bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics of autosomal recessive non‐syndromic mental retardation: recent advances
Authors: Basel‐Vanagaite L
Published: August 2007

The identification of the genes mutated in autosomal recessive non‐syndromic mental retardation (ARNSMR) has been very active recently. This report presents an overview of the current knowledge on clinical data in ARNSMR and progress in research. To date, 12 ARNSMR loci have been mapped, and three genes identified. Mutations in known ARNSMR genes have been detected so far in only a small number of families; their contribution to mental retardation in the general population might be limited. The ARNSMR‐causing genes belong to different protein families, including serine proteases, Adenosine 5′‐triphosphate‐dependent Lon proteases and calcium‐regulated transcriptional repressors. All of the mutations in the ARNSMR‐causing genes are protein truncating, indicating a putative severe loss‐of‐function effect. The future objective will be the development of diagnostic kits for molecular diagnosis in mentally retarded individuals in order to offer at‐risk families pre‐natal diagnosis to detect affected offspring.
Cyclosporine pharmacokinetics and blood pressure responses after conversion to once‐daily dosing in maintenance liver transplant patients
Authors: Kovarik John M , Villamil Federico , Otero Alejandra , Levy Gary , Lynch Stephen , Cillo Umberto , Fischer Lutz , Nashan Björn , Pollard Steve , Carlis Luciano De
Published: August 2007

Abstract:  In this six‐month randomized multicenter trial, we characterized cyclosporine pharmacokinetics and blood pressure profiles in maintenance liver transplant patients converting from twice‐daily to once‐daily cyclosporine dosing. A total of 60 patients were randomized as follows: group A (n = 14) maintained twice‐daily dosing; group B (n = 24) converted to once‐daily dosing at the same total daily dose as pre‐conversion; and group C (n = 22) was treated the same as group B but with a 25% reduction in dose and C2 at two to three wk post‐conversion. After conversion to once‐daily dosing in groups B and C, trough blood levels (C0) did not change; whereas, C2 nearly doubled. The total daily area under the concentration–time curve AUC(0–24) increased by 29%. After the dose reduction in group C, the AUC(0–24) was similar to the pre‐conversion value. Hence, a 25–30% dose reduction can be considered after conversion to once‐daily dosing. In the study observation period in weeks 4–15, the median (25–75 percentile) C2 was 568 (469–750) ng/mL for group A; 1055 (840–1224) ng/mL for group B; and 764 (575–959) ng/mL for group C. Conversion to once‐daily dosing was associated with a decrease in nighttime mean arterial blood pressure.
Influence of immunosuppressive regimens on short‐term morbidity and mortality in heart transplantation
Authors: Aguero Jaime , Almenar Luis , Martínez‐Dolz Luis , Moro Jose A , Rueda Joaquin , Raso Rafael , Chamorro Carlos , Sanchez Juan M , Salvador Antonio
Published: August 2007

Abstract:  Background:  The goal of immunosuppressive therapy in heart transplantation is to maximize safety and efficacy while minimizing morbidity and mortality. We now have numerous drug combinations, but few have been compared with each other.

Aim:  To compare various immunosuppressive regimens assessing morbidity and mortality at one yr.

Methods:  A total of 351 patients transplanted between 1989 and 2005 were included and grouped by immunosuppressive regimen into group 1 (n = 52): Muronomab (OKT3) 10 d, cyclosporine (CSA), azathioprine (AZA), steroids; group 2 (n = 193): OKT3 seven d, CSA, AZA, steroids; group 3 (n = 22): OKT3 seven d, CSA, mycophenolate mofetil (MMF), steroids; and group 4 (n = 84): interleukin‐2 antagonists (IL‐2), CSA, MMF, steroids.

Results:  The incidence of acute graft failure and treated rejection was similar between groups (17% and 78% respectively). We found a statistically significant difference in the incidence of infections (p < 0.001), renal dysfunction (p = 0.011) and in diabetes mellitus (p = 0.023). There were no differences in survival at 30 d (97%), but differences were found at one yr (p = 0.011). The multivariate analysis showed a strong association between mortality and infection (p = 0.001) and between survival and the group 4 regimen (p < 0.001).

Conclusion:  There are differences in survival at one yr of heart transplant patients depending on the immunosuppressive regimen used. The best combination was induction with IL‐2 antagonists, followed by CSA, MMF and steroids.
Polymorphism of interleukin‐18 promoter influences the onset of kidney graft function after transplantation
Authors: Kolesar L. , Novota P. , Krasna E. , Slavcev A. , Viklicky O. , Honsova E. , Striz I.
Published: August 2007

It has been well recognized that the promoter polymorphisms of interleukin‐18 (IL‐18) influence the level of cytokine expression. In our previously published data, we showed constitutive IL‐18 expression in the epithelium of renal distal tubules in patients after kidney transplantation and significantly elevated IL‐18 expression during acute rejection. In this study, we evaluated the clinical significance of two functional promoter polymorphisms of the IL‐18 gene at positions −607 A/C (rs1946518) and −137 C/G (rs187238) in patients after kidney transplantation and looked for associations with the onset of graft function and the incidence of rejection episodes. Promoter polymorphisms in 124 patients and 103 unrelated controls were evaluated by sequence‐specific primer polymerase chain reaction and the allele, genotype and haplotype frequencies were statistically correlated. We found a statistically different distribution of the allele frequency of −607 A/C polymorphism between patients with immediate or delayed onset of kidney graft function. Data showed that the C allele, which contributes to higher IL‐18 expression, is more frequent in patients with delayed onset of function (P = 0.03, odds ratio = 1.93; 95% confidence interval  = 1.15–3.25). A/C single nucleotide polymorphisms of the IL‐18 promoter at position −607 may influence the onset of early kidney allograft function.
Recurrence of non‐alcoholic steatohepatitis after liver transplantation in a 13‐yr‐old boy
Authors: Jankowska Irena , Socha Piotr , Pawlowska Joanna , Teisseyre Mikolaj , Gliwicz Dorota , Czubkowski Piotr , Kalicinski Piotr , Cielecka‐Kuszyk Joanna , Socha Jerzy
Published: August 2007

Abstract:  Nonalcoholic steatohepatitis (NASH) is the most severe form of non‐alcoholic fatty liver disease (NAFLD). The aim of our study was to highlight NASH as a rare but possible problem in children. We present a case of 13‐yr‐boy with a well‐established diagnosis of liver cirrhosis secondary to NASH, who underwent orthotopic liver transplantation (OLT) at the age of 13 years. Six months after transplantation recurrence of NASH in the graft was diagnosed. In the treatment metformin was used with good effect.
Host shift by the burying beetle,Nicrophorus pustulatus, a parasitoid of snake eggs
Authors: SMITH G. , TRUMBO S. T. , SIKES D. S. , SCOTT M. P. , SMITH R. L.
Published: August 2007

Recent work [Ecoscience (2000) vol. 7, 395–397] suggests that the burying beetleNicrophorus pustulatusmay have undergone a remarkable host shift, exploiting snake eggs rather than carrion as resources for breeding. We conducted behavioural and physiological experiments to examine the hypothesis of a host shift and to formulate hypotheses on its origin. Two congeners ofN. pustulatus,Nicrophorus orbicollisandNicrophorus defodiensdid not respond to snake eggs with typical breeding behaviour. WhenN. pustulatusmale–female pairs (n = 14) were presented with clutches of snake eggs, the number of offspring but not the mean size of offspring varied with snake egg mass, indicating effective regulation of brood size. When breeding on turtle eggs,N. pustulatushad a more variable response than when exploiting snake eggs, suggesting that turtle eggs are not a primary resource for breeding.Nicrophorus pustulatuspresented with both snake eggs and a mouse carcass combined and exploited the two resources within the same nest (10 of 12 trials). Mouse carcasses and snake eggs were treated differently. Carcasses were moved, buried and stripped of hair in a manner characteristic of burying beetles, whereas snake eggs were not moved or buried. Females that discovered a mouse carcass also had a significantly greater juvenile hormone increase than did females discovering snake eggs. Some responses to the two resources, however, were similar. FemaleN. pustulatusoviposited rapidly in response to either a mouse carcass or snake eggs, and males elevated sex pheromone emission in response to either resource. The efficient use of snake eggs, the ability to regulate brood size and the different responses to snake eggs and carrion suggest thatN. pustulatusis well adapted to exploiting snake eggs for breeding. The use of snake eggs byN. pustulatushas potential implications for conservation of oviparous reptiles.
Why have meta‐analyses of randomized controlled trials of the association between non‐white‐blood‐cell‐reduced allogeneic blood transfusion and postoperative infection produced discordant results?
Authors: Vamvakas E. C.
Published: August 2007

Intention‐to‐treat analyses of randomized controlled trials (RCTs) of the association between non‐white‐blood‐cell (WBC)‐reduced allogeneic blood transfusion (ABT) and postoperative infection were reported as the reason why meta‐analyses of RCTs of this association have produced discordant results. We examined three possible reasons for disagreements between meta‐analyses: (i) sources of medical heterogeneity and integration of RCTs despite extreme heterogeneity; (ii) reliance on as‐treated (vs. intention‐to‐treat) comparisons; and (iii) inclusion (or not) of the three most recent RCTs. When nine RCTs reported up to 2002 were combined despite extreme heterogeneity, both intention‐to‐treat and as‐treated comparisons found an association between non‐WBC‐reduced ABT and postoperative infection [summary odds ratio (OR) = 1·38, 95% confidence interval (CI) 1·03–1·85, P < 0·05; and summary OR = 1·56, 95% CI 1·06–2·31, P < 0·05, respectively]. When 12 RCTs reported up to 2005 were integrated despite extreme heterogeneity, both intention‐to‐treat and as‐treated comparisons found no association of non‐WBC‐reduced ABT with postoperative infection (summary OR = 1·24, 95% CI 0·98–1·56, P > 0·05; and summary OR = 1·31, 95% CI 0·98–1·75, P > 0·05, respectively). In both analyses, the separate integration of four RCTs transfusing red blood cells (RBCs) or whole blood filtered after storage showed an association between non‐WBC‐reduced ABT and postoperative infection, whereas the separate integration of six (or nine) RCTs, reported through 2002 or 2005, and transfusing prestorage‐filtered RBCs showed no association, whether intention‐to‐treat or as‐treated comparisons were used. Thus, the published meta‐analyses have produced discordant results because they did (or did not) investigate medical sources of heterogeneity and did (or did not) include the most recent RCTs. Intention‐to‐treat and as‐treated comparisons produced concordant results.
Fungal foot infections in patients with diabetes mellitus – results of two independent investigations
Authors: Eckhard M. , Lengler A. , Liersch J. , Bretzel R. G. , Mayser P.
Published: August 2007

In diabetic patients, mycotic infections may increase the risk of developing diabetic foot syndrome. However, little data are available on the prevalence of fungal foot infections in patients with diabetes. In a first study published using data obtained during a conference attended by patients with long‐term diabetes mellitus type 1 (DM1), 78/95 patients (82.1%) showed probable pedal fungal infections, of which 84.6% (66/78) were mycologically confirmed by direct microscopy and/or culture. The dermatophyte Trichophyton rubrum was the most common (69.2% of isolates). Significant correlation was found between infection and the gender (men more frequently affected) and the age of the patients. Marked mycoses on the soles of the feet were often considered to be dry skin by the patients. In a second study, 174 [31 DM1, 112 DM2 and 29 healthy accompanying persons (HAP), family members without DM] participants at a regional patients’ symposium on diabetes took part in an examination for fungal infections and neuropathy of the feet. In addition to the items of the first study, we gathered data on the quality of blood glucose control (HbA1c), peripheral neuropathy (neuropathy symptome and deficit score) and measurement of sudomotoric activity by Neuropad™. Mean duration of disease was 23.6 (DM1) and 11.2 (DM2) years, mean HbA1c 7.56% (DM1) and 6.89% (DM2) and fungal foot infections were confirmed at 35.5% (DM1), 53.1% (DM2) and 37.9% (HAP) respectively. In DM2, the prevalence of positive fungal samples is significantly higher for participants with less controlled blood glucose (higher HbA1c) (P = 0.04). Mycotic foot infection is also correlated with age, gender and duration of diabetes disease. Of special interest is the finding of relatively high numbers of black fungi (‘Dematiaceae’) (n = 10), Phialophora europea (n = 3) being the most common one. The sudomotoric activity was impaired in a very high number of participants [107/171 (61.5%)], and was found positively correlated with the prevalence of fungal foot infection in DM2 but not in DM1 and HAP. The high prevalence of fungal infections detected in DM1 as well as in DM2 diabetics is remarkable, especially considering this highly motivated collective. Therefore, it appears that the feet of diabetics require more diagnostic, therapeutic and preventive care in terms of mycotic infections and sudomotoric dysfunction than previously thought.
Atypical manifestations of tinea corporis
Authors: Ziemer Mirjana , Seyfarth Florian , Elsner Peter , Hipler Uta‐Christina
Published: August 2007

Tinea corporis classically presents as an erythematous annular plaque with a scaly, centrifugally advancing border. However, sometimes vesicles and pustules are observed. Occasionally, even frank bullae appear secondary to severe inflammation. Diagnostic difficulties arise when atypical manifestations mimic other inflammatory skin diseases, including atopic or seborrheic dermatitis, subacute cutaneous lupus erythematosus, or vesicular diseases. We report five cases of atypical tinea corporis, where the initial clinical diagnosis was different from dermatophytosis. The differential diagnoses and the diagnostic difficulties related to atypical manifestations of fungal infections are discussed. Moreover, our cases emphasise the importance of conventional histological examination, which enables a fast, correct diagnosis.
Consequences of a decentralized participatory barley breeding programme on changes in SSR allele frequency and diversity in one cycle of selection
Authors: Fufa F. , Baum M. , Grando S. , Kafawin O. , Ceccarelli S.
Published: August 2007

Changes in allele type, allele frequency and genetic diversity because of selection by individual farmers and breeders were assessed using simple sequence repeats (SSRs) during one cycle of selection in a decentralized participatory barley breeding programme. Selection by both breeders and farmers resulted in the loss of a number of alleles in the majority of the locations, with more alleles lost in the heterogeneous breeding materials than in the fixed genotypes, indicating selection against undesirable traits uncovered in the heterogeneous breeding materials that are presumably linked to SSR alleles. After selection, significant allelic frequency changes were observed at several loci in both the germplasm groups. As the selection was conducted independently in each location, an allele had a chance of being selected in more than one location, and therefore considering the whole study area the allelic composition and diversity of the original genetic materials was maintained after the selection. The study showed the importance of decentralized participatory plant breeding in maintaining genetic diversity that helps stabilize and sustain production in unpredictable production conditions.
Spermatozoal RNA as Reservoir, Marker and Carrier of Epigenetic Information: Implications for Cloning
Authors: Miller D
Published: August 2007

Contents

The mammalian male gamete is transcriptionally silent as a consequence of the highly condensed architecture of its chromatin and there is also little or no cytoplasm capable of supporting translation; however, we now understand that under certain conditions, spermatozoa can translate their mRNAs de novo and that spermatozoal RNA can potentially affect phenotypic traits in offspring. This epigenetic phenomenon may involve the transmission of extra‐chromosomal episomal elements. Recent evidence indicates that spermatozoal RNA may play a role in the progressive shutdown of transcription during spermiogenesis. The presence of RNA in the sperm nucleus and its potential as a carrier of eipgenetic information to the egg may prove insightful with regard to the abysmal success rates for cloning of domestic species by somatic nuclear transfer procedures.
The Horse Genome Project – Sequence Based Insights into Male Reproductive Mechanisms
Authors: Leeb T
Published: August 2007

Contents

The growing knowledge on physiology, cell biology and biochemistry of the reproductive organs has provided many insights into molecular mechanisms that are required for successful reproduction. Research directed at the investigation of reproduction physiology in domestic animals was hampered in the past by a lack of species‐specific genomic information. The genome sequences of dog, cattle and horse have become publicly available in 2005, 2006 and 2007 respectively. Although the gene content of mammalian genomes is generally very similar, genes involved in reproduction tend to be less conserved than the average mammalian gene. The availability of genome sequences provides a valuable resource to check whether any protein that may be known from human or mouse research is present in cattle and/or horse as well. Currently there are more than 200 genes known that are involved in the production of fertile sperm cells. Great progress has been made in the understanding of genetic aberrations that lead to male infertility. Additionally, the first genetic mechanisms are being discovered that contribute to the quantitative variation of fertility traits in fertile male animals. Here, I will review some selected aspects of genetic research in male fertility and offer some perspectives for the use of genomic sequence information.
Application of Doppler Ultrasonography in Cattle Reproduction
Authors: Herzog K , Bollwein H
Published: August 2007

Contents

The development of Doppler processing extended the scope of sonographic imaging from an anatomical to a physiological basis. This technique became established as a clinical tool in human gynaecology. For example, it has been discussed that the implantation of an embryo is influenced by the uterine blood flow. In cows, this uterine blood flow was investigated, using surgically implanted Doppler ultrasonic or electromagnetic blood flow probes prior to the introduction of colour Doppler sonography in bovine medicine. Therefore, the aims of our studies were to use transrectal Doppler sonography for the non‐invasive measurement of uterine and ovarian blood flow in cows and to determine changes in genital perfusion during the oestrous cycle, pregnancy and puerperium, respectively. The results of our studies show that transrectal flow imaging can be used to obtain blood flow velocity waveforms from the uterine arteries at any time during the oestrous cycle, pregnancy and puerperium. During all these phases, characteristic changes in the uterine blood flow could be observed. This uterine blood flow was low during diestrus and high during proestrus and oestrus. During pregnancy, an exponential rise in uterine blood supply could be detected. There was a positive relationship between the uterine blood flow volume (BFV) at the end of gestation and the birth weight of calves. During puerperium, the uterine BFV declined tremendously, especially during the first week after birth. In cows, with pathological disturbances of the pueperium a delayed decrease in the uterine BFV was observed. Characteristic alterations occurred also in the luteal blood flow during the oestrous cycle, which were highly related to those of the progesterone levels. Furthermore, it has been detected by the colour Doppler technique that there is no decrease, but an increase of the luteal blood flow at the beginning of luteolysis in cows. Another group has found that there are close relationships between the LH‐surge and the follicular blood flow before ovulation. In conclusion, these studies show that transrectal colour Doppler sonography is a useful technique for the investigation of the genital blood flow and provides new information about physiological changes of the genital organs during, all reproductive phases. The influence of the genital blood flow on fertility in cows needs to be examined further in future studies.
Transforming growth factor‐α accelerates hepatocyte repopulation after hepatocyte transplantation
Authors: Kosone Takashi , Takagi Hitoshi , Horiguchi Norio , Kakizaki Satoru , Sato Ken , Watanabe Yoshifumi , Mori Masatomo
Published: August 2007

Background and Aim:  Although hepatocyte transplantation could be an alternative to orthotopic liver transplantation, many problems, such as rejection, location, required volume, and hepatocyte activity are currently unresolved. We previously demonstrated an anti‐apoptotic effect in transgenic mice overexpressing transforming growth factor (TGF)‐α. We herein present the details of a successful hepatocyte transplantation using TGF‐α transgenic mice.

Methods:  We used transgenic (TG) mice which overexpressed human TGF‐α controlled by the metallothionein promoter. Wild‐type mice were used as the controls (WT). Parenchymal hepatocytes were isolated from an adult mouse by the modified in situ perfusion method. The proliferation and resistance to Fas‐induced apoptosis were examined in vitro. In addition, we transplanted the parenchymal hepatocytes into the peritoneal cavity of the WT mice.

Results:  The TG hepatocytes showed higher proliferative activity and more resistance to Fas‐induced apoptosis in comparison to the WT hepatocytes. Moreover, an immunohistochemical analysis demonstrated that the transplanted TG hepatocytes increased more in size and showed a higher expression of CD31 and vascular endothelial growth factor in comparison to the WT hepatocytes. We also observed that albumin was expressed in equal amounts in both types of transplanted hepatocytes.

Conclusion:  Cell transplantation with TGF‐α overexpressing hepatocytes could preserve hepatocyte function.
Chronic pancreatitis in primary hyperparathyroidism: Comparison with alcoholic and idiopathic chronic pancreatitis
Authors: Bhadada Sanjay K , Udawat Harsh P , Bhansali Anil , Rana Surinder S , Sinha Saroj K , Bhasin Deepak K
Published: August 2007

Background:  Primary hyperparathyroidism is a rare cause of chronic pancreatitis and there is a paucity of data on this interesting association. There is also no data comparing the clinical profile of chronic pancreatitis secondary to primary hyperparathyroidism with that of alcohol related and idiopathic chronic pancreatitis.

Methods:  The clinical and biochemical spectrum of chronic pancreatitis secondary to primary hyperparathyroidism was evaluated retrospectively and compared with nine age‐matched patients with alcohol related and idiopathic chronic pancreatitis.

Results:  Renal colic, nephrolithiasis, nephrocalcinosis, bone disease, palpable neck nodule, and psychiatric abnormality were significantly more common in chronic pancreatitis due to hyperparathyroidism in comparison to alcoholic and idiopathic groups. The corrected calcium (10.8 ± 0.9 vs 9.3 ± 0.6 vs 9.2 ± 0.8 mg/dL; P = 0.001) and intact parathormone (425 ± 130 [SE]vs 22.2 ± 14.3 [SE]vs 30 ± 27.3 [SE] pg/mL; P = 0.009) levels were significantly elevated, while levels of serum phosphate were significantly less (3.1 ± 0.4 vs 3.9 ± 0.5 vs 3.4 ± 0.7 mg/dL, respectively; P = 0.04) in chronic pancreatitis due to hyperparathyroidism in comparison to the alcoholic and idiopathic groups. No significant difference was observed in the frequency of steatorrea, diabetes mellitus, pancreatic calcification, and pseudocyst between the three groups. Six out of nine patients underwent parathyroidectomy and none had recurrence of pancreatic pain over 14.3 ± 13.8 months.

Conclusions:  Chronic pancreatitis due to hyperparathyroidism has important characteristics in its biochemical and clinical manifestations. Parathyroidectomy relieves pancreatic pain in majority of patients.
Cost‐effectiveness of the surveillance program of hepatocellular carcinoma depends on the medical circumstances
Authors: Nouso Kazuhiro , Tanaka Hironori , Uematsu Shuji , Shiraga Kunihiro , Okamoto Ryoichi , Onishi Hideki , Nakamura Shin‐ichiro , Kobayashi Yoshiyuki , Araki Yasuyuki , Aoki Noriaki , Shiratori Yasushi
Published: August 2007

Background and Aim:  The clinical features of hepatocellular carcinoma (HCC) and the medical environment are diverse in different geographic areas. The aim of this study is to evaluate the cost‐effectiveness of the surveillance of HCC in different medical circumstances.

Methods:  The Markov model focused on variables that differ from country to country and may change in the future, especially in regards to the proportion of small HCC detected incidentally. The target population was 45‐year‐old patients with Child‐Pugh class A cirrhosis, and the intervention was surveillance with ultrasonography every 6 months.

Results:  The additional cost of the surveillance was $US15 100, the gain in quality‐adjusted life years (QALYs) was 0.50 years, and the incremental cost‐effectiveness ratio (ICER) was $US29 900/QALY in a base‐case analysis (annual incidence of HCC = 4%). If 40% of small HCC were detected incidentally without surveillance, the gain in QALY decreased to 0.15 and the ICER increased to $US47 900/QALY. The increase in the annual incidence of HCC to 8% resulted in the increase of QALYs to 0.81, and the decrease of the ICER to $US25 400/QALY. The adoption of liver transplantation increased the gain in QALYs and the ICER to 0.84 and $US59 900/QALY, respectively.

Conclusions:  The gain in QALYs and the ICER due to the surveillance of HCC varies between different patient subgroups and it critically depends on the rate of small HCC detected incidentally without surveillance, as well as the annual incidence of HCC and the adoption of liver transplantation.
Effect of mosapride on gastrointestinal transit time and diagnostic yield of capsule endoscopy
Authors: Wei Wei , Ge Zhi‐Zheng , Lu Hong , Gao Yun‐Jie , Hu Yun‐Biao , Xiao Shu‐Dong
Published: August 2007

Background and Aim: Since its introduction, capsule endoscopy (CE) has made it possible to visualize the small intestine mucosa directly. However, owing to the limited battery life, only 60–80% of the capsules could reach the cecum and would possibly affect the diagnostic yield. The aim of this study was to determine the effect of oral mosapride on gastrointestinal transit time and the diagnostic yield of CE.

Method: Sixty patients were involved in this randomized, prospective and controlled study. The patients were randomly allocated to groups receiving either mosapride citrate or nothing. Patients in the mosapride group (n = 30) received 10 mg mosapride citrate 1 h before CE examination, while patients in the control group (n = 30) received no preparation. The gastrointestinal transit time, the number of CE reaching the cecum, and the diagnostic yield of each group were assessed in a single‐blinded fashion.

Result: Gastric emptying time was significantly shorter in the mosapride group than in the control group (13.5 minvs34 minP = 0.035). Compared with the control group, the complete transit rate was significantly higher in the mosapride group (93.3%vs66.7%P = 0.021). There was no significant difference between the two groups on the small bowel transit time and diagnostic yield.

Conclusion: Mosapride citrate accelerates the gastric emptying and completion rate of small bowel examination in patients undergoing CE.
Zonation of multidrug resistance‐associated protein 2 in rat liver after induction with dexamethasone
Authors: Micuda Stanislav , Fuksa Leos , Brcakova Eva , Osterreicher Jan , Cermanova Jolana , Cibicek Norbert , Mokry Jaroslav , Staud Frantisek , Martinkova Jirina
Published: August 2007

Background and Aim:  The present study was aimed to evaluate the hepatic zonation of multidrug resistance‐associated protein 2 (mrp2), an important drug transporter, and its potential changes during the induction of its expression by known inducer, dexamethasone (DEX).

Methods:  The hepatic expression of mrp2 was studied by immunohistochemistry with consequent quantification by measurement of integral optical densities of mrp2 staining in the periportal and perivenous areas of the liver acinus in control and DEX‐pretreated rats (1 mg/kg daily per os for 4 days). Overall changes in mrp2 expression and function produced by DEX were monitored using Western blotting and an in vivo clearance study of endogenous‐conjugated bilirubin, a mrp2 substrate.

Results:  In the control animals, a quantitative image analysis revealed the primary periportal localization of mrp2 within the liver acinus with the expression of mrp2 being 16.7‐fold of that in the perivenous area. After DEX pretreatment, the expression of mrp2 increased, especially in the perivenous hepatocytes. The overall expression of mrp2 increased 3.2‐fold in comparison with the control group. This observation was confirmed by Western blotting, which showed a 1.3‐fold increase in the mrp2 protein after DEX pretreatment. The functional consequences of the induced mrp2 protein in the livers of the DEX‐pretreated rats were demonstrated by the increased biliary excretion of conjugated bilirubin.

Conclusion:  In conclusion, these results indicate the zonation of mrp2 protein expression primarily to periportal hepatocytes. The induction by DEX produced spatially disproportional changes with an increase in the mrp2 protein being most prominent in the perivenous hepatocytes.
Comparison of three current staging systems for hepatocellular carcinoma: Japan integrated staging score, new Barcelona Clinic Liver Cancer staging classification, and Tokyo score
Authors: Chung Hobyung , Kudo Masatoshi , Takahashi Shunsuke , Hagiwara Satoru , Sakaguchi Yasuhiro , Inoue Tatsuo , Minami Yasunori , Ueshima Kazuomi , Fukunaga Toyokazu , Matsunaga Takashi
Published: August 2007

Background and Aim:  Although various staging systems for hepatocellular carcinoma (HCC) have been developed in recent years, there is no worldwide consensus which staging system is best. The aim of the present study was to compare the performance of the currently developed three staging systems: the Japan integrated staging (JIS) score, new Barcelona Clinic Liver Cancer (BCLC) staging classification, and the Tokyo score.

Methods:  A total of 290 consecutive patients with HCC before initial treatment at Kinki University between January 1999 and December 2001 were included. The patients were stratified according to the three staging systems, and the performance of the staging systems was compared using survival time as the only outcome measure.

Results:  There were significant differences between all stages in the JIS score, while no significant difference was found between stages C and D in the BCLC staging classification and between all the scores, except between scores 0 and 1 and 2 and 3 in the Tokyo score. For all patients (n = 290), the radical treatment group (n = 208) and the non‐radical treatment group (n = 82), the likelihood ratio χ2‐test showed the highest value, and the Akaike information criterion value was lowest in the JIS score.

Conclusion:  The JIS score provided the best prognostic stratification in a Japanese cohort of HCC patients who were mainly diagnosed at early stages and treated with radical therapies.
Major complications of ultrasound‐guided percutaneous radiofrequency ablations for liver malignancies: Single center experience
Authors: Chen Tsung‐Ming , Huang Pi‐Teh , Lin Lien‐Fu , Tung Jai‐Nien
Published: August 2007

Background and Aim:  Despite radiofrequency ablation (RFA) for malignant liver nodular lesions having promising therapeutic effects, the trade‐off between the risks and benefits must be acceptable. This study analyzed the major complications of ultrasound (US)‐guided percutaneous RFA procedures encountered at a single center, by a single physician.

Methods:  A total of 104 patients (total 183 tumors) underwent 172 US‐guided percutaneous RFA sessions between May 2003 and March 2006. The definition of major complications was according to the standardized Society of Interventional Radiology grading system (classification C‐E).

Results:  Eighty‐six patients had hepatocellular carcinoma (HCC) and 18 patients had hepatic metastatic tumors. Nine major complications occurred from 172 RFA sessions (9/172, incidence of 5.2% per session); namely, two cases of transient liver function impairment, two cases of infection (liver abscess and septicemia), two cases of tumor seeding along the ablated track, one case of colon perforation, one case of acalculous cholecystitis and, lastly, a case of hemocholecyst. We further analyzed the possible risk factors precipitating these complications, and found that only tumor size (Pearson's correlation coefficient, 0.324; P < 0.05) and baseline liver function reserve (compensated 0%, 0/148 vs decompensated 8.3%, 2/24; P = 0.019) were significant factors for the complication of transient liver function impairment.

Conclusion:  Radiofrequency ablation for liver malignancy is a safe procedure with acceptable incidence of complications. Decompensated baseline liver function reserve and large tumor size are precipitating factors for transient liver function impairment after RFA and warrant a close follow up.
Expression of inducible nitric oxide synthase in the liver is under the control of nuclear factor kappa B in concanavalin A‐induced hepatitis
Authors: Ma Xue‐Lian , Li Yue‐Hua , Gao Jian‐Xin , Li Jing , Guo Lin , Wu Cui‐Zhen
Published: August 2007

Background and Aim:  Both nuclear factor kappa B (NF‐κB) activation and inducible nitric oxide synthase (iNOS) expression increase in the liver injury, and there are NF‐κB binding sites in the iNOS promoter. The aim of this study was to investigate the correlation between iNOS expression and NF‐κB activation in hepatitis induced by concanavalin A (con A).

Methods:  Eighty‐eight male BALB/c mice were randomly divided into three groups: vehicle control group, con A group and pyrrolidine dithiocarbamate (PDTC) plus con A group. In the vehicle control group, the mice were treated with saline (0.3 mL, i.v.). In the con A group, the mice were treated with con A (20 mg/kg, i.v.). In the PDTC + con A group, the mice were pretreated with PDTC (120 mg/kg, i.p.) 30 min before administration of con A (20 mg/kg, i.v.). Blood samples were taken from the retro‐orbital venous plexus at 0.5, 1, 4, 8 and 16 h after con A injection and the mice were killed immediately. The plasma alanine aminotransferase (ALT) levels were measured by the standard photometric method. Nitric oxide (NO) levels in the liver homogenate were assayed by spectroscopy. Liver tissues were sectioned and stained with hematoxylin–eosin for histological examination. Activation of NF‐κB, degradation of inhibitor of kappa B alpha (IκBα), and expression of iNOS were measured by western blot.

Results:  In the con A group, the plasma ALT activity and NO levels in the liver increased significantly at 1 h (P < 0.05, n = 8) and reached a peak at 4 h after con A injection. The liver injury in this group was characterized by liver necrosis, cell swelling and fatty degeneration. Cytosolic IκBα decreased slightly at 30 min after con A challenge, was undetectable at 1 h and reappeared at 4 h. Correspondingly, the NF‐κB level in the nucleus was highest at 1 h. The iNOS expression increased at 30 min after con A injection and reached a maximum at 4 h. Pretreatment with PDTC prevented these changes and attenuated the liver injury.

Conclusion:  Con A‐induced iNOS expression in the liver is dependent on the activation of NF‐κB.
Predictive factors for platelet increase after partial splenic embolization in liver cirrhosis patients
Authors: Hayashi Hiromitsu , Beppu Toru , Masuda Toshiro , Mizumoto Takao , Takahashi Masashi , Ishiko Takatoshi , Takamori Hiroshi , Kanemitsu Keiichiro , Hirota Masahiko , Baba Hideo
Published: August 2007

Background and Aim:  Partial splenic embolization (PSE) is often performed for improving thrombocytopenia in cirrhotic patients. We investigated the largely unclear predictive factors for platelet increase at both 1 month and 1 year after PSE.

Methods:  Aimed at increasing the platelet count, PSE was performed in 42 cirrhotic patients with thrombocytopenia (platelets < 80 × 104/mL) caused by hypersplenism. The clinical data were analyzed to clarify the predictive factors for platelet increase at 1 month (n = 42) and 1 year (n = 38) after PSE.

Results:  The mean splenic infarction ratio was 76.7% ± 11.2%. The platelet count increased to 259% ± 112% and 228% ± 75% of the pretreatment values at 1 month and at 1 year after PSE, respectively. Stepwise multiple linear regression analysis showed that the infarcted splenic volume had a positive independent association with the increase in platelet count at both 1 month (P = 0.00004) and 1 year (P = 0.005) after PSE (increase in platelet count (×104/mL): at 1 month = 0.752 + 0.018 × infarcted splenic volume (mL), R2 = 0.344; at 1 year = 2.19 + 0.01 × infarcted splenic volume (mL), R2 = 0.203). Receiver operating characteristic analysis yielded a cut‐off value of 388 mL of infarcted splenic volume for achieving an increase of 5.0–8.0 × 104/mL in platelet count at 1 year.

Conclusions:  PSE can reduce the platelet pool and induce an increase in platelet count. This increase is greatly dependent on the infarcted splenic volume.
Combination adefovir–lamivudine prevents emergence of adefovir resistance in lamivudine‐resistant hepatitis B
Authors: Van Der Poorten David , Prakoso Emilia , Khoo Teh‐Liane , Ngu Meng C , McCaughan Geoffrey W , Strasser Simone I , Lee Alice U
Published: August 2007

Background and Aim:  The outcomes of lamivudine‐resistant chronic hepatitis B patients treated with long‐term adefovir dipivoxil have not been well described. This study aims to characterize the virological and biochemical response and to determine factors that may influence the development of resistance to adefovir.

Methods:  A retrospective review was conducted on all patients with lamivudine‐resistant chronic hepatitis B treated with adefovir for a minimum of 6 months at two tertiary referral centers.

Results:  Data on 161 patients were analyzed. Seventy‐two percent achieved an initial virological response with eventual normalization of alanine aminotransferase in only 67% of patients. Seventeen patients developed adefovir resistance with cumulative resistance rates of 3.2%, 8.8%, and 18% at 12, 24, and 36 months, respectively. Twelve (71%) of these patients had a biochemical breakthrough, with one death from fulminant hepatic failure. The median duration of lamivudine crossover was 1 month in adefovir‐resistant patients, compared with 12 months for the remainder of the cohort (P < 0.01). Longer crossover therapy reduced the adefovir resistance rate, but did not eliminate it. No adefovir resistance is reported in those who were continued on long‐term combination lamivudine–adefovir without a period of adefovir monotherapy.

Conclusions:  Combination lamivudine–adefovir therapy protected against the emergence of adefovir resistance.
Increased wild‐type p53‐induced phosphatase 1 (Wip1 or PPM1D) expression correlated with downregulation of checkpoint kinase 2 in human gastric carcinoma
Authors: Fuku Takeichi , Semba Shuho , Yutori Hirokazu , Yokozaki Hiroshi
Published: August 2007

Phosphorylation of checkpoint kinase 2 (Chk2) at Thr68 (pChk2) induced by DNA double‐strand breaks is required for inhibition of cell cycle progression in the G2 phase. The purpose of the present paper was to investigate the expression of wild‐type p53‐induced phosphatase 1 (Wip1 or PPM1D), a negative regulator of Chk2, to better understand its role in human gastric cancer. In non‐neoplastic gastric mucosa, most epithelial cells exhibited Wip1‐positive and pChk2‐negative immunoreactivity, whereas an inverse pattern of protein expression was detected at the surface of the foveolar epithelium. In tumor tissues, 74% of 53 gastric cancers had intense Wip1 immunoreactivity and close correlation with both tumor size (P = 0.0497) and Chk2 dephosphorylation (P = 0.0213). In MKN‐74 gastric cancer cells, ionizing radiation (IR)‐induced Wip1 upregulation was detected at protein levels, but the Chk2‐mediated cell cycle regulatory mechanism was disrupted. In addition, protease inhibitor Z‐Leu‐Leu‐Leu (ZLLL) effectively upregulated Wip1 levels in the presence or absence of IR, suggesting that Wip1 expression can be modulated post‐transcriptionally. Understanding the Wip1‐mediated signaling pathway in gastric cancer may provide useful information for the development of new chemo‐ and radiotherapies.
Immunohistochemical study of enterochromaffin‐like cell in human gastric mucosa
Authors: Tanaka‐Shintani Michiko , Watanabe Makoto
Published: August 2007

Enterochromaffin‐like (ECL) cell has been identified as the histamine‐containing argyrophil cell in rat gastric mucosa and vigorously studied. However, there are few reports of the distribution of ECL cell in human stomach. The aim of the present study was to determine the precise distribution of ECL cell by immunohistochemical staining of histidine decarboxylase (HDC) and gastrin–cholecystokinin B receptor (CCK‐BR) in human stomach, and the correlation between their distribution and that of parietal cells. Thirty specimens of surgically resected stomach were used. Parietal cell, Grimelius‐silver‐positive cell, gastrin, HDC‐ and CCK‐BR‐immunoreactive cell were studied on continuous cell counting in the restricted field along the lamina muscularis from the oral to the anal ends. The percentage of HDC‐immunoreactive cells of endocrine cells was smaller (15%) than that of a previous report (35%) in the fundic region. HDC‐ and CCK‐BR‐immunoreactive cells were found not only in the fundic region, but also in the intermediate and pyloric regions. In the pyloric region, HDC‐ and CCK‐BR‐immunoreactive cells were found mainly in the mucosa with intestinal metaplasia. Double‐positive cells were also found, but only in small numbers. This suggests that ECL cell, or a cell sharing its function, is present in the pyloric region.
Protein expression and mutational analysis of epidermal growth factor receptor in renal angiomyolipomas
Authors: Lim So Dug , Kim Wanseop , Ahn Geunghwan , Kwon Ghee Young
Published: August 2007

Renal angiomyolipoma (AML) is a benign but progressive tumor that occasionally requires non‐surgical therapy and there appears to be a possibility that epidermal growth factor (EGF) is associated with pathogenesis of renal AML. The response to gefitinib, anti‐epidermal growth factor receptor (EGFR) agent and a prime example of target therapy, reportedly has been correlated with the presence of mutations within the tyrosine kinase (TK) domain of EGFR or the expression of its truncated form, EGFR variant III. Therefore the purpose of the present paper was to investigate EGFR protein expression and gene mutations in exons 18, 19 and 21 in 40 renal AML. No EGFR gene mutations of TK domain were detected in any of the 40 cases studied and strong immunostaining was found in 5% of the renal AML cases. The present findings indicate that in renal AML, anti‐EGFR treatment may not be promising but that there is a possibility that EGFR is associated with renal AML pathogenesis.
Immunohistochemical analysis of nestin and c‐kit and their significance in pancreatic tumors
Authors: Ohike Nobuyuki , Sato Masashi , Hisayuki Tomokazu , Imataka Hiromi , Sato Shun , Wada Yukihiro , Saito Koji , Takahashi Manabu , Tajiri Takuma , Kunimura Toshiaki , Morohoshi Toshio
Published: August 2007

The purpose of the present study was to clarify the difference of expression of two stem cell markers, nestin and c‐kit, among various pancreatic epithelial tumors and evaluate their utility. Immunohistochemistry was done for 99 surgically resected pancreatic tumor specimens, including 20 ductal adenocarcinoma (DAC), two undifferentiated carcinomas (UC), 31 intraductal papillary‐mucinous neoplasms (IPMN), six mucinous cystic neoplasms (MCN), five serous cystadenomas (SCA), six acinar cell carcinomas, two pancreatoblastoma (PB), eight solid‐pseudopapillary neoplasms (SPN), and 19 endocrine neoplasms (EN). Nestin was widely expressed in four SPN, one PB, one SCA, sarcoma areas in two UC, one MCN, and one DAC, and an area of oncocytic component in one IPMN. Some of these SPN, SCA and sarcomatous or oncocytic components in which nestin was expressed, also coexpressed c‐kit. Additionally, partial (scattered) expression of c‐kit was observed in ductal elements of 16 DAC, eight IPMN, five MCN, and one UC, one SCA, and three EN. The eight c‐kit‐positive IPMN included four of 23 adenoma‐to‐border lesions and four of eight non‐invasive‐to‐invasive carcinomas. The three EN were all carcinomas. These indicate that expression of two stem cell markers is different by tumor type, but the utility of judging direction or degree of differentiation and malignant grade on the basis of their expression status is suggested.
Pituitary adenoma with rich folliculo‐stellate cells and mucin‐producing epithelia arising in a 2‐year‐old girl
Authors: Min Hye Sook , Lee Seung June , Kim Seung‐Ki , Park Sung‐Hye
Published: August 2007

Pituitary adenoma is a rare neoplasm in childhood, with prolactin and adrenocorticotropic hormone (ACTH)‐secreting adenomas predominating in this age group. Herein is reported a case of an ACTH‐producing macroadenoma with an unusual histology that occurred in a 2‐year‐old girl. Because of the patient's age and the macroadenoma's suprasellar location and large size (up to 4 cm in diameter), radical surgery was performed under the suspicion of craniopharyngioma or germ‐cell tumor. Pathologically, it was a unique pituitary adenoma composed of monotonous ACTH‐producing cells, smaller folliculo‐stellate cells (FSC), and mucin‐producing cells. The FSC, non‐hormone‐secreting pituitary cells of uncertain function, were confirmed by their S‐100 protein, glial fibrillary acidic protein and cytokeratin expression immunoprofiles. The abrupt transition between the prominent gland‐forming mucin‐producing epithelia and the FSC component suggested that the mucin‐producing epithelia might be derived from the FSC. This association might represent so‐called ‘retrodifferentiation’ of adenoma cells to the FSC and the precursor cells of Rathke's pouch.