied in order to elucidate mechanisms by which lysoPC immobilizes ghost membrane components [Golan, D. E., Brown, C. S., Cianci, C. M. L., Furlong, S. T., & Caulfield, J. P. (1986) J. Cell Biol. 103, 819-828]. Under standardized conditions 1.0-1.5 micrograms/mL egg lysoPC lysed 50% of RBCs and induced, in some ghosts, the formation of large patches of wrinkled membrane. Patches exhibited complete immobilization of glycophorin and band 3 and partial immobilization of the phospholipid analogue fluorescein phosphatidylethanolamine (Fl-PE), whereas adjacent smooth membrane areas manifested only partial immobilization of proteins and no immobilization of Fl-PE. Supralytic concentrations of lysoPC induced both progressive, homogeneous wrinkling of RBC ghost membranes and concentration-dependent decreases in the lateral mobilities of glycophorin, band 3, and Fl-PE. Complete immobilization of glycophorin and band 3 occurred at 8.4 micrograms/mL lysoPC and of Fl-PE at 16.8 micrograms/mL lysoPC. Monopalmitoylphosphatidylcholine (MPPC), the major component of egg lysoPC, induced both membrane wrinkling and a concentration-dependent decrease in Fl-PE mobility, with complete immobilization at 10 micrograms/mL. Other synthetic lysoPCs did not completely immobilize Fl-PE, although some caused membrane wrinkling. MPPC was incorporated into ghost membranes with a linear dependence (r = 0.97) on MPPC concentration. Relative to total membrane lipid, the lysoPC mole fraction increased from 0.2 +/- 0.1% at 0 micrograms/mL MPPC to 25 +/- 2% at 16 micrograms/mL MPPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol↗

Nutritional assessment of surgical patients.

In order to test the sensitivity and specificity of the East Orange Nutritional Screening Form (EONSF), nutritional assessments were performed on a random sample of 10% of general medical/surgical admissions at a large midwestern veteran's administration hospital. Patients were followed until discharge to determine if they met the standard criteria of additional nutritional support. The tool correctly identified patients at nutritional risk (sensitivity) 95% of the time and patients not at nutritional risk (specificity) 89% of the time. It proved to be an effective, low-cost tool for identifying patients at risk and for planning appropriate nutritional strategies.

Female↗

Class I major histocompatibility complex proteins diffuse isotropically on immune interferon-activated endothelial cells despite anisotropic cell shape and cytoskeletal organization: application of fluorescence photobleaching recovery with an elliptical beam.

Interferon gamma induces striking phenotypic alterations in confluent cultures of human vascular endothelial cells (HEC), including cell shape change from polygonal to elongated and cytoskeletal actin rearrangement from dense peripheral bands to longitudinal bundles of stress fibers. Since many transmembrane proteins, including class I major histocompatibility complex (MHC) proteins, interact with cytoskeletal actin, an interferon-gamma-induced anisotropic arrangement of stress fibers might cause anisotropic lateral diffusion of HEC class I MHC proteins. To test this hypothesis, we adapted the fluorescence photobleaching recovery technique to allow measurement of anisotropic diffusion of fluorescently labeled molecules on two-dimensional surfaces. A highly eccentric elliptical Gaussian laser beam was used to photobleach the sample and to monitor fluorescence recovery. In this technique, named "line fluorescence photobleaching recovery," lateral diffusion is measured along that axis of the sample that is perpendicular to the major axis of the elliptical beam. The lateral diffusion coefficient and fractional mobility are obtained by fitting the experimental data to a theoretical recovery curve, the form of which is determined by the solution to a modified version of the diffusion equation in which a tensor is used to describe diffusion in two orthogonal directions. Fluorescein-conjugated murine monoclonal antibodies were used to label class I MHC proteins on interferon-gamma-treated HEC and human dermal fibroblasts. These two cultured human cell types were found to be similar in their elongated shape and anisotropic stress fiber organization. Class I MHC protein lateral mobility was compared to that of fluorescein-labeled phosphatidyl-ethanolamine, a membrane phospholipid probe. Class I MHC proteins diffused anisotropically on human dermal fibroblasts, whereas fluorescein-labeled phosphatidylethanolamine diffused isotropically on this cell type. In contrast, both class I MHC proteins and fluorescein-labeled phosphatidylethanolamine diffused isotropically on interferon-gamma-treated HEC. These data suggest that neither elongated shape nor anisotropic stress fiber arrangement is sufficient to induce anisotropic diffusion of proteins on the HEC plasma membrane.

Algorithms↗

Monoamine oxidase inhibitors: safety and efficacy issues.

Controversy has historically centered on the use of monoamine oxidase inhibitors (MAOI) in the treatment of depression because of safety and efficacy issues. Hypertensive crisis following ingestion of foods containing tyramine is the most feared problem associated with MAOI therapy. The authors conclude that only four tyramine-containing foods clearly warrant absolute prohibition, but indicate situations where moderation should apply. Although MAOI remain second-line agents in the treatment of endogenous depression, it is unclear whether MAOI or tricyclic antidepressants should be the drugs of choice in atypical depression and this question necessitates future research.

Depressive Disorder↗

Short- and long-term effects of auxiliary labels on patient knowledge of precautionary drug information.

The purpose of this study was to determine the efficacy of auxiliary prescription labels in educating outpatients about medicines at two different time periods. Five hundred fifty-nine patients were randomly assigned either to an experimental group or a control group; each person in the experimental group received a prescription bottle to which one study auxiliary label ("sticker") had been affixed, and those in the control group received bottles with no study sticker attached. Patients were interviewed by telephone approximately one week or two months after prescription pick up. Patients who had the study sticker affixed to their prescription bottle were significantly more knowledgeable after one week about precautionary information than those patients who did not receive stickers; however, sticker-group patients receiving the delayed interview incorrectly attributed many precautions to their medication. This is the first controlled study to document that auxiliary labels increase short-term knowledge about medications, and to suggest that the same labels may result in an inappropriate generalization over time.

Drug Labeling↗

Compensable back pain and migrants.

Ten years of cases of compensable back pain from a rehabilitation centre were reviewed for evidence that is relevant to the strongly negative stereotypes that are held commonly about migrant workers. The prevalence of migrant workers with back injuries was found to be similar to that in the occupations with higher accident liabilities in the surrounding municipalities. The relative proportion of musculoligamentous injuries and the more objectively confirmable back injuries was not related to the country of birth. Better predictors of treatment outcome were: the time that had elapsed between the injury and admission to the Centre; whether the referral was direct or indirect after the previous treatment; and the degree of fluency in English. It is concluded that the stereotypes that describe migrant workers as accident-prone or malingerers cannot be supported and that the vulnerability of migrant workers to the "accident-victim syndrome" can be accounted for without reference to ethnic characteristics.

Accidents, Occupational↗

Lateral mobility of class I histocompatibility antigens in B lymphoblastoid cell membranes: modulation by cross-linking and effect of cell density.

We have studied the lateral mobility of class 1 major histocompatibility complex (MHC) proteins in the membranes of human Epstein-Barr virus-transformed B cells using fluorescence photobleaching recovery. Class I MHC antigens were labeled with either W6/32 monoclonal antibody or its Fab fragment directly conjugated to fluorescein isothiocyanate. The diffusion coefficient of class I antigens labeled with Fab fragments of W6/32 was identical to that of a lipid analogue, fluorescein phosphatidylethanolamine, and was 10-fold greater than that of antigens labeled with intact W6/32. Furthermore, antigens labeled with Fab fragments but not with intact W6/32 had fractional mobilities identical to that of the lipid probe. The lateral mobility of class I antigens was dependent on the time of incubation with fluorescent antibody and on the presence of antibody microaggregates. Finally, class I MHC proteins labeled with intact W6/32 but not with Fab fragments were immobilized in the membranes of most cells grown in suspension at high cell density. These results suggest that, in the unperturbed state, class I MHC antigens diffuse as rapidly as membrane lipid, i.e., without cytoskeletal constraint. Cross-linking with bivalent ligand and growth to high cell density may trigger membrane events leading to slowing and immobilization of these proteins.

Antibodies, Monoclonal↗

Association between type of medication instruction and patients' knowledge, side effects, and compliance.

The authors measured knowledge about medication and its side effects, impact of side effects, and compliance in 30 chronic outpatients before and after they participated in two instruction sessions about their medication held one month apart. Instruction consisted of a verbal or a written and verbal presentation and minimum or maximum information about side effects. All patients' medication knowledge increased after both sessions. Those on high doses of neuroleptics given verbal and written information gained significantly more medication knowledge than those given only verbal information. After instruction, more patients knew about specific side effects, including tardive dyskinesia, and both patients given only verbal instruction and those given minimum information about side effects had fewer problems with side effects. Instruction did not affect compliance.

Adult↗

Gene conversion-like mechanisms may generate polymorphism in human class I genes.

The nucleotide sequences of the human class I major histocompatibility complex genes HLA-B27k and HLA-B27w have been determined. They differ by only four nucleotides over a stretch of 14 bp in exon 2, resulting in three amino acid exchanges at positions 77 (Asp to Asn), 80 (Thr to Ile) and 81 (Leu to Ala). The distribution of these nucleotide substitutions suggests a gene conversion-like event responsible for the generation of these HLA-B27 subtypes. The mechanisms underlying the generation of new polymorphic variants in man are therefore probably identical to the gene conversion-like events postulated in the generation of H-2Kbm class I mutants in the mouse.

Amino Acid Sequence↗

Mapping human chromosomes in somatic cell hybrids using a low-copy-number repetitive sequence.

We have isolated a human-specific repetitive sequence with a copy number of several hundred (p11L26). Using Southern blots of EcoR1-digested DNA from somatic cell hybrids containing one or a few human chromosomes, band patterns specific for those chromosomes can be generated by hybridization with p11L26. Genomic copies of the sequence have also been mapped to subchromosomal regions using translocations. The probe offers a useful addition to the standard techniques for mapping human chromosomes in hybrid cell lines.

Animals↗

Ratings of intelligibility of esophageal and tracheoesophageal speech.

Audio-recorded oral reading and continuous discourse speech samples were obtained from esophageal and tracheoesophageal speakers. The samples were rated twice by each of two groups of listeners, one experienced and the other inexperienced with alaryngeal speech. The main finding was that reliable mean ratings of intelligibility of both types of speech can be obtained from experienced and from inexperienced judges. The experienced and inexperienced listeners tended to rank the speakers similarly with regard to the intelligibility of their speech samples. The reading and discourse samples also tended to be ranked similarly with regard to intelligibility. The tracheoesophageal speakers' samples as a group were rated as more intelligible than were those of the esophageal speakers.

Humans↗

Prescription-writing with a PC.

We described the development of an automated system to perform writing of prescriptions and associated advice. A prototype computer program has been in operation in a dermatologist's office for three years. All prescriptions are routinely generated using the system. The program, originally developed for a multi-user computer system, now operates in a self-contained personal computer. The program is constructed to use external human-readable files as the drug formulary or data base. Experience with this system and efforts to expand its applicability to another ambulatory care setting (gastroenterology) are described. Rapid access to drug names and related information is achieved using diagnosis-specific subsets contained in the personally defined formulary. This organization supports rapid pruning of the list of drugs. From this point, a prescription of the selected drug is displayed on a video terminal. The base-level prescription is easily modified using only five keys organized in a cluster. Preliminary training and performance studies are summarized.

Computers↗

Schistosomula of Schistosoma mansoni use lysophosphatidylcholine to lyse adherent human red blood cells and immobilize red cell membrane components.

Human red blood cells (RBCs) adhere to and are lysed by schistosomula of Schistosoma mansoni. We have investigated the mechanism of RBC lysis by comparing the dynamic properties of transmembrane protein and lipid probes in adherent ghost membranes with those in control RBCs and in RBCs treated with various membrane perturbants. Fluorescence photobleaching recovery was used to measure the lateral mobility of two integral membrane proteins, glycophorin and band 3, and two lipid analogues, fluorescein phosphatidylethanolamine (Fl-PE) and carbocyanine dyes, in RBCs and ghosts adherent to schistosomula. Adherent ghosts manifested 95-100% immobilization of both membrane proteins and 45-55% immobilization of both lipid probes. In separate experiments, diamide-induced cross-linking of RBC cytoskeletal proteins slowed transmembrane protein diffusion by 30-40%, without affecting either transmembrane protein fractional mobility or lipid probe lateral mobility. Wheat germ agglutinin- and polylysine-induced cross-linking of glycophorin at the extracellular surface caused 80-95% immobilization of the transmembrane proteins, without affecting the fractional mobility of the lipid probe. Egg lysophosphatidylcholine (lysoPC) induced both lysis of RBCs and a concentration-dependent decrease in the lateral mobility of glycophorin, band 3, and Fl-PE in ghost membranes. At a concentration of 8.4 micrograms/ml, lysoPC caused a pattern of protein and lipid immobilization in RBC ghosts identical to that in ghosts adherent to schistosomula. Schistosomula incubated with labeled palmitate released lysoPC into the culture medium at a rate of 1.5 fmol/h per 10(3) organisms. These data suggest that lysoPC is transferred from schistosomula to adherent RBCs, causing their lysis.

Animals↗

Current concepts in clinical therapeutics: major affective disorders, Part 1.

The epidemiology, pathophysiology, diagnosis and clinical features, and treatment of unipolar (depressive) and bipolar (manic-depressive) affective disorders are described. Disturbances of mood are the most common psychiatric disorders in adults, with 18-23% of women and 8-11% of men having at least one major depressive episode. Genetic factors are important in both depression and manic-depressive illness. Depression is characterized by a persistent dysphoric mood accompanied by feelings of sadness or hopelessness nearly every day for at least two weeks. The essential feature of a manic episode is an elevated, expansive, or irritable mood associated with symptoms such as hyperactivity and lack of judgment. Treatment involves nonpharmacologic and pharmacologic interventions. Psychotherapy in patients with depression is most useful in improving social functions, while antidepressant drugs reduce relapse rates. Electroconvulsive therapy is indicated in depressed patients at immediate risk of suicide or extreme incapacitation. Tricyclic antidepressants (amitriptyline, imipramine, doxepin, notriptyline, desipramine, trimipramine), second-generation antidepressants (maprotiline, amoxapine, trazodone, bupropion), monoamine-oxidase inhibitors (phenelzine, isocarboxazid, tranylcypromine, pargyline), and lithium are useful in treating patients with affective disorders. Tricyclic agents are the mainstay of treatment for depression; newer second-generation agents should be used in specific subgroups of patients. Lithium is the drug of choice for prophylaxis in bipolar patients, whereas combinations of lithium and tricyclic agents are useful during acute episodes of depression in bipolar patients. Major affective disorders occur commonly and require a careful balance of pharmacologic and nonpharmacologic interventions for proper therapy.

Antidepressive Agents↗

Covalent affinity labeling, detergent solubilization, and fluid-phase characterization of the rabbit neutrophil formyl peptide chemotaxis receptor.

The formyl peptide chemotaxis receptor of rabbit neutrophils and purified rabbit neutrophil plasma membranes has been identified by several affinity labeling techniques: covalent affinity cross-linking of N-formyl-Nle-Leu-Phe-Nle-125I-Tyr-Lys (125I-hexapeptide) to the membrane-bound receptor with either dimethyl suberimidate or ethylene glycol bis(succinimidyl succinate) and photoactivation of N-formyl-Nle-Leu-Phe-Nle-125I-Tyr-N epsilon-[6-[(4-azido-2-nitrophenyl)amino]hexanoyl]Lys(125I-PAL). These techniques specifically identify the receptor as a polypeptide that migrates as a broad band on sodium dodecyl sulfate-polyacrylamide electrophoresis, with Mr 50 000-65 000. The receptor has been solubilized in active form from rabbit neutrophil membranes with the detergents 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and digitonin and from whole cells with CHAPS. Chemotaxis receptor activity was measured by the ability of the solubilized membrane material to bind 125I-hexapeptide or fMet-Leu-[3H]Phe with gel filtration or rapid filtration through poly(ethylenimine)- (PEI) treated filters as assay systems. 125I-PAL was specifically cross-linked to the same molecular weight material in the CHAPS and digitonin solubilized extract, but no specific labeling of the receptor was seen when membranes were extracted with Nonidet P-40 and Triton X-100. Therefore, although a large number of detergents are able to solubilize the receptor, it appears that some release the receptor in an inactive form. The ligand binding characteristics of fMet-Leu-[3H]Phe to the CHAPS-solubilized receptor shared properties with the membrane-bound formyl peptide receptor, both of which showed curvilinear, concave-upward Scatchard plots. Computer curve fitting with NONLIN and statistical analyses of the binding data indicated that for both the membrane-bound and solubilized receptors a two saturable sites model fitted the data significantly better (p less than 0.01) than did a one saturable site model. The characteristics of the two saturable sites model for the soluble receptor were a high-affinity site with a KD value of 1.25 +/- 0.45 nM and a low-affinity site with a KD value of 19.77 +/- 3.28 nM. A total of 35% of the two sites detected was of the higher affinity. In addition, a Hill coefficient of 0.61 +/- 0.12 was observed.

Affinity Labels↗

Serum and lymphocyte, aluminum and nickel in chronic renal failure.

In the past decade, aluminum has been recognized as a toxic metal in patients with chronic renal failure. It is, however, possible that other trace metals, such as nickel, may also have toxic actions in these patients. The plasma concentration of a metal, such as aluminum or nickel, may not provide a valid index of either tissue content or total body burden. In the study reported here, the aluminum and nickel content of lymphocytes was measured and compared with plasma concentrations in normal controls and patients with chronic renal failure. The findings suggest that lymphocytes may be of value as a nucleated 'tissue' for the assessment of trace metal status.

Adult↗