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Biomedical subjects

C S Brown

Publications and source records attributed to C S Brown.

At least 19 recordsLinked to original sources
PubMed1992

Recombinant parvovirus B19 capsids as a new substrate for detection of B19-specific IgG and IgM antibodies by an enzyme-linked immunosorbent assay.

A new enzyme-linked immunosorbent assay for the detection of B19-specific IgG and IgM antibodies was established using B19 capsids synthesized in a baculovirus expression system. These B19 capsids, consisting of either coat protein VP2 alone or of both VP1 and VP2, have been shown to be similar to native virus in size and appearance. The results obtained for the detection of B19-specific antibodies showed good correlations with a radioimmunoassay which uses native B19 virus and an immunofluorescence assay based on insect cells expressing coat protein VP1. The course of the antibody response could be followed by determining the titers of sequential serum samples taken after a recent B19 infection. Both types of recombinant capsids form an excellent source of antigen for the detection of both B19 IgG and IgM antibodies and are a very promising substitute for native virus.

Antibodies, Viral↗
PubMed1992

Localization of an immunodominant domain on baculovirus-produced parvovirus B19 capsids: correlation to a major surface region on the native virus particle.

An immunodominant region on baculovirus-produced parvovirus B19 VP2 capsids was localized between amino acids 259 and 426 by mapping the binding sites of a panel of monoclonal antibodies which recognize determinants on the particles. The binding sites of three monoclonal antibodies were fine-mapped within this antigenic domain. Six VP2-specific monoclonal antibodies recognized determinants common to both the empty capsids and native parvovirus. The defined antigenic region is most probably exposed on the native B19 virion and corresponds to part of the threefold spike on the surface of canine parvovirus particles.

Amino Acid Sequence↗
PubMed1992

Cardiac surgery in the elderly: the critical care phase.

A growing number of elderly patients (aged 70 years and older) are seen in critical care units after valve surgery or coronary artery bypass grafting. While studies show that the elderly demonstrate overall successful results after cardiac surgery, the mortality and morbidity risks are higher than in younger adults. The elderly patient is more likely to experience postoperative complications, prolonging the recovery phase. Commonly reported postoperative complications include dysrhythmias, pneumonia, cerebral vascular accidents, and infection. Elderly surgical candidates must be evaluated preoperatively to determine risk factors that may affect the critical care recovery phase. The length of stay tends to be longer in the intensive care unit, requiring nursing care that takes the aging process into consideration. The following article focuses on trends in cardiac surgery in the elderly, physiologic factors that affect outcome and recovery, and nursing interventions aimed at preventing or limiting postoperative complications.

Aged↗
PubMed1991

Assembly of empty capsids by using baculovirus recombinants expressing human parvovirus B19 structural proteins.

Empty parvovirus B19 capsids were isolated from insect cells infected with a recombinant baculovirus expressing parvovirus B19 VP2 alone and also with a double-recombinant baculovirus expressing both VP1 and VP2. That VP2 alone can assemble to form capsids is a phenomenon not previously observed in parvoviruses. The stoichiometry of the capsids containing both VP1 and VP2 was similar to that previously observed in parvovirus B19-infected cells. The capsids were similar to native capsids in size and appearance, and their antigenicity was demonstrated by immunoprecipitation and enzyme-linked immunosorbent assay with B19-specific antibodies.

Animals↗
PubMed1991

Treatment of attention deficit hyperactivity disorder: a critical review.

This review evaluates the treatment of attention deficit hyperactivity disorder. Current evidence supports the belief that stimulants are the most effective and least toxic of the drugs used in the treatment of hyperactivity. Tricyclic antidepressants (TCAs), however, are preferable in subpopulations with concomitant anxiety or depressive disorders. Studies comparing stimulants with TCAs are evaluated and studies that have examined other antidepressants are summarized. In addition, TCAs and stimulants are compared according to adverse-effect profiles, pharmacokinetic properties, and subgroup responses. Based on these data and the recently reported sudden deaths in children receiving desipramine, treatment recommendations are made.

Antidepressive Agents, Tricyclic↗
PubMed1991

A placebo-controlled trial of nadolol in the treatment of neuroleptic-induced akathisia.

BACKGROUND: Although propranolol has been documented to be useful in treatment of neuroleptic-induced akathisia, preliminary anecdotal reports on the efficacy of nadolol in treatment of this condition are contradictory. METHOD: To evaluate the efficacy of nadolol in treatment of this condition, a double-blind, placebo-controlled trial was conducted in 20 psychiatric inpatients. Patients with akathisia of at least moderate severity were randomly assigned to receive nadolol 40 to 80 mg/day or placebo. Patients were rated daily for 4 days, then every other day for 15 days by means of the Extrapyramidal Symptom Rating Scale. RESULTS: No significant differences were found between or within groups in subjective restlessness scores. In objective akathisia scores, there were no significant differences between groups; however, beginning at Day 9, both groups showed significant improvement compared with Day 1. There was no difference between groups in number of responders. CONCLUSIONS: The authors' data do not support the efficacy of nadolol in the treatment of neuroleptic-induced akathisia and do not provide support for a peripheral site of action for beta-blockers in treatment of this condition.

Adolescent↗
PubMed1990

An immunofluorescence assay for the detection of parvovirus B19 IgG and IgM antibodies based on recombinant viral antigen.

An indirect immunofluorescence assay for serum IgG and IgM antibodies to human parvovirus B19 was established using recombinant B19 viral antigen, the capsid protein VP1, which had been produced in a baculovirus expression system. This protein gives a strong and characteristic signal in the immunofluorescence assay, making it a suitable candidate for this test system. The test results showed a good correlation with results obtained with a solid-phase capture radioimmunoassay (Cohen et al., 1983). 76% of sera from a random selection of blood donors were positive for B19 IgG which agrees with previous findings. The course of the IgM and IgG antibody response to B19 infection could be followed with the immunofluorescence assay by determining the titers of series of sera taken after a recent B19 infection. Investigation of 24 sera containing rubella-specific IgM showed no cross-reactivity with the recombinant B19 VP1 used in this test system. The test described here has the advantage of being based on a renewable source of antigen and will be further evaluated for routine diagnostic use in comparison with radioimmunoassay.

Animals↗
PubMed1990

Antigenic parvovirus B19 coat proteins VP1 and VP2 produced in large quantities in a baculovirus expression system.

Two baculovirus expression vectors derived from Autographica californica nuclear polyhedrosis virus (AcNPV) were prepared containing the complete 2.5 kb coding region for parvovirus B19 coat protein VP1 (AcB19VP1L) and the 1.8 kb coding region for VP2 (AcB19VP2L), placed under the control of the polyhedrin promoter. The recombinant viruses were used to infect Spodoptera frugiperda cells and the proteins expressed were analysed using appropriate antibodies. AcB19VP1L-infected cells produced B19 VP1 as shown by its reaction with 13 human sera containing B19-specific antibodies in Western blot analysis and indirect immunofluorescence. The signal seen with VP1 in immunofluorescence makes it suitable for the development of a diagnostic assay based on this technique. VP1 also reacted with two monoclonal antibodies (mAbs) specific for the B19 protein part of a 196 kDa beta-galactosidase B19 fusion protein expressed in E. coli. Cells infected with AcB19VP2L produced B19 VP2 which reacted with the same human sera in indirect immunofluorescence and with five of the 13 sera in Western blots. VP2 did not react with the fusion protein-specific mAbs. The large amounts of viral antigen produced in this system means the development of widely available diagnostic tests for B19 infection and the further characterization of the B19 structural proteins are within reach.

Antibodies, Viral↗
PubMed1990

A drug utilization review of prescribing patterns for trazodone versus amitriptyline.

The second-generation antidepressant trazodone has been thought by some clinicians to exert a less robust antidepressant effect than do tricyclic agents. This impression differs from the findings of numerous published clinical trials. In an effort to determine whether this discrepancy may be due to possible inappropriate dosing or use of trazodone for different patient subtypes, a retrospective chart review of 138 depressed inpatients treated with amitriptyline and of 42 depressed inpatients treated with trazodone was performed to compare their respective prescribing patterns. While these two groups did not differ with regard to most demographic variables, results revealed that patient prescribed trazodone were older (trazodone, mean +/- SD age = 54.5 +/- 8.8 years versus amitriptyline, 43.2 +/- 12.9 years; p less than .001), more often had a recurrent depressive disorder (trazodone = 57.1%, amitriptyline = 39.1%, p less than .06), and more frequently had a history of unresponsiveness to other antidepressants (trazodone = 47.6%, amitriptyline = 11.6%; p less than .001). In addition, initially prescribed daily doses of trazodone were below the recommended starting dose of 150 mg/day (mean +/- SD starting dose = 113.7 +/- 42.1 mg/day), while starting daily doses for amitriptyline (mean +/- SD = 69.8 +/- 20.1 mg/day) were judged to be more adequate relative to the recommended daily dose of 75 mg/day. Final trazodone dosage (mean +/- SD final dose = 217.9 +/- 87.5 mg/day) could be judged to have been far short of optimal levels of 250 to 350 mg/day and of up to 600 mg/day for inpatients and 400 mg/day for outpatient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Possible influence of carbamazepine on plasma imipramine concentrations in children with attention deficit hyperactivity disorder.

The effect of carbamazepine on the plasma concentration of imipramine and its metabolite desipramine was examined retrospectively in 36 sex- and age-matched children with attention deficit hyperactivity disorder. One-half of the children received imipramine and the other half received combined carbamazepine and imipramine for 1-6 months. The imipramine dosage was significantly higher in the combined treatment group than in the imipramine-only group. Despite receiving larger doses, the combined treatment group had significantly lower mean levels of imipramine, desipramine, and total tricyclic antidepressant compared with those children receiving imipramine alone. Lowered plasma concentrations of tricyclic antidepressants with carbamazepine coadministration have not been reported previously. Although more rigorous studies are needed to confirm these findings, our data suggest that increased imipramine doses may be necessary for adequate response in children on combined therapy. Moreover, toxicity could result upon withdrawal without imipramine dosage adjustment.

Adolescent↗
PubMed1990

Ocular cicatricial disease. Drug effects in vitro on cell proliferation, contraction, and viability.

Fluoroorotate, tunicamycin, and actinomycin D exhibit optimal effects on cell contractility if cells are exposed to the drug for 72 hr, followed by 24 hr of exposure during the contractility assay. Under these conditions, fluoroorotate and tunicamycin inhibit contractility at concentrations very similar to those required to inhibit proliferation, and at higher concentrations affect cell viability. In contrast, the concentrations at which actinomycin D inhibits cell contractility and viability are very similar, and the concentration at which it inhibits cell proliferation is much lower. These results suggest that fluoroorotate and tunicamycin inhibit cell contractility by inhibiting membrane protein glycosylation. Actinomycin D, which inhibits RNA synthesis, appears to block cell contractility only by blocking cell viability, and its most potent effect inhibits only cell proliferation. Daunomycin exhibits very similar effects on cell contractility if cells are exposed to drug for 48 or 72 hr prior to the assessment of contractility, and its effects are not appreciably increased by the further inclusion of the drug for 24 hr during the contractility assay. Daunomycin also has appreciable effects on contractility if cells are exposed to the drug only for the 24 hr of the contractility assay. Similar to actinomycin D, daunomycin inhibits cell contractility and viability at similar concentrations, and inhibits cell proliferation at much lower concentrations. Moreover, daunomycin can appreciably inhibit cell viability in 24 hr of exposure. Therefore, daunomycin appears only to block cell contractility by blocking cell viability, and its most potent effect inhibits only cell proliferation.

Animals↗
PubMed1990

Psychiatric applications of bromocriptine therapy.

Bromocriptine, an ergot alkaloid derivative that possesses both dopamine agonist and antagonist activity, has been studied in a broad spectrum of psychiatric illnesses. The literature consists primarily of case reports and small trials limited by methodological shortcomings. The authors critically review these reports, focusing on efficacy, mechanistic issues, dosing, side effects, predictors of response, monitoring parameters, and practical guidelines. Preliminary data suggest bromocriptine may have promise in the treatment of neuroleptic malignant syndrome, cocaine withdrawal, and depression. At present, the agent appears less efficacious in the treatment of tardive dyskinesia, mania, and schizophrenia; however, doses in these trials may have been excessive, producing primarily postsynaptic agonist effects. More extensive clinical trials are required to clearly define the role of bromocriptine in psychiatry.

Bromocriptine↗
PubMed1989

A monoclonal antibody to LFA-3, the CD2 ligand, specifically immobilizes major histocompatibility complex proteins.

T cells are activated when the antigen-specific T cell receptor recognizes antigen in association with major histocompatibility complex (MHC) proteins. The T cell surface protein CD2 (T11, LFA-2, the T erythrocyte receptor) and its target or stimulator cell ligand, lymphocyte function-associated antigen-3 (LFA-3), are also involved in T cell adhesion and activation. The molecular mechanisms by which the CD2/LFA-3 interaction affects T cell adhesion and activation are unclear. The CD2/LFA-3 interaction may be modeled by the interaction between LFA-3 and anti-LFA-3 monoclonal antibody (mAb). We used the fluorescence photobleaching recovery technique to investigate the effect of anti-LFA-3 mAb on the lateral mobility of MHC proteins in plasma membranes of JY, a human Epstein-Barr virus-transformed B cell line. Anti-LFA-3 mAb induced immobilization of class I MHC proteins labeled with bivalent but not monovalent fluorescein-conjugated W6/32 mAb. Anti-LFA-3 mAb also caused immobilization of class II MHC proteins labeled with bivalent fluoresceinated LB3.1 mAb. In contrast, anti-LFA-3 mAb did not affect the mobilities of either a B cell membrane protein labeled with bivalent fluoresceinated anti-CD45 (human leukocyte antigen) mAb or a membrane lipid analogue. Unlike anti-LFA-3 mAb, anti-LFA-1 mAb did not affect class I MHC protein mobility. These results suggest that CD2 binding to LFA-3 may trigger a physiological response in which target cell MHC proteins, cross-linked by receptors on the T cell surface, are immobilized at and thereby localized to the T cell-target cell interface.

Antibodies, Monoclonal↗
PubMed1989

Blood platelet uptake of serotonin in episodic aggression.

Blood platelet uptake of 3H-serotonin (5HT uptake), a potential marker of serotonergic function, was determined in male outpatients with episodic aggression (n = 15) and in age- and sex-matched nonaggressive controls (n = 15). Correlations with rating scales of "impulsivity" (Barratt Impulsivity Scale, 10th revision) and "anger" (Spielberger Anger Expression Scale) were performed. Mean 5HT uptake was 18% lower in patients with episodic aggression. A significant negative correlation between % difference in platelet 5HT uptake and impulsivity score was observed, but the correlation between 5HT uptake and anger was not significant. These results support the hypothesis of disturbed serotonergic function in aggression and suggest that the primary relationship is in the "control" of aggression. The blood platelet may be useful in identifying impulsive subtypes.

Adolescent↗
PubMed1989

Targeted drug delivery: a two-compartment growth inhibition assay demonstrates that fluorodeoxyuridine and fluorodeoxyuridine monophosphate are liposome-independent drugs.

The targeted delivery to cells by liposomes and leakage under delivery conditions of fluorodeoxyuridine (FdUR) and fluorodeoxyuridine monophosphate (FdUMP) have been evaluated using a two-compartment growth inhibition assay. Under cell culture conditions, FdUR leaks 100% from all liposomes regardless of charge or phase transition temperature. Under the same conditions, FdUMP leaks 100% from egg yolk phosphatidylglycerol liposomes, 47% from distearoylphosphatidylglycerol liposomes, 44% from egg yolk phosphatidylcholine liposomes, and 10% from distearoylphosphatidylcholine liposomes. All liposomes were prepared from a 67:33 mixture of phospholipid and cholesterol. The two-compartment assay demonstrates directly that neither of these drugs is delivered selectively to the target cells by the liposomes, suggesting that they are liposome independent drugs.

Biopharmaceutics↗
PubMed1989

Transcription, organization, and sequence of an auxin-regulated gene cluster in soybean.

We have characterized a soybean gene cluster that encodes a group of auxin-regulated RNAs (small auxin up RNAs). DNA sequencing of a portion of the locus reveals five homologous genes, spaced at intervals of about 1.25 kilobases and transcribed in alternate directions. At least three of the genes are transcriptionally regulated by auxin. An increase in the rate of transcription is detected 10 min after application of auxin to soybean elongating hypocotyl sections. Each of the genes contains an open reading frame that could encode a protein of 9 kilodaltons to 10.5 kilodaltons. Sequence comparisons among the five genes reveal several areas of high homology. Two regions of high homology begin about 250 base pairs upstream of the open reading frames and two regions of homology have been identified in sequences downstream of the open reading frames. One of the latter sequences occurs in the 3'-untranslated region of the RNAs. The other occurs far downstream, 618 base pairs to 741 base pairs from the stop codon. Conservation of these sequences among the five different genes suggests that they may be important for the regulation of expression of the genes.

Amino Acid Sequence↗
PubMed1989

Characterizing anticholinergic abuse in community mental health.

To identify factors associated with anticholinergic abuse in patients taking antipsychotics and anticholinergics and to document the extent of extrapyramidal side effects in anticholinergic abusers, 21 anticholinergic abusers were matched with 21 controls without a history of anticholinergic abuse for diagnosis and antipsychotic dose. Data were collected prospectively, and extrapyramidal side effects and abnormal involuntary movements were evaluated using the Modified Simpson Angus Scale and the Abnormal Involuntary Movement Scale. The abuse group reported significantly more subjective effects from anticholinergic agents than did those in the control group (mean +/- SD = 10.5 +/- 5.4 vs. 6.5 +/- 3.7, p less than 0.05). The abuse group was significantly more likely to report feeling a buzz (p less than 0.05) and difficulty learning (p less than 0.05) when taking anticholinergic medications. Abusers reported abusing significantly more drugs in the past (2.7 +/- 2.1 vs. 0.8 +/- 0.9, p less than 0.01) and had taken antipsychotics (12.7 +/- 6.3 vs. 8.7 +/- 5.4 years, p less than 0.05) and anticholinergics (10.9 +/- 3.1 vs. 6.1 +/- 4.6 years, p less than 0.01) significantly longer than controls had. Patients in the control group spent significantly more years working full-time than did abusers (6.2 +/- 7.3 vs. 0.7 +/- 1.4, p less than 0.01). There was a nonsignificant trend for abusers with a longer duration of antipsychotic use to have higher Abnormal Involuntary Movement Scale scores (r = 0.40, p less than 0.10). Although these drugs are potentially abusable, the term "anticholinergic abuse" should be reevaluated in light of accumulating evidence that many patients taking these drugs report improved functioning, with improvement in negative symptoms and minimal or no adverse anticholinergic effects.

Adult↗