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Biomedical subjects

A R Brown

Publications and source records attributed to A R Brown.

At least 19 recordsLinked to original sources
PubMed1994

Chamber for testing metered-dose propellant-driven aerosols of immunologically relevant proteins.

A small aerosol chamber was developed for testing and delivery of aerosols of immunologically important proteins to the respiratory tracts of rodents. The chamber was designed to accommodate the small aerosol volumes produced by metered-dose propellant-driven aerosol canisters. Metered bursts of protein aerosols released into the chamber could be sampled for their particle sizes or used to expose the noses of up to six mice to the aerosols. The chamber consisted of a polyethylene tank with two removable plexiglass end plates. One end plate accommodated the propellant-driven, metered-dose, aerosol vial. The other end of the tank was fitted with a plate accepting aerosol sampling devices or a plate containing mouse restrainers. Uniform concentrations of aerosolized proteins were obtained at different positions in the chamber when sampled for particles of respirable size. Respirable-sized protein particles produced by propellant-driven aerosols ranged from 5 to 50% of total aerosolized protein. Propellant-driven aerosols of proteins released in the chamber produced aerosol particles equivalent to 15-26 micrograms of total protein exposure to the respiratory tract of each mouse. The chamber permitted aerosol releases without risk of operator exposure. This aerosol chamber will permit the testing of protein aerosols for their immunologic consequences to the respiratory tract. Potential proteins for testing in this device include immunizing vaccine antigens, immunomodulating cytokine proteins, and passive antibody aerosol therapies against respiratory infections.

Aerosols↗
PubMed1994

Pharmacokinetics and pharmacodynamics of a new cardiotonic vasodilator agent, 349U85, in normal subjects.

OBJECTIVE: To assess the pharmacodynamics and pharmacokinetics of single oral doses of a new vasodilator-cardiotonic agent, 349U85 hydrochloride [6-piperidino-2(1H)-quinolinone hydrochloride], in healthy male subjects. METHODS: This randomized, parallel, double-blind, placebo-controlled, dose escalation trial was conducted at a university-based clinical research center among 27 healthy male subjects. Data measurements used in the study included cardiac index, supine and standing blood pressure, 24-hour ambulatory electrocardiography, and 12-lead electrocardiography. RESULTS: Doses from 2 mg to 250 mg were well tolerated. Cardiac index, supine heart rate, and orthostatic hypotension, indicators of inotropic, chronotropic, and vasodilator effects, respectively, correlated to plasma concentrations of 349U85 and of its metabolite, 661U88. Results suggest that 349U85 may be more responsible for inotropic effects, whereas 661U88 may be more responsible for vasodilatory and chronotropic effects. These results are consistent with the preclinical pharmacologic profile for these two compounds. Headache, orthostatic dizziness, and hypotension tended to occur more frequently at higher doses and were temporally related to drug administration. Pharmacokinetic analyses indicate nonlinearity of 349U85 and 661U88, suggestive of saturation of metabolism and large interindividual variability in maximum plasma drug concentration and area under the plasma concentration-time curve. The source of the variability is not known. The time to maximum distribution was approximately 0.7 hours for both 349U85 and 661U88; the terminal elimination half-life was 1 hour for 349U85 and 3 hours for 661U88. Holter monitoring revealed asymptomatic increases in ventricular and supraventricular ectopic activity in some volunteers; ectopy appeared to be related to the dose of 349U85 and generally occurred at higher doses.

Adult↗
PubMed1993

Interscalene block for shoulder arthroscopy: comparison with general anesthesia.

Arthroscopic shoulder surgery can be performed under regional or general anesthesia. The objective of this study was to demonstrate that regional anesthesia has several benefits over general anesthesia for this type of surgery, particularly in the ambulatory patient. Forty patients received general anesthesia and 63 an interscalene block. The regional block was found to be safe and effective, with a high degree of patient acceptance. It provided excellent intraoperative analgesia and muscle relaxation. Postoperatively, regional anesthesia resulted in fewer side effects, fewer hospital admissions, and a shorter hospital stay than did general anesthesia.

Adolescent↗
PubMed1993

Laparoscopic management of acute small bowel obstruction.

Acute small bowel obstruction is commonly due to band adhesions. In the past it has had an overall mortality rate of up to 11% for elderly patients. In this paper we report three cases of small bowel obstruction, treated by laparoscopic division of the causative bands. All patients recovered rapidly and were discharged within 5 days of surgery.

Acute Disease↗
PubMed1992

Stereoselective high-performance liquid chromatographic assay with fluorometric detection for the isomers of mivacurium in human plasma.

A high-performance liquid chromatographic assay with fluorometric detection was developed for the analysis of the stereoisomers of mivacurium, a new short-acting neuromuscular blocker, in plasma. The isomers were isolated from plasma by solid-phase extraction with C18 and anion-exchange cartridges. The extracts were chromatographed on a LiChrosphere 60 RP Select B column (125 mm x 4.6 mm I.D.) using a mobile phase of acetonitrile-water (4:6, v/v) containing 0.005 M octanesulfonic acid. The fluorescence excitation and emission wavelengths were 202 and 320 nm, respectively. The accuracy and precision of the assay, expressed as the percentage deviation of measured values from true values and the percentage coefficient of variation, respectively, were less than or equal to 10% at all concentrations except for the percentage coefficient of variation at the lower limit of quantitation (5 ng/ml). The assay has been successfully used for the analysis of plasma samples from a pharmacokinetic study in human volunteers.

Chromatography, High Pressure Liquid↗
PubMed1992

In situ detection of autoanti-idiotype antibody-forming cells induced by influenza virus infection.

In situ immunocytochemical-staining methods combined with computer-aided image analysis were employed to examine autoanti-idiotype antibody-forming cell expansion in vivo. Autoanti-idiotype antibody-forming cells were demonstrated in the spleens of C57BL/6J (B6) strain mice intranasally infected with the influenza virus A/Hong Kong/168/(H3N2)[R] X-31. Autoanti-idiotype B cells were detected and elevated in spleen tissues after secondary influenza infections compared to normal B6 mice, and were specific for a dominant idiotype antibody called PY206 reactive with the influenza virus hemagglutinin. Influenza virus-infected BALB/c mice, which make little PY206 Id, did not have increased autoanti-Id against PY206 compared to normal mice. Results provide evidence for an idiotype network-mediated stimulation of autoanti-idiotype B cell production during influenza virus infection.

Animals↗
PubMed1992

Immunological functions of splenic B-lymphocytes.

The spleen is a key lymphoid organ for generating B-lymphocyte (B cell)-mediated humoral immunity. This review examines the key features and functions of splenic B cells. Splenic B cell subsets, including virgin, memory, and CD5+ B cells, are characterized by their phenotypic markers and functions. Structural aspects of the spleen, including red pulp, follicles, periarterial lymphoid sheaths (PALS), and germinal centers, are related to the B cells localized in these areas. The migratory behavior of B cells in these splenic compartments is considered in the context of antigen exposure, adhesion molecules, and migratory stimuli. Antigen-specific B cells in the spleen are examined with an emphasis on their in situ characteristics assessed by immunocytochemical methods. This includes the detection of antigen-binding antibody-forming cells (AFC), idiotype-producing AFC, and the application of computer-aided imaging to analyze these cells. Interactions between splenic B cells and other cell types, such as T-lymphocytes (T cells) and antigen-processing/presenting cells like macrophages and dendritic cells, are briefly examined. Cytokines that influence splenic B cells are reviewed. Interactions between B cells and the neuroendocrine system are discussed briefly. The functions of splenic B cells are considered. Antibody production, cytokine synthesis, and potential immunoregulatory activities are considered.

Antibody Formation↗
PubMed1991

A dominant idiotype in the antibody response against the influenza virus hemagglutinin. Serum and in situ analyses.

PY206 is an Id associated with a BALB/c murine mAb described as being specific for the influenza A virus hemagglutinin. However, production of this Id by BALB/c mice immunized with influenza is low. This report shows that the PY206 Id is a dominant component of the anti-influenza antibody response in C57BL/6J strain mice infected intranasally with the influenza A/Hong Kong/168/(H3N2)[R] X-31 virus. High PY206 Id expression was linked to the IgHb Ig allotype locus. PY206 Id+ antibody-forming cells were identified in situ in cryostat sections of lymphoid tissues and idiotypic heterogeneity was identified among PY206+ B cells. Uninfected adult C57BL/6J mice had PY206 Id in their serum that lacked influenza binding specificity. In situ analysis of prenatal and neonatal spleen of uninfected C57BL/6J mice showed that the expansion of PY206 Id+ B cells occurred early in development. PY206+ cells were demonstrated in the lungs of influenza-infected mice but not in normal mice, establishing the capability to study this B cell population in the lung. This model offers the opportunity to manipulate the anti-influenza A virus hemagglutinin B cell response and to study the proliferation and migration of influenza-specific B cells in their native tissue environments.

Administration, Intranasal↗
PubMed1990

Tumor necrosis factor-alpha analyzed within individual macrophages by combined immunocytochemistry and computer-aided image analysis.

Immunocytochemical staining procedures were combined with computer-aided image analysis to quantitate the relative intracellular production of tumor necrosis factor-alpha (TNF) within individual macrophages. Optimal conditions for time and methods for the activation of TNF production, fixation of cells for optimal immunocytochemical staining, and image analysis methods were determined. Thioglycolate elicited peritoneal macrophages were readily activated to significantly increased levels of intracellular TNF, as early as 1 hr after activation with lypopolysaccharide (LPS) + interferon-gamma: maximum intracellular TNF was evident after 2-3 hr. Both LPS and interferon-gamma was necessary to increase intracellular TNF. Normal alveolar macrophages also readily produced increased intracellular TNF, but normal peritoneal and splenic macrophages were poorly activated to TNF production. Acid stripping of receptor bound TNF allowed discrimination between intracellular TNF/integral membrane TNF, and TNF-receptor-bound TNF. Results stress the importance of studying these TNF forms early after activation. Applications for TNF quantitation by these means are discussed.

Animals↗
PubMed1990

Prevalence of maternal HIV infection based on anonymous testing of neonates, Sydney 1989.

The presence of antibody to human immunodeficiency virus (HIV) in post-partum women may be inferred by screening the blood of their newborn babies, since maternal IgG antibodies freely cross the placenta. We tested a sample of 10,217 newborns from 10 hospitals covering three areas in Sydney and other metropolitan centres in New South Wales from April to July, 1989. None of the specimens gave a positive test for antibody to HIV. Thus, the prevalence of HIV positive serology in this sample of newborns was found to be zero. It was estimated that the seroprevalence of antibody to HIV among all neonates in the study area was between zero and 0.045% (99% confidence interval). Because newborns are an accessible group for the study of HIV, and can act as surrogates for their mothers, anonymous testing of this sentinel group will remove some of the limitations generalizing the information in the present database of HIV infection in Australia. This study provides baseline data and suggests that there is not a widespread epidemic of HIV infection among heterosexual persons in Australia at the present time and that routine antenatal testing of women for antibody to HIV may not be cost-effective. However, it will be important to repeat this study at regular intervals to detect any increase in HIV seroprevalence.

Adult↗
PubMed1990

Combined immunocytochemical staining and image analysis for the study of lymphocyte specificity and function in situ.

Immunocytochemical staining methods were combined with computer-aided image analysis to quantitate relative intracytoplasmic and cell membrane products within single lymphoid cells. Lymphoid cells fixed to microscope slides were immunocytochemically stained and the densities of immunocytochemical stains for individual lymphoid cells were determined on video-camera-captured microscopic images to quantitate synthesized and fully assembled antibody molecules detected by an anti-idiotypic antibody. Similarly, expression of a lymphoid cell membrane molecule, Ly-1, was comparatively quantitated in individual lymphoid cells. Densitometric analysis of tissue sections was utilized to measure tissue areas and quantitate cell nuclei in tissues. Two-color immunocytochemical staining and sequential image analyzer-determined locations of individual cells in tissues allowed unambiguous identification of doubly stained cells in their native tissue environment. This analysis was applied to the in situ identification of antibody forming cells producing the CRIc idiotype of the BALB/c anti-arsonate response and a determination of the mu chain usage by those individual cells. Applications of combined immunocytochemistry and computerized image analysis to studies of in vivo immunologic functions are discussed.

Animals↗
PubMed1989

In situ analysis of antibody-forming cells from the BALB/c CRIc idiotype family: idiotopic heterogeneity among clustered cells.

Immunocytochemical staining methods were applied toward defining the in situ expansion of the BALB/c mouse antibody-forming cells (AFC) that express the CRIc idiotype (id) family associated with the antibody response against the p-azophenylarsonate (Ar) hapten. CRIc+ AFC dominated the early primary anti-Ar response but represented a decreased fraction of the anti-Ar AFC during secondary responses. Two subsets of the CRIc family, CRIc1 and CRIc2, differed in their relative expression, with CRIc1 more pronounced during primary responses and CRIc2 better expanded in secondary responses. Idiotopic differences among AFC in very close proximity suggested convergent migration among B cells having similar but not identical V regions or possibly V region mutations among clonally derived cells. The approach also allowed in situ idiotypic analysis of polyclonally activated B AFC.

Adjuvants, Immunologic↗
PubMed1988

Detection of antibody, idiotype, and anti-idiotype forming cells by in situ immunocytochemical staining.

Methods are described for the immunocytochemical staining of cryostat sections of lymphoid tissue with enzyme conjugates of antigen, idiotype (Id) and anti-idiotype. Results established this as a useful approach, for simultaneously detecting Id and anti-Id antibody forming cells (AFC) in situ. As a model, the 5AF6 Id family associated with the BALB/c mouse antibody response against the p-azophenyl-arsonate (Ar) epitope was examined by two-color immunocytochemical staining, allowing the simultaneous detection of both Id+ and Id- anti-Ar AFC. Spleens from mice secondarily immunized with Ar antigen but not normal mice contained anti-Id AFC stained with the 5AF6 Id but not with another immunoglobulin of the same isotype. A sequential staining method was developed which allowed the detection of both Id and anti-Id AFC in the same tissue, thus providing a means of examining Id and anti-Id antibody networks in intact lymphoid tissues.

Animals↗
PubMed1988

Newborn screening for cystic fibrosis using an enzyme linked immunoabsorbent assay (ELISA) technique.

Neonatal screening for cystic fibrosis (CF) has been conducted using conventional radioimmunoassay. An alternative immunoassay approach has been developed and applied to screening 35,550 newborns. Seventeen confirmed CF infants were detected by both assays. This monoclonal antibody-based enzyme immunoassay using microtitre plate ELISA technology has proved effective in case finding and offers a number of advantages. A reduced labour component, ease of handling, use of nonradioactive reagents, long reagent shelf-life, greater specificity and a reduction in potential sample handling and transposition errors combine to make this technology appropriate for a large volume neonatal screening laboratory.

Antibodies, Monoclonal↗