bluuebunny/crossref_metadata_2025 huggingface dataset:
Rad18/Rad5/Mms2‐mediated polyubiquitination of PCNA is implicated in replication completion during replication stress
Authors: Branzei Dana , Seki Masayuki , Enomoto Takemi
Published: October 2004

Ubiquitination of proteins was previously shown to modulate various processes of DNA metabolism. PCNA, a processivity factor with essential functions in replication and repair, is modified with ubiquitin at K164. In addition, PCNA is sumoylated at K127 and K164. We found that the rad18Δ mutation suppresses the temperature sensitivity of the polymerase δ mutants hys2‐1 and cdc2‐1 as well as the synthetic lethality of cdc2‐1 pol32Δ mutants, suggesting a role for Rad18 in modulating DNA replication. As Rad18 mediates ubiquitination of PCNA, we examined whether PCNA modifications affected its function in replication. Multicopy PCNA alleviated the replication defects of rfc5‐1 strains, but not those of polδ mutants. In contrast, multicopy PCNA‐K164R had reduced ability to suppress the replication defects of rfc5‐1, but alleviated those of polδ mutants. The roles of sumoylated and ubiquitinated PCNA in rfc5‐1 and hys2‐1 mutants were addressed by using mutant backgrounds that selectively affected sumoylation (siz1Δ), ubiquitination (rad18Δ), polyubiquitination (rad5Δ, mms2Δ), or the ability of cells to perform translesion synthesis (polζΔ, polηΔ). Our results are consistent with the idea that the Rad18/Rad5/Mms2 polyubiquitination pathway is important for replication completion, perhaps by promoting a template switch type of DNA synthesis.
ASC is essential for LPS‐induced activation of procaspase‐1 independently of TLR‐associated signal adaptor molecules
Authors: Yamamoto Masatatsu , Yaginuma Katsuyuki , Tsutsui Hiroko , Sagara Junji , Guan Xin , Seki Ekihiro , Yasuda Koubun , Yamamoto Masahiro , Akira Shizuo , Nakanishi Kenji , Noda Tetsuo , Taniguchi Shun’ichiro
Published: October 2004

Toll‐like receptors (TLRs) initiate a signalling cascade via association with an adaptor molecule, myeloid differentiation factor 88 (MyD88) and/or TIR domain‐containing adaptor inducing‐IFN‐β (Trif), to induce various pro‐inflammatory cytokines for microbial eradication. After stimulation of TLR4 with lipopolysaccharide (LPS), both IL‐1β and IL‐18 are processed, depending on the activation of caspase‐1, although its mechanism remains unclear. ASC is an adapter protein possibly involved in the activation of procaspase‐1. To unravel the requirement of ASC, we generated Asc−/– mice. Upon stimulation with LPS, Asc−/– macrophages failed in the processing of procaspase‐1 and maturation of pro‐IL‐1β and pro‐IL‐18, but normally produced other pro‐inflammatory cytokines including TNF‐α and IL‐6. MyD88−/– and Trif−/– macrophages showed normal activation of caspase‐1, demonstrating a dispensable role for MyD88 and Trif. After, LPS‐challenged Asc−/– mice lacked serum elevation of IL‐1β and IL‐18. Moreover, the Asc−/– mice exhibited neither acute liver injury nor lethal shock. These results demonstrate critical roles for ASC in the release of IL‐1β/IL‐18 via activation of caspase‐1 and provide new insights into the inflammatory responses for host defence and diseases.
Targeted disruption of the mouse ELYS gene results in embryonic death at peri‐implantation development
Authors: Okita Keisuke , Kiyonari Hiroshi , Nobuhisa Ikuo , Kimura Naoki , Aizawa Shinichi , Taga Tetsuya
Published: October 2004

Early mouse development is a complicated process that is controlled by various proteins including transcription factors. Recently, we identified a putative transcription factor, ELYS (embryonic large molecule derived from yolk sac), using a subtraction strategy. To elucidate the role of ELYS in vivo, we generated ELYS‐deficient mice by homologous recombination. Although heterozygous mice appeared to be healthy, fertile and normal, embryos homozygous for the ELYS mutation died between embryonic day (E) 3.5 and 5.5. Null mutant blastocysts collected from the uterus at E3.5 were viable and indistinguishable from wild‐type littermates. However, when cultured in vitro, they showed impaired proliferation of the inner cells, because of apoptosis. The expression of ELYS mRNA was detected in both the inner cell mass (ICM) and the trophectoderm at the blastocyst stage, and persisted throughout the developing embryo during E4.5 to 6.5. These results indicate that ELYS is a critical factor for early mouse development and is essential for the survival of the inner cells.
Peroxisome proliferator‐activated receptor γ‐dependent and ‐independent growth inhibition of gastrointestinal tumour cells
Authors: Rumi M. Azharul Karim , Ishihara Shunji , Kadowaki Yasunori , Ortega‐Cava C. F. , Kazumori Hideaki , Kawashima Kousaku , Yoshino Nagisa , Yuki Takafumi , Ishimura Norihisa , Kinoshita Yoshikazu
Published: October 2004

Peroxisome proliferator‐activated receptor γ (PPARγ) acts as a ligand‐activated transcription factor. Although ligand‐induced cellular differentiation and growth inhibition have been mostly studied on human cancers expressing PPARγ, it is unclear if the transcriptional activation of PPARγ is the main mechanism of growth inhibition. In this study, we investigated whether there is a link between growth inhibitory effect and transcriptional activation of PPARγ in several gastrointestinal tumour cell lines. The transcriptional activation potential of PPARγ was assessed by reporter gene assay employing a PPRE‐luciferase vector, and growth inhibitory effect of PPARγ was investigated by 3H‐thymidine incorporation assay, in the presence or absence of thiazolidinedione ligands, rosiglitazone and troglitazone. As expected, in the case of cell lines positive for the transcriptional activation potential of PPARγ (T.Tn, MKN‐45 and LoVo), both the ligands induced growth inhibition. However, in case of some other cell lines negative for the transcriptional activation potential of PPARγ (TT, AGS and HCT‐15), troglitazone still showed a growth inhibitory effect. Administration of the PPARγ antagonist GW9662 did not reverse this growth inhibitory activity of troglitazone. The introduction of dominant negative mutants of PPARγ did not suppress the activity either. These observations suggest that while rosiglitazone inhibits cellular growth predominantly through transcriptional activation of PPARγ, troglitazone can induce it both in PPARγ‐dependent and ‐independent pathways.
Immune responses of barramundi,Lates calcarifer(Bloch), after administration of an experimentalVibrio harveyibacterin by intraperitoneal injection, anal intubation and immersion
Authors: Crosbie P B B , Nowak B F
Published: October 2004

Barramundi,Lates calcarifer(Bloch), were immunized with an experimentalVibrio harveyibacterin via intraperitoneal injection, immersion and anal intubation. Both specific and non‐specific immune parameters were measured to compare responses to bacterin after delivery by various methods. Elevated antibody activities in sera were found in all treatment groups with barramundi injected intraperitoneally displaying significantly higher antibody activity than the other groups. In addition, there was evidence of memory induction with a heightened antibody response in the intraperitoneally injected group only. Bacteriostatic assays indicated activity againstV. harveyiin the sera of all bacterin‐treated groups; again this activity was significantly higher in the intraperitoneally injected groups. There was no enhancement noted in head kidney macrophage phagocytic activity or in serum lysozyme levels.
Inguinal hernia of seminal vesicle cyst
Authors: INOUE KATSUKI , HIGAKI YOSHIO , YOSHIDA HIDEKI
Published: October 2004

Seminal vesicle cysts are uncommon abnormalities in the pelvis. The case of a seminal vesicle cyst that extended through the inguinal canal is reported. A 35‐year‐old man presented with left inguinal swelling. He was diagnosed with a left inguinal hernia. However, the interpretative diagnosis was a spermatic cord tumor. The operation was changed to tumor resection. The tumor existed along with the vas deferens from part of the parietal peritoneum outside the inguinal tunnel to the deep pelvic space. The cylinder‐shaped tumor was 3 cm in diameter and 20 cm long. Pathological examination revealed a seminal vesicle cyst that extended through the inguinal canal. To the best of our knowledge, this is the first case report of a seminal vesicle cyst inguinal hernia.
THIS ARTICLE HAS BEEN RETRACTED Electroporation‐mediated muscarinic M3 receptor gene transfer into rat urinary bladder
Authors: OTANI MASAYUKI , YOSHIDA MASAKI , IWASHITA HITOSHI , KAWANO YOSHIAKI , MIYAMAE KOUICHI , INADOME AKITO , NISHI TORU , UEDA SHOICHI
Published: October 2004

Background: Muscarinic M3 (M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Under the hypothesis that overexpression of M3 receptor in the urinary bladder would enhance urinary bladder contractions, we have transferred the M3 receptor gene into rat bladders using electroporation (EP) and evaluated the functional expression of the transferred gene.

Methods: Plasmids expressing luciferase, a green fluorescence protein and M3 receptor were injected into the rat bladder and square‐wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining was performed and the contractile responses from isolated bladder strips, which were induced KCl, carbachol and electrical field stimulation (EFS), were evaluated.

Results: The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300‐fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti‐M3 receptor, an increase in immunoactivity was observed in the M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the transferred M3 receptor gene, carbachol‐ and EFS‐induced maximum contractile responses of bladder smooth muscle strips significantly increased.

Conclusions: These findings suggest that an in vivo EP procedure is an useful method for gene transfer into the bladder and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity.
Ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary internal iliac aneurysm
Authors: MINETA KAORI , NOMURA MASAYOSHI , FUJIMOTO NAOHIRO , TAKAHASHI KOICHI , MATSUMOTO TETSURO
Published: October 2004

We report a case of ureteral obstruction due to retroperitoneal fibrosis secondary to a solitary left internal iliac aneurysm. It has been reported that as a cause of ureteral obstruction, an internal iliac aneurysm without aortic and/or common iliac aneurysms is very rare. In the present case, magnetic resonance imaging was a useful modality to diagnose retroperitoneal fibrosis secondary to an internal iliac aneurysm as a direct cause of ureteral obstruction.
Transsphincteric repair of rectourethral fistulas following laparoscopic radical prostatectomy
Authors: DAFNIS GEORGE , WANG YU‐HUI , BORCK LEIF
Published: October 2004

Rectourethral fistula is a serious complication following laparoscopic radical prostatectomy. We report our experience with a transsphincteric approach in the repair of this uncommon complication. The rectourethral fistula was repaired in a three‐stage procedure comprising fecal diversion, transsphincteric repair of the fistula and, finally, closure of the stoma. Two patients with rectourethral fistulas underwent this procedure and the postoperative course was uneventful. In conclusion, a transsphincteric approach in the repair of rectourethral fistula by a three‐stage procedure is safe and may be the treatment of choice.
Bladder cancer in Sri Lanka: Experience from a tertiary referral center
Authors: GOONEWARDENA S.A.S. , DE SILVA W.A.S. , DE SILVA M.V.C.
Published: October 2004

Background: Bladder cancer is one of the most common malignancies occurring worldwide. No published data exists on bladder cancer in Sri Lanka. The objective of the study was to determine the clinicopathological characteristics of histologically confirmed transitional cell carcinoma (TCC) of the bladder in Sri Lanka.

Methods: Three hundred and one patients were diagnosed with primary bladder cancer during a 7.5‐year period from 1993 to 2000. Two hundred and eighty‐one patients (239 men and 42 women; mean age, 66 years; range, 26–88) with TCC of the bladder were evaluated with regard to clinical presentation, cystoscopic findings and histopathological data.

Results: Transitional cell carcinoma accounted for 93.4% of primary bladder cancer. There was a male predominance with a sex ratio of 6 : 1. The majority of patients (63.7%) were in the 7th and 8th decades of life. Painless hematuria was the most common presenting symptom (52.7%), followed by painful hematuria (39.2%). The median duration of hematuria for all TCC patients, as well as for muscle‐invasive TCC patients, was 3 months. Papillary configuration at cystoscopy, was found in 89.7% of non‐invasive urothelial tumors. In contrast, 77.8% of invasive TCC patients had a solid/mixed tumor configuration. One hundred and forty‐five patients (51.6% of TCC) had non‐invasive urothelial tumor and 136 patients (48.4%) had muscle‐invasive disease. In the non‐invasive urothelial tumor category, 61 patients (42.0%) had pTa tumors and 84 patients (58.0%) had pT1 tumors. Of newly diagnosed TCC cases, 5.3% were found to be T1G3 urothelial carcinomas. Fifty‐six patients (38.6%) with non‐invasive urothelial tumor had a tumor greater than 5 cm in size.

Conclusions: More than 90% of primary bladder tumors in Sri Lanka are TCC, with nearly half the patients having muscle‐invasive diseases on initial presentation. Even in non‐invasive urothelial tumors, the majority (58.0%) have lamina propria invasion.
Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinoma
Authors: IMAO TETSUYA , EGAWA MASAYUKI , TAKASHIMA HIROSHI , KOSHIDA KIYOSHI , NAMIKI MIKIO
Published: October 2004

Background: Although a correlation between microvessel density (MVD) and tumor aggressiveness has been established for several malignancies, the data for renal cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD, we investigated the relationships between MVD and tumor stage, grade, size, occurrence of metastasis and patient survival.

Methods: Tumor specimens from 70 patients with primary renal cell carcinoma were examined by immunohistochemical staining for CD34.

Results: There was a tendency for MVD to decrease from G1 to G3 tumors or from stage T1 to T3 tumors, although this was not statistically significant. However, the MVD for 56 non‐metastatic and 14 metastatic tumors were significantly different (P = 0.005) at 109 ± 67 and 58 ± 35 per ×400 field (mean ± SD), respectively. Microvessel density for 36 large and 34 small tumors was also significantly different (P < 0.0001) at 48 ± 22 and 142 ± 54 per ×400 field, respectively. The survival rate of patients with small, low grade and hypervascular tumors was significantly higher than that of patients with large (P = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional hazards regression analysis showed that tumor grade and size emerged as independent prognostic factors.

Conclusion: High MVD in RCC was inversely associated with tumor aggressiveness, but MVD was not the independent prognostic factor.
Sublingual sildenafil in the treatment of erectile dysfunction: Faster onset of action with less dose
Authors: DEVECI SERKAN , PEŞKIRCIOǦLU LEVENT , AYGÜN CEM , TEKIN M. İLTERIŞ , DIRIM AYHAN , ÖZKARDEŞ HAKAN
Published: October 2004

Background: The aim of the present study was to show the efficacy and safety of sublingual sildenafil and to determine whether lower doses cause the same effect with a faster onset of action in this mode of application.

Methods: Fourty consecutive patients with erectile dysfunction for more than three months were included in the study. The mean age was 55 years (range, 25–65). Serum glucose and testosterone levels, lipid profile and erectile function scores were obtained in all patients. Twenty patients received placebos and the other 20 patients received 20 mg sublingual sildenafil in a double blind randomized design.

Results: The effect of sildenafil on erection was significantly higher than that of placebo. Sixty‐five percent of patients (13/20) who received sublingual sildenafil achieved satisfying erections and coitus, whereas the rate was 15% in the placebo group (3/20). The mean onset of action with sublingual sildenafil was 15.5 min and lasted for an average of 40 min. Minimal headaches, sweating and flushing were noted as the side‐effects.

Conclusions: 20 mg sublingual sildenafil is safe and effective in the treatment of erectile dysfunction. Sublingual administration has some advantages as it is not effected by food ingestion and quickly appears in the circulation. These advantages provide a faster onset of action with a lower dose when compared to oral sildenafil. Sublingual use of sildenafil may be more cost‐effective and possibly provides a more predictable onset of action.
Estimation of damaged tubular epithelium in renal allografts by determination of vimentin expression
Authors: MURAMATSU MASAKI , MIYAGI MORIATSU , ISHIKAWA YUKIO , AIKAWA ATSUSHI , MIZUIRI SONOO , OHARA TAKEHIRO , ISHII TOSHIHARU , HASEGAWA AKIRA
Published: October 2004

Background: Various invasive and non‐invasive methods have been investigated for their prognostic value in predicting the outcome of renal allografts. In the present study, vimentin expression in tubular epithelial cells (TEC) was determined by the immunohistochemical examination of biopsy specimens and the prognostic value of this method was assessed.

Methods: Ninety‐two renal transplant recipients were recruited for the present study. Protocol biopsy of the renal graft was performed 1, 3 and 5 years after transplantation in each case. All biopsy specimens were treated with conventional stains and immunostained with an antivimentin antibody. The correlation between vimentin expression and glomerular filtration rate (GFR) and the association between vimentin expression and histopathological findings were determined.

Results: Vimentin was localized in TEC adjacent to interstitial lesions with lymphocyte infiltration and also in TEC with tubulitis or in atrophic tubules. Vimentin positivity significantly correlated with GFR and both vimentin positivity and GFR were significantly associated with the extent of chronic allograft nephropathy, but not with acute rejection. Additionally, vimentin expression and GFR 3 and 5 years after transplantation were higher in cases where graft loss occurred between 5 and 7 years after transplantation compared with graft survival cases.

Conclusions: These results suggest that immunohistochemistry using antivimentin antibodies on protocol biopsy specimens is useful for the detection of injured TEC and as a predictor of allograft outcome.
Large intestinal type‐urachal adenocarcinoma with focal expression of prostatic specific antigen
Authors: KATO HARUAKI , HAYAMA MASAYOSHI , KOBAYASHI MIKIKO , OTA HIROYOSHI , NISHIZAWA OSAMU
Published: October 2004

We present a case of colonic‐type adenocarcinoma, which might arise from an urachal remnant through a villous adenoma. The cancer tissue in the present case showed focal immunoreaction to prostate‐specific antigen (PSA). This is the first report of urachal adenocarcinoma expressing PSA.
Risk factors for febrile urinary tract infection in children with myelodysplasia treated by clean intermittent catheterization
Authors: SEKI NARIHITO , MASUDA KATSUAKI , KINUKAWA NAOKO , SENOH KOUHEI , NAITO SEIJI
Published: October 2004

Objective: To identify the factors involved in the incidence of febrile urinary tract infection (UTI) in a retrospective study of children with myelodysplasia who were treated by clean intermittent catheterization.

Methods: A total of 76 myelodysplastic children were included in the present study. Any factors, including urodynamic parameters and urinary tract abnormalities, that may have been associated with the incidence of febrile UTI were evaluated using both a univariate analysis and a multiple logistic regression analysis.

Results: Of the 76 patients, 19 (25%) had one or more episodes of febrile UTI. A univariate analysis showed low bladder compliance (<10 mL/cmH2O), detrusor overactivity, bladder trabeculation and the presence of vesico‐ureteral reflux (VUR) to be significant factors in the incidence of febrile UTI. The presence of detrusor overactivity and a low bladder compliance, in addition to the presence of VUR, were found to be significant factors for the incidence of febrile UTI using a multivariate analysis.

Conclusion: These results demonstrate that, in addition to VUR, urodynamics linked to bladder storage function disorder appear to be directly correlated with the cause of febrile UTI in children with myelodysplasia.
Laparoscopic partial nephrectomy for a renal tumor with tumor‐feeding artery ligation: Left renal cell carcinoma in the posterior mid zone
Authors: SHICHIRI YASUMASA , TAKAO NORIYASU , OIDA TOMOYUKI , KANAMARU HIROSHI , SHIMIZU YOSUKE
Published: October 2004

The most serious problem regarding a laparoscopic partial nephrectomy is how to perform bloodless excision without causing renal ischemia in a limited working space. We report the case of a 65‐year‐old man with left small renal cell carcinoma in the posterior mid zone who underwent a laparoscopic partial nephrectomy through a retroperitoneal approach by carrying out the ligation of the tumor‐feeding artery, but without clamping the renal pedicle. Both preoperative abdominal computed tomography (CT) and intraoperative ultrasonography revealed the tumor to be fully encapsulated. The tumor‐feeding artery could be exposed by dissection from the renal hilum and, after an arterial ligation, tumor resection with a safety margin was smoothly performed with minimal bleeding. Postoperatively, CT revealed a limited defect of the renal parenchyma and excretory pyelography showed no urine leakage or urinary tract obstruction. The preoperative and postoperative creatinine levels were 0.66 and 0.69 mg/dL, respectively. As a result, a tumor‐feeding artery ligation with a laparoscopic partial nephrectomy for left renal cell carcinoma in the posterior mid zone is considered to be an effective surgical modality which avoids renal ischemia and pelvic heat injury.
Distribution, mechanisms and evolutionary significance of clonality and polyploidy in weevils
Authors: Stenberg P. , Lundmark M.
Published: October 2004

Abstract 1 Genetical mtDNA relationships of 41 taxa of weevils were examined using cladistics. Ingroup taxa belong toOtiorhynchus scaberandO. nodosusand outgroup comparison was made withO. singularis. All three species are minor forest pests.

2 Otiorhynchus scaberspecimens are either diploid sexuals or diploid, triploid and tetraploid clones, from two different populations (Slovenia and Austria) that belong to two different evolutionary lineages.Otiorhynchus nodosusspecimens are tetraploid clones. Both species show geographical parthenogenesis, as do many otherOtiorhynchusspecies.

3 Mitochondrial data indicate thatO. nodosusclones are more closely related to Slovenian sexuals ofO. scaberthan these are to sexuals from Austria. It also shows that almost all clones ofO. scabercollected in one of the two regions where sexuals are found are more closely related to sexuals from the other region.

4 Three different hypotheses that may explain the distribution ofO. scaber, mechanisms important for the evolution of the clones and implications of the presence ofWolbachiaare discussed.

5 We conclude that parthenogenesis is likely to be linked to hybridization inO. scaberand that hybridization events between ancestors ofO. nodosusandO. scaberare the probable cause of the presence ofO. nodosusin the ingroup. We also find that polyploid clones are superior colonizers compared to sexuals and diploid clones, inO. scaber.

6 The results suggest that systems where both sexuals and clones exist are more complex than previously suggested. The mapping of genetic variation in clonal complexes and the tracing of clonal origins may be useful in pest management.
Effects of trimethoprim–sulfadiazine on tear production and the fluctuations of Schirmer tear test values in horses
Authors: Rothschild Chantal M. , Sellon Debra C. , Bryan Gary M. , Gay John M. , Hines Melissa T.
Published: October 2004

The objectives of this study were to observe the effects of trimethoprim–sulfadiazine on equine tear production and to determine normal fluctuations in Schirmer tear test (STT) values in horses. A randomized, placebo‐controlled, blinded clinical trial measuring STT values in 15 horses over an 8‐week period was performed. The treatment group (eight horses) received 30 mg/kg trimethoprim–sulfadiazine orally once a day and the control group (seven horses) received placebo (flour) at the same time. All horses were housed outdoors throughout the study. Schirmer tear test values were measured at 0, 2, 4, 6 and 8 weeks, and 4 weeks after discontinuation of treatment. There were no significant differences in tear production between the treated and control groups. Fluctuations in STT were observed and may result from individual and environmental variations. Trimethoprim–sulfadiazine did not decrease tear production in the horses in this study. Horses normally experience periodic fluctuations in STT values.
Three cases of prolapse of the nictitans gland in cats
Authors: Chahory Sabine , Crasta Manuela , Trio Stefania , Clerc Bernard
Published: October 2004

We report three cases of adult cats showing a prolapse of the gland of the third eyelid. Three different breeds were affected: Burmese, Persian and Domestic Short‐haired. In all cases, the disorder occurred spontaneously, without any other ocular sign. Surgical replacement of the gland was performed using the Morgan pocket technique. Good esthetic results were obtained, and no recurrence occurred.
Profiles of matrix metalloproteinase activity in equine tear fluid during corneal healing in 10 horses with ulcerative keratitis
Authors: Ollivier F. J. , Brooks D. E. , Van Setten G. B. , Schultz G. S. , Gelatt K. N. , Stevens G. R. , Blalock T. D. , Andrew S. E. , Komaromy A. M. , Lassaline M. E. , Kallberg M. E. , Cutler T. J.
Published: October 2004

Objective  Levels of tear film matrix metalloproteinases (MMPs) activity are significantly elevated in horses with ulcerative keratitis and contribute to the excessive breakdown of stromal collagen. Changes in the amount of proteolytic activity in horse tear film during corneal healing and stromal remodeling have not yet been reported, but we hypothesize they should decrease. In the present study we analyzed serial tear fluid from horses with ulcerative keratitis to identify any changes in MMP activity during corneal healing and stromal remodeling.

Procedures  Samples of tear fluid were obtained from both eyes of 10 horses with ulcerative keratitis on the day of admission (day 1) at the hospital and then at various time points until complete healing of the cornea. Tear film MMP2 and MMP9 activity was determined by quantitative gelatin zymography. In all cases medical treatment included topical applications of equine serum, antibiotics, atropine and systemic administration of anti‐inflammatory drugs. Surgical procedures were performed in several cases on day 2 in addition to the medical treatment.

Results  The mean total MMP activity (± SD) measured in relative standard units (RSU) in the tear fluid of the ulcerated eye (2.44 ± 1.44) of the 10 horses was significantly higher than the mean in the contralateral eye (0.81 ± 0.68) (P = 0.006), on the day of admission at the VMTH. The mean MMP activity in these ulcerated eyes significantly decreased (−82.4%) between the first day of admission and the day when the ulcer had completely healed (P = 0.0002). The activity level in the healed eye (0.43 ± 0.17) was not significantly different to the one in the contralateral eye (0.36 ± 0.18) on the day of complete corneal healing (P = 0.374). The level of MMP activity in the contralateral eye also decreased from 0.81 ± 0.68–0.36 ± 0.18 but this decrease (56%) was not significant (P = 0.069).

Conclusions  Ulcerative keratitis in horses is associated with initially high levels of tear film proteolytic activity that decrease as the ulcers heal. The success of medical and surgical treatment of the corneal ulcers is reflected by the enzyme activity in tears. In horses successful treatment does lead to a rapid reduction in tear film proteolytic activity that corresponded with the improvement in the clinical signs of corneal ulceration. Measurement of MMP activity in the tear film might represent a way to monitor the progression of corneal healing in horses with ulcerative keratitis.
Malignant teratoid medulloepithelioma with brain and kidney involvement in a dog
Authors: Aleksandersen Mona , Bjerkås Ellen , Heiene Reidun , Heegaard Steffen
Published: October 2004

Animal studied  A tumor of the left eye with involvement of the brain and kidney was diagnosed in a 4‐year‐old Neapolitan mastiff.

Procedure  The dog presented with acute glaucoma of the left eye. Peripheral corneal vascularization and severe corneal edema obscured examination of deeper structures. Because of concurrent progressive neurologic signs the dog was euthanized and a postmortem examination was performed. The eyes, brain and samples from the lung, heart, liver and kidneys were fixed in 4% neutral buffered formalin and embedded in paraffin wax. Sections were examined by light microscopy including histochemical and immunohistochemical staining.

Results  The ocular tumor originated from the ciliary body and was composed of small islets and cords of poorly differentiated, oval to polyhedral cells surrounded by abundant ground substance. Areas with chondroid differentiation were observed. Rosettes were not found. Metastases with the same morphology were present in the brain and in one kidney.

Conclusion  An intraocular malignant teratoid medulloepithelioma with metastases to the brain and kidney is presented.
DID TIME INCONSISTENCY CONTRIBUTE TO THE GREAT INFLATION? EVIDENCE FROM THE FOMC TRANSCRIPTS
Authors: Chappell Henry W. , McGregor Rob Roy
Published: October 2004

We use evidence from detailed records of FOMC deliberations to argue that time inconsistency theory can help explain the excessive monetary expansion that characterized Arthur Burns's tenure as Federal Reserve Chairman (1970–1978). The records suggest that the Fed perceived a Phillips curve tradeoff and political pressures that made it difficult to adopt disinflationary policies; the tendency toward excessively expansionary policy was exacerbated by the short‐run planning horizon the Committee faced in each of its meetings. We argue that comparative static predictions of the time inconsistency model are consistent with the rise of inflation during the Burns years and its subsequent fall.
VOTING TRANSPARENCY, CONFLICTING INTERESTS, AND THE APPOINTMENT OF CENTRAL BANKERS
Authors: Gersbach Hans , Hahn Volker
Published: October 2004

We examine whether the publication of the individual voting records of central‐bank council members is socially desirable when the preferences of the central bankers differ. We identify two positive effects of transparency. First, central bankers whose preferences differ from those of society may act in the interest of society in order to increase their re‐appointment chances. Second, transparency enhances the efficiency of the appointment process since the government can align the preferences of the central‐bank council with those of the public over time. In a monetary union, our findings about the desirability of transparency may be reversed.
The Influence of New Public Management Practices on Product Costing and Service Pricing Decisions in Dutch Municipalities
Authors: Groot Tom , Budding Tjerk
Published: October 2004

New Public Management reforms are aimed at improving effectiveness and efficiency of performance by a great variety of different organisational, managerial and accounting reforms. In the last decade, a great number of the 572 Dutch municipalities have been implementing some NPM reforms, most notably decentralisation of responsibilities to lower organisational levels and restructuring of the budget and financial reports into a product based format. This study comprises a survey among 114 municipalities to assess the relationship between NPM reforms and municipalities’ decisions on costing and pricing of their services. As expected, decentralised municipalities monitor more strictly the degree in which costs are covered by revenues. Moreover, municipalities applying product budgeting systems use more sophisticated cost accounting methods in calculating full product costs of services. Given the fact that decentralisation may help municipalities to make operational managers more accountable for performance and that product budgeting systems enhance cost consciousness among municipal managers, we expect NPM measures to contribute to lower prices for services rendered to citizens. The results show that the two NPM measures do not have any relation with price setting for garbage collection. However, the NPM decentralisation measure is significantly related to higher prices for contracting marriages. In this paper we try to come up with some alternative explanations for these unexpected findings.
APETALA3 and PISTILLATA homologs exhibit novel expression patterns in the unique perianth of Aristolochia (Aristolochiaceae)
Authors: Jaramillo M. Alejandra , Kramer Elena M.
Published: October 2004

Summary
Several lines of evidence suggest that sterile floral organs, collectively known as the perianth, have evolved multiple times during the evolution of the angiosperms. In the family Aristolochiaceae, the perianth is formed by two whorls of organs in the genus Saruma but by only one whorl in the remaining genera, including Aristolochia. Although the morphology of Saruma is similar in appearance to the core eudicot perianth, with leaf‐like sepals and showy colored petals, the unipartite perianth of Aristolochia combines morphological aspects of both calyx and corolla. To investigate the organ identity program functioning in the novel perianth of Aristolochia, we identified homologs of the B‐class genes APETALA3 (AP3) and PISTILLATA (PI) in both Saruma and Aristolochia. The expression patterns of these genes in Saruma indicate they are functioning in the development of the second whorl petaloid organs and third whorl stamens. In Aristolochia, however, the expression of AP3 and PI homologs in the perianth does not suggest a role in organ identity but, rather, in promoting late aspects of cell differentiation. The implications of these findings for the evolution of both petaloidy and B gene function are discussed.
Exceptionally Symmetric Crystal Structure of (Pentabenzylcyclopentadienyl)(cyclooctatetraene)titanium(III)
Authors: Císařová Ivana , Varga Vojtech , Horáček Michal , Kubišta Jiří , Mach Karel
Published: October 2004

Complex [Ti(III)(η8-C8H8)(η5-C5Bn5)] (1) was prepared by salt metathesis reaction of [TiCl(η8-C8H8)(thf)]2 with LiC5Bn5 and characterized by ESR and UV-near-IR spectra. Its crystal structure is symmetric with respect to a mirror plane involving the titanium atom and one of the benzyl groups.
Synthesis and Conformational Analysis of New 17-Alkyl Derivatives of Lupanine and Their Perchlorate Salts
Authors: Jasiewicz Beata , Boczoń Władysław , Kurek Joanna
Published: October 2004

New 17-alkyl derivatives of lupanine and their perchlorate salts have been synthesised. Substituents at C-17 are introduced by treatment of C(17)=N(16) immonium perchlorate 2 with alkylmagnesium compounds. NMR spectra of the new compounds have been taken to study the chemical shift changes caused by the introduced alkyl substituents, ethyl and butyl. In 17-alkyl derivatives (17-ethyl- (3) and 17-butyllupanine (4)) the substituent is equatorially oriented. All the lupanine derivatives analysed have the same structure, i.e. ring C in a boat conformation. The reaction of 17-butyllupanine (4) and 17-cyanolupanine (5) with methyllithium has led to 17-butyl-2-methyl-2,3-didehydrosparteine (6), 17-butyl-2-methylsparteine (7) and 17-cyano-2-methyl-2,3-didehydrosparteine (8).
Warfarin reversal
Authors: Hanley J P
Published: October 2004

Warfarin is the most commonly used oral anticoagulant in the UK. It is associated with few side effects apart from haemorrhage. The most appropriate way to reverse the anticoagulant effect of warfarin depends on the clinical circumstances. In serious bleeding, rapid reversal is required, whereas in minor bleeding or asymptomatic over anticoagulation, a more leisurely approach is usually appropriate. This review discusses the current approaches to warfarin reversal in clinical practice. The development of a uniform approach to warfarin reversal in the Northern Region is described.
Extracutaneous infantile haemangioma is also Glut1 positive
Authors: Drut R M , Drut R
Published: October 2004

Aim:To investigate whether extracutaneous infantile haemangioma-like tumours are immunohistochemically similar to cutaneous infantile haemangiomas.

Methods:Mammary, salivary gland, liver (one each), and placental (two cases) capillary haemangiomas and typical examples of cutaneous (eight cases) infantile haemangioma were investigated immunohistochemically for α smooth muscle actin and Glut1, a proposed marker for the skin localised lesion. Positive internal controls included red blood cells, perineurium, trophoblast, and endothelial cells of the placental capillaries. Extralesional vessel endothelium acted as a negative control (except in the placenta). The liver haemangioma and both chorioangiomas presented in patients with Beckwith-Wiedemann syndrome.

Results:The endothelial cells of all the vascular lesions were Glut1 positive. These were consistently surrounded by a rim of α smooth muscle actin positive pericytic cells. Controls reacted appropriately.

Conclusions:All infantile haemangiomas were immunohistochemically positive for Glut1: expression of this molecule was not limited to infantile haemangiomas of the skin. These tumours comprise proliferations of both endothelial and pericytic cells. The association with Beckwith-Wiedemann syndrome may provide a clue to the molecular genetics of infantile haemangioma.
Use of tissue microarray for interlaboratory validation of HER2 immunocytochemical and FISH testing
Authors: Kay E , O’Grady A , Morgan J M , Wozniak S , Jasani B
Published: October 2004

Aims:To evaluate the use of tissue microarray (TMA) technology as a validation tool for HER2 testing by both immunocytochemistry (ICC) and fluorescence in situ hybridisation (FISH) in the diagnostic setting.

Methods:TMA constructs from 57 cases of breast cancer were evaluated for HER2 (by ICC and FISH) by two centres. The results were compared.

Results:There was a high level of concordance for both ICC and FISH. In five “discrepant” cases only three would have had a potential impact on patient management.

Conclusions:Validation of HER2 analysis in the clinical setting by ICC and FISH is essential. The use of TMAs provides for an economy of scale and would be practical in the setting of interlaboratory and intralaboratory validation. It is suggested that routine HER2 ICC and FISH should continue to be performed in laboratories on whole sections. Following this, TMAs would be constructed for all cases of breast cancer. ICC and FISH would be performed on these to validate the results. The TMAs would be available for circulation to other centres for validation purposes. The standardisation of testing between centres, the potential difficulty of minimum case numbers, and the workload issues surrounding validation would all be facilitated by this approach.
Karyometry detects subvisual differences in chromatin organisation state between non-recurrent and recurrent papillary urothelial neoplasms of low malignant potential
Authors: Scarpelli M , Montironi R , Tarquini L M , Hamilton P W , López Beltran A , Ranger-Moore J , Bartels P H
Published: October 2004

Aim:To analyse nuclear chromatin texture in non-recurrent and recurrent papillary urothelial neoplasms of low malignant potential (PUNLMPs).

Materials:Ninety three karyometric features were analysed on haematoxylin and eosin stained sections from 20 PUNLMP cases: 10 from patients with a solitary PUNLMP lesion, who were disease free during at least eight years’ follow up, and 10 from patients with unifocal PUNLMP, one or more recurrences being seen during follow up.

Results:Kruskal-Wallis analysis was used to search for features showing significant differences between recurrent and non-recurrent cases. Significance was better than p<0.005 for more than 20 features. Based on significance, six texture features were selected for discriminant analysis. Stepwise linear discriminant analysis reduced Wilk’s λ to 0.87, indicating a highly significant difference between the two multivariate data sets, but only modest ability to discriminate (70% correct case classification). A box sequential classifier was used based on data derived from discriminant analysis. The classifier took three classification steps and classified 19 of the 20 cases correctly (95% correct case classification). To determine whether significant case grouping could also be obtained based on an objective criterion, the merged data sets of non-recurrent and recurrent cases were submitted to the unsupervised learning algorithm P-index. Two clusters were formed with significant differences. The subsequent application of a Cooley/Lohnes classifier resulted in an overall correct case classification rate of 85%.

Conclusions:Karyometry and multivariate analyses detect subvisual differences in chromatin organisation state between non-recurrent and recurrent PUNLMPs, thus allowing identification of lesions that do or do not recur.
The metabolic marker tumour pyruvate kinase type M2 (tumour M2-PK) shows increased expression along the metaplasia–dysplasia–adenocarcinoma sequence in Barrett’s oesophagus
Authors: Koss K , Harrison R F , Gregory J , Darnton S J , Anderson M R , Jankowski J A Z
Published: October 2004

Background:Proliferating and tumour cells express the glycolytic isoenzyme, pyruvate kinase type M2 (M2-PK). In tumours cells, M2-PK usually exists in dimeric form (tumour M2-PK), causing the accumulation of glycolytic phosphometabolites, which allows cells to invade areas with low oxygen and glucose concentrations.

Aims:To investigate the expression of tumour M2-PK during the metaplasia–dysplasia–adenocarcinoma sequence of Barrett’s oesophagus, and to assess the prognostic usefulness of tumour M2-PK in oesophageal cancer.

Materials/Methods:One hundred and ninety cases selected from the histopathology archives as follows: 17 reflux oesophagitis, 37 Barrett’s oesophagus, 21 high grade dysplasia, 112 adenocarcinomas, and three control tumours. Sections were stained immunohistochemically with antibody to tumour M2-PK.

Results:Tumour M2-PK was expressed in all cases, and increased cytoplasmic expression was seen with progression along the metaplasia–dysplasia–adenocarcinoma sequence. All cases of adenocarcinoma showed 100% staining so that tumour M2-PK was not a useful prognostic marker.

Conclusions:Tumour M2-PK is not a specific marker of Barrett’s adenocarcinoma, but may be important as a marker of transformed and highly proliferating clones during progression along the metaplasia–dysplasia–adenocarcinoma sequence.
Erdheim-Chester disease: case report with multisystemic manifestations including testes, thyroid, and lymph nodes, and a review of literature
Authors: Sheu S-Y , Wenzel R R , Kersting C , Merten R , Otterbach F , Schmid K W
Published: October 2004

Erdheim-Chester disease is a rare non-Langerhans’ cell histiocytosis with characteristic radiological and histological features. This entity is defined by a mononuclear infiltrate consisting of lipid laden, foamy histiocytes that stain positively for CD68. About half of those affected have extraskeletal manifestations, including involvement of the hypothalamus–pituitary axis, lung, heart, retroperitoneum, skin, liver, kidneys, spleen, and orbit. This report describes the case of a 50 year old white man who presented with hypogonadism and diabetes insipidus. At necropsy, extensive organ involvement was found, including the testes, thyroid, and lymph nodes. This is the first report of thyroid and lymph node infiltration in this disease. Because of the endocrinological symptoms, neurosarcoidosis and hypophysitis are important diseases in the differential diagnosis. This report also includes a review of the literature concerning rare organ manifestations and patients presenting primarily with similar symptoms.
Miniature tissue microarrays for HercepTest® standardisation and analysis
Authors: Gulmann C , Loring P , O’Grady A , Kay E
Published: October 2004

Aims:To assess the practicality of using a miniature tissue microarray (TMA) with several examples of each HercepTest® score from 0 to 3+ as a control for routine HercepTest immunohistochemistry.

Methods:A TMA was constructed from in house cases of breast cancer where HercepTest on the whole sections showed scores 0, 1+, 2+, or 3+. The TMA, which measured 5 × 5 mm, was designed with four rows (each representing scores 0, 1+, 2+, and 3+), with five 0.6 mm cores from separate cases. In all, 20 individual cases were represented and the TMA took less than one hour to construct. Fifty sequential 4 µm sections were cut from the TMA to maximise the number of available sections. They were stored at 4°C for 1–270 days and when a case needed HercepTest staining the section was added to the TMA tissue control slide.

Results:All slides contained tissue spots and immunohistochemical staining was consistent throughout the time period.

Conclusions:The miniature TMA with examples of all HercepTest scores described here is an ideal tissue control and can be used as a visual reference for scoring a case. Slides stored at 4°C could be used for up to 270 days.
WHO reclassification of breast lymphomas: Table 1
Authors: Loughrey M B , Windrum P , Catherwood M A , Alexander H D , Markey G M , McManus D T , Morris T C M
Published: October 2004

Fourteen cases of breast lymphoma, identified from hospital records between 1990 and 2004, were reclassified according to the World Health Organisation criteria. Primary cases occurred more frequently and all cases were of B cell origin, predominantly involving the right breast. Most primary cases were diffuse large B cell lymphomas, whereas secondary cases were heterogeneous in type and most had a poor prognosis.
LOCAL FIELDS IN BOUNDARY CONFORMAL QFT
Authors: LONGO ROBERTO , REHREN KARL-HENNING
Published: October 2004

Conformal quantum field theory on the half-space x>0 of Minkowski space-time ("boundary CFT") is analyzed from an algebraic point of view, clarifying in particular the algebraic structure of local algebras and the bi-localized charge structure of local fields. The field content and the admissible boundary conditions are characterized in terms of a non-local chiral field algebra.