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Biomedical subjects

D Lenz

Publications and source records attributed to D Lenz.

16 recordsLinked to original sources

Circulating endothelial progenitor cells are inversely correlated with the median oxygen tension in the tumor tissue of patients with cervical cancer.

Tumor hypoxia leads to adaptive responses in cancer cells, including an induction of vasculogenesis initiated by circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs). The aim of the present study was to correlate the number of EPCs and CECs with the oxygenation of cervical cancer. Blood concentrations of EPCs were detected by FACS analysis with antibodies for CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). CECs were evaluated by double staining for 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Di-LDL) and lectin in a cell culture assay. Ten patients with cervical cancer were compared with ten healthy volunteers. Intratumoral oxygen tension was assessed polarographically with the computerized Eppendorf histography system. Analysis of CEC numbers revealed no difference between patients and controls. However, patients had lower concentrations of CD34-positive hematopoietic stem cells (HSCs) but a significantly higher fraction of EPCs related to the number of HSCs (1.09% versus 0.53%). This fraction was significantly inversely correlated to the median oxygen tension (r = -0.74, p = 0.015). Our study shows for the first time a significant inverse correlation between the fraction of EPCs and intratumoral oxygen tension. We conclude that the fraction of EPCs should be further evaluated as a useful and convenient marker in the prediction of tumor tissue oxygenation.

Endothelium, Vascular↗

Transforming growth factor beta1 inhibits aldosterone and cortisol production in the human adrenocortical cell line NCI-H295R through inhibition of CYP11B1 and CYP11B2 expression.

Transforming growth factor beta1 (TGFbeta1) has been shown to exert strong inhibitory effects on adrenocortical cell steroidogenesis. However, the molecular targets of TGFbeta1 in adrenocortical cells appear to differ between species. Here, we report the first characterization of the regulatory effects of TGFbeta1 on the steroidogenic functions of the human adrenocortical tumor cell line NCI-H295R. After treatment with 2 ng/ml TGFbeta1 for 24 h, basal production of corticosterone, cortisol and androstenedione was dramatically decreased. When TGFbeta1 was added simultaneously with forskolin, the production of cortisol and 11-hydroxyandrostenedione was decreased by 85% whereas that of deoxycortisol was increased. When TGFbeta1 was added simultaneously with angiotensin II, aldosterone production was reduced by 80%. We observed that TGFbeta1 strongly inhibits forskolin-induced steroid 11beta-hydroxylase activity and CYP11B1 mRNA levels, as well as angiotensin II-induced aldosterone synthase activity and CYP11B2 mRNA levels. CYP11B1 and CYP11B2 gene products thus appear as the major steroidogenic enzymes down-regulated by TGFbeta1 in the human adrenocortical tumor cell line NCI-H295R.

Adrenal Cortex↗

Zone-specific localization of cytochrome P45011B1 in human adrenal tissue by PCR-derived riboprobes.

Cytochrome P45011B1 (11 beta-hydroxylase) was detected in the human adrenal cortex and in human adenomas by in situ hybridization methods. Specific riboprobes were generated by in vitro transcription of 11 beta-hydroxylase--specific synthetic oligonucleotides with attached T7 and SP6 polymerase promotors. [35S]- and digoxigenin-labeled riboprobes were hybridized to sections of an aldosterone-producing adenoma (APA), the non-tumour portion of the corresponding adrenal gland, and two adenomas not related to hyperaldosteronism using standard protocols and varying washing conditions. After exposure of the radiolabeled sections to X-ray film, the signals were quantified and compared by statistical tests. Following autoradiography or immunohistochemical detection of the digoxigenin cytochrome P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis of non-tumour portion of an human adrenal with an APA. Zona glomerulosa, medulla and connective tissue were free of label. As revealed by the semi-quantitative analysis, 11 beta-hydroxylase mRNA signals in the APA were significantly lower than those in the attached non-tumour portion and the other two adenomas. The results confirm known observations on the occurrence of cytochrome P45011B1 in the adrenal cortex of other species, but show, contrary to several immunohistochemical studies, that the enzyme is obviously not expressed in the zona glomerulosa.

Adenoma↗

Structural and functional studies on the human hepatic interleukin-6 receptor. Molecular cloning and overexpression in HepG2 cells.

cDNAs coding for the human hepatic interleukin-6 receptor (IL-6-R) have been isolated from a library made from poly(A) RNA of dexamethasone-treated human hepatoma cells (HepG2). We found the hepatic IL-6-R to be identical to the one expressed by leucocytes. A polyclonal antiserum was raised in rabbits against the IL-6-R protein expressed in Escherichia coli. Although the entire IL-6-R protein was used for immunization, only antibodies to the cytoplasmic domain of the IL-6-R were obtained. It is demonstrated by affinity cross-linking and subsequent immunoprecipitation with antibodies against the ligand as well as against the receptor that the cloned cDNA codes for the functional IL-6-R on HepG2 cells. When the hepatic IL-6-R cDNA was overexpressed in HepG2 cells, these cells became more sensitive to low concentrations of IL-6 with respect to the induction of gamma-fibrinogen mRNA.

Amino Acid Sequence↗

Structural and functional studies on the human interleukin-6 receptor. Binding, cross-linking, internalization, and degradation of interleukin-6 by fibroblasts transfected with human interleukin-6-receptor cDNA.

A cDNA coding for the human interleukin-6 receptor (IL-6-R) has been expressed stably in murine NIH/3T3 fibroblasts. Transfected cells exhibited a single class of binding sites for 125I-labeled recombinant human interleukin-6 (125I-rhIL-6) (Kd = 440 pM, 20,000 receptors per cell). Affinity cross-linking of 125I-rhIL-6 to the IL-6-R-expressing NIH/3T3 cells led to the detection of three 125I-rhIL-6-containing protein complexes with molecular masses of 100, 120, and 200 kDa suggesting a complex organization of the IL-6-R in the plasma membrane. IL-6 added to the transfected NIH/3T3 cells exerted growth inhibition. This anti-growth effect was observed by the measurement of cell numbers and ornithine decarboxylase mRNA expression. IL-6-R overexpressing fibroblasts internalized 125I-rhIL-6. Intracellular limited proteolysis of IL-6 could be demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible implication of skin fibroblasts in the catabolism of IL-6 is discussed.

Autoradiography↗

Studies on the structure and regulation of the human hepatic interleukin-6 receptor.

Affinity cross-linking of 125I-labeled recombinant human interleukin-6 (IL-6) to human hepatoma cells (HepG2) allowed the detection of three IL-6-containing complexes with molecular masses of 100 kDa, 120 kDa and 200 kDa. Treatment of HepG2 cells with dexamethasone led to a time- and dose-dependent up-regulation of IL-6-receptor mRNA levels. By the use of cross-linking this effect was also seen at the protein level, where all three IL-6-binding complexes increased upon incubation of HepG2 cells with dexamethasone. Under conditions of IL-6-receptor up-regulation by dexamethasone, gamma-fibrinogen mRNA induction by IL-6 is stronger and occurs earlier than without dexamethasone. We propose therefore that the expression of the IL-6 receptor might be a rate-limiting step in acute-phase-protein induction.

Carcinoma, Hepatocellular↗

[Profile of a respiratory allergy department from computerized data collected between 1968 and 1984 (3962 cases)].

A prospective study of clinical, cutaneous and biological sensitivity to the common air-borne allergens was conducted over a 16-year period in a total of 3,962 patients who reported to a hospital consultation for respiratory allergy. The study confirmed certain widely recognized semiological features, but it did it on the basis of a real population with a large number of subjects and therefore was a true textbook of allergology with a live material. In addition, the study benefited from the major advantage of computer data processing: an accurate and rapid analysis. Yet some uncertainties and omissions remained concerning answers to certain questions, but such gaps are inherent in the natural subjectivity of allergic patients and their doctors.

Adolescent↗

[Clinical aspects of occupational asthma].

Although on the increase overall, the actual prevalence of occupational asthma is difficult to assess because of variations seen according to periods, countries, jobs, and the agents responsible. In the authors' experience, this prevalence is slightly less than 10%. Three principal mechanisms, sometimes present together, not always elucidated: immunological, reflex and irritative, are responsible for such asthma. Whilst a positive diagnosis raises few problems, the aetiological diagnosis is difficult and involves two stages: recognition of the occupational characteristic of the asthma and attribution of this asthma to an allergen or substance in the occupational environment. Skin tests and in vitro tests, but above all exposure tests, make an important diagnostic contribution. Personal examples are used to illustrate the principal aetiological factors in occupational asthma of animal, vegetable or chemical origin.

Asthma↗

[Surgical treatment of endometriosis of the large intestine (author's transl)].

Endometriosis is a sufficiently common disease that should always be considered in the differential diagnosis of colon lesions in women of child bearing age. Six selected cases illustrate problems of diagnosis and management of endometriosis of the colon. Characteristics of colon endometriosis are typical large-bowel symptoms such as colicky pains and hemorrhage usually situated in the sigmoid and rectosigmoid region, extramucosal radiologic appearance of a marked smooth-walled stenosis, and the difficult endoscopic and histological preoperative diagnosis. Suspected malignancy and the presence of the symptoms of a colon lesion are indications for bowel resection, which is an effective form of therapy.

Adult↗

[Ectopic pregnancy near term (case-report) (author's transl)].

Description of a case of ectopic pregnancy during the last 3 months with a living, malformed and underdeveloped neonate. Possible treatment is discussed: where as in our case there is a secondary ectopic pregnancy (i.e.a pregnancy started primarily in the tube and still in vascular contact with it but secondarily ectopic) removal of placenta following ligation of the main vessels arising from the tube is possible and recommended. In the much rarer primary ectopic pregnancy with primary nidus in the abdomen, removal of the placenta is dangerous and not advised because of the danger of diffuse hemorrhage.

Cesarean Section↗

Human adrenal CYP11B1: localization by in situ-hybridization and functional expression in cell cultures.

CYP11B1 was detected in the human adrenal cortex and in human adenomas by in situ-hybridization methods. Specific riboprobes were generated and hybridized to sections of an Aldosterone Producing Adenoma (APA), the non-tumour portion of the corresponding adrenal gland and two adenomas not related to hyperaldosteronism. P45011B1 mRNA was clearly localized in the zona fasciculata/reticularis. Semi-quantitative analysis has been performed and seems to be applicable for a further classification of adrenal tumours. Stable expression of CYP11B1 cDNA was performed in V79 cells. The interference of different substances (metyrapone, spironolactone and different imidazole derivatives) with CYP11B1 activity was studied using this cell line. The cell line revealed to be suitable for analysis of the active site of CYP11B1 as well as for analysis of side effects of drugs on steroidogenesis.

Adenoma↗