bluuebunny/crossref_metadata_2025 huggingface dataset:
Gains and losses of warfarin therapy as performed in an anticoagulation clinic
Authors: NJAASTAD A. M. , ABILDGAARD U. , LASSEN J. F.
Published: January 2006

Background.  Knowledge of the net benefit of warfarin therapy in routine care is needed to define realistic management recommendations, but lack of randomized controls precludes conventional risk–benefit analysis.

Objective.  Assess risk and benefit of routine warfarin therapy in an anticoagulation clinic.

Design.  Retrospective observational analysis.

Patients.  A total of 1435 outpatients on warfarin for a total of 1613 patient years, treated to prevent the target events recurrent venous thromboembolism (VTE) or myocardial infarction (MI), and stroke in patients with atrial fibrillation (AF) or mechanical heart valves.

Measurements.  Major bleeding and thromboembolic (TE) events and all deaths.

Calculations.  Expected annual target event rates without warfarin were from published data. Differences between combined major events observed with warfarin, and expected without warfarin were calculated.

Results.  In the total material, annual rates were 3.0% major TE events, 1.1% major bleeding events, 0.12% fatal bleeding, and a benefit/risk ratio of 3.8. The net gain, expressed in reduced combined bleeding and target TE annual event rate, was 9.9% in secondary prophylaxis in AF, 4.4% in VTE patients, 2.7% in post‐MI patients, 2.4% in primary prophylaxis in AF and 0.6 in patients with mechanical heart valves. The apparent benefit/risk ratio was 3.9 in VTE patients, 5.8 in AF patients and 1.1 in patients with mechanical heart valves.

Conclusion.  Net effects of prolonged warfarin therapy in patients with VTE and AF performed in an anticoagulation clinic have an acceptable risk/benefit ratio, comparable with what has been obtained in elective clinical trials.
Switching to adefovir monotherapy after emergence of lamivudine‐resistant mutations in patients with liver cirrhosis
Authors: Liaw Y.‐F. , Lee C.‐M. , Chien R.‐N. , Yeh C.‐T.
Published: January 2006

Summary.  Switching to adefovir (ADV) monotherapy is effective in patients with lamivudine (LAM)‐resistant hepatitis B virus (HBV) mutations (rtM204 I/V). However, it was recommended to continue LAM therapy for months after starting ADV therapy for safety concern. The safety and efficacy of switching to ADV monotherapy was examined in compensated and decompensated patients with liver cirrhosis. The clinical, biochemical and virological responses were compared between ADV monotherapy in 18 cirrhotic patients and ADV add‐on LAM therapy in 10 comparable cirrhotic patients with LAM‐resistant rtM204 I/V. After switching to ADV monotherapy, Child‐Pugh's score, serum alanine aminotransferase (ALT), bilirubin, albumin and HBV DNA levels improved significantly (P < 0.01). Serum HBV DNA response, defined as HBV DNA decreased to below 105 copies/mL or ≥2 log10 reduction form baseline, was achieved in all patients. A transient ALT flare without concurrent changes in serum bilirubin or prothrombin time was observed in only two patients (11%). The efficacy and safety profile was similar to those with ADV add‐on LAM therapy. In conclusion, switching to ADV monotherapy after emergence of LAM‐resistant rtM204 I/V is effective and safe in cirrhotic patients, even in those with hepatic decompensation. To stop LAM and switch to ADV in patients with breakthrough is a reasonably safe and cost‐effective approach.
Eukaryotic ribosomal proteins lacking a eubacterial counterpart: important players in ribosomal function
Authors: Dresios John , Panopoulos Panagiotis , Synetos Dennis
Published: January 2006

The ribosome is a macromolecular machine responsible for protein synthesis in all organisms. Despite the enormous progress in studies on the structure and function of prokaryotic ribosomes, the respective molecular details of the mechanism by which the eukaryotic ribosome and associated factors construct a polypeptide accurately and rapidly still remain largely unexplored. Eukaryotic ribosomes possess more RNA and a higher number of proteins than eubacterial ribosomes. As the tertiary structure and basic function of the ribosomes are conserved, what is the contribution of these additional elements? Elucidation of the role of these components should provide clues to the mechanisms of translation in eukaryotes and help unravel the molecular mechanisms underlying the differences between eukaryotic and eubacterial ribosomes. This article focuses on a class of eukaryotic ribosomal proteins that do not have a eubacterial homologue. These proteins play substantial roles in ribosomal structure and function, and in mRNA binding and nascent peptide folding. The role of these proteins in human diseases and viral expression, as well as their potential use as targets for antiviral agents is discussed.
A pathway branching in transcription initiation in Escherichia coli
Authors: Susa Motoki , Kubori Tomoko , Shimamoto Nobuo
Published: January 2006

In transcription initiation, all RNA polymerase molecules bound to a promoter have been conventionally supposed to proceed into elongation of transcript. However, for Escherichia coli RNA polymerase, evidence has been accumulated for a view that only its fraction can proceed into elongation and the rest is retained at a promoter in non‐productive form: a pathway branching in transcription initiation. Proteins such as GreA and GreB affect these fractions at several promoters in vitro. To reveal the ubiquitous existence of the branched mechanism in E. coli, we searched for candidate genes whose transcription decreased by disruption of greA and greB using a DNA array. Among the arbitrarily selected 11 genes from over 100, the atpC, cspA and rpsA passed the test by Northern blotting. The Gre factors activated transcription initiation from their promoters in vitro, and the results demonstrated that the branched mechanism is exploited in vivo regulation. Consistently, decrease in the level of the GreA in an anaerobic stationary condition accompanied a decrease in the levels of transcripts of these genes.
Arabidopsis CDKA;1, a cdc2 homologue, controls proliferation of generative cells in male gametogenesis
Authors: Iwakawa Hidekazu , Shinmyo Atsuhiko , Sekine Masami
Published: January 2006

The protein kinase cdc2 is conserved throughout eukaryotes and acts as a key regulator of the cell cycle. In plants, A‐type cyclin‐dependent kinase (CDKA), a homologue of cdc2, has a role throughout the cell cycle. Here we show that a loss‐of‐function mutation in CDKA;1, encoding the only Arabidopsis CDKA, results in lethality of the male gametophyte. Heterozygous plants produced mature siliques containing about 50% aborted seeds, and segregation distortion was observed in paternal inheritance. Microspores normally undergo an asymmetric cell division, pollen mitosis I (PMI), to produce bicellular pollen grains. The larger vegetative cell does not divide, but the smaller generative cell undergoes mitosis, PMII, to form the two sperm cells, thereby generating tricellular pollen grains. The cdka‐1 mutant, however, produces mature bicellular pollen grains, consisting of a single sperm‐like cell and a vegetative cell, due to failure of PMII. The mutant sperm‐like cell is fertile, and preferentially fuses with the egg cell to initiate embryogenesis. As the central cell nucleus remains unfertilized, however, double fertilization does not occur. In heterozygous plants, the embryo is arrested at the globular stage, most likely because of loss of endosperm development, whereas it is arrested at the one‐ or two‐cell stage in presumptive homozygous plants. Thus, CDKA;1 is essential for cell division of the generative cell in male gametogenesis.
Validation of RNAi silencing specificity using synthetic genes: salicylic acid‐binding protein 2 is required for innate immunity in plants
Authors: Kumar Dhirendra , Gustafsson Claes , Klessig Daniel F.
Published: January 2006

RNA interference (RNAi) is widely used to specifically silence the expression of any gene to study its function and to identify and validate therapeutic targets. Despite the popularity of this technology, recent studies have shown that RNAi may also silence non‐targeted genes. Here we demonstrate the utility of a quick, efficient and robust approach to directly validate the specificity of RNAi as an alternative to indirect validation of RNAi through gene expression profiling. Our approach involves reversing (complementing) the RNAi‐induced phenotype by introducing a synthetic version of the target gene that is designed to escape silencing. This synthetic gene complementation approach can also be used for mutational analysis of the target gene, or to provide a functional version of a defective protein after silencing the defective gene by RNAi. Using this approach we demonstrate that the loss of systemic acquired resistance, a form of innate immunity in plants, is indeed due to the silencing of salicylic acid‐binding protein 2 rather than to off‐target effects.
Communal Relationships in a Social Spider Mite,Stigmaeopsis longus(Acari: Tetranychidae): An Equal Share of Labor and Reproduction between Nest Mates
Authors: Mori Kotaro , Saito Yutaka
Published: January 2006

The social spider mite,Stigmaeopsis longus(Saito), builds web‐nests and shares resources with fellow nest members. It does not show any distinct morphological castes. In this study, we observed whether there is any division of labor in reproductive and non‐reproductive tasks. Under experimental conditions, female density per nest did not affect per capita fecundity, even though the nest area allocated to an individual female, in which it feeds and oviposits, decreased with increased female density. Video observations on the behavior of either one or two females showed that there were no differences between these situations in the time budgets of all behaviors, nor in the nest‐weaving behavior of females. Furthermore, detailed behavioral analyses between the two situations suggested thatS. longusfemales share reproduction and labor evenly with their nest mates, probably mediated through physical or chemical communication. Therefore, we concluded that the sociality of this mite species should be categorized as communal.
Influence of Shape on Egg Discrimination in American Robins and Gray Catbirds
Authors: Underwood Todd J. , Sealy Spencer G.
Published: January 2006

The eggs of some obligate brood parasites are more spherical than the eggs of their non‐parasitic relatives and hosts, which contributes to the increased strength of their shells. We examined whether egg shape, including the more spherical shape of brown‐headed cowbird eggs (Molothrus ater), influenced egg discrimination in American robins (Turdus migratorius) and gray catbirds (Dumetella carolinensis). We added a series of artificial objects to robin and catbird nests that varied in shape from a control host egg, a rounded, cowbird‐like egg, to odd‐shaped objects. Real cowbird eggs were significantly more spherical than catbird and robin eggs, which confirmed a potential cue for egg recognition. Object shape significantly influenced the probability of rejection and time to rejection in both robins and catbirds. However, rounded eggs and spheres were rejected infrequently and at frequencies similar to control eggs. Therefore, the shape of a brood parasite's egg does not appear to influence egg discrimination in these two rejecters. Robins and catbirds rejected significantly more odd‐shaped objects than egg‐shaped objects and odd‐shaped objects were rejected significantly sooner than egg‐shaped objects. The rejection of odd‐shaped objects likely represents an expression of nest‐sanitation behaviour where debris is removed from the nest. By comparison with other studies of accepters of cowbird eggs, robins and catbirds appear to reject higher proportions of odd‐shaped objects, which suggests they may have more refined abilities to discriminate against foreign objects in their nests.
Evidence that Mating Plug is Related to Null Female Mating Activity in the ScorpionVaejovis punctatus
Authors: Contreras‐Garduño Jorge , Peretti Alfredo V. , Córdoba‐Aguilar Alex
Published: January 2006

We document a case in which the mating plug of the scorpionVaejovis punctatusseems correlated with a reduction in female sexual receptivity. We used two morphological and behavioral analyses. The mating plug was dissected and described from both males and females: it bears a set of spines and two enlarged terminations which possibly allow anchoring to the female inside and impede removal. Behavioral observations support this view: after sperm transfer ended, the female tried to remove the plug by rubbing the ventral side of her body using her second and third pair of legs. This pattern was also performed after mate separation. All females seemed unable to displace the plug and rejected male mating attempts. The mating plug suffered a progressive degradation into the female. This degradation was completed 2 or 3 mo prior to parturition, so that the plug did not seem a barrier for the emergence of embryos. Furthermore, females bearing mating plugs in different degradation stages did not accept another mating during the reproductive season, and sexual acceptance was reinitiated only after parturition. The mating plug therefore seems to correlate with a lost in mating activity. The comparison of this structure with that of other scorpion species allows us to hypothesize a sexual coevolutionary scenario in which the effectiveness of the plug to inhibit female remating may lie at the center of such interaction.
Bacteriuria, pyuria and bacteremia frequency following outpatient cystoscopy
Authors: TURAN HALE , BALCI UGUR , ERDINC F. SEBNEM , TULEK NECLA , GERMIYANOGLU CANKON
Published: January 2006

Aim:  The assumed necessity of antimicrobial prophylaxis prior to cystoscopy is controversial. In this study, the rate of bacteriuria, pyuria and bacteremia in outpatients who underwent cystoscopy without antimicrobial prophylaxis is investigated prospectively.

Methods:  The study included 75 patients who underwent cystoscopy for various indications and had sterile urine prior to intervention. A clean midstream urine sample was obtained 24 h before and 48 h after the procedure. Blood cultures were taken 1 h after cystoscopy. Patients were questioned for newly developed symptoms 48 h after cystoscopy. Blood cultures were taken again from patients who presented with fever.

Results:  Six patients (8%) developed significant bacteriuria, and six patients (8%) developed pyuria without significant bacteriuria. Bacteremia was not determined in any of the patients. The association between presence of pyuria prior to the procedure and development of bacteriuria after the procedure was significant (P < 0.05). Four patients out of six who had bacteriuria were asymptomatic. In our study we found significant bacteriuria after cystoscopy in 8% of patients, and no bacteremia.

Conclusions:  Thus we conclude that cystoscopy is a safe and well‐tolerated procedure. Antimicrobial prophylaxis should not be administrated unless specific indications are present.
Establishment and characterization of human urothelial cancer xenografts in severe combined immunodeficient mice
Authors: ABE TAKASHIGE , TADA MITSUHIRO , SHINOHARA NOBUO , OKADA FUTOSHI , ITOH TOMOO , HAMADA JUN‐ICHI , HARABAYASHI TORU , CHEN QINZHONG , MORIUCHI TETSUYA , NONOMURA KATSUYA
Published: January 2006

Aim:  To establish and characterize a murine xenograft model of human urothelial cancer in severe combined immunodeficient (SCID) mice for therapeutic simulation.

Methods:  Pieces of 30 freshly resected urothelial tumors (24 obtained from bladder and 6 from ureter or pelvis) were implanted subcutaneously into SCID mice, and xenograft tumors were passed in tumorigenic cases. At each passage, histopathology, TP53 mutational status assessed by yeast p53 functional assay, and the Ki‐67 labeling index (LI) were examined to evaluate the preservation of original features. A growth delay assay after single‐dose irradiation was performed in four representative xenografts.

Results:  Tumor growth was observed in 18 mice (60%, 18/30). Histologically, 15 of the 18 were epithelial carcinomas similar to the original tumors, whereas the other 3 were Epstein–Barr virus‐associated lymphoproliferative disease, resulting in a 50% (15/30) take rate. No correlation was found between the tumor take rate and the clinicopathologic features, TP53 mutational status, or Ki‐67 LI of the patients’ tumors. Of these 15 xenografts, 11 xenografts were passed from 3 to 10 generations. TP53 mutational status remained stable during the passages, and the Ki‐67 LI of eight xenografts was within a range of 50% of the LI of the original tumors, although the other three xenografts increased by over 50%. Specific growth delay after irradiation, independent of the original tumor growth speed and Ki‐67 LI, was observed in four xenografts.

Conclusions:  SCID mice are useful recipients for investigations of human urothelial cancer with a wide biological range. This easy‐to‐handle xenograft system can help to develop a better in vivo preclinical evaluation system for therapeutic agents as well as the investigation of tumor pathophysiology.
Transperineal extended biopsy improves the clinically significant prostate cancer detection rate: A comparative study of 6 and 12 biopsy cores
Authors: TAKENAKA ATSUSHI , HARA RYOUEI , HYODO YOJI , ISHIMURA TAKESHI , SAKAI YUTAKA , FUJIOKA HITOSHI , FUJII TOMOHIRO , JO YOSHIMASA , FUJISAWA MASATO
Published: January 2006

Background:  We evaluated the improvement in the rate of prostate cancer detection when using a 12‐core transperineal biopsy protocol including transitional zone biopsy.

Methods:  Between April 2003 and November 2004, 247 consecutive men underwent transperineal systemic 12‐core biopsy of the prostate. Six cores were obtained at the peripheral zone, four at the transitional zone and two at the apex. We examined the cancer detection rate in each of the 12 cores, and also determined the improvement of cancer detection resulting from the extensive 12‐core versus standard 6‐core biopsy.

Results:  Using the extensive 12‐core biopsy, prostate cancer was detected in 98 cases (39.7%). Prostate‐specific antigen (PSA), PSA density, the positive rate in digital rectal examination and transrectal ultrasound findings were significantly higher in the prostate cancer group than in the non‐prostate cancer group, and prostate volume was larger in non‐prostate cancer group. Every site showed almost the same positive rate, between 17.8 and 21.5%. There were 20 cases which were positive in the extended biopsy, but negative in the sextant. The detection improved significantly (20.4%). The improvement of cancer detection in extended biopsy was better in men with PSA levels of 10 ng/mL or less (28.9%), PSA density 0.3 or less (25.8%), negative digital rectal examination (23.3%), and negative transrectal ultrasound (21.6%). Of these twenty patients, no cases with insignificant tumor were detected in the six prostatectomy cases. In particular, three cases of the six were transitional‐zone‐only cancer.

Conclusion:  Transperineal extended 12‐core biopsy including 4 transitional zone cores is a more useful procedure than transperineal 6‐core biopsy. Routine transitional zone biopsy, that is different from transrectal biopsy, might be useful for detecting biologically significant cancer.
Videomanometry of the pelvic organs: A comparison of the normal lower urinary and gastrointestinal tracts
Authors: ITO TAKASHI , SAKAKIBARA RYUJI , UCHIYAMA TOMOYUKI , ZHI LIU , YAMAMOTO TATSUYA , HATTORI TAKAMICHI
Published: January 2006

Background:  Both the lower urinary tract (LUT) and the caudal part of the lower gastrointestinal tract (LGIT) are innervated by the sacral spinal cord. We aimed to compare the normal physiology of the LUT and LGIT using the same videomanometry method.

Methods:  We recruited fifteen healthy volunteers (eight men and seven women; mean age, 60 years). The videomanometric measures included fluoroscopic images, subtracted bladder/rectal pressures, urethral/anal sphincter pressures, sphincter electromyography, and urinary/fecal flow.

Results:  During the resting phase, the urethral/anal sphincter pressures showed almost the same values (mean, 70 cmH2O and 68 cmH2O, respectively). During the storage phase, the volumes at first sensation and maximum capacity for the LGIT (129 mL and 320 mL) were slightly smaller than those for the LUT (170 mL and 405 mL). Compliance of the LGIT (65 mL/cmH2O) was almost as high as that of the LUT (99 mL/cmH2O). However, the LGIT showed spontaneous phasic rectal contractions (SPRC) that were never seen in the bladder. None of the subjects experienced leakage during bladder/rectal filling. During the evacuation phase, rectal contraction on defecation (14 cmH2O) was present, but was weaker than bladder contraction on micturition (42 cmH2O; P < 0.01). Abdominal strain on defecation (70 cmH2O) was greater than that on micturition (25 cmH2O; P < 0.01). Sphincter pressure increase on defecation (13 cmH2O) was greater than that on micturition (−52 cmH2O). An illustrative case of SPRC that were seen during urodynamic recording was shown.

Conclusion:  SPRC and abdominal strain are features of the LGIT, whereas micturition bladder contraction is a feature of the LUT. These features can aid in understanding the possible rectal ‘artifacts’ of videourodynamics and neurogenic pelvic organ dysfunction.
Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbits
Authors: SARAC BULENT , YILDIRIM MUSTAFA K. , BAGCIVAN IHSAN , KAYA KEMAL , KILICARSLAN HAKAN , YILDIRIM SAHIN
Published: January 2006

Background:  The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25–35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men.

Methods:  In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls.

Results:  Carbachol‐induced relaxation responses and electrical field stimulation (EFS)‐induced frequency‐dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)‐induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS‐induced frequency‐dependent contractions were significantly decreased in the hypothyroid group.

Conclusions:  We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density.
Sexual activity in Korean male patients on clean intermittent catheterization with neurogenic bladder due to spinal cord injury
Authors: KU JA HYEON , OH SEUNG‐JUNE , JEON HWANG GYUN , SHIN HYUNG‐IK , PAIK NAM‐JONG , YOO TAIWOO , KIM SOO WOONG
Published: January 2006

Background:  The aim of this study was to assess the sexual function and activity in male patients on clean intermittent catheterization with neurogenic bladder due to spinal cord injury.

Methods:  Eighty‐nine patients (mean age 37.6 years with a range of 18–66) were included in the study. We requested all subjects to complete a questionnaire including the 5‐item version of the International Index of Erectile Function (IIEF‐5).

Results:  Of 89 patients, 60 (67.4%) reported having attempted no sexual intercourse over the past 6 months and 28 (31.5%) presented with IIEF‐5 scores less than or equal to 21 points. When subjects were stratified according to the years since injury, 50.0% (16 of 32) with less than 2 years post‐injury had no sexual activity, while 77.2 (44 of 57) with 2 years or more post‐injury did (P = 0.027). Patients with sexual activity were 40.4% (23 of 57) and 18.8% (6 of 32) in patients who were able and unable to perform self‐catheterization, respectively (P = 0.037). Patients with less than 2 years post‐injury had 3.3‐fold higher risk (odds ratio 3.33; 95% confidence interval 1.01–10.97; P = 0.048) of no sexual activity than those with 2 years or more post‐injury on the multivariate model. The other parameters were not appreciably related to sexual activity.

Conclusion:  Our results demonstrate that sexual activity as well as erectile function is poor in this population. In addition, our findings suggest that years since injury may influence sexual activity of patients with spinal cord injury.
Renal tuberculosis simulating xanthogranulomatous pyelonephritis with contagious hepatic involvement
Authors: SHAH HEMENDRA N , JAIN PRITESH , CHIBBER PERCY J
Published: January 2006

Abstract  Xanthogranulomatous pyelonephritis (XGPN) is a chronic renal infection typically associated with nephrolithiasis and a non‐functioning kidney. Renal tuberculosis is a major cause of morbidity in developing countries. Despite recent advances in diagnosis, it is sometimes difficult to differentiate renal tuberculosis preoperatively from XGPN. We present herewith a case report of a patient who was preoperatively diagnosed with a right non‐functioning kidney due to renal calculus with stage 3 XGPN and adjacent liver abscess on computed tomography. Subsequent histopathological examination of the nephrectomised specimen revealed renal tuberculosis. To our knowledge this is the first case of renal tuberculosis spreading to the liver and causing liver abscess formation which was misdiagnosed as XGPN preoperatively.
Huge epidermoid cyst of the spermatic cord in an adult patient
Authors: KATERGIANNAKIS VAGELOGIANNIS , LAGOUDIANAKIS EMMANUEL E , MARKOGIANNAKIS HARIDIMOS , MANOURAS ANDREAS
Published: January 2006

Abstract  Tumors arising in the spermatic cord are uncommon and form a heterogeneous group of neoplasms. A variety of both benign and malignant lesions have been demonstrated. Benign tumors represent 80% of the total, but unfortunately clinical and sonographic features are not specific and they cannot safely differentiate a teratomatous or a malignant neoplasm from benign tumors. We report a case of a huge epidermoid cyst of the spermatic cord in an adult patient confirmed after local excision. The etiology, differential diagnosis, and management alternatives are discussed.
Partial androgen insensitivity syndrome with thermolability in the androgen receptor
Authors: HIRAOKA KENJI , KAWAUCHI AKIHIRO , SOH JINTETSU , OHE HIROSHI , SHIMA HIROKI , MIKI TSUNEHARU
Published: January 2006

Abstract  We report case of partial androgen insensitivity syndrome in a 12‐year‐old boy referred to our clinic complaining of bilateral gynecomastia and left undescended testicle. Laparoscopy for undescended testicle and bilateral mastectomy were performed, and the left testicle was absent. When skin fibroblasts of the scrotum obtained during surgery were cultured to analyse the androgen receptors, a slight thermolability was observed. Genomic examination of the androgen receptor gene could not detect any mutations.
Primary retrovesical hydatidosis causing chronic renal failure
Authors: SINGH SHRAWAN K , WADHWA PANKAJ , CHANDRAMOHAN V
Published: January 2006

Abstract  Hydatidosis is an endemic, widely distributed zoonosis, which involves the liver, lung and other organs. Isolated retrovesical involvement is an uncommon location of occurrence, which may rarely cause chronic renal failure. We profile the presentation, management and outcome of three such cases.
Malignant peripheral nerve sheath tumor of the kidney
Authors: WILLIAMS STEPHEN B , SZLYK GREGORY R , MANYAK MICHAEL J
Published: January 2006

Abstract  Malignant peripheral nerve sheath tumors are rare in the genitourinary organs, with few reports of occurrence in the kidney. We describe a patient with a renal malignant peripheral nerve sheath tumor, discovered after excision of a malignant peripheral nerve sheath scalp lesion, with additional masses in the lung and shoulder on metastatic evaluation. This patient underwent neoadjuvant intravenous doxorubicin therapy, followed by surgical resection of the scalp, lung and shoulder lesions in addition to a radical nephrectomy.
Absence of synapsin I and II is accompanied by decreases in vesicular transport of specific neurotransmitters
Authors: Bogen Inger Lise , Boulland Jean‐Luc , Mariussen Espen , Wright Marianne S. , Fonnum Frode , Kao Hung‐Teh , Walaas S. Ivar
Published: January 2006

Studies of synapsin‐deficient mice have shown decreases in the number of synaptic vesicles but knowledge about the consequences of this decrease, and which classes of vesicles are being affected, has been lacking. In this study, glutamatergic, GABAergic and dopaminergic transport has been analysed in animals where the genes encoding synapsin I and II were inactivated. The levels of the vesicular glutamate transporter (VGLUT) 1, VGLUT2 and the vesicular GABA transporter (VGAT) were decreased by approximately 40% in adult forebrain from mice devoid of synapsin I and II, while vesicular monoamine transporter (VMAT) 2 and VGLUT3 were present in unchanged amounts compared with wild‐type mice. Functional studies on synaptic vesicles showed that the vesicular uptake of glutamate and GABA was decreased by 41 and 23%, respectively, while uptake of dopamine was unaffected by the lack of synapsin I and II. Double‐labelling studies showed that VGLUT1 and VGLUT2 colocalized fully with synapsin I and/or II in the hippocampus and neostriatum, respectively. VGAT showed partial colocalization, while VGLUT3 and VMAT2 did not colocalize with either synapsin I or II in the brain areas studied. In conclusion, distinct vesicular transporters show a variable degree of colocalization with synapsin proteins and, hence, distinct sensitivities to inactivation of the genes encoding synapsin I and II.
Mutations in amyloid precursor protein and presenilin‐1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid β‐peptide (1–42), H2O2 and kainic acid: implications for Alzheimer's disease
Authors: Mohmmad Abdul Hafiz , Sultana Rukhsana , Keller Jeffrey N. , St. Clair Daret K , Markesbery William R. , Butterfield D. Allan
Published: January 2006

Oxidative stress is observed in Alzheimer's disease (AD) brain, including protein oxidation and lipid peroxidation. One of the major pathological hallmarks of AD is the brain deposition of amyloid beta‐peptide (Aβ). This 42‐mer peptide is derived from the β‐amyloid precursor protein (APP) and is associated with oxidative stress in vitro and in vivo. Mutations in the PS‐1 and APP genes, which increase production of the highly amyloidogenic amyloid β‐peptide (Aβ42), are the major causes of early onset familial AD. Several lines of evidence suggest that enhanced oxidative stress, inflammation, and apoptosis play important roles in the pathogenesis of AD. In the present study, primary neuronal cultures from knock‐in mice expressing mutant human PS‐1 and APP were compared with those from wild‐type mice, in the presence or absence of various oxidizing agents, viz, Aβ(1–42), H2O2 and kainic acid (KA). APP/PS‐1 double mutant neurons displayed a significant basal increase in oxidative stress as measured by protein oxidation, lipid peroxidation, and 3‐nitrotyrosine when compared with the wild‐type neurons (p < 0.0005). Elevated levels of human APP, PS‐1 and Aβ(1–42) were found in APP/PS‐1 cultures compared with wild‐type neurons. APP/PS‐1 double mutant neuron cultures exhibited increased vulnerability to oxidative stress, mitochondrial dysfunction and apoptosis induced by Aβ(1–42), H2O2 and KA compared with wild‐type neuronal cultures. The results are consonant with the hypothesis that Aβ(1–42)‐associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD.
Regulatory issues in aging pharmacology
Authors: Hefti Franz F. , Bales Roxanne
Published: January 2006

Many current drugs increase the average lifespan by preventing fatal diseases or by slowing down the progressive degenerative diseases that increase mortality. The existing strategies and guidelines for the development and regulatory approval of new drugs are designed for such compounds. Rapid advances in understanding molecular mechanisms of aging make it possible to envisage future drugs that extend the lifespan by regulating aging mechanism outside of disease pathways. Strategies for development and regulatory approval of such drugs remain to be defined. Since the drug candidates will be given to healthy, elderly subjects, safety requirements will be extremely high. Clinical studies of many years’ duration will be necessary to prove changes in longevity. These time intervals may exceed those of patent protection and thus minimize commercial incentives. Despite these challenges, two broadly defined pathways are feasible. First, it may be possible to obtain public funding for studies with voluntary participation of humans consuming existing drugs or natural compounds in the ‘expected to be safe’ category. Second, the development of novel drugs may proceed on the basis of well‐defined biomarkers of aging that can serve as surrogate end points in clinical studies. The emerging approaches will prompt the regulatory agencies into taking the first steps towards regulatory guidance.
Automatic Evaluation of Mixed‐mode Stress Intensity Factors Utilizing Digital Image Correlation
Authors: Yoneyama S. , Morimoto Y. , Takashi M.
Published: January 2006

Abstract:  A method for determining mixed‐mode stress intensity factors from displacement fields obtained by digital image correlation is studied. To perform automatic evaluation, not only stress intensity factors but crack‐tip location, higher‐order terms in the series expansion of displacement fields and rigid‐body displacement components are also determined simultaneously using nonlinear least squares based on the Newton–Raphson method. Experimental results show that the mixed‐mode stress intensity factors are evaluated accurately from either radial or circumferential displacement components. As mixed‐mode stress intensity factors can be evaluated easily, simply and automatically by the technique with digital image correlation and nonlinear least squares, it is expected that the proposed method can be applied to solve various fracture problems.
The effect of water table depth on emissions of N2O from a grassland soil
Authors: Dobbie K. E. , Smith K. A.
Published: January 2006

Nitrous oxide (N2O) emissions were measured by the closed chamber technique from five plots along a transect in a nitrogen‐fertilised grassland, together with soil water content, soil temperature and water table depth, to investigate the effect of water table depth on N2O emissions. N2O fluxes varied from <1 g N2O‐N ha−1 day−1 to peaks of around 500–1200 g N2O‐N ha−1 day−1 after N fertiliser applications. There was no significant difference in overall average water table depth between four of the five plots, but significant short‐term temporal variations in water table depth did occur. Rises in the water table were accompanied by exponential increases in N2O emissions, through the associated increases in the water‐filled pore space of the topsoil. Modelling predicted that if the water table could be managed such that it was kept to no less than 35 cm below the ground surface, fluxes during the growing season would be reduced by 50%, while lowering to 45 cm would reduce them by over 80%. The strong implication of these results is that draining grasslands, so that the water tables are only rarely nearer to the surface than 35 cm when N is available for denitrification, would substantially reduce N2O emissions.
GEOCHEMICAL PROVENANCE OF OBSIDIAN ARTEFACTS FROM THE MSA SITE OF PORC EPIC, ETHIOPIA*
Authors: NEGASH AGAZI , SHACKLEY M. S.
Published: January 2006

Obsidian geochemical analysis has become an indispensable tool in archaeological research and has wide applications. However, in spite of the abundance of geological and archaeological obsidian, there has been virtually no such investigation in Ethiopia. Recent instrumental characterization of 31 obsidian artefacts from the Middle Stone Age site of Porc Epic and numerous obsidian geological sources show that artefacts were being transported from as far as 250 km away. We believe this has relevance to the understanding of the emergence of modern human behaviour.
LEAD ISOTOPE ANALYSIS OF ARCHAEOLOGICAL METALS BY MULTIPLE‐COLLECTOR INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY*
Authors: BAKER J. , STOS S. , WAIGHT T.
Published: January 2006

Lead isotope ratios in archaeological silver and copper were determined by MC–ICPMS using laser ablation and bulk dissolution without lead purification. Laser ablation results on high‐lead metals and bulk solution analyses on all samples agree within error of TIMS data, suggesting that problems from isobaric interferences and/or mass bias variations due to the presence of matrix elements are insignificant. Inaccurate laser ablation analyses on low‐lead copper reflect erroneous mass bias corrections from use of a non‐matrix matched standard. However, in most cases, silver and copper are analysable for lead isotopes by bulk dissolution or laser ablation MC–ICPMS with simplified sample preparation.
NEW RADIOCARBON ACCELERATOR DATES ON ARTEFACTS FROM THE EARLY MESOLITHIC SITE OF STAR CARR, NORTH YORKSHIRE*
Authors: DARK P. , HIGHAM T. F. G. , JACOBI R. , LORD T. C.
Published: January 2006

For the well‐known early Mesolithic site of Star Carr, dating of organic artefacts by accelerator mass spectrometry (AMS) has been hampered by treatment of bone and antler recovered during the original excavations with preservatives. Some, untreated, artefacts were, however, collected after Clark's excavation in 1950. Four of these artefacts were AMS dated in 1995, but two of the dates were significantly younger than the others, and were questionable due to their low collagen yields. These suspect samples have now been re‐analysed, demonstrating that all four artefacts are of similar date. The significance of these dates for the chronology of Star Carr is discussed.
The role of p28GANK in rat oval cells activation and proliferation
Authors: Shan Yun‐Feng , Zhou Wei‐Ping , Fu Xiao‐Yong , Yan He‐Xing , Yang Wen , Liu Shu‐Qin , Cao Hui‐Fang , Kang Bin , Wu Meng‐Chao , Wang Hong‐Yang
Published: January 2006

Abstract: Background: Human gankyrin gene product (p28GANK) is a novel oncogenic protein ubiquitously overexpressed in hepatocellular carcinoma and also plays a role in cell cycle progression in normal hepatocytes and liver regeneration. However, little is known about the physiological role of p28GANK in the liver oval cell activation and proliferation. We investigated the possible involvement of p28GANK in oval cell‐mediated liver regeneration and cell cycle progression.

Methods: We examined the different p28GANK expression in 2‐acetylaminofuorene/partial heptectomy (2‐AAF/PH) rats, as a model of oval cell activation, and PH rats by Western blot and immunohistochemistry. Oval cells isolated from 2‐AAF/PH rat model were cultured in our study. p28GANK expression was examined in the oval cells after mitogenic stimulation.

Results: In 2‐AAF/PH rats, p28GANK was expressed in the activated oval cells and located in the nucleus. p28GANK protein expression was increased in 2‐AFF/PH rats after hepatectomy lasting for 96 h when retinoblastoma maintained hyperphosphorylation status at Ser‐795. The isolated oval cells express AFP, OV6, CK19, CD34, CD45, c‐kit and albumin. After epidermal growth factor stimulation, p28GANK protein was up‐regulated in oval cells from 24 to 72 h, which coincided with increased expression of CyclinD1, CDK4 and decreased of Rb protein.

Conclusions: p28GANK expression was increased in oval cell‐mediated liver regeneration and oval cells after mitogenic stimulation. Thus, p28GANK may play a role in oval cell‐mediated liver regeneration and liver oval cell cycle progression.
Serum lipid and lipoprotein alterations represent recovery of liver function after hepatectomy
Authors: Kawamoto Masaki , Mizuguchi Toru , Nagayama Minoru , Nobuoka Takayuki , Kawasaki Hiroyuki , Sato Taishi , Koito Kazumitsu , Parker Susan , Katsuramaki Tadashi , Hirata Koichi
Published: January 2006

Abstract: Background: The assessment of liver function during human liver regeneration is necessary to prevent unexpected liver failure and to prepare for further treatment. We selected patients prospectively and measured serum lipid and lipoprotein levels to identify which lipids and lipoproteins could represent recovery of liver function in human liver regeneration.

Methods: Thirty selected patients who underwent hepatectomy were divided into three groups depending on the serum hyaluronate (HA) level and the type of liver resection.

Results: We found three patterns of lipid and lipoprotein alterations after hepatectomy. Among the lipids and lipoproteins examined, the serum β‐lipoprotein and low‐density lipoprotein (LDL) levels were significantly different among the groups at 7 days after hepatectomy. The alteration of the apolipoprotein (Apo) B level was similar to that of LDL. The LDL level was correlated with both β‐lipoprotein and Apo B before hepatectomy (r=0.653 and 0.894, respectively) and at 7 days after hepatectomy (r=0.841 and 0.943, respectively).

Conclusion: Serum HA before hepatectomy can reflect postoperative liver function depending on the type of liver resection. Recovery of the β‐lipoprotein and LDL levels can reflect the recovery of liver function in human liver regeneration within the early period in association with the Apo B level.
Ablation of Nonautomatic Focal Atrial Tachycardia in Children and Adults with Congenital Heart Disease
Authors: SESLAR STEPHEN P. , ALEXANDER MARK E. , BERUL CHARLES I. , CECCHIN FRANK , WALSH EDWARD P. , TRIEDMAN JOHN K.
Published: January 2006

Introduction: Nonautomatic focal atrial tachycardia (NAFAT) has been characterized in adults with structurally normal hearts. This article characterizes NAFAT in a population of patients with complex congenital heart disease.

Methods and Results: Electrophysiologic and electroanatomic mapping data and acute outcomes were reviewed in patients undergoing mapping and ablative procedures for atrial tachycardia at Children's Hospital, Boston, between January 1999 and December 2003. Twenty‐two NAFAT foci were identified in 17 patients out of 216 patients studied. Fourteen of these 17 patients had congenital heart disease. The average age of the patients with a NAFAT mechanism was 27 years and there was no gender predilection. The presumptive diagnosis based on clinical grounds and surface ECG assessment in 11 of 17 patients with NAFAT was atrial flutter. None of the 17 patients were suspected of having a NAFAT mechanism by noninvasive assessment. Four of the 10 patients had both NAFAT and macroreentrant atrial tachycardias. NAFAT cycle lengths varied widely (200–680 ms) between patients. Sixteen of the 22 NAFAT foci were mapped to the anatomic right atrium (RA). Acute ablative success was achieved in 17 out of 22 foci (77%).

Conclusion: NAFAT is relatively uncommon in a pediatric tertiary care setting, and in that setting occurs most often in adults with congenital heart disease. NAFAT is indistinguishable from other forms of atrial tachycardia by noninvasive means and can mimic other forms of atrial tachycardia on electrocardiogram. The foci were predominantly found in the RA and were, in most cases, acutely amenable to catheter ablation therapy.
Symptomatic and Asymptomatic Atrial Fibrillation in Patients Undergoing Radiofrequency Catheter Ablation
Authors: VASAMREDDY CHANDRASEKHAR R. , DALAL DARSHAN , DONG JUN , CHENG ALAN , SPRAGG DAVID , LAMIY SAMEH Z. , MEININGER GLENN , HENRIKSON CHARLES A. , MARINE JOSEPH E. , BERGER RONALD , CALKINS HUGH
Published: January 2006

Introduction: The goals of this study were to (i) evaluate the feasibility and results of monitoring patients prior to and following catheter ablation of AF with the mobile cardiac outpatient telemetry (MCOT) system and to (ii) correlate symptoms and the presence or absence of atrial fibrillation (AF).

Methods and Results: A total of 19 consecutive patients (12 men [63%]; age 60 ± 6 years) with highly symptomatic drug refractory AF underwent catheter ablation. Each was provided with a MCOT monitor (CardioNet, USA) and asked to wear it 5 days immediately before the ablation, and 5 days per month starting with the ablation for 6 consecutive months. When patients experienced any symptoms, they were asked to activate the system and to record associated symptoms. A total of 494 days (11,856 hours) were monitored. Out of the total 390 events triggered by patient's symptoms, 40% were confirmed as AF events (156) and 60% were confirmed as non‐AF events (234). Only shortness of breath and chest discomfort were highly associated with AF (P < 0.05). At the end of 6 months of follow‐up, out of 10 patients that completed the study, 7 (70%) patients were free of symptomatic AF recurrences whereas only 5 (50%) patients achieved success when asymptomatic AF recurrences were included in the outcome.

Conclusions: The results of this study demonstrate the potential utility of wireless monitoring systems in the follow‐up of AF ablation patients, while also identifying poor patient compliance with an intensive monitoring protocol as an important limitation.
Analysis of Fruiting Body Development in the Aggregative Ciliate Sorogena stoianovitchae (Ciliophora, Colpodea)
Authors: SUGIMOTO HIROKI , ENDOH HIROSHI
Published: January 2006

ABSTRACT. The fruiting body‐forming ciliate Sorogena stoianovitchae is a protist that is multicellular in one stage of its life cycle. When nutrient levels are depleted, a number of Sorogena cells aggregate beneath the water surface to form an aerial fruiting body. Based on morphologies and the inhibition of protein synthesis, fruiting body development is divided into five distinct stages: (1) aggregation before sunrise, (2) compact aggregation after sunrise, (3) secretion of mucous matrix, (4) stalk‐elongation, and (5) completion of the fruiting‐body. In the aggregation stage, the cells were trapped in a matrix material that stained orange with 4′,6‐diamino‐2‐phenylindole (DAPI), but differed from the mucous matrix in the later stage. A short interruption of the dark period, at 6–8 h after the onset of dark, inhibited fruiting body development. Irrespective of the length of the dark period (10–16 h), the cells remained in the aggregation stage until the beginning of the light period. Therefore, an uninterrupted dark period of more than 8 h is critical for the initial aggregation of cells, but subsequent development is triggered by light.