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Biomedical subjects

A Azuma

Publications and source records attributed to A Azuma.

At least 109 records · Page 6Linked to original sources
PubMed1995

Nucleosides and nucleotides. 141. Chemical stability of a new antitumor nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine in alkaline medium: formation of 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine and its antitumor activity.

We have designed 2'-C-cyano-2'-deoxy-1-beta-D-arabino- pentofuranosylcytosine (CNDAC) as a potential mechanism-based DNA-strand-breaking nucleoside, which showed potent tumor cell growth inhibitory activity against various human tumor cell lines in vitro and in vivo. When measuring the pKa of the 2' alpha-proton of CNDAC, we found that CNDAC epimerized to 2'-C-cyano-2'-deoxy-1-beta-D-ribo-pentofuranosylcytosine (CNDC) with concomitant degradation of both CNDAC and CNDC to cytosine and 1,4-anhydro-2-C-cyano-2-deoxy-D-erythro-pent-1- enitol. Kinetic analysis of these reactions showed that abstraction of the acidic 2'-proton of CNDAC and CNDC initiated the reactions, which quickly reached an equilibrium. In the equilibrium, a concentration ratio of CNDAC and CNDC was about 3:5. Concomitant degradation of these nucleosides was found to be rather slow. Deuterium incorporation experiments with CNDAC in a D2O buffer suggested the mechanism of the beta-elimination reactions is an E1cB type. These epimerization and degradation reactions were found even in neutral conditions (pH 7.5) and also occurred in RPMI 1640 cell culture medium. The discovery of which nucleoside possesses the predominate tumor cell growth inhibitory activity was important. While both nucleosides showed potent tumor cell growth inhibitory activity against three human tumor cell lines (colon carcinoma WiDr, small cell lung carcinoma SBC-5, and stomach carcinoma MKN-74 cells) in 48 h of incubation, in 20 min of incubation, CNDAC was 11-50 times more effective than CNDC. In vivo antileukemic activity of these nucleosides against a mouse P388 model, CNDAC was obviously superior to CNDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Augmented lung adenocarcinoma cytotoxicity by the combination of a genetically modified anti-Lewis Y antibody and antibodies to complement regulatory proteins.

Complement-dependent cytotoxicity (CDC) mediated by a chimeric anti-Lewis Y monoclonal antibody (cH18A; human IgG1) was investigated in this study. Human lung adenocarcinoma cell lines (PC7, PC9, and PC14) were used as the target cells. PC7 and PC9 cells, expressed Lewis Y antigen and were lysed by cH18A as effectively as by the parent mouse anti-Lewis Y antibodies (mH18A) in a concentration-dependent manner. PC14 cells did not express Lewis Y antigen and were not lysed by either cH18A or mH18A. cH18A mediated CDC activity against PC7 and PC9 cells was enhanced by the combined use of monoclonal antibodies directed against CD46(MCP), CD55(DAF), and CD59. These molecules are complement-regulatory proteins which protect host cells from CDC. PC7 and PC9 cells, showed high levels of surface expression of these proteins, PC7 cells were more susceptible to cH18A-mediated CDC than PC9 cells. Use of multiple blocking antibodies to the complement-regulatory proteins produced more enhancement of cH18A-mediated CDC than a single antibody. Moreover, expression of CD55 and CD59 by PC7 and PC9 cells was decreased after treatment with PI-PLC, resulting in increased susceptibility to cH18A-mediated CDC. Although the reason is unknown, PC7 cells became more susceptible to CDC than PC9 cells after PI-PLC treatment even in the absence of cH18A. These data suggest that chimeric monoclonal antibodies can be used to induce CDC against lung adenocarcinoma, and that such CDC is potentiated by a variety of antibodies blocking compliment-regulatory proteins on the tumour cell surface.

Adenocarcinoma↗
PubMed1995

[Antibodies of IgM type against small cell lung carcinoma and 29 kD neuronal antigen of rat in a patient with paraneoplastic sensory neuropathy].

62-year old man who had small cell lung carcinoma (SCLC) with subacute sensory neuropathy had an antibody (IgM) recognizing the antigen on peripheral nerves. The antibody in the serum recognized cell surface antigen on small cell carcinoma cell lines and also reacted with peripheral nerves simultaneously, but not with central nervous system. Two months before admission, he felt difficulty in walking because of paresthesias in the extremities. He was found to have a tumor shadow in chest X-ray, and was diagnosed as SCLC by biopsy of right supraclavicular lymph node. Western blot analysis demonstrated that auto-antibody (IgM) in the serum recognizing the antigen on the neuronal axon with single band at 29 kD. Pathogenesis of carcinomatous neuropathy is still unexplained, but the findings presented here have given rise to the possibility that anti-SCLC antibody may cross-react with neuronal antigen, primarily resulting in neuronal disorder.

Animals↗
PubMed1995

[Clinical evaluation of 123I-metaiodobenzylguanidine myocardial scintigram in patients with valvular heart disease].

Myocardial sympathetic nerve function can be evaluated by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Congestive heart failure is closely related to myocardial sympathetic nerve function. This study evaluated the severity of congestive heart failure in 30 patients with valvular heart disease [aortic regurgitation (AR): n = 20, mean age = 70 +/- 13 years; mitral regurgitation (MR): n = 10, mean age = 61 +/- 18 years], who had chronic heart failure by MIBG myocardial scintigraphy. Single photon emission computed tomography (SPECT) and anterior planar myocardial images were obtained 15 minutes (initial images) and 4 hours (delayed images) after injection of MIBG (111MBq). Defect score was determined by the delayed SPECT images visually as a semi-quantitative index. Myocardial MIBG uptake was quantified by the heart to upper mediastinum uptake ratio on the delayed anterior planar images (H/M) and mean cardiac MIBG washout rate during 4 hours was calculated from the bull's eye display data (clearance). These indices were compared with the NYHA class and echocardiographic findings of the patients. MIBG regional defect in the delayed image was most frequently seen in the inferoposterior wall, and defect score and clearance were significantly higher and the H/M ratio was significantly lower in NYHA class III patients than in class II patients. In patients with AR, clearance significantly correlated with left ventricular end-systolic dimension. In patients with MR, both the H/M ratio and clearance significantly correlated with left atrial dimension. Defect score, H/M, and clearance were closely related to the severity of AR and MR. These results indicate that MIBG scan can be used to assess the severity of valvular heart disease.

3-Iodobenzylguanidine↗
PubMed1995

[Assessment of myocardial fatty acid metabolism in patients with vasospastic angina using 123I-BMIPP myocardial SPECT].

Myocardial perfusion and fatty acid metabolism may be unpaired in the patients of vasospastic angina (VSA), because abnormal regional wall motion of left ventricle has been shown in some cases of VSA without apparent history of myocardial infarction. To study the clinical utility of 123I-BMIPP scintigraphy in diagnosis of myocardial ischemia in VSA, both 123I-BMIPP (rest) and 201T1 (exercise) SPECT were performed in the 20 patients of VSA diagnosed by coronary angiography. Defect scores were calculated visually from the 17 segments of myocardial images and were compared with patient's anginal history, period from last attack, numbers of attack, left ventricular (LV) ejection fraction and severity of regional LV wall motion abnormality. 123I-BMIPP SPECT images showed decreased tracer uptake in 14 cases of 20 (70%) VSA patients. Exercise 201T1 SPECT images showed decreased tracer uptake in 3 cases of 20 (15%) of patients. Severity of regional LV wall motion abnormality was correlated with defect score of BMIPP. Though total defect score of BMIPP did not correlate with patient's anginal history, number of symptoms and LV ejection fraction, correlated inversely with period from last attack. It was suggested that 123I-BMIPP myocardial SPECT images in VSA patients showed "memories" of myocardial ischemic damages induced by vasospasm. In summary, 123I-BMIPP myocardial SPECT images could be a useful test for diagnosis and evaluation of VSA.

Angina Pectoris, Variant↗
PubMed1994

Potentiation of long-term-cultured lymphokine-activated killer cell cytotoxicity against small-cell lung carcinoma by anti-CD3 x anti-(tumor-associated antigen) bispecific antibody.

Lymphokine-activated killer (LAK) cells exhibit a potent cytotoxicity to malignant cells in vitro. However, a satisfactory effect has not been obtained in many clinical studies except for a few cases. One of the most important reasons why cytolytic activity could not be exhibited in vivo is that LAK cells do not accumulate in the tumor tissue because of a lack of specificity. In the present study, we show the effect of a bispecific antibody (bsAb) on the accumulation of LAK cells around the small-cell lung carcinoma (SCLC) cell and the subsequent enhancement of LAK cell cytotoxicity against SCLC. When short-term(4 days)-cultured LAK cells were used, OKT3 x LU246 bsAb, which direct CD3+ T-LAK cells to the target cell, induced a similar level of cytotoxicity to that induced by 3G8 x LU246 bsAb, which directs CD16+ LAK cells. Long-term(21 days)-cultured LAK cells exhibited a reduced spontaneous cytotoxicity but retained high cytotoxic activity, which could be directed by OKT3 x LU246 or 3G8 x LU246 bsAb. The inhibitory effect of LAK cells on tumor cell clonogenicity in soft agar was also enhanced by both bsAb. These results indicate that application of the therapy with LAK cells and OKT3 x LU246 bsAb to SCLC patients might be a promising new method of adoptive immunotherapy.

Antibodies, Monoclonal↗
PubMed1994

[Detection of myocardial viability by delayed imaging after 201Tl reinjection].

Recent studies have demonstrated that some underestimation of myocardial viability remained to be not resolved even using reinjection method. So we devised a new technique of reinjection and reimaging, and using this we studied the detectability of myocardial viability in 32 patients of CAD. Exercise imaging (EX) was acquired after initial injection of thallium (111 MBq). Three hours after EX, the second dose thallium (37 MBq) was reinjected, and then the first reinjection image (Re1) was performed. Furthermore, the second reinjection image (Re2) was obtained at 3 hours after the second dose reinjection. SPECT images were divided in basal, mid and apical parts, and totally 13 segments were analyzed by visual scoring (0: severe, 1:moderate, 2:mild hypoperfusion and 3:normal). Twenty-seven (13.4%) of 202 segments of low score (0 to 2) shown in EX were improved in Re2, compared with Re1. Twenty-one (42.0%) of 50 segments of score 0 or 1 shown in Re1 were improved in Re2. These results showed that our devised new method of reimaging 3 hours after the second dose injection was useful to improve in detectability of myocardial viability.

Aged↗
PubMed1994

[Evaluation of myocardial perfusion and ventricular shape in hypertrophic cardiomyopathy using 99mTc-tetrofosmin scintigraphy: comparison with 201Tl myocardial scintigraphy].

Hypertrophic cardiomyopathy (HCM) is known to have the impairment of myocardial perfusion as well as irregularly hypertrophic myocardium. To evaluate myocardial perfusion and ventricular shape in HCM, 99mTc-Tetrofosmin scintigraphy was performed after exercise (Ex) and at resting state (Re) in 10 patients with HCM and was compared with early image (Ea) and delayed image (De) of 201Tl scintigraphy performed after exercise. SPECT images of both 99mTc-Tetrofosmin and 201Tl scintigraphy were analyzed with five scaled visual scores set in 18 segments. The complete concordance ratio between 99mTc-Tetrofosmin (Ex and Re) and 201Tl (Ea and De) images in segmental analysis was 75%. Image quality of 99mTc-Tetrofosmin was seemed to be superior to that of 201Tl scintigraphy. In 9 patients with HCM, 99mTc-Tetrofosmin scintigraphy was performed under the ECG gating and the thickness of septal and free wall was measured. Good correlation was observed with the data by ultrasound cardiography (r = 0.79, p < 0.002 in wall thickness, r = 0.84, p < 0.01 in the ratio of septal wall thickness to free wall thickness). Left ventricular shape (ventricular long axis) was closely resemble to that of left ventriculography by contrast medium. In conclusion, 99mTc-Tetrofosmin scintigraphy is useful for the evaluation of myocardial morphology as well as perfusion abnormality.

Adult↗
PubMed1993

Nucleosides and nucleotides. 122. 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine and its derivatives. A new class of nucleoside with a broad antitumor spectrum.

Design, synthesis, and tumor cell growth inhibitory effects of 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosyl derivatives of cytosine (1i, CNDAC), thymine (6a), uracil (6c), and adenine (6d) have been described. The synthesis of the target compounds was achieved from the corresponding 2'-keto nucleosides 2a-d. Cyanohydrins of 2a-d were converted to thionocarbonates, which were deoxygenated to give the desired 2'-beta-cyano-2'-deoxy derivatives 5a-d, followed by deprotection to furnish the target nucleosides. Of these nucleosides, CNDAC was the most potent inhibitor of cell growth with an IC50 value of 0.53 microM against L1210 cells. In vitro cytotoxicity of CNDAC against human tumor cell lines was also examined; compared with that of 1-beta-D-arabinofuranosylcytosine (ara-C) and 5-fluorouracil (5-FU), CNDAC was more cytotoxic to several cell lines refractory to ara-C. The in vivo effect of CNDAC on M5076 mouse reticulum cell sarcoma was very strong; 99% tumor volume inhibition on day 20 was achieved when it was administrated orally on days 1, 4, 7, 10, 13, and 16 at a dose of 400 mg/kg/day, while 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-FU caused only 50% inhibition at a dose of 500 mg/kg/day and 28% inhibition at a dose of 50 mg/kg/day, respectively, on the same schedule. These results indicated that CNDAC may have potential as a new antineoplastic agent with a broad antitumor spectrum.

Adenine↗
PubMed1993

[Assessment of myocardial perfusion abnormalities in patients with apical hypertrophic cardiomyopathy using exercise 201Tl scintigraphy].

Regional myocardial perfusion abnormalities commonly occur during exercise in patients with hypertrophic cardiomyopathy (HCM). Exercise 201Tl myocardial scintigraphy has provided a noninvasive means of identifying myocardial perfusion abnormalities in patients with HCM. On the other hand, apical hypertrophic cardiomyopathy (APH) is reported as a subtype of HCM. Whether APH is essentially equal to HCM or not is controversial. To assess myocardial ischemia in patients with APH, we studied 28 patients with APH, with exercise 201Tl SPECT. Myocardial perfusion images were obtained immediately after submaximal exercise and again after a 3-hour delay. Regional perfusion defects during exercise were identified in 19 of the 28 patients (68%) with APH. Complete reversible defects were observed in 15 (79%) patients with APH. Although perfusion defects were present in all regions of the left ventricle in patients with HCM, they were present only in the apical region in patients with APH. Thus, reversible 201Tl perfusion abnormalities commonly occur during exercise in patients with APH as well as in patients with HCM.

Adult↗
PubMed1993

[Recent AIDS-related topics].

AIDS has become a problem for not only researchers and medical staff but also for humankind, since its discovery 10 years ago. To prevent and control AIDS, one must understand the pathology of HIV infection, which is the cause of AIDS, in addition to mass education on correct measures for prophylaxis. In this review, we present the present status of HIV infection in Japan, especially in relation to pulmonary disease and tumor, and we introduce the basic research being carried out for the development of HIV vaccine.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Assessment of reverse redistribution on exercise 201Tl myocardial SPECT in patients with hypertrophic cardiomyopathy].

Reverse redistribution is revealed on exercise 201Tl myocardial SPECT in some cases with hypertrophic cardiomyopathy. Ten patients with hypertrophic cardiomyopathy without coronary artery disease who showed reverse redistribution visually were studied. Reverse redistribution was evaluated by the early and delayed images of exercise 201Tl myocardial SPECT. Relation between reverse redistribution and distribution of left ventricular hypertrophy estimated by echocardiography and magnetic resonance imaging was investigated, and the mechanism of reverse redistribution was analyzed by referring to Bull's eye display of washout rate. Reverse redistribution was displayed in non-hypertrophic region and washout rate was normal in that region and low in hypertrophic region. In conclusion, in order to interpret reverse redistribution it is necessary to recognize hypertrophic region and to refer to washout rate.

Adult↗
PubMed1993

[The relation between the anaerobic threshold and exercise-induced myocardial ischemia in patients with ischemic heart disease].

The aim of this study was to clarify whether the anaerobic threshold (AT) in patients with ischemic heart disease is determined by exercise-induced myocardial ischemia. A) The reproducibility of the VO2 at the AT (AT VO2) were studied. In 13 patients with exercise-induced myocardial ischemia, submaximal Treadmill exercise tests were performed twice using a cardiopulmonary monitoring system. The reproducibility of the AT VO2 was good (r = 0.92), and the mean +/- SD was -1.3 +/- 8.2%. B) The change of the AT VO2 after percutaneous transluminal coronary angioplasty (PTCA) was studied. In 30 patients who underwent successful PTCA, submaximal Treadmill exercise tests were performed before and after PTCA using a cardiopulmonary monitoring system. After PTCA both the exercise duration and the peak VO2 increased significantly (569.0 +/- 200.8 sec vs 681.9 +/- 206.9 sec, p < 0.001: 19.5 +/- 3. 4ml/min/kg vs 21.3 +/- 3.7ml/min/kg, p < 0.001). On the other hand, the AT VO2 did not increase (13.7 +/- 3.0 ml/min/kg vs 13.9 +/- 3.2ml/min/kg, NS). The significant increase of the AT VO2, more than 15.1%, was recognized only in 5 patients. Neither did the AT VO2 increase even in patients without hibernating myocardium. In conclusion, there are many cases in which AT is not determined by exercise-induced myocardial ischemia.

Aged↗
PubMed1993

[Transthoracic Doppler color imaging of the blood flows in the left coronary septal branches].

This study characterized blood flow signals derived from the left coronary septal branches by transthoracic Doppler color flow imaging. In the anterior ventricular septum, the signal was detected in 7 of 13 patients with aortic stenosis, 8 of 34 with hypertrophic cardiomyopathy, and 5 of 144 patients with other diseased states. The peak diastolic flow velocity assessed by a pulsed Doppler technique ranged 21-115 cm/s (mean 57). Systolic signal was depicted in 13 of the 20 with the diastolic signal, indicating retrograde flow direction in all of them. The peak negative systolic component ranged 11-80 cm/s (mean 40). Peak diastolic flow velocity of the left anterior descending artery was higher in patients with the septal branch flow signal than in those without the signal (53 +/- 24 vs 31 +/- 11 cm/s). Patients with the signal showed larger transvalvular pressure gradient in aortic stenosis, and greater septal thickness in hypertrophic cardiomyopathy than in those without the signal. In conclusion, transthoracic visualization of the septal branch flow signal by Doppler color flow mapping is attributable to increased coronary blood flow at rest which is probably due to excessive load and/or septal hypertrophy. Augmented systolic retrograde flow may play additional role in the diastolic high velocity flow in the septal perforator.

Adolescent↗
PubMed1993

[A case of stunned myocardium: dual SPECT findings similar to acute myocardial infarction (AMI)].

Emergent cardiac catheterization was performed on a 70-year-old female patient who was admitted for further evaluation of acute myocardial infarction. Coronary angiography didn't reveal any significant stenotic lesion, but levogram showed extensively abnormal contractility around the center of the apex region. On the second hospital day, 99mTc-PYP/201TlCl dual SPECT gave findings similar to those found in acute myocardial infarction, but myocardium--released enzyme stayed within the normal range. Two weeks after, 201TlCl myocardial scintigraphy showed disappearance of the perfusion defect, and normal contractility was observed on the levogram of the chronic phase. Since this case was clinically denied to be myocardial infarction, it was considered a typical case of stunned myocardium which showed prolonged left ventricular abnormal contractility with transient myocardial ischemia. This is a case suggestive for estimations of myocardial reversibility in patients with myocardial perfusion and metabolic disorder in dual SPECT.

Aged↗
PubMed1993

[Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy: evaluation by exercise 201Tl SPECT].

Effect of verapamil on myocardial ischemia in patients with hypertrophic cardiomyopathy (HCM) was evaluated by exercise stress myocardial 201Tl SPECT (EX-Tl). EX-Tl were performed before and after 8.8 weeks of oral verapamil (240 mg/day) in 12 patients with HCM who showed transient 201Tl perfusion defects under control conditions. 201Tl perfusion defect was visually scored and judged for 4 grades as normal (0), mild defect (1), moderate defect (2), and severe defect (3). Transient Dilation Index (TDI) was calculated as an index of subendocardial ischemia. Improvements of defect score were demonstrated in 10 patients after administration of verapamil. Two patients showed no change of defect score. Mean defect score decreased significantly from 5.50 to 3.03 (p < 0.001). Although 11 of 12 patients showed abnormal TDI under control conditions, 10 of them revealed improvements of TDI and 7 of those 10 patients disclosed normal TDI after verapamil. Mean TDI decreased from 1.263 to 1.090 significantly (p < 0.01). In conclusion, verapamil may improve myocardial ischemia in patients with HCM.

Adult↗