julilili42/papers huggingface dataset:
The silent PPARγ exon 6 CACHis → CATHis polymorphism does not affect the plasma leptin levels in a collective of first degree relatives of type 2 diabetes patients from South West Germany
2000-12-31

The peroxisome proliferator activated receptors-gamma (PPARgamma) belong to the superfamily of nuclear transcription factors acting as master genes regulating events in adipocyte differentiation. Thus, PPARgamma is a candidate gene for affecting insulin sensitivity and the pathogenesis of insulin resistance. PPARs trigger endocrine response of two important adipose tissue-derived signalling factors, leptin and tumor necrosis factor-alpha. Leptin is the afferent signal in a negative feedback loop regulating adipose tissue mass and energy balance. It generates insulin-like signals for glucose transport and glycogen synthesis via leptin receptors and the PI3-kinase and could, therefore, play a role as a mediator of obesity-related insulin resistance. Recently, a silent substitution in the coding sequence of the PPARgamma2 gene, leading to the substitution of a C by a T in exon 6 (nt 161), was described. In a recent study, it was proposed that mutations in PPARgamma could play a role in individuals who are at increased risk for developing obesity and type 2 diabetes mellitus by influencing leptin levels. We therefore examined the prevalence of the CAC(His) --> CAT(His) mutation in non-diabetic first degree relatives of subjects with type 2 diabetes to determine a possible association of this mutation to leptin levels and insulin sensitivity. 138 probands were characterised by oral glucose tolerance tests, euglycemic-hyperinsulinemic glucose-clamp and by measuring leptin levels. We found 93 (67.4%) probands without the CAC(His) --> CAT(His) substitution and 45 heterozygotes (36.6%). When the whole group was analysed for an association of the mutation with plasma leptin concentration and insulin sensitivity, no statistical significance could be demonstrated. Independently of the mutation, leptin levels were significantly (p<0.001) higher in female subjects.
Inhibition of proliferation and differentiation by RU 486 in human endometrial stromal and epithelial cells in vitro
2000-12-31

The effects of progesterone and RU 486 on cellular proliferation and differentiation in long term cultures of mixed human endometrial cells were studied. The endometrial tissue was obtained from women with normal menstrual cycles who were undergoing hysterectomy for benign growths. Estradiol supplemented cultures were treated with progesterone and/or RU 486 for 27 days. Cell number was measured by crystal violet assay, and prolactin secretion was used as a marker of differentiation. Progesterone doubled the rate of proliferation, but the addition of RU 486 reduced it to baseline again. The gestagen increased prolactin secretion up to 30 times, while the addition of RU 486 suppressed it to baseline levels. When administered to cells that were pretreated with progesterone for 15 days RU 486 abolished the progesterone effects. RU 486 alone was without any effect. Our results indicate that (1) in vitro progesterone is essential for the initiation and maintenance of proliferation and differentiation of endometrial cells and (2) RU 486 acts as a pure progesterone antagonist in our culture model.
Fluvastatin combined with 17β-estradiol: Effect on the oxidation of human low density lipoprotein
2000-12-31

The in vitro effect of a statin and an estrogen on oxidation of human LDL was investigated for the first time, comparing the monosubstances fluvastatin and 17beta-estradiol as well as the effect of the combination. Fluvastatin significantly delayed the onset of LDL oxidation (controls = 90 min) by 23 min at 1 microM, by 110 min and by 221 min at 5 and 10 microM, respectively. 17Beta-estradiol significantly impeded the onset by 70 min at 1 microM and by more than 300 min at 5 and 10 microM. The combination of 1 microM 17beta-estradiol with 1, 5 and 10 microM fluvastatin showed an additive antioxidative effect; the onset was delayed by 100 min, by 167 min and by more than 300 min, respectively. It can be concluded that treatment of postmenopausal women with fluvastatin and 17beta-estradiol may have not only beneficial effects on lipid disorders but may also elicit a direct potent anti-atherosclerotic action on the vasculature.
Nuclear Receptor Response Elements Mediate Induction of Intestinal MDR1 by Rifampin
2001-01-01

Intestinal P-glycoprotein, which is encoded by the MDR1 gene, plays an important role in the absorption and presystemic elimination of many xenobiotics. Hence, an understanding of the factors regulating its expression and function is of substantial interest. In addition to genetic factors, exposure to drugs such as rifampin can profoundly affect its expression. So far, the mechanisms by which rifampin induces MDR1 expression are poorly understood. Recent studies demonstrate that the nuclear receptor PXR (pregnane X receptor) is involved in xenobiotic induction of CYP3A4. Because CYP3A4 and MDR1 are often co-induced, we investigated whether a similar mechanism is also involved in MDR1 induction. The human colon carcinoma cell line LS174T was used as an intestinal model to study induction because in these cells the endogenous MDR1 gene is highly inducible by rifampin. The 5'-upstream region of human MDR1 was examined for the presence of potential PXR response elements. Several binding sites were identified that form a complex regulatory cluster at about -8 kilobase pairs. Only one DR4 motif within this cluster is necessary for induction by rifampin. We conclude that induction of MDR1 is mediated by a DR4 motif in the upstream enhancer at about -8 kilobase pairs, to which PXR binds.
Brain–computer communication: Unlocking the locked in.
2001-01-01

With the increasing efficiency of life-support systems and better intensive care, more patients survive severe injuries of the brain and spinal cord. Many of these patients experience locked-in syndrome: The active mind is locked in a paralyzed body. Consequently, communication is extremely restricted or impossible. A muscle-independent communication channel overcomes this problem and is realized through a brain-computer interface, a direct connection between brain and computer. The number of technically elaborated brain-computer interfaces is in contrast with the number of systems used in the daily life of locked-in patients. It is hypothesized that a profound knowledge and consideration of psychological principles are necessary to make brain-computer interfaces feasible for locked-in patients.
MATINGBEHAVIOR ANDCHEMICALCOMMUNICATION IN THEORDERHYMENOPTERA
2001-01-01

▪ Abstract Insects of the order Hymenoptera are biologically and economically important members of natural and agro ecosystems and exhibit diverse biologies, mating systems, and sex pheromones. We review what is known of their sex pheromone chemistry and function, paying particular emphasis to the Hymenoptera Aculeata (primarily ants, bees, and sphecid and vespid wasps), and provide a framework for the functional classification of their sex pheromones. Sex pheromones often comprise multicomponent blends derived from numerous exocrine tissues, including the cuticle. However, very few sex pheromones have been definitively characterized using bioassays, in part because of the behavioral sophistication of many Aculeata. The relative importance of species isolation versus sexual selection in shaping sex pheromone evolution is still unclear. Many species appear to discriminate among mates at the level of individual or kin/colony, and they use antiaphrodisiacs. Some orchids use hymenopteran sex pheromones to dupe males into performing pseudocopulation, with extreme species specificity.
Malignant glioma biology: Role for TGF-? in growth, motility, angiogenesis, and immune escape
2001-01-01

Characteristics of human malignant glioma are excessive proliferation, infiltrative growth, angiogenesis and suppression of anti-tumor immune surveillance. Transforming growth factor-beta (TGF-beta), a versatile cytokine, is intimately involved in the regulation of these processes. Here, we discuss the interactions of TGF-beta with growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and platelet derived growth factor (PDGF), metalloproteinases (MMP-2, MMP-9) and their inhibitor, plasmin activator inhibitor-1 (PAI-1), and immune cells, like natural killer cells, T-cells and microglia. The differential effects of TGF-beta in glioma biology are outlined with emphasis on the induction of a survival advantage for glioma cells by enforced cell growth, migration, invasion, angiogenesis and immune paralysis. By virtue of its growth regulatory and immunomodulatory properties, TGF-beta promises to become a novel target for the experimental therapy of human malignant glioma.
Determination of enantiomerization barriers by dynamic and stopped‐flow chromatographic methods
2001-01-01

Abstract In recent years, dynamic chromatography and stopped‐flow chromatographic techniques have become versatile tools for the determination of enantiomerization and isomerization barriers. Increasing demands for the stereochemical safety of chiral drugs contributed to the rapid development of new techniques. New computer‐aided evaluation systems allow the on‐line determination of interconversion barriers from the experimental chromatograms. Both dynamic chromatography and stopped‐flow chromatography have been applied to the entire range of chromatographic methods (GC, SFC, HPLC, CE). Chirality 13:403–414, 2001. © 2001 Wiley‐Liss, Inc.
Frequency of Overinstrumentation with an Acceptable Radiographic Working Length
2001-01-01

The aim of this in vitro study was to determine how frequent a seemingly accurate working length ending radiographically 0 to 2 mm short of the radiographic apex resulted in an instrumentation beyond the apical foramen. Under simulated clinical conditions working lengths of 169 root canals were radiographically determined in 91 extracted teeth. In all cases the measuring files adjusted to the final working length (Iwork) were located 0 to 2 mm short of the radiographic apex. Iwork was subsequently compared with the actual reference length (Iref) representing the distance between the apical foramen and the coronal reference. Instrumentation beyond the apical foramen (Iwork > ref) occurred in premolars in 51% (95% confidence interval: 36%; 66%) of the cases, in molars in 22% (95% confidence interval: 14%; 30%), and in anterior teeth in no case. These results suggest that in premolars and molars a radiographically working length ending 0 to 2 mm short of the radiographic apex provides, more often than expected, a basis for unintentional overinstrumentation.
Effects of Very Long (up to 10 Years) Proton Pump Blockade on Human Gastric Mucosa
2001-01-01

&lt;i&gt;Background:&lt;/i&gt; Long-term use of proton pump inhibitors (PPI) has been reported to worsen oxyntic mucosa gastritis and the resulting gland atrophy has been considered a potential risk factor for neoplastic changes in the gastric mucosa. &lt;i&gt;Aims:&lt;/i&gt; The present study examines the effect of extended continuous PPI treatment for up to 10 years on the exocrine and endocrine stomach of patients with acid-related diseases of the upper GI tract. &lt;i&gt;Methods:&lt;/i&gt; Biopsies from the antral and oxyntic mucosa taken at regular time intervals were examined for gastritis, atrophy, intestinal metaplasia, &lt;i&gt;Helicobacter pylori&lt;/i&gt; and argyrophil cells and correlated to serum gastrin levels. &lt;i&gt;Results:&lt;/i&gt; A general amelioration of antral gastritis without relevant changes of atrophy or intestinal metaplasia, contrasted with the worsening of gastritis and gland atrophy seen in the oxyntic mucosa of reflux esophagitis (but not gastric or duodenal ulcer) patients in the presence of &lt;i&gt;H. pylori&lt;/i&gt; infection. In association with PPI- induced hypergastrinemia, argyrophil cell hyperplasia (but not dysplasia or neoplasia) developed in the oxyntic mucosa. &lt;i&gt;Conclusion:&lt;/i&gt; The present results outline the milder pretreatment pattern and higher proneness to PPI-related, &lt;i&gt;H. pylori&lt;/i&gt;-restricted worsening of oxyntic mucosa gastritis in reflux esophagitis compared to gastric ulcer or duodenal ulcer patients. In addition, they confirm a substantial safety of long-term PPI therapy as concerns neoplastic changes in the exocrine and endocrine human stomach.
Epidemiology of Cutaneous Melanoma in Germany and Worldwide
2001-01-01

Rising incidence rates of cutaneous melanoma have been observed during the last three decades. At the beginning of the 1970s 3 cases and in the 1990s 9 cases per 100,000 inhabitants and year were reported by the Saarland Cancer Registry in Germany. Other incidence studies from Germany in the 1990s even reported 10–12 cases per 100,000 inhabitants and year, which is more likely to be the representative melanoma incidence in Western Germany. In a worldwide comparison this is a medium incidence rate as compared to clearly higher incidence rates in the United States (10–20 cases per 100,000 inhabitants and year) and in Australia (40–60 cases per 100,000 inhabitants and year). In Europe the highest incidence rates have been reported from Scandinavia (about 15 cases per 100,000 inhabitants and year) and the lowest from the Mediterranean countries (about 5–7 cases per 100,000 inhabitants and year). Mortality rates likewise increased in Germany between 1970 and 1995 in males from 1.7 to 3.2 cases and in females from 1.6 to 2.0 cases per 100,000 inhabitants and year. In the 1990s, in Germany and in many other countries a leveling off of mortality rates was observed. 48,928 melanoma patients have been recorded by the Central Malignant Melanoma Registry from the German-speaking countries in the time period from 1983 to September 2000, and clinico-epidemiological analysis of cutaneous melanoma is based on this data material. While 2/3 of all melanoma patients in Germany were females in the 1970s, there is now a more balanced gender distribution with more than 45% of patients being males. Age distribution does not significantly change during the last three decades. Most melanomas are diagnosed in the age group between 50 and 60 years, 22% of all melanomas are diagnosed before the 40th year of age. A clear decrease of Breslow’s tumor thickness was found from the beginning of the 1980s to the mid-1990s with the median thickness decreasing from 1.3 to 0.8 mm. Lower Breslow’s tumor thickness at first diagnosis of cutaneous melanoma has only been reported from Australia. This development indicates improved early recognition of cutaneous melanoma which is presently the main factor for a more favorable prognosis.
The multidrug resistance protein MRP1 mediates the release of glutathione disulfide from rat astrocytes during oxidative stress
2001-01-01

The release of glutathione disulfide has been considered an important process for the maintenance of a reduced thiol redox potential in cells during oxidative stress. In cultured rat astrocytes, permanent hydrogen peroxide‐induced oxidative stress caused a rapid increase in intracellular glutathione disulfide, which was followed by the appearance of glutathione disulfide in the medium. Under these conditions, the viability of the cells was not compromised. In the presence of cyclosporin A and the quinoline‐derivative MK571, inhibitors of multidrug resistance proteins (MRP1 and MRP2), glutathione disulfide accumulated in cells and the release of glutathione disulfide from astrocytes during H 2 O 2 stress was potently inhibited, suggesting a contribution of MRP1 or MRP2 in the release of glutathione disulfide from astrocytes. Using RT‐PCR we amplified a cDNA from astroglial RNA with a high degree of homology to MRP1 from humans and mouse. In contrast, no fragment was amplified by using primers specific for rat MRP2. In addition, the presence of MRP1 protein in astrocytes was demonstrated by its immunolocalization in cells expressing the astroglial marker protein glial fibrillary acidic protein. Our data identify rat astrocytes as a MRP1‐expressing brain cell type and demonstrate that this transporter participates in the release of glutathione disulfide from astrocytes during oxidative stress.
Free radicals, exercise, apoptosis, and heat shock proteins.
2001-01-01

Free radicals are an integral part of metabolism and are formed continuously in the body. Many sources of stress heat, irradiation, hyperoxia, inflammation and any increases in metabolism including exercise, injury, and even repair processes lead to increased production of free radicals and associated reactive oxygen or nitrogen species (ROS/RNS). Evidence is accumulating that free radicals have important functions in the signal network of cells, including induction of growth and apoptosis and as killing tools of immunocompetent cells. Endogenous and nutritional antioxidant systems have to be adjusted to ensure adequate removal of radicals during stress to prevent damage to membranes, proteins, or nucleic acids. Excessive stress will induce DNA damage in the form of oxidized nucleosides, strand breaks, or DNA-protein crosslinks. Possible consequences of DNA damage are repair, apoptosis/necrosis, or defective repair leading to DNA sequence alterations and possibly to the development of cancer or, in case of mitochondrial DNA, to metabolic dysfunction. Excessive exercise will also induce DNA damage in peripheral leukocytes. The good message is that moderate stress in form of regular exercise/training may have protective effects against exercise-induced DNA damage. Up-regulation of endogenous antioxidant defense systems and complex regulation of repair systems such as heat shock proteins (HSP 70, HSP 27, HO 1) are seen in response to training and exercise. Up-regulation of antioxidants and modulation of the repair response may be mechanisms by which exercise can beneficially influence our health. Massive intervention into the redox state by pharmaceutical doses of exogenous antioxidants should be regarded with caution due to the ambiguous role of free radicals in regulation of growth, apoptosis, and cytotoxicity by immunocompetent cells.
Lipid A and O‐chain modifications cause Rhizobium lipopolysaccharides to become hydrophobic during bacteroid development
2001-01-01

Modifications to the lipopolysaccharide (LPS) structure caused by three different growth conditions were investigated in the pea‐nodulating strain Rhizobium leguminosarum 3841. The LPSs extracted by hot phenol–water from cultured cells fractionated into hydrophilic water and/or hydrophobic phenol phases. Most of the LPSs from cells grown under standard conditions extracted into the water phase, but a greater proportion of LPSs were extracted into the phenol phase from cells grown under acidic or reduced‐oxygen conditions, or when isolated from root nodules as bacteroids. Compared with the water‐extracted LPSs, the phenol‐extracted LPSs contained greater degrees of glycosyl methylation and O‐acetylation, increased levels of xylose, glucose and mannose and increased amounts of long‐chain fatty acids attached to the lipid A moiety. The water‐ and phenol‐phase LPSs also differed in their reactivity with monoclonal antibodies and in their polyacrylamide gel electrophoretic banding patterns. Phenol‐extracted LPSs from rhizobia grown under reduced‐oxygen conditions closely resembled the bulk of LPSs isolated from pea nodule bacteria (i.e. mainly bacteroids) in their chemical properties, reactivities with monoclonal antibodies and extraction behaviour. This finding suggests that, during symbiotic bacteroid development, reduced oxygen tension induces structural modifications in LPSs that cause a switch from predominantly hydrophilic to predominantly hydrophobic molecular forms. Increased hydrophobicity of LPSs was also positively correlated with an increase in the surface hydrophobicity of whole cells, as shown by the high degree of adhesion to hydrocarbons of bacterial cells isolated from nodules or from cultures grown under low‐oxygen conditions. The implications of these LPS modifications are discussed for rhizobial survival and function in different soil and in planta habitats.
Salvage Treatment With Paclitaxel, Ifosfamide, and Cisplatin Plus High-Dose Carboplatin, Etoposide, and Thiotepa Followed by Autologous Stem-Cell Rescue in Patients With Relapsed or Refractory Germ Cell Cancer
2001-01-01

PURPOSE: To study feasibility and efficacy of a new salvage regimen in patients with relapsed and/or refractory germ cell tumors. PATIENTS AND METHODS: Between May 1995 and February 1997, 80 patients were entered onto a phase II study. Conventional-dose salvage treatment with three cycles of paclitaxel 175 mg/m 2 , ifosfamide 5 × 1.2 g/m 2 , and cisplatin 5 × 20 mg/m 2 (TIP) was followed by one cycle of high-dose chemotherapy (HDCT) with carboplatin 500 mg/m 2 × 3, etoposide 600 mg/m 2 × 4, and thiotepa 150 to 250 mg/m 2 × 3 (CET). In 23 patients, one additional cycle of paclitaxel 175 mg/m 2 and ifosfamide 5 g/m 2 (TI) was given immediately before TIP to improve stem-cell mobilization. RESULTS: Fifty-five (69%) of 80 patients responded to TIP, 24 (30%) of 80 patients had stable disease (n = 5) or tumor progression (n = 19), and one patient died. Only 62 (78%) of 80 patients received subsequent HDCT. Among those, 41 (66%) of 62 patients responded and 20 (32%) of 62 patients had stable disease (n = 3) or tumor progression (n = 17). One patient died after HDCT from multiorgan failure. Survival probabilities at 3 years were 30% for overall and 25% for event-free survival. Peripheral neurotoxicity with sensorimotor impairment grade 2 through 4 in 29%, paresthesias grade 2 through 4 in 24%, and skin toxicity grade 2 through 3 in 15% of patients were the most relevant side effects. CONCLUSION: Treatment with TIP followed by high-dose CET is feasible and can induce long-term remissions in 25% of patients with relapsed or refractory germ cell tumors. Peripheral nervous toxicity in approximately one third of patients is a disadvantage of this salvage strategy.
Cartilage Oligomeric Matrix Protein (Thrombospondin-5) Is Expressed by Human Vascular Smooth Muscle Cells
2001-01-01

Abstract —Cartilage oligomeric matrix protein (COMP/thrombospondin [TSP]-5) belongs to the thrombospondin gene family and is an extracellular glycoprotein found predominantly in cartilage and tendon. To date, there is limited evidence of COMP/TSP-5 expression outside of the skeletal system. The aim of the present study was to investigate the expression of COMP/TSP-5 in cultured human vascular smooth muscle cells and human arteries. COMP/TSP-5 mRNA and protein expression was detected in cultured human vascular smooth muscle cells with both Northern blotting and immunoprecipitation. Serum, as well as transforming growth factor (TGF)-β1 and TGF-β3, stimulated COMP/TSP-5 mRNA expression. COMP/TSP-5 was detected in normal as well as atherosclerotic and restenotic human arteries with immunohistochemistry. The majority of COMP/TSP-5 was expressed in close proximity to vascular smooth muscle cells. In vitro attachment assays demonstrated strong adhesion of smooth muscle cells to COMP/TSP-5–coated surfaces, with the majority of cells spreading and forming stress fibers. In addition, COMP/TSP-5 supported the migration of smooth muscle cells in vitro. The present study shows that COMP/TSP-5 is present in human arteries and may play a role in the adhesion and migration of vascular smooth muscle cells during vasculogenesis and in vascular disease settings such as atherosclerosis.