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M Leonhardt

Publications and source records attributed to M Leonhardt.

At least 19 recordsLinked to original sources
PubMed2004

Rate-limiting reactions determining different activation kinetics of Kv1.2 and Kv2.1 channels.

To identify the mechanisms underlying the faster activation kinetics in Kv1.2 channels compared to Kv2.1 channels, ionic and gating currents were studied in rat Kv1.2 and human Kv2.1 channels heterologously expressed in mammalian cells. At all voltages the time course of the ionic currents could be described by an initial sigmoidal and a subsequent exponential component and both components were faster in Kv1.2 than in Kv2.1 channels. In Kv1.2 channels, the activation time course was more sigmoid at more depolarized potentials, whereas in Kv2.1 channels it was somewhat less sigmoid at more depolarized potentials. In contrast to the ionic currents, the ON gating currents were similarly fast for both channels. The main portion of the measured ON gating charge moved before the ionic currents were activated. The equivalent gating charge of Kv1.2 ionic currents was twice that of Kv2.1 ionic currents, whereas that of Kv1.2 ON gating currents was smaller than that of Kv2.1 ON gating currents. In conclusion, the different activation kinetics of Kv1.2 and Kv2.1 channels are caused by rate-limiting reactions that follow the charge movement recorded from the gating currents. In Kv1.2 channels, the reaction coupling the voltage-sensor movement to the pore opening contributes to rate limitation in a voltage-dependent fashion, whereas in Kv2.1 channels, activation is additionally rate-limited by a slow reaction in the subunit gating.

Animals↗
PubMed2004

Prenatal stress induces intrauterine growth restriction and programmes glucose intolerance and feeding behaviour disturbances in the aged rat.

There is growing evidence that prenatal adversities could be implicated in foetal programming of adult chronic diseases. Since maternal stress is known to disturb the foetal glucocorticoid environment, we examined the consequences of prenatal stress on foetal growth, on glucose-insulin metabolism and on feeding behaviour in the aged male rat. In foetuses at term, maternal stress reduced body, adrenal and pancreas weight as well as plasma corticosterone and glucose levels. In aged male rats (24 months of age), prenatal stress induced hyperglycaemia and glucose intolerance and decreased basal leptin levels. Moreover, after a fasting period, they showed an increased food intake. These data suggest that maternal stress induces a long-lasting disturbance in feeding behaviour and dysfunctions related to type 2 diabetes mellitus. This programming could be linked to the early restricted foetal growth and to the adverse glucocorticoid environment in utero.

Adrenal Glands↗
PubMed2001

Semiquantitative morphology of human prostatic development and regional distribution of prostatic neuroendocrine cells.

BACKGROUND: The neuroendocrine cells of the human prostate have been related to proliferative disorders such as prostatic cancer. Their origin, distribution, and development have therefore been studied and discussed in terms of current stem cell concepts in the prostate. METHODS: Prostatic tissue specimens (n = 20) from human fetuses (n = 8), prepubertal and pubertal children (n = 8) and mature men (n = 4) were studied immunohistochemically using antibodies directed against neuroendocrine, epithelial as well as secretory markers. Semiquantitative computer-assisted evaluation of different epithelial and stromal components based on stereological principles was performed on azan-stained sections representative of all developmental stages. RESULTS: By the end of gestational Week 9, neuroendocrine (NE) cells appear in the epithelium of the urogenital sinus and are subsequently closely associated with the formation of urethral prostatic buds. The fetal and postnatal distribution pattern of NE cells within the gland is characterized by a relatively constant number of cells per gland similar to prostatic smooth muscle cells. Likewise, a density gradient exists with the highest density in the large collicular ducts and almost no NE cells in subcapsular peripheral acini. In peripheral ducts, the distribution is random. Maturation of the NE cells precedes that of the secretory cells by about 10-16 years. CONCLUSIONS: A second prostatic stem cell lineage, different from the urogenital sinus (UGS)-lineage is hypothesized originating from immature neuroendocrine cells. Being morphologically indistinguishable from the UGS-derived prostatic secretory cell lineage, it gives rise to neuroendocrine cells. Their presence is apparently important for proliferation regulation of the UGS-derived lineage of the prostate.

Adolescent↗
PubMed2000

Factors which predict unsuccessful mobilisation of peripheral blood progenitor cells following G-CSF alone in patients with non-Hodgkin's lymphoma.

INTRODUCTION: High-dose therapy with haematopoietic progenitor cell support has increasingly been utilised for patients with haematological malignancies. Peripheral blood is the stem cell source of choice, however, various mobilisation strategies are used by different centres. PATIENTS AND METHODS: Over a 2-year period, 52 patients with non-Hodgkin's lymphoma (median age 47 years, range 16-64 years) underwent peripheral blood progenitor cell mobilisation using G-CSF alone (16 microg/kg/day). The harvest was considered successful if > or =1 x 10(6) CD34(+) cells/kg were collected by leukapheresis. The histological subtypes of non-Hodgkin's lymphoma comprised: follicular (24 patients), diffuse large B-cell (14 patients), lymphoplasmacytoid (four patients), mantle cell (three patients), lymphoblastic lymphoma (one patient) and small lymphocytic lymphoma/chronic lymphocytic leukaemia (six patients). The median interval from diagnosis of non-Hodgkin's lymphoma to mobilisation was 27 months (range 2 months to 17 years). The median number of prior treatment episodes was 2 (range 1-5); 26 patients had received fludarabine alone or in combination. At the time of peripheral blood progenitor cell mobilisation, 20 patients were in 1st remission and 32 were in > or =2nd remission; 30 patients were in partial remission and 22 were in complete remission; the bone marrow was involved in nine patients. RESULTS: Peripheral blood progenitor cell mobilisation/harvest was unsuccessful in 19 out of 52 (37%) patients (mobilisation: 18, harvest: 1). The factors associated with unsuccessful mobilisation or harvest were: prior fludarabine therapy (P=0.002), bone marrow involvement at diagnosis (P=0.002), bone marrow involvement anytime prior to mobilisation (P=0.02), histological diagnosis of follicular, mantle cell, or lymphoplasmacytoid lymphoma, or small lymphocytic lymphoma/chronic lymphocytic leukaemia (P=0.03) and female gender (P=0.04). CONCLUSION: Although peripheral blood progenitor cells can be successfully mobilised and harvested from the majority of patients with non-Hodgkin's lymphoma after treatment with G-CSF alone, the latter is unsuccessful in approximately one-third of patients. These factors should be taken into account when patients are being considered for high-dose treatment.

Adolescent↗
PubMed1999

Localization of protein gene product 9.5 immunoreactivity in derivatives of the human Wolffian duct and in prostate cancer.

BACKGROUND: Protein gene product 9.5 (PGP 9.5) has been considered to be a neuronal marker, but it is also present in extraneuronal tissues, e.g., the human mammary gland and rat epididymis. Its presence and distribution in the developing and adult male human genital tract have been unknown. METHODS: Immunohistochemical reactions were performed on human embryonic and postnatal specimens of the male genital tract, using commercial monoclonal and polyclonal antibodies. RESULTS: PGP 9.5 immunoreactivity was found in the Wolffian duct of human embryos (55-85 mm crown-rump length). Strong reactivity was observed in mesonephric tubular cells and at the apical rim of Wolffian duct cells. Owing to their PGP 9.5 immunoreactivity, these cells could also be identified on the surface of the embryonic verumontanum, extending from the orifices of the Wolffian duct to a small stretch of the urogenital sinus. There they contrasted sharply against non-Wolffian cells. In the adult human genital tract, PGP 9.5 immunoreactive material was present in the supranuclear portion of some epithelial cells of the epididymal efferent ductules, in isolated cells of the ejaculatory ducts, and in prostate cancer specimens. In the ejaculatory ducts, the PGP 9.5-immunoreactive cells were free of immunoreactivity for semenogelin, the major secretory product of the ejaculatory-vesicular-ampullary complex, and they also lacked chromogranin A-immunoreactivity. In prostate cancer specimens, PGP 9.5 immunoreactivity was never observed in secretory cells (immunoreactive for prostate-specific antigen), but was restricted to neuroendocrine cells, where it occurred either alone or coexpressed with chromogranin A-immunoreactivity. CONCLUSIONS: PGP 9.5-immunoreactivity is prenatally distributed in the Wolffian duct and its derivations; postnatally, it is restricted to a few cells derived from the initial and terminal segment of the Wolffian duct, and to neuroendocrine cells in prostate cancer specimens.

Adult↗
PubMed1999

New approaches in the pharmacological treatment of obesity.

Many new substances are currently being investigated for their usefulness in the pharmaco-therapy of obesity. Most drugs interfere with monoamine neuro-transmitter (serotonin, noradrenalin, dopamine and histamine) effects and act as an appetite suppressant. Other approaches are to primarily increase thermogenesis (e.g. beta 3-adrenoceptor agonists), or to decrease fat absorption by inhibiting the pancreatic lipase (orlistat). New promising agents are substances that increase the effect of corticotropin releasing factor (CRF) or urocortin in the brain (CRF-binding protein ligand inhibitor) and a neuropeptide Y (NPY) Y5 receptor antagonist. The clinical relevance of leptin in the therapy of obesity is probably limited, but can not be fully evaluated at the moment. As obesity has a multifactorial basis, all these substances have in common the fact that they can not cure obesity. They should only be used as an adjunct to classical strategies like diet and exercise in severe obesity. For developing new, perhaps even more specific pharmacological agents, further research is needed to understand the individually different genetic and physiological basis of obesity.

Animals↗
PubMed1999

Neurogenic origin of human prostate endocrine cells.

OBJECTIVES: To determine the histogenetic origin of prostate neuroendocrine cells in human embryos. METHODS: Prostatic tissue in human fetuses, ranging in gestational age from early week 10 to term, and infantile and pubertal glands were studied immunohistochemically. The distribution of neuroendocrine cells within the developing gland was semiquantitatively determined. Antibodies against the neuroendocrine markers chromogranin A (CgA) and protein gene product 9.5 (PGP), along with markers of prostatic secretion (prostate-specific antigen [PSA], prostatic acid phosphatase [PAP]), were used. They were applied either individually or in double-labeling experiments, as well as in experiments combining CgA immunohistochemical analysis with in situ hybridization or in situ end-labeling. RESULTS: In embryos of less than 65-mm crown-rump length (CRL) (ie, younger than 12 weeks of gestation), the epithelium of the urogenital sinus was free of endocrine cells. On either side of the future prostatic mesenchyme, paraganglia containing CgA-immunoreactive cells are present, which start to penetrate the urogenital mesenchyme. In the late 10th week, these CgA-immunoreactive cells are found dispersed in the urogenital mesenchyme. In embryos of 65-mm CRL, when prostatic anlagen start to sprout from the urogenital epithelium, very few (but typically shaped) neuroendocrine cells appear in the urogenital sinus epithelium. Later, after the 12th week, when solid prostatic ducts have started forming, CgA-immunoreactive neuroendocrine cells are also present in these buds. The number of neuroendocrine cells in the urethral epithelium is considerably increased, and with the continuous sprouting and lumen formation of prostatic anlagen, neuroendocrine cells are transported into the future gland. Neuroendocrine cells observed in stroma of prenatal and postnatal prostates may also contribute to the neuroendocrine cell population of the gland. CONCLUSIONS: Our results provide the first evidence that human prostate neuroendocrine cells represent a cell lineage of their own, being of neurogenic origin and therefore distinct from the urogenital sinus-derived prostate secretory and basal cells.

Adolescent↗
PubMed1998

[Benefits and risks of electroconvulsive therapy (ECG) in elderly patients with cardiovascular risk factors].

Between January 1995 and June 1996, 24 inpatients at our hospital (mean age 55.6 years) were treated with electroconvulsive therapy (ECT). Clinical improvement was observed in 80% of the patients, including those without risk factors (NRG, n = 16), as well as those with concomitant cardiovascular diseases (RG, n = 8). During a mean period of observation of 224 days after the end of ECT 7 patients (35%) relapsed. The rate of relapse was higher in RG than in NRG patients (57.1 vs 23.1%). In all cases ECT was well tolerated; 285 applications of ECT did not result in mortality or persistent morbidity. However, RG patients may be at increased risk for the development of minor cardiovascular complications, which were noted in three RG patients (37.5%), but only in one patient (6.2%) in the NRG (Fisher's test, P = 0.09). Taken together, our results demonstrate that ECT is a safe treatment regimen for depression even in medically ill patients of old age.

Adult↗
PubMed1997

Available iron and zinc in major lean meat cuts and their contribution to the recommended trace element supply in Switzerland.

The objective of the present study was to analyze iron and zinc in major lean meat cuts in order to estimate the contribution of the average lean meat consumption in Switzerland (1995) for these trace elements. Iron, heme iron and zinc contents were analyzed in following muscles: pork (longissimus dorsi muscle and shoulder), beef (longissimus dorsi muscle and shoulder), veal (longissimus dorsi muscle) and chicken (breast and thigh). Beef and pork shoulder were the best sources of iron, heme iron and zinc. Pork and veal longissimus dorsi muscle and chicken were relatively poor in these trace elements. With an average daily lean meat consumption of 105 g, iron and zinc intake were about 1.1 mg/d and 3.8 mg/d, respectively. Recommendations for daily iron intake were met to 11% (men) and 7% (women) and for zinc to 25% (men) and 32% (women). Applying a modified Monsen model, the requirements for absorbed iron were met in the range of 10-30% and 7-20% for men and women, respectively. Taking into account a zinc absorption rate from meat of about 20-36%, the daily requirements for absorbed zinc were covered to 32-56%. In conclusion, the average amount of lean meat as consumed in Switzerland was high enough to be an important source of available iron and zinc, particularly for people with low iron and zinc status.

Adult↗
PubMed1997

Vitamin E content of different animal products: influence of animal nutrition.

The alpha-tocopherol content of different meat cuts was examined. Chicken thigh had the highest vitamin E content, followed by chicken breast and pork shoulder (p < 0.05). The lowest concentrations were found in longissimus dorsi muscle from pork, beef, veal and in beef shoulder. Considering the average daily lean meat consumption (105 g) in Switzerland, recommendation for daily vitamin E intake was met to 3%. Supplementation of 200 mg alpha-tocopherol acetate/kg feed to pigs and laying hens significantly increased the alpha-tocopherol content in all examined products. The alpha-tocopherol accumulation differed according to the following ranking: egg yolk > liver > adipose tissue > musculus longissimus dorsi. The alpha-tocopherol:energy ratios were 28.8, 7.3, 0.9 and 1.2 mg/MJ for egg yolk, liver, adipose tissue and longissimus dorsi muscle of the vitamin E supplemented groups, respectively. The results showed that meat, with the exception of chicken thigh, is not an important supplier of vitamin E, not even from animals fed a vitamin E enriched diet. Egg yolk became a good source of vitamin E for human nutrition by dietary modification.

Animal Nutritional Physiological Phenomena↗
PubMed1996

[Hermann F. Hoffmann (1891-1944)--Tübingen psychiatry on the way to national socialism].

This study covers the life and scientific work of Hermann F. Hoffmann who was a disciple of Robert Gaup and in 1936 took over from him as head of the psychiatric clinic at the University of Tübinge. As a scientist, Hoffmann was especially involved in research into genetic problems in psychiatry. He introduced a new approach to some premises of the so-called Tübingen Psychiatric School. In 1933, he joined the NSDAP and became one of the most prominent members of the National Socialist party at the University of Tübingen. From then on, he saw himself as a prophet of a new "biological" philosophy of life. From the present point of view, Hoffmann is something of a contradiction. On the one hand, he was a good doctor and a serious scientist; on the other, he promoted biologistic ideology and a criminal regime. These biographical inconsistencies point to some inconsistencies in the history of psychiatry itself with its dialectics of philanthropy and discrimination.

Eugenics↗
PubMed1995

[The neuroleptic malignant syndrome].

HISTORY AND CLINICAL FINDINGS: A 22-year-old oligophrenic patient had on several occasions over several months been given various neuroleptics (haloperidol, benperidol, levomepromazine) for exacerbations of paranoid schizophrenia. For a few days before hospitalization he had become quiet and withdrawn, but on the day of admission 100 mg chlorprothixene was administered intramuscularly when he had become agitated. At admission he was somnolent, his general condition was disturbed. He had hyperhidrosis and hypersalivation, as well as tachycardia (112/min) with a normal body temperature of 37.8 degrees C. He also exhibited the cogwheel phenomenon of the limbs and neck, as well as tremor of the hands. The differential diagnosis included inflammatory disease of the brain, sinus thrombosis and, especially, malignant neuroleptic syndrome and febrile catatonia. INVESTIGATIONS: The activities of creatine kinase (3840 U/l), GOT (75 U/l) and GPT (88 U/l) were all increased. Serum myoglobin was 77 micrograms/l. CSF contained blood and there was pleocytosis of 50/3 cells. The ECG showed sinus tachycardia. EEG, chest radiogram, computed tomography, magnetic resonance imaging and cerebral angiography showed no abnormalities. Febrile catatonia could not be excluded. TREATMENT AND COURSE: 4 hours after admission the patient began to respond with normal orientation. Shortly afterwards he was able to walk a few steps, i.e. there was no catatonia. But rigor, tremor, hypersalivation and tachycardia persisted and 12 hours later he developed a fever (up to 39.2 degrees C). Blood pressure varied with peak pressures up to 190/110 mm Hg. After 2 days muscle tone had clearly increased so much that voluntary movement was hardly possible. After amantadine administration (200 mg daily) the rigor improved and for the first time body temperature became normal again. There were no signs pointing to psychotic symptoms. CONCLUSION: Neuroleptic malignant syndrome is difficult to distinguish from febrile catatonia and the diagnosis can often only be made through the clinical course.

Adult↗
PubMed1993

[Dorsolateral approach to the left subphrenic area, to the bursa omentalis and to the cauda pancreatis].

We are reporting on a dorsolateral access left to the bursa omentalis and to the left subphrenium carried out in order to relieve infectious processes in this region. The access has proved a success above all in the later postoperative period, e.g. when the protecting conglutinations towards ventral isolate the process from the abdominal cavity. At the lying patient this access allows the drainage of the exsudation over the deepest point. The results of 23 surgical interventions are being demonstrated with references to possible complications caused by the intervention.

Adult↗