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The correlation between oostegite formation and ovarian maturation was investigated in the isopod Armadillidium vulgare. Females whose ovaries had been removed and males whose androgenic glands had been removed were used in these experiments. Ovariectomy of puberal females did not stop oostegite formation. Whether oostegites develop in puberal females whose ovaries have been removed depends upon the degree of maturation of the ovaries at the time of removal. On the other hand, ovariectomized juvenile females and andrectomized juvenile males were unable to form oostegites when they attained puberty. An extract of vitellogenic ovaries induced oostegite formation in ovariectomized females and andrectomized males, but not in intact males. The ability of ovarian extracts to induce oostegite formation was dose-dependent. The nature of this ovarian factor that induces oostegite formation in A. vulgare remains to be elucidated.

Evidence is presented for the first time for the complete sex-reversal of genetic males of the terrestrial isopod Armadillidium vulgare into functional females folloing partial gonadectomy. Fifth-instar males were used. The anterior half of their rudimentary reproductive organs along with the attached androgenic glands were removed. Six months later these animals formed oostegites and laid eggs, and when bred with normal males, produced only male offspring. These results show that in the absence of the androgenic gland, female sex characteristics differentiate and oogenesis occurs in genetic males.

The mefenamic acid (MFA)-casein solid dispersions were prepared for the purpose of enhancing the dissolution properties of MFA by two different methods, lyophilization and solvent evaporation.In the case of the solid dispersions prepared by the lyophilization method, the X-ray diffraction patterns indicated that MFA in the solid dispersion lost its crystalline property. But diffraction peaks still remained in the solid dispersion prepared by the solvent evaporation method.The dissolution rate of solid dispersions prepared by lyophilization method markedly increased, and the solid dispersion at 1: 3 w/w mixing ratio of MFA to casein gave the maximum amount of dissolution which was three times as much as that of MFA alone.It was suggested that supersaturation of MFA in dissolution medium was caused by the crystalline inhibitory effect of the casein.In the case of the solid dispersions prepared by the lyophilization method, the X-ray diffraction patterns indicated that MFA in the solid dispersion lost its crystalline property. But diffraction peaks still remained in the solid dispersion prepared by the solvent evaporation method.The dissolution rate of solid dispersions prepared by lyophilization method markedly increased, and the solid dispersion at 1: 3 w/w mixing ratio of MFA to casein gave the maximum amount of dissolution which was three times as much as that of MFA alone.It was suggested that supersaturation of MFA in dissolution medium was caused by the crystalline inhibitory effect of the casein.

Interactions of carbamazepine (CBZ) with α-, β-and γ-cyclodextrin (CyD) in aqueous solution were investigated by the solubility method.The apparent stability constant of CBZ/γ-CyD complex was found to be largest among the three CyD complex. The solid complex of CBZ with γ-CyD in the molar ratio of 1: 1 was prepared by the saturated solution method, and the interaction between host and guest molecule was confirmed by X-ray diffractometry, differential scanning calorimetry (DSC), infrared analysis (IR) and proton nuclear magnetic resonance spectroscopy (1H-NMR).The dissolution rate of CBZ in the solid complex was larger than that of CBZ crystalline alone.

The non-invasive methods of treatments have been studying for the improvement of quality of life (QOL) of patients undergoing treatment. A photodynamic therapy (PDT) is one of the non-invasive treatments. PDT is the methods of treatment using combination of a laser and a photosensitizer. PDT has few risks for patients. Furthermore, PDT enables function preservation of a disease part. PDT has been used for early cancer till now, but in late years it is applied for age-related macular degeneration (AMD). AMD is one of the causes of vision loss in older people. However, PDT for AMD does not produce the best improvement in visual acuity. The skin photosensivity by an absorption characteristic of a photosensitizer is avoided. We examined new PDT using combination of an ultra-short pulsed laser and indocyanine green (ICG).

Inchinkoto (ICKT), a herbal medicine, has been recognized in Japan and China as a “magic bullet” for jaundice. To explore potent therapeutic agents for cholestasis, the effects of ICKT or its ingredients on multidrug resistance-associated protein 2 (Mrp2/ MRP2)-mediated choleretic activity, as well as on antioxidative action, were investigated using rats and chimeric mice with livers that were almost completely repopulated with human hepatocytes. Biliary excretion of Mrp2 substrates and the protein mass, subcellular localization, and mRNA level of Mrp2 were assessed in rats after 1-wk oral administration of ICKT or genipin, a major ingredient of ICKT. Administration of ICKT or genipin to rats for 7 days increased bile flow and biliary excretion of bilirubin conjugates. Mrp2 protein and mRNA levels and Mrp2 membrane densities in the bile canaliculi and renal proximal tubules were significantly increased in ICKT- or genipin-treated rat livers and kidneys. ICKT and genipin, thereby, accelerated the disposal of intravenously infused bilirubin. The treatment also increased hepatic levels of heme oxygenase-1 and GSH by a nuclear factor-E2-related factor (Nrf2)-dependent mechanism. Similar effects of ICKT on MRP2 expression levels were observed in humanized livers of chimeric mice. In conclusion, these findings provide the rationale for therapeutic options of ICKT and its ingredients that should potentiate bilirubin disposal in vivo by enhancing Mrp2/MRP2-mediated secretory capacities in both livers and kidneys as well as Nrf2-mediated antioxidative actions in the treatment of cholestatic liver diseases associated with jaundice.

Enhancement of the lidocaine penetration without ablation using an MIR-FEL. Lidocaine flux at 0.5 hour with the irradiated skin using an MIR-FEL was enhanced 10 fold faster than with the non-irradiated skin.

Objective We longitudinally examined the changes of brachial to ankle distensibility using pulse wave velocity (PWV) throughout pregnancy and its difference between normal pregnancy and pregnancy-induced hypertension (PIH) groups. Study design One hundred and eighty-three pregnant women were included in this study. The PWV examinations were performed in a longitudinal way during the first, second, and third trimesters of pregnancy, and immediately and 1 month after delivery. Results In normal pregnancies, the PWV significantly decreased at the second trimester, increased from the third trimester through immediately after delivery, and decreased again at 1 month after delivery. In PIH patients, it increased in proportion to the progression of gestation. Conclusion We monitored the longitudinal changes in PWV and constructed a PWV normogram during pregnancy. The predictive value of PWV and blood pressure for PIH was higher than that of blood pressure alone, suggesting the usefulness of measuring PWV to predict PIH.

The objective of this study was to provide preliminary toxicity data of multiple-cycle combination chemotherapy with intraperitoneal (IP) carboplatin and intravenous (IV) paclitaxel for further clinical trials. The toxicity data of 42 patients with müllerian carcinoma who underwent IP carboplatin therapy in combination with IV paclitaxel were retrospectively analyzed. Chemotherapy was repeated through the Bard IP port placed at initial surgery using IV paclitaxel at 175 mg/m2 followed by IP carboplatin. The doses of carboplatin were either at area under the curve (AUC) = 5, 6, 6.5, 7, or 7.5. The toxicity data in a total of 237 cycles were analyzed. The median number of cycles for IP chemotherapy was 6 (range: 3–12). The incidences of maximal grade toxicities in all cycles were: grade (G)2/3 nausea/vomiting, 23.8%; G2/3 constipation, 42.9%; G2 abdominal pain, 28.6%; G2/3 sensory neuropathy, 14.3%; motor neuropathy, 4.8%; myalgia/arthralgia 33.4%; G3/4 neutrocytopenia, 85.4%; and G3/4 anemia, 35.4%. These were not related to the dose of carboplatin. The incidences of G3 thrombocytopenia in relation to the dose of carboplatin were AUC = 5, 0%; 6, 31.6%; 6.5, 44.4%; 7, 25.0%; and 7.5, 80%. G4 thrombocytopenia did not occur. A dose of carboplatin between AUC = 6 and 7 with IV paclitaxel at 175 mg/m2 is warranted for further evaluation.

A cholesterol ester is selective dissociated by MIR-FEL irradiation with wavelength of 5.75 μm correspond to C=O stretching vibration of ester bond. To evaluate the optimum irradiation condition for cholesterol ester decomposition without normal endothelium cell damage, we perform a 5.75 μm-FEL irradiation to a two-layer vessel model which is cholesterol oleate as a model of atherosclerotic lesions and gelatin as a model of endothelial cells. The ester decomposition and gelatin damege depends on total power density of 5.75 μm-FEL provided the two-layer model. Exposure of the FEL with power density exceed 17.8 W/cm 2 decomposed cholesterol ester thorough gelain layer of 15 μm thickness. If FEL with power density of 25.0 W/cm 2 is exposed during 10 seconds, the gelatin is evaporized. Therefore, the optimum condition for ester decomposition without gelatin evaporation is between 75 J/cm 2 from 20 J/cm 2 in the case of 15 μm gelatin layer thickness. The maximum ester decomposition rate without gelatin vaporization is 71% on FEL of power density of 17.8 W/cm 2 for 10 seconds.

Phosphorylation and dephosphorylation, which are the most remarkable posttranslational modifications, are considered to be important chemical reactions that control the activation of proteins. In regenerative medicine, it has been reported that phosphorylated proteins are instrumental in the calcification of osteoconnective tissue. We examine the phosphorylation analysis method by measuring the infrared absorption peak of phosphate group that observed at about 1070 cm -1 (9.4 mm) with Fourier Transform Infrared Spectrometer (FT-IR). This result indicates that it is possible to identify a phosphorylation by measuring the infrared absorption peak of phosphate group observed at about 1070 cm -1 with FT-IR method. And we examine laser-dephosphorylation using Free Electron Laser (FEL) as a novel dephosphorylation method. After irradiation of 9.4mm-FEL, infrared absorption peak of phosphate group is reduced. It is suspected that this lowering of the peak of phosphate group is the effect like dephosphorylation. These novel methods can be applied to quality control technology in regenerative medicine.

A 44-year-old man was referred to Hakodate Chuo Hospital because of progressive fatigue in April 2001, and was diagnosed as having adult T-cell leukemia (ATL; acute type). Complete remission was not obtained even with the application of multiple anti-leukemic agents including CHOP-V-MMV. The patient received an allogeneic bone marrow transplant from his HLA-identical, HTLV-I antibody-negative sibling donor in June 2002. The conditioning regimen consisted of cyclophosphamide, etoposide and total body irradiation. Cyclosporine A and a short course of methotrexate were given as prophylaxis for graft-versus-host disease (GVHD). Engraftment was achieved on day 16, while ATL cells were detected in the peripheral blood throughout the transplantation. ATL cells were also detected in bone marrow on day 20. Withdrawal of the immunosuppressant induced the eradication of the residual ATL cells in the peripheral blood on day 24 and in the bone marrow on day 40. Grade III of acute GVHD developed in the bowel on day 40, which lasted for over 5 months and was gradually resolved by administration of prednisolone and tacrolimus. The patient remains in complete remission 23 months after the transplantation. The clinical consequence of our case clearly shows that a graft-versus-leukemia (GVL) effect combined with graft-versus-host disease (GVHD) plays a curative role even in an early phase after bone marrow transplantation for patients with adult T-cell leukemia.

Treatment guidelines for patients with idiopathic thrombocytopenic purpura (ITP) have been changed recently due to the clinical application of Helicobacter pylori (H. pylori) eradication but there has been no detailed multi-center analysis of the hematological effects of H. pylori eradication. The Clinical Hematology Forum consists of 11 large hematological departments and divisions in the Hokkaido area. We sent questionnaires to these 11 hematological departments and divisions in March 2003 to obtain information on current treatment strategies for patients with ITP and hematological results after the eradication of H. pylori. Questionnaires were returned by 9 (81.8%) of the 11 departments. Doctors in all hospitals had experience in diagnosis and treatment of H. pylori infection. Diagnostic examinations for H. pylori infection were performed in 54.3% of the registered cases. H. pylori infection was detected in 68.1% of the examined cases, and eradication treatment was performed in 87.7% of H. pylori-positive patients. H. pylori was eradicated in 52 (83.9%) of the 62 patients in whom the results of treatment could be evaluated. Among the patients whose platelet counts were less than 10.0 x 10(4)/microl, platelet recovery was observed in 48.8% of cases with successful eradication, a percentage similar to previously reported percentages in Japan. There was no prognostic factor to predict good responders before eradication treatment. Since the side effects of eradication treatment, including gastrointestinal symptoms and skin eruptions, were not serious, this method might become a front-line treatment for patients with ITP. Patient selection for eradication as an up-front treatment, analysis of the pathophysiology of platelet recovery after eradication and long-term effects should be investigated to make new treatment guidelines for newly diagnosed patients with ITP.

Tryptophan pyrrole ring cleavage enzymes were assayed in pregnant uterus of mouse. The highest activity was observed at 6.5 days post-coitus (dpc) with a small activity shoulder at 9.5 to 12.5 dpc concepti and placenta. The highest peak at early concepti of 6.5 dpc was coincided with gene expression of tryptophan 2,3-dioxygenase (TDO). And the shoulder from 9.5 dpc was coincided with the expression of indoleamine 2,3-dioxygenase (IDO). These enzymes showed a different inhibitory behavior to a proper IDO inhibitor, 1-methyl tryptophan. In situ hybridization analysis revealed that TDO was expressed in the decidua of the early concepti. This is the first report of the extra hepatic TDO.

Cdt1 is a licensing factor for DNA replication, the function of which is tightly controlled to maintain genome integrity. Previous studies have indicated that the cell cycle-dependent degradation of Cdt1 is triggered at S phase to prevent re-replication. In this study, we found that Cdt1 is degraded upon DNA damage induced by either UV treatment or gamma-irradiation (IR). Although the IR-triggered degradation of Cdt1 was caffeine-insensitive, the UV-triggered degradation of Cdt1 was caffeine-sensitive. This indicates that the cells treated with UV utilize the checkpoint pathway, which differs from that triggered by IR. A recent study has suggested that Cdt1 is phosphorylated, ubiquitylated, and degraded at the G(1)/S boundary in the normal cell cycle. Treatment with MG132, a proteasome inhibitor, inhibited the degradation of Cdt1 and resulted in the accumulation of the phosphorylated form of Cdt1 after UV treatment. In the case of UV treatment, phosphorylation of Cdt1 induced the recruitment of Cdt1 to a SCF(Skp2) complex. Moreover, ectopic overexpression of Cdt1 after UV treatment interfered the inhibition of DNA synthesis. These results indicate that Cdt1 is a target molecule of the cell cycle checkpoint in UV-induced DNA damage.

To explain the pain and dysfunction of neck during jaw movement associated with malocclusion, the physiologic relationships between jaw and cervical movement should be understood. However the complicated reflex effects made it difficult to investigate the biomechanical relationship between the head-neck components. For this reason we have created a model for mechanical system dynamic analysis of the normal stomatognathic system to assess the biomechanics of the cervical movement and muscle activity during jaw movement. We have also statistically validated the model and quantitatively verified the model to the human subject by the amounts and conditions of cervical muscle activity. During jaw opening-closing phases the movement of the model was highly correlated to the subject with an identical movement. However low consistency was achieved during intercuspid phase. These findings indicate the establishment of a valid system, which can be used to evaluate the biomechanical relationships between jaw and cervical movement. Moreover the model verification of cervical muscle activity indicate the mechanical action of jaw can be the primary factor to modify cervical muscles, and cervical muscles coordinate to resist changes in head balance during jaw movement to maintains head posture.

The present study investigated the potency of the mannosylated cationic liposomes (Man liposomes) that we have developed in novel DNA vaccine carrier. Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. The potency of the Man liposome/pCMV-OVA complex was compared with naked pCMV-OVA and that complexed with DC-Chol liposomes. In cultured mouse peritoneal macrophages, MHC class I-restricted antigen presentation of the Man liposome/pCMV-OVA complex was significantly higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. After intravenous administration, OVA mRNA expression and MHC class I-restricted antigen presentation on CD11c+ cells and inflammatory cytokines, such as TNF-alpha, IL-12, and IFN-gamma, that can enhance the Th1 response of the Man liposome/pCMV-OVA complex were higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. Also, the spleen cells from mice immunized by intravenous administration of the Man liposome/pCMV-OVA complex showed the highest proliferation response and IFN-gamma secretion. These findings suggest that the targeted delivery of DNA vaccine by Man liposomes is a potent vaccination method for DNA vaccine therapy.

Objective Currently, no long-term follow-up data are available on intraperitoneal (IP) carboplatin-based chemotherapy for ovarian carcinoma. In this study we evaluated retrospectively the survival and recurrence of a retrospective cohort of patients with epithelial ovarian cancer treated with first-line IP carboplatin-based therapy. Methods Records were reviewed of 174 patients with epithelial ovarian cancer who received IP carboplatin-based therapy between 1990 and 2000. All patients underwent surgical staging, and implantable port systems were placed regardless of residual tumor size. The pathological slides were submitted and reviewed, and then nine patients were excluded because of borderline malignancies ( n = 8), and wrong histology ( n = 1). Therefore, the records of 165 patients were analyzed for survival. Tumor grade was determined by the Universal grading system. Statistical analysis included tests for association between potential prognostic factors, and between prognostic factors and survival. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a Cox regression model. Results The mean age of the patients was 53.7 years (range 21–83). The median follow-up was 41 months. The distribution by stage and histology was as follows: high risk (grade 2/3, clear cell, capsule rupture) stage I, 54; II, 21; III, 72; IV, 18; and serous, 75; clear cell, 30; mucinous, 27; endometrioid, 20; others, 13. The chemotherapy regimen was either carboplatin alone ( n = 22) or in combination with cyclophosphamide ( n = 116) or paclitaxel ( n = 27). Catheter-related complications occurred in 16 (9.7%) cases. The chemotherapeutic response in 54 patients with measurable disease was 66.4%. The 5-year survival was 94.4% for stage I, and 87.9% for stage II. The median survival for optimal and suboptimal stage III/IV patients was 51 months and 34 months, respectively. The median survival of patients with stage III/IV disease was 51 months with carboplatin doses of 400 mg/m 2 or more, but it was only 25 months with carboplatin doses smaller than 400 mg/m 2 . Poor prognostic factors, determined by Cox regression multivariate analysis, were clear cell histology ( P 2 ( P = 0.002). Conclusions Survival of patients who underwent carboplatin-based IP chemotherapy was excellent when the dose of carboplatin was higher than 400 mg/m 2 . A prospective evaluation of IP carboplatin therapy with modern combination is warranted.

In this study, we examined the affinities of many (21) compounds such as hormones, pharmaceuticals, industrial chemicals, and phytoestrogens to the estrogen receptor (ER) by ER binding assay using fluorescence polarization (FP). This method is based on the competitive binding assay using fluorescein-labeled estradiol (F–E2), in which the polarization values decreased with the addition of the compounds (competitors). The obtained sigmoidal inhibition curves were transformed into the pseudo-Hill plots, and the concentrations at 50% inhibition (IC50) and Hill coefficients were obtained from the regression equations. We examined the relationship between the chemical structures and estrogenic activities, and finally classified the tested compounds into three categories, agonists, partial agonists and antagonists based on their Hill coefficients.

To develop new fluorescent derivatization reagents, we investigated the relationship between the chemical structures and the fluorescence quantum yields (phi(f)) of coumarins, quinoxalinones and benzoxadinones. Forty-six compounds were synthesized and their fluorescence spectra were measured in n-hexane, ethyl acetate, methanol and water. The energy levels of these compounds were calculated by combination of the semi-empirical AM1 and INDO/S (CI = all) methods. The deltaE(Tn(n,pi*), S1(pi,pi*)) (the energy gap between the Tn(n,pi*) and S1(pi,pi*) states) values were well correlated with the phi(f) values, which enables us to predict the phi(f) values from their chemical structures. Based on this relationship, 3-phenyl-7-N-piperazinoquinoxalin-2(1H)-one (PQ-Pz) and 7-(3-(S)-aminopyrrolidin-1-yl)-3-phenylquinoxalin-2-(1H)-one (PQ-APy) were developed as fluorescent derivatization reagents for carboxylic acids. The derivatives of the carboxylic acids with PQ-Pz and PQ-APy showed large phi(f) values even in polar solvents, suggesting that these reagents are suitable for the microanalysis of biologically important carboxylic acids by reversed phase HPLC.

Tryptophan pyrrole ring cleavage enzymes were assayed in pregnant uterus of mouse. The highest activity was observed at 6.5 days post-coitus (dpc) with a small activity shoulder at 9.5 to 12.5 dpc concepti and placenta. The highest peak at early concepti of 6.5 dpc was coincided with gene expression of tryptophan 2,3-dioxygenase (TDO). And the shoulder from 9.5 dpc was coincided with the expression of indoleamine 2,3-dioxygenase (IDO). These enzymes showed a different inhibitory behavior to a proper IDO inhibitor, 1-methyl tryptophan. In situ hybridization analysis revealed that TDO was expressed in the decidua of the early concepti.

Over the past 20 years, the management of vulvar cancer has changed dramatically. The radical vulvectomy that was previously believed to be the only effective treatment for vulvar cancer has now been replaced by more individualized treatments. These include conservative surgery for patients with isolated lesions, omission of groin lymph node dissection in T1A tumors with stromal invasion1 mm, elimination of routine pelvic lymphadenectomy, groin lymph node dissection with separate groin incision, omission of contralateral groin lymph node dissection in T1 tumor with negative ipsilateral node metastasis, use of preoperative radiotherapy to avoid pelvic exenteration in advanced cases, and postoperative radiotherapy to decrease the incidence of groin recurrence in patients with multiple positive groin nodes. In addition to these changes, the identification of sentinel lymph nodes and chemoradiation therapy are currently under investigation. In this review, we discuss these issues along with the evidence upon which these therapies are based.

Whereas mobilization to inflammatory sites is an important function of neutrophils, it remains to be determined whether granulocyte colony-stimulating factor (G-CSF) stimulates the mobilization of neutrophils to the inflammatory sites. This study compared the expression of more than 9000 genes in neutrophils treated with and without G-CSF with the use of a DNA microarray system to determine the effects of G-CSF on the function of neutrophils. It was found that messenger RNA expression of epithelial cell–derived neutrophil attractant-78 (ENA-78), which has been reported to be a chemotactic factor for neutrophils, was induced by G-CSF in neutrophils. The study demonstrated that the supernatant of G-CSF–treated neutrophils induced the chemotaxis of neutrophils and that anti–ENA-78 antibody and anti–CXCR-2 antibody inhibited the chemotaxis. These data suggest that G-CSF may enhance the mobilization of neutrophils and consequently augment the accumulation of neutrophils in the inflammatory sites through the secretion of ENA-78.

We report a rare case of chronic eosinophilic leukemia (CEL) with a chromosomal abnormality of t(6;11)(q27;q23). The patient was diagnosed as having thyroid cancer with metastases to the lung and cervical lymph nodes in 1993. Percutaneous ethanol injection therapy (PEIT), total thyroidectomy, and radiotherapy were performed. The patient was also diagnosed as having prostatic cancer with bone metastasis in July 1999, and hormonal therapy was performed. At the time of the diagnosis of prostatic cancer, leukocytosis with eosinophilia was also revealed. Thereafter, cytogenetical analysis and reverse transcriptase polymerase chain reaction (RT-PCR) analysis of bone marrow showed t(6;11)(q27;q23) translocation and MLL/AF6 fusion products, respectively. No transcripts of the BCR/ABL chimeric gene were found by RT-PCR in bone marrow. Analysis of serum cytokines revealed a slight elevation of GM-CSF but no elevation of IL-3 or IL-5. Tissue damage due to infiltration of eosinophils was not observed throughout the clinical course. On the basis of the cytogenetic and molecular abnormality, the patient was diagnosed as having CEL, rather than reactive eosinophilia due to thyroid or prostatic cancer or other reactive inflammation. This is the first case report of CEL with t(6;11)(q27;q23) translocation.

A 21-year-old male patient with non-Hodgkin's lymphoma (diffuse large T-cell type, clinical stage IV) received allogeneic bone marrow transplantation (BMT) from a partially HLA-mismatched unrelated donor in July 1998 and achieved complete remission. Thereafter, he suffered from chronic graft-versus-host disease (GVHD) and was continuously administered immunosuppressive drugs for a long time. Two years after the BMT, he complained of severe pain in the right knee, which was swollen, and was diagnosed as having pneumococcal purulent genual arthritis. He underwent arthroscopic synovectomy and was administered systemic and intra-articular antibiotics, leading to a gradual improvement. Streptococcal infections are often seen in patients in the late phase after allogeneic BMT because of immunodeficiency associated with chronic GVHD and hyposplenism. Most streptococcal infections are respiratory tract infections and septicemia, and there have been very few reports on cases of purulent genual arthritis. Administration of prophylactic antibiotics and control of chronic GVHD, which is a risk factor of pneumococcal infection, seem to be important to prevent purulent genual arthritis.

Reverse seroconversion of hepatitis B virus (HBV) after allogeneic BMT is rare. We present a case of HBV reactivation late after allogeneic BMT which responded well to lamivudine therapy. A 35-year-old woman with CML received an allogeneic BMT. Before BMT, the patient had immunity to HBV, with serum antibodies against hepatitis B surface antigen (HBsAb), and the donor was completely negative for HBV. Four years after BMT, acute hepatitis occurred with a detectable level of HBV-DNA. Lamivudine rapidly reduced transaminase and bilirubin levels, and serum HBV-DNA decreased to negative. Retrospective analysis revealed that there had been a gradual decrease in serum HBsAb titers after BMT. Administration of lamivudine immediately after HBV replication may be more effective than vaccination of hepatitis B surface antigen-negative donors before BMT.

Osteopetrosis is a rare genetic disorder in which the function of osteoclasts is defective, resulting in impaired bone resorption. This disease is usually accompanied by myelosuppression due to decreased marrow space and by osteomyelitis, especially in the submandibular bone. We report the case of a 72-year-old woman with an autosomal dominant form of osteopetrosis who suffered from peripheral T-cell lymphoma. Accurate clinical and pathological diagnoses and staging were difficult due to nonspecific reactive hyperplasia of the lymph nodes, even though we used several scintigraphic techniques and [18F]fluorodeoxyglucose positron emission tomography. We also paid special attention to myelosuppression and exacerbation of osteomyelitis after combination chemotherapy. Severe infectious complications were avoided by early administration of G-CSF for leukocytopenia and by continuous oral administration of antibiotics. The patient achieved complete remission after four courses of chemotherapy and this status has been maintained for 6 months.

Primary lymphomas of spermatic cord are extremely rare. In a review of the world medical literature, until now, only fourteen cases of spermatic cord lymphoma have been reported, and, furthermore, they have a poor prognosis even in patients with stage I disease. Herein, we report a new case of primary non-Hodgkin's lymphoma of the spermatic cord. In August, 1993, 76-year-old man visited an urological hospital with a compaint of a right intrascoral mass, and underwent orchiectomy. Macroscopically no invasive lesion in the testis was observed, and the tumorous lesion was restricted to the epididymis. The histopathological study indicated that he suffered from primary malignant lymphoma of the spermatic cord (B-cell, diffuse medium-sized cell type). As radiographic investigations showed no other invasive lesion, the patient was diagnosed to be in stage IE. He was followed only with clinical observation, and, in August, 1996, relapsed with extensive disease in the abdoninal cavity, and was transferred to our hospital. Fourty months after the orchiectomy, he died of progression of disease irrespective of the salvage radio-chemotherapies given to him.

A 21-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation from an HLA-identical sibling donor. The patient also had chronic hepatitis B and the donor was an HBV carrier. To decrease HBV and improve hepatic dysfunction before BMT, the patient had received lamivudine for 6 months. After marrow transfusion, administration of lamivudine was continued to inhibit replication of donor-derived HBV. The patient showed hematological engraftment on day 13 without any serious liver dysfunction. Eight months after BMT, she is now alive and well without chronic liver GVHD or reactivation of hepatitis B. HBV-DNA was not detected in the patient's serum. Administration of lamivudine to a BMT recipient with chronic hepatitis B may be a safe and promising way to prevent fatal liver dysfunction in the setting of allogeneic BMT, even in the event of BMT from an HBV-positive donor.

A 21-year-old woman with severe aplastic anemia received an allogeneic bone marrow transplant (allo-BMT) from an HLA-matched and ABO-matched sibling donor after conditioning with cyclophosphamide, rabbit ATG (Lymphoglobuline; Aventis-Pharma), and total lymphoid irradiation. She had a long history of cyclosporin A (CsA) therapy before conditioning. She complained of severe headache and convulsions on day 0, and findings on magnetic resonance images suggested CsA-induced encephalopathy. CsA was immediately stopped, and tacrolimus for prevention of graft-versus-host disease (GVHD) was started on day 2. Hematological engraftment was observed on day 14 without serious GVHD. Prompt diagnosis, replacement of immunosuppressive agents, and careful monitoring of serum drug concentrations are thought to have contributed to the patient's good clinical course, since CsA-induced encephalopathy tends to be recurrent but to improve completely without any sequelae.

An enzyme with both inorganic polyphosphate [poly(P)]- and ATP-dependent NAD kinase activities was isolated from Micrococcus flavus. The enzyme was a dimer consisting of 34 kDa subunits, and was named poly(P)/ATP-NAD kinase. Internal amino acid sequences of the enzyme showed homologies with some function-unknown proteins released on the GenBank database. Among such proteins, hypothetical Rv1695 protein (Accession No. Z98268-16), which was encoded by a gene named "Rv1695" on genomic DNA of Mycobacterium tuberculosis H37Rv, was proposed to be poly(P)-dependent NAD kinase. By cloning and expression in Escherichia coli, Rv1695 was shown to encode poly(P)/ATP-NAD kinase and named ppnk. The ppnk product, recombinant-poly(P)/ATP-NAD kinase (Ppnk) was purified and characterized. The enzyme was a tetramaer consisting of 35 kDa subunits when expressed in E. coli. Poly(P)/ATP-NAD kinases of M. flavus and Ppnk of M. tuberculosis H37Rv specifically and completely phosphorylated NAD by utilizing commercially available poly(P)s and nucleoside triphosphates as phosphoryl donors.

Association rule is a kind of important knowledge extracted from databases. However, a large number of association rules may be extracted. It is difficult for a user to understand them. How to select some “representative” rules is thus an important and interesting topic. In this paper, we proposed a distance-based approach as a post-processing for association rules on numeric attributes. Our approach consists of two phases. First, a heuristic algorithm is used to cluster rules based on a matrix of which element is the distance of two rules. Second, after clustering, we select a representative rule for each cluster based on an objective measure. We applied our approach to a real database. As the result, three representative rules are selected, instead of more than 300 original association rules.

Objective. Intraperitoneal chemotherapy for minimal residual ovarian cancer has been shown to be effective. However, evaluation of the response without a second-look laparotomy (SLL) is impossible because such disease is unmeasurable by radiographic studies. In this prospective pilot study, we evaluated the relationship between implantable port system (IPS)-cytology and findings by SLL in patients with unmeasurable diseases. Methods. Patients eligible for this study were those who had either unmeasurable residual disease at the time of initial surgery or measurable residual disease which became unmeasurable before second-look laparotomy. At the time of the initial surgery, the IPS was placed and intraperitoneal chemotherapy was administered. To obtain IPS-cytology, approximately 500 ml of saline was infused, with the patients changing their position to wash the peritoneal surface as thoroughly as possible. More than 20 ml of saline was recovered for cytological evaluation. SLL was performed after 4 to 10 courses of chemotherapy. Results of IPS-cytology obtained immediately before SLL and the SLL findings were compared. Results. Forty-four patients were entered into this study. Twenty-nine patients had unmeasurable residual disease at the time of initial surgery and 15 had measurable residual disease which became unmeasurable before SLL. Only 40 patients were eligible for evaluation because catheter failure occurred in 4 patients. Three of the 26 patients who had negative IPS-cytology results were found to have positive SLL results. All 14 patients who had positive IPS-cytology results also had positive SLL results. Conclusions. IPS-cytology can detect intraperitoneal persistent disease in patients with unmeasurable residual ovarian cancer. Persistent positive IPS-cytology can indicate a negative response to chemotherapy, thus making it possible to avoid SLL. Further study with a larger number of patients is required to determine the role of negative IPS-cytology.

Male F-344 rats were exposed by inhalation to gaseous formaldehyde at 0.3, 2, and 15 ppm 6 h/day, 5 days/week for 28 months. Nasal tumors were macroscopically evident in the 15 ppm group from the 14th month and 8 of 32 rats bore such tumors at the 24th month. Histopathological examination revealed both squamous cell papillomas and carcinomas. No nasal tumors were observed in the lower exposure groups (0.3 and 2ppm groups). In the high exposure group (15 ppm group), frequent face washing, coughing and/or crouching position, lacrimation, nasal discharge, and yellow discoloration of the haircoat were observed. Significant decrease in food consumption and body weight was noted, and 20 (88.3%) rats died by the 24th month. Reduced triglyceride levels and liver weights, presumed to be related to the drop in food intake, were also seem in the 15 ppm group. Epithelial cell hyperplasia, hyperkeratosis, and the squamous metaplasia were apparent in all exposure groups. Inflammatory cell infiltration, erosion or edema were evident in all groups, including the 0 ppm and room (RC group) controls. In this; study, a no effect level of formaldehyde vapor could not be obtained because toxicological signs were obvious even with the low exposure group. The benchmark doses for squamous metaplasia and epithelial hyperplasia were 0.25 and 0.24 ppm, respectively.

The androgenic glands (AG) of crustaceans are responsible for differentiation of male sexual characters. The process of gonadal differentiation in females was studied morphologically in Armadillidium vulgare given a masculinizing AG implant. Gonadal masculinization was induced by implantation of an AG into females at various stages of postembryonic development. Functional sex reversal always occurred when an AG was implanted into females that were in stages 5 and 6 of development. Partial formation of testes was induced after implantation of an AG into stage 7 and 8 females. When an AG was implanted into a stage 9 female, development of a functional testis was not observed, but the ovaries were partially masculinized. These results show that after the onset of sex differentiation female gonads retain sexual bipotentiality through several stages of postembryonic development. Implantation of one AG into a female is enough to induce gonadal masculinization and sex reversal in this species. The AG implant up to stage 6 (3.4 mm in body length) is an experimental procedure certain to transform a genetic female into a functional male. The process of gonadal development in female A. vulgare is discussed.

Groups of 30 Wistar rats of each sex were treated with 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (MBEBP) in the diet at levels of 0, 0.03, 0.1 and 0.3% for up to 18 months. In both sexes, survival rates of treated groups were similar to those of the controls. Body weight gain was depressed (0.3% group in males, 0.1 and 0.3% groups in females). Slight anaemia (0.3% groups in both sexes) and increase of blood urea nitrogen (0.3% groups in both sexes) were observed. Histopathologically, vacuolization of the parathyroid gland cells (0.3% group in males and all treated groups in females) and degenerative changes of the kidney (0.1 and 0.3% groups in males) were observed. No neoplastic responses following MBEBP administration were noted. From these results, the no-observed-adverse-effect level (NOAEL) for MBEBP toxicity was estimated as 12 mg kg-1 body wt. day-1 in male rats. In female rats, the lowest-observed-adverse-effect level (LOAEL) was estimated as 15 mg kg-1 body wt. day-1.

Abstract 2641 INTRODUCTION: Since the introduction of the anti-CD20 monoclonal antibody rituximab, the outcomes of B-cell non-Hodgkin lymphoma (B-NHL) have improved markedly. However, fulminant hepatitis due to reactivation of hepatitis B virus (HBV) infection has emerged as a serious problem. Recently, rituximab plus corticosteroid containing chemotherapy (R-chemo) has been identified as a risk factor for HBV reactivation in hepatitis B surface antigen (HBsAg)-negative B-NHL patients. Currently, there is no standard management to prevent HBV reactivation in HBV-resolved patients without HBsAg, but with antibodies against hepatitis B core antigen (anti-HBc) and/or HBsAg (anti-HBs). PATIENTS AND METHODS: We conducted a multicenter prospective observational study to estimate the incidence of HBV reactivation by serial monthly monitoring of HBV DNA in HBV-resolved patients with B-NHL during and just after R-chemo, and to establish preemptive antiviral therapy guided by this monitoring. The major eligibility criteria included previously untreated CD20-positive B-NHL with prior HBV-resolved infection, and planned treatment with 6 to 8 cycles of R-chemo defined by protocol. The baseline HBV status was evaluated on enrollment at each institute, comprising HBsAg, anti-HBc, and anti-HBs serology. Patients were excluded if they were seropositive for hepatitis C virus or human immunodeficiency virus. Plasma HBV DNA levels were measured independently at a central laboratory, using an automated real-time TaqMan polymerase chain reaction assay after enrollment. The primary end point was the incidence of HBV reactivation defined as HBV DNA levels of 1.8 log copies per mL or more. If HBV DNA levels of less than 1.8 log copies per mL were confirmed at baseline, the serial monitoring of HBV DNA (without prophylaxis of antiviral drugs) was performed with assessments every 4 weeks after enrollment for 1.5 years. Prompt antiviral treatment with an anti-HBV nucleoside analogue (entecavir, 0.5 mg per day) was highly recommended in patients with confirmed HBV reactivation. An ancillary study was conducted to identify risk factors for HBV reactivation using the preserved specimens. The protocol was approved by the Institutional Review Board of each participating institution. All patients gave written informed consent. The planned interim analysis was performed after the enrollment of 200 patients, using data available up to June 30, 2011. RESULTS: Between Sept. 2008 and Sept. 2010, a total of 187 patients (50.8% male) with a median age of 63 years (range, 26 to 79) from 45 institutes were analyzed. Histologic subtypes of B-NHL were diffuse large B-cell lymphoma (n=121, 64.7%), follicular lymphoma (n=57, 30.5%), MALT lymphoma (n=5, 2.7%) and other types (n=4, 2.0%). The number (%) of patients positive for both anti-HBc and anti-HBs was 132 (70.6%), 35 (18.7%) were positive for anti-HBc but negative for anti-HBs, and 19 (10.2%) were negative for anti-HBc but positive for anti-HBs. One patient was positive for anti-HBc but lacked anti-HBs measurement. 168 (89.8%) patients received 6 to 8 cycles of R-CHOP (n=151) or other R-chemo (n=17). With a median follow-up of 549 days (range, 35 to 939), HBV reactivation was observed in 16 out of 187 analyzed patients. The incidence of HBV reactivation at 1 year was 7.7% (95% confidence interval [CI], 4.7 to 12.7). HBV reactivation was diagnosed at a median time of 158 days (range, 33 to 490) after enrollment. No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were 1.8 to 3.1 log copies per mL. Multivariate analysis of the ancillary study showed that an anti-HBs baseline titer less than 10 mIU per mL was an independent risk factor for HBV reactivation, compared to a titer of 100 mIU per mL or more (adjusted hazard ratio, 5.3; 95% CI, 1.3 to 21.8; p=0.02). HBV mutations of precore (G1896A) or basal core promoter (A1762T/G1764A) that enhanced HBV replication were identified in 4 patients, two of whom had both mutations. Our strategy could inhibit such highly replicative clones and prevent hepatitis. CONCLUSIONS: Monthly monitoring of HBV DNA is highly effective for preventing hepatitis due to HBV reactivation in HBV-resolved B-NHL patients treated with R-chemo. (UMIN-CTR 000001299) (This study was supported by the Ministry of Health, Labour and Welfare of Japan.) Disclosures: Kusumoto: Bristol-Myers Squibb: Honoraria; Zenyaku Kogyo: Honoraria; Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Abbott: Honoraria. Tanaka:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria; Abbott: Honoraria. Tanaka:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Kinoshita:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria. Ogura:Chugai Pharmaceutical Co., LTD.: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Zenyaku Kogyo: Honoraria, Research Funding. Mizokami:Chugai Pharmaceutical Co., LTD.: Honoraria; Abbott laboratories: Honoraria. Ueda:Chugai Pharmaceutical Co., LTD.: Research Funding.

Objective: Glucagon-like peptide-2 (GLP-2) is an endogenous meal-stimulated hormone secreted by L-cells of terminal ileum and colon. In clinical trials with GLP-2 in short bowel syndrome (SHS) we noted increased redness and size of stoma nipples. GLP-2 receptors are co-localized with endothelial nitric oxide synthase (eNOS) and prerequisites for blood flow effects of GLP-2 are fulfilled. We used native GLP-2 in combination with saline and to study laser Doppler flow (LDF) in jejunal stomas in man. Methods: 5 patients with SBS; small bowel

G A A b st ra ct s induced gastric lesions at 6, 12 and 24 h upon 3.5 h of WRS exposure (series B). In separate series, rats with chronic gastric ulcers induced by serosal application of acetic acid (ulcer area=28 mm2) were treated daily for 9 and 15 days with: 1) vehicle (saline); 2) Hp2-20 (0.5 25 mg/kg i.g.) or 3) control peptide Hp1 (10 mg/kg i.g.) with or without non-selective and selective inhibitors of cNOS and iNOS, L-NNA (20 mg/kg-d i.p.) and L-Nil (5 mg/kgd i.p.) without or with the combination with L-arginine (200 mg/kg-d s.c.). The gastric juice was collected for acid output assessment and the number and area of WRS lesions and ulcers were determined planimetrically, the gastric blood flow (GBF) was determined by H2-gas clearance technique and luminal NOx concentration, plasma VEGF levels, the expression of mRNAs for VEGF and FPR mRNA and protein were assessed by ELISA, RTPCR and Western Blot. Hp2-20 dose-dependently inhibited the gastric acid secretion and decreased the number of WRS-induced gastric lesions at 6h, 12 h and 24 h by 16%, 38% and 46%, respectively. Hp2-20 reduced the area of acetic acid ulcers; the dose inhibiting by 50% (ID50) of ulcer area at day 9 upon ulcer induction being 10 mg/kg and this was accompanied by the rise in GBF at ulcer margin, luminal NOx levels and VEGF concentration. Treatment with L-NNA and L-Nil which by themselves increased the area of gastric ulcer significantly reduced the healing effects of Hp2-20 and accompanying rise in the GBF and plasma NOx concentration. These increase in the area of gastric ulcers and accompanying fall in GBF and NOx content induced by L-NNA and L-Nil were reversed by L-arginine added to NOS inhibitors. Upregulation of mRNA and protein for VEGF and FPR at ulcer marginwas observed inHp2-20-treated animals and these effects were significantly attenuated by L-NNA or L-Nil. We conclude that Hp2-20 enhances the mucosal recovery from WRSinduced lesions and accelerates the healing of preexisting gastric ulcers due to upregulation of FRP receptors via mechanism involving inhibition of gastric acid secretion, an activation of NO/NOS pathway and an overexpression and release of VEGF at the ulcer margin responsible for new microvessels formation.

The influence of three serum separators, A, B and C, on biochemical values was examined. With A or B, changes in the values of ChE, LAP, UN, K, P, Cl and Ca in rat serum; ChE, UN, Cl and Ca in dog serum; and K and P in monkey serum took place over a period of 20 min after blood collection. Therefore, the biochemical values of whole blood were considered to be stable after 20 min. Thus, biochemical tests were conducted on serum from the three serum separators after allowing the blood to stand 20 min. The values obtained for each separator were not markedly different from those of the control. These results suggest that a serum separator is useful for separation of serum of experimental animals under the proper conditions.