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The complement and coagulation systems are ancestrally related mechanisms of serine protease-induced protein activation. Recent studies have shown that the complement system enhances platelet aggregation by activating platelets and vascular endothelial cells. This system is also involved in the expression of tissue factor, which induces the coagulation reaction. Activated platelets and coagulation factors are also known to activate the complement system. In diseases involving the complement system, such as paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, and atypical hemolytic uremic syndrome, excessive activation of this system contributes to complement-mediated thrombosis. The anti-C5 antibody eculizumab has shown a remarkable thromboprophylactic effect in these complement diseases. The recent surge in development of new anti-complement agents has raised expectations for the advancement of treatments and preventive measures for thrombosis associated with complement disorders. This review outlines the crosstalk between these two systems, and describes the mechanisms of several diseases featuring both thrombosis and complement activation.

Objective: The purpose of this study was to clarify the characteristics of female elderly participants of a group exercise organized by the participants themselves and the changes in their physical, mental, and social health, and life function. Findings of this study will be used for promoting effective preventive care., Methods: The subjects whose characteristics were analyzed were 394 participants and 757 nonparticipants of the group exercise. Those whose changes in health were analyzed were 52 participants and 114 nonparticipants. Locomotion Check and self-rated health score were used as indices of physical health. World Health Organization-Five well-being (S-WHO-5-J) index and self-rated life satisfaction level were used as indices of mental health. Satisfaction level of social activities was one of indices of social health. The Tokyo Metropolitan Institute of Gerontology Index of Competence was used as an index of life function. The health-examination data analyzed were Body Mass Index, waist circumference, blood pressure, lipid profiles, and HbA1c level., Results: In the participant group, the proportions of those who lived alone, who were affluent, and who had no job were higher than those in the nonparticipant group. The indices of physical, mental and social health and life function were higher in the participant group. There was no significant difference in the 5-year trend of health-examination data between the two groups. There was no significant difference in the yearly change in the indices of physical health and life function. The S-WHO-5-J index, self-rated life satisfaction level, and satisfaction level of social activities were maintained or improved in the participant group., Conclusion: The results suggest the possible usefulness of the group exercise for maintaining the mental and social health of elderly women.

Objective: This study was aimed at clarifying the experience of weight loss and its related factors of thin females who still wished to lose weight among junior high school students., Methods: The subjects were 1,302 males and females in the second and third grades in 17 junior high schools in A area in Wakayama Prefecture, Japan. The anonymous self-administered questionnaire included items on attributes, items relevant to weight loss, lifestyle, subjective symptoms, and items relevant to stress. A logistic regression analysis (likelihood ratio) was used with the question items showing a statistically significant difference when comparing the two groups as independent variables to identify the factors related to the experience of weight loss., Results: There were 1,168 respondents (response rate, 89.7%). Eighty females who were less than -10% of the standard for obesity, but who still wished to lose weight, were selected from among 544 females. They were divided into two groups: those who had experienced losing weight (N=31, dieting group) and those who had never experienced losing weight (N=49, nondieting group). Between the two groups, there was a statistically significant difference in eight question items. The logistic regression analysis showed that believing oneself to be heavy by self-assessment, going to bed after midnight, and a short attention span were factors related to the experience of losing weight., Conclusion: Forty percent of the thin females who still wished to lose weight experienced weight loss. Distortion in the self-assessment of one's figure, inappropriate lifestyle, and subjective symptoms were designated as related factors.

A case of hyponatremia following the first course of systemic adjuvant chemotherapy with cisplatin (CDDP) and 5-FU in a previously treated patient with esophageal cancer is reported. A 61-year-old man was admitted to our hospital for adjuvant chemotherapy after transthoracic esophagectomy and 3-field lymphadenectomy for esophageal cancer. Six days following chemotherapy, his serum sodium concentration was found to be 118 mEq/L, without edema or dehydration. This hyponatremic state was diagnosed as the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) induced by CDDP, based on the hypo-osmolality of his serum and urine, and an inappropriate level of plasma vasopressin.

We evaluated the therapeutic effect of TS-1, a novel oral fluoropyrimidine, in combination with leucovorin with in vivo experiments using a murine tumor xenograft model fed a low folate diet. The reduced folate levels in the tumors of mice fed a low folate diet were significantly lower than those in the tumors of mice fed a normal diet. In addition, the basal reduced folate levels in the tumors of mice fed a low folate diet were comparable to those in human colorectal cancer tissues. Furthermore, when leucovorin was orally administered, the reduced folate levels in the tumors of mice fed a low folate diet were more than two-fold higher than those of mice fed the normal diet. The leucovorin-induced potentiation of TS-1 antitumor activity was obviously higher in COL-1 tumor-bearing mice fed a low folate diet than in mice fed a normal diet. The remarkable increase in reduced folate levels following the administration of leucovorin contributed to the leucovorin-induced potentiation of TS-1 antitumor activity in this low-folate-diet animal model. These results suggest that rodent models fed a low folate diet are suitable for in vivo evaluation of reduced folate drugs like leucovorin. In this model, the combination of leucovorin with TS-1 resulted in a higher antitumor efficacy than TS-1 alone or the combination of UFT and leucovorin, suggesting that TS-1 and leucovorin combination therapy may be an effective regimen for patients with colorectal cancer.

It is well known that various kinds of humoral mediators are discovered by the progress of a molecule biological method in recent years, and those humoral mediators that was produced excessively play an important role in the pathogenesis of SIRS and sepsis. However, it is impossible to measure those humoral mediators quickly in a present stage. The establishment of the fast measurement method of humoral mediators is indispensable for the judgment of septic conditions that change day by day. In this manuscript, we discussed that the role of humoral mediators in the SIRS and septic conditions and the clinical significance of established method for rapid measurement of humoral mediators.

Although peritoneal cancer metastasis has the highest frequency of postoperative recurrence among digestive organ malignant tumors, there is no still decisive treatment. Dextran sulfate (DS) as a prophylaxis for cancer metastasis was examined with respect to its effect on cultured cells. DS was made to act on a strong adhesive neoplasm cell, and the action and acting mechanism were examined with respect to 1. readhesiveness, 2. cell cycle, and 3. gene analysis. The results suggest that: i) Once tumor cells are detached by DS, the free cells do not attach even when DS is removed, and ii) DS causes the cells to stop in the G1/G0 phase.

To estimate the relationship between the expression of thymidylate synthase (TS) in tumors and clinical response and prognosis in cancer patients treated with 5-fluorouracil (5-FU), the anti-TS polyclonal antibody against recombinant human TS (rhTS) was prepared and purified. At the initial stage, we attempted to clarify the relationships between the expression of TS protein and the cytotoxicity of 5-FU in established human cancer cells in vitro. Our purified anti-TS antibody was demonstrated to react specifically with intracellular TS as revealed by western blot analysis and immunohistochemistry. Furthermore, it was revealed that the expression of TS proteins correlated with cytotoxicity (IC50 value) of 5-FU against human colorectal tumor cells, both sensitive and those with acquired resistance to 5-fluoropyrimidines, and other cancer cell lines as well. These results suggest that our anti-TS polyclonal antibody (IgG) is suitable for clinical prospective and retrospective studies on TS expression in various cancers as a prognostic factor and 5-FU response-predicting parameter.

A new dosage formulation (MTX-CH), composed of fine activated carbon particles absorbing methotrexate (MTX), distributes concentrated MTX for long periods of time to the regional lymph nodes as well as to the injection site, in animal experiments. MTX-CH would enhance the therapeutic effects not only on the primary lesion but also on the lymphatic metastasis. As clinical trials, (A) in five patients with early gastric cancer, MTX-CH at 50 to 200 mg/person of MTX was injected endoscopically in and around the primary lesion before operation. Surgically removed specimens showed that three out of the 5 primary lesions had disappeared or were necrotic, and the remaining two lesions had shrunk. (B) Three patients with contraindication to surgery received the endoscopic injection of MTX-CH. The MTX-CH injected at 250 to 1,500 mg/person into and around the primary lesion of relatively early gastric cancer resulted in the complete disappearance of the primary lesions for 14 to 24 months up to the present time without enlargement of the lymph nodes. It was thought that local injection of MTX-CH will be effective therapy, especially for gastric cancer with potential lymphatic metastasis in patients with contraindications to surgery.

In order to perform therapy for carcinomatous peritonitis by a new angiogenesis inhibitor, TNP-470, we investigated the effective timing and the optimal doses for intraperitoneal administration using two mice models. In both carcinomatous peritonitis models caused by M 5076 tumor and B 16 melanoma, the early administration of TNP-470 within one week after tumor inoculation extended the survival times of the mice receiving the drugs, whereas the administration of TNP-470 one week or later after inoculation did not affect the survival time. However, there were significant differences in the effective therapeutic doses of TNP-470 between the two models. It is important to select the best timing and doses for intraperitoneal administration of TNP-470 based on the state of angiogenesis and the sensitivity of the tumor tissues to TNP-470.

A new dosage formulation (5-FU-MS), composed of 5-fluorouracil (5-FU) incorporated in polyglactin microspheres, was studied by animal experiments, which revealed the following results. Intraperitoneal 5-FU-MS delivered greater concentrations of 5-FU for longer periods selectively to the intraperitoneal tissues, whereas it delivered a lower concentration to the blood plasma, than 5-FU solution did in rats. In mice, the 50% lethal dose value of intraperitoneal 5-FU-MS was 535 mg/kg. The toxicity of 5-FU-MS was less than 1/2 that of intraperitoneal 5-FU solution, of which the 50% lethal dose value was 242 mg/kg. Intraperitoneal 5-FU-MS at 200 mg of 5-FU/kg improved the survival curve of mice with peritoneal carcinomatosis better than the identical dose of 5-FU solution.

A new dosage formulation (ACR-CH), composed of aclarubicin (ACR) bound to fine activated carbon particles, was developed for the treatment of lymph node metastases in patients with breast cancer. In a mice experimental model, ACR-CH had superior therapeutic effects on lymph node metastases compared to the same dose of ACR aqueous solution. In clinical trials, patients with breast cancer received a local injection of 10 mg/person of ACR in the form of ACR-CH or ACR aqueous solution just before mastectomy. In the regional lymph nodes removed by the operation, the ACR concentration of 40.7 micrograms/g in patients given ACR-CH was higher than the 25.1 micrograms/g in patients given ACR aqueous solution, whereas in blood plasma the concentration was higher in patients given ACR aqueous solution than in those given ACR-CH.

A new drug dosage form comprising activated carbon particles absorbing mitomycin C (MMC-CH) has the advantage of being retained in the peritoneal cavity and distributes a larger amount of mitomycin C for a long time. Some 113 patients with gastric cancer and serosal infiltration were randomly assigned intraperitoneal treatment with MMC-CH and no anti-cancer drugs. There were significant differences in survival rate between the patients who have no visible peritoneal dissemination with MMC-CH and without. Thus, intraoperative intraperitoneal treatment with MMC-CH improves survival after gastrectomy for gastric cancer and seems effective against peritoneal recurrence.

A new dosage format (MMC-CH) of mitomycin C, which is composed of mitomycin C on activated carbon particles, was efficacious for prevention of peritoneal recurrence of gastric cancer. However, it had no such excellent therapeutic effect on the survival of patients with peritoneal dissemination. Out of 50 patients with peritoneal dissemination of gastric cancer treated by intraperitoneal administration of MMC-CH, 4 patients have survived for long periods of time (39-80 months). However, all of the other 50 patients, who did not receive intraperitoneally administered MMC-CH, died of peritoneal carcinomatosis within two years.

We have developed a new dosage form, PEP-CH, consisting of peplomycin adsorbed onto small activated carbon particles. Ten patients with inoperable advanced esophageal cancer were treated with endoscopic local injection of PEP-CH combined with radiation using 60Co. Two of 5 patients who completed the treatment have survived over one year (19 and 23 months) now.

TNP-470, an analog of fumagillin, is one of the new angiogenesis inhibitors. Five days after an intraperitoneal inoculation of 10(7) cells of Walker 256 carcinosarcoma to SD rats, TNP-470 was injected intraperitoneally in the form of TNP aqueous solution or TNP-oil solution. Mean survival time of rats given TNP-oil solution or TNP aqueous solution was statistically prolonged, compared with that of the control rats. Our results showed that TNP-470 is an effective therapeutic drug for carcinomatous peritonitis.

A new dosage format (MTX-CH) of methotrexate (MTX) comprises MTX adsorbed onto fine activated carbon particles which has strong affinity to lymphatics. MTX-CH was tested for its therapeutic effects on lymph node metastases in mice experimental model. It is known that metastases have been established in the regional lymph nodes of all mice 7 days after subcutaneous inoculation with P388 leukemia cells at 5 x 10(5) cells/mouse in left hind foot pad, and that assay mice survival time becomes short in proportion to log [P388 cell number inoculated intraperitoneally]. Therefore, drug treatment was carried out on day 7, and the regional nodes were extirpated and transferred intraperitoneally to assay mice on day 10. The survival time of mice to whom transferred were the nodes of mice treated with MTX-CH was significantly longer compared with those treated with MTX aqueous solution.

Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.

To elucidate the mechanism of the action of mazindol, an anorectic drug, mazindol effects on behaviors of rats such as feeding, drinking and activities were examined. Mazindol (40 mg/100 g of diet) addition to the diet elicited the transient decrease in food and water intakes, and increases in Animex and running wheel activities compared to those behaviors seen before the mazindol addition. The mazindol addition essentially did not affect the circadian rhythms of the above behaviors. Continuous infusion of mazindol (1-10 ng/h) into the brain reduced the total food intake and increased the light period food intake. The strongest effect of mazindol on food intake was observed when it was infused into a site of median eminence which was 2 mm posterior to the suprachiasmatic nucleus of the hypothalamus. This fact suggests that the site of the anorectic action of mazindol might be located in this area. Since food efficiency (= body weight increase per day/food intake per day) reduced during the period of mazindol addition to the diet in the above experiment, metabolic alterations due to mazindol were examined in rats. The results suggest that mazindol administration enhances degradations of proteins and amino acids and increases gluconeogenesis in the liver.