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Biomedical subjects

K Havemann

Publications and source records attributed to K Havemann.

At least 109 records · Page 6Linked to original sources
PubMed1990

NCAM: a surface marker for human small cell lung cancer cells.

Immunocytochemical and immunochemical techniques were used to study the expression of the neural cell adhesion molecule (NCAM) by human lung cancer cell lines. Intense surface staining for NCAM was found at light and electron microscopic levels on small cell lung cancer cells. The NCAM polypeptide of Mr 140,000 (NCAM 140) was detected by immunoblotting in all of 7 small cell lung cancer cell lines examined and in one out of two of the closely related large cell cancer cell lines: it was not detected in cell lines obtained from one patient with a mesothelioma, in two cases of adenocarcinoma, nor in two cases of squamous cell cancer. In contrast, neuron-specific enolase was found by immunoblotting in all the lung cancer cell lines tested and synaptophysin in all but the adenocarcinoma cell lines. These antigens were localized intracellularly. The specific expression of NCAM 140 by human small and large cell lung carcinomas suggests its potential as a diagnostic marker.

Biomarkers, Tumor↗
PubMed1990

Differentiation capacity of human non-small-cell lung cancer cell lines after exposure to phorbol ester.

Three cell lines of squamous-cell carcinoma and 3 of large-cell carcinoma origin were investigated for the expression of differentiation markers and functional parameters (proliferation, morphology, cornified envelope formation, involucrin staining, transglutaminase activity, adhesiveness and migration) under normal cell culture conditions and after treatment with the tumor promoter phorbol-12-myristate-13-acetate (PMA). Although all original tumors had been described as poorly differentiated by histological grading, we found significant heterogeneity in the expression of differentiation markers in cell culture. A systematic grading of the cell lines became possible only after PMA stimulation. PMA generally increased expression of differentiation markers in cell lines of comparably low grades of differentiation, as indicated by dose-dependent inhibition of proliferation and cloning efficiency, induction of squamous markers, and decreased adhesiveness and cell motility. In contrast, cell lines of apparently higher differentiation by these criteria showed little response to PMA. The results presented show that the assessment of differentiation capacity by comparison of differentiation markers under normal cell culture and PMA-stimulated conditions in established NSCLC cell lines allows for a refined cell culture grading, which might advance the classification and characterization of such cell lines which, otherwise, appear to be very heterogeneous. It may also help to correlate cellular functions with various states of differentiation in vitro.

Biomarkers, Tumor↗
PubMed1990

Sonographic patterns of the affected spleen in malignant lymphoma.

Sonographic examination showed spleen involvement in 43 patients with histological evidence of malignant lymphoma. In 23% of these cases the spleen was of normal size and 77% exhibited variable splenomegaly. Focal lesions could be seen in 27 patients, 16 exhibiting diffuse, small-nodule transformation of the sonographic parenchymal texture. Hodgkin lymphomas caused both focal (7 of 16) and diffuse (9 of 16), splenic lesions. All non-Hodgkin lymphomas of high-grade malignancy exhibited focal lesions, which are larger than 3 cm in diameter in 11 out of 13 patients. In non-Hodgkin lymphomas of low-grade malignancy, focal sites and diffuse destruction of splenic tissue texture were found, lesions of under 3 cm in diameter (11 of 13) being characteristic of this subtype.

Adult↗
PubMed1990

High-dose chemotherapy with noncryopreserved autologous bone marrow transplantation for acute myeloid leukemia in first complete remission.

Seven patients with acute myeloid leukemia (AML) in first complete remission were treated with escalating high doses of cyclophosphamide, etoposide, and cytosine arabinoside (Ara-C). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored in blood bags in a refrigerator for 48-72 h at 4 degrees C and then reinfused over a central line. All patients had a full hematological recovery. The mean time of neutropenia (neutrophils less than 500/microliters) was 14 days (range 9-24 days), and the mean time of thrombocytopenia (platelets less than 20,000/microliters) was 9 days (range 7-11 days). The nonhematological toxicity was tolerable with mild to moderate nausea/vomiting, mucositis and diarrhea, and so far not dose-limiting. Six patients remain in complete remission 17+, 9+, 5+, 5+, 4+, and 1+ months after autotransplantation. One patient relapsed 8 months after autotransplantation. High-dose chemotherapy with noncryopreserved bone marrow autotransplantation may be useful as intensified consolidation for patients with AML in first complete remission.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines.

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1990

Latent inhibition of granulocyte function by cyclosporine A.

According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages.

Adult↗
PubMed1990

Stimulation of neutrophil elastase and myeloperoxidase release by IgG fragments.

Human leucocyte elastase (HLE) cleaves IgG into Fab and Fc fragments. The Fc fragment bears an elastase-specific antigen and has previously been reported to be found in synovial fluid during rheumatoid arthritis. In addition, biological activity of elastase-specific Fc fragments has been described in modulating granulocyte oxidative metabolism. To investigate further regulatory effects of the elastase-induced IgG cleavage products, we tested the elastase and myeloperoxidase release of granulocytes. IgG fragments induce no enzyme release of unstimulated neutrophils. But elastase and myeloperoxidase release of cytochalasin b/FMLP-treated neutrophils is stimulated in a dose-dependent manner by the Fab fragments. The extent of stimulation depends on stimulus concentration and is at its maximum for low (e.g. 2.5 x 10(-8) M) FMLP concentration. Ten nanomoles Fab/4 x 10(6) PMN augment elastase release to 206% and myeloperoxidase release to 155% after pre-stimulation with 2.5 x 10(-8) M FMLP. Fc fragments stimulate elastase release to 162% but no MPO release. Untreated IgG1 and analog Fab and Fc fragments produced by papain cleavage react similarly. Elastase-generated IgG fragments may therefore up-regulate their concentration by simulating elastase release. The concomitantly stimulated release of myeloperoxidase may influence bactericidal activity and termination of oxidative burst.

Cytochalasin B↗
PubMed1990

Alternating chemotherapy in small cell lung cancer.

Based on the hypothesis of Goldie and Coldman, rapid cyclic alternating chemotherapy has been supposed to be a favorable treatment modality in small cell lung cancer. This approach has been tested in a large series of trials since the late 70's. A few trials performed randomization between alternating and continuous treatment after a period of initial common continuous therapy. The results of these studies are controversial and their interpretation is complicated by the effects of the continuous pretreatment. Recently, most trials were designed as 2-arm approaches with a comparison of continuous standard therapy based on the CAV- or CMC-protocol with an alternating schedule often consisting of the CAV- or CMC-derived combinations and a second regimen including cisplatinum and/or etoposide. In these trials the addition of the second regimen in the alternating treatment arms has improved the treatment results. However, these trials could not clarify whether this advantage was due to the concept of alternating treatment or to the high activity of new drugs given early in the course of therapy in the alternating treatment arms. To ameliorate this weakness, 3 studies were designed as 3-arms approaches using both alternating protocols as continuous control arms. Whereas one investigation noticed an advantage of the alternating schedule, the two others observed no difference. These studies did not report their criteria for shifting non-responding patients from continuous treatment to second line therapy. The longer these patients stayed on the continuous protocol the more the study design favoured the alternating therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Cytochemical determination of intracellular polymorphonuclear leukocyte elastase content in patients with severe bacterial infection and septicaemia correlated with coagulation parameters.

Haemorrhagic disorders are known to occur during septicaemia. We studied the role of elastase-like protease (ELP) of human granulocytes in the activation and consumption of clotting factors and their specific inhibitors. Patients with septicaemia and severe bacterial infection were examined for ELP content in polymorphonuclear leukocytes (PNL), as well as plasma levels of ELP complexed to alpha-1 protease inhibitor, total alpha-1 protease inhibitor (alpha-1 PI), clotting factor VII and partial thromboplastin time (PTT). In all patients, a decrease in ELP content of PNL was accompanied by an increase in plasma ELP complexes. The degree to which ELP content of PNL was lowered was related both to the clinical diagnosis and the course of illness. The ELP content of PNL showed a significant positive correlation with plasma factor VII and significant negative correlations with PTT and alpha-1 PI. These data suggest that ELP release is accompanied by stimulation of the production of alpha-1 PI, and may contribute in vivo to the consumption of coagulation factors. The correlation with PTT might point to an activation of Hageman factor, which may activate both intrinsic coagulation and ELP release. The estimation of ELP content in PNL in patients with septicaemia is likely to represent intravascular ELP release during the inflammatory process. It appears to be useful in combination with the assay of ELP complex in plasma the level of which is influenced by the capacity of the reticuloendothelial system for clearance.

Adult↗
PubMed1990

Inhibition of neutrophil oxidative burst by elastase-generated IgG fragments.

IgG1 is cleaved in vitro by granulocyte elastase into Fc, Fab and Fabc fragments. The cleaved products have been isolated by a series of chromatographic procedures and characterized with regard to molecular mass and isoelectric point. The Fc fragment has been previously shown to express at its N-terminal site a neoantigen which is specific for elastase (Kolb, G., Eckle, I., Heidtmann, H.-H., Neurath, F. & Havemann, K. (1988) Scand. J. Rheumatol. S75, 179-189). The production of superoxide radical anions in prestimulated neutrophils is inhibited dose-dependently by the elastase-generated Fc and Fabc fragments. Native IgG1 and Fab fragments show no inhibitory effect, nor do papain-generated Fc fragments. The degree of inhibition depends on the stimulus applied: half-maximal inhibition is obtained by 6 microM Fc after stimulation with 4 beta-phorbol and 2.4 microM after stimulation with fMet-Leu-Phe; neutrophils stimulated with serum-activated zymosan are not inhibited by IgG fragments. The effect of Fc is purely cellular; no inhibition of O2 generation can be produced by applying Fc to the xanthine oxidase/xanthine system. The fragments have no effect on the activation or activity of crude NADPH oxidase, which is the O2-forming enzyme system of neutrophils. Possible mechanisms are discussed by which Fc acts on stimulated neutrophils.

Dose-Response Relationship, Drug↗
PubMed1990

High affinity binding of immunoglobulin G fragments to human polymorphonuclear leukocytes.

Human neutrophil elastase splits IgG into Fc, Fabc, and Fab fragments. The Fc and Fabc fragments bind with high affinity (KD 2.1 and 2.5 nM respectively) to a small number of binding sites (1175 and 1370 sites/cell respectively) on untreated human polymorphonuclear leukocytes. Molecular mass determination of the binding site by crosslinking of Fc fragments to the neutrophils followed by SDS electrophoresis yields one band corresponding to a molecular mass of 67 kDa for the binding site. Incubation of neutrophils with rIFN-gamma (50 ng/ml, 18 h, 37 degrees C) enhances the expression of binding sites by about 6 fold to about 14,500 sites/cell, while the binding affinity and the molecular mass of the ligand receptor complex remain constant. By comparison with known affinities of leukocyte Fc receptors it is concluded that IgG fragments bind to the high affinity FcRI receptor of human neutrophils.

Cells, Cultured↗
PubMed1990

Prognostic value of response to chemotherapy using ultrasound in lung cancer with metastatic liver involvement.

Between January 1981 and December 1989, a total of 205 patients with lung cancer were treated in different multicenter trials in our hospital. In 130 cases, small cell lung cancer (SCLC), and in 75 cases, non-small cell lung cancer (NSCLC) was diagnosed. Abdominal sonography for pretreatment staging revealed liver metastasis in 59 patients (42 SCLC, 17 NSCLC), sonographic patterns of liver metastasis were described and the prognostic significance of evaluation of response according to abdominal ultrasound after the first two cycles of treatment was investigated. For both histological types of lung cancer, the hypoechoic or isoechoic (80%), small noduled (97%) liver metastasis with multifocal spread (86%) was found to be typical. Sonographic follow-up examinations for liver metastasis were performed in 46 patients (35 SCLC, 11 NSCLC), and 134 chemotherapy cycles. Response to chemotherapy according to abdominal ultrasound was seen in only 3 out of 11 patients with NSCLC (27%) and 17 out of 35 with SCLC (49%). Best response was achieved after the first two cycles with only 6 patients (6 SCLC, 0 NSCLC) exhibiting complete liver metastasis remission. All other patients exhibited on ultrasound a progressive or non-responsive illness. In summary, sonography is reliable with respect to the diagnosis and follow-up examination of liver metastases in lung cancer. A lack of metastasis regression subsequent to the first two cycles of therapy is associated with poor prognosis and continued treatment cannot be justified in such patients.

Adult↗
PubMed1990

Kinetics of pulmonary leukocyte sequestration in man during hemodialysis with different membrane-types.

Although it has been suggested that pulmonary sequestration of leukocytes could account for membrane-dependent white blood cell depletion in HD, direct evidence in patients is still lacking. Therefore a study was initiated to test whether and how leukocytes distribute in the lung circulation during HD with different membranes. Thirteen patients suffering from chronic renal failure underwent lung scintigraphy during HD with cuprophane (n = 3), hemophane (n = 8) and polysulfone (n = 2) lowflux capillary dialyzers. Isolated autologous leukocytes were labelled with 99m-Technetium and reinfused before starting HD. Distribution of leukocyte related activity was registered by lung scintigraphy. In comparison to normal lung scintigraphy performed without HD, an impressive redistribution peak was demonstrated 10-20 min after the start of HD with cuprophane and also to a lesser extent with hemophane. When HD was performed with polysulfone the decrease in activity was delayed but no real redistribution was obtained. In accordance with other phenomena, such as peripheral leukopenia and changes in granulocyte oxidative metabolism, pulmonary sequestration of leukocytes takes place in man in the initial phase of HD and appears to be strongly dependent on the type of membrane.

Humans↗
PubMed1990

Flow-cytometric analysis of lymphocyte subsets in patients with advanced periodontitis.

Peripheral blood lymphocytes from 36 patients with advanced periodontitis and from 34 healthy subjects were examined using a panel of monoclonal antibodies and fluorescence flow cytometry. The absolute and relative counts of B-cells, T-cells, T-helper (TH), T-suppressor/cytotoxic (TS) cells, activated T-cells and natural killer cells were assessed and the TH/S ratio was calculated. In the periodontitis patients, the TH/S ratio was 1.56 +/- 0.62 and in the controls 1.35 +/- 0.55. This was not statistically significant. A classification on the basis of sex also did not show significant differences in the TH/S ratio. B-cells and activated T-cells were slightly increased in the periodontitis group. However, all determined lymphocyte subpopulations revealed no significant differences between the groups. These results indicate that local inflammatory reactions and immunoregulatory dysfunction are limited to the periodontium in the patients with advanced periodontitis, with no significant quantitative effects on the peripheral lymphocyte subpopulations.

Adult↗
PubMed1990

Assay of functional activity of alpha 1-antichymotrypsin in plasma.

We introduce a novel assay for measuring active alpha 1-antichymotrypsin (alpha 1X) in human plasma. The assay works on the principle that cathepsin G, immobilized in microtiter plates, preferentially binds alpha 1X, which then can be specifically quantified immunologically. alpha 1X activity can be detected even after 50,000-fold dilution of normal plasma. A linear range was defined for reproducible quantification. There was no interference by alpha 1-proteinase inhibitor or alpha 2-macroglobulin. The assay is designed to detect conditions having decreased alpha 1X activity to further elucidate the biological function of this prominent acute-phase protein.

Cathepsin G↗