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Urinary immunoglobulins in healthy individuals and children with acute pyelonephritis.

Urine samples obtained from children with acute pyelonephritis and from healthy children and adults were analysed with regard to the molecular form and specific antibody activity of urinary immunoglobulins. The urinary IgA and IgG levels were quantified in unconcentrated urine by radioimmunoassay. The children with urinary tract infection had significantly higher levels of IgG and IgA than age-matched controls but not higher than healthy adults. After tenfold concentration, the urine was fractionated on an Ultrogel AcA 22 column, and the IgA, secretory IgA, and IgG in the fractions were determined by radioimmunoassay. IgA in urine from healthy adults was predominantly represented by polymeric IgA linked to secretory component; small quantities of monomeric IgA were also present. IgG eluted in the position of the serum standard. Increased proportions of IgG and monomeric IgA were found in the infected patients. Specific antibody activity of the IgG and IgA classes to antigens of the infecting Escherichia coli strain was detected in whole and in fractionated urine from children with acute pyelonephritis. The specific antibody activity in healthy adults and children was low.

Acute Disease↗

Antibodies to Escherichia coli and anti-adhesive activity in paired serum, hepatic and gall bladder bile samples.

Human bile contains a mixture of immunoglobulins excreted through the liver and produced in the biliary tract. This study examines the specific antibody activity of the biliary immunoglobulins against Escherichia coli antigens. Paired samples of serum, hepatic bile, and gall bladder bile were obtained from 23 patients with gallstones and five patients with healthy gall bladders. Antibody activity against E. coli antigens was found in all the sera and most of the bile samples. The levels of IgA, IgM, IgG, and secretory component (SC)-combined antibodies were lower in bile than in serum. Selective treatment of IgA by the liver was suggested by the finding of a correlation between the serum and the bile IgA antibody activity. IgG antibodies were only found in inflamed gall bladders. The bile was shown to have antibacterial activity against E. coli, i.e. an ability to inhibit the attachment to epithelial cells, but the inhibitory activity was not restricted to the immunoglobulin fraction of the bile.

Adhesiveness↗

Acquired IgA deficiency.

During a prospective study of the ontogeny of the mucosal immune system using saliva, one subject acquired a selective IgA deficiency at 3 years 6 months of age. Prior to this time the infant had normal ontogeny patterns for salivary immunoglobulins and the salivary IgA was confirmed to be dimeric IgA containing secretory component. Two respiratory tract infections at 3 years 4 months and 3 years 5 months were reported prior to the collection of a saliva sample which was deficient in IgA. All subsequent saliva collections remained IgA deficient. Serum and saliva collected at 11 years of age confirmed persistent IgA deficiency. There was a family history of organ-specific autoimmune disease. The prospectively collected data indicate in this subject that the IgA deficiency was not congenital, but was acquired closely associated with two episodes of respiratory tract infections, against a genetic background of disturbed immune regulation.

Adolescent↗

Bovine-associated mucoprotein: I. Distribution among adult and fetal bovine tissues and body fluids.

Bovine-associated mucoprotein (BAMP), solubilized with water from the delipidated membranes of bovine milk fat globules, is not restricted to fat globules or to the alveolar epithelial cells from which they are formed. BAMP also has a widespread distribution on other bovine glandular epithelial cells and on undifferentiated cells in lymphoid germinal centers and in several fetal tissues. Free BAMP is present in bovine colostrum, milk, other secretory fluids, and in fetal serum but is absent from adult and colostrum-deprived calf sera. In bronchoalveolar fluids, BAMP is preferentially found in the mucus-rich fraction. BAMP is antigenically distinct from all adult serum proteins, free secretory component, beta 2-microglobulin, lactoferrin, alpha-lactalbumin, beta-lactoglobulin, and five different caseins. BAMP as a free protein constitutes one-sixth of the total amount of BAMP present in milk. The BAMP-related component of fetal serum lacks antigenic determinants present on the BAMP of milk as demonstrated by immunoprecipitation and partial blocking of immunofluorescence. The fetal component is not fetuin or alpha 1-fetoprotein. These data suggest that BAMP may be useful in studies of the membranes of proliferating or differentiating epithelial cells.

Animals↗

[Prenatal development of the mandibular gland and parotid gland in cats].

The prenatal development of the cat's mandibular and parotid gland was examined by means of serial section of 36 cat embryos at 14-62 days of development. Both glands were excised from the epithelium of the primitive oral cavity and branched up to day 36 of the branching phase into a specific connective tissue. This tissue contained besides fine collagenous fibres, a high amount of proteoglycans. In the subsequent separation phase, ducts and acini differentiated themselves in primitive lobules which were separated by connective tissue. In the prenatal differentiation phase, from about day 50 up to birth, intercalated ducts and striated ducts were formed. In the acini, mucous and serous cells contained different amounts of complex carbohydrates. This secretory component changed shortly before birth.

Animals↗

Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis.

BACKGROUND: Inflammatory bowel disease (IBD) affects approximately 4 million people worldwide and can be caused by dysregulated mucosal immune responses to the intestinal commensal microflora. Immunoglobulin A (IgA) is considered to be the principal antibody in intestinal secretions and functions to prevent commensals and pathogenic organisms from gaining access to epithelial cell surfaces. Immunoglobulin A deficiency in humans has been associated with celiac disease and ulcerative colitis. However, the precise role of IgA in the pathogenesis of these disorders is yet to be fully understood. METHODS: Mice with a targeted disruption in IgA production (IgA(-/-) mice) and polymeric immunoglobulin receptor (pIgR(-/-) mice) were analyzed for the contribution of secretory immunity in the pathogenesis of dextran sulfate sodium (2.5%)-induced colitis. RESULTS: It was found that dextran sulfate sodium-treated pIgR(-/-) mice displayed greater loss of bodyweight and had severe clinical illness compared to similarly treated IgA(-/-) mice and wild-type animals. Additionally, colonic tissues from the pIgR(-/-) mice exhibited progressively and significantly greater degrees of mucosal edema, ulceration, crypt abscesses and macrophage infiltration when compared to similarly treated IgA(-/-) mice and wild-type animals. CONCLUSIONS: The results indicate that secretory immunoglobulins contribute to protection of the colonic mucosa against dextran sulfate sodium-induced epithelial injury, although the isotype of the secretory immunoglobulin (IgA or IgM) may not be a decisive factor in such protection. Collectively, the pIgR and/or the secretory component are important for the maintenance of epithelial integrity and mucosal homeostasis in the colonic epithelium.

Animals↗

Pancreatic carcinoma in childhood.

A case of pancreatic carcinoma in a 14-year-old Japanese boy is reported. He complained of general fatigue, anorexia, abdominal distension, and abdominal mass. At autopsy, a whitish tumor was found from the head to the body of the pancreas. Metastasis was found in the liver, lungs, gall bladder, and various lymph nodes such as stomach, hilus, and periaorta. The tumor was histologically determined to be moderately differentiated adenocarcinoma (cribriform type) of duct cell origin. However, the tumors showed PAS-positive diastase-resistant mucus in the cytoplasm. Histocytology showed the positivity for alpha 1-antitrypsin, secretory component (sc), and CEA, but no S-amylase was detected in the cytoplasm. Electron microscopy revealed zymogen-like granules in the cytoplasm suggesting acinar differentiation.

Adolescent↗

Pleomorphic adenoma with a predominantly myoepithelial proliferation of the vagina.

A case of pleomorphic adenoma of the vagina in a 44-year-old woman was described. The tumor was a submucosal mass measuring 3.5 X 2 X 2 cm and located in the left lateral wall 1.5 cm inside the introitus. Histologically, it was predominantly composed of sheets and strands of spindle-shaped or polygonal cells focally dispersed in the myxoid tissue to form pseudomicrocysts. Ultrastructure demonstrated the basal lamina, desmosomes, variable amounts of filaments of both intermediate and microfilament, and occasionally microvilli in these tumor cells indicating that dominant cells were myoepithelial in nature. With immunohistochemical studies, keratin and cytokeratin were positive, whereas, S-100 protein, glial fibrillary acidic protein, vimentin, secretory component, and lysozyme were negative. The previously published cases were reviewed and compared with the present case.

Adult↗

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↗

Histochemical and immunohistochemical evidence of glandular differentiation in thymic carcinoma.

Eighteen cases of primary thymic carcinoma were reviewed from the viewpoint of glandular differentiation. Squamous differentiation was evident in 14 cases (83%). Immunohistochemical study revealed secretory component (SC)-positive carcinoma cells in 12 cases (67%), most of which were also associated with squamous differentiation. Three of these 12 cases contained areas with a definite glandular or microcystic structure with occasional epithelial mucin, and were diagnosed as adenosquamous carcinoma. Review of patients' medical records revealed that thymic carcinomas with a glandular element were more often resectable at surgery, and had a much better prognosis than those without a glandular element. However, further study on larger number of cases is necessary to confirm this relationship. Because SC-positive epithelial cells do exist in the non-neoplastic thymus, the presence of a glandular component suggests another direction of morphological and/or functional differentiation of thymic carcinoma cells in addition to the well-known squamous differentiation.

Biomarkers, Tumor↗

Basaloid-squamous carcinoma of the esophagus with marked deposition of basement membrane substance.

A 71-year-old Japanese man with basaloid-squamous carcinoma of the esophagus is reported. The carcinoma contained basaloid cells, a few small cornified foci, and a large amount of eosinophilic hyaline substance, which reacted positively upon periodic acid-Schiff, type IV collagen, and laminin staining. Ultrastructural examination revealed markedly replicated basement membranes (BM). The morphological findings suggested that this tumor secreted abundant BM substance. Small nests of cancer cells were attached to the dysplastic esophageal epithelium. The tumor cells exhibited negative staining for mucin, secretory component, lactoferrin, and carcinoembryonic antigen. These findings, as well as the observed keratinization and attachment between the carcinoma nests and mucosal epithelium, indicate that the tumor originated in the mucosal epithelium of the esophagus.

Aged↗

Reticular crypt epithelium and intra-epithelial lymphoid cells in the hyperplastic human palatine tonsil: an immunohistochemical analysis.

Extensive immunohistochemical analyses of the hyperplastic human palatine tonsil disclosed variegated B cell phenotypes on the lymphoid cells among the crypt epithelium. The reticular epithelial network was evident by cytokeratin immunostaining. The reticular epithelium near the crypt lumen was positive for lysozyme. Secretory component was negative, while HLA-DR was frequently expressed. Intramucosal small lymphocytes, densely distributed in the luminal side, consisted mainly of B cells expressing CD19, CD20, CD21, CD22, CD45R, CD74, DBB42, HLA-DR, HLA-DQ, bcl-2 protein and surface IgM. Some B cells revealed mantle zone phenotypes (surface IgD+, CD5+, CD24+, DBA44+, CD10-, DNA7-). Cells of germinocyte phenotype (CD10+, DNA7+) were sparsely seen. A good number of intramucosal lymphoid cells were further labeled for CD11b, a phenotype of so-called B-1 cells. Plasma cells were clustered within the basal half. IgG was their major immunoglobulin class, followed by IgA, IgM and IgD classes. A smaller number of T cells (CD2+, CD3+, CD5+, CD45RO+, TCR alpha beta+) were identified among the epithelium. CD4+ cells predominated over CD8+ cells. TCR gamma delta+ cells were rare. Macrophages (CD68+), dendritic histiocytes (S-100 protein+, CD1+), and natural killer cells (CD16+ or CD57+) were also dispersed. Another unique feature of this lymphoepithelial complex was the existence of HLA-DR- intramucosal intramucosal microvasculature, where lymphocyte recirculation was suggested. Proliferating cell nuclear antigen was detected commonly in the epithelial cells but rarely in the lymphoid cells. Possible lymphoepithelial interactions and morphologic similarities to the thymic medulla are discussed.

Adolescent↗

Cell renewal and functional morphology of human lactating breast: presentation of a new mode of cell death ('magentosis') characterized by nuclear periodic acid-Schiff reactivity.

Cell kinetics and functional morphology of the human lactating breast were analyzed using 21 paraffin-embedded specimens of the lactating breast obtained by biopsy or surgery and two of the 'resting' breast. Four types (I-IV) of lactating lobules were categorized histologically, and were well correlated with their functional status demonstrated by immunohistochemistry for epithelial membrane antigen, beta-casein, lipase, lactoferrin, secretory component and IgA. Type I corresponded to a pre-lactating state, type II to an actively lactating state, type III to an early stage of regression, and type IV to an advanced stage of regression. Cell proliferation monitored by Ki-67 (MIB-1) immunostaining was at the highest level in type I lobules followed by type IV, while the labeling indices were low in types II and III. Apoptosis demonstrated by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-biotin nick end-labeling (TUNEL) method showed labeling profiles comparable with the proliferative activity. Holocrine-type desquamative cells with intact-appearing nuclei were frequently recognized in type II lobules. In type III, a peculiar form of cell death, designated 'magentosis', was demonstrated. These degenerative cells occasionally shedding into the acinar lumen possessed homogeneous pale, TUNEL-negative nuclei with diastase-resistant periodic acid-Schiff (PAS) reactivity. 'Magentosis' specifically identified in an early phase of involution of the human lactating breast might represent a unique mode of cell death distinguishable from apoptosis and necrosis.

Adult↗

Histological evidence for cell proliferation activity in cystic tumor (endodermal heterotopia) of the atrioventricular node.

Cystic tumor (endodermal heterotopia) of the atrioventricular (AV) node in a 95-year-old female is described. Electrocardiograms showed complete AV blockage with a narrow QRS morphology resulting from the long-standing first degree of AV blockage since age 61. A cardiac pacemaker was implanted at age 83. The patient died of pneumonia at age 95. Autopsy demonstrated a normal heart weight (320 g), normal coronary artery and normal myocardium. Histological examination of the conduction system revealed a marked fibrotic sinoatrial (SA) node and a cystic lesion in the lower right atrium, including the approaches to the AV node. The bundle of His and its branches were completely intact. Cellular nests and cystically dilated tubules were scattered within a loose tissue stroma, which measured 18 x 12 x 5 mm. There were several mitotic figures among the tubules, as well as nuclear fragments similar to apoptotic bodies and exfoliation of the tumor cells. Immunohistochemical studies demonstrated a positive reaction for epithelial membrane antigen, carcinoembryonic antigen, CA19-9, cytokeratin and secretory component in the tubular cells, and a negative reaction for thrombomodulin. Endocrine cells among the tubules were positive only for calcitonin and serotonin. Ultrastructurally, sparse microvilli and desmosome-like structures between the tumor cells were observed. These findings support that this lesion originates from the endoderm. Moreover, it is likely that progression in the degree of AV block may be explained by the cell proliferation activity of the tumor.

Aged↗

Conditional mutations in OutE and OutL block exoenzyme secretion across the Erwinia carotovora outer membrane.

The phytopathogen Erwinia carotovora subspecies carotovora secretes pectinases and cellulase via the general secretory pathway, a process requiring at least 13 proteins encoded by the out gene cluster. By exploiting delta::Tn5, a generalised transducing phage (psi KP) and localised mutagenesis of the out gene cluster, we have produced a histidine auxotroph and 19 new secretory mutants, including two (HJN1003 and HJN1004) which were conditional (temperature sensitive) for secretion. All of the mutants accumulated pectinases and cellulase in the periplasm, but in the case of HJN1003 and HJN1004, only at the restrictive temperature. HJN1003 and HJN1004 were complemented by the outE and outL wild-type genes, respectively, and both mutant alleles were cloned and sequenced to reveal single missense substitutions. HJN1003 carries an Arg166 to His alteration in OutE and HJN1004 carries a Pro159 to Leu alteration in OutL. Topology mapping of OutL using a beta-lactamase probe confirmed that OutL is a type II bitopic trans-inner membrane protein and that the mutated Pro159 residue in HJN1004 is located in the cytoplasmic domain of OutL. Hence, the secretion of exoenzymes across the outer membrane is critically dependent on the conformation of secretory components located at the cytoplasmic face of the inner membrane.

Bacterial Outer Membrane Proteins↗

Simultaneous expression of cytoplasmic IgM and IgG in plasma cells in a patient with IgG paraproteinaemia.

A dual expression of IgM and IgG was found in the cytoplasm of nearly all plasma cells in the bone marrow from a patient with an IgG1 paraprotein in the serum. These cells were morphologically and immunologically mature plasma cells. They lacked the B-cell markers surface Ig, CD19 and HLA-Dr, and were positive for HAN-PC1 and CD38. The cells were weakly positive for anti-J-chain and did not bind secretory component, indicating that the IgM was monomeric or aberrant. These findings show that class switch by deletion of DNA regions in mature plasma cells is not obligatory for the secretion of immunoglobulin classes other than IgM.

Aged↗

Product definition of pleomorphic adenoma of minor salivary glands.

Thirteen cases of pleomorphic adenoma were studied by both immunohistochemical and other histochemical methods. The exocrine cells and myoepithelial cells appear to produce similar cell products as their normal salivary gland counterparts. Keratin was found in both exocrine cells and myoepithelial cells. CEA, secretory component, and lactoferrin were detected only in the tumor exocrine cells with adenoid differentiation. S-100 protein, ferritin, fibronectin, laminin and elastin were detected only in the myoepithelial cells. The residual sugars glucosyl, mannosyl, galactosyl and fucosyl were identified in both cell types, in variably detectable amounts.

Adenoma, Pleomorphic↗

Histochemical studies of obstructive adenitis in human submandibular salivary glands. I. Immunohistochemical demonstration of lactoferrin, lysozyme and carcinoembryonic antigen.

Immunohistochemical detection of lactoferrin (LF), lysozyme (LZ) and carcinoembryonic antigen (CEA) was made in obstructive adenitis of the submandibular glands. Atrophic and altered acinar cells in the early stage of the lesion stained strongly for LF, whereas they were unreactive or stained slightly for LZ. Ductal cells usually stained for LZ. Staining for CEA was strong and irregularly distributed in altered acinar cells. Duct-like structures and dilated ductal segments in the chronic stage were generally negative for LF, LZ and CEA. Secretory components in luminal cavities gave abundant staining for LF, LZ and CEA. Histocytes which infiltrated into the connective tissue in the later stage showed a positive LZ reaction.

Acute Disease↗