Biomedical subjects

T Inomata

Publications and source records attributed to T Inomata.

At least 19 recordsLinked to original sources

PubMed2001

New antimetastatic hypoxic cell radiosensitizers: design, synthesis, and biological activities of 2-nitroimidazole-acetamide, TX-1877, and its analogues.

We designed, based on the molecular orbital (MO) calculation, synthesized, and evaluated the biological activities of the new antimetastatic hypoxic cell radiosensitizer, 2-nitroimidazole-acetamide, TX-1877, and its analogues. Each analogue has an electron-affinic imidazole group, an acetamide group and a certain hydrophilic group to control its biological effect, toxicity, and pharmacokinetics. In in vitro radiosensitization assay, most TX-1877 analogues, which have an electron affinity (EA) of more than 0.9 eV and partition coefficient (P) of more than 0.021, showed satisfactory enhancement ratios (ER > 1.60) at doses of I mM. On the other hand, imidazole analogues, such as TX-1908 (EA = 0.67 eV), TX-1910 (EA = -0.34 eV) and TX-1931 (EA = -0.37 eV), which have low electron affinities, had an ER of 1.31 or less. TX-1877 and KIN-806 effectively inhibited tumor regrowth when administered with irradiation in vivo at a dose of 0.4 mg/g. Tumor lung metastasis was inhibited by treatment with either TX-1877 or KIN-806 without irradiation at a dose of 0.4 mg/g. TX-1877 reduced markedly the mean number of metastatic lung nodules in comparison with KIN-806. Moreover, TX-1877 and KIN-806 enhanced macrophage and helper T lymphocyte infiltration for 3 weeks after drug treatment. TX-1877 shows a high EA value and has the C2 of HOMO localizing on N-methylamide and the C2 of LUMO localizing on 2-nitroimidazole group. The MO data might be useful for designing a bifunctional hypoxic cell radiosensitizer. TX-1877 and its analogues are potential antimetastatic hypoxic cell radiosensitizers, which would improve the efficiency of radiotherapy and quality of life in cancer treatment.

Animals↗

PubMed2001

Generation of live rat offspring by intrauterine insemination with epididymal spermatozoa cryopreserved at -196 degrees C.

This study reports the development of a reliable method for cryopreservation of rat epididymal spermatozoa and the production of live young by artificial insemination using these cryopreserved spermatozoa. The motility and membrane integrity of rat spermatozoa were investigated after spermatozoa had been subjected to physical stress and frozen with various concentrations of glycerol (0, 3 and 6%) either in the presence or absence of Equex Stem as cryoprotective agents. The ability of cryopreserved spermatozoa to generate normal offspring by intrauterine insemination was also evaluated. Rat spermatozoa that had been centrifuged at 700 g for 5 min showed a significant decrease in motility compared with non-centrifuged spermatozoa. In addition, after centrifugation three times the percentage of membrane-intact spermatozoa decreased to approximately 0%. The percentage of membrane-intact spermatozoa was significantly higher (P < 0.01) in semen samples that had been frozen in medium without glycerol than in samples frozen in medium with 3% glycerol. Although the addition of 0.7% Equex Stem to medium without glycerol or with 3% glycerol did not influence rates of sperm motility after freezing and thawing, the percentage of membrane-intact spermatozoa was improved by the presence of 0.7% Equex (P < 0.05). Therefore, rat spermatozoa were handled gently to avoid physical stress and were frozen in medium containing 23% egg yolk, 8% lactose monohydrate and 0.7% Equex Stem, at pH 7.4 adjusted with 10% Tris(hydroxymethyl)aminomethane solution. Thirteen female rats were inseminated into the oviductal end of both uterine horns with frozen-thawed spermatozoa. Forty-one normal live offspring were obtained from nine of the inseminated females. These results indicate that frozen-thawed rat spermatozoa can generate normal offspring. To our knowledge, this procedure is the first successful production of offspring using spermatozoa cryopreserved in liquid nitrogen.

Animals↗

PubMed2001

[Two cases of canine histoplasmosis in Japan].

Histoplasmosis is distributed in tropical, subtropical and temperate zones of the world. The disease is one of the imported mycoses in Japan. To date, although more than 30 human and one canine case of histoplasmosis have been reported in Japan, some including that of the canine might have been infected domestically, since the patients have no history of going abroad. The pathogen of histoplasmosis is thus believed to be present in our country. We examined skin biopsies from two dogs in Tokyo and Kumamoto, and found fungal elements 1-2 or 2-4 microEm in diameter in the macrophages. The homology of DNA sequences for the ITS rRNA gene were correspondent to Ajellomyces capsulatus at a rate of more than 97.4%. Therefore, the two dogs were diagnosed as having been infected with Histoplasma capsulatum which is the anamorph of A. capsulatus. Since the dogs had no history of having been outside Japan and had not been brought from an endemic area, they might have been infected domestically. Further epidemiological surveys on canine histoplasmosis may be able to estimate autochthonous human cases in Japan.

Animals↗

PubMed2001

[High-dose rate Iridium-192 brachytherapy with flexible applicator--a trial toward decrease of stress during treatment and improvement of quality of life].

PURPOSE: We tried to improve the materials and methods of high-dose rate Iridium-192 brachytherapy for localized prostate cancer and evaluated the stress during the treatment in 20 patients with whom the therapy was performed. MATERIALS AND METHODS: Rigid applicators made of stainless steel of 1.6 mm in diameter were indwelt with a template as usual for 30 hours in 14 patients (group A). Flexible applicators made of polyoxymethylene rosin (POM) of 2.0 mm in diameter were indwelt without a template for 30 hours after the applicator insertion in 6 patients (group B). We made inquiries about lumbago, inconvenience and necessity of assistant help and sleep in the course of therapy, and urinary incontinence and erectile function after the course of therapy as the QOL. RESULTS: The stress during the course of therapy in the patients of group B was obviously less than that of group A. There were no significant differences in urinary incontinence and erectile function after the course of therapy between group A and B. CONCLUSION: In this study, our trial successfully reduced the stress during the course of therapy in the patients with localized prostate cancer in the course of high-dose rate Iridium-192 brachytherapy.

Aged↗

PubMed2001

[High-dose rate iridium-192 brachytherapy combined with external beam radiotherapy for localized prostate cancer].

PURPOSE: We report our technique and also preliminary results in the cases with localized prostate cancer treated by the combination of high-dose rate Iridium-192 (HDR-Ir192) brachytherapy and external irradiation. MATERIALS AND METHODS: From June 1999 to August 2000, 17 patients were treated by the combination of HDR-Ir 192 and external beam. The mean age of patients was 72 years (range, 48-81 years). The clinical stage was B1 in 5, B2 in 7 and C (no cancer with seminal vesicle) in 5 cases. Of 10 patients without neoadjuvant hormonal therapy, the median initial pretreatment PSA was 15.3 ng/ml (6.93-222.32 ng/ml). The treatment was given by HDR-Ir 192 brachytherapy (6 Gy x 3 times/2 days) and external beam irradiation (40 or 45 Gy). The brachytherapy was given using TRUS guided percutaneously inserted temporary needles with a high dose rate remote afterloading control. Local control was evaluated by digital rectal examination. TRUS-guided biopsies and serum PSA evaluations. Follow-up ranged from 2 to 14 months, with a median of 8 months. RESULTS: In 4 (40.0%) of 10 patients without neoadjuvant hormonal therapy the level of serum PSA was decreased to less than 4.0 ng/ml within 3 months after the therapy. The effective grade in the biopsy specimens of 8 patients without neoadjuvant hormonal therapy was Grade Ob in 4, Grade 1 in 1, Grade 3 in 3 cases at 3 months after the therapy. No severe intra- or peri-operative complications occurred. CONCLUSION: The combined radiotherapy treatment is safe and effective for use in the patients with localized prostate cancer. However, more comprehensive studies involving long-term follow-up and great numbers of the cases with localized prostate cancer treated by the combination of HDR-Ir 192 brachytherapy and external irradiation will be necessary to determine whether this therapy contributes to better prognosis.

Aged↗

PubMed2001

[Heart failure].

Explore the source record for details and available documents.

Adult↗

PubMed2000

Soft dipole resonance in the neutron-skin nucleus 6He

A candidate for a soft dipole resonance, a dipole oscillation mode between a core cluster and a neutron skin, was observed at Ex = 4+/-1 MeV and with a width of 4+/-1 MeV in 6He via the 6Li( 7Li, 7Be) reaction at an incident energy of 65A MeV and forward scattering angles including 0 degrees. Its cross section is deduced to be sigma(0 degrees ) = 0.9+/-0.2 mb/sr. This value is comparable to that of the giant dipole resonance simultaneously measured.

Journal Article↗

PubMed2000

Experimental autoimmune myocarditis and its pathomechanism.

The pathomechanisms of autoimmune myocarditis are quite different from viral infection. In this type of myocarditis, cardiac myosin fragments, proper dendritic cells and autoreactive T cells are the 3 major elements in initiating and promoting the inflammation. The causative epitope is locating on the S2 rod portion of the myosin heavy chain (MHC). Through our recombinant study, the peptide was found to be located on the latter half of MHC residues 1070 to 1165. Activity of antigenicity was not different between alpha and beta chain. The cardiac dendritic cell presents a unique structure with large mononuclear and interdigitating processes. This antigen presenter is quickly activated and suppressed by the antigen. The autoreactive T cell is closely linked with cytokine production. In the initial stage of myocarditis, IL-2 and IL-12 are increased. According to the progression of inflammatory changes, a great amount of IL-1b, INF-gamma and TNF-alpha is released around the diseased tissue. At the same time, NO is massively produced from infiltrating macrophages. Cytokines secreted from inflammatory cells accelerate T cell induction from Th0 to Th1. In the convalescent stage, production of TGF-beta 1 and IL-10 become dominant. They contribute to cell induction from Th0 to Th2.

Animals↗

PubMed2000

Microvasculature of hydronephrotic kidneys in KK-A(Y) mice.

Spontaneous hydronephrosis in KK-A(Y) mice was studied using light and electron microscopy and scanning electron microscopy of resin casts to evaluate micro vascular changes in the kidney. The renal parenchyma was extremely thin as a result of tubular atrophy. Histologically, varying degrees of glomerulosclerosis were observed. Ultrastructurally, marked thickenings of the glomerular basal lamina, an increase in mesangial cells and matrix, and marked effacement of foot processes were observed. In resin casts, a marked reduction in number of glomeruli was evident. The capillaries were thin, strangulated and tom-off to varying degrees in severely affected glomeruli. In the medulla, the three-dimensional capillary network running along the tubules was lost and changed to a two-dimensional vascular bed. Despite severe hydronephrosis, the glomerular capillary network was relatively well preserved, being either slightly or moderately injured in approximately 60% of surviving glomeruli.

Animals↗

PubMed2000

Effect of recombinant human granulocyte colony stimulating factor on lymphocyte blastogenesis in healthy dogs.

Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the number and blastogenesis of lymphocytes were evaluated in clinically healthy dogs treated subcutaneously with rhG-CSF at a dose of 2.5 microg/kg for 3 days. Significant increases in the number of leukocytes and segmented neutrophils were observed after the administration of rhG-CSF. The number of lymphocytes also increased on days 1 and 2 after the treatment. Activities of phytohemagglutinin, concanavalin A, and pokeweed mitogen-induced lymphocyte blastogenesis (LB) were augmented to twice the pretreatment levels by the administration of rhG-CSF. These results suggested that administration of rhG-CSF activated lymphocyte functions such as LB in healthy dogs.

Animals↗

PubMed2000

Anti-CD2 monoclonal antibodies prevent the induction of experimental autoimmune myocarditis.

We investigated the effect of a monoclonal antibody against CD2 molecules (OX34) in preventing the induction of experimental autoimmune myocarditis (EAM) induced by immunizing Lewis rats with cardiac myosin. Administration of OX34 before immunization, on Days -6, -4, -2 and 0, completely prevented EAM. On the other hand, treatment with OX34 just before the appearance of myocardial lesions, on Days 9, 11, 13 and 15, had only a partial effect in preventing the disease. Flow cytometric analysis of lymph node cells showed that CD3+ T cells were immediately depleted with the administration of OX34 but had largely recovered on Day 21. Lymph node cells in OX34-treated rats had no proliferative responses to cardiac myosin-rod, but the proliferation was restored when recombinant IL-2 was added. Ultimate production of the anti-myosin antibody was not inhibited by the treatment with OX34. These results suggest that the prevention of EAM by administering the anti-CD2 monoclonal antibody OX34 resulted from T cell depletion during the induction phase, and might in addition result from T cell anergy of Th1, but not Th2 cells.

Animals↗

PubMed2000

Influence of castration on development of the thymus in neonatal male rats.

The influence of castration on the development of the thymus in neonatal rats was studied to elucidate when after birth the thymus comes under inhibitory regulation by the testis in rats. The relative and absolute weights of the thymus were measured five days after castration these cases. No excessive changes in the weights of the thymus with castration were observed by 31 days after birth. Significant changes in the thymus appeared in the relative weight at 36-day-castration. The absolute weight of the thymus was also significantly increased after 41-day-castration. These findings suggest that in rats the inhibitory regulation of the thymus by testis development does not appear before at least 31 days of age.

Aging↗

PubMed2000

Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment.

We have described fatty liver, diagnosed by computed tomography scanning (CT) in more than 30% of patients with breast cancer who received tamoxifen. Therefore, it is urgent to elucidate the frequency and the degree of fatty liver induced by toremifene, an analogue of tamoxifen, which is also used in breast cancer. We enrolled 52 breast cancer patients who were treated with breast-conservation treatment and administered oral toremifene for 3-5 years as adjuvant endocrine therapy. We evaluated the degree of fatty liver by abdominal CT performed annually. CT demonstrated toremifene-induced fatty liver in four (7.7%) of 52 breast cancer patients. Toremifene-induced fatty liver did not correlate with abnormal levels of AST, ALT, GGT or total cholesterol. One patient who demonstrated moderate fatty liver by CT was histologically diagnosed as non-alcoholic steatohepatitis (NASH) by liver biopsy. The incidence of toremifene-induced fatty liver was significantly lower than that induced by tamoxifen. Accordingly, in terms of fatty liver and NASH, toremifene is considered to be more appropriate agent than tamoxifen. Though toremifene is less likely to induce fatty liver, the possibility remains that toremifene-induced steatohepatitis occurs. Because the diagnosis of fatty liver or NASH can be easily missed if only a blood test is performed, it is necessary to screen fatty liver by annual CT examination for patients who receive an antiestrogen agent.

Alanine Transaminase↗

PubMed2000

Ionizing radiation-induced apoptosis in human lymphoma cell lines differing in p53 status.

Most of malignant lymphomas have been shown to be relatively radiosensitive clinically, but some, especially recurrent ones, are frequently highly radioresistant. To clarify the origin of the difference, we examined ionizing radiation (IR)-induced apoptosis in three closely related human lymphoma cell lines (DL-40, DL-95, and DL-110) that differ in p53 status. DL-95 and DL-110 cells have a wild-type p53, whereas DL-40 cells carry a T to G transition in exon 5 of the p53 gene, resulting in a change of Cys to Phe at codon 176. Irradiation of DL-40 cells (mutant-type p53) with 5 Gy gamma-rays resulted in delayed apoptosis with membrane changes (annexin-V expression) 13 h after IR, and caspase-3 activation 23 h after IR, whereas apoptotic response was not identified in DL-95 cells until 48 h after IR in spite of their normal p53 status. Concerning DL-110 cells, delayed and reduced apoptotic response was revealed both microscopically and by DNA fragmentation assay. These results suggested that IR-induced apoptosis in DL-40 cells is mediated by a mechanism involving the caspase-3 cascade of the p53-independent pathway, and that some unknown mechanism inhibited IR-induced apoptosis in existence of wild-type p53, especially for DL-95 cells.

Annexin A5↗

PubMed1999

Late pathologic changes in guinea pig kidneys irradiated with conventional fractionation and hyperfractionation.

PURPOSE: The aim of this study was to determine the differences in renal damage particularly associated with the effect of a small dose per fraction with a constant total dose. METHODS AND MATERIALS: Guinea pigs, 12-week-old English Hartley females, were used. The animals were divided into five groups according to irradiation schedule: No irradiation (control group); 2.0 Gy x 1/day, 5 fraction (f)/week (wk), 40 f, total 80 Gy (Group CF-2.0 [CF = conventional fractionation]); 1.0 Gy x 2/day, 10 f/wk, 80 f, total 80 Gy (Group HF-1.0 [HF = hyperfractionation]); 3.0 Gy x 1/day, 5 f/wk, 27 f, total 81 Gy (Group CF-3.0); and 1.5 Gy x 2/day, 10 f/wk, 54 f, total 81 Gy (Group HF-1.5). Only unilateral irradiation was performed. A histologic analysis was performed before irradiation and at 6 and 12 months after the completion of irradiation. The severity and severity ratios of urinary tubule atrophy, the number of large nuclei per unit area in the renal tubules, the average diameter of the glomeruli, and the number of cells composing the glomerulus were used as parameters for evaluating renal damage. RESULTS: In Groups CF-2.0 and CF-3.0 (the conventional fractionation [CF] groups), all the renal tubules showed severe atrophy 12 months after irradiation. On the other hand, only 20% of the renal tubules showed slight atrophy in Group HF-1.0 at 12 months. In Group HF-1.5, 70% of the renal tubules were atrophic at 12 months. The number of large nuclei markedly increased in Groups HF-1.0 and HF-1.5 (the hyperfractionation [HF] groups) at 12 months, whereas the number was very low in the CF groups at 12 months. Only in Group HF-1.0 had the average diameter of glomeruli not shrunk at 12 months. The number of cells composing the glomerulus in the CF groups markedly decreased at 12 months. The number of cells in the HF groups was also reduced, however the reduction was not as severe as that observed in the CF groups. CONCLUSION: 1.0 Gy per fraction delivered by HF greatly reduces renal damage even in the 80 Gy-irradiated kidney, which is one of the most radiosensitive organs.

Animals↗

PubMed1999

Transgenic Lewis rats overexpressing the proteolipid protein gene: myelin degeneration and its effect on T cell-mediated experimental autoimmune encephalomyelitis.

Transgenic Lewis rats overexpressing proteolipid protein (PLP) genes in peripheral and central nervous myelin were produced by microinjecting murine genomic PLP sequences into fertilized eggs. The mouse PLP gene shares 98.7% homology in the nucleotide sequence with its rat counterpart, but both are fully identical on protein level. Homozygous rats show tremors early in postnatal life, eventually develop seizures, and die before they reach weaning age, while hemizygous animals are phenotypically normal and have a normal life expectancy. Transgene expression in the central nervous system (CNS) has profound consequences for myelin formation and maintenance: approximately twofold overexpression of PLP/DM-20, as seen in homozygotes, results in apoptosis of mature, and a developmental arrest of the remaining immature oligodendrocytes. Severe dysmyelination ensues, associated with reactive astrogliosis and microglia activation/proliferation. Activation of microglia is also prominent in hemizygous rats with low levels of transgene overexpression. In these animals, myelin sheaths remain intact, but there is low-grade myelin degeneration throughout life witnessed by myelin uptake and activation of microglia and astrocytes, in the absence of the expression of major histocompatibility complex class II gene products. There were no spontaneous lymphocytic infiltrates in areas of myelin degeneration. However, hemizygous LEW.PLP rats were more sensitive to experimental autoimmune encephalomyelitis mediated by T cells specific for PLP, but not another encephalitogenic myelin protein, MBP.

Animals↗

PubMed1999

Evaluation of free radical scavenging activities of antioxidants with an H(2)O(2)/NaOH/DMSO system by electron spin resonance.

An H(2)O(2)/NaOH/DMSO system has been developed for the formation of three free radicals, and the application of the system was examined with the antioxidants ascorbic acid and tocopherol. Superoxide anion, hydroxyl radical,and methyl radical are simultaneously generated in this system. The scavenging activity of ascorbic acid and tocopherol for these radicals was estimated by 5, 5'-dimethyl-1-pyrroline-N-oxide spin trapping electron spin resonance. Both water-soluble and oil-soluble antioxidants could be evaluated by using this system. Ascorbic acid specifically inhibited the superoxide anion and hydroxyl radical, whereas tocopherol suppressed the methyl radical.

Antioxidants↗

PubMed1999

Collagen fiber arrangement in canine hepatic venules.

Cell-maceration/scanning electron microscopy, serial sections and scanning electron microscopy of vascular resin casts were employed to demonstrate the arrangement of collagen fibers in the terminal hepatic venules, involving the central, intercalated and collecting veins in dog liver. In cell-maceration specimens, each collagen fiber was observed to run in various directions, forming a sheath with a compact meshwork of collagen fibers. The collagenous meshwork in the hepatic venules was looser than those of the terminal portal venules and hepatic arterioles. Some collagen fibers formed bundles with an elongated spiral arrangement encircling the wall of the terminal hepatic venules. In resin casts, these venules were observed as a twisted configuration caused by spiral collagen bundles. A helical modification of such connective tissue bundles might provide a mechanically stable vascular structure and permit reversible changes in linear and circumferential vascular dimensions at the terminal tributaries of veins. Round or oval pores with diameters of approximately 9 microns were also observed in the sheath of collagen fibers. These pores, together with the relatively loose collagenous meshwork in the hepatic venules, might play a role in lymphocyte migration from these venules into the surrounding tissue and provide high permeability to the venule walls. No such helical configuration and pores were observed in either the portal venules or the hepatic arterioles.

Animals↗