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Biomedical subjects

Y Nakada

Publications and source records attributed to Y Nakada.

At least 37 records · Page 2Linked to original sources

Effect of Bacillus subtilis spore administration on activation of macrophages and natural killer cells in mice.

The effect of Bacillus subtilis (strain A102) spores on the activation of murine macrophages and natural killer cells (NK) was examined. The macrophage activity and NK activity were enhanced by oral administration of A102 spores, and slightly enhanced by oral administration of culture supernatant. There was no difference in the results of macrophage activity and NK activity using other live or dead spores. The NK activity and macrophage activity were increased with increments of concentration up to 0.1 g per mouse, and both activities were decreased at concentration of more than 0.15 g per mouse. The NK activity was increased 1 and 2 days after oral administration of A102 spores, and the activity level 2 days after administration was about 3-fold higher than the level prior to treatment. Macrophage activity was also increased from 1 to 3 days after oral administration of A102 spores, and the activity level 3 days after administration was about 3-fold higher than the level prior to treatment. The induction of interferons at 1 day after oral administration in mouse serum was 5-fold higher than that in controls. These findings indicate that oral administration of A102 gave rise to the induction of interferons, and it is likely that macrophages and NK cells were activated by interferons.

Animals↗

Microencapsulation of hepatitis B core antigen for vaccine preparation.

PURPOSE: To prepare poly(lactide-co-glycolide)(PLGA) microspheres containing recombinant hepatitis B core antigen (HBcAg; Mw = 3,600,000) by a w/o/w emulsion/solvent evaporation method and evaluate the possibility of this system as a potent long-acting carrier for hepatitis B core antigen in mice. METHODS: Various additives had been incorporated in the internal aqueous phase during the process of microencapsulating HBcAg, HBcAg antigenicity in the medium extracted from the prepared microspheres were measured by ELISA. Shape confirmation of the HBcAg antigen was performed by a sucrose gradient velocity centrifugal technique. For in vivo study, prepared microspheres were administered subcutaneously to Balb/C mice, and the serum IgG level was determined by ELISA. RESULTS: The inactivation of HBcAg by methylene chloride was dramatically reduced by the addition of gelatin (4-8% (w/v)) to the internal aqueous phase during the preparation. Further improvement of the loading efficiency to almost 61% resulted with cooling (4 degrees C). The prepared microspheres (4.27 microm+/-1.23 microm) containing 0.15% HBcAg displayed burst release (50-60% within 2 days). In subcutaneous inoculation, the adjuvant effect of PLGA microspheres was almost the same as that of the complete Freund's adjuvant. Whereas oral inoculation using the microspheres was not effective. CONCLUSIONS: The pH of the added gelatin seemed to be the key to the stabilization of HBcAg from various stability tests and CD spectrum study. Finally, the possibility of using this system as a potent long-acting hepatitis B vaccine was demonstrated.

Animals↗

Pharmacokinetics of danaparoid sodium, dalteparin sodium and heparin determined by inhibitory effect on the activated coagulation factor X activity after single intravenous administration in rabbits.

The inhibitory effect on the activated coagulation factor X activity (anti-Xa activity) in plasma and urine of danaparoid sodium (DAS, CAS 9005-49-6) was compared with that of dalteparin sodium (DLS, CAS 9041-08-1) and heparin (CAS 9005-49-6) after single intravenous administration at a dose of 640 anti-Xa U/kg to male rabbits. The elimination of half-life of DAS was 9.90 h and was 6.0 times longer than that of DLS and 16.5 times longer than that of heparin. The area under the plasma concentration-time curve (AUC) of DAS was 47.13 +/- 14.55 anti-Xa U.h/ml and was 2.4 times larger than that of DLS and 2.9 times larger than that of heparin. The urinary cumulative excretion of anti-Xa activity of DAS and DLS was 42.6 +/- 6.4% and 16.4 +/- 0.8% of dose, respectively, in 24 h after dosing, respectively. But the anti-Xa activity in urine was not detected at any sampling points after administration of heparin. DAS has a longer elimination half-life and a higher renal excretion of anti-Xa activity than that of DLS and heparin. Therefore, in comparison to DLS and heparin, it seems that the anticoagulant activity of DAS has a long duration.

Animals↗

Relationship between radical production and natural killer cytotoxic factor (NKCF) in canine natural killer (NK) cell-mediated cytotoxicity.

The relationship between radical production and natural killer cytotoxic factor (NKCF) release via canine natural killer (NK)-mediated cytotoxic mechanism was examined. Radical production and NKCF release was induced in NK cells stimulated with either dead target cells, or their cytoplasmic membranes, as well as live target cells. Canine NKCF evoked target cell lysis but did not induce radical production. Radical production was inhibited by the addition of Tiron or n-propyl gallate, whereas NK-mediated cytotoxicity and NKCF release were only inhibited by the addition of n-propyl gallate. These results suggested that radical production and NKCF release may be induced by the contact and binding of NK cells to the target cell cytoplasmic membrane. Therefore, the release of NKCF from NK cells attached to the target cell cytoplasmic membrane may be associated with the production of radicals, especially hydroxyl radicals.

Animals↗

Characterization of natural killer cytotoxic factor (NKCF) from canine NK cells.

We investigated the presence of canine natural killer cytotoxic factor (NKCF). Canine natural killer (NK) cell-mediated cytotoxicity measured by 51chromium (51Cr) release assay was found to be highest in the T-cell population, which was fractionated into the 35-40% Percoll fraction by discontinuous gradient centrifugation. The cytotoxicity of NKCF in the culture supernatant showed a similar tendency to NK activity. Release of NKCF was rapid after contact with target cells, and reached a plateau in 60 min. The cytotoxicity of NKCF could be detected within at least 15 min in coculture with CL-1 target cells, reaching a plateau in 60 min. We also characterized canine NKCF and found it to be a protein, which was stable against both heat and cold treatment. These findings suggest that canine NK cells release NKCF immediately after recognition and binding to the target cell, and that NKCF plays an important role in canine NK-mediated cytotoxicity.

Animals↗

Pharmacokinetics and biodistribution of oligonucleotide adsorbed onto poly(isobutylcyanoacrylate) nanoparticles after intravenous administration in mice.

PURPOSE: The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. METHODS: Pharmacokinetic and tissue distribution were carried out in mice by measuring radioactivity associated to the model oligothymidylate 33P-pdT16 loaded to poly(isobutylcyanoacryate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT16. RESULTS: Organ distribution study has shown that nanoparticles deliver 33P-pdT16 specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT16 against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. CONCLUSIONS: Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver.

Adsorption↗

Definitions of severely mentally and physically disabled children in Japan: do the differences affect the prevalence rates of these children?

The prevalence rate of severely mentally and physically disabled children (SDC) aged 6-15 years in Okinawa prefecture on 1 May 1989 was 0.74/1000 (143/192,038) according to Oshima's classification, compared with 0.89/1000 (170/192,038) according to the Ministry of Education's classification with minor modifications. The number of children in region classes 1, 2, 3 and 4 of Oshima's classification for SDC were 100, 34, 6 and 3, respectively. The difference (n = 27) between the total numbers of SDC according to the two classifications was mainly because of 21 children categorized as "walking with support' who were included as SDC according to the Ministry of Education's classification but not as SDC according to Oshima's classification. Only region class 1 of Oshima's classification corresponded with region class 25 of the Ministry of Education's classification. The results of the present study indicate that the differences between the two definitions of SDC affect the reported prevalence rates of SDC. Therefore, changing patterns in the prevalence of SDC should be assessed by serial surveys using the same method in each district.

Adolescent↗

Effect of renal failure on neurotoxicity of ranitidine in rats.

We investigated the effect of acute renal failure on the neurotoxicity of ranitidine in rats. Experimental acute renal failure was produced by bilateral ureteral ligation. Ranitidine was infused into the ureter ligated (UL) and control rats at the rate of 3.25 mg/min through the jugular vein until the onset of clonic convulsion. In UL rats, the onset time of convulsion was shorter and ranitidine concentrations in plasma and cerebrospinal fluid (CSF) were lower than those of control rats. However, the ranitidine concentration in the brain at the onset of convulsion was not different between the UL and control rats. From these findings, we concluded that acute renal failure is one of the risk factors for ranitidine neurotoxicity, and the increased sensitivity to the drug on the central nervous system may contribute to the increased toxicity of ranitidine in renal failure.

Acute Kidney Injury↗

Instability of bovine insulin in poly(lactide-co-glycolide) (PLGA) microspheres.

Biodegradable poly(lactide-co-glycolide) (PLGA; 50/50) microspheres containing bovine insulin as a model protein was prepared by an oil-in-oil (o/o) emulsion solvent evaporation process. When aluminum tristearate (0.15% (w/v)) was employed as a dispersing agent, the loading efficiency of insulin was almost 100% and the yield was over 80%. The average diameter of the PLGA microspheres always ranged between 100 and 200 microns. Morphology study using a scanning electron micrograph showed smooth, spherical, fairly monodispersed PLGA microspheres containing insulin. In relation to release profile, the very low release rate of insulin was demonstrated (only 1% of insulin released after 7 d release test in pH 7.4 Tris buffer) for the PLGA microspheres. Nevertheless, the degradation of bovine insulin in PLGA microspheres was confirmed by high performance liquid chromatography. This degradation seemed to be caused by an acidic condition caused by poly(lactide-co-glycolide) polymer.

Animals↗

Effect of chitosan implantation on activation of canine macrophages and polymorphonuclear cells after surgical stress.

The effect of cotton type chitosan implantation under the skin on the immunological response mediated by macrophages and whole blood was evaluated by chemiluminescence (CL) in dogs. The number of white blood cells was significantly decreased until 120 hr after operation in the control group (p < 0.05), while chitosan implantation increased the number of white blood cells, particularly neutrophils, from 24 to 96 hr after implantation (p < 0.05). The CL response of whole blood in the control group seemed to be reduced at 48 and 96 hr after operation (p < 0.05), but in the chitosan groups it maintained higher activity until 120 hr after implantation (p < 0.05). The macrophage activity measured by CL assay in the control group was markedly decreased from 24 to 120 hr after operation, and that for the 5 mg/kg chitosan group was also decreased at 24 and 48 hr after implantation (p < 0.05), although high activity was observed from 72 to 120 hr after implantation (p < 0.05). Neither 5 mg/kg nor 10 mg/kg chitosan groups showed any reduction in CL response of macrophages after operation, and the 20 mg/kg chitosan group retained high CL response of macrophages until 120 hr after operation (p < 0.05). These findings suggest that chitosan may be an efficacious and useful immunopotentiator for preventation of immunosuppression after surgery.

Adjuvants, Immunologic↗

Activation of canine monocytes and polymorphonuclear cells by serum thymic factor (FTS) in vivo.

The effect of serum thymic factor (FTS) was evaluated from the immunoresponse augmented in canine monocytes and polymorphonuclear cells (PMN) using the chemiluminescence technique. FTS did not affect the number of leukocytes and differential count of leukocytes. CL activity of the whole blood was significantly elevated by FTS from 72 hr to 120 hr after administration (p < 0.05), and that at 96 hr after administration was about 3-fold higher than that before the administration. The CL response of PMN was significantly elevated by FTS administration from 24 hr to 96 hr after administration (p < 0.05), and that at 48 hr after administration was about 7-fold higher than prior treatment. FTS also significantly elevated the CL response of monocyte from 24 hr to 96 hr after administration (p < 0.01), and the CL count of monocyte in 24 hr and 48 hr was about 100-fold higher than that before FTS administration. These findings suggested that FTS may be efficacious and useful immuno-potentiator for canine monocytes and PMN.

Animals↗

[Percutaneous endoscopic gastrostomy in patients with swallowing difficulties--home care and long-term result].

We studied the possibility of home care of patients who are unable to swallow. Postsurgical complications during the short term (within a week), medium term (within a month) and long term (more than a month) were recorded along with survival time. We also retrospectively studied the number of patients who were discharged after percutaneous endoscopic gastrostomy from November 1989 to March 1995. The percentage of patients with short-term postsurgical complications was 12.1%. Vomiting was the most frequent complication during the medium term and the long term. The weekly rate of complication development (total complications number/total survival time) was highest in the short term and decreased year by year. It was lower in those who were discharged from the hospital than in those who were not discharged. The average survival time was 460.2 days (544.7 days: home care group, 419.0 days: hospital group). The one-year survival rate was 58%, and the two-year survival rate was 36%. One third (32.8%) of patients were cared for at home after gastrostomy (average duration of care at home: 338.5 days) and the average duration of care at home as a percentage of survival time was 58.8%. We conclude that Percutaneous endoscopic gastrostomy can improve the quality of life of patients who are unable to swallow, and may allow them to be cared for at home.

Activities of Daily Living↗

[MR imaging of cerebral palsy].

We evaluated 35 patients with cerebral palsy on the basis of MR imaging findings in the brain. The types of palsy were spastic quadriplegia (n = 11), spastic diplegia (n = 9), spastic hemiplegia (n = 2), double hemiplegia (n = 1), athetosis (n = 10) and mixed (n = 2). Of all patients, 28 (80%) generated abnormal findings. In spastic quadriplegia, although eight cases revealed severe brain damage, two cases showed no abnormal findings in the brain. One of the three had cervical cord compression caused by atlanto-axial subluxation. In spastic diplegia, the findings were divided according to whether the patient was born at term or preterm. If the patient had been born prematurely, the findings showed periventricular leukomalacia and abnormally high intensity in the posterior limbs of the internal capsule on T2-weighted images. MR imaging in spastic hemiplegia revealed cerebral infarction. In the athetoid type, half of all cases showed either no abnormal findings or slight widening of the lateral ventricle. Three cases showed abnormal signals of the basal ganglia. The reason why athetoid-type palsy did not show severe abnormality is unknown. We believe that MR imaging is a useful diagnostic modality to detect damage in the brain in cerebral palsy and plays an important role in the differentiation of cerebral palsy from the spastic palsy disease.

Adolescent↗

[The prevalence rate and etiology of severe motor and intellectual disabilities syndrome in Okinawa].

We studied sixty-three children of severe motor and intellectual disabilities syndrome aged between 3 and 5 years, who live in Okinawa. Severe motor and intellectual disabilities syndrome were defined as those who belong to classes 1 approximately 4 of Ohshima's classification (incapable of walking with IQs not more than 35). The prevalence rate was about 1.12/1,000 live births. Forty-four% of the total children belonged to class 1 of Ohshima's classification (bedridden and IQs less than 20). The factors were: congenital 31.7%, perinatal 38.1%, postnatal 14.3%, and unknown 15.9%. The perinatal factor was still relatively high as compared with the others.

Child, Preschool↗

Correlation between canine NK cell mediated cytotoxicity and radical production.

We investigated the relationship between natural killer (NK) mediated cytotoxicity and radical production in canine peripheral blood lymphocytes (PBLs). Canine NK cell mediated cytotoxicity, measured by 51Cr release assay, was found to be the highest in the T-cell (Thymus cell) subpopulation which partitioned into the 35-40% percoll fraction by centrifugation through a discontinuous gradient. Radical production showed a similar tendency in luminol-dependent chemiluminescence (CL) assay. Furthermore, enrichment of large granular lymphocytes (LGL) was observed in the cell fraction from the same percoll density. These results suggest that NK cell mediated cytotoxicity is related to radical production in canines.

Animals↗

Effect of acute renal failure on neurotoxicity of cimetidine in rats.

PURPOSE: We investigated the effect of acute renal failure on the neurotoxicity of cimetidine in rats. METHODS: Experimental acute renal failure was produced by bilateral ureteral ligation. Cimetidine was intravenously infused to ureter ligated (UL) and control rats, and cimetidine concentration in plasma, brain and cerebrospinal fluid (CSF) were compared. RESULTS: The cimetidine concentration in plasma was rapidly increased in UL rats as compared to control rats. The cimetidine concentration in CSF at the onset of convulsion did not depend on the infusion rate, suggesting that cimetidine in CSF equilibrates rapidly with the site of action for clonic convulsion. The cimetidine concentration in CSF of UL rats at the onset of clonic convulsion was lower than those of control rats. CONCLUSIONS: Increased sensitivity to the drug on the central nervous system may contribute to increased toxicity of cimetidine with renal failure.

Acute Kidney Injury↗

Androgen status in adolescent women with acne vulgaris.

Androgens are essential for the development of acne. The object of this study was to elucidate the androgen status of women with adolescent (Tanner's stage IV-V) acne alone and compare them to age-matched normal controls. We measured serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate (DHEA-S) in 15 women with adolescent acne and 13 age-matched healthy controls. No significant differences were found between the mean levels of T, FT or DHT levels in patients and controls. However, the mean levels of DHEA-S in the patient population (1886 +/- 829 ng/ml) were significantly (p < 0.05) higher than normal controls (1287 +/- 620 ng/ml). There was also no correlation between androgen levels and acne severity. Thus it is unlikely that serum androgens play a principal role in women with adolescent acne.

Acne Vulgaris↗

Multiple arteriovenous malformations of spinal cord and brain in a child.

A case of concurrent intracranial and spinal cord arteriovenous malformations (AVMs) is described. A 3-year-old girl presented with paraparesis, bladder-bowel disturbances and bilateral dysesthesia of the lower extremities due to a spinal hematoma, resulting from a spinal AVM. Magnetic resonance imaging revealed a hematoma and abnormal vessels in the spinal cord. The AVM was embolized with polyvinyl alcohol particles and silk sutures and was surgically removed. Later, this girl presented with disturbance of consciousness due to an intraventricular hemorrhage, resulting from a cerebral AVM. The cerebral AVM was surgically resected. The coexistence of bleeding cerebral and spinal AVMs is very rare.

Angiography, Digital Subtraction↗