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Biomedical subjects

H Huber

Publications and source records attributed to H Huber.

At least 145 records · Page 8Linked to original sources

Interleukin-6 in multiple myeloma: correlation with disease activity and Ki-67 proliferation index.

Interleukin-6 (IL-6) is supposed to be a growth factor in multiple myeloma (MM). Applying a bioassay and a modified ELISA, we measured serum IL-6 values in 64 patients with overt MM, seven patients with smouldering myeloma (SMM), 57 patients with monoclonal gammopathy of undetermined significance (MGUS) and 40 healthy volunteers as controls. IL-6 failed to discriminate between MGUS and MM, stage I, whereas comparison of MM, stage I and stage II/III (p = 0.0143), or comparison of stable disease/remission and progressive disease (p < 0.0001) revealed significant differences. Furthermore, we found significantly higher IL-6 values in overt MM compared to SMM (p = 0.0018). Using a Ki67/CD38 immunohistological double staining method we found a significant correlation between proliferation of bone marrow myeloma cells and serum IL-6 values in 15 patients (p = 0.005). These data demonstrate that IL-6 is a parameter of disease activity in MM and, beside its role in tumor biology, may become a valuable supplement to the established risk factors when selecting patients with unfavourable clinical course for more aggressive treatment modalities.

Biological Assay↗

[The wrist joint in chronic polyarthritis--a new classification based on the type of destruction in relation to the natural course and the consequences for surgical therapy].

Existing classifications of rheumatoid wrist involvement are based on the degree or stage of destruction of the wrist. We suggest to classify rheumatoid wrist involvement according to the type rather than the extent of destruction. In order to recognize the nature of wrist destruction at an early stage of the disease as well as in late stages, a continuous series of 63 patients with definitive rheumatoid arthritis for over 20 years and wrist involvement of more than ten years were analysed both clinically and radiologically. Based on radiological appearance of the late stage, three different types of wrist involvement can be recognized: Group I--Type I: rheumatoid arthritis--ankylosis Group II--Type II: rheumatoid arthritis--(secondary) osteoarthrosis Group III--Type III: rheumatoid arthritis--destabilization Spontaneous ankylosis is characteristic for patients with a juvenile onset of rheumatoid arthritis, however, it also occurs in patients with a later consent of the disease. Patients in group II (type II) demonstrate a tendency to develop secondary arthrosis. Articular surface cartilage loss progresses at a rate which remains in relative equilibrium with processes typical of arthrosis, stabilizing the carpal architecture. In group III (type III), all wrists develop an unstable radiocarpal joint as evidenced by ulnar and palmar subluxation of the carpus relative to the radius and progressive loss of carpal height. When early surgical treatment is considered, it is crucial to recognize patients with type III wrist destruction. For these patients, an osseous stabilizing procedure is essential for long-term stabilization of the wrist. It is important that any evidence of progressive loss of carpal height or of ulnar radiocarpal translocation not be ignored.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

[Bronchial cancer--development, diagnosis, therapy, prognosis].

Lung cancer is the most frequent cause of death from cancer in men. In addition its prevalence among women is currently rapidly increasing. Main risk factors are smoking, exposure to asbestos and genetic factors. Current screening methods do not allow early detection and, hence, lung cancer is usually diagnosed at an advanced stage. The stage of the disease affects survival. In non-small cell lung cancer the probability of 5-year survival for patients is about 43% with stage I, 23% with stage II, 17% with stage IIIA and 2% with stage IIIB disease. Surgery plays a major role in patients with non-small cell lung cancer in stages I, II and maybe IIIA. In small cell lung cancer the probability of 5-year survival is about 10% for patients with limited disease and less than 1% for patients with extended disease. Although surgery plays a role in stage I to stage IIIA, chemotherapy remains the most important mode of therapy in small cell lung cancer. In stages I to IIIA, however, combined treatment modalities might improve outcome of the patients with small cell lung cancer.

Carcinoma, Bronchogenic↗

Voluntary subluxation of the shoulder in children. A long-term follow-up study of 36 shoulders.

We reviewed 25 children who presented consecutively with voluntary (habitual) subluxation of the shoulder. Thirty-six shoulders were involved and symptoms had been present for an average period of 12 years. Eighteen children were managed by 'skillful neglect': all these had become fully active in the profession of their choice and were satisfied with the outcome. Two of them had required shoulder surgery in adult life but only after trauma. Seven children (ten shoulders) had undergone stabilising operations during childhood with the aim of preventing later degenerative arthritis. These patients were also active in their selected professions, but only three (five of the ten shoulders) had good results: two shoulders had recurrent instability, two were painful and one was stiff. None of the shoulders in either group had developed osteoarthritic changes. There was no association with emotional or psychiatric problems. We conclude that voluntary subluxation of the shoulder in children has a favourable prognosis and that there is no indication for surgical intervention during childhood.

Adolescent↗

Adhesion to high endothelial venules: a model for dissemination mechanisms in non-Hodgkin's lymphoma.

The interaction of human lymphoma cells with high endothelial venules (HEVs) on sections of lymphatic tissues was studied in 44 cases of non-Hodgkin's lymphoma (NHL) with the in vitro HEV binding assay. The relative adherence ratio (RAR) of lymphoma cells to HEVs as related to that of reactive lymphocytes was 0.29 to 4.64 in 38 cases of B chronic lymphocytic leukemia (CLL), 1.15 and 1.54 in two cases of immunocytic NHL, 1.12 and 0.70 in two cases of centrocytic NHL, 1.98 in one case of a peripheral T-NHL, whereas plasma cell leukemia cells adhered very weakly (RAR 0.1). Among the patients suffering from CLL a pronounced HEV binding ability of tumor cells correlated significantly with the more unfavorable Binet stages B and C (median 1.32) as well as with a widespread lymphatic dissemination, which strongly indicates a hematogenous, HEV-mediated spread (median 1.34). In contrast, weak adherence to HEVs was associated with Binet stage A (median 0.85; P < .05) and with a lacking or only localized clinical involvement of lymph nodes (median 0.84; P < .01). Thus, specific HEV recognition processes even operate in lymphoid neoplasms and via this mechanism seem to influence the dissemination of tumors.

Cell Adhesion↗

Structure, expression, and phylogenetic relationships of a family of ypt genes encoding small G-proteins in the green alga Volvox carteri.

In addition to the previously described gene yptV1 encoding a small G-protein we have now identified and sequenced four more ras-related ypt genes (yptV2-yptV5) from the green alga Volvox carteri. The four new genes encode polypeptides consisting of 203 to 217 amino-acid residues that contain the typical sequence elements (GTP-binding domains, effector domain) of the ypt/rab subgroup of the Ras superfamily. Comparison of the derived amino-acid sequences from the V. carteri ypt gene products and their Ypt homologs from other species revealed similarity values ranging from 60% to 85%, whereas intraspecies similarities were found to approach only 55%. The coding sequences are interrupted by 5-7 introns of variable size (70-1000 nucleotides) occupying different positions in the genes. Reverse-transcribed samples of stage-specific RNAs were PCR-amplified with primers specific to yptV1, yptV3, yptV4, and yptV5 to determine if yptV transcription might be restricted to either cell type or to a specific stage of the life cycle. These experiments demonstrated that each of these genes is expressed throughout the entire Volvox life cycle and in both the somatic and the reproductive cells of the alga. The transcription start sites of yptV1 and yptV5 were mapped by primer extension. Expression of recombinant yptV cDNA in E. coli yielded recombinant proteins that bound GTP specifically, demonstrating a property which is typical for small G-proteins. The derived YptV polypeptide sequences were used to group them into four distinct classes of Ras-like proteins. These are the first proteins of the Ras superfamily to be identified in a green alga. We discuss the possible role of the YptV-proteins in the intracellular vesicle transport of Volvox.

Amino Acid Sequence↗

Treatment of 11 patients with chronic myelogenous leukemia with interferon-alpha-2C and low-dose cytosine arabinoside.

Patients with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) and on interferon (IFN)-alpha-2c treatment for at least two months were entered in the present pilot study. IFN-alpha treatment was maintained identically and cytosine arabinoside (Ara-C) was added at monthly cycles of 10 mg/m2/day for ten days subcutaneously. In the case of a leukocyte nadir above 10 G/l, the Ara-C dose was increased to 20 mg/m2/day for 10 days per month. Ten of the eleven patients entered in this study were evaluable for toxicity and response. They received a total of 87 IFN-alpha/Ara-C cycles (3-14/patient). Five patients received 1-5 cycles with Ara-C dose intensification to 20 mg/m2/day. The following gastrointestinal and hematological toxicities were attributable to Ara-C, as they had not been observed in these patients during the preceding IFN-alpha monotherapy period. Gastrointestinal side effects consisted of nausea grade 1 (n = 5) and diarrhea grade 2 (n = 1). Hematotoxicity was observed in eight patients, grade 1 in five patients and grades 2, 3 and 4 in one of the patients each. Both episodes of grades 3 and 4 toxicity were seen during dose escalation to 20 mg/m2. Small cytogenetic responses (4-14%) were observed in 3 patients and a larger one (50%) in one patient, hematological improvement or stable disease in an additional three patients. These preliminary data suggest that the combination of IFN-alpha and low-dose Ara-C is active in inducing cytogenetic responses in CML patients at an acceptable rate of toxicity and therefore warrant further investigation.

Adult↗

Flow cytometric detection of cytoplasmic antigens in acute leukemias: implications for lineage assignment.

This study aimed at optimizing the conditions for flow cytometric detection of myeloperoxidase (MPO), cytoplasmic CD3 (cCD3), and cytoplasmic CD22 (cCD22), which seem to be more reliable lineage-associated markers in acute leukemia than surface antigens. Fixation methods employing saponin as detergent resulted in accurate detection of MPO and cCD3, whereas cCD22 was detectable only after buffered-formaldehyde-acetone fixation. MPO was detected in 16/17 AML, but only in 1/6 ALL, the MPO positive ALL being also CD13 positive. MPO was detectable in 3/4 AML with T-lymphoid features; a case of myeloid antigen-positive T-ALL, however, was MPO-negative. cCD3 was expressed only in T-ALL, and five cases of lymphoid antigen-positive AML were cCD3-negative. We suggest that these flow cytometric assays are useful for the lineage assignment of poorly differentiated leukemias and contribute to the identification of truly biphenotypic acute leukemias.

Acute Disease↗

Long-term follow-up of patients with hairy cell leukaemia treated with pentostatin: lymphocyte subpopulations and residual bone marrow infiltration.

Peripheral blood lymphocyte (PBL) subsets and bone marrow biopsies were analysed in six patients with hairy cell leukaemia (HCL) treated with 2'-deoxycoformycin (pentostatin, DCF) according to a phase II trial of the EORTC Leukemia Cooperative Group. All patients responded to DCF with four complete and two partial remissions according to conventional criteria. Within the PBL subsets, major changes concerned the CD4+ T cells, which during DCF therapy were distinctly suppressed to nadir values of 0.038-0.18 (median 0.126) x 10(9)/l. In five patients these cells returned to normal 3.0-49.5 (median 14.5) months after the last DCF injection. CD8+ cells were decreased to a lesser extent, and NK cell numbers improved during treatment. Bone marrow immunohistology applying the MoAb B-ly7 demonstrated residual hairy cells (HCs) in all of the six patients following DCF treatment with nadir HC numbers of 0.2-3.0% of bone marrow cells. Immunoglobulin gene rearrangement analysis of DNA obtained from these biopsies showed only germline bands, whereas rearranged bands had been present on the pretreatment specimens. Within the observation period of 15.5-54.0 (median 47.0) months after discontinuation of DCF therapy, immunohistology demonstrated a continuous increase in HC numbers in five of the six patients with clonal rearrangement detectable in bone marrow specimens from three of these patients at last follow-up date. Although established on the basis of a small number of patients, these data suggest that DCF treatment as currently employed in HCL is unable to eradicate the malignant B cell clone.

Adult↗

Antimicrobial effects of the tetrachlorodecaoxygen-anion complex on oropharyngeal bacterial flora: an in vitro study.

The susceptibility of 276 different strains of bacteria derived from the oropharyngeal flora to the tetrachlorodecaoxygen-anion complex (TCDO) was tested using the agar dilution method. The results showed that at therapeutic concentrations of the drug the growth of all the strains tested was inhibited, with the exception of Candida albicans. The pathogenic anaerobes proved to be particularly sensitive to TCDO.

Bacteria↗

Subpopulations of normal peripheral blood and bone marrow cells express a functional multidrug resistant phenotype.

The multidrug-resistance gene, MDR1 is expressed in many normal tissues, but little is known about its expression in normal hematopoietic cells. Using the monoclonal antibody C219 and flow cytometric analysis, P-glycoprotein (P-gp) was found to be expressed in all peripheral blood (PB) subpopulations (CD4, CD8, CD14, CD19, CD56) except granulocytes. To specifically determine MDR1 gene expression, these PB subpopulations were isolated by fluorescence-activated cell sorting (FACS) and analyzed for MDR1 mRNA by polymerase chain reaction (PCR). All subsets were positive by PCR, but only minimal MDR1 mRNA was detected in monocytes and granulocytes. Significant efflux of Rhodamine-123 (Rh-123), a measure of P-gp function, was detected in CD4+, CD8+, CD14+, CD19+, and CD56+ cells but not in granulocytes. Next, PCR-analysis was performed on FACS-sorted bone marrow (BM) cells to assess MDR1 expression in different maturational stages. Precursors (CD34+), early and late myeloid cells (CD33+/CD34+, CD33+/CD34-) as well as lymphocytes of the B-cell lineage (CD19+/CD10+, CD19+/CD10-) expressed the MDR1 gene. BM monocytic cells (CD33++/CD34-) were negative, and a very weak signal was detected in erythroid cells (glycophorin A+). Significant Rh-123 efflux was found in CD34+, CD10+, CD33+, and CD33++ BM cells, but not in glycophorin A+ cells. We conclude that PB and BM lymphocytes, PB monocytes, BM progenitors, and immature myeloid cells, but not late BM monocytes, erythroid cells, and PB granulocytes, express MDR1 mRNA and a functional P-gp. These results have to be taken into account when MDR1 expression is determined in tumor samples containing normal blood cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The yptV1 gene encodes a small G-protein in the green alga Volvox carteri: gene structure and properties of the gene product.

Small G-proteins encoded by ras-like genes are ubiquitous in eukaryotic cells. These G-proteins are believed to play a role in central processes, such as signal transduction, cell differentiation and membrane vesicle transport. By screening genomic and cDNA libraries of the colonial alga, Volvox carteri f. nagariensis, with ypt DNA probes from Zea mays, we have identified the first member of a ypt gene family, yptV1, within a green alga. The 1538-bp yptV1 gene of V. carteri consists of nine exons and eight introns and has three potential polyadenylation sites 210, 420 and 500 bp downstream from the UGA stop codon. The derived 203-amino-acid polypeptide, YptV1, exhibits 81% similarity with Ypt1 from mouse, with the corresponding genes sharing four identical intron positions. Recombinant YptV1 (reYptV1) produced in Escherichia coli retains the ability to bind GTP after SDS-PAGE and immobilization on nitrocellulose. Immunological studies using polyclonal antibodies against reYptV1 indicate that the protein is present in the membrane fraction of a V. carteri extract and is expressed throughout the whole life-cycle of the alga. Similar to other Ras-like proteins, YptV1 contains two conserved C-terminal cysteine residues suggesting post-translational modification(s), such as isoprenylation or palmitoylation, required for membrane anchoring. The presumptive role of YptV1 in cytoplasmic vesicle transport is briefly discussed.

Amino Acid Sequence↗

Flow cytometric determination of atypical antigen expression in acute leukemia for the study of minimal residual disease.

The aim of this study was to investigate to which extent acute leukemias could be monitored for residual disease by using atypical antigen combinations as leukemia-related markers. Atypical antigenic features were determined by double color flow cytometry and included coexpression of lymphoid and myeloid related antigens, unphysiological coexpression of immature and mature antigens, and lack of an antigen that is normally expressed during maturation. Atypical immunophenotypes were detected in 35 of 68 patients with AML (51.5%) and 15 of 24 patients with ALL (62.5%). When 12 patients with leukemia-associated markers were again analyzed at relapse, the relevant antigen combinations were retained in 11 of them. The sensitivity of this two color flow cytometric assay as determined in dilution experiments was 1 in 10(3) to 10(4) cells. Follow-up studies of bone marrow samples revealed that, after induction chemotherapy cells with leukemia-associated markers were detectable in several patients at a frequency of 0.5 to 4%, but only patients in whom the cells with atypical antigens never disappeared suffered from relapse. In contrast, patients who became negative for the atypical cells remained in complete remission (median remission duration after the first negative bone marrow assessment by flow cytometry 52 weeks, range 20-102). We conclude that atypical antigen combinations, which are present in a meaningful number of acute leukemias, are a valuable means of monitoring acute leukemia patients during follow-up. This flow cytometric approach can complement other strategies to get a more accurate definition of remission in acute leukemia.

Acute Disease↗

Thiobacillus plumbophilus spec. nov., a novel galena and hydrogen oxidizer.

From an uranium mine three strains of rod-shaped, mesophilic, chemolithouautotrophic bacteria were isolated. They grow by oxidation of H2S, galena (PbS) and H2. Angelsite (PbSO4) is formed from galena. No ferrous iron is oxidized by the isolates. They grow between pH 4 and 6.5 at temperatures of about 9 to 41 degrees C (optimum around 27 degrees C). The G + C content of the DNA is around 66 mol %. Based on their ability to oxidize sulfur compounds, the new organisms belong to the genus Thiobacillus. No significant homology with Thiobacillus ferrooxidans and Thiobacillus cuprinus was detected by DNA-DNA hybridization. Therefore the new isolates represent a new species within the genus Thiobacillus. Based on the unusual growth on galena, we name the new species Thiobacillus plumbophilus (type strain Gro7; DSM 6690).

Base Composition↗

Multimodal therapy of small cell lung cancer in TNM stages I through IIIa.

Since 1977, Innsbruck University Hospital has been employing a multimodal therapy concept for small cell bronchial carcinomas in stages I to IIIa. This concept includes all three treatment forms effective in this tumor, namely, chemotherapy, surgery, and radiotherapy. The therapy scheme is stage-dependent and begins in stages T1-3 N0-1 with lung resection and in stage N2 with chemotherapy. To date, 45 patients have been included in a prospective, nonrandomized (phase II) trial: 7 in TNM stage I, 11 in stage II, and 27 in stage IIIa (6 T3 and 21 N2). The actuarial 5-year survival rate of the entire group (including therapy-related lethality, early recurrences, and protocol violations) is 36%; it is 57% for those in stage I, 28% for those in stage II, and 34% for those in stage IIIa. Median survival time is 18 months. Patients with completed multimodal treatment have a 5-year survival rate of 56% regardless of disease stage. Three patients died of tumor-unrelated causes after 47, 52, and 54 months.

Adult↗