Biomedical subjects

U Klueppelberg

Publications and source records attributed to U Klueppelberg.

11 recordsLinked to original sources

PubMed1998

Alleles of the alpha-1-antitrypsin phenotype in patients with aortic aneurysms.

OBJECTIVE: To examine the possible significance of homo- or heterozygous alpha-1-antitrypsin deficiency in the pathogenesis of aortic aneurysms (AA). DESIGN: Prospective investigation. SETTING: University hospital. PATIENTS: 300 controls representing the general population in our region of Southern Germany and 126 patients with aneurysmectomy and graft insertion. METHODS: The alpha-1-antitrypsin phenotype was determined by employing isoelectric focusing. Each patient was also evaluated for hypertension, lipometabolic dysfunction, smoking, hyperuricemia, and diabetes mellitus. MAIN OUTCOME MEASURES: The frequency and distribution of alpha-1-antitrypsin phenotypes and risk factors. RESULTS: 115 of 126 patients presented with one or several of the conventional risk factors: hypertension (61.5%), lipometabolic dysfunction (36.9%), smoking (58.4%), hyperuricemia (13.8%), or diabetes mellitus (6.9%). The following frequencies of alpha-1-antitrypsin phenotypes were determined: PiMM (82.5%), PiMV (4.7%), PiML (1.5%), PiMS (7.1%), PiSS (0.7%), PiMZ (3.0%). Indeed, when compared to the general population (control group) the percentage of the normal PiMM phenotypes was lower in the group of patients with AA (p<0.001). However, in our study this significant difference was not primarily due to the presence of patients homozygous or heterozygous for deficiency alleles PiMS, PiSS and PiMZ (p=0.0523) as has been previously reported, but rather to the high prevalence of the variants PiMV (p<0.005). CONCLUSIONS: Our study suggests that not only Pi-deficiency alleles, previously identified as being associated with AA, but also that Pi variants may play a pivotal role in the pathogenesis of AA.

Adult↗

PubMed1997

On the unique structural organization of the Saccharomyces cerevisiae pyruvate dehydrogenase complex.

Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components attach. We have determined the structures of the truncated 60-mer core dihydrolipoamide acetyltransferase (tE2) of the Saccharomyces cerevisiae pyruvate dehydrogenase complex and complexes of the tE2 core associated with a truncated binding protein (tBP), intact binding protein (BP), and the BP associated with its dihydrolipoamide dehydrogenase (BP.E3). The tE2 core is a pentagonal dodecahedron consisting of 20 cone-shaped trimers interconnected by 30 bridges. Previous studies have given rise to the generally accepted belief that the other components are bound on the outside of the E2 scaffold. However, this investigation shows that the 12 large openings in the tE2 core permit the entrance of tBP, BP, and BP.E3 into a large central cavity where the BP component apparently binds near the tip of the tE2 trimer. The bone-shaped E3 molecule is anchored inside the central cavity through its interaction with BP. One end of E3 has its catalytic site within the surface of the scaffold for interaction with other external catalytic domains. Though tE2 has 60 potential binding sites, it binds only about 30 copies of tBP, 15 of BP, and 12 of BP.E3. Thus, E2 is unusual in that the stoichiometry and arrangement of the tBP, BP, and E3.BP components are determined by the geometric constraints of the underlying scaffold.

Freeze Fracturing↗

PubMed1997

[Is heterozygote alpha 1-antitrypsin deficiency a risk factor in the etiology of aortic aneurysm?].

A potential role of homozygous or heterozygous alpha-1-antitrypsin deficiency alleles Pi*Z or Pi*S in the pathogenesis of aortic aneurysms has been debated in recently published papers. Therefore, we have determined the alpha-1-antitrypsin phenotype in 103 patients with aortic aneurysms using isoelectric focusing. The vast majority of patients (92.2%) had one or more of the established risk factors: hypertension (65.0%), lipometabolic dysfunction (34.9%), smoking (65.0%), hyperuricemia (16.5%) or diabetes mellitus (8.7%). In our patients, the deficiency alleles Pi*Z and Pi*S were more frequent than in the general population of our region, but these differences did not reach statistical significance (PiMS 6.7 versus 3.4%, PiMZ 3.8 versus 2.5%, PiSS 0,9 versus 0.2%). Furthermore, the patients with heterozygous or homozygous antitrypsin deficiency had similar patterns of risk factors to those of the patients with normal phenotypes. In one patient we found a heterozygous PiMZ antitrypsin deficiency associated with Marfan's syndrome. These data do not support the results of recently published studies of fewer cases that suggest a higher prevalence of antitrypsin deficiency alleles in patients with aortic aneurysms. A heterozygous alpha-1-antitrypsin deficiency as a cause or predisposing factor for the development of aortic aneurysms appears to be of little or no importance.

Adult↗

PubMed1995

Gallstone recurrence after direct contact dissolution with methyl tert-butyl ether.

To determine the rate and characteristics of gallstone recurrence after direct contact dissolution with methyl tert-butyl ether, 60 consecutive patients were followed for up to 4.5 years (median 2.2 years) after complete disappearance of all stone residues and debris and cessation of adjuvant bile acid therapy. Initial gallstones had been multiple in all but four patients. Twenty-eight of the 60 patients developed recurrent gallstones. The cumulative risk of gallstone recurrence (actuarial analysis) was 23 +/- 6%, 34 +/- 7%, 55 +/- 8%, and 70 +/- 9% at one, two, three, and four years, respectively. The recurrent stones were usually multiple and small (6 +/- 4 mm). Gallstone recurrence was associated with recurrent biliary pain in two patients, one of whom developed acute cholecystitis. Recurrent stones were cleared completely by bile acid medication with or without shock-wave lithotripsy in 61 +/- 15% of patients at one year (actuarial analysis). In conclusion, gallstone recurrence after successful contact dissolution of multiple stones with methyl tert-butyl ether has to be expected in a high percentage of patients. Most patients, however, remain free of biliary pain during long-term follow-up.

Actuarial Analysis↗

PubMed1994

Gallstone recurrence after shock-wave therapy.

BACKGROUND/AIMS: The long-term outcome of nonoperative gallstone therapy depends on both absence of stones and absence of biliary pain. The aim of the present study was to determine the rate of stone recurrence and the rate of symptoms within 5 years after successful shock wave lithotripsy combined with bile acid therapy. METHODS: One hundred consecutive patients (single stones, n = 89; 2 or 3 stones, n = 11) were followed up for a median of 4.3 years after stone disappearance and discontinuation of bile acids. RESULTS: Twenty-three of the 100 patients developed recurrent stones. Calculated by actuarial analysis, the recurrence rate was 7% +/- 3%, 11% +/- 3%, 13% +/- 4%, 20% +/- 5%, and 31% +/- 7% (mean +/- SD) at 1, 2, 3, 4, and 5 years, respectively. The recurrent stones were small (6 +/- 5 mm) and were associated with recurrent biliary pain in 14 (61%) of the 23 patients. Repeated shock wave lithotripsy and/or bile acid medication resulted in stone disappearance in only 10 of 20 patients with recurrence. CONCLUSIONS: The long-term rate of stone recurrence after lithotripsy of primarily solitary gallbladder calculi is lower than expected from post-bile acid dissolution trials. Recurrence of stones frequently is associated with recurrence of biliary pain.

Adult↗

PubMed1991

Dissolution of bile duct stones by a hydrophilized glyceromonooctanoin-bile-acid-EDTA emulsion.

The clinical suitability of conventional glyceromonooctanoin (GMOC) and ethylenediaminetetraacetic acid (EDTA) containing solvents for the dissolution of common bile duct stones is questionable. To improve the solvent-stone contact and the miscibility with bile, GMOC was hydrophilized by the addition of polyethyleneglycol-caprylglyceride, polyethyleneglycol-sorbitan-etheroleyl-ester, and polyethyleneglycol-sorbitanlauryl-ester (PEG-GMOC). This product was mixed with a bile acid-EDTA (BA-EDTA) solution in a ratio of 1:2 (v/v) for cholesterol solubilizing and calcium complexing capacities. To determine clinical efficiency, the new solvent was infused via a nasobiliary tube in 16 patients with endoscopically nonextractable common bile duct stones and compared with a group of 16 patients treated with an alternating GMOC/BA-EDTA regimen. Continuous perfusion with PEG-GMOC-BA-EDTA led to a total (12 patients) or partial (3 patients) disappearance of the stones within 2-15 days. Similarly, alternating GMOC and BA-EDTA treatment dissolved the stones in 12 patients. The average volume of PEG-GMOC-BA-EDTA infused contained only 27% of the GMOC applied during the alternating therapeutic regime. This reduction of the GMOC dose was associated with a significant reduction of adverse effects such as emesis, diarrhea and biliary pain. We concluded that GMOC is equally efficient in the new hydrophilized form but it is clearly superior as far as side effects are concerned. In all, this supports its clinical suitability for the dissolution treatment of common bile duct stones.

Aged↗

PubMed1987

Analysis of conjugated bile acids in human serum by high-performance liquid chromatography using post-column enzyme reaction and off-line fluorimetric determination.

An assay for glycine and taurine conjugates of cholic (GC, TC), chenodeoxycholic (GCDC, TCDC), deoxycholic (GDC, TDC) and ursodeoxycholic (GUDC, TUDC) acids in human serum by high-performance liquid chromatography using an immobilized 3-alpha-hydroxysteroid dehydrogenase post-column reaction and an off-line spectrofluorimetric detection is described. The detection limit is 0.2 microM. Recoveries of extraction and chromatographic analysis range from 89.50 to 91.68% and from 96.75 to 98.83%, respectively. The analysis in serum reveals a coefficient of variation for reproducibility between 16.2% for GC and 4.7% for TDC; inter-assay variability ranges between 4.06% for TCDC and 8.24% for TUDC.

Bile Acids and Salts↗

PubMedDate not supplied

Clinical correlates of infection with human herpesvirus-6.

Human herpesvirus-6 is a lymphotropic virus which infects susceptible individuals during the first year of life and usually causes life-long latency. In a variable percentage primary infections are followed by a short acute disease, exanthema subitum. Older individuals may suffer from infectious mononucleosis-like illnesses or from Kikuchi-Fujimoto's disease. In addition, there is a fairly wide spectrum of lymphoid and hematopoietic diseases or autoimmune disorders, which are associated with elevated titers of HHV-6 antibody, and from which replicating virus may be isolated. Such diseases include atypical polyclonal lymphoproliferation, Hodgkin's disease, chronic fatigue syndrome and systemic lupus erythematosus. The present article reviews the current knowledge of such associations.

Adolescent↗

PubMedDate not supplied

Semi-quantitative in situ hybridization and immunohistology for antigen expression of human herpesvirus-6 in various lymphoproliferative diseases.

Fifty patients with various hyperplastic and malignant lymphoproliferative diseases were investigated for evidence of human herpesvirus-6 infection. Virus DNA and antigen expression was investigated in lymph node biopsies by in situ hybridization and immunohistology and was correlated with data of immunophenotyping. Supplemental immunoglobulin- and T cell receptor gene rearrangement studies were used to support the classification of the proliferative lymphoid lesion. Elevated numbers of cells carrying HHV-6 DNA and/or antigens were found in cases of Hodgkin's lymphoma and follicular center cell non-Hodgkin's lymphoma as well as atypical polyclonal lymphoproliferation (APL), yet not in reactive lymphoid hyperplasia and in most other lymphomas. Immunophenotyping showed that virus -infected cells were primarily lympho-histiocytic elements, less frequently Hodgkin's- and Reed-Sternberg cells, and not malignant B lymphocytes as in follicular center cell lymphomas. This suggests that the virus is rather not the causative oncogen in these cases, yet does not exclude a cocarcinogenic effect of it during the development and ths course of uncontrolled lymphoproliferation.

Antigens, Viral↗

PubMedDate not supplied

Demonstration of active and latent Epstein-Barr virus and human herpevirus-6 infections in bone marrow cells of patients with myelodysplasia and chronic myeloproliferative diseases.

After previous serological screening for Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV) showed elevated antibody titers against EBV and HHV-6 in more than 50% of patients with myelodysplasia and chronic myeloproliferative diseases, the present study was carried out in order to investigate viral antigen expression and distribution in bone marrow cells of these patients. Trephine biopsies were studied from 60 patients with myelodysplasia (MDS), 36 patients with chronic myelogenous leukemia (CML) and 18 patients with osteomyelofibrosis (PMF). Elevated anti-EBV EA titers were found in 62% of the MDS cases, in 33% of the CMLs and in 62% of the OMF patients. HHV-6 titers were elevated in 18% of the MDS cases, but in only one case each of CML and OMF. Antigen expression in bone marrow cells was even more frequent: EBV-EA was 76% in MDS cases, 77% in CML and 40% in OMF. HHV-6 p41 was observed in 47% of the MDS cases, in 54% of the CML cases and in 20% of the OMFs. In comparing these data with those from the literature and with our own studies in Hodgkin's disease, it is hypothesized that the reactivated herpesviruses may contribute to the pathogenesis of these hematopoietic disorders by interfering with the cytokine regulation of cell proliferation and differentiation.

Antibodies, Viral↗

PubMedDate not supplied

Non-specific interstitial pneumonia (NIP): immunohistologic screening of etiologic agents.

Non-specific interstitial pneumonia (NIP) occurs frequently in patients with HIV-infection. To elucidate the etiology of this pulmonary disorder, we searched for 13 different microorganisms in transbronchial biopsies from 15 patients with NIP, 15 patients with Pneumocystis carinii pneumonia (PCP) and 20 patients with lung diseases not related to HIV-infection using monoclonal antibodies and the APAAP- or PAP-technique for immunostaining. Chlamydia trachomatis and parainfluenza III were detected frequently and in great number. Adenovirus, influenza B, varicella zoster and cytomegalovirus were also found frequently, but not in great number. Measles virus, respiratory syncytial virus, influenza A and herpesviruses 1&2 were not found. Also not found were parainfluenza I, mycoplasma pneumoniae and coronavirus. In seven out of fifteen NIP patients at least one organism was shown, compared to nine out of fifteen patients with PCP and eight out of twenty patients in the control group.

AIDS-Related Opportunistic Infections↗