Biomedical subjects

M Zeitz

Publications and source records attributed to M Zeitz.

221 records · Page 13Linked to original sources

PubMedDate not supplied

Whipple's disease with aortic regurgitation requiring aortic valve replacement.

Cardiac involvement in Whipple's disease is well established. However, clinical consequences beside antibiotic therapy have rarely been reported. Our observation of a middle-aged man with increasing dyspnea, fatigue, chest pain, and dizziness leading to admission to a cardiology department demonstrates that cardiac symptoms may represent the main symptoms in patients with Whipple's disease. The diagnosis was not made prior to upper endoscopy, performed because of diarrhea, and revealed Whipple's agent now classified as Tropheryma whippelii, which is a PAS-positive rod-shaped bacterium in the macrophages of the intestinal lamina propria. The aortic valve was replaced after the intestinal symptoms were resolved by antibiotic treatment reducing the number of infectious agents in the duodenal mucosa. Histological analysis of the aortic valve demonstrated the presence of PAS-positive rod shaped material as the most likely cause of aortic insufficiency. Five months after valve replacement, the patient had completely recovered from intestinal and cardiac symptoms. Still under antibiotic treatment 16 months later, no more PAS-positive macrophages were detectable in the intestinal mucosa.

Aortic Valve↗

PubMedDate not supplied

Novel adapter protein AP162 connects a sialyl-Le(x)-positive mucin with an apoptotic signal transduction pathway.

Glycoproteins modified with a sialyl-Le(x)-moiety are important sensors for extracellular signals regulating cellular recognition, adhesion and migration. The transduction pathways and signals mediated by these glycoproteins within the cell are largely unknown. In search of novel glycoproteins modified with sialyl-Le(x)-moiety, we screened a human colonic cDNA expression library with a rabbit antiserum produced against sialyl-Le(x)-positive mucins. The antiserum detected a new protein, named B2, which was cloned and characterised in detail. The analysis of the B2 gene revealed a 5.7 kb RNA transcript detectable in all investigated tissues and a complete coding sequence of 2778 bp. The B2 protein exhibited two putative PH (pleckstrin homology) domains and a leucine zipper motif but no homology to any known proteins. Monospecific antibodies against the B2-protein precipitated from the solubilised membrane fraction of the colon carcinoma cell line LS 174T a protein with an apparent Mr = 162 kDa and, additionally, a mucin-like glycoprotein with an apparent Mr = 220 kDa. Protein fractionation on a CsCl gradient, Western blots and sandwich ELISA showed that the 220 kDa mucin carries the sialyl-Le(x) moiety and is tightly bound to the 162 kDa protein. The expression of the recombinant B2-protein enhanced staurosporine-induced apoptosis in epithelial cancer cell lines. These data indicate that B2 is a novel, ubiquitously expressed protein with a putative adapter function. The protein has been named AP162 (adapter protein 162). In colon carcinoma cells B2-protein is tightly associated with a sialyl-Le(x)-positive mucin and has a potential for involvement in sialyl-Le(x)-mediated transduction of apoptotic signals.

Adaptor Proteins, Signal Transducing↗

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↗

PubMedDate not supplied

The interleukin-2-deficient mouse model.

Interleukin-2-deficient (IL-2(-/-)) mice develop colitis with striking clinical and morphological similarities to ulcerative colitis. Since transport and barrier properties are impaired in ulcerative colitis, we studied transport and barrier functions in IL-2(-/-) mice in order to gain insight for the first time into the general pathomechanisms of disturbed transport and barrier function of the intestine during inflammation. Alternating current impedance analysis was used to determine tissue conductance in the inflamed proximal colon of IL-2(-/-) mice and to discriminate between pure epithelial and subepithelial conductance. Surprisingly, epithelial conductance was not increased but diminished in IL-2(-/-) mice compared to controls (20.2 +/- 1.3 versus 28.8 +/- 2.8 mS/cm(2)). Concomitantly, conductance of the subepithelial tissue layers was decreased in IL-2(-/-) mice as a result of edema and infiltration with inflammatory cells. In the distal colon, electrogenic Na(+) transport (J(Na)) mediated by the epithelial Na(+) channel (ENaC) was measured 8 h after stimulation with 3.10(-9) M aldosterone in vitro as the drop in I(SC) (short circuit current) after addition of 10(-4) M amiloride. In controls, J(Na) was 6.9 +/- 0.9 micromol x h(-1) x cm(-2), whereas it was abolished in IL-2(-/-) mice. In conclusion, the inflamed colon of IL-2(-/-) mice exhibits a severe disturbance in Na(+) uptake via the ENaC in the absence of a barrier defect. Thus, reduced expression of active absorptive transport and not a barrier defect is responsible for the diarrhea in this model of intestinal inflammation. This makes this model suitable for studying the general pathomechanisms of the inflammatory downregulation of intestinal transport proteins.

Aldosterone↗

PubMedDate not supplied

Treatment of Crohn's disease.

The treatment of Crohn's disease depends on disease location and disease activity. It can be divided into medical and surgical treatment. While surgery is reserved for complications such as abscesses or failure of pharmacological treatment (fistulae, perianal disease, or strictures) medical treatment aims at induction and maintenance of remission. In order to achieve these goals supportive and therapeutic strategies must be used. Supportive measures include substitution of vitamins, particularly fat-soluble vitamins, and minerals in deficiencies due to resection or disease involvement of the small bowel. All patients on long-term steroids should receive calcium and vitamin D in order to prevent osteoporosis. Therapeutic options include drug treatment (corticosteroids, antibiotics, salicylates, and immunosuppressives), nutrition (parenteral or enteral), and endoscopy (dilatation of strictures). Depending on disease location different pharmacologic preparations of salicylates or corticosteroids should be used, e.g., enemas for distal colitis. The most potent drugs for long-term control are immunosuppressive agents, particularly azathioprine. It is the most widely investigated immunosuppressive agent in Crohn's disease and should be the first line treatment for patients with steroid refractory, chronic steroid dependent, fistulating, and stenosing courses. In the future, more potent drugs and better risk stratification criteria should improve the treatment of Crohn's disease.

Adrenal Cortex Hormones↗