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Biomedical subjects

M Hoshi

Publications and source records attributed to M Hoshi.

At least 55 records · Page 3Linked to original sources
PubMed2001

Treatment of human renal cell carcinoma by a conditionally replicating herpes vector G207.

PURPOSE: Surgical removal remains the only potentially curative therapy for renal cell carcinoma. In this study we evaluated the inhibitory effect of the replication competent engineered herpes simplex virus type 1, G207, for renal cell carcinoma in vitro and in vivo. MATERIALS AND METHODS: The nature of G207 enables it to replicate within cancer cells, thus, causing cytolysis, but replication is restricted within normal cells. The susceptibility of the human renal cancer cell lines ACHN and A498 to G207 at a multiplicity of infection of 0.1 was examined. In addition, the growth characteristics of G207 was assessed. In vivo athymic mice bearing subcutaneous tumors were inoculated with 1 x 10(7) plaque forming units of G207 intra-neoplastically. For pathological analysis subcutaneous tumors were stained with X-gal. RESULTS: Two cell lines were efficiently destroyed by G207 within 1 week. The viral yields of G207 increased in a time dependent manner. In vivo the intra-neoplastic inoculation of G207 caused significantly decreased tumor growth in athymic mice harboring subcutaneous human renal cancer cells. On day 14 the mean growth ratio of ACHN and A498 lesions was significantly inhibited in G207 treated compared to control tumors (p <0.005 and <0.0001, respectively). CONCLUSIONS: These results suggest that G207 should be considered another potential therapeutic agent for renal cell carcinoma.

Animals↗
PubMed2000

Intravesical and intravenous therapy of human bladder cancer by the herpes vector G207.

G207, a conditionally replicating herpes vector, efficiently kills human bladder cancer cells in vitro. To evaluate the therapeutic potential of G207, we have established three in vivo models similar to the clinical situation. In vivo, G207 was intraneoplastically, intravesically, or intravenously inoculated in nude mice. Intraneoplastic inoculation into subcutaneous tumor caused significant tumor growth inhibition. Intravesical inoculation of G207 also caused decreased tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple intravenous inoculation markedly inhibited subcutaneous tumor growth. These results suggest that intravesical therapy with G207 is effective for localized bladder tumor, especially for carcinoma in situ (CIS), and intravenous therapy with G207 is promising for invasive or metastasized bladder tumor.

Animals↗
PubMed2000

Characterization and identification of (CT)n microsatellites in soybean using sheared genomic libraries.

Three small insert (300 to approximately 600 bp) sheared genomic libraries were constructed by pipetting and DNase I treatment of soybean DNA. About 15,000 clones from each library were screened for CT- simple sequence repeats (CT-SSRs). The CT-SSRs were abundant in the soybean genome at an estimated frequency of approximately one SSR per 110 kb of genomic DNA. Following the sequencing of 129 positive clones, the repeat types and frequency of CT repeats among the positive clones were characterized. Forty-nine primer pairs were designed and preliminarily evaluated for their ability to amplify genomic DNA from a set of six varieties, including parents of a mapping family. Amplified products were analyzed by 10% PAGE. Eighty-eight percent of the designed primers were able to amplify all these genomic DNAs using a single PCR profile of 53 degrees C annealing temperature, of which 22 (45%) were polymorphic in the six varieties, and 14 of them were polymorphic in the parents of the mapping family. The polymorphic primer sets were further assessed for allelic information using DNA from 16 soybean cultivars. The average number of alleles was 4, ranging from 2 to 7 with the highest polymorphism information content value 0.84. Fourteen of these SSRs were mapped, using an existing soybean RFLP map. The findings presented here will advance our understanding of the soybean genome, and assist in the mapping genome and discrimination of closely related varieties of this species.

Chromosome Mapping↗
PubMed2000

A 130-kDa membrane protein of sperm flagella is the receptor for asterosaps, sperm-activating peptides of starfish Asterias amurensis.

Spermatozoa of the starfish, Asterias amurensis, have a specific receptor for asterosap, a sperm-activating peptide isolated from the jelly coat of homologous eggs. We characterized the receptor by using several asterosap derivatives. Analysis of equilibrium binding of radioactive di-iodinated Bolton-Hunter reagent-labeled asterosap ((125)I(2)-BHP15) to the spermatozoa indicated that the cell has 1.1 x 10(5) binding sites of high affinity (K(d) = 57 pM), and also the receptor showed positive cooperativity for asterosap binding. When spermatozoa were treated with fluorophore-labeled asterosap, the sperm flagella were labeled, indicating that the receptors are mostly localized in the sperm tail. When spermatozoa were reacted with radioactive asterosap prelabeled with photoaffinity cross-linkers, a single 130-kDa membrane protein of sperm flagella was specifically radiolabeled. This result was reproducible regardless of the length of spacer arm of cross-linkers so far studied. Therefore, the 130-kDa protein is likely to be the receptor for asterosaps. Modification of asterosap at the N-terminal region with bulky molecules such as carboxyfluorescein did not affect the activity of asterosap, suggesting that the N-terminus of asterosap is not involved in the ligand-receptor interaction. On the other hand, S-alkylated asterosaps did not compete with (125)I(2)-BHP15 for binding to the receptor, indicating that disulfide linkage of asterosap is essential for the ligand-receptor interaction. The properties of the receptor, high affinity and high concentration, enabled us to apply the fluorescence polarization technique to study the molecular interaction between asterosap and the receptor. Using this method, we performed binding experiments in almost real time and found that divalent cations are significantly involved in the interaction between asterosap and the receptor.

Affinity Labels↗
PubMed2000

Deletion mapping of 14q32 in human neuroblastoma defines an 1,100-kb region of common allelic loss.

BACKGROUND: We analyzed loss of heterozygosity (LOH) in 54 primary neuroblastomas (NBs) using 12 microsatellite markers on 14q32, and found that 31% (17/54) NBs showed LOH. PROCEDURE: The smallest region of overlap (SRO) was identified between D14S62 and D14S987. RESULTS: There was no statistical correlation between LOH and any clinicopathologic features, including age, stage, amplification of MYCN, and ploidy. A sequence-ready bacterial artificial chromosome (BAC) contig was constructed, and the minimum tiling path of six BACs covered the SRO; the physical length of this region was no larger than 1,000 kb. CONCLUSIONS: Our findings support the existence of a putative tumor-related gene on 14q32 for the tumorigenesis of NB.

Alleles↗
PubMed2000

p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1.

p33/ING1s (the growth inhibitor ING1 and candidate tumor suppressor ING1) are key players in the suppressive pathways for human tumorigenesis. We analyzed their complete transcripts, primary structures, and expression. The results led us to discover two novel and related alternatively spliced transcripts encoding p24/ING1-ALT1 and p47/ING1-ALT2. They share C-terminal residues with the candidate tumor suppressors p33/ING1. The candidate tumor suppressors p33/ING1 and p24/ING1-ALT1 were coexpressed in a variety of fetal and adult human tissues, but p47/ING1-ALT2 was minimally expressed.

Adult↗
PubMed2000

Dosimetry studies in Zaborie village.

Dosimetry studies in Zaborie, a territory in Russia highly contaminated by the Chernobyl accident, were carried out in July, 1997. Studies on dosimetry for people are important not only for epidemiology but also for recovery of local social activity. The local contamination of the soil was measured to be 1.5-6.3 MBq/m2 of Cs-137 with 0.7-4 microSv/h of dose rate. A case study for a villager presently 40 years old indicates estimations of 72 and 269 mSv as the expected internal and external doses during 50 years starting in 1997 based on data of a whole-body measurement of Cs-137 and environmental dose rates. Mean values of accumulated external and internal doses for the period from the year 1986 till 1996 are also estimated to be 130 mSv and 16 mSv for Zaborie. The estimation of the 1986-1996 accumulated dose on the basis of large scale ESR teeth enamel dosimetry provides for this village, the value of 180 mSv. For a short term visitor from Japan to this area, external and internal dose are estimated to be 0.13 mSv/9d (during visit in 1997) and 0.024 mSv/50y (during 50 years starting from 1997), respectively.

Adult↗
PubMed2000

Antitumoral effects of defective herpes simplex virus-mediated transfer of tissue inhibitor of metalloproteinases-2 gene in malignant glioma U87 in vitro: consequences for anti-cancer gene therapy.

We set up experiments to evaluate the effects of defective herpes simplex virus (HSV)-mediated in vitro gene transfer of tissue inhibitor of metalloproteinases-2 (TIMP-2) in malignant glioma cells. Intrinsic TIMPs are known to be inhibitors of the strong invasive activities of matrix metalloproteinases in malignant gliomas. The defective HSV vectors dvSRaTIMP2 was engineered to express human TIMP-2 (hTIMP-2) with a combination of replication-competent HSV mutant, temperature-sensitive HSV-tsK, and amplicon plasmid-containing hTIMP-2. The hTIMP-2 gene was driven by the simian virus 40 promoter. The helper virus (HSV-tsK) was thermosensitive; consequently, this vector could proliferate only at 31.5 degrees C. After infection of U87 human glioblastoma cells with the vector in vitro, expression of TIMP-2 was confirmed by reverse zymography. The U87 cells infected in vitro either with dvSRaTIMP2 or HSV-tsK were efficiently destroyed under replication-permissive conditions (at 31.5 degrees C) and significantly lowered under replication-nonpermissive conditions (at 37 degrees C). The invasive activity of U87 was clearly inhibited by dvSRaTIMP2 infection at both 31.5 degrees C and 37 degrees C. Our studies suggest that TIMP-2 expressing the defective HSV vector is possibly useful for the treatment of malignant brain tumors.

Animals↗
PubMed2000

Detailed deletion mapping of chromosome band 14q32 in human neuroblastoma defines a 1.1-Mb region of common allelic loss.

Neuroblastoma (NB) is a well-known malignant disease in infants, but its molecular mechanisms have not yet been fully elucidated. To investigate the genetic contribution of abnormalities on the long arm of chromosome 14 (14q) in NB, we analysed loss of heterozygosity (LOH) in 54 primary NB samples using 12 microsatellite markers on 14q32. Seventeen (31%) of 54 tumours showed LOH at one or more of the markers analysed, and the smallest common region of allelic loss was identified between D14S62 and D14S987. This region was estimated to be 1-cM long from the linkage map. Fluorescence in situ hybridization also confirmed the loss. There was no statistical correlation between LOH and any clinicopathologic features, including age, stage, amplification of MYCN and ploidy. We further constructed a contig spanning the lost region using bacterial artificial chromosome and estimated this region to be approximately 1.1-Mb by pulsed-field gel electrophoresis. Our results will contribute to cloning and characterizing the putative tumour-associated gene(s) in 14q32 in NB.

Alleles↗
PubMed2000

Calculation of the neutron W value for neutron dosimetry below the MeV energy region.

The effective neutron W value for tissue-equivalent gas in the energy region from 5 keV to 5.7 MeV has been calculated using W values for recoil particles (protons, alpha particles, oxygen, carbon and nitrogen ions), which are produced by incident neutrons. The W value is assumed to be an energy-fluence-average over the W values of the recoil particles. The energy fluence spectra for the recoil particles are calculated by using a continuous slowing down approximation (CSDA). For the W values of recoil particles in the low-energy region, the recently evaluated data by Siebert et al and Taylor et al were used. Results are presented which show that the effective neutron W value depends strongly on energy in the low-energy region. This result indicates that neutron dose measurements using ionization chambers need a considerable correction of the W value in the low-energy region.

Carbon↗
PubMed2000

Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.

Animals↗
PubMed2000

Developmental changes in localization of the main ganglioside during sea urchin embryogenesis.

Ganglioside M5 (NeuGcalpha2-6Glcbeta1-1'Cer), the main ganglioside in sea urchin and sand dollar eggs, exists mainly in the endoplasmic reticulum and yolk granules in unfertilized eggs. To study the localization of ganglioside M5 after fertilization, early embryos were stained with an anti-ganglioside M5 monoclonal antibody. Using immunofluorescent and immunoelectron microscopy, intense label was observed in the outer surface and cytoplasm of embryos. These results indicate that ganglioside M5 was secreted during embryogenesis and localized in the extracellular matrix (ECM). When living embryos were incubated in sea water containing 7-nitrobenz-2-oxa-1,3-diazole labeled-ganglioside M5 (NBD-M5), the ECM and plasma membrane were strongly stained. Since the localization of NBD-M5 in the ECM was similar to that of extracellular M5, NBD-M5 was likely to be useful to examine the fate of extracellular ganglioside M5. Interestingly, NBD-M5 was incorporated in subcortical vesicles during embryogenesis, suggesting that the extracellular ganglioside M5 is transported into the cytoplasm. When fertilized eggs were incubated with NBD-M5 and tetramethylrhodamine dextran (a marker dye for endocytotic vesicles), colocalization of the dyes was observed in the vesicles. Thus, it was concluded that NBD-M5 in the ECM and/or plasma membrane was internalized in the cells by endocytosis, suggesting that extracellular M5 is transported from the ECM to endocytotic vesicles.

Animals↗
PubMed2000

Relationship between the 137Cs whole-body counting results and soil and food contamination in farms near Chernobyl.

We measured the radioactivity in the soil and child food samples from farms near Mogilev (56-270 GBq km(-2) 137Cs), Gomel (36-810 GBq km(-2) 137Cs), and Klincy (59-270 GBq km(-2) 137Cs), who had whole-body 137Cs counting results measured as part of a health examination in the Chernobyl Sasakawa Health and Medical Cooperation Project. Soil contamination on the family farm seems to be the main source of human contamination because most of the people in the area live on small farms and they and their domestic animals eat crops from the farms. A clear correlation was found between the children's whole-body 137Cs counting results and the radioactivity in their food (correlation coefficient: 0.76; confidence level of correlation: 3.2 x 10(-9)). There were also significant correlations between the whole-body 137Cs counting results and both the radioactivity of the soil samples (correlation coefficient: 0.22; confidence level of correlation: 0.0107) and the average contamination level of their current residence (correlation coefficient: 0.20; confidence level of correlation: 0.0174).

Cesium Radioisotopes↗
PubMed2000

Radiocesium in children residing in the western districts of the Bryansk Oblast from 1991-1996.

Measurements of 137Cs body burden were carried out in 1991-1996 for children residing in the western part of Bryansk Oblast (Russia) where area contamination with 137Cs following the Chernobyl accident varied from 0.03-3.7 MBq m(-2). The mean and median values of 137Cs specific activity (SA) in the bodies of children 5-15 y old for the whole period of surveillance averaged for 26,029 measurements was 85 Bq kg(-1) and 49 Bq kg(-1), respectively. Mean values in different places of residence varied from 30-342 Bq kg(-1) for the settlements where the number of examinees was not less than 50. There is a moderately strong relationship between mean SA in the settlement and the level of area contamination with 137Cs. A strong seasonal effect on 137Cs body burden was found. The ratio of average SA values is 1:1.75 for spring to autumn 1992-1995 in the settlement where the largest number of children was examined. This effect might be attributed to a seasonal change in diet. Based on questionnaire information on individual consumption of locally produced foods, the descending rank of contribution of food items to 137Cs intake by children was found to be: meat-mushrooms-milk-vegetables. Assuming that the dose distribution would follow the distribution of SA values, internal doses to the whole body from ingested 137Cs were assessed. The mean value of annual internal dose averaged for the whole set of measurements is 0.21 mSv, and the median of the individual dose distribution is 0.12 mSv y(-1) For 2% of the total sample the annual dose exceeded 1 mSv, with the highest individual dose being 9 mSv in 1994 for a 7-y-old girl.

Adolescent↗
PubMed2000

Oncolytic viral therapy for human prostate cancer by conditionally replicating herpes simplex virus 1 vector G207.

Over the last few years, a conditionally replicating herpes simplex virus 1 (HSV-1) vector, G207 has been used for the treatment of several malignant tumors. In this article we evaluate the anti-tumoral effect of G207 against prostate cancer in vitro and in vivo. The susceptibility of the human prostate cancer cell lines, DU145 and PC3 to G207 at a multiplicity of infection (MOI) of 0.1 was examined. In addition, the growth characteristics of G207 were assessed. Athymic mice with s.c. tumors were inoculated in vivo intraneoplastically with 1 x 10(7) plaque-forming units (PFU) of G207. For the pathological analyses, s.c. tumors were stained with X-gal. DU145 and PC3 were efficiently destroyed by G207 within 7 days. The viral yields of G207 increased time-dependently. In vivo, the intraneoplastic inoculation of G207 induced a significant inhibition of the tumor growth. The mean tumor growth ratio was significantly inhibited in the G207-treated tumors (DU145, P < 0.0001; PC3, P < 0.001 versus controls). In a pathological study, many lacZ-positive cells were diffusely present in the G207-treated tumors. G207 showed a significant antitumoral effect against human prostate cancer cell lines, and thus may be considered a useful agent for the treatment of prostate cancer.

Animals↗
PubMed2000

High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves' disease treated with propylthiouracil.

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves' disease. Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves' disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs. These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves' disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves' disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves' disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

Adolescent↗
PubMed2000

Antioxidant activity of eugenol and related monomeric and dimeric compounds.

Since the inhibitory effect of eugenol (a), which was isolated as an antioxidative component from plant, Caryopylli flos, on lipid peroxidation was less than that of alpha-tocopherol, we synthesized the eugenol-related compounds dieugenol (b), tetrahydrodieugenol (c), and dihydroeugenol (d), to find new strong antioxidants and assessed them for their inhibitory effect on lipid peroxidation and scavenging ability for superoxide and hydroxyl radicals. The antioxidative activities were in the order: (b)>(c)>(d)>(a) for the thiobarbituric acid reactive substance (TBARS) formation. These results suggest that the dimerized compounds have higher antioxidant activities than that of the monomers. Electron spin resonance (ESR) spin trapping experiments revealed that eugenol and its dimer, having allyl groups in the structure, scavenged superoxide, and that only eugenol trapped hydroxyl radicals under the conditions used. These finding suggest that eugenol and dieugenol have a different mechanism of antioxidation, i.e. eugenol may inhibit lipid peroxidation at the level of initiation, however, the related dimeric compounds may inhibit lipid peroxidation at the level of propagation of free radical chain reaction like alpha-tocopherol.

Antioxidants↗