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Biomedical subjects

R Ullrich

Publications and source records attributed to R Ullrich.

At least 109 records · Page 6Linked to original sources

Differential expression of the protooncogene bcl-2 in normal and osteoarthritic human articular cartilage.

OBJECTIVE: To investigate the expression of bcl-2 in healthy and osteoarthritic articular cartilage at the transcriptional level and at the protein level. METHODS: bcl-2 mRNA was detected by reverse transcriptase/polymerase chain reaction. The expression of bcl-2 protein was studied using flow cytometry analysis with a monoclonal antibody against intracellular bcl-2 and by immunohistochemistry. RESULTS: mRNA for bcl-2 was detectable in chondrocytes of both healthy and osteoarthritic cartilage. bcl-2 protein was present in the chondrocytes of the middle layer of cartilage by immunohistochemical staining. In osteoarthritis (OA), chondrocytes adjacent to cartilage defects expressed a particularly high signal intensity. Flow cytometry analysis demonstrated the presence of bcl-2 protein in virtually all chondrocytes. CONCLUSION: Our results show that bcl-2 is expressed in healthy adult and osteoarthritic human cartilage. The increased staining of chondrocytes adjacent to osteoarthritic defects indicates a differential regulation of programmed cell death during the degenerative process in OA.

Adult↗

Cell differentiation and proliferation in the gastrointestinal tract with respect to the local immune system.

Human intestinal lamina propria T cells have a low expression of the CD45RA antigen and a high expression of the CD45RO antigen. This phenotype is characteristic for memory T cells. In addition, T cells in the effector compartment of the mucosa bear surface antigens that are very rarely found in other sites of the immune system. Intestinal T cells also express functional IL-2 receptors, and IL-2 receptor alpha-chain mRNA, and are able to synthesize high amounts of IL-2. However, other markers of memory T cells, as CD29, are not expressed in high density in the lamina propria, indicating that lamina propria T cells differ from "classical" memory T cells. This is supported by functional studies in nonhuman primates infected rectally with Chlamydia trachomatis that show that lamina propria T cells do not proliferate after stimulation with antigen but rather provide helper function for immunoglobulin synthesis. These findings indicate a specific state of differentiation of lamina propria T cells that is adapted to the specific requirements in the gut. In inflammatory bowel disease (IBD) and in celiac disease, an increase in the number of CD25-positive activated T cells is found in involved mucosa. It has been shown that mucosal T-cell activation induces epithelial cell damage and mucosal transformation. Thus, a T cell-mediated damage may contribute to the pathogenesis of IBD. HIV-infected patients have a decreased number of CD4-positive T cells in the intestinal lamina propria. The number of CD25-positive activated T cells is also significantly decreased in the intestine compared to controls. Correlating with the presence of HIV-infected mononuclear cells in the mucosa, mucosal atrophy with hyporegeneration and enterocyte dysmaturation is observed. HIV might thus cause impairment and depletion of activated regulatory T cells in the intestinal lamina propria, which could lead not only to a breakdown of the mucosal immune barrier, resulting in a variety of opportunistic infections, but also to malabsorption, due to mucosal atrophy or enterocyte dysfunction. These findings indicate a close relationship between mucosal T cells and enterocyte proliferation and maturation.

Animals↗

[Anesthesia in acute respiratory tract obstructions caused by high degree laryngeal and tracheobronchial stenoses].

UNLABELLED: Stenotic process of the laryngeal and/or tracheobronchial system may lead to dyspnoea which can become life threatening. OBJECTIVE: The object of our study was to determine whether sufficient gas exchange can be ensured in patients with a massive stenosis of the respiratory tract applying the Superimposed High-Frequency-Jet-Ventilation (SHFJV) via the jet laryngoscope. Further, it was to be determined whether SHFJV can be applied for insertion of endoluminal stents into the tracheo-bronchial system. METHOD: SHFJV was applied using the Bronchotron-ventilator (capable of generating simultaneous low frequency and high frequency jets) and the laryngoscope, basically a modified endoscopy tube permitting simultaneous application of two jet modes. SHFJV was performed in 14 patients (including 4 children) suffering from massive laryngeal stenosis and in further 12 patients with stenosis of the tracheo-bronchial system. In all patients total intravenous anaesthesia was performed. RESULTS: In the patients with laryngeal stenosis the average paO2 was 117.5 +/- 43 mmHg, and the mean paCO2 47.3 +/- 11.6 mmHg. In the patients with stenosis of the tracheo-bronchial system the mean paO2 was 125 +/- 77 mmHg and the average paCO2 53.3 +/- 18 mmHg. CONCLUSIONS: The SHFJV technique presents the possibility to ventilate the patients continuously for surgical procedures even with massive stenosis of the respiratory tract. The application of SHFJV via the jet laryngoscope not only enables the anaesthesist to ventilate this group of patients but also helps the surgeon and therefore results in more safety for the patient.

Adult↗

[3-D endoscopy for laryngeal interventions in tubeless superimposed high frequency jet ventilation. A clinical trial].

UNLABELLED: Surgery by 3-dimensional (3D) endoscopy is being used routinely in abdominal surgery and, in special cases, in thoracic surgery; however, it has not been reported to be used in laryngeal surgery. METHODS: We inserted a 3-D endoscope into a jet laryngoscope and studied the pressure properties at the tip of the jet laryngoscope as well as the intrapulmonary pressures while applying SHFJV. The studies were conducted initially using a lung simulator, and then in 6 patients undergoing endoscopic laryngeal surgery. RESULTS: Due to the rather large 3-D endoscope the diameter of the jet laryngoscope was reduced between 25.2% and 70.9% depending on the size of the jet laryngoscope. The measurements on the lung simulator revealed that the reduction of the diameter of the jet laryngoscope leads to an increase in the following parameters: expiratory resistance, tidal volume, and peak inspiratory pressure. The mean FiO2 was 0.74 +/- 0.1; the mean airway pressure was 19 +/- 5.3 mmHg prior to the insertion of the endoscope and 12.3 +/- 6.9 mmHg after the insertion. The mean PEEP values increased from 2 +/- 0.6 to 3.6 +/- 2.3 mmHg. Reduction of the working pressure resulted in regaining the initial inspiratory pressures and tidal volumes. CONCLUSIONS: In the clinical application of 3-D endoscopy via a jet laryngoscope it was possible to achieve sufficient ventilation, inspection of the surgical field and performance of the surgical procedure. A CO2 laser was used without changing the ventilation regime.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Serum carotene deficiency in HIV-infected patients. Berlin Diarrhoea/Wasting Syndrome Study Group.

OBJECTIVE: To assess total serum carotene concentration in HIV-infected patients as an indicator of fat malabsorption in correlation with diarrhoea, secondary enteric infections, and blood lymphocyte subsets. DESIGN: Prospective study. SETTING: Two referral-based tertiary care centres in Berlin, Germany. PATIENTS: A total of 33 controls and 116 HIV-infected patients who had complete microbiological evaluation of stools and biopsies obtained at upper endoscopy because of diarrhoea (n = 54), or other symptoms (n = 62), were studied. MAIN OUTCOME MEASURES: Total serum carotene concentration was determined spectrophotometrically. RESULTS: Total serum carotene concentration was abnormal (< 0.88 mumol/l) in 77% of HIV-infected patients and significantly decreased compared with controls [0.47 mumol/l (range, 0.06-1.69 mumol/l) versus 1.37 mumol/l (range, 0.88-2.92 mumol/l); P < 0.0001]. Total serum carotene concentration did not differ between AIDS patients and patients at earlier disease stages, between patients with or without secondary enteric infections, or between patients with or without fever. In patients at earlier disease stages, but not in AIDS patients, total serum carotene concentration was lower for patients with than without diarrhoea. The percentage of CD4 lymphocytes (r = 0.364; P < 0.001), CD4 count (r = 0.28; P = 0.0013), and CD4/CD8 ratio (r = 0.38; P < 0.001) in the peripheral blood correlated with total serum carotene levels in HIV-infected patients. CONCLUSION: HIV-infected patients frequently have abnormal total serum carotene concentrations indicating fat malabsorption which may contribute to diarrhoea. Furthermore, total serum carotene concentrations correlate with immunologic abnormalities in HIV infection.

CD4-Positive T-Lymphocytes↗

Abnormalities in subset distribution, activation, and differentiation of T cells isolated from large intestine biopsies in HIV infection. The Berlin Diarrhoea/Wasting Syndrome Study Group.

Intestinal T cells have a unique state of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized, but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by three-colour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxic phenotype. Activated and resting CD4 T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased, respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.

Acquired Immunodeficiency Syndrome↗

Magnetic resonance imaging in the diagnosis of acute Lyme carditis.

Lyme disease is a multisystem disease, which can involve the heart causing myopericarditis. We describe 1 patient with serological and histological evidence of Lyme borreliosis and demonstration of pathologic myocardial signal enhancement in magnetic resonance imaging.

Acute Disease↗

[Gastrointestinal manifestations of HIV infection].

The intestinal (in particular rectal) mucosa is the main portal of entry for HIV in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4-positive T cells, macrophages and follicular-dendritic cells in the intestinal mucosa. HIV may be transported through M-cells directly to mucosal lymph follicles. Alternatively HIV may infect enterocytes via Fc-receptor by antibody-bound HIV or via a CD4-independent receptor. By successive budding on the basolateral side of the enterocytes HIV may be released into the lamina propria. The loss and functional impairment of activated CD4-positive lamina propria T-cells could be responsible for both the decreased immune defense and altered structure and function of the mucosa. The common intestinal symptoms in HIV-infected patients may be caused by a variety of mechanisms. The high number of secondary opportunistic or non-opportunistic infections and secondary malignancies of the gut may be responsible for the observed symptoms. However, the pathogenic relevance of some of these pathogens is questionable since there is often no correlation between symptoms and presence of the pathogen. In addition, there is a considerable percentage of symptomatic patients without identifiable microorganisms. Yet unidentified pathogens, small intestinal bacterial overgrowth, damage of intestinal nerve fibres, or secretory diarrhea may contribute to the pathogenesis of gastrointestinal symptoms. The findings of a pathogen-negative diarrhea, of HIV-infected mononuclear cells in the gut, and of epithelial hypoproliferation and enterocyte dysmaturation is in agreement with the hypothesis that there is an enteropathy caused by HIV itself.

AIDS-Related Opportunistic Infections↗

[Histologic classification of epithelial salivary gland tumors].

A precise and reproducible histopathological classification, in combination with grading and staging, is the basis for determining the prognosis and treatment of salivary gland tumors. The 2nd edition of WHO Histological Typing of Salivary Gland Tumors, as well as the staging according to UICC 1989, is oriented towards the routine work of surgical pathologists. Knowledge about the important entities of this classification is an indispensable foundation for successful therapy and interdisciplinary cooperation.

Adenoma↗

Indium 111-monoclonal antimyosin antibody and magnetic resonance imaging in the diagnosis of acute Lyme myopericarditis.

BACKGROUND: Lyme borreliosis is a tick-borne multisystem disorder that may present as self-limiting early or persistent chronic diseases of the skin, nervous system, joints, heart, and other organs. Cardiac involvement has mainly been reported as acute atrioventricular conduction disturbances or transient ventricular dysfunction. METHODS AND RESULTS: We treated a patient with clinical signs of acute myopericarditis and serologic evidence of Lyme borreliosis confirmed by silver staining of endomyocardial biopsy specimens and indium 111-monoclonal antimyosin antibody scan, which we believe has not been reported previously. Additionally, magnetic resonance imaging revealed epicardial and myocardial areas of increased intensity. CONCLUSION: Indium 111-monoclonal antimyosin antibody scanning and magnetic resonance imaging might play an additional important role in assessing and confirming the diagnosis of Lyme carditis in the presence of clinical symptoms and positive serologic findings.

Acute Disease↗

Reactive oxygen species and neutrophil respiratory burst cytochrome b558 are produced by kidney glomerular cells in passive Heymann nephritis.

Reactive oxygen species (ROS) have been implicated in the production of glomerular damage in passive Heymann nephritis (PHN), an experimental form of membranous nephropathy with neutrophil-independent proteinuria. Immunohistochemistry with monoclonal antibodies specific for cytochrome b558 (a major component of the oxidoreductase complex of the respiratory burst in stimulated neutrophilic granulocytes) showed that this enzyme is localized within visceral glomerular epithelial cells (GECs) in a dense, granular pattern in rats with PHN and proteinuria. By immunoelectron-microscopy, the cytochrome was found in membrane vesicles within the GEC and also extracellularly on the GEC membranes facing the glomerular basement membrane (GBM). By immunoblotting, cytochrome b558 was detected in highest concentration in lysates of isolated glomeruli from proteinuric rats. By contrast, only traces were found in normal glomeruli by immunohistochemistry. Depletion of complement abolished the expression of the cytochrome. Using an ultrastructural cerium-H2O2 histochemistry technique, the functional activity of the glomerular ROS-generating system was demonstrated exclusively in proteinuric PHN, where H2O2 was found in highest concentration within the GBM. These results provide evidence that in rats with PHN and proteinuria, the GECs express and externalize respiratory-burst enzymes that generate ROS in a manner similar to neutrophilic granulocytes, which could then lead to glomerular damage.

Animals↗

Bacillary angiomatosis in a German patient with AIDS.

A 52-year old male homosexual patient with acquired immunodeficiency syndrome (AIDS) presented in our clinic with multiple nodular papules (more than 100) spread over the whole body which had developed within 3 months. Bacillary angiomatosis was suspected, which is a bacterial infectious disease recognized recently mainly in patients with AIDS. Histological and immunohistochemical examinations of extirpated skin lesions were in agreement with the diagnosis, and the detection of rod-shaped bacteria in the lesions by Warthin-Starry silver stain confirmed it. The patient was treated with 2 x 100 mg doxycycline per day. The fever disappeared, and the cutaneous lesions showed a slight tendency to improve. However, after 5 days of therapy the patient showed increasing weakness, with muscle and bone pain. The patient died 10 days after the doxycycline therapy had been started. The cutaneous lesions in bacillary angiomatosis may resemble Kaposi's sarcoma and may therefore be misdiagnosed. The disease may be fatal, but timely antibiotic treatment is usually effective; therefore, the diagnosis of bacillary angiomatosis is important. Although many cases have been reported from the United States, only one case is known from Europe. Our finding of bacillary angiomatosis in a German AIDS patient supports the concept of a worldwide distribution of this bacterial agent.

AIDS-Related Opportunistic Infections↗

Secretogranin IV immunoreactivity in medullary thyroid carcinoma: an immunohistochemical study of 62 cases.

The presence and intracellular distribution of secretogranin IV (Sg IV) was determined on light microcop by the avidin-biotin peroxidase complex method with the monoclonal antibody (mAb) Hisl-19 in normal and hyperplastic C-cells, in 62 primary medullary thyroid carcinomas (MTCs) and in 17 MTCs in tissue from synchronous and/or metachronous lymph node metastases and in one liver metastasis. Sg IV immunoreactivity was present in almost all normal-looking and hyperplastic C-cells, in 59 of 62 (96%) of the primary tumours, in 18 of 26 (69%) lymph node metastases and in distant metastasis. Sg IV reactivity ranged from small foci of positive tumour cells to a reaction in virtually every malignant cell. Two different staining patterns were obvious: a granular cytoplasmic reactivity and a perinuclear cluster-type signal. Normal-appearing and hyperplastic C-cells were characterized by a uniform granular staining often coexisting with discrete cluster-type immunoreactivity. Various combinations of these staining patterns were observed in C-cell carcinomas. The pure cluster-type reactivity was restricted to malignant C cells and was not detected in normal-appearing and hyperplastic C-cells. In serial sections immunohistochemical results for Sg IV, calcitonin (Ct) and chromogranin A (Cg A) showed only partial correlation. Depending on the area of the tumour chosen, immunohistochemical reactivity for Ct and Cg A might not be demonstrated in neoplastic C-cells, while staining for Sg IV was retained. The amount and type of Sg IV reactivity of MTCs was not correlated with the biological behaviour of the tumours. These results indicate that mAb Hisl-19 is an excellent marker for normal, hyperplastic and neoplastic C-cells. MAb Hisl-19 is especially useful in cases with weak or questionable reactivity for Ct and Cg A. The switch from the granular pattern to the perinuclear distribution seems to indicate a malignant transformation of C-cells and might prove useful an an additional diagnostic clue.

Antibodies, Monoclonal↗

Serum-soluble CD4 as clinical and immunological marker in patients with dilated cardiomyopathy.

Serological markers of cell-mediated immunity, i.e., soluble CD4, soluble interleukin-2 (Il-2) receptor and beta 2-microglobulin, were determined in 60 patients with dilated cardiomyopathy. Compared with normal healthy donors (n = 30) and controls who had coronary artery disease with preserved left ventricular function (n = 20), significantly increased levels associated with the New York Heart Association functional classes have been found in the cardiomyopathy patients, irrespectively of the etiology. Out of the immunological variables tested, serum-soluble CD4 most closely reflected the clinical and hemodynamic stage, predicted the presence of lymphocytic aggregates in the myocardium and correlated with the CD4/CD8 ratios of endomyocardial lymphocytes (r = 0.6, P < 0.05). Conversely, focal mononuclear infiltration of the myocardium was associated with significantly elevated CD4/CD8 ratios (2.1 +/- 0.6 vs. 1.3 +/- 0.2, P < 0.05), higher total numbers and percentages of endomyocardial lymphocytes expressing the pan T-markers CD2 and CD3, more CD45RO/UCHL1-positive cells and more CD4-positive T-helper cells, compared with non-reactive cases the lymphocytes of which were scattered throughout the myocardium. In conclusion, in a subset of cardiomyopathy patients lymphocytic clusters in the myocardium indicated an enhanced cellular immune response predominantly mediated by CD4-positive T-helper lymphocytes with active memory function. This immunopathological condition in the heart can be monitored by serum-soluble CD4.

CD4 Antigens↗

The HIV-1 Nef protein shares an antigenic determinant with a T-cell surface protein.

OBJECTIVE: To characterize antigens on uninfected T lymphocytes reactive with monoclonal antibodies (MAb) directed against the HIV-1 Nef protein, and to search for antibodies directed against this epitope in HIV-1-infected individuals. DESIGN: Murine MAb directed against an epitope of Nef defined by amino acids 60-73 reacted with cell surface antigens of normal peripheral blood lymphocytes and permanent human T-cell lines. METHODS: The specificity of the MAb reaction was investigated by flow cytometry and immunofluorescence. The antigen was precipitated from lysates or uninfected cells using MAb or sera from HIV-1-infected individuals and analysed by Western blot and isoelectrofocusing. RESULTS: An antigen with an apparent relative molecular mass of 137,000 and an isoelectric point of 8.45 was immunoprecipitated with the cross-reactive MAb from uninfected human T cells. Sera from HIV-positive individuals recognizing a Nef epitope partially overlapping with the binding site of the cross-reactive MAb stained the 137 kD protein precipitated with the MAb in Western blot analysis, while HIV-positive sera without antibodies to this Nef region and sera from uninfected individuals were negative. CONCLUSION: The induction of autoantibodies cross-reactive with cellular surface proteins may play a role in the pathogenesis of AIDS.

Amino Acid Sequence↗

Use of varicose veins as arterial bypass grafts.

Varicose veins are not generally used as arterial bypass grafts despite their physiological endothelial flow surface. The large, irregular diameter and the thin wall renders these veins inadequate. Experimental studies have shown that a considerable reduction in the diameter of veins can be achieved by external wrapping without the generation of obstructing folds of the vein wall. A Dacron mesh tube surrounding varicose veins was used as a bypass graft in 13 infrainguinal arterial reconstructions. Ligated larger side branches and connections of the mesh segments caused irregularities of the otherwise smooth flow surfaces. Ten grafts were patent after a mean follow-up of 17 months. Two grafts have remained patent despite severe outflow obstruction in one and proximal occlusion in the other; both underwent successful interventions. The antithrombogenic properties of these grafts were partly due to a marked increase of the vasa vasorum. Externally constricted varicose veins may be used as arterial bypass conduits with good intermediate-term patency.

Aged↗