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Biomedical subjects

M Tani

Publications and source records attributed to M Tani.

At least 289 records · Page 16Linked to original sources

[Enhancement of susceptibility to ouabain in ischemic rat heart].

During 10 mins of reperfusion after 25 mins global ischemia, subtoxic doses of ouabain (50, 100 microM) were used and followed by 20 mins reperfusion with standard buffer. At these doses ouabain had no harmful effects with 29% and 45% increase in developed pressure in aerobic hearts. Intracellular Na+ (Nai), 45Ca2+ uptake and recovery of ventricular function were measured. Nai increased from 15 to 64 mumol/g dw with no increase in 45Ca2+ uptake during ischemia. Upon reperfusion with standard buffer, additional gain in Nai at 2 mins (73 mumol/g dw) was followed by a rapid decline (at 10 mins: 48 mumol/g dw). 45Ca2+ uptake increased from 0.8 to 7.5 mumol/g dw after 30 mins reperfusion with decreased recovery of function (45%) and increased LVEDP (29 mmHg). Reperfusion with ouabain accelerated initial rise in Nai (2 mins: 79 and 83 mumol/g dw) and decline of Nai was retarded (10 mins: 65 and 83 mumol/g dw). Consequently, 45Ca2+ uptake and depression of function were augmented (Ca: 10.0, 11.5 mumol/g dw; function: 27%, 18%; LVEDP: 47, 48 mmHg) even when hearts were switched back to standard buffer. Combination of high K+ (20mM) reversed the effect of ouabain. The results suggested increased susceptibility to ouabain was caused by inhibited outward Na+ transport resulting in enhanced Ca2+ influx through Na+/Ca2+ exchange.

Animals↗

[Coronary flow reserve and stenosis as the determinant of exercise capacity in patients with stable effort angina].

The coronary flow reserve was evaluated in 33 patients with stable effort angina and single vessel disease of the left anterior descending artery. We used a catheter-tip Doppler flow probe with injection of contrast media to the vessel in order to induce so-called reactive hyperemia. The reactive change was used as an index of the flow reserve of the coronary artery. In 15 patients out of 33, PTCA was performed and the change in the coronary flow reserve was evaluated. There was a good correlation between the coronary flow reserve and the exercise capacity in the treadmill ECG exercise test. As theoretically expected, the exercise capacity was determined by the coronary flow reserve. There was a poor correlation between the degree of stenosis shown in coronary arteriography and the coronary flow reserve. The degree of stenosis did not relate with the exercise capacity. The coronary flow reserve was increased with the procedure of PTCA. Though the patho-anatomic findings in coronary angiography give us important information to evaluate patients with ischemic heart disease, we concluded that these findings were still insufficient to allow us to estimate the flow reserve in the coronary artery. The exercise capacity did not relate well with the degree of stenosis.

Adult↗

[Fibrinogen and factor VII levels in patients under estrogen-progestin therapy].

During a 3 month period the Authors have evaluated the possible modification of some coagulation parameters which can be of relevance for thrombophilic state. Fibrinogen and factor VII were measured and following 3 months of oestro-progestinic treatment in 11 women in good general health and without known controindications to contraceptive treatment. No significant difference in some levels of fibrinogen and factor VII were found. We conclude that in the short term fibrinogen and factor VII are not significantly altered but a longer period of follow up is indicated in order to estimate the risk of cardiovascular accidents.

Blood Coagulation Disorders↗

[Coronary flow characteristics in hypertrophic cardiomyopathy--a study with Doppler catheter].

UNLABELLED: We compared the pattern and reserve of coronary flow in 8 cases of hypertrophic non-obstructive cardiomyopathy (H) with those in 20 cases of chest pain not accompanied by organic heart disease (N). A catheter-tip Doppler velocimeter was positioned in the proximal portion of the left anterior descending (LAD), circumflex (LCX) and right coronary (RCA) arteries. Coronary flow velocity (Vs: systolic peak, Vd: diastolic peak, Vm: mean) was recorded and the area under the velocity curve was divided into systole (* s) and diastole (* d). The time interval between the dicrotic notch in aortic pressure and the peak of diastolic flow velocity was measured (Tpv). Vm was measured before and after intracoronary injection of 6 ml of contrast media, and peak to resting velocity ratio (PRVR) was calculated as an index of coronary flow reserve. RESULT: In LAD, N showed diastolic predominant coronary flow pattern without backward flow. In H, diastolic predominance was more prominent with systolic backward flow, resulting in decrease in * s/* d(H: 0.07 +/- 0.04, N: 0.25 +/- 0.02, p less than 0.01). In H, Vd (H: 20.1 +/- 2.8, N: 9.2 +/- 1.4 cm/sec, p less than 0.05) and Vm(H: 9.5 +/- 1.3, N: 4.9 +/- 0.7 cm/sec, p less than 0.05) were higher, while PRVR was lower (H: 1.7 +/- 0.1, N: 2.6 +/- 0.1, p less than 0.05). In both N and H, the flow pattern of LCX was diastolic predominant with two peaks (one in systole and the other in diastole).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Real-time coronary blood flow measurement in patients with atrial fibrillation: a study using a catheter-tip Doppler velocimeter].

To clarify the influence of changes in the cardiac cycle length (R-R) and aortic pressure on the coronary blood flow, a catheter-tip Doppler velocimeter was applied for 16 patients with chronic atrial fibrillation (11 with valvular heart disease, 2 with coronary artery disease, 2 with cardiomyopathy and one with atrial septal defect). An area under the coronary flow velocity curve during systole (integral of S), diastole (integral of D) and one cardiac cycle (integral of T) for the proximal portion of the left anterior descending artery (LAD: 12 cases) or the right coronary artery (RCA: 10 cases) was calculated in beat-by-beat. Then, the correlations between each area and the R-R, systolic period (S), diastolic period (D) and aortic pressure were assessed. In both the LAD and RCA, prolongation of R-R associated with prolonged D increased integral of D, which caused an increase of integral of T. Integral of D correlated with D (p < 0.05), but integral of S did not correlate with S, and the degree of change in integral of S or S was much less than that in integral of D or D. R-R or D of the preceding beat correlated inversely (p < 0.05) with integral S in 11 of 12 LAD cases. In the RCA, positive correlations between R-R or D of the preceding beat and integral of S were observed in cases with mitral stenosis (n = 6) or coronary heart disease (n = 1), but not in other cases; a case with aortic regurgitation or hypertrophic cardiomyopathy, negative, and dilated cardiomyopathy, no correlation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Release of endothelin from isolated perfused human umbilical vein. I: Effect of ionomycin].

Endothelin-like immunoreactivity (ET-LI) was directly measured in the perfusate from the isolated human umbilical vein perfused with Krebs-Ringer solution. The identity of the immunoreactive peptide was confirmed as ET-1 by high-performance liquid chromatography. The rate of release of ET-LI was 86.7 +/- 25.9 (SE) fmol during the first perfusion period of 30 min, and it remained stable at least for 4 hours. Calcium ionophore ionomycin, added to the perfusion medium (10(-7)-10(-6) M), stimulated the ET-LI release in a dose-dependent fashion; it increased the rate of release by 29.1% and 143.4% over the control at the concentrations of 10(-7) and 10(-6) M, respectively. These results taken together with previous observations of synthesis of ET in cultured vascular endothelium provide direct evidence for local generation and subsequent release of ET from vascular beds of human beings.

Calcium↗

[The reversal of the protective effects of intermittent perfusion on ischemic myocardium by hypoxic, no-substrates, zero-K+ perfusate].

Intermittent perfusion during ischemia protected ischemic myocardium and improved recovery of function. These protective effects were reversed when hearts were perfused intermittently with hypoxic, no-substrates, zero-K+ buffer instead of oxygenated standard buffer containing substrates. We investigated the mechanisms of this reversal in isolated rat hearts. After 40 mins of sustained global ischemia, intracellular Na (Nai) increased by 6 times along with decrease in ATP and accumulation of lactate. During 30 mins of reperfusion, 45Ca2+ uptake reached 10.0 mumol/g dry with reduced recovery of ventricular function (LVEDP from 1 to 48 mmHg). When the 40 min period of ischemia was interrupted at 10 min intervals by 3 mins of IP, Nai didn't increase and reperfusion resulted in no increase in 45Ca2+ uptake (0.5 mumol/g dry). Recovery of function was 100% of the preischemic value without elevation of LVEDP. When hypoxic buffer without substrate and K+ was used for IP, Nai increased more rapidly with less recovery of function and more increased 45Ca2+ uptake (8 times) than sustained ischemia. These results indicate that disappearance of prevention of an increase in Nai with increased Ca2+ overload in hypoxic, no-substrates, zero-K+ IP, which resulted from accelerated ATP depletion and inhibition of Na/K pump is probably the main cause of the reversal of the protective effects.

Adenosine Triphosphate↗

[Combination of adoptive immunotherapy and chemotherapy against advanced cancer with peritoneal dissemination].

In a case of advanced gastric cancer with bilateral Krukenberg's tumors and peritonitis carcinomatosa, total gastrectomy, splenectomy and bilateral oophorectomy was performed. Since progressive peritoneal dissemination was recognized, 150 mg of CDDP and 10 mg of MMC which were proved to be effective by chemosensitivity test of anticancer drugs were administered intraperitoneally. After one month, ascites increased. So LAK cells and TIL were transferred intraperitoneally 6 times. With this treatment ascitic collection remarkably decreased, the performance status improved and serum level of IAP and CA125 normalized. Thus, it is clarified that the combination of adoptive immunotherapy and chemotherapy possesses therapeutic efficacy against advanced gastric cancer with peritonitis carcinomatosa.

Adenocarcinoma, Mucinous↗

Effect of delapril hydrochloride on angiotensin II release from isolated rat hind legs.

The effect of the newly developed angiotensin-converting enzyme (ACE) inhibitor, delapril hydrochrolide (CV-3317), on the release of immunoreactive angiotensin II (irAng II) from isolated rat hind legs was compared with that of captopril. Both ACE inhibitors, added to the perfusion medium (2 X 10(-9) - 10(-6) M), suppressed irAng II release in a dose-dependent manner, but the inhibition was greater with delapril than with captopril. The results provide further support for the concept that vascular tissues produce Ang II and release it in a regulated fashion. The results also suggest a possible link between the antihypertensive mechanism of ACE inhibitors, including delapril, and the suppression of vascular Ang II release.

Angiotensin II↗

Clinical evaluation of chemotherapy under angiotensin II-induced hypertension in patients with advanced cancer.

The clinical efficacy and indications for Angiotensin II (AT II)-induced hypertension chemotherapy were evaluated as a drug delivery system in 101 patients with advanced carcinoma. The sites of primary tumor studied included stomach (44), pancreas (18), colon (16), esophagus (6), bile duct (4), liver (3), breast (7) and 3 other single organs. Seventy four cases had distant metastases (lymph node (25), liver (29), peritoneum (16), and lung (4)). Additionally, the protocol was used 12 cases as postoperative adjuvant chemotherapy and 15 cases following exploratory laparotomy. The blood pressure was elevated to a level 1.5 times base-line. The regimens used consisted of MMC + ADR (55), FAM (38) and CDDP (8). The dosages administered were MMC 7 mg/m2, ADR 14 mg/m2 and 5-FU 350 mg/m2. The cancer chemotherapy protocol with AT II was repeated for an average of 2.6 cycles with a 2-3 week interval. The drug concentration in tumor tissues was increased 1.7 fold by AT II treatment. The response rate was 15.8% (CR 7 and PR 9), and in those patients with lymph node, liver and peritoneal metastases was 48.0, 6.9 and 6.3%, respectively. The serum levels of tumor markers decreased in 9 patients. Subjective symptoms, such as hoarseness, edema and pain, were improved. The mean survival in patients with distant metastasis who responded was 343 days, and in nonresponders was only 168 days (p less than 0.05). The side effects of this therapy were slight, typically being grade 1 and 2. Thus, the chemotherapeutic agents studied in conjunction with AT II were effective in patients with lymph node metastasis. Additionally, this regimen could be performed safely with minimal side effects.

Aged↗

[Augmentation of cytotoxic activity by combination with interleukin 2 and interferon gamma].

The synergy of cytotoxic activity by Interleukin 2 (IL-2) and Interferon gamma (IFN-gamma) was evaluated in human peripheral blood mononuclear cells (PBMC) and spleen cells. PBMC incubated with IL-2 (10 IU/ml) and IFN-gamma (200 IU/ml) for 4 days showed the maximum cytotoxic activity against K562, MOLT-4 and Daudi cells. Combination with IL-2 and IFN-gamma induced stronger activity than IL-2 or IFN-gamma alone. In order to investigate the sequential roles of IL-2 and IFN-gamma in the synergy of killer cell function, IFN-gamma was stimulated after washing-out IL-2 or stimulated at various timing and duration without washing-out IL-2. IL-2 was essential to induce the synergistic effect of IL-2 and IFN-gamma to killer activity. The similar augmentation of killer activity was observed by the addition of IFN-gamma at any incubation period with IL-2, compared with that of stimulations IL-2 and IFN-gamma stimulation. The phenotypes of the killer cells by stimulation of IL-2, IFN-gamma alone or IL-2 and IFN-gamma were mainly CD2+, CD16+, namely, the phenotype of activated natural killer cells.

Cytotoxicity, Immunologic↗

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes].

The tumor-infiltrating lymphocytes (TIL) were cultured with interleukin 2 (IL-2) to induce the cytotoxic T lymphocytes possessing autologous tumor-killing activity from 21 cancer patients (11 with solid tumor and 10 with malignant peritoneal or pleural effusions), and transferred into 7 patients as IL-2-activated TIL adoptively. The clinical application of activated TIL by adoptive transfer could result the complete regression of malignant pleural effusions in a patient with pancreatic cancer, and the nearly complete regression of malignant ascites in a patient with gastric cancer. The autologous tumor cells were isolated at the purity of more than 90% by Ficoll-Hypaque and Percoll discontinuous gradients, and then the TIL were cultured with IL-2 until 4 weeks. The optimal concentration of IL-2 was 1,500 IU/ml to obtain maximum proliferation and autologous tumor killing activity. The cytotoxic activities of activated TIL at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 22 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. By negative selection method, it was clarified that the killer cells recognizing autologous tumor consisted of CD4 or CD8 positive T lymphocyte in 43% of patients. The CD8 positive cells and CD56 positive cells increased, the CD4 positive cells and CD16 positive cells decreased by flow cytometry. The activated TIL could lyse not only cultured tumor cell lines, also other autologous tumor cells. The CD56+ cells were isolated by the Panning method, these cells could not lyse autologous tumor cells. Thus, it was indicated that the cytotoxic T lymphocytes recognizing autologous tumor could be generated from TIL and the adoptive immunotherapy of activated TIL was effective in cancer therapy.

Adult↗

[Defective autologous mixed lymphocyte reaction (AMLR) in gastric cancer patients].

Autologous mixed lymphocyte reaction (AMLR) is an important reaction regulating the immune system in the various diseases. This is the first report investigating AMLR not only in peripheral blood but also in the spleen of gastric cancer patients. AMLR in the spleen of gastric cancer patients was significantly suppressed compared with that of peripheral blood of gastric cancer patients and patients without cancer. In investigation of AMLR composed of peripheral blood cells and spleen cells of gastric cancer patient, AMLR on splenic non-T cells as a stimulator was significantly suppressed compared with peripheral blood non-T cells as a stimulator. It suggests that abnormalities of non-T cells caused suppression of AMLR in the spleen of gastric cancer patients.

Female↗

Successful adoptive immunotherapy with OK432-inducible activated natural killer cells in tumor-bearing mice.

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo priming and subsequent in vitro challenge with a streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy-1+, asialo GM1+, suggesting that the activated cells were of NK lineage (OK-NK cell). We had also clarified that IL-2 played a major role in inducing the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on syngeneic tumors in mice. Mice were implanted with SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or intratumorally, adoptively. By the adoptive transfer of OK-NK cells, 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was significantly increased. The intratumoral remnants of 125I-labelled OK-NK cells were 61, 27 and 8% at 4, 12 and 36h after intratumoral transfer, respectively. By multiple transfer of OK-NK cells, the antitumor effect was more effectively augmented than that of a single transfer. Results in this study suggested that OK-NK cells could be useful for the therapy of cancer patients.

Adenocarcinoma↗

Functional and phenotypic analyses of interleukin 2-activated tumor-infiltrating lymphocytes.

The tumor-infiltrating lymphocytes (TILs) were cultured with interleukin 2 (IL-2) to induce the activated killer cells possessing autologous tumor-killing activity, and analysed their cell surface phenotypes and assessed anti-tumor killing activity. Furthermore, the activated TILs were transferred into 7 patients adoptively resulting in complete remission in a patient with pancreatic cancer and partial remission in another patient with gastric cancer. The cytotoxic activities of activated TILs at 3 weeks-incubation was 72 +/- 15, 42 +/- 26, 27 +/- 21 and 25 +/- 15% against K562, Daudi, KATO-III and autologous tumor, respectively. The negative selection method, indicated that the killer cells recognizing autologous tumor cells consisted of CD4- or CD8-positive T lymphocytes and CD16- or CD56-positive natural killer cells. The activated TILs could not only lyse cultured tumor cell lines, but also autologous tumor cells.

Adult↗

Impairment of autologous mixed lymphocyte reaction in the spleen and peripheral blood lymphocytes of patients with idiopathic portal hypertension.

The etiology of idiopathic portal hypertension (IPH) is unknown, although many studies have suggested that it might be an autoimmune disease. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect immune control mechanisms in vivo. The AMLRs in the spleen and peripheral blood of three patients with IPH were measured and it was shown that the AMLRs both in the spleen and peripheral blood were significantly suppressed compared to those of normal healthy subjects. By allogeneic MLR, there was a tendency that the disturbance of non-T cells was more intensive than that of T cells. The AMLR of peripheral blood did not improve by splenectomy. Thus, the depressed cause of AMLR in patients with IPH was suggested mainly to disturbance of the antigen-presenting ability of non-T cells, and it was suggested that not only the spleen cells, but systemic immune disturbance caused the impairment of AMLR in IPH.

Aged↗