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Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 235 records · Page 13Linked to original sources

Randomised trial for the prevention of delayed emesis in patients receiving high-dose cisplatin.

Despite recent advances in control of acute emesis following cisplatin-based chemotherapy regimens, delayed emesis remains a significant cause of treatment-related morbidity and factors associated with delayed emesis have not yet been evaluated. A prospective randomised trial was conducted to compare the efficacy and toxicity of granisetron, dexamethasone plus prochlorperazine with granisetron alone in controlling cisplatin-induced delayed emesis and to identify the important factors that influence its occurrence and severity. Seventy cisplatin-naive patients with inoperable solid tumors participated in the trial. Patients who received 80 mg m-2 or 100 mg m-2 of cisplatin were randomly assigned to receive either granisetron 40 micrograms kg-1 intravenously (i.v.) on day 1, dexamethasone 20 mg i.v. on days 2 and 3 and prochlorperazine 5 mg orally thrice daily on days 1-5 or granisetron 40 micrograms kg-1 i.v. on day 1 alone. There was no difference in their acute antiemetic efficacy. A combination regimen was more effective than granisetron alone in preventing delayed symptoms, with superior rates of complete plus major responses of 77% vs 51% (P = 0.0460). Treatment arm was the only determinant factor for the occurrence of delayed emesis (P = 0.0101).

5-Hydroxytryptophan↗

Dose-escalation study of oral etoposide and carboplatin in patients with advanced lung cancer.

A dose-escalation study of daily etoposide and carboplatin was carried out on 23 patients with advanced lung cancer using a starting dose of 40 mg/m2/day etoposide given orally for 21 days and 250 mg/m2 carboplatin given intravenously (IV) on day 1. A total of 41 courses were given. Myelosuppression was the major dose-limiting toxicity. The maximum tolerated dose was reached at the fourth level with 40 mg/m2/day etoposide for 21 days and 400 mg/m2 carboplatin on day 1, once every 4 weeks. Non-hematological toxicities were generally mild or reversible. The recommended doses of this combination chemotherapy are 40 mg/m2/day etoposide for 21 days and 350 mg/m2 carboplatin on day 1. The response rate for non-small cell lung cancer and small cell lung cancer was 16.7% and 60% (95% confidence intervals of 3.6% to 41.4%, and 14.7% to 94.7%), respectively. A phase II study is necessary to define the efficacy and safety of this combination chemotherapy.

Administration, Oral↗

Bacterial changes in neonatal intensive care unit.

Organisms routinely cultured from throat swabs and infectious agents of sepsis and/or meningitis were reviewed. During the last 12 years, Klebsiella pneumoniae and Escherichia coli have been replaced by Staphylococcus aureus and Pseudomonas aeruginosa as the predominant isolates from throat swabs after admission. These change in the etiologic pattern of infectious agents of sepsis and/or meningitis, i.e., K. pneumoniae, E. coli, S. aureus, P. aeruginosa and staphylococcus epidermidis, were in agreement with the organisms isolated from the throat swabs after admission. The S. aureus isolated from throat swabs after admission showed a decrease in the bacterial activity of cloxacillin, cephazolin and cefotaxime since 1978.

Bacteria↗

Plasma concentration of granulocyte-colony-stimulating factor in neonates.

We determined the plasma concentration of granulocyte-colony-stimulating factor (GCSF) and the neutrophil count in 108 infants (gestational age 23-41 weeks; birthweight 478-4935g). The GCSF levels in the very low birthweight infants without infection were comparable to those in the full-term infants. Infants as premature as 23 weeks of gestation showed similar GCSF levels to mature neonates. GCSF levels decreased significantly by day 7 after birth. The levels were not significantly correlated with the neutrophil count. The mean plasma level of GCSF increased significantly when infection developed and was significantly higher in the infants with sepsis than in those with non-septic infections (p < 0.01). The results suggest that GCSF may be the major determinant of neutrophil kinetics both during fetal life and after birth.

Birth Weight↗

Prolactin enables normal development of ACh-stimulated current in cultured larval bullfrog skin.

The response to acetylcholine (ACh) can be used as a marker for larval-type bullfrog skin because apically applied ACh induces an increase in short-circuit current (SCC) in larval-type but not adult-type skin. EDTA-treated larval skin, which contains only basal cells and does not respond to ACh, was used as the starting material for our culture. ACh, carbamylcholine, and choline stimulated SCC in skin that had been cultured with aldosterone (5 x 10(-7) M) supplemented with prolactin (PRL; 2 micrograms/ml). Atropine and d-tubocurarine each inhibited the ACh-induced stimulation of SCC in skin so cultured. Eserine, an inhibitor of acetylcholinesterase, also inhibited the ACh response. Amiloride stimulated SCC itself, but it reduced the ACh response. All of these results are quite similar to those seen in intact larval skin, suggesting that a larval-skin had differentiated from the basal cells used as the starting point for our culture. This is the first physiological report that PRL induces differentiation in vitro into a true larval-type bullfrog skin.

Acetylcholine↗

Nitric oxide and endothelin 1 during postnatal life.

Nitric oxide (NO) is a potent vasodilator produced by endothelial cells. Endothelin 1 (ET-1), another agent made by endothelial cells, is the most potent vasoconstrictor known to date. Endogenous NO and ET-1 may play a part in the normal physiological pulmonary vascular changes during the postnatal period. However, the changes of NO and ET-1 in healthy neonates have not been defined. We determined serum NO metabolites, i.e., nitrites and nitrates, and plasma ET-1 in 19 healthy neonates at birth (cord blood) and at ages 5 and 30 days. The sums of serum nitrite and nitrate (NOx) levels were 27.5 +/- 12.8, 53.8 +/- 14.2, and 38.3 +/- 13.2 mumol/l at birth, age 5 days, and age 30 days, respectively. The plasma ET-1 concentrations were 3.9 +/- 1.6, 1.1 +/- 0.2, and 1.1 +/- 0.2 x 10(6) mumol/l at birth, age 5 days, and age 30 days, respectively. These changes in healthy neonates suggest the presence of active physiological roles for NO and ET-1 in circulatory adaptation to extra-uterine life.

Aging↗

Prolactin antagonizes the corticoid-promoted development of adult-type epidermis in cultured larval bullfrog skin.

EDTA-treated larval bullfrog skin, in which apical and skein cells had been removed and only basal cells remained, was cultured in one of four media. These contained either aldosterone (Aldo) or a mixture of Aldo, hydrocortisone (HC) and corticosterone (C), each either supplemented with prolactin (PRL) or lacking PRL. Skin cultured with Aldo alone or with the corticoid mixture (Aldo + HC + C) developed an adult-type epidermis: (i) both types of skin reacted to human blood group antigen A, a marker for the adult-type epidermis of bullfrog skin; (ii) amiloride decreased the short-circuit current Isc in these skin preparations, but acetylcholine (ACh) had no effect on the Isc. It seemed to make little difference to the results whether the skin was cultured with Aldo or with the corticoid mixture. PRL antagonized the action of Aldo and induced the development of a larval-type epidermis in both skin preparations: (i) the skin preparations did not react to human blood group antigen A; (ii) acetylcholine and amiloride each stimulated Isc in these preparations. Since ACh and amiloride each stimulated the Isc in skin with apical cells, ACh/amiloride-stimulated channels may be located on these cells.

11-Hydroxycorticosteroids↗

Aconitine, a main component of aconite, increases spontaneous acetylcholine release from the frontal cerebral cortex of freely moving rats.

We investigated whether peripherally administered aconitine increases spontaneous acetylcholine (ACh) release from the frontal cerebral cortex in freely moving rats using in vivo microdialysis, as it relates to aconitine-induced bradycardia estimated by a tail-artery cuff technique in unilateral anterior hypothalamus (AH)-lesion mice. Intraperitoneally administered aconitine significantly increased cortical ACh release within 15 min at 10 and 30 micrograms/kg. The increasing effect disappeared 30 min after the administration of aconitine. Aconitine-induced ACh release was not inhibited by intracerebroventricularly preadministered atropine (1 and 3 micrograms/rat). Atropine (1 micrograms/mouse) preadministered into the contralateral intact AH in mice did not affect aconitine (30 micrograms/kg, i.p.)-induced bradycardia. These results indicate that the cortical ACh release caused by peripherally administered aconitine does not occur through activation of the central muscarine receptor, and thus its ACh release may not be concerned with the occurrence of bradycardia.

Acetylcholine↗

Bioavailability and diuretic effect of furosemide following administration of tablets and retarded capsules to human subjects.

Two kinds of dosage forms (tablets and retarded capsules) of furosemide (F) were compared in vitro dissolution profile and in vivo absorption studies. The dissolution of F from retarded capsules was extremely restricted in the first fluid of the JP XII disintegration test (within 0.8%), while the dissolution of F from tablets and retarded capsules in the second fluid of JP XII disintegration test were both complete. Metabolite specific assay of F showed F, conjugation of F with glucuronic acid (FG) and acyl migration isomers of FG (FG-iso) in urine or plasma. The mean cumulative urinary excretion of F following administration of the tablets during 24 h was twice that of retarded capsules. The mean area under the plasma concentration-time curve (AUC) of F following administration of tablets was 1.5 times that of retarded capsules. The mean cumulative urine volume during 24 h, however, was not significantly different between the two dosage forms. Clockwise hysteresis relationships between the diuretic response and the urinary excretion rate of F was observed after administration of retarded capsules. A straight relation between logarithm of the diuresis and logarithm of the urinary excretion of F was observed after maximum excretion rate of F following administration of both dosage forms.

Absorption↗

[The transport of enoxacin in cultured kidney epithelial cells LLC-PK1].

In this study, the transport of enoxacin (ENX) was investigated in a LLC-PK1 kidney epithelial cell line. The uptake of ENX by LLC-PK1 monolayers cultured in plastic dishes was shown to be temperature-dependent and concentration-dependent. Cimetidine and guanidine inhibited the uptake of ENX, whereas TEA and NMN did not. The basolateral to apical flux of ENX across LLC-PK1 monolayers cultured on permeable supports was about two times larger than the apical to basolateral flux. The basolateral to apical flux of ENX was remarkably inhibited by guanidine, whereas it was not inhibited by TEA, NMN and cimetidine. The apical to basolateral flux of ENX was inhibited by cimetidine and guanidine, whereas it was not inhibited by TEA and NMN.

Animals↗

Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents.

Serum levels of total insulin-like growth factor I (IGF-I) correlate with growth hormone (GH) secretory status and are a useful parameter in the diagnostic evaluation of GH deficiency. Serum total IGF-I levels represent the combined quantity of free or unbound IGF-I and IGF-I that is bound to specific IGF binding proteins. Free IGF-I (fIGF-I), which is postulated to be the bioactive fraction, accounts for only a small fraction of the total amount. We have recently developed a new immunoradiometric assay (IRMA) for plasma fIGF-I and have investigated fIGF-I in relation to GH status. The simple, non-extraction assay procedure involves the capture of unbound IGF-I by anti-IGF-I antibody coated to polystyrene beads and detection by a radiolabelled anti-IGF-I antibody directed to a separate epitope. Preliminary studies demonstrated that the fIGF-I IRMA does not measure IGF-I that is complexed to IGF-binding proteins and that the equilibrium between the free and bound fractions is not disturbed during the assay. Free IGF-I levels were compared to total IGF-I levels measured in the same IRMA after acid-ethanol extraction of the samples. Normal levels of fIGF-I from infancy through adulthood were found to have a close correlation with total IGF-I levels, with the lowest levels occurring in infancy and peak levels during puberty. Patients with complete GH deficiency had low levels of both fIGF-I and total IGF-I, with 94% and 100% of the levels below the 5ht percentile for age, respectively. On the other hand, approximately 90% of patients with normal IGF binding protein-3 levels among partial GH deficiency and normal short children had free and total IGF-I levels above the 5th percentile for age. These data indicate that the clinical utility of plasma fIGF-I measurements is similar to measurements of total IGF-I in the evaluation of childhood GH deficiency.

Adolescent↗

Preparation of corn peptide from corn gluten meal and its administration effect on alcohol metabolism in stroke-prone spontaneously hypertensive rats.

Corn peptide (CP) was prepared from corn gluten meal by proteolysis with alkaline protease from alkalophilic Bacillus A-7. Free amino acids were not found in the CP product. Gel filtration on a Shodex OH-packed column revealed that the molecular weight distribution of the CP was less than about 2,000, characteristic of dipeptides to decapeptides, i.e. oligopeptides. The amino acid pattern of CP was similar to that of corn gluten meal, which was rich in alanine and branched-chain amino acids, but poor in basic amino acids. The effect of the CP administration on alcohol metabolism was examined with SHR-SP, which were given ethanol orally through a gastric tube at the rate of 1.0 g/kg. Prior administration of CP at 1.0 g/kg resulted in fast disappearance of ethanol and its oxidative product acetaldehyde from the blood relative to the control without administration. Hence, it is suggested that CP, rather than its constituent amino acids such as alanine and proline, effectively takes part in enhancing the metabolism of ethanol as well as acetaldehyde.

Acetaldehyde↗

[Indications of parathyroidectomy for bone disease associated with secondary hyperparathyroidism].

BACKGROUND: The indications and suitable operative time of parathyroidectomy for secondary hyperparathyroidism were discussed. METHODS: From October 1978 to September 1994 parathyroidectomy was performed for 71 patients who had bone and/or joint pain due to secondary hyperparathyroidism. There were 37 men and 34 women (mean age 48.4 years). The duration of dialysis treatment before parathyroidectomy was 0.8 to 19 years, with a mean of 10.9 years. RESULTS: Postoperative subjective improvement was noted in 69% of the patients. No significant difference was observed between the improved and non-improved groups regarding age and the duration of dialysis treatment. But the improvement rate in female patients was significantly lower than that in male patients. CONCLUSION: Patients with high carboxyl-terminal PTH level and generalized fibrous osteitis were good suitable objects for parathyroidectomy. But, those with high serum aluminum level were unsuitable objects for it. Furthermore, 99mTc-Pyrophosphate bone scintigraphy and bone mineral determination using dual photon absorptiometry (DPA) or dual energy X-ray absorptiometry (DEXA) were proved to be valuable for patient selection for parathyroidectomy.

Adult↗

The involvement of the rho gene product, a small molecular weight GTP-binding protein, in polyploidization of a human megakaryocytic cell line, CMK.

The role of rho proteins, which are ras p21-related small GTP-binding proteins, in megakaryocyte endomitosis was examined using a botulinum C3 exoenzyme (C3), a rho inactivating enzyme. The megakaryocytic leukemia cell line CMK expressed high levels of rhoA and rhoC mRNAs, whereas rhoB mRNA was expressed at a very low level. The addition of C3 to the culture medium caused ADP-ribosylation of the rho proteins in CMK cells in a dose- and time-dependent manner. This procedure also induced a higher frequency of polyploid cells with increased glycoprotein (GP) IIb/IIIa antigens on the cells. This effect of C3 on both ploidy and the antigen expression was abolished by prior incubation of C3 with an anti-C3 monoclonal antibody. Cytochalasin B, an actin polymerization inhibitor, also induced polyploid cells; however, it did not stimulate the expression of GP IIb/IIIa antigens in CMK cells. This finding suggests that C3-induced increase in the expression of GP IIb/IIIa antigens was not through the actin microfilament disassembly. The present study suggests that the rho p21 is a partly regulatory component in polyploidization and GP IIb/IIIa antigen expression of a human megakaryocytic cell line, CMK.

ADP Ribose Transferases↗

[Long-term effect after total parathyroidectomy with autotransplantation for secondary hyperparathyroidism].

Although the short-term outcome of total parathyroidectomy combined with autotransplantation in cases of renal osteodystrophy has been reported by many investigators, few studies have been made on the long-term outcome of this surgical technique. We recently examined the long-term outcome of this surgery by following 19 cases for more than one year (range: 12-70 months, mean: 31.7 months). During the follow-up period, changes in subjective symptoms, biochemical parameters and bone mineral density (BMD) were monitored. At the end of the follow-up period, C-parathyroid hormone (C-PTH) and alkaliphosphatase (ALP) were significantly lower than their preoperative levels. Ca, P and %BMD showed no significant change from their preoperative levels, although %BMD tended to be higher than its preoperative level. Depending on the presence or absence of osteoarticular pain at the end of the follow-up period, the patients were divided into the improved group and the non-improved group. Of the 5 patients allocated to the non-improved group, 4 were female and only 1 was male. C-PTH and ALP were significantly higher in the non-improved group. %BMD was higher in the improved group than in the non-improved group, although this difference was not significant. In the non-improved group, 2 patients were suspected of having extra parathyroids, 1 was suspected of having recurrence, and 2 were suspected of having postoperative osteomalacia. Postoperative reduction in BMD was only seen in females, suggesting its relationship to postmenopausal osteoporosis.

Adult↗