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Objectives: To identify appropriate clinical tests for determining the demand for personal care in older Japanese people., Design: Cross-sectional observation study., Setting: Obu Study of Health Promotion for the Elderly (Obu, Aichi) and Tsukui Ordered Useful Care for Health (241 day-care centres) cohorts in Japan., Participants: A total of 10 351 individuals aged 65 years or older (6791 with personal care and 3560 without personal care) participated in the study., Measures: Physical performance tests included grip strength, the chair stand test, walking speed at a comfortable pace, and the timed up-and-go test. Personal care was defined as participants who had been certified in the national social long-term care insurance in Japan., Results: Individuals who received personal care showed a significantly poorer performance than those without personal care for all physical performance tests (p<0.001). Gait speed was the most useful of the physical performance tests to determine the demand for personal care (receiver operating characteristic curve statistics: men, 0.92; women, 0.94; sensitivity: men, 86; women, 90; specificity: men, 85; women, 85). After adjustment for age, sex, cognitive impairment and other physical tests, all physical performance tests were individually associated with the demand for personal care. A slow gait speed (<1 m/s) was more strongly correlated with the demand for personal care than other performance measures (gait speed OR: 5.9; 95% CI: 5.0 to 6.9)., Conclusions: Clinical tests of physical performance are associated with the demand for personal care in older people. Preventive strategies to maintain physical independence may be required in older adults who show a gait speed slower than 1 m/s. Further research is necessary to confirm these preliminary results.

Purpose: To assess the long-term effects of nilvadipine on the progression of central visual field defect in retinitis pigmentosa (RP)., Methods: Patients with RP were randomly divided into a treated group receiving oral nilvadipine and a control group. Progression of RP was evaluated with MD slope and the average sensitivity of the central 2° (ΔCENT4)., Results: The mean MD slopes were -0.55/-0.39 (right/left eyes, n = 19) dB/year in the treated group and -1.37/-1.15 (right/left eyes, n = 22) dB/year in the control group (P = 0.016/0.050, resp.). In both eyes, however, no statistical difference was observed between the two groups for the ΔCENT4 values., Conclusion: Although we confirmed that nilvadipine significantly retarded the progression of the average of MD value defects in the central 10°, it was not specific for the central 2° of the visual field in RP.

A series of 4-aryl-1,1-dicyanobutenes (1a-1f) with different substituents were synthesized to control the intramolecular donor-acceptor or charge-transfer (C-T) interactions in the ground state. Photoexcitation of these C-T substrates led to competitive cyclization and rearrangement, the ratio being critically controlled by various environmental factors, such as solvent polarity, temperature and static pressure, and also by excitation wavelength and supramolecular confinement (polyethylene voids). In non-polar solvents, the rearrangement was dominant (>10 : 1) for all examined substrates, while the cyclization was favoured in polar solvents, in particular at low temperatures. Selective excitation at the C-T band further enhanced the cyclization up to >50 : 1 ratios. More importantly, the cyclization/rearrangement ratio was revealed to be a linear function of the C-T transition energy. However, the substrates with a sterically demanding or highly electron-donating substituent failed to give the cyclization product.

Purpose: The purpose of this study was to investigate the inhibitory effect of solid hyaluronic acid-carboxymethylcellulose film on the formation of wound adhesion after strabismus surgery on rabbit eyes., Methods: The authors performed strabismus surgery on rabbit eyes with hyaluronic acid film applied under and above the muscles. Histological examination was performed 90 days postoperatively using Masson trichrome staining. The length of adhesion tissues in the operated area was quantitatively compared between film-treated and control eyes., Results: Hyaluronic acid film significantly prevented the formation of adhesions between muscle, conjunctiva, and sclera after strabismus surgery (t test, P < .05)., Conclusion: The current results indicate that hyaluronic acid film can inhibit the formation of postoperative adhesion around conjunctiva, muscle, and sclera to some extent. The authors conclude that this substance offers potential benefits for ophthalmic surgery, not only with strabismus surgery but also procedures such as scleral buckle., (Copyright 2011, SLACK Incorporated.)

Purpose: To assess the effects of nilvadipine on the progression of central visual field defect in retinitis pigmentosa (RP)., Design: Prospective, randomized, nonmasked, single-center trial., Methods: Patients with RP were randomly divided into a treated group receiving oral nilvadipine at 4 mg/day for ≥30 months and a control group receiving tocopherol nicotinate at 300 mg/day, helenien at 15 mg/day or no medication for the same periods. Progression of RP was evaluated using the 10-2 SITA Fast Program of the Humphrey Visual Field Analyzer, and regression coefficients calculated from the time courses of mean deviation (MD slope) were compared between groups., Results: Nineteen patients in the treated group and 14 patients in the control group completed the follow-up for ≥30 months. The mean (±standard deviation) duration of observation was 48.8 ± 11.8 months (median 48 months, range 30-66 months) for the treated group and 49.2 ± 18.1 months (median 48 months, range 30-90 months) for the control group (p = 0.94). Mean (±standard error of the mean, SEM) regression coefficients of the averaged MD values for the initial 30 months were -0.35 ± 0.17 dB/year in the treated group and -0.75 ± 0.06 dB/year in the control group (p < 0.01). Mean (±SEM) MD slopes for total observational periods were -0.49 ± 0.17 dB/year in the treated group and -0.89 ± 0.16 dB/year in the control group (mean ± SEM, p = 0.042)., Conclusion: Nilvadipine at 4 mg/day significantly retarded progression of central visual field defects in RP in this small patient series., (Copyright © 2010 S. Karger AG, Basel.)

Trehalose is a disaccharide which plays an important role in preserving cells from completely dehydrated circumstances. In this study, we investigated effects of trehalose on proliferative activity of fibroblasts and epithelial cells both in vitro and in vivo. As in vitro assessment, normal human dermal fibroblasts and normal human epidermal keratinocytes were cultured in media containing various concentrations of trehalose. Growth activities of cells were evaluated with MTT assay and diff-quick™ staining. Expressions of vimentin and α smooth muscle actin (α-SMA) changed by trehalose were semiquantitatively measured by Western blot. As an in vivo study, 5% or 10% trehalose was topically instilled onto rabbit eyes after simple conjunctival incision or trabeculectomy. Condition of the surgical wound was evaluated by morphologically and immunohistochemically using isolectin B4 and antibodies specific for vimentin and α-SMA. Intraocular pressures (IOPs) after trabeculectomy were compared between eyes treated with trehalose and 0.04% mitomycin C (MMC). Results obtained by in vitro experiments showed that growth activities of cultured fibroblasts and keratinocytes were inhibited by trehalose in a dose-dependent manner. Fibroblasts were strongly inhibited by trehalose concentrations ≧ 5% of trehalose, whereas keratinocytes were less inhibited compared to fibroblasts. Expressions of vimentin and α-SMA were reduced by trehalose. With in vivo experiments, postoperative application of trehalose resulted in less firm adhesion between conjunctiva and sclera compared to controls. Immunohistochemical studies showed reduced staining of isolectin B4, vimentin and α-SMA in conjunctival wounds treated by topical trehalose. Also, after trabeculectomy, IOP remained in a low range during instillation of topical trehalose solution. We concluded that trehalose has inhibitory effects on proliferation of fibroblasts and vascular tissues, partially due to inhibition of transformation of fibroblasts into myofibroblasts in wound tissues. The present results imply that trehalose can be a potential agent for preventing postoperative fibrous scar formation after ocular surgery such as glaucoma filtration surgery., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

General electronic medical records systems remain insufficient for ophthalmology outpatient clinics from the viewpoint of dealing with many ophthalmic examinations and images in a large number of patients. Filing systems for documents and images by Yahgee Document View (Yahgee, Inc.) were introduced on the platform of general electronic medical records system (Fujitsu, Inc.). Outpatients flow management system and electronic medical records system for ophthalmology were constructed. All images from ophthalmic appliances were transported to Yahgee Image by the MaxFile gateway system (P4 Medic, Inc.). The flow of outpatients going through examinations such as visual acuity testing were monitored by the list "Ophthalmology Outpatients List" by Yahgee Workflow in addition to the list "Patients Reception List" by Fujitsu. Patients' identification number was scanned with bar code readers attached to ophthalmic appliances. Dual monitors were placed in doctors' rooms to show Fujitsu Medical Records on the left-hand monitor and ophthalmic charts of Yahgee Document on the right-hand monitor. The data of manually-inputted visual acuity, automatically-exported autorefractometry and non-contact tonometry on a new template, MaxFile ED, were again automatically transported to designated boxes on ophthalmic charts of Yahgee Document. Images such as fundus photographs, fluorescein angiograms, optical coherence tomographic and ultrasound scans were viewed by Yahgee Image, and were copy-and-pasted to assigned boxes on the ophthalmic charts. Ordering such as appointments, drug prescription, fees and diagnoses input, central laboratory tests, surgical theater and ward room reservations were placed by functions of the Fujitsu electronic medical records system. The combination of the Fujitsu electronic medical records and Yahgee Document View systems enabled the University Hospital to examine the same number of outpatients as prior to the implementation of the computerized filing system.

A 75-year-old man undergoing operations for rectal cancer was given adjuvant chemotherapy for 6 months. Fourteen months after surgery, peritoneal dissemination was found, so mFOLFOX6 therapy was started. After 34 courses of mFOLFOX6 therapy, peritoneal dissemination progressed. As a second-line treatment, we administered FOLFIRI therapy. The patient visited our emergency unit with the chief complaint of a fever thirteen days after the second course was completed. A chest imaging study showed diffuse infiltrative shadow and ground glass shadow bilaterally. Chemical interstitial pneumonia was suspected from his clinical findings. In the ICU, respiratory care by BiPAP and steroid pulse therapy(mPSL 1 g/day for three days)were performed. Steroid therapy improved his respiratory status and chest image findings, and he was able to leave the ICU on the seventh day. We continued steroid internal use treatment and he was discharged on the 70th day. The agent causing interstitial pneumonia was thought to be CPT-11 from the administration history. The incidence of interstitial pneumonia as an adverse event of CPT-11 is low, but it can be fatal without adequate attention. Steroid pulse therapy was validated for treatment, and it served to prolong life.

We report a 37-year-old woman who complained of chest discomfort as of August 2004, and was found to have advanced esophageal cancer in the upper thoracic area in December 2004.S he was diagnosed as Stage IVa (T4N1M0) because chest computed tomography (CT) indicated trachea invasion and lymph node metastasis. We diagnosed it to be a case of unresectable esophageal cancer, and she underwent chemoradiation therapy. CT showed regression of the main tumor and metastatic lymph nodes when the CRT course was completed. The main tumor disappeared macroscopically. We again considered an operation, but the CRT was so effective that the patient wished to continue CRT and underwent three courses. Endoscopy showed disappearance of the main tumor and Lugol's solution. Following this, 10 courses of the treatment with CDDP alone (CDDP 10 mg/weekly) were continued until the appearance of renal dysfunction. S-1 (100 mg/body/day)was started in September 2005. The treatment is currently ongoing, and no recurrence or metastases had occurred as of March 2009.

The patient was a 54-year-old male. In July 2004, he underwent resection of the pancreatic body tail region to treat pancreatic body tail cancer. On histopathological examination, the stump of the extirpated specimen was positive for tumor cells. After surgery, 10 courses of therapy with gemcitabine hydrochloride(GEM, 1, 000 mg/m(2), 3-week administration followed by 1-week discontinuation)were performed, and follow-up was continued. In February 2006, local relapse was detected. Chemotherapy with GEM was administered for 1 year and 9 months. However, in November 2007, an increase in the recurrent lesion size and right lung metastasis were noted. The regimen was switched to combination therapy with S-1 and GEM(S-1 60 mg/m(2) day, continuous administration on days 1 to 14 and 2-week discontinuation; and GEM 1, 000 mg/ m(2), administered on days 8 and 15). After the end of the 11th course, PET-CT revealed the disappearance of FDG accumulation in the recurrent and metastatic lesion sites. During the treatment period, there were no grade 3 or higher adverse reactions. The patient is being treated at the outpatient clinic (as of January 2009).

Objective: To investigate the inhibitory effect of solid hyaluronic acid-carboxymethyl cellulose film (hyaluronic acid film) on the formation of postoperative wound adhesion on rabbit eyes., Methods: We first created a conjunctival flap under which hyaluronic acid film was inserted. Then, we performed trabeculectomy on other rabbit eyes with hyaluronic acid film applied under and above the scleral flaps. Expression of proliferative cell nuclear antigen and alpha-smooth muscle actin (alpha-SMA) were histologically and immunohistochemically examined., Results: Hyaluronic acid film significantly prevented adhesions after both kinds of surgery. Particularly, subconjunctival scar formation was significantly inhibited when the film was simply inserted under the wound. Furthermore, the adhesion around the scleral flap of trabeculectomy was less formed in eyes treated with hyaluronic acid film than in control eyes. Immunoreactivity to proliferative cell nuclear antigen almost disappeared after 28 days postoperatively in both treated and control groups. The alpha-SMA-positive cells appeared much less around the film-treated wound than the control eye., Conclusion: The present results indicate that hyaluronic acid film can inhibit the formation of postoperative adhesion around the conjunctiva and sclera., Clinical Relevance: The results of this study indicate that this substance has potential benefits for improving ophthalmic surgery, such as filtering surgery for glaucoma.

To examine rhodopsin (Rho) functions in P23H rat, kinetics of Rho regeneration and dephosphorylation were investigated by spectrophotometric analysis and immunofluorescence labeling method using specific antibodies toward phosphorylated 334Ser or 338Ser site. Rho dephosphorylation at both sites was extremely delayed in P23H retina as compared to normal ones. Kinetics of Rho regeneration was not altered between normal and P23H rats under dark adaptation. Next, to study the effects of several Ca(2+)channel blockers on this model, retinal function and morphology were evaluated. Among them, nilvadipine showed a significant protective effect against P23H retinal degeneration. Neurotrophic factor, fibroblast growth factor-2 and Arc, known to suppress the apoptosis in the central nervous system, were significantly upregulated upon administration of nilvadipine. The present study indicates that misregulation of Rho phosphorylation may be involved as an important step in retinal degeneration of P23H and administration of nilvadipine may be a potential therapeutic agent for the retinal degenerations.

The effects of aflatoxin (AF), a hepatotoxic agent and the strongest carcinogen in nature, on polymorphonuclear leukocyte (PMN) chemotaxis and chemiluminescence (CL) were studied. Luminol-dependent CL activity, which reflects the production of reactive oxygen species (ROS) from PMNs, was up-regulated to approximately 150% when PMNs were treated with 0.05 ng/ml of AFB1 upon stimulation with N-formyl-methionine-leucine-phenylalanine (fMLP) or zymosan. On the other hand, PMN CL activity was down-regulated to approximately 25% of the control when PMNs were treated with 50 ng/ml of AFB1 upon stimulation with zymosan. The effect of AFB1 on PMN chemotaxis was also investigated using the Boyden chamber method. The chemotactic ability of PMNs when interleukin (IL)-8 was used as a chemoattractant was inhibited in a dose-dependent manner at AFB1 concentrations of >10 ng/ml. In reverse transcriptase (RT)-PCR analysis, gene expression levels of CXC chemokine receptor (CXCR)1/2, whose ligands are IL-8, granulocyte chemotactic protein (GCP)-2, neutrophil attractant-activation protein (NAP)-2, and epithelial neutrophil-activating protein (ENA)-78, which regulate PMN chemotaxis, were also down-regulated in a dose-dependent manner by 50 ng/ml AFB1. mRNA expression levels of CXCR1/2 were down-regulated to approximately 85% of that in the controls when PMNs were treated with 100 ng/ml AFB1. These results suggest that a high concentration of AFB1 reduces the chemotactic ability of PMNs via the CXCR1/2 cascade indirectly.

A 73-year-old woman underwent chemotherapy, radiotherapy, and hormonal therapies for right advanced breast cancer (T4, N3, M1, Stage IV) in 1993. She obtained a complete response in pathological evaluation (pCR) in 1998. For adjuvant therapies, she had been treated with hormonal therapies for five years until 2003. After the interruption of hormonal therapies, the serum levels of tumor markers had been elevated, and she had a right axillary local recurrence and a right ovarian metastasis detected by a FDG-PET/CT in February 2006. The right axillary local recurrence lesion was then resected, and she has since been treated with hormonal therapy of aromatase inhibitor (AI). The serum levels of tumor markers have been remarkably reduced, and FDG-PET/CT has showed the disappearance of the right axillary local recurrence, and the decrease of FDG accumulation of the right ovarian metastases in February 2007. We present a case of non-operated advanced breast cancer with local recurrence surviving successfully long term when treated with AI.

In February, 19 9 8, a 48-year-old female patient underwent an operation for breast cancer. In November 2003, abdominal MRI revealed metastatic lesions in S 3 and S 5 of the liver, and chemotherapy (trastuzumab+weekly paclitaxel) was started, after which the metastatic lesions quickly reduced in size. No lesions could be detected by April 2004, and she was diagnosed as a complete response (CR). She now visits our hospital as an outpatient without any evidence of recurrence or any side effects of chemotherapy for 8 years and 8 months after surgery. For advanced breast cancer, there is no standard criteria regarding the time when to stop chemotherapy after obtaining a CR. This time, we experienced a case of liver metastasis of breast cancer responding to a regimen of trastuzumab plus weekly paclitaxel chemotherapy maintaining CR for a long period. We discuss the timing of the termination of chemotherapy in such a case in light of our experience and the literature.

The patient was a 63-year-old man who suffered from advanced pancreatic cancer (T 4 N 3 M 0, Stage IVb). Palliative operation was performed for obstructive jaundice. He was treated with chemotherapy of gemcitabine (GEM) alone as first-line, and combined chemotherapy of GEM and S-1 as second-line. Both therapies were effective for this patient. Tumor marker (CA 19-9) decreased after chemotherapies (first-line: 5,692 U/mL to 70 U/mL, second-line: 4,877 U/mL to 562 U/mL). No toxic events were observed due to these therapies, so he was treated as an outpatient for about 2 years. It was considered that he had a good quality of life.

Microarray and RT-PCR analyses were performed for the transgene and Ras-related genes in forestomach squamous cell carcinomas (SCCs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rasH2 mice; these results were compared with our previous molecular data of N-ethyl-N-nitrosourea-induced forestomach SCCs and urethane-induced lung adenomas in rasH2 mice. Overexpression of the transgene was detected in the DMBA-induced SCCs, suggesting that the transgene plays an important role in enhanced carcinogenesis in rasH2 mice. In addition, the mouse endogenous ras genes were up-regulated in the DMBA-induced SCCs, and are probably involved in the tumorigenesis of forestomach SCCs. Genes such as osteopontin, Cks1b, Tpm1, Reck, gelsolin, and amphiregulin that were commonly altered in these three different carcinogen-induced tumors may contribute to the development of tumors in rasH2 mice.

The patient was a 61-year-old man who suffered from advanced gastric cancer, and a distal gastrectomy was performed (T3N2P1CY1, Stage IV). He was treated with chemotherapy of TS-1 alone (100 mg/day, days 1-28 with two weeks rest). Six months later he complained of lumbago and appetite loss, then was admitted to the hospital with obstructive jaundice. Total bilirubin (T-Bil) was increased to 11.3 mg/dl. CT scan examination revealed peritoneal dissemination with much ascites and dilatation of intrahepatic bile ducts. Endoscopic drainage was tried, but was discontinued due to stenosis of gastroduodenal anastomosis. Ultimately, T-Bil was elevated to 25.2 mg/dl, and he could not sleep comfortably because of a severe itch and an irritating feeling. Weekly paclitaxel therapy was started (70 mg/m(2), day 1, 8, 15, once a week for 3 weeks followed by a week rest as one cycle). One month after the first infusion therapy, the obstructive jaundice was notably improved and the ascites disappeared completely, so he was discharged. For about one year, he was treated with this chemotherapy as an outpatient. The toxic events were anemia (grade 3) and alopecia (grade 1).

Purpose: The effects of various light-induced stresses on the retina were examined in the retinal degenerative rat model., Methods: Retinal morphology and electroretinograms (ERGs) were analyzed after application of light-induced stress of several intensities (650, 1300, 2500, or 5000 lux). For evaluation of rhodopsin (Rho) function, the kinetics of Rho regeneration and dephosphorylation were studied by spectrophotometric analysis and immunofluorescence labeling with antibodies specifically directed toward the phosphorylated residues (334)Ser and (338)Ser in the C terminus of Rho. Retinal cGMP concentration was determined by ELISA. Expression levels of neurotrophic factors (FGF2, brain-derived neurotrophic factor [BDNF], platelet-derived growth factor [PDGF], and ciliary neurotrophic factor [CNTF]) were evaluated quantitatively by RT-PCR., Results: Light intensity-dependent deterioration of ERG responses and thinning of the retinal outer nuclear layer were observed in wild-type and Royal College of Surgeons (RCS) rat retinas. Under dark adaptation after light-induced stress, the kinetics of Rho regeneration were not different between wild-type and RCS rat retinas. Rho dephosphorylation at (334)Ser and (338)Ser was extremely delayed in RCS rat retinas compared with wild-type without light-induced stress, but Rho dephosphorylation at those sites became slower in both RCS and wild-type rat retinas. In terms of expression of neurotrophic factors, almost no significant changes were observed between the animals after light-induced stress., Conclusions: The present study indicates that light-induced stress causes intensity-dependent deterioration in retinal function and morphology in wild-type and RCS rat retinas. Disruption of the phototransduction cascade resulting from slower kinetics of Rho dephosphorylation appears to be involved in retinal degeneration.

Our previous study suggested the possibilities that dicyclanil (DC), a nongenotoxic carcinogen, produces oxidative stress in the liver of the two-stage hepatocarcinogenesis model of mice and the stress induced probably causes secondary oxidative DNA damage. However, clear evidences demonstrating the relationship between DC-induced hepatocarcinogenesis, oxidative stress, and oxidative DNA damage have not been obtained. To clarify the relationship, further investigations were performed in the liver of the partially hepatectomized (PH) mice maintained on diet containing 1,500 ppm of DC for 13 and 26 weeks after intraperitoneal injection of dimethylnitrosamine (DMN). Significant increases in mRNA expressions of some metabolism- and oxidative stress-related genes with a formation of gamma-glutamyltranspeptidase (GGT) positive foci were observed in the DMN + DC + PH group by the treatment of DC for 13 and 26 weeks. The levels of 8-hydroxy-deoxyguanosine (8-OHdG) in the liver DNA also significantly increased in mice of the DMN + DC + PH group at weeks 13 and 26 and mice given DC alone for 26 weeks. The in vitro measurement of reactive oxygen species (ROS) generation from the mouse liver microsomes showed a significant increase of ROS production in the presence of DC. These results suggest that DC induces oxidative stress which is probably derived from its metabolic pathway, partly, and support our previous speculation that oxidative stress plays one of the important roles in the DC-induced hepatocarcinogenesis in mice.

Purpose: To study the effects of antiglaucoma drugs on metabolism within the extracellular matrix (ECM) of the ocular surface, including corneal, conjunctival, and subconjunctival tissue., Method: Several antiglaucoma drugs--including beta-blockers, alpha/beta-blockers, alpha1-blocker, alpha2-agonist, and prostaglandin derivative-were topically administrated to rat eyes daily for 2 weeks or were incubated with human corneal cells or human fibroblasts for 72 hours. Thereafter, expression and enzymatic activity of the matrix metalloproteinases (MMPs), a group of enzymes proteolyzing ECM and their inhibitors, called tissue inhibitors of metalloproteinase (TIMPs), were evaluated., Results: Quantitative RT-PCR revealed significantly upregulated and downregulated expression of MMPs and TIMPs, respectively, in rat conjunctival and subconjunctival tissue on the administration of alpha/beta-blockers, alpha1-blocker, alpha2-agonist, and prostaglandin derivative, suggesting that these drugs may enhance ECM degradation. However, in contrast, beta-blocker administration caused reverse effects--that is, upregulation and downregulation of TIMPs and MMPs, respectively. Enzymatic activity of MMPs in rat conjunctival and subconjunctival tissue analyzed by biochemical assay and zymography was markedly enhanced on the administration of alpha/beta-blockers, alpha1-blocker, alpha2-agonist, and prostaglandin derivative, but not of beta-blockers. Similar effects of these antiglaucoma drugs were observed in cultured human corneal cells and human fibroblast cells., Conclusions: The present experimental observations suggest that some alpha/beta-blockers, alpha1-blocker, alpha2-agonist, and prostaglandin derivative stimulate ECM degradation of ocular surface tissue by modulating the balance between MMPs and TIMPs.

To evaluate the carcinogenic susceptibility of rasH2 mice to 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 7-week-old rasH2 mice and their wild-type littermates (non-Tg mice) of both the sexes were fed a diet containing 0 or 300 ppm IQ for 26 weeks. Microscopical examinations revealed that the proliferative lesions of the forestomach, including squamous cell hyperplasias, papillomas, and carcinomas, were frequently encountered in male and female rasH2 mice fed with IQ. In non-Tg mice, no significant differences in the incidence of forestomach lesions were observed between the 0 ppm and 300 ppm groups. Histopathological changes such as periportal hepatocellular hypertrophy and oval cell proliferation in the liver were more apparent in female rasH2 and non-Tg mice than in males, and the incidence of hepatocellular altered foci significantly increased in female rasH2 mice in the 300 ppm group as compared to that in the 0 ppm group. These results suggest that the carcinogenic potential of IQ can be detected in rasH2 mice by a 26-week, short-term carcinogenicity test.

Purpose: To study the effects of antiglaucoma eye drops on N-methyl-D-aspartate (NMDA)-induced retinal damage., Methods: Several antiglaucoma eye drops, beta-blockers, alpha/beta-blockers, an alpha1-blocker, an alpha2-agonist, and a prostaglandin derivative, were topically administrated to NMDA-treated rat eyes daily for 2 weeks, and the retinal thickness, the number of retrograde-labeled retinal ganglion cells (RGCs), and the results of a cDNA microarray analysis were studied., Results: Intravitreal administration of NMDA caused a significant decrease in the thickness of the retinal layers and induced upregulation of glial fibrillary acidic protein (GFAP). Topical administration of beta-blockers (timolol, betaxolol, and carteolol) and a prostaglandin derivative (latanoprost) showed almost no significant effects on retinal thickness, the number of RGCs, or expression of GFAP. In contrast, the alpha/beta-blockers (nipradilol and levobunolol), the alpha1-blocker (bunazosin HCl), and the alpha2-agonist (brimonidine) showed preservation effects on retinal thickness and the number of RGCs, and marked suppression of NMDA-induced upregulation of GFAP. Among 1101 genes related to cellular regulatory mechanisms, the expression of two genes, both for insulin-like growth factors, (IGF-1) and ErbB3, was altered upon administration of the alpha/beta-blockers, the alpha1-blocker, and the alpha2-agonist., Conclusion: Our present study suggests that modulations of the alpha-adrenergic receptor, alpha1-blocking and alpha2-stimulation, by antiglaucoma eye drops may cause beneficial effects on NMDA-induced retinal damage in the rat.

Background/aims: The usefulness of the diagnostic criteria of the International Consensus Meeting (criteria A) has been previously reported. However, these criteria are not clinically adaptable in Japan where allergic reaction is one of the major etiologies of drug-induced liver injury and thus it was revised and reported in the Digestive Disease Week-Japan of 2002 as DDW-J criteria (criteria B). It remains controversial whether the revised criteria can exclude drugs not causing liver injury., Methodology: Two new diagnostic criteria (criteria C and D) were designed to supplement the DDW-J criteria. Usefulness and limitations of the four criteria were retrospectively examined using cases of drug-induced liver injury experienced in 8 hospitals., Results: It was confirmed that the sensitivity of criteria B is excellent for diagnosis of drug-induced liver injury. However, diagnostic criteria B were found to be disadvantageous in relation to specificity, while diagnostic criteria D were disadvantageous in relation to sensitivity. Sensitivity of diagnostic criteria C was a little superior to that of diagnostic criteria A., Conclusions: On the basis, the significant sensitivity of criteria B was confirmed again, however, modification should be done for increasing specificity. Criteria C appear to be the best for their sensitivity and specificity.

To develop gene therapy that can be applied to glaucoma-filtering surgery, we studied effects of transfection of matrix metalloproteinase-3 (MMP-3) cDNA into rabbit conjunctiva by electroporation (EP) on changes of intraocular pressure (IOP) and bleb formation after glaucoma filtering surgery. pTracer-CMV2 vector containing MMP-3 cDNA was transfected into rabbit conjunctiva by EP and MMP-3 expression was studied by reverse transcription (RT)-PCR, zymography and western blot analysis. Three days after the EP transfection of MMP-3 cDNA or vector alone into rabbit conjunctiva, trabeculectomy was performed at the place of transfection in the presence or absence of 0.04% mitomycin C (MMC). Then changes in IOPs and bleb formation were compared with each other. Expression of MMP-3 was detected in conjunctiva until 30 days after transfection by EP. Trabeculectomy following MMP-3 transfection caused significantly longer survival of filtering bleb and decreased levels of IOP in comparison with controls (trabeculectomy alone or trabeculectomy following vector transfection), and these levels were almost identical to those of trabeculectomy with MMC. The present study indicates that EP is effective to transfect some genes that promote the filtering bleb formation in glaucoma surgery, such as MMP-3 gene, and this may be potentially applicable to glaucoma-filtering surgery in glaucoma patients.

Silicon carbide (SiC) has a range of useful physical, mechanical and electronic properties that make it a promising material for next-generation electronic devices. Careful consideration of the thermal conditions in which SiC [0001] is grown has resulted in improvements in crystal diameter and quality: the quantity of macroscopic defects such as hollow core dislocations (micropipes), inclusions, small-angle boundaries and long-range lattice warp has been reduced. But some macroscopic defects (about 1-10 cm(-2)) and a large density of elementary dislocations (approximately 10(4) cm(-2)), such as edge, basal plane and screw dislocations, remain within the crystal, and have so far prevented the realization of high-efficiency, reliable electronic devices in SiC (refs 12-16). Here we report a method, inspired by the dislocation structure of SiC grown perpendicular to the c-axis (a-face growth), to reduce the number of dislocations in SiC single crystals by two to three orders of magnitude, rendering them virtually dislocation-free. These substrates will promote the development of high-power SiC devices and reduce energy losses of the resulting electrical systems.

To evaluate their defense level against bacterial infection of patients with liver cirrhosis, we compared the luminol-dependent chemiluminescence (CL) response of peripheral blood from 40 patients with that from 40 healthy volunteers. Small quantities of heparinized whole blood (100 microl; final dilution, 1:10) were used for phagocytes, and CL was measured on addition of nonopsonized zymosan or Escherichia coli without special opsonization. Whole blood CL in cirrhotic patients was significantly lower than that in the healthy controls. The incidence of lower CL response in patients increased as disease stage advanced. Polymorphonuclear leukocytes (PMN) from cirrhotic patients exhibited a slightly lower CL response than those from controls, but this was not statistically significant. In contrast, the CL response of monocytes in patients was significantly lower than that of controls. The opsonizing capacity of the patients' sera and ascitic fluid was also decreased. In fact, the levels of opsonins such as complement in the patients' sera and both immunoglobulins and complement in the ascitic fluids were found to be lower in cirrhotic patients. On the basis of these findings, defect of opsonophagocytic function seems to participate in the increased susceptibility to infection in cirrhotic patients. Furthermore, whole blood CL induced by nonopsonized zymosan at the onset of relatively severe bacterial infections such as sepsis, pneumonia, or spontaneous bacterial infection was less augmented in the blood of cirrhotic patients than that in noncirrhotic patients. To clarify the reason why whole blood exhibits a lower CL response in the acute phase of bacterial infections, we investigated the priming effects of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha), well-known CL activators, on the CL response of whole blood obtained from cirrhotic patients in comparison with that from healthy persons. The priming effects were significantly decreased in patients' blood when compared with that of healthy persons. These low responses of patients' blood to LPS or TNF-alpha support our finding that phagocytes are not fully activated when gram-negative bacterial infections occur.

We have used the ability of opsonized bacteria to stimulate luminol-enhanced chemiluminescence (CL) of human polymorphonuclear leukocytes (PMN) to examine the opsonic capabilities of commercially available human intravenous immunoglobulin (i.v.Ig) preparations. The method was tested against 14 strains of drug-resistant gram-positive bacteria (including methicillin-resistant Staphylococcus aureus, hetero-vancomycin-resistant S. aureus, vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae), and 23 strains of gram-negative bacteria (including extended-spectrum beta-lactamase-producing bacteria, metallo-beta-lactamase-producing bacteria, beta-lactamase-negative ampicillin-resistant Haemophilus influenzae). An Fc-intact i.v.Ig preparation treated with polyethylene glycol (PEG) was evaluated for opsonization effectiveness against these bacteria in vitro. The opsonization of these organisms was enhanced by an Fc-intact i.v.Ig, and the opsonic activity was dose dependent. A pepsin-treated i.v.Ig preparation exhibited poor opsonic activity for all bacteria tested. These results suggest that Fc-intact i.v.Ig, which augments opsonic activity against various drug-resistant bacteria, will be a useful addition to the treatment of severe bacterial infections in immunocompromised patients with impaired serum opsonic capacity.

Purpose: To report clinical and immunologic aspects of cancer-associated retinopathy (CAR)., Design: Observational consecutive case series., Methods: A retrospective review was made of 18 consecutive patients with cancer-associated retinopathy who had antiretinal antibody determination by Western blot testing., Results: Clinically, a variety of ophthalmic observations including electroretinography impairment, retinal vessel narrowing, deterioration of visual acuity, visual field changes, and uveitis were frequently observed. As retinal autoantigens in the 18 cases, recoverin was found in all 18 cases (100%), heat shock cognate protein 70 (HSC70) was found in six cases (33%), and other proteins were found in four cases (20%). These antibodies were detected in only 60% of the patients at the initial examination, however, and then became increasingly apparent on the subsequent testing that was performed three times on serum samples obtained sequentially during the following months., Conclusion: For diagnosis of cancer-associated retinopathy, the presence of serum autoantibody toward recoverin is essentially required in addition to the characteristic clinical aspects noted above.

Two hundred and eighty seven Japanese cases of drug induced liver injury were assessed by the diagnostic scale of the International Consensus Meeting (ICM). They were classified to the hepatocellular (55%), mixed (24%) and cholestatic (22%) type according to the type of liver injury. Five cases were diagnosed as 'unrelated', since the reaction occurred more than 15 days after stopping the drug. The remaining 282 cases were classified to 69 cases of 'highly probable', 170 cases of 'probable', 39 cases of 'possible', and four cases of 'unlikely'. The cases with positive drug-lymphocyte stimulation test (DLST) and with eosinophilia distributed to higher scores. Although the diagnostic scale of the ICM was found to be also useful for Japanese cases, the modification of the scale including the data of DLST and eosinophilia together with some other modifications were recommended in the view of the present status of Japan. Using the modified diagnostic scale, the 287 cases were classified to 173 cases of 'highly probable', 102 cases of "probable', 11 cases of 'possible', and one case of 'unlikely'. Although the modified diagnostic scale seems better than the original one, further assessment of the modified scale using many Japanese cases is needed for the further improvement of the scale.

Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme that catalyzes hydrolysis of PAF and is important for regulation of serum PAF concentration. Twenty-seven patients with hyperbililubinemic hepatobiliary diseases (eight patients with liver cirrhosis, five with acute hepatitis and 14 with obstructive cholestasis) were studied. Serum PAF-AH activity was elevated in hyperbilirubinemic condition associated with liver cirrhosis, obstructive cholestasis or acute hepatitis. There was a significant correlation of serum PAF-AH activity with serum cholesterol (r=0.891, P=0.014 in liver cirrhosis, r=0.813, P=0.002 in obstructive cholestasis) or low density lipoprotein (LDL) cholesterol (r=0.771, P=0.007 in obstructive cholestasis). Serum PAF-AH activity/cholesterol ratio and PAF-AH activity/LDL cholesterol ratio were elevated in the three types of hyperbilirubinemic liver disease. LDL cholesterol increased and PAF-AH/LDL cholesterol ratio decreased in acute hepatitis after remission. On the other hand, LDL cholesterol decreased and PAF-AH/LDL cholesterol ratio did not change after treatment in obstructive cholestasis. These findings suggest that, though serum LDL is a factor influencing serum PAF-AH activity in obstructive jaundice, other factors, i.e. reduced biliary PAF-AH excretion, may also influence serum PAF-AH activity in hyperbilirubinemic hepatobiliary diseases.