bluuebunny/crossref_metadata_2025 huggingface dataset:
Laparoscopic surgery for ulcerative colitis – a meta‐analysis
Authors: Tan J. J. Y. , Tjandra J. J.
Published: March 2006

Objective  To assess the safety and feasibility of laparoscopic surgery for patients with ulcerative colitis.

Methods  A search of published studies in English between January 1992 and September 2005 was obtained, using the MEDLINE and PubMed databases and the Cochrane Central Register of Controlled Trials. Two independent assessors reviewed the studies using a standardized protocol. Where raw data, means and standard deviations were available, meta‐analysis was performed using the Forest plot review. Studies where medians and ranges were presented were separately analysed.

Results  The duration of surgery for laparoscopic and open procedures were similar (weighted mean difference 62.92 min, P = 0.19). Patients were able to tolerate oral intake significantly earlier, with a weighted mean difference of 1.39 days (P = 0.002), but recovery of bowel function was similar (weighted mean difference 0.73 days, P = 0.36). The length of hospital stay was shorter for patients who had undergone laparoscopic surgery, with a weighted mean difference of 2.64 days (P = 0.003). The complication rate was higher in open colectomy, compared to laparoscopic colectomy (67.6%vs 39.7%, P = 0.005). For restorative proctocolectomy, complication rates were comparable between the laparoscopic and open groups (P = 0.25).

Conclusions  The time taken to perform laparoscopic surgery is similar to open surgery. Patients are able to tolerate oral intake earlier, and have a shorter hospitalization. Laparoscopic colectomy was safer compared to the open procedure, but both were equally safe for patients who had restorative proctocolectomy. Thus, laparoscopic surgery for ulcerative colitis is both safe and feasible.
Does functional capacity evaluation predict recovery in workers’ compensation claimants with upper extremity disorders?
Authors: Gross D P , Battié M C
Published: March 2006

Objectives:Functional capacity evaluations (FCEs) are commonly used to determine return-to-work readiness and guide decision making following work related injury, yet little is known of their validity. The authors examined performance on the Isernhagen Work Systems’ FCE as a predictor of timely and sustained recovery in workers’ compensation claimants with upper extremity disorders. A secondary objective was to determine whether FCE is more predictive in claimants with specific injuries (that is, fracture) as compared to less specific, pain mediated disorders (that is, myofascial pain).

Methods:The authors performed a longitudinal study of 336 claimants with upper extremity disorders undergoing FCE. FCE indicators were maximum performance during handgrip and lift testing, and the number of tasks where performance was rated below required job demands. Outcomes investigated were days receiving time-loss benefits (a surrogate of return to work or work readiness) in the year following FCE, days until claim closure, and future recurrence defined as whether benefits restarted, the claim reopened, or a new upper extremity claim was filed. Cox and logistic regression were used to determine the prognostic effect of FCE crudely and after controlling for potential confounders. Analysis was performed separately on claimants with specific and pain mediated disorders.

Results:Most subjects (95%) experienced time-loss benefit suspension within one year following FCE. The one year recurrence rate was 39%. Higher lifting performance was associated with faster benefit suspension and claim closure, but explained little variation in these outcomes (r2 = 1.2–11%). No FCE indicators were associated with future recurrence after controlling for confounders. Results were similar between specific injury and less specific groups.

Conclusions:Better FCE performance was a weak predictor of faster benefit suspension, and was unrelated to sustained recovery. FCE was no more predictive in claimants with specific pathology and injury than in those with more ambiguous, pain mediated conditions.
PHASE-FIELD SIMULATIONS OF EUTECTIC SOLIDIFICATION USING AN ADAPTIVE FINITE ELEMENT METHOD
Authors: DANILOV DENIS , NESTLER BRITTA
Published: March 2006

A finite element method with a semi-implicit time update and an adaptive mesh refinement is used to numerically simulate characteristic growth morphologies in binary eutectic alloys for varying process conditions. The evolution equations are based on a recently developed phase-field model.1 Microstructure formations in typical temperature-composition regions of the eutectic phase diagram are computed showing single cellular primary phase growth, melting of eutectics, eutectic and off-eutectic solidification. We consider 2D and 3D lamellar two-phase growths, analyze the angle conditions at the eutectic triple junctions for different surface entropy data and discuss the occurrence of wetting along the solid-solid interface.
THEORETICAL AND EXPERIMENTAL STUDY ON OPTICAL NEAR AND FAR FIELD TRANSMISSION OF THIN METALLIC FILMS WITH RANDOMLY DISTRIBUTED SUBWAVELENGTH HOLES
Authors: XIAO MUFEI , RAKOV NIKIFOR , ALVAREZ LYDIA
Published: March 2006

We present theoretical calculations of the optical transmission through subwavelength apertures in a conducting screen of finite thickness. The results are employed to study the origin of the enhanced transmission observed in experiments where randomly distributed small holes of various subwavelength sizes are fabricated in a thin gold film. In the wavelength spectrum from 350 nm to 650 nm, a number of strongly enhanced transmission peaks are observed. These transmission peaks can only be observed in the near field. We discuss the experimental results in the light of the model calculations.
CHAOS SYNCHRONIZATION OF FRACTIONAL-ORDER DIFFERENTIAL SYSTEMS
Authors: LI CHANGPIN , DENG WEIHUA
Published: March 2006

Chaos synchronization of the Duffing, Lorenz and Rössler systems with fractional orders are studied theoretically and numerically. Three methods are applied in this paper: combination of active-passive decomposition (APD) and one-way coupling methods, Pecora–Carroll method, bidirectional coupling method. The sufficient conditions of achieving synchronization between two identical fractional systems are derived by using the Laplace transform theory. Numerical simulations demonstrate the effectiveness of the proposed synchronization schemes for these fractional systems.
NOVEL LIQUID CRYSTALLINE PHASES IN QUANTUM HALL SYSTEMS
Authors: WEXLER CARLOS , CIFTJA ORION
Published: March 2006

Since 1999, experiments have shown a plethora of surprising results in the low-temperature magnetotransport in intermediate regions between quantum Hall (QH) plateaus: the extreme anisotropies observed for half-filling, or the re-entrant integer QH effects at quarter filling of high Landau levels (LL); or even an apparent melting of a Wigner Crystal (WC) at filling factor ν = 1/7 of the lowest LL. A large body of seemingly distinct experimental evidence has been successfully interpreted in terms of liquid crystalline phases in the two-dimensional electron system (2DES). In this paper, we present a review of the physics of liquid crystalline states for strongly correlated two-dimensional electronic systems in the QH regime. We describe a semi-quantitative theory for the formation of QH smectics (stripes), their zero-temperature melting onto nematic phases and ultimate anisotropic-isotropic transition via the Kosterlitz–Thouless (KT) mechanism. We also describe theories for QH-like states with various liquid crystalline orders and their excitation spectrum. We argue that resulting picture of liquid crystalline states in partially filled LL-s is a valuable starting point to understand the present experimental findings, and to suggest new experiments that will lead to further elucidation of this intriguing system.
Distinctive Glycinergic Currents With Fast and Slow Kinetics in Thalamus
Authors: Ghavanini Amer A. , Mathers David A. , Kim Hee-Soo , Puil Ernest
Published: March 2006

We examined functional properties of inhibitory postsynaptic currents (IPSCs) evoked by medial lemniscal stimulation, spontaneous IPSCs (sIPSCs), and single-channel, extrasynaptic currents evoked by glycine receptor agonists or γ-aminobutyric acid (GABA) in rat ventrobasal thalamus. We identified synaptic currents by reversal at ECl and sensitivity to elimination by strychnine, GABAA antagonists, or combined application. Glycinergic IPSCs featured short (about 12 ms) and long (about 80 ms) decay time constants. These fast and slow IPSCs occurred separately with monoexponential decays, or together with biexponential decay kinetics. Glycinergic sIPSCs decayed monoexponentially with time constants, matching fast and slow IPSCs. These findings were consistent with synaptic responses generated by two populations of glycine receptors, localized under different nerve terminals. Glycine, taurine, or β-alanine applied to excised membrane patches evoked short- and long-duration current bursts. Extrasynaptic burst durations resembled fast and slow IPSC time constants. The single, intermediate time constant (about 22 ms) of GABAAergic IPSCs cotransmitted with glycinergic IPSCs approximated the burst duration of extrasynaptic GABAA channels. We noted differences between synaptic and extrasynaptic receptors. Endogenously activated glycine and GABAA receptor channels had higher Cl− permeability than that of their extrasynaptic counterparts. The β-amino acids activated long-duration bursts at extrasynaptic glycine receptors, consistent with a role in detection of ambient taurine or β-alanine. Heterogenous kinetics and permeabilities implicate molecular and functional diversity in thalamic glycine receptors. Fast, intermediate, and slow inhibitory postsynaptic potential decays, mostly attributed to cotransmission by glycinergic and GABAergic pathways, allow for discriminative modulation and integration with voltage-dependent currents in ventrobasal neurons.
Mechanisms Underlying Oxytocin-Induced Excitation of Supraoptic Neurons: Prostaglandin Mediation of Actin Polymerization
Authors: Wang Yu-Feng , Hatton Glenn I.
Published: March 2006

In nonneuronal tissues, activation of oxytocin receptors (OTRs), like other Gαq/11 type G-protein-coupled receptors (Gαq/11/GPCRs), increase prostaglandin (PG) expression. This is not known for the OTRs expressed by central OT neurons. We examined mechanisms underlying OT's effects on supraoptic nucleus (SON) OT and vasopressin (VP) neurons in hypothalamic slices from lactating rats. OT application (10 pM, 10 min) significantly increased firing rates of OT and VP neurons, both of which expressed OTRs. Indomethacin, an inhibitor of PG synthetases, blocked these increases. OTR (but not a V1 receptor) antagonist blocked OT effects without blocking the excitatory effect of PGE2. Tetanus toxin blocked OT effects on fast synaptic inputs and firing activity of SON neurons but not OT-evoked depolarization, suggesting involvement of both pre- and postsynaptic neurons. Indomethacin also blocked the excitatory effects of phenylephrine, another Gαq/11/GPCR activating agent but not those of PGE2, a non-Gαq/11/GPCR activating agent in the SON. OT or phenylephrine, but not glutamate or KCl, enhanced cyclooxygenase 2 expression at cytosolic loci in SON neurons and nearby astrocytes, as revealed by immunocytochemistry. This OT effect was not blocked by TTX. Western blot analyses showed that OT significantly increased cyclooxygenase 2 but not actin expression. OT promoted the formation of filamentous actin (F-actin) networks at membrane subcortical areas of both OT and VP neurons. Indomethacin blocked enhancement of F-actin networks by OT but not by PGE2. These results indicate that PGs serve as a common mediator of Gαq/11/GPCR-activating agents in neuronal function.
A pathway analysis of poly(I:C)-induced global gene expression change in human peripheral blood mononuclear cells
Authors: Huang C. Chris , Duffy Karen E. , San Mateo Lani R. , Amegadzie Bernard Y. , Sarisky Robert T. , Mbow M. Lamine
Published: March 2006

To gain global pathway perspective of ex vivo viral infection models using human peripheral blood mononuclear cells (PBMCs), we conducted expression analysis on PBMCs of healthy donors. RNA samples were collected at 3 and 24 h after PBMCs were challenged with the Toll-like receptor-3 (TLR3) agonist polyinosinic acid-polycytidylic acid [poly(I:C)] and analyzed by internally developed cDNA microarrays and TaqMan PCR. Our results demonstrate that poly(I:C) challenge can elicit certain gene expression changes, similar to acute viral infection. Hierarchical clustering revealed distinct immediate early, early-to-late, and late gene regulation patterns. The early responses were innate immune responses that involve TLR3, the NF-κB-dependent pathway, and the IFN-stimulated pathway, whereas the late responses were mostly cell-mediated immune response that involve activation of cell adhesion, cell mobility, and phagocytosis. Overall, our results expanded the utilities of this ex vivo model, which could be used to screen molecules that can modulate viral stress-induced inflammation, in particular those mediated via TLRs.
Correlation between the UDP-Glucuronosyltransferase (UGT1A1) TATAA Box Polymorphism and Carcinogen Detoxification Phenotype
Authors: Fang Jia-Long , Lazarus Philip
Published: March 2006

Of the hepatic UDP-glucuronosyltransferases (UGTs), only UGT1A1 and UGT1A9 exhibit activity against benzo(a)pyrene-trans-7R,8R-dihydrodiol [BPD(−)], precursor to the highly mutagenic anti-(+)-benzo(a)pyrene-7R,8S-dihydrodiol-9S,10R-epoxide. The UGT1A1*28 allelic variant contains an additional (TA) dinucleotide repeat in the “TATAA” box [(TA)6>(TA)7] of the UGT1A1 promoter that has been linked to decreased expression of the UGT1A1 gene and decreased bilirubin conjugation, leading to the relatively nondebilitating condition known as Gilbert’s syndrome. To determine whether the UGT1A1 TATAA box polymorphism may play a role in the overall glucuronidation of BPD(−) in humans, we compared UGT1A1 TATAA box genotype with BPD(−) glucuronidating activity in normal liver microsomes. Significant decreases in UGT1A1 protein (P < 0.005) and bilirubin conjugation activity (P < 0.001) were observed in liver microsomes from subjects homozygous for the UGT1A1*28 allelic variant compared with subjects homozygous for the wild-type UGT1A1*1 allele. Significant decreases in BPD(−) glucuronidation activity (P < 0.02) were observed in subjects with the UGT1A1(*28/*28) genotype compared with subjects having the wild-type UGT1A1(*1/*1) genotype in assays of liver microsomes that included 0.1 mm α-naphthylamine, a competitive inhibitor of UGT1A9 and not UGT1A1. Similar phenotype:genotype correlations were observed when we compared subjects with the UGT1A1(*28/*28) genotype with subjects having the UGT1A1(*1/*28) genotype. In assays with α-naphthylamine, the Km of liver microsomes against BPD(−) was similar to that reported for UGT1A1-overexpressing baculosomes (319 μm versus 290 μm; Fang et al., Cancer Res., 62: 1978–1986, 2002). These data suggest that the UGT1A1 TATAA box polymorphism plays a role in an individual’s overall ability to detoxify benzo(a)pyrene and in cancer risk.
Methionine Synthase D919G Polymorphism, Folate Metabolism, and Colorectal Adenoma Risk
Authors: Goode Ellen L. , Potter John D. , Bigler Jeannette , Ulrich Cornelia M.
Published: March 2006

Methionine synthase [5-methyltetrahydrofolate-homocysteine S-methyltransferase (MTR)] is involved in folate-mediated one-carbon metabolism, a pathway known to play a role in colorectal carcinogenesis. We investigated whether the MTR D919G polymorphism was associated with risk of colorectal adenoma in a colonoscopy-based study of 513 cases and 609 controls from Minneapolis, MN. Adenoma risk appeared nonsignificantly increased among women with DG or GG genotype [adjusted odds ratio (OR) versus DD, 1.4; 95% confidence interval (CI), 0.9–2.1] but not men (OR, 1.0; 95% CI, 0.7–1.5). An interaction with methionine intake was observed among women, such that low versus high intake was associated with a 2.3-fold increased risk only among those with DG or GG genotype (95% CI, 1.1–4.9; P for interaction = 0.05). Similarly, risk associated with alcohol intake was not elevated among women with the DD genotype; however, consumption of >7 g of alcohol/day versus none was associated with an increased risk among women with DG or GG genotype (adjusted OR, 2.5; 95% CI, 1.4–4.4; P for interaction = 0.03). An interaction between MTR D919G and the thymidylate synthase (TS or TYMS) 3′-untranslated region polymorphism 1494del6 was also observed among women (P for interaction = 0.007). No evidence of interaction with intake of folate, vitamin B12, or vitamin B6 or with genotype at MTHFR C677T or the TS enhancer region 28-bp repeat polymorphism was seen. These findings add to what is known about the complexities of genetic variations in one-carbon-metabolizing enzymes in relation to colorectal carcinogenesis.
Serum Insulin-Like Growth Factor-I Is Positively Associated with Serum Prostate-Specific Antigen in Middle-Aged Men without Evidence of Prostate Cancer
Authors: Oliver Steven E. , Barrass Barney , Gunnell David J. , Donovan Jenny L. , Peters Tim J. , Persad Raj A. , Gillatt David , Neal David E. , Hamdy Freddie C. , Holly Jeff M. P.
Published: March 2006

We have examined the relationship between serum insulin-like growth factor-I (IGF-I) and prostate-specific antigen in 367 healthy men without evidence of prostate cancer and found a positive association (P = 0.05). In men without prostate cancer, serum prostate-specific antigen is closely related to prostate size, and our findings, therefore, suggest that IGF-I may induce prostatic epithelial proliferation. Higher circulating levels of IGF-I have been associated with increased risk of both prostate cancer and possibly benign prostatic hyperplasia. Greater rates of cell proliferation induced by IGF-I may be a key biological pathway underlying these disorders.
Helicobacter pylori
Eradication and Gastric Preneoplastic Conditions
Authors: Ley Catherine , Mohar Alejandro , Guarner Jeannette , Herrera-Goepfert Roberto , Figueroa Luz Sanchez , Halperin David , Johnstone Iain , Parsonnet Julie
Published: March 2006

Helicobacter pylori causes gastric adenocarcinoma; whether treatment of H. pylori infection prevents this cancer remains unknown. In a randomized, double-blind, placebo-controlled trial of H. pylori eradication, we determined whether treatment for H. pylori decreases gastric cancer risk, using preneoplastic conditions as surrogate markers. A total of 248 healthy volunteers (age >40 years) randomly received H. pylori treatment (omeprazole, amoxicillin, clarythromycin; n = 122) or matched placebo (n = 126) for 1 week. Endoscopy was performed at baseline and at 6 weeks and 1 year. Seven biopsies from each endoscopy were reviewed by two pathologists using the revised Sydney classification. Outcome measures were both a consensus “worst biopsy” diagnosis and a weighted index score that incorporated degrees of severity of preneoplasia from all biopsies. We compared change in these outcomes over time between the two treatment groups. H. pylori cure rates for compliant subjects in the treatment arm were 79.2% and 75.7% at 6 weeks and 1 year, respectively. No statistically significant change in the worst biopsy diagnosis was observed from 6 weeks to 1 year between placebo and treated subjects (for improvement/worsening, placebo, 19.4%/10.5%; treatment, 22.5%/8.3%; P = 0.74). Change in index score was favorably greater in treatment compared with placebo subjects (intention-to-treat analysis, P = 0.03); this finding was particularly evident in the antrum. H. pylori eradication gave more favorable gastric histopathologies over 1 year than no treatment. Such incomplete regression suggests but does not prove that eradication of H. pylori decreases cancer risk.
Genetic Variants of
GPX1
and
SOD2
and Breast Cancer Risk at the Ontario Site of the Breast Cancer Family Registry
Authors: Knight Julia A. , Onay U. Venus , Wells Sean , Li Hong , Shi Ellen J. Q. , Andrulis Irene L. , Ozcelik Hilmi
Published: March 2006

There are several genes that code for enzymes, including various forms of superoxide dismutase and glutathione peroxidase, that protect the cell against oxidative damage that, in turn, can lead to carcinogenesis. There are a few common genetic polymorphisms in these genes that lead to altered proteins. Three that have been identified are SOD2 Val-9Ala, GPX1 Pro198Leu, and the GPX1 GCG repeat (three alleles with four, five, or six repeats). The SOD2 variant has been associated with increased breast cancer risk in two studies. The GPX1 variants have not been studied with respect to breast cancer, but Pro198Leu has been associated with lung cancer. We conducted a case-control study of these three polymorphisms in incident, invasive breast cancer in Caucasian women under 55. There were 399 cases and 372 controls genotyped, of whom 488 were premenopausal, 208 postmenopausal, and 75 of unknown menopausal status. We were unable to replicate the previously observed association with SOD2 Val-9Ala and also found no association between breast cancer and GPX1 Pro198Leu. However, the allele of GPX1 containing four GCG repeats was significantly associated with breast cancer risk in premenopausal women (odds ratio, 1.55; 95% confidence interval, 1.04–2.30 for carriers versus noncarriers). There is a significant trend of increasing risk with increasing number of alleles with four GCG repeats (P = 0.03). This variant has not previously been reported to be associated with breast cancer.
Expert Review of Non-Hodgkin’s Lymphomas in a Population-Based Cancer Registry
Authors: Clarke Christina A. , Glaser Sally L. , Dorfman Ronald F. , Bracci Paige M. , Eberle Erin , Holly Elizabeth A.
Published: March 2006

Incidence rates of non-Hodgkin’s lymphomas (NHLs) have nearly doubled in recent decades. Understanding the reasons behind these trends will require detailed surveillance and epidemiological study of NHL subtypes in large populations, using cancer registry or other multicenter data. However, little is known regarding the reliability of NHL diagnosis and subtype classification in such data, despite implications for the accuracy of incidence statistics and studies. Expert pathological re-review was completed for 1526 NHL patients who were reported to the Greater Bay Area Cancer Registry and who participated in a large population-based case-control study. Agreement of registry diagnosis with expert diagnosis and with International Classification of Diseases for Oncology-2 (Working Formulation) subtype classifications was measured with positive predictive values and κ statistics. Agreement of registry and expert diagnoses was high (98%). Thirty patients were found on review not to have NHL; most of these had leukemia. For subtypes, agreement of registry and expert classification was more moderate (59%). Agreement varied substantially by subtype from 5% to 100% and was 77% for the most common subtype, diffuse large cell lymphoma. Seventy-seven percent of 128 registry-unclassified lymphomas were assigned a subtype on re-review. Our analyses suggest excellent diagnostic reliability but poorer subtype reliability of NHL in cancer registry data information that is critical to the interpretation of lymphoma time trends. Thus, overall NHL incidence and survival statistics from the early 1990s are probably accurate, but subtype-specific statistics could be substantially biased, especially because of high (15–20%) proportions of unclassified lymphomas.
Dietary Carotenoids and Risk of Lung Cancer in a Pooled Analysis of Seven Cohort Studies
Authors: Männistö Satu , Smith-Warner Stephanie A. , Spiegelman Donna , Albanes Demetrius , Anderson Kristin , van den Brandt Piet A. , Cerhan James R. , Colditz Graham , Feskanich Diane , Freudenheim Jo L. , Giovannucci Edward , Goldbohm R. Alexandra , Graham Saxon , Miller Anthony B. , Rohan Thomas E. , Virtamo Jarmo , Willett Walter C. , Hunter David J.
Published: March 2006

Intervention trials with supplemental β-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7–16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. β-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87–1.11; highest versus lowest quintile). The RRs for α-carotene, lutein/zeaxanthin, and lycopene were also close to unity. β-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67–0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in β-cryptoxanthin, such as citrus fruit, may modestly lower the risk.
Ataxia-Telangiectasia-Mutated (
ATM
) Gene in Head and Neck Squamous Cell Carcinoma
Authors: Ai Lingbao , Vo Quynh N. , Zuo Chunlai , Li Liwen , Ling Wenhua , Suen James Y. , Hanna Ehab , Brown Kevin D. , Fan Chun-Yang
Published: March 2006

The Ataxia-telangiectasia-mutated (ATM) gene product is a well-characterized tumor suppressor that plays a key role in maintenance of genomic stability. We have recently documented that the ATM promoter is a target for epigenetic silencing in cultured tumor cells. Here we show that aberrant methylation of the ATM promoter occurs in a significant percentage (25%) of head and neck squamous cell carcinomas. The presence of methylated ATM promoter shows a statistically significant correlation with an earlier age of initial diagnosis and decreased overall survival, particularly in early-stage tumors. These findings indicate that ATM promoter hypermethylation occurs in head and neck squamous cell carcinoma, and this feature is a potentially useful prognostic marker in this tumor type.
p53 Codon 72 Polymorphism and Cervical Neoplasia
Authors: Koushik Anita , Platt Robert W. , Franco Eduardo L.
Published: March 2006

The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. We reviewed the published literature to summarize the association and to identify methodological features that may have contributed to the heterogeneity. Information on specific methodological features of studies addressing this topic published between 1998 and 2002 were obtained. Study-specific odds ratios (ORs) were combined in a meta-analysis, assuming random effects. To identify characteristics that significantly contributed to heterogeneity, we used meta-regression analysis. We identified 50 articles, of which 45 were included in the meta-analyses and regressions. No evidence of association or heterogeneity was detected for preinvasive lesions. For invasive cervical cancer with undefined histology, the Arg/Arg genotype was not found to affect risk (OR, 1.1; 95% confidence interval (CI), 0.9–1.3). However, a slightly increased risk was observed for squamous cell carcinoma (OR, 1.5; 95% CI, 1.2–1.9) and adenocarcinoma (OR, 1.7; 95% CI, 1.0–2.7). Meta-regression analysis identified that the most important factor contributing to heterogeneity among results for invasive lesions was departures from Hardy-Weinberg equilibrium in the control group. Summary ORs for studies in equilibrium were essentially null. A possible susceptibility role by the p53 codon 72 polymorphism at a late carcinogenetic stage in cervical cancer cannot be ruled out. However, various methodological features can contribute to departures from Hardy-Weinberg equilibrium and consequently to less than ideal circumstances for the examination of this polymorphism. Future investigations require appropriate attention to design and methodological issues.
Association between Insulin-Like Growth Factor-I
Authors: Sandhu Manjinder S. , Gibson J. Martin , Heald Adrian H. , Dunger David B. , Wareham Nicholas J.
Published: March 2006

Several prospective observational studies have suggested that elevated circulating IGF-I levels are associated with an increased risk of cancer. These observations may provide a potential mechanism through which previously identified metabolic and anthropometric factors, such as obesity and elevated insulin and glucose levels, may operate. We therefore examined metabolic and anthropometric influences on circulating levels of insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-1 (IGFBP-1), and the IGF-I:IGFBP-1 ratio in a middle-aged population of 349 men and 492 women. IGF-I showed only modest inverse associations with indices of adiposity. However, we found that low IGFBP-I levels and an increased IGF-I:IGFBP-1 ratio were strongly associated with increased levels of insulin and glucose in men and women. Body mass index was also positively related to the IGF-I:IGFBP-1 ratio in men (P < 0.001) and women (P < 0.001), independent of metabolic correlates of IGFBP-1 and IGF-I. Similarly, waist:hip ratio and waist circumference were also associated with an increased IGF-I:IGFBP-1 ratio and low circulating IGFBP-1 levels. These findings suggest that individuals with greater fat mass and upper body obesity may have elevated levels of bioavailable or free IGF-I, which could, in part, mediate the reported associations among metabolic and anthropometric factors and cancer risk.
Are Short Boys with Constitutional Delay of Growth and Puberty Candidates for rGH Therapy according to FDA Recommendations?
Authors: Krajewska-Siuda E. , Malecka-Tendera E. , Krajewski-Siuda K.
Published: March 2006

Background/Aims: According to FDA-approved guidelines, boys whose height predictions fall to 160 cm or less are considered for treatment with recombinant growth hormone (rGH). The aim of this study was to analyze the value of different height prediction methods by accurately identifying those boys with constitutional delay of growth and puberty (CDGP) in whom final height (FH) prognosis was poor (≤160 cm) and who might therefore be candidates for this treatment modality. Methods: In 69 boys with CDGP diagnosed at a mean age of 14.9 ±1.2 years, FH prediction was calculated by means of Bayley-Pinneau (BP), Roche-Wainer-Tissen (RWT), Tanner-Whitehouse II (TWII) and target height (TH) methods. At the age of 22.6 ± 3.5 years their height was remeasured and the accuracy of height prediction was analyzed. Results: In 6 men (8.7%) measured FH was ≤160 cm. Depending on the prediction method, different individual patients within the 14- to 16-year age range would have been candidates for rGH treatment. The BP method would have recruited 8 subjects of whom only 3 had FH ≤160 cm (sensitivity 50%, specificity 92%). The RWT and TW II methods identified only one recruit, and this patient did achieve FH ≤160 cm (sensitivity 17%, specificity 100%). None of the 8 subjects with FH ≤160 cm would have qualified for GH treatment using the TH method. In three boys none of the four methods predicted their final height ≤160 cm. Conclusion: Although some boys with CDGP may be considered the candidates for rGH treatment according to FDA recommendations, none of the available methods of prediction are sufficiently sensitive to reliably recruit 14- to 16-year-old boys whose final height will fall at or below 160 cm.
Growing Kidney in the Frog
Authors: Chan Techuan , Asashima Makoto
Published: March 2006

An understanding of the regulation of kidney development has increased dramatically in the past decade. The pronephros, mesonephros, and metanephros represent three distinct renal organs that function, in succession, as the vertebrate excretory system during development of the kidney. These three organ systems are derived from the intermediate mesoderm and develop in a well-defined temporal and spatial sequence. The pronephros, which consists of a tubule, duct and glomus, is established first and is the simplest of the excretory organs in vertebrates. Xenopus pronephros serves as an ideal model for investigating organogenesis and development of renal function in vertebrates. In this article, we highlight the advantages of Xenopus for analyzing kidney organogenesis and the latest research in pronephros development.
Ischemia-Induced Renal Expression of Hyaluronan and CD44 in Diabetic Rats
Authors: Melin Jan , Hellberg Olof , Funa Keiko , Hällgren Roger , Larsson Erik , Fellström Bengt C.
Published: March 2006

Background/Aims: Unilateral renal ischemia during 30 min causes severe, non-reversible renal damage in diabetic (DM) rats, but not in nondiabetic rats. Hyaluronan (HA) is a glycosaminglycan involved in various forms of renal injury. We examined the role of HA and CD44, a major receptor for HA, in the development of postischemic renal injury in DM rats. Methods: The left renal artery of streptozotocin diabetic Wistar rats was clamped for 30 min. The HA content in the kidneys was measured. A biotinylated HA-binding probe was used to localize HA. Inflammatory cells and other cells expressing CD44 were identified by immunohistochemistry. Results: In ischemic DM kidneys the renal HA-content started to increase already after 24 h and significantly so after 1–8 weeks after ischemia/reperfusion (I/R). The relative water content of the kidneys increased in parallel. HA started to appear in the cortex of ischemic DM kidneys 1 week after I/R. In contrast, the non-DM ischemic kidneys showed no increase of HA and water content after 1–8 weeks after I/R. The tubular cells in the cortex and outer medulla demonstrated increased staining for CD44. In the same compartments the increased numbers of infiltrating inflammatory cells also expressed CD44. Conclusion: HA-accumulation in the renal cortex might contribute to the renal damage seen after transient ischemia in DM rats by promoting inflammation through interaction between HA and CD44 expressing inflammatory cells. Furthermore, HA accumulation may contribute to an interstitial renal edema.
Cytotoxicity of Phenanthrenes Extracted from Aristolochia contorta in Human Proximal Tubular Epithelial Cell Line
Authors: Wen Yu-jie , Su Tao , Tang Jia-wei , Zhang Cui-ying , Wang Xuang , Cai Shao-qing , Li Xiao-mei
Published: March 2006

Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is predominantly a result of aristolochic acid I (AA-I) intoxication. However, other unidentified phytotoxins have indeed been postulated as the cause of this unique interstitial nephropathy. The purpose of this study was to investigate the cytotoxicity of other phenanthrene derivatives extracted from Aristolochia contorta in the human proximal tubular epithelial cell line HK-2. Methods: After HK-2 cells were incubated with an indicated concentration of test compounds for 24 h, cell viability was assessed by lactate dehydrogenase (LDH) leakage assay (cell membrane damage) in combination with MTT assay (metabolic capability). Cellular morphologic assessments were performed with a phase-contrast inverted microscope and transmission electron microscope. Results: In all test compounds at 5 µg/ml, AA-I, 7-methoxy-aristololactam IV and aristololactam IVa showed cytotoxic activity in HK-2 cells in both MTT assay and LDH leakage assay (p < 0.01). At high concentration (5–80 µg/ml), these three compounds caused a dose-dependent decrease in MTT reduction and a dose-dependent increase in LDH leakage compared to non-treated cells (p <0.01). In LDH leakage assay, 40 µg/ml 7-methoxy-aristololactam IV induced a 1.58-fold LDH leakage compared to AA-I at the same concentration (p < 0.01). Moreover, the IC50of these three compounds were 16.675 µg/ml for AA-I, 4.535 µg/ml for 7-methoxy-aristololactam IV, and 30.244 µg/ml for aristololactam IVa in MTT assay. The cellular morphologic assessments suggest interactions with cell membrane and intracellular structures such as lysosome and mitochondria are likely to be involved in cell injury induced by these three compounds. Conclusion: The potency of cytotoxic activity of aristololactam IVa and 7-methoxy-aristololactam IV extracted from A. contorta is similar to or even stronger than that of AA-I.
Effects of Co-Administration of an iNOS Inhibitor with a Broad-Spectrum Reactive Species Scavenger in Rat Renal Ischemia/Reperfusion Injury
Authors: Zahmatkesh M. , Kadkhodaee M. , Arab H.A. , Shams S.
Published: March 2006

Background: It is generally believed that reactive oxygen species (ROS) formation and nitric oxide (NO) generation by the inducible isoform of nitric oxide synthase (iNOS) are the key mediators of ischemia-reperfusion (IR)-induced damage to the kidney. The present study was designed to investigate the effects of ROS and NOS inhibition in prevention of renal IR injury. MnTBAP (Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin), a broad-spectrum reactive species scavenger was administered to inhibit ROS formation and L-Nil (N6-(1-iminoethyl)-L-lysine hydrochloride) was used for iNOS inhibition. Methods: Ischemic acute renal failure (ARF) was induced by 40-min clamping of the renal arteries followed by a 6-hour reperfusion. Rats were administered saline, MnTBAP (10 mg/kg i.v.), L-Nil (3 mg/kg i.v. bolus followed by infusion of 1 mg/kg/h) or co-administration of MnTBAP and L-Nil. Plasma creatinine (Cr) and BUN levels as well as fractional excretion of Na+ (FENa+) and urinary N-acetyl-β-D-glucosaminidase (NAG) activities were measured. Renal damages were evaluated by light microscopy. Results: MnTBAP, L-Nil and their co-administration significantly improved renal functional and histological indices. Co-administration of the mentioned drugs did not demonstrate significant difference with the administration of either drug alone. Conclusion: These results suggest that the significant portion of ROS and iNOS nephrotoxicities in this model of ARF may be mediated by peroxynitrite (ONOO–). These results emphasize the multifactorial nature of ARF and the need for a multidrug therapy in the future.
Proteomic Profiling of Urinary Protein Excretion in the Factor H-Deficient Mouse
Authors: Braun Michael C. , Li Li , Ke Baozhen , Dubinsky William P. , Pickering Mathew C. , Chang Jui-Yoa
Published: March 2006

Background: Since the 1970s a variety of experimental techniques have been employed in an attempt to identify urinary biomarkers of renal injury. While these approaches have met with some success, modern proteomic tools now permit broad based high-throughput analysis of the urinary proteome. Methods: Using the ICAT isotopic labeling based LC/MS/MS approach, comparative urinary protein profiling was performed in a murine model of membranoproliferative glomerulonephritis. Paired samples were analyzed mice with a targeted deletion of the complement regulatory protein factor H (FH–/–) and control mice. Results: 25 distinct urinary proteins were identified of which 7 were differentially expressed in the FH–/– mice. Two proteins were markedly altered in the urine of FH–/– mice compared to controls: uromodulin (5.5-fold lower) and the MHC class II molecule H2e (8.6-fold higher). Differential expression was confirmed by Western blot and RT-PCR. Immunofluorescent staining demonstrated a marked increased expression of H2e and a reduction of uromodulin expression in the tubular epithelium of FH–/– mice. Conclusions: These findings provide insight into early complement-dependent alterations in tubular protein expression which may play critical roles in the development of tubulointerstitial disease, and provide experimental support for the use of urinary proteomic profiling in murine models of renal injury.
A Role for Heme Oxygenase-1 in the Antioxidant and Antiapoptotic Effects of Erythropoietin: The Start of a Good News/Bad News Story?
Authors: Calò Lorenzo A. , Davis Paul A. , Piccoli Antonio , Pessina Achille C.
Published: March 2006

Erythropoietin (EPO) is the major regulator of erythropoiesis. EPO’s actions have been shown to be antiapoptotic and dependent on JAK2 signaling and Akt phosphorylation. These effects serve as link between EPO and heme oxygenase-1 (HO-1). HO-1 is an inducible enzyme with potent antioxidant and antiapoptotic activities which are regulated by Akt signaling. EPO’s ability to alter cellular systems that involve apoptosis and oxidants suggests that EPO treatments are likely to have multiple and different effects which may start a good news/bad news story. Recombinant human EPO is the recognized treatment of choice to address anemia and to stimulate erythropoiesis in chronic renal failure patients, through its antiapoptotic action which likely involves HO-1. On the other hand, EPO treatment to address anemia in cancer patients, while providing significant improvements in cancer patients’ quality of life, its effects on survival are equivocal, likely due to its linkage with HO-1. Two clinical trials of EPO in patients with solid tumors have, in fact, shown specific negative effects on survival. However, EPO’s effect on tumor growth and survival is not uniformily pro growth and pro survival, as EPO may act synergistically with chemotherapy to induce apoptosis. Finally, compounds have been synthesized that do not trigger EPO receptor and thus may allow experimental distinction and, therefore, at least potentially affect at the clinical level the tissue-protective effects of EPO (e.g., antiapoptosis) without provoking its other potentially detrimental effects.
Continuum Mechanics of Deformation Twinning – A Review
Authors: Dieter Fischer Franz , Schaden Thomas , Appel Fritz , Clemens Helmut
Published: March 2006

In terms of continuum mechanics a twin is represented by the sudden appearance of a shear eigenstrain state in a distinct region. The corresponding elastic strain energy, the interface energy and the energy dissipated due to the irreversible character of the deformation process are investigated. If the total amount of these energy terms, spent by the twinning process, can be provided by the interaction energy of an external and/or internal stress state with respect to the twin shear eigenstrain, then either a deformation twin band or a twin nucleus may appear. Realistic estimations of the dimensions of deformation twins can be presented. This energetic interpretation of twinning is experimentally demonstrated for intermetallic TiAl.
Semi‐Active Control Wind Tunnel Tests of Wing/Store System Flutter with an Electro‐Magnetic Damper
Authors: weibing Hu , Kuisheng Zhu
Published: March 2006

Wind tunnel tests of wing/store system flutter semi‐active suppression are shown in this paper. A wind tunnel test model for semi‐active suppression with an Electro‐Magnetic damper and circuit control system are designed and worked out .The results of these wind tunnel tests show that the flutter response of wing/store system can be suppressed and the method of the tests is reasonable.
Population Pharmacokinetics of Oxycodone in Children 6 Months to 7 Years Old
Authors: El‐Tahtawy Ahmed , Kokki Hannu , Reidenberg Bruce E.
Published: March 2006

Young children are often undertreated for pain. One barrier to effective pain treatment is understanding the pharmacokinetic behavior of analgesics in this age group. Oxycodone is a commonly prescribed opioid for severe pain, yet little is known about its pharmacokinetics in young children. This article used population pharmacokinetic modeling to synthesize pharmacokinetic data from several studies into a model. A single population model that described the observed pharmacokinetics was developed. The combined data were best described with a 2‐compartment linear model with different first‐order absorption rates depending on route of administration. Weight was found to significantly influence both clearance (CL) and volume of distribution (Vd). The following model adequately describes the population pharmacokinetic profile of oxycodone where absolute bioavailability (F) is estimated for each administration route: CL/F = 55 × (body weight/70)0.87; V/F= 86 × (body weight/70)1.16. The interindividual coefficients of variation in CL and Vd were 20.2 and 19.7%, respectively. This finding confirms that the allometric scaling using the above model explained most of the variability in exposure observed among children. This model confirms using a weight‐based dose for oxycodone without adjustment for age between 6 months and 7 years and is valuable for evaluating dosing schedules and dosing routes.
Altered Methylprednisolone Pharmacodynamics in Healthy Subjects With Histamine N‐Methyltransferase C314T Genetic Polymorphism
Authors: Hon Yuen Yi , Jusko William J. , Spratlin Vicky E. , Jann Michael W.
Published: March 2006

This study investigated the potential differences in methylprednisolone pharmacodynamics between healthy subjects with different histamine N‐methyltransferase (HNMT) C314T genotypes. Six individuals with C/C genotype and 4 with C/T genotype were administered a single intravenous dose of methylprednisolone 0.6 mg/kg ideal body weight in a randomized 2‐period manner. Methylprednisolone plasma concentrations were fitted with a 1‐compartment model. Cortisol and whole blood histamine suppression were assessed by indirect response models, with circadian baseline cortisol analyzed by Fourier analysis. The area between the baseline and effect curve and the area under the effect versus time curve suppression ratio were used to characterize plasma histamine suppression. Methylprednisolone pharmacokinetics and plasma and whole blood histamine suppression were similar between the 2 genotype groups. Median nadir of cortisol and the 50% inhibitory concentration for cortisol were significantly higher in subjects with C/T genotype than those with C/C genotype (P = .031 and .033, respectively, Wilcoxon rank sum test). Subjects who are heterozygous for the T314 variant allele thus appeared less sensitive to the suppressive effects of methylprednisolone on cortisol secretion.
The Comparability of Etanercept Pharmacokinetics in Healthy Japanese and American Subjects
Authors: Kawai Shinichi , Sekino Hisayuki , Yamashita Noriaki , Tsuchiwata Shinichi , Liu Hanjui , Korth‐Bradley Joan M.
Published: March 2006

Thirty Japanese (J) and 32 American (A) healthy subjects received single doses of etanercept by subcutaneous injection, in 3 separate trials. Serum samples were collected for 480 hours after dosing. Concentrations were determined using enzyme‐linked immunosorbent assay methods. Pharmacokinetic parameters were calculated using both noncompartmental and compartmental methods. Etanercept was slowly absorbed, with mean ± SD time to maximum serum concentration of 47 ± 15 hours (J), and 51 ± 20 hours (A). The maximum serum concentration and area under the concentration time curve increased for doses 10 mg, 25 mg, and 50 mg, in a linear relationship. Etanercept was slowly eliminated, with observed mean ± SD half‐life of 80 ± 25 hours (J) and 75 ± 15 hours (A) and mean ± SD apparent clearance of 144 ± 65 mL/h (J) and 132 ± 74 mL/h (A). Very low concentrations of etanercept were observed in the urine samples collected in the Japanese subjects. All adverse reactions observed resolved without issue, and none required discontinuation from the study.