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Biomedical subjects

M Oguro

Publications and source records attributed to M Oguro.

At least 37 records · Page 2Linked to original sources
PubMed1993

A comparative study of CHOP versus MEVP (mitoxantrone, etoposide, vindesine, prednisolone) therapy for intermediate-grade and high-grade non-Hodgkin's lymphoma: a prospective randomized study.

To evaluate a new combination chemotherapy with mitoxantrone (MXT), etoposide (VP-16), vindesine (VDS), and prednisolone (MEVP therapy) as a front-line chemotherapy for non-Hodgkin's lymphoma (NHL), a prospective randomized study comparing this therapy (28 patients) with CHOP therapy (29 patients) was conducted in 57 patients with intermediate-grade or high-grade NHL with stages II-IV. The MEVP therapy consisted of 10 mg/m2 of MXT intravenously on day 1, 2 mg/m2 of VDS intravenously on day 1, 200 mg/m2 of VP-16 orally on days 1-3, and 40 mg/m2 of prednisolone orally on days 1-5. This regimen was repeated every 3 weeks for up to 10 courses. Complete responses (CR) were achieved in 17 (63.0%) of the 27 evaluable patients treated with MEVP therapy, and in 20 (71.4%) of the 28 evaluable patients treated with CHOP therapy. Relapse-free survival rates and overall survival rates at 3 years were 58.8% and 46.4%, respectively, for the MEVP group and 70.0% and 54.0%, respectively, for the CHOP group. Granulocytopenia was more severer and associated infection episodes were more frequent in the MEVP group. MEVP therapy was effective as a front-line chemotherapy for intermediate- and high-grade NHL, although it was not superior to CHOP therapy in treatment effect and was not less toxic than CHOP.

Adolescent↗
PubMed1992

Role of sympathetic nerve inhibition in the vasodepressor effect of bromocriptine in normotensive and hypertensive rats.

This study aimed to elucidate the mechanism of the hypotensive effect of bromocriptine (BRC), and to investigate whether or not the effects of BRC on the sympathetic nervous system are altered in hypertension. BRC was administered intravenously to normotensive and spontaneously hypertensive rats (SHR). It elicited hypotensive effects dose-dependently in urethane-anaesthetized normotensive rats, an effect which was antagonized with metoclopramide. Pretreatment with intravenous hexamethonium attenuated the hypotensive effect of BRC. BRC decreased plasma norepinephrine (NE) without inhibiting the sympathetic nerve spikes recorded from the postganglionic sympathetic nerve bundle. The hypotensive effect of BRC was significantly greater in SHR than in Wistar Kyoto Rats (WKY). Decrease in NE by BRC was also significantly greater in SHR than in WKY. These results suggest that the hypotensive effect of BRC is induced by suppression of NE release, not by inhibition of sympathetic nerve spikes, and that the dopaminergic presynaptic inhibition is attenuated in SHR.

Animals↗
PubMed1992

Calcium suppresses central angiotensin II pressor response less in SHR.

To determine whether calcium alters central cardiovascular regulation, cardiovascular responses to intracerebroventricular (ICV) injection of calcium were recorded in conscious Wistar rats. Calcium injection consistently produced dose-dependent decreases in mean parterial pressure and heart rate. Pretreatment with a calcium channel blocker, diltiazem, attenuated cardiovascular responses to calcium. Decreases in plasma norepinephrine indicated the contribution of sympatho-inhibition to vasodepression by calcium. Preceding calcium injection reduced pressor responses to ICV-injected angiotensin II. These findings suggest that there is a pharmacological interaction between calcium and angiotensin II in the central nervous system. In spontaneously hypertensive rats (SHR), cardiovascular responses to calcium was larger than Wistar Kyoto rats (WKY). By contrast, calcium reduced pressor responses to angiotensin II only in WKY but not in SHR. Because the central interaction between calcium and angiotensin II has been different in SHR, our results imply that this difference may be related to the maintenance of high blood pressure in SHR.

Angiotensin II↗
PubMed1992

[BH-AC.nitrosourea-therapy for refractory or relapsed malignant lymphoma].

Thirty patients with refractory or relapsed non-Hodgkin's lymphoma were treated with behenoyl ara-C (BH-AC) and nitrosoureas. Sixteen patients (53%) had a diffuse, large cell lymphoma and 22 patients (73%) had a stage IV disease. BH-AC, 250 mg/body, in combination with ACNU or MCNU, 50 mg/body, was administered by drip infusion for two days (Day 1, 2) every 3 to 4 weeks. Six patients (20%), all of them relapsed cases of diffuse lymphoma, obtained complete remission lasting one to six (mean: 2.5) months and 15 patients (50%) obtained partial remission lasting one to five (mean: 2.7) months. The major side effect was thrombocytopenia, and nine patients (30%) had required platelet-transfusions. There was no case complicated by infection due to prolonged neutropenia. Therefore, we conclude that BH-AC.Nitrosourea-therapy is very useful for the salvage chemotherapy of malignant lymphoma.

Adult↗
PubMed1991

The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver.

The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver.

Adenoma, Bile Duct↗
PubMed1991

Sympathetic inhibition and attenuation of spontaneous hypertension by PVN lesions in rats.

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.

Animals↗
PubMed1991

Altered noradrenergic projection to hypothalamus via baroreflex in spontaneously hypertensive rats.

To determine whether noradrenergic projections to the posterior hypothalamus via baroreflex are altered in the hypertensive state, the extracellular norepinephrine (NE) content of the posterior hypothalamus was measured in both spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) after sinoaortic denervation (SAD) or sham operation. In WKY, blood pressure (BP) and extracellular NE content 24 h after SAD were significantly higher than those of sham-operated rats. Contrarily, SAD did not increase both BP and NE in the posterior hypothalamus of SHR. These results suggest that the noradrenergic pathway via the baroreflex is impaired in SHR. This mechanism may play an important role in the development and maintenance of hypertension in SHR.

Adrenergic Fibers↗
PubMed1991

Enhanced norepinephrine release in hypothalamus from locus coeruleus in SHR.

The hypothesis that a functional projection from the locus coeruleus (LC) to the posterior hypothalamus contributes to the development of hypertension in SHR, was tested by measuring norepinephrine (NE) in the posterior hypothalamus by brain dialysis after injections of L-glutamate (L-glu) into LC. L-glu elicited a prolonged elevation of blood pressure in both SHR and WKY. Pressor effects were significantly larger in SHR than in WKY. Extracellular NE in the posterior hypothalamus increased after LC stimulation; NE release was significantly higher in SHR than in WKY. Injections of 6-hydroxydopamine (6-OHDA) into posterior hypothalamus lowered the resting blood pressure and attenuated the pressor responses to L-glu injections into the LC in SHR. These findings suggest that the LC projects functionally to the posterior hypothalamus and that the projection can contribute to the development of hypertension in SHR.

Animals↗
PubMed1991

[Combination cancer chemotherapy using a DNA topoisomerase inhibitor CPT-11, as a core agent--the in vitro evaluation].

CPT-11, a derivative of camptothecin, has drawn attention to cancer chemotherapy because of the specific mode of action, and the clinical study is now under progress. Liu et al. proved that camptothecin was a DNA topoisomerase I inhibitor, and some kinds of antitumor agents have been recognized as DNA topoisomerase II inhibitors. Based on these findings, DNA topoisomerases have emerged as target enzymes of antitumor agents in cancer chemotherapy. This paper dealt with investigation on the cytotoxic effects induced by combined use of DNA topoisomerase targeting antitumor agents, especially using CPT-11 as a core antitumor agent. Synchronous administration of CPT-11 with other antitumor agents induced cytotoxic effects less than metachronous administration of CPT-11 with other antitumor agents, especially preceding use of CPT-11. Dose of antitumor agents was not necessarily correlated to the cytotoxic effects. In some instances, small doses of the agents showed better therapeutic effects than large doses. The cytotoxic effects of vincristine, vindesine, and hydroxyurea were reduced by combination with CPT-11. On the other hand, non-cytotoxic agents such as aphidicolin, novobiocin, propentofylline, pentoxifylline, norfloxacin, and tosufloxacin enhanced the cytotoxic effects of CPT-11. Hypothetical consideration of cell killing and acquisition of drug resistance was proposed.

Antineoplastic Agents, Phytogenic↗
PubMed1991

[In vitro effect of combined use of BH-AC and nitrosourea derivatives against adriamycin-resistant human leukemia cell line].

Cytocidal effects of combined use of BH-AC and nitrosourea derivatives (MCNU, and ACNU) were evaluated in vitro against adriamycin-resistant human leukemia cell line (K-562/ADR-I). K-562/ADR-I cells were resistant to six kinds of agents (vindesine, mitoxantrone, aclacinomycin, cisplatin, MCNU, and BH-AC) of 14 agents tested and this cell line proved to be a multi-drug resistant line. Combined use of BH-AC and MCNU did not achieve additive effects on K-562, parent cell line and BH-AC and MCNU were less effective to K-562/ADR-I by single use. However, combination of BH-AC and MCNU showed additive effects. These results supported the evidence that combination of BH-AC with MCNU was effective in patients with multi-drug resistant malignant lymphomas.

Antineoplastic Agents↗
PubMed1990

[A case of pheochromocytoma with an AMI-like ECG change corrected by an alpha-blocking agent].

A 59 year-old housewife was admitted to the emergency service with a sudden onset of chest pain and nausea. Initially she was treated as an acute myocardial infarction, but conventional treatments were not effective, and she was sent to our hospital for further evaluation. Her ECG showed several abnormal findings including T-wave inversion, atrial flutter, QT-time prolongation, ST-segment depression or elevation, and frequent ventricular ectopic beats. The echocardiogram, 201thallium scintigram and coronary angiography were almost normal. Both urinary and plasma levels of catecholamines were remarkably increased, and the plasma epinephrine was extremely high during attacks. Abdominal echotomography and CT-scanning showed a large left adrenal tumor. The 131MIBG scintiscan revealed a high accumulation in this tumor. Then the patient was diagnosed as having pheochromocytoma and catecholamine-induced myocarditis. The administration of phentolamine (10 mg) normalized the inversion of T-wave and the high blood pressure. But when propranolol (2 mg) was administrated in addition to phentolamine, the ECG showed a biphasic low T-wave change. According to these phenomena, we supposed that the alpha-adrenergic receptor was involved in the development of the ST-T changes of the ECG, and the alpha-adrenergic receptor of this patient might be sensitive under excessive catecholamines, according to the inhibition of the beta-receptor by propranolol.

Adrenal Gland Neoplasms↗
PubMed1990

Collateral drug sensitivity induced in CPT-11 (a novel derivative of camptothecin)-resistant cell lines.

Collateral drug sensitivity was induced in CPT-11-resistant cell lines (CPT-K and T). Ten of the 19 kinds of antineoplastic agents (especially, 5 of 6 kinds of DNA topoisomerase II inhibiting agents) were effective in inducing collateral drug sensitivity. Alteration of DNA topoisomerase I seemed to be unrelated to acquisition of multidrug resistance.

Antineoplastic Agents, Phytogenic↗
PubMed1990

Clonidine abolishes exaggerated pressor responses to shaker stress in spontaneously hypertensive rats.

To determine whether clonidine would attenuate exaggerated pressor responses to stress in spontaneously hypertensive rats (SHR), pressor responses to shaker stress were recorded following intracerebroventricular (icv) injections of clonidine in conscious SHR. Pressor responses to shaker stress were significantly larger in SHR than in Wistar-Kyoto rats (WKY). Increased sympathetic nerve responses to shaker stress were also significantly greater in SHR than in WKY. Exaggerated pressor responses in SHR were partly attenuated by adrenalectomy and abolished by clonidine (icv). By contrast, 1-Sar,8-Ile angiotensin II (icv) was ineffective. These findings suggest that in SHR, the alpha-adrenergic system in the brain may contribute to exaggerated pressor responses to shaker stress, but not the brain renin-angiotensin system.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1990

Chronic central GABAergic stimulation attenuates hypothalamic hyperactivity and development of spontaneous hypertension in rats.

To determine whether chronic central gamma-aminobutyric acid (GABA) stimulation would attenuate development of hypertension, tail-cuff systolic pressures were measured in male spontaneously hypertensive rats (SHR) treated with either an inhibitor of GABA breakdown (valproate, VPA), or a GABA-receptor agonist (muscimol). When VPA was injected intraperitoneally (i.p.) daily for 4 weeks, tail-cuff systolic pressures were decreased during the last 2 weeks. On the other hand, continuous infusion of muscimol into the lateral cerebral ventricle for 14 days using an osmotic minipump decreased systolic pressures throughout the 10-day observation period. During terminal experiments under urethane anesthesia, pressor and sympathetic nerve responses to electrical stimulation of the ventromedial hypothalamus were reduced in VPA- or muscimol-treated SHR. Pressor responses to intravenously (i.v.) injected norepinephrine (NE) were unaltered by either treatment, indicating that diminished pressor responsiveness to hypothalamic stimulation was not due to diminished cardiovascular reactivity. Regardless of either VPA acid or muscimol treatment, basal blood pressure (BP), heart rate (HR), and responses to hypothalamic stimulation were lower in normotensive Wistar-Kyoto controls (WKY) than in SHR. In addition, chronic treatment with either drug had weaker hypotensive and hypothalamic depressant effects in WKY than in SHR. Our results suggest that in SHR the central GABAergic system is impaired and that chronic treatment with GABAergic stimulants can attenuate development of spontaneous hypertension by reducing hypothalamic overactivity.

Animals↗
PubMed1990

Combination chemotherapy with pirarubicin (THP), cyclophosphamide, vincristine, and prednisolone (VEP-THP therapy) in the treatment of non-Hodgkin's lymphoma.

Twenty-eight patients with non-Hodgkin's lymphoma (NHL) were treated with a combination of (2''-R)-4'-o-tetrahydropyranyladriamycin (pirarubicin, THP), cyclophosphamide, vincristine, and prednisolone (VEP-THP therapy). Eleven (45.8%) of twenty-four evaluable patients achieved complete response (CR). CR rate (52.8%) was higher in the intermediate-grade histology group than in high- or low-grade group. Toxicity was generally acceptable although leukopenia less than 2,000/microliters was observed in 17 (60.7%) of 28 patients. Clinical signs of cardiotoxicity were not observed and alopecia was mild. Therefore, VEP-THP therapy is useful as a first-line chemotherapy in the treatment of NHL, particularly for the patients with intermediate-grade histology. Higher CR rate and longer relapse-free survival can be expected by administering a greater dose of THP or employing a schedule of fractionated low doses.

Adult↗
PubMed1990

A lectin-based monoclonal enzyme immunoassay to distinguish fucosylated and non-fucosylated alpha-fetoprotein molecular variants.

Purified alpha-fetoprotein (AFP), fucosylated AFP mixtures, and 40 sera from patients with AFP-producing hepatocellular carcinoma were analysed by monoclonal enzyme immunoassay (EIA) to distinguish fucosylated and nonfucosylated AFP molecular variants. FUC-AFP-25 was discriminated from FUC-AFP-75 by the EIA using monoclonal antibody 18H4 in the range of total AFP concentrations from 100 to 800 ng/mL. In addition, sera from 40 patients with hepatocellular carcinoma, with AFP concentrations from 100 to 1270 ng/mL and with fucosylated AFP from 0 to 100% by conventional cross immuno-affinoelectrophoresis, were also analysed by the present EIA. A statistically significant correlation was obtained between the data from the present EIA and from the conventional crossed immuno-affinoelectrophoresis in the range of fucosylated AFP more than 20% and the serum concentration of AFP more than 100 ng/mL. These results indicate that the present EIA is useful for clinical detection of hepatocellular carcinoma during the follow-up of patients with chronic liver diseases.

Antibodies, Monoclonal↗
PubMed1990

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

Adolescent↗