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Biomedical subjects

M Brown

Publications and source records attributed to M Brown.

At least 397 records · Page 22Linked to original sources
PubMed1993

Effect of corticotropin releasing factor on acid-base alterations and bacterial translocation in a murine model of thermal injury.

Corticotropin-releasing factor (CRF) is a 41 amino acid polypeptide produced by the hypothalamus which has been shown to decrease inflammation and tissue oedema when administered following burns, cold and acid injuries in some animal models, and to increase mesenteric blood flow. We determined whether systemic administration of CRF to burned mice would decrease metabolic acidosis and protect the gastrointestinal (GI) tract from ischaemic injury leading to bacterial translocation (BT). Synthetic CRF was administered by intraperitoneal injection in doses of 20 and 200 micrograms/kg to mice immediately following 25 and 32 per cent TBSA burn injuries; the doses were repeated at 8 and 16 h postburn. Severe metabolic acidosis, measured 12 h after burn injury, was not improved in mice which received CRF treatment. Bacterial translocation, measured by quantifying bacteria in mesenteric lymph nodes harvested from animals 48 h postburn, was also not decreased with CRF treatment. CRF does not improve general tissue perfusion nor decrease GI derangements leading to bacterial translocation in this animal model of burn injury.

Acid-Base Equilibrium↗
PubMed1993

Factors affecting uniformity in interpretation of planar thallium-201 imaging in a multicenter trial. The Multicenter Study on Silent Myocardial Ischemia (MSSMI) Thallium-201 Investigators.

OBJECTIVES: This study was designed to assess factors affecting interobserver agreement in interpretation of planar thallium-201 stress imaging in the Multicenter Study on Silent Myocardial Ischemia (MSSMI). BACKGROUND: Five hundred fifty-six planar thallium-201 images were interpreted in 24 clinical centers and in a Radionuclide Core Laboratory. The trial's Coordinating and Data Center observed that the participating clinical centers interpreted a significantly greater number of thallium-201 stress studies as abnormal (i.e., myocardial ischemia or scar) than the Core Laboratory, and overall agreement was poor (kappa 0.27). METHODS: Agreement in image interpretation between clinical centers and the Radionuclide Core Laboratory was analyzed by kappa statistics. The reproducibility of the Core Laboratory results on 41 randomly selected test studies was excellent (kappa 0.77). In contrast, the reproducibility of interpretation in the clinical centers on their own studies was at best fair (kappa 0.45). It was hypothesized that the poor agreement and reproducibility in the clinical centers were caused by lack of standardization of image display and lack of objective criteria for image interpretation. To test the effect of standardization, 13 clinical investigators interpreted the same 41 test studies using 1) uniform image display, and 2) uniform quantification of images. RESULTS: The agreement in interpretation between clinical investigators and the Radionuclide Core Laboratory improved modestly with uniformity of image display (kappa 0.57) but improved markedly (kappa 0.66) with quantitative circumferential profile analysis. CONCLUSIONS: Lack of standardization in image display and lack of objective criteria for interpretation of thallium-201 images are responsible for suboptimal reproducibility and poor interlaboratory agreement in the interpretation of thallium-201 stress imaging. The adoption of a uniformly accepted method for computer quantification of myocardial perfusion images is crucial to improve agreement in interpretation.

Exercise Test↗
PubMed1993

Characterization of a new IL-6-dependent human B-lymphoma cell line in long term culture.

We have established a cell line (DS-1) of B-cell lineage in long-term culture. It was derived from an immunodeficient patient with intestinal lymphangiectasia and lymphoma by culturing malignant pleural effusion cells with IL-6 in vitro. The cell surface phenotype was; PCA-1, HLA Class II(+); CD25, CD19, CD20, CD30, CD38(-). Cell proliferation was poor in medium and exhibited an eight-fold, dose-dependent increase of proliferation in response to rIL-6 of human but not murine origin. The secretion of IgG into culture supernatants by DS-1 was not enhanced by rIL-6. While constitutive production of IL-6 was not detected by bioassay using murine B9 hybridoma cells or by ELISA, the presence of IL-6 message was detected in polyA+ selected mRNA by Northern analysis. Spontaneous proliferation of DS-1 cells was inhibited by neutralizing polyclonal antibodies to IL-6 (37%) and mAb to IL-6 (54%) and IL-6R (53%). DS-1 expressed both high and low affinity IL-6 receptors (Kd 1.2 x 10(-11) and 6.7 x 10(-10), respectively) by radiolabelled binding and Scatchard analysis. Thus, DS-1 represents an autocrine IL-6-producing cell line of B-cell lineage which resembles lymphoid malignancies arising in patients with AIDS and other immunodeficiency diseases. Despite constitutive IL-6 production, the in vitro growth of DS-1 is dependent upon exogenous IL-6. DS-1 may thus be useful as a model of IL-6 dependency. This cell line may also facilitate development of strategies for diagnosis and treatment of B-cell lymphomas in immunocompromised patients.

Adult↗
PubMed1993

Comparison of temperature measurements by an aural infrared thermometer with measurements by traditional rectal and axillary techniques.

OBJECTIVE: To compare temperatures obtained with glass-mercury axillary and aural infrared thermometers with temperatures obtained with glass-mercury rectal thermometers. DESIGN: Blind comparison with criterion standard. SETTING: Well-baby nursery at a private teaching hospital. PATIENTS: Convenience sampling of 200 term newborn infants. INTERVENTION: Temperatures were measured simultaneously with glass-mercury rectal and axillary thermometers for a 3-minute period by one investigator. In a blinded fashion, a second investigator obtained three aural temperatures by using two tympanic membrane thermometers. One tympanic membrane reported infants' rectal-equivalent temperatures, and a second reported oral equivalent temperatures. RESULTS: Temperatures obtained with glass-mercury rectal and axillary thermometers for the population were similar (37 degrees +/- 0.4 degree C vs 36.8 degrees +/- 0.3 degrees C, respectively), but 25% of measurements at these two sites differed by > 0.3 degree C. Oral-equivalent tympanic membrane temperatures were more accurate than rectal-equivalent temperatures in predicting an infant's glass-mercury axillary and rectal temperatures (75% of oral-equivalent temperatures vs fewer than 50% of rectal-equivalent temperatures were within 0.3 degree C of either glass-mercury rectal or axillary measurements). CONCLUSIONS: Temperatures obtained with glass-mercury axillary and rectal thermometers are similar in most cases. However, temperatures obtained with tympanic membrane thermometers either in the rectal-equivalent mode or in the oral-equivalent mode did not accurately reflect an infant's rectal or axillary temperature. We believe that tympanic membrane temperatures should not be substituted for rectal or axillary temperatures in assessments of newborn infants.

Axilla↗
PubMed1993

Blastocystis hominis in inflammatory bowel disease.

We retrospectively examined the hospital course of 12 patients with exacerbated inflammatory bowel disease (IBD), who also had stool specimens positive for Blastocystis hominis to determine the effect of B. hominis on their disease. Bloody bowel movements were common with ulcerative colitis patients and watery diarrhea with Crohn's disease; other findings included abdominal pain, fever, nausea, and vomiting. All patients responded favorably to medical therapy. Three responded to treatment with corticosteroids alone, and one patient improved with bowel rest without medications. Five patients failed to improve on metronidazole; four of them responded to a subsequent course of corticosteroids, whereas the fifth patient became asymptomatic after erythromycin treatment for concomitant Campylobacter jejuni. Finally, three patients responded to treatment with metronidazole alone, which is known to eradicate B. hominis but may also have a beneficial effect on IBD. In no case did corticosteroid treatment worsen the condition. Our findings indicate that B. hominis is not a significant pathogen in IBD and treatment must be directed toward the underlying illness.

Adult↗
PubMed1993

Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

Base Sequence↗
PubMed1993

Electrophysiology of type II mesangiocapillary glomerulonephritis with associated fundus abnormalities.

The retinal electrophysiology is reported in four patients with type II mesangiocapillary glomerulonephritis and partial lipodystrophy with associated fundus abnormalities and no visual symptoms. The histological hallmark of the condition is that of widespread electron dense deposits in the renal glomerulus and in the choriocapillaris and Bruch's membrane of the eye. Three of the four patients had the typical fundal appearance of multiple, yellow, drusen-like lesions at the posterior pole of the eye with normal visual acuity. These three patients had abnormally low Arden ratios on electro-oculography with normal electroretinography responses. This is the first clinical model of disease known to be isolated to the choriocapillaris and Bruch's membrane causing an electro-oculographic abnormality without any clinically detectable deficit in visual function.

Adult↗
PubMed1993

Cloning of a virulence factor of Entamoeba histolytica. Pathogenic strains possess a unique cysteine proteinase gene.

Cysteine proteinases are hypothesized to be important virulence factors of Entamoeba histolytica, the causative agent of amebic dysentery and liver abscesses. The release of a histolytic cysteine proteinase from E. histolytica correlates with the pathogenicity of both axenic strains and recent clinical isolates as determined by clinical history of invasive disease, zymodeme analysis, and cytopathic effect. We now show that pathogenic isolates have a unique cysteine proteinase gene (ACP1). Two other cysteine proteinase genes (ACP2, ACP3) are 85% identical to each other and are present in both pathogenic and nonpathogenic isolates. ACP1 is only 35 and 45% identical in sequence to the two genes found in all isolates and is present on a distinct chromosome-size DNA fragment. Presence of the ACP1 gene correlates with increased proteinase expression and activity in pathogenic isolates as well as cytopathic effect on a fibroblast monolayer, an in vitro assay of virulence. Analysis of the predicted amino acid sequence of the ACP1 proteinase gene reveals homology with cysteine proteinases released by activated macrophages and invasive cancer cells, suggesting an evolutionarily conserved mechanism of tissue invasion. The observation that a histolytic cysteine proteinase gene is present only in pathogenic isolates of E. histolytica suggests that this aspect of virulence in amebiasis is genetically predetermined.

Amino Acid Sequence↗
PubMed1993

Conceptual metaphors are not automatically accessed during idiom comprehension.

Do conceptual analogies motivate idiom use and comprehension in discourse? For example, a story in which a person is described as fuming would be analogically consistent with an idiom such as blew her top, but inconsistent with an idiom such as bite his head off. Earlier work by Nayak and Gibbs (1990) had suggested that people use such analogical information during idiom comprehension. We replicated their findings in an idiom choice task, suggesting that people can indeed make use of such knowledge. However, when reading times were used to assess idiom comprehensibility, no effects of analogical consistency were found. We conclude that conceptual analogies play little, if any, role in idiom comprehension unless people have the time (and motivation) to make considered judgments.

Adult↗
PubMed1993

Getting to go in managed care.

The challenge for leadership and the required changes are great. Our personal limitations include a limited view of the world and the threat of an overwhelming risk if one gets too far out on the limb. "Getting to go" will open up new and strange territories that will provide opportunity and failure for leaders. Capable leaders will pursue the opportunity. Threatened leaders will resist the change. For those leaders who feel that the managed care existing today provides the most cost-effective, quality outcome for the individual, his or her sponsor in the community, they will go no further. Unfortunately for many of us, managed care means a third party trying to micromanage patients (deductions, authorizations, and so on), employers (claims, incentives, and so forth), and providers (approvals, forums, payment, tricks, and the like). Providers need to go ahead and master efficient care. We owe that to the community and the third party nightmare of administrative overkill must be laid to rest. For those healthcare leaders who believe that managed care as a system focused on improving the health status of our communities is superior to our existing system, their individual goals and leadership focus must be changed accordingly. We cannot sit by idly and wait for the system to change us. Instead our obligation is to lead our organizations toward a new era in health care.

Comprehensive Health Care↗
PubMed1993

Using Dirichlet mixture priors to derive hidden Markov models for protein families.

A Bayesian method for estimating the amino acid distributions in the states of a hidden Markov model (HMM) for a protein family or the columns of a multiple alignment of that family is introduced. This method uses Dirichlet mixture densities as priors over amino acid distributions. These mixture densities are determined from examination of previously constructed HMMs or multiple alignments. It is shown that this Bayesian method can improve the quality of HMMs produced from small training sets. Specific experiments on the EF-hand motif are reported, for which these priors are shown to produce HMMs with higher likelihood on unseen data, and fewer false positives and false negatives in a database search task.

Amino Acid Sequence↗
PubMed1993

Cholesterol levels in 1,084 healthy New Orleans males.

It is widely recognized that elevated cholesterol levels constitute a major risk factor for the development of atherosclerosis and coronary heart disease. Most of the previous surveys conducted in an effort to learn more about incidence of hypercholesterolemia involved patients who had other concurrent risk factors such as hypertension, obesity, diabetes mellitus, cigarette smoking, or a history of myocardial infarction. Relatively few studies have been conducted in younger populations or in healthy individuals. Because we had access to baseline cholesterol data on 1,084 relatively young, otherwise completely healthy, nonobese males, we elected to determine the prevalence of hypercholesterolemia in this population. Elevated cholesterol levels (> 200 mg/dL) were found in 25.2% of our healthy subjects. These findings help to confirm the presence of a potentially serious public health problem existing among otherwise healthy, relatively young men in our community.

Adult↗
PubMed1993

Nosocomial adenovirus infection: molecular epidemiology of an outbreak.

Nosocomial transmission of adenovirus type 3 associated with fatalities in infants has not been frequently reported. This report describes the nosocomial spread of adenovirus types 2 and 3 among infants with bronchopulmonary dysplasia in a chronic (transitional) care facility. The index case developed pneumonia with a clinical deterioration in respiratory status 8 days after admission. Within the next 10 to 30 days 9 other infants and 2 health care personnel became ill with respiratory symptoms. Three of these 10 infants had progressive respiratory failure and 2 of them died. All of these infants had underlying chronic lung disease of bronchopulmonary dysplasia. The overall attack rate was 30% (10 of 33). Further spread of adenovirus was prevented by using barrier precautions and masks while performing tracheostomy care. Adenovirus isolates were serotyped as Ad3 in 4 patients and 1 staff member, as Ad2 in 3 patients, and as a combination of Ad2 and Ad3 in 1 patient. Two fatalities were associated with Ad3 infection. Three isolates from 2 patients and 1 staff member were not available for typing. Restriction endonuclease analysis was performed on all of these isolates of Ad3 and Ad2. There was no genetic heterogeneity in the isolates, suggesting a common source.

Adenovirus Infections, Human↗
PubMed1993

Pathology of benign and malignant kidney tumors.

This article includes brief discussions of several renal parenchymal neoplasms. Gross and histologic findings are described. New techniques that can provide diagnostic and prognostic information are summarized where applicable.

Adenoma↗
PubMed1993

Cloned murine bradykinin receptor exhibits a mixed B1 and B2 pharmacological selectivity.

We have isolated DNA clones encoding functional bradykinin receptors from human, rat, and mouse sources. Genomic bradykinin receptor clones have been isolated from mouse and human cosmid libraries and cDNA clones have been isolated from the human lung fibroblast cell line W138, from the neuroblastoma/glioma hybrid NG108-15, and from rat dorsal root ganglion cells. The receptor protein is encoded by an intronless region of the gene in both mouse and human. There is evidence of a splice acceptor site 8 bases upstream from the initiation codon in all three species. The function of the expressed receptor proteins from mouse, rat, and human was tested by electrophysiological assays after injection of cRNA into Xenopus laevis oocytes and also by binding assays with membranes from COS-7 cells transfected with cloned receptor-encoding DNA. The receptors from human and rat showed the pharmacological properties of B2 receptors in both expression systems when tested with a variety of bradykinin analogues, but receptors from mouse divided into two populations, one population with pharmacological properties of B1-like receptors and another, larger, population with properties of B2 receptors.

Amino Acid Sequence↗