bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinctive characteristics of transcriptional profiles from two epithelial cell lines upon interaction with Actinobacillus actinomycetemcomitans
Authors: Mans J. J. , Baker H. V. , Oda D. , Lamont R. J. , Handfield M.
Published: July 2006

Transcriptional profiling and gene ontology analyses were performed to investigate the unique responses of two different epithelial cell lines to an Actinobacillus actinomycetemcomitans challenge. A total of 2867 genes were differentially regulated among all experimental conditions. The analysis of these 2867 genes revealed that the predominant specific response to infection in HeLa cells was associated with the regulation of enzyme activity, RNA metabolism, nucleoside and nucleic acid transport and protein modification. The predominant specific response in immortalized human gingival keratinocytes (IHGK) was associated with the regulation of angiogenesis, chemotaxis, transmembrane receptor protein tyrosine kinase signaling, cell differentiation, apoptosis and response to stress. Of particular interest, stress response genes were significantly – yet differently – affected in both cell lines. In HeLa cells, only three regulated genes impacted the response to stress, and the response to unfolded protein was the only term that passed the ontology filters. This strikingly contrasted with the profiles obtained for IHGK, in which 61 regulated genes impacted the response to stress and constituted an extensive network of cell responses to A. actinomycetemcomitans interaction (response to pathogens, oxidative stress, unfolded proteins, DNA damage, starvation and wounding). Hence, while extensive similarities were found in the transcriptional profiles of these two epithelial cell lines, significant differences were highlighted. These differences were predominantly found in pathways that are associated with host–pathogen interactions.
Porphyromonas gingivalis survives within KB cells and modulates inflammatory response
Authors: Eick S. , Reißmann A. , Rödel J. , Schmidt K.‐H. , Pfister W.
Published: July 2006

Background/aims:  The purpose of the study was to investigate the intracellular survival of Porphyromonas gingivalis as a possible mechanism for maintaining periodontitis.

Methods:  P. gingivalis strains, the strain ATCC 33277 and seven clinical isolates, were co‐cultured with KB cells. The number of intracellular bacteria was determined up to 3 days after infection. In addition, the numbers of KB cells per well, the concentrations of the cytokines interleukin‐1β (IL‐1β), IL‐6, IL‐8 and tumour necrosis factor‐α (TNF‐α) and the arginine‐specific amidolytic activity were measured. The 16S rRNA of P. gingivalis and the mRNA expression of IL‐1β, IL‐6, IL‐8, TNF‐α and rgpA were also determined.

Results:  All the P. gingivalis strains studied were able to survive within KB cells. In contrast to the reduced values of colony‐forming units at day 3, equal and higher levels of 16S rRNA were seen in comparison to day 0. Arginine‐specific amidolytic activity declined in all samples during infection. Expression of mRNA for rgpA was not found after infection of KB cells by P. gingivalis strains. IL‐8 was detectable in all samples 2 days after infection with P. gingivalis strains. Principal components analysis underlined a correlation between the arginine‐specific amidolytic activity 1 h after infection and both the released IL‐8 and the mRNA expression of IL‐8. Associations were found between the cultivable numbers of intracellular P. gingivalis and the mRNAs of IL‐1, IL‐6 and TNF‐α at the day of infection.

Conclusion:  The results indicate survival of P. gingivalis within epithelial cells, possibly in a non‐cultivable stage. Invasion into cells modulates the virulence properties of P. gingivalis as well as the inflammatory response of the cells.
Frequency of hyperuricemia and effect of calcineurin inhibitors on serum uric acid levels in liver transplanted children
Authors: Tumgor Gokhan , Arikan Cigdem , Kilic Murat , Aydogdu Sema
Published: July 2006

Abstract:  Hyperuricemia is common after renal and cardiac transplantations, but it is rarely reported after liver transplantations. The aim of this study is to determine the frequency of hyperuricemia in children following orthotopic liver transplantation and the effects of calcineurin inhibitors tacrolimus and cyclosporine) on blood uric acid levels. Between September 1997 to January 2004, 76 liver transplantations were performed in 70 children (male/female; 39/31) at Ege University, Organ Transplantation Center (37 deceased donation and 39 live donors). Patients who had been transplanted within the last three months and patients who died within six months after liver transplantation were excluded from the study. Finally 59 patients were included in this study. Uric acid levels were measured before transplantation and after transplantation within six months intervals for two yr. In these series 17 cases had increased uric acid levels after liver transplantation (28.8%). Serum uric acid levels in both groups (tacrolimus or cyclosporine) were detected to be significantly higher than initial values at 12th months (p < 0.05). Hyperuricemia developed in eight patients receiving cyclosporine (eight of 11; 72%) whereas nine patients receiving tacrolimus developed hyperuricemia (nine of 48; 18%). However, the rate of having high uric acid levels was significantly higher in cyclosporine group compared tacrolimus group (p = 0.001, OR: 11.5, CI 95% 2.5–52.4). Uric acid levels were also significantly higher in cyclosporine group in 12th and 18th months (respectively, p = 0.003 and p = 0.003). Serum creatinine levels at 12th, 18th and 24th months were significantly higher in cyclosporine group than tacrolimus group (respectively, p = 0.009, p = 0.04 and p = 0.02). Hyperuricemia is a common complication after liver transplantation in children. Cyclosporine may cause hyperuricemia more often in respect to tacrolimus and this may be related to the impairment of renal functions. Complications developing because of hyperuricemia such as gout disease or renal calculi are quite rare in children.
Pediatric living donor lobar lung transplantation
Authors: Sweet Stuart C.
Published: July 2006

Abstract:  Living donor lobar lung transplantation (LDLLT) was developed in order to mitigate the growing competition for deceased donor (DD) lungs and resultant increase in waiting list mortality. Because each of the two donor lobes serves as an entire lung for the recipient, donors who are taller than the recipient are preferred. Therefore LDLLT is particularly well suited for pediatric recipients for whom adults serve as donors. Although long‐term outcomes after LDLLT reported by the Organ Procurement and Transplantation Network (OPTN) are worse compared with DD recipients, overall pediatric outcomes as well as single center reports from the most experienced programs are more promising. Particularly encouraging are the findings that bronchiolitis obliterans (OB) is less frequent or less severe in LDLLT recipients in comparison to DD recipients. Moreover, outcomes may be improved by careful selection of donors to ensure adequately sized donor lobes and minimization of infectious risks. Although no donor deaths have been reported, there is a moderate risk of significant short‐term complications. Long‐term follow‐up has not been reported. The use of LDLLT has decreased in recent years, and the recent change by the OPTN to an urgency/benefit allocation system for DD lungs in patients 12 yr and older may further reduce the demand. Nonetheless, we anticipate that LDLLT will continue to be utilized in select circumstances, particularly in children under 12 where access to DD organs remains challenging.
Chimerism in a child with severe combined immunodeficiency: A case report
Authors: Aureli Anna , Piancatelli Daniela , Monaco Palmina I. , Ozzella Giuseppina , Canossi Angelica , Piazza Antonina , Isacchi Giancarlo , Caniglia Maurizio , Adorno Domenico
Published: July 2006

Abstract:  Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders in which there is a combined absence of T‐lymphocyte and B‐lymphocyte function. Children with SCID die within two years of age, if untreated. The effective treatment for SCID is a hematopoietic stem cell transplantation (HSCT). It has been repeatedly described that in peripheral blood of infants with SCID maternal T cells can be found. Here we report a case of blood chimerism in a one‐year‐old boy with SCID.
Reduced fluid gain during cardiopulmonary bypass in piglets using a continuous infusion of a hyperosmolar/hyperoncotic solution
Authors: Farstad M. , Haugen O. , Kvalheim V. L. , Hammersborg S. M. , Rynning S. E. , Mongstad A. , Nygreen E. , Husby P.
Published: July 2006

Background:  The aim of this study was to evaluate how a continuous infusion of a hyperosmolar/hyperoncotic solution influences fluid shifts and intracranial pressure during cardiopulmonary bypass in piglets.

Methods:  Fourteen animals, randomized to the control (CT) group or the hypertonic saline/hydroxyethyl starch (HyperHaes®) (HSH) group, received acetated Ringer’s solution as prime and supplemental fluid. The HSH group received, in addition, HyperHaes® 1 ml/kg/h. After 1 h of normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass (28 °C) was initiated and continued for 90 min. Fluid balance, plasma volume, tissue water content, acid–base parameters and intracranial pressure were recorded, and protein masses and fluid extravasation rates were calculated.

Results:  At the start of normothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.06) to 1.57 (0.71) and 0.19 (0.09) to 0.82 (0.14) in the CT and HSH groups, respectively, with no between‐group differences (P = 0.081) During hypothermic cardiopulmonary bypass, the fluid extravasation rates (ml/kg/min) increased from 0.19 (0.14) to 0.51 (0.10) (P < 0.01) and 0.15 (0.08) to 0.33 (0.08) (P < 0.05), respectively, with significantly lower extravasation rates in the HSH group (P < 0.01). In the HSH group, the total fluid gain during cardiopulmonary bypass decreased by about 50% (P < 0.05) and the tissue water content was significantly lower in the left and right heart as well as in the lungs. The intracranial pressure remained stable in the HSH group, but increased in the CT group.

Conclusions:  A continuous infusion of HSH (HyperHaes®) during cardiopulmonary bypass reduced the fluid extravasation rate and the total fluid gain during bypass. No electrolyte or acid–base disturbances were present. The intracranial pressure remained stable in the HSH group.
Ammonium chloride and α‐ketoglutaric acid increase glutamine availability in the early phase of induced acute metabolic acidosis
Authors: Nordgren A. , Karlsson T. , Wiklund L.
Published: July 2006

Background:  Glutamine deficiency in critical illness is associated with increased morbidity and mortality. We hypothesized that ammonium chloride (NH4Cl) and α‐ketoglutaric acid (α‐KGA) infusions could increase glutamine availability possibly through de novo synthesis in the liver.

Methods:  Anesthetized post‐absorptive pigs were allocated to four groups (n = 8). The study groups received either a 4‐h intravenous infusion of α‐KGA, 11.4 μmol/kg/min and NH4+, 9.7 μmol/kg/min (group 1), or α‐KGA, 2.85 μmol/kg/min and NH4+, 46.3 μmol/kg/min (group 2), or α‐KGA, 11.4 μmol/kg/min (group 3), or isotonic saline (control group). Plasma concentrations of glutamine and glutamine exchange in liver, intestine and skeletal muscle were investigated.

Results:  Plasma glutamine concentrations in group 1 (58% increase) were greater (P < 0.05) compared with the control group (14% decrease) and group 3 (13% decrease), and in group 2 (91% increase) compared with the control group, group 3 (P < 0.0001) and group 1 (P < 0.05). Intestinal glutamine extractions in group 2 were significantly greater (P < 0.01) compared with all other groups. Neither the liver nor the hind leg increased its release of glutamine. Arterial pH decreased (all P < 0.001) to 7.39 ± 0.01 in the control group, 7.30 ± 0.01 in group 1, 7.19 ± 0.01 in group 2 and 7.35 ± 0.01 in group 3.

Conclusion:  Infusions of α‐KGA and NH4Cl, to a pH range of 7.20–7.30, did not enhance hind leg or hepatic glutamine release. The increased plasma concentrations of glutamine were effects of NH4Cl, not α‐KGA, and caused either by de novo synthesis or decreased degradation.
Comparison of malignant potential between serrated adenomas and traditional adenomas
Authors: Song Sang Yong , Kim Young‐Ho , Yu Min Kyu , Kim Jeong Hwan , Lee Ji Min , Son Hee Jung , Rhee Poong‐Lyul , Kim Jae J , Paik Seung Woon , Rhee Jong Chul
Published: July 2006

Background:  Serrated adenoma is a discrete colorectal epithelial neoplastic lesion that can evolve into colorectal cancer. However, the degree of malignant potential has not been firmly established as yet. The purpose of the present paper was to compare the malignant potential and clinicopathological features between serrated and traditional adenomas.

Methods:  A total of 124 serrated adenomas from 116 patients were assessed, and 419 traditional adenomas from 200 were randomly selected. The combination of nuclear dysplasia and serration of ≥20% of crypts was regarded as serrated adenoma. The clinicopathological features of serrated and traditional adenomas were compared, and multivariate analysis performed to confirm whether the malignant potential of serrated adenoma was similar to that of traditional adenoma.

Results:  The differences in age, sex, total number of adenomas, and synchronous lesions including adenoma with high‐grade dysplasia and carcinoma between subjects with and without serrated adenoma were not significant. Serrated adenomas were more frequently located in the rectum and sigmoid colon (P < 0.001), and the average size of serrated adenomas was greater than that of traditional adenomas (P < 0.05). The incidence of malignant lesions including high‐grade dysplasia and carcinoma in serrated adenomas was found to be lower than in traditional adenomas (3.2% vs 9.3%, P < 0.05). In the multivariate analysis, adenoma type and polyp size constituted the risk factors for the incidence of high‐grade dysplasia and carcinoma.

Conclusions:  Serrated adenoma is a premalignant lesion, but it has a lower potential for the development of malignancy than traditional adenomas.
Urokinase plasminogen activator stimulates function of active forms of stromelysin and gelatinases (MMP‐2 and MMP‐9) in cirrhotic tissue
Authors: González‐Cuevas Jaime , Bueno‐Topete Miriam , Armendariz‐Borunda Juan
Published: July 2006

Background:  The authors’ previous data support the notion that adenoviral‐driven urokinase plasminogen activator (u‐PA) expression results in reversion of experimental liver cirrhosis. The specific aim of the present study was to decipher the mechanisms involved in the regulation by endogenous/gene‐delivered u‐PA of matrix metalloproteinases (MMP) and related proteins engaged in degradation of excessive hepatic connective tissue.

Methods:  Tissue slices from cirrhotic rat livers were incubated with u‐PA‐rich supernatants from 24‐h‐cultured hepatic stellate cells (HSC). Matrix metalloproteinase‐2, ‐9 and tissue inhibitor of metalloproteinases‐1 (TIMP‐1) were detected by western blot and biologic activity. The HSC that discontinued u‐PA production were transfected with the adenovector Adu‐PA and serum‐free supernatants evaluated for proteolytic activity by MMP‐3, MMP‐2 and MMP‐9. Collagen I, transforming growth factor‐β1 (TGF‐β1), plasminogen activator inhibitor‐1 (PAI‐1) and TIMP‐1 mRNA levels were also evaluated.

Results and Conclusion:  Endogenous u‐PA from cultured HSC significantly induced the active forms of MMP‐2 (68 kDa) and MMP‐9 (78 kDa) in cirrhotic tissue slices. The TIMP‐1 molecular forms demonstrated that u‐PA pushed the presence of ‘free’ TIMP‐1 (not complexed with MMP; 71%) in cirrhotic tissue. When non‐producing u‐PA‐HSC were transfected with adenoviral vector coding for the functional human protein u‐PA (Adhu‐PA), an overactivation of MMP‐3, MMP‐2 and MMP‐9 (800%, 48% and 100%, respectively) was found as compared with HSC transfected with control adenovirus encoding green fluorescent protein (Ad‐GFP). Finally, gene expression of collagen I, TGF‐β1, PAI‐1 and TIMP‐1 were downregulated by Adhu‐PA action as well.
Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis
Authors: Furuta Ryuichi , Ando Takafumi , Watanabe Osamu , Maeda Osamu , Ishiguro Kazuhiro , Ina Kenji , Kusugami Kazuo , Goto Hidemi
Published: July 2006

Background: The clinical efficacy of corticosteroids in the treatment of ulcerative colitis (UC) is well‐established. However, prolonged usage of these drugs can result in serious complications. Rebamipide {2‐(4‐chlorobenzoylamino)‐3[2‐(1H)‐quinolinon‐4‐yl] propionic acid}, a cytoprotective agent, has been reported to have anti‐inflammatory activity and to repair mucosal injury in animal colitis models. The aim of the present study was to assess the clinical efficacy and safety of a novel Rebamipide enema therapy in UC patients.

Methods: Twenty patients with the active distal type of UC in whom corticosteroid treatment had been unsuccessful were treated with rectal administration of Rebamipide twice a day for 3 weeks, during which corticosteroid dosage was kept constant. The efficacy of treatment was assessed from clinical symptoms and endoscopic findings. The anti‐inflammatory effect of Rebamipide was also examined by monitoring changes in the intensity of histological inflammation and levels of cytokine activity in the rectal mucosa.

Results: At 3 weeks after the initiation of Rebamipide enema therapy, 11 patients (55%) achieved clinical remission. Sixteen (80%) were colonoscopically judged to be responders, with decreased levels of interleukin (IL)‐1β but not of IL‐8, and an increased ratio of IL‐1 receptor antagonist/IL‐1β in organ cultures of mucosal tissues. The change in the number of infiltrating neutrophils was not significantly correlated with the clinical response to this therapy. No side‐effects were noted in any patients.

Conclusion: Rebamipide enema therapy proved to be safe and useful in corticosteroid‐refractory patients with the active distal type of UC.
Immune response in addicts with chronic hepatitis C treated with interferon and ribavirine
Authors: Sergio Neri , Salvatore Travali , Gaetano Bertino , Davide Pulvirenti , Claudio Italiano , Massimo Libbra , Barbara Mauceri , Giuseppe Abate , Stefano Calvagno , Danila Cilio , Aikaterini Tsami , Luca Ignaccolo , Daniela Callari , Luciano Caruso
Published: July 2006

Background:  The role played by the immune system in the progression of chronic hepatitis C (CHC) is not completely clear. Opioids may facilitate the outbreak of infections through marked immunomodulating effects on the immune response against a virus. To asses if addicts can be treated successfully with interferon (IFN) during detoxification treatment, we evaluated some immune response mediators in addicts affected by CHC.

Method:  A cohort of heroin users with CHC were enrolled during the detoxification period, divided into two groups and treated with IFN pegilate plus ribavirin (group A treated during methadone administration and group B treated at week 8 after methadone treatment completed). A group of patients with CHC and no history of drug addiction were enrolled as controls. Leukocyte subpopulation NK, CD4+, CD8+ and some cytokines Th1 (IFNγ, interleukin [IL]2) and Th2 (IL‐6, IL‐10) were evaluated prior to, during and after methadone treatment. Sustained virological response was evaluated 24 weeks after antiviral treatment was completed.

Results:  During methadone treatment, significantly (P < 0.05) higher cytokine Th1 and NK and lower cytokine Th2 levels were observed in groups A and B compared with levels obtained before treatment in the same groups. Relapse occurred at 56 ± 8 weeks in 34/55 group A patients, at 24 ± 8 weeks in 33/52 group B patients and at 24 ± 4 weeks in group C, there being a significant difference (P < 0.05) between group A and B and between group A and C. No significant differences between all groups were detected in CD4+ and CD8+ cell counts.

Conclusions:  Our results revealed that drug addicts with CHC can be treated successfully with IFN pegilate and ribavirin. This therapy can be recommended during the early phase of detoxification treatment to achieve a sustained response.
Altered alpha adrenergic vasoresponsiveness in a non‐cirrhotic portal hypertension model of E. coli injection
Authors: Rizvi Moattar Raza , Omanwar Swati , Fahim Mohammad , Sarin Shiv Kumar
Published: July 2006

Background and Aim:  Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamic circulation in cirrhosis. Animal models of cirrhosis and portal vein ligation have helped in our understanding of portal hypertension. The etiopathogenesis of non‐cirrhotic portal fibrosis (NCPF), a common cause of portal hypertension, is still poorly understood. The aim of this study was to investigate the pathophysiology of NCPF in a rabbit model.

Methods:  An indwelling cannula was inserted into the gastrosplenic vein of rabbits. Animals were randomly injected with saline (Group I, n = 13) or lipopolysaccharide (Group II, n = 13) from heat killed Escherichia coli at 0, 1, 2, 7, 14 and 28 days. Portal pressure was measured at 3 months and vasoresponsiveness studied in isolated aortic rings in intact and in endothelium‐denuded tissues from both groups.

Results:  In all group II compared with group I animals, the splenic weight (0.89 ± 0.16 vs 0.62 ± 0.1 g, P < 0.05) and the portal pressure (14.99 ± 0.56 vs 7.04 ± 0.42 mmHg, P < 0.05) were higher at 3 months. The group II animals showed reduced responsiveness to phenylephrine showing maximal contraction of 1.25 ± 0.08 at 10−4 mol/L as compared to 2.85 ± 0.33 g tension in Group I (P < 0.05). Endothelium denudation of aortic rings had no effect on reduced reactivity in Group II animals. Acetylcholine induced an increase in vasorelaxation at lower concentrations in preconstricted aortic rings in Group II compared to Group I animals, but this decreased in higher concentrations. Nifedipine produced comparable vasodilatation in preconstricted rings in both the groups of animals.

Conclusions:  Repeated injection of lipopolysaccharide into the gastrosplenic vein leads to the development of portal hypertension. This non‐cirrhotic model of portal hypertension is characterized by generalized arterial hyporeactivity to vasoconstrictors akin to other models of portal hypertension.
Effect of a gastro‐protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: A double‐blind placebo‐controlled study in Japan
Authors: Miwa Hiroto , Osada Taro , Nagahara Akihito , Ohkusa Toshifumi , Hojo Mariko , Tomita Toshihiko , Hori Kazutoshi , Matsumoto Takayuki , Sato Nobuhiro
Published: July 2006

Background and Aim:  Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well‐controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4‐week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia.

Methods:  In a double‐blinded, randomized, placebo‐controlled, single‐center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32.

Results:  Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per‐protocol analysis (P = 0.048 and P = 0.031, respectively).

Conclusions:  Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks’ treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.
Maternal hepatitis B virus (HBV) DNA positivity and sexual intercourse are associated with HBV intrauterine transmission in China: A prospective case–control study
Authors: Shao Zhong‐Jun , Xu De‐Zhong , Xu Jian‐Qiu , Li Jing‐Hua , Yan Yong‐Ping , Men Ke , Wang Xue‐Ping , Zhang Zhi‐Ying , Jiang Qin‐Wu , Zhang Lei
Published: July 2006

Background and Aim:  Hepatitis B virus (HBV) intrauterine transmission from infected mothers contributes significantly to the persistence of the high number of HBV carriers. The aim of this study was to identify potential risk factors for HBV intrauterine transmission.

Methods:  A case–control study was performed on pregnant women tested positive for HBsAg at Shaanxi Maternal and Neonatal Health Hospital, Xi’an, China, from September 2002 to October 2004. Serum samples were taken from infected women and their newborn infants and used for the detection of HBsAg. A structured standard questionnaire was used to collect demographic, medical and maternal data, and maternal HBV DNA, HBeAg, anti‐hepatitis C virus and anti‐hepatitis D virus were also assessed. Ten neonates validated as having HBV intrauterine transmission were selected as cases and others as controls.

Results:  The univariate analysis indicated that maternal HBeAg positivity (odds ratio [OR] = 5.96, 95% confidence interval [CI]: 1.61–22.12), HBV DNA positivity (OR = 12.09, 95% CI: 2.97–40.17) and sexual intercourse in the second trimester (OR = 9.15, 95% CI: 1.08–202.99) were significantly associated with an increased risk for HBV intrauterine transmission, whereas contraceptive measures before pregnancy (OR = 0.21, 95%CI: 0.04–0.99) were associated with a decreased risk. The multivariate analysis, however, identified maternal HBV DNA positivity (OR = 19.18, 95%: CI: 3.26–118.73) and sexual intercourse in the second trimester (OR = 1.29, 95%: CI: 1.00–1.66) as the only independent risk factors for HBV intrauterine transmission.

Conclusions:  The risk of HBV intrauterine transmission increased with increased frequency of sexual intercourse. Therefore, it is concluded that maternal HBV DNA positivity and sexual intercourse in the second trimester are independent risk factors for HBV intrauterine transmission.
Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis
Authors: Izzo Francesco , Montella Maurizio , Orlando Antonio Pio , Nasti Guglielmo , Beneduce Gerardo , Castello Giuseppe , Cremona Francesco , Ensor C. Mark , Holtzberg Frederick W. , Bomalaski John S. , Clark Mike A. , Curley Steven A. , Orlando Raffaele , Scordino Fabrizio , Korba Brent E.
Published: July 2006

Background:  The arginine‐degrading enzyme, arginine deiminase conjugated to polyethylene glycol (ADI‐SS PEG 20 000 mw), reduces extracellular arginine, has minimal toxicity, decreases tumor burden and improves liver function in patients with chronic hepatitis C virus infection (HCV) and inoperable hepatocellular carcinoma (HCC). Reduced extracellular arginine inhibits viral replication through unknown mechanisms. It is hypothesized that ADI‐SS PEG 20 000 mw reduces HCV viral titers through nitric oxide (NO)‐dependent effects.

Methods:  The effects of ADI‐SS PEG 20 000 mw (dose, 160 IU/m2; three cycles of four once‐weekly i.m. injections) on HCV titers, serum NO and plasma arginine, were evaluated using archived plasma from patients with HCC and HCV and in vitro cell model measurements of HCV replication.

Results:  ADI‐SS PEG 20 000 mw selectively inhibited HCV replication in vitro (IC50 = 0.027 IU/mL). Fifteen HCC/HCV patients completed treatment. The HCV titers were reduced by up to 99% in five out of 10 (50%) HCV‐serotype 1b patients (P = 0.0093). These patients also experienced significant improvements in liver function (P = 0.0091). There were concomitant reductions of plasma arginine and serum NO levels. The HCV titer was not reduced in HCV‐type 2c patients.

Conclusion:  Reduction of extracellular arginine by ADI‐SS PEG 20 000 mw in HCC patients reduces HCV viral titers and improves liver function, possibly through suppression of NO.
Acute hepatitis C in Israel: A predominantly iatrogenic disease?
Authors: Lurie Yoav , Landau Dan‐Avi , Blendis Laurence , Baruch Yaacov , Veitsman Ella , Ackermann Zvi , Zelber‐Sagie Shira , Halpern Zamir , Oren Ran
Published: July 2006

Background and Aims: Acute hepatitis C virus infection in the era of universal screening of blood products has not disappeared, and is thought to be transmitted primarily via injecting drug use. A growing body of evidence supports iatrogenic transmission as an important mode of transmission. The aim of this study was to examine transmission routes and clinical characteristics in a group of patients with acute hepatitis C in Israel.

Methods: A retrospective chart review was conducted in three different liver clinics in Israel, of all new hepatitis C patients. Patients identified as possible acute hepatitis C were re‐interviewed and all other sources such as blood bank records and pre‐employment check‐ups reviewed in order to establish the diagnosis of acute hepatitis C infection and to identify the transmission route.

Results: Twenty‐nine patients were found to have acute hepatitis C, representing 0.75% of all new referrals for hepatitis C. The most frequent (65%) mode of transmission was iatrogenic involving several, often minimal, procedures and clinical settings. The group in which iatrogenic transmission was suspected was older and the patients more often in monogamous relationship compared with other transmission routes groups. Injecting drug use was the second most common route of infection. Spontaneous seroconversion has occurred in approximately one third of the patients.

Conclusions: Acute hepatitis C in the post universal blood products screening era was found to be predominantly an iatrogenic disease in the investigated localities. This finding should direct attention and resources towards the development and implementation of preventive measures.
Combination therapy of poly (ADP‐ribose) polymerase inhibitor 3‐aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells
Authors: Jacob Dietmar A , Bahra Marcus , Langrehr Jan M , Boas‐Knoop Sabine , Stefaniak Robert , Davis John , Schumacher Guido , Lippert Steffen , Neumann Ulf P
Published: July 2006

Background and Aim:  Poly (ADP‐ribose) polymerase (PARP) inhibitors such as 3‐aminobenzamide (3‐ABA) enhance the in vitro cytotoxicity of DNA mono‐functional alkylating agents such as radiation or chemotherapeutic agents. The aim of this study was to test an approach combining the PARP inhibitor 3‐ABA with standard gemcitabine therapy in human pancreatic cancer cells.

Methods:  Cell viability was determined by proliferation assay (XTT). Cell‐cycle analysis (FACS), ELISA (M30 Apoptosense), Western blot for caspase 8 and PARP, and electron microscopy were used to identify apoptosis. Tumor growth and survival was assessed in nude mice by subcutaneously injected Capan‐1 cells. In addition, Ki67 staining was performed on tumors for cell proliferation and in vivo apoptosis induction was measured by TUNEL assay and ELISA.

Results:  Combination therapy of gemcitabine and 3‐ABA suppressed tumor cell growth more than gemcitabine alone in XTT, FACS and ELISA analysis.

Conclusion:  This in vivo study demonstrated a significantly reduced tumor weight and increased survival up to 40 days after cell inoculation with combination therapy compared to animals treated with PBS, gemcitabine or 3‐ABA alone. Furthermore, TUNEL assay revealed a significant apoptosis induction and reduced proliferation in the combination group.
Comparison of the efficacy, safety, and tolerability of propiverine and oxybutynin for the treatment of overactive bladder syndrome
Authors: ABRAMS PAUL , CARDOZO LINDA , CHAPPLE CHRISTOPHER , SERDAREVIC DZELAL , HARGREAVES KATHERINE , KHULLAR VIKRAM ,   THE 1032 STUDY GROUP
Published: July 2006

Aim:  To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring (AUM) parameters, safety, and tolerability in patients with overactive bladder.

Methods:  This was a randomized, double‐blind, placebo‐controlled, multicentre, crossover study. Patients (n = 77) received two of the following treatments during two 2‐week periods: propiverine 20 mg once daily, propiverine 15 mg three times daily, oxybutynin 5 mg three times daily, and placebo. AUM parameters, salivary flow, visual near point, and heart rate were assessed.

Results:  A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions (IDCs; oxybutynin 15 mg ≤ propiverine 45 mg ≤ propiverine 20 mg). Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints. Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate (oxybutynin 15 mg < both propiverine regimens) and in heart rate variability (both propiverine regimens < oxybutynin 15 mg). All active treatments lengthened visual near point. The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group. Treatment with propiverine 45 mg resulted in the highest rates of constipation, lengthening of the visual near point, and effects on heart rate.

Conclusions:  Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients. The primary differences between the two drugs were the incidence and type of adverse events, which varied with the antimuscarinic receptor specificity of each agent.
Value of frozen sections of lymph nodes in pelvic lymphadenectomy in patients with invasive bladder tumor
Authors: UGURLU OZGUR , ADSAN OZTUG , TUL MESUT , KOSAN MURAT , INAL GURDAL , CETINKAYA MESUT
Published: July 2006

Aim:  We examined the reliability of classical lymph node evaluation methods. We compared the results of preoperative computed tomography (CT) and perioperative frozen section examination of lymph nodes in patients on whom radical cystectomy was performed because of invasive bladder tumors.

Methods:  A total of 142 patients, in whom radical cystectomy was performed because of invasive bladder tumors between the years 1994 and 2005 in our clinic, and 284 pelvic lymph node regions were evaluated retrospectively. For each of the pelvic lymph node region, the conditions of the lymph nodes according to CT and in frozen sections were compared with the final pathology reports of the surgical specimens.

Results:  Lymph node involvement was found in 36 pelvic regions out of 284 in the final pathology. It had been possible to show only two of the 36 positive lymph nodes in preoperative CT. Frozen section results of the 29 pelvic lymph node regions out of 36 that were involved according to the final pathology were positive also according to frozen section results. On the other hand, in all the 29 lymph node regions those that were positive according to frozen section had lymph node involvement in the final pathology.

Conclusions:  We recommend the performance of frozen section examination on obturator plus internal iliac lymph nodes when deciding extended lymph node dissection, and the performance of extended lymph node dissection only if the result is positive.
5‐year interval change in voiding function of orthotopic ileal neobladder
Authors: ARAI YOICHI , TAKEDA ATSUSHI , TAKI YOJI , OKADA YUSAKU , OGAWA OSAMU ,   THE TOHOKU‐KYOTO URINARY RECONSTRUCTION STUDY GROUP
Published: July 2006

Aim:  We report the 5‐year interval change in voiding function of orthotopic ileal neobladder.

Methods:  Voiding function was evaluated at two points with an interval of 5 years in 49 patients with orthotopic ileal neobladder. The first and second surveys were performed in May, 1998 (1998 survey) and in April 2003 (2003 survey), respectively. Median age at operation was 67 years, ranging 47–77. Median follow‐up times at the first and the second surveys were 19.5 months (range, 3–87) and 67.5 months (range, 62–145), respectively.

Results:  There was no significant change in daytime continence status between the 1998 and 2003 surveys. More than 95% never or only occasionally suffered daytime incontinence in the two surveys. On the other hand, 15 (34.1%) and 14 (31.8%), respectively, experienced night‐time incontinence, despite regular voiding during the night. When voiding patterns were analysed, 11 patients (23.4%) sometimes or often performed catheterization because of difficulty in urinating or incomplete emptying of the neobladder in the 1998 survey. Three patients (6.4%) were unable to void and required regular catheterization. In the 2003 survey, however, such poor voiders increased to nine (19.1%), although the difference was not significant. During the study period of 5 years, there was no change in renal function.

Conclusions:  Continence status, either at daytime or at nighttime, was stable during the study period. The number of the patients who needed regular catheterization tended to increase, suggesting deterioration of voiding function with time. Careful long‐term follow up is warranted.
Polyenylphosphatidylcholine pretreatment ameliorates ischemic acute renal injury in rats
Authors: DEMIRBILEK SAVAŞ , KARAMAN ABDURRAHMAN , BAYKARABULUT AYSUN , AKİN MELIH , GÜRÜNLÜOǦLU KUBILAY , TÜRKMEN EMINE , TAŞ ERKAN , AKSOY RAUF TUǦRUL , EDALİ MEHMET NACI
Published: July 2006

Aim:  Polyenylphosphatidycholine has been demonstrated to have antioxidant, cytoprotective and anti‐inflammatory effects. Whether polyenylphosphatidycholine pretreatment affects ischemia/reperfusion‐induced renal damage in vivo is not known and was investigated here in rats.

Methods:  Forty female Sprague–Dawley rats were divided into three groups. Group 1 (n = 10) was given saline (control, sham operated). Group 2 (n = 15) were given saline, and Group 3 (n = 15) were given polyenylphosphatidycholine (100 mg/day for 10 days prior to experiment). Groups 2 and 3 were subjected to bilateral renal ischemia (60 min) followed by reperfusion (6 h). After the reperfusion period, the rats were sacrificed and kidney tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde and myeloperoxidase levels, plasma aspartate aminotransferase, blood urea nitrogen and creatinine concentrations, and nuclear factor kappa beta expression were determined.

Results:  Serum levels of aspartate aminotransferase, blood urea nitrogen and creatinine were significantly decreased (P < 0.05) in the treatment group compared to those in the ischemic group. There were significant differences between treatment and ischemic groups regarding the tissue superoxide dismutase, glutathione, total nitrite and nitrate, malondialdehyde, and myeloperoxidase levels (P < 0.05). In addition, polyenylphosphatidycholine pretreatment reduced nuclear factor kappa beta expression in ischemic kidney tissue. Kidneys obtained from rats pretreated with polyenylphosphatidycholine demonstrated marked reduction of the histological features of renal injury compared to kidneys obtained from Group 2 rats, including a little vacuolization, pyknosis and necrosis.

Conclusions:  Polyenylphosphatidycholine pretreatment provided significant protection against ischemia/reperfusion injury to the kidney. This treatment could be therapeutic in kidney transplantation and other conditions associated with ischemia/reperfusion injury to the kidney.
Subtyping of uropathogenic Escherichia coli according to the pathogenicity island encoding uropathogenic‐specific protein: Comparison with phylogenetic groups
Authors: KANAMARU SOJUN , KURAZONO HISAO , NAKANO MASAYUKI , TERAI AKITO , OGAWA OSAMU , YAMAMOTO SHINGO
Published: July 2006

Background:  Phylogenetic analysis has been used widely to characterize extraintestinal pathogenic Escherichia coli in molecular epidemiological studies. We have recently reported a putative pathogenicity island (PAI), carrying uropathogenic‐specific protein (usp) and a unique mosaic structure of small open reading frames following usp, providing four subtypes of PAIusp classified from their sequential patterns.

Methods:  A total of 427 E. coli isolates from uncomplicated urinary tract infections (194 cystitis, 76 pyelonephritis, and 107 prostatitis) and 50 fecal isolates were examined for phylogenetic grouping and PAIusp subtyping as well as the prevalence of virulence factors (VF) and O serogroups.

Results:  Both phylogenetic group B2 and usp‐positive strains were equally predominant in cystitis, pyelonephritis and prostatitis (B2, 80.9%, 86.8%, and 86.9%; usp, 79.4%, 93.4%, and 88.8%, respectively). Furthermore, each PAIusp subtype was shown to be closely associated with several VF genes as well as several common O serogroups of uropathogenic E. coli.

Conclusions:  In molecular epidemiological studies, PAIusp subtyping will provide additional informative findings of E. coli strains belonging to phylogenetic group B2.
Fluorescence in situ hybridization analysis of c‐myc amplification in stage T3N0M0 prostate cancer in Japanese patients
Authors: SATO HIROTAKA , MINEI SADATSUGU , HACHIYA TAKAHIKO , YOSHIDA TOSHIO , TAKIMOTO YUKIE
Published: July 2006

Objective:  Genetic aberration such as the amplification of c‐myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c‐myc gene), related to the progression and survival in advanced (Stage C) prostate cancer.

Materials and methods:  We used dual‐probe fluorescence in situ hybridization with a centromere‐specific probe for chromosome 8 (8cen), and with a region‐specific probe for c‐myc (8q24) to evaluate genetic changes in tumor samples from 50 patients who had undergone radical retropubic prostatectomy from 1986 to 2001.

Results:  We classified the 8cen and c‐myc copy numbers as normal, gain and amplification. The carcinoma foci with extra copies of c‐myc, which was defined in 35 cases (70%), were divided into two groups: (a) a simple gain of the whole chromosome 8 (no increase in the c‐myc copy number relative to the chromosome 8 centromere), which was identified in 15 cases (30%); and (b) a substantial amplification of c‐myc (additional increases [AI] in the c‐myc copy number relative to the chromosome 8 centromere), which was detected in 20 cases (40%). AI‐c‐myc was strongly associated with higher histopathological grades and Gleason’s scores (P = 0.0330, 0.0190, respectively). Patients with the AI‐c‐myc had earlier disease progression (P = 0.0029) and earlier cancer death (P = 0.0087) than did patients with normal patterns.

Conclusion:  Identification of an AI‐c‐myc may serve as a potential marker of prostate cancer progression.
Role of transcription factors Ad4bp/SF‐1 and DAX‐1 in steroidogenesis and spermatogenesis in human testicular development and idiopathic azoospermia
Authors: KOJIMA YOSHIYUKI , SASAKI SHOICHI , HAYASHI YUTARO , UMEMOTO YUKIHIRO , MOROHASHI KEN‐ICHIRO , KOHRI KENJIRO
Published: July 2006

Background:  Ad4bp/SF‐1 and DAX‐1 are orphan members of the nuclear hormone receptor superfamily of transcription factors. In order to obtain better understandings of human testicular steroidogenesis and spermatogenesis, we examined the expression levels of both factors in human normal and idiopathic azoospermic testes and investigated their physical meaning.

Methods:  First, we examined the expression level of Ad4bp/SF‐1 and DAX‐1 by quantitative reverse transcription–polymerase chain reaction (RT–PCR), immunohistochemistry and western blotting analysis using eight normal human testicular tissues from infants to adults. Second, we performed quantitative RT–PCR using testicular biopsy samples obtained from 22 idiopathic azoospermic patients to examine the expression of Ad4bp/SF‐1 and DAX‐1, and analysed the correlation between the expression levels of both factors and the serum hormone levels or histological evaluation to study their potential correlation with steroidogenesis and spermatogenesis on idiopathic azoospermia.

Results:  The expression levels of both factors in the normal testes increased with testicular development. Ad4bp/SF‐1 was abundantly expressed in Leydig cell, whereas DAX‐1 was expressed in Sertoli cells. The expression level of Ad4bp/SF‐1 in idiopathic azoospermic patients testes positively correlated with serum testosterone (P < 0.05). The average expression levels of DAX‐1 mRNA for patients with maturation arrest (0.39 ± 0.19) and Sertoli cell‐only syndrome (0.13 ± 0.08) were lower than that with hypospermatogenesis (1.60 ± 1.32) and normal spermatogenesis (1.30 ± 1.41).

Conclusion:  Ad4bp/SF‐1 is important for the maintenance of steroidogenesis in the human testis. DAX‐1 plays a critical role in spermatogenesis in the human testis, and Sertoli cell‐only syndrome and maturation arrest may result from abnormal Sertoli cell function that disrupts the normal progression of spermatogenesis.
Adrenal insufficiency in T‐cell lymphoma
Authors: TSAI WEN‐CHIUAN , HSIEH CHENG‐DA , CHENG MING‐FANG , LIN CHIH‐KUNG
Published: July 2006

Abstract  Primary adrenal lymphoma (PAL) is an extremely rare neoplasm of T‐cell origin. Here we describe a 42‐year‐old woman who suffered from intermittent fevers and night sweats of 3 months duration. Laboratory results, imaging, pathology, and immunohistological examination led to a final diagnosis of primary adrenal T‐cell lymphoma (PATL) with adrenal insufficiency. The patient received combination chemotherapy and prednisolone but expired 2 months after the treatment. Most reported PAL patients who have received only one therapeutic modality have unsatisfactory survival rates resulting from tumor recurrence and/or postchemotherapy infections. In contrast, one patient who received an adrenectomy followed by low‐dose radiotherapy experienced long‐term survival. A combination of therapeutic modalities may improve prognosis for patients with PATL, although the case numbers are too small to draw any conclusions.
A case of renal cell carcinoma with multiple lung metastases refractory to interferon‐α showing complete remission by interleukin‐2 monotherapy
Authors: HAYASHI TETSUYA , MIYAGAWA YASUSHI , TSUJIMURA AKIRA , NONOMURA NORIO , MINAMI MASATO , OKUYAMA AKIHIKO
Published: July 2006

Abstract  We report a case in which a regimen of interleukin‐2 (IL‐2) achieved pathologically complete remission against renal cell carcinoma with multiple lung metastases. A 63‐year‐old man was admitted to the Osaka University Hospital with a right renal tumor and multiple lung metastases. Right radical nephrectomy was performed and the histological diagnosis was clear cell carcinoma, G3 > G2, INFβ, pT3a, pN0. Postoperatively, despite treatment with interferon‐α, the lung metastases progressed. Consequently, intravenous administration of IL‐2 was started at a dose of 70 × 104 JRU/day five times per week. After 16 weeks of IL‐2 therapy, most of the multiple lung metastases completely vanished and the largest metastatic lung mass was reduced in size. Resection of this residual lung mass was performed and pathological examination revealed no viable cancer cells.