Coexistence of choriocarcinoma and adenocarcinoma in the rectum: Molecular aspects

Choriocarcinoma, a malignant tumor of usually placental origin, in divided into two groups; the gestational and non-gestational types, the latter being rate. Non-gestational choriocarcinoma occurs in the lung, mediastinum, kidney, stomach, and small intestine, but rarely appears in the large intestine. We treated a 29-year-old woman with choriocarcinoma of the rectum with adenocarcinoma. Despite the rarity of the condition and the obscurity of the histogenesis, reports of similar cases and the occurrence of the tumors in the digestive tract suggest that the condition constitutes a clinical entity of a digestive tumor.     

Successful re-reconstruction for complete disruption of the right main bronchus by blunt chest trauma

A 22 year-old man was brought to our hospital about twenty-three minutes following a high-speed motorbicycle accident in which he had blunt chest trauma. He was in severe respiratory distress with marked dyspnea and restless with extensive subcutaneous emphysema involving anterior chest wall, cervical and bilateral inguinal regions. A chest X-ray revealed bilateral pneumothorax involving mediastinal emphysema and also fracture of right submandibular and clavicula. In spite of orotracheal intubation and insertion of bilateral chest tube, continuous air leak and pneumothorax did not improve. Bronchoscopy revealed the disruption of mucosa of the right main bronchus at the bifurcation. Emergency right thoracotomy was performed and there was the complete disruption of the right main bronchus. Anastomosis of the right main bronchus with circumferential resection was undertaken on May 30, 1987 about two hours after trauma. About three months after reconstruction, bronchoscopic examination revealed stomal stenosis with deformation of tracheobronchial cartilage and granulation. The stenosis showed severe irregularity by deformed cartilage and thickened scar, so widening by Nd-YAG laser vaporization was inadequate in effect. Seven months after first reconstruction, we performed re-reconstructive operation, right upper sleeve lobectomy with partial resection of carcina and right wall of trachea for scar with severe deformation of cartilage. Following the operation, the patient suffered from sepsis with pneumonitis accompanied by lung edema. This complication was treated successfully. We considered that acute pneumonitis was caused by reventilation with increase of perfusion after tracheobronchial reconstruction. Consequently, we thought it important to treat such patients with long term IPPB postoperatively with adequate medication for respiratory system.     

Molecular mechanism of ubiquitin recognition by GGA3 GAT domain

GGA (Golgi-localizing, gamma-adaptin ear domain homology, ARF-binding) proteins, which constitute a family of clathrin coat adaptor proteins, have recently been shown to be involved in the ubiquitin-dependent sorting of receptors, through the interaction between the C-terminal three-helix-bundle of the GAT (GGA and Tom1) domain (C-GAT) and ubiquitin. We report here the crystal structure of human GGA3 C-GAT in complex with ubiquitin. A hydrophobic patch on C-GAT helices alpha1 and alpha2 forms a binding site for the hydrophobic Ile44 surface of ubiquitin. Two distinct orientations of ubiquitin Arg42 determine the shape and the charge distribution of ubiquitin Ile44 surface, leading to two different binding modes. Biochemical and NMR data strongly suggest another hydrophobic binding site on C-GAT helices alpha2 and alpha3, opposite to the first binding site, also binds ubiquitin although weakly. The double-sided ubiquitin binding provides the GAT domain with higher efficiency in recognizing ubiquitinated receptors for lysosomal receptor degradation.     

The process and outcome of a programme for preventing early childhood caries in Thailand

OBJECTIVE: To evaluate the process and outcomes of a participatory dental health education (DHE) programme for preventing early childhood caries (ECC). DESIGN: A one-year intervention programme. SETTING: 21 health centres. PARTICIPANTS: 520 mothers/caregivers of 6-19 month-old children who lived in a rural area of Thailand. INTERVENTION: Small group discussion with active involvement in the intervention group and the national teaching DHE programme in the control group. MAIN OUTCOME MEASURES: Health centre staff impact evaluation, children's dental cavitated carious increment and stated changes in oral health behaviour. RESULTS: After one-year, the percent of subjects using a toothbrush and tooth brushing with fluoride toothpaste was 93% and 87% respectively in the intervention group, significantly higher (p<0.01) than the control group (73% and 58% respectively). Night time bottle-feeding, falling asleep with a bottle and sweet snack diet behaviour appeared the same in both groups. The net cavitated carious increment was 3.5 (SD=3.4) teeth in the intervention and 3.2(SD=3.5) in the control group. Health centre staff were very supportive of the programme and suggested extending the participatory format to other child health topics. CONCLUSIONS: The participatory dental health education model was shown to be a practical and effective method for increasing oral hygiene practice, but was not sufficient to prevent the development of ECC. This single intervention in the short term is not seen as sufficient to prevent the development of ECC.     

Primary sclerosing cholangitis and hepatitis C virus infection

Two cases of primary sclerosing cholangitis with hepatic C virus infection in a 62-year-old man and a 60-year-old woman are presented. The infection in the man was eradicated with interferon therapy in 1992. Seven years thereafter, endoscopic retrograde cholangiography revealed a diffuse 2.5-cm-long stenotic lesion in the common bile duct which was consequently resected. Histological examination of the resected specimen revealed proliferation of epithelial cells, plasma cell infiltration, and fibrosis in the submucosal layer of the common bile duct. The human leukocyte antigen DR loci were 2 and 9. In the woman, a 6-month course of interferon therapy in 1992 failed to eradicate the infection. Cholangiography in 1999 revealed multiple narrowings and dilatations of intra- and extrahepatic bile ducts. Ultrasound guided biopsy of the liver in 1992 had revealed onionskin lesions around the bile duct epithelium in the portal tract. The human leukocyte antigen DR locus was 2. From these findings, the 2 cases were diagnosed as primary sclerosing cholangitis. Further studies may provide insights into the relation between the pathogenesis of the disease and the infection.     

Obesity and risk of cancer in Japan

We conducted a population-based prospective cohort study in Japan to examine the relationship between body mass index (BMI) and the risk of incidence of any cancer and of cancer at individual sites. Body mass index was calculated from self-administered body weight and height at baseline. Relative risks (RR) and 95% confidence intervals (CI) were calculated in multivariate proportional-hazards models. Among 27,539 persons (15,054 women and 12,485 men) aged 40 years or older who were free of cancer at enrollment in 1984, 1,672 (668 women and 1,004 men) developed cancer during 9 years of follow-up. In women, after adjustment for potential confounders, the RR of all cancers associated with different BMI, relative to a BMI of 18.5-24.9, were 1.04 (95% CI = 0.85-1.27) for BMI = 25.0-27.4, 1.29 (1.00-1.68) for BMI = 27.5-29.9 and 1.47 (1.06-2.05) for BMI >/=30.0 (p for trend = 0.007). Higher BMI was also significantly associated with higher risk of cancers of the colorectum, breast (postmenopausal), endometrium and gallbladder in women. In men, we observed significantly increased all-cancer risk among only never-smokers. Overweight and obesity could account for 4.5% (all subjects) or 6.2% (never-smokers) of the risk of any cancer in women and -0.2% (all subjects) or 3.7% (never-smokers) in men. The value for women was within the range among women reported from Western populations (3.2%-8.8%). Our data demonstrate that excess weight is a major cancer risk among Japanese women.     

Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor

The chemopreventive efficacies of raloxifene and nimesulide, an anti-estrogen but with anti-androgen action and a cyclooxygenase-2 (COX-2) selective inhibitor, respectively, were evaluated in probasin/SV40 T antigen (Tag) transgenic (TG) rats. The treatment groups were placebo, nimesulide (400 p.p.m. in basal diet p.o.), raloxifene (slow-release pellets implanted s.c., 5 mg/kg/day), raloxifene (5 mg/kg/day) plus nimesulide (400 p.p.m.), and raloxifene (10 mg/kg/day) plus nimesulide (400 p.p.m.). Animals were killed at 17 weeks of age, and prostate tissues were harvested and weighed by lobes. Tissues were evaluated by histology, immunohistochemistry, and western blot analyses and blood was collected to measure the testosterone levels. All the animals in the placebo group had tumors in each lobe compared with only 43% each in the dorsolateral (DLP) and anterior prostate (AP) of the animals treated with raloxifene (10 mg/kg/day) plus nimesulide. The total prostate weights and adenocarcinoma portions were significantly reduced in the three raloxifene-treated groups, whereas atrophic glands were increased. There were no significant differences between the nimesulide alone and placebo groups or between the raloxifene (5 mg/kg/day) alone and raloxifene (5 mg/kg/day) plus nimesulide group, suggesting a lack of cancer preventive effects of the COX-2 inhibitor in this animal model. PCNA positive rates in ventral prostate (VP) and DLP, and androgen receptor (AR) levels in VP were significantly reduced in the three raloxifene-treated groups. Furthermore, circulating testosterone was decreased after raloxifene (10 mg/kg/day) plus nimesulide treatment. These results demonstrate that raloxifene, but not nimesulide, inhibits prostate carcinogenesis in SV40 Tag TG rats associated with a decline in circulating testosterone levels and a loss of AR expression, as well as an inhibition of cell proliferation.     

Expression of SOCS3 mRNA in bone marrow cells from CML patients associated with cytogenetic response to IFN-alpha

Previously, we have demonstrated that constitutive expression of suppressor of cytokine signaling-3 (SOCS3) affects the sensitivity of chronic myelogenous leukemia (CML) cell lines to interferon-alpha (IFN-alpha). In the present study, we analyzed the expression of SOCS3 mRNA in bone marrow cells from patients with CML at diagnosis, with the aid of real-time polymerase chain reaction. SOCS3 mRNA expression in bone marrow cells from CML patients who responded well to IFN-alpha therapy was significantly lower than that in cells from healthy volunteers and patients who were resistant to IFN-alpha therapy. Methylation of SOCS3 promoter was absent in bone marrow cells from all CML patients examined. These results indicate that the expression of SOCS3 mRNA is inversely associated with the sensitivity to IFN-alpha both in vitro and in vivo and that differences in SOCS3 mRNA expression are not due to the methylation status of SOCS3 promoters.     

Tumor necrosis factor alpha promotes invasiveness of cholangiocarcinoma cells via its receptor, TNFR2

We studied the effect of TNF-alpha stimulation on a cholangiocarcinoma cell line, CCKS1. CCKS1 expressed only one type TNF receptor, TNFR2. Treatment of CCKS1 with TNF-alpha substantially activated NFkappaB, MAPK and Akt signalings which in turn activated matrix metalloproteinase-9 (MMP-9) secretion and in vitro invasiveness of CCKS1. Pretreatment of cells with anti-TNFR2 neutralizing antibody inhibited the TNF-alpha-dependent signaling and MMP-9 secretion and subsequently blocked invasion in vitro. Moreover, an inhibitor for matrix metalloproteinase, Galardin, suppressed the invasion in a dose-dependent manner. Similarly, pharmacological inhibition of signaling clearly suppressed the TNF-alpha dependent MMP-9 secretion. These results strongly suggest that TNF-alpha-TNFR2 signaling plays an important role to convert the cholangiocarcinoma cells to be more aggressive one.     

Infantile Case of Occlusive Microvascular Retinopathy After Bone Marrow Transplantation

Background A variety of anterior and posterior segment ocular complications following bone marrow transplantation (BMT) have been well documented in adults and children, but retinal complications after BMT in infants have rarely been reported.Case A 6-month-old male infant developed occlusive microvascular retinopathy after BMT to treat acute lymphocytic leukemia.Observations Four months after the transplantation, retinal edema, hemorrhage, soft exudates, and neovascularization were found in the posterior pole fundus of the right eye and in the peripheral fundus of the left eye. After oral prednisolone was administered, the retinal lesions regressed and cicatrices with chorioretinal atrophy and fibrous tissue formed.Conclusions Neovascularization following occlusive microvascular retinopathy after BMT in infant eyes responds well to oral prednisolone. The visual prognosis depends on the foveal involvement of the retinopathy. Jpn J Ophthalmol 2005;49:318–320 © Japanese Ophthalmological Society 2005