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Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A popular method for detecting changes in the probability distribution of a sequence of observations is CUSUM, which proceeds by sequentially evaluating a log-likelihood ratio test statistic and comparing it to a predefined threshold; a change point is detected as soon as the threshold is exceeded. It is desirable to choose the threshold such that the number of false alarms is kept to a specified level. Traditionally, the number of false alarms is measured by the average run length - the expected stopping time until the first false alarm. However, this is does not in general allow one to control the number of false alarms at every particular time instance. Thus, in this paper two stronger false alarm criteria are considered, for which approximation methods are investigated to facilitate the selection of a threshold. [ABSTRACT FROM AUTHOR]

Summary Low vitamin D status is common in patients with heart failure and may influence bone health. A daily vitamin D dose of 4000 IU (moderately high dose) for 3 years had however no effect on parameters of bone metabolism, even in patients with very low vitamin D status. Introduction Low vitamin D status is common in patients with heart failure (HF) and has been related to disturbed bone turnover. The present study investigated the effect of a daily vitamin D3 dose of 4000 IU on bone turnover markers (BTMs) in patients with advanced HF and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L. Methods In this pre-specified secondary analysis of a randomized controlled trial, we assessed in 158 male HF patients (vitamin D group: n = 80; placebo group: n = 78) between-group differences in calciotropic hormones (25OHD, 1,25-dihydroxyvitamin D [1,25(OH)2D], intact parathyroid hormone [iPTH]), and BTMs (cross-linked C-telopeptide of type I collagen, bone-specific alkaline phosphatase, undercarboxylated osteocalcin). Comparisons were performed at the end of a 3-year vitamin D supplementation period with adjustments for baseline values. Results Compared with placebo, vitamin D increased 25OHD on average by 54.3 nmol/L. At study termination, 25OHD and 1,25(OH)2D were significantly higher (P < 0.001 and P = 0.007, respectively), whereas iPTH tended to be lower in the vitamin D group than in the placebo group (P = 0.083). BTMs were initially within their reference ranges and did not differ significantly between groups at study termination, neither in the entire study cohort nor when data analysis was restricted to the subgroup of patients with initial 25OHD concentrations < 30 nmol/L (n = 54) or to patients with initial hyperparathyroidism (n = 65) (all P values > 0.05). Conclusions A daily vitamin D3 dose of 4000 IU did not influence BTMs. Data indicate that vitamin D supplementation will not lower bone turnover in male patients with heart failure. [ABSTRACT FROM AUTHOR]

Purpose: Stroke and mortality risk in patients with left ventricular assist device (LVAD) implants continue to be high. Whether nonclassical cardiovascular risk markers such as vitamin D metabolites and fibroblast growth factor (FGF)-23 contribute to this risk remains to be studied, and this was the objective of our work. Methods: In 154 LVAD patients (91 HeartWare and 63 HeartMate II implants), we measured circulating 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25[OH]D), parathyroid hormone (PTH) and FGF-23 shortly before LVAD implantation and investigated their association with stroke and mortality risk during 1-year follow-up. Results: Of the study cohort, 34.4 and 92.2 %, respectively, had deficient 25OHD (<25 nmol/l) and 1,25(OH)D (<41 pmol/l) values, whereas 42.6 and 98.7 %, respectively, had elevated PTH levels (>6.7 pmol/l) and FGF-23 values above the reference range (100 RU/ml). One-year freedom from stroke was 80.9 %, and 1-year survival was 64.3 %. The multivariable-adjusted hazard ratio of stroke was 2.44 (95 % CI: 1.09-5.45; P = 0.03) for the subgroup of 25OHD levels <25 nmol/l (reference group: 25OHD levels ≥25 nmol/l). The multivariable-adjusted hazard ratio of 1-year mortality was 2.78 (95 % CI: 1.52-5.09; P = 0.001) for patients with 25OHD levels <25 nmol/l compared with patients with 25OHD levels ≥25 nmol/l. PTH, FGF-23 and 1,25(OH)D were not associated with stroke or mortality risk. Conclusions: In LVAD patients, deficient 25OHD levels are independently associated with high stroke and mortality risk. If confirmed in randomized controlled trials, preoperative correction of deficient vitamin D status could be a promising measure to reduce stroke and mortality risk in LVAD patients. [ABSTRACT FROM AUTHOR]

Objective: The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. Design: A 1-year phase I proof-of-concept study. Setting: The Department of Psychiatry and Psychotherapy at the University of Cologne. Participants: We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. Intervention: Bilateral low-frequency DBS of the nucleus basalis of Meynert. Measurements: Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. Results: With a normal body mass index (BMI) at baseline (mean 23.75 kg/m) and after 1 year (mean 24.59 kg/m), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = −0.829, p = 0.042). Conclusion: Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies. [ABSTRACT FROM AUTHOR]

The fronto-striatal circuits are considered to mediate inhibitory control over action. The aim of this study was to investigate the contribution of the internal segment of the pallidum (GPi), one of the final output pathways from the basal ganglia to the cortex, in inhibition. We examined the effect of deep brain stimulation (DBS) of the GPi (GPi-DBS) in patients with Parkinson's disease who performed a conditional stop signal task, with DBS on and off. Modulation of GPi activity was associated with significantly faster Go reaction times with DBS on than off, but stop signal reaction times were not altered. Application of the drift diffusion model indicated that GPi-DBS was associated with significantly lower response thresholds compared to GPi-DBS off. However, the drift rate was significantly lower than healthy controls with both GPi-DBS on and off. These results suggest that the GPi plays a crucial role in the 'Go' pathway, perhaps facilitating reaching the required threshold to initiate actions. However, GPi-DBS does not alter the functioning of the indirect 'NoGo' pathway, and other basal ganglia nuclei, such as the STN, may play a greater role in reactive response inhibition and conflict resolution. [ABSTRACT FROM AUTHOR]

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [18F]- fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or nontransitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated. [ABSTRACT FROM AUTHOR]

Four patients who had completed chemotherapy for malignant disease are presented. Unexpected findings of pulmonary infiltrates on chest radiographs of two patients and solitary and/or confluent nodules on CT in all four led to open lung biopsy. Histologic diagnosis in each case was bronchiolitis obliterans-organizing pneumonia (BOOP). This usually innocuous disorder can be differentiated histologically from the more severe pure bronchiolitis obliterans and should be considered in the differential diagnosis of pulmonary lesions associated with malignant disease. [ABSTRACT FROM AUTHOR]

We have performed CT scans on 15 children and 2 young adults with severe renal inflammatory disease. Most children with urinary tract infections do not require such evaluation. We have, however, found CT helpful in defining the nature of renal abnormality and in defining the extent of disease in selected patients who either presented as diagnostic dilemmas or who did not respond initially to proper medical treatment. We therefore use CT scanning as our initial examination in such problem patients. [ABSTRACT FROM AUTHOR]

Four children with histiocytosis-X had large solid mediastinal masses at diagnosis. Follow-up studies in three showed large air cysts occupying the sites of the original masses; the fourth patient had small air cysts at the periphery of the mass. All patients survived. One patient was explored and the large air cysts were in the mediastinum with adherence to the adjacent lung. Lesser pulmonary involvement was noted in the lungs of three of the four patients. Cavitation within mediastinal masses in histiocytosis-X appears to reflect two processes. The first is necrosis within the masses themselves. The second is involvement of adjacent lung with adherence of lung and pleura to the mediastinum allowing air to fill the mediastinal cavities. [ABSTRACT FROM AUTHOR]

The correlation between nephroblastomatosis and Wilms' tumor has been established in the pathology literature. Two cases of multifocal nephroblastomatosis in the kidney contralateral to a Wilms' tumor are presented. The importance of these lesions and their recognition is discussed. [ABSTRACT FROM AUTHOR]

The exceptional ability of dendrimers to coordinate metal ions yields the potential for many applications including wastewater remediation, which is the focus of this study. Here, the comparison of metal ion removal rate from simulated wastewater by generation 4 dendrimers with external hydroxyl functional groups (G4-OH) is evaluated for Ni, Fe, and Fe ions. Ni to amine complexation occurred more rapidly than Fe, which was more rapid than Fe complexation. These results indicate that both charge density and d-electron configuration are important toward the chelation rate. The impact of both factors is discussed in light of existing models in which precursor aquation rates have been proposed as a key intermediate step. Additionally, the application of the dendrimers as chelation agents is further advanced by immobilizing the dendrimer to titania and re-evaluating its chelation ability for Ni removal. The dendrimer immobilization decreased the pseudo-first-order rate coefficient for Ni-amine complexation at a pH of 7 by a factor of 7.5. This result is significant as it suggests that mass transfer becomes important following immobilization of the dendrimer to titania. [ABSTRACT FROM AUTHOR]

Background: As an established treatment for movement disorders, the application of deep brain stimulation (DBS) for psychiatric indications has been investigated for almost 15 years. A CE label (also FDA approval) has recently been obtained for treatment of refractory obsessive-compulsive disorder (OCD). Objectives: This article aims at illustrating the current state of DBS in the treatment of refractory OCD. In addition, initial experimental approaches to investigate the potential use of DBS in substance addiction and anorexia nervosa (AN) will also be outlined as both disorders share some common features with OCD. Materials and methods: The present review is based on a keyword literature search (PubMed) while taking into account relevant references and own investigations Results: Although the number of clinical trials for treatment of refractory OCD is limited and sample sizes are small, there is some evidence for a substantial improvement, a so-called full response of OCD symptoms under DBS. However, not all patients benefit from the intervention. Regarding substance addiction and AN, data are scarce and are only indicative of a potential benefit at most. Discussion: Present data regarding the clinical benefits of DBS in OCD are encouraging and open up new avenues for the treatment of therapy refractory patients. However, several aspects, such as mechanisms of action, predictors and long-term side effect profiles, are incomplete or even unknown. In the case of addiction and AN, DBS remains purely experimental, at least for the moment. Hence, clinical trials should remain the gold standard for all three indications. [ABSTRACT FROM AUTHOR]

TAG vaccine is a novel 'triad vaccine' that involves transfection of autologous tumor with a dual plasmid, TGFβ2 antisense gene and GM-CSF gene. Patients with advanced cancer who failed standard therapy were treated. IFN-γ ELISPOT analysis (Enzyme-Linked Immunospot Assay for Interferon Gamma) using TAG autologous vaccine target cells was performed prior to vaccination and at week 12 after the third vaccination. The purpose of this assessment was to correlate the IFN-γ ELISPOT immune response with long-term survival of advanced cancer patients who received TAG vaccination. Twenty-three of 28 patients received 3 TAG vaccinations (two patients withdrew consent and three had disease progression prior to the third vaccination). Eleven patients demonstrated a positive ELISPOT response (>10 spots and 2 × baseline) at week 12 and 12 patients did not (P=0.002). Median survival from time of treatment between ELISPOT-positive and -negative groups was significantly different (550 vs 159 days, P=0.036), as was median survival from the time of procurement (627 vs 257 days, respectively, P=0.043). In conclusion, the IFN-γ ELISPOT assay may provide an effective measure of immune response following treatment with 'triad vaccines', but additional patient numbers and/or other immune modulatory parameters are necessary for future testing. [ABSTRACT FROM AUTHOR]

A composite NiO-YZrO (YSZ) agglomerated feedstock having nanoscale NiO and YSZ primary particles was used to fabricate anodes having sub-micrometer structure. These anodes were incorporated into two different metal-supported SOFC architectures, which differ in the order of electrode deposition. The composition of the composite Ni-YSZ anodes is controllable by selection of the agglomerate size fraction and standoff distance, while the porosity is controllable by selection of agglomerate size fraction and addition of a sacrificial pore-forming material. A bi-layer anode was fabricated having a total porosity of 33% for the diffusion layer and 23% porosity for the functional layer. A power density of 630 mW/cm was obtained at 750 °C in humidified H with cells having the bi-layer anode deposited on the metal support. Cells having the cathode deposited on the metal support showed poor performance due to a significant number of vertical cracks through the electrolyte, allowing excessive gas cross-over between the anode and the cathode compartments. [ABSTRACT FROM AUTHOR]

Photocatalytic process has shown recently a great potential as an environmental friendly and clean remediation technology for organic pollutants in wastewater. This work described the synthesis of silver-based bimetallic nanoparticles using colloid chemistry and the subsequent immobilization onto titania to form composite photocatalytic materials (titania-supported Ag-Pt nanoparticles). The photocatalysts were characterized by X-ray diffraction, electron microscopy, and nitrogen physisorption. The catalytic activity of the photocatalysts was evaluated by photocatalytic degradation of phenol and 2-chlorophenol (2-CP) in synthetic wastewater solutions. The photocatalytic processes were conducted in a batch photoreactor containing appropriate solutions of phenol and 2-CP with UV irradiation of 450 W. UV-visible spectrophotometer was used for analyzing the concentration of phenol and 2-CP in solutions. Parameters affecting the photocatalytic process such as the solution pH, phenol and 2-CP concentrations, and catalyst concentration were investigated. The results obtained revealed that TiO-supported Ag/Pt nanoparticles showed a higher activity for UV-photocatalytic degradation of both phenol and 2-CP pollutants in the solution (as compared to the plain rutile TiO). The photodegradation processes were optimized by the 0.5-g/L catalyst with a pollutant concentration of 50 mg/L for all the samples. Complete degradation for both phenol and 2-CP was achieved after 120 min. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

RNA interference (RNAi) is a natural cellular regulatory process that inhibits gene expression by transcriptional, post-transcriptional and translational mechanisms. Synthetic approaches that emulate this process (small interfering RNA (siRNA), short hairpin RNA (shRNA)) have been shown to be similarly effective in this regard. We developed a novel 'bifunctional' RNAi strategy, which further optimizes target gene knockdown outcome. A bifunctional construct (bi-sh-STMN1) was generated against Stathmin1, a critical tubulin modulator that is overexpressed in human cancers. The bifunctional construct is postulated to concurrently repress the translation of the target mRNA (cleavage-independent, mRNA sequestration and degradation) and degrade (through RNase H-like cleavage) post-transcriptional mRNA through cleavage-dependent activities. Bi-sh-STMN1 showed enhanced potency and durability in parallel comparisons with conventional shRNA and siRNAs targeting the same sequence. Enhanced STMN1 protein knockdown by bi-sh-STMN1 was accompanied by target site cleavage at the mRNA level showed by the rapid amplification of complementary DNA ends (RACE) assay. Bi-sh-STMN1 also showed knockdown kinetics at the mRNA level consistent with its multieffector silencing mechanisms. The bifunctional shRNA is a highly effective and advantageous approach mediating RNAi at concentrations significantly lower than conventional shRNA or siRNA. These results support further evaluations. [ABSTRACT FROM AUTHOR]

Recent whole-genome sequencing efforts led to the identification of IDH1(R132) mutations in acute myeloid leukemia (AML) patients. We studied the prevalence and clinical implications of IDH1 genomic alterations in pediatric and adult AML. Diagnostic DNA from 531 AML patients treated on Children's Oncology Group trial COG-AAML03P1 (N=257), and Southwest Oncology Group trials SWOG-9031, SWOG-9333 and SWOG-9500 (N=274), were tested for IDH1 mutations. Codon R132 mutations were absent in the pediatric cohort, but were found in 12 of 274 adult patients (4.4%, 95% CI 2.3-7.5). IDH1(R132) mutations occurred most commonly in patients with normal karyotype, and those with FLT3/ITD and NPMc mutations. Patients with IDH1(R132) mutations trended toward higher median diagnostic white blood cell counts (59.2 x 10(9) vs 29.1 x 10(9) per liter, P=0.19) than those without mutations, but the two groups did not differ significantly in age, bone marrow blast percentage, overall survival or relapse-free survival. Eleven patients (2.1%) harbored a novel V71I sequence alteration, which was found to be a germ-line polymorphism. IDH1 mutations were not detected in pediatric AML, and are uncommon in adult AML. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Based on the preclinical evidence of topoisomerase I (Topo-1) upregulation by mitomycin C(MMC) and decreased NF-κB activation by celecoxib, we evaluated combinations of irinotecan/MMC and irinotecan/MMC/celecoxib in patients with advanced solid malignancies. Initially, patients received MMC on day 1 and irinotecan on days 2, 8, 15 and 22, every 6 weeks. MMC dose was fixed at 6 mg/m2 and cumulative doses of >36 mg/m2 were not permitted. Irinotecan was escalated in 25 mg/m2 increments. Due to late-onset diarrhea, the schedule was subsequently shortened to 4 weeks, omitting irinotecan on days 15 and 22. In the second part of the study, celecoxib 400 mg orally twice daily was added to irinotecan/MMC regimen. Potential pharmacokinetic interactions and Topo-1 and DT-diaphorase (NQ01) gene expressions in peripheral-mononuclear cells were evaluated. Forty-five patients were enrolled. Irinotecan 125 mg/m2 on days 2 and 8 in combination with MMC 6 mg/m2 on day 1 every 4 weeks is recommended for future studies; myelosuppression and diarrhea are dose-limiting. The addition of celecoxib resulted in unacceptable toxicities despite reductions on irinotecan’s dose. No relevant pharmacokinetic interactions occurred between irinotecan and MMC, and mean increases in Topo-1, were observed. Sixteen of 36 patients evaluable for response-assessment had discernable anti-tumor activity, including 1 complete, 4 partial, 10 minor and 1 tumor marker response. Four patients had prolonged (>4 months) disease-stability (stable disease, not included in CR or PR). Patients experiencing complete and partial responses had higher increments in Topo-1 expression. Modulation of irinotecan by MMC is feasible, devoid of pharmacological interactions and active in solid malignancies. The lack of improvement in therapeutic index does not support the addition of celecoxib. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and objectives:Long term evaluation of bariatric surgery must include quality of life measurement.Methods:Quality of life (QoL) was evaluated using the original Moorehead–Ardelt questionnaire for 200 patients operated for massive obesity in a single centre between 1994 and 2003. QoL and physical data were obtained by retrospective mail questionnaire. Surgical procedures were vertical-banded gastroplasty according to Mason (VBGM) and adjustable gastric banding (AGB) in 61 and 39% of patients, respectively. The aim of the study was to assess the nutritional outcome and QoL according to the procedure.Results:Overall, the body mass index (BMI) decreased from 50±8 kg/m2 before surgery to 35.2±7.5 kg/m2 at the time of the questionnaire. The percentage of weight loss was 28.8±12.2%. In the group treated with VBGM, the mean initial weight (P=0.003) and the percentage of weight loss (P<0.001) were significantly higher, and the QoL was better (P=0.003) than in the group treated with AGB. On the basis of the time spent since surgery, a regular weight loss was observed during the first 5 years, whereas weight subsequently increased over the five following years. Similarly, the total QoL score gradually improved during the first 5 years and worsened thereafter. However, it remained better than before surgery. A linear regression analysis showed a positive correlation between the percentage of weight loss and the QoL score (P<0.001).Conclusions:This study suggests that the bariatric surgery, particularly the VBGM technique, improved the QoL of obese patients, at least in the first 5 years following surgery.European Journal of Clinical Nutrition (2008) 62, 1022–1030; doi:10.1038/sj.ejcn.1602808; published online 1 August 2007 [ABSTRACT FROM AUTHOR]

To identify signature targets associated with patient-specific cancer lesions based on tumor versus normal tissue differential protein and mRNA coexpression patterns for the purpose of synthesizing cancer-specific customized RNA interference knockdown therapeutics. Analysis of biopsied tissue involved two-dimensional difference in-gel electrophoresis (2D-DIGE) analysis coupled with MALDI-TOF/TOF mass spectrometry for proteomic assessment. Standard microarray techniques were utilized for mRNA analysis. Priority was assigned to overexpressed protein targets with co-overexpressed genes with a high likelihood of functional nodal centrality in the cancer network as defined by the interactive databases BIND, HPRD and ResNet. HPLC-grade small interfering RNA (siRNA) duplexes were utilized to assess knockdown of target proteins in expressive cell lines as measured by western blot. Seven patients with metastatic cancer underwent biopsy. One patient (RW001) had biopsies from two disease sites 10 months apart. Seven priority proteins were identified, one for each patient (RACK 1, Ras related nuclear protein, heat-shock 27 kDa protein 1, superoxide dismutase, enolase1, stathmin1 and cofilin1). Prioritized proteins in RW001 from the two disease sites over time were the same. We demonstrated >80% siRNA inhibition of RACK 1 and stathmin1 of inexpressive malignant cell lines with correlated cell kill. Identification of functionally relevant target gene fingerprints, unique to an individual's cancer, is feasible ‘at the bedside’ and can be utilized to synthesize siRNA knockdown therapeutics. Further animal safety testing followed by clinical study is recommended.Cancer Gene Therapy (2007) 14, 686–695; doi:10.1038/sj.cgt.7701057; published online 1 June 2007 [ABSTRACT FROM AUTHOR]

The xylosyltransferases I and II (XT-I, XT-II, EC 2.4.2.26) catalyze the transfer of xylose from UDP-xylose to selected serine residues in the proteoglycan core protein, which is the initial and ratelimiting step in glycosaminoglycan biosynthesis. Both xylosyltransferases are Golgi-resident enzymes and transfer xylose to similar core proteins acceptors. XT-I and XT-II are differentially expressed in cell types and tissues, although the reason for the existence of two xylosyltransferase isoforms in all higher organisms remains elusive. Serum xylosyltransferase activity was found to be a biochemical marker for the assessment of disease activity in systemic sclerosis and for the diagnosis of fibrotic remodeling processes. Furthermore, sequence variations in the XT-I and XT-II coding genes were identified as risk factors for diabetic nephropathy, osteoarthritis or pseudoxanthoma elasticum. These findings point to the important role of the xylosyltransferases as disease modifiers in pathologies which are characterized by an altered proteoglycan metabolism. The present review discusses recent advances in mammalian xylosyltransferases and the impact of xylosyltransferases in proteoglycan-associated diseases. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cellular entry of enveloped viruses is often dependent on attachment proteins expressed on the host cell surface. Viral envelope proteins bind these receptors, and, in an incompletely understood process, facilitate fusion of the cellular and viral membranes so as to introduce the viral core into the cytoplasm. Only a small fraction of viral receptors have been identified so far. Recently, a novel coronavirus was identified as the etiological agent of severe acute respiratory syndrome (SARS). The fusion protein gene of SARS coronavirus (SARS-CoV) was cloned and characterized, and shortly thereafter, angiotensin-converting enzyme 2 (ACE2) was shown to be its functional receptor. Identification of ACE2 as a receptor for SARS-CoV will likely contribute to the development of antivirals and vaccines. It may also contribute to the development of additional animal models for studying SARS pathogenesis, and could help identify the animal reservoir of SARS-CoV. [ABSTRACT FROM AUTHOR]

The feasibility of a measurement of the electric and magnetic nucleon form factors at B- meson factories through the radiative return is studied. Angular distributions allow for a separation of the contributions from the two form factors. The distributions are presented for the laboratory and the hadronic rest frame, and the advantages of different coordinate systems are investigated. It is demonstrated that Q² values up to 8 or even 9 GeV² are within reach. The Monte Carlo event generator PFIOKFIARA is extended to nucleon final states, and results are presented which include next-to-leading order radiative corrections from initial-state radiation. The impact of angular cuts on rates and distributions is investigated and the relative importance of radiative corrections is analyzed. [ABSTRACT FROM AUTHOR]

Objective. To examine the release of counterregulatory hormones and consecutive glimepiride serum concentrations during severe hypoglycaemia (SH) associated with glimepiride therapy. Methods. In nine type-2 diabetic patients [age 81±9 (65–93) years; diabetes duration 9±4 (3–15) years; initial blood glucose 33±16 (10–54) mg/dl (1.8±0.9 mmol/l); HbA1c 7.2±1.1 (5.6–8.7)%; creatinine clearance 49±33 (15–107) ml/min] who experienced SH associated with glimepiride therapy with neuroglucopenic presentation, insulin, C-peptide, glucagon, epinephrine, norepinephrine, cortisol, adenocorticotrophic hormone (ACTH), human growth hormone (HGH) and pancreatic polypeptide (PP) were determined in blood samples taken at 4-h intervals prior to and during treatment with glucose i.v. Serum from the same samples was screened for sulphonylurea-type oral antidiabetics. Glimepiride concentrations were determined by a validated atmospheric pressure chemical ionization liquid chromatographic-mass spectrometry (APCI-LC-MS) assay. Results. Once treatment had begun, normoglycaemia was maintained; most glimepiride levels were below the limit of detection (LOD <0.01 mg/l) and further sulphonylureas could be excluded. The secretion of glucagon and epinephrine as counterregulatory hormonal responses was unaffected. In addition, protracted marked increases of cortisol and norepinephrine levels were demonstrated. Protracted stimulation of insulin and C-peptide occurred in a period of up to 24 h after SH. No significant protracted responses were observed for ACTH, HGH or PP. Conclusion. In SH associated with glimepiride therapy, no correlation between glimepiride serum concentrations and the protracted stimulation of insulin and C-peptide was observed. The secretion of glucagon and epinephrine as counterregulatory hormonal responses was unaffected. Protracted increased release of cortisol might be a medium-term indicator of glimepiride-associated SH. [ABSTRACT FROM AUTHOR]

DjlA is a bitopic inner membrane protein, which belongs to the DnaJ co-chaperone family in Escherichia coli. Overproduction of DjlA leads to the synthesis of colanic acid, resulting in mucoidy, via the activation of the two-component regulatory system RcsC/B that controls the cps ( capsular polysaccharide) operon. This induction requires both the co-chaperone activity of DjlA, in cooperation with DnaK and GrpE, and its unique transmembrane (TM) domain. Here, we show that the TM segment of DjlA acts as a dimerisation domain: when fused to the N-terminal DNA-binding domain of the lambda cI repressor protein, it can substitute for the native C-terminal dimerisation domain of cI, thus generating an active cI repressor. Replacing the TM domain of DjlA by other TM domains, with or without dimerising capacity, revealed that dimerisation is not sufficient for the induction of cps expression, indicating an additional sequence- or structurally specific role for the TM domain. Finally, the conserved glycines present in the TM domain of DjlA are essential for the induction of mucoidy, but not for dimerisation. [ABSTRACT FROM AUTHOR]

Netrins are secreted molecules capable of attracting or repelling growing axons. They and their receptors, along with other netrin-interacting proteins, are widely conserved among animals from a broad range of phyla. We have raised and purified an antibody against a recently cloned leech netrin, which has allowed us to characterize embryonic netrin expression by cells in peripheral tissues and in the central nervous system. During early gangliogenesis, netrin expression was detected at particularly high levels in five bilateral pairs of central neurons. Towards the end of the period of axonal outgrowth, netrin expression was observed to be restricted to only six central neurons, comprising two bilateral pairs and two unpaired cells. A pair of netrin-producing central neurons, the bipolar cells, was identified by their expression of the antigen recognized by the monoclonal antibody Laz1–1. Double staining of sensory afferents from segmental sensilla with the monoclonal antibody Lan3–2 and the bipolar cells with the netrin antibody revealed that the terminals of these afferents grow up to the bipolar cells and turn anteriorly or posteriorly, without extending any further medially. Peripheral netrin expression was found to be restricted to longitudinal muscle cells in the ventral half of the body wall. Extracellular, secreted netrin was detected in a broad longitudinal stripe located symmetrically with respect to the ventral midline. The pattern of expression of netrin in leech embryos is consistent with observed expression patterns in other animals, suggesting that developmental netrin functions are conserved among all bilateral animals. [ABSTRACT FROM AUTHOR]

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We report a case in a neonate of concurrent bronchial atresia and bronchogenic cyst. An accurate, noninvasive, preoperative diagnosis of this unusual combination of anomalies was made by ultrafast computed tomography (UFCT). This case supports the hypothesis that bronchial atresia results from an event occurring in the 5th-6th week of embryological development, rather than after the 16th week as previously believed. [ABSTRACT FROM AUTHOR]

Aberrant thymic tissue, particularly when it is located posteriorly, can present a diagnostic dilemma. Once a mediastinal "lesion" is defined on the plain film, MR is the most efficient and best diagnostic test for defining the nature of the mass and showing its relationship to other mediastinal structures. Two cases of aberrant thymic tissue, one on the right side and one on the left, are presented to elucidate the unique role of MRI. [ABSTRACT FROM AUTHOR]

The global power of the differences of altimetric sea heights at collocated points in the first 44 cycles of the Topex/Poseidon (T/P) mission, apparently shows the influence of errors in the major tides and long period ocean signals. Results show the principal semidiurnal tides (M2/S2 lumped together) in the Cartwright and Ray (1991) model are probably in error globally by 3-4 cm (rms). The dominant fluctuation in the differences over the 44 cycles (14 months total) arises from an annual signal of 4-6 cm (rms), significantly greater than long term climate data suggests (but with considerable uncertainty due to unresolved semiannual effects). [ABSTRACT FROM AUTHOR]

The localization of autologous antiperoxidase immunoglobulin G (IgG) was studied in the choroid plexus of Lewis rats immunized against horseradish peroxidase (HRP). This experiment was performed to study the permeability of the choroid plexus to intravascular IgG. It was shown that autologous IgG was present in the extravascular spaces. The transendothelial transfer appeared to occur mainly via the fenestrations and some interendothelial junctions. No transfer of IgG at the level of epithelial cells toward the cerebrospinal fluid was demonstrated. Interstitial spaces in contact with the connective-tissue cells of the choroid stroma were strongly labeled. The significance of these spaces remains hypothetical and raises the question of the fate of IgG from the interstitial space. [ABSTRACT FROM AUTHOR]

We have studied the pharmacokinetics and the effects of BIM 23014 (BIM), a new, long-acting octapeptide somatostatin analogue, on basal and stimulated GH secretion in normal men. BIM 250 μg sc significantly reduced a GHRH-induced increase in plasma GH. The continuous sc administration of BIM for 24 h dramatically blunted spontaneous GH secretion; 2000 and 3000 μg daily reduced GH secretion to a greater extent than 1000 μg daily. During these experiments a significant negative correlation (r−0.66) was found between plasma GH and BIM levels. Acute sc administration of 1000 μg BIM significantly reduced the rise in plasma GH observed in the second part of the oral glucose tolerance test. Plasma BIM levels peaked around 30 min, and the elimination half life was 90 min. Plasma BIM levels were below 1 ng/ml 6 h after the injection of 1000 μg BIM, and at that time GH started to rise again. We conclude that BIM 23014 250 to 1000 μg sc is able to reduce the plasma GH response to GHRH or to the fall in glucose following an oral glucose tolerance test; a constant infusion of BIM, in doses 1000 μg daily, dramatically suppresses spontaneous GH secretion; 2000 μg/day by chronic subcutaneous infusion was the most effective dose of BIM in the suppression of GH secretion, and was associated only with minor adverse effects. [ABSTRACT FROM AUTHOR]

Forty-seven infants and children had excretory urography, ultrasound, and computed tomography with the renal and perirenal areas as the primary regions of interest. Ultrasound is an excellent screening procedure and is often diagnostic especially in renal cystic disease. Computed tomography best demonstrated the extent of renal injury and best delineated the geography, character, and extent of solid renal and perirenal neoplasms (screened by ultrasound). Excretory urography in these patients was at times incorrect, often underestimated the extent of the pathologic process, and is often unnecessary. [ABSTRACT FROM AUTHOR]

The defect of an appendiceal abscess on a barium enema is most often seen on the medial aspect of the cecum. However, the site of involvement may vary depending on the location of the appendix. This paper illustrates some of the unusual radiographic findings that were found on barium enemas in six pediatric patients with appendiceal abscess that were not involving the medial cecum. [ABSTRACT FROM AUTHOR]

Observations made during the 1991 total solar eclipse and recent observations from NSO/Sac Peak are discussed. The ground-based density measurements will be complimentary to SOHO observations, particularly SOHO electron density measurements. [ABSTRACT FROM AUTHOR]