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Biomedical subjects

K H Frank

Publications and source records attributed to K H Frank.

At least 19 recordsLinked to original sources
PubMed2000

Association of the TNFa13 microsatellite with systemic sclerosis in Japanese patients.

OBJECTIVES: To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by comparing the allele distribution among populations with different HLA susceptibility genes in SSc. METHODS: TNFa and TNFb microsatellite polymorphisms were determined by PCR in 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR genotyping was carried out by PCR-SSCP. RESULTS: The frequency of TNFa13 was significantly increased in Japanese SSc (p=0. 011, OR=8.53, 95% confidence intervals (95%CI)=2.46, 32.51, and p<1. 0 x 10E-5, OR=10.35, 95%CI=4.88, 22.09) and SSc with antitopoisomerase I antibody (a-Scl-70) (p=0.021, OR=33.25, 95%CI=3. 39, 800.76, and p<1.0 x 10E-5, OR=24.42, 95%CI=8.40, 72.83), compared with the German patient group and German controls, respectively. This increase was not only attributable to a higher prevalence of TNFa13 in Japanese compared with Germans (p=0.005, OR=3.55, 95%CI=1.60, 7.85) but was also caused by an increase in SSc, especially in the a-Scl-70 positive patients (p=0.028, OR=6.88, 95%CI=1.16, 22.60) compared with Japanese controls. TNFa13 was positively in linkage disequilibrium with HLA-DRB1*1502 (LD=0.053, t=2.69). Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13 were significantly increased and prevalences of TNFa2, and 7 were significantly decreased in Japanese controls as compared with German controls. CONCLUSION: TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese patients. Various differences in the prevalences of TNFa alleles between Japanese and German controls were established.

Adult↗
PubMed2000

Neuropsychiatric symptoms in active construction painters with chronic solvent exposure.

A cross-sectional study was performed to assess whether chronic solvent exposure of painters is associated with increased neuropsychologic symptoms. 401 painters and 209 construction workers without solvent exposure, both groups with at least 10 years of employment, were subjected to extensive clinical examinations. Standardized questionnaires were used for medical and occupational history. Painters reported an excess of specific symptoms that could be assigned to mood and behaviour. The differences between specific and unspecific questionnaire outcomes as well as the positive correlation between chronic exposure index and symptom scores support the hypothesis of solvent induced effects. These symptoms are related to life-long solvent exposure rather than current exposure levels. At present the questions of time course and reversibility or irreversibility of symptoms cannot be answered. The predictive value of these symptoms for subsequent neuropsychiatric morbidity remains to be elucidated in a future follow-up study.

Adult↗
PubMed1999

A multidisciplinary cross-sectional study on solvent-related health effects in painters compared with construction workers.

OBJECTIVES: The main aim of the study was to examine possible solvent-associated effects on the nervous system in currently employed painters. Special attention was paid to evaluate subtle health effects. MATERIALS AND METHODS: A total of 401 painters and 209 construction workers without solvent exposure with at least 10 years of professional experience were subjected to a clinical, neurological, psychiatric, neuropsychological and neurophysiological examination. For personal medical and occupational history, standardized questionnaires were used. A quantitative rating of exposure was obtained by expert rating of the respective occupational history without knowledge of the individual test results. RESULTS: There was no excess of somatic disorders or solvent-associated adverse effects on the nervous system. No distinct effects of solvent exposure on nerve conduction velocities (NCV) or cognition were found. Discrete NCV deficits in painters were not considered a sign of subclinical polyneuropathy. Painters, however, reported an excess of specific symptoms that could be assigned to "mood and behaviour". The differences between specific and non-specific questionnaire outcomes on the one hand and the positive correlation between chronic exposure index and symptom scores on the other hand support the hypothesis of solvent-induced effects. Because data is lacking on past solvent exposure, it is not possible to relate these effects to current exposure limits. CONCLUSIONS: Currently employed painters differ from controls not exposed to solvents with respect to the frequency of certain symptoms in mood and behaviour. These symptoms are related to life-long solvent exposure rather than to current exposure. At present, the issue of time course and reversibility or irreversibility of these symptoms cannot be answered. The predictive value for subsequent neuropsychiatric morbidity remains to be elucidated in follow-up studies.

Construction Materials↗
PubMed1999

Th2 cells as effectors in postirradiation pulmonary damage preceding fibrosis in the rat.

PURPOSE: Radiation-induced pneumonitis and subsequent pulmonary fibrosis are important dose-limiting complications of radiotherapy. Their pathogenesis is known only in part. T-lymphocytes comprise a significant part of the infiltrating cells but little is known about their role. The aim of this study was to define the function of T-lymphocytes during development of postirradiation pneumonitis and pulmonary fibrosis. MATERIALS AND METHODS: Rats received a unilateral lung irradiation of 20 Gy. Kinetics of T-lymphocytes isolated from irradiated and non-irradiated lungs were analysed. Subsequent CD4 depletion experiments were performed to affirm the importance of CD4+ T-cells in the development of lung fibrosis. Finally, the T helper-cell subtype of the T-lymphocytes was analysed by determining the cytokine mRNA by RT-PCR. RESULTS: A selective increase of CD4+ T-cells was observed peaking 4 weeks after irradiation in the irradiated lungs. When rats were depleted of these cells, the postirradiation thickening of parenchyma was significantly reduced as determined by morphometric analysis of lung tissue sections. In addition, it was found that IL-4 mRNA was selectively increased in the CD4+ T-cells isolated from irradiated lungs, which indicates a lymphocyte reactivity dominated by Th2 cells. CONCLUSION: The results suggest a critical role for Th2 CD4+ T-lymphocytes in the pathogenesis of radiation-induced pneumonitis preceding lung fibrosis.

Animals↗
PubMed1998

Different distribution of HLA class II and tumor necrosis factor alleles (TNF-308.2, TNFa2 microsatellite) in anti-topoisomerase I responders among scleroderma patients with and without exposure to quartz/metal dust.

OBJECTIVE: To investigate the influence of quartz/ metal dust exposure on the pathogenesis of systemic sclerosis (SSc; scleroderma), by an immunogenetic comparison of HLA class II and tumor necrosis factor (TNF) alleles in patients with and without exposure. METHODS: A retrospective study of 30 SSc patients exposed to quartz/metal dust (qSSc) and 50 patients with idiopathic SSc (iSSc) was conducted by DNA-based typing of HLA, TNF-308, and TNFa/b microsatellite alleles. RESULTS: A neutral or protective haplotype in iSSc anti-topoisomerase I (anti-topo I) responders was found to be a susceptibility haplotype in qSSc patients. HLA-DRB1*0301 (DR3), a component of the extended haplotype HLA-DQA1*0501;B1*0201;DRB1*0301; TNF-308.2;TNFa2/b3, had a decreased frequency in iSSc anti-topo I responders compared with non-responders (P = 0.03, odds ratio [OR] 0.11, 95% confidence interval [95% CI] 0.00-0.95), but a significantly increased frequency in qSSc anti-topo I responders compared with controls and with iSSc anti-topo I responders (P = 0.00004, Pcorr = 0.006, OR 11.38, 95% CI 3.17-44.35 and P = 0.0002, Pcorr = 0.02, OR 30.0, 95% CI 2.05-986, respectively). In contrast, DRB1*1104 (DR5) and DRB1*11/15 (DR5/DR2) with no TNF-308.2 and TNFa2 alleles were prevalent in only the iSSc anti-topo I responders compared with controls (P = 0.0005, Pcorr = 0.04, OR 11.0; 95% CI 2.68-45.93 and P = 0.0002, Pcorr = 0.02, OR 12.43, 95% CI 3.65-40.04, respectively). CONCLUSION: The mechanisms that lead to the development of anti-topo I in qSSc and iSSc patients are suggested to be distinct, although it is not clear that the two diseases themselves are different.

Autoantibodies↗
PubMed1998

TNFa and b microsatellites in Germany.

Allele frequencies of TNFa and TNFb microsatellites were determined from 315 healthy unrelated Germans (mothers and putative fathers) by means of PCR. They were stably inherited and segregated in a Mendelian way. New mutations were not observed.

Alleles↗
PubMed1998

The pathogenic 16/6 idiotype in patients with silica associated systemic lupus erythematosus (SLE) and uranium miners with increased risk for development of SLE.

OBJECTIVE: To investigate the prevalence of the 16/6 idiotype (16/6 Id), a major cross reactive idiotype of anti-DNA antibodies involved in the pathogenesis of experimental lupus, in subjects with an exogenous risk for the development of systemic lupus erythematosus (SLE). METHODS: The titer of 16/6 Id was determined by ELISA in sera of uranium miners exposed to heavy quartz dust: 15 developed definite and 12 probable SLE, 34 had clinical symptoms, and 27 had only serological signs (medium to high titer anti-dsDNA antibodies) of possible connective tissue disease (CTD) development. RESULTS: The prevalence of 16/6 Id was higher in all groups compared to healthy blood donors. It was 18.5% in miners with SLE (definite and probable) and 22.2-26.5% in miners with clinical and/or serological signs for developing CTD. All 16/6 Id positive miners were positive for anti-dsDNA antibodies and other autoantibodies associated with CTD. The prevalence of 16/6 Id in anti-dsDNA positive miners correlated slightly with CTD/SLE symptoms: 55.6% in patients with SLE, 47.4% in miners with possible CTD/SLE, and 22.2% in miners without CTD symptoms. Further, at short term followup, disease progressed in 2 miners of the 16/6 Id positive, but not in 16/6 Id negative miners. CONCLUSION: The detection of 16/6 Id in miners exposed to quartz dust may indicate a higher risk for development of SLE, warranting further studies of the role of 16/6 Id in the development of SLE in a cohort with the same sex, ethnicity, geographic region, and occupation.

Aged↗
PubMed1997

Local production of interleukin-4 during radiation-induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4.

Fibrosis of lung tissue is a frequent and serious consequence of radiotherapy of mammary carcinoma. The pathogenesis of radiation-induced pulmonary fibrosis remains unclear. Cytokines such as transforming growth factor beta (TGFbeta) and interleukin-4 (IL-4) have been reported to stimulate collagen synthesis in fibroblasts in vitro. The aim of this study was to document the presence of IL-4 during the development of post-irradiation lung fibrosis. Right lungs of male Fischer rats were irradiated with a single dose of 20 Gy and IL-4 expression in the irradiated lungs was monitored for a period of three months. IL-4 gene transcription as determined by ribonuclease protection assay (RPA) as well as IL-4 synthesis as shown by Western blotting increased in the irradiated lungs reaching a plateau concentration within 3 weeks after irradiation. Enhanced IL-4 production was still detected at day 84 after irradiation. The cellular origin of IL-4 was analyzed by in situ hybridization and two-color immunofluorescence on lung tissue sections and on cytospin preparations of leukocytes obtained from bronchoalveolar lavages. These experiments revealed a substantial IL-4 production by macrophages during development of post-irradiation lung fibrosis.

Animals↗
PubMed1996

Monitoring of flaps by measurement of intracapillary haemoglobin oxygenation with EMPHO II: experimental and clinical study.

OBJECTIVE: To find out whether measurements of intracapillary haemoglobin oxygenation made with the non-invasive Erlangen microlightguide spectrophotometer (EMPHO II) provided accurate data about the oxygen supply as well as the blood flow to free flaps in rats and humans. DESIGN: Experimental, and prospective open clinical study. SETTING: University hospital, Germany. ANIMALS and SUBJECTS: Thirty male Wistar rats and 20 patients who underwent microsurgical transplant of free flaps (radial forearm, n = 8; osteocutaneous fibula, n = 7; and myocutaneous from the lateral thigh, n = 5). INTERVENTIONS: Measurement of the haemoglobin oxygenation of the skin before, during, and after transfer of the flap. MAIN OUTCOME MEASURES: Reproducibility and mean curves for haemoglobin oxygenation and haemoglobin concentration. RESULTS: All values were reproducible, and there were only slight fluctuations. Uninjured skin in rats (baseline value) oxygenation of the total haemoglobin concentration ranged from 15% to 45% (mean 23%). After the flaps were raised there was a slight increase (to a mean of 37%), probably as a result of reactive hyperaemia. There was a rapid decrease within a few minutes of arterial occlusion, and residual oxygenation of up to 20% after perfusion stopped. The flap was totally deoxygenated after 1 h. Venous occlusion caused a similar pattern and all flaps were deoxygenated by 30 min. In the clinical study ligation of the vascular pedicle caused a massive reduction in values but after anastomosis there was significantly higher haemoglobin oxygenation (P = 0.05) and this continued to increase postoperatively. There were no complications and oxygenation gradually and continuously decreased from the base of the flap to the periphery. CONCLUSION: The non-invasive EMPHO II provides reliable and easily assessable data about the circulation and supply of oxygen to a transplanted free flap.

Anastomosis, Surgical↗
PubMed1996

Molecular analysis of HLA-DPB1 alleles in idiopathic systemic sclerosis patients and uranium miners with systemic sclerosis.

According to clinical mainifestation and autoantibody pattern [anti-Scl-70, anti-centromere antibodies (ACAs)], systemic sclerosis is a connective tissue disease with heterogenous subgroups. PCR-sequence-specific-oligonucleotide typing was used to study the genetic association of HLA-DPB1 alleles in 54 patients with idiopathic systemic sclerosis, 26 uranium miners with systemic sclerosis and 70 unrelated healthy control subjects. Systemic sclerosis patients with and without former employment in mines were divided into two subgroups according to their scleroderma-typical autoantibody specificities--anti-Scl-70 positive and ACA positive--and third subgroup comprising the rest. Statistical analysis revealed a significantly increased frequency of DPB1*1301(p=0.0001, corrected p=0.011) in idiopathic anti-Scl-70-positive systemic sclerosis cases when compared with unexposed controls. In the same group, we observed an enhanced frequency of DPB1*0601 and *1701 alleles. Since these three alleles carry the information for a glutamic acid residue in position 69 of DPB1, we tested the association of this residue with anti-Scl-70 expression. A strong association between anti-Scl-70 positivity in idiopathic systemic sclerosis patients and amino acid residue 69 of DPB1 was observed when compared with anti-Scl-70-negative idiopathic systemic sclerosis patients (p=0.0009) or unrelated controls (p=0.0007). ACA expression was not associated with the presence of any DPB1 allele tested. The data show that anti-Scl-70 expression in idiopathic systemic sclerosis patients is linked with DPB1*1301 whereas anti-Scl-70-positive miners do not show such a DPB1 association. Futhermore, the data indicate that glutamate 69 of DPB1 might be involved in the susceptibility to idiopathic anti-Scl-70 expression.

Alleles↗
PubMed1996

Systemic lupus erythematosus after heavy exposure to quartz dust in uranium mines: clinical and serological characteristics.

Epidemiological, clinical and serological data of uranium miners with symptoms of connective tissue diseases (CTD) were collected during the control examinations for occupational lung diseases since 1975. Twenty eight definite (four or more ARA criteria) and 15 probable (2-3 ARA criteria) SLE were diagnosed. The estimated prevalence among heavily silica exposed uranium miners was up to 93 in 100,000. The only significant differences to nonexposed SLE patients were decreased frequency of arthritis and photosensitivity and the absence of anti-Sm and anti-U1-RNP antibodies. ANA were found in all definite SLE patients examined with the following specificities: anti-dsDNA (in 44.4%), & anti-Ro/SSA (in 55.6%, four cases together with anti-dsDNA) and anti-La/SSB (in 22.2%). The autoantibody profiles of patients with probable SLE were similar, but with a lower frequency of ANA, anti-dsDNA and anti-Ro/SSA. Middle to high-titred autoantibodies to dsDNA, Ro/SSA and La/SSB were detected in 3.2% uranium miners with no (N = 1229) and in 20.6% with some symptoms (one ARA criterion and/or two or more of other CTD typical symptoms, N = 68) of CTD development. We conclude, that the strong exposure to dust with a high content of silica may predispose to or initiate the development of SLE. The detection of SLE-typical antibodies in quartz dust-exposed miners may indicate a higher risk for the development of systemic autoimmune disease.

Adult↗
PubMed1995

Measurements of tissue blood flow by the hydrogen clearance technique (HCT): a comparative study including laser Doppler flowmetry (LDF) and the Erlangen micro-lightguide spectrophotometer (EMPHO).

The purpose of this study was to compare the hydrogen clearance technique (HCT) with two different, well-established techniques, i.e., the laser Doppler flowmetry (LDF) and the Erlangen micro-lightguide spectrophotometer (EMPHO), for tissue blood flow measurements in an experimental setting. For the animal experiments, we chose a rat model for arterial and venous flap thrombosis, using the epigastric groin flap. Forty male dark Aguty rats were included in the study. The animals were divided into eight groups, each with a different vascular thrombotic model. HCT was used to collect 1,467 measurements, and 2,934 graphs were recorded; 27 measurements (54 graphs) had to be discarded due to faulty electrode placements and electronic noise. In 19 of the 27 discarded measurements the cause of failure was moving of the awaking animal with disruption of the decay signal. The LDF and EMPHO measurements were performed continuously during each measuring phase. Simple and multiple linear regression and paired t-tests were used to compare the three techniques. The reproducibility of registered blood flow values in phases 1, 3, 6 and 7 varied between 7.8% and 13.6% which is in about the same range as LDF and EMPHO. We could not find a significant difference between the three techniques in this regard. The correlation coefficient for HCT and LDF was r = 0.89. For HCT and EMPHO we found r = 0.67. Sensitivity and specificity values for HCT were both 1.0 in detecting arterial and venous flap thrombosis; for LDF we found values of 0.89 and 0.92, respectively. Sensitivity and specificity values for EMPHO were 0.92 and 0.95, respectively. After careful evaluation of three different techniques (HCT, LDF, and EMPHO) for measurements of local tissue blood flow we came to the conclusion that HCT must be favoured as a reliable tool for quantitative measurement of local tissue blood flow and early diagnosis of arterial and venous flap thrombosis.

Animals↗
PubMed1995

Anti-CENP-B response in sera of uranium miners exposed to quartz dust and patients with possible development of systemic sclerosis (scleroderma).

OBJECTIVE: To look for anti-CENP-B antibodies and their diagnostic relevance in patients negative and positive for anticentromere antibodies (ACA) with different risk for the development of systemic sclerosis (SSc), including uranium miners exposed to quartz dust. METHODS: We studied sera of 107 patients with SSc, 121 patients with possible SSc, 202 uranium miners heavily exposed to quartz dust, 14 patients with vibration induced white fingers, and 240 control patients. Subjects were screened for ACA by indirect immunofluorescence on HEp-2 cells (IIF-ACA) and then for anti-CENP-B autoantibodies by an ELISA using eukaryotically expressed human full length recombinant CENP-B protein. RESULTS: All IIF-ACA positive sera of "idiopathic" SSc (N = 19), "idiopathic possible" SSc (N = 6) and other patients (N = 11), and 17 of 19 IIF-ACA positive sera of miners exposed to silica with (N = 13) and without (N = 6) symptoms of SSc reacted with CENP-B in this assay. Of the 622 IIF-ACA negative sera, 28 were found positive for anti-CENP-B. There was a significant increase of the prevalence of anti-CENP-B antibodies in IIF-ACA negative patients with possible SSc (11 of 109) and in miners exposed to silica (11 of 196) compared to a group of men older than 60 years with diseases or symptoms not related to SSc (1 of 138). CONCLUSION: (1) CENP-B is also the major target of the IIF-ACA response in diseases other than scleroderma and in the risk group of miners exposed to quartz dust. (2) Anti-CENP-B antibodies can be found in IIF-ACA-negative sera, particularly in those at risk for SSc. (3) The detection of anti-CENP-B antibodies in miners exposed to quartz dust may indicate a high risk group for developing SSc and reveals possibilities for the study of early pathogenetic changes as well as exogenic and endogenic factors involved in the development of this disease.

Autoantibodies↗
PubMed1993

Amino acid sequence of the region of beta 2-glycoprotein 1 (gp1) which mediates binding of autoantibodies to the cardiolipin-gp1 complex in humans.

Anticardiolipin antibodies (ACA) in sera from patients with autoimmune and infectious diseases were tested for binding to beta 2-glycoprotein 1 (gp1) in order to determine whether human gp1 acts as a cofactor for the binding of ACA to cardiolipin (CL) or as an antigen recognized by ACA. While none of the ACA-positive sera tested recognized gp1 by itself, gp1 was necessary for the binding of ACA to CL in sera from four patients with autoimmune diseases. In three of the four sera the presence of lupus anticoagulant (LA) was detected by prolonged partial thromboplastin time (PTT). Examinations using the bovine equivalent of human gp1 contained in fetal calf serum (FCS) and adult bovine serum (ABS) showed that the human protein can be replaced by the bovine equivalent in the enzyme-linked immunosorbent assay (ELISA). Using affinity-purified antibodies directed against the CL-gp1 complex it was shown that the binding of these antibodies is dependent on the concentration of the bovine gp1 equivalent contained in the formed complex. Similar results found with the human gp1 confirmed this assertion. In order to find out which region of gp1 might mediate the binding between ACA and cardiolipin, we examined to what extent selected oligopeptide sequences of gp1 can substitute for the protein. Peptide P2 (representing the amino acids at positions 268-278 of the gp1 molecule) and gp1 showed about the same binding capacity. Histidine in this peptide seems to be essential for the binding to CL as we found decreased binding with peptides modified in this position. Conclusions from this work show that gp1 does not act as a relevant antigen for ACA, but occupies an essential function in the complex formed with cardiolipin for a certain group of ACA.

Amino Acid Sequence↗
PubMed1992

[Salvaging a mass grave from 1945--Lieberose Labor Camp of the Sachsenhausen concentration camp].

It is reported about a recovering a common grave of 577 skeletons from 1945. Investigations of the age of the victims, the cause of death etc. were carried out. There were gunshot fractures at 541 skeletons. In 93.7% out of all cases there were gunshot fractures of the skull and the cervical vertebra. Difficulties arose from root interpretations in addition to intertwinings owing to the location of the skeletons. Indications to belonging to nationality of the victims are discussed by means the results from AB0-analysis and denture works.

Burial↗
PubMed1991

[Sialic acid--an acute phase reactant and a concomitant of tumors].

Sialic acid is an acute phase reagent with tumour burden reflecting fluctuations of serum level. The parameter is unsuitable for an early recognition of cancer. Sialic acid could be used as a parameter in questions concerning tumour burden: the diagnosis of tumour stage, the control of growth after therapy, the prediction of recidivation. The small specificity of an increased serum level of sialic acid will presumably be only of little use in tumour diagnostics.

Biomarkers, Tumor↗