William R. Brown

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.

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 Crohns 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 Crohns disease.

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.

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.

Search for a specific marker of mucosal dysplasia in chronic ulcerative colitis.

We have tried to identify a histochemical or immunohistochemical marker that would reliably detect mucosal dysplasia in chronic ulcerative colitis. Colonic biopsy specimens were taken from patients with long-standing ulcerative colitis undergoing surveillance colonoscopy. Control tissue was obtained from the margins of colonic resections performed for neoplastic or nonneoplastic diseases. Sections of the specimens were examined by periodic acid-Schiff staining, high iron diamine Alcian blue staining for sialomucins and sulfomucins, and binding of the lectins peanut agglutinin, Ulex europeus agglutinin I, and Ricinis communis I agglutinin. Sections were reacted also with anticarcinoembryonic antigen antibodies to determine whether a nonpolar surface distribution of the antigen was a feature of dysplasia. We found that changes in colonic mucin, characterized by periodic acid-Schiff-positive mucin outside of goblet cells, an increase in binding of peanut agglutinin, and an increase in the relative amount of sialylated mucin, were associated with morphologic dysplasia. However, identical alterations were observed, albeit less commonly, in colitis without dysplasia, particularly in the presence of active inflammation. No abnormality in the surface distribution of carcinoembryonic antigen or Ricinis communis I agglutinin was observed. Thus, we did not identify a reliable corollary test to the histologic diagnosis of mucosal dysplasia in ulcerative colitis. With regard to these histochemical markers, the colonic mucosa appears to respond similarly to inflammation and neoplasia.

In vitro studies on bile acid deconjugation and lipolysis inhibition byGiardia lamblia

In vitro studies were conducted to determine whetherGiardia lamblia can deconjugate bile acids or inhibit lipolysis. CulturedG. 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 ofG. lamblia sonicate. Heating the sonicate for 20 min at 60° C abolished the inhibitory effect; dialysis of the sonicate did not affect inhibition. We conclude that culturedG. lamblia trophozoites do not deconjugate bile acids and that sonicatedG. lamblia inhibit lipolysisin vitro.

Necrophilia, brief review and case report

SummaryThe authors present a brief review of the literature on necrophilia and describe an example of inhibited necrophilia, in which the necrophilic fantasies were brought to light through a series of sodium amytal interviews. The psychodynamic origins of the perversion are discussed, with emphasis on the sadistic elements. It is suggested that necrophilic fancies are more common than is generally realized.

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.

Studies on translocation of immunoglobulins across intestinal epithelium.

The issue of how immunoglobulins are transported across the intestinal epithelium into the gut lumen was examind by immunohistocytochemical techniques. IgA, IgM, IgG and secretory component (SC) in human small intestine at light and electron microscopic levels were localized by the peroxidase‐labeled antibody technique. By light microscopy, IgA, IgM and SC, but not IgG, were found associated with columnar epithelial cells in gland crypts. By electron microscopy, SC was found in the perinuclear membranes, rough endoplasmic reticulum and Golgi complexes of these cells. IgA and IgM as well as SC were found in the basolateral plasma membranes and cytoplasmic vacuoles of the cells. It was concluded that in the human small intestine 1) SC is synthesized by columnar secretory epithelial cells; 2) IgA and IgM, but not IgG, are transported through these cells; 3) IgA and IgM could combine during transport with SC on plasma membranes or within the cytoplasm of these cells. In additional experiments, in vitro binding of peroxidase‐labeled dimeric IgA to specific sites, corresponding to the sites of SC, on human intestinal epithelial cells, was demonstrated.

Radioimmunologic Measurements of Naturally Occurring Antibodies. III. Antibodies Reactive with Escherichia coli or Bacteroides fragilis in Breast Fluids and Sera of Mothers and Newborn Infants

Extract: Immunoglobulin (Ig) A antibodies to Bacteroides fragilis and Escherichia coli in breast fluids and serum of lactating women, and IgG antibodies to E. coli in cord and maternal sera of mother-infant pairs were measured by a radioimmunoassay. Antibody concentrations were expressed as micrograms of antibody per milliliter or per milligram of IgA or IgG. For concentrations (mean ± SD) of IgA antibodies, see Table 1.Concentrations of secretory IgA in breast fluids were 36.7 ± 25.3 mg/ml on day 1, 1.66 ± mg/ml on day 4, and 0.71 ± 0.31 mg/ml 6 weeks after delivery. Both the amount of IgA antibodies (μg/ml) and total IgA in colostrum fell abruptly and reached serum levels by the 4th postpartum day. The 23–30-fold greater quantity of IgA antibodies per milliliter for day 1 colostrum than IgA antibodies per milliliter of serum at delivery corresponded to a 21-fold higher total concentration of IgA in colostrum than in serum at these times. Concentrations of antibodies to B. fragilis and E. coli were not significantly different.Concentrations of IgG antibodies to E. coli in 10 maternal sera at delivery (2.1 ± 1.6 μg/ml; 0.33 ± 0.29 μg/mg IgG) were slightly but not significantly lower than those in corresponding cord sera (2.5 ± 2.0 μg/ml; 0.29 ± 0.22 μg/mg IgG). Concentrations of serum IgA anti-E. coli antibodies were similar in nursing and non-nursing mothers both at delivery and 6 weeks later, and these concentrations were similar to those in nonpregnant women.Findings of the study indicate that (1) the large quantities of IgA antibodies to E. coli and B. fragilis in colostrum result from the presence of large quantities of IgA rather than from IgA that is richer than serum IgA in specific antibodies; (2) concentrations of IgA antibodies to E. coli and B. fragilis in maternal serum and colostrum are similar, even though Bacteroides greatly outnumber coliforms in gut contents of adults; (J?) concentrations of IgG antibodies to E. coli are similar in maternal and fetal circulation; (4) nursing and pregnancy do not influence concentrations of serum IgG antibodies to the bacteria studies.Speculation: During lactation, the breast synthesizes IgA with constant levels of specific antibodies to commensal intestinal bacteria. Ingested breast fluid antibodies to B. fragilis could suppress growth of Bacteroides in the gut and account for the relatively low numbers of these anaerobes in intestinal content of breast-fed infants.