Biomedical subjects
Publications and source records attributed to C Wolf.
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BACKGROUND: In a single-blind placebo-controlled study design we investigated the efficacy of acupuncture additionally applied to drug treatment in major depression. METHODS: We randomly included 70 inpatients with a major depressive episode in three different treatment groups: verum acupuncture, placebo acupuncture and a control group. All three groups were pharmacologically treated with the antidepressant mianserin. The verum group received acupuncture at specific points considered effective in the treatment of depression. The placebo group was treated with acupuncture at non-specific locations and the control group received pharmacological treatment plus clinical management. Acupuncture was applied three times a week over a period of 4 weeks. Psychopathology was rated by judges blind to verum/placebo conditions twice a week over 8 weeks. RESULTS: Patients who experienced acupuncture improved slightly more than patients treated with mianserin alone. CONCLUSIONS: Additionally applied acupuncture improved the course of depression more than pharmacological treatment with mianserin alone. However, we could not detect any differences between placebo and verum acupuncture.
A gene has been identified that is expressed specifically in stromal cells surrounding invasive breast carcinomas. On the basis of its sequence, the product of this gene, named stromelysin-3, is a new member of the family of metalloproteinase enzymes which degrade the extracellular matrix. The suggestion is that stromelysin-3 is one of the stroma-derived factors that have long been postulated to play an important part in progression of epithelial malignancies.
The efficacy of simple interventions for the improvement of memory performance in patients with dementia of Alzheimer type (DAT) has rarely been evaluated. Therefore, we examined the effects of presentation duration and task practice on word list learning in this sample: 19 patients with DAT and 21 control subjects (with remitted major depression) repeatedly performed modifications of a word list learning task using five different presentation durations (i.e. 1, 2, 5, 10 or 20 s/word). In agreement with previous observations, prolonged visual presentation of words significantly improved recall and recognition in demented subjects, whereas task practice did not improve memory performance. The performance in the demented sample after long presentation times (20 s/item) does not reach the level of performance of the comparison group after short presentation times (1 s/item). Consequently, it seems unlikely that memory dysfunction is caused by increased item processing times in patients with dementia. To reach comparable performance of demented and controls for intervention or activation studies, presentation times must be shortened below 1 s/item in the control sample.
Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms, and as a consequence, they induce different profiles of effects. For example, in utero treatment with the androgen receptor (AR) antagonist, flutamide, produces ventral prostate agenesis and testicular nondescent, while in contrast, finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT) synthesis, rarely, if ever, induces such malformations. In this regard, it was recently proposed that dibutyl phthalate (DBP) alters reproductive development by a different mechanism of action than flutamide or vinclozolin (V), which are AR antagonists, because the male offsprings display an unusually high incidence of testicular and epididymal alterations--effects rarely seen after in utero flutamide or V treatment. In this study, we present original data describing the reproductive effects of 10 known or suspected anti-androgens, including a Leydig cell toxicant ethane dimethane sulphonate (EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day-1), p,p'-DDE (100 mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone (P, 100 mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1 day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1 day-1), and polychlorinated biphenyl (PCB) congener no. 169 (single dose of 1.8 mg kg-1). Our analysis indicates that the chemicals discussed here can be clustered into three or four separate groups, based on the resulting profiles of reproductive effects. Vinclozolin, P, and DDE, known AR ligands, produce similar profiles of toxicity. However, p,p'-DDE is less potent in this regard. DBP and DEHP produce a profile distinct from the above AR ligands. Male offsprings display a higher incidence of epididymal and testicular lesions than generally seen with flutamide, P, or V even at high dosage levels. Linuron treatment induced a level of external effects consistent with its low affinity for AR [reduced anogenital distance (AGD), retained nipples, and a low incidence of hypospadias]. However, L treatment also induced an unanticipated degree of malformed epididymides and testis atrophy. In fact, the profile of effects induced by L was similar to that seen with DBP. These results suggest that L may display several mechanisms of endocrine toxicity, one of which involves AR binding. Chlozolinate and iprodione did not produce any signs of maternal or fetal endocrine toxicity at 100 mg kg-1 day-1. EDS produced severe maternal toxicity and a 45% reduction in size at birth, which resulted in the death of all neonates by 5 days of age. However, EDS only reduced AGD in male pups by 15%. Ketoconazole did not demasculinize or feminize males but rather displayed anti-hormonal activities, apparently by inhibiting ovarian hormone synthesis, which resulted in delayed delivery and whole litter loss. In summary, the above in vivo data suggest that the chemicals we studied alter male sexual differentiation via different mechanisms. The anti-androgens V, P, and p,p'-DDE produce flutamide-like profiles that are distinct from those seen with DBP, DEHP, and L. The effects of PCB 169 bear little resemblance to those of any known anti-androgen. Only in depth in vitro studies will reveal the degree to which one can rely upon in vivo studies, like those presented here, to predict the cellular and molecular mechanisms of developmental toxicity.
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OBJECTIVE: Primary myoadenylate deaminase deficiency (MADD) is probably the most frequent inborn metabolic myopathy with a prevalence of up to 2%. It is the result of mutations in the AMPDI gene, the most common of which is a C34-T transition in exon 2. The importance of the more rare mutation G468-T in exon 5 is uncertain. Primary objective was to elucidate the clinical significance of the enzyme disorder, which remains unclear since its first description in 1978. We further examined the existence of an association of MADD with other muscle disorders, such as malignant hyperthermia and rhabdomyolysis, as was suspected in earlier studies. MATERIAL AND METHODS: In a large collection of 1673 muscle biopsies that had been stored deep frozen we identified 33 cases of primary MADD, 12 of which without any other coinciding muscle diseases, by histochemical, biochemical and molecular genetic examinations. Clinical and laboratory data was collected. By additional examination of randomly chosen blood samples we identified one person carrying the rare compound heterozygosity C34-T/ G468-T, who was examined in clinical respects and a muscle biopsy was taken. RESULTS: As underlying mutation, the most common transition C34-T/C 143-T was detected in 33 cases. One patient carried the compound heterozygosity C34-T/G468-T. The overall frequency of MADD in the contingent was 1.8%. Only three patients out of 12 with isolated primary MADD suffered from muscle complaints, one of whom did not experience the typical symptoms of exercise related myalgia, muscle cramps and weakness as described by Fishbein. The patient carrying C34-T/G468-T was a fully healthy female. She had never experienced any muscle complaints. Any association with other neuromuscular disorders, if not completely ruled out, was found to be very unlikely. CONCLUSION: The results suggest that MADD itself is unlikely to be solely responsible for the manifestation of muscular symptoms. It is probable that either the loss of a compensation mechanism or coexistent disturbances in muscle metabolism which are unidentified so far are required for the emergence of complaints.
The effect of asymmetric phospholipids, such as platelet-activating factor (PAF), lyso-PAF and lysophosphatidylcholine, on phosphatidylcholine bilayers has been examined using ESR, 31P-NMR and X-ray diffraction methods. ESR and 31P-NMR experiments have been performed on oriented multibilayers. ESR measurements of 5-doxyl stearic acid, as a spin probe, show that PAF disorients phosphatidylcholine bilayers when present at molar ratios greater than 40%. This is manifest as a broadening of the local director orientation distribution, a parameter required to simulate the lineshape. Despite the marked change of the regular in-plane orientation of the films, there are only slight changes in the order parameter of the acyl chains. Cholesterol orients films containing asymmetric phospholipids, in a way consistent with the formation of 1/1 stoichiometric complexes between cholesterol and the asymmetric phospholipid. Such complexes can be detected with 3-doxyl cholestane, a spin-labelled sterol analogue interacting with lyso-PAF and PAF. Simulations of 31P-NMR resonance linewidth of oriented multibilayers of PAF/egg lecithin mixtures indicate a rippled structure which accounts for the perturbed distribution of the local director observed by ESR spin probe measurements. Micellisation of the film can be discounted on the basis of the 31P-NMR linewideth for the concentration range investigated. X-ray diffraction studies of liposomes of dimyristoyl- and dioleoyl-phosphatidylcholine containing PAF relate the disorientation of the film with the emergence of a lamellar interdigitated phase of reduced (4.2 nm) repeat distance. This interdigitated phase coexists with the lecithin lamellar phase (repeat spacing 6.0 nm) at temperatures below and above the gel-to-liquid crystal transition temperature of the lecithin. Cholesterol/PAF mixtures give X-ray diffraction patterns indexing a lamellar repeat distance of 6.7 nm. Cholesterol also prevents formation of interdigiatated lamellae with the various asymmetric phospholipids. A model is proposed where the asymmetric phospholipid segregates from lecithin to form 'blister-like' structures within the film consisting of thin interdigitated lamellae. Formation of complexes between cholesterol and the asymmetric lipid prevents the creation of these structures.
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Stromelysin-3 (ST3) belongs to the family of matrix metalloproteinases, a group of proteolytic enzymes which are believed to play a role in tumor invasion and metastasis. In the present study, we report that the ST3 gene, which was initially identified in invasive breast carcinoma, is expressed in most other invasive human carcinomas, but rarely in sarcomas and other nonepithelial tumors. In carcinomas, both ST3 RNA and protein were specifically detected in fibroblastic cells immediately surrounding the cancer cells. In agreement with this observation, the carcinomas which are known to progress without inducing a prominent tumor stroma are also those which usually do not express the ST3 gene. ST3 gene expression was also observed in noninvasive carcinomas of the breast, uterus cervix and bladder, where the probability of detecting ST3 RNA and protein positively correlated with the known risk of these lesions evolving towards invasion. Taken together, these observations further support the hypothesis that ST3 may contribute to tissue-remodeling processes associated with carcinoma progression, and may represent a new prognostic factor to define populations of aggressive tumors.
BACKGROUND: The aim of the present study was to investigate immunohistochemically the distribution of secretoneurin, a novel 33 amino acid peptide, in comparison to chromogranin A, chromogranin B, and secretogranin II in carcinoids of the appendix. MATERIALS AND METHODS: Paraffin-embedded tissues from 47 carcinoids were incubated with antibodies specific for chromogranin A, chromogranin B, the secretogranin II derived peptide LF- 19, and secretoneurin. RESULTS: 44 tumors (94%) were positive for secretoneurin, whereas only 39 tumors (83%) were immunoreactive for chromogranin A. There was no significant correlation between neuropeptide expression and type of carcinoid, tumor size, vascular infiltration, serosal involvement or mesoappendiceal infiltration. CONCLUSIONS: Our investigations revealed that secretoneurin is detected more frequently than chromogranin A in carcinoids of the appendix. This supports the theory that tumor cells of appendiceal carcinoids are of a different origin than other midgut carcinoids. No special tumor entity with a characteristic secretoneurin-chromogranin pattern could be identified.