bluuebunny/crossref_metadata_2025 huggingface dataset:
Redirecting the substrate specificity of heparan sulfate 2-
O
-sulfotransferase by structurally guided mutagenesis
Authors: Bethea Heather N. , Xu Ding , Liu Jian , Pedersen Lars C.
Published: November 2008

Heparan sulfate (HS) is a polysaccharide involved in essential physiological functions from regulating cell growth to blood coagulation. HS biosynthesis involves multiple specialized sulfotransferases such as 2-
O
-sulfotransferase (2OST) that transfers the sulfo group to the 2-OH position of iduronic acid (IdoA) or glucuronic acid (GlcA) within HS. Here, we report the homotrimeric crystal structure of 2OST from chicken, in complex with 3′-phosphoadenosine 5′-phosphate. Structural based mutational analysis has identified amino acid residues that are responsible for substrate specificity. The mutant R189A only transferred sulfates to GlcA moieties within the polysaccharide whereas mutants Y94A and H106A preferentially transferred sulfates to IdoA units. Our results demonstrate the feasibility for manipulating the substrate specificity of 2OST to synthesize HS with unique sulfation patterns. This work will aid the development of an enzymatic approach to synthesize heparin-based therapeutics.
Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G
Authors: Chelico Linda , Pham Phuong , Goodman Myron F
Published: November 2008

Activation-induced (cytidine) deaminase (AID) efficiently introduces multiple and diversified deaminations in immunoglobulin (Ig) variable and switch regions. Here, we review studies of AID, and the APOBEC family member, APOBEC3G, demonstrating that both enzymes introduce multiple deaminations by processive action on single-stranded DNA and that deaminations occur stochastically at hot- and cold-spot targets. In a more detailed analysis of AID, we examine phosphorylation-null mutants, particularly, S38A and S43P. S43P mutant AID has been identified in a patient with hyper-IgM immunodeficiency syndrome. The phosphorylation-null mutants have essentially the same specific activity, processivity and ability to undergo transcription-dependent deamination compared with wild-type (WT) AID. Although the phosphorylation-null mutants still deaminate 5′-WR
C
hot spots, the mutant deamination spectra differ from WT AID. The mutants strongly prefer two motifs, 5′AG
C
and 5′GG
C
, which are disfavoured by WT AID. Differences in deamination specificities can be attributed primarily to the replacement of Ser rather than to the absence of phosphorylation. The 5′GGC motif occurs with exceptionally high frequency on the non-transcribed strand of human switch regions, IgG
4
and IgE. The potential for S43P to catalyse large numbers of aberrant deaminations in switch region sequences suggests a possible relationship between non-canonical AID deamination specificity and a loss of antibody diversification.
Phosphatidylserine surface expression and integrin αIIbβ3 activity on thrombin/convulxin stimulated platelets/particles of different sizes
Authors: Rukoyatkina Natalia , Begonja Antonija J. , Geiger Jörg , Eigenthaler Martin , Walter Ulrich , Gambaryan Stepan
Published: November 2008

Platelets stimulated by a combination of thrombin/convulxin have been shown to develop two to three populations characterized by different phosphatidylserine (PS) surface expression and integrin αIIbβ3 activity. To determine how these markers are distributed on the surface of platelets/particles, we studied Annexin V and PAC‐1 binding to platelets/particles of different sizes by flow cytometry analysis and evaluated influences of calpain and caspase inhibitors on thrombin/convulxin‐activated platelets. Analysed platelets/particles were divided by their sizes, according to the standard size beads, into seven populations from 0·37 to 4·8 μm. PAC‐1 binding/μm2 was almost equal in platelets/particles ranging from 1·2 to 4·8 μm and was significantly lower on smaller‐sized particles sizes (0·37–0·7 μm). PS surface exposure/μm2 was high in the particles of 0·37–1·2 μm and very low in platelets (2·6–4·8 μm). Upon thrombin/convulxin stimulation caspase inhibitors prevented microparticle (MP) formation, while a calpain inhibitor stimulated MP formation. It was also shown that stimulated platelets are heterogeneous not only in their ability to activate αIIbβ3 integrin complex and expose PS on their surface, but also in the distribution of activation markers, which strongly depends on platelet/particle size and that platelets/particles of different sizes provide different responses to the same stimulus.
Beyond a consensus classification for idiopathic interstitial pneumonias: progress and controversies
Authors: Myers Jeffrey L , Katzenstein Anna‐Luise A
Published: November 2008

Histopathological classification schemes provide the underpinnings for separating idiopathic interstitial pneumonias into clinically meaningful groups. An interdisciplinary classification system based on a combination of evidence and expert opinion was published in 2002 and set the stage for controversy in several areas, including not only nomenclature but also the role of surgical lung biopsy and pathologists in diagnosis. We provide a brief overview of the clinical and histological features of the idiopathic interstitial pneumonias, and focus on selected topics of interest that have emerged in recent years.
Distribution and molecular detection of Theileria and Babesia in questing ticks from northern Spain
Authors: GARCÍA‐SANMARTÍN J. , BARANDIKA J. F. , JUSTE R. A. , GARCÍA‐PÉREZ A. L. , HURTADO A.
Published: November 2008

Abstract A total of 562 questing adult ixodid ticks, collected during 2003−05 in 10 recreational mountain areas in northern Spain, were analysed for piroplasm infection. Reverse line blot (RLB) analysis using a panel of probes for 23 piroplasm species identified 16 different piroplasms, with an overall prevalence of 9.3%. Most were Theileria spp.‐positive (7.7%), 3.0% were positive for Babesia spp. and 1.4% of ticks harboured both genera. Ixodes ricinus (Linnaeus, 1758), the most abundant tick in the vegetation, ranked third with regard to piroplasm infection prevalence (11.4%) after Rhipicephalus bursa (Canestrini & Fanzago, 1878) (16.0%) and Haemaphysalis punctata (Canestrini & Fanzago, 1878) (13.5%). Infection was detected in 6.2% of Dermacentor reticulatus (Fabricius, 1794) and in 1.1% of Haemaphysalis inermis (Birula, 1895), but was absent from Haemaphysalis concinna (Koch, 1844). Ixodes ricinus carried more piroplasm species (13), followed by H. punctata (10), D. reticulatus (8), R. bursa (3) and H. inermis (1). Although most of the positive ticks harboured a single infection (76.9%), mixed infections with two or three different piroplasm species were also detected (23.1%). The various tick−pathogen associations found are discussed and prevalences of infection in ticks are compared with previous results on piroplasms infecting animals in the same region.
Hepatobiliary scintigraphy for the assessment of biliary strictures after pediatric liver transplantation
Authors: Concannon Rebecca C. , Howman‐Giles Robert , Shun Albert , Stormon Michael O.
Published: November 2008

Abstract: HBS is used in the management of liver transplantation, a significant complication of which is biliary stricture. Strictures may be intraparenchymal within segments and main duct (non‐anastomotic) or at the biliary‐enteric anastomosis (anastomotic). Strictures are definitively diagnosed, and often managed, by PTC. This is invasive, technically challenging, and requires general anesthesia in young children. HBS may allow early detection of these complications and is non‐invasive. The aim of this study was to review the scintigraphic pattern of biliary strictures using99mTcDISIDA HBS following pediatric orthotopic liver transplantation, and to assess its role in the diagnostic algorithm of suspected biliary strictures. All available hepatobiliary studies performed post‐transplant in 101 episodes of liver transplantation in 92 pediatric patients were reviewed. Twenty‐three (23%) patients had known biliary strictures. Twenty‐two patients had adequate studies available for review; five had intrahepatic (non‐anastomotic) strictures alone, nine had a stricture of the anastomosis alone, and eight had both intrahepatic and anastomotic strictures. HBS patterns (either segmental or global changes) correlated very highly with clinically significant biliary strictures. All patients with known strictures had abnormal HBS; hence, in patients with abnormal liver function tests post‐liver transplant, a normal HBS makes strictures very unlikely. We propose that HBS can thus be used to determine if further investigation is required.
Expression and Localization of Gap Junctional Connexins 26 and 43 in Bovine Periovulatory Follicles and in Corpus Luteum During Different Functional Stages of Oestrous Cycle and Pregnancy
Authors: Berisha B , Bridger P , Toth A , Kliem H , Meyer HHD , Schams D , Pfarrer C
Published: November 2008

Contents

The aim of this study was to characterize the regulation of connexins (Cx26 and Cx43) in the bovine ovary (experiment 1–3). Experiment 1: ovaries containing preovulatory follicles or corpora lutea (CL) were collected at 0, 4, 10, 20, 25 (follicles) and 60 h (CL) relative to injection of GnRH. Experiment 2: CL were assigned to the following stages: days 1–2, 3–4, 5–7, 8–12, 13–16, >18 (after regression) of oestrous cycle and of early and late pregnancy (<4 and >4 months). Experiment 3: induced luteolysis, cows on days 8–12 were injected with PGF2α analogue (Cloprostenol), and CL were collected by transvaginal ovariectomy before and 0.5, 2, 4, 12, 24, 48 and 64 h after PGF2α injection. Real‐time RT‐PCR was applied to investigate mRNA expression and immunofluorescence was utilized for protein localization. Cx26 mRNA increased rapidly 4 h after GnRH injection (during LH surge) and decreased afterwards during the whole experimental period. Cx43 mRNA expression decreased continuously after GnRH application. Cx26 mRNA in CL increased significantly in the second part of oestrous cycle and after regression. In contrast, the highest mRNA expression for Cx43 in CL was detected during the early luteal phase. After induced luteolysis the mRNA expression of Cx26 increased significantly at 24 h. As shown by immunofluorescence, Cx26 was predominantly localized in the connective tissue and blood vessels of bovine CL, whereas Cx43 was present in the luteal cells and blood vessels. This resulted in a strong increase of Cx26 expression during the late luteal phase and after luteal regression. Subsequently, Cx43 expression was distinctly decreased after luteal regression. These data suggest that Cx26 and Cx43 are involved in the local cellular mechanisms participating in tissue remodelling during the critical time around periovulation as well as during CL formation (angiogenesis), function and regression in the bovine ovary.
Uterine Expression of Epidermal Growth Factor Family During the Course of Pregnancy in Pigs
Authors: Kim Y‐J , Lee G‐S , Hyun S‐H , Ka H‐H , Choi K‐C , Lee C‐K , Jeung E‐B
Published: November 2008

Contents

To stably maintain pregnancy, several genes are expressed in the uterus. In particular, the endometrial expression of genes encoding growth factors appears to play a key role in maternal–foetal communication. The previous studies characterized the endometrial expression kinetics of the genes encoding epidermal growth factor (EGF), its receptor (EGFR), transforming growth factor‐alpha (TGF‐α), amphiregulin (Areg), heparin‐binding (Hb) EGF and calbindin‐D9k (CaBP‐9k) in pigs during implantation. Here, we further characterized the expression patterns of these molecules during the entire porcine pregnancy. Porcine uteri were collected at pregnancy days (PD) 12, 15, 30, 60, 90 and 110 and subjected to RT‐PCR. EGF and EGFR showed similar expression patterns, being highly expressed around implantation and then disappearing. TGF‐α and Areg expression levels rose steadily until they peaked at PD30, after which they gradually decreased to PD12 levels. This Areg mRNA expression pattern was confirmed by real‐time PCR and similar Areg protein expression patterns were observed. Immunohistochemical analysis of PD60 uteri revealed Areg in the glandular and luminal epithelial cells. Hb EGF was steadily expressed throughout the entire pregnancy, while CaBP‐9k was expressed strongly on PD12, and then declined sharply on PD15 before recovering slightly for the remainder of the pregnancy. Thus, the EGF family may play a key role during implantation in pigs. In addition, CaBP‐9k may help to maintain uterine quiescence during pregnancy by sequestering cytoplasmic Ca2+.
Changes in Ovarian Follistatin Levels During the Oestrous Cycle in Sheep may Serve as an Intraovarian Regulator
Authors: Xia Y , O’Shea T , Almahbobi G , McFarlane JR
Published: November 2008

Contents

The expression and concentration of follistatin and activin change during oestrous cycle suggesting their involvement in the regulation of follicular development. The aim of this study was to determine the level, source and potential role of follistatin in the sheep ovary. Follistatin in ovarian venous blood, measured by radioimmunoassay, remained at its low level from follicular phase (day −1 and 0) to mid‐luteal phase (days 11–13) phase but were significantly elevated during the late luteal phase (days 14 and 15) when corpora lutea underwent regression. Western blot analyses of follicular fluid at day 15 of the cycle showed two strong bands at 42 and 45 kDa and weakly stained bands at 39 and 31 kDa. At day 0, these bands became weaker and the 39 kDa band became undetectable. However, there were no differences in follistatin concentrations between ovaries with and without functional corpus luteum (CL) during the whole luteal phase. In addition, although the ovaries of Booroola ewes normally contain more corpora lutea than those of normal merino ewes, follistatin concentrations in both jugular and ovarian venous blood were similar in Booroola and normal merino ewes. It is concluded that the secretion of follistatin from the ovary is not related to the formation of CL or high ovulation rate of Booroola ewes. The elevation in follistatin concentration in follicular fluid and ovarian blood during late luteal phase may indicate a dual role of follistatin in the luteolysis of existing CL and development of new follicle cohort.
The Tri‐focal model of care: Advancing the teaching‐nursing home concept
Authors: O’Connell Beverly , Ostaszkiewicz Joan , Sukkar Khalil , Plymat Kay
Published: November 2008

Providing residential aged care is challenging because of the complexity of residents’ health status, difficulties recruiting and retaining skilled staff, and financial and regulatory constraints. This paper discusses some of these challenges and describes an innovative model of care, termed ‘The Tri‐focal model of care’. This model was developed based on the concepts of ‘partnership‐centred care’, ‘positive work environment’ and the need for evidence‐based practice to underpin all aspects of care. It is envisaged that the implementation of this model will provide a rich learning environment that advances the teaching‐nursing home concept and the quality of residential aged care.
A non‐randomized comparison of e‐learning and classroom delivery of basic life support with automated external defibrillator use: A pilot study
Authors: Moule Pam , Albarran John W , Bessant Elizabeth , Brownfield Chris , Pollock Jon
Published: November 2008

This pilot study investigated whether computer‐based learning package followed by practical instruction and traditional classroom methods were comparable in developing knowledge and skills in basic life support with automated external defibrillator. Eighty‐three mental health care professionals were allocated to one of two groups. Twenty‐eight completed an e‐learning package, and the remaining 55 received delivery of content in a classroom. Using standardized assessment methods, comparisons of participant knowledge gain and performance in resuscitation were made. Significant increases in knowledge followed training. No differences were found with basic resuscitation skills or in the time taken to the first shock; however, both groups were inaccurate with electrode pad placement. E‐learners performed slightly better in 21 of the 30 observed skills. Overall group performance did not differ suggesting computer‐based education has the potential to prepare learners in resuscitation knowledge and skills to comparable levels of classroom courses.
Loss of hepatic B cells following lipopolysaccharide injection and polymicrobial sepsis
Authors: Matsumoto Atsushi , Tsujimoto Hironori , Ono Satoshi , Kinoshita Manabu , Habu Yoshiko , Kawabata Toshinobu , Shinomiya Nariyoshi , Seki Shuhji
Published: November 2008

Background and Aim:  B cells possess pleiotropic functions and are important for both humoral as well as cellular immune responses. However, there is little information about how hepatic B cells respond to lipopolysaccharide (LPS) and/or sepsis.

Methods:  We evaluated the changes in the number of hepatic and splenic B cells, and the expression of immunoglobulins after injecting pathogens, such as LPS, flagellin and CpG oligonucleotides in mice. In addition, we examined the role of natural killer (NK) cells in these changes using mutant bg/bg mice with genetically impaired NK cell functions.

Results:  Significant temporal loss of hepatic B cells, but not splenic B cells, was seen following LPS treatment. We have shown that bacterial components other than LPS were also responsible for such decline in hepatic B cells. However, loss of hepatic B cells was not seen following LPS treatment in bg/bg mice. In addition, loss of hepatic B cells and systemic immunoglobulin G2a production after LPS treatment was at least in part mediated by interleukin‐12, γ‐interferon and tumor necrosis factor‐α, all of which substantially enhanced the NK cell activity.

Conclusion:  Hepatic B cells play an essential role during sepsis by synergistically interacting with NK cells. However, whether decline of hepatic B cells after LPS treatment and/or polymicrobial sepsis is simply a phenomenon or has a substantial clinical importance is yet to be determined.
The preoperative positivity for serum hepatitis B e antigen did not affect overall survival after curative resection of hepatitis B virus‐related hepatocellular carcinoma
Authors: Choi Gi Hong , Kim Dong Hyun , Choi Sae Byeol , Kang Chang Moo , Kim Kyung Sik , Choi Jin Sub , Lee Woo Jung , Han Kwang Hyub , Chon Chae Yoon , Kim Byong Ro
Published: November 2008

Background and Aim:  Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified.

Methods:  A total of 190 Hepatitis B surface antigen‐positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease‐free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence.

Results:  The 5‐year disease‐free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease‐free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post‐recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence.

Conclusions:  The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long‐term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.
Are repeat upper gastrointestinal endoscopy and colonoscopy necessary within six months of capsule endoscopy in patients with obscure gastrointestinal bleeding?
Authors: Gilbert David , O'Malley Sue , Selby Warwick
Published: November 2008

Background and Aim:  Medicare reimbursement for capsule endoscopy for the investigation of obscure gastrointestinal bleeding in Australia requires endoscopy and colonoscopy to have been performed within 6 months. This study aims to determine the diagnostic yield of repeating these procedures when they had been non‐diagnostic more than 6 months earlier.

Methods:  Of 198 consecutive patients who were referred for the investigation of obscure gastrointestinal bleeding, 50 underwent repeat endoscopy and colonoscopy solely to enable reimbursement (35 females and 15 males; mean age 59.4 [range: 21–82] years). The average duration of obscure bleeding was 50.16 (range: 9–214) months. The mean number of prior endoscopies was 3 (median: 2) and 2.8 colonoscopies (median: 2). The most recent endoscopy had been performed 18.9 (median: 14; range: 7–56) months, and for colonoscopy, 19.1 (median 14; range 8‐51) months earlier.

Results:  A probable cause of bleeding was found at endoscopy in two patients: gastric antral vascular ectasia (1) and benign gastric ulcer (1). Colonoscopy did not reveal a source of bleeding in any patient. Capsule endoscopy was performed in 47 patients. Twenty four (51%) had a probable bleeding source identified, and another five (11%) a possible source. These included angioectasia (17 patients), mass lesion (2), non‐steroidal anti‐inflammatory drug enteropathy (2), Cameron's erosions (2), and Crohn's disease (1). Four patients undergoing repeat capsule endoscopy had a probable bleeding source detected.

Conclusion:  The yield of repeat endoscopy and colonoscopy immediately prior to capsule endoscopy is low when these procedures have previously been non‐diagnostic. Such an approach is also not cost‐effective.
Natural history of hepatic fibrosis progression in chronic hepatitis C virus infection in India
Authors: Hissar Syed S , Kumar Manoj , Tyagi Pankaj , Goyal Ankur , PV Suneetha , Agarwal Sriram , Rastogi Archana , Sakhuja Puja , Sarin Shiv K
Published: November 2008

Background and Aim:  The rate of fibrosis progression per year can predict the time for the development of cirrhosis in chronic hepatitis C (CHC). We assessed the rate of fibrosis progression and the predictors of disease severity in Indian CHC patients.

Methods:  Of the 355 treatment‐naïve, histologically‐proven CHC patients, the precise duration of infection (from the time of exposure to HCV until liver biopsy) could be determined in 213 patients (age = 41.6 ± 14.7 years, male : female = 139 : 74, genotype 3 = 75%). The rate of fibrosis progression per year was calculated. The correlation of the advanced degree of fibrosis and age, duration of infection, age at the onset of infection, sex, mode of infection, hepatitis C virus (HCV) genotype, histological activity index (HAI), and the presence of diabetes mellitus were studied.

Results:  The median rate of fibrosis progression per year was 0.25 (0.0–1.5) fibrosis units. The fibrosis progression rate was higher in patients who acquired infection at > 30 years of age, those < 30 years (0.33 vs 0.15; P < 0.001), and those who acquired HCV infection with a history of blood transfusion than with other modes of transmission (0.25 vs 0.19; P = 0.04). The median time to progress to cirrhosis was 16 years. The multivariate analysis found that the HAI score (odds ratio [OR]= 14.03; P < 0.001) and the duration of infection > 10 years (OR = 4.83; P < 0.001) correlated with severe liver disease (fibrosis ≥ 3).

Conclusion:  The median rate of fibrosis progression per year in Indian CHC patients is 0.25 fibrosis units. A higher HAI and longer duration of infection are associated with a significant risk of advanced liver disease, and merit early therapeutic interventions.
Dose comparison study of pegylated interferon‐α‐2b plus ribavirin in naïve Japanese patients with hepatitis C virus genotype 2: A randomized clinical trial
Authors: Kawaoka Tomokazu , Kawakami Yoshiiku , Tsuji Keiji , Ito Hiroyuki , Kitamoto Mikiya , Aimitsu Shiomi , Kawakami Hiroiku , Jeong Soo Cheol , Imamura Michio , Aikata Hiroshi , Takahashi Shoichi , Chayama Kazuaki
Published: November 2008

Background and Aim:  To compare the efficacy and safety of pegylated interferon (PEG‐I) at 1 and 1.5 µg/kg, and in combination with ribavirin (RBV) for 24 weeks in naïve Japanese patients infected with hepatitis C virus genotype 2.

Methods:  The present study was an open‐label, randomized trial of 55 patients receiving PEG‐I (1 or 1.5 µg/kg body weight [BW], subcutaneously, once a week) and RBV for 24 weeks. The patients were followed up for 24 weeks without treatment.

Results:  The intention‐to‐treat analyses showed that the proportion of patients with a sustained virological response (SVR) in the 1‐µg/kg PEG‐I–RBV group (38.5%, 10/26) was lower than that of the 1.5‐µg/kg PEG‐I–RBV group (74.1%, 20/27; P = 0.013). The PEG‐I dose was reduced in two of the 26 patients of the 1‐µg/kg PEG‐I–RBV group (one because of thrombocytopenia at 2 weeks, and one because of generalized fatigue at 20 weeks), and four of the 27 patients of the 1.5‐µg/kg PEG‐I–RBV group (one because of neutropenia at 20 weeks, and three because of generalized fatigue at 1, 5, and 8 weeks). The multivariate analysis identified age (< 60 years) and dose of PEG‐I (1.5 µg/kg) as significant determinants of SVR.

Conclusion:  The dose of PEG‐I to be used at the start of therapy should be 1.5‐µg/kg BW in naïve Japanese patients infected with hepatitis C virus genotype 2.
Proliferating cell nuclear antigen shRNA treatment attenuates chronic proliferative cholangitis in rats
Authors: Li Fu‐Yu , Cheng Nan‐Sheng , Cheng Jing‐Qiu , Mao Hui , Zhou Yong , Jiang Li‐Sheng , Li Ning
Published: November 2008

Background and Aim:  Chronic proliferative cholangitis (CPC) is currently considered as a pathological basis and major cause for the high recurrence rate of intrahepatic stones. Since CPC is a form of chronic proliferative disease, this study was designed to preliminarily investigate the inhibitory effect of proliferating cell nuclear antigen (PCNA) shRNA on the hyperplastic behavior and lithogenic potentiality of CPC.

Methods:  The rat model of CPC was given an intralumenal administration of 0.5 mL PCNA shRNA through a 20‐gauge venous retained needle. PCNA shRNA‐mediated effects on CPC‐associated hyperplastic behavior and lithogenic potential were assessed by investigating histological changes, immunohistochemistry for Ki‐67, biochemistry for β‐glucuronidase, real‐time polymerase chain reaction, and western blot analysis of PCNA, procollagen I, and mucin‐3.

Results:  PCNA shRNA treatment could efficiently inhibit the mRNA and protein expressions of the proliferation‐related gene, PCNA, and Ki‐67, which efficiently inhibited the hyperplastic behavior of the biliary epithelium, submucosal gland, and collagen fibers in the diseased bile duct wall. This novel treatment could efficiently inhibit the formation of acidic mucus glands, the expression of mucin‐3 mRNA, and the secretion of endogenous β‐glucuronidase, thus effectively inhibiting the lithogenic potentiality of CPC. A further analysis revealed that PCNA shRNA‐1 might display a more robust inhibitory effect on CPC‐associated hyperplastic behavior and lithogenic potential than other gene sequences targeted in this study.

Conclusions:  PCNA shRNA‐1 treatment could effectively inhibit the hyperplastic behavior and lithogenic potentiality of CPC, which might facilitate the prevention of stone recurrence and biliary restenosis.
Visualizing jet lag in the mouse suprachiasmatic nucleus and peripheral circadian timing system
Authors: Davidson Alec J. , Castanon‐Cervantes Oscar , Leise Tanya L. , Molyneux Penny C. , Harrington Mary E.
Published: November 2008

Circadian rhythms regulate most physiological processes. Adjustments to circadian time, called phase shifts, are necessary following international travel and on a more frequent basis for individuals who work non‐traditional schedules such as rotating shifts. As the disruption that results from frequent phase shifts is deleterious to both animals and humans, we sought to better understand the kinetics of resynchronization of the mouse circadian system to one of the most disruptive phase shifts, a 6‐h phase advance. Mice bearing a luciferase reporter gene for mPer2 were subjected to a 6‐h advance of the light cycle and molecular rhythms in suprachiasmatic nuclei (SCN), thymus, spleen, lung and esophagus were measured periodically for 2 weeks following the shift. For the SCN, the master pacemaker in the brain, we employed high‐resolution imaging of the brain slice to describe the resynchronization of rhythms in single SCN neurons during adjustment to the new light cycle. We observed significant differences in shifting kinetics among mice, among organs such as the spleen and lung, and importantly among neurons in the SCN. The phase distribution among all Period2‐expressing SCN neurons widened on the day following a shift of the light cycle, which was partially due to cells in the ventral SCN exhibiting a larger initial phase shift than cells in the dorsal SCN. There was no clear delineation of ventral and dorsal regions, however, as the SCN appear to have a population of fast‐shifting cells whose anatomical distribution is organized in a ventral–dorsal gradient. Full resynchronization of the SCN and peripheral timing system, as measured by a circadian reporter gene, did not occur until after 8 days in the advanced light cycle.
Background sodium current underlying respiratory rhythm regularity
Authors: Chevalier Marc , Ben‐Mabrouk Faiza , Tryba Andrew K.
Published: November 2008

Rhythm‐generating neural circuits underlying diverse behaviors such as locomotion, sleep states, digestion and respiration play critical roles in our lives. Irregularities in these rhythmic behaviors characterize disease states – thus, it is essential that we identify the ionic and/or cellular mechanisms that are necessary for triggering these rhythmic behaviors on a regular basis. Here, we examine which ionic conductances underlie regular or ‘stable’ respiratory activities, which are proposed to underlie eupnea, or normal quiet breathing. We used a mouse in vitro medullary slice preparation containing the rhythmogenic respiratory neural circuit, called the preBötzinger complex (preBötC), that underlies inspiratory respiratory activity. We varied either [K+]o or [Na+]o, or blocked voltage‐gated calcium channels, while recording from synaptically isolated respiratory pacemakers, and examined which of these manipulations resulted in their endogenous bursting becoming more irregular. Of these, lowering [Na+]o increased the irregularity of endogenous bursting by synaptically isolated pacemakers. Lowering [Na+]o also decreased the regularity of fictive eupneic activity generated by the ventral respiratory group (VRG) population and hypoglossal motor output. Voltage clamp data indicate that lowering [Na+]o, in a range that results in irregular population rhythm generation, decreased persistent sodium currents, but not transient sodium currents underlying action potentials. Our data suggest that background sodium currents play a major role in determining the regularity of the fictive eupneic respiratory rhythm.
Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11β‐hydroxysteroid dehydrogenase type 2
Authors: Lucassen P. J. , Bosch O. J. , Jousma E. , Krömer S. A. , Andrew R. , Seckl J. R. , Neumann I. D.
Published: November 2008

Prenatal stress (PS) produces persistent abnormalities in anxiety‐related behaviors, stress responsivity, susceptibility to psychopathology and hippocampal changes in adult offspring. The hippocampus shows a remarkable degree of structural plasticity, notably in response to stress and glucocorticoids. We hypothesized that PS would differentially affect hippocampal neurogenesis in rats selectively bred for genetic differences in anxiety‐related behaviors and stress responsivity. Pregnant dams of high anxiety‐related behavior (HAB) and low anxiety‐related behavior (LAB) strains were stressed between days 5 and 20 of pregnancy. The survival of newly generated hippocampal cells was found to be significantly lower in 43‐day‐old HAB than in LAB male offspring of unstressed pregnancies. PS further reduced newly generated cell numbers only in HAB rats, and this was paralleled by a reduction in doublecortin‐positive cell numbers, indicative of reduced neurogenesis. As maternal plasma corticosterone levels during PS were similar in both strains, we examined placental 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2), which catalyses rapid inactivation of maternal corticosterone to inert 11‐dehydrocorticosterone and thus serves as a physiological ‘barrier’ to maternal glucocorticoids. PS significantly increased placental 11β‐HSD2 activity in LAB, but not HAB, rats. We conclude that PS differentially affects the number of surviving newly generated cells and neurogenesis in HAB and LAB rats. The high sensitivity of hippocampal neurogenesis to PS in HAB rats is paralleled by a failure to increase placental 11β‐HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress‐induced placental 11β‐HSD2 expression may be critical in protecting the fetal brain from maternal stress‐induced effects on adult neurogenesis.
Do rats with retrosplenial cortex lesions lack direction?
Authors: Pothuizen Helen H. J. , Aggleton John P. , Vann Seralynne D.
Published: November 2008

The retrosplenial cortex is seen as a convergence point for different classes of spatial cue, yet aside from allocentric processing, little is known about other cue types that depend on the integrity of this area. Rats with bilateral retrosplenial cortex lesions were, therefore, trained on a sequence of reinforced spatial alternation tasks designed to isolate different spatial strategies. Using a standard T‐maze alternation procedure, which could be solved using multiple strategies, only a marginal lesion effect was observed. Next, by using two T‐mazes set side‐by‐side in the light, and then the dark, it was possible to examine alternation around a fixed bearing (direction alternation). Retrosplenial cortex lesions only disrupted the latter (direction alternation) condition. Direction alternation is of particular interest as it presumably taxes head‐direction information, and so provides a way of behaviourally assessing the contribution of this navigation system. Finally, rats were tested on a spatial working memory task in a radial‐arm maze. A retrosplenial lesion deficit appeared when the maze was rotated mid‐trial, as repeatedly found in previous studies. The pattern of findings in the present study strongly indicates that retrosplenial cortex lesions impair the use of direction cues for alternation, in addition to previously established impairments for allocentric‐based navigation and path integration.
CLINICAL AND METABOLIC OBSERVATIONS ON OSTEOMALACIA FOLLOWING URETEROSIGMOIDOSTOMY1
Authors: Harrison A. R.
Published: November 2008

Three cases of osteomalacia following ureterosigmoidostomy are described. At the time of diagnosis all had a hyperchlorzmic acidosis, a low plasma inorganic phosphate, a low or normal plasma calcium, and a raised plasma alkaline phosphatase.

Radiological evidence of osteomalacia was present in all three cases. In two cases the presence of a long‐continued acidosis could be confirmed by biochemical investigations; in one there was strong presumptive evidence that such a state had also existed.

Methods of obtaining calcium balance data are described and the results of calcium balance studies recorded.

The absence of nephrocalcinosis and the impossibility of separating urine and fzcal calcium outputs are discussed in relation lo pathogenesis. The evidence is in favour of the view that osteomalacia is the result of a long‐continued acidosis, and the calcium balance studies lend some support to this view.

The early symptoms of osteomalacia are not pathognomonic of the disease, and diagnosis depends on biochemical and radiological investigations.

Treatment consists in correction of the acidosis and administration of vitamin D. The balance studies reveal the importance of vitamin D in treatment.
The Angiographic Evaluation of Renal Pelvic Carcinoma
Authors: POLLEN J. J. , LEVINE E. , BLERK P. J. P. VAN
Published: November 2008

The angiographic findings are described in 6 cases of renal pelvic carcinoma.

An angiographic finding which has not hitherto been emphasised is a diminished branching of arteries in the kidney segment related to the pelvi‐calyceal tumour—the “pruned‐tree” appearance. This is generally associated with a deficiency of the nephrogram in the same segment. These appearances may be due to invasion of the renal parenchyma by tumour.

However, the findings may occur also in the absence of parenchymal invasion by the tumour and therefore do not necessarily reflect the stage of the disease.
The Value of Intestinal Valves in Urinary Diversion — an Experimental Study
Authors: KNOX A. J. S. , JAGO R. H.
Published: November 2008

It has been shown in experimental animals that an ileorectal valve incorporated into the operation of uretero‐ileosigmoidostomy cannot be relied upon to prevent ascending urinary tract infection.

However, a colorectal valve, not previously described, has been effective in preventing the development of a metabolic acidosis in piglets in whom this method of urinary diversion has been carried out.
In‐vivo Determination of Error in the Measurement of Urethral Pressure by the Method of Brown and Wickham
Authors: BROWN MALCOLM
Published: November 2008

A method of determining the error caused by the infusion of water into the urethra during urethral wall pressure and urethral pressure profile measurements is described and discussed. The test is conducted in vivo and the measured pressure is related to the actual urethral wall pressure. The “intrinsic error” is found to be approximately 1·0 cm H2O for every ml/min of infusion rate.

Incidental findings concerned with changes in urethral resistance are also reported.
The Microbial Flora of the Vagina and its Relationship to Bacteriuria in Diabetic and Non‐Diabetic Women
Authors: WILLIAMS D. N. , KNIGHT A. H. , KING HELEN , HARRIS D. M.
Published: November 2008

The vaginal and urinary flora have been studied in 57 diabetic and 33 non‐diabetic patients.

In both populations, no correlation was found between urogenital symptoms and colonisation of the vagina. There was no greater prevalence of potentially pathogenic organisms in diabetic patients, even when control was poor. However, although not statistically significant, group B streptococci were isolated more frequently from poorly controlled diabetics.

Bacteriuria was not significantly more common in diabetics.

Gram‐negative bacilli were found in the vagina significantly more often in bacteriuric patients; the prevalence of such organisms being four‐fold greater after the menopause.
The Nitrofurans as Sperm Immobilising Agents: their Tissue Toxicity and their Clinical Application
Authors: ALBERT PETER S. , MININBERG DAVID T. , DAVIS JOSEPH E.
Published: November 2008

Nitrofurantoin sodium and nitrofurazone in certain critical concentrations have the ability to cause sperm immobilisation.

Intraoperative vas irrigation with these solutions in 24 patients have produced sterility in the immediate postoperative period.
The Management of Pyocystis following Ileal Conduit Urinary Diversion in Children
Authors: STEVENS PETER S. , ECKSTEIN HERBERT B.
Published: November 2008

27 cases of pyocystis following ileal conduit urinary diversion are discussed.

In those cases not responding to medical treatment, vagino‐vesicostomy is recommended as an alternative to cystectomy.

The operation of prophylactic vagino‐vesicostomy at the time of the original diversion is discussed.
Prolonged Bladder Distension in the Treatment of the Unstable Bladder
Authors: WHITFIELD H. N. , MAYO M. E.
Published: November 2008

11 patients underwent 12 prolonged bladder distensions for bladder instability.

In no case did the cystometrogram revert from an unstable to a stable pattern, though 6 patients noted symptomatic improvement which was attested as moderate by 2 and marginal by 4.
The Nature of the Abnormality in Bladder Neck Obstruction
Authors: BATES C. P. , ARNOLD E. P. , GRIFFITHS D. J.
Published: November 2008

We have compared the pressure exerted by the bladder neck at rest with the bladder pressure generated during micturition in a series of 26 male patients, 13 unobstructed and 13 obstructed at the bladder neck.

We find that the degree of obstruction caused by a bladder neck cannot be determined from the pressure it exerts at rest and that this pressure is too low to explain the resistance of the obstructive bladder neck to dilation by the high pressures generated during voiding. It follows that the obstruction is functional in nature and is caused by a tightening of the bladder neck during micturition.

In addition, we find that shape of the urethral resistance relation is quite different in unobstructed and obstructed patients and deduce that, during micturition, an obstructive bladder neck forms a narrow nozzle of approximately constant diameter, usually about 2 mm (6F).
The Influence of Vesical Distension on Urethral Resistance to Flow: the Expulsion Phase
Authors: GHONEIM M. A. , FRETIN J. A. , GAGNON D. J. , SUSSET J. G.
Published: November 2008

The influence of vesical distension of the urethral pressure profile was studied in female dogs, using a model in which the bladder and urethra were separated.

There was a reduction in the urethral resistance involving its smooth and striated muscle components. This reduction was completely blocked by ganglion blocking agents. Atropine did not influence these changes. Propranolol could only partially block this reflex.

The other possible mechanisms that could be involved were discussed.
Cysts of the Prostate
Authors: FISCHELOVITCH J. , MEIRAZ D. , LAZEBNIK. J.
Published: November 2008

2 rare cases of prostatic cysts are described. The first was considered to be a congenital cyst originating in the Müllerian system and the second a large retention cyst of the prostate.

The problems arising from the present classification of prostatic cysts are briefly noted.
Equivocal Pelvi‐ureteric Obstruction
Authors: WHITAKER ROBERT H.
Published: November 2008

A series of 40 studies have been used to assess whether or not there is obstruction in the pelviureteric region in 27 kidneys. The perfusion test which is discussed has provided an answer in all cases where the technique was possible and allowed a logical decision to be taken concerning management.
Ring Ureterostomy
Authors: WILLIAMS D. INNES , CROMIE WILLIAM J.
Published: November 2008

A method is described for temporary cutaneous ureterostomy which combines the advantage of loop ureterostomy with a well vascularised stoma with those of the Sober Y operation allowing easy restoration of ureteric integrity.
The Therapeutic Application of Hyperthermia in the Bladder
Authors: ENGLAND H. R. , ANDERSON J. D. , MINASIAN H. , MARSHALL V. R. , MOLLAND E. A. , BLANDY J. P.
Published: November 2008

Experience with 10 cases of hyperthermic irrigation of the bladder suggests that irrigation with saline at 80°C for 10 to 15 min will stop bleeding and destroy epithelium and muscle layers without causing visceral injury or systemic disturbance.

It may be preferable to cystectomy in certain poor‐risk patients, or in those who refuse cystectomy for fear of impotence.
Sexual Function in Hypospadiacs
Authors: KENAWI M. M.
Published: November 2008

The sexual function of 82 patients treated for hypospadias was assessed. It was concluded that the sexual function in these patients was unsatisfactory only following incomplete or incorrect surgery. The aim of surgery should be to achieve a straight penis with an adequate urethral lumen and a urethral orifice situated at the tip of the glans. Proper assessment of chordee and meticulous care in surgical technique are the prerequisites for success. They are the only preventive measures of the physical, psychic, sexual and social handicaps to which hypospadiacs are subjected.
The Immunological Integrity of Matrix Substance A and its Possible Detection and Quantitation in Urine
Authors: MOORE SHEILA , GOWLAND G.
Published: November 2008

There would seem to be no doubt that most stone‐forming patients at some time during the course of their disorder excrete substances not present in normal urine. However, considerable doubt must now exist that “Matrix Substance A” is a single antigenic entity or that its presence is confined to the active formation of renal calculi.
Hypernephroma with Polycythaemia: a Postoperative Complication
Authors: MENZIES‐GOW N.
Published: November 2008

A case of acute renal failure following radical nephrectomy for hypernephroma in a 72‐year‐old man is presented. It is postulated that this was a direct result of vascular weakness from pre‐operation treatment of the overdistended vessels by repeated venepuncture over too short a period, with resultant loss of vascular tone.
Urinary Infection and Prostatectomy
Authors: JACKAMAN F. R. , CHISHOLM G. D.
Published: November 2008

The incidence of urinary infection before and after operation for benign prostatic hypertrophy has been reviewed in 140 patients.

Repeated screening for bacteriuria was used throughout the hospital admission. Infection was present in 24% before operation and there was a significant correlation between the incidence of infection and the duration of preoperative catheterisation.

Postoperative infection developed in 31 % and there was no relation between this incidence and the type of prostatectomy; specific antibacterial therapy was significantly more effective in eradicating urinary infection acquired after operation than before. At the time of discharge from the ward, 10% had infected urine, but only 3% of patients had persistent infection at follow‐up 6 weeks after operation.
Measurement of the Volume of Residual Urine using 131I‐Hippuran and the Gamma Camera
Authors: KALIS E. , LIKOURINAS M. , DERMENTZOGLOU F. , SAMARA B. , GOULANDRIS N.
Published: November 2008

A modification of the method of determining the volume of residual urine in the bladder using 131I‐Hippuran and the gamma camera is described. The method was applied to 26 patients with either normal or impaired renal function and proved to be both reliable and accurate.