Search

Mihori Kita, Yukiko Fujii, Naoaki Kawagoe, Sachiyo HamaDepartment of Ophthalmology, National Hospital Organization Kyoto Medical Center, Kyoto, JapanAbstract: A young patient who showed rhegmatogenous retinal detachment with preoperatively undetected retinal break was successfully treated by scleral buckling using a noncontact wide-angle viewing system.Keywords: retinal detachment, retinal breaks, scleral buckling, noncontact wide-angle viewing system

Background: Optimal medical therapy (OMT) is increasingly recognized as a cornerstone in managing chronic coronary syndrome (CCS), offering a non-invasive alternative to percutaneous coronary intervention (PCI). Case Presentation: A 38-year-old male with diabetes, dyslipidemia, and hypertension was treated with early and comprehensive OMT, including statins, ezetimibe, sodium-glucose cotransporter 2 inhibitors (SGLT2i), pioglitazone, and renin-angiotensin system inhibitors. Insulin was introduced during the acute phase to stabilize glycemic control. His HbA1c decreased to 6.3% within 4 months. Results: Over 8 months, the patient experienced a reduction in coronary plaque burden and an improvement in fractional flow reserve (FFR) from 0.75 to 0.90, indicating enhanced coronary blood flow. Plaque volume burden decreased from 85% to 52% in key coronary segments. Conclusions: This case highlights the effectiveness of OMT, including statins, ezetimibe, SGLT2i, and pioglitazone, in achieving outcomes comparable to PCI. FFR-computed tomography follow-up is critical in guiding treatment decisions. Continued OMT is recommended if plaque stabilization is observed. If no improvement is observed, OMT should be intensified, and PCI considered as appropriate.

Background: Although the percentage of the population with a high degree of obesity (body mass index [BMI] ≥ 35 kg/m 2 ) is low in Japan, the prevalence of obesity-related diseases in patients with high-degree obesity is greater than that in patients with a BMI < 35 kg/m 2 . Therefore, treatment for high-degree obesity is important. However, clinical studies have reported that 20-50% of patients with obesity discontinue weight-loss treatment in other countries. The circumstances surrounding antiobesity agents are quite different between Japan and other countries. In this study, we investigated the predictors of treatment discontinuation in Japanese patients with high-degree obesity., Methods: We retrospectively reviewed the medical charts of 271 Japanese patients with high-degree obesity who presented at Toho University Sakura Medical Center for obesity treatment between April 1, 2014, and December 31, 2017. The patients were divided into non-dropout and dropout groups. Patients who discontinued weight-loss treatment within 24 months of the first visit were defined as "dropouts." Multivariate Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were performed to examine the factors predicting treatment withdrawal., Results: Among the 271 patients, 119 (43.9%) discontinued treatment within 24 months of the first visit. The decrease in BMI did not significantly differ between the two groups. No prescription of medication and residential distance from the hospital exceeding 15 km were the top contributors to treatment discontinuation, and the absence of prescription medication was the most important factor. The dropout-free rate was significantly higher in patients with medication prescriptions than in those without and in patients who lived within 15 km of the hospital than in those who lived farther than 15 km from the hospital., Conclusions: No medication prescription and longer residential distance from the hospital were associated with treatment dropout in Japanese patients with high-degree obesity; therefore, the addition of antiobesity medications and telemedicine may be necessary to prevent treatment discontinuation in such patients., (© 2024. The Author(s).)

The C3 carbon of glucose molecules becomes the C1 carbon of pyruvate molecules during glycolysis, and the C1 and C2 carbons of glucose molecules are metabolized in the tricarboxylic acid (TCA) cycle. Utilizing this position-dependent metabolism of C atoms in glucose molecules, [1- 13 C], [2- 13 C], and [3- 13 C]glucose breath tests are used to evaluate glucose metabolism. However, the effects of chronic ethanol consumption remain incompletely understood. Therefore, we evaluated glucose metabolism in ethanol-fed rats using [1- 13 C], [2- 13 C], and [3- 13 C]glucose breath tests. Ethanol-fed (ERs) and control rats (CRs) (n = 8 each) were used in this study, and ERs were prepared by replacing drinking water with a 16% ethanol solution. We administered 100 mg/kg of [1- 13 C], [2- 13 C], or [3- 13 C]glucose to rats and collected expired air (at 10-min intervals for 180 min). We compared the 13 CO 2 levels (Δ 13 CO 2 , ‰) of breath measured by IR isotope ratio spectrometry and area under the curve (AUC) values of the 13 CO 2 levels-time curve between ERs and CRs. 13 CO 2 levels and AUCs after administration of [1- 13 C]glucose and [2- 13 C]glucose were lower in ERs than in CRs. Conversely, the AUC for the [3- 13 C]glucose breath test showed no significant differences between ERs and CRs, although 13 CO 2 levels during the 110-120 min interval were significantly high in ERs. These findings indicate that chronic ethanol consumption diminishes glucose oxidation without concomitantly reducing glycolysis. Our study demonstrates the utility of 13 C-labeled glucose breath tests as noninvasive and repeatable methods for evaluating glucose metabolism in various subjects, including those with alcoholism or diabetes.

[1'- 13 C]Citric acid (1) was efficiently prepared from dimethyl 1,3-acetonedicarboxylate in two steps as a probe for a breath test. The synthetic method was selected because of the yield and reproducibility. Compound 1 was orally administrated to rats, and the time course of the increase of 13 CO 2 / 12 CO 2 ratios (Δ 13 CO 2 ) in their breath was successfully followed, indicating the metabolism of 1. Thus, the 13 C-breath test using 1 is a promising method to evaluate tricarboxylic acid (TCA) cycle flux., (© 2024 John Wiley & Sons Ltd.)

Background: Although stakeholder involvement in policymaking is attracting attention in the fields of medicine and healthcare, a practical methodology has not yet been established. Rare-disease policy, specifically research priority setting for the allocation of limited research resources, is an area where evidence generation through stakeholder involvement is expected to be effective. We generated evidence for rare-disease policymaking through stakeholder involvement and explored effective collaboration among stakeholders., Methods: We constructed a space called 'Evidence-generating Commons', where patients, family members, researchers, and former policymakers can share their knowledge and experiences and engage in continual deliberations on evidence generation. Ten rare diseases were consequently represented. In the 'Commons', 25 consecutive workshops were held predominantly online, from 2019 to 2021. These workshops focused on (1) clarification of difficulties faced by rare-disease patients, (2) development and selection of criteria for priority setting, and (3) priority setting through the application of the criteria. For the first step, an on-site workshop using sticky notes was held. The data were analysed based on KJ method. For the second and third steps, workshops on specific themes were held to build consensus. The workshop agendas and methods were modified based on participants' feedback., Results: The 'Commons' was established with 43 participants, resulting in positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants. The difficulties faced by patients with rare diseases were classified into 10 categories. Seven research topics were identified as priority issues to be addressed including 'impediments to daily life', 'financial burden', 'anxiety', and 'burden of hospital visits'. This was performed by synthesising the results of the application of the two criteria that were particularly important to strengthen future research on rare diseases. We also clarified high-priority research topics by using criteria valued more by patients and family members than by researchers and former policymakers, and criteria with specific perspectives., Conclusion: We generated evidence for policymaking in the field of rare diseases. This study's insights into stakeholder involvement can enhance evidence-informed policymaking. We engaged in comprehensive discussions with policymakers regarding policy implementation and planned analysis of the participants' experiences in this project., (© 2023. The Author(s).)

Background: Alcoholism is regarded as a risk factor for vitamin B 12 (VB 12 ) deficiency. Because VB 12 serves as a coenzyme of methylmalonyl-CoA mutase, a key enzyme in propionate metabolism, the 13 C-propionate breath test (PBT) has been studied as a non-invasive diagnostic modality for VB 12 deficiency. However, the conventional PBT requires 2 h, which is inconvenient in clinical practice. We hypothesized that a faster PBT can be used to evaluate propionate metabolism and is more easily adaptable for clinical practice., Aim: To evaluate a faster PBT for assessing the effects of long-term ethanol consumption on propionate metabolism in ethanol-fed rats (ERs)., Methods: ERs were obtained by replacing standard drinking water (for control rats, CRs) with 16% ethanol solution in descendants of F344/DuCrj rats. Faster PBT was performed by administering 13 C-propionate aqueous solution to male and female ERs and CRs by inserting a metal tubule from the mouth to the stomach; exhaled gas was collected in a bag to measure its 13 CO 2 / 12 CO 2 isotope ratio via infrared isotope spectrometry. Serum VB 12 and alanine transaminase (ALT) levels were measured via chemiluminescence immunoassay and the lactate dehydrogenase-ultraviolet method, respectively. We evaluated statistical differences in mean body weight, change in 13 CO 2 (Δ 13 CO 2 ‰), peak Δ 13 CO 2 ‰, and serum VB 12 and ALT, between males and females and between ERs and CRs using the t -test and Mann-Whitney U test for normally and non-normally distributed variables, respectively., Results: Males weighed significantly more than females ( P < 0.001); CRs weighed significantly more than ERs ( P < 0.008). Δ 13 CO 2 reached a peak (C max ) at 20 min and 30 min in females and males, respectively, decreasing after 20-30 min without rebound in all groups. Males had significantly higher C max and Δ 13 CO 2 at 15-45 min than females ( P < 0.05; for all pairs). Propionate metabolism was enhanced in male ERs relative to male CRs, whereas metabolism did not differ markedly between ERs and CRs for females. Males had higher serum VB 12 levels than females, without prominent differences between the ER and CR groups. Male CRs had notably higher ALT levels than male ERs. Thus, chronic ethanol consumption may trigger fatty acid production via intestinal bacteria and changes in gut microbiome composition., Conclusion: Faster PBT shows that 16% ethanol consumption promotes propionate metabolism without inducing liver injury. This PBT may be used clinically to evaluate gut flora status., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

BACKGROUND Given the unavailability of reliable biomarkers for vitamin B₁₂ (VB₁₂) deficiency in clinical settings, the usefulness of the ¹³C-propionate breath test (PBT), utilizing VB₁₂ as a coenzyme of methylmalonyl-CoA in propionate metabolism, as a diagnostic modality for VB₁₂ deficiency has been studied. However, a collection time of 2 h reduces its convenience. Hence, we evaluated the effectiveness of 1-h PBT for detecting VB₁₂ deficiency in 49 patients with suspected VB₁₂ deficiency. MATERIAL AND METHODS We collected 100-200 mL breath gas every 10 min until 1 h after the administration of 1 g of ¹³C-propionate from 49 patients (31 men, 18 women; median age, 70 years) with clinically suspected VB₁₂ deficiency and calculated the ¹³CO₂ recovered in the breath per hour as the recovery rate (RR [%dose/h]) from ¹³CO₂/¹²CO₂ using infrared isotope spectrometry. We compared the RRs between groups: (1) with serum VB₁₂ levels ≥145 pg/mL and <145 pg/mL, (2) with mean corpuscular volume ≤100 fL and >100 fL, and 3) pre- and post-VB₁₂ supplementation. RESULTS The RRs peaked within 30 min. The RRs at 20 min (RR20) and 30 min (RR30) were significantly lower in macrocytotic patients (41.28 vs 50.07, p=0.026 and 37.82 vs 43.93, P=0.003). The RR30 was higher in the supplemented patients (41.93 vs 32.84, P=0.024). There was no significant difference in RRs between the patients with normal and low serum VB₁₂ levels. CONCLUSIONS The 1-h PBT can be a diagnostic modality for VB₁₂ deficiency because 1 h is a sufficient collection time.

Introduction: Metastatic ureteral tumors are difficult to diagnose pathologically. Treatment is only available for the primary disease, and prognosis is generally poor., Case Presentation: A 63-year-old patient with a history of gastric cancer presented with asymptomatic right-sided hydronephrosis. Ureteroscopic examination revealed tissue in the ureter consistent with gastric cancer. The lesion was localized, and the patient was treated with chemotherapy and radiotherapy as part of a multidisciplinary treatment. The prognosis was better than in other reports. To the best of our knowledge, this is the first case of a patient with metastatic gastric cancer who received multidisciplinary treatment including radiotherapy and had a good prognosis., Conclusion: In cases where a localized metastatic ureteral tumor cannot be ruled out, ureteroscopy is an effective therapeutic strategy., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. IJU Case Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Urological Association.)

Background: Presepsin is a diagnostic and prognostic biomarker of both bacterial infection and sepsis; however, elevated presepsin levels have also been observed without sepsis. We conducted several analyses to evaluate the clinical laboratory parameters affecting presepsin levels., Method: We analyzed the association between sequential organ failure assessment (SOFA) scores and plasma presepsin levels and then analyzed clinical laboratory parameters in 567 patients with univariate and multivariate regression analysis and analysis of covariance (ANCOVA). We also determined presepsin in the bile of 11 patients and examined the presepsin immunostaining in liver., Results: Spearman's rank correlation analysis with log e change revealed that presepsin levels were closely associated with log e -transformed SOFA score (ρ = 0.541), alkaline phosphatase (ALP); (ρ = 0.454) and gamma-glutamyl transferase; (ρ = 0.505). Multivariate regression analysis revealed that log e -transformed SOFA score (β-coefficient = 0.316), ALP level (β-coefficient = 0.380), and creatinine level (β-coefficient = 0.290) independently and significantly affected log e presepsin levels. ANCOVA revealed that presepsin levels were significantly higher in patients with hepatobiliary disease. Patients who presented with dilatation of the bile ducts and elevated ALP levels or total bilirubin levels exhibited high presepsin levels in the bile. Presepsin production in liver Kupffer cells was also confirmed by immunostaining., Conclusion: Presepsin levels is correlated with the elevation of biliary enzymes in patients without renal dysfunction or sepsis. Additionally, presepsin exists with high concentrations in the bile and is positive in Kupffer cells., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Laparoscopic sleeve gastrectomy (LSG) significantly increases high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL) in pre-heparin serum (pre-heparin LPL levels). LPL is a regulator of serum triglyceride (TG) and HDL-C production; this may be the mechanism for HDL-C increase after LSG. This study aimed to elucidate the mechanism of increase in HDL-C levels by examining the relationship between changes in serum HDL-C levels and LPL after LSG., Methods: We retrospectively reviewed 104 obese patients, who underwent LSG and were followed up for 12 months. We analyzed the relationship between changes in serum HDL-C levels and various clinical parameters after LSG., Results: A significant decrease was observed in the patients' BMI and serum TG levels after LSG. Conversely, HDL-C levels and pre-heparin LPL levels were significantly increased after LSG. Simple linear regression showed that changes in HDL-C levels were significantly correlated with total weight loss percentage, change in TG levels, abdominal fat areas, and pre-heparin LPL levels. Additionally, the multiple regression model revealed that a decrease in TG levels and an increase in pre-heparin LPL levels were correlated with increased HDL-C levels after LSG., Discussion/conclusion: These results show that a decrease in TG levels and an increase in LPL are mechanisms for increased HDL-C levels after LSG., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Introduction: We previously reported that preoperative serum insulin-like growth factor-1 (IGF-1) is a predictor of total weight loss percentage (%TWL) after laparoscopic sleeve gastrectomy (LSG). IGF-1 may suppress muscle loss after surgery. IGF-1 almost accurately reflects the growth hormone (GH) secretion status, and GH has lipolytic effects. Therefore, IGF-1 may influence both the maintenance of skeletal muscle and the reduction of adipose tissue after LSG. The identification of the relationship between preoperative serum IGF-1 and body composition changes after LSG can help in understanding the pathophysiology of obesity., Methods: We retrospectively reviewed 72 patients with obesity who underwent LSG and were followed up for 12 months. We analyzed the relationship between preoperative serum IGF-1 levels and body composition changes after LSG. A multiple regression model was used., Results: LSG led to a significant reduction in body weight. Both body fat mass and skeletal muscle mass decreased after LSG. Preoperative serum IGF-1 levels significantly correlated with %TWL, changes in skeletal muscle mass, and body fat mass after LSG. The multiple regression model showed that preoperative serum IGF-1 levels were related to decreased body fat mass and maintaining skeletal muscle mass after LSG., Discussion/conclusion: Preoperative IGF-1 measurement helps predict not only successful weight loss but also decreases body fat mass and maintains skeletal muscle mass after LSG., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

We describe the case of a 65-year-old patient who presented to our hospital with femoral pain. MRI and CT scan revealed a retroperitoneal abscess. We treated him with early surgical drainage and antibiotic treatment. The urine and draining pus cultures grew Achromobacter xylosoxidans . An iliopsoas abscess may show unique signs depending on its volume. To the best of our knowledge, this is the second reported case of retroperitoneal abscesses due to A. xylosoxidans . Surgical drainage appears to be effective when abscess is large., Competing Interests: No potential conflict of interest to this article was reported., (© 2020 The Author.)

Aims: 13 C-glucose breath tests are reported as an alternative non-invasive method to evaluate glucose metabolism. However, the metabolic results differ based on the site of the carbon atom in the glucose. The aim of this study was to evaluate changes in the metabolism of carbon atoms contained in glucose in patients with diabetes using [1, 2, 3- 13 C]glucose breath tests., Methods: Sixteen healthy participants and 20 diabetic patients were enrolled in the study. Three types of breath tests, [1- 13 C], [2- 13 C], and [3- 13 C]glucose breath tests, were performed after an overnight fast. Breath samples were taken at baseline and at 10-min intervals over 150 min, and 13 CO 2 excretion curves were expressed using non-dispersive infrared isotope spectrometry., Results: 13 CO 2 levels increased more rapidly, and the peak value of 13 CO 2 (C max ) was highest after the administration of [3- 13 C]glucose followed by [2- 13 C] and [1- 13 C]glucose in controls. Delayed 13 CO 2 excretion and a low area under the curve through 150 min (AUC 150 ) were obtained in diabetic patients. The group with severe diabetes had a significantly lower C max and AUC 150 in the [1- 13 C]glucose breath test., Conclusions: The [1- 13 C]glucose breath test, which has been used to evaluate glucose metabolism, is suitable for patients with late-stage diabetes, whereas the [2- 13 C]glucose breath test is ideal in the early stages. Although the [3- 13 C]glucose breath test is theoretically useful for evaluating the uptake of glucose and the anaerobic glycolysis system, it can be used in practice to distinguish reduced uptake from impaired oxidation of glucose in combination with the other two tests.

Chronic alcohol consumption can cause dysbiosis, but it is difficult to determine the effect of alcohol on the structure and activity of gastrointestinal tract microbiota. We therefore designed a noninvasive hydrogen breath test (HBT) to investigate the alteration in the chemical profile of gut microbiota in ethanol-fed rats. Thirteen F344/DuCri rats were fed on a commercial mash food with 16% ethanol solution drinking fluid from 4 weeks of age. HBTs were carried out on six 8-week-old and seven 24-week-old ethanol-fed rats. As controls, HBTs were carried out on sixteen 8-week-old, six 24-week-old, and five 48-week-old male rats. Six 24-week- old male rats were examined twice at 1-week intervals. HBTs were performed after fasting for 24 hr. Rats were orally administrated 4 mL/kg of 65% lactulose solution and housed in an animal chamber. The expired air was collected in a breath-sampling bag at 10-min intervals for 180 min. The hydrogen (H2) and methane (CH4) levels in the breath sample were measured using a breath analyzer and were expressed.as parts- per million (ppm). Elevated H2 and CH4 levels were more frequent in male rats. Maximal values of H2 and CH4 were highest in 8-week- old rats, followed by 48-week-old and 24-week-old rats. No ethanol-fed rat exhaled more than 2 ppm of H2 or CH4 until 180 min after the oral administration of lactulose, unlike the controls. This alteration was more obvious than that of aging or gender differentiation. We conclude that there is a close association between chronic ethanol consumption and H2 and CH4 production. An asymptomatic heavy drinker might have dysbiosis that involves gut microbiota with lower fermentation performance.

This study aimed to evaluate changes in glucose metabolism at the early stage and onset of diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Specifically, after the oral administration of [1, 2, 3-13C]glucose, the levels of exhaled 13CO2, which most likely originated from pyruvate decarboxylation and tricarboxylic acid, were measured. Eight OLETF rats and eight control rats (Long-Evans Tokushima Otsuka [LETO]) were administered 13C-glucose. Three types of 13C-glucose breath tests were performed thrice in each period at 2-week intervals. [3-13C]glucose results in a 13C isotope at position 1 in the pyruvate molecule, which provides 13CO2. The 13C at carbons 1 and 2 of glucose is converted to 13C at carbons 2 and 1 of acetate, respectively, which produce 13CO2. Based on metabolic differences of the labeled sites, glucose metabolism was evaluated using the results of three breath tests. The increase in 13CO2 excretion in OLETF rats was delayed in all three breath tests compared to that in control rats, suggesting that OLETF rats had a lower glucose metabolism than control rats. In addition, overall glucose metabolism increased with age in both groups. The utilization of [2-13C]glucose was suppressed in OLETF rats at 6-12 weeks of age, but they showed higher [3-13C]glucose oxidation than control rats at 22-25 weeks of age. In the [1-13C]glucose breath test, no significant differences in the area under the curve until 180 minutes (AUC180) were observed between OLETF and LETO rats of any age. Glucose metabolism kinetics were different between the age groups and two groups of rats; however, these differences were not significant based on the overall AUC180 of [1-13C]glucose. We conclude that breath 13CO2 excretion is reduced in OLETF rats at the primary stage of prediabetes, indicating differences in glucose oxidation kinetics between OLETF and LETO rats.

Objective: We assessed the prevalence of sleep disordered breathing (SDB) and characteristics among patients who visited a urology clinic complaining of nocturia (URO group) and those who visited a sleep apnea (SA) clinic complaining of excessive daytime sleepiness (EDS) (SA group). Additionally, we evaluated the effects of continuous positive airway pressure (CPAP) therapy in the URO group patients with nocturia and SDB resistant to conventional therapy for nocturia., Methods: Questionnaires were used to assess EDS, nocturia and lower urinary tract symptoms in 34 URO group patients and 49 age-matched SA group patients. We also compared these factors in the male patients in both groups and the male and female patients in the SA group. Significant SDB was diagnosed as a 3% oxygen desaturation index (3%ODI) on pulse oximeter of >5/h. The treatment response was analyzed in six URO group patients treated with CPAP after not responding to the conventional medical treatment., Results: SDB was found in 91.8% of the SA group patients and 70.6% of the URO group patients. The level of EDS and lower urinary tract symptoms were similar in both groups. The SA group showed higher 3%ODI values, while the frequency of urination during bedtime was higher in the URO group. The frequency of nocturnal urination was reduced after CPAP in the subjects resistant to conventional therapy., Conclusion: SDB is as prevalent in patients who visit a urology clinic complaining of nocturia as in those who visit a sleep apnea clinic. Patients who complains of nocturia must be assessed for SDB before starting therapy for nocturia.

Aim: Although the prevalence of Helicobacter pylori (H. pylori) increases with age and the main period of acquisition is childhood, the route of transmission of H. pylori infection remains unclear. This study aims to evaluate the relationship between prevalence of children and grandparents., Methods: A total of 838 consecutive children who attended the Urita clinic and whose blood was taken for work up were enrolled in the present study. They were 449 boys and 389 girls, with a mean age of 12.4 years. H. pylori serology of their family members who were living together in one house was picked up to analyse intra-familial clustering of H. pylori infection. The family members of these children consisted of 448 fathers, 597 mothers, 205 grandfathers, 361 grandmothers and 589 siblings., Results: The seropositive rates of mothers, grandmother and siblings in seropositive children were significantly higher than those in seronegative children. H. pylori infection in mothers and grandmothers was a marked risk factor for infection in the index children. Larger family size was not a risk factor for H. pylori infection. In contrast, having an infected father or grandfather was not an independent predictor for children infection., Conclusions: Our data demonstrate that not only mother-to-child transmission but also grandmother-to-child transmission is an important mechanism for the spread of H. pylori in a three-generation household., (© 2013 The Authors. Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Purpose: Cancer-associated retinopathy (CAR) leads to progressive loss of visual functions and a small number of reports have described effective treatment for the disease. We herein report a case of a CAR patient whose visual acuity improved with corticosteroid and a radical treatment of the tumor., Case: A 70-year-old man with rapidly progressive loss of visual acuity and visual field was referred to our clinic. The visual acuity of the patient had decreased to finger count OD and 20/30 OS at the initial visit, though visual acuity three weeks before the initial visit was 20/16 in both eyes. The patient suffered from night blindness, Goldmann perimetry revealed ring-like scotoma, and the electroretinogram was negative. Fundus examination showed only attenuation of the vessels but no apparent sign of retinal degeneration. Chest computed tomography (CT) revealed a small cell carcinoma in the lung of 1.2 cm diameter. One week after the initial visit, as the visual acuity in both eyes decreased to hand motion, the patient was treated with chemotherapy, radiation, and corticosteroid pulse therapy. After the treatment, the visual acuity of the patient improved to 20/50 OD and 20/67 OS, but the visual field of the patient did not improve. The tumor in the lung was disappeared on CT., Conclusion: Corticosteroid treatment for CAR patients may be effective when performed rapidly after clinical symptoms appear.

Purpose: To evaluate the association between the third high-reflectance band on high-resolution optical coherence tomography (OCT), fundus autofluorescence (AF), and kinetic perimetry results in patients with typical retinitis pigmentosa (RP)., Design: Retrospective, observational case series., Methods: Thirty-four patients with typical RP who were referred to our institute were examined, with a diagnosis made by full-field electroretinography. We evaluated the fundus AF and the third high-reflectance band by high-resolution OCT, both qualitatively and quantitatively. We investigated whether the vertical length of the AF diameter or the third high-reflectance band correlated with Goldmann kinetic perimetry results., Results: We classified three types of abnormal fundus AF: ring AF, central AF, and the absence of both patterns. In eyes with ring AF, the length of the third high-reflectance band was almost equal to the diameter of the abnormal ring AF with significant correlation (P < .001), whereas the band length did not correlate with the diameter of the visual field (P = .237). Eyes with central AF did not have a continuous third high-reflectance band. In eyes with neither ring nor central AF, the length of the third high-reflectance band correlated with the AF length and the diameter of the visual field (P = .024 and P < .001, respectively)., Conclusions: A novel classification based on the fundus AF and the third high-reflectance band determined by OCT suggests different patterns of pathogenesis in the retinal pigment epithelium and photoreceptor degeneration in the progression of RP.

Purpose: To assess light sensitivity and morphologic changes of capillary nonperfused areas in diabetic retinopathy., Design: Prospective, observational cross-sectional study., Methods: Seventeen consecutive patients (20 eyes) with areas of capillary nonperfusion resulting from severe nonproliferative or proliferative diabetic retinopathy were included in the study. All eyes underwent fluorescent angiography and fundus-related microperimetry. Nonperfused areas of the retina were scanned with optical coherence tomography (OCT)., Results: In all 20 diabetic eyes, areas of capillary nonperfusion detected by fluorescein angiography were associated with the loss of retinal sensitivity. At the edges of the nonperfused area, retinal sensitivity tended to be reduced. The OCT images suggested a structural disturbance of the inner retina and high-reflectivity deposition located between the outer segments of photoreceptor and the retinal pigment epithelium corresponding to the areas of capillary nonperfusion., Conclusions: Areas of capillary nonperfusion resulting from severe nonproliferative or proliferative diabetic retinopathy show morphologic changes of the retinal structure, which may lead to a loss of sensitivity.

Purpose: To report novel mutations in the GRK1 gene in Japanese patients with Oguchi disease., Design: Observational case report., Methods: Two unrelated Japanese patients with Oguchi disease were examined. After informed consent was obtained, the coding regions of SAG and GRK1 were analyzed by direct sequencing., Results: Although no mutation was found in SAG, two novel homozygous mutations in GRK1, c.1079 del T and c.1408-1412 CCCCC to CCC, were identified. Both mutations are expected to generate null alleles of GRK1., Conclusions: The authors found two different novel mutations in Japanese patients. The results indicate that a considerable number of GRK1 mutations exist in the Japanese population.

Purpose: To diagnose an atypical retinal degenerative disease with choroidal neovascularization by means of gene diagnosis., Case: A 47-year-old woman had good visual acuity at the first examination. She had scattered chorioretinal degeneration and pigmentation in the peripheral retina. There was a symmetrical visual field defect in the upper and temporal periphery in both eyes. Seven years later, choroidal neovascular membrane (CNV) developed in the fovea of her left eye and visual acuity deteriorated to 0.4 in this eye. Optical coherence tomography revealed type 2 CNV with minimal subretinal fluid. Fluorescein angiography showed very little leakage from the CNV. We used denaturing high performance liquid chromatography(DHPLC) to perform gene diagnosis and found a peripherin/RDS gene mutation of Gly167-Ser., Conclusion: Our case had moderate peripheral retinal degeneration with CNV. It is possible that cases like this tend to be misdiagnosed as AMD (age-related macular degeneration) or CNV with high myopia. Evaluation of the gene mutation was useful for diagnosis in this case.

We report a 25-year-old Japanese man with ventricular fibrillation associated with severe hypokalemia. He developed arm and leg paralysis. He had received 2 g of methylprednisolone because thoracic epidural hematoma had been suspected in another hospital. His serum potassium was 0.8 mEq/l on arrival at our hospital. Half an hour after arrival ventricular fibrillation occurred. Treatment with electric defibrillation 8 times was successful. Afterward Graves' disease was diagnosed, therefore, his clinical symptom was diagnosed as thyrotoxic periodic paralysis. We considered that the unusual condition of hyperthyroid-related hypokalemia worsened by steroid therapy induced the ventricular fibrillation.

We have reported that heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG, syndecan-1) expression significantly increased in the rat kidney during calcium oxalate (CaOx) nephrolithiasis. Although the exact role of syndecan still remains unclear, HS/syndecan-1 is thought to have some important role in the CaOx crystal formation. Mardin-Darby canine kidney (MDCK) cells are most commonly used in kidney stone research. It was reported that MDCK cells do not express syndecan-1. In the present study, we established a novel MDCK cell line (KIC-synd-1) that expressed the human syndecan-1 gene. In this cell line, we confirmed stable expression of both sndecan-1 gene and core protein. Immunohistochemical study revealed positive staining of syndecan-1 monoclonal antibody in the basolateral and cytosolic area of the KIC-synd-1 cells. We also investigated the composition of glycosaminoglycans (GAGs) side chains in MDCK cells and KIC-synd-1 cells by using high-performance liquid chromatography (HPLC). Four types of HS chains were identified in both cells as follows; delta diHS-NS, delta diHS-6S, delta diHS-diS1, delta diHS-diS2. Increased production of delta diHS-NS and delta diHS-diS2 were shown in KIC-synd-1 cells compared with production in MDCK cells (p < 0.05). In contrast, only a small amount of delta diHS-6S and delta diHS-diS1 was contained in both cell lines. Total amount of HS was significantly increased in the KIC-synd-1 cells compare with that in the wild type MDCK cells (p < 0.05). Scanning electron microscopy revealed no significant difference between cell surface of wild type MDCK cells and that of KIC-synd-1 cells in normal conditions. However, calcium oxalate crystal attachment was apparently decreased in the KIC-synd-1 cells. These results suggested that cell surface HS/syndecan-1 has preventive role for calcium oxalate nephrolithiasis via creation of a charge barrier against COM crystal attachment.

Purpose: We recently reported that SART3 tumor rejection antigen is recognized by HLA class I restricted cytotoxic T lymphocytes from patients with esophageal cancer. We now investigate the expression of SART3 antigen in renal cell carcinoma to identify an appropriate molecule that may be used in specific immunotherapy of renal cell carcinoma., Materials and Methods: Renal cell carcinoma and nontumorous kidney tissues were obtained at surgery. A section of each sample was minced with scissors and stored at -80C until use. SART3 antigen expression was examined in uncultured renal cell carcinoma and nontumorous kidney tissues. We also evaluated the ability of derived peptides to include cytotoxic T lymphocytes in peripheral blood mononuclear cells from patients with renal cell carcinoma., Results: The SART3 antigen was detected in all renal cell carcinoma cell lines, primary cultures of renal cell carcinoma and nontumorous kidney tissues, and in the cytosol of 57% and 15% of renal cell carcinoma and nontumorous kidney tissues, respectively. HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes (KE4) used in cloning of the SART3 gene were significantly cytotoxic to cells from renal cell carcinoma cell lines and primary cultures of renal cell carcinoma tissue but they did not lyse normal cells, including those from primary cultures of nontumorous kidney tissue. The SART3 peptides derived from positions 109-118 and 315-323 induced HLA-A24 restricted cytotoxic T lymphocytes to renal cell carcinoma cells from peripheral blood mononuclear cells of patients with renal cell carcinoma., Conclusions: The SART3 antigen and derived peptides may be applied to the specific immunotherapy of HLA-A24+ renal cell carcinoma.

Problem: The molecular basis of allo-reactivity in reproductive immunity has not been fully clarified., Method of Study: Cytotoxic T lymphocytes (CTLs) were established from tumor-infiltrating lymphocytes (TILs). The allo-reactivity of the CTLs against various tumor cell lines or human leukocyte antigen (HLA)-A allele-transfected COS-7 cells was measured by 51Cr-release or interferon-gamma production assay., Results and Conclusions: We have established CTLs reacting to an HLA-A0206 molecule that matched a spouse's HLA-A allele from the TILs of a 68-year-old multiparous patient with gastric cancer. The amino acids at positions 66 and 88 in the alpha1 domain of HLA-A0206, both of which were common in the other HLA-A2 subtypes, were involved in the recognition by the CTLs. Endogenous peptides in the groove were not involved in the recognition. These results suggest the presence of long-lasting memory CTLs raised by the reproduction process, and may facilitate a better understanding of the molecular basis of allo-recognition during reproduction.

We recently isolated a human SART3 (hSART3) gene encoding a tumor-rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes (CTLs). The hSART3 was also found to exist as an RNA-binding nuclear protein of unknown biological function. In this study, we cloned and analyzed the homologous mouse SART3 (mSART3) gene in order to understand better the function of hSART3, and to aid in establishing animal models of specific immunotherapy. The cloned 3586-bp cDNA encoded a 962-amino acid polypeptide with high homology to hSART3 (80% or 86% identity at the nucleotide or protein level, respectively). Nonapeptides recognized by the HLA-A2402-restricted CTLs and all of the RNA-binding motifs were conserved between hSART3 and mSART3. The mSART3 mRNA was ubiquitously expressed in normal tissues, with low level expression in the liver, heart, and skeletal muscle. It was widely expressed in various organs from as early as day 7 of gestation. mSART3 was mapped to chromosome 5, a syntenic region for human chromosome 12q23-24, and its genomic DNA extended over 28-kb and consisted of 19 exons. This information should be important for studies of the biological functions of the SART3 protein and for the establishment of animal models of specific cancer immunotherapy.