Okayama University Medical School

The aim of this study is to clarify visual symptoms and compliance with spectacle wear in children kusing progressive addition lenses (PALs). Ninety-two children, participating in a randomized, doublemasked, crossover trial to determine whether PALs reduce myopia progression (mean+/-SD age: 11.0+/-1.6 years; refractive errors: 3.11+/-1.34 D), wore PALs (1.50 D near addition) or single vision lenses (SVLs) for 18 months, alternately. A questionnaire survey was performed 6 and 12 months after the beginning of the use of the lenses (6-month survey), and the results were compared between PAL- and SVL-wearing periods. In the PAL-wearing period, the children reported difficulty in adapting to newly provided spectacles (36%), disturbances in distance vision (22%), vertigo in the lateral gaze (11%), and difficulty in ascending and descending stairs (9%). However, the frequency of these symptoms was not significantly different from that reported in the SVL-wearing period. There was no difference in compliance with spectacle wear between the PAL- and SVL-wearing periods, and 98% of the children wearing PALs reported excellent compliance. The results of this study indicate that, compared with SVLs, the PALs provide a similar level of comfort and compliance with spectacle wear for myopic children.

Testicular Sertoli cells highly express dynamin 2 and amphiphysin 1. Here we demonstrate that dynamin 2 is implicated in phosphatidylserine (PS)-dependent phagocytosis in Sertoli cells. Immunofluorescence and dual-live imaging revealed that dynamin 2 and amphiphysin 1 accumulate simultaneously at ruffles. These proteins are specifically bound in vitro. Over-expression of dominant negative dynamin 2 (K44A) inhibits liposome-uptake and leads to the mis-localization of amphiphysin 1. Thus, the cooperative function of dynamin 2 and amphiphysin 1 in PS-dependent phagocytosis is strongly suggested.

Abscess formation of the round ligament of the liver is very rare. We report a case of a 70-year-old female with abscess of the round ligament after an endoscopic papillotomy for choledocholithiasis. On the 21st day following papillotomy, abscess formation of the round ligament was found by ultrasonographic examination. Surgical treatment was performed because conservative therapy was not effective. The purulent fluid and necrotic tissue at the round ligament were completely removed. Cultures obtained from the abscess grew Staphylococcus epidermidis, but the mechanism of abscess formation in this case remains unclear.

Anorectal melanoma is a rare malignant tumor with a poor prognosis. However, several studies have reported cases of long-term survival. In this report, we present a patient with anorectal melanoma who has survived for 9 years after endoscopic mucosal resection. An 85-year-old man was referred to our hospital for further examination and treatment of an anal tumor 2cm in size. Endoscopic ultrasonography revealed that the depth of tumor invasion was confined to the submucosal layer. Endoscopic mucosal resection was performed, and the tumor was diagnosed as a malignant melanoma. The patient was followed without any additional treatment, which was per his wishes. Although melanoma recurred 4 times thereafter, endoscopic mucosal resection was performed for each recurrent lesion. Thus, he has been alive for 9 years since the first endoscopic mucosal resection without distant metastases. If the depth of tumor invasion is shallow, endoscopic mucosal resection is a useful option among other therapeutic modalities.

The molecular defects in the catalase gene, levels of m-RNA and properties of the residual catalase studied by scientists are reviewed in human (Japanese, Swiss and Hungarian) and non-human (mouse and beagle dog) acatalasemia with reference to the bioinformatics. Japanese acatalasemia-I, the G to A transition at the fifth position of intron 4 of the catalase gene, limited the correct splicing of the mRNA and synthesized trace catalase with normal properties. Hungarian acatalasemia type C showed a splicing mutation. In the Japanese acatalasemia II and the type A and B of Hungarian acatalasemia, the deletion or insertion of nucleotides was observed in the coding regions, and the frame shift altered downstream amino acid sequences and formed truncated proteins. In the Hungarian acatalasemia D, the substitution of a nucleotide in the exon was found. In mouse and beagle dog acatalasemia, the substitution of nucleotides in the coding regions was also observed. Studies of residual catalase in Swiss, mouse and beagle dog acatalasemia showed that aberrant catalase protein degrades more quickly than normal catalase in cells. The experimental research in genetic toxicology concerning the effect of oxidative stressors (nitrogen monoxide, nitrogen dioxide and so on) on Japanese acatalasemic blood and acatalasemic mice is described. The clinical features of Japanese and Hungarian acatalasemic subjects are also described.

To evaluate morbidity in Hybrid Radical Prostatectomy (HRP, hybridized laparoscopic and open retropubic radical prostatectomy). The operative and pathological outcomes obtained in 25 consecutive patients who underwent HRP were reviewed. The median operating time was 220min, median blood loss was 550ml, and no patient required an allogenic blood transfusion. No severe postoperative complications were observed. The surgical margin was positive in 12% of all patients, and in 1 patient with pT2 or less (4.5%). These results indicate that HRP is safe and may be able to combine the benefits of both laparoscopic and open procedures.

We previously reported the effectiveness of loxoprofen sodium (loxoprofen), a non-steroidal anti-inflammatory drug, for patients with lower urinary tract symptoms (LUTS) complaining of nocturia. In this study, we explored the mechanism of loxoprofen in the treatment of nocturia. Fifty-six patients complaining of nocturia were enrolled. They took a single 60-mg tablet of loxoprofen at bedtime for 14 days. The effects of this treatment were assessed by bladder diaries. Nocturia improved (nocturia decreased ≥1 void/night) in 40 patients (71.4%). Nocturnal urine volume was reduced in 31 of 40 (77.5%) without nocturnal single-void volume increase. Nocturnal single-void volume increased in 4 of 40 (10.0%) without nocturnal urine volume reduction. Two of 40 (5.0%) demonstrated both nocturnal urine volume reduction and nocturnal single-void volume increase. Three (7.5%) were exceptions to the above. In conclusion, the main mechanism of loxoprofen is the reduction of nocturnal urine volume for the treatment of nocturia and the second mechanism is the increased bladder capacity.

We treated 2 different types of intersexual patients who underwent a vaginoplasty with the pudendal-thigh flap. One was a female with testicular feminization syndrome for whom we reconstructed the total vagina with a pudendal-thigh flap, and the other was a female with an adrenogenital syndrome for whom we enlarged the introitus of the vagina with the same approach. There were no complications such as a flap necrosis. In addition, there was no stricture of the neo-vagina and no urinary problem.

Aeromonas are water-borne pathogens. They are halotolerant, which means that they can survive in environments whose salt content corresponds to that of seawater (3.0% NaCl). However, the presence of Aeromonas in seawater is extremely rare compared with that in river water. In this study, we tested the ability of Aeromonas sobria to produce toxins in river water and seawater. First, we cultured A. sobria on skim milk agar plates supplemented with either river water (SARW) or seawater (SASW). The bacteria grew on both plates. A clear zone around the bacteria was generated in SARW. However, such a zone was not observed in SASW, suggesting that proteases were not generated in SASW. Subsequently, we cultured A. sobria in a nutrient broth supplemented with either river water (NRW) or with seawater (NSW), and examined the protease activity of their culture supernatants. The protease activity of the culture supernatant from NSW was extremely low compared to that from NRW. The immunoblotting analysis showed that serine protease (ASP) was not produced by the culture in NSW. By contrast, aerolysin-like hemolysin was produced in all conditions examined in this study. This indicates that the salinity of water is deeply involved in the production of ASP by A. sobria.

Our study aimed to investigate the potential radioprotective effects of N-acetylcysteine (NAC) by comparing its biochemical effects with those of WR-2721, as a representative of clinically used radioprotectors, in preventing oxidative damage caused by gamma irradiation (single dose, 6Gy) in normal rat tissue. The rats (n=40) were divided randomly and equally into 4 groups:Control (C), Radiation (R), R+NAC (received irradiation and 1,000mg/kg NAC) and R＋WR-2721 (received irradiation and 200mg/kg WR-2721) rats. Liver tissues and blood samples were harvested and utilized for reduced glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) detection. Serum and tissue GSH levels of R rats decreased compared to those of other groups (p<0.01). Tissue MDA levels of R+NAC and R+WR-2721 rats decreased compared to R rats (p<0.01;p<0.05, respectively). Tissue MPO activities of R+NAC and R+WR-2721 rats were higher than those of R rats (p<0.001). Serum MPO levels of R+WR-2721 rats were lower than those of C rats and R rats (p<0.01, p<0.001, respectively). In conclusion, the study suggests that the radioprotective effect against radiation-induced oxidative damage of NAC may be similar to that of WR-2721.

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.

The insulin-like growth factor I receptor (IGF-IR) is exceptionally overexpressed in many cervicalcancer-derived cell lines. It is postulated that a decrease of p53 protein levels due to human papillomavirus (HPV) infection may contribute to the up-regulation of IGF-IR expression in cervical cancer cells because transcription of IGF-IR is strictly down-regulated by p53. To evaluate this fact in clinical cervical cancer specimens, we checked the expression levels and activated status of IGF-IR by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens obtained by conization or hysterectomy were stained with anti-IGF-IR and with an antibody recognizing phosphorylated tyrosine at its c-terminus. The expression levels of IGF-IR were significantly high in cervical intraepithelial neoplasia (CIN) III and invasive cancer specimens. Phosphorylation of IGF-IR was promoted in all CIN and invasive cancer specimens, and its intensity was related to the promotion of lesions. Interestingly, IGF-IR overexpression was missing in the basal layer of CIN I and II lesions, whereas it was evenly distributed in CIN III and invasive cancer lesions. This IGF-IR overexpression pattern may be utilized in the diagnosis of HPV infection status in CIN lesions.

Autoimmune hepatitis (AIH) is a chronic and progressive disease characterized by histological interface hepatitis, hypergammaglobulinemia, and circulating autoantibodies. Multiple factors, including molecular mimicry, a genetic background including major histocompatibility complex class II, and defective function of regulatory T-cells, are involved in the pathogenesis. The diagnosis is made based on the scoring system of the International Autoimmune Hepatitis Group, the sensitivity and specificity of which are90%, respectively. AIH is classified into 3 sub-types based on the profiles of circulating autoantibodies: anti-nuclear antibody and/or smooth muscle antibody-positive (type 1), anti-liver-kidney microsomal antibody-positive (type 2), and anti-soluble liver antigen/liver-pancreas antigen antibody- positive (type 3). Recently, however, the number of atypical cases lacking the usual features has increased-for example, patients with acute-onset or fulminant-type AIH, autoantibody-negative patients, male patients, and patients with bile duct injury-and thus the clinical features of AIH have been diversified. AIH is responsive to immunosuppressive treatment in most cases; however, relapse occurs in more than 80% of patients within 1 year after immunosuppressive treatment withdrawal. The 10-year survival rate and the 10-year hepatocellular carcinoma-free rate are90%, respectively, indicating that some patients reach liver failure or develop hepatocellular carcinoma. To improve the prognosis of these patients, persistent normalization of transaminase is required.

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95%Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.

Percutaneous cardiopulmonary support (PCPS) has been applied for cardiopulmonary arrest (CPA). We have developed a novel method of cardiopulmonary resuscitation using PCPS combined with liposome-encapsulated hemoglobin (TRM645) to improve oxygen delivery to vital organs. Ventricular fibrillation was electrically induced to an adult goat for 10 min. Next, PCPS (30 ml/kg/min, V/Q: 1) was performed for 20 min. Then, external defibrillation was attempted and observed for 120 min. The TRM group (n5) was filled with 300 mL of TRM645 for the PCPS circuit. The control group (n5) was filled with the same volume of saline. The delivery of oxygen (DO2) and oxygen consumption (VO2) decreased markedly by PCPS after CPA, compared to the preoperative values. DO2 was kept at a constant level during PCPS in both groups, but VO2 slowly decreased at 5, 10, and 15 min of PCPS in the control groups, demonstrating that systemic oxygen metabolism decreased with time. In contrast, the decreases in VO2 were small in the TRM group at 5, 10, and 15 min of PCPS, demonstrating that TRM645 continuously maintained systemic oxygen consumption even at a low flow rate. AST and LDH in the TRM group were lower than the control. There were significant differences at 120 min after the restoration of spontaneous circulation (p<0.05).

It is well known that priming stimulation promotes the motivational effects of intracranial self-stimulation(ICSS) behavior. An experimental methodology using the runway method could separately study the reward and motivational effects of ICSS behavior. In the present study, we examined the motivational effect of nicotine as measured by the runway method using priming stimulation of ICSS behavior. Electrodes were implanted chronically into the medial forebrain bundle (MFB) in rats. A lever for stimulation of the MFB was set on the opposite side of the start box in the apparatus, and rats were trained to get a reward stimulation (50-200 microA, 0.2 ms, 60 Hz) of MFB when the goal lever was pressed. After the rats were trained to press the lever, a priming stimulation of the MFB was performed. After receiving the priming stimulation, rats were placed at the start box of the runway apparatus, and the running time duration until the goal lever was pressed was measured. Subcutaneous injection of nicotine at a dose of 0.2mg/kg produced an increase in running speed to obtain the reward stimulation, and priming stimulation facilitated the motivational effect to obtain the electrical brain stimulation reward in the rats. These results suggest that nicotine significantly enhanced the motivational effect on ICSS behavior as determined using the runway method. The runway method using priming stimulation of ICSS behavior may become the new experimental methodology with which to measure the motivational effect of some drugs.

The purpose of this study is to compare the performance of laparoscopic partial nephrectomy (LPN) with and without clamping of the renal artery and to evaluate the impact of clamping on postoperative renal function. A total of 20 patients underwent LPN, 13 without and 7 with clamping of the renal artery. The 2 groups were compared with respect to complications, blood loss, operative time, mean tumor size, and incidence of positive margins. Renal function was evaluated by pre- and postoperative renal scintigraphy using ^99mTechnetium-mercaptoacetyltriglycine (^99mTc-MAG3). Intraoperative blood loss was significantly higher in the group without clamping than in the group with clamping (p0.04). In the group with clamping, the median warm ischemic time was 35min (range 25-40min). The serum creatinine values and the renal scintigraphy showed no influence on postoperative renal function with or without clamping. In the group without clamping, 2 cases were showed positive surgical margins. The procedure performed with clamping of the renal artery is superior to the procedure performed without clamping as it provides the advantages of controlling hemorrhaging without injury to renal function and prolonging the surgical time and allowing for more accurate resection of renal tumors.

We evaluated the infection risks in the neonatal intensive care unit (NICU) using data of NICU infection surveillance data. The subjects were 871 NICU babies, consisting of 465 boys and 406 girls, who were cared for between June 2002 and January 2003 in 7 medical institutions that employed NICU infection surveillance. Infections were defined according to the National Nosocomial Infection Surveillance (NNIS) System. Of the 58 babies with nosocomial infections, 15 had methicillin-resistant Staphylococcus aureus (MRSA) infection. Multiple logistic regression analysis demonstrated that the odds ratio for nosocomial infections was significantly related to gender, birth weight and the insertion of a central venous catheter (CVC). When the birth weight group of more than 1, 500g was regarded as the reference, the odds ratio was 2.35 in the birth weight group of 1,000-1,499g and 8.82 in the birth weight group of less than 1,000g. The odds ratio of the CVC () for nosocomial infection was 2.27. However, other devices including artificial ventilation, umbilical artery catheter, umbilical venous catheter, and urinary catheter were not significant risk factors. The incidence of MRSA infection rapidly increased from 0.3% in the birth weight group of more than 1,500g to 2.1% in the birth weight group of 1,000-1,499g, and to 11.1% in the birth weight group of less than 1,000g. When the birth weight group of more than 1,500g was regarded as the reference, multiple logistic regression analysis demonstrated that the odds ratio was 7.25 in the birth weight group of 1,000-1,499g and 42.88 in the birth weight group of less than 1,000g. These odds ratios were significantly higher than that in the reference group. However, the application of devices did not cause any significant differences in the odds ratio for MRSA infection.

In order to make the mechanism concerned with the sound-susceptibility in the organ of Corti clear, we observed the organ of Corti with the phase-contrast microscope, after the microdissection of the cochleae in human, dogs, guinea pigs and hamsters by Engstroöm's surface preparation technique. As a result, we have formulated a hypothesis for the mechanism of the sound-susceptibility in the organ of Corti. Further, we have inferred the contrary recruitment phenomenon (hypothesis), by explaining theoretically such a clinical fact as the recruitment phenomenon or the cochlear hearing loss by applying our first formula of hypothesis. Finally, we described the application of the contrary recruitment phenomenon (hypothesis) to the early discovery or diagnosis of the false normal ear or cochlea, in other words, latent hearing loss.

For the purpose to study the citrate metabolism in liver diseases, blood citrate, blood glucose and serum non-esterified fatty acids (NEFA) in fasting state were measured in the subjects with chronic hepatitis and with liver cirrhosis. Citrate and glucose were measured by the enzymatic methods. NEFA was measured colorimetrically. Fasting blood citrate level was investigated in relation to the type and extent of these liver diseases.Results revealed the following: 1. Fasting blood citrate level rose with the severity of liver diseases, especially in decompensated liver cirrhosis. 2. No significant difference in fasting blood citrate level was found between the subjects with and without glucose intolerance. 3. Fasting blood citrate level had a closer correlation with serum NEFA level than with blood glucose level. From these results, it has been concluded that the increase in blood citrate level in liver diseases is due to the impaired uptake of citrate by the liver and the increased release of citrate from peripheral tissues.