Biomedical subjects

Y Kanaya

Publications and source records attributed to Y Kanaya.

At least 19 recordsLinked to original sources

PubMed2006

Maturational alterations of peripheral T cell subsets and cytokine gene expression in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion syndrome is a common disorder characterized by thymic hypoplasia, conotruncal cardiac defect and hypoparathyroidism. Patients have a risk of infections and autoimmunity associated with T lymphocytopenia. To assess the immunological constitution of patients, the numerical changes and cytokine profile of circulating T cells were analysed by flow cytometry and real-time polymerase chain reaction (PCR). CD3+, CD4+, T cell receptor (TCR)alphabeta+ or CD8alphaalpha+ cell counts were lower, and CD56+ cell counts were higher in patients than in controls during the period from birth to adulthood. The ageing decline of CD3+ or CD4+ cell counts was slower in patients than in controls. The proportion of CD8alphaalpha+ cells increased in controls, and the slope index was larger than in patients. On the other hand, both the number and proportion of Valpha24+ cells increased in patients, and the slope indexes tended to be larger than in controls. The positive correlation of the number of T cells with CD8alphaalpha+ cells was observed only in patients, and that with Valpha24+ cells was seen only in controls. No gene expression levels of interferon (IFN)-gamma, interleukin (IL)-10, transforming growth factor (TGF)-beta, cytotoxic T lymphocyte antigen 4 (CTLA4) or forkhead box p3 (Foxp3) in T cells differed between patients and controls. There was no significant association between the lymphocyte subsets or gene expression levels and clinical phenotype including the types of cardiac disease, hypocalcaemia and frequency of infection. These results indicated that T-lymphocytopenia in 22q11.2 deletion patients became less severe with age under the altered composition of minor subsets. The balanced cytokine profile in the limited T cell pool may represent a T cell homeostasis in thymic deficiency syndrome.

Adolescent↗

PubMed2000

Whisker growth of l-menthol in coexistence with various excipients.

The purpose of the present study was to clarify the mechanism for l-menthol whisker growth. l-Menthol was mixed with an excipient, and the interaction was examined by IR measurement, thermal analysis and powder X-ray diffraction. Then we examined the involvement of the capillary condensation using the pore size distribution measurement. By mixing l-menthol with an excipient with whisker growth, the hydroxyl group stretching band of l-menthol was shifted to the higher wavenumber in the IR spectrum, the melting point and heat of fusion of l-menthol became lower in the thermal analysis, and the diffraction intensity of l-menthol became lower in the powder X-ray diffraction. The excipients with whisker growth showed the tendency to have the meso-pore involved in the capillary condensation in the pore size distribution measurement. From the above results, the whisker growth mechanism is considered as follows. When l-menthol was mixed with an excipient with whisker growth, the crystallinity of l-menthol was lowered and the vapor pressure was increased by the interaction mainly consisting of the hydrogen bond. The generated l-menthol vapor entered meso-pore, the saturated vapor pressure was lowered by the capillary condensation, and the nucleation occurred. The vapor was further supplied, generating the growth of whisker.

Crystallization↗

PubMed2000

Application of Carbopol to controlled release preparations I. Carbopol as a novel coating material.

We investigated the application of Carbopol(R) (CP) as a novel coating material prepared with various grades of CP having different degrees of cross-linking and molecular weights. Viscosity and spray mist size of CP aqueous solutions at various concentrations of CP were measured. Core tablets containing theophylline (TP), as a model drug, were coated with CP at various coating ratios. The TP release profile from the CP-coated tablets was studied by the JP13 paddle method. CP tablets were prepared by compressing CP powder, and the swelling behavior of the CP tablets in JP 1st fluid, purified water, and JP 2nd fluid was observed. The spray mist size of all CP aqueous solutions was small at a concentration of 1% and below, and drastically increased over a concentration of 1%. This result suggests that the appropriate concentration of the CP solution for coating is 1% or below. Sustained release of TP from the CP-coated tablets at a coating ratio of only 3% was observed in the JP 1st fluid and purified water, although fast release was observed in the JP 2nd fluid. The fast release in the latter fluid may be due to the fact that CP is an acid material. These results suggest that it is feasible to control the drug release by use of an extremely small amount of CP coating and that CP is useful as a novel coating material.

Acrylic Resins↗

PubMed2000

Controlled release from solid dispersion composed of poly(ethylene oxide)-Carbopol interpolymer complex with various cross-linking degrees of Carbopol.

Solid dispersion composed of the poly(ethylene oxide) (PEO)-Carbopol((R)) (CP) interpolymer complex containing phenacetin (PHE) was prepared by using six grades of CP having various cross-linking degrees. We attempted to control the medicine release from the PEO-CP solid dispersion by varying the CP grade. The powder X-ray diffraction pattern and differential scanning calorimetry curves suggested that PHE existed in the amorphous state, and PEO in the crystalline state disappeared in the solid dispersions. The release profile of PHE varied depending on the CP grade. A small release rate was observed at CP910 and CP971P that are cross-linked at low and middle degrees, respectively. The Fourier transform-infrared (FT-IR) spectra showed that the amount of the PEO-CP complex formed by hydrogen bonding changed depending on the CP grade. With the cross-linked CP, a good correlation was observed between the hydrogen bonding percent and the percent released of the PHE after 60 min (D(60 min)), indicating that PHE release was controlled by the amount of PEO-CP complex formation in the solid dispersion. These results show that it is feasible to control the medicine release from PEO-CP solid dispersion by varying the CP grade.

Acrylic Resins↗

PubMed2000

Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia.

A 7-year-old boy with Diamond-Blackfan anemia (DBA) developed lymphoproliferative disease (LPD) after a cord blood transplant (CBT). 3.1 x 107/kg mononuclear cells from an HLA one-locus mismatched CB were transplanted after conditioning with total body irradiation (8 Gy), cyclophosphamide (200 mg/kg) and antithymocyte globulin (10 mg/kg). Complete engraftment occurred on day 33 post transplant. Despite the resolution of grade II graft-versus-host disease (GVHD), he died of lymphoma on day 130 post transplant. The tumor was of donor origin, indicating clonal proliferation of Epstein-Barr virus (EBV)-infected B cells. This is the first report of EBV-LPD after CBT. Post-transplant LPD can be a serious EBV-associated complication of CB grafts. Bone Marrow Transplantation (2000) 25, 209-212.

Blood Component Transfusion↗

PubMed2000

[A case of breast cancer with multiple organ metastases responding remarkably to combination therapy of CAF (cyclophosphamide, adriamycin and 5-FU), 5'-DFUR and MPA (medroxyprogesterone acetate)].

A 52-year-old woman complaining of breast tumor was diagnosed as having advanced breast cancer (T4bN1M1-Stage IV), with metastasis of multiple organs (lung, liver, mediastinal and unilateral axillary lymph nodes) after which she underwent tumorectomy. Postoperative adjuvant therapy was performed using combined chemoendocrine therapy (CAF + 5'-DFUR + MPA). Following the endocrine therapy, the metastatic lesions of the liver and lung had disappeared. The adverse effects were not remarkable. Complete remission was continued for 2 years and 3 months, and the patient enjoyed a favorable quality of life.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1999

Mouse cyclin-dependent kinase (Cdk) 5 is a functional homologue of a yeast Cdk, pho85 kinase.

Mouse cyclin-dependent kinase (Cdk) 5 and yeast Pho85 kinase share similarities in structure as well as in the regulation of their activity. We found that mouse Cdk5 kinase produced in pho85Delta mutant cells could suppress some of pho85Delta mutant phenotypes including failure to grow on nonfermentable carbon sources, morphological defects, and growth defect caused by Pho4 or Clb2 overproduction. We also demonstrated that Cdk5 coimmunoprecipitated with Pho85-cyclins including Pcl1, Pcl2, Pcl6, Pcl9, and Pho80, and that the immunocomplex could phosphorylate Pho4, a native substrate of Pho85 kinase. Thus mouse Cdk5 is a functional homologue of yeast Pho85 kinase.

Animals↗

PubMed1999

Reduction of tablet coloration at tableting for oily medicine (tocopheryl nicotinate).

The powder (TN-PO) which adsorbed D,L-tocopheryl nicotinate (TN) as an oily medicine was prepared using porous calcium silicate (Florite(R)RE, FLR) as an adsorbing carrier. Tablets (TN-TAB) were produced by compression of TN-PO at different compression pressures. As TN-PO was compressed at the higher TN content in TN-PO and compression pressure, the more TN was exuded from TN-PO, and an increase in the degree of tablet coloration was observed. Therefore, FLR or colloidal silica (AEROSIL(R)200, AER) was newly added to TN-PO at compression to reduce the degree of tablet coloration. Further, the effects of addition of FLR or AER on the crushing strength, friability, porosity and disintegration property of the tablet and the dissolution property of TN from the tablet were studied. After addition of FLR or AER, a similar reduction of tablet coloration was observed. When the addition percentage of FLR to TN-PO exceeded 30%, the crushing strength of the tablet increased significantly. On the other hand, when TN-PO added with AER was compressed, no change was observed in the crushing strength of the tablet. The disintegration time of the tablet with added FLR was shorter than that of the tablet with added AER. At every addition percentage studied, the tablet with added FLR showed a higher releasing ability of TN compared with the tablet with added AER. These results indicate that it is possible to reduce tablet coloration by adding FLR or AER at compression of TN-PO. Further, it is considered that the differences in the crushing strength, disintegration property and dissolution property of TN between the tablets with added FLR or AER resulted in different liquid adsorbing and holding mechanisms of FLR particles and AER particles.

Antihypertensive Agents↗

PubMed1999

Control of medicine release from solid dispersion composed of the poly(ethylene oxide)-carboxyvinylpolymer interpolymer complex by varying molecular weight of poly(ethylene oxide).

Solid dispersion composed of the poly(ethylene oxide) (PEO)-carboxyvinylpolymer (CP) interpolymer complex containing phenacetin (PHE) was prepared by using nine grades of PEO having different molecular weights from 2000 to 4500000. We attempted to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO. The physicochemical properties of the solid dispersion were analyzed by powder X-ray diffractometry and thermal analysis. The interaction between PEO and CP was analyzed by IR spectroscopy. Transmittance of the polymer solution was measured to study the complexation between PEO and CP. The release profile of PHE varied depending on the molecular weight of PEO. The minimum release rate was observed at the PEO molecular weight of 35000. It was found that the amount of the PEO-CP complex formation by hydrogen bonding changed depending on the molecular weight of PEO. These results indicate that it is feasible to control the medicine release from the PEO-CP solid dispersion by varying the molecular weight of PEO.

Analgesics, Non-Narcotic↗

PubMed1999

Suppression of agglomeration in fluidized bed coating. II. Measurement of mist size in a fluidized bed chamber and effect of sodium chloride addition on mist size.

It has been reported that the degree of particle agglomeration in fluidized bed coating is greatly affected by the spray mist size of coating solution. However, the mist size has generally been measured in open air, and few reports have described the measurement of the mist size in a chamber of the fluidized bed, in which actual coating is carried out. Therefore, using hydroxypropylmethyl cellulose (HPMC) aqueous solution as a coating solution, the spray mist size of the coating solution in a chamber of the fluidized bed was measured under various coating conditions, such as the distance from the spray nozzle, fluidization air volume, inlet air temperature and addition of sodium chloride (NaCl) into the coating solution. The mist size in the fluidized bed was compared with that in open air at various distances from the spray nozzle. Further, the relationship between the spray mist size and the degree of suppression of agglomeration at various NaCl concentrations during fluidized bed coating was studied. The mist size distribution showed a logarithmic normal distribution in both cases of the fluidized bed and open air. The number-basis median diameter of spray mist (D50) in the fluidized bed was smaller compared with that in open air. D50 increased with the increasing distance from the spray nozzle in both cases. In the fluidized bed, D50 decreased with the increasing fluidization air volume and inlet air temperature. The effect of NaCl concentration on the mist size was hardly observed, but the degree of suppression of agglomeration during coating increased with the increasing NaCl concentration in the coating solution.

Chemistry, Pharmaceutical↗

PubMed1999

Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice.

The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.

Animals↗

PubMed1999

Suppression of agglomeration in fluidized bed coating. III. Hofmeister series in suppression of particle agglomeration.

PURPOSE: Fourteen kinds of salts consisting of various cations and anions in the Hofmeister series were used as additives for suppression of particle agglomeration in the fluidized bed coating. We attempted to clarify the relationship between the suppression effect of the salts and the Hofmeister series of their consistent ions. METHODS: Fluidized bed coating was carried out with hydroxypropylmethyl cellulose (HPMC) aqueous coating solution containing the salts and Celphere as core particles. To elucidate the salting-out power of the salts for HPMC, the transmittance of the coating solutions at 600 nm was measured at various temperatures and the phase separation temperature (T(PS)) was determined from the values at 50% transmittance. RESULTS: A high suppression effect was observed when the salts including high order ions in the Hofmeister series were added to the coating solution. T(PS) decreased in the presence of the salts except for sodium iodide and sodium thiocyanate and lowered with the higher order ion in the Hofmeister series. The particle agglomeration was suppressed with decrease in T(PS) of the HPMC aqueous coating solution. CONCLUSIONS: It has been suggested that the suppression effect of a salt on the particle agglomeration depended on the salting-out power of the salt. We regard sodium citrate and potassium citrate as very useful pharmaceutical additives for the suppression of particle agglomeration in actual pharmaceutical coating.

Algorithms↗

PubMed1999

Effects of L-arginine on lower limb vasodilator reserve and exercise capacity in patients with chronic heart failure.

OBJECTIVE: To determine whether the reactive hyperaemic response of the lower limb increases with improved exercise capacity after acute supplementation with L-arginine, the precursor of nitric oxide, in patients with chronic heart failure. METHODS: 19 patients with chronic heart failure were enrolled in the study. Rest calf blood flow and femoral occlusion induced calf blood flow changes were measured by venous occlusion plethysmography before and after intravenous infusion of 10% L-arginine solution (5 ml/kg for 30 minutes) or placebo. Postexercise calf blood flow was also measured after the experimental infusion. During both postinfusion periods, several exercise capacity indices were determined by a symptom limited cardiopulmonary exercise test using a bicycle ergometer. RESULTS: Baseline calf blood flow, systemic blood pressure, and heart rate showed no significant changes in either of the two experimental conditions. However, the occlusion induced blood flow response was significantly enhanced by L-arginine infusion (mean (SEM) peak flow, 19.6 (1.5) v 28.9 (3.1) ml/min/dl calf tissue; p < 0.01), but not by placebo (peak flow, 19.1 (1.4) v 20.9 (1.8) ml/min/dl calf tissue; NS). Calf blood flow response after exercise was also higher after L-arginine infusion than after placebo (peak flow, 4.8 (0.4) v 6.0 (0.8) ml/min/dl calf tissue; p < 0.05). L-arginine infusion had no significant effect compared with placebo on exercise capacity indices such as peak oxygen uptake (17.1 (1.0) v 15.8 (1.1) ml/min/kg; NS), anaerobic threshold (10.5 (0.6) v 10.4 (0.7) ml/min/kg; NS), and exercise time (296 (23) v 283 (22) s; NS). CONCLUSIONS: Acute supplementation with the nitric oxide precursor L-arginine increased lower limb reactive hyperaemia but did not lead to any significant improvement in exercise capacity in patients with chronic heart failure.

Adult↗

PubMed1998

Studies on development of dosage forms for pediatric use (V) oral mucosal irritation study of gummi drugs in hamster cheek pouch.

In the present study we investigated irritation of the oral mucosa and the safety of gummi drugs containing acetaminophen (AAP). The oral mucosae of hamsters were macroscopically examined for any evidence of irritation after gummi drugs were inserted into the cheek pouch and left there for 1 h. The cheek pouch tissue was also macroscopically and microscopically examined 24 h after gummi drugs were withdrawn from the cheek pouch. As a result, no evidence of irritation was found macroscopically 1 h after insertion, or macroscopically and microscopically 24 h after the withdrawal of the gummi drugs or placebos as compared with negative controls (saline). Considering these results, the gummi drugs administered in the present study produced no irritation to the oral mucosa.

Acetaminophen↗

PubMed1998

Formation of water-insoluble gel in dry-coated tablets for the controlled release of theophylline.

Sodium alginate (ALNa) of a natural polysaccharide is known to form a water-insoluble gel when combined with a bivalent metal. In this study, we prepared tablets containing ALNa and calcium gluconate (GLCa) as a bivalent metal, and studied the application of the water-insoluble gel involving the controlled release of a test drug by permeation of water. Dry-coated tablets containing theophylline (TP) as a model drug, ALNa and GLCa were prepared by the dry power compression method. The controlled release of TP was evaluated by the dissolution test according to JP XIII. The release rate was extremely high for the tablets which contained only TP and GLCa. A zero order or sigmoidal release profile was observed for the tablets that contained only TP and ALNa. On the other hand, the lowest dissolution rate and a sigmoidal release profile were observed for the tablet containing TP and GLCa in its core and ALNa in its outer phase. These results suggest that dry-coated tablets containing ALNa and GLCa and prepared by the direct powder compression method would be useful for the controlled release of drugs.

Alginates↗

PubMed1997

Improvement in lower limb vasodilatory reserve and exercise capacity in patients with chronic heart failure due to valvular heart disease.

AIMS: Reduced skeletal muscle blood flow during exercise is an important factor contributing to exercise intolerance in patients with chronic heart failure. Reactive hyperaemic blood flow is the maximum flow response necessary to protect tissue against ischaemia and hypoperfusion. We examined the vasodilatory response of the lower limb to ascertain whether response was increased with the improvement in exercise capacity observed after intracardiac surgery in patients with chronic heart failure due to valvular heart disease. METHODS AND RESULTS: Calf blood flow in 23 patients was measured by venous occlusion plethysmography at rest and after a 5 min period of femoral occlusion. Immediately after this evaluation, peak oxygen uptake and anaerobic threshold were assessed by a symptom-limited cardiopulmonary exercise test using a bicycle ergometer. Both baseline calf blood flow and peak calf blood flow during reactive hyperaemia were significantly increased after surgery (baseline calf blood flow; from 2.6 +/- 0.2 to 3.8 +/- 0.4 ml.min-1 per 100 ml calf volume, P < 0.05: peak calf blood flow; from 17.5 +/- 1.3 to 25.4 +/- 2.6 ml.min-1 per 100 ml calf volume, P < 0.01). There was a significant correlation between changes in peak calf blood flow and improvement in exercise capacity (peak oxygen uptake; r = 0.42, P < 0.05; anaerobic threshold; r = 0.68, P < 0.0010). CONCLUSION: These results indicate that exercise tolerance is improved with increased lower limb vasodilatory capacity after recovery from chronic heart failure.

Aged↗

PubMed1996

Effects of grinding and tableting on physicochemical stability of an anticancer drug, TAT-59.

The effects of grinding and tableting on the physicochemical stability of TAT-59, (E)-4-[1-[4-[2-(dimethylamino)ethoxy]phenyl]-2-(4-isopropyl) phenyl]-1-butenyl]phenyl monophosphate, were studied. The crystallinity of TAT-59 ground in a planetary ball mill for 0-120 min or compressed at 0-4500 kg/cm2 was evaluated by X-ray diffraction analysis and differential scanning calorimetry (DSC). The surface of TAT-59 was measured under a scanning electron microscope (SEM). The physicochemical stability of TAT-59, ground or compressed, was determined by measurements of water content, crystallinity and the amount of hydrolysis product, DP-TAT-59, formed. The crystallinity of ground TAT-59 decreased with increasing grinding time, and the amount of DP-TAT-59 increased with decrease in the crystallinity. Similar to ground TAT-59, the crystallinity of TAT-59 tablet gradually decreased with increasing compression pressure, and the amount of DP-TAT-59 tended to increase with decreasing crystallinity. These findings suggested that the decrease of the crystallinity of TAT-59 by mechanical force, such as grinding and tableting, raised the drug's reactivity and affected its stability.

Antineoplastic Agents↗

PubMed1996

Studies on internal structure of tablets. VI. stress dispersion in tablets by excipients.

The aim of this study was to reduce the stress concentration of a medicine by dispersing the stress in tablets at tableting by addition of excipients. The mechanism of the stress dispersion was elucidated. Phenacetin (PHE) was used as a model of crystalline medicine with a high brittleness, and the degree of stress dispersion was evaluated by the change in the exposed surface area of PHE. To learn the mechanical strength of tablets, the crushing strength and friability were measured, their internal structure was analyzed by the porosity and pore size distribution, and stress relaxation experiments were performed. The results were as follows. Calcium silicate (Florite RE, FLR) showed a high stress dispersion effect, adding a high formability and mechanical strength to tablets. It was thought that the high stress dispersion resulted from the rapid stress relaxation caused by the plastic deformation and brittleness fracture of pores in FLR under a low compression pressure. Thus the stress caused locally on PHE particles may disperse.

Drug Compounding↗