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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 577 records · Page 32Linked to original sources
PubMed1987

Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine.

A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg-1 which was escalated up to 24 mg kg-1. Major side effects were nausea, vomiting and anorexia, and mild myelosuppression was noted at 12 mg kg-1 or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg-1 or more and became frequent at 7 mg kg-1 or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg-1 or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg-1 day-1 of PLAC.

Administration, Oral↗
PubMed1986

Immunotherapy with bestatin for acute nonlymphocytic leukemia in adults.

In a cooperative randomized control study of immunotherapy with bestatin in combination with chemotherapy in adults with acute nonlymphocytic leukemia (ANLL), 101 patients (48 in the bestatin group and 53 in the control group) out of 115 patients registered were evaluated as eligible. The bestatin group achieved a statistically significant prolongation of survival compared with the control group in overall ANLL and acute myelogenous leukemia. In the analysis of patient age, the bestatin group achieved a statistically significant prolongation of both the remission duration and survival in patients aged 50 to 65 years, while the differences were not significant in the 15 to 49 age group. The bestatin group tended to achieve a higher rate of reinduction of remission in patients who had recurrence of leukemia. Side effects developed in only 5 (9.6%) of 52 patients treated with bestatin. None of these side effects were particularly serious in nature. It is concluded that bestatin is useful for prolongation of survival of adult patients with ANLL, making for a longer remission duration especially in elderly patients and with few side effects.

Acute Disease↗
PubMed1986

Serum testosterone, testicular connective tissue protein and testicular histology in rats treated with hyperbaric oxygen.

This study was done to ascertain whether hyperbaric oxygenation really affects testicular activity in rats. We evaluated serum testosterone concentration, testicular content of connective tissue protein and histological analysis of testes in each rat treated with 2 or 3 atmospheric pressures associated with oxygen saturation, together or singly for 90 minutes daily for 58 days. There were no significant differences in serum testosterone concentrations between the examined groups. The amounts of collagen, non-collagenous protein or elastin in testis were similar in all groups except one set of determinations. In addition, no prominent histological differences were noted in the testes of the animals. Thus, the pressure environment of this study, which can be regarded as almost the same as that of the hyperbaric oxygenation chamber in clinical use, appears to be nontoxic to rat testes.

Animals↗
PubMed1986

Effects of human atrial natriuretic peptide on renal function and vasopressin release.

To assess the effects of atrial natriuretic peptide (ANP) on the renal function, cardiovascular system, renin-angiotensin-aldosterone system, and vasopressin release, synthetic human ANP (alpha-hANP) was administered at a dose of 0.08 microgram X kg-1 X min-1 iv for 40 min into anesthetized dogs (n = 6). In the control study (n = 6), saline alone was infused. alpha-hANP brought about a significant increase in renal plasma flow, urinary Na and K output, urine flow, and osmolar clearance and a significant decrease in urinary osmolality, free water clearance, and filtration fraction (FF), with no changes in glomerular filtration rate. Plasma Na concentrations and osmolality did not change significantly, but plasma K concentrations fell progressively. Mean arterial blood pressure decreased without any changes in heart rate. Plasma renin activity (PRA), plasma aldosterone concentrations (PAC), and plasma vasopressin concentrations did not rise, but rather PRA and PAC tended to fall during alpha-hANP infusion. In the control study, there were no changes in these parameters except a progressive fall in FF and plasma K concentrations. These results indicate that the alpha-hANP-induced increase in renal blood flow plays an important role in producing natriuresis, but vasopressin may not be involved in the process of diuresis.

Aldosterone↗
PubMed1986

Methionine-enkephalin and vasopressin in SHR: effects of dehydration.

Enkephalins are found in the posterior pituitary, can alter vasopressin secretion, and have greater pressor effects in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto (WKY) rats. Measurement of the plasma methionine-enkephalin concentration (PMet-Enk) has provided equivocal results in humans and has not been reported in rats. We have developed a highly specific and sensitive Met-Enk radioimmunoassay and determined that Met-Enk circulates in rats but that PMet-Enk is no different between SHR and WKY rats (7.6 +/- 0.8 and 9.2 +/- 0.8 pg/ml, respectively). Water deprivation for 48 h increased the plasma vasopressin concentration (PADH) and 24-h urinary vasopressin excretion (UADHV) in SHR and WKY rats, but PMet-Enk was not altered. There were no differences in PADH and UADHV between SHR and WKY rats in either the euhydrated or dehydrated state. These results suggest that it is unlikely that circulating Met-Enk contributes importantly to the maintenance of hypertension in SHR. There was also no evidence for a greater secretion of vasopressin in SHR than in WKY rats, in contrast to previous reports.

Animals↗
PubMed1986

Role of intracerebral angiotensin receptors in the regulation of vasopressin release and the cardiovascular system.

In order to investigate the physiological role of the brain renin-angiotensin system in the regulation of vasopressin (ADH) release, angiotensin II (Ang II, 10 ng/kg/min) or 1-Sar-8-Ile-Ang II (50 ng/kg/min), an Ang II antagonist, was administered intracerebroventricularly to dogs (n = 42) anesthetized with urethane and chloralose after morphine sedation. The effects of the intravenous infusion of either 0.15 M or 2.5 M NaCl (0.1 ml/kg/min, 75 min) were also studied. In control dogs, artificial cerebrospinal fluid (ACSF) was administered at a rate of 10 microliter/min for 105 min. ACSF given intracerebroventricularly plus 0.15 M NaCl given intravenously did not affect ADH release, but 2.5 M NaCl given intravenously raised the plasma ADH level in parallel with the rise in plasma osmolality. Heart rate and blood pressure did not change significantly in ACSF along with 0.15 M NaCl, but heart rate increased significantly in ACSF along with 2.5 M NaCl. Ang II along with 0.15 M NaCl significantly raised plasma ADH and decreased heart rate without any changes in blood pressure. Ang II along with 2.5 M NaCl brought about a significant rise in plasma ADH level, arterial blood pressure, heart rate, and plasma osmolality. But simultaneous application of Ang II and 2.5 M NaCl did not result in a larger rise in plasma ADH than that expected from the effects of the two stimulations given separately. Namely, Ang II did not potentiate ADH release elicited by osmotic stimulation. Ang II antagonist given intracerebroventricularly neither affected ADH release and the cardiovascular system in 0.15 M NaCl nor inhibited ADH release in response to osmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Effects of acute water load, hypertonic saline infusion, and furosemide administration on atrial natriuretic peptide and vasopressin release in humans.

A new specific RIA for alpha-human atrial natriuretic hormone (alpha hANP) was used to determine whether changes in plasma volume elicited by acute water loading, hypertonic saline infusion, and furosemide administration caused changes in ANP release and resultant changes in renal and cardiovascular function in normal subjects. In addition, changes in plasma arginine vasopressin (AVP), PRA, and aldosterone concentrations were studied simultaneously. Mean plasma alpha hANP and AVP levels were 51.3 +/- 16.0 (+/- SE) and 3.1 +/- 0.6 pg/ml, respectively, in the basal state. Plasma alpha hANP rose to 77.8 +/- 27.6 in response to a 4.5% increase in plasma volume induced by water loading, increased further to 134.1 +/- 28.9 in response to a 23% volume increase induced by hypertonic saline, and fell to 70.2 +/- 15.8 pg/ml in response to a decrease in plasma volume after furosemide treatment (P less than 0.01-0.05). On the other hand, plasma AVP fell to 1.8 +/- 0.1 pg/ml after the water load, rose to 4.1 +/- 0.6 after hypertonic saline, and rose further to 5.8 +/- 0.8 pg/ml after furosemide (P less than 0.01-0.05). Water and hypertonic saline loading decreased PRA, but plasma aldosterone concentrations did not change; subsequent furosemide administration increased both (P less than 0.01-0.05). Arterial pressure and heart rate did not change significantly. Increases in urinary Na excretion and osmolar clearances were associated with a rise in plasma alpha hANP after water loading and hypertonic saline infusion (P less than 0.01-0.05), but changes in urine flow were mainly associated with alterations in AVP release. associated with alterations in AVP release.

Adult↗
PubMed1986

[Cyclic alternating combination chemotherapy of small cell carcinoma of the lung].

Twenty-six consecutive previously untreated patients with small cell carcinoma of the lung were treated with cyclic alternating combination chemotherapy. COAM consists of cyclophosphamide 140 mg/m2 i.v. day 1 through 5, vincristine 1.3 mg/m2 i.v. day 1 and 15, ACNU 50 mg/m2 i.v. day 1, methotrexate 7 mg/m2 i.v. day 1 through 5 repeated at 4 week intervals. VAP consists of VP-16 100 mg/m2 p.o. day 1 through 5, adriamycin 30 mg/m2 i.v. day 1, procarbazine 100 mg/m2 p.o. day 1 through 14 repeated at 4 week intervals. The order of alternating course was determined by the time of entry into the study. There were 12 complete and partial responses (86%) among 14 patients treated with COAM-VAP including 6 complete responses (43%), whereas there were 12 responses (100%) including 4 complete responses (33%) among 12 patients treated with VAP-COAM. There was no significant difference between patients receiving COAM-VAP and VAP-COAM with respect to response, duration of response, and survival. Overall median survival was 9.8 months. There was no significant difference between patients with and without distant metastasis with respect to response, duration of response and survival. Two patients were alive at 24 months. The addition of second combination chemotherapy did not increase the response rate. Most patients had mild or moderate leukopenia. Four patients developed interstitial pneumonia.

Aged↗
PubMed1986

[Recent advances in the management of chemotherapy-induced emesis].

Nausea and vomiting induced by cisplatin are very severe and intractable to standard antiemetics. During the past several years, many studies of antiemetic management in the patients receiving cisplatin have been performed. In this paper recent advances in the management of cisplatin-induced emesis were reviewed. To date, high dose (2 mg/kg every 2 hours 3-5 times) metoclopramide is considered to be the most effective drug against emesis induced by high-dose (100-120 mg/m2) cisplatin, and a combination therapy of metoclopramide, dexamethasone, diphenhydramin and lorazepam appears to be the most effective. In antiemetic management the problem of anticipatory emesis and delayed or persistent emesis must be considered as well as acute chemotherapy-induced emesis. On the other hand, we have experienced that antiemetic trials are more ineffective in women than in men, so it is more important to control chemotherapy-induced emesis in women. For obtaining more effective control of cisplatin-induced emesis, a combination of antiemetic agents affecting more than one of several neurotransmitter receptors is necessary. In Japan, antiemetic trials have only strated, so we must make an effort to work towards reducing the distressing emesis induced by cisplatin.

Antiemetics↗
PubMed1986

[New directions for the use of monoclonal antibodies in leukemia diagnosis and therapy].

It has been just a decade since the advent of hybridoma technology, which has made it possible to obtain monoclonal antibodies using the method of Köhler and Milstein. The basic utilization and clinical application of monoclonal antibodies have been developed and generalized in leukemia and lymphoma. In addition, new exciting and specific approaches based on current knowledge of molecular biological techniques have been introduced, together with use of monoclonal antibodies. This paper introduces the following recent topics. Standardization of monoclonal antibodies detecting differentiation antigens. Chromosomal assignment of cell surface antigens. Immunoglobulin and T cell receptor genes as tumor markers. Autologous bone marrow transplantation with the use of antibodytoxin conjugates. Mouse-human chimeric monoclonal antibody.

Animals↗