Effects of lisinopril on brain atrial natriuretic factor in uremic rats.
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Angiotensin II↗
Biomedical subjects
M Hofmann
Publications and source records attributed to M Hofmann.
Participation in normal immune responses of a metastasis-inducing splice variant of CD44.
A variant of the glycoprotein CD44 (CD44v) that shares sequences with variants causally involved in metastasis formation is transiently expressed on B and T lymphocytes and macrophages after antigenic stimulation and in the postnatal period. Antibodies to the variant hinder in vivo activation of both B and T cells. The observation that a protein domain that is expressed on CD44 and required for the lymphatic spread of tumor cells can catalyze an essential step in the process of lymphocyte activation supports the idea that metastasizing tumor cells mimic lymphocyte behavior.
Animals↗
[Peak flow profile and expert testimony. The significance of peakflow self assessment for pneumological expert testimony].
Quantitative assessment of pulmonary obstructive diseases, such as asthma, may be difficult because of variability of obstruction. This is particularly true with regard to expert evidence pulmonary physicians deliver to insurances. Severity of obstruction, degree of impairment by an obstructive ventilatory defect, and temporal relationship of bronchial obstruction to exposure, may not be detected by physiological measurements in the pulmonary function laboratory. Much of the expert's opinion on these matters will depend on the credibility he assigns to the insured individual. The insured individual, in the other hand, has no other proof available than the description of his complaints, which puts him at a disadvantage. Serial peak flow measurements can be instrumental in clarifying such issues. They add an objective dimension to the case history. Six cases in which expert evidence was commissioned by insurances are described in detail, to exemplify how the thinking of the experts was modified by peak flow profiles. The greater usefulness of serial peak flow measurements in occupational asthma is emphasized and problems that may arise with peak flow measurements are discussed.
Adult↗
Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity.
An empirical clustering technique was applied to data obtained from 321 male and female alcoholics to identify homogeneous subtypes having discriminative and predictive validity. The clustering solution identified two "types" of alcoholics who differed consistently across 17 defining characteristics in the male and female samples. One group, designated type A alcoholics, is characterized by later onset, fewer childhood risk factors, less severe dependence, fewer alcohol-related problems, and less psychopathological dysfunction. The other group, termed type B alcoholics, is characterized by childhood risk factors, familial alcoholism, early onset of alcohol-related problems, greater severity of dependence, polydrug use, a more chronic treatment history (despite their younger age), greater psychopathological dysfunction, and more life stress. The two types also differed with respect to treatment outcome assessed prospectively at 12 and 36 months. The results are consistent with historical and contemporary typological theories that have postulated similar subgroups of alcoholics. The findings suggest that an empirically derived, multivariate typology of alcoholism has theoretical implications for explaining the heterogeneity among alcoholics and may provide a useful basis for predicting course and estimating treatment response.
Adult↗
Liquid chromatography coupled with high-field proton NMR for profiling human urine for endogenous compounds and drug metabolites.
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Chromatography, High Pressure Liquid↗
[Clinical experiences with the Gianturco-Z stent in endotracheal and -bronchial stenoses].
We inserted Gianturco-Z stents in 17 patients with tracheobronchial stenoses on 18 occasions. Three patients had benign, all others malignant stenoses due to compression of the tracheobronchial tree by metastasising malignancies. In all cases the stents could be easily positioned and the patients experienced relief of their severe dyspnea. In one case there was fatigue breakage of the stent. The patient was therefore given a silicone tracheal stent.
Aged↗
Types of alcoholics: concurrent and predictive validity of some common classification schemes.
This study evaluated the discriminative power and predictive validity of five common typological schemes used to classify alcoholics for theoretical or clinical purposes. A heterogenous sample of 321 alcoholics was classified according to primary vs secondary alcoholism, parental alcoholism, Fellinek's gamma-delta distinction, gender, and subtypes derived from MMPI profiles. A prospective longitudinal cohort design was employed to compare the relative ability of these typologies to differentiate alcoholics according to natural history, alcohol-related consequences, response to treatment, and post-treatment adjustment. The findings indicate that while 'one-dimensional' typologies discriminate subgroups in terms of etiological variables, presenting symptoms, and drinking patterns, none of the classification systems emerges as a strong predictor of outcome status. In addition, these typologies do not discriminate well with respect to the alcoholic's drinking patterns and presenting symptoms, except in areas closely connected with the model (e.g. alcoholics with antisocial personality (ASP) indicate more social problems related to alcohol use than do primary alcoholics). Because there is a great deal of overlap among certain subtypes identified within different typological models (e.g. alcoholics with primary ASP tended to have a positive family history and a gamma pattern of impaired control), we hypothesize that empirical clustering techniques that search for naturally occurring commonalities among alcoholics may be a better way to identify homogeneous subtypes.
Adult↗
CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines.
One of several splice variants of CD44 expressed in metastasizing cell lines of rat tumors has been shown to confer metastatic potential to the non-metastatic variant of a rat pancreatic carcinoma line (U. Günthert et al., Cell, 65: 13-24, 1991). The variant-specific rat CD44 sequences were used to detect RNA expression in human cell lines: in carcinoma lines from lung, breast and colon; and in keratinocyte lines. By polymerase chain reaction amplification, complementary DNAs encoding human homologues were isolated and sequenced. The largest splice variant has been found in a large cell lung carcinoma line and in keratinocyte cell lines. It carries at least 5 additional domains (exons) encoding a total of 338 amino acids in the membrane-proximal extracellular region of the standard CD44. Various alternative splice products have been detected in other human tumor cell lines. The distribution of CD44 splice variants is consistent with the speculation that they fulfill functions in only a few restricted differentiation pathways and that in tumor cells these pathways have been reactivated.
Amino Acid Sequence↗
A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells.
Using a monoclonal antibody (MAb1.1ASML) raised against a surface glycoprotein of the metastasizing rat pancreatic carcinoma cell line BSp73ASML, cDNA clones have been isolated that encode glycoproteins with partial homology to CD44, a presumed adhesion molecule. In one of the clones, pMeta-1, the epitope marks an additional extracellular domain of 162 amino acids inserted into the rat CD44 protein between amino acid positions 223 and 247 (by analogy to human and murine CD44). The new variants are expressed only in the metastasizing cell lines of two rat tumors, the pancreatic carcinoma BSp73 and the mammary adenocarcinoma 13762NF; they are not expressed in the non-metastasizing tumor cell lines nor in most normal rat tissues. Overexpression of pMeta-1 in the nonmetastasizing BSp73AS cells suffices to establish full metastatic behavior.
Amino Acid Sequence↗
Urokinase-type and tissue-type plasminogen activators are essential for in vitro invasion of human melanoma cells.
This study evaluates the contribution of two types of plasminogen activators (PAs; tissue-type PA (tPA) versus urokinase-type PA (uPA) toward the invasiveness of human melanoma cells in a novel in vitro assay. We identified two human melanoma cell lines, MelJuso and MeWo, expressing uPA or tPA as shown at mRNA, protein, and enzyme activity level. MelJuso cells produced uPA as well as plasminogen activator inhibitor-1 (PAI-1). The latter was, however, not sufficient to neutralize the cell-associated or secreted uPA activity. MeWo cells secreted tPA, but the enzyme was not found to be cell-associated. PAI-1 production by these cells was not detectable. Plasminogen activation and fibrinolytic capacity of both cell lines were reduced by anticatalytic monoclonal antibodies specific for the respective type of PA or by aprotinin. In a novel in vitro invasion assay, antibodies to PA as well as aprotinin decreased the invasiveness of both cell lines into a fibrin gel, Matrigel, or intact extracellular matrix. Our results confirm the importance of uPA-catalyzed plasminogen activation in tumor cell invasiveness. Furthermore, we provide evidence that tPA, beyond its key role in thrombolysis, can also be involved in in vitro invasion of human melanoma cells.
Collagen↗
[Long-term treatment with amiodarone].
The aim of this study was to investigate the efficacy and the side effects of a long-term treatment with amiodarone. We analyzed the data of 41 patients in whom amiodarone therapy had been initiated between 1974 and 1984. Twenty-one patients had dilative cardiomyopathy, 14 patients had chronic myocardial infarction, four patients suffered from WPW syndrome with intermittent atrial fibrillation, one patient had aortic valve surgery, whereas in one patient there was no clinical evidence of a heart disease. All patients had salvos of ventricular extrasystoles, ventricular tachycardia or documented intermittent ventricular fibrillation. There have been seven drop-outs up to the present time. In each patient, the lowest antiarrhythmically effective dose was applied, which was generally higher in patients with low ejection fraction. Effective treatment of the ventricular tachycardia was achieved in 55-92% of patients and did not depend on the duration of treatment. In 10 patients in whom amiodarone therapy had to be stopped for various reasons. Sudden cardiac death was slightly more frequent than in the 24 patients treated with amiodarone, though the difference was not significant. In cases with a history of syncope the prognosis was poor, even with amiodarone therapy. Due to side effects, a dosage reduction or discontinuation of amiodarone treatment became necessary in 14 patients. Amiodarone proved to be an effective drug also for the long-term treatment of ventricular tachycardia, and possibly for the prevention of sudden cardiac death. With the exception of blue skin color, there was no accumulation of side effects, even during long-term treatment of several years.
Adult↗
[Effect of amiodarone on signal-averaged and long-term ECG].
This prospective study examined the influence of long-term amiodarone therapy on the parameters of the signal-averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose, 23 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and high-grade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after 2 months and, subsequently, every 3 months, a resting ECG, a signal-averaged ECG by Simson's method, and Holter monitoring were performed. Compared to the initial measurement, we found a significant increase in the duration of the total filtered QRS complex from an average of 114 +/- 24 ms to 127 +/- 35 ms, while the change in voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone; 10 patients showed a constant late potential, 12 patients had no late potential, and one patient with coronary heart disease developed a new late potential. In the long-term follow-up, we ascertained a relatively high responder rate under amiodarone between 41% and 81%. No relation could be detected between the results of the signal-averaged ECG and those of 24-h Holter monitoring.
Aged↗
[Free fatty acids as an indicator of preoperative stress and effects of premedication with flunitrazepam, morphine and promethazine on blood fatty acid level].
We investigated the influence of different oral premedication given to 50 male and 50 female patients on the plasmaconcentration of free fatty acids (FFA) as an indicator of preoperative stress and compared them with patients given no premedication at all. FFA are measured with a gaschromatographic method. FFA were measured four times: Time 1 (t1): the first day in hospital, t2: After the anesthesiologist's visit, t3: In the morning of the operation, t4: Before starting anesthesia. The groups are: I. 20 male and 20 female patients without any premedication; II. every 10 patients of both sexes given 2 mg Flunitrazepam (p.o.) on the preoperative night; III. every 10 patients given Morphium (0.15 mg i.m.) and Promethazin (50 mg i.m.) and, last, IV. every 10 patients getting the same premedication as group II and IV. 98 patients had a significant decrease of FFA from t1 to t2. The FFA of all increased from t2 to t3. Moreover, there was an increase from t3 to t4. We conclude from this that no premedication we had investigated is able to lower the physiological and biochemical stress-response as far as shown by FFA. Apart from myristic-acid, there was no difference in the groups. However, with no statistic significance, both 'Flunitrazepam-groups' showed the lowest increase. Further, in 28 from 32 cases, females had a higher FFA-level than males (in 16 cases with statistical significance).
Adolescent↗
[FTIR-microspectrophotometry for high resolution and highly sensitive detection of the carboxyhemoglobin complex].
Our recently developed method for rapid quantitative evaluation of carboxyhemoglobin in liquid as well as in dried blood samples has been considerably improved by the incorporation of an infrared microscope. Besides the characteristic bands at V = 1953 (cm-1) in liquid and V = 1968 (cm-1) in dry blood we found, upon addition of D2O, a dislocation of the bands at V = 1949 (cm-1). This reversible dislocation still permits a reliable identification of the COHb complex at the extremes of the capacity range of the measuring unit. Thus identification of the COHb complex was successful even in isolated erythrocytes. By means of this improved technique reliable quantitative evaluation may be carried out in a concentration range of between 2% and 0.05% whereas semiquantitative evaluation was possible at concentration down to 0.01%, allowing for instance the evaluation of the effects of a single inhalation of cigarette smoke. The positive identification of endogenous COHb fractions as well as of exogenous agents (smoking, environmental factors) which this method permits is prerequisite for a dependable interpretation of forensic-toxicologically relevant COHb findings.
Carboxyhemoglobin↗
Relation between epicardial electrograms and signal-averaged electrocardiograms after acute myocardial infarction in dogs.
Signal-averaged electrocardiograms allow the non-invasive detection of late potentials which represent locally delayed conduction in the myocardium. To validate this method, it is necessary to compare the signal-averaged data with electrograms recorded directly from the heart. However, the studies performed to date involve only a consecutive collection of the invasively and non-invasively obtained data. To obtain a more direct comparison, we examined this relation at operation by simultaneous epicardial and signal-averaged measurements. Acute infarction in animals was chosen, because the ischemic area is a zone of delayed conduction whose presence can be verified in a signal-averaged electrocardiogram. For this purpose, the left anterior descending artery, proximal of large septal and diagonal branches, was tied off in nine mongrel dogs after thoracotomy. Before infarction, a signal-averaged electrocardiogram was recorded from the body surface. At the same time, epicardial electrograms were performed using bipolar electrodes both from the supply area of the left anterior descending artery and from that of the circumflex artery. Five minutes after coronary ligation, both the epicardial measurements and the signal-averaged electrocardiogram were repeated on the open thorax. Before occlusion of the left anterior descending artery, narrow activation complexes occurred in general in the epicardial electrograms and no late potentials were recorded in any dog by the signal-averaged electrocardiogram. Five minutes after coronary ligation, fractionated and prolonged electrograms occurred in the epicardial recordings from the ischemic zone, while the activation complexes in the uninfarcted supply area of the circumflex artery remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Primary structure and functional expression of the alpha-, beta-, gamma-, delta- and epsilon-subunits of the acetylcholine receptor from rat muscle.
The isolation and characterization of five clones carrying sequences of the alpha-, beta-, gamma-, delta- and epsilon-subunit precursors of the rat muscle acetylcholine receptor (AChR) are described. The deduced amino acid sequences indicate that these polypeptides contain 457-519 amino acids and reveal the structural characteristics common to subunits of ligand-gated ion channels. The pattern of subunit-specific mRNA levels in rat muscle shows characteristic changes during development and following denervation, suggesting that innervation of muscle reduces the expression of the alpha-, beta- and delta-subunit mRNAs, suppresses the expression of the gamma-subunit mRNA, and induces expression of epsilon-subunit mRNA. Subunit-specific cRNAs generated in vitro were injected into Xenopus laevis oocytes, resulting in the assembly of two functionally different AChR channel subtypes. The AChR gamma, composed of the alpha-, beta-, gamma- and delta-subunits, has functional properties similar to those of the native AChRs in fetal muscle. The AChR epsilon, composed of alpha-, beta-, delta- and epsilon-subunits, corresponds to the end-plate channel of the adult muscle. Thus in rat skeletal muscle the motor nerve regulates the expression of two functionally different AChR subtypes with different molecular composition by the differential expression of subunit-specific mRNAs.
Amino Acid Sequence↗
[Isocyanate-induced respiratory tract diseases in Switzerland].
From 1980 to 1986 the Swiss National Accident Insurance Company (SUVA) recognized isocyanate-induced airway diseases as an occupational illness in 245 cases, which are presented retrospectively. Since isocyanates are widely used they are found at a large variety of workplaces. At present, isocyanates are the most frequent cause of occupational asthma in the Swiss industrial field. After complete avoidance of any further exposure respiratory symptoms persisted or airway obstruction could still be documented in one third of patients. An unfavourable prognosis is significantly associated with the following factors: (1) bronchial obstruction (FEVl/VC) at first pulmonary function test; (2) RAST positive for isocyanates; (3) long latency period between onset of symptoms and end of exposure. Therefore, individuals with isocyanate-induced airway diseases must be immediately removed from any further exposure to these substances.
Adolescent↗
[Treatment of coronary heart disease in the aged. When balloon dilatation, when surgery?].
Data from 3029 consecutive patients (2474 men, 555 women, mean age 59 [20-88] years) in whom coronary heart disease had been diagnosed by coronary angiography were studied with the object of identifying those patients in the older age group who are suitable for treatment by balloon angioplasty. There were 884 patients with a mean age of 70 (65-88) years, and 2145 patients with a mean age of 54 (20-64) years. Single vessel disease was less common in older patients (30% vs 44%; P less than 0.001), double vessel disease was equally common in both groups (28% vs 30%) and triple vessel disease was commoner in the elderly group (42% vs 26%; P less than 0.001). For elderly patients with single vessel disease conservative treatment was chosen in 50%, angioplasty in 49% and operative treatment in only 1%. Of elderly patients with involvement of two arteries, 44% were treated conservatively, 40% by angioplasty and 16% surgically. Of elderly patients with triple artery disease, 23% were treated conservatively, 8% by angioplasty and 69% operatively. This pattern was similar to that among younger patients. The success rate and the incidence of complications after percutaneous transluminal coronary angioplasty were similar in both age groups. In elderly patients with disease of only one or two coronary arteries the prospects of success and the risks are comparable to those in younger patients, but patients with triple artery disease often need bypass surgery.
Adult↗