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Biomedical subjects

T Ishikawa

Publications and source records attributed to T Ishikawa.

At least 253 records · Page 14Linked to original sources
PubMed2000

Gamow-teller strengths of the inverse beta transition 176Yb-->176Lu for spectroscopy of proton-proton and other sub-MeV solar neutrinos

Discrete Gamow-Teller (GT) transitions 176Yb-->176Lu at low excitation energies have been measured via the ( 3He,t) reaction at 450 MeV and at 0 degrees. For 176Yb, two low-lying states are observed, setting low thresholds Q(nu) = 301 and 445 keV for neutrino ( nu) capture. Capture rates estimated from the measured GT strengths, the simple two-state excitation structure, and the low Q(nu) in Yb-Lu indicate that Yb-based nu detectors are well suited for a direct measurement of the sub-MeV solar electron-neutrino ( nu(e)) spectrum including pp neutrinos.

Journal Article↗
PubMed2000

Transmission of human TT virus of genotype 1a to chimpanzees with fecal supernatant or serum from patients with acute TTV infection.

Fecal supernatant or serum containing TT virus (TTV) of genotype 1a (10(5) copies/ml) from patients with acute TTV infection was inoculated intravenously into two naive chimpanzees. Serum samples were obtained weekly and tested for TTV DNA by genotype 1-specific polymerase chain reaction. TTV DNA was detected in chimpanzee 228 at weeks 5-15 after inoculation with 0.5 ml of serum, and in chimpanzee 234 at weeks 7-19 after inoculation with 1 ml of fecal supernatant. The TTV DNA titer peaked at weeks 12 and 13 in chimpanzee 228 and at weeks 14-16 in chimpanzee 234. Mild biochemical and histological changes in biopsied liver samples were observed in both chimpanzees in association with the reduction in TTV titer. TTV DNA was transient in chimpanzee 228, but in chimpanzee 234 it reappeared at week 21 and persisted through week 30. These results indicate that TTV in feces is infectious and suggest that TTV has hepatitis-inducing capacity.

Acute Disease↗
PubMed2000

Modified guanidines as potential chiral superbases. 1. Preparation Of 1,3-disubstituted 2-iminoimidazolidines and the related guanidines through chloroamidine derivatives

Modified guanidines were explored as potential chiral superbases. Thus, chiral 1,3-dimethyl-2-iminoimidazolidines with or without 4, 5-diphenyl groups, their guanidinium salts, and the 2-iminoimidazolidines with (S)-1-phenylethyl groups on the ring nitrogens were prepared by treatment of 2-chloroimidazolinium chlorides with appropriate amines. Bicyclic guanidines were also prepared from a prolinamide using a similar procedure.

Journal Article↗
PubMed2000

Modified guanidines as potential chiral superbases. 2. Preparation Of 1,3-unsubstituted and 1-substituted 2-iminoimidazolidine derivatives and a related guanidine by the 2-chloro-1, 3-dimethylimidazolinium chloride-induced cyclization of thioureas

Simple preparation methods for modified guanidines were explored for new chiral superbases. Thus, (4S,5S)-4,5-diphenyl- and diastereomeric cyclohexane-fused 2-iminoimidazolidines were prepared from (1S,2S)-1,2-diphenylethylenediamine and (1R,2R)- or (1S,2S)-1, 2-diaminocyclohexanes through cyclization of protected thiourea intermediates with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) as a key reaction. In the (4S,5S)-4,5-diphenyl series 1-methyl-2-iminoimidazolidines and 2-diethylaminoimidazoline were also prepared as related guanidines.

Journal Article↗
PubMed2000

Modified guanidines as potential chiral superbases. 3. Preparation Of 1,4,6-triazabicyclooctene systems and 1,4-disubstituted 2-iminoimidazolidines by the 2-chloro-1,3-dimethylimidazolinium chloride-induced cyclization of guanidines with a hydroxyethyl substituent

Simple preparation methods of modified guanidines have been explored as potential chiral superbases. Thus, 3,7,8-trisubstituted and 3,6,7, 8-tetrasubstituted 1,4,6-triazabicyclooctene systems were prepared from (1S,2S)-1,2-diphenylethylenediamine through stepwise 2-chloro-1, 3-dimethylimidazolinium chloride (DMC)-induced cyclizations of protected thioureas to the corresponding 2-iminoimidazolidines and then of 2-(2-hydroxyethylimino)imidazolidines to the bicyclic systems. Linear guanidines with a 2-hydroxyethyl functional group were prepared by the reaction of carbodiimides with 2-amino alcohols. Reaction of linear-type guanidines with DMC followed by base treatment afforded 1,4-disubstitued 2-iminoimidazolidines. Furthermore, another type of 1,4,6-triazabicyclooctene was also prepared through double DMC-induced cyclization of guanidines with two 2-hydroxyethyl substituents.

Journal Article↗
PubMed2000

A nuclear localization signal is essential for stress-induced dimer-to-trimer transition of heat shock transcription factor 3.

Expression of heat shock genes is regulated mainly at the level of transcription by heat shock transcription factors (HSFs). In avian, HSF1 and HSF3 are maintained in a cryptic monomer and dimer form, respectively, in the cytoplasm in the absence of stress. Upon heat stress, they undergo conformational change associated with the formation of a trimer and nuclear translocation. In this study, we identified regions that are necessary for the dimer-to-trimer transition of chicken HSF3 (cHSF3) upon stress conditions. One of these regions coincides with a functional nuclear localization signal (NLS) of cHSF3 that was recognized by a nuclear transport receptor importin alpha. Point mutations of basic amino acids in the NLS inhibit both nuclear translocation and trimer formation of cHSF3. These results demonstrate that the NLS acts positively on the trimer formation of cHSF3 upon stress conditions.

Amino Acid Sequence↗
PubMed2000

Three-dimensional observations of spatial arrangement of hepatic zonation and vein system in mice and house musk shrews.

The three-dimensional (3D) relationship among the hepatic domains and the efferent central and afferent portal veins was investigated by macroscopy, microscopy, and computer-aided 3D reconstruction methods. To clearly distinguish the pericentral domain from the periportal, we used CCl(4)-treated mice and diabetic house musk shrews, which show typical pericentral necrosis and deposition of fat, respectively. The 3D findings obtained were verified against normal control animals using advantages of our unique observations by light and fluorescent microscopy, which made it possible to differentiate the two domains well. The pericentral domains in the mice and shrews appeared three-dimensionally as continuous branched columns, and the periportal domains exist in a sponge-like network that fills the parenchymal space among the columnar pericentral domains. The efferent central veins were concentrically surrounded by the pericentral domain, and segments of the central veins flowed into large sublobular and lobar veins. The walls of these large veins faced the pericentral domain at the confluence with the central veins; the remaining portions of the walls faced the periportal domain. The afferent portal veins were placed at the two-dimensional center of the network of the periportal domain and gave off smaller portal branches radially at the intersections of the network. Three types of liver lobules-classic, portal, and acinar-have been discussed repeatedly at the (2D) level. At the 3D level, it is reasonable to consider that the liver parenchyma consists of the two continuous domains corresponding to the distribution of the vessels that we found.

Animals↗
PubMed2000

Cytokeratins 8 and 19 in the mouse placental development.

To investigate the expression and biological roles of cytokeratin 19 (K19) in development and in adult tissues, we inactivated the mouse K19 gene (Krt1-19) by inserting a bacterial beta-galactosidase gene (lacZ) by homologous recombination in embryonic stem cells, and established germ line mutant mice. Both heterozygous and homozygous mutant mice were viable, fertile, and appeared normal. By 7.5-8.0 days post coitum (dpc), heterozygous mutant embryos expressed lacZ in the notochordal plate and hindgut diverticulum, reflecting the fact that the notochord and the gut endoderm are derived from the axial mesoderm-originated cells. In the adult mutant, lacZ was expressed mainly in epithelial tissues. To investigate the possible functional cooperation and synergy between K19 and K8, we then constructed compound homozygous mutants, whose embryos died approximately 10 dpc. The lethality resulted from defects in the placenta where both K19 and K8 are normally expressed. As early as 9. 5 dpc, the compound mutant placenta had an excessive number of giant trophoblasts, but lacked proper labyrinthine trophoblast or spongiotrophoblast development, which apparently caused flooding of the maternal blood into the embryonic placenta. These results indicate that K19 and K8 cooperate in ensuring the normal development of placental tissues.

Animals↗
PubMed2000

Growth-stimulating effect of dienogest, a synthetic steroid, on rodent, canine, and primate mammary glands.

We observed hyperplasia of the mammary gland in female beagle dogs, but not in female rats and monkeys, in 91-day toxicity studies on dienogest. In order to elucidate a possible mechanism for its development and to account for this species difference, we determined the plasma level of growth hormone (GH) in dogs, rats, and monkeys treated orally with dienogest for 91 days. As a result, dogs with mammary hyperplasia showed a prominent, dose-dependent increase in their GH level; and, contrarily, rats and monkeys without the hyperplasia of this organ failed to show any such increase. These results were supported by evidence from immunohistochemical and morphometric analysis of the pituitary gland. In addition, dienogest and medroxyprogesterone acetate (MPA) stimulated the growth of canine mammary epithelial cells in the presence of estradiol in vitro, but had no effect on rat and human mammary epithelial cells incubated under the same conditions. In conclusion, dienogest with progestational activity caused proliferation of the mammary gland in beagle dogs by increasing the secretion of GH, as do other progestational compounds. This change may be partially dependent on the direct effect of the drug.

Animals↗
PubMed2000

Impaired reductive regeneration of ascorbic acid in the Goto-Kakizaki diabetic rat.

Ascorbic acid (AA) is a naturally occurring major antioxidant that is essential for the scavenging of toxic free radicals in both plasma and tissues. AA levels in plasma and tissues have been reported to be significantly lower than normal in diabetic animals and humans, and might contribute to the complications found at the late stages of diabetes. In this study, plasma and hepatic AA levels and AA regeneration were studied in the Goto-Kakizaki diabetic rat (GK rat) to elucidate the mechanism of decreasing plasma and hepatic AA levels in diabetes. AA concentrations in the plasma and liver were significantly lower in GK than in control rats. AA levels in primary cultured hepatocytes derived from GK rats were lower than those derived from control Wistar rats with or without dehydroascorbic acid (DHA) in the medium. Among various enzyme activities that reduce DHA to AA, the NADPH-dependent regeneration of AA in the liver was significantly suppressed in GK rats. Northern blot analysis revealed that only the expression of 3-alpha-hydroxysteroid dehydrogenase (AKR) was significantly suppressed in these rats. These results suggest that decreased AA-regenerating activity, probably through decreased expression of AKR, contributes to the decreased AA levels and increased oxidative stress in GK rats.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Serum CYFRA 21-1 is one of the most reliable tumor markers for breast carcinoma.

BACKGROUND: The search for new tumor markers for breast carcinoma has been an area of vigorous study; nonetheless, to the authors' knowledge little new information has emerged beyond the clinical usefulness of CA 15-3. The authors studied serum CYFRA 21-1 in breast carcinoma based on evidence that breast carcinoma expresses cytokeratin 19 fragments and that CYFRA 21-1 is a specific antigen for cytokeratin 19 fragments. METHODS: The serum samples of 86 patients with primary breast carcinoma, 14 patients with recurrent breast carcinoma, 22 patients with benign mammary disease, and 25 healthy controls were provided for measurements of CYFRA 21-1, carcinoembryonic antigen (CEA), and CA 15-3. The relation between clinicopathologic features, prognosis, and disease free survival with serum CYFRA 21-1 titers was studied. RESULTS: There was no difference between the serum CYFRA 21-1 titers from patients with benign mammary disease and those from healthy controls. The sensitivities of CYFRA 21-1 for patients with International Union Against Cancer Stage IV and recurrent tumors were 60% and 64.2%, respectively, which were as high as those for CA 15-3 and superior to those for CEA. The hematogenous recurrence showed a very high sensitivity of 89%. According to the increments of T, N, and M factor numbers, the serum CYFRA 21-1 titers were elevated. No correlation between CYFRA 21-1 and CEA was observed and the correlation between CYFRA 21-1 and CA 15-3 was weak. The univariate and multivariate analyses for survival revealed that serum CYFRA 21-1 levels were an independent indicator of prognosis. CONCLUSIONS: The measurement of the serum CYFRA 21-1 titer in patients with breast carcinoma may be useful in monitoring for recurrence and evaluating the therapeutic effect in patients with advanced disease.

Antigens, Neoplasm↗
PubMed2000

Molecular design of polyvinylpyrrolidone-conjugated interleukin-6 for enhancement of in vivo thrombopoietic activity in mice.

Functional polyvinylpyrrolidone (PVP) was synthesized as a novel polymeric modifier for polymer-conjugated cytokines, and its efficiency and applicability as a drug delivery system (DDS) were evaluated. PVP with a carboxyl group at one end of the main chain was prepared by radical polymerization (M(n): 6000, M(w)/M(n): 1.14) with the aid of 4,4'-azobis(4-cyanovaleric acid) as a radical initiator and 3-mercaptopropionic acid as a transfer agent. Interleukin-6 (IL-6) was covalently conjugated via the formation of amino bonds between the lysine amino groups of IL-6 and PVP. PVP-conjugated IL-6, in which 60% of the fourteen lysine amino groups of IL-6 were estimated to be coupled with PVP (M-PVP-IL-6), showed more than 50-fold greater thrombopoietic potency in vivo than native IL-6. No side effects, such as body weight loss, were observed in the M-PVP-IL-6 treated mice. These results indicate that PVP as a polymeric modifier is a promising DDS for clinical application of cytokines and other therapeutic agents.

Animals↗
PubMed2000

Intraocular Lens Calculation for Cataract Treated with Photorefractive Keratectomy Using Ray Tracing Method.

Purpose: Conventional methods (such as the SRK-II formula) do not accurately calculate the power of the intraocular lens (IOL) after refractive surgery. Therefore, we compared a new formula including a ray tracing method to the conventional method for foldable IOL lens implantation.Method: Foldable IOLs (MA 60 BM) were implanted in 26 patients (32 eyes) using the phakoemulsification technique. The power of the IOL was measured preoperatively using the SRK-II formula in all cases. From the results of postoperative refractive errors of these cases, the power of IOL calculated by the ray tracing method was compared to the SRK-II formula. Cataract patients first treated with photorefractive keratectomy (PRK) received IOL implants using our ray tracing method and their postoperative refraction was measured.Results: The average postoperative refractive error was 1.32 D in SRK-II formula, 0.95 D in the ray tracing method with Ray 1 used and 0.89 D with Ray 2 used. Postoperative refraction of both eyes first treated with PRK was -1.00 D.Conclusion: The average postoperative refractive error was reduced in the ray tracing method using Olsen's predicted ACD (Ray 2) compared to SRK-II formula. This new tracing method appears to be useful for determination of IOL power and it may be applied for IOL calculation for cataract surgery after refractive surgery.

Journal Article↗
PubMed2000

Effect of hydroxypropylmethylcellulose (HPMC) on the release profiles and bioavailability of a poorly water-soluble drug from tablets prepared using macrogol and HPMC.

The aim of the present study was to investigate the effect of hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled release of drug, on the release profiles and bioavailability of the poorly water-soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG-HPMC tablet) was markedly increased with increasing compression force used during the preparation from 20 to 200 MPa. The values reached their maximal levels (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the improvement of its dissolution rate in the presence of PEG. NP dissolution was complete at the latest within 1 h. On the other hand, dissolution of NP from the NP-PEG-HPMC tablet was significantly delayed with an increase in the concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC also increased. Interestingly, the same peak plasma NP concentration (C(max)) and the area under the plasma NP concentration-time curve (AUC(0-10)) were observed for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max) (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC tablet was orally administered to rabbits. We describe here a preparation method of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules (prepared with PEG) and HPMC.

Administration, Oral↗
PubMed2000

Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats.

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.

Age Factors↗
PubMed2000

Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis.

To clarify the role of the H-Ras in vivo, we generated H-ras null mutant mice by gene targeting. In spite of the importance of the Ras in cell proliferation and differentiation, H-ras null mutant mice grew normally and were fertile. The oldest H-ras mutant mice grew to be more than 30 months old. We used the H-ras deficient mice to study the importance of the H-ras and other ras genes in the development of skin tumors induced by initiation with 7, 12-dimethylbenz(a)anthracene (DMBA) followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). We showed that H-ras null mutant mice develop approximately six times less papillomas compared with wild-type littermates after 20 weeks of TPA treatment. While all papillomas examined (17 out of 17) in wild-type mice have mutations of H-ras at codon 61, 13 (62%) out of 21 papillomas in H-ras null mutant mice have mutations of K-ras gene at codon 12, 13, or 61 and another eight (38%) papillomas have no mutations in these codons of K-ras or N-ras genes. This suggests that the activation of H-ras gene is critical in the wild-type mice, but the activation of K-ras gene can replace the H-ras activation in the initiation step of skin tumor development in the H-ras deficient mice. Oncogene (2000).

Animals↗