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Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 217 records · Page 12Linked to original sources
PubMed1995

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 9: Effects of the mixing solution volume on anticancer drug release from homogeneous drug-loaded cement.

The effects of mixing solution volume (0.25-0.65 mL/g) on in vitro drug release from a self-setting bioactive calcium phosphate cement containing the anticancer agent 6-mercaptopurine (6-MP) as a model compound were investigated. The drug release profiles from isolated planar surfaces as well as the entire surfaces of cement systems containing 5% 6-MP were measured in simulated body fluid at pH 7.25 and 37.0 degrees C. The drug release rate from both cement system geometries increased with increasing mixing solution volume. Drug release profiles from the planar-release and entire-surface-release cement matrix systems were analyzed by and found to agree with the Higuchi and Cobby equations, and the kinetic parameters were estimated with a nonlinear least-squares computer program. Linear relationships were found between the mixing solution volume and the drug release rate constants or time required for 50% drug release for both cement release geometries. Furthermore, the total pore volume of the cements, as measured by mercury porosimetry, increased with increasing mixing solution volume.

Antineoplastic Agents↗
PubMed1995

Effect of cogrinding with various kinds of surfactants on the dissolution behavior of phenytoin.

The physicochemical properties of phenytoin (PHT) combined with various kinds of surfactants at 40 w/w % such as sodium lauryl sulfate (SLS), sodium deoxycholate (DCNa), and the sucrose ester of stearic acid (SE) by a cogrinding method were investigated by X-ray diffraction analysis, Fourier transformed infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and dissolution kinetics in 2nd fluid (Japanese Pharmacopoeia XII, pH 6.8, 37 degrees C). All X-ray diffraction peak intensities of the coground mixtures were decreased by grinding, and the product with DCNa grinding for 3 h transformed into a noncrystalline solid, but the products with SE and SLS were not. The solubilities of ground products with SLS and SE were almost the same as those of respective physical mixtures. However, the apparent solubility of ground products with DCNa was 28.7 times higher than that of the physical mixture.

Calorimetry, Differential Scanning↗
PubMed1995

Characteristics of substance P-evoked release of amino acids from neonatal rat spinal cord.

The characteristics of release of amino acids evoked by substance P from the neonatal rat spinal cord were examined. A hemisected spinal cord was continuously perfused and the release of amino acids into the perfusate was measured using high-performance liquid chromatography with a precolumn derivatization technique. Substance P (10 microM) evoked a significant increase in the release of aspartate, glutamate, GABA, glycine and taurine. The substance P-evoked release of these five amino acids was not reduced by Ca(2+)-free medium, but was blocked by [D-Pro4,D-Trp] substance P4-11 (10 microM). Perfusion of the spinal cord with low-Na+ medium (22 mM) induced a marked increase in the high-K+ (90mM)-evoked release of GABA, glutamate and glycine. In contrast, the substance P-evoked release of the five amino acids was significantly decreased by the low-Na+ medium. Similarly, perfusion of the spinal cord with low-Cl- medium (8 mM) increased the high-K(+)-evoked release of GABA and glycine, but decreased the substance P-evoked release of GABA, glycine and taurine. The substance P-evoked release of the five amino acids was dose-dependently blocked by d-tubocurarine (3-10 microM), whereas it was not blocked by tetrodotoxin (0.2 microM) or amiloride (30 microM). Compound 48/80 (10 micrograms/ml), a histamine-releasing agent on mast cells, evoked release of the amino acids from the spinal cord with characteristics similar to those of substance P-evoked amino acid release.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1995

Nigrofrontal dopaminergic function as assessed by 18F-dopa PET.

The existence of the nigrofrontal dopaminergic pathway has been demonstrated in neuroanatomical studies. We evaluated the presynaptic nigrofrontal dopaminergic function using 18F-dopa (FD) positron emission tomography (PET). The multiple time PET data in the frontal cortex from 20 to 70 min post-injection for FD were evaluated by Patlak analysis using the cerebellar time-activity curve as an input function. The frontal FD uptake rate constants could not be determined in 5 of 12 normal volunteers because of large deviations in the plots. There were no significant differences between the subjects among whom the frontal FD uptake rate constants could or could not be determined regarding the amount of FD injected, the frontal 18F counts, or whether or not they were pretreated with carbidopa. The uptake constants were determined in 9 or 12 patients with parkinsonian syndrome. While the mean (+/- S.D.) uptake constants in patients with Parkinson's disease (2.89 +/- 0.06 x 10(-3), n = 4) and in patients with progressive supranuclear palsy (2.81 +/- 0.10 x 10(-3), n = 3) were not significantly different from those in the normal volunteers (2.93 +/- 0.14 x 10(-3)), those in two patients with corticobasal degeneration (2.42 and 2.46, respectively) decreased in comparison to the control values. Differences in the nigrofrontal presynaptic dopaminergic function as assessed by FD-PET may explain the different pathogenesis and also help to differentiate between corticobasal degeneration and other parkinsonian syndromes, such as Parkinson's disease and progressive supranuclear palsy.

Adult↗
PubMed1995

Subtypes of tachykinin receptors on tonic and phasic neurones in coeliac ganglion of the guinea-pig.

1. Intracellular recording techniques were used to investigate the characteristics of tachykinin receptors and their subtypes in tonic and phasic neurones, which constituted two major neuronal populations in the coeliac ganglion of the guinea-pig. 2. In 95% of phasic neurones a long-lasting after-hyperpolarization (LAH), 5-8 s in duration and 10-20 mV in amplitude, was observed following action potentials evoked by passing a train of depolarizing current pulses into the neurones. In contrast, LAH was observed in only 4% of tonic neurones. 3. In most tonic neurones, substance P (SP), neurokinin A (NKA) and senktide induced depolarizations, whereas in phasic neurones they usually inhibited LAH but rarely induced depolarization. 4. Tonic and phasic neurones were further classified into three groups based on their responses (depolarization for tonic neurones and LAH inhibition for phasic neurones) to these tachykinin receptor agonists: (1) neurones responsive to SP, NKA and senktide (71-78%); (2) those responsive to senktide but not to SP and NKA (12-23%) and (3) those not responsive to any of the three agonists (7-11%). 5. GR71251 (5 microM), an NK1-selective tachykinin receptor antagonist, depressed the depolarization in tonic neurones and the LAH inhibition in phasic neurones induced by SP and NKA, but not those induced by senktide. 6. Selective NK2 receptor agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, were without effect in both tonic and phasic neurones. Furthermore, an NK2 receptor antagonist, L659,877, did not inhibit the depolarization induced by NKA, SP or senktide in tonic neurones. 7. It is suggested that NK1 and NK3 receptors are present on a large proportion of coeliac ganglion neurones. In tonic neurones both subtypes of tachykinin receptors are coupled to membrane depolarization,whereas in phasic neurones activation of these receptors leads to inhibition of LAH. The present study also suggests that NKA evokes the depolarization in tonic neurones and the LAH inhibition in phasic neurones via NK1, but not NK2 receptors.

Animals↗
PubMed1995

Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A.

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.

Animals↗
PubMed1995

Combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) for the acute or lymphoma type adult T-cell leukemia.

43 patients with the acute or lymphoma type ATL were treated with the new combination chemotherapy (RCM protocol: response-oriented cyclic multidrug protocol) between January 1989 and December 1991. Complete response (CR) and partial response (PR) were achieved in 20.9% and 65.1% of all treated patients respectively. The median duration of survival was 6.0 months. The survival duration of patients with a high serum lactate dehydrogenase (LDH) value (> or = 1,000 unit) and/or a poor performance status (PS) (PS 3 or 4) were also improved but not in patients with a severe leukocytosis (> or = 35,000/microliters). Toxicity was mild (grade 1 or 2) except hematologic toxicity in 4 patients (9.3%) and alopecia in one patient (2.3%). In spite of many patients with a poor PS (PS 3 or 4), our chemotherapeutic results are equal or superior to other previous reports. It seems that response-oriented chemotherapy is suitable for the ATL patients with poor prognostic factors. These results indicate that the RCM protocol is very useful as the first choice chemotherapy for the acute or lymphoma type ATL.

Adult↗
PubMed1995

Synthesis and protein tyrosine phosphatase inhibitory activity of dephostatin analogs.

We have synthesized derivatives of dephostatin, a protein tyrosine phosphatase (PTPase) inhibitor, to study the structure-activity relationships of this inhibitor. Inactive analogs revealed some insight into structural requirements or PTPase inhibitory activity of dephostatin. Both a nitroso group and phenolic hydroxyl groups were found to be essential for the inhibitory activity. Among the dephostatin derivative synthesized, one of the regioisomers of dephostatin showed PTPase inhibitory activity equivalent to that of dephostatin, and also had increased stability.

Enzyme Inhibitors↗
PubMed1995

[Double cancer in patients with adult T cell leukemia].

We have studied the incidence and characteristics of associated neoplasms in 210 ATL patients. Twelve patients had other primary neoplasms and the incidence of double cancer was 5.7%. The additional malignancies in ATL patients consisted of 4 cases of stomach, 3 cases of colon and one of each lung, ovary, uterus, liver and bladder cancer. In metachronous double cancer patients, the neoplasm was found before the time of diagnosis of ATL in 5 out of 6 patients. Immunodeficiency due to HTLV-I infection as well as chemotherapy for the preceding neoplasm are suggested to be related to the leukemogenesis of ATL.

Aged↗
PubMed1995

[Intra-arterial 5-FU/intra-venous MTX therapy for metastatic liver lesions].

We have performed intra-arterial 5-fluorouracil (5-FU)/intra-venous methotrexate (MTX) therapy for 4 patients with multiple metastatic liver tumors at out-patient clinic. Primary lesions were of the stomach (one patient, synchronous) and colon (3 patients, two were synchronous and one was metachronous). 5-FU (250-350 mg/day) was continuously infused for two weeks into the hepatic artery through the reservoir using the Baxter Infuser (multi-day type). MTX (100 mg/m2) was infused into the peripheral vein on days 1, 8 and 15. Leucovorin calcium (15 mg) was orally administered three times after MTX infusion. All patients partially responded, and no remarkable side effect was detected. We propose that this new combination therapy, that is intra-arterial 5-FU and intra-venous MTX for metastatic liver cancer, can be useful and safe even for out-patients.

Administration, Oral↗
PubMed1995

[Evaluation of preoperative blood preparation and blood consumption for implementation of type and screen and maximum surgical blood order schedule].

We analyzed preoperative blood preparation and intraoperative blood transfusion in Kagawa Prefectural Central Hospital and evaluated the effectiveness of maximum surgical blood order schedule (MSBOS) and Type and Screen (T&S). Forty seven kinds of surgery were performed on 1,283 cases from May, 1991 to April, 1992. Transfusion was performed in 179 cases of them. All of 1,884 units of blood that had been prepared, were crossmatched and 1,078 of them were actually transfused. The Crossmatched to Transfused ratio (C/T ratio) was 1.71. If we adopted MSBOS and T&S in 13 elective surgery, 766 units of blood and labour work for preoperative blood preparation could have been saved. MSBOS and T&S are beneficial for efficient usage of blood transfusion in surgery.

Blood Loss, Surgical↗
PubMed1995

[Clinical value of rapid clearance in resting sestamibi cardiac SPECT in patients with acute myocardial infarction].

Resting 99mTc sestamibi (MIBI) SPECT and exercise-reinjection thallium-201 (T1) SPECT were performed in fourteen patients with acute myocardial infarction (AMI). MIBI SPECT were obtained 90 min (MIBI-90) and 300 min (MIBI-300) after injection of 370 MBq of MIBI at rest. MIBI-90 and MIBI-300 were compared with exercise T1 imaging (T1-EX) and T1 reinjection imaging (REINJ). Each SPECT image was divided into 22 segments and myocardial uptake was scored visually. Abnormal perfusion defects were observed in 94 myocardial regions. Worsening of the score was observed in 79 segments (84%) on MIBI-300 compared with MIBI-90. Total MIBI-300 uptake score per person was significantly greater than that at MIBI-90 (14.8 +/- 8.6 vs. 7.7 +/- 7.9, p = 0.001). The concordance rate of defect score between MIBI-90 and REINJ was significantly higher than that between MIBI-300 and REINJ (55% vs. 17%, p = 0.001). In nine patients without recanalization of an infarct-related artery, perfusion defects were seen in 74 segments. The concordance rate of defect scores between MIBI-300 and T1-EX was significantly higher than that between MIBI-90 and T1-EX (45% vs. 16%, p = 0.001). In conclusion, rapid clearance of MIBI was observed frequently in patients with AMI. MIBI-90 and MIBI-300 may reflect myocardial viability and areas at risk for AMI, respectively.

Contrast Media↗
PubMed1994

Computer modeling analysis for enediyne chromophore-apoprotein complex of macromolecular antitumor antibiotic C-1027.

On the basis of the van der Waals and electrostatic potential energy calculations and energy minimization (EM), a model for the apoprotein-chromophore complex of C-1027 has been constructed by docking the apoprotein (Apo-C1027) and the chromophore (C1027-Chr). The model of the apoprotein-chromophore complex also suggests the most probable stereochemistry of the chromophore (8R,9S,13R,17R), specific interactions between Apo-C1027 and C1027-Chr, and the origin of the stabilization of the chromophore by the apoprotein. The acetylenic bond of C1027-Chr appears to be stabilized by (1) hydrophobic interactions with the bottom of the pocket of Apo-C1027, (2) orbital interaction with Cys36-Cys45 disulfide bond, (3) van der Waals contact with Pro76, and (4) pi-pi stacking with the benzene moiety of the chromophore. In this model, molecular dynamics (MD) simulation of the chromophore indicates that the acetylene bond distance (C2-C7) of the apoprotein-bound chromophore is longer than that of the unbound chromophore.

Amino Acid Sequence↗
PubMed1994

Simple and sensitive determination of 2,3-butanediol in biological samples by gas chromatography with electron-capture detection.

2,3-Butanediol was quantitatively oxidized into diacetyl by reaction with MnO4- at 20 degrees C for 30 min under neutral conditions. The reaction of diacetyl with 4,5-dichloro-1,2-diaminobenzene afforded 6,7-dichloro-2,3-dimethyl-quinoxaline (DCDMQ), which was extracted with n-hexane and determined by gas chromatography with electron-capture detection. As an internal standard 1,2-cyclohexanediol was used. The detection limit of DCDMQ (or 2,3-butanediol) was 10 fmol/microliter in the extract, and the determination limit of DCDMQ (or 2,3-butanediol) was at least from 50 fmol/microliter to 20 pmol/microliter in the extract. Recoveries from normal rat urine and rat liver homogenate were 97.8 +/- 3.4% and 98.4 +/- 2.9%, respectively. The method is very simple and sensitive and is applicable to the determination of 2,3-butanediol in normal rat tissues.

Animals↗
PubMed1994

Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T-cell leukemia.

Levels of the soluble form of the leukocyte surface antigen CD4 (sCD4) were measured by enzyme linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of patients with adult T-cell leukemia (ATL) and other malignant and non-malignant diseases. All patients with ATL and meningeal infiltration had markedly elevated levels of sCD4 in the CSF (53.7 +/- 34.9 U/ml). ATL patients without CSF pleocytosis often had elevated levels of sCD4 (15.1 +/- 9.2 U/ml). Non-ATL patients with CSF pleocytosis had elevated levels of sCD4 (23.3 +/- 12.2 U/ml) and those without CSF pleocytosis also showed elevation of sCD4 levels (16.8 +/- 9.3 U/ml). However, the mean levels of sCD4 in CSF from these patients were significantly lower than ATL patients with meningeal infiltration. Soluble CD4 in the CSF from healthy volunteers were below the detectable limit. We conclude that meningeal infiltration of CD4(+) ATL cells is strongly associated with elevated sCD4 levels in CSF, and some part of sCD4 in CSF may be originated from the native cells in the CNS as a response of inflammatory stimulations. Therefore, measurement of sCD4 may be useful in the diagnosis of meningeal infiltration and/or meningeal irritation in patients with ATL.

CD4 Antigens↗
PubMed1994

A novel skeletal drug-delivery system using self-setting calcium phosphate cement. 3. Physicochemical properties and drug-release rate of bovine insulin and bovine albumin.

A novel drug-deliver device based on a self-setting bioactive cement formed from tetracalcium phosphate and dicalcium phosphate has been developed and tested in vitro using bovine insulin and bovine albumin as model polypeptide drugs. Equimolar mixtures of the calcium phosphate powders containing bovine insulin and bovine albumin were transformed into a hydroxyapatite cement after being mixed with a dilute phosphoric acid solution. X-ray diffraction and FT-IR spectra results suggested that the raw materials transformed into lower crystallinity of hydroxyapatite as it hardened. In vitro drug release from cement pellets into a 0.1 mol/L phosphate buffer at pH 7.40 and 37 degrees C continued for more than 3 weeks. Release from the drug-loaded cements followed the Higuchi model equation.

Bone Cements↗