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D Brown

Publications and source records attributed to D Brown.

At least 541 records · Page 30Linked to original sources
PubMed1994

A 28 kDa sarcolemmal antigen in kidney principal cell basolateral membranes: relationship to orthogonal arrays and MIP26.

Two recently cloned water channels, CHIP28 and WCH-CD, are homologous to MIP26, an integral membrane channel-forming protein found in lens fiber plasma membranes. CHIP28 is found in basolateral and apical plasma membranes of kidney proximal tubules and thin descending limbs of Henle, whereas WCH-CD is apically located in collecting duct principal cells. So far, the putative water channel that may be responsible for the high constitutive permeability of principal cell basolateral membranes has not been identified. Interestingly, freeze-fracture electron microscopy has shown that characteristic orthogonal arrays of intramembrane particles (OAPs) are found on the basolateral plasma membranes of collecting duct principal cells, and that morphologically identical OAPs present in lens fiber cell plasma membranes contain the protein MIP26. Similar OAPs have also been detected on plasma membranes of other cell types including gastric parietal cells, astroglial cells and skeletal muscle fibers. By indirect immunofluorescence, western blotting and northern blotting, MIP26 was found only in lens fibers. In addition, functional studies on reconstituted and oocyte-expressed MIP26 excluded the possibility that MIP26 might be a basolateral water channel in the kidney. However, a polyclonal antibody raised against skeletal muscle sarcolemmal vesicles, which are enriched in OAPs, produced an intense staining of principal cell basolateral plasma membranes in kidney collecting duct and immunoprecipitated a 28 kDa protein from kidney papilla. The immunoprecipitated protein from papilla was not recognized by anti-CHIP28 or anti-MIP26 antibodies, indicating that principal cell basolateral membranes contain a novel member of the CHIP/MIP family. Because this antibody also stained brain astrocyte end feet, which are enriched in OAPs, it is possible that the 28 kDa protein is related to these structures. We conclude that OAPs probably contain related but distinct proteins that may have different membrane channel functions in different cell types.

Animals↗
PubMed1994

Expression of gp330 and gp330/alpha 2-macroglobulin receptor-associated protein in renal tubular differentiation.

The gp330/alpha 2-macroglobulin receptor-associated protein (RAP) is a 39- to 45-kd protein that binds to the low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor and to gp330, a major glycoprotein of the brush border of proximal tubule cells. Despite evidence that gp330 functions as a receptor for several ligands and that soluble RAP inhibits ligand binding to gp330 in vitro, the physiologic function of RAP is unknown. Given the predominant location of RAP within the rough endoplasmic reticulum (RER), RAP might be involved in the intracellular processing and/or transport of gp330. The developing rat kidney was used as a dynamic model to study in detail the relationship between gp330 and RAP in vivo by immunohistochemical techniques. RAP was expressed in the renal vesicle and continued to be present, with a vesicular and perinuclear pattern of staining, in both proximal tubule cells and glomerular cells at subsequent stages. Immunoperoxidase electron microscopy demonstrated RAP in cisternae of the RER and in large subapical vesicles. gp330 was initially expressed in early proximal tubule cells in S-shaped bodies and was located in the perinuclear envelope and cytoplasmic vesicles as well as at the apical surface. Cytoplasmic gp330 staining was more evident at a stage subsequent to the S-shaped body, possibly related to more active biosynthesis. By comparative analysis of the patterns of immunofluorescence and immunoperoxidase staining, gp330 and RAP colocalized in the RER and in some large subapical vacuoles, but no definite RAP staining could be detected at the surface of proximal tubule cells at any stage, despite the presence of abundant gp330 in this location. The expression of gp330 at the apical surface of immature tubular cells was associated with the onset of fluid-phase endocytosis of fluoroscein isothiocyanate-dextran and, therefore, of reabsorption of material from the tubular lumen, in the absence of concomitant changes in RAP expression in the same cells. These findings indicate that the role of endogenous RAP may not be directly related to ligand binding of gp330 at the surface of proximal tubule cells, although RAP may be involved in the processing and the intracellular trafficking of newly synthesized gp330, in particular in the delivery of gp330 to the plasma membrane.

Animals↗
PubMed1994

Characterization of an endogenous metalloproteinase in human vitreous.

The vitreous is a gel-like connective tissue that undergoes liquefaction during aging and pathological processes. We isolated and characterized a degradative enzyme from the vitreous of different species and identified it to be matrix metalloproteinase-2 (MMP-2). This enzyme was found in a latent form and may be associated with endogenous inhibitors. Vitreous isolated from both non-diabetic and diabetic patients contained MMP-2 in the same concentrations. However, the diabetic samples had an additional gelatinase activity at 92 kDa which may be associated with a compromised vasculature. These results suggest that the normal human vitreous contains an endogenous MMP and the appearance of an additional activity is associated with pathologic conditions.

Adult↗
PubMed1994

Disaster preparedness. Ready for earth, air, fire and water (and who knows what else)?

Already the 1990s might be described as a decade of disasters: From the devastation of hurricanes on the East Coast to the havoc of floods in the Midwest to the destruction of earthquakes and civil unrest on the West Coast, the past few years clearly show that disasters can strike anywhere--and at any time. For health facilities caught in the middle of these crises, emergency preparedness means much more than just meeting the basic requirements of the Joint Commission on Accreditation of Healthcare Organizations or complying with state and local regulations. Rather, for most health facilities, preparing for disasters is an integral part of ensuring that they can continue to provide adequate, high-quality patient care under almost any circumstances. This report, the first in a series of articles, examines how health facility managers coped once they found themselves in the midst of major disasters, what lessons they learned about emergency preparedness as a result of their experiences, and what others can learn from these difficult situations.

California↗
PubMed1994

Consensus from Cairo.

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Conservation of Natural Resources↗
PubMed1994

Family views on sterilization for their mentally retarded children.

Eighty-eight parents of adolescents or adults with mental retardation answered written and/or telephone questionnaires concerning sterilization and reproductive health choices for their children with mental retardation. The 36 parents whose children were still living at home were more concerned about the capacity for sexual activity in their disabled child than were the 52 parents whose children were living outside the home. Otherwise, the two groups of parents were very similar in their attitudes. The reasons for considering sterilization were parental fear of sexual abuse, unwanted pregnancy and failure of birth control methods. Almost all the parents in this study wanted to participate in decisions concerning the sterilization of their disabled child.

Activities of Daily Living↗
PubMed1994

Managing PEG tubes.

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Enteral Nutrition↗
PubMed1994

Cochlear traveling-wave delays estimated by distortion-product emissions in normal hearing adults and term-born neonates.

Functional aspects of human cochlear maturation were studied with distortion-product otoacoustic emissions (DPE). Cochlear travel times were measured on basis of the phase-frequency relationship for DPEs in 54 term-born babies (36 to 42 weeks conceptional age [CA]) for f2 frequencies from 1.7 to 10 kHz, and the results were compared with a normaltive data set based on 36 adult ears. At the two extremes of the f2 frequency range used, 1.7 kHz and 2.4 kHz on the low end and 7 kHz and 10 kHz on the high end, the travel times for neonates were similar to those in adult ears. In the mid-frequency range (3.4 kHz and 4.8 kHz) the mean values were significantly smaller than those for adults. We attempt to explain these findings on the basis of the maturation of two partially compensating (i.e., with cochlear travel time) cochlear mechanisms: the maturation of the characteristic frequency (CF)-place relationship in the cochlea (the "shifting place" principle) and the maturation of the cochlear amplifier.

Adult↗
PubMed1994

GPI-anchored proteins and detergent-resistant membrane domains.

Glycosylphosphatidylinositol (GPI)-anchored proteins are expressed on the apical surface of polarized epithelial cells. The anchor may act as an apical sorting signal by associating with clusters or rafts of apically directed glycosphingolipids (GSL). We have previously shown that endogenous GPI-anchored proteins and stably transfected placental alkaline phosphatase (PLAP) can be isolated from detergent lysates of cultured epithelial cells in association with a detergent-insoluble membrane that is rich in GSL. Here, we investigate the behavior of a hybrid GPI-anchored protein, GThy, that contains the ectodomain of the vesicular stomatitis virus glycoprotein (VSV-G) and a GPI-anchor from the Thy1 protein. We have previously shown that GThy is efficiently (85-90%) targeted to the apical surface of MDCK cells. Here we show that the protein also becomes insoluble in Triton X-100 as it moves through the secretory pathway of these cells. However, the degree of Triton X-100 insolubility is never as great as that seen for PLAP. This may result from the fact that it is an engineered protein, as the same behavior has been reported for another hybrid GPI-anchored protein. In addition, GThy is rapidly lost from MDCK cells by release into the media, with a t1/2 of about 50 min. This turnover appears to be mediated by a cell-surface protease that may recognize viral glycoproteins.

Alkaline Phosphatase↗
PubMed1994

Percutaneous coronary rotational atherectomy: New Jersey experience.

Complex coronary lesions can be approached percutaneously with rotational atherectomy. The first 70 procedures were performed at Newark Beth Israel Medical Center with a success rate of 94 percent. Despite treating a high-risk patient population, the complication rate was low.

Atherectomy, Coronary↗
PubMed1994

Expression of the X-linked agammaglobulinemia gene, btk in B-cell acute lymphoblastic leukemia.

The gene which causes X-linked agammaglobulinemia, btk, has recently been identified as a cytoplasmic tyrosine kinase expressed almost exclusively in B cells, and at all stages of B-cell differentiation. To assess the possibility of involvement of this gene in childhood B-cell malignancies, cells from 23 pediatric patients with B-cell acute lymphoblastic leukemia were examined for expression and alteration of the Btk protein and also for mutations in the btk gene. Btk proteins, similar in both molecular weight and quantity to those seen in unaffected individuals, were detected in whole cell lysates from the blasts of 12/12 patients indicating that no abnormal protein was present. cDNAs from the leukemic blasts of all 23 patients were screened with specific primers covering the coding region of the btk cDNA for mutations using single strand conformation polymorphism (SSCP) analysis. No mutations were found but a nucleotide polymorphism was identified in 4/23 patients at the 3' end of btk. Although the sample size in this study was relatively small, these data suggest that btk does not appear to play a critical role in childhood B-cell leukemias.

Adolescent↗
PubMed1994

Obstructive sialadenitis: a rat model.

Obstructive adenitis of major salivary glands is a common entity. Although the pathologic features are well recognized, the various cell types involved in the atrophy and subsequent regeneration of the obstructed salivary gland have been controversial. For this reason, an animal model of obstructive sialadenitis that induced atrophy in the rat parotid gland was developed. A clamp was devised that would occlude the main excretory duct of the gland inducing atrophy, but that, following removal, left the duct patent and allowed regeneration to occur. Both atrophy and regeneration were studied, and the results presented. The number and location of cycling acinar, intercalated, striated, and excretory duct cells were identified, using an antibody to proliferating cell nuclear antigen (PCNA). All cell types were induced to cycle during both the atrophy and regeneration phase, but the degree of cycling was more pronounced during regeneration. Three days after release of the duct obstruction, cycling acinar cells had increased 40-fold, while striated and intercalated ducts increased 6.5- and 5.0-fold, respectively. More importantly, peak cycling of acinar cells preceded, but paralleled, the increase in acinar cell composition of the gland. This model of obstructive sialadenitis indicates that all cell types are responsible for regeneration in the obstructed rat parotid gland.

Animals↗
PubMed1994

Hepatitis C virus genotypes: an investigation of type-specific differences in geographic origin and disease.

Because of the nucleotide sequence diversity of different isolates of hepatitis C virus, it has become important to clarify whether distinct genotypes of hepatitis C virus vary with respect to pathogenicity, infectivity, response to antiviral therapy and geographic clustering. We assessed nucleotide sequence variability in the 5' noncoding region of hepatitis C virus, using restriction enzymes to analyze the distribution of hepatitis C virus genotypes, in 80 patients with chronic hepatitis C virus infection. Genotypes were correlated with demographic, clinical and histological features. Thirty-seven patients were infected with type 1, 10 had type 2 and 8 had type 3, and another 23 were infected with a new distinct hepatitis C virus type now classified as type 4. Two were infected with variants whose classification are uncertain. Types 1, 2 and 3 were found in patients from the United Kingdom, southern Europe, Asia, Africa and South America. Nineteen of 23 type 4 genotype isolates were from Middle Eastern patients, compared with 0 of 37 type 1 isolates (p < 0.001). Of 21 Middle Eastern patients, 19 (90.4%) had type 4 hepatitis C virus (p = 0.001, odds ratio = 9). We found no significant difference between the mean ages or mean serum aminotransferase concentrations between the various types. Types 1, 2, 3 and 4 were found in patients with mild-to-moderate disease or severe disease. However, 21 of 29 (72.4%) patients with type 1 who underwent liver biopsy had severe chronic hepatitis, cirrhosis or hepatocellular carcinoma histologically; 8 had mild or moderate chronic hepatitis without cirrhosis (p = 0.03, odds ratio = 2.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Intravaginal misoprostol versus dinoprostone as cervical ripening and labor-inducing agents.

OBJECTIVE: To compare dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for ripening the cervix and inducing labor at term. METHODS: Sixty-three women were randomized to receive 100 micrograms misoprostol or 3 mg dinoprostone, both as intravaginal tablets. RESULTS: There was no statistical difference between the groups for pre-induction status. The mean Bishop scores before drug insertion were almost identical. Twelve hours after insertion, the mean change in the Bishop score was significantly higher in those receiving misoprostol (5.0 versus 3.3) (P = .008). However, there were no significant differences in induction-to-delivery interval, spontaneous labor rates, type of delivery, fetal outcome, or maternal complications. CONCLUSION: Misoprostol is as effective as dinoprostone for inducing labor at term.

Administration, Intravaginal↗
PubMed1993

Conglutinin acts as an opsonin for influenza A viruses.

Since the 1940's, non-Ig inhibitors of influenza A virus (IAV) hemagglutination activity and infectivity have been recognized in mammalian sera. Recently, the heat labile (beta) inhibitor of this type was identified by indirect methods as the lectin, conglutinin. In support of this hypothesis, we found that purified conglutinin strongly inhibited hemagglutination activity and infectivity of IAV. By using IAV strains with specific variations in glycosylation of the hemagglutinin molecule, we showed these effects to be mediated by binding of conglutinin to high mannose carbohydrate attachments on the viral hemagglutinin. Through the same mechanism conglutinin caused aggregation of IAV particles. Human neutrophils produce hydrogen peroxide upon exposure to IAV. Also, after a brief period of exposure to IAV, neutrophils exhibit depressed responsiveness (deactivation) upon exposure to other stimuli (e.g., chemotactic peptides). These phenomena may be related to the in vivo inflammatory response during IAV infection, and to the propensity of IAV-infected subjects to suffer bacterial superinfection. Pre-incubation of IAV with conglutinin markedly potentiated human neutrophil hydrogen peroxide production in response to the virus. This effect correlated with the ability of conglutinin to aggregate the virus. IAV treated with conglutinin also caused significantly less neutrophil deactivation than did the unopsonized virus. These enhancements of neutrophil respiratory burst responses by conglutinin were again mediated by binding of the lectin to viral carbohydrates. The mammalian C-type lectin family includes conglutinin, mannose-binding protein, and surfactant proteins A and D. These lectins may be important constituents of the initial host response to IAV, by inhibiting IAV infectivity directly, causing viral aggregation, and acting as opsonins to enhance phagocyte responses to the virus.

Animals↗
PubMed1993

Tay-Sachs disease--carrier screening, prenatal diagnosis, and the molecular era. An international perspective, 1970 to 1993. The International TSD Data Collection Network.

OBJECTIVES: To provide an update of the international experience with carrier screening and prenatal diagnosis for Tay-Sachs disease (TSD), to assess the impact of these efforts, and to review the recent developments in DNA technology with application to TSD carrier detection and screening. DESIGN: Through the International TSD Testing, Quality Control, and Data Collection Center, all testing centers in the world were surveyed annually to assess overall experience with carrier testing and prenatal diagnosis. Quality control and laboratory surveillance of testing centers were performed through an annual assessment, using samples provided by the center. SETTING: Tay-Sachs disease testing centers around the world. PARTICIPANTS: Nearly 1 million young adults from both Jewish and non-Jewish populations. INTERVENTION: Gene product screening (enzyme testing) and DNA-based mutation analysis (in some populations). MAIN OUTCOME MEASURE: Impact of screening program on disease incidence. RESULTS: Data from all centers in the international TSD network on experience with TSD carrier testing and prenatal diagnosis since 1974 indicated that more than 36,000 heterozygotes were identified and 1056 couples found to be at risk for TSD in their offspring. A total of 2416 pregnancies at increased risk for TSD were monitored by amniocentesis or chorionic villus sampling. A dramatic decrease in the incidence of TSD in the Jewish populations was demonstrated. With both serum and leukocyte proficiency testing, there have been only 16 instances (of 845 cumulative laboratory evaluations) of one or more errors reported by a laboratory since 1983 resulting in nonaccreditation. CONCLUSIONS: This analysis represents a prototypic effort in coordinating adult education, carrier testing, and genetic counseling directed toward prospective prevention of a uniformly fatal childhood disease and demonstrates that such an effort can dramatically affect disease incidence.

Clinical Enzyme Tests↗