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Biomedical subjects

K Havemann

Publications and source records attributed to K Havemann.

At least 37 records · Page 2Linked to original sources
PubMed1991

Inhibition of neutrophil chemotaxis by elastase-generated IgG fragments.

IgG1 is cleaved in vitro by granulocyte elastase into Fc and Fab fragments. The elastase-specific Fc fragment has been previously detected in vivo. Biological activity of the fragments has been described in modulating neutrophil oxidative metabolism and enzyme release. To investigate further effects granulocyte chemotaxis (CT) was tested. The CT was assayed in Boyden chambers and the chemotactic index (CI) was calculated which represents the mean distance travelled by the activated cells. Stimulation of leucocyte CT by casein, activated serum and FMLP gives maximal values of delta CI = 46.7, 26.4 and 7.2 microns, respectively. Native IgG1 and the elastase-produced IgG fragments do not stimulate leucocyte CT. FMLP-stimulated CT is specifically inhibited by the elastase-produced Fc fragments. Addition of 7 nmol Fc to stimulus concentrations of 16 to 125 nM FMLP results in total inhibition of chemotaxis demonstrated by CI values which are lower than those for unstimulated cells. The inhibition of CT is concentration dependent in the range of 2 to 7 nmol Fc/10(6) PMN. Number and affinity of FMLP receptors are not influenced by Fc fragments, so Fc binds neither to FMLP nor the FMLP receptor. CT stimulated by casein shows a large portion of chemokinesis. Only at suboptimal casein concentrations do Fc and IgG have an inhibitory effect on CT (0.63 mg casein/ml, 10 nmol peptide/10(6) PMN). C5a-stimulated CT is not influenced by IgG or IgG fragments which indicates that the samples are not cytotoxic. So the FMLP and casein-stimulated CT is specifically inhibited by the elastase-produced Fc fragments in a low concentration range.

Binding Sites↗
PubMed1991

Gingival crevicular fluid elastase-inhibitor complex: correlation with clinical indices and subgingival flora.

This investigation analyzed, in a cross-sectional study, the possible relationship between gingival crevicular fluid (GCF) elastase-like protease (ELP) levels and the periodontal clinical parameters or the presence of specific bacteria in subgingival plaque. A total of 388 periodontal sites from 8 adult periodontitis patients were examined for plaque index (PII), gingival index (GI), pocket depth (PD) and alveolar bone loss (ABL). GCF ELP levels were determined as ELP alpha-1 protease inhibitor (ELP-alpha 1-PI) complex levels with a commercially available ELISA. Subgingival plaque samples were tested for the presence of Bacteroides gingivalis, B. intermedius and Actinobacillus actinomycetemcomitans by indirect immunofluorescence (IF) microscopy. GCF ELP-alpha 1-PI levels were then correlated with clinical periodontal indices and proportions of IF-positive bacteria per site. Statistically significant positive correlations were found between GCF ELP-alpha 1-PI concentrations and subgingival Bacteroides proportions. When the sites examined were analyzed depending on the level of each clinical parameter, the levels of these correlations changed. A. actinomycetemcomitans correlated highly (r = 0.716) with ABL for sites with low GI score. The correlations between GCF ELP-alpha 1-PI and B. gingivalis (r = 0.642) or B. intermedius (r = 0.774) were the highest for ABL less than or equal to 20% and PD less than or equal to 3 mm, respectively. The strong association between GCF ELP-alpha 1-PI concentrations and subgingival bacteria previously associated with advancing periodontitis indicates that measurement of GCF ELP-alpha 1-PI concentrations may be useful in the evaluation of periodontal sites, especially those with very little or no tissue destruction.

Actinobacillus↗
PubMed1991

The role of membrane contact in hemodialysis-induced granulocyte activation.

Besides complement, interleukin-1 and beta 2-microglobulin, activation of granulocyte function has been found out to be the major parameter in the determination of dialyzer biocompatibility. Unfortunately, the term 'granulocyte activation' has been widely used without restriction to distinct functions or definition of the related metabolic pathways. Therefore, the present study aims to elucidate the influence of hemodialysis (HD) pure membrane contact on granulocyte O2- release. The activation of this metabolic pathway which is also known as the so-called oxidative burst has been generally accepted as the initial signal in the granulocyte inflammatory activation cascade. Two membranes which have been previously shown to differ most widely in biocompatibility, cuprophane and polysulfone, have been selected. During HD with cuprophane the stimulatable O2- release was initially decreased, whereas polysulfone HD was effectless on granulocyte oxidative metabolism. The inhibition was due to a prestimulation of the granulocyte by pure interaction of the cell with the surface of the dialyzer membrane which could be proved by evaluating a plasma-free model. Activation of oxidative metabolism was strongly correlated with granulocyte adherence, showing a significantly higher rate of cell adherence in the case of cuprophane. Nevertheless, sheer forces were able to prevent granulocytes becoming adherent directly to the dialyzer membrane, but sheer forces were not able to influence the oxidative burst reaction, suggesting that the membrane-related stimulation of oxidative metabolism occurs immediately after a very short, possibly a single and hasty contact of the cell to the surface of the dialyzer membrane.

Aged↗
PubMed1991

Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex.

Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.

Acute Kidney Injury↗
PubMed1991

Protein C degradation in vitro by neutrophil elastase.

Purified protein C is completely degraded into small peptides by in vitro incubation with purified elastase. Protein C is a rather sensitive substrate as degradation is already accomplished by low elastase concentrations (molar enzyme-to-substrate ratio 1:510) and short incubation periods (5 min-60 min). Protein C in a PPSB coagulation factor concentrate is equally degraded and similar split products are detected by blotting techniques. The protein C activity (measured by a chromogenic substrate) is faster reduced by elastase than the protein C concentration (measured by an ELISA). Incubation of normal plasma with high elastase concentrations (5.7 nmol/ml plasma) results in reduction of the protein C band while no split products are detectable. The pathophysiologic significance of the effects of elastase on protein C remains to be elucidated.

Blood Coagulation Factors↗
PubMed1991

Focal involvement of malignant lymphoma in the liver.

In this study the sonographic findings of 30 patients with hepatic lymphoma have been reviewed. Lesions have been confirmed by autopsy (n = 1), laparatomy (n = 1), sonographically guided biopsy (n = 15), and during long-term follow-up (n = 13). Ten patients had Hodgkin's disease (HD) and 20 non-Hodgkin lymphomas (NHL). Focal lesions, less than 3 cm in diameter, were seen in 20 patients. The remaining ten cases presented large-nodule transformation of the parenchymal texture. All lesions were predominantly hypoechoic with a halo sign in two cases. No diffuse involvement of the liver was observed, and no correlation between histological lymphoma subtyping and patterns of hepatic infiltration was found.

Adolescent↗
PubMed1990

Growth regulation by insulin-like growth factors in lung cancer.

Lung cancer is a major health problem, with over 38,000 new cases expected every year in West Germany. A more complete understanding of the biology of lung cancer will hopefully lead to therapeutic modalities. The possible autocrine growth regulation in small-cell lung cancer and non-small-cell lung cancer has been demonstrated for bombesin/GRP, vasopressin, neurotensin, EGF/TGF alpha, transferrin-related peptides and insulin-like growth factors. This contribution concentrates on recent data concerning binding sites, growth promoting effects and secretion of IGFs in lung cancer cell lines. The production of IGF-binding proteins which were also produced by lung cancer cell lines modifies the autocrine/paracrine model for IGFs since then proteins can either enhance or inhibit the effect of IGFs on tumor growth.

Humans↗
PubMed1990

Multiple myeloma of the bladder and vagina.

A case is described of multiple myeloma with involvement of the urinary bladder and vagina. The patient was admitted with hematuria and postrenal obstruction. She was treated successfully with local radiotherapy and combination chemotherapy with vincristine, Adriamycin (doxorubicin), and dexamethasone (VAD).

Aged↗
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↗