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PubMed2001

Characterization of tubular functional capacity in humans using para-aminohippurate and famotidine.

BACKGROUND: Renal drug excretion by glomerular filtration and active tubular secretion may be altered by factors such as acute and chronic renal disease, nephrotoxins, and drug interactions. Thus, accurate and reproducible methods for quantitation of glomerular filtration rate (GFR) and tubular functional capacity are critical. METHODS: We utilized a four-step sequential infusion method to characterize anionic [para-aminohippurate (PAH)] and cationic (famotidine) tubular functional capacity in healthy volunteers. Filtration and secretion rates were quantitated from renal clearance and iothalamate-derived GFR determinations. RESULTS: Concentration-dependent renal clearance of PAH was observed at plasma concentrations> 100 mg/L; renal clearances were 442 +/- 131 (mean +/- SD), 423 +/- 94, 233 +/- 45, and 152 +/- 18 mL/min/1.73 m2 at plasma concentrations of 18 +/- 2, 92 +/- 5, 291 +/- 47 and 789 +/- 28 mg/L, respectively. The apparent affinity (Km) and maximum secretory capacity (TmPAH) were 141 +/- 70 mg/L and 71 +/- 16 mg/min/1.73 m2, respectively. The unbound renal clearance and tubular secretory clearance of famotidine were 384 +/- 70 and 329 +/- 78 mL/min/1.73 m2, respectively, and were not significantly correlated with the unbound plasma concentrations, which ranged from 126 to 2659 ng/mL. The rate of tubular secretion was linear at unbound plasma concentrations up to 2659 ng/mL. CONCLUSIONS: These data indicate that a sequential infusion method using PAH may be used to characterize the anionic secretory component of proximal tubular function. The tubular clearance of famotidine may be a suitable index of the cationic secretory capacity of the proximal tubule in humans. Saturation of the cationic secretory pathway was not observed, and further investigation into parallel pathways of cationic secretion, such as p-glycoprotein, may be warranted.

Adult↗

PubMed1986

Secretory meningioma. A distinct subtype of meningioma.

Six meningiomas with abundant hyaline inclusions (pseudopsammoma bodies) were studied. As seen by light and electron microscopy, hyaline inclusions are composed of material of varying structures located in intracellular lumina lined by microvilli. A remarkable pericytic proliferation within the vessel walls was found in five cases. In all six cases, immunohistochemical examination for multiple antigens showed positive staining for carcinoembryonic antigen and epithelial membrane antigen in inclusions and surrounding cells. Weak positivity was found for keratin and secretory component in five cases and for alpha-1-antitrypsin and IgM in four cases. It is concluded that secretory meningioma is a distinct type of meningioma, usually meningothelial in type. It shows characteristic light-microscopic, ultrastructural, and immunohistochemical features of epithelial and secretory differentiation with accumulation of secretory material in the form of hyaline inclusions; marked vascular pericytic proliferation is also frequently present.

Aged↗

PubMed1996

The relationship between the content of aggressive and protective components in gastric juice and endoscopic findings after naproxen sodium and acetaminophen administration.

OBJECTIVES: To evaluate the diagnostic value of residual gastric juice, we assessed various secretory components before and after placebo, acetaminophen, or naproxen sodium administration. METHODS: In a double-blind, randomized, cross-over study in 30 asymptomatic volunteers, mucin, hydrophobicity, protein, pepsin, and pH were measured in residual gastric juice before and after placebo, naproxen sodium (660 mg/d), or acetaminophen (4000 mg/d) administration. Mucus layer thickness in biopsy specimens was assessed, and mucosal damage was endoscopically evaluated. RESULTS: All parameters were unchanged after 7 days of placebo. Naproxen caused a 46% (p = 0.008) increase in the rate of luminal mucin release, an 18% increase (p = 0.510) in protein release, and a 61% decrease (p = 0.001) in hydrophobicity. Antral and duodenal mucus gel thickness were compromised, and hemorrhagic and erosive endoscopic changes were noted. Acetaminophen resulted only in a significant decline of pepsin. In subjects without endoscopic damage after naproxen, a nonsignificant decrease in hydrophobicity was noted. However, in subjects with endoscopic changes, a 55% decrease (p = 0.002) in hydrophobicity and a 42% increase (p = 0.024) in the rate of luminal mucin release were demonstrated. The initial mucin of subjects who developed endoscopic mucosal changes after naproxen was 53% higher than in subjects without damage. Subjects with endoscopic changes also exhibited a 48% lower initial hydrophobicity and a 43% lower pepsin than subjects without endoscopic changes. CONCLUSIONS: Gastric mucosal damage after naproxen sodium results in profound changes within the gastric mucosal barrier, and analysis of residual gastric juice components adequately reflects these changes. In contrast, acetaminophen results in only minimal gastric juice changes. Analysis of residual gastric juice may be useful in monitoring the extent of mucosal damage and identifying patients likely to develop mucosal damage.

Acetaminophen↗

PubMed2000

[Immunogenetic aspects in pathogenesis of acute pancreatitis].

Acute pancreatitis is characterized by essential decrease of the activity of the complement C1-C5 system components which is more marked under destructive form of the disease. The increased consumption of the components of the complement may be determined by forming immune complexes under interaction of the antibodies with structural and secretory components of the pancreas and direct proteolytic conversion under influence of trypsin. The revealed associations with HLA I antigens suggest the presence of genetic determination of the changes in the complement system. It may be also possible that components of the complement system, in particular C4 which is immune product of the HLA class III region, exert regulating influence on humoral immune reactions in acute pancreatitis.

Acute Disease↗

PubMed2003

[Morphofunctional organization of pancreatic secretory activity (a new paradigm)].

This is a review of physiological, morphological and clinical studies of pancreas secretion with the emphasis placed on pancreatic enzymes. It was established that different parts of the duodenal mucous coat have different chemosensory thresholds to the stimulators and inhibitors of pancreatic secretion. Secretory regions of the pancreas having a modular organization are also functionally different. The module is a set of pancreatic acinar and ductal cells (a secretory component), a system of ducts with their valve structures and a microdepository of secretion (a transport component) with control mechanisms specific for the module. Pancreatic secretion is a result of stimulation and inhibition of specialized secretory and transport modules.

Animals↗

PubMed1994

Large dense-core vesicles in rat adrenal after reserpine: levels of mRNAs of soluble and membrane-bound constituents in chromaffin and ganglion cells indicate a biosynthesis of vesicles with higher secretory quanta.

Rats were injected with a large dose of reserpine known to stimulate the adrenal medulla. Various times after drug treatment the mRNA levels of several constituents of large dense-core vesicles were determined by northern blot analysis and in situ hybridization. The latter method allowed detection of changes in mRNA levels not only in chromaffin cells, but also in the ganglion cells found in adrenal medulla. Levels of the mRNAs of secretory components of large dense-core vesicles (chromogranins A and B, secretogranin II, VGF, and neuropeptide Y) increased in chromaffin cells by 215-857% after 1-3 days of drug treatment. For partly membrane-bound components (dopamine beta-hydroxylase, prohormone convertase 2, carboxypeptidase H, and peptidylglycine alpha-amidating monooxygenase) the changes ranged from 182 to 315%, whereas for glycoprotein III and for intrinsic membrane proteins (cytochrome b561 and vesicle monoamine transporter 2) no change occurred. In ganglion cells the mRNAs that could be detected for VGF, neuropeptide Y, secretogranin II, carboxypeptidase H, and vesicle monoamine transporter 1 showed an analogous pattern of change, with significant increases for the secretory proteins and no change for the membrane components. From these and previous results we suggest the following concept: Long-lasting stimulation of chromaffin cells or neurons does not induce the biosynthesis of a larger number of vesicles but rather leads to the formation of vesicles containing higher secretory quanta of chromogranins and neuropeptides.

Adrenal Glands↗

PubMed1997

Entamoeba histolytica stimulates interleukin 8 from human colonic epithelial cells without parasite-enterocyte contact.

BACKGROUND & AIMS: The mechanisms involved in the initiation of host mucosal inflammation in amebiasis are not fully understood. This study characterized the effect of Entamoeba histolytica components on interleukin 8 (IL-8) gene expression in human colonic cells. METHODS: Colonic cells were stimulated with amebic proteins, secretory components, or live trophozoites (separated with 0.45-microm pores), and the levels of IL-8 messenger RNA (mRNA) and protein were detected. RESULTS: Live amebae or their components enhanced IL-8 mRNA levels in the colonic cells (T84, LS174T, and Caco-2). In T84 cells, the accumulation of IL-8 mRNA induced by amebic components occurred in a dose- and time-dependent fashion. Increased secretion of IL-8 was noted after 12-hour stimulation; neutralizing antibodies against IL-15 or tumor necrosis factor alpha did not inhibit IL-8 production. Nuclear run-on assays showed that amebae-induced IL-8 gene occurred by a posttranscriptional mechanism. Cycloheximide treatment resulted in superinduction of IL-8 mRNA; however, dexamethasone inhibited E. histolytica-induced IL-8 gene expression. CONCLUSIONS: E. histolytica can directly stimulate the induction of IL-8 by colonic cells in the absence of cell-cell contact or injury.

Animals↗

PubMed1998

Biliary secretory immunoglobulin A is a major constituent of the new group of cholesterol crystal-binding proteins.

BACKGROUND & AIMS: Recently we described a new group of lectin-bound biliary proteins that bind to cholesterol crystals, modify crystal morphology, and inhibit cholesterol crystallization. The aim of the current study was to characterize and identify individual members of this group of cholesterol crystal-binding proteins. METHODS: Crystal-binding proteins were purified from human gallbladder bile by lectin affinity chromatography and preparative gel electrophoresis. Purified crystal-binding proteins were characterized by using cholesterol crystal-growth assays, immunoblotting, and amino acid analysis. For comparison, identified biliary proteins were isolated from gallbladder bile by lectin affinity and immunoaffinity chromatography. RESULTS: The individual crystal-binding proteins with molecular weights of 74, 63, and 28 kilodaltons inhibited cholesterol crystallization in a dose-dependent manner (2.5-10 micrograms/mL). Immunoblotting with specific antibodies and N-terminal amino acid sequences revealed that the 74-kilodalton crystal-binding protein is the secretory component, the 63-kilodalton protein is the heavy chain, and the 28-kilodalton protein is the light chain of human secretory immunoglobulin (Ig) A. Isolated biliary IgA showed a potent inhibitory effect on cholesterol crystallization in model bile even at levels less than physiological concentrations (1-100 micrograms/mL). CONCLUSIONS: Biliary secretory IgA is a major constituent of the previously described group of cholesterol crystal-binding proteins. Crystal-binding IgA may be an important modulator of crystal agglomeration into stones and stone growth in vivo.

Amino Acid Sequence↗

PubMed1998

Structure and diversity of cestode epithelia.

Eucestodes have a simple aceolomate body structure and are conservative in terms of the numbers and nature of their cell types. Nevertheless, the cestodes form a diverse group with many strikingly different forms distinguished by the structure of their holdfasts, sexual tissues and embryos. These morphological adaptations have their origins in subtle variations in the structure of their cells and extracellular matrices. This review is concerned with the biology of eucestode epithelia and examines their structure and functions, interrelationships with other tissues, and gives insight into how their components are modified among the many taxa. Three features of cestode epithelia, namely, the occurrence of regional specialisation, microtriches and secretory components, are described. In addition, evidence is presented to suggest that some cestode epithelia are involved in developmental processes such as the nurture of embryos and maintenance of surrounding tissues.

Animals↗

PubMed1994

Secretory immunity in the female reproductive tract.

PROBLEM: Antibodies and antibody-producing cells display a different and characteristic distribution in body fluids and tissues. METHOD: We have investigated the tissues of the female reproductive tract to determine whether the distribution of immunoglobulin-producing cells and the contents of cervical secretions were similar to those found in tissues of the secretory immune system. RESULTS: Immunohistochemical examinations of female genital tissues revealed the presence of plasma cells that secrete IgA (and in lower numbers IgM and IgG) especially in the subepithelial layers of the uterine endo- and ectocervix, fallopian tubes, and vagina. Both IgA1- and IgA2-producing plasma cells were found in approximately equal proportions. The presence of J-chain in the IgA-secreting cells suggests the synthesis of polymeric IgA (pIgA). Epithelial cells lining the fallopian tube and endocervix were positive for secretory component (SC), which is required for the transepithelial transport of pIgA into external secretions. Cervical mucus was collected and the molecular forms of IgA were separated using column chromatography. Approximately 80% of IgA in cervical mucus was polymeric compared with 55% in the vaginal fluid. CONCLUSIONS: These data indicate that all effector components of the mucosal immune system are present in the female reproductive tract. The immunization routes that lead to a secretory IgA (S-IgA) response need to be further explored.

Adult↗

PubMed1994

[The current pathogenetic aspects of diarrhea in ulcerative colitis].

The authors consider different mechanisms participating in progression of diarrhea in ulcerative colitis. The involvement of osmotic component was suggested in view of incomplete hydrolysis of carbohydrates by small intestinal glucoamylase under mono- and bisubstrate digestion, whereas diarrhea secretory component develops in participation of cyclic nucleotides. Motor mechanism is also present in diarrhea as evidenced by high concentrations of blood motilin and changes in intestinal evacuation and motility. Polycomponent dysbioses detected in ulcerative colitis patients may also be essential for pathogenesis of diarrhea. Determination of the leading component in each diarrhea case is thought helpful in valid choice of individual therapeutic policy.

Adolescent↗

PubMed1994

Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) of preterm neonates is associated with an increased recruitment of inflammatory cells into the airways. To evaluate further the role of inflammation in the pathogenesis of BPD, tracheobronchial aspirate fluid of neonates with birth weight < 1200 g (n = 59) was sequentially analyzed in a prospective study. METHODS: Tracheobronchial aspirate fluid was assessed for chemotactic activity, neutrophil cell count, concentrations of elastase-alpha 1-proteinase inhibitor and activity of free elastase, concentrations of chemoattractants (complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8), and albumin concentrations as well as alpha 1-proteinase inhibitor activity. The secretory component for immunoglobulin A was used as reference protein. Only specimens without evidence of microbiological colonization were studied. RESULTS: In neonates with prolonged respiratory disease (BPD-risk neonates, n = 24, fraction of inspired oxygen > or = 0.3 and/or peak inspiratory pressure > or = 16 cm H2O at day 10 postnatal age, birth weight 892 +/- 36 g, gestational age 27.2 +/- 0.3 weeks) chemotactic activity, cell count, concentrations of the chemoattractants complement component C5-derived anaphylatoxin, leukotriene B4, interleukin-8, as well as levels of elastase-alpha 1-proteinase inhibitor were significantly higher at day 10 and/or day 15 of postnatal age compared with neonates without chronic pulmonary disease (total n = 35; day 10, n = 11; day 15, n = 8). There was no difference in free elastolytic activity. Concentrations of albumin as well as alpha 1-proteinase inhibitor activity were higher in BPD-risk patients on day 15, indicating an increased pulmonary leak. CONCLUSION: We conclude that preterm neonates at risk for the development of BPD show an enhanced inflammatory reaction in the lungs and an associated increase in pulmonary microvascular permeability. We speculate that inflammation may play an important role in the pathogenesis of BPD.

Albumins↗

PubMed1993

Determination of human immunoglobulin A and secretory immunoglobulin A in bronchoalveolar lavage fluids by solid phase enzyme immunoassay.

Solid phase enzyme immunoassay methods for the determination of secretory immunoglobulin A (IgA) and the total amount of serum and secretory IgA in bronchoalveolar lavage fluids (BALF) were developed. The solid phase was prepared by immobilizing rabbit anti-human IgA. Horseradish peroxidase-conjugated goat anti-secretory component or horseradish peroxidase-conjugated goat anti-human IgA (Fc) were used as labeled antibodies. The minimum detectable amounts of secretory IgA and total IgA were 2 and 0.5 ng/well, respectively. These assay methods were successfully applied to the determination of secretory and total IgA levels in BALF samples obtained from 44 subjects including healthy non-smokers, smokers and patients with the following lung diseases: idiopathic pulmonary fibrosis, sarcoidosis and hypersensitivity pneumonitis. The secretory and total IgA levels in BALF collected from healthy non-smokers (n = 9) were 10.5 +/- 3.6 and 25.4 +/- 15.5 (S.D.) micrograms/ml, respectively. In healthy smokers, the secretory IgA concentration was significantly decreased and in idiopathic pulmonary fibrosis, the total IgA was increased. These results indicate that the quantitation of secretory and total IgA may be useful for the investigation of lung disease.

Bronchoalveolar Lavage Fluid↗

PubMed1982

Secretory granules of murine salivary glands. A morphological, biochemical and morphological, biochemical and immunochemical study of submandibular and parotid granules.

Two secretory granular fractions from murine submandibular glands (SM) and one fraction from murine parotid glands (Par) were isolated by centrifugation on two discontinuous sucrose gradients. From the parotid glands the granular fraction was layered on 1.9 M sucrose (ParB), and in addition a second fraction was layered on 2.1 M sucrose (SMc). The contamination of the granular fractions by other cellular organelles was determined. The membranes of both the Parb and SMb granular fraction contained a major protein fraction with a molecular weight of 12-14,000 designated PMC and MMC, respectively. Their total amino acid composition was similar, but not their carbohydrate composition and immunochemical properties. The major protein within the Parb granules was amylase, and in addition AM2-glycoprotein was also present. Both secretory components had exclusively an acinar localization in the parotid glands, indicating the acinar origin of the Parb granules. In the SMb granular fraction, consisting of large secretory granules, amylase activity was detected by enzymatic method, and in addition the nerve growth factor and epidermal growth factor were demonstrated by immunochemical methods. These activities could only be localized in the SM granular tubular (GCT) cells, pointing to a GCT cellular origin of the SMb granules. On the other hand, immunoreactive amylase, AM2-glycoprotein, and submandibular mucin (MSM) were present in the SMc granular fraction. In the SM tissue sections these components were localized in the acinar cells. So, it is likely that the SMc granules are seromucous acinar granules.

Amylases↗

PubMed1989

Morphological heterogeneity of esophageal carcinoma.

To clarify the morphological heterogeneity of esophageal carcinoma, the adenocarcinomatous, basaloid, and sarcoma-like components of 178 esophageal carcinomas were studied with regard to histopathology, mucin histochemistry, immunohistochemistry, and ultrastructure. Adenocarcinomatous components with mucicarminophilic cells and/or glandular structures, basaloid components, and sarcoma-like components were found in 55 lesions (30.9%), 17 lesions (9.3%), and five lesions (2.8%) respectively. Carcinoembryonic antigen staining was positive in 52 lesions (29.2%), secretory component staining was positive in 15 (8.4%), and lactoferrin staining was positive in 12 (6.7%). Eight intraepithelial carcinomas were found to have no adenocarcinomatous components, and two intramucosal carcinomas had adenocarcinomatous components in the invasive portions. These findings strongly suggest that the adenocarcinomatous components do not arise from the ductal epithelium, but occur during the process of invasion. There were no significant clinicopathological differences between the carcinomas with adenocarcinomatous components and those without. Ultrastructurally, the adenocarcinomatous components were seen to possess intracellular microcysts, intercellular lumina, and bundles of tonofilaments, having features of both glandular and squamous epithelia. On the basis of the concept that the basaloid components are histological variants of squamous cell carcinoma and that sarcoma-like components arise from mesenchymal metaplasia of squamous cell carcinoma, it is possible that the three components may originate from the squamous component. The present study thus demonstrated a high incidence of histological variation among esophageal carcinomas.

Adult↗

PubMedDate not supplied

Decreased Helicobacter pylori-specific gastric secretory IgA antibodies in infected patients.

Despite an increase in local Helicobacter pylori-specific IgA production in H. pylori infection, the bacterium is able to persist over decades. We focused on IgA and secretory IgA (sIgA) in gastric juice because sIgA is more relevant in local protection and more resistant to degradation than nonsecretory IgA. H. pylori-specific IgA and sIgA in gastric juice, saliva, and serum of H. pylori-infected patients were compared. Samples from 28 H. pylori-positive and 16 negative patients were tested by means of immunoblotting for the presence of H. pylori-specific IgA and sIgA. In gastric juice the majority of H. pylori-specific IgA was not of the secretory type, whereas total IgA was bound mainly to the secretory component as shown by immunoblot and slot blot. In contrast H. pylori-specific IgA antibodies in saliva of infected patients were of the secretory type as shown by immunoblot. The presence of specific, nonsecretory IgA may be a consequence of the damaged mucosal epithelium at the site of H. pylori infection allowing IgA to bypass the secretory transport system. Considering the resistance of secretory IgA against hydrolysis and proteolysis, these data suggest that the predominantly nonsecretory IgA specific for H. pylori may lead to a decreased protection against H. pylori.

Adult↗

PubMed2004

Genetic analysis of soluble N-ethylmaleimide-sensitive factor attachment protein function in Drosophila reveals positive and negative secretory roles.

The N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP) are cytosolic factors that promote vesicle fusion with a target membrane in both the constitutive and regulated secretory pathways. NSF and SNAP are thought to function by catalyzing the disassembly of a SNAP receptor (SNARE) complex consisting of membrane proteins of the secretory vesicle and target membrane. Although studies of NSF function have provided strong support for this model, the precise biochemical role of SNAP remains controversial. To further explore the function of SNAP, we have used mutational and transgenic approaches in Drosophila to investigate the effect of altered SNAP dosage on neurotransmitter release and SNARE complex metabolism. Our results indicate that reduced SNAP activity results in diminished neurotransmitter release and accumulation of a neural SNARE complex. Increased SNAP dosage results in defective synapse formation and a variety of tissue morphological defects without detectably altering the abundance of neural SNARE complexes. The SNAP overexpression phenotypes are enhanced by mutations in other secretory components and are at least partially overcome by co-overexpression of NSF, suggesting that these phenotypes derive from a specific perturbation of the secretory pathway. Our results indicate that SNAP promotes neurotransmitter release and SNARE complex disassembly but inhibits secretion when present at high abundance relative to NSF.

Alleles↗

PubMed1998

Regulation of the biosynthesis of large dense-core vesicles in chromaffin cells and neurons.

1. The proteins of large dense-core vesicles (LDV) in neuroendocrine tissues are well characterized. Secretory components comprise chromogranins and neuropeptides. Intrinsic membrane proteins include cytochrome b-561, transporters, SV2, synaptotagmin, and synaptobrevin. 2. The effects of stimulation and of second messengers on the biosynthesis of LDV have been studied in detail. 3. Regulation of biosynthesis is complex. The cell can adapt to prolonged stimulation either by producing vesicles of normal size filled with a higher quantum of secretory peptides or by forming larger vesicles. In addition, some components, e.g., enzymes, can be upregulated specifically.

Animals↗