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Biomedical subjects

K Fujimaki

Publications and source records attributed to K Fujimaki.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stimulation of adenylyl cyclase and induction of brain-derived neurotrophic factor and TrkB mRNA by NKH477, a novel and potent forskolin derivative.

The present study was undertaken to examine whether NKH477, a novel and potent water-soluble forskolin derivative, stimulates adenylyl cyclase and regulates brain-derived neurotrophic factor (BDNF) and TrkB expression in the rat brain. Administration of NKH477 at a dose of 1.0 mg/kg, but not 0.1 mg/kg, increased levels of cyclic AMP (cAMP) in a time-dependent manner in frontal cortex and hippocampus. Repeated administration of NKH477 (1.0 mg/kg) for 7 or 14 days also increased levels of cAMP in these two brain regions, indicating that the response does not desensitize with chronic treatment. In addition, administration of NKH477 at the 1 mg/kg dose increased the expression of BDNF and TrkB mRNA in frontal cortex and hippocampus. This effect was observed after single, as well as repeated (7 or 14 days), administration of NKH477. These results demonstrate that NKH477 administration rapidly increases cAMP levels in brain and provides evidence that stimulation of this second messenger system increases the expression of BDNF and TrkB mRNA.

Adenylyl Cyclases↗
PubMed1999

Primary esophageal T cell lymphoma.

A 60 year-old woman with primary esophageal T-cell lymphoma in clinical stage I(E)B is presented. Immunohistologic examination showed tumor cells to be positive for anti-LCA, anti-UCHL-1, anti-MT-1, anti-CD3 antibodies, and negative for anti-L26 antibody. Disappearance of dysphagia and improvement in esophageal findings were noted after 65 Gy of irradiation, and biopsy specimens from the esophagus revealed no malignancy. Primary esophageal lymphoma is extremely rare, and this T-cell lymphoma is only the fourth case reported in the literature.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

[Pulmonary function after allogeneic hematopoietic stem cell transplantation].

This study was undertaken to identify the factors influencing pulmonary function in patients who underwent hematopoietic stem cell transplantation (HCT). Pulmonary function tests were evaluated before and after HCT in 51 adult patients who underwent HCT between 1993 and 1998. The patients with hematologic malignancies were given total body irradiation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Six patients suffered from acute GVHD above grade II and 27 patients suffered from chronic GVHD. The post-transplant % diffusing capacity (%DLco) 100 days after HCT was significantly lower than pretransplant values (82 +/- 21% versus 71 +/- 15%, p < 0.01). The %DLco at 100 days was significantly lower in patients with chronic GVHD than in patients without chronic GVHD (66 +/- 16% versus 77 +/- 9%, p < 0.05). These findings suggested chronic GVHD is related to the decreased %DLco values observed 100 days after HCT.

Adolescent↗
PubMed1998

The gene for human protein Z is localized to chromosome 13 at band q34 and is coded by eight regular exons and one alternative exon.

Human protein Z is a vitamin K-dependent plasma glycoprotein, deficiency of which leads to a mild bleeding tendency. Protein Z appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. In this study, to characterize the gene for protein Z, its organization and structure were determined by a combination of PCR amplification of leukocyte DNA and isolation of phage clones from a human genomic library. The gene spanned about 14 kb and consisted of 9 exons including one alternative exon. It was of note that the gene organization was essentially identical to that of other vitamin K-dependent proteins, such as factors VII, IX, and X and protein C. The nucleotides in introns at exon/intron boundaries for eight regular exons were the consensus GT-AG sequences. In contrast, the sequence at an optional exon/intron junction was found to be GC rather than GT. The extra exon inserts a unique peptide consisting of 22 amino acids in the prepro-leader sequence. A similar situation was previously observed in factor VII, but not in other vitamin K-dependent plasma proteins. We also assigned the gene for protein Z to chromosome 13 by PCR amplification of genomic DNAs from human/hamster cell hybrids. Fluorescence in situ hybridization, employing a genomic clone coding for human protein Z, further localized the gene to band q34, where the genes of three other vitamin K-dependent proteins are clustered. These genes may have evolved via duplication of an ancestral gene at this locus.

Alternative Splicing↗
PubMed1998

[Chronic myelogenous leukemia with long-term hypoplasia induced by alpha-interferon and hydroxyurea].

A 48-year-old woman was admitted with chronic myelogenous leukemia in November, 1996 and was treated with hydroxyurea (HU), because of marked leukocytosis; WBC 404,000/microliter. On January 29, 1997, administration of HU was stopped, and treatment of alpha-interferon (IFN alpha) was started with 6x 10(6)U, every day. However, the WBC count rose from 19,600/microliter to 56,800/microliter, and the combination of IFN and 2,000 mg of HU was started on February 4. The dose of HU was reduced to 500 mg on February 27, and the IFN administration was reduced to 3 times a week from April 4, because the WBC count was less than 10,000/microliter. Pancytopenia was revealed in May. The bone marrow biopsy specimen demonstrated marked hypoplastic changes, and chromosome analysis of bone marrow cells showed Philadelphia chromosome in all 20 metaphases. Treatment was interrupted for 7 months, but hematologic parameters did not recover. There were 9 cases reported in detail with bone marrow hypoplasia induced by IFN. One patient received IFN alone and 8 patients received anti-cancer drugs before treatment of IFN. We concluded that great care must be taken for IFN treatment of CML.

Antineoplastic Agents↗
PubMed1997

T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170 microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581, 9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119 microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581, 71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379 microgram/ml. Against systemic candidiasis in mice, the 50% effective doses (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412, 0.392, and > 320 mg/kg of body weight, respectively. Against systemic aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T-8581 was more effective than fluconazole and itraconazole in prolonging the life span. The high concentrations of T-8581 were observed in the sera of mice, rats, rabbits and dogs. Species differences in half-lives and areas under the concentration-time curves were observed, with the values for mice, rats, rabbits, and dogs increasing in that order. These results suggest that T-8581 would be a potentially effective antifungal drug for oral and parenteral use.

Animals↗
PubMed1996

DNA topoisomerase II inhibitors enhance random integration of transfected vectors into human chromosomes.

To study the involvement of DNA topoisomerase (topo) II on nonhomologous (illegitimate) recombination, we examined the effect of topo II inhibitors on random integration of exogenous vectors into human chromosomes. We transfected human cell lines PA1, HeLa and EJ-1 with linearized plasmid pSV2neo by electroporation, treated with topo II inhibitors and determined the frequency of Geneticin-resistant (G418r) colonies. We found that three topo II inhibitors, etoposide (VP-16), ICRF-193 and amsacrine (m-AMSA), greatly enhanced the frequency of G418r colonies. These effects were maximally expressed by as little as 12 hrs treatment with the drugs. Similar enhancements were found with different vectors (closed-circular and linear), different cell types, or by different transfection methods (calcium precipitation and lipofection). In contrast, the inhibitor treatments did not affect the transient expression of chloramphenicol acetyltransferase and beta-galactosidase activity following transfection with pSV2CAT and pCH110, respectively. Southern blot analysis revealed that the integration pattern of transfected pSV2neo into PA1 chromosomes was random and not characteristic for each inhibitor. These results suggest that topo II inhibitors directly act at a nonhomologous recombination reaction, promoting the integration process of transfected vectors into human chromosomes. We discuss the enhancement mechanism with a special emphasis on DNA strand breaks induced by the inhibitors.

Amsacrine↗
PubMed1995

[Intermittent-dose ara-C/daunomycin therapy combined with cyclosporin-A and G-CSF led to a fourth remission in a patient with acute promyelocytic leukemia].

A 50-year-old female was admitted with acute promyelocytic leukemia (APL) in August, 1988. She was treated with behenoyl-ara-C, daunomycin, 6-mercaptopurine and prednisolone (BH-AC.DMP), which led to a complete remission. Thereafter, she was treated with 2 courses of BH-AC.DM and discharged from hospital. Intensification therapy was performed twice a year, with 1 course of BH-AC.DM and 5 courses of intermittent-dose ara-C/mitoxantrone which ended in March, 1992. She had a relapse in September, 1993 and was treated with all-trans retinoic acid, which led to a second remission. A second relapse occurred in May, 1994, and intermittent-dose ara-C/mitoxantrone, combined with granulocyte colony-stimulating factor (G-CSF), led to a third remission. However, she had a third relapse in September, 1994. She was treated with a trial of G-CSF (300 micrograms/body, day 1-7), to stimulate dormant leukemic cells to enter the cell cycle, and cyclosporin-A (78 mg/kg, day 2-5), in order to overcome daunomycin resistance in refractory leukemia, combined with daunomycin (45 mg/m2, day 3-5) and ara-C (1.4 g/m2, day 3-7), after obtaining informed consent. The fourth remission needed 46 days after combination chemotherapy because of severe myelosuppression. It was suggested that intermittent-dose ara-C/daunomycin therapy combined with G-CSF and cyclosporin-A may be useful for relapsed and refractory leukemia.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Determination of T-3761 in body fluids by high-performance liquid chromatography].

A high-performance liquid chromatographic procedure was developed for determination of T-3761 in human serum and urine. The method was based on column switching for serum, and direct injection for urine. The peaks were monitored by ultraviolet detection. The calibration curve was linear and quantitative in the concentration range of 0.01-30 micrograms/ml for serum and 0.5-900 micrograms/ml for urine. The intra-assay coefficient of variation was less than 7%. The intra-day and inter-day coefficient of variation were less than 4%.

Anti-Infective Agents↗
PubMed1994

[Diagnostic value of glass microfibre-based basophil histamine release test in food allergic children. Comparison with specific IgE antibody and skin scratch test].

We evaluated the diagnostic value of the glass microfibre-based histamine release test (HRT), which allows measurements to be performed using small amounts of whole blood, in 50 children with food allergy case histories. The patients were evaluated by radioallergosorbent tests (RAST), skin scratch tests (ST) and food challenge tests. Of the 50 patients, 39 had a confirmed clinical diagnosis of food allergy from food challenge tests and case histories, and were affected by a total of 60 positive allergens (egg 37, milk 11, soy beans 4, wheat 5, rice 3). The concordance, sensitivity, and specificity of HRT with the clinical diagnosis were 85.3%, 66.7% and 92.1%, those of RAST were 59.4%, 90.0% and 48.2%, and those of ST were 84.7%, 71.8% and 88.7%, respectively. The positive predictive values of HRT, RAST and ST were 75.5%, 38.8% and 66.7%. The false positive ratio of HRT (24.5%) was the lowest among all the tests. There was a significant correlation between HRT and RAST (r = 0.513, p < 0.001). However, the concordance of HRT with respect to RAST was 56.0%. The concordance and specificity of HRT in relation to the clinical diagnosis were higher than RAST and the same as ST. The sensitivity of RAST was higher than that of HRT. From these results, we concluded that RAST is good for the screening of allergens and that HRT is a useful diagnostic method for the confirmation of a clinical allergy.

Basophils↗
PubMed1993

Experimental pneumonia produced by clinical isolates of Pseudomonas cepacia in mice.

An experimental Pseudomonas cepacia lung infection was induced in ddY mice pretreated with cyclophosphamide. A single dose of 250 mg of cyclophosphamide per kg resulted in leukopenia which lasted for four days. At the lowest PMN levels, the mice were exposed to various doses of bacteria by either intratracheal inoculation or aerosol inhalation. Experimental pneumonia was established by intratracheal inoculation of 1 x 10(7) - 2 x 10(8) colony-forming units of P. cepacia. The duration of survival time of the mice and the number of viable bacteria in their lungs were determined. A dramatic rise in the viable counts of P. cepacia was found within 24 hours after intratracheal inoculation of 1 x 10(8) colony-forming units of P. cepacia. It was impossible to establish P. cepacia pneumonia by aerosol inhalation, since the bacteria were immediately cleared from the lung. Mice which had not been treated with cyclophosphamide remained healthy and did not show any lung lesions. Thus, neutrophils appear to play an important role in the early defense mechanisms of the lung against P. cepacia. This animal model could be of use in evaluating additional therapies for the infection, and the pathologic determinants of infection caused by P. cepacia.

Animals↗
PubMed1989

Quinolone resistance in clinical isolates of Serratia marcescens.

The uptakes of norfloxacin by quinolone-resistant and -susceptible strains of Serratia marcescens were almost the same and 50% inhibitory concentrations for DNA gyrase and the MICs of quinolones were correlated, suggesting that DNA gyrase alterations are the basis of quinolone resistance.

Anti-Infective Agents↗