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Biomedical subjects

M Oguro

Publications and source records attributed to M Oguro.

At least 55 records · Page 3Linked to original sources

[A markedly effective combination therapy of 5'-DFUR and MMC in advanced gastric cancer--a case report].

We performed a combination therapy with two drugs, 5'-DFUR and MMC, which proved to be markedly effective in one patient. The patient was 73-year-old female with tumor, advanced cancer gastric lower third portion. Borrmann type 3, an poorly differentiated adenocarcinoma. Since the patient rejected an operation, the drug therapy was selected. Oral administration of 5'-DFUR 800 mg daily was combined with intermittent intravenous administration of mitomycin C. In 3 years, the cancerous site got scarred and no distant metastasis was observed. Presently, she feels well, receiving an outpatient treatment.

Adenocarcinoma↗

[Prominent lymphadenopathy and double Ph1 chromosomes as initial and recurrent manifestations of chronic myelogenous leukemia in blast crisis: report of a case and review of the literature].

A 60-year-old woman was admitted because of fatigue. Physical examination revealed prominent peripheral lymphadenopathy, marked tonsillar swelling and hepatosplenomegaly. The leukocyte count was 68,900/microliters with 75% lymphoid blasts and 5% basophils. The karyotype of the blood cells was 46, XX, Ph1/47, XX, Ph1, +Ph1. The diagnosis of CML in blast crisis was made. After chemotherapy using adriamycin, cyclophosphamide, vincristine, and prednisolone (CHOP), lymphadenopathy and splenomegaly reduced and lymphoid blasts disappeared from the blood and bone marrow. At that time only single Ph1 (46, XX, Ph1) clone was detected in her bone marrow. Four months later, hematological relapse accompanied by lymphadenopathy occurred and DNA analysis of the blasts showed the rearrangement of bcr gene. The simultaneous chromosomal analyses of the blood, bone marrow and lymph node revealed that almost all cells examined had the karyotype "47, XX, Ph1, + Ph1". In spite of repeated chemotherapy the patient did not improve and died. This case suggests a relationship between lymphadenopathy and double Ph1 chromosomes in CML.

Blast Crisis↗

[Transient monocytic skin infiltrate during preleukemic phase of acute myelomonocytic leukemia].

An acute myelomonocytic leukemia presenting transient skin rash during preleukemic phase was described. Following four years of unexplained leukopenia, a generalized exanthema developed and subsequently regressed spontaneously. The skin biopsy and immunohistochemistry revealed monocytic infiltration into the dermis. Twenty-eight months later, the patient became leukemic and died. The skin lesions, however, did not occur after leukemic transformation. Probably transient monocytic skin infiltrate was a symptom of preleukemia, a stem cell neoplasm manifested by functionally abnormal maturation.

Aged↗

Paraventricular nucleus lesions attenuate the development of hypertension in DOCA/salt-treated rats.

To determine whether paraventricular nucleus (PVN) can play a role in the hypertension in DOCA/salt-treated rats, DOCA/salt hypertension was produced in PVN lesions and sham-operated rats. In lesioned rats, the development of hypertension was significantly attenuated (day 7: 132 +/- 3 v 157 +/- 5 mm Hg, P less than 0.01; day 14: 132 +/- 3 v 157 +/- 5 mm Hg, P less than 0.01; day 21: 189 +/- 2 v 224 +2- 6 mm Hg, P less than 0.01). Lesions lowered systolic blood pressure in even control rats. Mean blood pressure (mBP) from awake free moving rats was also significantly lower in lesioned DOCA/salt-treated rats than those of sham-operated DOCA/salt-treated rats (155 +/- 14 mm Hg v 193 +/- 13, P less than 0.01), while mBP was not different between lesioned and sham-operated control rats. The reduction of mBP by hexamethonium injections was significantly larger in sham-operated DOCA/salt-treated rats than those of lesioned DOCA/salt rats. (-53 +/- 3% v -45 +/- 2, P less than 0.05). Plasma norepinephrine and epinephrine were significantly elevated in DOCA/salt-treated rats, however, PVN lesions inhibited significantly those elevations. 1-Deaminopenicillamine, 4-valine, 8-D-arginine Vasopressin (dPVDAVP) injections did not affect BP and heart rate in all rats. Body weight, water intake, urine volume, urine Na, K, and vasopressin excretion, and urine osmorality were not altered by lesions. These findings suggest that PVN contributes to development of hypertension in DOCA/salt-treated rats with sympathetic nervous activations.

Animals↗

Transection of aortic depressor nerve fails to raise blood pressure in spontaneously hypertensive rats.

Although central resetting via the aortic depressor nerve (ADN) has been known to occur in spontaneously hypertensive rats, the function of the ADN is not yet clear in these animals. To determine whether a baroreflex via the ADN can act to regulate blood pressure during hypertension, blood pressures were measured following ADN transection in spontaneously hypertensive and normotensive rats, and the reflex changes of heart rate and the sympathetic nerve activity were recorded during the pressor response to phenylephrine infusions. Blood pressures were significantly raised 1 day after ADN transections in normotensive rats and continued so for 7 d. Blood pressures were not changed in sham operated rats. In spontaneously hypertensive rats, ADN transections did not alter blood pressures in comparison with sham operated controls. On the seventh day after transections, all rats were anaesthetised with urethane and pressor responses to phenylephrine were examined. Bradycardic and sympathoinhibitory responses to the elevation of blood pressure caused by phenylephrine infusions were significantly smaller in ADN transectioned normotensive rats than in sham operated controls. In spontaneously hypertensive rats, the bradycardic and sympatho-inhibitory responses were not reduced by ADN transections. These findings suggest that the impaired baroreflex via the ADN can contribute to the development of hypertension in the spontaneously hypertensive rat.

Animals↗

Central baroreflex regulation by the renal nerves in anesthetized rats.

To determine whether the renal nerves affect central baroreflex regulation, the aortic depressor nerve (ADN) was stimulated electrically, while blood pressure, heart rate, and splanchnic nerve activity were recorded in renal denervated and sham-operated rats anesthetized with urethane. Tail cuff systolic pressure fell 6 days after renal denervation, but mean blood pressure recorded after anesthetizing with urethane did not differ between renal denervated and sham-operated rats. Urinary sodium excretion was greater in renal denervated than in sham-operated rats. ADN stimulation produced frequency-dependent falls in blood pressure accompanied by inhibitions of sympathetic nerve activity and heart rate. Depressor and sympathetic inhibitory responses to ADN stimulation were significantly smaller in renal denervated than in sham-operated rats. These findings suggest that the renal nerves can regulate baroreflexes centrally.

Anesthesia↗

[Red cell hypoplasia following autoimmune hemolytic anemia associated with T-CLL: report of a case and review of the literature].

A 78-year-old woman, who had axillary lymphadenopathy but no hepatosplenomegaly, was admitted because of lymphocytosis. The leukocyte count was 18.1 x 10(9)/l with 72% abnormal cells. Neither anemia nor thrombocytopenia was present. Many abnormal cells and erythroblasts were seen in the bone marrow. These abnormal cells had irregular nuclei but no granules in the cytoplasm. The surface markers of these cells were positive for E-rosette, CD 2, CD 3, and Leu 7 but negative for CD 4, CD 8, CD 11 (OKM 1), CD 16 (Leu 11), and HLA-DR. The DNA analysis revealed the rearrangement of T-cell receptor beta-chain genes. Direct Coombs test was positive and red-cell life-span (51Cr) was T 1/2 = 19.5 days. The patient was diagnosed as having T-CLL with mild autoimmune hemolysis and was followed without treatment. Seven months later, the leukemia cells of peripheral blood increased to 62.6 X 10(9)/l and the frank autoimmune hemolytic anemia developed. After prednisolone, vincristine and cyclophosphamide were administered, leukemia cells of blood decreased. Anemia with reticulocytopenia, however, persisted and direct Coombs test became negative. In the bone marrow at that time, many neutrophils and megakaryocytes besides leukemia cells were preserved, but erythroblasts were hardly seen, namely a pattern of red cell hypoplasia was observed. The patient deteriorated rapidly and died 26 months after initial recognition of lymphocytosis. When complement was added, the patient's serum obtained during red cell hypoplasia but not during autoimmune hemolysis inhibited BFU-E and CFU-GM in in vitro colony assays. This case indicates that not only B-CLL but also T-CLL is accompanied by immune hematocytopenia.

Aged↗

Intermediate-dose cytosine arabinoside in the treatment of recurrent or refractory non-Hodgkin's lymphoma.

Twelve patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with an intermediate-dose of cytosine arabinoside (CA) by continuous i.v. infusion in combination with daunorubicin (DNR). Of the 10 patients evaluated, one obtained a complete response (CR) and three partial responses (PR), and an almost complete disappearance of the tumor for three weeks (minor response) was seen in two patients. Severe myelosuppression was a dose-limiting factor. Intermediate-dose CA is effective for recurrent or refractory NHL but it needs to be combined with the proper partner drugs to obtain better therapeutic results.

Adult↗

Central attenuation of baroreflex by angiotensin II in normotensive and spontaneously hypertensive rats.

To determine whether angiotensin II (A II) can modify baroreflex centrally and contribute to the central resetting of baroreflex in spontaneously hypertensive rats (SHRs), the aortic depressor nerve (ADN) was electrically stimulated following intracerebroventricular (ICV) administration of A II and/or A II analog in urethane-anesthetized normotensive Wistar rats (WKYs) and SHRs. Electric stimulation of the ADN elicited frequency-dependent depressor, bradycardic, and sympatho-inhibitory responses. Angiotensin II, administered ICV, dose-dependently attenuated these responses induced by ADN stimulation in normotensive rats. We found, however, these attenuations could be abolished by ICV pretreatment with A II analog. Vasopressin (ICV) did not change any responses to ADN stimulation. The vasopressor and sympatho-inhibitory responses to ADN stimulation were significantly less in SHRs when compared with those in WKYs: In SHRs, A II analog completely cancelled the A II-attenuated responses to ADN stimulation. These findings suggest that A II can centrally attenuate baroreflex, which might be independent from vasopressin, and in the brain A II can contribute to the central resetting of baroreflex in SHRs.

Angiotensin II↗

Central attenuation of baroreflex precedes the development of hypertension in DOCA-salt-treated rats.

To determine whether baroreflex is changed centrally before the development of hypertension in DOCA-salt treated rats, aortic depressor nerve was stimulated electrically 5 days after DOCA-salt treatment in urethane-anesthetized rats: compared with those of sham-operated control rats, blood pressure was not elevated in either awake or anesthetized rats. Aortic depressor nerve (ADN) stimulation elicited frequency-dependent vasodepressor, bradycardiac, and sympatho-inhibitory responses in both DOCA-salt-treated and control rats. However, the responses to ADN stimulation were significantly smaller in DOCA-salt-treated rats. These findings suggest that baroreflex is attenuated centrally before the development of hypertension and this attenuation may contribute to the pathogenesis of DOCA-salt hypertension.

Animals↗

Increased extracellular concentration of norepinephrine in the hypothalamus by sinoaortic denervation.

To determine whether baroreflex can affect the norepinephrine system in the hypothalamus, the extracellular concentration of norepinephrine were measured by the brain dialysis technique in sinoaortic denervated rats (SAD). Twenty-four hours after sinoaortic denervation, systolic blood pressure and heart rate were significantly elevated, and norepinephrine concentration in perfusate of the posterior hypothalamus was significantly higher in SAD rats than in sham-operated rats. These results suggest that baroreflex could modify the activity of noradrenergic neuron projecting to the posterior hypothalamus.

Animals↗

Salt increases blood pressure with biphasic changes in hypothalamic responsiveness in rats.

Tail-cuff systolic pressures became elevated in male Wistar rats fed chow containing 8% NaCl for 4 weeks. After 4 weeks of salt loading, pressor and sympathetic responses to ventromedial hypothalamic stimulation were larger in salt-loaded rats. When similar experiments were done following sinoaortic denervation, all of the effects previously induced by dietary salt loading persisted. By contrast, after only 1 week of salt loading, pressor and sympathetic responses to hypothalamic stimulation were reduced, instead of being increased. Since circulating plasma volume was increased in week 1, it was considered possible that reduced hypothalamic responsiveness was due to enhanced cardiopulmonary baroreflexes. Supporting this interpretation, bilateral vagotomy reversed the hypothalamic inhibition occurring in week 1. Although neither the site nor mechanism causing sympathetic hyperactivity has been determined, our results indicate that chronic dietary salt loading has biphasic effects on the ventromedial hypothalamus: an initial inhibition in the first week followed by stimulation thereafter. These results could mean that dietary salt loading eventually increases sympathetic activity and thereby induces hypertension by stimulating the ventromedial hypothalamus.

Animals↗

Effects of salt and DOCA on hypothalamic and baroreflex control of blood pressure.

Cardiovascular and sympathetic nerve responses to electrical stimulation of either the aortic depressor nerve (ADN) or the posterior hypothalamus were recorded from rats treated with salt, DOCA, or DOCA/salt and compared with those from untreated controls. By the 7th day, tail-cuff systolic pressures were significantly elevated in rats treated with salt or DOCA/salt. And by the 21st day, all treated rats (i.e. with salt, DOCA, or DOCA/salt) had elevated pressures together with attenuated ADN responses and augmented hypothalamic responses. After 5 days, DOCA/salt treated rats already had attenuated responses to ADN stimulation and augmented responses to hypothalamic stimulation even though their systolic pressures were still unaltered. These findings suggest that combined treatment with salt and DOCA altered central blood pressure regulation even before hypertension developed.

Animals↗

[Biological function of DNA topoisomerases and its implication in cancer chemotherapy].

It has been generally recognized that in a variety of biological systems the structural changes such as circularization, looping and supercoiling of DNA play important roles in carrying out genetic processes such as replication, transcription, recombination etc. Since the discovery of DNA topoisomerase I in 1971 (then named omega protein) in E. coli type I and type II topoisomerases have been found in a wide variety of organisms. In addition the finding that these enzymes are the only ones which can cope with the torsional strain accumulating within the DNA molecules carrying out the genetic processes by swiveling the strands through breakage and rejoining of phosphodiester bonds strongly suggests that they are involved in various aspects of DNA metabolism such as replication, transcription, recombination, differentiation etc. In this article the function of DNA topoisomerases elucidated so far in prokaryotic and eukaryotic cells with special emphasis on their roles in gene expression has been briefly reviewed.

Antineoplastic Agents↗

(2"-R)-4'-o-tetrahydropyranyladriamycin, a new anthracycline derivative; its effectiveness in lymphoid malignancies.

Thirty-eight patients with adult acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) were treated intravenously with (2"-R)-4'-o-Tetrahydropyranyladriamycin (THP) at a dose of 10 mg/m2 for 5 consecutive days. Seven complete and 15 partial responses were observed in 35 evaluable patients (overall response rate, 62.8%). Both antitumor activity and antitumor spectrum were similar to those for doxorubicin. Since the patients who had had chemotherapy previously, including other kinds of anthracycline, responded rather poorly to THP, cross-resistance between THP and other anthracyclines may be present. Leukopenia and thrombocytopenia were dose-limiting factors. Nausea and vomiting episodes were mild, and epilation was also minimal. Although the observation period was short and a cumulative dose was not large enough to evaluate cardiotoxicity, there were no abnormal EKG changes or clinical signs of cardiotoxicity in this study. THP is a potent antitumor agent in the treatment of lymphoid malignancies.

Adult↗

Central effect of captopril on baroreflex.

To clarify effect of converting enzyme inhibitors (CEI) on heart rate regulation, captopril (2 mg/kg) was injected intravenously (i.v.) with or without pretreatment of atropine and also responses to intracisternal (i.c.) injections were examined. Captopril induced bradycardia with lowering blood pressure, and this bradycardia was abolished by pretreatment of atropine. Reduction of heart rate by i.c. injection of captopril was significantly larger than those of i.v. injection. Furthermore, to determine whether CEI can modify baroreflexes centrally, the aortic depressor nerve (ADN) was stimulated electrically in captopril treated rats. Vasodepressor and sympatho-inhibitory responses induced by ADN stimulation were significantly attenuated by captopril, while the bradycardiac response was not changed. These findings suggest that captopril attenuated centrally vasodepressor and sympatho-inhibitory responses of the baroreflex and activated centrally cardiac vagal efferent activity.

Animals↗