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Biomedical subjects

F Fujita

Publications and source records attributed to F Fujita.

At least 19 recordsLinked to original sources

Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro-oesophageal reflux disease: randomized-controlled study of gastro-oesophageal reflux disease.

BACKGROUND: The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged. AIM: To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease. PATIENTS AND METHODS: A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily. RESULTS: Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time. CONCLUSION: Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease.

Analysis of Variance↗

Human tumor necrosis factor-alpha mutant RGD-V29 (F4614) shows potent antitumor activity and reduced toxicity against human tumor xenografted nude mice.

The antitumor effects of human tumor necrosis factor-alpha (TNF) mutant RGD-V29 (code no. F4614), that includes the cell adhesive sequence (4)Arg-(5)Gly-(6)Asp and (29)Arg-->Val substitution, were evaluated. The therapeutic index, a measure of the extent of the therapeutically-effective range, using three constitutive administrations of RGD-V29 in Meth A-bearing mice was 4.8, whereas that of recombinant human TNF (rhTNF) ((1)SSS(4)RTPSDK...(29)RR...(155)L) was 2.8, clearly indicating that the effective RGD-V29 dose-range was extended. Furthermore, RGD-V29 showed potent antitumor activity against human lung cancer Mqnu-1 xenografted nude mice without severe gastrointestinal and other organ toxicities, even when administered at the maximal tolerated dose (MTD). In contrast, rhTNF induced severe toxicity at the MTD. Direct cytotoxicity of RGD-V29 against Mqnu-1 cells was similar to that of rhTNF. In addition, a cytotoxicity assay using a tumor-derived endothelial-like cell (tEC)/normal endothelial cell (nEC) system used to study TNF antitumor effects on tumor-associated endothelial cells, suggested that RGD-V29 showed preferential cytotoxicity toward tumor-associated endothelial cells compared with rhTNF. Thus, RGD-V29 appears to be a low-toxicity mutant of rhTNF that shows preferential activity towards tumors, and therefore merits further investigation in pre-clinical and clinical studies.

Amino Acid Sequence↗

Therapeutic potential of chimeric anti-(ganglioside GD3) antibody KM871: antitumor activity in xenograft model of melanoma and effector function analysis.

KM871 is a chimeric antibody recognizing ganglioside GD3, which is one of the major gangliosides expressed on the cell surface of human tumors of neuroectodermal origin. This study demonstrates the antitumor activity of KM871 against human melanoma xenografts in nude mice, and analyzes the effector function operating in mice. In a well-established tumor model, KM871 showed antitumor activity against H-15 and SK-MEL-28 human melanoma but not against H-187 and G361 human melanoma when administered intravenously 5 days/week for 2 weeks. The G361 tumor became sensitive when KM871 was first administered on the day of tumor inoculation. In this assay, it was observed that almost all the mice were tumor-free, but a few mice developed tumors. Therefore, we examined the amount and expression pattern of GD3 antigen on G361 tumors escaping from KM871 treatment, but no change was observed. Next we examined the optimal administration schedule for KM871 in mice, using H-15 melanoma. KM871 showed antitumor activity when administered intravenously either 5 days/week for 2 weeks or three biweekly doses. However, the effect of the former schedule was stronger than three biweekly doses. To compare the effector function in humans and mice, we studied the complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity and antibody-dependent macrophage-mediated cytotoxicity of KM871 using complement or effector cells prepared from humans and mice. It was found that the antibody-dependent cell-mediated cytotoxicity exerted by polymorphonuclear cells and antibody-dependent macrophage-mediated cytotoxicity were the only antitumor mechanism of KM871 in mice. However their action was very weak compared with that in humans, and complement-mediated cytotoxicity, which was strong in humans, was not observed in mice. Therefore, the antitumor activity of KM871 against human melanomas evaluated by the nude mouse model might be underestimated. These results indicate that KM871 shows good antitumor activity against GD3-positive human melanoma and the antitumor activity expected in humans might be superior to that of the nude mouse model.

Animals↗

Factors influencing the relation between extraversion and pleasant affect.

Factors that influence the relation between extraversion and pleasant affect were examined in 6 studies. In Studies 1 through 5, the authors used structural equation modeling techniques to test whether different extraversion and pleasant affect scales and the use of multiple methods of assessment influenced the strength of the relation. In Study 6, the authors conducted a meta-analysis of previous literature to calculate an average effect size and to assess the influence of moderator variables. Results from both the structural equation models and the meta-analysis showed that with only a few exceptions, the use of different extraversion and affect scales resulted in moderate to strong correlations. The use of "on-line" methods of mood assessment (moment reports or daily-diary reports) resulted in lower and more homogeneous correlations than did the use of global, retrospective measures of mood.

Adult↗

[Antitumor effects of TZT-1027, a novel dolastatin 10 derivative, on human tumor xenografts in nude mice].

TZT-1027 was evaluated for its antitumor effects in sixteen human tumors xenografted in nude mice from gastric (H-81, H-106, H-30, H-154), breast (H-31, H-62), colon (H-110, H-143), lung (LC-376, H-74, Mqnu-1, LC-351), liver (H-181), renal cell (H-12) and ovarian (H-OC-3, SOC-4) cancer lines. In the latter three and lung (Mqnu-1, LC-351) cancers the results were compared with those obtained with CPT-11, VCR, CDDP, ADM. TZT-1027 showed effective antitumor activity (IR > or = 58%) against fifteen of the tumor lines, all but LC-351, and showed markedly effective activity (IR > or = 80%) against twelve tumor lines, including drug-resistant colon (H-110), lung (H-74) and ovarian (SOC-4) cancer lines. The complete regression was shown in five H-OC-3 tumor-bearing mice out of seven. Moreover, TZT-1027 was shown to be more potent in three cancer models (Mqnu-1, H-81, SOC-4) than CPT-11, and to have markedly effective antitumor activity in two cancers (H-12, H-OC-3) in which VCR was ineffective and in ovarian cancer (SOC-4) in which CPT-11, CDDP and ADM were ineffective. The administration of TZT-1027 induced fewer side effects; transient reduction of body weight was observed in four lines out of sixteen tested. These results suggest that TZT-1027 is an excellent candidate for clinical trials for the treatment of cancer.

Animals↗

[Equilibration period for PaO2 following alteration of FIO2 in mechanically ventilated patients].

To determine arterial oxygen tension (PaO2) in mechanically ventilated patients, we repeatedly measured arterial blood gas (ABG) to examine changes in PaO2 until equilibration following alteration of fractional concentrations of oxygen in inspired gas (FIO2). Forty anesthetized patients with normal arterial oxygenation were randomly assigned to one of four groups. Group 1 (n = 10): Arterial blood samples were drawn every one minute during a 15-min period of equilibration after change of FIO2 from 1.0 to 0.21. Then FIO2 was returned to 1.0 and the similar sampling was repeated. Group 2 (n = 10): The protocol was same as in Group 1 except for FIO2 targeted for 0.8 and 0.4. Group 3 (n = 10): Blood sampling was every two minutes during a 14-min period and repeated while FIO2 was altered as in Group 1. Group 4 (n = 10): The protocol was same as in Group 3 except for the target FIO2 similar to Group 2. PaO2 was stabilized in 4 min at earliest and in 6 min at latest after change of FIO2 in every settings of this study. In mechanically ventilated patients with normal arterial oxygenation, PaO2 could be stabilized after a 6-min period of equilibration following alteration of FIO2.

Blood Gas Analysis↗

Negative regulation of Wingless signaling by D-axin, a Drosophila homolog of axin.

Wnt/Wingless directs many cell fates during development. Wnt/Wingless signaling increases the amount of beta-catenin/Armadillo, which in turn activates gene transcription. Here the Drosophila protein D-Axin was shown to interact with Armadillo and D-APC. Mutation of d-axin resulted in the accumulation of cytoplasmic Armadillo and one of the Wingless target gene products, Distal-less. Ectopic expression of d-axin inhibited Wingless signaling. Hence, D-Axin negatively regulates Wingless signaling by down-regulating the level of Armadillo. These results establish the importance of the Axin family of proteins in Wnt/Wingless signaling in Drosophila.

Adaptor Proteins, Signal Transducing↗

Identification and characterization of E-APC, a novel Drosophila homologue of the tumour suppressor APC.

BACKGROUND: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers. The product of the APC gene forms a complex with beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and Axin/conductin, and induces the degradation of beta-catenin. RESULTS: We have identified a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC. The E-APC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the 15-amino acid repeat, five copies of the 20-amino acid repeat, and one Axin/conductin binding site. E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of beta-catenin) in vitro, destabilizes intracellular beta-catenin, and suppresses beta-catenin/TCF-regulated transcription in APC-/- colon cancer cells. The E-APC mRNA is ubiquitously expressed throughout all developmental stages in Drosophila. CONCLUSION: Our findings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.

Adaptor Proteins, Signal Transducing↗

[Propofol-air-oxygen anesthesia reduces the incidence of sore throat after laryngeal mask anesthesia].

We investigated the effects of the presence or absence of N2O in propofol anesthesia using a laryngeal mask on the incidence of postoperative sore throat. In the N2O-combined anesthesia group (n = 25), score 0 (no sore throat) was observed in 11 patients; score 1 (slight pain and discomfort that improved on the next day of operation) in 9; and score 2 (persistent pain on the next day) in 5. In the non-N2O-combined anesthesia group (n = 25), score 0 was observed in 21 patients, score 1 in 3; and score 2 in 1, showing a significantly lower incidence of sore throat and milder sore throat than in the N2O-combined anesthesia group. These results suggest that propofol anesthesia using a laryngeal mask not combined with N2O reduces the incidence of postoperative sore throat.

Adult↗

Events and subjective well-being: only recent events matter.

The effect of life events on subjective well-being (SWB) was explored in a 2-year longitudinal study of 115 participants. It was found that only life events during the previous 3 months influenced life satisfaction and positive and negative affect. Although recent life events influenced SWB even when personality at Time 1 was controlled, distal life events did not correlate with SWB. SWB and life events both showed a substantial degree of temporal stability. It was also found that good and bad life events tend to covary, both between individuals and across periods of the lives of individuals. Also, when events of the opposite valence were controlled, events correlated more strongly with SWB. The counterintuitive finding that good and bad events co-occur suggests an exciting avenue for explorations of the structure of life events.

Adult↗

Resources, personal strivings, and subjective well-being: a nomothetic and idiographic approach.

The covariation of resources such as money, family support, social skills, and intelligence with subjective well-being (SWB) was assessed in 195 college students. Informant ratings provided an index of resources. Self-reports, daily experience sampling, and informant reports were used to measure SWB. The authors concluded that resources taken together are moderately strong predictors of SWB. This conclusion, however, was qualified by the fact that life satisfaction was more closely related to resources than was affective well-being and that social and personal resources were in general more strongly related to SWB than were material resources. The findings also supported the hypothesis that resources correlate more strongly with SWB when they are relevant to an individual's idiographic personal strivings. A tendency was found for people to choose personal strivings for which they have relevant resources, and the degree of congruence of individuals' goals with resources was predictive of SWB.

Achievement↗

Antitumor activity of the new selective protein kinase C inhibitor 4'-N-benzoyl staurosporine on murine and human tumor models.

CGP 41251 (4'-N-benzoyl staurosporine, CAS 120685-11-2) has been shown to exert increased selectivity for the inhibition of protein kinase C (PKC) activity. In the present study the effect of CGP 41251 formulated in gelucire as an antitumor agent was studied in various types of murine and human tumor models. When administered at a dose of 75 mg/kg 3 times daily for 9 days, CGP 41251 prolonged the life span of the mice bearing B16 melanoma (ILS = 36%). CGP 41251, administered orally at doses of 25-225 mg/kg once daily for 9 days, however, did not show distinct efficacy in four kinds of murine tumor models (B16 melanoma, colon 26, colon 38 and M5076). In s.c.inoculated human tumor xenograft models, CGP 41251, administered orally at a dose of 200 mg/kg once daily for 4 weeks showed a broad antitumor spectrum. CGP 41251 inhibited the growth of gastric cancer (H-55), colorectal cancer (H-26), breast cancer (H-31) and lung cancer (H-74 and LC-376) with inhibition rates of 58-80%. In a histopathologic study, increase in central necrosis and condensed nuclei and vacuolar degeneration were observed, but there was no structural destruction by the treatment of CGP 41251. In addition, CGP 41251 decreased the number of PCNA (proliferating cell nuclear antigen) immunoreactive cells in human tumor cells H-55, H-26 and H-74. These results indicate that CGP 41251 shows a broad antitumor spectrum against human tumors, and it is suggested that CGP 41251 is a promising oral antitumor agent which has a novel mechanism of action.

Animals↗

In vivo tumor growth inhibition produced by a novel sulfonamide, E7010, against rodent and human tumors.

The search for compounds active against solid tumors has led us to the discovery of a novel sulfonamide, E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4- methoxybenzenesulfonamide), which inhibits tubulin polymerization. When administered orally, E7010 showed good antitumor activity against various rodent tumors and human tumor xenografts. In tests on mouse tumor, E7010, administered in doses of 25-100 mg/kg daily for 8 days, inhibited the growth of colon 38 carcinoma inoculated s.c. in mice by 60-99%. E7010 was active against s.c. inoculated M5076 fibrosarcoma (75% tumor growth inhibition), s.c. inoculated Lewis lung carcinoma (84% increase in life span), and i.p. inoculated P388 leukemia (118% increase in life span). In a test on rat tumor, E7010 inhibited the growth of SST-2 mammary carcinoma inoculated s.c. in rats by 84%. In tests on s.c. inoculated human tumor xenografts, E7010, when administered orally, showed a broad spectrum of activity. E7010 inhibited the growth of: four kinds of gastric cancer, H-81, H-111, SC-2, and SC-6 by 60-78%; three kinds of colon cancer, H-143, COLO320DM, and WiDr by 58-83%; three kinds of lung cancer, LC-376, LC-6, and LX-1 by 63-82%; and two kinds of breast cancer, H-31 and MX-1 by 79-87%. In studies on drug-resistant P388 leukemia, E7010 was effective against vincristine-resistant P388, cisplatin-resistant P388, and 5-fluorouracil-resistant P388 sublines in mice. Because of its good activity against rodent tumors and human tumor xenografts, E7010 is currently undergoing Phase I clinical trials.

Aminophenols↗

Schizophrenia and personality: exploring the boundaries and connections between vulnerability and outcome.

This article discusses the issues and evidence concerning the relationship between schizophrenia and personality. We examine personality dimensions in individuals with schizophrenia, both before and after the onset of their psychoses, and in their relatives. Schizophrenia is associated with high levels of peculiarity and neuroticism and with low levels of extraversion. The relationships between schizophrenia and both psychopathy and creativity remain unclear. Personality dimensions vary in the manner in which they are associated with a variety of correlates of psychopathology, such as prognosis. We recommend that psychopathologists interested in schizophrenia devote more attention to the study of personality.

Creativity↗

[Antitumor activity of combination treatment combining gemcitabine with cisplatin or vindesine against human lung cancer xenografted in nude mice].

Gemcitabine is a new ara-C derivative and shows much more potent cytotoxic action than ara-C, which may be explained by the fact that its intracellular concentration can be maintained over a longer period. We investigated anti-tumor activity combining gemcitabine with cisplatin (CDDP) or vindesine (VDS) with a lung cancer line H-74 that was relatively insensitive to gemcitabine. Mice were observed for 8 weeks, including the 4 week treatment period and the subsequent 4 week drug-free period. The tumor growth inhibition rate, histological changes, and side effects were evaluated at 4 and 8 weeks after the initiation of therapy. The anti-tumor effects of treatment combining gemcitabine with CDDP or VDS were more potent and lasted longer than each drug separately. Statistical analysis shows that the treatment combining gemcitabine with CDDP was additive or synergistic at 4 and 8 weeks after initiation, whereas the treatment combining gemcitabine with VDS was only additive at 4 weeks after initiation and additive or synergistic at 8 weeks after initiation. The side effects of both combination groups were less than those observed in only CDDP or VDS-treated animals. These results suggest the usefulness of a combination therapy combining gemcitabine with CDDP or VDS in future clinical applications.

Adenocarcinoma, Papillary↗

[Acquired resistance and cross-resistance of gemcitabine to cisplatin or vindesine in human lung cancer xenografted in nude mice].

One of the problems in the treatment of cancer is the development of resistance to anti-tumor agents when used repeatedly. We described the induction of resistance, cross-resistance to cisplatin (CDDP) or vindesine (VDS) and the side effects of gemcitabine, a new Ara-C derivative, in human lung cancers, Mqnu-1 or H-74 xenografted in nude mice. We investigated the effects of 4-week observation period. Gemcitabine was effective and did not show the acquired resistance when given repeatedly. In contrast, CDDP but not VDS, when given repeatedly, showed a decrease of the anti-tumor effect in the second course. Gemcitabine was still effective to the large tumor grown after CDDP or VDS therapy. Thus, gemcitabine may not develop resistance nor show cross-resistance to CDDP or VDS. In addition, repeated treatment with gemcitabine was much safer than CDDP or VDS. These results suggest that gemcitabine is a candidate for the first choice drug in cancer treatment.

Adenocarcinoma, Papillary↗

[Combination chemotherapy of BOF-A2, a new 5-FU derivative, with various anticancer agents against human cancer xenografts in nude mice].

In order to select a suitable combination chemotherapy with BOF-A2 from the view of both anti-tumor effect (IR) and decrease of side effect, we studied a combination significance of BOF-A2 with CPT-11 that promised for a new anticancer drug, CDDP or mitomycin C (MMC) that used widely to many cancer patients and interferon-alpha (IFN-alpha) against colon, stomach and renal cancer, respectively, by using xenografted nude mice. The combination therapy of BOF-A2 with CDDP was effective against stomach cancer (H-111) from the cellular change and decreased side effect. The combination therapy of BOF-A2 with MMC showed additive effect against stomach cancer (H-111) from IR and cellular changes. The combination effect of BOF-A2 with IFN-alpha was additive and synergistic against renal cancer (H-12). The combination therapy with CPT-11 was effective (IR > or = to 58%) from antitumor effect, additive from IR and synergistic from cellular change against lung cancer (H-74) and colon cancer (H-110), to which conventional drugs were generally insensitive and spontaneously tolerant. BOF-A2 was expected to be a promising new anti-cancer agent in the future clinical trial.

Animals↗