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Biomedical subjects

M Lang

Publications and source records attributed to M Lang.

At least 19 recordsLinked to original sources
PubMed1992

Expression of pulmonary cytochrome P4501A1 and carcinogen DNA adduct formation in high risk subjects for tobacco-related lung cancer.

Cigarette smoking is the strongest risk factor for lung cancer (LC), but genetically determined variations in pulmonary metabolism of tobacco-derived carcinogens may affect individual risk. Results from a case-control study on LC patients demonstrated the pronounced effect of tobacco smoke on pulmonary xenobiotic metabolism and prooxidant state, and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated LC: LC patients who were recent smokers had significantly induced BP-3-hydroxylase (AHH) and ethoxycoumarin O-deethylase (ECDE) activities in lung parenchyma, when compared with smoking non-cancer patients. In recent smokers, lung AHH activity was positively correlated with the level of tobacco smoke-derived DNA adducts as determined by 32P-postlabelling. Pulmonary AHH activity also showed a good correlation with the intensity of immunohistochemical staining for cyt. P4501A by a monoclonal Ab in lung tissue sections: smoking and peripheral type of lung cancers were positively related to high levels of this cyt. P450 species, probably reflecting high rates of induction. These results suggest that high pulmonary CYP1A1 expression (controlling in part carcinogen DNA-adduct formation) in tobacco smokers, appears to be associated with LC risk. High risk subjects may thus be identifiable through genotyping assays for CYP1A1 polymorphism.

Aryl Hydrocarbon Hydroxylases↗
PubMed1992

Comparison of staple and Gambee techniques for enterotomy closure in the normal bovine jejunum.

Two suturing techniques for closure of jejunal enterotomies--the stapling and the Gambee technique--were compared in 7 bulls. Stapling was less time consuming (P less than 0.0001) and reduced the overall duration of surgery by 15%. Furthermore, the lumen diameter was significantly less decreased in the stapled intestine at 8 weeks after surgery (P less than 0.05). The diameter of the intestine increased significantly between 8 and 13 weeks after the Gambee suture had been applied (P less than 0.05) and the difference in diameter between intestines sutured according to Gambee and the stapled intestines disappeared. The intestinal diameter did not change significantly between 13 and 18 weeks in both techniques. The application of Gambee sutures resulted in fewer adhesions (P less than 0.01) and less thickening of the intestinal wall (P less than 0.0001). The surgery did not seem to affect the performance of the bulls significantly.

Animals↗
PubMed1991

Inducibility of P450Coh by pyrazole and its derivatives.

Pyrazole and several of its derivatives increase the hepatic microsomal coumarin 7-hydroxylase to a variable extent. The strongest inducers are pyrazole itself and those derivatives which have a hydroxy group or a halogen at the 4-position of the molecule. The increase in coumarin 7-hydroxylase is due to an increase in the microsomal P450Coh and the corresponding mRNA. The increase of P450Coh by pyrazole and 4-hydroxypyrazole is selective because several other mono-oxygenase enzymes and the total P450 content are either not affected or even decreased. These include the testosterone 15 alpha-hydroxylase (P45015 alpha), a close structural analogue of P450Coh, which is induced only marginally by pyrazole and even decreased by 4-iodopyrazole, and P450ac which is decreased by pyrazole and 4-hydroxypyrazole. Introducing a methyl residue at the 4-position will alter the induction properties of the compound essentially bymaking it less selective for P450Coh. These results demonstrate the special selective action of pyrazole and some of its derivatives on the hepatic microsomal mono-oxygenase complex and the unique mode of regulation of the cytochrome P450Coh even within the same subfamily of cytochromes P450.

Animals↗
PubMed1991

Fluorescence emission spectra of plant leaves and plant constituents.

The UV-B radiation (e.g. 337 nm) induced blue fluorescence (BF) and red chlorophyll fluorescence spectra (RF) of green leaves from plants with different leaf structure were determined and the possible nature and candidates of the blue fluorescence emission investigated. The blue fluorescence BF is characterized by a main maximum in the 450 nm region and in most cases by a second maximum/shoulder in the 530 nm region. The latter has been termed green fluorescence GF. The red chlorophyll fluorescence RF, in turn, exhibits two maxima in the 690 and 730 nm region. In general, the intensity of BF, GF and RF emission is significantly higher in the lower than the upper leaf side. The ratio of BF to RF emission (F450/F690) seems to vary from plant species to plant species. BF and GF emission spectra appear to be a mixed signal composed of the fluorescence emission of several substances of the plant vacuole and cell wall, which may primarily arise in the epidermis. Leaves with removed epidermis and chlorophyll-free leaves, however, still exhibit a BF and GF emission. Candidates for the blue fluorescence emission (lambda max near 450 nm) are phenolic substances such as chlorogenic acid, caffeic acid, coumarins (aesculetin, scopoletin), stilbenes (t-stilbene, rhaponticin), the spectra of which are shown. GF emission (lambda max near 530 nm) seems to be caused by substances like the alkaloid berberine and quercetin. Riboflavine, NADPH and phyllohydroquinone K1 seem to contribute little to the BF and GF emission as compared to the other plant compounds. Purified natural beta-carotene does not exhibit any blue fluorescence.

Chloroplasts↗
PubMed1991

Usefulness of antiplatelet drugs in the management of heparin-associated thrombocytopenia and thrombosis.

Heparin-associated thrombocytopenia and thrombosis is a severe complication of systemic heparin therapy. Its treatment is mainly based upon discontinuation of heparin therapy. However in some patients requiring emergency cardiac or vascular surgery, reexposure to heparin may be unavoidable. We report the management of two such patients by use of antiplatelet drugs for a vascular procedure. In the two cases, a combination of iloprost, a stable prostacyclin analogue (1 to 2 ng/kg/mn) with aspirin and dipyridamole was shown to inhibit ex vivo the heparin-induced platelet aggregation. These antiplatelet agents were continued during the perioperative period. A successful vascular procedure was achieved with full heparinization without subsequent thrombocytopenia or thrombotic or hemorrhagic complications. This experience supports the hypothesis that heparin can be readministered early to patients with heparin-associated thrombocytopenia and thrombosis, provided antiplatelet therapy is given.

Aged↗
PubMed1991

[Intestinal cellular reaction of cattle after infection by Fasciola hepatica].

Defence reactions of cattle against Fasciola hepatica take place not only in the liver but also on a prehepatic level. The aim of the present experiments is to identify and quantify the cellular response in the small intestine. Five groups of two bulls (Simmental x Red Holstein, 6 months old) were infected by oesophageal probe with metacercariae of F. hepatica (MC) according to two experimental procedures. Two groups of bulls served as controls. In the first experiment both infected groups received 1000 MC once or twice at an interval of five weeks. The intestinal tissue was taken before infection and 5, 10 and 19 weeks p.i., respectively 5 and 14 weeks p. reinf. (p.ri.). In the second experiment, three infected groups received 400, 2 x 400 MC (at an interval of five weeks) and 800 MC respectively. Biopsies were taken one week ante infectionem, 6, 11 and 19 weeks p.i., respectively 1, 6 and 14 weeks post reinfectionem (p. ri.). The biopsies of the small intestine were prepared for histology and the tissue sections stained as follows: Astra blue for mucosal mast cells (MMC), Lendrum for eosinophils (EOS) and Periodic Acid Schiff (PAS) for goblet cells (GC). The density of the three cell populations in the mucosa was determined microscopically and quantified. In both experiments the density of the MMC and EOS increased with each reinfection and depended on the infectious dose. There was no significant variation of the GC-numbers. The described intestinal cellular reactions suggest a participation of the small intestinal wall in the immunity against the common liver fluke.

Animals↗
PubMed1990

Highly selective inhibition of estrogen biosynthesis by CGS 20267, a new non-steroidal aromatase inhibitor.

CGS 20267 is a new non-steroidal compound which potently inhibits aromatase in vitro (IC50 of 11.5 nM) and in vivo (ED50 of 1-3 micrograms/kg p.o.), CGS 20267 maximally inhibits estradiol production in vitro in LH-stimulated hamster ovarian tissue at 0.1 microM with an IC50 of 0.02 microM and does not significantly affect progesterone production up to 350 microM. In ACTH-stimulated rat adrenal tissue in vitro, aldosterone production was inhibited with an IC50 of 210 microM (10,000 times higher than the IC50 for estradiol production); no significant effect on corticosterone production was seen at 350 microM. In vivo, in ACTH-treated rats, CGS 20267 does not affect plasma levels of corticosterone or aldosterone at a dose of 4 mg/kg p.o. (1000 times higher than the ED50 for aromatase inhibition in vivo). In adult female rats, a 14-day treatment with 1 mg/kg p.o. daily, completely interrupts ovarian cyclicity and suppresses uterine weight to that seen 14 days after ovariectomy. In adult female rats bearing estrogen-dependent DMBA-induced mammary tumors, 0.1 mg/kg p.o. given daily for 42 days caused almost complete regression of tumors present at the start of treatment. Thus compared to each other, CGS 16949A and CGS 20267 are both highly potent in inhibiting estrogen biosynthesis in vitro and in vivo. The striking difference between them is that unlike CGS 16949A, CGS 20267 does not affect adrenal steroidogenesis in vitro or in vivo, at concentrations and doses several orders of magnitude higher than those required to inhibit estrogen biosynthesis.

Animals↗
PubMed1990

A specific cis-acting element regulates in vitro transcription of sex-dependent mouse steroid 16 alpha-hydroxylase (C-P450(16 alpha)) gene.

The mouse steroid 16 alpha-hydroxylase (C-P450(16 alpha)) family consists of structurally similar genes with very divergent expressions (Wong, G., Itakura, T., Kawajiri, K., Skow, L., and Negishi, M. (1989) J. Biol. Chem. 264, 2920-2927). Of five family members, the C-P450(16 alpha) gene exhibits a male-specific expression whereas the P450cb gene is equally expressed in both males and females although the level of expression is much lower than that of the C-P450(16 alpha) gene. By DNase I footprinting and in vitro transcription of the C-P450(16 alpha) gene, we determined two cis-acting transcription elements. SDI (sex difference information) in the -84/-102 region from the transcription start site is one of the two cis-acting transcription elements, which is specific to the sex-specific C-P450(16 alpha) gene and confers a high transcription level of this gene. We substituted the nucleotide(s) in the SDI sequence to the corresponding base(s) in the P450cb gene promoter and tested each substituted gene promoter by in vitro transcription. The results indicate that the function of SDI as the transcription element depends most critically on the nucleotides at positions -100 to -98. Another cis-acting transcription element, CTE (common transcription element), is located between -44 and -68 in both C-P450(16 alpha) and P450cb genes. A column chromatography of nuclear extract indicates that the proteins bound to SDI and CTE are different. We speculate therefore that SDI is a specific and necessary element involved in the male-specific C-P450(16 alpha) gene transcription. The sequence comparisons of the corresponding regions of SDI and CTE among the mouse and the closely related rat P450 genes suggest that SDI is a newly evolved cis-acting element in the sex-specific C-P450(16 alpha) gene which arose through gene duplication and selective nucleotide substitution.

Animals↗
PubMed1990

ATP dependence of anion uptake by isolated vacuoles: requirement for excess Mg2+.

Vacuoles were isolated from barley mesophyll protoplasts. [14C]Malate or 36Cl- were taken up from the surrounding medium. Uptake was only slightly increased in the presence of equimolar levels of ATP and Mg2+ (as magnesium gluconate). In the presence of excess Mg2+ in the medium, ATP-stimulated uptake of malate and chloride increased several-fold. Stimulation by excess Mg2+ was not observed for ATP-stimulated amino acid uptake by isolated vacuoles. Stimulation of uptake by excess Mg2+ was observed at all malate concentrations upto 10 mmol.l-1. The content of Mg2+ needed for half-maximum stimulation was about 3.5 mmol.l-1 in the presence of 1 mmol.l-1 ATP. The increase in Mg2+ concentration had no effect on the tonoplast ATPase activity.

Adenosine Triphosphatases↗
PubMed1990

Parametric assessment of myocardial perfusion during interventional cardiac catheterization by means of X-ray densitometry-short-and long-term results.

X-ray densitometric evaluation of digital subtraction angiocardiograms allows an assessment of myocardial perfusion by means of the parameter 'MEAN RISE TIME' (MRT), defined as the time from the onset of local myocardial contrast medium opacification to the point of maximum opacification. Best results are obtained when the response of that parameter is compared before and after stimulation of coronary flow by papaverine. A prolongation of this parameter, especially after papaverine, was indicative of an impairment of myocardial perfusion, when compared to the results of TL-201 scintigraphy. In 50 patients with single vessel coronary artery disease the results of MRT pre and post papaverine before and after coronary angioplasty, as well as after 6 months were evaluated for 204 post-stenotic regions-of-interest. Before angioplasty papaverine induced a significant prolongation of post-stenotic MRT was measured 2.3 s +/- 0.9 s vs 3.1s +/- 0.8s; p less than 0.01), while after successful angioplasty post-stenotic MRT was measured significantly shorter after stimulation of coronary flow (2.6s +/- 1.0s vs. 1.9s +/- 0.9s; p less than 0.01). This indicated an improvement in myocardial perfusion. Nevertheless, 16/50 patients still presented pathological results of post-stenotic MRT after papaverine, although angioplasty was regarded successful. These patients presented a markedly higher rate of restenosis (14/16 patients after 6 months), a higher rate of dissections at the dilation site and a higher rate of dilated vessels, supplying myocardial areas after a Q-wave myocardial infarction. Thus, these results demonstrate the additional information about the short-and long-term outcome of an angioplasty procedure by densitometric myocardial perfusion analysis.

Absorptiometry, Photon↗
PubMed1990

The role of estrogens in schizophrenia gender differences.

The male/female differences that have been described in schizophrenia are important because they may ultimately shed light on factors that mediate the expression of schizophrenic illness. The hypothesis of this article is that estrogens, either directly or indirectly, modify symptom expression and account for many of the observed gender differences. The role of sex hormones is divided into organizational and activational effects. Organizational effects take place during a critical period in fetal life and put a permanent stamp on the developing brain. Activational effects are the direct influences of circulating hormones that appear when hormonal levels rise, and wane when hormonal levels drop. Because levels of sex hormones in adult women fluctuate during the menstrual cycle, cyclic effects of high and low female hormones may induce specific responses by the adult female brain. All these effects have implications for genetic, environmental, pharmacological, neurocognitive, clinical, and epidemiological research in schizophrenia.

Adult↗
PubMed1990

Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models.

During clinical trials, a clonidine transdermal device has been found to induce clonidine-specific allergic contact dermatitis in up to 25% of patients during a treatment period of 1 year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in-depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low-level clonidine allergy could be obtained only in a minority of animals, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV-treatments, C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man, with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even to extremely weak sensitizing drugs that can be safely used orally, and escape most currently available predictive contact allergy animal models. Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels.

Administration, Cutaneous↗
PubMed1990

Chronic schizophrenia: a risk factor for HIV?

Chronic mental patients may constitute a previously unrecognized high-risk group for the spread of the human immunodeficiency virus. This paper briefly reviews the literature on sexual awareness, sexuality, substance abuse, and schizophrenia, and addresses the problems of implementing sex education programs for chronic mental patients. Although problematic, such preventive programs are urgently needed.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Ile-Ser-bradykinin is an aberrant permeability factor in various human malignant effusions.

In this study we provide evidence for the presence of the aberrant peptide, Ile-Ser-bradykinin, in various human malignant exudates. The peptide was detected by deproteinisation of the effusion, application to reversed-phase HPLC, collection of the fractions containing Ile-Ser-bradykinin (retention time 6.90 min), degradation with carboxypeptidase B, and rechromatography of the resulting des-Arg-Ile-Ser-bradykinin (des-Arg-ISB) (retention time 13.5 min). In addition, all positive samples were confirmed by amino acid analysis and most of them (7/8) by amino-acid sequencing. In malignant effusions from 8 patients out of a group of 113 patients, Ile-Ser-bradykinin was found in concentrations between 12 and 520 mumol. In 44 malignant effusions, Ile-Ser-bradykinin was suspected, but could not be confirmed by the required additional methods (amino-acid analysis, sequencing) because of its low concentration. Sixty eight benign effusions were negative for Ile-Ser-bradykinin.

Amino Acid Sequence↗