julilili42/papers huggingface dataset:
Acute Hyperglycemia Causes Intracellular Formation of CML and Activation of ras, p42/44 MAPK, and Nuclear Factor κB in PBMCs
2003-03-01

Twenty-three nondiabetic volunteers were divided into three groups. In group A (n = 9), the glucose infusion was adjusted to maintain blood glucose at 5 mmol/l (euglycemic clamp). In group B (n = 9), the glucose infusion was adjusted to maintain blood glucose at 10 mmol/l (hyperglycemic clamp) over 2 h. Group C consisted of five volunteers who were studied as the control group. Peripheral blood mononuclear cells (PBMCs) were isolated before and at the end of a 2-h clamp. In group C, PBMCs were isolated before and after 2 h without performing a clamp. The euglycemic clamp as well as “no clamp” had no effects on all parameters studied. In contrast, a significant increase in carboxymethyllysine (CML) content and p21ras and p42/44 mitogen-activated protein kinase (MAPK) phosphorylation was observed at the end of a 2-h hyperglycemic clamp. The nuclear factor (NF)-κB (but not Oct-1) binding activity increased significantly in the hyperglycemic clamp. Western blots confirmed NF-κB-p65-antigen translocation into the nucleus. IκBα did not change significantly in both groups. Hyperglycemia-mediated NF-κB activation and increase of CML content, p21ras, and p42/44 MAPK phosphorylation was also seen in ex vivo–isolated PBMCs stimulated with 5 or 10 mmol/l glucose. Addition of insulin did not influence the results. Inhibition of activation of ras, MAPK, or protein kinase C blocked hyperglycemia-mediated NF-κB activation in ex vivo–isolated PBMCs stimulated with 10 mmol/l glucose. Similar data were obtained using an NF-κB-luciferase reporter plasmid. Therefore, we can conclude that an acute hyperglycemia-mediated mononuclear cell activation is dependent on activation of ras, p42/p44 MAPK phosphorylation, and subsequent NF-κB activation and results in transcriptional activity in PBMCs.
Vegetation response to rapid climate change in Central Europe during the past 140,000 yr based on evidence from the Füramoos pollen record
2003-03-01

Abstract The response of Central European vegetation to rapid climate change during the late Quaternary period (Eemian to Holocene) is assessed by data from the new pollen record of Füramoos, southwestern Germany. This record represents the longest late Quaternary pollen record north of the Alps as currently known. Its high degree of completeness allows detailed correlations with Greenland ice cores and sea–surface temperature records from the North Atlantic. Our data show that if climate deteriorations were not long or severe enough to extirpate refugia of arboreal taxa north of the Alps such as during marine oxygen isotope stage (MIS) 5 (i.e., Würm Stadial A, Stadial B, and Stadial C), reforestation with the onset of warmer conditions in Central Europe occurred on a centennial scale. If arboreal taxa became completely extinct north of the Alps such as during MIS 4 (i.e., Würm Stadial D), several thousand years were necessary for the reimmigration from refugia situated in regions south of the Alps. Thus, Dansgaard–Oeschger interstades (DOIS) 24 to 20 and 15 to 11 are expressed in Central European pollen records, whereas DOIS 19 to 16 are not recorded due to migration lags.
Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains
2003-03-01

The solute carrier gene family SLC26 consists of tissue-specific anion exchanger genes, three of them associated with distinct human recessive disorders. By a genome-driven approach, several new SLC26 family members have been identified, including a kidney- and pancreas-specific gene, SLC26A6. We report the functional characterization of SLC26A6 and two new alternatively spliced variants, named SLC26A6c and SLC26A6d. Immunofluorescence studies on transiently transfected cells indicated membrane localization and indicated that both NH 2 - and COOH-terminal tails of the SLC26A6 variants are located intracellularly, suggesting a topology with an even number of transmembrane domains. Functional expression of the three proteins in Xenopus oocytes demonstrated Cl − and SO[Formula: see text] transport activity. In addition, the transport of SO[Formula: see text] and Cl − was inhibited by DIDS and HCO[Formula: see text]. We demonstrated also that the COOH terminus of SLC26A6 binds to the first and second PDZ domains of the Na + /H + exchanger (NHE)3 kinase A regulatory protein (E3KARP) and NHE3 regulatory factor (NHERF) proteins in vitro. Truncation of the last three amino acids (TRL) of SLC26A6 abrogated the interaction but did not affect transport function. These results demonstrate that SLC26A6 and its two splice variants can function as anion transporters linked to PDZ-interaction pathways. Our results support the general concept of microdomain organization for ion transport and suggest a mechanism for cystic fibrosis transmembrane regulator (CFTR)-mediated SLC26A6 upregulation in pancreatic duct cells.
Disinhibition of the contralateral motor cortex by low-frequency rTMS
2003-03-01

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) results in a lasting decrease of motor evoked potentials (MEPs). Here we investigated the effects of supra-threshold rTMS (15 min, 1 Hz) to the left M1 on the excitability of the stimulated and homologous (unstimulated) M1 in healthy subjects by using single and double pulse TMS before and after rTMS. We found reduction of MEP amplitudes on the stimulated side and, most importantly, disinhibition of intracortical excitability of the homologous M1. This crossed effect of rTMS supports the concept of a physiological balance of reciprocal inhibitory projections and emphasizes that rTMS can induce remote effects that are relevant for the physiological interpretation of such interventions.
Radiotherapy with 16 Gy may fail to eradicate testicular intraepithelial neoplasia: preliminary communication of a dose-reduction trial of the German Testicular Cancer Study Group
2003-03-01

Low-dose radiotherapy to the testis is effective in eradicating testicular intraepithelial neoplasia (TIN, carcinoma in situ of the testis) at the risk of androgenic deficiency. The present trial was designed to define the lowest dose effective to control TIN assuming a dose-response relation of radiation-induced endocrinological damage. Patients with TIN in a solitary testicle or with bilateral TIN were treated with 18 Gy (14 patients) and 16 Gy (26 patients) (5 x 2 Gy per week). Biopsies to ascertain clearance of TIN were performed after 6 and 24 months. The median time of follow-up is 20.5 months. There were three adverse events. In one patient, relapse of TIN along with microinvasive seminoma was observed 2 years after 16 Gy irradiation. In two other patients, persistent spermatogonia were observed with the 16 and 18 Gy regimen after 6 and 24 months, respectively. All other post-treatment biopsies showed the Sertoli cell-only pattern. These results confirm that TIN is a radiosensitive lesion efficiently controlled in most cases with doses below 20 Gy. However, sporadic failures may occur. A dose of 16 Gy is probably unsafe and should no longer be used. Future investigations should not only focus on total dosage of irradiation but also on fractionation schedules.
Treatment of periprosthetic soft tissue infection of the groin following vascular surgical procedures by means of a polyvinyl alcohol‐vacuum sponge system
2003-03-01

Deep groin infections after prosthetic vascular surgical procedures represent a serious complication of surgical practice. Septicemia and/or erosive hemorrhage can both be consequences. In this situation, removal of the graft appears to be the only option. However, if the infection is detected early (type Szilagyi III), local treatment to eradicate the infection could serve as an alternative. Twenty‐four patients with confirmed infection of the soft tissue adjacent to the prosthetic material in the groin were treated locally by implantation of a vacuum sponge system. Duration of this treatment was 2 weeks. All patients showed excellent tissue granulation of the wound area and the microbial stains were negative at the end of therapy. In 21 patients the wound could be primarily closed after explantation of the sponge. Three patients underwent open treatment because of a skin defect. After 12 months, the wounds had healed well in all patients. Histologic evaluation revealed a physiological healing process. Deep soft tissue infections of the groin adjacent to prosthetic vascular material (type Szilagyi III) can be treated effectively and safely with the vacuum sponge system. The treatment is inexpensive, easy to perform, and the initial vascular reconstruction can be preserved. (WOUND REP REG 2003;11:104–109)
Let it be sexual: how health care transmission of AIDS in Africa was ignored
2003-03-01

The consensus among influential AIDS experts that heterosexual transmission accounts for 90% of HIV infections in African adults emerged no later than 1988. We examine evidence available through 1988, including risk measures associating HIV with sexual behaviour, health care, and socioeconomic variables, HIV in children, and risks for HIV in prostitutes and STD patients. Evidence permits the interpretation that health care exposures caused more HIV than sexual transmission. In general population studies, crude risk measures associate more than half of HIV infections in adults with health care exposures. Early studies did not resolve questions about direction of causation (between injections and HIV) and confound (between injections and STD). Preconceptions about African sexuality and a desire to maintain public trust in health care may have encouraged discounting of evidence. We urge renewed, evidence-based, investigations into the proportion of African HIV from non-sexual exposures.
Lack of biofilm contribution to bacterial colonisation in an experimental model of foreign body infection byStaphylococcus aureusandStaphylococcus epidermidis
2003-03-01

The contribution of in vivo biofilm-forming potential of Staphylococcus aureus and Staphylococcus epidermidis was studied in an experimental model of foreign body infections. Increasing inocula (from 10(2) to 10(7) organisms) of ica-positive strains of S. aureus and S. epidermidis and their ica-negative isogenic mutants (the ica locus codes for a major polysaccharide component of biofilm) were injected into subcutaneously implanted tissue cages in guinea pigs. Surprisingly, bacterial counts and time-course of tissue cage infection by ica-positive strains of S. aureus or S. epidermidis were equivalent to those of their respective ica-negative mutants, in the locally infected fluids and on tissue-cage-inserted plastic coverslips.
Behavioral significance of input-dependent plasticity of human somatosensory cortex
2003-03-01

Training and learning induce powerful cortical reorganizational changes, which are referred to as use- or experience-dependent plasticity. Using MEG, we investigated how rapid reorganization of human somatosensory cortex induced by tactile stimulation leads to improved spatial discrimination performance. Plastic changes were induced by several hours of tactile co-activation in separated receptive fields on the right index finger. Subjects did not attend the stimulation but performed their daily work. We found a 20% decrease in spatial two-point discrimination thresholds paralleled by a dipole shift in medio-lateral direction along the central sulcus. We conclude that reorganization of primary somatosensory cortex induced by purely passive tactile co-activation is sufficient to improve tactile discrimination performance without training, attention or reinforcement.
Palmitate-Induced Activation of the Hexosamine Pathway in Human Myotubes
2003-03-01

The nutrient sensing capacity of the hexosamine biosynthetic pathway (HBP) has been implicated in the development of insulin resistance of skeletal muscle. To study the molecular mechanism of the free fatty acid (FFA)-induced activation of the HBP myotubes obtained from muscle biopsies of metabolically characterized, subjects were stimulated with different fatty acids for 20 h. Incubation with the saturated fatty acids palmitate and stearate (0.5 mmol/l) resulted in a three- to fourfold increase in mRNA expression of glutamine:fructose-6-phosphate aminotransferase (GFAT), the key and rate-limiting enzyme of the hexosamine pathway. Unsaturated fatty acids or 30 mmol/l glucose had little or no effect. Palmitate increased the amount of GFAT protein nearly two-fold, and subsequently, the concentration of UDP-N-acetylglucosamine, the end product of the HBP, was 1.3-fold enhanced in the palmitate-stimulated myotubes. The nonmetabolized fatty acid bromopalmitate had no effect. The DNA binding activity of the transcription factor Sp1, a target downstream of the HBP, was increased by palmitate and completely lost after enzymatic removal of O-GlcNAc. No correlation was found between the palmitate-induced increase in GFAT protein and the insulin resistance in the respective subjects. The findings reveal a new mechanism for how FFAs induce the activation of the HBP.
Density-dependent parasite establishment suggests infection-associated immunosuppression as an important mechanism for parasite density regulation in onchocerciasis
2003-03-01

The modulation of human immune response by filarial parasites has yielded contradictory experimental findings and attracted much controversy. We address the unresolved question of acquisition, establishment and accumulation of Onchocerca volvulus by using a modelling approach that relates computer simulations to cross-sectional data concerning parasite burdens in 913 West African onchocerciasis patients. It is shown that the acquisition of O. volvulus is not constant with host age; instead, the analysis of age profiles of parasite burdens strongly indicate the operation of immunosuppressive processes within the human host, associated with the presence of adult parasites or microfilariae. It is suggested that these processes suppress immunity against incoming infective larvae (L3), which themselves act as an immune modulating component once they have successfully overcome the barrier of concomitant immunity. Suppression of parasite-specific immunity leads to parasite establishment rates which increase along with the parasite burden, but which hardly depend on hyperendemic annual transmission potentials. Children, still immunocompetent due to low parasite burdens, acquire 0.1-0.5 adult female parasites per year, whereas older people, immunosuppressed due to high burdens, acquire 2-4 adult female parasites per year. Differences in parasite establishment between the forest and the savannah strains of O. volvulus are quantified and dynamic aspects of density-dependent parasite establishment discussed.
Differential Effects of Immunophilin-Ligands (FK506 and V-10,367) on Survival and Regeneration of Rat Retinal Ganglion Cells In Vitro and after Optic Nerve Crush In Vivo
2003-03-01

Immunophilins belong to the large family of peptidyl-prolyl-cis-trans-isomerases known to be involved in many cellular processes (e.g., protein trafficking and transcriptional regulation). Beside the widespread therapeutic use of ligands of immunophilins as immunosuppressants, it has been shown that some of these compounds such as FK506 and V-10,367 may mediate neuroprotection and improve axonal regeneration following damage to peripheral nerve fibers. Here, we have analyzed the effects of these two compounds on neurite outgrowth of retinal explants in vitro and on axonal regeneration of retinal ganglion cells, a population of central intrinsic neurons, ten days following optic nerve crush in vivo. FK506 enhanced neurite outgrowth/regrowth in vitro in a dose dependent manner up to 135% (control = 100%), while V-10,367 was more effective (up to 168%). In vivo, intravitreal V-10,367 and FK506 significantly reduced the number of dying retinal ganglion cells as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Local application of FK506 into the vitreous body, but not V-10,367, immediately provided after the optic nerve crush induced the elongation of regenerating fibers across the lesion site for around 1.2 mm. Our data provide evidence that the ligands of the FK506-binding proteins FK506 and V-10,367 protect (otherwise dying) retinal ganglion cells from optic nerve crush-induced cell death, promote neurite outgrowth in vitro and that locally applied FK506 enhances the sprouting of axotomized central intrinsic neurons such as retinal ganglion cells in vivo after optic nerve crush.
The right supratemporal plane hears the distance of objects: neuromagnetic correlates of virtual reality
2003-03-01

The neural mechanisms of auditory distance perception, a function of great biological importance, are poorly understood. Where not overruled by conflicting factors such as echoes or visual input, sound intensity is perceived as conveying distance information. We recorded neuromagnetic responses to amplitude variations over both supratemporal planes, with and without auditory spatial simulations. In the absence of other cues for distance, including those provided by auditory virtual reality, amplitude changes elicited enhanced preattentive responses over the right temporal lobe, indicating hemispheric lateralization of the 'where' pathway in the human. Lesion studies in monkeys and humans have shown that the rostral part of the right superior temporal cortex contributes to spatial awareness in the visual domain. Our data indicate that the distance to a sound source is processed within the adjacent right auditory cortex, thus extending the recent model of a right-hemisphere temporal multisensory matrix that subserves the integration of space-related data across visual and auditory modalities.
Distinguishing between different pathways of bilayer disruption by the related antimicrobial peptides cecropin B, B1 and B3
2003-03-01

Different pathways of bilayer disruption by the structurally related antimicrobial peptides cecropin B, B1 and B3, revealed by surface plasma resonance analysis of immobilized liposomes, differential scanning calorimetry of peptide–large unilamellar vesicle interactions, and light microscopic analysis of peptide‐treated giant unilamellar vesicles, have been identified in this study. Natural cecropin B (CB) has one amphipathic and one hydrophobic α‐helix, whereas cecropins B1 (CB1) and B3 (CB3), which are custom‐designed, chimaeric analogues of CB, possess either two amphipathic or two hydrophobic α‐helices, respectively. Surface plasma resonance analysis of unilamellar vesicles immobilized through a biotin–avidin interaction showed that both CB and CB1 bind to the lipid bilayers at high concentration (&gt;10 μ m ); in contrast, CB3 induces disintegration of the vesicles at all concentrations tested. Differential scanning calorimetry showed the concentration‐dependent effect of bilayer disruption, based on the different thermotrophic phase behaviours and the shapes of the thermal phase‐transition curves obtained. The kinetics of the lysis of giant unilamellar vesicles observed by microscopy demonstrated that both CB and CB1 effect a continuous process involving loss of integrity followed by coalescence and resolution into smaller vesicles, whereas CB3 induces rapid formation of irregular‐shaped, nonlamellar structures which rapidly disintegrate into twisted, microtubule‐containing debris before being completely destroyed. On the basis of these observations, models by which CB, CB1 and CB3 induce lysis of lipid bilayers are discussed.
Magnetic Resonance-guided Transcortical Biopsy of Bone Marrow Lesions Using a Magnetic Resonance Imaging-compatible Piezoelectric Power Drill
2003-03-01

To test utility and specific properties of a commercially available MRI compatible power drill for MR guided transcortical bone biopsy.In 17 patients MR-guided bone biopsy was performed in an open low-field scanner (0.2 T), using a piezoelectrically powered drilling machine. Target lesions were osteoblastic in four and nonsclerosed intramedullary in 13 cases. Titanium drills sized 3 to 4 mm and an outer cannula were coaxially used for power assisted cortical trephination. For intramedullary lesion sampling, spring loaded biopsy guns and sharpened cannulas were additionally applied in seven and fluid aspiration in two patients, respectively.The piezoelectric device proved to be fully MR compatible. Trephination and subsequent biopsy was successful in all patients without major complications. The drilling procedure could entirely be performed inside the magnet in case of a lateral approach (n = 11). The net drilling time averaged 7.8 minutes for trephination of nonimpaired diaphyseal bone, but was up to 50 minutes in case of thickened femoral bone. Procedures were complicated by frequent drill loosening, drill obstruction by cortical bone (n = 4) and impaired periosteal grip (n = 5) with damage to the outer cannula (n = 3).The piezoelectric power drill can be applied safely in a low-field MRI environment and is a valuable tool to facilitate transcortical bone biopsy.
Mounting anomalies in the epidemiology of HIV in Africa: cry the beloved paradigm
2003-03-01

In North America Europe and many parts of Asia the ignition of regional epidemics and rapid HIV transmission has been associated principally with the sharing of contaminated injecting equipment and with anal intercourse. Though heterosexual intercourse has been virtually the sole explanation offered for the AIDS epidemic in sub-Saharan Africa to our knowledge in no other part of the world has penile-vaginal exposure (as opposed to “heterosexual sex”) been demonstrated to initiate or sustain rapid HIV propagation. HIV is not transmitted by “sex” but only by specific risky practices. It is not transmitted by “injections” but only by contaminated implements which need to be clearly differentiated as to type and frequency of injection and by the conditions of the exposure setting. In virtually all societies affected by HIV to date both routes seem to play important roles. If we are to understand and intervene in each of these epidemics well-designed studies at both the population and individual levels are urgently needed. It is vital that these be properly controlled for parenteral exposure specific sexual practices and other co-factors and the complex and specific social patterns and networks that accompany them. (excerpt)
Epigenetic control of E-cadherin (CDH1) by CpG methylation in metastasising laryngeal cancer
2003-03-01

Intercellular adhesion is promoted by many-fold structures formed by interacting molecules. One prominent protein family, called cadherins, consists of calcium-dependent proteins contributing to cell differentiation, migration and extracellular signal transduction. E-cadherin, regularly expressed in epithelial tissues, displays aberrant activity patterns in a variety of tumors. We have explored the mode of E-cadherin regulation in 98 biopsy samples from 76 patients with laryngeal carcinoma (80 primary tumors and 18 metastases). Transcriptional silencing of the gene (CDH1) achieved by promoter methylation was tested by a methylation-specific PCR. In primary tumors, CDH1 methylation was noted in 40%. However, 77% of the tested metastases showed CDH1 methylation, 23% remained unmethylated (p<0.01). These data suggest that the E-cadherin promoter is subjected to epigenetic control connected with biological aggressiveness of laryngeal cancer in advanced steps of neoplastic transformation.