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Biomedical subjects

B Gould

Publications and source records attributed to B Gould.

At least 19 recordsLinked to original sources
PubMed1998

Pretreatment of donor stimulator cells by 16,16 dimethyl prostaglandin E2 influences the recipient immune response.

BACKGROUND: Immunosuppressive strategies have largely ignored donor-derived stimulatory cells as a target. This study examined whether lipopolysaccharide (LPS) or 16,16 dimethyl prostaglandin E2 (dmPGE2) pretreatment of stimulator cells from B10.BR mice influences effector function of responder T lymphocytes from C3H/HeJ mice in vitro or in vivo. METHODS: B10.BR spleen cells were incubated in vitro in the presence or absence of dmPGE2 or or LPS before the cells were used as stimulators in a mixed lymphocyte culture (MLC) with T cells from C3H/HeJ mice. In parallel studies, B10.BR mice were treated in vivo with dmPGE2 or LPS; spleen cells from these animals were used as stimulators in an MLC and skin was harvested for skin grafts. Cells from untreated or pretreated mice were examined for expression of intercellular adhesion molecule-1 (ICAM-1), B7-1, and B7-2 by fluorescence-activated cell sorter analysis. ICAM-1 mRNA transcripts were determined by reverse transcriptase-polymerase chain reaction. RESULTS: Stimulation of B10.BR-derived spleen cells with LPS before their use as stimulator cells in a MLC resulted in an increase in responder T-cell proliferation compared with use of unstimulated spleen cells (P < 0.05). In contrast, pretreatment of stimulator spleen cells with dmPGE2 resulted in dose-dependent inhibition of the responder T-cell proliferation, with maximum effect seen using a concentration of dmPGE2 of 10(-5) mol/L. The decreased expression of interleukin-1, tumor necrosis factor, leukotriene B4 procoagulant activity, and ICAM-1 by the dmPGE2 pretreated spleen cells correlated with their inefficient in stimulating T-cell proliferation. Spleen cells harvested from B10.BR mice previously injected with dmPGE2 similarly were inefficient as stimulator cells. Skin graft survival was delayed, but not prevented, by in vivo pretreatment of donor mice with dmPGE2. CONCLUSIONS: These data demonstrate the effect of immunomodulation of allogeneic stimulator spleen cells on subsequent responder T-lymphocyte function and allograft survival.

16,16-Dimethylprostaglandin E2↗
PubMed1998

Ongoing physician guidance to achieve periodic mammography of women at an urban health center.

The use of a low-cost behavior prompt at an urban, hospital-based health center that encourages physicians to record and act upon cancer screening information is described. Brief audit forms were incorporated into medical records of all women 40+ years of age seen between June 1994 and March 1996 (approximately 4,700 office visits). Audit forms alerted physicians about women's breast and cervical cancer screening histories and encouraged them to note any screening done or recommended during an office visit. Patient attributes did not readily distinguish who was and was not screened with mammography at recommended intervals, nor whether physicians did or did not address those needs for examination. On the other hand, explicit, continuous monitoring in medical records of the cancer screening status of women was associated with outcome variables. Availability of information on prior cancer screening activities significantly increased the odds that women were "on-time" for examinations as well as that physicians addressed the needs of women who were "past due" for mammograms at the time of their office visits.

Adult↗
PubMed1997

The effect of immunomodulation of stimulator antigen presenting cells on subsequent responder T-cell function.

In this study, we examined whether lipopolysaccharide (LPS)-, interferon-gamma (IFN-gamma) or 16,16-dimethyl prostaglandin E2 (dmPGE2)-pretreatment of stimulator spleen cells from C57BL6 (B6) mice affects effector function of responder T-lymphocyte from C3H/HeJ mice. Stimulation of B6-derived splenic mononuclear cells (SMNCs) with LPS (10 micrograms/ml) prior to their utilization as stimulator cells in a mixed lymphocyte culture (MLC) resulted in an increase in responder T-lymphocyte proliferation compared to utilization of unstimulated SMNC (P < 0.05). IFN-gamma demonstrated similar effects in a dose dependent fashion with maximal stimulatory effect seen at 1000 U/ml. In contrast, pretreatment of stimulator SMNC with dmPGE2 resulted in dose-dependent inhibition of the responder T-lymphocyte proliferation with maximum inhibitory effect seen using a concentration of dmPGE2 of 10(-5) M. The presence of indomethacin in the MLC did not reverse this effect. These data demonstrate the effect of immunomodulation of stimulator spleen cells on subsequent T-lymphocyte function.

16,16-Dimethylprostaglandin E2↗
PubMed1996

The role of ICAM-1 in the induction of antigen-specific T cell hyporesponsiveness.

We have previously demonstrated that pre-transplant transfusion of allogeneic splenic mononuclear cells from B10.BR mice to C3H/HeJ recipient mice resulted in subsequent antigen specific skin graft prolongation and an associated predominance of IL-4-producing T lymphocytes. In this report, we examined the role of ICAM-1 in the induction of T cell hyporesponsiveness and skin graft prolongation following intrahepatic alloantigen delivery. C3H/HeJ mice receiving splenic cells from B10.BR mice intrahepatically showed antigen-specific enhanced skin graft survival. This graft survival was further prolonged following pre-treatment of infused cells with anti-ICAM-1. No such prolongation was seen following intravenous administration of cells in the presence or absence of anti-ICAM-1 pre-treatment. Anti-ICAM-1 infusion alone similarly had no effect when given intrahepatically or peripherally. T lymphocytes from the mice receiving intrahepatic splenic cells and anti-ICAM-1 produced significantly higher amounts of IL-4 compared to mice receiving intrahepatic cells alone or intravenous cells. PCR analysis of ICAM-1 mRNA transcripts demonstrated an increased expression of ICAM-1 in the spleen compared to the liver. These results suggest that ICAM-1 plays an important role in the induction of T cell hyporesponsiveness and allograft prolongation following the intrahepatic encounter of alloantigen.

Animals↗
PubMed1993

Lymphocyte phenotype and function in the chronic fatigue syndrome.

Lymphocytes of 18 patients meeting the Centers for Disease Control (CDC) case definition for the chronic fatigue syndrome (CFS), 10 similar, chronically fatigued patients not fully conforming to the CDC case definition, and 17 matched, healthy individuals were studied to determine the presence of abnormalities of peripheral cell phenotype and function. Extensive phenotypic analyses of B- and T-cell subsets, natural killer (NK) cells, and macrophages were performed using single-, dual-, and three-color flow cytometry. Compared to controls, in CFS patients the percentage of CD4 T cells and CD4,CD45RA, or naive T cells, was reduced. The CD4,CD45RO, or memory T-cell, subset was numerically normal but expressed increased levels of adhesion markers (CD29, CD54, and CD58). CFS patient lymphocytes showed reduced proliferative responses to phytohemagglutinin, concanavalin A, and staphylococcal enterotoxin B. Lymphocytes from fatigue patients not meeting the CDC definition showed similar abnormalities. These data indicate that peripheral T cells manifest an increased state of differentiation in CFS and related conditions. This may arise as a consequence of an underlying neuropsychiatric and/or neuroendocrine disorder or because of exposure to antigens or superantigens of an infectious agent.

Adolescent↗
PubMed1991

Clinical evaluation of intraperitoneal Pseudomonas exotoxin immunoconjugate OVB3-PE in patients with ovarian cancer.

OVB3-PE is an immunotoxin composed of a murine monoclonal antibody reactive with human ovarian cancer and conjugated to Pseudomonas exotoxin (PE). Twenty-three patients with refractory ovarian cancer were treated intraperitoneally (IP) with escalating doses of OVB3-PE to study toxicity, pharmacokinetics, antiimmunotoxin antibody formation, and antitumor response. Dose-limiting CNS toxicity occurred after repeated doses at 5 and 10 micrograms/kg. Other non-dose-limiting toxicities included transient elevation of liver enzymes, fever, and gastrointestinal toxicity. Pharmacokinetics of IP and serum OVB3-PE were determined in 16 patients. Peak peritoneal fluid levels exceeded the in vitro median effective dose at all doses tested. At doses of 1 to 2 micrograms/kg, the immunotoxin concentration in the peritoneal fluid remained constant for up to 8 hours and dropped to negligible levels after 12 hours. At the 5 and 10 micrograms/kg doses, levels remained high for up to 24 hours (greater than 100 ng/mL) and then gradually decreased and became undetectable (less than 4 ng/mL) after 72 hours. Serum levels of OVB3-PE were also analyzed in 16 patients. At doses of 1 micrograms/kg and 2 micrograms/kg, serum levels were not detectable (less than 5 ng/mL). However, after doses of 5 or 10 micrograms/kg, peak serum level occurred at 24 hours after each dose and dropped to negligible levels by 72 hours. Sera from 12 patients were analyzed for anti-PE antibodies and antibodies to mouse immunoglobulin (HAMA). All patients developed antibodies against PE within 14 days of therapy. Domain II of PE appeared to be the most immunogenic portion of the PE molecule. HAMA was detected on day 14 of therapy in nine patients, on day 21 in two, and on day 28 in one patient. No clinical antitumor responses were observed. We conclude that IP OVB3-PE at dose levels of 5 micrograms/kg (x 3) and 10 micrograms/kg (x 2) is accompanied by dose-limiting toxic encephalopathy. Neurologic toxicity is likely to be due to crossreactivity of OVB3 to normal human brain tissue, which was not appreciated during preclinical screening.

ADP Ribose Transferases↗
PubMed1990

The separation and detection of alkaline oligoclonal IgG bands in cerebrospinal fluid using immobilised pH gradients.

A method is described for the separation and detection of highly alkaline IgG bands in unconcentrated cerebrospinal fluid (CSF). These bands are frequently found in the cerebrospinal fluid of patients with inflammatory diseases of the central nervous system, particularly in the case of multiple sclerosis, and their detection is an important aid in clinical diagnosis. An isoelectric focusing technique using an immobilised pH gradient in polyacrylamide gel has been developed over the pH range 7-10, producing a linear and stable pH gradient with excellent resolution. After electrofocusing, the protein patterns were blotted onto polyvinylidene difluoride membranes and visualised using anti-human IgG followed by an enzyme-labelled second antibody. Blotting could be carried out by capillary diffusion for up to 16 h duration without any loss in resolution. Using this method, highly alkaline intrathecal IgG bands were found in the cerebrospinal fluid of all of the 14 multiple sclerosis patients. There were also 2 patients with alkaline IgG bands in their cerebrospinal fluid who were not diagnosed as multiple sclerosis. By contrast, no alkaline IgG bands with an isoelectric point (pI) greater than 8.6 were found in any of the serum samples studied (n = 50) from patients with various neurological disorders including multiple sclerosis.

Buffers↗
PubMed1988

Visual acuity changes with age: some new perspectives.

Snellen chart visual acuity is thought to change very little up to age 60 years. However, any changes in contrast in the retinal and/or neural image with age may only be detected in low contrast and low luminance testing conditions. Only under these conditions does contrast significantly influence visual acuity measurements. In this pilot experiment we show that low contrast visual acuity is considerably worse (two lines of Snellen acuity) for an older group (N = 8, mean age 57) than for a younger group (N = 9, mean age 24.6) in spite of the fact that each subject was referred to the study with 6/6 (20/20) or better acuity. At conventional contrast and luminance levels there is no significant difference between the two groups. The results also suggest that a simple measurement of contrast sensitivity for a small spot of light may allow a contrast correction factor to account for both age and luminance level differences in the contrast vs. acuity function.

Adult↗
PubMed1988

A residents' training program for the development of smoking intervention skills.

This article describes the results of a three-hour training program that teaches residents a patient-centered counseling approach to smoking cessation, emphasizing questioning and exploring feelings, rather than providing information. Fifty internal medicine and family practice residents affiliated with a university medical center were assessed before and after training using questionnaires and videotape documenting changes in their knowledge about smoking, attitudes concerning intervention, and intervention skills. The residents showed a significant increase in knowledge and perceived themselves as having significantly more influence on their patients who smoke after completion of the training program. Counseling skills improved significantly in the use of questions and exploring feelings as judged by blind evaluation of videotapes. The results of this three-hour training program suggest that physicians in training are responsive to the teaching of specialized skills deemed important for promoting health behavior changes in their patients.

Attitude of Health Personnel↗
PubMed1982

Rapid reduction of blood pressure with acute oral labetalol.

1 The effect of acute oral administration of labetalol on intra-arterial pressures in a group of ten hypertensive patients has been evaluated. 2 A single dose of 200 mg labetalol produced a significant reduction in systolic and diastolic pressures within 1 h of administration. 3 Within 24 h of initial administration, 200 mg three times daily produced a significant reduction in ambulant arterial levels of systolic pressure for 21 h and diastolic pressure for 14 h in the day. 4 Acute therapy lowered resting levels but there was no significant reduction in systolic pressure during either isometric or dynamic exercise. 5 Acute therapy was not associated with any significant postural hypotension.

Administration, Oral↗
PubMed1982

Cognitive learning in the health sciences: a case for self-instruction.

The health professions are faced today as never before with the need to find more effective ways of acquiring a growing volume of biomedical knowledge and of addressing the urgent concerns about learning processes--namely, the continued dependence on outmoded techniques of cognitive transfer. The author believes that greater incentives should be given for faculty and students to experiment with innovative approaches to cognitive learning while recognizing the need for increased emphasis on problem-solving skills in medical care. Proven self-learning techniques demand greater attention in curriculum and course design efforts. Finally, the author states that the process of educational planning must be viewed as continuous, dynamic, and never-ending if it is to best serve the needs of individual students, educational institutions, and the society to which both are ultimately accountable and committed to serve.

Computer-Assisted Instruction↗
PubMedDate not supplied

Evaluation of a satellite educational program.

OBJECTIVES: To evaluate the effectiveness of an educational program using a combination of live satellite programming and individualized instruction. A secondary goal was to develop an evaluation strategy that would be useful to other educators who provide distance-based educational programs. SETTING: A program designed for public health officers who would serve as laboratory directors in local public health laboratories was presented live by satellite in June 1993. PRACTICE DESCRIPTION: The course emphasized good laboratory practice as needed to direct a laboratory performing moderate complexity tests. Physicians who completed the course received 20 continuing medical education credits and qualified as laboratory directors under the Clinical Laboratory Improvement Amendments of 1988 (CLIA 88). MAIN OUTCOME MEASURES: Increase in participants' knowledge of good laboratory practices and application of the practices in their laboratories. RESULTS: Participant satisfaction levels in areas ranging from quality of the video transmission to meeting the course objectives were favorable. Participants demonstrated a significant gain in scores on a test given before and after the course. Problem solving exercises posed during the telecast demonstrated that the participants were actively involved and had completed the self-study material. A sample of participants surveyed several months after the course indicated that many had applied the course material in their workplaces. CONCLUSIONS: Distance-based education using a combination of interactive videoconferencing and self-study material can be a useful tool to enhance cognitive skills for a geographically diverse group of individuals. If carefully planned in advance, evaluation of distance-based educational programs can provide information that verifies the effectiveness of the program.

Education, Medical, Continuing↗