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R Ullrich

Publications and source records attributed to R Ullrich.

142 records · Page 8Linked to original sources

[Stented dilated or varicose veins as arterial bypass transplants: experimental and initial clinical results].

Dilated and varicose veins are usually not used as arterial bypass-grafts despite they are lined with functional endothelium. External support by a constrictive mesh tube could conform these veins into evenly calibrated bypass-grafts. Ovine jugular veins could be constricted from 15 to 6 mm diameter without forming folds on the inner flow surface. 6 months after implantation of 5 cm long jugular vein segments into the carotid arteries of 7 sheep the inner diameter was 19.5 +/- 3.3 mm for native veins (n = 4) and 7.6 +/- 0.8 mm for constricted veins (n = 10). Intimal hyperplasia was reduced from 0.4 +/- 0.2 mm in native to 0.23 +/- 0.07 mm in reinforced veins (p = 0.03). Mesh tube constricted varicose veins were used as bypass material in 11 infrainguinal reconstructions. All grafts were well calibrated at control angiography. External constriction by mesh tubes is a means to convert varicose veins into suitable bypass grafts.

Aged↗

The HML-1 antigen of intestinal lymphocytes is an activation antigen.

The Ag recognized by the mAb HML-1 is expressed on more than 90% of human intestinal intraepithelial lymphocytes, whereas in other lymphoid tissues it is rarely or not expressed. In the present study, we have investigated the percentage of HML-1-positive cells in the human intestinal lamina propria and the coexpression of HML-1 with different T cell subset markers. In addition, we studied the inducibility of HML-1 on PBL which normally are HML-1-negative. Flow cytometric analysis of isolated intestinal lamina propria lymphocytes (LPL) showed that about 40% of the cells expressed HML-1, the majority belonging to the CD8-positive subpopulation. Virtually all LPL expressed CD45RO, whereas the percentage of CD29-positive cells was only about 50%, similar to PBL. There were only few cells expressing CD45RA or Leu-8 in the lamina propria. HML-1-positive cells were almost exclusively CD45RA-negative, but were found in both the CD29-positive and the CD29-negative subpopulation of LPL. In vitro stimulation of PBL showed that the expression of HML-1 was inducible on T cells by mitogens, phorbolester, Ag, and rIL-2. Expression of HML-1 was induced with a different time course and with differences in the response to the investigated stimuli compared with CD25. Activated HML-1-positive PBL were also predominantly CD45RA-negative. The findings show that HML-1 is an Ag, which is expressed in vivo on a specific subset of previously activated T cells in the unique environment of the intestinal mucosa, and which can be induced in vitro by different activation signals on PBL.

Antibodies, Monoclonal↗

gamma delta T cells in the human intestine express surface markers of activation and are preferentially located in the epithelium.

We have investigated the expression of the alpha beta and the gamma delta T cell receptor (TCR) in the human intestine. By immunohistology we found that 39% of CD3+ intraepithelial lymphocytes (IEL) expressed the gamma delta TCR compared to 3% of CD3+ lamina propria lymphocytes (LPL). Cytofluorometric analysis of isolated cells revealed a significantly higher proportion of gamma delta T cells among CD3+ IEL compared to LPL and peripheral blood lymphocytes. This was due to an increase in both CD8+ (low density) and CD4-CD8- gamma delta T cells in IEL. Most alpha beta IEL expressed high-density CD8. About 30% of both IEL and LPL expressed CD25 (alpha-chain of the IL-2 receptor). HML-1 expression was detected on nearly all IEL and on 27% of LPL. CD25 and HML-1 were preferentially expressed on intestinal alpha beta and gamma delta T cells, respectively. Thus, human gamma delta T cells are located preferentially in the gut epithelium and are phenotypically different from alpha beta T cells, which constitute the majority of both LPL and IEL.

Adult↗

Molecular cloning of a cDNA encoding a major pathogenic domain of the Heymann nephritis antigen gp330.

Heymann nephritis is an experimental autoimmune disease in rats that is characterized by accumulation of immune deposits (IDs) in kidney glomeruli. The disease is initiated by the binding of circulating antibodies to a membrane glycoprotein, gp330, which is a resident protein of clathrin-coated pits on glomerular epithelial cells (podocytes). We have defined a domain representing about 10% of gp330 that appears to be responsible for the formation of stable glomerular IDs. A cDNA clone (clone 14) was isolated from a rat kidney cDNA expression library by screening with IgG eluted from glomeruli of rats in early stages (3 days) of passive Heymann nephritis. The clone 14 cDNA contains an open reading frame encoding the C-terminal 319 amino acids of gp330. The predicted amino acid sequence contains four internal repeats of 11 amino acids, which are also found in the putative ligand-binding region of carbohydrate-binding lectin-like receptors. An antibody raised against the clone 14 fusion protein recognized gp330 by immunoblotting and induced formation of subepithelial IDs typical of passive Heymann nephritis when injected into normal rats. When the clone 14 fusion protein was used to immunize rats, subepithelial IDs of active Heymann nephritis were found after 12 weeks. No IDs were formed by active or passive immunization of rats with fusion proteins derived from other regions of gp330. These results demonstrate that clone 14 encodes a region of gp330 responsible for antibody binding and ID formation in vivo.

Amino Acid Sequence↗

Mucosal atrophy is associated with loss of activated T cells in the duodenal mucosa of human immunodeficiency virus (HIV)-infected patients.

Gastrointestinal symptoms and malabsorption are frequent in HIV-infected patients even in the absence of opportunistic infections. In earlier studies we found indications that the gastrointestinal mucosa itself may be affected by HIV. Since there is evidence that the mucosal structure is influenced by changes in the gut-associated lymphoid tissue, we have investigated mucosal structure and immune cells in HIV-infected patients. Sixty patients (3 f, 57 m; age 21-61, median 37 years; 11 at CDC stage II or III, 49 at stage IV) with gastrointestinal complaints undergoing upper endoscopy were examined for enteric pathogens. Duodenal biopsies were labelled by immunohistology for HIV antigen p24 and for lymphocyte surface markers; mucosal architecture was studied by three-dimensional morphometry. Biopsies from HIV seronegative patients without abnormal findings served as controls. In 29 patients an enteric pathogen was identified. In 22 patients HIV-infected mononuclear cells were detected in the lamina propria. In the lamina propria CD25+ cells were decreased, CD3+ and CD8+ cells were increased in HIV-infected patients compared with controls, while the numbers of CD4+, Leu8+, and HML-1+ cells, and of macrophages were not different. Patients at stage IV had decreased numbers of CD4+ T cells compared with patients at stage II or III. Villus surface area was reduced in HIV-infected patients compared with controls. Crypt depth was increased in patients with intestinal infection compared with controls while numbers of mitotic figures were normal. Patients without intestinal infection and patients with mucosal HIV-infected cells had decreased numbers of mitotic figures and normal crypt depth compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Small intestinal structure and function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy.

STUDY OBJECTIVE: To determine small intestinal mucosal structure and function in patients with human immunodeficiency virus (HIV) infection. DESIGN: Prospective, consecutive sample study. SETTING: Referral-based medical clinics at a municipal and a university medical center. PATIENTS: Forty-five HIV-infected patients (44 men, 1 woman) with gastrointestinal complaints. INTERVENTIONS: All patients had esophagogastroduodenoscopy. Distal duodenal biopsy samples were examined morphometrically and by quantitative enzyme histochemical techniques. Immunohistologic studies were done to determine whether HIV antigen p24 was present. Biopsy and stool samples were examined for enteric pathogens and patients were evaluated for malabsorption. MEASUREMENTS AND MAIN RESULTS: Malabsorption was common in HIV-infected patients. In 15 of 38 patients mononuclear cells infected with HIV were found in the mucosa. In 15 of 25 patients there was no detectable lactase (beta-glucosidase) activity in the duodenal brush border; when measurable, lactase (beta-glucosidase) activity was decreased (P less than 0.02). Alkaline phosphatase activity was normal. Crypt depth was greater (P less than 0.05), villous surface area was slightly smaller, and mitotic figures per crypt were not different in HIV-infected patients compared with controls. Patients without additional intestinal infection had a reduced number of mitotic figures per crypt (P less than 0.05) and normal crypt depth. The reduction in mitotic figures was most pronounced in patients with mucosal HIV antigen p24. CONCLUSIONS: The HIV-infected patients with gastrointestinal symptoms show low-grade small bowel atrophy and a maturational defect in enterocytes, which may be caused exclusively by HIV. An additional intestinal infection can mask this mucosal atrophy.

Acquired Immunodeficiency Syndrome↗

Expression of the oncogenes mil and ras abolishes the in vivo differentiation of mammary epithelial cells.

Three carcinoma-associated oncogenes, two of which have been strongly implicated in human mammary tumorigenesis, have been introduced into a novel mouse mammary epithelial cell line, EF43, that retains many differentiated functions. The effect of oncogene expression upon classical transformation parameters as well as parameters specific for mammary epithelial cells such as growth in three-dimensional collagen matrices and the ability to repopulate the cleared mammary fat pad and to form alveolar structures in vivo has been investigated. Expression of v-myc in EF43 cells results in no obvious phenotypic changes, and does not confer tumorigenic potential upon the cells. Expression of v-Ha-ras confers upon EF43 cells the ability to grow rapidly, grow in an anchorage-independent manner, results in tumor formation in nude and syngeneic animals, abolishes their ability to repopulate the mammary gland and, instead, results in rapid induction of anaplastic tumors. The v-mil oncogene, an avian homolog of the mouse v-mht and human c-raf oncogenes, previously thought to be non-transforming in the absence of a co-operating oncogene, transforms EF43 cells, allowing them to grow in an anchorage-independent manner, form tumors in nude mice and abolishes their ability to repopulate the cleared mammary fat pad. In contrast to v-ras, however, the tumors arising from v-mil expression have a differentiated morphology, typical of adenocarcinomas. Thus, different oncogenes show varying degrees of inhibition of the differentiation of mammary epithelial cells in vivo.

Animals↗

The isoprostane 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human heart valves.

To date, little information is available concerning oxidative injury in human cardiac valves. Therefore, we sought to investigate whether the isoprostane, 8-epi-PGF(2alpha), a novel oxidative stress marker, is localized in aortic and pulmonary valves derived from explanted hearts of patients suffering from idiopathic dilative cardiomyopathy (IDC). By using semiquantitative immunohistochemistry, we demonstrated that 8-epi-PGF(2alpha) is localized in both valves with pulmonary valves accumulating more of this isoprostane compared to aortic valves (36.69+/-12.04% vs. 31.54+/-11.49%, P<.05). These results were confirmed by a radioimmunoassay (RIA) analysis showing a similar, but not significant, difference between the two valves (288.50+/-72.18 pg/mg protein in the pulmonary valves and 267.30+/-58.77 pg/mg protein in aortic valves, P=.09). Considering the data presented in this study, we suggest that 8-epi-PGF(2alpha) is a valuable indicator of oxidative injury in human semilunar valves.

Adult↗

Compliance and formation of distal anastomotic intimal hyperplasia in Dacron mesh tube constricted veins used as arterial bypass grafts.

Dilated and varicose veins constricted with a Dacron mesh tube were successfully used as arterial bypass grafts to avoid nonautogenous vascular prostheses. Mesh constriction has also been used to adapt the venous graft lumen to the diameters of grafted arteries. The influence of the external mesh on the wall elasticity of such venous grafts and the reactions of the host artery were not investigated. Elastic properties of mesh constricted autologous veins used as arterial grafts in femoropopliteal reconstructions, as well as consecutive formation of distal anastomotic intimal hyperplasia (DAIH), were investigated in this experiment. Twenty-four autologous venous grafts were implanted in 12 sheep. Grafts were left natural (Groups 1 and 3) or were constricted with an external Dacron mesh (Groups 2 and 4); their diameters were left unchanged (Groups 1 and 2) or were matched to the diameter of the host artery (Groups 3 and 4). Wall elasticity of the graft, distal anastomosis, and distal artery were measured by locally applied crystal transducers during surgery and follow-up. Formation and localization of DAIH was evaluated histomorphologically after a median of 8.3 months. Graft wall elasticity was found to be lower (54.6 vs. 147.9, P = 0.006) and overall DAIH was found to be higher in mesh tube grafts (49.42 vs. 20.8 microns, P = 0.001, Mann-Whitney U-test). No differences in elasticity and DAIH formation were observed between grafts with adapted and large diameters. Constriction of venous grafts by a Dacron mesh tube reduces graft wall elasticity and promotes formation of DAIH. To avoid such an increased mismatch in compliance while making use of the advantages of this method, the external mesh tube must not be brought close to the distal anastomotic area itself.

Anastomosis, Surgical↗

Cathepsin D and PAI-1 expression in human head and neck cancer.

In order to determine possible overexpression of cathepsin D and PAI-1 (plasminogen activator inhibitor) in head and neck tumours, cytosols from 92 primary squamous cell carcinomas (SCC), 19 lymph node metastases and 24 adjacent normal tissue samples were examined. For both cathepsin D and PAI-1, significantly elevated concentrations in SCC compared to normal tissue were found, even in pairwise comparison. Moreover, significantly higher cathepsin D and PAI-1 concentration in lymph node metastases than in corresponding normal tissue were also present. The conclusion was drawn that cathepsin D and PAI-1 may play a specific role in the biology of head and neck SCC.

Carcinoma, Squamous Cell↗

Sucrose permeability as a marker for NSAID-induced gastroduodenal injury.

OBJECTIVE: To evaluate sucrose permeability as a non-invasive test for the monitoring of upper gastrointestinal mucosal damage (uGMD) in patients treated with NSAIDs. METHODS: 40 patients with non-inflammatory joint pain were enrolled in a prospective study. Before and after 14 days of ibuprofen treatment (3 x 400 mg/day), the rates of urinary sucrose excretion after an oral sucrose load were assessed. Individuals with increased sucrose permeability underwent endoscopy. RESULTS: 8 patients (20%) showed abnormal sucrose permeability before taking any NSAID. In 5/20 patients (25%) who completed 2 weeks of ibuprofen medication, sucrose excretion increased above the normal level. Endoscopic examination and biopsy revealed mild uGMD, but no ulceration in 8/11 (72%) patients with increased permeability to this marker. CONCLUSION: Sucrose permeability testing is a sensitive procedure for research protocols on NSAID-induced gastropathy. Since this test also seems to detect slight and clinically insignificant mucosal damage, however, its use in clinical decision-making regarding gastroprotective medication is limited.

Adult↗