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M Hofmann

Publications and source records attributed to M Hofmann.

At least 37 records · Page 2Linked to original sources
PubMed1993

The two major CD44 proteins expressed on a metastatic rat tumor cell line are derived from different splice variants: each one individually suffices to confer metastatic behavior.

The metastatic pancreas carcinoma cell line BSp73ASML produces a variety of different splice variants of the transmembrane glycoprotein CD44. The NH2-terminal portions are identical and heavily glycosylated. The variant sequences are inserted just outside the transmembrane region of the molecules. The two most abundant variants have 162 and 85 extra amino acids, respectively. When individually expressed, these suffice to establish metastatic properties in the nonmetastatic tumor cell line BSp73AS, as assayed by the spontaneous metastasis protocol.

Adenocarcinoma↗
PubMed1993

Splicing choice from ten variant exons establishes CD44 variability.

The enormous heterogeneity of the surface protein designated CD44 is in part due to posttranslational modification, and in part due to differential splicing. Alternative splicing occurs within one particular region encoding the extracellular portion of the protein. Comparison of various cDNA clones with different 'inserts' in this variable region with sequences of genomic clones from the mouse has revealed the existence of at least ten exons from which sequences are chosen by alternative splicing. Various combinations of these exons account for the tremendous heterogeneity of CD44 molecules expressed in different tissues, and in progressing tumor cells. The existence of different isoforms of CD44 suggests a broad spectrum of yet unknown physiologic functions.

Amino Acid Sequence↗
PubMed1993

High-performance liquid chromatography coupled to high-field proton nuclear magnetic resonance spectroscopy: application to the urinary metabolites of ibuprofen.

The use of coupled reversed-phase high-performance liquid chromatography and high-field proton nuclear magnetic resonance spectroscopy (HPLC-NMR) for the detection and identification of the urinary metabolites of ibuprofen is described. Urine was obtained from a healthy human volunteer following a normal therapeutic dose of 400 mg of ibuprofen. Analysis was performed on both a freeze-dried urine concentrate and partially purified extracts obtained by solid-phase extraction onto C-18 bonded silica gel. Both continuous and stop-flow methods were used to obtain spectra enabling the major urinary metabolites of ibuprofen to be detected and identified.

Chromatography, High Pressure Liquid↗
PubMed1993

Prevention of tumor metastasis formation by anti-variant CD44.

A splice variant of CD44 (CD44v) originally discovered on metastases of a rat pancreatic adenocarcinoma (BSp73ASML) has been shown by transfection to confer metastatic behavior to nonmetastatic tumor cells (Günthert U., M. Hofmann, W. Rudy, S. Reber, M. Zöller, I. Haussmann, S. Matzku, A. Wenzel, H. Ponta, and P. Herrlich. 1991. Cell. 65:13). A monoclonal antibody (mAb), 1.1ASML, to the metastasis-specific domain of the CD44v molecule retards growth of lymph node and lung metastases of the metastatic tumor line BSp73ASML, and can efficiently prevent formation of metastases by the transfected line. The antibody is only effective when given before lymph node colonization. Anti-CD44v does not downregulate the expression of CD44v, and prevention of metastatic growth by anti-CD44v is not due to activation of any kind of immune defense. We suggest that the mAb interferes with proliferation of metastasizing tumor cells in the draining lymph node, most probably by blocking a ligand interaction. The interference with metastatic spread will greatly facilitate the exploration of the function of CD44v and, in particular, may also open new strategies for the therapy of human metastases.

Animals↗
PubMed1993

Coupling of HPLC with 19F- and 1H-NMR spectroscopy to investigate the human urinary excretion of flurbiprofen metabolites.

Results of an on-line HPLC-NMR analysis of human urine from a volunteer administered the anti-inflammatory drug flurbiprofen are reported. The two major human urinary metabolites, namely the glucuronides of flurbiprofen and of 4'-hydroxyflurbiprofen, have been identified using 1H- and 19F-NMR spectroscopy. In vivo conjugation of the racemic drug and its metabolites with D-glucuronic acid results in diastereomeric molecules which give resolved NMR spectra thereby permitting the diastereomeric proportions to be evaluated. The cause of the observed deviation from equal proportions is discussed. This study represents the first use of both 19F- and 600 MHz 1H-NMR spectroscopy coupled to HPLC.

Chromatography, High Pressure Liquid↗
PubMed1993

Expression of CD44 isoforms carrying metastasis-associated sequences in newborn and adult rats.

Expression of a splice variant of CD44, recognised by the monoclonal antibody (Mab) 1.1ASML, confers metastatic potential to non-metastasising tumour cells (Cell 1991, 65, 13-24). To explore whether the metastasis-associated variant of CD44 (CD44v) is expressed under physiological conditions, tissues of newborn and adult rats were stained with the Mab 1.1ASML. The 1.1ASML epitope is, indeed, expressed on the basal layer of the epidermis and the hair follicles as well as on cryptic epithelia in the gut. In addition, ductal epithelia of the pancreatic gland of newborn rats express CD44v. This pattern of expression differs from that of standard lymphocyte CD44 (CD44s). The anti-CD44s mAB Ox50 predominantly stains connective tissue. Although different variants of CD44 may express the epitope recognised by 1.1ASML, cells expressing CD44v share properties with metastasising tumour cells: the stage of proliferation and a restricted degree of mobility. Thus, during metastatic progression tumour cells may reactivate the expression of gene segments which serve highly specialised functions in embryonic and adult tissues.

Aging↗
PubMed1993

A human homologue of the rat metastasis-associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps.

A recently described splice variant of CD44 expressed in metastasizing cell lines of rat tumors has been shown to confer metastatic potential to a non-metastasizing rat pancreatic carcinoma cell line and to non-metastasizing sarcoma cells. Homologues of this variant as well as several other CD44 splice variants are also expressed at the RNA level in human carcinoma cell lines from lung, breast, and colon, and in immortalized keratinocytes. Using antibodies raised against a bacterial fusion protein encoded by variant CD44 sequences, we studied the expression of variant CD44 glycoproteins in normal human tissues and in colorectal neoplasia. Expression of CD44 variant proteins in normal human tissues was readily found on several epithelial tissues including the squamous epithelia of the epidermis, tonsils, and pharynx, and the glandular epithelium of the pancreatic ducts, but was largely absent from other epithelia and from most non-epithelial cells and tissues. In human colorectal neoplasia CD44 variant proteins, including homologues of those which confer metastatic ability to rat tumors, were found on all invasive carcinomas and carcinoma metastases. Interestingly, focal expression was also observed in adenomatous polyps, expression being related to areas of dysplasia. The distribution of the CD44 variants in human tissues suggests that they play a role in a few restricted differentiation pathways and that in colorectal tumors one of these pathways has been reactivated. The finding that metastasis-related variants are already expressed at a relatively early stage in colorectal carcinogenesis and tumor progression, i.e., in adenomatous polyps, suggests the existence of a yet unknown selective advantage linked to CD44 variant expression. The continued expression in metastases would be compatible with a role in the metastatic process.

Antibodies, Monoclonal↗
PubMed1993

Activated mouse astrocytes and T cells express similar CD44 variants. Role of CD44 in astrocyte/T cell binding.

The CD44 adhesion molecule is expressed by astrocytes, glial-type cells which exhibit features of accessory cells for immune responses in the central nervous system. In primary cultures of mouse astrocytes, we have observed that surface expression and mRNA levels of CD44 are induced following stimulation with either PMA, or tumor necrosis factor alpha plus gamma interferon. Comparison of CD44 splice variants expressed by astrocytes and a T cell hybridoma shows that upon activation, both cell types express a similar pattern of CD44 transcripts. Thus, in both cell types, CD44 transcripts are produced which contain additional exons, including the exon v6 (known to be expressed by in vivo activated lymphocytes and by metastatic variants of tumor cells) as well as variants of larger size. In the autoimmune disease multiple sclerosis, activated T cells cross the blood-brain barrier and lead to inflammation in the central nervous system. Analysis of mice with experimental allergic encephalomyelitis, frequently used as an animal model of multiple sclerosis, shows that CD44 is induced in vivo on glial cells surrounding inflammatory lesions. Using an in vitro model for adhesion between T cells and astrocytes, we have found a correlation between the activation state of these cells and their adhesion potential. Dose-dependent inhibition of adhesion by hyaluronate and by anti-CD44 monoclonal antibody KM81 shows that CD44 is involved in the adhesive interactions between T cells and astrocytes.

Animals↗
PubMed1993

[Plasma concentrations of non-esterified fatty acids and lipids in high-dose medroxyprogesterone therapy of metastatic breast cancer].

The objective of this study was to investigate the influence of high dose MPA on serum cholesterol, triglyceride, phospholipids as well as free fatty acids given to 17 patients with metastatic breast cancer. Before the therapy, the patients with cancer revealed higher level in serum cholesterol, triglyceride, phospholipids and C 12:0, C 18:0 as we found it in the control (13 patients without cancer). There was no significant change in lipid parameters by treatment with MPA whereas cortisol decreases and insulin increases under therapy. The results are discussed under biochemical aspects.

Blood Glucose↗
PubMed1993

[Fiberoptic intubation and stress].

Nasotracheal intubation of the trachea by means of fiberoptic endoscopy is an accepted approach to difficult airways. The associated avoidance of direct laryngoscopy may affect the stress response to nasotracheal intubation. We tested this hypothesis by means of a prospective, randomized, controlled clinical study. METHODS. Informed consent was obtained from 30 patients presenting for maxillofacial surgery for participation in this study. Patients were allocated to three groups: nasotracheal intubation to be performed either fiberendoscopically (group 1) or laryngoscopically, with (group 2) or without (group 3) topical anaesthesia of the larynx. Haemodynamic variables (arterial blood pressure and heart rate) and concentrations of catecholamines* in plasma (adrenaline, noradrenaline; HPLC) were documented at four (two*) time points, respectively: prior to induction of anaesthesia*, after induction, 1 min after tracheal intubation*, 5 min after tracheal intubation. Differences between time points and between groups were analysed with the chi-square test; a probability of P < 0.05 was considered statistically significant. RESULTS. With respect to age, body-weight and gender, the groups were comparable. No major hemodynamic or endocrine stress responses were observed in any group. Diastolic blood pressures were significantly lower in groups one and two, one minute after tracheal intubation. DISCUSSION. Nasotracheal intubation does not provoke a major stress response, when performed in accordance with the protocol of this study. However, topical anaesthesia of the larynx, as well as the fiberendoscopic approach proved superior to control with respect to diastolic arterial pressure. We conclude that fiberoptic nasotracheal intubation, or laryngoscopy preceded by topical anaesthesia of the larynx may be useful in patients for whom an increase in rate pressure product would be undesirable.

Adolescent↗
PubMed1993

Stability of amiodarone in serum samples under various storage conditions.

The present study was intended to examine the stability of amiodarone (Cordarex, CAS 1951-25-3) and its metabolite desethylamiodarone. For this purpose 20 ml of blood were taken from each of 12 patients treated with amiodarone and were stored, after centrifuging, at room temperature, +5 degrees C, -18 degrees C and -38 degrees C. The amiodarone and desethylamiodarone concentrations were determined by the HPLC method 30 min, 24 h, 48 h, 72 h, one and two weeks after blood-taking. It turned out that the serum levels decreased continuously as of the first day regardless of the storage temperature. Correction factors were therefore calculated for the amiodarone concentration: if the blood level determination takes place after 24 h one should add 8% to the obtained value, after 48 h 16%, after 72 h 19%, after one week 23% and after two weeks 32%.

Adult↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

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↗