Adult-type granulosa cell tumor (AGCT) is a rare class of malignant ovarian tumor with unique features, characterized by slow growth, late recurrence, relatively good prognosis and unified cause in almost all patients. The forkhead box L2 (FOXL2) gene encodes an essential transcription factor in the ovary. FOXL2 is important in female sex determination, follicle recruitment, and granulosa cell development. About 70-97% of AGCTs were reported to carry a somatic mutation c.402C>G (C134W) in the FOXL2 gene. However, it is unknown whether AGCTs of Japanese patients harbor the FOXL2 c.402C>G mutation. Here, we report a mutational analysis of the FOXL2 gene in four Japanese patients with AGCTs, and we review the literature to determine the precise incidence of FOXL2 mutations in AGCTs. All four patients were analyzed by immunohistochemistry for FOXL2. Genomic DNA was extracted from paraffin-embedded tissues, and was analyzed to detect the c.402C>G mutation in FOXL2 by direct sequencing. All tumors were stained with FOXL2. Three of the four tumors harbor the c.402C>G mutation. Based on the literature review, FOXL2 immunostaining is a highly specific marker for sex cord-stromal tumors (SCSTs), but it is not specific for AGCTs, one subtype of SCSTs. We identified 340 patients with the FOXL2 mutation (c.402C>G) and determined that the incidence of the mutation is 91.9% in AGCT patients. Therefore, this FOXL2 mutation is specific to AGCTs in the ovary and is useful for diagnosis of this disease.
Vesicoureteral reflux (VUR) is common condition in infants with febrile urinary tract infections (UTIs). Both VUR and febrile UTIs are risk factors for renal scars, characterized by glomerular hypertrophy with global or segmental sclerosis as cardinal features in pathology. Because renal scars may cause hypertension or chronic kidney diseases in later life, voiding cystourethrography (VCUG) has been mandatory for infants following their first febrile UTIs to identify VUR. However, increasing evidence suggests that the presence of VUR may not represent a direct risk factor for renal scars, which has led to an increase in the use of a stratified approach, in which VCUG is not performed for all patients. This study was conducted to verify whether the stratified approach is justified to identify infants at risk for renal scarring. The medical records of 306 infants with first febrile UTIs (median age, 4 months; 0-72 months) were reviewed. VUR was detected in 40.4% (67/166) of patients by the non-stratified approach, in which VCUG was performed in all patients. In contrast, VUR was identified in only 27.1% (38/140) of patients by the stratified approach, in which VCUG was performed only in the patients with high risk of developing renal scars. This difference in the discovery rate was significant (p = 0.02). Renal bladder ultrasonography had the sensitivities of as low as 45.7% and 52.9% in detecting VUR and in predicting renal scarring assessed by renal scintigraphy, respectively. In conclusion, VCUG should be performed in all infants after their first febrile UTIs.
Elevated alanine aminotransferase (ALT) in serum, relevant to nonalcoholic fatty liver disease, has been often reported from Asian countries and the U.S., and it may be associated with lifestyle behavior. To clarify whether specific dietary behavior is associated with hepatocellular injury, we explored liver markers and dietary lifestyles (e.g., breakfast-skipping, eating for lunch, and snacking) in 1,809 male employees, aged 19-59 years, belonging to a health insurance union of automobile dealerships in Japan. ALT, γ-glutamyltransferase, and asparate aminotransferase (AST) were positively correlated with age and body mass index (BMI) (P < 0.0001). Odds ratios (ORs) of instant noodle ingestion for lunch to ALT elevation (> 30 IU/L), after adjusting for possible confounders including age, BMI, and drinking, were 1.33 (95% confidence interval, 1.01-1.75) at 1-2 times/week and 1.47 (1.07-2.01) at ≥ 3 times/week, compared to those who seldom ate instant noodles. Likewise, the OR of the ingestion at ≥ 3 times/week to γ-glutamyltransferase elevation (> 50 IU/L) was 1.42 (1.02-1.99), but the OR to elevated AST (> 30 IU/L) was not statistically significant. Habitual ethanol intake was significantly associated with hepatocellular injury, though the threshold of daily ethanol intake differed among liver markers. Despite the low OR, habitual instant noodle ingestion for lunch is associated with ALT elevation. Since the average content of saturated fatty acids in instant noodles is considerably high among cereal foods in Japan, workers with this habit should be advised to avoid having unbalanced diets.
Renal biopsy is the gold standard for confirmation of disease severity and diagnosis of glomerulonephritis (GN), but its procedure is invasive with a risk of complications. Thus, a non-invasive monitoring method is desirable especially in pediatric patients. Fractalkine and monocyte chemoattractant protein-1 (MCP-1) are proinflammatory chemokines, and both have been reported to be involved in the pathogenesis of immunocomplex-mediated GN. Recently, it has been reported that urinary fractalkine and MCP-1 may serve as possible predictors of disease activity of adult patients with GN. We, therefore, examined whether urinary levels of fractalkine and MCP-1 correlate with clinical and histologic parameters. Twenty-six consecutive children with various types of GN were enrolled in this study, including lupus nephritis, IgA nephropathy, membranous nephropathy, acute GN, and thin basement membrane disease (served as a non-inflammatory control). Urinary fractalkine and MCP-1 concentrations in the first morning urine samples obtained at the time of renal biopsy were measured by enzyme-linked immunosorbent assay, and standardized for urinary creatinine concentrations. Urinary fractalkine concentration differed significantly among the disease categories. Urinary concentrations of fractalkine and MCP-1 showed a significant positive correlation with the degree of occult blood in urine and a significant inverse correlation with the estimated glomerular filtration rate. Furthermore, the urinary MCP-1 concentration was significantly correlated with histological chronicity indices in patients with lupus nephritis and IgA nephropathy. Measurement of urinary fractalkine and MCP-1 concentrations may be useful as a non-invasive method for predicting the disease activity of GN in children.
Insulin resistance (IR) is a common metabolic disorder in chronic kidney disease patients. In the elderly population, it is not clear whether IR is associated with lower glomerular filtration rate (GFR) and mortality. Here, we analyzed the association between IR and GFR, all-cause mortality (ACM), or cardiovascular mortality (CVM) in the elderly population. This was a community-based prospective study. Participants were selected by random sampling from those aged ≥ 65 years in Seongnam, a satellite city of Seoul, Korea. A total of 743 participants were analyzed. IR was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). The mean age was 76.4 ± 9.3 years. After multivariate analysis, HOMA-IR was negatively associated with GFR as a continuous variable (per 10 mL/min/1.73 m2 increase, β = −0.10, P = 0.004). Analyzing GFR as a categorical variable, HOMA-IR was still higher those with GFR < 60 mL/min/1.73 m2 (GFR < 60 vs. 60-89 and ≥ 90 mL/min/1.73 m2: 1.3 vs. 1.2 and 1.1, respectively; P = 0.025 and 0.019) by covariance analysis. During the follow-up period of 62.9 ± 16.9 months, there were 168 (22.6%) cases of ACM and 47 (6.3%) cases of CVM. Those in the third quintile HOMA-IR group showed the lowest ACM rate, compared with the other quintiles (P < 0.001). CVM was not significantly associated with HOMA-IR. In conclusion, a lower GFR is associated with higher IR in the elderly population. Moreover, the lowest or the highest levels of HOMA-IR are associated with higher mortality rates.
Sleep disorder and metabolic syndrome (MetS) are important health-related problems. Recently, sleep duration has decreased among Korean adults. In this study, we examined whether sleep quality is associated with MetS by analyzing 301 subjects, aged 20 years or over, without acute and severe illness who visited three primary care clinics. Sleep duration, sleep quality and the risk of sleep-related breathing disorder (SRBD) were assessed with a standardized sleeping-estimating instrument. MetS was defined according to the modified diagnostic criteria of the National Cholesterol Education Program Adult Treatment Panel-III using the Korean abdominal obesity definition. In the multiple logistic regression analysis, compared with the 7-hour sleep group, the adjusted odds ratios (ORs) of the ≤ 5- and ≥ 9-hour sleep groups for MetS were 4.89 and 5.98, respectively. Compared with the good-sleep quality and low-SRBD risk groups, the adjusted ORs of the poor-quality sleep and high-SRBD risk groups were 3.83 and 1.92, respectively (p < 0.05). In the ≤ 5- and ≥ 9-hour sleep groups, the prevalence of elevated triglyceride and high HOMA-IR was higher (p = 0.069). In the poor-quality sleep group, the prevalence of abdominal obesity, elevated triglyceride, low HDL cholesterol, high fasting insulin and high HOMA-IR were higher. In the high-SRBD risk group, the prevalence of abdominal obesity, obesity and elevated triglyceride were higher (p < 0.05). Overall, the ≤ 5- or ≥ 9-hour sleep duration, poor-quality sleep and high-SRBD risk are related with the high prevalence of MetS, perhaps through elevated insulin-resistance resulting from adiposity.
Brain development is composed of several processes, which are chronologically and mechanistically overlapping each other. However, the process of the earliest neural circuit formation in the rostral brain is less understood compared with other processes in brain development, in part because of the lack of appropriate molecular markers. Accordingly, the identification of molecular markers for nerve cells may accelerate the detailed analysis of neural development. Growth associated protein 43 (GAP-43) is a major growth cone protein that regulates F-actin dynamics, and it has been often used as a marker for developing neurons. To test whether GAP-43 can be used as a general marker for developing neurons in chick early embryos, we analyzed the expression pattern of GAP-43 protein in the brain. While the majority of the neurons were GAP-43 positive, the earliest neurons in the dorsal mesencephalon (future tectum) were GAP-43 negative. However, a subset of the GAP-43 negative neurons became positive at later stages. Such a difference in the expression of GAP-43 protein may contribute to the precise patterning of the neural circuits in the mesencephalon in the subsequent development. The earliest neurons in the telencephalon, which belong to the terminal nerve (TN), were also GAP-43 positive. Since the development of TN is poorly understood compared to other cranial nerves, GAP-43 could help the detailed analysis of the development of TN as the marker.
Falls are a major public health problem and the second leading cause of death due to unintentional accidental injury after road traffic accidents. Inactive, older individuals with several chronic illnesses fall more frequently than older individuals who are active and healthy. No population-based study has addressed the association of stroke, arthritis, hypnotic and other prescription medications with falls among the elderly simultaneously in a single population in Japan. We examined the prevalence of falls among community-dwelling elderly Japanese individuals, whom we randomly selected from a list of inhabitants aged ≥ 65 years compiled from the resident registration, and the associations between falls and each of stroke, arthritis, and hypnotic and other prescription medications. We interviewed 295 men and 307 women, and collected information about the number of falls during the latest one year, hemiplegia due to stroke, arthritis in the legs, and the number of hypnotic and other medications. We found that 46 men (16%) and 67 women (22%) had fallen at least once during the latest one year. Logistic regression analysis adjusted for age showed that hemiplegia due to stroke (p < 0.001), arthritis in the legs (p < 0.001), and taking at least four daily prescription medications (p < 0.05) were significantly associated with falls in men. Arthritis in the legs (p = 0.05) and taking at least four daily prescription medications (p < 0.05) were associated with falls in women. Treatment of fall-related diseases and medication management are important strategies for reducing falls among elderly persons.
Elderly patients with diabetes and peripheral neuropathy are more likely to experience falls. However, the information available on how such falls can be prevented is scarce. We investigated the effects of whole-body vibration (WBV) combined with a balance exercise program on balance, muscle strength, and glycosylated hemoglobin (HbA1c) in elderly patients with diabetic peripheral neuropathy. Fifty-five elderly patients with diabetic neuropathy were randomly assigned to WBV with balance exercise group, balance exercise (BE) group, and control group. The WBV and BE groups performed the balance exercise program for 60 min per day, 2 times per week, for 6 weeks. Further, the WBV group performed WBV training (up to 3 × 3 min, 3 times per week, for 6 weeks). The control group did not participate in any training. The main outcome measures were assessed at baseline and after 6 weeks of training; namely, we assessed the postural sway and one leg stance (OLS) for static balance; Berg balance scale (BBS), timed up-and-go (TUG) test, and functional reach test (FRT) for dynamic balance; five-times-sit-to-stand (FTSTS) test for muscle strength; and HbA1c for predicting the progression of diabetes. Significant improvements were noted in the static balance, dynamic balance, muscle strength, and HbA1c in the WBV group, compared to the BE and control groups (P < 0.05). Thus, in combination with the balance exercise program, the short-term WBV therapy is beneficial in improving balance, muscle strength and HbA1c, in elderly patients with diabetic neuropathy who are at high risk for suffering falls.
Sinonasal papilloma is a common benign epithelial tumor of the sinonasal tract and accounts for 0.5% to 4% of all nasal tumors. The etiology of sinonasal papilloma remains unclear, although human papilloma virus has been proposed as a major risk factor. Other etiological factors, such as anatomical variations of the nasal cavity, may be related to the pathogenesis of sinonasal papilloma, because deviated nasal septum is seen in patients with chronic rhinosinusitis. We, therefore, investigated the involvement of deviated nasal septum in the development of sinonasal papilloma. Preoperative computed tomography or magnetic resonance imaging findings of 83 patients with sinonasal papilloma were evaluated retrospectively. The side of papilloma and the direction of septal deviation showed a significant correlation. Septum deviated to the intact side in 51 of 83 patients (61.4%) and to the affected side in 18 of 83 patients (21.7%). Straight or S-shaped septum was observed in 14 of 83 patients (16.9%). Even after excluding 27 patients who underwent revision surgery and 15 patients in whom the papilloma touched the concave portion of the nasal septum, the concave side of septal deviation was associated with the development of sinonasal papilloma (p = 0.040). The high incidence of sinonasal papilloma in the concave side may reflect the consequences of the traumatic effects caused by wall shear stress of the high-velocity airflow and the increased chance of inhaling viruses and pollutants. The present study supports the causative role of human papilloma virus and toxic chemicals in the occurrence of sinonasal papilloma.
Renalase is a newly discovered amine oxidase and may lower blood pressure by metabolizing catecholamines. We have hypothesized that exercise and training may regulate renalase expression to control blood pressure. In this study, we investigated changes in renalase expression after exercise and training in white and red portion of the gastrocnemius muscle, kidney, and serum in rats. Rats were either untrained or subjected to six weeks of endurance training, which predominantly recruits red fibers. Rats from each group were sacrificed before (n = 10), immediately after (n = 10), or three hours (n = 10) following exercise. Renalase mRNA and protein levels were measured by RT-PCR and ELISA, respectively. There were no significant changes in renalase expression after prolonged training or acute exercise in the serum or red muscle of rats. However, in white muscle, renalase mRNA and protein levels decreased after acute exercise in untrained rats, whereas, in trained rats, its protein level remained unchanged, despite a decrease in mRNA. Thus, exercise influenced renalase expression only in white muscle fibers that are not predominantly recruited during exercise. The reduction of renalase protein in white muscle suggests that renalase may contribute to blood redistribution between contracting and non-contracting fibers during exercise. In the kidney, renalase protein levels decreased after training, while mRNA levels increased. The reduction in renalase protein levels may contribute to functional kidney hypoperfusion, which has been observed after training. In conclusion, exercise differentially regulates renalase expression in skeletal muscle and kidney.