Biomedical subjects
Publications and source records attributed to M Lang.
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.
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.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Cytochrome P-450coh from pyrazole-treated mice was shown to form a tight and specific complex with cytochrome b5 from mouse liver microsomes. The complex formation was found to result in type I spectral changes indicating a spin shift from the low to the high spin form. When added to a reconstituted system containing cytochrome P-450coh, NADPH-cytochrome P-450 reductase and phospholipid, cytochrome b5 stimulates hydroxylation of coumarin and O-deethylation of 7-ethoxycoumarin. The maximal stimulating effect is reached at a 1:1 stoichiometry. Mouse liver cytochrome b5 stimulates hydroxylation and deethylation by 100% and 60%, respectively. The stimulating effect of cytochrome b5 was found to result from the increase of the maximal rate of oxidation, being practically without effect on Km. Cytochrome b5 purified from rat and rabbit liver microsomes interacts with cytochrome P-450coh but fails to stimulate the oxidation reaction. At large excess, cytochrome b5 inhibits the oxidations catalyzed by cytochrome P-450coh. Immobilized cytochrome b5 either from mouse or rat and rabbit microsomes proved to be an efficient affinity matrix for cytochrome P-450coh purification.
Partial interruption of the inferior vena cava (IVCI) by a percutaneous endovenous filter (Günther filter n = 65, LEM filter n = 36) was undertaken in 100 patients with an average of 72 +/- 11 years for recent deep vein thrombosis. The indications were: contraindications to anticoagulant therapy (36.5%); recurrent pulmonary embolism (12%); threatening venous thrombosis with a previous embolic episode (12%); caval thrombosis (15.7%); prophylactic, with no previous pulmonary embolism (23.8%). The filters were evaluated at short and mid term. There were no technical problems. The mortality rate was 17.5%, one death being probably due to recurrent pulmonary embolism. No other recurrences of pulmonary embolism were observed, indicating an efficacy of 99 per cent. The early patency rate was 96.5%, there being no difference between the two filters used, independent of the initial site of venous thrombosis, of distal migration of the filter and associated medical treatment (anticoagulation). Distal migration was observed in 76% of IVCI by the Günther filter and 48.5% by the LEM filter (p less than 0.001); tilting was observed in 7.4% of Günther and 3% of LEM filters. Five LEM filters were incompletely opened. The IVC was transfixed by 3 Günther filters. One Günther filter had fractured spokes. There were 12 recurrences of lower limb deep vein thrombosis and 16 post-deep vein thrombosis complications were recorded. These percutaneous endovenous filters are similar to the Kimray Greenfield filter with respect to efficacy and permeability although the follow-up was relatively short. The advantages of these percutaneous filters are the facility, innocuity and rapidity of their insertion with, however, a higher incidence of distal migration.
Epithelioid hemangioma is a rare disorder in Europe, affecting the skin and subcutaneous tissue in young adults. The presented cases all involve the hand, and, in one case, the intrinsic muscles and periosteum.
We instilled 2 mg of pancreatic elastase into the lungs, and insufflated a further 2 mg into the trachea of 6 male ferrets. Six control animals were given 0.9% NaCl (lungs) and glucose powder (trachea). This combined treatment was administered on days 1, 8 and 15. On these days, and again on days 29 and 39, we obtained chest x-rays. On the 39th day, we removed the lungs and measured the mean linear intercept. In tracheal sections, we measured goblet cell density, glandular structure and function by quantitative histology and autoradiography. Although, up to day 39, no emphysema developed, both structural and functional changes occurred in the glands: the volume density of the serous glands (S) decreased, that of the mucous glands (M) increased, the ratio S/M decreased from 2.0 to 1.5 (p = 0.05). The turnover of radioactive sulphur (indication of mucus synthesis) was significantly increased in animals treated with elastase (p = 0.001). Goblet cells increased from 0.9 +/- 0.4 to 3.4 +/- 1.8 cells per mm epithelium (p = 0.05). The results show that elastase induces structural and functional changes in submucosal glands and goblet cell hyperplasia, independently of emphysema.
To investigate the mechanisms of action of nicotine we studied the effect of muscarinic and adrenergic receptor antagonists on nicotine-induced changes in the lungs and circulation. Nicotine increased mucus secretion from tracheal submucosal glands and caused bronchocon-striction. Cardiovascular effects were a bradycardia followed by tachycardia, hypertension and a biphasic increase in cardiac output. All of these effects were completely blocked by prior administration of hexamethonium. Propranolol and phentolamine prevented the increase in heart rate, and reduced the increase in blood pressure. Only atropine inhibited nicotine-induced hypersecretion and bronchocon-striction.
An immunochemical comparison of components of cholesterol side chain cleavage system from bovine adrenocortical and human placental mitochondria has been carried out. Antibodies against cytochrome P-450scc, adrenodoxin reductase and adrenodoxin from bovine adrenocortical mitochondria were shown to cross-react with corresponding antigens of human placental mitochondria. A highly sensitive immunochemical method for cytochrome P-450scc determination has been developed. Limited proteolysis of cytochrome P-450scc of human placental mitochondria was studied, and the products of trypsinolysis were identified using antibodies against cytochrome P-450scc and fragments of its polypeptide chain: F1, F2 and F3. Immunochemical relatedness of ferredoxins from bovine adrenocortical and human placental mitochondria allowed one to develop a fast and efficient method for cytochrome P-450scc purification from human placental mitochondria by affinity chromatography on adrenodoxin-Sepharose.
We identified type II P-450(15)alpha as mouse coumarin 7-hydroxylase (P-450coh). Unlike type I P-450(15)alpha, the other member within the mouse steroid 15 alpha-hydroxylase gene family, type II catalyzed little steroid 15 alpha-hydroxylase activity, yet structurally there were only 11 substitutions between type I and type II P-450(15)alphaS within their 494 amino acid residues (Lindberg et al., 1989), and the N-terminal sequence (21 residues) of P-450coh was identical with that of both P-450(15)alphaS. Induction by pyrazole of coumarin 7-hydroxylase activity correlated well with the increase of type II P-450(15)alpha mRNA in 129/J male and female mice. Pyrazole, on the other hand, was less in males or not effective in females in inducing the 15 alpha-hydroxylase activity and type I P-450(15)alpha mRNA. Expression of type I and II in COS-1 cells revealed that the latter catalyzed coumarin 7-hydroxylase activity at 10 to approximately 14 pmol min-1 (mg of cellular protein)-1. The former, on the other hand, had a high testosterone 15 alpha-hydroxylase but little coumarin 7-hydroxylase activity. It was concluded, therefore, that type II P-450(15)alpha is the mouse coumarin 7-hydroxylase. Identification of type II as the P-450 specific to coumarin 7-hydroxylase activity and characterization of its cDNA and gene, therefore, were significant advances toward understanding the basis of genetic regulation of this activity in mice (known as Coh locus).
Explore the source record for details and available documents.
We studied immunohistochemically cryostat sections made from fresh endometrial tissue, immediately frozen after removal (86 hysterectomy specimens, 6 curettages) for their content of oestrogen receptors (ER) using the ER-ICA assay. Routine histological sections were prepared from parallel specimens of the endometria for determining endometrial functions. The evaluation of the immunohistiological preparations showed that the ER content in the endometrium was closely related to the endogenous hormone stimulation. A further refinement and differentiation of that relationship became possible and correlated well with the various forms of follicle and corpus-luteum insufficiencies. The results indicated that it is now possible to recommend therapy of functional disorders of the endometrium, esp. in sterility cases, without need or knowledge of serum hormone levels. As the endometrial glandular proliferation increases, the density of the ER becomes more intense. In contrast, under therapy with predominantly gestagenic preparations or after these are discontinued, the ER are decreased more than found in normal glands at that degree of proliferation. Whereas the atrophic endometria of old age contained greatly diminished but still detectable ER, no ER could be found in endometrial atrophy induced by oral contraceptives. Carcinomatous endometria revealed a heterogeneous distribution of ER. The better the tumour cells were differentiated, the greater was the density of the ER. By contrast, the carcinomas derived from metaplastic Müllerian epithelium contained few or no ER. This difference is of practical importance, since an adjuvant anti-oestrogen therapy seems of value only with ER-positive carcinomas. The immunohistochemical determination of ER is more exact than the biochemical determination, for each single cell can be evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)
Etomidate, metomidate and metyrapone, all potent inhibitors of steroid metabolizing monooxygenases, inhibit preferentially coumarin 7-hydroxylase (COH) amongst several liver microsomal monooxygenase activities from control and pyrazole-treated D2 mice in vitro. SKF-525A, an inhibitor of phenobarbital-inducible monooxygenase activities has a much weaker effect on COH than the other three drugs, even though COH is a phenobarbital-inducible enzyme. Treatment of mice with eto- and metomidate decreases the microsomal COH also in vivo while the other activities remained unchanged (with the exception of 7-ethoxycoumarin O-deethylase (ECDE) in case of metomidate). Despite of the decrease in COH no parallel decrease in the amount of microsomal P450Coh (P450 isoenzyme highly active in the 7-hydroxylation of coumarin) could be found in dot immuno-binding analysis. These data suggest that among several liver microsomal P450 isoenzymes, metyrapone, eto- and metomidate interact preferentially with the P450Coh and that eto- and metomidate may alter selectively the catalytic properties of P450Coh leading to decreased enzyme activity. Two different Ks-values could be found for all three drug in their binding to microsomal cytochrome(s) P450. Based on substrate binding spectra, potassium ferricyanide treatment does not dissociate the complex between reduced P450 and metomidate and does it only partly for etomidate. Furthermore potassium ferricyanide treatment of microsomes does not increase COH after in vivo treatment of mice with eto- and metomidate. These data further suggest that the complex between P450Coh and eto- and metomidate may be particularly strong and independent from the redox state of the haem iron.
Complementary DNA (cDNA) probes were used to investigate the extrahepatic production of the major histocompatibility complex (MHC)-linked complement components C4, factor B and C2 in various normal human tissues. The presence of the corresponding messenger RNA (mRNA) was tested by Northern blot analysis. Complement C4 mRNA was found in liver, and with high intensity also in normal kidneys. In contrast, no C2 mRNA and only very low amounts of factor B mRNA could be detected in the kidney. Slot blot hybridization was performed to quantitate the amount of C4 mRNA, and the intensity of C4 mRNA hybridization in the kidney samples was about 25% compared with liver RNA. C4-specific transcripts were not present in isolated glomeruli but in the renal interstitium. Other human tissues, such as tonsil, spleen, thymus, brain, lung and peripheral mononuclear cells, contained no C4 mRNA. Low amounts of C4 mRNA were found in colon, thyroid gland, lymph node and breast carcinoma. The results obtained with lung, where C2 mRNA was found but no C4 mRNA, further indicate an independent, tissue-specific regulation of the class III gene expression. The results, showing that the complement C4 genes are transcribed very efficiently in normal human kidney, suggest a direct role of complement C4 in renal pathogenesis.
Twenty six patients with acute (less than 5 days) pulmonary embolism (PE) confirmed by bilateral pulmonary angiography with a Miller index greater than 15 were given tissue plasminogen activator (Alteplase) (rt-PA) intravenously (n = 20) or directly into the pulmonary artery (n = 6). The dosage was 100 mg/7 hours (bolus 10 mg + 40 mg/2 hours + 50 mg/5 hours). Heparin (5000 IV as a bolus and 1000 IV/hour) was associated in all cases. The Miller index decreased from 24 +/- 1 (n = 26) before treatment to 12 +/- 1 (n = 25) (p less than 0.001) after 100 mg of Alteplase, and from 25 +/- 0.4 (n = 14) to 22 +/- 0.5 (n = 14) (p less than 0.001) after 50 mg. The mean pulmonary arterial pressures fell from 30 +/- 2 mmHg to 21 +/- 2 mmHg after 50 mg (n = 26) (p less than 0.001) and to 14 +/- 1 (n = 25) (p less than 0.001) after 100 mg of Alteplase. A decrease in mean pulmonary artery pressures (-22%, p less than 0.001) and total pulmonary resistances (-29%, p less than 0.001) was obtained after one hour of thrombolysis in 12 monitored patients. There were no fatalities. Severe haemorrhage occurred in 6 cases. Therefore, Alteplase induced a rapid dissolution of recent intrapulmonary thrombi without inacceptable haemorrhagic complications. Its action could be particularly beneficial in patients with right ventricular failure due to life threatening pulmonary embolism.
In rat liver mitochondria there exists an AMP-dephosphorylating activity which converts external 5'-AMP to adenosine. It exhibits a pH optimum of 7.5 and a Km(AMP) of 0.085 mM. Furthermore, this activity is stimulated by magnesium (Km = 0.5 mM) and seems to be not affected by low concentrations of ATP or ADP. From the characteristics of the enzyme the existence of a 5'-nucleotidase in rat liver mitochondria which is localized on the outer surface of the inner mitochondrial membrane was concluded. The enzyme may be important for the production of cellular adenosine.