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Biomedical subjects

K Havemann

Publications and source records attributed to K Havemann.

At least 55 records · Page 3Linked to original sources
PubMed1994

Altered expression of the retinoblastoma gene product in human high grade non-Hodgkin's lymphomas.

The retinoblastoma gene (RB) is a growth suppressor gene on the human chromosome 13q14. It encodes a 105 kDa phosphoprotein (p105), with DNA-binding capacity. P105 is thought to be involved in cell cycle control. Inactivation of RB is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung cancer. In this study we looked at the RB-structure and expression in cell lines and primary lymphoma samples from patients with high grade non-Hodgkin's lymphoma (NHL). Forty five primary high grade NHL, the B-lymphoblastoid cell line IM-9 and the NHL cell line WSU-NHL were studied for RB structure by Southern blotting and for RB-expression by Northern blotting, Western blotting and immunocytochemistry. In all experiments freshly cryopreserved material was used. Southern and Northern experiments were performed with the 0.9 kb and 3.8 kb RB-cDNA probe. For the detection of p105 two different anti-p105-monoclonal antibodies were used in immunocytochemistry and Western blotting experiments. No RB mRNA and no p105 could be found in IM-9 cells. Twenty six high grade NHL samples (58%) showed no p105 expression. In the subgroup of centroblastic lymphomas 16 out of 21 and in Burkitt's lymphomas five out of eight showed no p105-expression. P105 expression is absent in 58% of high grade NHL, particularly in centroblastic and Burkitt's lymphomas, suggesting that inactivation of RB may play a crucial role in the pathogenesis of high grade NHL.

Blotting, Northern↗
PubMed1993

Evaluation of serum neural cell adhesion molecule as a new tumor marker in small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is distinguished from other histologic types of lung cancer by possessing a variety of neuroendocrine properties. Neuron-specific enolase (NSE) is the most frequently elevated tumor marker for patients with SCLC at diagnosis. To assess the value of neural cell adhesion molecules (NCAM), another possible tumor marker for small cell lung cancer, NCAM was evaluated in the sera of patients with histologically confirmed SCLC in two prospective multicenter trials. METHODS: The study includes 221 patients with SCLC, normal human blood donors (n = 34), patients with benign lung disease (n = 53), and patients with non-small cell lung cancer (n = 28). NCAM was determined by means of an enzyme immunoassay, NSE by a radioimmunoassay. RESULTS: The data show the following: (1) 51% (113 of 221) of all patients with SCLC had NCAM levels higher than 20 U/ml, 34% (75 of 221) had NSE levels higher than 25 ng/ml; (2) levels of both markers significantly differ between limited and extensive disease patients; (3) patients with pathologic NCAM and NSE levels have significantly shorter survival times; (4) a positive correlation between pretreatment NSE and NCAM levels was found (n = 221, r = 0.60); and (5) a correlation between serum marker levels and clinical status was found in follow-up studies of 19 patients. CONCLUSIONS: From these data, it is concluded that NCAM is, along with NSE, a potential tumor marker for SCLC.

Adult↗
PubMed1993

Activators of coagulation in cultured human lung-tumor cells.

Tumor matrix generation and tumor cell growth are supported by coagulation processes within the tumor tissue. Activators of coagulation were searched for in suspensions of 9 permanent human squamous-cell lung-cancer (EPLC 32MI, U1752), large-cell lung-cancer (LCLC 97TMI, LCLC 103H, U1810), and small-cell lung-cancer (N-592, H-526, DMS79, 86MI) cell lines. Incubation with these cells shortened the recalcification time in normal plasma (also in the presence of antibodies against tissue factor) or coagulation-factor-VII-, VIII-, IX- or X-deficient plasmas. The activators of coagulation in the 2 most active cell lines (U1752 and LCLC 103H) were further characterized in purified systems: the cleavage of chromogenic substrates, and the generation of markers of pro-thrombin activation were assessed. Three activators of coagulation were found in intact or sonicated cell suspensions and culture supernatants: (i) a tissue factor (TF)-like activity; (ii) an activity activating factor X, which in contrast to "cancer pro-coagulant" was not inhibited by iodoacetamide; and (iii) an activity-activating pro-thrombin, which was inhibited by the serine protease inhibitor PMSF and appeared to require plasmatic co-factor(s). The heterogeneous expression of coagulation activators by lung-tumor cell lines might be of significance for tumor biology and response to therapy.

Blood Coagulation↗
PubMed1993

Characterization of insulin-like growth factor II receptors in human small cell lung cancer cell lines.

Small cell lung cancer (SCLC) cell lines were investigated for the expression of insulin-like growth factor (IGF) II receptor by means of radioreceptor assays, cross-linking techniques, and Northern blot analysis. 125I-IGF II binds to both the IGF I and the IGF II receptor on intact SCLC cells. Detailed receptor assays performed on microsomal and plasma membranes gave evidence that 125I-IGF II binds with high affinity (70-80 pM) to the IGF I receptor and with low affinity (2-4 nM) to the IGF II receptor, and not conversely. The presence of mannose-6-phosphate enhanced the binding of 125I-IGF II to the IGF II receptor of SCLC. Mannose-6-phosphate also increased the efficiency of N-hydroxysuccinimide ester in cross-linking 125I-IGF II to the IGF II receptor and facilitated the cross-linking of 125I-IGF II to a second protein of 240-250 kDa. Soluble IGF II receptor was also detected in conditioned media of SCLC cell lines.

Blotting, Northern↗
PubMed1993

Pharmacokinetics of etoposide: correlation of pharmacokinetic parameters with clinical conditions.

The pharmacokinetic parameters of etoposide were established in 35 patients receiving the drug parenterally within the framework of different polychemotherapy protocols. A total of 62 data for 24-h kinetics were analysed. After sample extraction and high-performance liquid chromatography (HPLC) or thin-layer chromatographic (TLC) separation, etoposide was measured by means of [252Cf]-plasma desorption mass spectrometry (PDMS). This highly specific detection system proved to be very practicable and reproducible. The present study comprised two parts that were absolutely comparable in terms of clinical and pharmacokinetic parameters. In part II of the study, sensitivity was improved by modifying the analytical technique. After the exclusion of patients who had previously been given cisplatin or who exhibited renal impairment and of one patient who showed extremely high levels of alkaline phosphatase, gamma-GT and SGPT, the mean values calculated for the pharmacokinetic parameters evaluated were: beta-elimination half-life (t 1/2 beta), 4.9 +/- 1.2 h; mean residence time (MRT), 6.7 +/- 1.4 h; area under the concentration-time curve (AUC), 5.43 +/- 1.74 mg min ml-1; volume of distribution at steady state (Vdss), 6.8 +/- 2.7 l/m2; and clearance (Cl), 18.8 +/- 5.3 ml min-1 m-2. The pharmacokinetic parameters were correlated with 12 different demographic or biochemical conditions. Impaired renal function, previous application of cisplatin and the age of patients were found to influence etoposide disposition to a statistically significant extent. We suggest that the dose of etoposide should be reduced in elderly patients and/or in individuals with impaired renal function, especially in those exhibiting general risk factors such as reduced liver function with regard to the polychemotherapy.

Adult↗
PubMed1993

Generalised giant-cell tumour of bone: successful treatment of pulmonary metastases with interferon alpha, a case report.

We report on a 37-year-old female patient with generalised giant-cell tumour of the bone, whose tumour was refractory to conventional chemotherapy. Subsequent treatment with interferon alpha 2a in increasing dosage from 4 x 10(6) IU (three times a week) to 9 x 10(6) IU (three times a week) led to a significant decrease of pulmonary metastases and a stabilisation of the disease after 12 months of treatment. In progressive chemotherapy refractory giant-cell tumour interferon alpha 2a may be of therapeutic benefit.

Adult↗
PubMed1993

Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer.

Insulin-like growth factors are potent mitogenic factors in human lung cancer in vitro, acting via specific receptors. Using monoclonal antibodies we demonstrate the expression of insulin-like growth factor receptor I in bronchial epithelial cells of normal lung and in primary lung cancer (22/24 cases), being most prominent in squamous cell carcinoma. Electron microscopy on lung cancer cell lines reveals a distinct reaction pattern on the plasma membrane. Immunoreaction with a specific antibody directed against the insulin-like growth factor receptor II suggests a weak expression in primary lung cancer. Our findings underline the significance of the autocrine pathway of insulin-like growth factors in lung cancer.

Adenocarcinoma↗
PubMed1993

Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a county of Hesse, Germany.

The incidence of acute and chronic myelogenous leukemia has been compared for the two neighbouring regions of Marburg and Giessen in Hesse (Germany). The investigation was based on the incident cases of the years 1983-1989 which have been diagnosed in the hematological departments of the universities of the two regions. The epidemiological evaluation of the data has been carried out in terms of a historical follow-up study, and shows an increased relative risk for the region around Marburg with a particular elevation for one community within this region. Potential determinants are discussed and focus on trinitrotoluene (TNT) and decomposition products which are known to contaminate the soil of this community, in some places severely, due to insufficient removal of remnants of the TNT production in large underground plants during World War II.

Adult↗
PubMed1993

Differential expression of the intercellular adhesion molecule-1 (ICAM-1) in lung cancer cell lines of various histological types.

Ten small cell lung carcinoma and 12 non-small cell lung carcinoma cell lines of various histological types were studied for constitutive expression of the intercellular adhesion molecule-1 (ICAM-1). ICAM-1 was present in all squamous and large cell carcinoma cell lines whereas two out of five adenocarcinoma and all small cell lung cancer (SCLC) cell lines showed no basal ICAM-1 expression. ICAM-1 expression was upregulated by tumour necrosis factor-alpha (TNF-alpha) in a time- and dose-dependent manner in cell lines with basal ICAM-1 expression. Western blot analysis revealed a molecular size of 85 kDa for ICAM-1 in all but one cell line. The TNF-alpha-induced upregulation of ICAM-1 occurs on the transcriptional level. Adhesion of peripheral blood mononuclear cells to lung tumour cell lines could be inhibited by monoclonal antibodies (MAb) (CD11a;CD18) against the receptor of ICAM-1, the leukocyte function-associated antigen-1 (LFA-1), but not by a MAb (CD54) against ICAM-1 itself.

Blotting, Northern↗
PubMed1993

Molecular cloning of IGFBP-5 from SCLC cell lines and expression of IGFBP-4, IGFBP-5 and IGFBP-6 in lung cancer cell lines and primary tumours.

We showed recently that insulin-like growth factor binding protein (IGFBP)-1, -2 and -3 are differentially expressed in lung cancer and permanent lung cancer cell lines. Elevated levels of IGF binding capacity in serum of lung cancer patients were also reported. The function and tissue specificity of IGFBP are still obscure but they are probably local regulators of IGF action. Here we show the expression of IGFBP-4 transcripts in 11/11 small cell lung cancer (SCLC) cell lines, in nine out of 11 non-small cell lung cancer (NSCLC) cell lines, in 11/11 lung tumour specimens (10 derived from patients with NSCLC and one from SCLC origin) and in normal lung. In addition we isolated IGFBP-5 cDNA from lambda gt10 libraries of SCLC cell lines. With this IGFBP-5 cDNA we detected transcripts of different lengths in seven out of 11 SCLC cell lines, in 11/11 lung cancer specimens but only in one out of 11 NSCLC cell lines and in normal lung. IGFBP-6 was not detected in northern analysis of any tested SCLC cell line but it was expressed in nine out of 11 NSCLC cell lines and in nine out of 11 human lung cancer specimens and in normal lung.

Base Sequence↗
PubMed1993

Activation of coagulation and fibrinolysis in patients with lung cancer: relation to tumour stage and prognosis.

Activation of coagulation and fibrinolysis within tumour tissues is thought to be associated with tumour growth, angiogenesis, and metastasis. The plasma levels of markers of thrombin and plasmin generation are sensitive tools for monitoring activation of coagulation and fibrinolysis. We studied 47 patients with histologically confirmed lung cancer, 15 with small cell (SCLC) and 32 with non-small cell lung cancer (NSCLC). The plasma levels of the following markers were assessed:thrombin-antithrombin III complex (TAT), prothrombin activation fragment F1 + 2, plasmin-alpha 2-antiplasmin complex (PAP) and the split product from cross-linked fibrin, D-dimer. The first sample was obtained before receiving any specific antineoplastic treatment. The patients were followed thereafter until treatment was terminated. There was no difference in activation markers between patients with SCLC and NSCLC. Comparing patients with limited disease to those with extensive disease, there were significant differences in TAT (median 3.0 (1.9-9.8) vs 5.3 (1.8-35.6) micrograms/l,P = 0.021) and D-dimer (569 (135-1948) vs 1288 (120-2221) micrograms/l, P = 0.014). According to the response to subsequent treatment, those who achieved complete or partial tumour remission had significantly lower baseline levels samples than non-responders (TAT 2.9 (1.9-4.0) vs 4.7 (1.8-35.6) micrograms/l,P = 0.0047;D-dimer 527 (135-1149) vs 1242 (120-2221) micrograms/l, P = 0.0013). Thus, the increase of TAT and D-dimer appears to be related to tumour spread. The results suggest that high levels of these markers might be a sign of unfavourable prognosis in patients with lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1993

Sustained trilineage response in a patient with ALG-resistant severe aplastic anaemia after treatment with G-CSF, erythropoietin and cyclosporin A: association of recovery with marked elevation of serum alkaline phosphatase.

Aplastic anaemia is characterized by multilineage bone marrow failure resulting in pancytopenia. We have successfully treated a young woman with severe aplastic anaemia (SAA) who was resistant to antilymphocyte globulin (ALG) and corticosteroids, with a combination therapy consisting of erythropoietin, cyclosporin A and granulocyte-colony stimulating factor (G-CSF). The patient received erythropoietin and CSA for a period of 10 months without success before G-CSF treatment was started. After 6 weeks of G-CSF therapy she responded with a sustained trilineage recovery. This suggests that immunosuppression together with haemopoietic growth factors may be an effective treatment in patients with SAA who are ALG resistant and cannot be treated by BMT.

Adolescent↗
PubMed1993

Altered expression of the human retinoblastoma gene in monocytic leukaemias.

Inactivation of the retinoblastoma growth suppressor gene (RB) is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung carcinoma. Knowledge about the involvement of RB in the pathogenesis of myeloid leukaemias is still scarce. In this study we looked at the expression of the retinoblastoma gene product (p105) in 20 primary myelomonocytic and monoblastic leukaemias by Western blotting and immunocytochemistry using the anti-p105-monoclonal antibody PMG3-245. We found absence of or barely detectable levels of p105 in 11 patients (55%). Absence of or low levels of p105 were correlated with a higher leucocyte count at presentation (133 x 10(9)/l v 83 x 10(9)/l) and with the occurrence of extramedullary leukaemia (8/10 v 2/10). We conclude that abnormal expression of RB with absence of p105 or strongly reduced p105 levels occurs frequently in myelomonocytic and monoblastic leukaemias and that this may be correlated with a more malignant course of the disease.

Aged↗
PubMed1993

Granulocyte-monocyte colony-stimulating factor levels during hemodialysis-induced leukopenia.

Hemodialysis (HD), especially with cellulosic membranes, leads regularly to a transient but marked drop of peripheral neutrophils. Such neutropenia during the initial 10-30 min of HD is followed by a reincrease in granulocyte count up to a mild leukocytosis. Although this phenomenon accounts for the best documented side effect of HD, little is known about the underlying regulatory mechanisms. Therefore in this study the blood levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured during HD. Previous investigations have demonstrated that GM-CSF plays the central role in controlling the homeoiostasis of leukocytes by up- and downregulation of proliferation and efflux of cells out of the maturation compartment within the bone marrow. Three patients with chronic renal failure underwent HD with cuprophane membranes. In all cases a significant drop of peripheral granulocytes occurred, but GM-CSF levels remained unchanged and were found in the normal range during the whole period of the treatment. It is therefore concluded that GM-CSF may not be significantly involved in the regulation of peripheral leukocytes during HD.

Cellulose↗