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Biomedical subjects

S Umemoto

Publications and source records attributed to S Umemoto.

At least 55 records · Page 3Linked to original sources

Simple and safe method for operative cannulation of the portal vein.

A method of portal vein cannulation via the omental vasculator is described. This mode of vascular access, which requires only five or ten minutes of additional operating time, can be used for adjuvant or therapeutic portal vein infusion of chemotherapy.

Antineoplastic Agents↗

Hemodynamic benefits of long-term bunazosin (alpha-1 blocker) therapy in rats with myocardial infarction and heart failure.

To determine whether bunazosin (alpha 1-adrenoceptor blocking agent) can alter the hemodynamic profile of chronic heart failure secondary to myocardial infarction, the drug was administered to Wistar rats 4 weeks after coronary ligation, and continued for 4 weeks. In rats without bunazosin treatment, the left ventricular end-diastolic pressure (LVEDP) and the total vascular resistance index (TVRI) increased as a function of infarct size, while the cardiac index (CI) decreased. But in infarcted rats with bunazosin treatment, the mean aortic pressure and TVRI were reduced, the LVEDP was modestly lessened, and the CI was maintained. The greatest increase in CI after the treatment occurred in rats with infarcts of small and moderate size. Thus, long-term therapy with bunazosin improved LV dysfunction, relative to the size of infarction. This study suggests the beneficial effects of bunazosin therapy in patients with chronic heart failure.

Adrenergic alpha-Antagonists↗

[Topical chemotherapy of chronic periodontitis using controlled-release insert containing ofloxacin (PT-01) without root planing].

Topical chemotherapy of periodontal disease using several drug delivery systems (DDS) is currently being attempted. PT-01 is a DDS which consists of fast- and sustained- release parts containing ofloxacin as an antibacterial agent. Since PT-01 was found to sustain the antibacterial effect for 7 days in a periodontal pocket, it was used tor periodontal patients without root planing or scaling in this study. PT-01 and a placebo were applied to two separate and opposite pockets of 46 patients, once a week from the first visit (week 0) to week 3. The clinical parameters (plaque index, gingival index, tooth mobility, bleeding on probing, pus discharge, and probing depth) were evaluated from weeks 0 to 4. At the end of the test (week 4), global improvement at the two sites was assessed. The clinical parameters and the global improvement of the PT-01 and placebo-treated sites were compared statistically. All parameters at the PT-01 sites except for tooth mobility showed much greater improvement than at the placebo sites. The global improvement of PT-01 sites was also significantly greater than that of the placebo sites. No side effects could be seen in patients treated with PT-01. These results indicate that topical chemotherapy using PT-01 could be effective and safe for periodontal therapy.

Chronic Disease↗

[Antitumor effect of alpha-difluoromethylornithine (DFMO) changes in ornithine decarboxylase (ODC) activity and polyamine (PA) levels in human tumor transplanted into nude mice].

Three human carcinoma xenografts serially transplanted into nude mice were used for the study of antitumor effect of DFMO. One breast carcinoma (MX-1) and two colon carcinomas (Exp-42, Co-3) were inoculated into the subcutaneous tissue of BALB/c nude mice. When the tumor weights reached 100 -300mg, 0.5%, 1% and 2% DFMO was administrated ad libitum in tap water for 21 days, MMC was administrated ip q7d x 3(DAY 0, 7,14) at 0.5mg/kg or 2.0mg/kg. Combination of 1% DFMO and MMC 1mg/kg x 3 using a similar schedule was also made. After 21 days, the tumors were weighed and assays of ODC activity and analysis of PA in the tumors were done. The antitumor effects (the lowest value of TRW/CRW) of 2% DFMO against MX-1, Exp-42 and Co-3 were 4.83%, 35.8% and 73.4% respectively. Synergic effects of MMC were observed in all three tumors. With 2% DFMO, ODC and PUT levels were decreased to 16.4%, 2.89% of control in MX-1, 14.8%, 6.62% in Exp-42, 4.18%, 11.2% in Co-3 respectively. Of MX-1 and Exp-42, the dose of DFMO administrated, the antitumor effect and the PUT levels were correlated (p less than 0.05). DFMO is one of the potent chemotherapeutic agents and may be useful in combination chemotherapy.

Animals↗

[The influence of theophylline on polyamine metabolism and colonic carcinogenesis induced by 1.2-dimethylhydrazine in mice].

The administration of theophylline (120 mg/kg.day, 14 wk) to the drinking water of female BALB/c mice after treatment with 1,2-dimethylhydrazine (DMH) (30 mg/kg.sc, 1/wk, 14 wk) resulted in both an increase in number of colon carcinoma and increases in ornithine decarboxylase (ODC) activities and polyamine (PA) levels in colon tissue. This increase in number of colon carcinoma was about 3-fold to mice receiving same amount of DMH and drinking water without theophylline. ODC activities (pmoles 14CO2/hr/mg prot, mean +/- SD) in colon tissue were 122 +/- 10.6 (n = 6) in DMH with theophylline group, 28.3 +/- 2.13 (n = 8) in DMH alone group, 21.3 +/- 1.67 (n = 6) in control group respectively. Putrescine and spermidine levels (nmoles/g, mean +/- SD) were 31.0 +/- 10.5, 527 +/- 86.6 (n = 11) in DMH with theophylline group, 24.0 +/- 11.4, 464 +/- 129 (n = 11) in control group respectively. Thus with marked increase of ODC activities and slight increase of PA levels, theophylline has shown to significantly enhance the promoting phase of carcinogenic process with DMH.

Animals↗

Study of immunological mechanism in dilated cardiomyopathy.

To determine the immune disturbances involved in the pathogenesis of dilated cardiomyopathy (DCM), the conditions in humoral and cellular immunity of DCM patients were studied. To examine the status in humoral immunity in DCM patients, circulating anti-heart antibodies (AHAbs) were analyzed. Circulating-AHAbs were classified into 4 types "heterophile-like", "intracellular", "intercalated disc" and "nuclear" patterns by indirect immunofluorescence technique, and a high rate of heterophile-like antibody was found in DCM. The cytotoxicity of this antibody was examined in cultured myocardial cells using the two-step method of the complement dependent cytotoxic test. The mean cytotoxic index (CI) value of the heterophile-like antibody positive sera was 22.3, which showed an apparent cytotoxicity against the cultured cells and it may be complement dependent. In addition, the frequency of lymphocyte subsets using monoclonal antibodies (OKT4, OKT8, Leu7, Leu11) and natural killer (NK) activity were evaluated to determine whether DCM patients had an imbalance in cellular immune reactions, which support the hypothesis of an immune disturbance as the pathological mechanism of DCM. The peripheral lymphocyte counts were significantly lower in patients with DCM (1737 +/- 874/mm3) than in normal controls (NC, 2088 +/- 556/mm3) and in patients with ischemic heart diseases (IHD, 2395 +/- 469/mm3, both p less than 0.01). The percentage of T, B, OKT4 and OKT8 positive cells was not statistically different among DCM, IHD, and NC groups, whereas the percentage of T gamma cells was significantly reduced in DCM patients (6.5 +/- 5.0%, p less than 0.05). NK functional activity as tested in DCM patients was frequently deficient (24.1 +/- 16.7% in DCM, 36.7 +/- 12.2% in NC). After 4-hr incubation with recombinant interleukin2 (rIL2), rIL2 induced the enhancement of NK activity in 3 out of 4 DCM patients with low NK activity, although, there was a non-responder to rIL2 in this group. These results suggested that DCM patients have a low IL2 production and/or less numbers of mature cells with NK cell function. Therefore, an imbalance in humoral and cellular immune reactions may cause insidious myocardial damage and subsequently lead to development of DCM.

Angina Pectoris↗

Introduction of new indices into continuous avoidance test--a trial to detect the effects of sodium chloride and mannitol on avoidance behavior.

A personal computer was introduced in conditioned lever-press avoidance experiment in Sidman situation. Experimental data were analyzed with both classic indices such as response rate and shock rate and new indices introduced in this experiment. New indices include sum of squares of shock-shock intervals, mean of shock-response time and number of shock-response time less then 5 sec. Results obtained in diazepam-treated mice were consistent with those reported previously by the classic method. In mannitol-treated mice, significant changes of the avoidance behavior could be detected by both the classic index and our new indices. By the new indices other than classic indices, the effect of administration with sodium chloride on the avoidance behavior could be detected, whereas the classic indices could not detect the effect. Though the meanings of these indices i physiological and toxicological aspects should be appreciated in future study, the experimental system reported in this paper might be applicable in the toxicological research to detect the effect of administration with various substances on the avoidance behavior.

Animals↗

Study on lymphocyte subsets and NK cell function in patients with dilated cardiomyopathy.

An acquired defect or damage of a subpopulation of suppressor T lymphocytes is reported in connection with autoimmune diseases. In the present study, the role of immunity was examined in 7 patients with dilated cardiomyopathy (DCM). The frequency of lymphocyte subsets using monoclonal antibodies and natural killer (NK) cell activity was evaluated to determine whether DCM patients had lymphocyte abnormalities that would support the hypothesis that the pathological mechanism of DCM is an immune disturbance. The peripheral lymphocyte counts were significantly lower in patients with DCM and higher in patients with ischemic heart disease (IHD) than in normal controls (NC) (p less than 0.01). The percentage of T cells, B cells, OKT4 and OKT8 positive cells was not statistically different among the three groups studied here, whereas the percentage of T gamma cells was significantly reduced in DCM patients (p less than 0.05). NK cell functional activity as tested in DCM and IHD patients was frequently deficient (22.1 +/- 19.3% in DCM, 13.8 +/- 3.0% in IHD, 37.4 +/- 12.7% in NC). Our results suggest that an imbalance in cellular immune reactions partly explain the pathogenesis of DCM.

Adult↗

Immunological study of heart diseases with special reference to the cytotoxicity of the heterophile antibody against cultured myocardial cells.

In our previous study, a high rate of "heterophile antibody" was found in idiopathic cardiomyopathy. In the present investigation the cytotoxic activity of this antibody was examined in cultured myocardial cells. Trypsin treated cells cultured for 3 days were used in the two-step method of the complement dependent cytotoxicity test. The trypan blue dye-exclusion method was utilized to determine the percentage of surviving cells, and the cytotoxic effect was expressed by the cytotoxic index (CI). With fresh rabbit serum as complement, the mean CI value of the heterophile antibody positive sera was 20.7, which was in contrast to the value of anti-heart antibodies negative sera (p less than 0.01). As the cytotoxic effect to the heterophile antibody was absent without the complement, it may be complement dependent. Thus, our results suggest that the heterophile antibody may play a role in the pathogenesis or be an incremental factor of idiopathic cardiomyopathy.

Animals↗

Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1.

The preparation and analgesic activities of a series of the entitled compounds (5-22) and the optical isomers of the 1-cyclohexyl derivative 5 are described. Reactions of N,N-bis(2-chloroethyl)-1,2-diphenylethylamine (3) with ammonia and primary amines gave N-(1,2-diphenylethyl)piperazine (4) and N1-substituted derivatives (5-20, 22), respectively. The alkylation of 4 afforded 12-21. Compounds 5-18 and 22 were also obtained by the reactions of 1,2-diphenylethylamine (23) and N-substituted 2,2'-dichlorodiethylamine. Racemate 5 was resolved with (+)- or (-)-2'-nitrotartranilic acid into its optical isomers [(+)-5 and (-)-5], and the absolute configuration of (+)-5 was determined to be S configuration by the synthesis and optical rotatory dispersion measurements. The most active members in this series of compounds were 5-7, which were approximately as potent as (-)-morphine. In the case of 5, the more potent enantiomer (S)-(+)-5 has the opposite configuration to that of (-)-N,N-dimethyl-1,2-diphenylethylamine (Spa) or (-)-morphine with respect to the (C-9) asymmetric center and belongs to a new series of compounds having potent analgesic activity.

Analgesics↗