Treatment results for Stage Ib cervical cancer after stage subdivision by MRI evaluation.

PURPOSE OF INVESTIGATION: The authors analyzed treatment results for cervical cancer after subdividing Stage Ib into Stages Ib1 and Ib2 according to magnetic resonance imaging (MRI) information. MATERIALS AND METHODS: The subjects comprised 40 cases of Stage Ib cervical cancer treated by definitive radiotherapy in Kitasato University hospital and Tokyo University hospital from January 2000 to December 2008. The patients' ages ranged from 28 to 85 years (median: 68 years). The maximum tumor diameter measured with MRI ranged from undetectable to 60 mm (median: 25 mm). The authors classified tumors with the greatest dimension less than 40 mm as Stage Ib1 (29 cases) and those with the greatest dimension more than 40 mm as Ib2 (11 cases). All cases were treated with a combination of external beam irradiation and high-dose-rate intra-cavitary brachytherapy. Chemotherapy was combined with radiotherapy in 11 cases. RESULTS: The follow-up time was from four to 109 months (median: 53 months). At the time of last observation, 37 cases survived, local recurrence was seen in none, and two cases showed distant metastasis. The two- and five-year overall survival rates of all cases were 97.5% and 89.5%, respectively. When a stage was subdivided and examined, the five-year overall survival rate of Stage Ib1 was 100% and that of Stage Ib2 was 50.5% (p = 0.001). CONCLUSION: The authors suggest that the subdivision of stages using image information reflects the prognosis of Stage Ib cervical cancer.

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer.

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty-two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum-based chemotherapy. Median follow-up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1-, 2-, and 3-year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long-term survival to some patients. RT or CRT should be considered for LR.

Esophageal cancer: definitive chemoradiotherapy for elderly patients.

To investigate the efficacy and toxicity of definitive chemoradiotherapy (CRT) for elderly patients with locally advanced esophageal cancer. Twenty-two patients aged over 75 that performed definitive CRT were retrospectively reviewed. The regimen included concurrent CRT consisting of two cycles of chemotherapy (CTx) of platinum and 5-fluorouracil, and radiation therapy (RT) of 50-50.4 Gy (actual range: 45.4-71.4 Gy), and additional CTx where possible. Both CTx and RT were reduced in dose and field where necessary. The disease-free survival rate and the overall survival rate at 3 years were 33.3% ± 11.4% and 25.9% ± 10.8%. Grade 4 leukocytopenia and thrombocytopenia occurred in three (14%) and four (18%) patients. Treatment-related death was suspected in up to four (18%) patients at the most. Univariate analyses for disease-free survival showed that neither total radiation dose nor number of total cycles of CTx was significant. The pattern of relapse was predominantly more frequent in the intra-RT field than outside the RT field. For elderly patients, adverse events are frequent, and decreased organ reserve may cause treatment-related death. Reduction in CTx dose or RT field, appropriate only for two cycles of CTx, and careful monitoring may help to minimize toxicity. Physicians should not be too afraid of adverse events or be negative about CRT for elderly patients, as long as comorbidities and complications are managed carefully.

Concurrent chemoradiation alone with curative intent for limited-disease small-cell esophageal cancer in nine Japanese patients.

Small-cell carcinoma of the esophagus is a rare and aggressive tumor with early widespread dissemination. In this retrospective study, we report clinical outcomes of limited-disease small-cell carcinoma of the esophagus from the analysis of nine patients. Between 2003 and 2006, nine consecutive patients with small-cell carcinoma of the esophagus were treated in our single institution, representing 2.8% of all esophageal malignancies treated with curative concurrent chemoradiation during this period. All the patients received four cycles of etoposide (100 mg/m(2), days 1-3), combined with cisplatin (80 mg/m(2), day 1), plus radiation therapy (50 Gy in daily doses of 2 Gy, 5 days/week). At the time of analysis, the median follow-up time was 10.8 months (range: 4.2-42.8 months) and 21.8 months in five living patients (56%). Of all the nine patients, five patients (56%) had a complete response, and the actuarial 3-year overall survival rate was 55.6%. This regimen resulted in a favorable 3-year survival rate. We conclude that the optimum treatment seems to be the same as for small-cell carcinomas of the lung, that is, a multidrug combination chemotherapy regimen used with concurrent radiation.

Spin ordering and enhancement of electronic heat capacity in an organic system of (DI-DCNQI)(2)(Ag(1-x)Cu(x)).

Thermodynamic measurements on the organic system of (DI-DCNQI)(2)(Ag(1-x)Cu(x)) (x = 0,0.05, 0.71, 0.90) were performed to study the change from the charge-ordered (CO) insulating state to the π-d hybridized metallic state. A thermal anomaly associated with the antiferromagnetic transition that occurred in the charge-ordered lattice was observed at 6.2 K from the temperature dependence of the heat capacity of (DI-DCNQI)(2)Ag. We have found that the magnetic entropy around the peak is only 1.5% of Rln2, corresponding to the full entropy expected for the formula unit of (DI-DCNQI)(2)Ag. This anomaly is suppressed down to about 3 K in the x = 0.05 sample owing to the disorders induced in the CO lattice. In the metallic concentration of x = 0.90, the low-temperature electronic heat capacity coefficient, γ was found to be enhanced by up to about 63.6 mJ K(-2) mol(-1) probably owing to the cooperative effect of π-d hybridization and intersite Coulomb interaction (V).

Series of surveys for enteric viruses and indicator organisms in Tokyo Bay after an event of combined sewer overflow.

Combined sewer overflows (CSOs) have been recognised as one of the serious sources of pollution to the water environment during rain events, although field surveys to investigate the effect of their magnitude and duration on receiving waters have been very limited. The fates of enteric viruses (norovirus G1, G2, enteroviruses) and coliforms were determined in the wastewater treatment plant on a fine day and on a rainy day. Not all microorganisms were reduced in the primary treatment, but were reduced in the secondary treatment. Occurrences of enteric viruses and levels of coliforms were surveyed in the receiving coastal area after a CSO event, with the profiles of the enteric viruses in the coastal seawater being almost at the same positive ratio for 4 d after the CSO event.

Interleukin 1 polymorphisms, lifestyle factors, and Helicobacter pylori infection.

Associations between Helicobacter pylori (HP) infection and lifestyle factors have been reported by several authors, but little is known about the host factors associated with the infection. This study aims to examine the infection rate of HP according to gene polymorphisms of interleukin (IL)-1A, IL-1B, and IL-1RN, and to investigate the interactions with lifestyle factors. Subjects were 241 non-cancer outpatients who had participated in a HP eradication program. Polymorphisms at - 889 (T to C) of IL-1A, at - 31 (C to T; T allele makes a TATA box) and - 511 (C to T) of IL-1B, and at intron 2 (86-bp VNTR (variable number of tandem repeats)) of IL-1RN were genotyped by PCR (polymerase chain reaction), PCR-RFLP (restriction fragment length polymorphism) and PCR-CTPP (PCR with confronting two-pair primers). It was found that IL-1B polymorphisms at - 31 and - 511 were near-completely linked, but in the opposite way to that in Caucasians; - 31C / - 511T and - 31T / - 511C alleles were dominant in the present subjects. The HP infection rate was substantially different among the genotypes of IL-1B C - 31T; 45.2% (19 / 42) for the C / C, 67.7% (90 / 133) for the C / T, and 63.6% (42 / 66) for the T / T. The age-sex adjusted odds ratio (OR) relative to the C / C genotype was 2.32 (95%CI (confidence interval), 1.10 - 4.92) for the T / C genotype and 2.46 (1.06 - 5.74) for the T / T genotype. The OR for the T / T genotype was significantly modified by smoking status; interaction term = 14.6 (1.12 - 190). The polymorphisms of IL-1A and IL-1RN were not associated with the infection rate. The results suggested that the T allele of IL-1B C - 31T is associated with vulnerability to persistent HP infection, and that the vulnerability is modified by smoking.

TEM and HAADF-STEM study of a Au catalyst supported on a TiO2 nano-rod.

Gold nanoparticles were deposited on TiO2 nano-rods by a deposition precipitation method. This Au/TiO2 nano-rods catalyst is active for CO oxidation even at temperatures less than 273K and is as active as the catalyst of Au supported on conventional TiO2 particles. Transmission electron microscopy (TEM) showed that the TiO2 nano-rods were composed of a single anatase crystal and had a pillar shape with an axis along the <111> direction surrounded by flat four [101] planes. High angle annular dark field scanning TEM (HAADF-STEM) also revealed that a Au platelet with a thickness of 0.5-1 nm was formed at the interface between TiO2 nano-rods. The Au platelet was not observed when conventional round particles of TiO2 were used as a support.

Anti-tetanus toxoid antibody production and protection against lethal doses of tetanus toxin in hu-PBL-SCID mice.

BACKGROUND: In this study, severe combined immunodeficiency (SCID) mice, which permit the survival of lymphoid cells of human origin, were used to study the human anti-tetanus immune response. METHODS: Human peripheral blood lymphocytes (hu-PBL) obtained from 88 healthy donors (aged from 18 to 62) were transplanted into SCID mice, and anti-tetanus toxoid (Ttd) antibody production and protection against lethal doses of tetanus toxin (Ttx) were investigated in the hu-PBL-SCID mice. RESULTS: The transfer of human PBL evoked significant human anti-Ttd IgG antibody production for 37.5% of the donors. After in vivo immunization, the percentage of donors with PBL exhibiting positive anti-TtD IgG production in the mice increased to 54.5%. Mean anti-Ttd IgG levels in the sera were also significantly elevated in response to immunization. The mean IgG titer for the mice injected with PBL from donors under the age of 40 was significantly higher than that of the mice injected with PBL from donors aged 40 or older. Four weeks after the cell transfer, the mice were challenged with Ttx. The induction of protection against Ttx challenge was observed mostly in mice with PBL transferred from donors under the age of 40. In vivo immunization in SCID mice with Ttd increased the number of cases of resistance to Ttx. CONCLUSIONS: These results suggest that hu-PBL-SCID mice might serve as a tool for predicting the protective ability against pathogens in PBL donors and also for evaluating vaccine efficacy.

No association of the 5' promoter region polymorphism of CYP17 with breast cancer risk in Japan.

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5' promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and 0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother / sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5' promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.

Reaction of selenobenzophenones with olefins. Formation of 1H-2-benzoselenopyrans. Reaction of 1H-2-benzoselenopyrans with diazoalkanes

Selenobenzophenone reacts as a diene with dimethyl acetylenedicarboxylate (DMAD) to lead to dimethyl 1H-1-diphenylmethyl-1-phenyl-2-benzoselenopyran-3,4-dicarboxylate (5c) in moderate yield; the initial [4 + 2] cycloaddition is followed by the addition of another 1 mol equiv of selenobenzophenone. The reaction might proceed through carbene insertion of the primary cycloadduct. On the other hand, 4,4'-dimethoxyselenobenzophenone combines as a diene with DMAD furnishing dimethyl 1H-1-p-methoxyphenyl-6-methoxy-2-benzoselenopyran-3,4-dicarboxylate (4a). The reaction of benzoselenopyran derivative (4) with diaryldiazomethanes afforded another type of carbene insertion product.

[Antibody levels for diphtheria, tetanus and pertussis in young adult females immunized with whole cell pertussis-diphtheria-tetanus toxoid vaccine in infancy].

Antibody levels for diphtheria, tetanus and pertussis in 84 young adult females were measured. They had been immunized with whole cell pertussis-diphtheria-tetanus toxoid (DTwP) vaccine as a routine immunization in their infancy. Their history of DTwP vaccination were confirmed in their Maternal and Child Health Handbook, which includes their immunization record. Among the 84 cases, 4 cases (4.7%) had been immunized with the first dose of DTwP, 5 cases (6.0%) with the second dose, 23 cases (27.4%) with the third dose and 52 cases (61.9%) with the fourth dose. Of the 84 cases, 89.3% had received DTwP vaccine more than the third dose. In the 15-19 years after the last DTwP vaccination, the antibody positive rate for diphtheria and tetanus (> or = 0.01 IU/ml) were 86.9% and 94.0%, respectively. On the other hand, antibody positive rate for anti-pertussis toxin (anti-PT) and anti-filamentous hemaggulutinin (anti-FHA) (> or = 10 EU/ml) were 35.7% and 55.9%, respectively. The positive rate for pertussis compared with those for diphtheria and tetanus were lower. These findings suggested that DTwP vaccination in infancy does not provide sufficient immunity for young adults against pertussis, but DTwP vaccination provides adequate immunity against diphtheria and tetanus.

Virus entry is a major determinant of cell tropism of Edmonston and wild-type strains of measles virus as revealed by vesicular stomatitis virus pseudotypes bearing their envelope proteins.

The Edmonston strain of measles virus (MV) that utilizes the human CD46 as the cellular receptor produced cytopathic effects (CPE) in all of the primate cell lines examined. In contrast, the wild-type MV strains isolated in a marmoset B-cell line B95a (the KA and Ichinose strains) replicated and produced CPE in some but not all of the primate lymphoid cell lines. To determine the mechanism underlying this difference in cell tropism, we used a recently developed recombinant vesicular stomatitis virus (VSV) containing as a reporter the green fluorescent protein gene in lieu of the VSV G protein gene (VSVDeltaG*). MV glycoproteins were efficiently incorporated into VSVDeltaG*, producing the VSV pseudotypes. VSVDeltaG* complemented with VSV G protein efficiently infected all of the cell lines tested. The VSV pseudotype bearing the Edmonston hemagglutinin (H) and fusion (F) protein (VSVDeltaG*-EdHF) infected all cell lines in which the Edmonston strain caused CPE, including the rodent cell lines to which the human CD46 gene was stably transfected. The pseudotype bearing the wild-type KA H protein and Edmonston F protein (VSVDeltaG*-KAHF) infected all lymphoid cell lines in which the wild-type MV strains caused CPE as efficiently as VSVDeltaG*-EdHF, but it did not infect any of the cell lines resistant to infection with the KA strain. The results indicate that the difference in cell tropism between these MV strains was largely determined by virus entry, in which the H proteins of respective MV strains play a decisive role.

[A case received pre-exposure immunization against rabies by intradermal injection of rabies vaccine because of allergic reaction to the component of the vaccine].

A female, 25 years of age, came to our clinic to receive pre-exposure immunization against rabies. In another hospital she was tested to find out whether she was allergic to the components of rabies vaccine (PCEC) manufactured by the Chemo-Sero-Theraptic Research Institute (Kaketsuken) by cutaneous reaction using a 2,000-fold diluted PCEC. She showed a positive reaction. In our clinic she was again examined by skin test using 0.1 ml of 10-fold diluted PCEC. She showed wheal and flare reaction. Further we tested using 0.05 ml and 0.1 ml of non-diluted PCEC. Her skin reaction did not increase by several mm in diameter. So we decided to immunized her against rabies with intradermal injections of PCEC instead of subcutaneous injections that is indicated by the manufacturer. The second intradermal injections were done to right and left forearms a week later. Then the third shot was given 4 weeks after the second. At 2 weeks after the third injection her blood sample was taken to measure anti-rabies antibody titer by ELISA method with Platelia rabies kit (Diagnostic Pasteur, France). She had 6.7 U/ml of anti-rabies ELISA antibody that was much higher than the protective level (0.5 IU/ml) officially recognized by WHO. Therefore, it is concluded that she had produced sufficiently high level of anti-rabies antibody with intradermal injection of PCEC. It is reasonably recommended to investigate further if the intradermal injection of PCEC will be an effective method as a pre-exposure immunization against rabies.

Dermatomyositis associated with invasive thymoma.

We report a case of dermatomyositis (DM) associated with invasive thymoma in a 22-year-old woman who was admitted to our hospital complaining of dyspnea which required ventilation support. The reddened elevated scaly eruptions were prominent over the extensor surfaces. Chest X-ray and computed tomography showed mediastinal masses, which were diagnosed as mixed type thymoma. Muscle and skin biopsy specimens were compatible with DM. She was treated with methylprednisolone pulse therapy followed by extended removal of the anterior mediastinal tumor and subsequent radiotherapy. She has had a good clinical course without recurrence of thymoma or DM for more than 3 years. The role of thymoma in the development of DM is discussed.

Tea polyphenol intake and changes in serum pepsinogen levels.

Following a phase I study, a phase II study was conducted to evaluate the effects of two different doses of tea polyphenols on serum pepsinogen levels. Subjects were patients aged 40 to 69 years who had undergone gastroscopy between 1995 and 1997 at Aichi Cancer Center Hospital, and had been found to have no disease requiring medication. Those with pepsinogen I < 70 ng/ml and pepsinogen I/II ratio < 6 were included in this study. Capsules containing 100 mg of tea polyphenols were administered for 1 year: 1 capsule per day for 101 patients (42 males and 59 females), and 6 capsules (equivalent to 10 cups) per day for 83 patients (30 males and 53 females). The enrollment of the 1 capsule group preceded that of the 6 capsule group, in which re-participation was allowed. Blood samples were obtained 1 year after participation from 86 participants of the 1 capsule group and 77 participants (43 new participants and 34 re-participants) of the 6 capsule group. The compliance in polyphenol capsule intake ranged from 11.4 to 105.7% (87.6% on average) of the scheduled amount for the 1 capsule group and 3.2 to 112.3% (77.8% on average) for the 6 capsule group. No serious polyphenol-related adverse effects were reported. The difference in pepsinogen I between before and after 1 year intake of the polyphenol was 3.1 ng/ml for the 43 participants of the 6 capsule group, but 3.5 ng/ml for the 1 capsule group. The mean pepsinogen I/II ratio for the 43 participants increased from 2.37 by 0.08. This increase was not larger than that for the 1 capsule group (from 2.61 by 0.11). Among 34 participants in both interventions, no significant increase in pepsinogen I and I/II ratio for the 6 capsule intervention was observed. This result suggests that additional polyphenol intake for 1 year in Japanese does not improve pepsinogen levels, which are considered to reflect stomach atrophy, a high-risk condition for stomach cancer.

Identification of a novel bovine serum protein which is involved in human T-cell leukemia virus type I (HTLV-I)-induced syncytium formation.

By immunizing rats with cocultured HTLV-I-positive ILT8M2 and HTLV-I-negative MOLT-4-cells, we isolated a monoclonal antibody (mAb), designated as mAb R21, which enhances the syncytium formation induced by coculturing ILT8M2 cells with MOLT-4 cells. The antigen recognized by mAb R21 was found on the surface of all T-cell, fibroblastoid, and epithelial cells lines, and a part of B-cell and myelomonocytoid cell lines. MAb R21 reacted with an approximately 17-kDa protein from ILT8M2 and MOLT-4 cell lysates in both nonreducing and reducing conditions by immunoblotting. Immunoprecipitation experiments using surface-labeled cells revealed that a 17-kDa protein is present on the surface of both ILT8M2 and MOLT-4 cells. Since the enhancing activity by mAb R21 of syncytium formation was observed only in the presence of a factor contained in fetal calf serum (FCS) which seems to bind to mAb R21, we purified this serum factor from FCS using a mAb R21-coupled Sepharose 4B column. The purified protein, designated as R21 protein, was revealed to be O-glycosylated but not N-glycosylated protein of approximately 17 kDa. The partial amino acid sequence of this protein indicates that R21 protein is a novel bovine serum protein which has approximately 90% amino acid homology with bovine platelet factor 4, a member of CXC chemokine family. These results indicate that the R21 protein on the surface of cells and/or in FCS may play an important role in the process of HTLV-I-induced syncytium formation by as yet unknown mechanism.