bluuebunny/crossref_metadata_2025 huggingface dataset:
Allopurinol and Enalapril Failed to Conserve Urinary NOx and Sodium in Ischemic Acute Renal Failure in Spontaneously Hypertensive Rats
Authors: Radovic Milan , Miloradovic Zoran , Popovic Tamara , Mihailovic-Stanojevic Nevena , Jovovic Djurdjica , Tomovic Mina , Colak Emina , Simic-Ogrizovic Sanja , Djukanovic Ljubica
Published: August 2006

Background: Ischemia-reperfusion-induced acute renal failure (ARF) is associated with a high mortality in patients with hypertension and with an unfavorable outcome of kidney transplants from marginal donors. Aim: The influence of allopurinol and enalapril on urinary nitrate/nitrite (UNOx), glomerular filtration rate, plasma and urinary sodium, and hemodynamic parameters was examined in spontaneously hypertensive rats (SHR) with ARF. Methods: ARF was induced by right-kidney removal and clamping the left renal artery for 40 min in 50 male 26-week-old SHR weighing 300 ± 23 g. The rats were randomly allocated to five groups: (1) sham operated; (2) ARF; (3) ARF after pretreatment with 40 mg/kg allopurinol; (4) ARF after pretreatment with 40 mg/kg enalapril, and (5) ARF after pretreatment with 40 mg/kg allopurinol and 40 mg/kg enalapril. Creatinine clearance, UNOx (Griess reaction), cardiac output (dye dilution technique), mean arterial blood pressure, and renal blood flow were measured 24 h after reperfusion. Total vascular resistance and renal vascular resistance were calculated and compared between the groups. Results: A nonsignificant decrease was found in both daily UNOx excretion and creatinine clearance when pretreated ARF groups and the ARF group without pretreatment were compared (p > 0.05). Significantly lower plasma sodium values (139.5 ± 4.86 mmol/l) in the allopurinol-pretreated ARF group were found than in the ARF group without pretreatment, in the ARF group pretreated with enalapril, and in the sham SHR group (p = 0.029). The urinary sodium loss was greater in the enalapril-pretreated than in the allopurinol-pretreated ARF group (p = 0.047). Allopurinol and/or enalapril pretreatment decreased total vascular resistance (p = 0.003) in comparison with the sham SHR group. Conclusion: Neither allopurinol nor enalapril nor both were protective against ischemia-reperfusion injury in SHR, nor altered glomerular filtration rate and UNOx in a favorable direction.
Proximal Renal Tubular Acidosis in Pregnancy
Authors: Firmin C.J. , Kruger T.F. , Davids R.
Published: August 2006

Renal tubular acidosis is usually associated with chronic renal conditions and is rarely encountered in pregnancy. It may be inherited causing osteomalacia and rickets in children or acquired following autoimmune diseases or following exposure to nephrotoxic agents. It is known to worsen during pregnancy and if left untreated may cause maternal and foetal morbidity or death. We report a 28-year-old woman, gravida 3 para 2, who presented at 30 weeks gestation with lethargy, weakness and generalized myalgia. Investigation revealed severe hypokalaemia and a systemic metabolic acidosis due to proximal renal tubular acidosis. Her previous pregnancies were both complicated by foetal losses at term. Following prompt correction of her electrolyte disturbance and metabolic acidosis, she went on to deliver a healthy female infant at term. Regular evaluation up to 1 year post-partum revealed mild persistence of her hypokalaemia. At 1 year, the infant showed no signs of the disorder and is growing normally.
Fabric Selection for a Liquid Cooling Garment
Authors: Cao Huantian , Branson Donna H. , Peksoz Semra , Nam Jinhee , Farr Cheryl A.
Published: August 2006

The selection of an inner fabric layer is an important aspect in the development of a liquid cooling garment (LCG). The desired characteristics of an inner fabric layer in LCGs include good thermal conductivity, moisture management, and tactile properties. Good thermal conductivity can improve cooling efficiency, and good moisture management and tactile properties can make the wearer more comfortable. Eighteen fabrics that differed in fiber content, fabric structure and thickness were investigated in this study for their suitability for use as an inner fabric layer for a LCG. Thermal resistance, evaporative resistance, wicking, and water distribution were measured. Correlation among the three moisture management tests was studied. The effects of metal-containment and fabric thickness on thermal and evaporative resistance were determined. The most suitable fabric among the 18 tested fabrics was selected in this study.
c-Rel plays a key role in deficient activation of B cells from a non–X-linked hyper-IgM patient
Authors: Lu Kristina T. , Sinquett Frank L. , Dryer Rebecca L. , Song Charles , Covey Lori R.
Published: August 2006

Our previous results demonstrated that B cells from a patient (pt1) with non–X-linked hyper-IgM syndrome (HIGM) possess an atypical CD23lo phenotype that is unaffected by CD40-mediated activation. To investigate the molecular mechanism underlying defective CD23 expression in pt1 B cells, we used lymphoblastoid cell lines that express LMP1 under the control of a tetracycline-inducible promoter (LCLtet). Our analysis revealed that the CD23lo phenotype in the pt1-LCLtet cells is a direct consequence of diminished CD23 transcription. We demonstrate a marked decrease in c-Rel–containing complexes that bind to the proximal CD23a/b promoters in pt1-LCLtet extracts, resulting from an overall lower expression of c-Rel in pt1-LCLtet cells. Analysis of c-Rel mRNA revealed relatively equal amounts in pt1-LCLtet and control LCLtet cells, indicating that diminished c-Rel protein expression is unrelated to decreased transcription. Finally, a critical role for c-Rel in CD23 regulation was demonstrated by effectively altering c-Rel expression that resulted in the direct modulation of CD23 surface expression. Collectively, these findings demonstrate that low levels of c-Rel are the underlying cause of aberrant CD23 expression in pt1 B cells and are likely to play a critical role in the pathophysiology of this form of HIGM.
Annotation of novel neuropeptide precursors in the migratory locust based on transcript screening of a public EST database and mass spectrometry
Authors: Clynen Elke , Huybrechts Jurgen , Verleyen Peter , De Loof Arnold , Schoofs Liliane
Published: August 2006

Background

For holometabolous insects there has been an explosion of proteomic and peptidomic information thanks to large genome sequencing projects. Heterometabolous insects, although comprising many important species, have been far less studied. The migratory locust Locusta migratoria, a heterometabolous insect, is one of the most infamous agricultural pests. They undergo a well-known and profound phase transition from the relatively harmless solitary form to a ferocious gregarious form. The underlying regulatory mechanisms of this phase transition are not fully understood, but it is undoubtedly that neuropeptides are involved. However, neuropeptide research in locusts is hampered by the absence of genomic information.

Results

Recently, EST (Expressed Sequence Tag) databases from Locusta migratoria were constructed. Using bioinformatical tools, we searched these EST databases specifically for neuropeptide precursors. Based on known locust neuropeptide sequences, we confirmed the sequence of several previously identified neuropeptide precursors (i.e. pacifastin-related peptides), which consolidated our method. In addition, we found two novel neuroparsin precursors and annotated the hitherto unknown tachykinin precursor. Besides one of the known tachykinin peptides, this EST contained an additional tachykinin-like sequence. Using neuropeptide precursors from Drosophila melanogaster as a query, we succeeded in annotating the Locusta neuropeptide F, allatostatin-C and ecdysis-triggering hormone precursor, which until now had not been identified in locusts or in any other heterometabolous insect. For the tachykinin precursor, the ecdysis-triggering hormone precursor and the allatostatin-C precursor, translation of the predicted neuropeptides in neural tissues was confirmed with mass spectrometric techniques.

Conclusion

In this study we describe the annotation of 6 novel neuropeptide precursors and the neuropeptides they encode from the migratory locust, Locusta migratoria. By combining the manual annotation of neuropeptides with experimental evidence provided by mass spectrometry, we demonstrate that the genes are not only transcribed but also translated into precursor proteins. In addition, we show which neuropeptides are cleaved from these precursor proteins and how they are post-translationally modified.
Comparison of different methods in analyzing short-term air pollution effects in a cohort study of susceptible individuals
Authors: Peters Annette , von Klot Stephanie , Berglind Niklas , Hörmann Allmut , Löwel Hannelore , Nyberg Fredrik , Pekkanen Juha , Perucci Carlo A , Stafoggia Massimo , Sunyer Jordi , Tiittanen Pekka , Forastiere Francesco
Published: August 2006

Background

Short-term fluctuations of ambient air pollution have been associated with exacerbation of cardiovascular disease. A multi-city study was designed to assess the probability of recurrent hospitalization in a cohort of incident myocardial infarction survivors in five European cities. The objective of this paper is to discuss the methods for analyzing short-term health effects in a cohort study based on a case-series.

Methods

Three methods were considered for the analyses of the cohort data: Poisson regression approach, case-crossover analyses and extended Cox regression analyses. The major challenge of these analyses is to appropriately consider changes within the cohort over time due to changes in the underlying risk following a myocardial infarction, slow time trends in risk factors within the population, dynamic cohort size and seasonal variation.

Results

Poisson regression analyses, case-crossover analyses and Extended Cox regression analyses gave similar results. Application of smoothing methods showed the capability to adequately model the complex time trends.

Conclusion

From a practical point of view, Poisson regression analyses are less time-consuming, and therefore might be used for confounder selection and most of the analyses. However, replication of the results with Cox models is desirable to assure that the results are independent of the analytical approach used. In addition, extended Cox regression analyses would allow a joint estimation of long-term and short-term health effects of time-varying exposures.
HLA-DR expression on monocytes and systemic inflammation in patients with ruptured abdominal aortic aneurysms
Authors: Haveman Jan Willem , van den Berg Aad P , Verhoeven Eric LG , Nijsten Maarten WN , van den Dungen Jan JAM , The Hauw T , Zwaveling Jan Harm
Published: August 2006

Introduction

Mortality from ruptured abdominal aortic aneurysms (RAAA) remains high. Severe systemic inflammation, leading to multi-organ failure, often occurs in these patients. In this study we describe the level of HLA-DR expression in a consecutive group of patients following surgery for RAAA and compare results between survivors and non-survivors. A similar comparison is made for IL-6 and IL-10 levels and Sequential Organ Failure Assessment (SOFA) scores.

Methods

This is a prospective observational study. Patients with RAAA were prospectively analysed. Blood samples were collected on days 1, 3, 5, 7, 10 and 14. The fraction of CD-14 positive monocytes expressing HLA-DR was measured by flow-cytometry. IL-6 and IL-10 levels were measured by ELISA.

Results

The study included 30 patients with a median age of 70 years, of which 27 (90%) were men. Six patients died from multiple organ failure, all other patients survived. The SOFA scores were significantly higher in non-survivors on days 1 through 14. HLA-DR expression on monocytes was significantly lower on days 3, 5, 7, 10 and 14 in non-survivors. IL-6 and IL-10 levels were significantly higher in non-survivors on day 1 and days 1 and 3, respectively.

Conclusion

HLA-DR expression on monocytes was decreased, especially in non-survivors. All patients with RAAA displayed a severe inflammatory and anti-inflammatory response with an increased production of IL-6 and IL-10. Poor outcome is associated with high levels of IL-6 and IL-10 and a high SOFA score in the first three days after surgery, while low levels of HLA-DR expression are observed from day three after RAAA repair.
Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer
Authors: Hess Kenneth R. , Anderson Keith , Symmans W. Fraser , Valero Vicente , Ibrahim Nuhad , Mejia Jaime A. , Booser Daniel , Theriault Richard L. , Buzdar Aman U. , Dempsey Peter J. , Rouzier Roman , Sneige Nour , Ross Jeffrey S. , Vidaurre Tatiana , Gómez Henry L. , Hortobagyi Gabriel N. , Pusztai Lajos
Published: August 2006

Purpose

We developed a multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy and assessed its predictive accuracy on independent cases.

Patients and Methods

One hundred thirty-three patients with stage I-III breast cancer were included. Pretreatment gene expression profiling was performed with oligonecleotide microarrays on fine-needle aspiration specimens. We developed predictors of pCR from 82 cases and assessed accuracy on 51 independent cases.

Results

Overall pCR rate was 26% in both cohorts. In the training set, 56 probes were identified as differentially expressed between pCR versus residual disease, at a false discovery rate of 1%. We examined the performance of 780 distinct classifiers (set of genes + prediction algorithm) in full cross-validation. Many predictors performed equally well. A nominally best 30-probe set Diagonal Linear Discriminant Analysis classifier was selected for independent validation. It showed significantly higher sensitivity (92% v 61%) than a clinical predictor including age, grade, and estrogen receptor status. The negative predictive value (96% v 86%) and area under the curve (0.877 v 0.811) were nominally better but not statistically significant. The combination of genomic and clinical information yielded a predictor not significantly different from the genomic predictor alone. In 31 samples, RNA was hybridized in replicate with resulting predictions that were 97% concordant.

Conclusion

A 30-probe set pharmacogenomic predictor predicted pCR to T/FAC chemotherapy with high sensitivity and negative predictive value. This test correctly identified all but one of the patients who achieved pCR (12 of 13 patients) and all but one of those who were predicted to have residual disease had residual cancer (27 of 28 patients).
Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway—A Report of the Tumour Angiogenesis Research Group
Authors: Koukourakis Michael I. , Giatromanolaki Alexandra , Sivridis Efthimios , Gatter Kevin C. , Harris Adrian L.
Published: August 2006

Purpose

Lactate dehydrogenase 5 (LDH-5) regulates, under hypoxic conditions, the anaerobic transformation of pyruvate to lactate for energy acquisition. Several studies have shown that serum LDH may be an ominous prognostic marker in malignant tumors. The clinical significance of tissue LDH-5, however, remains largely unexplored.

Patients and Methods

We investigated the immunohistochemical expression of LDH-5 in a series of 128 stage II/III colorectal adenocarcinomas treated with surgery alone. In addition, markers of tumor hypoxia (hypoxia-inducible factor 1 alpha [HIF1α]), angiogenesis (vascular endothelial growth factor [VEGF] and phosporylated kinase domain receptor [pKDR]/flk-1 receptor) and the tumor vascular density (CD31 positive standard vascular density [sVD] and pKDR positive activated vascular density [aVD]) were assessed.

Results

The expression of LDH-5, together with that of HIF1α and pKDR, was both nuclear and cytoplasmic. Assessment, with minimal interobserver variability, was achieved using a previously described scoring system. LDH-5 was significantly associated with HIF1α (P = .01), aVD (P = .001) and, particularly, with pKDR expression in cancer cells (P = .0001). Tissue LDH-5 expression was linked with elevated serum LDH levels, but serum levels failed to reflect tissue expression in 71% of LDH-5 positive cases. In univariate analysis tissue LDH-5 was associated with poor survival (P = .0003, HR 15.1), whereas in multivariate analysis this isoenzyme was the strongest independent prognostic factor (P = .0009). VEGF, pKDR, aVD, sVD and vascular invasion were all significantly related to unfavorable prognosis.

Conclusion

The immunohistochemical assessment of tissue LDH-5 and pKDR provides important prognostic information in operable colorectal cancer. The strong association between LDH-5 and pKDR expression would justify their use as surrogate markers to screen patients for tyrosin kinase inhibitor therapy.
The Impact of Glucocorticoid Replacement Regimens on Metabolic Outcome and Comorbidity in Hypopituitary Patients
Authors: Filipsson Helena , Monson John P. , Koltowska-Häggström Maria , Mattsson Anders , Johannsson Gudmundur
Published: August 2006

Background: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features.

Objective: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy.

Method: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age.

Results: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects.

Conclusion: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
Vascular Endothelial and Smooth Muscle Function Relates to Body Mass Index and Glucose in Obese and Nonobese Children
Authors: Peña Alexia Sophie , Wiltshire Esko , MacKenzie Karen , Gent Roger , Piotto Lino , Hirte Craig , Couper Jennifer
Published: August 2006

Context: Endothelial and smooth muscle dysfunction are critical precursors of atherosclerosis. These can be detected in children at risk of cardiovascular disease.

Objective: The objective of this study is to evaluate endothelial and smooth muscle function and their determinants using flow-mediated dilatation (FMD) and glyceryl trinitrate-mediated dilatation (GTN) in obese, nonobese, and type 1 diabetes mellitus (T1DM) children.

Design: This is a cross-sectional study.

Subjects: The study subjects were 270 children [140 males, mean age 13.7 (2.8) yr] including 58 obese, 53 nonobese, and 159 T1DM children.

Measurements: Vascular function (FMD and GTN), body mass index (BMI) z-score, blood pressure, glucose, glycosylated hemoglobin, lipids, folate, homocysteine, and high sensitive C-reactive protein were measured.

Results: FMD and GTN were significantly lower in obese and T1DM compared with nonobese subjects (P < 0.001, P < 0.001). FMD and GTN were similarly reduced in obese and T1DM subjects (P = 0.22, P = 0.28). In all nondiabetic subjects (n = 111), both FMD and GTN were significantly and independently related to BMI z-score (r = −0.28, P = 0.003, β = −0.36, P < 0.001) and weight z-score (β = −0.31, P = 0.002; r = −0.52, P < 0.001). FMD related independently to total cholesterol (β = −0.22, P = 0.02). GTN related independently to vessel diameter (β = −0.49, P < 0.001). GTN related to glucose within the normal range (r = −0.34, P = 0.001).

Conclusions: Children with obesity and T1DM have a similar degree of vascular dysfunction. BMI and weight adjusted for age and sex relate to endothelial and smooth muscle function in nonobese and obese children. Glucose relates to smooth muscle function in nonobese nondiabetic children. This suggests a continuum effect of BMI and glucose within the normal range on vascular function in childhood.
The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men
Authors: Matthiesson Kati L. , McLachlan Robert I. , O’Donnell Liza , Frydenberg Mark , Robertson David M. , Stanton Peter G. , Meachem Sarah J.
Published: August 2006

Context:. Male hormonal contraception via gonadotropin and intratesticular androgen withdrawal disrupts spermatogenesis at two principal sites: 1) spermatogonial maturation, and 2) spermiation.

Objective: The objective of this study was to explore the relative dependence of each stage of germ cell development on FSH and LH/intratesticular androgen action.

Design, Setting, and Participants: Eighteen men enrolled in this prospective, randomized 14-wk study at Prince Henrys Institute.

Interventions: Subjects (n = 6/group) were assigned to 6 wk of 1) testosterone (T) implant (4 × 200 mg sc once)+depot medroxy progesterone acetate (DMPA; 150 mg im once); 2) T implant+DMPA+FSH (300 IU sc twice weekly); and 3) T implant+DMPA+human chorionic gonadotropin (hCG; 1000 IU sc twice weekly as an LH substitute). Men then underwent a vasectomy and testicular biopsy with previously reported control data used for comparison.

Main Outcome Measures: Germ cell number (assessed by the optical disector stereological approach) and intratesticular androgen levels were determined.

Results: T+DMPA alone significantly suppressed type B spermatogonia, preleptotene through to pachytene spermatocytes, and round spermatids from control (P < 0.05). All germ cell subtypes were maintained at control levels by either FSH or LH activity, except pachytene spermatocytes, which were found to be lower in the hCG vs. FSH (P < 0.01) and control groups (P < 0.05).

Conclusions: FSH and LH maintained spermatogenesis independently in this gonadotropin-suppressed model. Compared with LH, FSH showed better maintenance of pachytene spermatocyte number, whereas improved conversion to round spermatids was suggested with hCG treatment. Future contraceptive treatment strategies must consider independent regulation of spermatogenesis by both FSH and LH/intratesticular androgens for maximum efficacy.
Differential Effects of a Perioperative Hyperinsulinemic Normoglycemic Clamp on the Neurohumoral Stress Response during Coronary Artery Surgery
Authors: van Wezel H. B. , Zuurbier C. J. , de Jonge E. , van Dam E. W. C. M. , van Dijk J. , Endert E. , de Mol B. A. , Fliers E.
Published: August 2006

Background: Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG.

Methods: Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU·kg−1·h−1) normoglycemic (plasma glucose between 3.0 and 6.0 mmol·liter−1) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD).

Results: There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol·liter−1. In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group.

Conclusion: A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.
Recruitment dynamics of GAK and auxilin to clathrin-coated pits during endocytosis
Authors: Lee Dong-won , Wu Xufeng , Eisenberg Evan , Greene Lois E.
Published: August 2006

Cyclin G-associated kinase (GAK), the ubiquitous form of the neuronal-specific protein auxilin 1, is an essential cofactor for Hsc70-dependent uncoating of clathrin-coated vesicles. Total internal reflectance microscopy was used to determine the timing of GAK binding relative to dynamin and clathrin binding during invagination of clathrin-coated pits. Following transient recruitment of dynamin to the clathrin puncta, large amounts of GAK are transiently recruited. GAK and clathrin then disappear from the evanescent field as the pit invaginates from the plasma membrane and finally these proteins disappear from the epifluorescence field, probably as the clathrin is uncoated from the budded vesicles by Hsc70. The recruitment of GAK is dependent on its PTEN-like domain, which we found binds to phospholipids. This suggests that interaction with phospholipids is essential for recruitment of GAK and, in turn, Hsc70, but Hsc70 recruitment alone might not be sufficient to induce irreversible clathrin uncoating. When budding of clathrin-coated pits is inhibited by actin depolymerization, there is repeated flashing of GAK on the clathrin-coated pit but neither scission nor irreversible uncoating occur. Therefore, budding as well as synchronous recruitment of GAK might be required for irreversible clathrin uncoating.
Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology
Authors: Zacharias Ute , Rauch Uwe
Published: August 2006

The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the lectican family show an overlapping distribution in the developing brain, have been implicated in similar cellular processes and form a complex network of interactions. Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1.

Here, we describe competition and cooperation between TN-R, lecticans and contactin 1, and their functional consequences for tectal cells. Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size. This blocking effect is due to competition of lecticans with binding of TN-R to its neuronal receptor contactin 1, as shown by a sandwich-binding assay. Interaction of aggrecan with TN-R fibronectin type III domains 4-A is necessary for its inhibitory effect on both microprocess formation and TN-R binding to contactin 1. However, the chondroitin sulfate chains are not involved. Time-lapse video microscopy showed that aggrecan has no acute effect on motility and morphology of microprocesses and growth cones but induces long-term neurite retraction after pre-treatment with TN-R.

In contrast to the competition described above, TN-R cooperates with brevican and neurocan to induce attachment of tectal cells and neurite outgrowth, probably by forming a bridge between the lectican substrate and contactin 1 as the neuronal receptor.

Our findings suggest that a complex network of protein-protein interactions within the brain extracellular matrix, as shown here for TN-R and lecticans, is important for the fine-regulation of developmental processes such as microprocess formation along the neurite and neurite outgrowth.
Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse
Authors: Swailes Nathan T. , Colegrave Melanie , Knight Peter J. , Peckham Michelle
Published: August 2006

The interaction of non-muscle myosins 2A and 2B with actin may drive changes in cell movement, shape and adhesion. To investigate this, we used cultured myoblasts as a model system. These cells characteristically change shape from triangular to bipolar when they form groups of aligned cells. Antisense oligonucleotide knockdown of non-muscle myosin 2A, but not non-muscle myosin 2B, inhibited this shape change, interfered with cell-cell adhesion, had a minor effect on tail retraction and prevented myoblast fusion. By contrast, non-muscle myosin 2B knockdown markedly inhibited tail retraction, increasing cell length by over 200% by 72 hours compared with controls. In addition it interfered with nuclei redistribution in myotubes. Non-muscle myosin 2C is not involved as western analysis showed that it is not expressed in myoblasts, but only in myotubes. To understand why non-muscle myosins 2A and 2B have such different roles, we analysed their distributions by immuno-electron microscopy, and found that non-muscle myosin 2A was more tightly associated with the plasma membrane than non-muscle myosin 2B. This suggests that non-muscle myosin 2A is more important for bipolar shape formation and adhesion owing to its preferential interaction with membrane-associated actin, whereas the role of non-muscle myosin 2B in retraction prevents over-elongation of myoblasts.
A MO Theoretical Study of Organic Dyes I. Effect of Chemical Softness on the Electronic Spectra
Authors: Nishimoto Kichisuke
Published: August 2006

In order to obtain reasonable results for the π-electronic spectra of organic dyes with simple semi-empirical MO methods, a new approximation for the two-center electron repulsion integral (new gamma) is proposed which takes the chemical softness of the π-conjugated system into account. New gamma was successfully applied to PPP calculations of the electronic spectra of linear polyenes, simple cyanines, and simple merocyanines. The calculated results agree satisfactorily with the experimental data. On the contrary, a calculation based on the conventional PPP parameters gives shorter wavelengths for the absorption maxima of the electronic spectra of charge-resonance systems, such as cyanines and merocyanines. Furthermore, they give very strange electronic spectral shifts for merocyanines (see text), due to an inbalance between the one- and two-electron parts of the electronic transition energy.
Pulse Mode Product-Yield-Detected ESR on the Photoreduction of Anthraquinone in SDS Micellar Solution: Reaction Control by a Microwave Pulse
Authors: Okazaki Masaharu , Toriyama Kazumi
Published: August 2006

A pulse mode PYESR (Product-Yield-Detected ESR) spectrometer was developed by using an excimer laser and a TWT microwave amplifier as the components. The effect of ESR transition of the transient radical pair on the yield of the spin adduct of one of the component radicals was observed at a high microwave power of up to 16 W without microwave heating of the solvent. The spin adduct yield of the SDS radical in the photoreduction of anthraquinone in SDS micellar solution initiated by a laser pulse of 308 nm was modulated by up to 45% by a microwave pulse of 10 μs with a peak power of 16 W, which is resonant on the ESR transition of the transient anthrasemiquinone radical. The ESR spectrum of the radical pair was obtained by tracing this modulation as a function of the magnetic field, under which the photoreaction occurred. From the dependence of the product yield on the microwave pulse duration, we could obtain a time profile of the appearance of the transient radical pair.
The Hydration Structure of NO3− in Concentrated Aqueous Sodium Nitrate Solutions
Authors: Kameda Yasuo , Saitoh Hiroki , Uemura Osamu
Published: August 2006

Time-of-flight neutron diffraction measurements have been carried out on 10 mol% NaNO3 solution in D2O. The isotopic substitution technique was applied to nitrogen atoms in the solution in order to determine both hydration structure around the nitrate ion, NO3−, and intramolecular geometry of NO3− in the aqueous solution. It has become apparent that there exist 5.0 ± 0.5 water molecules coordinated to NO3− with the intermolecular distance r(N···D) = 2.80 Å. The intramolecular bond distance and the root mean square amplitude in NO3− have been determined to be rNO = 1.253 ± 0.006 Å and lNO = 0.058 ± 0.008 Å, respectively.
Crystal Structure and Conductivity of Chiral Radical Ion Salts (Me2ET)2X
Authors: Matsumiya Shigeki , Izuoka Akira , Sugawara Tadashi , Taruishi Tomohiro , Kawada Yuzo , Tokumoto Madoka
Published: August 2006

Radical ion salts of both chiral (R,R) and racemic organic donor, (Me2ET)2X (Me2ET = trans-dimethylbis(ethylenedithio)tetrathiafulvalene, X = PF6, ClO4, and ReO4) were electrochemically prepared and their crystal structures were analyzed. The donor molecules are stacked in a twist-type column to reduce steric repulsion caused by methyl groups. The anions are contained in the cavities formed both by methylated and unsubstituted ethylene groups of the donor molecules, and their orientation is fixed through hydrogen bonds to methine and methylene protons. The structural difference between chiral and racemic salts is discussed. In spite of the difference in the crystal structure, their conductivity is almost identical, reflecting similarity of side-by-side S–S contacts between the donor molecules.
Voltammetric Study on the Transfer of Alkali and Alkaline Earth Metal Ions at the Aqueous/Organic Interface Facilitated by Phosphine Oxides
Authors: Ogura Kaoru , Kihara Sorin , Umetani Shigeo , Matsui Masakazu
Published: August 2006

The transfer of alkali metal and alkaline earth metal ions (Mz) from aqueous to nitrobenzene (NB) phases, facilitated by mono-, bi-, or tridentate phosphine oxides (PO), was investigated in terms of the voltammetry for the ion transfer across the interface of two immiscible electrolyte solutions. The complex formation of Mz with PO in the vicinity of the interface and the transfer process of Mz were clarified based on an analysis of the current-potential curves, while referring to information obtained from the synergistic ion-pair extraction of Mz(ClO4−)z with PO. The stability constants of Mz–PO complexes in NB were evaluated based on the half-wave potentials in the ion transfer voltammograms, and were related to the properties of Mz and PO.
Formation of Cyclopropanes and Epoxides from Vinylselenonium Salts
Authors: Watanabe Yoshihiko , Ueno Yoshio , Toru Takeshi
Published: August 2006

Treatment of vinyl- and (5-oxo-1-cyclopentenyl)selenonium tetrafluoroborates 2 and 4 with a variety of carbanions gives cyclopropane derivatives 3 and 5 in good yields. The reaction of vinylselenonium salt 2 with sodium alkoxides in the presence of aldehydes gives various kinds of glycidyl ethers 7 in excellent yields. The reaction of 2 with hydroxyacetone in the presence of K2CO3 affords cyclized products 8 and 9 together with the Michael addition product 10.
Dehydrooligopeptides. XV. Useful Syntheses of Dehydrodipeptides by the Enzymatic Coupling of α-Dehydroglutamate with Various α-Amino Acid Amides Using Proteases
Authors: Shin Chung-gi , Seki Masashi , Kakusho Takeshi , Takahashi Nobuyuki
Published: August 2006

Novel enzymatic syntheses of various dehydrodipeptides by the coupling of α,γ-dimethyl N-benzyloxycarbonyl(Z)-α-dehydroglutamate [Cbz–ΔGlu(OMe)–OMe; 1] with α-amino acid amides (H–AA–NHR) using proteases, such as papain and α-chymotrypsin A (CT), are described. It was found that there was conspicuous difference between the catalytic actions of papain and CT toward 1. In the case of papain, the selective coupling of α-ester of 1 with H–AA–NHR took place to give Cbz–ΔGlu(OMe)–AA–NHR, while in the case of CT the coupling of γ-ester of 1 proceeded predominantly to give Cbz–ΔGlu(AA–NHR)–OMe. The present study suggests that both papain and CT may become a versatile tool for the organic synthesis by the coupling of not only ΔGlu derivatives but also the other α-dehydroamino acids with α-amino acids or peptides.
Electropolymerization of Bis(4-cyano-1-pyridinio) Derivatives for the Preparation of Polyviologen Films on Electrodes
Authors: Saika Tetsuyuki , Iyoda Tomokazu , Shimidzu Takeo
Published: August 2006

Six bis(4-cyano-1-pyridinio) derivatives have been synthesized and deposited onto electrodes by cathodic electropolymerization (ERed = −0.64 — −0.74 V vs. SCE) under basic conditions. The deposited films were constructed of polyviologens that showed characteristic electrochromisms with colorless or slightly yellow to blue- or red-violet. The derivative was reduced to 4-cyano-1,4-dihydro-4-pyridyl radicals, which were coupled successively to form a polyviologen film on the electrode with an elimination of cyanide ions. Characteristically, the polyviologen films deposited by this electropolymerization were insoluble in water and common organic solvents with a spontaneous cross-linking. Especially, a polyanion as a supporting electrolyte forced the polyviologen to form a polyelectrolyte complex in situ. The current efficiency of surface coverage with the polyanion electrolyte (23% in the typical case) was about four-times larger than those with monomeric anions.
Regioselectivity of Reductive Cleavage of Methyl 4,6-O-Benzylidene-3-deoxyhexopyranosides Containing Fluorine at the 2- or 3-Position with LiAlH4–AlCl3
Authors: Mori Yoko , Morishima Naohiko
Published: August 2006

Reductive ring-opening reactions of the 4,6-O-benzylidene derivatives of methyl 3-deoxy-β-d-arabino-, 3-deoxy-α-d-ribo-, and 2-O-benzyl-3-deoxy-α-d-ribo-hexopyranosides with LiAlH4 and AlCl3 in the molar ratio of 4 : 4 gave the 4- and 6-O-benzyl derivatives in a ratio of 7 : 3. The product ratios for the reactions of methyl 4,6-O-benzylidene-2,3-dideoxy-2-fluoro-α-d-arabino- and β-d-ribo-hexopyranosides and methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-3-fluoro-α-d-gluco- and β-d-allopyranosides were 3 : 2, 2 : 3, 1 : 1, and 3 : 7, respectively. When the molar ratio of the reagents was 2 : 4, however, the product ratios for the reactions of all the above-mentioned 4,6-O-benzylidene derivatives were approximately equal to 4 : 1. The influence of fluorine at C-2 or C-3, as well as that of the molar ratios of LiAlH4 and AlCl3, on the regioselectivity of the reductive cleavage of 4,6-O-benzylidenehexopyranosides are discussed.
The Arbuzov Reaction of Alkyl Diphenylphosphinites with 10-Methylacridinium Ion. Kinetic Study on the Formation and the Decomposition of Phosphonium Intermediates
Authors: Yasui Shinro , Shioji Kosei , Yoshihara Masakuni , Maeshima Toshihisa , Ohno Atsuyoshi
Published: August 2006

Alkyl diphenylphosphinites (1) react rapidly with 10-methylacridinium iodide (2a) to afford the corresponding phosphonium ions (3), which gradually decompose to phosphine oxide, the expected Arbuzov product. Large difference in the rate of the first (phosphonium-forming) and the second (phosphonium-decomposing) steps enables us independent kinetic investigation for both steps, with which it has been found that the first step obeys second-order kinetics with first-order with respect to 1 and 2a, respectively. The second step proceeds according to either the SN2 mechanism when alkyl substituent in 1 is primary or secondary, in which iodide ion acts as a nucleophile, or the SN1 mechanism when the substituent is tertiary. Closer examination on the first step with activation parameters reveals that the transition state of this step becomes more reactant-like as the substituent in 1 becomes bulkier. For the second step, survey of the activation parameters shows that the breaking of the carbon–oxygen bond in 3 predominates over the formation of the oxygen–phosphorus double bond.
Kinetic Stability as Monomeric Forms of 2-Alkyl-5,6-dihydro-3-thioacetyl-2H-naphtho[1,2-b]thiopyrans
Authors: Moriyama Satoshi , Karakasa Takayuki , Saito Takao , Motoki Shinichi
Published: August 2006

2-Alkyl-5,6-dihydro-3-thioacetyl-2H-naphtho[1,2-b]thiopyrans (2) exist stably in the form of monomers at room temperature, whereas unsubstituented ones at the 2-position are apt to dimerize. Based on the X-ray analysis of (2g), UV spectral study of (2), and on semi-empirical calculations, this difference of the stability could be rationalized mainly by steric reason around the heterodiene C=C–C=S system.
Fluorescence and Fluorescence-Excitation Spectra of Benzo[f]quinoline during the Sol–Gel–Xerogel Transitions of Mixed Silicon–Aluminum Alkoxide Systems
Authors: Mabuchi Toshiaki , Fujii Tsuneo
Published: August 2006

The fluorescence and fluorescence-excitation spectra of doped benzo[f]quinoline (BQ) during the sol–gel–xerogel transitions of two reaction systems of mixed alkoxides that were catalyzed by HCl and NaOH (or NH3) have been observed as a function of time. The mixed alkoxides were comprised of tetraethyl orthosilicate (TEOS) and diisobutoxyaluminum triethyl silicate (SAE) (Si : Al = 10 : 0 and 9 : 1). During the reaction, it was found that BQ forms three different fluorescent species, neutral, protonated, and an ion pair. The neutral form was seen in the first stage of the reaction and emitted a structured fluorescence. The protonated form appeared in the next reaction stage and it gave a broad and structureless band with a peak around 440 nm. The ion-pair form, produced from BQ and an –OH group of –O–Si–O– and/or –O–Si–O–Al–O– networks, appeared in the last stage of the reaction and its fluorescence peak was located at around 400 nm. The ion pair could not be detected in solutions, but it was found in the xerogel state. The appearance and disappearance of the three species of BQ reflect the condition of microenvironment around the doped BQ during the sol–gel reaction of the TEOS and TEOS+SAE systems. Therefore, the measurements of the fluorescence spectra of BQ are useful for the photophysical investigation on the sol–gel–xerogel transitions of systems containing metal alkoxides such as TEOS and TEOS+SAE.
2-(2-Furyl)-3-hydroxy-4H-chromen-4-one as an Analytical Reagent for Molybdenum(VI)
Authors: Dass Rameshwar , Mehta Jaswant Ram
Published: August 2006

2-(2-Furyl)-3-hydroxy-4H-chromen-4-one (FHC) has been used as an analytical reagent for the spectrophotometric determination of molybdenum. Molybdenum(VI) in the presence of several cations except Sb(V), Bi(III), and Ce(IV), anions and complexing agents except oxalate forms a yellow 1 : 2 complex with FHC. The complex was extractable into chloroform from 0.01—0.25 mol dm−3 acetic acid (pH 4.2—2.9) and was stable for 2 h. The complex showed an absorption maximum at 414 nm with a molar absorptivity of 4.99 × 104 dm3 mol−1 cm−1 and Sandell’s sensitivity equal to 0.0019 μg Mo cm−2. Beer’s law was obeyed over the concentration range of 0—2.9 ppm. The equilibrium constant was found to be 6.70 × 10−12. For 1 μg Mo cm−3 the standard deviation was 0.004 with a relative mean error of ±0.7%. The method is simple, selective, precise and rapid and has been applied to the determination of molybdenum in synthetic and standard samples.
Conjugation-Extended Tetrathiafulvalene Analogues Involving a Central Aromatic 5-Membered Heterocyclic Linking Group
Authors: Takahashi Kazuko , Nihira Takayasu , Yoshifuji Masaaki , Tomitani Kensuke
Published: August 2006

Conjugation-extended tetrathiafulvalene analogues, 2,5-bis(1,4-dithiafulven-6-yl)thiophene (2a), 2,5-bis[2,3-bis(methoxycarbonyl)-1,4-dithiafulven-6-yl]thiophene, and 2,5-bis(1,4-dithiafulven-6-yl)furan, involving an aromatic heterocyclic linking group have been synthesized by the Wittig condensation reaction of 2,5-thiophene- and 2,5-furandicarbaldehydes with 1,3-dithiol-2-ylidenetributylphosphorane and its 4,5-bis(methoxycarbonyl) derivative. The electrochemical redox properties of these compounds in solution have been investigated by cyclic voltammetry in order to evaluate the effect of the linking group on the donating ability and the thermodynamic stability of the radical cations. Whereas the radical cations are not so stable, complexes of 2a with 2,3-dichloro-5,6-dicyano-p-benzoquinone and iodine were found to show relatively high conductivities ((1.0—1.1) × 10−3 S cm−1) on a compressed pellet at room temperature.
Tris(trimethylsilyl)silyl Radical Induced Bicyclization of 1,6-Dienes and 1,6-Enynes Providing 3,3-Bis(trimethylsilyl)-3-silabicyclo[3.3.0]octanes and 3-Silabicyclo[3.3.0]oct-1-enes
Authors: Miura Katsukiyo , Oshima Koichiro , Utimoto Kiitiro
Published: August 2006

Treatment of 1,6-dienes with tris(trimethylsilyl)silane in the presence of Et3B or α,α′-azobis(isobutyronitrile) afforded 3,3-bis(trimethylsilyl)-3-silabicyclo[3.3.0]octanes in addition to monocyclized cyclopentanes. Bicyclization of 1,6-enynes provided the corresponding 3-silabicyclo[3.3.0]oct-1-enes.
Photosubstitution of Dicyanobenzenes by Allylic Silanes, Germanes, and Stannanes via Photoinduced Electron Transfer
Authors: Nakanishi Kazuhisa , Mizuno Kazuhiko , Otsuji Yoshio
Published: August 2006

Photoreactions of 1,2- and 1,4-dicyanobenzenes (o- and p-DCB) with allylic silanes, germanes, and stannanes in acetonitrile were studied under various conditions. In these photoreactions, one of cyano groups of o- and p-DCB was replaced by allylic groups. With trimethyl(3-methyl-2-butenyl)silane, -germane, and -stannane, the photosubstitution occurred at both α- and γ-positions of the allylic moiety in a constant ratio, regardless of the kinds of metals. 1,3-Dicyanobenzene (m-DCB) was less reactive to the photosubstitution reaction. The reactivity of group 14 organometallic compounds increased in the order: Si- < Ge- < Sn-compounds. The photoreactions were sensitized by aromatic hydrocarbons such as phenanthrene and triphenylene, and also accelerated by adding Mg (ClO4)2 and alkylbenzenes. Quantum yields for the formation of the substitution products increased with decreasing oxidation potentials of group 14 organometallic compounds. A key step for the photoreactions is the reaction of radical anions of dicyanobenzenes with allylic radicals that are generated by cleavage of radical cations of group 14 organometallic compounds. The mechanistic features of these photoreactions are discussed.