Expression of membrane-bound and soluble receptor activator of NF-kappaB ligand (RANKL) in human T cells

The receptor activator of NF-kappaB ligand (RANKL) and its receptor RANK are critical regulators for immune responses as well as bone remodeling. RANKL is a type II transmembrane protein that has two forms-a membrane-anchored protein and a secreted protein. In this report, we demonstrate for the first time the kinetical expression of two forms of RANKL in human T cells using two monoclonal antibodies (mAbs) against human RANKL, which we newly derived. Freshly isolated T cells rarely expressed mRANKL, while the activation of T cells induced a substantial but minimal level of mRANKL as well as the accumulation of considerable amounts of sRANKL. The addition of the metalloprotease inhibitor KB-R8301 efficiently suppressed the release of sRANKL from activated T cells or RANKL-transfectants, and reciprocally enhanced the mRANKL expression. The membrane form of RANKL was also expressed on the infiltrating T cells in the rheumatoid synovial fluid and in the gingival tissues of patients with periodontitis. Our results demonstrate that the expression of mRANKL on T cells is strictly limited, and the majority of RANKL protein produced by T cells may be active in the soluble form after shedding. The mAbs that were derived in this study may be useful for investigating the regulation and function of RANKL in immune responses and bone remodeling.     

Clinicopathological features of hereditary breast cancer

The possible role of germline mutations ofBRCA1 andBRCA2 as causative agents of familial breast cancer was assessed. Their possible involvement in the carcinogenesis of hereditary breast cancer was investigated using 63 clinically suspect families. Twenty-one lineages (33.3%) had mutations in one of the twoBRCA genes. This relatively low incidence suggested that germline mutations in unknown genes are involved in the carcinogenesis of hereditary breast cancer in the Japanese population. However, the clinicopathological features characteristic of hereditary breast cancer, such as early disease onset, a high incidence of bilateral breast cancer, and a high incidence of multiple primary carcinomas in other organs were confirmed in the present study.     

Efficacy of postoperative adjuvant therapy for stage ilia breast cancer: Futraful vs futraful+tamoxifen for er-positive patients and futraful vs futraful + adriamycin for er-negative breast cancer

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located throughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage IIIa breast cancer. Patients with estrogen receptor-positive [ER( + )] breast cancer were treated with two types of regimens, ie, cyclophosphamide + adriamycin + fluorouracil (CAF; 2 cycles) + Futraful (FT) or CAF (2 cycles) + FT + tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER( + ) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation. The 5-year survival rate was 77.2% for the CAF + FT group and 74.6% for the CAF + FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF + FT + TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF + FT + TAM group was significantly higher than that for the corresponding patients in the CAF + FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF + FT+TAM group than in the CAF + FT group). Patients with estrogen receptor-negative [ER( -)] breast cancer were treated with two types of regimens, ie, CAF + FT or CAF + FT + adriamycin (ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478 (93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF + FT group and 63.0% for the CAF + FT + ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF + FT and CAF + FT + ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF + FT+ADR group than in the CAF + FT group.     

Advertisements in newspapers and magazines about patent medicines in the Meiji era (the first dissertation) (Part 3)

After the conclusion of the trial was carried out on december 25th in the 18th year of the Meiji era, write-ups decreased graduallly. Under these circumstances, the traders of medicine began their own publication at their convenience and they put advertisements in them. "Eisei-tebako" by "Kishida ginko" and "Houtan-keikenroku" by "Morita Jihei" were the typical of them. While patent medicines were extremely popular, pharmacists at that time never denied the necessity of patent medicines. Junichiro Shimoyama and Keizo Tanba, who were representatives of pharmacists in Japan, suggested that pharmacists had ought to manage patent medicines and pointed out that excessive write-ups exacerbated the situation.     

Advertisements in newspapers and magazines about patent medicines in the Meji era (The first dissertation) (Part 1)

In February 1869, the government first permitted newspapers to be published. The Yokohama-mainichi, the Tokyo-nichi-nichi, the Nisshin-shinjishi and so on were published. The traders of medicine quickly turned their attention to the newspapers. Jihei Morita put an advertisement about "Houtan" in the newspaper issued in July in the 4th year of the Meiji era (1871) and Ginko Kishida put an advertisement about "Seikisui" in the Mainichi in Yokohama dated August 18th in the 4th year of the Meiji era. After that, the traders of medicine advertised in newspapers one after another, and the contents of advertisements were expressly the efficacy of medicine. As Yukichi Fukuzawa doubted if the trend was really desirable, he carried his comment against the trend in the Katei Sodan published by Keio-Gijuku, but the contents of advertisements were not changed. Advertisements emphasising the efficacy of medicine were prominent.     

Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study.

BACKGROUND: The present study examined the relation between fish consumption and mortality from all causes, ischemic heart disease, and stroke. METHODS: The fish consumption data in 1961-1963, 1979-1981, and 1989-1991 and mortality data, age-standardized to 45-74 years, mean of the latest available 3 years, mostly around 1992-1993, in 36 countries, were obtained from the Food and Agriculture Organization and the World Health Organization, respectively. RESULTS: There exists an inverse univariate correlation between log fish consumption in 1961-1963, 1979-1981, and 1989-1991 and log all-cause (P < 0.01 to < 0.001) and ischemic heart disease (P < 0.05 to < 0.01) mortality in both sexes. An inverse univariate correlation between log fish consumption and log stroke mortality was found only for the period 1961-1963 in both sexes (P < 0.05). Log fish consumption was independently, significantly, and inversely associated with log all-cause (all P < 0.001), ischemic heart disease (P < 0.01 to < 0.001), and stroke (P < 0.05 to < 0.001) mortality in all three time periods in both sexes, after adjusting for confounding factors. These associations remained significant even after exclusion of Iceland and Japan, countries with the highest amount of fish consumption and the lowest all-cause mortality rate. CONCLUSIONS: Fish consumption is associated with a reduced risk from all-cause, ischemic heart disease, and stroke mortality at the population level.     

Intrathoracic omental herniation through the esophageal hiatus: Report of a case

(Received for publication on Dec. 8, 1997; accepted on July 7, 1998)     

Endosalpingiosis of nonmetastatic lymph nodes along the stomach in a patient with early gastric cancer: Report of a case

We report herein the case of a 32-year-old woman who underwent distal gastrectomy with D2 lymph node dissection for gastric cancer. Microscopic examination of the resected specimen revealed signet-ring cell carcinoma of the stomach with lymph node metastases, and endosalpingiosis in the normal lymph nodes. There was no evidence of malignancy in the peritoneal cavity. To our knowledge, no other case of endosalpingiosis in the lymph nodes along the stomach has ever been reported. The possible significance of endosalpingiosis is discussed following this case report.     

Current trends in cataract and refractive surgery in Japan: 1997 survey.

PURPOSE: A sixth annual survey was carried out by mail in January 1998, to investigate the current trends in cataract and refractive surgery in Japan. RESPONDENTS: Questionnaires were sent to 816 ophthalmologist members of the Japanese Society of Cataract and Refractive Surgery. Data received from 409 (50.1%) of the recipients were cross-analyzed and compared with those from the previous surveys. RESULTS AND CONCLUSION: In cataract surgery, there have been trends toward more surgical procedures performed by a surgeon, shorter period of hospitalization, and increased number of outpatient surgery. Ninety-two percent of respondents preferred phacoemulsification, 54% used the self-sealing wound-closure technique, and 19% used topical anesthesia for phacoemulsification. As for refractive surgery, surgeons remained rather conservative; with 28% and 7% of surgeons doing astigmatic keratotomy and refractive keratotomy, respectively. Photorefractive keratectomy, laser in situ keratomileusis, and phakic intraocular lens were judged to be useful refractive surgical procedures by 56.6%, 43.3%, and 25.1% of the respondents, respectively.