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Biomedical subjects

H Huber

Publications and source records attributed to H Huber.

At least 181 records · Page 10Linked to original sources

[Nuclear spin tomography in synovitis: experimental and clinical results].

We report our experimental and clinical results in the evaluation of synovitis using magnetic resonance imaging (MRI), and discuss them in the light of the literature. Using rheumatoid arthritis in the rat as a model, we have shown that MRI is more sensitive than physical examination and X-ray for the diagnosis of early soft-tissue inflammation in arthritis. On the basis of MRI findings, in patients with morning stiffness we have found an incidence of tenosynovitis higher than that reported in the literature. Because other groups have demonstrated the usefulness of MRI for the evaluation of inflammatory cartilage and bony lesions in arthritis as well, we anticipate that this method will assume increasing importance in the diagnosis and monitoring of rheumatoid arthritis and related diseases.

Animals↗

Stimulation of colony formation of various human carcinoma cell lines by rhGM-CSF and rhIL-3.

We studied the effects human recombinant granulocyte-macrophage colony-stimulating factor and human recombinant interleukin-3 on the colony formation of three human solid tumor cell lines. Using a modified double-layer soft agar clonogenic assay rhGM-CSF enhanced colony formation of all cell lines tested in a dose dependent manner (up to twofold for the breast cancer cell line BT-20, up to 163% of the control for the hypernephroma cell line C 94 and up to 147% for the non-small cell lung cancer cell line CCL 185 at a concentration of 100 ng/ml). RhIL-3 stimulated colony formation of the cell lines C 94 and BT-20, whereas on the cell line CCL 185 rhIL-3 had no effect even at the highest dose level tested (100 ng/ml). Combinations of growth factors showed subadditive stimulation on two cell lines tested (BT-20, C 94). These data indicate that haematopoietic growth factors exert a growth promoting activity on certain solid tumor cells in vitro at physiological concentrations. Therefore our results suggest that the application of these factors in immuno- and myelosuppressed cancer patients after high dose chemotherapy should be seen in light of a possible co-stimulation of the malignant cells.

Agar↗

Value of urinary neopterin in the differential diagnosis of bacterial and viral infections.

Neopterin is released by stimulated macrophages. In this study we analyzed the diagnostic potential of urinary neopterin concentrations in patients with bacterial and viral infection. All but one of 17 patients with viral infection had increased urinary neopterin concentrations. Patients with bacterial urinary tract infection also showed increased neopterin concentrations, whereas patients with bacterial pneumonia had significantly lower neopterin levels. In addition, patients with acute bacterial pneumonia had lower neopterin levels than patients with protracted infection. A significant inverse correlation between urinary neopterin and hemoglobin concentrations was found. Neopterin concentrations could serve as a helpful additional marker of infectious diseases. Combined with other clinical and laboratory parameters it is a useful parameter for distinguishing between viral and bacterial origins of infection, as was shown by multivariate stepwise linear discriminant analysis.

Adult↗

Operation for N2 small cell lung carcinoma.

Of 48 patients with limited small cell lung carcinoma treated by different modes, but always including radical operation, a series of 25 patients with N2 lymph node metastases is reported. In a first period (1970 to 1977) treatment consisted solely of radical resection in 3 patients; chemotherapy was added to operation in 6, and local radiotherapy was added in 2. Since 1977, 14 patients were treated according to a comprehensive therapy protocol including radical resection (six pneumonectomies, one bilobectomy, seven lobectomies), chemotherapy, local radiotherapy, and prophylactic cranial irradiation. Eleven patients, in whom N2 disease was confirmed preoperatively, received chemotherapy as the first step, followed by "adjuvant" resection. Projected 5-year survival rate is 25% for the entire N2 group and 47% for the comprehensively treated group. Seven patients of this latter group are alive 12, 19, 30, 48, 66, 73, and 74 months after comprehensive therapy, equivalent to an observed 2-year survival rate of 38%. This is the largest reported series of patients with resected small cell lung carcinoma in the N2 stage treated at a single institution; the results are so encouraging that we can no longer advocate general refusal of radical lung resection for small cell lung carcinoma in the N2 stage if it is part of a multimodal therapeutic protocol.

Adult↗

Structural chromosomal abnormalities in gynecologic malignancies.

Surgical specimens taken from four patients with gynecologic malignancies were cultured, and metaphase chromosomes were prepared after staining with chromamycin-A, distamycin, and DAPI. Four specially selected karyotypes and their structural aberrations are discussed in this study and compared with those (also from carcinomas) previously described in the literature.

Adenocarcinoma↗

Correlation between neopterin, interferon-gamma and haemoglobin in patients with haematological disorders.

In this study, we further investigated a possible link between activation of cell-mediated immunity and anaemia in patients with haematological neoplasias. We compared serum concentrations of interferon-gamma and neopterin with haemoglobin levels. Significantly increased interferon-gamma and neopterin concentrations indicated persistent activation of cell-mediated immunity. Neopterin levels correlated significantly to interferon-gamma concentrations and inversely to haemoglobin levels. The data indicate an association between activated macrophages and the development of anaemia in patients with haematological neoplasias.

Adult↗

Thiobacillus cuprinus sp. nov., a Novel Facultatively Organotrophic Metal-Mobilizing Bacterium.

Five strains of mesophilic, facultatively organotrophic, ore-leaching eubacteria were isolated from solfatara fields in Iceland and a uranium mine in the Federal Republic of Germany. The new organisms are aerobic gram-negative rods. They can use sulfidic ores or elemental sulfur as sole energy source, indicating that they belong to the genus Thiobacillus. Alternatively, they grow on organic substrates such as yeast extract, peptone, and pyruvate. In contrast to the other leaching bacteria known so far, the new isolates are unable to oxidize ferrous iron. They consist of extreme and moderate acidophiles growing optimally at pH 3 and 4, respectively. The extreme acidophiles showed leaching characteristics similar to those shown by Thiobacillus ferrooxidans, while the moderate acidophiles exhibited a pronounced preference for copper leaching on some chalcopyrite ores. The G+C content of the DNA is between 66 and 69 mol%, depending on the isolate. In DNA-DNA hybridization experiments, the new strains showed homologies among each other of >70%, indicating that they belong to the same species. No significant DNA homology to Thiobacillus reference strains was detectable. Therefore, the new isolates represent a new species of Thiobacillus, which we name Thiobacillus cuprinus. Isolate Hö5 is designated as the type strain (DSM 5495).

Journal Article↗

Thiobacillus ferrooxidans, a facultative hydrogen oxidizer.

The type strain (ATCC 23270) and two other strains of Thiobacillus ferrooxidans were able to grow by hydrogen oxidation, a feature not recognized before. When cultivated on H2, a hydrogenase was induced and the strains were less extremely acidophilic than during growth on sulfidic ores. Cells of T. ferrooxidans grown on H2 and on ferrous iron showed 100% DNA homology. Hydrogen oxidation was not observed in eight other species of the genus Thiobacillus and in Leptospirillum ferrooxidans.

DNA, Bacterial↗

[Cytologic molecular detection of oncogene expression: possibilities and prospects in hemato-oncology].

Proto-oncogenes, the normal equivalents to the transforming genes of mammalian tumorigenic retroviruses, are implicated in essential biological processes of normal human cells, like differentiation and proliferation. In vivo and in vitro studies clearly demonstrate that activation of proto-oncogenes with subsequent transformation in tumorigenic oncogenes plays an important role in induction and acceleration of the malignant disease, and also determines metastatic spread and development of resistance to chemotherapy in certain neoplasias. Investigation of these genes and analysis of their activation state should routinely be introduced in staging of hematological neoplasias, thus contributing to refinement of histopathological classification, clearer discrimination between reactive and neoplastic conditions and understanding of pathophysiological processes. Furthermore, impact on definition of high risk patients and novel therapeutic concepts based on a better definition of tumour biology may be expected from these studies. "Molecular cytology" combines detection of oncogenetic mRNA and the relevant oncoprotein on the single cell level by using "mRNA-in situ hybridization" and immuno-histochemistry. Application of this technique will allow to determine the mechanisms regulating the expression of oncogenes to define functional heterogeneity of tumour cell subsets and to clarify the relevance of minimal residual disease.

Cell Transformation, Neoplastic↗

Monoclonal antibody B-ly7: a sensitive marker for detection of minimal residual disease in hairy cell leukemia.

The new monoclonal antibody (MoAb) B-ly7 was tested for its value in bone marrow diagnosis in patients with hairy cell leukemia (HCL). Cryostat sections of bone marrow biopsies were examined by an indirect immunoperoxidase technique. Lymphoma cells from all of 26 HCL cases investigated displayed strong surface membrane staining with the MoAb B-ly7, whereas tumor cells from only one of 63 patients with other lymphoproliferative disorders of B cell type reacted with this antibody. The strong reactivity of hairy cells (HCs) with this marker was not altered after therapy as demonstrated on control biopsies taken from patients treated with interferon(IFN)-alpha-2 or 2'deoxycoformycin(DCF) six-64 weeks after start of treatment. This fact as well as the very low number of B-ly7 positive cells found in a series of 13 normal bone marrow biopsies (mean: 0.3% of bone marrow cells, range: 0.0%-1.0%), which could easily be distinguished from HCs by their lower staining intensity and their morphological appearance, provided the basis for the detection of even single HCs. In our hands, in terms of sensitivity the immunohistological detection of HCs using the MoAb B-ly7 was not only superior to classical morphological techniques but also to other immunohistological parameters usually applied for this purpose. Therefore, this MoAb provides a marker for the identification of HCs, hence monitoring disease activity in HCL, and particularly for a critical response evaluation in patients undergoing treatment with IFN-alpha or DCF.

Antibodies, Monoclonal↗

[Tumor markers in bronchus cancer].

Small cell lung cancers are neuroendocrine tumours and therefore produce a lot of peptide hormones (calcitonin, ACTH, ADH), as well as the neuropeptide chromogranin A, which are all useful tumour markers. Furthermore, the tumour-associated antigens CEA and TPA, as well as the enzymes neuron specific enolase (NSE) and creatine kinase BB are used as markers in small cell lung cancer. At present, NSE appears to be the best marker for small cell lung cancer; elevated serum NSE levels are found in 65 to 85% of the patients. The serum level of the tumour markers is related to the stage of the tumour. When tumour regression occurs following therapy, elevated pretreatment levels decrease to the normal range. If the marker level increases again, tumour progression is indicated and this can be an early and sensitive sign denoting recurrence. Metastases in the central nervous system can be detected early by marker determination in the cerebrospinal fluid. At present, CEA appears to be the most valuable tumour marker for non-small cell lung cancer, but TPA may also be a useful marker.

Biomarkers, Tumor↗

Simultaneous flow cytometric analysis of surface markers and nuclear Ki-67 antigen in leukemia and lymphoma.

The monoclonal antibody Ki-67 identifies an antigen present during the late G1, S, G2, and M phases of the cell cycle, whereas resting cells do not express this antigen. Immunostaining with Ki-67 provides a simple method with which to determine the growth fraction of a malignant cell population without requiring a laborious procedure or use of radioactive materials. Thus far, detection of Ki-67-positive cells by flow cytometry was limited because of nuclear location of the antigen. In this study, periodate-lysine-paraformaldehyde (PLP) fixation of cells in suspension, labeling with Ki-67, and the subsequent flow cytometric analysis of the tumor growth fraction is described. Fixation with PLP at -10 degrees C for 15 min rendered the plasma membrane permeable without destroying cell surface antigens. Thus double immunofluorescence studies using both a surface marker and Ki-67 could be performed. This offers the additional advantage of being able to define the phenotype of proliferating cells. This method was applied to determine the growth fraction in peripheral blood and bone marrow samples of patients with leukemia and non-Hodgkin's lymphoma. The results of Ki-67 studies in 91 patients are shown. A wide variability of individual Ki-67 values was observed within each entity. Use of this flow cytometric procedure substantially facilitates the quantification of proliferating cells in pathological blood and bone marrow samples.

Antibodies, Monoclonal↗

IgG, IgA and IgE gliadin antibody determinations as screening test for untreated coeliac disease in children, a multicentre study.

The diagnostic value of gliadin IgG, IgA and IgE antibody (AB) determinations using the fluorescent immunosorbent test was examined in 586 children with malabsorptive disorders and/or failure to thrive. All patients underwent jejunal biopsy and were on a gluten-containing diet. IgG AB were found in all patients (331/331) with untreated coeliac disease (CD) in our study, but IgA AB in only 295/331 (89%). Therefore a screening test based only on IgA AB determinations is not recommended. By contrast, 203 (80%) of 255 children with other malabsorptive disorders had no gliadin AB, 43 (16.5%) had only IgG AB and only 9 (3.5%) had IgG and IgA AB. IgE AB proved to be of no additional value as a diagnostic tool because they were found in a quarter of the children without CD. Statistical evaluation of combined IgG and IgA AB determination showed at least 96% sensitivity and a specificity of 97%. The subjective ("Bayesian") probability that an actual patient with a given AB test result has CD, is considered: a patient very probably has CD in the case of positive IgG and IgA AB, and no CD in the case of a negative AB result. In the case of negative IgA AB but positive IgG AB the physician's judgement ("prior probability") influences the ("posterior") probability of CD for an actual patient. In contrast to IgG AB, IgA AB decline rapidly after the introduction of a gluten-free diet and may be used for diet control after diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunohistological assessment of bone marrow biopsies from patients with hairy cell leukemia: changes following treatment with alpha-2-interferon and deoxycoformycin.

Forty-six bone marrow biopsies from twelve hairy cell leukemia (HCL) patients, treated with either interferon(IFN)-alpha-2 (n = 8) or 2'deoxycoformycin(DCF) (n = 4), were examined using cryostat sections and an immunoperoxidase technique. Using this sensitive method we were able to demonstrate residual hairy cell (HC) infiltration in five cases, in which evaluation with conventional staining techniques on plastic embedded biopsies revealed complete remission. The amount of HCs in these five samples ranged from 1 to 7% (mean: 3%) of bone marrow cells. Consecutive biopsies in individual HCL patients revealed no changes of the immunological phenotype (CD19, CD22, CD25, CD10, CD11c, FMC7, HLA-DR, surface immunoglobulins) during IFN and DCF treatment. Within the infiltrated bone marrow a considerable number of "reactive" T lymphocytes was identified with prevalence of the T-helper (CD4+) subtype in untreated cases, whereas T-suppressor/cytotoxic (CD8+) cells were within the normal range. IFN treatment resulted in a reduction of CD4+ T lymphocytes (p less than 0.02). Minor alterations of CD8+ T lymphocytes and NK cells (HNK-1 + lymphoid cells) were found in bone marrow during IFN treatment. In DCF-treated patients bone marrow T lymphocytes were markedly reduced below the values of normal bone marrow. This DCF-induced T-cell depression might be related to the clinical observation of persistent cellular immune dysfunctions in HCL patients despite a DCF-induced remission.

Adult↗