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H Huber

Publications and source records attributed to H Huber.

At least 55 records · Page 3Linked to original sources
PubMed2000

Ignicoccus gen. nov., a novel genus of hyperthermophilic, chemolithoautotrophic Archaea, represented by two new species, Ignicoccus islandicus sp nov and Ignicoccus pacificus sp nov. and Ignicoccus pacificus sp. nov.

Two species of novel, chemolithoautotrophic, sulfidogenic micro-organisms were isolated from submarine hydrothermal systems in the Atlantic (at the Kolbeinsey Ridge north of Iceland) and in the Pacific (at 9 degrees N, 104 degrees W). The coccoid cells grew within a temperature range of 70-98 degrees C (optimum around 90 degrees C). They gained energy by reduction of elemental sulfur using molecular hydrogen as the electron donor. 165 rDNA-based sequence comparisons revealed that the organisms are members of the crenarchaeal branch of the Archaea. They represent a new, deeply branching lineage within the family of the Desulfurococcaceae. In DNA-DNA hybridization experiments both strains exhibited low levels of hybridization to each other and to further representatives of this family. Therefore, they represent a new genus, for which the name Ignicoccus gen. nov. is proposed. At present it consists of two new species, Ignicoccus islandicus sp. nov. (type strain is Kol8T = DSM 13165T = ATCC 700957T) and Ignicoccus pacificus sp. nov. (type strain is LPC33T = DSM 13166T = ATCC 700958T).

Base Composition↗
PubMed2000

Crystallization and preliminary X-ray analysis of adenylylsulfate reductase from Archaeoglobus fulgidus.

A group of anaerobic microorganisms use sulfate as the terminal electron acceptor for energy conservation. The process of sulfate reduction involves several enzymatic steps. One of them is the conversion of adenylyl sulfate (adenosine-5'-phosphosulfate) to sulfite, catalyzed by adenylylsulfate reductase. This enzyme is composed of a FAD-containing alpha-subunit and a beta-subunit harbouring two [4Fe-4S] clusters. Adenylylsulfate reductase was isolated from Archaeoglobus fulgidus under anaerobic conditions and crystallized using the hanging-drop vapour-diffusion method using PEG 4000 as precipitant. The crystals grew in space group P2(1)2(1)2(1), with unit-cell parameters a = 72.4, b = 113.2, c = 194.0 A. The asymmetric unit probably contains two alphabeta units. The crystals diffract beyond 2 A resolution and are suitable for X-ray structure analysis.

Archaeoglobus fulgidus↗
PubMed2000

Towards the ecology of hyperthermophiles: biotopes, new isolation strategies and novel metabolic properties.

Ecological studies have shown that water-containing terrestrial, subterranean and submarine high-temperature environments harbor a great diversity of hyperthermophilic prokaryotes, growing fastest at temperatures of 80 degrees C or above. The investigations included cultivation, isolation and detailed analysis of these hyperthermophiles as well as in situ 16S rRNA gene sequence analysis and in situ hybridization studies. For a safe and fast isolation of novel hyperthermophiles from mixed cultures, a new, plating-independent isolation technique was developed, based on the use of a laser microscope ('optical tweezers'). This method, combined with 16S rRNA gene sequence analysis and whole-cell hybridization using fluorescently labelled oligonucleotide probes, even allows the recovery of pure cultures of phylogenetically predicted organisms harboring novel 16S rRNA gene sequences. In their natural habitats, hyperthermophiles form complex food webs, consisting of primary producers and consumers of organic material. Their metabolic potential includes various types of aerobic and anaerobic respiration and different modes of fermentation. In hydrothermal and geothermal environments, hyperthermophiles have important ecological functions in biogeochemical processes. Members of the Sulfolobales are able to mobilize heavy metals from sulfidic ores like pyrite or chalcopyrite. Biomineralization processes of hyperthermophiles include the formation of magnetite from iron or the precipitation of arsenate as realgar, a reaction performed by a novel hyperthermophile that was isolated from Pisciarelli Solfatara, Naples, Italy.

Archaea↗
PubMed2000

Predictive role of interphase cytogenetics for survival of patients with multiple myeloma.

PURPOSE: Recent metaphase cytogenetic studies suggested that specific chromosomal abnormalities are of prognostic significance in patients with multiple myeloma (MM). Because the true incidence of chromosomal abnormalities in MM is much higher than that detected by metaphase analysis, we used interphase fluorescence in situ hybridization (FISH) to determine the prognostic value of specific chromosomal aberrations. PATIENTS AND METHODS: Bone marrow plasma cells from 89 previously untreated patients with MM were studied consecutively by FISH to detect the deletions of 13q14, 17p13, and 11q and the presence of t(11;14)(q13;q32). FISH results were analyzed in the context of clinical parameters (response to treatment and survival after conventional-dose chemotherapy), and a multivariate analysis of prognostic factors was performed. RESULTS: By FISH, the deletion of 13q14 occurred in 40 patients (44.9%), deletion of 17p13 in 22 (24.7%), and 11q abnormalities in 14 (15.7%; seven with t(11;14)). Deletions of 13q14 and 17p13 were associated with poor response to induction treatment (46.9% v 77.3% in those without deletions, P =.006 and 40.0% v 73.2%, P =.008, respectively) and short median overall survival (OS) time (24.2 v 88.1 months, P =. 008 and 16.2 v 51.3 months, P =.008, respectively). Short median OS time was also observed for patients with 11q abnormalities (13.1 v 41.6 months, P =.02). According to the number of unfavorable cytogenetic features (deletion of 13q14, deletion of 17p13, and aberrations of 11q) that were present in each patient (0 v 1 v 2 or 3), patients with significantly different OS times could be discriminated from one another (102.4 v 29.6 v 13.9 months, P <.001, respectively). CONCLUSION: For patients with MM who were treated with conventional-dose chemotherapy, interphase FISH for 13q14, 17p13, and 11q provides prognostically relevant information in addition to that provided by standard prognostic factors. This observation may be considered for risk-adapted stratifications of MM patients in future clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The biology of multiple myeloma.

Multiple myeloma (MM) is a B-cell malignancy originating from pre-switched, follicle center B-lymphocytes which differentiate to plasma cells accumulating in the bone marrow. MM cells are characterized by a profound genetic instability resulting in a complex set of numerical and structural chromosomal abnormalities. Among these abnormalities, translocations involving 14q32, the immunoglobulin heavy-chain locus, are the most frequent aberrations, but translocation partners are remarkably heterogeneous. Chromosome 13q14 may harbor a critical tumor suppressor gene since MM patients with deletion of 13q14 experience short overall survival after conventional-dose and high-dose chemotherapy. Bone marrow stroma cells support growth and survival of MM cells, which in turn influence the bone marrow microenvironment. This is particularly evident by the markedly increased bone marrow vascularization observed in most patients with active MM.

Chromosomes, Human, Pair 13↗
PubMed2000

[Clinical value of FDG PET using coincident gamma cameras in staging and restaging of malignant lymphoma--compared with convenitonal diagnostic methods].

UNLABELLED: AIM of the present retrospective study was to validate the clinical value of F-18-FDG PET imaging in lymphoma patients with a dual head camera modified for coincidence detection. Staging before and after oncological treatment was compared with a conservative diagnostic approach. METHODS: 48 patients (28 non-Hodgkin lymphoma, 20 Hodgkin's disease) received FDG-Hybrid-PET scans. Pretherapeutic staging was realized in 28 patients, 9 of them had control studies after they had completed therapy. Totally 29 persons were examined for post-therapeutic restaging. Computed tomography imaging and lymph node sonography was performed in all cases. Results were validated by clinical follow-up, in three cases a recidive was proven by biopsy. RESULTS: CT and ultrasound detected 77 lesions in 28 patients compared with 100 visualized by PET, but this difference in pretherapeutic staging did not reach significance at p > 0.05 by Fisher's t-test. Hybrid-PET obtained a sensitivity of 93%, a specificity of 79%, a positive of 82% and a negative predictive value of 92% for detection of residual disease. The values for CT + US were 87%, 64%, 72% and 88% respectively. CONCLUSION: FDG Hybrid-PET is as or even more accurate than standard morphologic diagnostic methods for prestaging in malignant lymphoma. Additionally, there is a substantial benefit for therapy monitoring of residual disease using coincidence detection PET with a 3/4-inch crystal gamma camera.

Adult↗
PubMed1999

The proteolipid of the A(1)A(0) ATP synthase from Methanococcus jannaschii has six predicted transmembrane helices but only two proton-translocating carboxyl groups.

The proteolipid, a hydrophobic ATPase subunit essential for ion translocation, was purified from membranes of Methanococcus jannaschii by chloroform/methanol extraction and gel chromatography and was studied using molecular and biochemical techniques. Its apparent molecular mass as determined in SDS-polyacrylamide gel electrophoresis varied considerably with the conditions applied. The N-terminal sequence analysis made it possible to define the open reading frame and revealed that the gene is a triplication of the gene present in bacteria. In some of the proteolipids, the N-terminal methionine is excised. Consequently, two forms with molecular masses of 21,316 and 21,183 Da were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The molecular and biochemical data gave clear evidence that the mature proteolipid from M. jannaschii is a triplication of the 8-kDa proteolipid present in bacterial F(1)F(0) ATPases and most archaeal A(1)A(0) ATPases. Moreover, the triplicated form lacks a proton-translocating carboxyl group in the first of three pairs of transmembrane helices. This finding puts in question the current view of the evolution of H(+) ATPases and has important mechanistic consequences for the structure and function of H(+) ATPases in general.

Mass Spectrometry↗
PubMed1999

Expression of c-erbB-4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3.

Nuclear steroid/retinoid and memgbrane c-erbB receptor tyrosine kinase signaling control proliferation and differentiation of mammary epithelial cells. Recently, we reported that retinoic acids are efficient repressors of c-erbB-2 and -3, but not of c-erbB-1 gene expresson. Here we demonstrate that retinoid acid- mediated growth inhibition is accompanied with reduced expression of c-erbB-4/HER4 in T47D breast cancer cells as determined by FACS, Western, and RT-PCR. All-trans and 9-cis retinoic acid reduce c-erbB-4 expression to 30%-60% of control, depending on the concentration. Dexamethasone (Dex) is inactive on D3 (D3), in contrast, acts as a strong inducer, elevation more that twofold at the mRNA, but does not significantly affect cell growth. We concolude that retinoic acids are efficient growth inhibitors and repressors of cell growth and c-erbB-4, whereas D3 represents a highly efficient inducer of c-erbB-4 expression with affecting cell proliferation.

Base Sequence↗
PubMed1999

[Primary lymphoma of the thyroid with contralateral recurrence--case report].

Primary lymphomas located in the thyroid gland are rare clinical findings. The therapy and the subsequent monitoring of the disease continue to be a subject of debate. We present the case of a 63-year-old female patient in whom a hemi-thyroidectomy was performed because of a growing goiter. Histological examination of the excised tissue revealed a large-cell B-lymphocytic lymphoma which extended to neighboring lymph nodes. The patient received chemotherapy which led to remission of disease for two years. The disease re-occurred in the remaining thyroid lobe. Subsequently, the patient was treated with involved-field radiation therapy which lead to long term remission. We conclude that total thyroidectomy should be considered in the treatment of lymphomas located in the thyroid gland.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

The unusual iron sulfur composition of the Acidianus ambivalens succinate dehydrogenase complex.

The succinate dehydrogenase complex of the thermoacidophilic archaeon Acidianus ambivalens was investigated kinetically and by EPR spectroscopy in its most intact form, i.e., membrane bound. Here it is shown that this respiratory complex has an unusual iron-sulfur cluster composition in respect to that of the canonical succinate dehydrogenases known. The spectroscopic studies show that center S3, the succinate responsive [3Fe-4S]1+/0 cluster of succinate dehydrogenases, is not present in membranes prepared from aerobically grown A. ambivalens, nor in partially purified complex fractions. On the other hand, EPR features associated to the remaining centers, clusters S1 ([2Fe-2S]1+/2+) and S2 ([4Fe-4S]2+/1+), could be observed. Similar findings were made in other archaea, namely Acidianus infernus and Sulfolobus solfataricus. Kinetic investigations showed that the A. ambivalens enzyme is reversible, capable of operating as a fumarate reductase - a required activity if this obligate autotroph performs CO2 fixation via a reductive citric acid cycle. Sequencing of the sdh operon confirmed the spectroscopic data. Center S3 ([3Fe-4S]) is indeed replaced by a second [4Fe-4S] center, by incorporation of an additional cysteine, at the cysteine cluster binding motif (CxxYxxCxxxC-->CxxCxxCxxxC). Genomic analysis shows that genes encoding for succinate dehydrogenases similar to the ones here outlined are also present in bacteria, which may indicate a novel family of succinate/fumarate oxidoreductases, spread among the Archaea and Bacteria domains.

Amino Acid Sequence↗
PubMed1999

Hyperdiploidy and apparent aneusomy in mesothelial cells from non-malignant effusions as detected by fluorescence in situ hybridization (FISH).

Interphase cytogenetics by fluorescence in situ hybridization (FISH) can be used to detect malignant cells characterized by chromosomal aneuploidy. However, apparent aneusomy in normal "control" tissues has to be considered when using FISH as diagnostic tool. In effusions as model tissue exposed to metastasis, the definition of cut-off levels for background aneusomy by FISH was aimed in this study. Using centromeric probes representing chromosomes 7, 8, 11, 12, 17 and 18, extensive chromosome copy number enumeration by single-color FISH analysis was performed in pleural and ascitic effusions derived from 15 patients with various, non-malignant diseases. In all effusions, cells with gain of hybridization signals for several or all chromosomes tested were found (in up to 1.94% of cells). A consistent finding was high grade hyperdiploidy (>4 centromeric signals). Mesothelial elements mainly contributed to hyperdiploidy in effusions, as demonstrated by a combined analysis of FISH and immunocytochemistry with staining for cytokeratin. Dual-color FISH analysis showed that hyperdiploidy was predominantly corresponding to polyploidization; however, there were always minor cell populations classified as aneuploid by dual-color FISH. In conclusion, stringent criteria have to be applied to distinguish malignancy-related aneuploidy from background aneusomy by FISH.

Adult↗
PubMed1999

Advanced non-small-cell lung cancer: adjunctive interferon gamma in induction and maintenance therapy.

PURPOSE: To evaluate the feasibility of interferon gamma (IFNgamma) as an adjunct to chemotherapy in advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 32 patients were recruited and received 25 mg/m2 cisplatin and 100 mg/m2 etoposide on days 8, 10 and 12 every 3 weeks for a total of three cycles. A dose of 100 microg IFNgamma was given subcutaneously three times weekly from days 1 to 8 and between days 15 and 29. After induction, all patients except those with progressive disease were offered IFNgamma maintenance therapy: 100 microg three times weekly. RESULTS: The following responses were obtained: partial response, 5 (16%); minor response, 12 (37%); stable disease, 4 (13%); progressive disease, 11 (34%). The survival rates after 1 and 2 years were 47% and 25% respectively. Patients receiving maintenance IFNgamma had a 2-year survival rate of 58%. Toxic side-effects were rare and included grade III/IV fever (7%/1%) and grade III/IV leucopenia (4%/1%). CONCLUSIONS: In patients with advanced NSCLC, an adjunctive dose of 100 microg IFNgamma, given three times weekly in the induction and maintenance phase, is feasible. Survival data seem favourable so this regimen may warrant further investigation in a phase III study.

Adult↗
PubMed1999

The influence of antibody and complement removal with a Ig-Therasorb column in a xenogeneic working heart model.

OBJECTIVE: Organ transplantation is limited by the number of brain-dead human donors. Xenotransplantation could be an alternative to guarantee a constant supply of organs. A major problem of xenotransplantation are xenogeneic natural antibodies (XNAb) directed against species-specific antigens of a discordant donor species (e.g. pig). They trigger the hyperacute xenograft rejection (HXR). Re-usable immunoapheresis (LA)-columns Ig-Therasorb (Therasorb, Baxter) were used to adsorb these XNAb. The effect of immunoapheresis of the perfusing human blood was investigated in ex vivo working pig hearts. METHODS: Hearts of 12 landrace pigs (body weight 14-31 kg) were explanted after inducing cardiac arrest with 4 degrees C Celsior solution. Human blood (500 ml, heparinized) was obtained from healthy volunteers. In group 1 (G1, n = 6), blood as perfusate remained untreated. In group 2 (G2, n = 6), native blood was separated by plasmapheresis into cellular components and plasma. The latter passed through the Ig-Therasorb column for removal of immunoglobulins (so-called immunoadsorption or immunoapheresis). After back-table preparation the hearts were mounted to the working heart model. After 20 min of reperfusion in Langendorff mode, the working heart mode was established. Blood samples were taken isochronously for measurement of: CK(-MB), LDH, ASAT, troponin, immunoglobulins, complement activity, anti-pig antibodies and others. After cessation of the heart, atrial and ventricular tissue samples were taken for histological examinations (light/electron microscopy and immunohistochemistry). RESULTS: Two cycles of immunoapheresis reduced the levels of IgG by 84%, IgM by 83.3% and IgA by 76%. In G2, the antibody immunoadsorption of blood prolonged the duration of the working heart mode significantly to 335+/-37.5 min. In contrast, hearts of group 1 (control) failed after 125+/-31.3 min. Heart rate was significantly different between both groups (G1, 77.3+/-6.1 beats/min; G2, 86.5+/-5.5 beats/min). In G2 cardiac output was 118% and mean coronary flow was 154.6% higher than in G1. CK, LDH and ASAT showed no differences in the two groups. Heart weight increased significantly more in group 1 than in G2. Histological examination indicated specific signs of HXR in G1 after 1.5 h, whereas in G2 only slight unspecific damages were found after 6 h. CONCLUSION: Antibody removal by means of immunoapheresis results in a significantly improved xenogeneic cardiac function. Immunoapheresis may, therefore, become an important adjunct in future pig-to-man clinical xenotransplantation.

Animals↗
PubMed1999

Effects of prolonged cold storage time in xenotransplantation.

BACKGROUND: Ischemia and reperfusion injury after prolonged ischemic time (IT) has a marked influence on hyperacute xenograft rejection (HXR). The aim of the study was to investigate the impact of different cold ischemic times on the HXR of ex vivo "working pig hearts" perfused with human blood. Xenoreactive natural antibodies (XNAb) as the trigger of HXR were reduced by immunoadsorption (IA) using an Ig-Therasorb column. METHODS: Hearts of 24 Landrace pigs (13-31 kg) were harvested after cardioplegia with Celsior-solution and split into 4 groups. In Group C1 (n = 6) the short ischemic time (IT) lasted 48.9+/-10 minutes on the average prior to start of xenoperfusion, in Group I1 IT lasted 4 hours instead. Groups C2 and 12 experienced the same IT as C1 and I1, respectively, but underwent 2 cycles of IA in addition. IA removed immunoglobulins IgG, IgM and IgA from the perfusate. In the working heart mode hemodynamic parameters were measured in defined intervals. Blood samples were collected at the same time to determine myocardial enzymes, immunoglobulins, complement and anti-pig-antibodies. At the end of the study (cardiac arrest) tissue was sampled for histologic examination (light/electron microscopy (LM/EM) and immunohistochemistry). RESULTS: Survival time of the control Group C1 was 125 minutes. IA resulted in an extension of perfusion time to 6.5 hours in C2. Four hours of IT (I1) prolonged the working time of hearts when compared with C1. IA had no additional impact (I2). Heart weight increased significantly in C1 without IA. Cardiac output and coronary flow in C1 were significantly lower when compared with the other 3 groups. IA improved cardiac output (CO) in C2 (vs C1, p < 0.001). Histologic signs of HXR (LM/EM) could be found in C1 in contrast to the other groups. Serologic parameters for myocardial damage were higher in groups with prolonged IT than in groups with short IT. CONCLUSION: Prolonged ischemia and reperfusion injury showed controversial effects in this specific xenogeneic heart transplant model. In contrast to observations in allogeneic transplantation 4 hours of IT showed a beneficial behaviour of the xenografts. Reasons could be either a protective effect of the Celsior solution or changes of the endothelial cell surface (in terms of glycosylation or loss of alpha1-3Gal-epitopes). Tolerance of prolonged IT would allow transportation of xenografts over long distances.

Animals↗
PubMed1999

Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c-erbB and retinoic acid receptor expression in MCF-7 breast cancer cells.

Nuclear steroid/thyroid/retinoid receptors and c-erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c-erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross-connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c-erbB-2, and between ER and retinoic acid receptor(RAR)-alpha have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12-O-tetradecanoylphorbol-13-acetate, TPA), on growth and expression of c-erbB and RARs in MCF-7 breast cancer cells, which contain high levels of RAR-alpha and -gamma, and which express significant amounts of c-erbB-2 and -3. All trans-retinoic acid (tRA), the anti-estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17beta-estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c-erbB-2 and -3, whereas tamoxifen, Forsk and TPA up-regulated c-erbB-2. c-erbB-3 was co-regulated with c-erbB-2. Northern analysis demonstrated that RAR-alpha was down-regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up-regulated RAR-alpha. RAR-gamma expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c-erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.

Blotting, Northern↗
PubMed1999

Treatment of small cell lung cancer patients.

Small cell lung cancers, comprising approximately 20% of lung cancers, are rapidly growing and disseminating carcinomas which are initially chemosensitive but acquire drug resistance during the course of disease. Thus, outcome is poor with median survival of 10-16 months for patients with limited and 7-11 months for patients with extensive disease. Polychemotherapy with established drugs (platins, etoposide, anthracyclines, cyclophosphamide, ifosfamide and Vinca alkaloids) plays the major role in the treatment of this disease and results in overall response rates between 80%-95% for limited disease and 60%-80% for extensive disease. Dose-intensified chemotherapy and high-dose chemotherapy with peripheral blood progenitor cell support were tested in several trials but their exact impact on outcome remains to be determined. New drugs including the taxanes (paclitaxel, docetaxel), the topoisomerase I inhibitors (topotecan, irinotecan), vinorelbine and gemcitabine are currently evaluated in clinical trials. In limited disease, thoracic radiotherapy improves survival and prophylactic cranial irradiation should be administered to those with a reasonable chance of cure.

Antineoplastic Agents↗
PubMed1999

[Short-term follow-up of a series of 21 uncemented total ankle prostheses].

GOALS OF THE STUDY: To analyse the short term results of 21 non cemented meniscal-bearing total ankle arthroplasties. MATERIAL AND METHODS: [corrected] 21 ankle arthroplaties were performed in 21 patients with a mean age of 63.5 years. Diagnoses include primary and post-traumatic osteoarthritis. Our mean follow-up is 21 months. RESULTS: We evaluated the patients with the Koefod ankle score. We present only the results of the patients whose follow-up exceed one year. Eleven patients had an excellent result, seven a good and two a medium result. One case was a failure and needed an arthrodesus. DISCUSSION: The non-cemented meniscal-bearing ankle prosthesis leads to good relieve of pain and good function but fair improvement of the mobility. These first results are encouraging but definitive conclusions cannot be drawn yet.

Adult↗