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Biomedical subjects

D Lange

Publications and source records attributed to D Lange.

At least 19 recordsLinked to original sources
PubMed1999

Gender differences in sympathetic nervous system regulation.

1. Females are protected against the development of hypertension. The purpose of the current review is to present the evidence for gender differences in the regulation of the sympatho-adrenal nervous system and to determine if these differences support the hypothesis that, in females, the regulation of the sympathetic nervous system (SNS) is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented. 2. The central control of sympatho-adrenal function is different in females and responses vary during the oestral and menstrual cycles. Pathways regulating the SNS appear to be less sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in females compared with males. 3. Gender differences in arterial baroreflex sensitivity suggest that females may have a greater baroreflex sensitivity, such that alterations in blood pressure are more efficiently controlled than in males. Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in females, possibly resulting in a greater renal excretory function. 4. An attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline (NA), suggests that gender differences in noradrenergic neurotransmission may protect females against sympathetic hyperactivity. Gender differences in the regulation of NA release via presynaptic alpha 2-adrenoceptors, the vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of catecholamines are consistent with this hypothesis. 5. Similarly, attenuated stress-induced increases in plasma catecholamines in women suggest that females are less sensitive and/or less responsive to adrenal medullary activation. This is supported by findings of gender differences in adrenal medullary catecholamine content, release and degradation. 6. We conclude that there is strong evidence that supports the hypothesis that, in females, the regulation of the SNS is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented.

Adrenal Medulla↗
PubMed1999

Eccrine sweat glands: expression of transforming growth factor-beta and bone morphogenetic protein type I receptors and their intracellular signalling Smad proteins.

The transforming growth factor-beta superfamily is thought to be involved in the regulation and control of growth and differentiation. These growth factors signal through transmembrane serine/threonine kinase receptors. The activation of type I receptor kinase phosphorylates a family of intracellular signalling proteins called Smads. In the present study, we wanted to localize type I and type II receptors and Smad proteins in human eccrine sweat glands. Expression of transforming growth factor-beta type I receptor was restricted to myoepithelial cells only, whereas bone morphogenetic protein receptor IA was found selectively within the duct epithelium of both the dermal portion and the acrosyringium. Bone morphogenetic protein receptor IB antibody gave a faint staining of secretory epithelium and myoepithelial cells. Smad proteins were identified in different parts of the eccrine sweat gland apparatus. In particular, Smad 1 and Smad 3 were localized within myoepithelial cells, whereas coils were stained weakly for Smad 1 and Smad 3. Smad 3 protein was also expressed by the duct epithelium. Smad 2, Smad 4, Smad 5, Smad 6 and Smad 7 were not identified in eccrine sweat gland epithelia. Our data provide evidence for transforming growth factor-beta/bone morphogenetic protein signalling in the eccrine sweat gland and the selective expression of Smad proteins. Myoepithelial cells and duct cells have been identified as major targets of the transforming growth factor-beta pathway. Possible functions are growth inhibition and control of myoepithelial differentiation.

Bone Morphogenetic Protein Receptors, Type I↗
PubMed1999

Short-time extracorporeal photochemotherapy in the treatment of drug-resistant autoimmune bullous diseases.

BACKGROUND: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are potentially severe diseases. In drug-resistant PV and pemphigus foliaceus, long-term adjuvant treatment with extracorporeal photochemotherapy (photopheresis, ECP) has been reported to induce remission. Only limited numbers of patients have been reported so far. No information about the effectiveness in drug-resistant BP is available. PATIENTS AND METHODS: Seven patients with drug-resistant autoimmune bullous diseases have been referred to the photopheresis center of Jena (3 x PV, 3 x BP, 1 x pemphigus foliaceus). The age ranged from 31 to 85 years. ECP was performed on 2 consecutive days once a month. Oral 8-methoxypsoralen was used as photosensitizer. Previous immunosuppressive treatment with either prednisolone or prednisolone/ azathioprine was continued. RESULTS: Complete remission (absence of skin or mucous membrane lesions) was achieved in the 6 patients with PV and BP after 1-4 cycles. In the patient suffering from pemphigus foliaceus, a partial remission (> 50% improvement) was observed; in all except this patient, the immunosuppressive treatment could be tapered. Long-term remission was achieved. No severe side effects were observed. The treatment was well tolerated. CONCLUSIONS: Short-time ECP is an effective and safe adjuvant treatment for patients with drug-resistant autoimmune bullous diseases. It can induce remission and allows dose tapering of the immunosuppressive drugs.

Adult↗
PubMed1999

Autocrine endothelial regulation in brain stem vessels of newborn piglets.

Vasoactive intestinal peptide (VIP) is known as a potent regulator for the development of the central nervous system (CNS). The neonatal period of brain development is characterised by rapid cellular proliferation in parallel with neuronal differentiation and angiogenesis. We examined the expression of native VIP and the VIP receptor-associated protein by immunohistochemistry as well as the expression of VIP mRNA by in situ hybridisation in the brain stem of newborn piglets. We found both the mRNA and the protein of VIP as well as the VIP receptor-associated protein in endothelial cells of veins, arteries and capillaries in the marginal zone of brain stem tissue sections, especially in pons and mesencephalon, as well as in pial vessels. The coexpression of native VIP, VIP mRNA and the VIP receptor-associated protein within the endothelium suggests the presence of an autocrine loop, which has been detected so far only in neuroblastoma cells. This expression pattern gives evidence to the immaturity of endothelial cells at birth and the presence of an adaptive response in the VIP-regulated system during the change from intra- to extrauterine life.

Animals↗
PubMed1999

Expression of TGF-beta related Smad proteins in human epithelial skin tumors.

Members of the transforming growth factor (TGF)-beta family regulate cell growth and differentiation activating intracellular Smad proteins. Their role in skin and skin tumorigenesis is not well understood. Therefore we investigated the expression of TGF-beta type I receptor (TbetaR-I) and Smad-proteins involved in the TGF-beta-pathway, e.g. Smad2, Smad3, Smad4, Smad6 and Smad7. We examined the effects of TGF-beta1, -beta2, BMP2, BMP7 on five epithelial cell lines in vitro. TGF-beta1-mediated growth inhibition of HaCaT and HSC4 were observed with half maximal effects at approximately 7 pg ml-1 and 20 pg ml-1, respectively. However, malignant HSC2 and A431 cells were unresponsive to TGF-beta1. A differentiation was seen after 5 days in HaCaT and HSC4 cells only. We compared the reactivity with specific antisera against TbetaR-I and Smad proteins among the different skin tumors: seborrheic keratoses (SK), actinic keratoses (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There were statistically significant differences of the ratio between the expression in tumor and that in non-tumorous epithelial cells in each tissue specimen. There was a tendency for the lower level of TbetaR-I expression of SCC compared with SK (p=0.08). This was accompanied by the decreased expression of the TbetaR-I. We found a markedly decreased expression of all antigens in BCC. conversion of normal keratinocytes to tumorigenic cells may in part be due to an acquisition of resistance to TGF-beta and loss of expression of intracellular signalling Smad proteins.

Activin Receptors, Type I↗
PubMed1998

Tolerance induction ameliorates allograft vasculopathy in rat aortic transplants. Influence of Fas-mediated apoptosis.

Based on successful induction of donor-specific unresponsiveness by alloantigenic stimulation in several animal models of acute rejection, we hypothesized that similar immune manipulations would also inhibit the evolution of chronic rejection and transplant vasculopathy. To induce immune tolerance, DA rats received a PVG heart allograft and were immunosuppressed with cyclosporine for 30 d. At day 100 the animals were challenged with a PVG aortic allograft after either 1 or 18 h of cold ischemia. 8 wk after the aortic transplantation, the grafts were investigated for morphological changes, infiltrating cells, apoptosis, and Fas-Fas ligand expression. Control allografts showed advanced transplant arteriosclerosis, whereas tolerance-induced aortic allografts displayed reduced neointimal formation, less medial atrophy, fewer apoptotic cells, and fewer Fas- and FasL-expressing cells. Prolonged ischemic storage time did not profoundly alter the morphological changes of the allografts. Fas expression was found in T cells, macrophages, vascular smooth muscle cells, and endothelial cells, whereas FasL was expressed mainly by T cells and macrophages. FasL mRNA expression was evident throughout the entire allograft wall. In conclusion, induction of allospecific tolerance can effectively prevent transplant arteriosclerosis. Cold ischemia damage does not abrogate the beneficial effect of tolerance, but creates a separate identity of mainly endothelial lesions. Furthermore, Fas-mediated apoptosis appears to be involved in the pathological lesions seen in chronic rejection.

Animals↗
PubMed1998

Molecular basis for the dominant white phenotype in the domestic pig.

The change of phenotypic traits in domestic animals and crops as a response to selective breeding mimics the much slower evolutionary change in natural populations. Here, we describe that the dominant white phenotype in domestic pigs is caused by two mutations in the KIT gene encoding the mast/stem cell growth factor receptor (MGF), one gene duplication associated with a partially dominant phenotype and a splice mutation in one of the copies leading to the fully dominant allele. The splice mutation is a G to A substitution in the first nucleotide of intron 17 and leads to skipping of exon 17. The duplication is most likely a regulatory mutation affecting KIT expression, whereas the splice mutation is expected to cause a receptor with impaired or absent tyrosine kinase activity. Immunocytochemistry showed that this variant form is expressed in 17- to 19-day-old pig embryos. Hundreds of millions of white pigs around the world are assumed to be heterozygous or homozygous for the two mutations. [The EMBL accession numbers for porcine KIT1*0101, KIT1*0202, KIT2*0202, and KIT2*0101 are AJ223228-AJ223231, respectively.]

Alternative Splicing↗
PubMed1997

Effect of a cola beverage on the bioavailability of itraconazole in the presence of H2 blockers.

Thirty-three healthy individuals participated in an open-label, randomized, three-way crossover study designed to compared the bioavailability of a single 200-mg oral dose of itraconazole when administered alone or after treatment with ranitidine, both with and without coadministration of a cola beverage. Each treatment phase was separated by a 2-week washout period. Participants pretreated with ranitidine were required to have a gastric pH of at least 6.0 before receiving itraconazole. An analysis of the area under the curve (AUC) and peak plasma concentration (Cmax) data indicated that the bioavailability of itraconazole was significantly reduced when the gastric pH was increased by pretreatment with ranitidine but showed that this effect was counteracted by the coadministration of an acidic solution (e.g., a cola beverage) that transiently reduced the gastric pH. These findings suggest that the coadministration of an acidic beverage with itraconazole may be an effective approach in improving the bioavailability of itraconazole in patients who are hypochlorhydric or who are taking gastric acid suppressants.

Adult↗
PubMed1997

Probing the structure of the ligand binding cavity of lipocalins by fluorescence spectroscopy.

The lipocalin superfamily constitutes a phylogenetically conserved group of more than 40 proteins that function in the binding and transport of a variety of physiologically important ligands. Members of this family subserve diverse functions as carriers of retinoids (retinol binding protein), odorants (odorant binding proteins), chromophores (insecticyanin, INS), pheromones (aphrodisin) and sterols (apolipoprotein D, apoD). Despite the pivotal importance of the ligand binding function of these proteins, a suitable approach for characterizing the molecular determinants of such binding has not been available. In studies using three homogeneously purified lipocalins INS, beta-lactoglobulin (BLG) and human apoD, we find that the fluorescence reporter BIS (1,1'-bi(4-anilino) naphthalene-5,5'-disulfonic acid) is an ideal candidate for use in rapid kinetic experiments and in fluorescence resonance energy transfer (FRET). These methods require only small amounts of reagents and yield molecular coordinates of the ligand binding cavity of lipocalins in solution that are in remarkably close agreement to those obtained from crystallographic work with solids. Extremely fast ligand binding dynamics is indicated.

Animals↗
PubMed1997

[The case of myoepithelioma of the parotid gland].

Myoepithelioma of the parotid gland occurs relatively rarely. In the literature was described only 33 cases of this tumors. It's growth's slow and distension. Basing upon the case of 48-year old woman, the authors discuss the difficulties of diagnostic, treatment and the course of the disease.

Female↗
PubMed1996

Blood superoxide dismutase, catalase and glutathione peroxidase activities in familial and sporadic amyotrophic lateral sclerosis.

Recent studies have implicated free radicals in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal, paralytic disorder of motor neurons. Herein we report on measurements of erythrocyte activity of the three main free radical scavenging enzymes: copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase, and glutathione peroxidase. We studied 31 patients with sporadic ALS, 18 with familial ALS, and 24 controls, Mean Cu/Zn-SOD activity was reduced in eight familial ALS patients with mutations of Cu/Zn-SOD but was normal in patients with both familial ALS without identified Cu/Zn-SOD mutations and sporadic ALS. Glutathione peroxidase activity was significantly reduced only in sporadic ALS patients treated with insulin-like growth factor I (100 micrograms/kg). Catalase activity was normal in sporadic and familial ALS. Neither glutathione peroxidase nor catalase activities correlated significantly with duration of symptoms or age at onset. Vitamin E, vitamin C, and beta-carotene did not affect any of the three enzyme activities. These observations indicate that disturbances of catalase and glutathione peroxidase function are not likely to be central factors in the pathogenesis of ALS.

Age of Onset↗
PubMed1996

[Methodical evaluation of immunoluminometric determination of thyroid peroxidase in serum].

With the identification of thyroid peroxidase (TPO) as the specific autoantigen in autoimmune diseases of the thyroid, the development of a commercial assay for detection of TPO in human serum became possible. The diagnostic value of this TPO assay was evaluated in 194 patients with various thyroidal diseases. The assay appeared to be easily affected by specific and/or unspecific interferences such as TPO-auto-antibodies in the patient's blood samples. To analyze these effectors every sample was checked in a parallel recovery test. In most of the cases with elevated anti-TPO levels an exact determination of TPO could not be estimated correctly. Whenever a correct measurement of TPO was possible, to none of the different examined groups of thyroid diseases a correlation of TPO-levels could be demonstrated. Moreover, the value of TPO determination as a tool in the follow-up of differentiated thyroid carcinoma was not provable. For the time being our studies do not suggest TPO measurements being helpful in thyroidal diagnosis.

Autoimmune Diseases↗
PubMed1996

Sequential combination of radio-chemotherapy (5-fluorouracil, cis-platinum and irradiation) in the management of locally advanced head and neck cancers.

Thirty-seven previously untreated patients with advanced, inoperable head and neck were treated with a sequential courses combining hypofractionated irradiation with chemotherapy (5-fluorouracil and cis-platinum). Each course was repeated every 4 weeks. Tumor response was evaluated and for 15 patients (41%) with a partial or complete regression after 3 radio-chemotherapy courses conventional radiotherapy was added. Eleven percent of all patients were in complete remission at the end of a treatment. This tumor response rate and the 50% rate of pain subside after first course for symptomatic patients contributed for a good palliative effect in the present study. However, the median survival of 7.2 months was considered unsatisfactory.

Adult↗
PubMed1996

Expression of transforming growth factor beta isoforms and their receptors during hair growth phases in mice.

Transforming growth factor beta (TGF-beta) is a family of potent growth inhibitor proteins, often produced as a precursor and often secreted in a complex with the latent TGF-beta binding protein (LTBP). We investigated the expression of TGF-beta 1, -beta 2, -beta 3, LTBP, TGF-beta receptor proteins type I and type II (T beta R-I and -II) during induced hair growth in C57 BL-6 mice. We here demonstrated that TGF betas and T beta R-I are expressed in hair follicle epithelium and have found a positive reactivity for LTBP and T beta R-I in ++sebocytes. Dermal tissue was weakly stained for LTBP and TGF-beta 3. In early anagen the inner hair root sheath epithelium expressed TGF-beta 1, whereas outer hair root was positive for T beta R-I during anagen/catagen switch. T beta R-II was found in sebaceous glands without significant variations during the hair cycle. We may conclude that in follicle epithelium TGF-beta 1 is not produced in a complex together with LTBP. On the other hand, it is possible that other types of LTBP, like LTBP-2 and LTBP-3, are present, which are not detected by the antibody we used. Furthermore, a very rapid secretion of LTBP from producing cells may prevent immunohistochemical detection. TGF-beta 1 released by inner hair root sheath may regulate outer root sheath growth. A bidirectional interaction of sebocytes and hair follicle epithelium in the TGF-beta/LTBP seems possible. Sebocytes can be considered to be a target for TGFs since they express both T beta R++-I and -II. The general properties of TGF-beta as a growth inhibitor of epithelial cells may suggest a possible involvement in either the abrogation of extensive growth at the end of anagen or the initiation of catagen for the follicle epithelium as well as growth control for sebaceous glands.

Animals↗