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Biomedical subjects

W R Brown

Publications and source records attributed to W R Brown.

At least 163 records · Page 9Linked to original sources

Abnormal topological distribution of surface glycoprotein on neoplastic epithelial cells.

Immunohistochemically, carcinoembryonic antigen (CEA) was found at the apex and secretory component (SC) on the basal lateral surface of normal colonic epithelial cells. On neoplastic colon cells, both glycoproteins when present were distributed all around the cells. Little or no CEA and SC were found on normal gastric epithelial cells. CEA and SC appeared on intestinal metaplastic cells in a pattern similar to that of the normal colonic epithelium. In gastric carcinoma, both glycoproteins when present were found all around the neoplastic cells. The observations suggest that neoplastic transformation of epithelial cells is accompanied by a loss of the normal polar distribution of surface glycoproteins.

Carcinoembryonic Antigen↗

Identification of a glycophorin-like molecule at the cell surface of rat thymocytes.

There are three predominant glycoproteins in the rat thymocyte plasma membrane. Two of these have carbohydrate compositions that are characteristic of structures N-glycosidically linked to protein. The other glycoprotein is very different, having about 20 O-glycosidically linked carbohydrate units per 100 amino acids. It has similarities to the major sialoglycoprotein of human erythrocytes.

Amino Acids↗

In vitro studies on bile acid deconjugation and lipolysis inhibition by Giardia lamblia.

In vitro studies were conducted to determine whether Giardia lamblia can be deconjugate bile acids or inhibit lipolysis. Cultured G. lamblia trophozoites failed to deconjugate either glycine- or taurine-conjugated cholic acid, deoxycholic acid, or chenodeoxycholic acid. However, sonicated trophozoites significantly inhibited the hydrolysis of tributyrylglycerol by porcine pancreatic lipase. This inhibition was not dependent upon the presence of bile acids but was dependent upon the concentration of G. lamblia sonicate. Heating the sonicate for 20 min at 60 degrees C abolished the inhibitory effect; dialysis of the sonicate did not affect inhibition. We conclude that cultured G. lamblia trophozoites do not deconjugate bile acids and that sonicated G. lamblia inhibit lipolysis in vitro.

Bile Acids and Salts↗

Pneumoconiosis of shale miners.

Four patients are described in whom pneumoconiosis was diagnosed towards the end of a lifetime's work in shale mines. All developed complicated pneumoconiosis, diagnosed in two cases at necropsy, in one by lobectomy, and in one radiologically. Two of the patients were found at necropsy also to have peripheral squamous lung cancer. The clinical and histological features of the disease resembled the pneumoconioses of coalminers and kaolin workers and the lungs of three of the patients were shown to contain dust composed predominantly of kaolinite, mica, and silica. Shale miners' complicated pneumoconiosis has not previously been described. Although the British shale industry is now defunct, oil production from shale is expanding in other countries, notably the USA. It is suggested that control should be exercised over dust exposure levels in this industry and that epidemiological studies should be carried out to quantify the risks of both pneumoconiosis and bronchial carcinoma.

Aged↗

Ultrastructural evidence of transport of secretory IgA across bronchial epithelium.

To define the mechanisms for transport of secretory IgA (sIgA) into bronchial secretions, IgA and secretory component in human bronchial mucosa were localized by immunoelectron microscopy. IgA was identified in plasma cells located near glandular epithelial cells and on the basolateral plasmalemma and endocytic vesicles of the epithelial cells, especially of mucous cells. Secretory component was localized to the perinuclear spaces, endoplasmic reticulum, Golgi complexes, basolateral plasmalemma and endocytic vesicles of glandular epithelial cells, as well as those of ciliated epithelial cells. These findings are consistent with a model for IgA transport in which IgA dimers, synthesized in plasma cells, are complexes with secretory component on the basolateral plasmalemma of epithelial cells in bronchial glands and transported across the cells in endocytic vesicles to the gland lumina.

Biological Transport, Active↗

IGA in human bile and liver.

Hepatic bile IgA from 6 patients was measured by radioimmunoassay and characterized immunochemically. The concentration of IgA was 0.14 to 0.88 mg/ml. IgA associated with secretory component (SC) as well as unassociated with SC was demonstrated in all 6 samples; The proportion associated with SC (secretory IgA) was 72% to 95%. IgA and SC were localized immunocytochemically in liver and bile duct tissues by the peroxidase-labeled antibody method. Evidence favoring endocytic, SC-mediated transfer of IgA by intrahepatic and extrahepatic biliary epithelium, but not by hepatocytes, was found.

Bile↗

IgG antibody to Giardia lamblia detected by enzyme-linked immunosorbent assay.

A sensitive, reproducible enzyme-linked immunosorbent assay using unfixed, intact Giardia lamblia trophozoites as antigen is described. Employing this assay, we demonstrated that 81% of 59 symptomatic giardiasis patients and 12% of 17 uninfected control subjects had circulating IgG antibodies to G. lamblia. Eleven out of 15 patients tested serially had detectable antibody from 2 wk to 15 mo after therapy for acute infection. The prevalence of antibody in 197 unselected individuals in the Washington, D.C. area was 14%. Specificity of the antibodies was demonstrated by the ability of live G. lamblia trophozoites, but not Entamoeba histolytica or Trichomonas vaginalis trophozoites, to absorb the antibody activity. High titers of antibody were detected in 5 out of 7 patients with recurrent infection. The enzyme-linked immunosorbent assay described here may help to further characterize the antibody response to infection with G. lamblia.

Adult↗

Neoplastic human colon cells in studies on the translocation of dimeric IgA.

The translocation of dimeric IgA across epithelial cells was studied by immunoelectron microscopy in an in vitro system with cultured neoplastic human colon cells (HT-29). Ultrastructurally, the cells were found to be well-polarized epithelial cells connected by intercellular junctions. Secretory component (SC) was localized to the basolateral plasma membranes. Dimeric human IgA, when reacted with the cells at 0 C, bound selectively to SC. When incubated at 37 C, the bound dimeric IgA was internalized by pinocytosis and transported apically through the cytoplasm in vesicles. The vesicles were opened to the lumen at the apical surfaces or discharged into the lumen. We conclude that the translocation of dimeric IgA across intestinal epithelial cells has been defined at the ultrastructural level in cultured neoplastic colon cells in vitro.

Biological Transport, Active↗

The distribution of intestinal nodular lymphoid hyperplasia in immunoglobulin deficiency.

Six patients with the variable immunodeficiency syndrome and associated nodular lymphoid hyperplasia of the intestine were studied. Contrary to earlier reports, the nodules were found to be widespread in the large bowel and occurred in all six patients. Nodules were also present in the small bowel in all cases and these were seen predominantly distally. The full significance of the lesions is as yet undetermined but their presence should at least raise the possibility of an immunodeficiency. The importance of employing accurate radiological techniques using a combination of the double contrast enema and small bowel enteroclysis is stressed.

Adolescent↗

Secretory component in immmunoglobulin deficiency: and immunoelectron microscopic study of intestinal epithelium.

The ultrastructural sites of secretory component (SC) in the intestinal epithelium of severely immunoglobulin-deficient and immunologically intact persons were compared. SC was found in the same sites in the immunoglobulin-deficient and normal epithelium: perinuclear spaces, rough endoplasmic reticulum, Golgi complexes, external surfaces and endocytic invaginations of the basolateral plasmalemma, and in membranous vesicles throughout the cytoplasm. These observations suggest that the synthesis, external expression and transcellular migration of SC occur independent of the presence of immunoglobulins. The migration of SC from the basolateral cell surfaces to apical surfaces may be an inherent property of epithelial cells and the primary event in the translocation of polymeric immunoglobulins across the cells to external body fluids.

Cell Membrane↗

Lhermitte-Duclos disease: case report with computerized tomographic scan.

Lhermitte-Duclos disease is a rare, benign cerebellar condition that mimics a posterior fossa mass and has never been diagnosed preoperatively. Grossly, the diseased cerebellar tissue is tough and poorly demarcated; microscopically, the cortex has a thick outer layer of nerve fibers, an inner layer of abnormal ganglion cells, and the absence of normal Purkinje cells. The prognosis, based on cases treated surgically since 1955, is good. A case is reported in which cranial computerized tomography performed 5 years after the partial removal of abnormal tissue showed neither enhancement nor radiolucency.

Abducens Nerve↗

An immunofluorescence test to detect serum antibodies to Giardia lamblia.

We used an indirect immunofluorescence test with Giardia lamblia trophozoites as antigen to detect anti-G. lamblia antibodies in serum. Seventy-one patients and control subjects were studied in a blinded protocol. Titers in 29 of 30 patients with symptomatic giardiasis (1:16 to 1:1024) did not overlap titers in 19 healthy control subjects (1:2 to 1:4); titers in 15 patients with hookworm, Entamoeba histolytica, or intestinal bacterial overgrowth were 1:16 or less Absorption of giardiasis patients' sera with G. lamblia trophozoites but not with E. histolytica, Trichomonas vaginalis, or Escherichia coli reduced the titers to, or nearly to, control values. Titers in individual sera were 93.9% reproducible within a fourfold or less dilution. Our results indicate that G. lamblia, an intestinal parasite often regarded as noninvasive, induces a systemic antibody response. The indirect immunofluorescence test for anti-G. lamblia antibodies is specific and reproducible; it may be useful in epidemiologic and immunologic studies of giardiasis.

Adult↗

3W approach to the investigation, analysis, and prevention of human-error aircraft accidents.

Human error is the largest cause of U.S. Army aircraft accidents. An approach to this problem is presented which is based on a model of the human-error accident. This 3W approach identifies what task error (TE) caused or contributed to the accident, what inadequacy (I) in the aviation system caused or allowed the TE to occur, and what remedial measure (R) is required to correct the I. There were 82 human-error accidents analyzed to identify TEIR information. Statistically important is were identified which could be remedied based on accident costs. Then, potentially cost-effective remedial actions were ranked on a cost-benefit totem pole. The totem pole was given to the aviation system manager as a management tool to assist in determining priorities for corrective actions.

Accidents, Aviation↗

Comparative ultrastructure and cytochemistry of epidermal responses to tape stripping, ethanol and vitamin A acid in hairless mice.

The responses of hairless mouse epidermis to tape stripping, ethanol and vitamin A acid were compared using electron microscopy and cytochemistry. Stripping the skin 4 times with cellophane tape removed most of the stratum corneum and caused the development of enlarged intercellular spaces and dense intramitochondrial inclusions. These changes began within an hour, reached a maximum by 24 hr, and subsided by about 4 days. There was also some accumulation of glycogen and the development of occasional basal lamina breaks and a few intracellular lipid droplets by 24 hr. Topically applied ethanol (95%) produced a similar response, though less damaging. In addition, ethanol induced the formation of numerous lipid droplets in the cytoplasm of keratinocytes by 24 hr and often caused sloughing of the stratum corneum. Vitamin A acid (3%) was dissolved in propylene glycol for application to the skin. We found the application of propylene glycol alone to produce no epidermal changes. Vitamin A acid produced mild damaging effects with small intercellular spaces and intramitochondrial inclusions, but no lipid droplets or glycogen were detected. Vitamin A acid also caused dramatic inhibition of keratinization by 24 hr. Intramitochondrial inclusions were digested by protease, indicating a protein component and they also stained with silver methenamine, indicating the presence of glycogen or glycoprotein.

Animals↗

Immunocytochemical characterization of the lymphocytes in nodular lymphoid hyperplasia of the bowel.

The immunoglobulin constituents of hypertrophied lymphoid nodules in the intestinal tracts of six patients with the variable immunodeficiency syndrome and one patient with selective IgA deficiency were evaluated by the peroxidase-labeled antibody technique. The nodules were found to contain a dense population of IgM-bearing lymphocytes and much intercellular IgM. Evidence that the cells were engaged in IgM synthesis was the presence of the immunoglobulin in the perinuclear spaces and endoplasmic reticulum. Most of the IgM lymphocytes also had surface membrane IgM, and both kappa and lambda light chains were found in lymphocytes of individual nodules. Only a few cells containing IgD, IgG, or J chain, and none containing IgA, were found. We conclude that the intestinal lymphoid nodules associated with hypogammaglobulinemic states are populated principally by IgM B-lymphocytes of polyclonal origin.

Adult↗

Translocation of dimeric IgA through neoplastic colon cells in vitro.

We studied the translocation of dimeric IgA across epithelium, using neoplastic human colon cells in culture as a source of epithelial cells, and immunoelectronmicroscopy with peroxidase-labeled antigens and antibodies. The cells had some of the ultrastructural characteristics of normal, mature epithelial cells, i.e., polarity, desmosomal junctions, and secretory component on their basal and lateral plasma membranes. Horseradish peroxidase-labeled dimeric IgA, exposed to the cells at 0 degrees C, bound selectively to secretory component on the cell surfaces. At 37 degrees C, the bound dimeric IgA was taken into the cells by endocytosis and transported apically through the cytoplasm in vesicles. After 30 min, IgA was discharged across the apical surface. Neither colchicine (10(-4) M) nor cytochalasin B (10(-5) M) interfered with binding or endocytosis of dimeric IgA, but colchicine inhibited intracellular transport of the IgA-containing vesicles. These experiments demonstrated that dimeric IgA can be transported through living intestinal epithelial cells in vitro. The transport includes 1) specific binding of IgA dimers to secretory component on plasma membranes, 2) endocytosis of IgA in vesicles, 3) transcytoplasmic transport of the IgA-containing vesicles by a process involving microtubules, and 4) discharge of IgA at the apical surfaces.

Binding Sites, Antibody↗

Studies on translocation of immunoglobulins across intestinal epithelium. III. Failure of cholera enterotoxin to stimulate secretion of IgA by rabbit intestine.

We tested the hypothesis that the secretion of IgA into intestinal fluids is modulated by increases in epithelial cell cyclic AMP. Cholera enterotoxin instilled into intestinal loops of rabbits did not induce IgA secretion, even though an appropriate fluid response was obtained. The findings, therefore, do not support the hypothesis.

Animals↗