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W R Brown

Publications and source records attributed to W R Brown.

At least 91 records · Page 5Linked to original sources
PubMed1990

Structure and polymorphism of human telomere-associated DNA.

We have analyzed the DNA sequences associated with four different human telomeres. Two are members of distinct repeated sequence families which are located mainly but not exclusively at telomeres. Two are unique in the genome, one deriving from the long arm telomere of chromosome 7 and the other from the pseudoautosomal telomere. One telomere-associated repeated sequence has a polymorphic distribution among the chromosome ends, being present at a different combination of ends in different individuals. These data thus identify a new source of human genetic variation and indicate that the canonical features of the organization of telomere-associated DNA are widely conserved in evolution.

Animals↗
PubMed1990

Functional similarities of hepatic cystic and biliary epithelium: studies of fluid constituents and in vivo secretion in response to secretin.

Hepatic cysts are a frequent manifestation of autosomal dominant polycystic kidney disease, but little is known about their functional characteristics. The goals of our study were to define the composition of hepatic cyst fluid and to determine whether hepatic cysts secrete in response to intravenously administered secretin. We percutaneously punctured five hepatic cysts and one proximal renal cyst from six subjects with autosomal dominant polycystic kidney disease and one solitary hepatic cyst from a subject without autosomal dominant polycystic kidney disease. Most fluids had an electrolyte composition similar to serum. Fluid from all hepatic cysts had glutamyltranspeptidase concentrations above those found in serum [( cyst]/[serum] = 4.93 +/- 5.92), contained secretory component (the epithelial receptor for polymeric IgA) and had glucose concentrations less than 15 mg/dl. Fluid from both hepatic and renal cysts of subjects with autosomal dominant polycystic kidney disease, but not from the subject with the solitary hepatic cyst, demonstrated extensive changes in the electrophoretic mobility of several serum proteins. Initial intracystic pressures ranged from 16 to 40 cm H2O, were reduced 57% to 97% after aspiration of a portion of cyst fluid and were held constant during the secretion study. Within 8 min of the intravenous administration of secretin, secretion of fluid increased in two of three hepatic cysts and in the renal cyst. The electrolyte composition of cyst fluids was not altered by secretin. These data suggest that hepatic cystic epithelium has functional characteristics of biliary epithelium and that secretion by both hepatic and renal cysts may be hormonally regulated.

Aged↗
PubMed1990

A dose-response study of UVB-induced suppression of contact photosensitivity in the mouse.

A marked contact photosensitivity (CPS) response to 3,3',4',5 tetrachlorosalicylanilide (TCSA) plus UVA was induced in mice. Cyclophosphamide (Cy), given prior to sensitization, caused a further increase in ear swelling. When UVB radiation was given at a site distant from that used for sensitization it caused a dose-related suppression of CPS. Cy did not eliminate the UVB-induced suppression.

Allergens↗
PubMed1990

Telomere cloning and mammalian chromosome analysis.

Although eucaryotic chromosomes vary in size over five orders of magnitude and are constituents of diverse genetic systems the fundamental features of their telomeres appear to be almost completely conserved. This can be exploited to enable molecular cloning of human telomeres in yeast and suggests that many of the ideas that will arise from studies of telomeres in the experimentally tractable ciliates and yeasts will hold true of mammalian telomeres. The particular value of cloned mammalian telomeres is that they contribute reagents for mapping mammalian chromosomes and that they provide one set of elements for the construction of artificial mammalian chromosomes.

Animals↗
PubMed1989

Identification of a unique IgG Fc binding site in human intestinal epithelium.

In experiments to determine whether serum antibodies in patients with Crohn's disease could be used as probes for detecting potentially etiologic Ag in the patients' tissues, we found that peroxidase (HRP)-labeled IgG from healthy persons, as well as from the patients, bound to normal colonic and small intestinal epithelium, mostly or entirely to goblet cells. The binding was due to a reaction involving the Fc region of IgG because HRP-labeled Fc fragments of IgG bound, but HRP-Fab, HRP-IgA, and HRP-bovine albumin did not, and because binding of HRP-IgG was inhibited competitively by unlabeled IgG or Fc fragments but not by IgG Fab fragments or IgA. These immunohistochemical results were confirmed by ELISA with microtiter wells coated with a sonicated homogenate from human colonocytes. The epithelial IgG Fc binding site was characterized by SDS-PAGE as consisting of a high Mr (greater than 200,000 Da) and a 78,000-Da component. It bound all four subclasses of human IgG and bound aggregated as well as monomeric IgG. It is distinct from known human Fc-gamma R by lack of recognition by mAb to those receptors and differences in affinity for various subclasses of human and murine IgG. This unique IgG Fc binding site might be involved in immunologic defense of the gut, perhaps by mediating reactions between foreign Ag and the contents of goblet cells.

Animals↗
PubMed1989

Molecular cloning of human telomeres in yeast.

Telomeres are the DNA sequences found at the ends of linear chromosomes. They define the boundaries of the genetical and physical maps of such chromosomes and so are particularly important for the complete mapping of large genomes that is now being attempted. Telomeres have been intensively studied in the yeast Saccharomyces cerevisiae and in ciliated protozoa: in these organisms the telomeric DNA consists of arrays of tandemly repeated short sequences in which one strand is guanosine-rich and oriented 5' to 3' towards the chromosome end. The conservation of these structural features is reflected in the observation that telomeric DNA from a variety of protozoa will function as telomeres on artificial linear mini-chromosomes in yeast. Tandem arrays of the sequence TTAGGG have been identified at the telomeres of humans and other mammals and also of trypanosomes. This indicates that the structural features of telomeres are conserved between higher and lower eukaryotes and implies that human telomeric DNA could function in yeast. I have used this idea to develop a strategy to isolate a specific human telomere as a molecular clone in yeast and have devised a simple and effective way of cloning other human telomeres and their associated sequences.

Animals↗
PubMed1989

The liver and IgA: immunological, cell biological and clinical implications.

Secretory immunoglobulin A is the characteristic and predominant immunoglobulin of the mucosal immune system; it participates in immunological protection at the level of mucous membrane surfaces. During the past 10 to 15 years, a great deal of experimental and clinical evidence has shown that the liver is very much involved in the sIgA system. In certain animals (rats, mice, rabbits), polymeric forms of IgA are efficiently cleared by the liver and transported into bile by a receptor-mediated vesicular pathway across hepatocytes. Taking advantage of this easily accessible pathway, investigators have defined many of the events in the external secretion of pIgA, including details about the synthesis and secretion of its receptor, secretory component. In the rat hepatocyte, secretory component is synthesized as a transmembrane glycoprotein and is expressed preferentially on the sinusoidal plasma membrane; circulating pIgA that binds to secretory component is internalized into endocytic vesicles and transported across the hepatocyte to the bile canalicular membrane, where the pIgA is released into bile as a soluble complex with a portion of the secretory component, the complex being secretory IgA. In some other animals (dog, guinea pig, sheep) as well as man, biliary epithelial cells, not hepatocytes, express secretory component and perform the transcytosis and secretion of pIgA into bile. In those species, much of the pIgA that reaches bile is synthesized locally in plasma cells that populate the biliary tree; this design is analogous to the release of sIgA into various mucosae in the body. The major biological functions ascribed to the secretion of IgA into bile are enhancement of immunological defense of the biliary and upper intestinal tracts and the clearance of harmful antigens from the circulation as IgA-antigen complexes. However, the importance of biliary IgA antibodies is largely unclarified, and man lacks the capacity for effective clearance of IgA-antigen complexes via the secretory component-mediated transhepatocellular pathway; whether this deficit contributes to the propensity for man to develop IgA immune complex diseases should be clarified. Among liver diseases, alcoholic disease is most closely linked to alterations in IgA metabolism. This association is manifested principally by the deposition of IgA along the sinusoids in the livers of the majority of alcoholics and in the renal mesangium of many.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Optimization of tetrachlorosalicylanilide and ultraviolet A doses at sensitization and challenge for contact photosensitivity in the mouse.

We studied contact photosensitivity (CPS) to tetrachlorosalicylanilide (TCSA) in BALB/cJ mice with various doses of TCSA and UVA at sensitization and challenge. From these studies we recommend the following protocol: sensitization on days 0 and 1 with 50 microliters of 1% TCSA followed by 3 J/cm2 of UVA, and challenge on day 7 with 10 microliters of 3% TCSA followed by 6 J/cm2 of UVA. This gave an ear swelling response of 27.4 +/- 0.6 x 10(-3) (mean +/- standard error). We also demonstrated that there is reciprocity between volume and concentration of TCSA at sensitization but not between TCSA and UVA doses at sensitization.

Allergens↗
PubMed1989

Protein-losing enteropathy in systemic lupus erythematosus. Observations by magnifying endoscopy.

We report a 35-year-old man with systemic lupus erythematosus and an associated protein-losing enteropathy that was most likely due to mesenteric venulitis or thrombosis. Evaluation of the patient's intestinal abnormality was aided by the use of magnifying endoscopy; the duodenal villi were lustrous and swollen and of various size, a pattern different from that previously described for intestinal lymphangiectasia. The patient was treated with corticosteroids, resulting in a good clinical response and return of the villi to normal shape and size.

Adult↗
PubMed1989

Immunohistochemical examination for mycobacteria in intestinal tissues from patients with Crohn's disease.

We conducted an immunohistochemical search for mycobacteria in the intestinal tissues of patients with Crohn's disease. Tissues obtained by biopsy or surgical resection and fixed by a variety of methods (formalin, periodate-lysine-paraformaldehyde, fresh-frozen) were reacted by an immunoperoxidase method with antibodies to (a) Mycobacterium paratuberculosis strain linda, (b) M. tuberculosis, and (c) the common mycobacterial antigen, lipoarabinomannan. Each of the antibody preparations was shown capable of detecting a variety of typical and atypical mycobacteria (M. tuberculosis, M. kansasii, M. fortuitum, M. chelonei, M. paratuberculosis, and cell wall-defective as well as cell wall-intact forms of M. avium intracellulare) under conditions identical to those used for staining the patients' tissues. We did not detect mycobacteria in any of the 67 specimens from 30 patients examined. These results, in conjunction with those of our previous serologic studies, do not support the hypothesis that infection with a Mycobacterium causes Crohn's disease.

Antibodies, Monoclonal↗
PubMed1989

Age-related changes in contact photosensitivity differ among mouse strains.

There are differences among mouse strains in the age-related changes in reactivity to the contact photosensitizer tetrachlorosalicylanilide (TCSA). We found a tendency to lower reactions in older mice, with some strains showing declines from an early age (BALB/cJ, MRL/MpJ +/+, MRL/MpJ lpr/lpr and SJL/J). Others had increasing reactions until about 30-50 weeks of age before declining (DBA/1J, C3H/HeJ, and A/J) and one strain (C57BL/6J) had increased reactivity with age. There are also differences in the role of cyclophosphamide-sensitive T-suppressor cells in these age-related changes. In some mouse strains, BALB/cJ, C57BL/6J, A/J, DBA/1J and C3H/HeJ, age-related changes in reactivity to TCSA are independent of changes in cyclophosphamide-sensitive suppressor cells. In other strains, MRL/MpJ +/+, MRL/MpJ lpr/lpr and SJL/J, the development of cyclophosphamide-sensitive suppressor cells is responsible for the initial, though not later, stages of the age-related decline in reactivity.

Aging↗
PubMed1989

Histopathological evaluation of proliferative liver lesions in rats fed trans-anethole in chronic studies.

In a two-year study of rats fed trans-anethole--a flavouring that is Generally Recognized As Safe by the US Food and Drug Administration--a slight increase in proliferative lesions of the liver was observed. These results were reviewed by a Pathology Working Group (PWG) and their findings are detailed here. The increased incidence of non-neoplastic lesions in male and female rats fed 0.25, 0.5 or 1.0% trans-anethole was considered by the PWG to be treatment related. Male and female rats fed 0.25% trans-anethole in their diet (25 to 29 times the postulated maximum human intake) had no significant treatment-related microscopic lesions in the liver, although there was a slight increase in parenchymal cell hyperplasia. Rats fed 0.5% trans-anethole had hepatic changes consistent with those caused by chronic exposure of rodents to compounds with enzyme-inducing activity. Male and female rats fed 1.0% trans-anethole revealed increased incidence and severity of hepatic changes as seen in the mid-dose rats, and a low incidence of hepatocellular neoplasms. These neoplasms were not increased in male rats in any dietary group or in female rats of the low- (0.25%) and mid-dose (0.5%) groups. The slightly increased incidence of hepatocellular neoplasms in the high-dose females is not considered to be of significance to human safety and it is concluded that trans-anethole does not constitute a carcinogenic risk for man. The slightly increased tumour incidence was seen only in the highest dose group of one sex; it has not been observed in studies of mice fed trans-anethole--the metabolism of trans-anethole in the mouse is similar to that in man. The extremely high exposure was associated with other liver changes which may have contributed to the findings.

Allylbenzene Derivatives↗
PubMed1989

Assessment by mouse model of the ultraviolet A protective effect of topical sunscreens.

We have developed an animal model to assess the ultraviolet A (UVA) protective effect of topical sunscreens with the use of BALB/cJ mice in which contact photosensitivity to 3, 3', 4', 5 tetrachlorosalicylanilide had been induced. The mice were sensitized on the clipped dorsal skin and challenged on the ears. Changes in ear thickness after challenge were used to measure the degree of photosensitivity. The efficacy of two doses of each topical sunscreen was assessed by the degree of suppression of the contact photosensitivity response at challenge. Control studies were performed with the base of each sunscreen. Some but not all sunscreens that contained UVA-absorbing chemicals showed active suppression of contact photosensitivity in this test system. Several sunscreens gave greater suppression at 5 microliters/cm2 than at 2 microliters/cm2, which suggests a dose-related effect. One sunscreen, however, gave greater suppression at 2 microliters/cm2. Several of the bases tested also suppressed the contact photosensitivity response. An unexpected finding was an enhancement of the contact photosensitivity reaction by two of the bases tested.

Administration, Topical↗
PubMed1989

Phosphorylation of RAS1 and RAS2 proteins in Saccharomyces cerevisiae.

RAS1 and RAS2 proteins of Saccharomyces cerevisiae are guanine nucleotide-binding proteins involved in the regulation of adenylate cyclase. In this paper, we report that these proteins are phosphorylated. The phosphorylation of RAS1 protein is demonstrated by treating with alkaline phosphatase as well as by labeling with [32P]orthophosphate. The phosphorylation occurs exclusively on serine residues and phosphorylated RAS1 protein is predominantly membrane localized. The phosphorylation of RAS2 protein is demonstrated by similar 32P-labeling experiments. The phosphorylation occurs exclusively on serine residues and phosphopeptide analyses suggest that only two major phosphorylated tryptic peptides are generated from the RAS2 protein. These results provide evidence for the phosphorylation of RAS proteins in vivo. Furthermore, our demonstration that the phosphorylation occurs exclusively on serine residues and that the RAS2 protein contains only two major phosphorylated tryptic peptides argues that the phosphorylation may be physiologically significant.

Alkaline Phosphatase↗
PubMed1989

Studies on the relationships of IgA to human liver. IgA deposition in non-alcoholic liver diseases.

An investigation was conducted to clarify the relationships of IgA to the human liver. Immunocytochemical studies were performed on biopsy specimens from patients with cirrhosis and chronic hepatitis without any apparent history of alcohol abuse. The results showed that 1) a large amount of IgA is associated with the sinusoidal surface of hepatocytes, endothelial cells and Kupffer cells, 2) this IgA contains J chain and can form a complex with secretory component, and 3) this mainly belongs to the IgA1 subclass, 4) IgA in vesicles within hepatocytes and Kupffer cells is always associated with acid phosphatase activity, and 5) IgA containing vesicles within ductular epithelial cells always lack such enzyme activity. We conclude that 1) the IgA bound to the surface of hepatocytes, sinus endothelial cells and Kupffer cells is polymeric IgA1 uncomplexed with SC, and 2) this IgA occasionally enters these cells, and may be degraded in the lysosomes. 3) Polymeric IgA combines with SC in the ductular epithelium and may be secreted into bile. These findings suggest that J chain-linked polymeric IgA bound to the surface of hepatocytes and Kupffer cells has a certain pathological significance in liver diseases and might be involved in the clearance of excess IgA from the circulation.

Cell Membrane↗