LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density

Osteoporosis is a multifactorial trait with low bone mineral density (BMD). We report results of an association study between BMD and nine candidate genes (TGFB1, TGFBR2, SMAD2, SMAD3, SMAD4, IFNB1, IFNAR1, FOS and LRP5), as well as of a case-control study of osteoporosis. Samples for the former association study included 481 general Japanese women. Among the nine candidate genes examined, only LRP5 showed a significant association with BMD. We identified a strong linkage disequilibrium (LD) block within LRP5. Of five LPR5 single nucleotide polymorphisms (SNPs) that are located in the LD block, three gave relatively significant results: Women with the C/C genotype at the c.2220C>T SNP site had higher adjusted BMD (AdjBMD) value compared to those with C/T and T/T (p=0.022); and likewise, G/G at IVS17–30G>A and C/C women at c.3989C>T showed higher AdjBMD than those with G/A or A/A (p=0.039) and with C/T or T/T (p=0.053), respectively. The case-control study in another series of samples consisting of 126 osteoporotic patients and 131 normal controls also gave a significant difference in allele frequency at c.2220C>T (²=6.737, p=0.009). These results suggest that LRP5 is a BMD determinant and also contributes to a risk of osteoporosis.     

Discrepancy in diagnosis of gastric submucosal tumor among esophagogastroduodenoscopy, CT, and endoscopic ultrasonography: a retrospective analysis of 93 consecutive cases

Purpose

Evidences on diagnostic ability of esophagogastroduodenoscopy (EGD), CT, and endoscopic ultrasonography (EUS) for gastric submucosal tumor (SMT) are insufficient. For investigating a suitable diagnostic strategy, we retrospectively investigated diagnostic accuracy of EGD and CT for SMT, in comparison to EUS findings.

Methods

Ninety-three consecutive lesions in which gastric SMT was suspected by EGD were investigated by EUS from March 2009 to June 2011, including 55 lesions evaluated also by CT 4?months before or after EUS. Frequency of possibly malignant SMTs as a detection rate of EGD, and sensitivity and specificity of CT in detection of SMT were retrospectively analyzed. Factors influencing the ability for CT to detect SMT were also investigated.

Results

EUS revealed possibly malignant SMT in 60 cases (64.5%). In 32 out of 55 cases, possibly malignant SMT was suspected by CT. Sensitivity and specificity of CT was 80.6% and 84.2%, respectively. The mean size of possibly malignant SMT detected and not detected by CT was 27.4 and 11.0?mm, respectively, with a statistically significant difference (p?=?0.0001).

Conclusion

This study elucidated that approximately one-third of suspected SMTs by EGD might not need clinical care. EUS for suspected SMTs is indispensable for extracting possibly malignant SMTs from others, and CT may be insufficient as an alternative to EUS in detecting especially small ones.     

Skeletal muscle susceptibility to clofibrate induction of lesions in rats

Morphological changes induced by clofibrate in type-1 predominant soleus, type-2 predominant tensor fasciae latae, and type-1 and -2 mixed biceps femoris muscles and diaphragm in rats were investigated. Administration of the agent at 500 or 750 mg/kg/day by oral gavage for 14 or 28 days caused lesions in the soleus muscle and diaphragm, bur no changes in the tensor fasciae latae and biceps femoris muscles. In soleus muscle, vacuolation of muscle fibers was observed in all animals treated with clofibrate, and degeneration of muscle fibers and infiltration of leukocytes were noted at 750 mg/kg/day. In diaphragm, vacuolation of muscle fibers was also observed in all animals treated with clofibrate, and these lesions were located in type-1 skeletal muscles densely stained with NADH-TR. The vacuoles seen in soleus muscle and diaphragm were positive for oil red O staining. In addition, increase of lipid droplets and mitochondrial hypertrophy was seen in soleus muscle, ultrastructurally. These data suggest that sensitivity to clofibrate-induced muscle toxicity differs among muscles, with type-1 fibers being susceptible.     

The malaris muscle: its morphological significance for sustaining the intraorbital structures

The orbicularis oculi muscle, an important mimetic muscle, was investigated to ascertain its anatomical relation to facial aging—especially its orbital part (Oo). Previous studies of the distinct muscle bundles frequently found inferior to the Oo have provided various definitions, including that of the malaris muscle. This study aimed to examine these muscle bundles and clarify their function in facial aging. Twelve heads of Japanese cadavers (average age: 82.5 years old) were dissected to observe the muscles, focusing in particular on those in the periorbital region. Six specimens were further dissected from the inner surfaces to examine the patterns of facial nerve branches under the operating microscope. Histological examinations of two head halves were carried out to investigate the relationship between the muscle bundles and the intraorbital structures. Muscle bundles consisting of lateral, medial, and U-shaped suspending bundles were observed in the region inferior to the Oo. Lateral and suspending bundles were found in all specimens, while the medial bundles were noted in only 9 of 22 specimens. Some branches of the facial nerve penetrated through the lateral, medial, and suspending bundles. The relationship between the suspending bundles and the protruding orbital fat was assessed. The muscle bundles found in this study were regarded as the malaris muscle—a transitional muscle between the superficial and deep facial layers. The suspending bundle may play a role in sustaining the intraorbital structures.     

An epidemiological study of children with status epilepticus in Okayama, Japan

BACKGROUND: The incidence of status epilepticus (SE) in Asian children, including Japanese, has not been reported. METHODS: In 2003, we performed an epidemiological study of SE on Japanese children (31 days or older to <15 years of age) in Okayama City by ascertaining all lifetime first episodes of SE. RESULTS: Thirty-seven patients (22 males and 15 females) were identified. The annual incidence of SE was 38.8 per 100,000 population (95% CI: 24.5-49.5). Febrile SE in the absence of CNS infection accounted for 17. Acute symptomatic etiologies other than febrile SE were observed in eight patients, including three cases of influenza encephalitis/encephalopathy. Five were classified as remote symptomatic and the remaining seven as cryptogenic. The highest incidence (155.1/100,000) was seen in the age range of 31 days or older to <1 year, followed by 101.5/100,000 in the age range of one year, and the incidence decreased after eight years. In 26 of the 37 patients, SE was their first seizure. As for seizure types, 32 had convulsive SE, including tonic status in one. Five others showed nonconvulsive SE, including complex partial SE in four and absence status in one. No one died of SE. Two patients who brought on SE because of influenza encephalitis/encephalopathy suffered from motor disturbance with or without mental disturbance after SE. CONCLUSIONS: The incidence of SE tended to be higher in Japanese children than reported in Caucasians. The Japanese had an age-specific incidence pattern similar to that of Caucasians.     

Identification and partial characterization of a novel CYP2C9 splicing variant encoding a protein lacking eight amino acid residues

CYP2C9 is known as an enzyme responsible for the metabolism of various clinically important drugs. Recently, we cloned a cDNA corresponding to a CYP2C9 splicing variant (SV), which seemed to have an open reading frame of a protein with 482 amino acid residues. To investigate whether or not the SV can be translated as a functionally active protein, we expressed the CYP2C9SV in insect cells, and spectrophotometric and enzymatic properties were characterized. The CYP2C9SV protein showed a typical reduced CO-difference spectrum, indicating that the translated protein binds a heme moiety. However, CYP2C9SV did not metabolize tolbutamide or diclofenac at all, suggesting that the SV protein appeared to lack the ability to catalyze reactions mediated by CYP2C9. Although the CYP2C9SV mRNA was detected in all human liver samples examined in this study by real-time PCR, the level was generally low, ranging between 0.7 and 9.6% of the normal CYP2C9 mRNA. These results suggest that the CYP2C9SV protein is unlikely to contribute to CYP2C9 activities, although it appears to be expressed in most individuals.     

Surgical site infection in patients submitted to digestive surgery: risk prediction and the NNIS risk index

BACKGROUND: Some problems have been reported with the power of the National Nosocomial Infection Surveillance (NNIS) risk index to predict the risk of surgical site infections (SSI) for specific procedures. OBJECTIVES: To develop an alternative risk prediction index for SSI and to compare the performance with the NNIS index. METHODS: A prospective cohort study was carried out with all (609) patients submitted to digestive tract surgery in 2 general teaching hospitals in the city of S?o Paulo, Brazil, from August 2001 through March 2002. RESULTS: The final incidence rate of SSI was 24.5%; 149 cases of SSI were identified: 33 (22.1%) during hospitalization and 116 (77.9%) after discharge. Logistic multivariate analysis was used for construction of the model. Obesity, surgery risk, adjusted duration, and video laparoscopic surgery were statistically significant (P < .05) for all previous procedures. The performance of the NNIS model in this study showed a low predictive capacity for the occurrence of SSI as determined by the receiver operating characteristic (ROC) curve (0.627; 95% CI: 0.575-0.678) compared with the alternative model developed with this population (0.732; 95% CI: 0.685-0.779). CONCLUSION: The presence of obesity, adjusted duration, and surgery risk significantly increased the risk for SSI. The NNIS risk index was not significant for SSI in the sample studied, and laparoscopic access was associated with a significant reduction in the risk for SSI. Although the NNIS index is a well-known and simple index, other models depicting variables related to SSI with a better sensitivity and specificity can be developed. Additional studies are required to confirm our results.