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Biomedical subjects

I Adachi

Publications and source records attributed to I Adachi.

At least 163 records · Page 9Linked to original sources
PubMed1994

Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.

S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg/kg, p.o. and 15.0 (10.2-23.7) mg/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg/kg, s.c.) or bemegride (40 mg/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy.

Administration, Oral↗
PubMed1994

[Assessment of myocardial contraction and relaxation with 99mTc-tetrofosmin multi-gated myocardial SPECT].

Myocardial relaxation at the diastolic phase was not evaluated by multi-gated myocardial SPECT, although myocardial contraction at the systolic phase was studied by percent wall thickening and Bull's eye methods. We make out a myocardial volume curve and report to evaluate the myocardial relaxation using multi-gated myocardial SPECT. The study population consisted of 3 normal human subjects (3 male, 32-37 years old), 10 idiopathic cardiomyopathy, 10 coronary artery disease and 1 hypertensive heart disease combined with aortic regurgitation. All cases were injected 555 MBq of 99mTc-tetrofosmin (Amersham Healthcare Corporation) intravenously at rest. A triple detector gamma-camera (GCA-9300A, Toshiba Medical, Japan) and a data processing computer (GMS-5500A, Toshiba Medical, Japan) were used in this study. A cardiac cycle (R-R interval) was divided by 16 frames (50-80 msec per 1 frame). Eight myocardial volume curves were calculated at the anterior wall, apex and inferior wall of the vertical long axis view and were calculated at the septal wall, apex and lateral wall of the horizontal long axis view, respectively. The patterns of the myocardial volume curves were classified into 5 patterns (Normal pattern (N), Delayed Contraction pattern (DC), Delayed Relaxation pattern (DR), Mixed pattern (M) and Normal pattern with Decreased amplitude (ND)). Myocardial uptake was evaluated visually of grading into severe hypertrophy (5), hypertrophy (4), normal (3), mild hypoperfusion (2), hypoperfusion (1) and perfusion defect (0). We compared patterns of the myocardial volume curves to myocardial uptake in the same segments. It was possible to detect myocardial edge of the total 16 frames with 50-60% threshold in the normal volunteer and in patients with hypertrophic cardiomyopathy and to make a myocardial volume curve. The region of the severe myocardial perfusion defect could be detected with 20% threshold in patients with old myocardial infarction. In comparison with myocardial volume curves and myocardial uptake, 74.6% in the N pattern had a normal uptake (3), 66.7% in the ND pattern had a normal uptake (3), 61.5% in the DC pattern had a hypoperfusion segment (0, 1 or fill-in to normal uptake), 44.4% in the DR pattern had a hypertrophic segment (4, 5 or fill-in to increased uptake). The pattern of myocardial volume curve indicates myocardial contractility and relaxation in each myocardial segment.

Adult↗
PubMed1994

[An early phase II clinical study of RP56976 (docetaxel) in patients with breast cancer].

An early phase II clinical study of RP56976 (docetaxel), a new anticancer agent of plant origin, was conducted in patients with breast cancer at 20 Japanese collaborative institutions. Docetaxel was administered at two or more doses of 60 mg/m2 by intravenous infusion with dose-free intervals of 3-4 weeks, and the efficacy and safety was evaluated. Of the 51 patients enrolled, 50 patients completed the scheduled course of treatment. Two patients showed a complete response (CR) and 19 showed a partial response (PR) with a response rate of 42.0%. The response rates based on the efficacy for metastatic lesions in soft tissue, liver and lung, were 46.2% (18/39), 37.5% (3/8), and 38.5% (5/13), respectively. Of the 50 patients who completed the study, 48 patients had previously been treated for the present malignancy. Forty-seven patients had previously been treated with chemotherapy and showed a response rate of 40.4% (19/47). The response rate in those who had received chemotherapy composed of anthracyclines and other agents was 44.1% (15/34). Grade 3 or more severe leukopenia and neutropenia developed in 43 patients (84.3%) and 48 patients (94.1%), respectively. Other adverse reactions which occurred in a Grade 3 or more severe form included nausea/vomiting (1 patient), anorexia (5 patients), diarrhea (4 patients), fatigue (2 patients), and alopecia (20 patients). Except for alopecia, most adverse reactions were generally transient and reversible without any specific treatment.

Adult↗
PubMed1994

[A comparison among 123I-IMP SPECT, EEG and MRI in patients with temporal lobe epilepsy].

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT), electroencephalography (EEG), and magnetic resonance imaging (MRI) were performed in 19 patients with temporal lobe epilepsy during interictal stage. MRI demonstrated abnormal signal in mesial temporal lobe (hippocampus) in 10 of 19 patients and 123I-IMP SPECT showed a hypoperfusion area in 15 of 19 patients. When compared with EEG and MRI data, disagreement of the affected area was observed in 3 cases. In comparison of EEG and 123I-IMP SPECT data, disagreement of the affected area was observed in 6 cases. Although there were no disagreement in comparison of MRI and 123I-IMP SPECT. We made a reprojection data parallel to the hippocampus in 123I-IMP SPECT. These data demonstrated obviously a hypoperfusion area around the hippocampus. In cases within one month from seizure attack, wide hypoperfusion area was showed on 123I-IMP SPECT in comparison of abnormal signal area on MRI. It could be considered that a reprojection data parallel to the hippocampus was useful to know extent of hypoperfusion area in temporal lobe epilepsy.

Adult↗
PubMed1994

[Chemotherapy of breast cancer--past experience and future prospects].

Based on the results of randomized clinical trials as multi-center studies in patients with advanced recurrent breast cancer, we discussed the future direction of chemotherapy for breast cancer and node 4 conclusions: 1) Concerning the combination of endocrine therapy and chemotherapy, ACT therapy with ADM, CPA, and tamoxifen seemed to be appropriate as the standard therapy. 2) Concerning the chemotherapy period, continuous administration seemed to be more standard than intermittent administration in terms of the QOL of patients. 3) There are limits in chemotherapy that increases the dose intensity by combination with G-CSF or bone marrow transplantation to overcome drug resistance and achieve a cure. However, the effectiveness of this method can be expected in selected patients in the future. 4) There are new promising drugs for chemotherapy such as taxanes. These drugs are expected to contribute to the development of treatment methods. From these aspects, we discussed the future direction of chemotherapy in clinical treatment and studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Clinical evaluation of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) on advanced and recurrent breast cancer. Clinical study group of CMF for breast cancer in Japan].

The clinical efficacy of "CMF" chemotherapy, (cyclophosphamide, methotrexate, 5-fluorouracil), was evaluated on advanced and recurrent breast cancer. The response rate was 36.1% in 61 evaluable cases, including four CR and eighteen PR. In terms of efficacy classified by metastatic lesion, the effective rates were 51.4% in soft tissue, 28.6% in viscera, and 20.0% in bone metastases. The main side effects were nausea/vomiting, anorexia, and leucopenia. In this study, CMF chemotherapy resulted in good clinical effects, and its response rate was almost the same as that to CMF chemotherapy in Europe and USA, but slightly lower than that to CAF chemotherapy. As to the side effects, the incidence of leucopenia, thrombocytopenia or alopecia was lower in CMF chemotherapy than in CAF chemotherapy. Also, unlike CAF chemotherapy, CMF chemotherapy had no cumulative dose-limitation and showed no cardiotoxicity. In conclusion, CMF chemotherapy is considered to be one of the most useful treatments for advanced and recurrent breast cancer.

Administration, Oral↗
PubMed1994

[Clinical evaluation of 99mTc-MAG3 renal imaging: comparison with 99mTc-DTPA, 99mTc-DMSA and 131I-OIH].

The newly developed 99mTc-labeled renal imaging agent, mercaptoacetyltriglycine (MAG3), is a tubular secreted compound. It is expected the most suitable agent to measure renal function and image urinary tract because of the excellent imaging properties and availability of 99mTc and preferred biological qualities of radiohippurates. We examined 15 patients (8 males, 7 females, mean age 55 years old) with renal and urinary tract disease. After drinking 400 ml of water, 185, 370 or 555 MBq of 99mTc-MAG3 was injected with the supine position. Dynamic scans were acquired for 20 minutes on a large field of view gamma camera (ZLC-7500 Siemens Medical Inc.) linked to a computer system (Scintipac-2400 Shimadzu Co.) in a 64 x 64 matrix. Regions of interest (ROI) were placed around each kidney. Curves of 12 seconds frame rate were generated from all two ROIs over the 20 minutes study. The time to peak count (Tmax) and time from peak count to a half count (T1/2) were calculated from the curve data. 99mTc-DTPA renal imaging was examined to the same patients with the same method like 99mTc-MAG3. The renogram of 131I-orthoiodohippurate (OIH) was performed with probe method. The excellent quality of the renal image was obtained with 185-555 MBq of 99mTc-MAG3 compared with the same dose of 99mTc-DTPA respectively. The diagnostic value of 99mTc-MAG3 renal imaging was as well as 99mTc-DMSA renal imaging. The Tmax of 99mTc-MAG3 renogram was same value of that of both 99mTc-DTPA and 131I-OIH renogram. The T1/2 of 99mTc-MAG3 renogram was significantly lower than that of 99mTc-DTPA renogram. The T1/2 of 99mTc-MAG3 renogram was slightly higher that of 131I-OIH renogram. We conclude that the renal imaging of 99mTc-MAG3 was able to acquire the most excellent image and the proper renogram pattern as same as 131I-OIH renogram.

Adult↗
PubMed1994

[Early phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section].

A multi-institutional early phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 15 nationwide hospitals. KW-2307 was intravenously administered once weekly at doses of 15 to 25 mg/m2. Sixty-five among the enrolled 69 patients were eligible. Response rates were 11.8% (2/17) with 15 mg/m2, 28.0% (7/25) with 20 mg/m2 and 17.4% (4/23) with 25 mg/m2, and the overall response rate was 20.0%. Once-weekly intravenous administration of 20 mg/m2 was estimated to be the optimal dose of KW-2307 from the results. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included anorexia, nausea-vomiting, phlebitis, fever, general fatigue and stomatitis, but none of them was serious.

Adult↗
PubMed1994

[Late phase II study of KW-2307 in advanced or recurrent breast cancer. KW-2307 Cooperative Study Group (Breast Cancer Section)].

A multi-institutional late phase II study of KW-2307 (vinorelbine), a new vinca alkaloid derivative, in advanced or recurrent breast cancer was conducted in 26 nationwide hospitals. KW-2307 was intravenously administered at a dose of 20 mg/m2 once weekly. Eighty among the enrolled 82 patients were eligible. The overall response rate was 30.0% (24/80) with 4 CR, 20 PR, 5 MR, 22 NC, 17 PD and 12 unevaluable patients. The major side effect was leucopenia, which was the dose-limiting factor in this study. Other subjective or objective side effects included general fatigue, nausea-vomiting, anorexia, paresthesia, fever and stomatitis, but none of them was serious.

Adult↗
PubMed1993

Determination of c-erbB-2 protein in primary breast cancer tissue extract using an enzyme immunoassay.

The c-erbB-2 protein in breast cancer tissue extract was determined by using an enzyme-immunoassay (EIA) to see whether the quantitative determination of the oncoprotein correlates with the results of immunohistochemistry and other prognostic factors. Primary breast cancer from 104 patients was assayed for c-erbB-2 protein with an EIA that used two monoclonal antibodies directed against the extracellular domain of the protein. Pelleted tissue homogenate prepared routinely for hormone receptor assay was used as the starting material. The mean quantity of c-erbB-2 protein was 695 unit/mg protein (range 23 to 5939), and this correlated well with the results of immunohistochemical staining (P < 0.00001). It was found that 17.3% (18/104) of all tumors contained amounts of c-erbB-2 protein exceeding 1000 units/mg protein. All tumors with negative or weakly positive staining contained the oncoprotein as less than 1000 units/mg protein. The content of c-erbB-2 protein was correlated with the histologic grade (P = 0.0022), mitotic index (P = 0.0002) and degree of nuclear atypia (P = 0.013). It was inversely correlated with progesterone receptor (P = 0.006) and less strongly with estrogen receptor status (P = 0.016). Values of hormone receptor concentration and c-erbB-2 protein content showed a hyperbolic relationship that suggested biological interactions between c-erbB-2 protein and steroid hormone receptors. We conclude that c-erbB-2 protein in tissue extracts of primary breast cancer can be determined reliably by EIA, and it seems feasible to explore further the advantages of introducing EIA as a routine laboratory examination for providing additional information about the biological aspects of breast cancer.

Adult↗
PubMed1993

Inhibitory effects of tannins on NADH dehydrogenases of various organisms.

We examined the effects of purified tannins and related compounds (33 species) on NADH-ubiquinone-1 oxidoreductase activity in four kinds of organism (Paracoccus denitrificans, Bacillus subtilis, Photobacterium phosphoreum, and Thermus thermophilus HB-8) and rat liver mitochondria. In addition to pentagalloylglucose, which was reported as a potent inhibitor of NADH dehydrogenases (NDH), sanguiin H-11, oolonghomobisflavan A, and polymerized procyanidin are potent inhibitors for both types of NDH (NDH-1 and NDH-2). We found that some other tannins contained in tea are also inhibitors of NDH from all organisms.

Animals↗
PubMed1993

[Possibility of lymphatic absorption of epidermal growth factor from intestine].

Epidermal growth factor (EGF) in the milk fat globule membrane (MFGM) emulsion enhanced the absorption of this factor from the intestine, especially to the intestinal lymph. Most of the radioactive EGF administered was degraded to small molecular weight materials. These degraded materials were absorbed and appeared in both the intestinal lymph and portal vein blood. However, a certain portion of EGF, although small, appeared in the lymph maintaining the original molecular mass. The MFGM emulsion used enhanced the lymphatic absorption of intact EGF, suggesting that this dosage form increased the absorption of EGF, protected the degradation of EGF in the intestine or promoted the absorption of intact EGF. The enhancing effect on the absorbed dose percentage of EGF recovered using MFGM emulsion was also observed in the portal vein plasma. However, the effect on the absorption of intact EGF was much larger in the lymph than in the portal vein.

Animals↗
PubMed1993

Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 1st communication: comparative studies on the cardiovascular effects of methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2,3- b]pyridine-5-carboxylate and its two enantiomers in experimental animals.

Antihypertensive effects in conscious spontaneously hypertensive rats (SHR), cardiovascular effects in anesthetized dogs, and calcium antagonistic effects in the rabbit isolated basilar arteries and guinea-pig isolated coronary arteries of S-312 (methyl-4,7-dihydro-3-isobutyl-6-methyl-4- (3-nitrophenyl) thieno [2,3-b] pyridine-5-carboxylate) and its two enantiomers were comparatively investigated. The antihypertensive effect in SHR and hypotensive effect in anesthetized dogs of S-312-d (CAS 120056-57-7) were approximately 2 times more potent than those of S-312, but these effects of S-312-l were very weak even at 10 to 100 times higher doses. Increases of vertebral blood flow in dogs with S-312 and S-312-d were almost corresponding. The IC50 concentrations of S-312-d, S-312, S-312-l in the rabbit isolated basilar arteries contracted with high K+ solution were 1.4 x 10(-10) mol/l, 2.2 x 10(-10) mol/l, and 4.6 x 10(-9) mol/l, respectively. The relaxing effect of S-312-d in the isolated coronary arteries was most potent, followed by those of S-312 and S-312-l. It is concluded that the cardiovascular and calcium antagonistic effect of S-312-d are mainly responsible for those effects of S-312.

Animals↗
PubMed1993

Pharmacological studies on a new Dihydrothienopyridine calcium antagonist. 2nd communication: effects of S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4- (3-nitrophenyl)thieno[2,3-b]pyridine-5-carboxylate on the 1,4-dihydropyridine binding sites in the brain and on isolated arteries in the Cynomolgus monkey.

The effects of S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3- nitrophenyl)thieno[2,3-b]pyridine-5-carboxylate, CAS 120056-57-7) on the 1,4-dihydropyridine binding sites using membrane fractions prepared from monkey cerebral cortex, hippocampus, and cerebellum and on isolated monkey arteries were investigated. Specific binding of [3H]-(+)-isradipine was saturable and reversible, and of high affinity. 1,4-Dihydropyridine calcium channel antagonists competed for the binding in the order of S-312-d = nilvadipine = nicardipine > nifedipine. The effect of S-312-d on the binding was due mainly to alterations in the dissociation constant (Kd), without alterations in the binding density (Bmax). In the helical strips of cerebral, coronary, renal mesenteric, and femoral arteries contracted with K+ or prostaglandin (PG) F2 alpha, the addition of S-312-d caused a concentration-dependent relaxation. Relaxant activities of S-312-d in the cerebral arteries contracted with U-46619 (a thromboxane A2 mimetic) or endothelin-1 did not differ significantly from those in the arteries contracted with K+ or PGF2 alpha. Potencies of relaxations induced by S-312-d and 1,4-dihydropyridine calcium channel antagonists in the K(+)-depolarized mesenteric arteries correlated well with those of the binding experiment. Ca(2+)-induced contractions in the mesenteric arteries previously exposed to Ca(2+)-free medium and depolarized by excess K+ were attenuated by S-312-d, whereas PGF2 alpha-induced contractions of the arteries exposed to Ca(2+)-free medium were unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 4th communication: prophylactic and therapeutic effects of S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate in stroke-prone spontaneously hypertensive rats.

The prophylactic and therapeutic effects of S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate, CAS 120056-57-7) were compared with those of nimodipine or nicardipine using male stroke-prone spontaneously hypertensive rats (SHRSP). The survival rate of SHRSP was dose-dependently increased by once a day oral administration of S-312-d (0.3, 1, and 3 mg/kg) or nimodipine (10 mg/kg), while all non-treated SHRSP fed with high Na+ diet died within 40 days after the start of the experiment. All SHRSP treated with 3 mg/kg S-312-d survived during the 60-day experiment periods. Marked decreases of body weights and various neurological symptoms were also inhibited with S-312-d or nimodipine. Moderate diuretic effects were observed with S-312-d at doses of 1 and 3 mg/kg. The appearance of urinary occult blood in control SHRSP was markedly inhibited with S-312-d at 1 mg/kg and nimodipine at 10 mg/kg. Histological examination of the brain of SHRSP showed that cerebral stroke lesion including edema, hemorrhage, and/or softening was dose-dependently inhibited with S-312-d. Once a day oral administration of S-312-d (1, 3, or 10 mg/kg) dose-dependently increased the body weights and improved the neurological symptoms of diseased SHRSP. The appearance of proteinuria and of occult blood in the urine of SHRSP were also markedly inhibited with S-312-d or nicardipine. Histological examination of the brain of SHRSP showed that the arbitrary neurotoxic index (ANI) for stroke lesion dose-dependently decreased with S-312-d at 1, 3, and 10 mg/kg as follows: 4.8, 3.0, 2.3. The ANI for non-treated SHRSP was 7.6. The therapeutic effects of nicardipine (ANI 3.9) at 10 mg/kg corresponded to those of S-312-d at 3 mg/kg. Thus, S-312-d can be recommended for the treatment of cerebral insufficiency or vasospasm following stroke as well as in essential hypertension.

Animals↗
PubMed1993

[A case of benign paraganglioma arising in the middle mediastinum; 201Tl-SPECT for differentiation from malignant tumor].

A case of benign paraganglioma arising in the middle mediastinum was reported. 201Tl SPECT showed high accumulation in tumor on early images at 15 min and reduced on late images at 3 hours after infusion. The patient was a 57 year old female. In the contrast enhanced CT, 3 x 4 cm tumor with intensive enhancement was recognized at the right middle mediastinum. Under the radiological images, the tumor was surgically removed. The pathologic diagnosis was a low atypical nonfunctioning aortico-pulmonary paraganglioma. This report was suggested that 201Tl SPECT was useful for differential diagnosis of benign neurogenic mediastinal neoplasms.

Diagnosis, Differential↗