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Biomedical subjects

F Weber

Publications and source records attributed to F Weber.

At least 181 records · Page 10Linked to original sources
PubMed1994

[Management of indoor air pollution by polychlorinated biphenyl compounds exemplified by two Hagen schools].

An indoor pollution of polychlorinated biphenyls (PCB) of about 4000 ng/m3 could be reduced by an average amount of 68% by temporary sealing of the primary source in combination with intensive cleaning. The costs were around DM 100,000.- for the school building containing 12 classrooms. Due to this procedure a continued usage of the building is possible until a concept of decontamination is available. In another building the PCB indoor pollution was reduced by 73% in a representative trial restoration, whereas the stripping of the paint with a chemical caustic substance induced a significant reduction of the PCB concentration. The usage of special air conditioners--called "Luftwäscher"--in the classrooms did not reduce the PCB concentration. The realisation of disturbing factors such as the fluctuation of the temperature is of great importance for judging the efficiency of decontamination procedures. The possible misinterpretation regarding the results and the data of decontamination procedures can be excluded by parallel measurements in control rooms. Costs induced by these additional analyses will be reduced by the early realization of ineffective steps.

Adolescent↗
PubMed1993

Transformation of human T-cell clones by Herpesvirus saimiri: intact antigen recognition by autonomously growing myelin basic protein-specific T cells.

Herpesvirus saimiri has recently been shown to immortalize human T cells. It was unknown, however, whether Herpesvirus saimiri transformation affects T-cell receptor (TCR) expression and signal transduction. In the present study, we have transformed CD4+ human T-cell clones specific for human myelin basic protein. The transformed T cells were grown in interleukin 2 and divided in the absence of antigen and antigen-presenting cells. They retained the membrane phenotype of activated T cells and secreted the cytokines interferon gamma and lymphotoxin, but interleukin 4 was not detected. Further, the transformed T cells continued to express the original TCR as demonstrated by TCR variable-region-V beta-specific monoclonal antibodies and TCR sequencing. Antigen-specific recognition and signal transduction by the TCR were demonstrated by myelin-basic-protein-induced HLA-DR-restricted secretion of interferon gamma and lymphotoxin and by myelin-basic-protein-specific proliferation. Antigen specificity and reactivity have been maintained for > 1 year after transformation. Transformation with Herpesvirus saimiri now allows the production of virtually unlimited numbers of (auto)antigen-specific T cells expressing functional TCR and a stable membrane phenotype. This technology will facilitate studies of the pathogenesis of putative autoimmune diseases, such as multiple sclerosis, and may be of help in TCR-targeted immunotherapy.

Antigens, CD↗
PubMed1993

Human T cell autoimmunity against myelin basic protein: CD4+ cells recognizing epitopes of the T cell receptor beta chain from a myelin basic protein-specific T cell clone.

We have investigated whether the normal immune system contains T cells that are able to recognize T cell receptor (TcR) determinants of autologous autoantigen-specific T cells. The T cell clone HW.BP3, specific for myelin basic protein (MBP) was isolated from a healthy donor. HW.BP3 is restricted by HLA-DR2a, and reacts to human MBP 139-153. The expressed alpha beta TcR genes of HW.BP3 were cloned and sequenced, and the sequences analyzed for potential T cell epitopes. Two synthetic peptides, one from the VDJ beta junctional (beta 1) and one from the V beta region (beta 2) of the TcR of HW.BP3, were used to select four TcR peptide-specific T cell lines from the donor of HW.BP3. All anti-TcR lines had the phenotype CD3+/CD4+/HLA-DR+/CD25+/CD45RO+, and recognized the antigen in the context of HLA-DR. Three anti-TcR lines, which had been selected for reactivity to peptide beta 1, recognized exclusively this peptide restricted by HLA-DR2b. One anti-TcR line, selected for peptide beta 2, responded to both peptides beta 1 and beta 2 when presented by autologous blood mononuclear cells, but not by HLA-DR2a- or HLA-DR2b-transfected L cells. All TcR peptide-specific T cell lines were efficiently cytotoxic. They specifically lysed autologous macrophages or HW.BP3 line cells in the presence of exogenous peptide antigen. In contrast, HW.BP3 did not present endogenous TcR peptides to the anti-TcR lines. The results demonstrate that the normal human immune system contains not only autoantigen-specific T cells, but also T cells that recognize antigenic determinants of autologous autoreactive TcR.

Amino Acid Sequence↗
PubMed1993

Changes of telomere lengths in human intracranial tumours.

The termini of human chromosomes comprise stretches of G-rich repeats that are about 5-20 kilobase (kb) in length. The size of the telomeres can be determined by hybridization with probes specific for these (ttaggg)n sequences after digestion of chromosomal DNA with appropriate restriction enzymes and electrophoretic separation of the fragments. Here, probing with the 32P-labelled synthetic (TTAGGG)3 oligonucleotide revealed length changes of the telomeres occurring in intracranial tumours. Among 60 samples, analysed, 41.7% showed telomere elongation, and 21.7% telomere reduction, whereas 36.7% of the tumours exhibited equal lengths compared with the patients' peripheral blood leukocytes. Most of the elongated glioma telomeres exceeded in length those of untransformed astrocytes derived from human fetal tissue.

Adolescent↗
PubMed1993

Myelin basic protein-specific T lymphocyte repertoire in multiple sclerosis. Complexity of the response and dominance of nested epitopes due to recruitment of multiple T cell clones.

The human T cell response to the myelin basic protein (MBP) has been studied with respect to T cell receptor (TCR) usage, HLA class II restriction elements, and epitope specificity using a total of 215 long-term MBP-specific T cell lines (TCL) isolated from the peripheral blood of 13 patients with multiple sclerosis (MS) and 10 healthy donors. In most donors, the anti-MBP response was exceedingly heterogeneous. Using a panel of overlapping synthetic peptides spanning the entire length of human MBP, at least 26 epitopes recognized by human TCL could be distinguished. The MBP domain most commonly recognized was sequence 80-105 (31% of MS TCL, and 24% of control TCL). Sequence 29-48 was recognized more frequently by control-derived TCL (24%) than by TCL from MS patients (5%). The MBP epitopes were recognized in the context of DRB1 *0101, DRB5*0101, DRB1*1501, DRB1*0301, DRB1*0401, DRB1*1402, and DRB3*0102, as demonstrated using a panel of DR gene-transfected L cells. The TCR gene usage was also heterogeneous. V beta 5.2, a peptide of which is currently being used in a clinical trial for treatment of MS patients, was expressed by only one of our TCL. However, within this complex pattern of MBP-specific T cell responses, a minority of MS patients were found to exhibit a more restricted response with respect to their TCL epitope specificity. In these patients 75-87% of the TCL responded to a single, patient-specific cluster of immunodominant T cell epitopes located within a small (20-amino acid) domain of MBP. These nested clusters of immunodominant epitopes were noted within the amino acids 80-105, 108-131, and 131-153. The T cell response to the immunodominant epitopes was not monoclonal, but heterogeneous, with respect to fine specificity, TCR usage, and even HLA restriction. In one patient (H.K.), this restricted epitope profile remained stable for > 2 yr. The TCR beta chain sequences of TCL specific for the immunodominant region of HK are consistent with an oligoclonal response against the epitopes of this region (80-105). Further, two pairs of identical sequences were established from TCL generated from this patient at different times (June 1990 and June 1991), suggesting that some TCL specific for the immunodominant region persisted in the peripheral repertoire. The possible role of persistent immunodominant epitope clusters in the pathogenesis of MS remains to be established.

Adult↗
PubMed1993

Tumor infiltrating lymphocytes in malignant brain tumors.

When treated with CD3 moAB (aCD3) (1 microgram/ml) and human natural IL-2 (nIL-2) 1000 U/ml, during the exponential phase of growing: 200 U/ml tumor infiltrating lymphocytes (TIL's) from brain tumors could be expanded. Due to the low percentage of lymphocytes in malignant brain tumor tissue (1%) it was not possible to separate the tumor bearing lymphocytes from the tumor cells by a Ficoll Hypaque gradient separation. This resulted in a co-culture of both lymphocytes and tumor cells in which a serum free medium was used. To generate TIL's at all, it was necessary to supplement this culture medium with 20% of the supernatant of cultures of lymphokine--activated killer cells. In 9 out of 12 cases we obtained total growth factors in the range between 10(4) and 10(14) (average 3.6 x 10(7)). These growth were reached after 6 to 13 weeks including up to 3 weeks of an initial lag period during which no cell growth was observed. We noted a decrease in CD8+ cells, whereby the predominant cell type at the end of the cultures was CD3+ and CD4+. The levels of their cytotoxic activities against K-562 and Raji cells were low in contrast to those of CD3 and nIL-2 stimulated cells which were obtained from carcinomas.

Adult↗
PubMed1993

Ultrasonography in the initial evaluation and follow-up of blunt abdominal injury.

BACKGROUND: Ultrasonography has been routinely performed in the assessment of blunt abdominal injury at our department of surgery since 1980. To establish its reliability, a retrospective study was carried out on 818 consecutive patients in the years 1980 to 1990. METHODS: Seven hundred twenty six patients underwent real-time ultrasonographic examination of the abdomen. Indication for ultrasonography included all cases evaluated for blunt abdominal trauma. Ninety two patients before 1985 were excluded. RESULTS: Two hundred seventy (37.2%) patients underwent laparotomy, 252 patients (34.7%) because of ultrasonographic diagnosis. Celiotomy was nontherapeutic in 28 patients; 26 of these patients had positive findings from ultrasonography (false positive, 3.6%). Eighteen patients with negative findings from ultrasonography also underwent laparotomy, which was nontherapeutic in two patients (false negative, 2.2%). Four hundred fifty six patients (62.8%) were managed without operation, relying on initial and follow-up ultrasonography, which was negative in 386 (53.2%) and positive in 70 patients (9.6%). The accuracy of ultrasonography was 94.2%, with 91.9% sensitivity, 96.0% specificity, and 94.9% predictive value. The rate of delayed recognition of documented visceral injury was 5.1%, but no false-negative findings from ultrasonography were noted among these patients. CONCLUSIONS: Ultrasonography has proved to be a thoroughly reliable, cost efficient, and noninvasive modality in primary evaluation and follow-up of blunt abdominal trauma.

Abdominal Injuries↗
PubMed1992

[Self measurement of blood pressure: automation and management problems].

In the Federal Republic of Germany, the introduction of clinical testing of devices designed for the self-measurement of blood pressure resulted in an improvement of quality of these devices during the last ten years. Further progress seems to be possible by more restrictive administrative prescriptions. Now, electronic devices have the same accuracy as stethoscope devices. They facilitate self-measurement especially in handicapped persons. Devices working by the oscillometric method do not measure blood pressure more accurately than Korotkow devices, but they are a bit less sensitive for wrong placing of the bladder. In most devices automation of the prescribed deflation rate (2 to 3 mmHg/s) was successful.

Blood Pressure Determination↗
PubMed1992

Endothelium-dependent relaxations are augmented in rats chronically treated with the angiotensin-converting enzyme inhibitor enalapril.

The study was designed to evaluate the effects of chronic inhibition of angiotensin-converting enzyme (ACE) on the reactivity of the endothelium and the smooth muscle to vasoconstrictor and vasodilator stimuli in normal rats. Male rats were treated orally for 6 weeks with enalapril (10 mg/kg/day, n = 10) or with placebo (n = 10). Endothelium-dependent relaxations to acetylcholine and adenosine diphosphate were augmented in aortic rings from rats treated with enalapril compared with controls, whereas the response to the endothelium-independent vasodilator SIN-1 were similar. Contractions induced by phenylephrine and angiotensin II remained unchanged. Thus, the results suggest that chronic ACE inhibition enhances the release of relaxing factors from the endothelium in normotensive rats.

Acetylcholine↗
PubMed1991

Noninvasive assessment of coarctation of the aorta: comparative measurements by two-dimensional echocardiography, magnetic resonance, and angiography.

Fifteen patients, aged between 9 and 21 years (mean, 15.1), with native coarctation of the aorta (CoA) or suspected recoarctation after surgical repair, underwent three different diagnostic procedures. Two-dimensional echocardiography (2D echo) and magnetic resonance imaging (MRI) of the thoracic aorta were performed in all patients; 14 patients underwent aortography, and digital subtraction angiography of the aorta was performed in one (after injection via a central venous catheter). Conventional electrocardiographic (ECG) gated MRI was performed, using the sagittal plane, a 256 x 256 acquisition matrix, multi-slice technique and a slice thickness of 10 mm. Diameters at the coarctation site were determined by all methods. Additional diameters of the descending aorta and the aortic arch were measured by MRI and echocardiography, respectively. All noninvasively obtained diameters were compared with angiographic data. Ultrasound imaging of the aortic isthmus was achieved in seven of 15 patients and of the aortic arch in nine of 15. The mean difference compared with angiographically determined diameters was 1.7 (0-7) mm, being greater for the coarctation site [mean, 2.2 (0-4)]. MRI images of the aortic isthmus were obtained in all patients, but the difference to angiographically determined diameters was slightly higher [mean, 3.2 mm (0-8)] than the ultrasound results. This deviation was presumably due to technical conditions, such as slice thickness and orthogonal imaging planes. Including all diameters, the correlation to invasive measurements was r = 0.82 (SEM = 3.1) for MRI and r = 0.89 (SEM = 2.3) for echo recordings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗