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Biomedical subjects

W R Brown

Publications and source records attributed to W R Brown.

At least 145 records · Page 8Linked to original sources
PubMed1984

Rat liver membrane secretory component is larger than free secretory component in bile: evidence for proteolytic conversion of membrane form to free form.

Secretory component is a receptor for polymeric immunoglobulins on epithelial cells and hepatocytes that facilitates transport of polymeric immunoglobulins into external secretions. Little is known about the transcellular migration of secretory component-polymeric IgA complexes or the membrane forms of secretory component. We therefore examined rat bile and liver membranes to identify and compare the various molecular species of secretory component. Bile or liver membrane proteins were electrophoresed in sodium dodecyl sulfate-polyacrylamide gels and electrophoretically transferred to nitrocellulose membranes. Protein profiles on blots were probed with antisecretory component antiserum, and the immunoreactive bands were visualized by indirect immunoperoxidase staining. Bile collected in the presence of proteolytic inhibitors showed an immunoreactive doublet band (Mr = 82,000 and 78,000) in the molecular weight range of free secretory component. By contrast, free secretory component in bile collected in the absence of proteolytic inhibitors and purified by affinity chromatography migrated as a single protein with an Mr = 70,000. Both components of the free secretory component doublet bound dimeric IgA when blots were probed with human dimeric IgA. Crude liver membranes prepared in the presence of proteolytic inhibitors showed two immunoreactive secretory component-containing bands, Mr = 107,000 and 99,000, whereas membranes prepared without proteolytic inhibitors showed two smaller immunoreactive bands; one of these proteolytically severed proteins comigrated with the 82,000-dalton free secretory component in bile. These results indicate that membrane forms of secretory component are present in rat liver. The observations that the membrane secretory component is larger than biliary free secretory component and yields biliary SC-like forms of secretory component upon proteolysis support the hypothesis that free secretory component in bile is a proteolytic product of larger liver membrane-associated secretory component.

Animals↗
PubMed1984

Ultrastructural immunocytochemical localization of the asialoglycoprotein receptor in rat hepatocytes.

The asialoglycoprotein receptor is present on the plasma membrane of rat hepatocytes and mediates the endocytosis of exogenous asialoglycoproteins. The intracellular locations of the receptor are incompletely defined, and whether the receptor is present on the canalicular membrane is controversial. To investigate these unresolved issues, we localized the asialoglycoprotein receptor on the surfaces of and within rat hepatocytes in the absence of exogenous asialoglycoprotein. Cryostat sections of perfusion-fixed livers of fasted rats were incubated with peroxidase-labeled antibodies to the rat asialoglycoprotein receptor and were examined by light and electron microscopy. The asialoglycoprotein receptor on the surface of hepatocytes was present on the sinusoidal plasma membrane and was concentrated in coated pits; it was present also on the lateral plasma membrane but was absent from the bile canalicular membrane. Within hepatocytes, the receptor was present in saccules of the Golgi complexes and occasionally in segments of the endoplasmic reticulum. Definite endocytic vesicles containing receptor were absent, and lysosomes were devoid of the receptor. These observations indicate that in the absence of exogenous asialoglycoprotein (a) the asialoglycoprotein receptor on the plasma membrane of hepatocytes is present only on the sinusoidal and lateral surfaces, (b) the receptor is being synthesized and assembled, (c) endocytic internalization of the receptor is minimal or absent, and (d) lysosomes are devoid of the receptor.

Animals↗
PubMed1984

Cellular distribution of the asialoglycoprotein receptor in rat liver. Implications for hepatic accumulation of desialylated lymphocytes.

It has been postulated that the selective accumulation of circulating desialylated cells in the mammalian liver results from the binding of desialylated glycoproteins on surfaces of the cells to asialoglycoprotein receptors in the liver. Since circulating cells in the liver are in contact predominantly with sinusoidal lining cells (Kupffer cells and endothelial cells), this postulate requires the presence of asialoglycoprotein receptors on the luminal surface of the sinusoidal lining cells. Whether the receptor is present on these cells, however, remains controversial. To clarify this issue, we used an indirect immunoelectron microscopic method to determine the distribution of the receptor on the surfaces of hepatic cells accessible to the circulation. F(ab')2 fragments of antireceptor antibodies were perfused in situ via the portal vein prior to tissue fixation. After perfusion fixation, sections were reacted with peroxidase-labeled antibodies to the antireceptor F(ab')2. The plasma membranes of Kupffer cells, endothelial cells, and fat-storing cells were devoid of the asialoglycoprotein receptor. In contrast, the receptor was associated with hepatocytes, where it was present diffusely on the sinusoidal plasma membranes and concentrated within coated pits. We conclude that it is unlikely that circulating desialylated cells bind to the asialoglycoprotein receptor in the liver unless a breach in the continuity of sinusoidal lining cells exists.

Animals↗
PubMed1984

B cell numbers and responses in patients with common variable immunodeficiency and nodular lymphoid hyperplasia of the bowel.

Nodular lymphoid hyperplasia ( NLH ) of the intestine is a lymphoid proliferation which occurs in patients with common variable immunodeficiency disorders ( CVID ). The nodules contain B cells but their pathogenesis is unknown. To determine whether the presence or absence of NLH might be associated with blood B cell abnormalities we studied CVID patients with and without NLH . CVID patients with NLH had a higher percentage of B cells in their blood than those without NLH . Blood lymphocytes from both groups of CVID patients proliferated less well in Cowan Staph. A stimulated cultures than control lymphocytes. Similar trends were observed in cultures stimulated with pokeweed mitogen and analyzed by karyotype. Our results suggest that blood B cells from patients with NLH are relatively unresponsive to B cell mitogens despite their near-normal numbers.

Adolescent↗
PubMed1984

Studies of Campylobacter jejuni in patients with inflammatory bowel disease.

Cultures, serology, and immunohistochemical tests for Campylobacter jejuni were performed on 74 patients with inflammatory bowel disease of various disease activity and in healthy and diseased control populations. Fecal cultures were negative in all groups tested. Antibodies to C. jejuni were assessed both by a complement fixation assay and an enzyme-linked immunosorbent assay to multiple serotypes of the organism. Antibody titers in inflammatory bowel disease patients and control populations were similar, and titers in these groups were significantly lower than in patients with acute Campylobacter enteritis. Intestinal tissues examined for Campylobacter antigens by an indirect fluorescent antibody assay were negative. These data do not etiologically implicate C. jejuni in Crohn's disease or chronic ulcerative colitis.

Antibodies, Bacterial↗
PubMed1983

1976 Hanford americium exposure incident: psychological aspects.

Accidents involving exposure to radiation or radioactive materials may involve an unusual degree of emotional trauma. Methods that may be employed in dealing with such trauma are discussed in relation to a specific accident in which a radiation worker was injured and seriously contaminated with 241Am.

Accidents, Occupational↗
PubMed1983

IgA plasma cells in biliary mucosa: a likely source of locally synthesized IgA in human hepatic bile.

IgA synthesized in hepatobiliary tissues accounts for about one-half of the IgA present in human hepatic bile, but the location of the IgA synthesizing cells has been in doubt because few plasma cells are present in normal liver. Therefore, we immunocytochemically localized IgA, J chain and secretory component in bile duct tissues of six patients operated upon for biliary duct obstruction. Numerous plasma cells containing IgA and J chain were found surrounding the accessory glands of the major bile ducts and in the area just beneath the surface epithelium of the ducts. At the ultrastructural level, IgA and SC in the epithelial cells had the features characteristic of secretory component-mediated endocytic translocation of IgA. We conclude that plasma cells in biliary duct mucosa are the likely source of much of the locally synthesized IgA that is secreted into human hepatic bile. The IgA probably reaches the bile by direct transfer across biliary epithelium.

Aged↗
PubMed1982

Ultrastructural localization of carcinoembryonic antigen in normal intestine and colon cancer: abnormal distribution of CEA on the surfaces of colon cancer cells.

The distribution of carcinoembryonic antigen (CEA) in normal small intestine, normal colon, and colon cancer of humans was determined immunocytochemically by the peroxidase-labeled antibody method at the light and electron microscopic levels. In the small intestine, CEA was found in protein synthetic organelles, in the mucus, on the microvilli of goblet cells, and on some microvilli of columnar cells adjacent to goblet cells. In the normal colon, CEA was found in protein synthetic organelles of the fully differentiated columnar cells and goblet cells, as well as on the microvilli of the cells. In two well-differentiated colon cancers, the normal preferential surface expression of CEA on the microvilli was maintained, but in six poorly differentiated cancers, CEA was distributed equally over the entire cell surface. We conclude that CEA is a product of goblet cells in the small intestine, columnar and goblet cells in the colon, and colonic cancer cells. CEA on the surfaces of the normal epithelial cells is expressed in a polar manner. This polarity is lacking in undifferentiated neoplastic colon cells, which suggests that failure to establish or maintain the polar expression of normal cell-surface glycoproteins is a characteristic of the neoplastic cells.

Carcinoembryonic Antigen↗
PubMed1982

Common variable hypogammaglobulinemia with T-cell nodular lymphoid interstitial pneumonitis and B-cell nodular lymphoid hyperplasia: different lymphocyte populations with a similar response to prednisone therapy.

Intestinal lymphoid hyperplasia and recurrent pulmonary infections by pyogenic bacteria are well-recognized accompaniments of common variable (late onset) hypogammaglobulinemia. A 35-yr-old woman with this illness had progressive pulmonary insufficiency caused by nodular lymphoid interstitial pneumonitis, rather than by infectious lung damage, and intestinal lymphoid nodular hyperplasia. B cells were abundant in the intestinal nodules but absent in the pulmonary nodules by immunoperoxidase staining. Pulmonary lymphocytes isolated in single-cell suspension from the biopsy were 0.5% B cells and 82% T cells. Prednisone therapy improved pulmonary function and decreased the intestinal lymphoid nodules. Lymphocytic interstitial pneumonitis should be considered in patients with hypogammaglobulinemia and restrictive lung disease.

Adult↗
PubMed1982

Farmer's lung in an iron foundry.

Two cases are described of the development of an allergic alveolitis in women working with straw as a packing material in an iron foundry. The clinical picture and results of investigations supported a diagnosis of farmer's lung qualifying the patients for payment of industrial disablement benefit.

Adult↗
PubMed1982

A search for an enriched source of polymeric IgA in human thoracic duct lymph, portal vein blood and aortic blood.

Because human bile contains a lot of secretory IgA, it has been suspected that the human liver, like rat liver, transfers polymeric IgA from plasma to bile. Hence, a rich source of polymeric IgA might enter the general circulation of man. We examined human thoracic duct lymph, portal vein blood and aortic blood for content and molecular size of IgA. None of the fluids was found to have either a higher total concentration of IgA or a higher proportion of polymeric IgA than that found in peripheral venous blood. It is possible that hepatic clearance of plasma IgA does not occur in man to the extent that it does in the rat, and a relatively larger proportion of human biliary IgA might originate from synthesis in hepatobiliary tissues.

Aged↗
PubMed1982

Lymphocyte cell surface glycoproteins which bind to soybean and peanut lectins.

In cellular immunology, peanut (Arachis hypogaea) lectin has been used to selectively agglutinate immature lymphoid cells and soybean (Glycine max-lectin to agglutinate B lymphocytes. We have used affinity chromatography to study the surface glycoproteins of rat and mouse lymphoid cells which bind to these lectins. Thymocyte and T and B lymphocyte glycoproteins were analysed either without modification (native) or after the removal of sialic acid with neuraminidase (asialo). The only native glycoprotein which was seen to bind to peanut lectin was the 95,000 mol. wt sialoglycoprotein from thymocytes. The equivalent molecules from T lymphocytes bound to peanut lectin only after neuraminidase digestion. Thus the selective agglutination of thymocytes by peanut lectin would seem to be due to a partial lack of sialic acid residues on the O-glycosidically-linked oligosaccharides of the thymocyte sialoglycoprotein. The B lymphocyte form of the leucocyte-common antigen was the only prominent native glycoprotein which was seen to bind to soybean lectin and this probably accounts for the specific binding of this lectin to B cells. The leucocyte-common antigens, in their asialo forms, from thymocytes and B and T lymphocytes differed in their binding to the lectins and this establishes that these glycoproteins which share antigenic determinants differ in their carbohydrate structures.

Animals↗
PubMed1982

Ultrastructural events in the translocation of polymeric IgA by rat hepatocytes.

It has been proposed that polymeric IgA is translocated from plasma to bile across hepatocytes of the rat liver by a secretory component-mediated, vesicular transport. To define the ultrastructural details of the proposed transport mechanism, we employed peroxidase-labeled antibody immunocytochemistry to localize secretory component in the rat liver and monitor the hepatic translocation of homologous myeloma polymeric IgA infused i.v. Secretory component was found associated with the endoplasmic reticulum, Golgi complexes, cytoplasmic vesicles, and plasma membranes of the sinusoidal and canalicular surfaces of hepatocytes; secretory component at the sinusoidal surface was most prominent in micropinocytic invaginations or pits. Livers were examined for the sites of polymeric IgA 5, 15, and 30 min after infusion. Evidence was obtained that polymeric IgA is translocated across hepatocytes by a series of events: 1) polymeric IgA binds selectively to secretory component on the external surface of the sinusoidal plasma membrane; 2) secretory component-IgA complexes are internalized in endocytic vesicles; 3) the vesicles migrate through the cytoplasm without association with lysosomes or Golgi complexes; 4) the vesicles fuse with the cytoplasmic surface of the bile canalicular membrane, where secretory component-IgA complexes are released into bile by exocytosis.

Animals↗
PubMed1982

Changes in the U.S. Army aviator selection and training program.

The Army's aviator selection program began in the mid 1950's. The first Flight Aptitude Selection Test (FAST) was implemented in 1966 and remained in use until 1980 when changes in personnel, aircraft, and tactics necessitated an improved or revised FAST (RFAST). This paper presents an overview of 1) the composition of the FAST and RFAST; 2) the advantages of the RFAST; and 3) the predictive validity estimates for the FAST and RFAST. Also presented are examples of current research projects which show promise for increasing effectiveness and for broadening the scope of the Army aviator selection program.

Aerospace Medicine↗