Association analysis of toll-like receptor 4 polymorphisms in Japanese primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often result in liver failure. Toll-like receptor (TLR) 4 recognizes lipopolysaccharides of Gram-negative bacteria. Infectious agents have been suspected to play a crucial role in PBC pathogenesis since TLR4 expression was found in bile duct epithelial cells and periportal hepatocytes in liver tissues of PBC. To assess the potential contribution of TLR4 SNPs to the development of this disease, we genotyped five SNPs in TLR4 in 261 PBC patients and 359 controls using a TaqMan assay. No significant positive associations with either PBC susceptibility or progression were uncovered. These results indicate that TLR4 polymorphisms do not play a prominent role in the development of PBC in Japanese patients.     

Rotational acetabular osteotomy for acetabular dysplasia of the hip with a giant acetabular bone cyst: a case report

In acetabular dysplasia of the hip joint accompanied by a giant acetabular bone cyst, rotational acetabular osteotomy may cause serious complications, such as bone necrosis after surgery or fracture of the fragile acetabulum during the operation. In a patient with this condition, we performed a two-stage operation: first, autogenous bone grafting supplemented with hydroxyapatite filling, then rotational acetabular osteotomy (after new bone formation had been assured). Radiographs and CT scans showed favorable fusion of the grafted bone. Some 18 months after the second operation, arthrograms showed no inflow of contrast medium from the articular cavity into the bone cyst region, although this had been observed before treatment. Thus, an effective remodeling of bony congruency was indicated in the mobile acetabulum 5 years after the second operation. This two-stage operation appears to be useful for correcting acetabular dysplasia accompanied by a giant bone cyst and to carry a reduced risk of serious complications, such as deterioration of the articular surface of the acetabulum or necrosis of the translocated acetabulum.     

Synchrotron radiation microtomography of brain hemisphere and spinal cord of a mouse model of multiple sclerosis revealed a correlation between capillary dilation and clinical score

Multiple sclerosis is a neurological disorder in which the myelin sheaths of axons are damaged by the immune response. We report here a three-dimensional structural analysis of brain and spinal cord tissues of a mouse model of multiple sclerosis, known as experimental autoimmune encephalomyelitis (EAE). EAE-induced mice were raised with or without administration of fingolimod, which is used in the treatment of multiple sclerosis. Brains and spinal cords dissected from the EAE mice were lyophilized so as to reconstitute the intrinsic contrast of tissue elements, such as axons, in X-ray images. Three-dimensional structures of the brain hemispheres and spinal cords of the EAE mice were visualized with synchrotron radiation microtomography. Microtomographic cross sections reconstructed from the X-ray images revealed dilation of capillary vessels and vacuolation in the spinal cord of the EAE mice. Vacuolation was also observed in the cerebellum, suggesting that the neuroinflammatory response progressed in the brain. The vessel networks and vacuolation lesions in the spinal cords were modelled by automatically tracing the three-dimensional image in order to analyze the tissue structures quantitatively. The results of the analysis indicated that the distribution of vacuolations was not uniform but three-dimensionally localized. The mean vessel diameter showed a linear correlation with the clinical score, indicating that vasodilation is relevant to paralysis severity in the disease model. We suggest that vasodilation and vacuolation are related with neurological symptoms of multiple sclerosis.     

Relationship between ultrasonographically low-echoic lesions under the skin,wheelchair sitting time,and interface pressure on ischial region in individuals with chronic spinal cord injury

Objective: To determine the relationship between physical findings, wheelchair sitting time, and interface pressure on ischial region in subjects with spinal cord injury (SCI).Design: Cross-sectional study.Setting: Rehabilitation center in Japan.Participants: Manual wheelchair users with chronic SCI (n = 45).Interventions: Pressure ulcers (PU) were diagnosed by inspection, palpation, and ultrasonography. Self-reports were obtained on wheelchair sitting time and pressure mapping was recorded while the subject was seated on the wheelchair.Outcome measures: Subjects were divided into those with ultrasonographically low-echoic lesions (PU-positive group, n = 11) and no such lesions (PU-negative group, n = 34). Outcome measures included wheelchair sitting time and interface pressure at bilateral ischial regions.Results: Using ultrasonography, 13 low-echoic lesions were identified in 11 subjects of the PU-positive group. The pressure duration was longer and interface pressure was significantly higher in subjects of the PU-positive group compared with those of the PU-negative group (P < 0.05 and P < 0.001, respectively).Conclusions: This is the first study to evaluate the interrelationship between physical findings, sitting time, and ultrasonographically measured interface pressure on ischial region area in subjects with spinal cord injury. To prevent pressure ulcers, we recommend avoidance of prolonged wheelchair sitting and measures that can reduce the interface pressure. These variables should be carefully tailored to the needs of the individual subjects with SCI.     

The evolution of Epstein-Barr virus inferred from the conservation and mutation of the virus glycoprotein gp350/220 gene

To study variations of Epstein-Barr virus (EBV), we analyzed the gp350/220 gene for several cell lines and Japanese wild isolates using direct sequencing. The N-terminal region was highly conserved in all EBVs except for Jijoye/P3HR-1 and a few isolates. The variation of the region coincided with EBV types A and B (also referred to as types 1 and 2) and were, respectively, designated as the types a and b. The type A/a was detected in most Japanese cell lines and wild isolates, and was classified as China1 type with latent membrane protein (LMP) 1 gene. The type B/b was detected in only a few wild isolates with the Med and China2 types. The C-terminus had more diversity than the N-terminus and lacked the divergence between types A/a and B/b. The phylogenetic analyses of the gp350/220 and LMP1 genes may suggest a mode of EBV evolution into types A/a and B/b and then to LMP1 subtypes.     

Loss or Somatic Mutations of hMSH2 Occur in Hereditary Nonpolyposis Colorectal Cancers with hMSH2 Germline Mutations

Hereditary nonpolyposis colorectal cancer (HNPCC) is a major cancer susceptibility syndrome known to be caused by the inheritance of mutations in DNA mismatch repair genes, such as hMSH2, hMLH1, hPMS1 and hPMS2 . To investigate the role of genetic alterations of hMSH2 in HNPCC tumorigenesis, we analyzed 36 Japanese HNPCC kindreds as to hMSH2 germline mutations. Moreover, we also examined somatic mutations of hMSH2 or loss of heterozygosity at or near the hMSH2 locus in the tumors from the hMSH2 -related kindreds. Germline mutations were detected in five HNPCC kindreds (5/36, 14%). Among them, three were nonsense mutations, one was a frameshift mutation and the other was a mutation in an intron where the mutation affected splicing. Loss of heterozygosity in four and somatic mutations in one were detected among the eight tumors with hMSH2 germline mutations. All these alterations were only detected in genomic instability(+) tumors, i.e., not in genomic instability(-) ones, indicating that mutations of hMSH2 were responsible for at least some of the tumors with genomic instability. These data establish a basis for the presymptomatic diagnosis of HNPCC patients, and constitute further evidence that both DNA mismatch repair genes and tumor suppressor genes may share the same requirement, i.e., two hits are necessary to inactivate the gene function.     

Ammonium acid urate urinary stone caused by a low-caloric diet: a case report

A 32-year-old woman complained of right back pain and pyuria. The plain radiograph (KUB) and drip infusion pyelography (DIP) demonstrated a right renal stone and hydronephrosis. The stone was successfully treated using extracorporeal shock wave lithotripsy. Infrared spectrophotometry revealed that the stone was composed of pure ammonium acid urate. The patient had a 3-year history of excessive anorexia. The low-caloric diet was considered to have caused the disease.     

Beta 1-integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen-activated protein kinase dependent pathway

BACKGROUND: beta 1-integrin modulates cellular phenotype by mediating signals from the extracellular matrix (ECM). Although overexpression of integrin molecules in hepatocellular carcinoma (HCC) has been reported, the role of overexpressed beta 1-integrin in the disease process of HCC is not fully understood. The authors investigated the effects of beta 1-integrin on apoptosis in hepatoma cells. METHODS: Human hepatoma cell lines HepG2, Huh7, and HLE were stably transfected with full-length beta 1-integrin. Cells underwent apoptosis induced by chemotherapeutic reagents, including cis-platinum (II)-diammine dichloride, etoposide, and docetaxel. Cell survival and intracellular signaling pathways dependent on beta 1-integrin-mediated apoptosis effects were analyzed by treating cells with PD98059 (ERK inhibitor), SB203580 (p38MAP kinase inhibitor), wortmannin (phosphatidyl inositol-3-kinase inhibitor), and herbimycin A (tyrosine kinase inhibitor). RESULTS: All three hepatoma cell lines overexpressing beta 1-integrin were protected from apoptosis induced by chemotherapeutic reagents, whereas parental or mock transfected cells were not. Treatment with PD98059 or SB203580 abolished the protective effect on apoptosis in cells overexpressing beta 1-integrin. Neither herbimycin nor wortmannin blocked the protective effects of beta 1-integrin overexpression. CONCLUSIONS: These data suggest that overexpression of beta 1-integrin confers resistance to apoptosis in hepatoma cells via a MAP kinase dependent pathway. beta1-integrin mediated signaling from the ECM in HCC cells may contribute to chemotherapy resistance.     

Pulse steroid therapy in adult respiratory distress syndrome following petroleum naphtha ingestion

CASE REPORT: A suicide attempt by a 23-year-old woman involved ingestion of 1000 mL of petroleum naphtha. Early chemical pneumonitis was complicated by life-threatening, diffuse interstitial lung consolidation with pneumatoceles. Pulse steroid therapy beginning on day 17 was associated with remarkable resolution of interstitial consolidation, although an enlarging secondarily infected pneumatocele ruptured to produce a bronchopleural fistula. Thoracic surgery and antibiotic therapy resulted in improvement of the patient's respiratory condition, and she was discharged with no residual respiratory symptoms. High-dose corticosteroid therapy appears to be a useful addition to aggressive supportive treatment in late adult respiratory distress syndrome following hydrocarbon ingestion.