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Biomedical subjects

N Hoshino

Publications and source records attributed to N Hoshino.

At least 19 recordsLinked to original sources
PubMed2001

Efficient ex vivo generation of human dendritic cells from mobilized CD34+ peripheral blood progenitors.

We tried to efficiently generate human dendritic cells (DCs) from CD34+ peripheral blood hematopoietic progenitor cells mobilized by high-dose chemotherapy and subsequent administration of granulocyte colony-stimulating factor, using a liquid suspension culture system. Among various combinations, the combination of c-kit ligand, flt-3 ligand, c-mpl ligand (TPO), and interleukin (IL)-4 most potently generated the number of CD1a+CD14- DCs in cultures containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The delayed addition of IL-4 on day 6 of culture gave rise to an additional increase in the yield of CD1a+CD14-DCs that were characterized by the expression of HLA-ABC, HLA-DR, CD80, CD86, and CD83. The majority of the sorted CD1a-CD14+ cells derived from 6-day culture of CD34+ cells gave rise to CD1a+CD14- DCs and CD1a-CD14+ macrophages on day 12 of culture in the presence and absence of IL-4, respectively. These findings suggest that IL-4 promotes the differentiation of CD1a- CD14+ cells derived from mobilized CD34+ peripheral blood hematopoietic progenitors to CD1a+ CD14- DCs. The majority of these DCs expressed CD68 but not the Langerhans-associated granule antigen, a finding that suggests they emerge through the monocyte differentiation pathway. The addition of TPO and IL-4 to cultures did not affect the potential of DCs to stimulate the primary allogeneic T-cell response. These findings demonstrated that the combination of c-kit ligand plus flt-3 ligand plus TPO with GM-CSF plus TNF-alpha, followed by IL-4, is useful for ex vivo generation of human DCs from mobilized CD34+ peripheral blood progenitors.

Antigens, CD1↗
PubMed2001

An open study of a lotion formulation to improve tolerance of tacrolimus in facial atopic dermatitis.

BACKGROUND: We identified 19 patients with facial atopic eczema who failed to respond to tacrolimus (FK506) ointment, although tacrolimus ointment has shown excellent benefit for the treatment of recalcitrant facial erythema in most patients with atopic dermatitis. OBJECTIVES: We attempted to determine the efficacy of an original lotion formulation of tacrolimus for facial atopic dermatitis resistant to tacrolimus ointment. PATIENTS/METHODS: Recalcitrant facial erythema of these 19 patients was treated with an original tacrolimus lotion preparation for 6 months. Patch testing with white petrolatum was performed in both the 19 patients and in 30 other atopic dermatitis patients who had experienced excellent results with tacrolimus ointment. RESULTS: Of the 19 resistant patients, those whose symptoms were greatly or moderately improved by the lotion were 95%, 89% and 89% after 2 weeks, 3 months and 6 months of treatment, respectively. Further, patch testing to petrolatum showed positive reactions in several (six of 19) patients, compared with none of 30 controls with atopic eczema that had responded to topical tacrolimus ointment. CONCLUSIONS: The tacrolimus lotion had a significant effect on the recalcitrant facial erythema in adult patients with atopic dermatitis who were resistant to tacrolimus ointment. We suggest that one reason for the unresponsiveness to tacrolimus ointment may be because of contact sensitivity to white petrolatum.

Adolescent↗
PubMed2001

Efficient ex vivo generation of dendritic cells from CD14+ blood monocytes in the presence of human serum albumin for use in clinical vaccine trials.

Dendritic cells (DC) with the potential to induce anti-tumour immunity represent one of the promising candidates for cancer vaccines. Efficiency of ex vivo DC generation depends on culture conditions, especially protein components in the plasma or serum used. Using human serum albumin (HSA), we devised a constant and reproducible culture method for DC generation from peripheral blood CD14+ cells. The number of DC obtained with 2% HSA-supplemented cultures containing granulocyte-macrophage colony-stimulating factor and interleukin 4 were consistently higher than in cultures with various concentrations of autologous plasma or serum. The concentrations and time points tested for plasma or serum considerably affected the number of DC recovered. DC prepared with HSA acquired the ability to uptake dextran, and expressed high levels of major histocompatibility (MHC) and co-stimulatory molecules similar to DC cultured with autologous plasma or serum. Although DC cultured with autologous plasma or serum consisted of CD1a+ and CD1a- populations, DC differentiated in the presence of HSA expressed CD1a. DC obtained with HSA primed and induced immunogenic peptide-specific cytotoxic T lymphocytes against a tumour rejection antigen, HER2. These findings suggest that our method for preparation of DC with HSA should prove valuable in DC generation for immunotherapy.

Cancer Vaccines↗
PubMed2000

Adsorption and pharmacokinetics of cyclosporin A in relation to mode of infusion in bone marrow transplant patients.

Two main factors that affect the pharmacokinetics of cyclosporin A (CsA) during 24-h durable intravenous (DIV) administration have been reported, namely physiological changes after bone marrow transplantation, and blood sampling through indwelling lines. In addition, it has been found that infusion sets made of polyvinyl chloride (PVC) markedly adsorb CsA. We conducted in vitro adsorption studies of CsA on infusion sets, and the administration routes that are used in the treatment of patients with bone marrow transplantation. We also examined the effects of administration route on CsA pharmacokinetics in clinical practice. The in vitro adsorption study using 30-mm segments of lumen from commercially available infusion sets showed that the degree of CsA adsorption per area of lumen made of PVC was significantly higher than that in those made of polyethylene (PE) or polybutadiene (PB), which showed no adsorption of CsA. Due to its adsorption, use of infusion sets made of PVC resulted in about a 40-50% loss of CsA dose, which affected the pharmacokinetic parameters during 24-h DIV, while those made of PE and PB did not. The use of non-PVC infusion sets should allow for accurate monitoring of CsA results, and provide cost benefit in the treatment of bone marrow transplantation.

Adsorption↗
PubMed2000

Bactericidal activity of catechin-copper (II) complexes against Staphylococcus aureus compared with Escherichia coli.

The bactericidal activity of catechin-copper (II) complexes against Staphylococcus aureus compared with Escherichia coli was investigated in relation to the generation of hydrogen peroxide and the binding of Cu(II) ion onto the bacteria. The bactericidal activity of catechin-Cu(II) complexes against Staph. aureus (Gram-positive) was much lower than that against E. coli (Gram-negative), suggesting that the binding of copper ions to the surface of bacterial cells plays an important role in the bactericidal activity of catechin-Cu(II) complexes.

Anti-Bacterial Agents↗
PubMed2000

Factors that affect absorption behavior of cyclosporin a in gentamicin-induced acute renal failure in rats.

Factors that affect the absorption of cyclosporin A (CsA) were examined in gentamicin-induced acute renal failure (ARF) rats. In ARF rats, the area under the blood CsA concentration-time curve after oral administration was significantly decreased in comparison with that of control rats; 5.81 +/- 0.55 vs 11.30 +/- 1.59 mg h mL(-1)(mean+/-s.e.m.), respectively, and the relative bioavailabilities in ARF and control rats after oral administration were 15.2% and 43.4%, respectively. The flow rate of bile and the amount of bile acids in ARF rats were markedly decreased to about 61% of control, and 41% of control, respectively. The amount of CsA uptaken into the evened sac of jejunum, transferred to serosal side, and metabolized in tissues was significantly decreased in ARF rats without verapamil, while with 0.3 mM verapamil, the amount in ARF rats recovered to the levels of control rats. The absorption clearance of CsA in ARF rats was significantly decreased, however it was significantly improved by adding bile or bile acid. Adenosine triphosphate released from enterocytes in ARF rats was significantly decreased in the presence of 2.0 microM CsA, 0.3 mM verapamil, or both, in comparison with control rats. From these findings, we concluded that a reduction of CsA bioavailability during ARF is caused by depression in bile excretion and renal function-dependent depression of uptake from intestinal tract via maybe P-gLycoprotein in enterocytes. They are main two factors that reduce the absorbed fraction of CsA in ARF rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Gastrointestinal stromal tumors of the small intestine that expressed c-kit protein.

We report two patients with gastrointestinal stromal tumors (GISTs) of the small intestine that expressed c-kit protein (CD117). One was a 68-year-old woman with epigastralgia and vomiting. A submucosal tumor of the upper jejunum was detected, and partial resection was carried out. The histology revealed a GIST negative for CD34 but positive for CD117. The other was a 42-year-old woman with progressive anemia, melena and lower abdominal pain. Intussusception was detected, and a partial resection was carried out. A submucosal tumor of the lower jejunum was noted. The histology revealed a GIST positive for both CD34 and CD117.

Adult↗
PubMed1999

Damage to the cytoplasmic membrane of Escherichia coli by catechin-copper (II) complexes.

In the presence of a nonlethal concentration of Cu(II), washed Escherichia coli ATCC11775 cells were killed by (-)-epigallocatechin (EGC) and (-)-epicatechin (EC). Cell killing was accompanied by a depletion in both the ATP and potassium pools of the cells, but the DNA double strand was not broken, indicating that the bactericidal activity of catechins in the presence of Cu(II) results from damage to the cytoplasmic membrane. Induction of endogenous catalase in E. coli cells increased their resistance to being killed by the combination of catechins and Cu(II). In all cases studied, EGC and EC with Cu(II) were found to generate hydrogen peroxide, but its concentration was too low to account for the bactericidal activity. The bactericidal activity of EGC in the presence of Cu(II) was completely suppressed by ethylenediaminetetraacetate, bathocuproine, catalase, superoxide disumutase (SOD), heated catalase, and heated SOD, but not by dimethyl sulfoxide. When catalase, either heated or unheated, was added to the cells incubated with EGC in the presence of Cu(II), it completely inhibited further killing of the cells. These findings suggest that recycling redox reactions between Cu(II) and Cu(I), involving catechins and hydrogen peroxide on the cell surface, must be important in the mechanism of the killing.

Catalase↗
PubMed1999

Influence of glycerol-induced acute renal failure on the pharmacokinetics of cyclosporin in rats.

Although it is widely believed that renal dysfunction has no effect on the pharmacokinetics of cyclosporin, many clinical reports suggest that renal dysfunction after renal transplantation is closely related to the pharmacokinetics of cyclosporin. To clarify the relationship between renal dysfunction and the pharmacokinetics of cyclosporin, we examined the influence of acute renal failure (ARF) on its pharmacokinetics in glycerol-induced ARF rats. The values of indicators of renal function (serum creatinine, blood urea nitrogen), but not those of indicators of hepatic function, were significantly increased in ARF rats that received glycerol compared with values for control rats. The area under the blood cyclosporin concentration-time curve after oral administration (AUCpo) were 4.976+/-0.847 mghL(-1) for ARF rats and 9.684+/-1.100 mghL(-1) for control rats; AUCpo in ARF was significantly reduced in a manner dependent on renal function. The oral clearance of cyclosporin in ARF and control rats was 1.172+/-0.207 and 0.544+/-0.062Lh(-1) kg(-1), respectively, whereas total body clearance in ARF and control rats was 0.151+/-0.008 and 0.183+/-0.010Lh(-1)kg(-1), respectively. The relative bioavailability of cyclosporin in ARF and control rats was 0.118 and 0.336, respectively. In an in-vitro study using everted sac and liver-slice methods, the apparent first-order rate constants for cyclosporin uptake (k(uptake)) and metabolism (k(metab)) in gut tissues were reduced, whereas k(uptake) and k(metab) in liver were increased. Gastric emptying, measured by use of paracetamol, was significantly reduced in ARF rats. These results suggest that glycerol-induced ARF results in several changes in the pharmacokinetics of cyclosporin in rats. From these results, we conclude that reduction of the absorbed fraction of cyclosporin strongly contributes to the decrease in AUCpo in the presence of ARF.

Acetaminophen↗
PubMed1999

DNA cleavage activities of (-)-epigallocatechin, (-)-epicatechin, (+)-catechin, and (-)-epigallocatechin gallate with various kinds of metal ions.

The DNA cleavage activities of (+)-catechin (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), and (-)-epigallocatechin gallate (EGCg) were examined with 16 different metal ions. Cu(2+) with all the catechins facilitated DNA cleavage, while Ag+ with EGC and EC showed a strong repressive effect. The other metal ions examined showed little effect.

Animals↗
PubMed1998

Simultaneous determination of glucocorticoids in plasma or urine by high-performance liquid chromatography with precolumn fluorimetric derivatization by 9-anthroyl nitrile.

A new method for simultaneous determination of glucocorticoids (GCs) in plasma or urine by high-performance liquid chromatography (HPLC) with fluorimetric detection has been developed. Following extraction with ethyl acetate using a reversed-phase disposable cartridge, the six GCs [cortisol (F), cortisone (E), prednisolone (PL), prednisone (PN), 6beta-hydroxycortisol (6beta-OHF) and 6beta-hydroxyprednisolone (6beta-OHP)] and an internal standard (6beta-hydroxycotortisone) were derivatized by treatment with 9-anthroyl nitrile (9-AN) in a mixture of basic catalysts (triethylamine and quinuclidine) to give the fluorescent esters through the 21-hydroxyl group. The GC derivatives so obtained were then cleaned by a straight-phase disposable cartridge and chromatographed on a straight-phase column with an isocratic HPLC technique. The fluorescence derivatives of the GCs, including the internal standard, were separated as clear single peaks and no interfering peaks were observed on the chromatograms. The lower limits of detection for F, E, PL and PN in plasma or urine were 0.1 ng/ml and those for 6beta-OHF and 6beta-OHP in plasma or urine were 0.5 ng/ml, at a signal-to-noise ratio of 3. The analytical recovery of known amounts of the GCs added to plasma or urine were almost 100%. This method can be applied to the determination of plasma or urinary F in renal transplant patients who received PL and can be applied for other metabolic investigations in relation to the change in blood pressure via 11beta-hydroxysteroid dehydrogenase or in hepatic metabolizing via CYP3A4.

Adult↗
PubMed1998

Bactericidal activity of catechin-copper (II) complexes on Escherichia coli ATCC11775 in the absence of hydrogen peroxide.

Washed Escherichia coli ATCC11775 cells were killed by (-)-epigallocatechin (EGC) in the presence of a non-lethal concentration of Cu2+ (1 mumol l-1) without additional H2O2, but not by (-)-epicatechin (EC). EGC alone (< 0.1 mmol l-1) did not reduce the viability of the cells. The survival curve obtained in the presence of EGC and Cu2+ was similar to that obtained in the presence of (-)-adrenaline (EN) and Cu2+.

Catechin↗
PubMed1998

Skin sensitization and photosensitization studies of hydrophobically modified hydroxypropyl methylcellulose in guinea pigs.

Skin sensitization and photosensitization tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC), a new cellulose derivative used as a thickener for topical pharmaceuticals, were conducted using guinea pigs. An aqueous dispersion of HM-HPMC (3 w/v %) was applied in the tests. Skin reaction was not observed in any animal in the HM-HPMC-treated group or control group. In the photosensitization test, no skin reaction was found in any animal in the test-preparation group or the control group. It was concluded that HM-HPMC dispersion does not exhibit skin sensitizing or photosensitizing activity under the condition of this test.

Adjuvants, Pharmaceutic↗