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Biomedical subjects

H Iwai

Publications and source records attributed to H Iwai.

At least 91 records · Page 5Linked to original sources
PubMed1994

Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice.

PURPOSE: In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. METHODS AND MATERIALS: The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three or four times at 2-h intervals. RESULTS: At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. CONCLUSION: Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity.

Animals↗
PubMed1994

KIN-804 vs. KU-2285 as a radiosensitizer for clinical use.

PURPOSE: The in vitro and in vivo effects of two promising hypoxic cell radiosensitizers, KIN-804 (KIN) and KU-2285 (KU), were compared using four types of assays, and the acute toxicity and pharmacokinetics of KIN were investigated to evaluate the clinical applicability of the compounds. METHODS AND MATERIALS: To evaluate the in vitro effect at low radiation doses (1-4.5 Gy), the cytokinesis-block micronucleus (MN) assay using SCCVII or EMT-6 cells and the chromosomal aberration (CA) assay using EMT-6 cells were performed. In addition, an in vivo-in vitro colony assay, a growth delay assay, and a pharmacokinetic study were performed using C3H mice bearing SCCVII tumors, and the LD50/7 was determined in ICR mice. RESULTS: In the in vitro MN assay, the sensitizer enhancement ratio (SER) at 0.1, 0.25, 1, and 5 mM with SCCVII cells, and at 1 mM with EMT-6 cells was respectively, 1.45, 1.61, 2.57, 4.22, and 1.96 for KIN, and 1.57, 1.62, 2.59, 5.66, and 2.21 for KU. In the in vitro CA assay, the SER at 1 mM was 1.78 for KIN and 1.79 for KU. In the in vivo-in vitro colony assay, the SER of KIN at 50, 100, and 200 mg/kg was 1.24, 1.30, and 1.45, respectively, while the SER of KU at 100 mg/kg was 1.41. In the growth delay assay, the growth delay time for 100 and 200 mg/kg of the drug plus 20 Gy of radiation was respectively, 16.5 and 19.1 days for KIN, and 18.9 and 24.0 days for KU. In all experiments, the sensitizing effect of KIN was almost equal to that of KU. The LD50/7 of KIN was 3.6 g/kg by intraperitoneal injection, while that of KU was 3.6 g/kg by intraperitoneal injection, and the pharmacokinetic study of KIN revealed a low uptake of the drug by the brain. CONCLUSION: Both KIN and KU had a definite sensitizing effect even at lower drug concentrations or doses, suggesting their potential usefulness in clinical radiotherapy.

Animals↗
PubMed1994

Comparison of the genomes of attenuated equine herpesvirus-1 strains with their parent virulent strain.

To elucidate the virulence factors of equine herpesvirus-1 (EHV-1), we compared the genomic architecture of the HH1 strain, a Japanese isolate of EHV-1, with that of its four descendant strains obtained by serial passage in bovine kidney (BK) cells, i.e. BK77, BK161, BK271, and BK343. In preliminary studies high-passaged BK271 and BK343 lost virulence in colts, and in the present study digestion with restriction endonuclease BamHl showed that the DNAs of BK271 and BK343 differed markedly from the DNA profiles of HH1, BK77, and BK161. Employing all the molecularly cloned BamHl fragments of the HH1 strain as probes, Southern blot analysis revealed seven variable fragments. All BamHl fragments of BK343 were subsequently cloned into plasmid pUC18 and on mapping to the HH1 DNA maps, two additional variable fragments were disclosed. Finally, the precise variable regions identified in these nine fragments were fine mapped on the viral prototype genome, and among the open reading frames (ORFs) located in the variable fragments, three (ORFs 1,24, and 71) were found to have changed via serial passage in the BK cells. Thus these three ORFs are thought to play an important role on the pathogenicity of EHV-1.

Animals↗
PubMed1994

Synthesis and characterization of sapecin and sapecin B.

Two insect defencins, sapecin and sapecin B, were chemically synthesized to confirm their structure and antibacterial activity and also to examine the possibility that these peptides bind to the same site on the large conductance calcium-activated potassium channel as charybdotoxin. Both synthetic peptides showed the same antibacterial activity as native sapecins, indicating that the synthetic peptides folded correctly in the chemical synthesis. Synthetic sapecins did not show an inhibitory effect on [125I]charybdotoxin binding to rat brain synaptic membranes, suggesting that sapecin B recognizes a different binding site from that of charybdotoxin despite the similar structural motif.

Amino Acid Sequence↗
PubMed1994

Inhibition of adsorption of human T-cell-leukemia virus type 1 by a plant lectin, wheat-germ agglutinin.

Thirty-six lectins that recognize various sugar chains were examined for inhibitory activities against infection with human T-cell leukemia virus type I (HTLV-I). Wheat-germ agglutinin (WGA) was the most inhibitory among them: plating of the pseudotype of vesicular-stomatitis virus (VSV) bearing envelope antigens of HTLV-I was markedly inhibited by treatment of indicator cells with WGA just before adsorption, but not by treatment after virus adsorption. Treatment with WGA before adsorption, however, could not inhibit the plating of VSV, VSV pseudotypes of bovine leukemia virus, Moloney murine leukemia virus and human immunodeficiency virus type I. Syncytium formation induced by HTLV-I was also inhibited by WGA upon co-cultivation of U-251 MG human glioma cells or MOLT-4 human T-cells with HTLV-I-producing C91/PL cells. Formation of proviral DNA detected one day after infection was also inhibited when indicator cells had been treated with WGA before adsorption of HTLV-I, but not after its adsorption. These findings indicated that WGA specifically inhibits plating of HTLV-I when added to culture just before adsorption and suggested that a substance(s) containing sugar chains recognized by WGA might be involved in an adsorption step of HTLV-I.

Adsorption↗
PubMed1994

Bone marrow transplantation therapy using resistant donors for retrovirus-induced leukaemia in mice.

Infection with Rauscher leukaemia virus (RLV) causes erythroleukaemia, anaemia, viraemia, and splenomegaly, features which develop very quickly in mice of strains susceptible to RLV but more slowly or not at all in strains resistant to RLV. We compared the effects of bone marrow transplantation (BMT) of donor cells obtained from a mouse strain resistant to the virus with the effects of BMT of donor cells obtained from strains susceptible to the virus, in recipient virus-susceptible mice which had previously been inoculated with RLV. Our results indicated that bone marrow transplantation from a marrow-resistant donor, but not from a susceptible donor, delayed the expression of leukaemia and delayed death, although such treatment did not appear to inhibit viral infection in susceptible recipients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Evaluation of pertussis treatment with erythromycin ethylsuccinate and stearate according to age.

Although erythromycin estolate has been fully assessed for pertussis treatment, the evaluation of erythromycin ethylsuccinate and stearate, the main erythromycin preparations used in Japan and the US, is inadequate. We evaluated these preparations to establish an appropriate treatment for pertussis according to age. Sixty-six patients with culture-confirmed pertussis were treated with erythromycin administered at a dosage of 40-50 mg/kg/day (maximum, 1.2 g/day). Negative culture was obtained in 39% (15/38) of patients aged 0-2 years within one week and in 71% (27/38) within two weeks, in 78% (7/9) of those aged 3-15 years within one week and in 100% (9/9) within two weeks. All 12 adult patients had a negative culture within one week. The efficacy of erythromycin for the eradication of B. pertussis was significantly lower in children aged 0-2 years than in older children. In conclusion, it is desirable to administer erythromycin for three weeks to children aged 0-2 years, two weeks to those aged 3-15 years and one week to adults.

Administration, Oral↗
PubMed1994

[Histologic and cell kinetic alteration of gastric mucosa under continuous duodenal regurgitation in experimental dog model].

The experimental models for duodenal regurgitation were established using Schimilinisky-McCann's procedure in dogs. Histology, cell kinetics, and degree of DNA methylation in the gastric mucosa of those models were examined at 3, 6, and 12 month periods after the procedure and compared with those in normal mucosa. Histologically, minor changes of gastric mucosa such as superficial gastritis and erosion, were observed at the 3 month period, whereas hyperplasia and atrophy of the mucosa were observed at the 6 and 12 month periods, respectively. Cell kinetic analysis using bromodeoxyuridine (BrdU) and anti-BrdU antibodies revealed a significantly higher labeling index (L.I.) in the hyperplastic mucosa and also revealed a tendency of high L.I. in the atrophic mucosa at the 6 month period in comparison with that in normal mucosa. A high level of DNA methylation was identified in the mucosa that showed a high L.I. of BrdU at the 6 and 12 month periods. These results suggest that hyperplastic and subsequent atrophic changes of the gastric mucosa under continuous duodenal regurgitation are closely related with rapid cell proliferation and a high level of DNA methylation, and that the duodenal juice could play a crucial role in the carcinogenesis of the stomach.

Animals↗
PubMed1993

Solution conformation of an antibacterial peptide, sarcotoxin IA, as determined by 1H-NMR.

The solution conformation of sarcotoxin IA, which is an antibacterial peptide isolated from Sarcophaga peregrina with a molecular mass of 4 kDa, was determined by NMR spectroscopy and hybrid distance geometry/dynamical simulated annealing calculations. On the basis of 227 experimental constraints, including 185 distance constraints obtained from NOE and 42 constraints associated with 21 hydrogen bonds, a total of 18 converged structures of sarcotoxin IA were obtained. The final 18 converged structures exhibit backbone-atomic root-mean-square differences about the averaged coordinate positions of 0.070 +/- 0.027 nm for residues 3-23 and 0.040 +/- 0.017 nm for residues 28-38. It has been indicated that sarcotoxin IA consists of two amphiphilic alpha-helical regions, i.e. helix I (Leu3-Gln23) and helix II (Ala28-Ala38), with a hinge region (Gly24-Ile27), which connects helix I and helix II. We conclude that these two amphiphilic helical segments of sarcotoxin IA are of importance for the expression of the antibacterial activity.

Amino Acid Sequence↗
PubMed1993

Theileria sergenti infection in the Bo-RBC-SCID mouse model.

We have previously developed the Bo-RBC-SCID mouse model for Theileria sergenti infection. In the present study, this model was further examined to delineate the models of parasite infection. The Bo-RBC-SCID mice were prepared by periodically transfusing uninfected bovine erythrocytes (Bo-RBCs) into splenectomized SCID mice via the intraperitoneal (i.p.) route. The mice, separated into three groups, were inoculated i.p., intravenously (i.v.), or subcutaneously (s.c.) with T. sergenti-infected Bo-RBCs. Examination of samples of peripheral blood demonstrated that the parasite infected mice inoculated via any one of the three routes. The mice inoculated i.v., however, developed parasitemia earlier than those inoculated i.p. or s.c. When Bo-RBC-SCID mice prepared without splenectomy were infected with T. sergenti, a high-level parasitemia appeared only once. After that, not only the level of parasitemia but also the number of Bo-RBCs in the peripheral blood rapidly decreased despite the continuation of Bo-RBC transfusions. The results suggest that T. sergenti proliferates primarily in the circulating blood in Bo-RBC-SCID mice and that in response to the parasites growth, the spleen may play an important role in the removal of both parasitized and unparasitized Bo-RBCs from the blood circulation.

Animals↗
PubMed1993

The genomic diversity among equine herpesvirus-1 strains isolated in Japan.

The DNAs from nine Japanese field isolates of equine herpesvirus-1 (EHV-1) were analyzed by digestion with the restriction endonuclease Bam HI and Southern hybridization. Comparing restriction profiles among the EHV-1 strains, there was no considerable difference between isolates before and after vaccine application, but some minor variations in the mobility of Bam HI fragments were observed. To identify these variable fragments, all genomic DNA sequences of the Japanese prototype of EHV-1 have been cloned as Bam HI restriction fragments into the plasmid pUC-18. Physical maps of the virus DNA were constructed by a combination of Southern blot analysis and double enzyme digestion of the cloned fragments. By using these cloned fragments as probes in Southern blot analysis, the areas of heterogeneity observed among the field EHV-1 isolates were located in both terminals of UL, the center of UL, IR, US and TR regions of the genome.

Animals↗
PubMed1993

The Bo-RBC-SCID mouse model for evaluating the efficacy of anti-theilerial drugs.

We have previously developed a mouse model which allowed the proliferation of Theileria sergenti in severe combined immunodeficiency (SCID) mice with circulating bovine erythrocytes (Bo-RBC). In the present study, this model was utilized to test the efficacy of anti-theilerial drugs. Bo-RBC-SCID mice were created by giving periodic transfusions of T. sergenti-free Bo-RBC, and subsequently infecting with T. sergenti. Three anti-protozoal compounds, Pamaquine (Yamanouchi Pharmaceutical Co. Ltd), Ganaseg (Japan CIBA-GEIGY Ltd) and Buparvaquone (Coopers Animal Health Ltd), were subcutaneously administered into the mice at doses recommended for cattle therapy. Blood examinations demonstrated that all three drugs significantly reduced the level of parasitemia although Ganaseg was effective only at a dose five times higher than that recommended for cattle therapy. Administration of the drugs neither caused any sign of acute toxicity nor changed the rate of Bo-RBC in the SCID mice's circulating blood cells. The results indicate that the Bo-RBC-SCID mouse model may offer a useful in vivo system for evaluating the efficacy of anti-protozoal drugs against T. sergenti.

Aminoquinolines↗
PubMed1993

Changes in the hybridization patterns of populations of Theileria sergenti during infection.

Restriction fragment length polymorphisms (RFLPs) of Theileria sergenti DNA were analysed using probes of a genomic DNA fragment (pTs 2) and a cDNA corresponding to this genomic probe (C-Ts 2). Each of the probes detected RFLPs in DNA from different stocks of Theileria sergenti. Additionally, using these probes, alterations in hybridization patterns were observed in samples of the parasites harvested at different times after individual calves had been infected with Theileria sergenti. This result suggests that the Theileria sergenti stocks used were mixed parasite populations.

Animals↗
PubMed1993

Detection and identification of equine herpesvirus-1 and -4 by polymerase chain reaction.

A rapid method for detection and identification of equine herpesvirus-1 and -4 (EHV-1 and EHV-4) was developed using polymerase chain reaction (PCR). Primers for PCR were designed from aligned nucleotide sequences of glycoprotein B genes of EHV-1 and EHV-4 to amplify specific regions for EHV-1 or EHV-4 or a common region of both viruses. By using type specific primer mixture, amplified fragments were identified as EHV-1 or EHV-4 in a one-step reaction. We have applied this technique on specimens from aborted fetuses. The samples contained only EHV-1 and there was complete accordance between the results of PCR and virus isolation. Our PCR system could differentiate the two virus types rapidly in a one-step reaction.

Animals↗
PubMed1993

Equid herpesvirus 1 infection in mice.

When the HH1 strain of equid herpesvirus 1 was intranasally inoculated to mice, the virus propagated in mouse lungs and the animals showed clinical signs such as ruffled fur, hunched posture, depression and body weight loss. Mice recovered from these signs by day 12 and cleared the virus from their lungs and produced antibody by 7th day after infection. These convalescent mice did not allow growth of the rechallenged virus. Athymic nude mice, however, failed to clear the virus from their lungs. Most of field isolates from aborted fetuses were propagated in murine lungs but attenuated strains originated from the HH1 were not.

Animals↗
PubMed1993

Menière's disease and autoimmunity: clinical study and survey.

In order to clarify whether autoimmune mechanisms form part of the etiopathogenesis of Meniere's disease, sera and endolymphatic sac tissues from 30 patients with Meniere's disease were analyzed according to the clinical criteria for autoimmune diseases stated by Mackay & Burnet. Several cases showed hyper gamma-globulinemia, antibody elevation to Type II collagen in the serum and endolymph, positive staining to immunoglobulins and C3 or infiltration of immuno-competent cells in the endolymphatic sac, good response to prednisolone and combination with systemic immune disorders. Other examinations showed a significant elevation of OKT 4/8 ratio and a decrease of OKT8-positive cells, and elevated levels of circulating immune complex and antiviral antibody titers. It is suggested that certain cases of Meniere's disease may have an altered immunological background, which may be attributed to an autoimmune mechanism dependent on humoral and/or cellular responses.

Adult↗
PubMed1993

Effects of acetazolamide on acid-base balance in the endolymphatic sac of the guinea pig.

The effects of acetazolamide, a carbonic anhydrase inhibitor, on acid-base parameters in the endolymphatic sac of the guinea pig were investigated using ion-selective microelectrodes. Bicarbonate concentration was reduced and pH shifted to being acidic immediately after administration of acetazolamide. Chloride concentration in the endolymphatic sac increased after carbonic anhydrase inhibition. These findings provide evidence of an active function of carbonic anhydrase in the endolymphatic sac and suggest that carbonic anhydrase activity is involved in the formation of endolymphatic sac fluid.

Acetazolamide↗