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Biomedical subjects

Y Obata

Publications and source records attributed to Y Obata.

At least 73 records · Page 4Linked to original sources

18 years of conformation radiotherapy at Nagoya University Hospital.

Conformation radiotherapy is one of the best techniques for minimizing the radiation dose absorbed by the surrounding normal tissue while delivering a high dose to a cancerous target area. The cases of all patients who underwent external irradiation at Nagoya University Hospital from 1975 to 1992 were reviewed. A total of 5740 patients with 6179 lesions were irradiated during this time, and 3795 treatment plans involved radical intended irradiation. Of the 5740 patients, 1017 had head and neck cancer, 982 had cervical cancer, 506 had lung cancer, 439 had primary brain tumors, 308 had esophageal cancer, 1213 had metastatic tumors, and 1275 had other types of tumors. The total number of treatment plans per year decreased from 442 in 1975 to 292 in 1992. Likewise, the percentage of conformation radiotherapy performed in all patients decreased from 29.4% (130/442) in 1975 to 8.6% (25/292) in 1992. It occupied 14.5% (982/6179) of all intended plans, and 20% (775/3795) of radical treatment plans. The conformation technique was used in cases of cervical cancer (72%), esophageal cancer (65%) and primary brain tumors (25%). Boost Conformation radiotherapy represented 2% of all treatment planning and 29% of the conformation radiotherapy. Boost Conformation radiotherapy has recently become more popular and now represents more than 50% of conformation radiotherapy. With respect to cases of cervical cancer, the rates of local recurrence and late complications in cases treated by conformation radiotherapy were lower than in cases treated by two parallel opposed radiotherapy.

Female↗

[Evaluations of a specified number of inhalations and how to assess the contents in metered-dose inhalers].

Many kinds of Metered-Dose Inhalers (MDI) have been clinically available for bronchial asthma. Although manufacturers demonstrate the specified number of inhalations per canister on an attached document or on a plastic bag, the information provided are usually inadequate and inconsistent. They provide no information on the problems of the Metered-Dose Inhalers beyond the maximum specified number of actuations and the time when to exchange for a new one. We examined the technique how to evaluate the contents of MDI and their accuracy. Patients and their parents depended on inaccurate methods, such as shaking the inhalers to listen to the sound of contents, estimating the weight of the canisters and the size of emissions, and only a half of them were able to distinguish between 1/3 and 2/ 3 of remaining doses. Three Metered-Dose Inhalers with anti-inflammatory drugs and one MDI with beta-stimulant supplied consistent doses until they reached the maximum specified number. The 4 MDIs floated in the water in different ways and provided information when to replace for new ones in some MDIs.

Adolescent↗

Inhibitory effect of KBT-3022, a new anti-platelet agent, on infiltration of polymorphonuclear leukocytes induced by leukotriene B4 or formyl-methionyl-leucyl-phenylalanine in mice.

We devised a method for evaluating polymorphonuclear leukocyte (PMN) infiltration in vivo employing an air bleb technique combined with measurement of myeloperoxidase (MPO) activity, and the effects of some anti-platelet agents were evaluated. KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and cilostazol inhibited the increase in MPO activity in the connective tissue around the air bleb induced by leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine (fMLP). Indomethacin inhibited only the fMLP-induced increase in MPO activity, but ticlopidine hydrochloride and acetylsalicylic acid had no effect. Histologic observation confirmed the inhibition of PMN infiltration by KBT-3022. These results indicate that KBT-3022 may be a potent inhibitor of both LTB4- and fMLP-induced infiltration of PMNs.

Animals↗

Stimulating effect of excess iron feeding on spontaneous lung tumor promotion in mice.

This study was undertaken to estimate if dietary iron could stimulate factors which promote spontaneous lung tumorigenesis in A/J mice, by measuring biochemical parameters of oxidative stress on pulmonary nuclei, ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SAT) activities as markers of tumor promotion. Feeding excessive iron (500%) to A/J mice for 28 weeks significantly elevated pulmonary DNA single strand break (DNA-SSB) as well as nuclear thiobarbituric acid reactive substances (TBARS) in connection with the increase of nuclear nonheme iron level. In contrast, nuclear alpha-tocopherol levels in the iron-loaded group significantly decreased as compared to that in the control group. Pulmonary ODC and SAT activities showed increasing tendency on feeding excess iron for 28 weeks. These results suggest that dietary iron stimulates spontaneous lung tumor promotion in A/J mice, partly due to the enhancement of oxidative damage to the pulmonary nuclei.

Acetyltransferases↗

Vitamin E acts as a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice.

The present study was designed to evaluate whether vitamin E could be a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice. Starting at 6 weeks of age, groups were divided into three groups, i.e. A/J mice fed a control diet (A/J control), A/J mice fed a vitamin E-supplemented diet (A/J vitamin E) and ddY mice fed a control diet (ddY control). At the 28th experimental week, nuclear NADPH-driven active oxygen generation, thiobarbituric acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in A/J mice fed a control diet were significantly higher than those in the ddY control group. A/J mice fed Vitamin E for 28 weeks could decrease the levels of TBARS and DNA-SSB with a significant difference, as compared with those in A/J control mice. The nuclear alpha-tocopherol levels in A/J controls were significantly lower than those in ddY controls, on the contrary, the vitamin feeding to A/J mice increased nuclear alpha-tocopherol levels more than that in the ddY controls. At the 40th experimental week, lung tumor incidence and tumor multiplicity (percentage of mice with tumors) in A/J controls were reduced and brought close to those in ddY control mice by vitamin E. Then the alpha-tocopherol level in plasma of A/J controls was significantly lower than the level in plasma of ddY controls, and the level in tumor-bearing mice in A/J controls also showed a lower level with significant difference as compared to that in non-tumor-bearing mice of A/J controls. These results suggest that the difference in susceptibility to spontaneous lung tumorigenesis between A/J and ddY mice partly depends on the difference of oxidative stress on the pulmonary nuclei, and vitamin E can act as a useful chemopreventive agent to reduce spontaneous lung tumorigenesis in mice.

Animals↗

Structure, function, and evolution of mouse TL genes, nonclassical class I genes of the major histocompatibility complex.

In contrast to well-studied "classical" class I genes of the major histocompatibility complex (MHC), the biology of nonclassical class I genes remains largely unexamined. The mouse TL genes constitute one of the best defined systems among nonclassical class I genes in the T region of the MHC. To elucidate the function and the evolution of TL genes and their relationship to classical class I genes, seven TL DNA sequences, including one from a Japanese wild mouse, were examined and compared with those of several mouse and human classical class I genes. The TL genes differ from either classical class I genes or pseudogenes in the extent and pattern of nucleotide substitutions. Natural selection appears to have operated so as to preserve the function of TL, which might have been acquired in an early stage of its evolution. In a putative peptide-binding region encoded by TL genes, the rate of nonsynonymous (amino acid replacing) substitution is considerably lower than that of synonymous substitution. This conservation is completely opposite that in classical class I genes, in which the peptide-binding region has evolved to diversify amino acid sequences so as to recognize a variety of antigens. Thus, it is suggested that the function of TL antigens is distinct from that of classical class I antigens and is related to the recognition of a relatively restricted repertoire of antigens and their presentation to T-cell receptors.

Amino Acid Sequence↗

[Experience and results of application of remote afterloading system (RALS) optimization program for intracavitary treatment of squamous cell carcinoma of the uterine cervix].

An optimization program for a remote after-loading system (RALS) for intracavitary treatment of cancer of the uterine cervix was established in 1982 by Tabushi and his co-workers. This system has been used in our hospital since 1986, using MODULEX. Seventy-three cases of untreated squamous cell carcinoma of the uterine cervix have been treated under RALS, 29 under conventional RALS and 44 under the RALS optimization program. The cumulative 5-year survival rates were obtained for the groups treated under each system by the Kaplan-Meier method. The 5-year survival rate of stage II cases treated under the RALS optimization program was 68.2%, and that of stage III cases 58.5%. On the other hand, that of stage II cases treated under conventional RALS was 56.3%, and that of stage III cases 44.9%. There was no significant difference between these two groups. Local control rates for stage II and III cases were higher than 5 year-survival rates. Among complications, the frequency of grade 2 radiation colitis was 15.9% with the RALS optimization program cases, and that of grade 2 radiation cystitis was 4.5%. We consider the RALS optimization program to be a clinically useful method for the intracavitary treatment of squamous cell carcinoma of the uterine cervix.

Adult↗

TL antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells.

In contrast to broadly expressed classical class I antigens of the major histocompatibility complex, structurally closely related TL antigens are expressed in a highly restricted fashion. Unlike classical class I antigens, TL antigens are not known to be targets of cytotoxic T cells or to mediate graft rejection. Whereas classical class I antigens function as antigen-presenting molecules to T cell receptors (TCR), the role of TL is yet to be defined. To elucidate the function of TL, we have derived transgenic mice expressing TL in most tissues including skin by introducing a TL gene, T3b of C57BL/6 mouse origin, driven by the H-2Kb promoter. By grafting the skin of transgenic mice, we demonstrate that TL can serve as a transplantation antigen and mediate a TCR-alpha/beta+ CD8+ cytotoxic T cell response. This T cell recognition of TL does not require antigen presentation by H-2 molecules. Furthermore, we show that C57BL/6 F1 mice develop CD8+ T cells that are cytotoxic for C57BL/6 TL+ leukemia cells, providing further support for the concept that aberrantly expressed nonmutated proteins such as TL can be recognized as tumor antigens.

Animals↗

Enhancing effect of high dietary iron on lung tumorigenesis in mice.

In our previous reports we indicated that oxidative stress on pulmonary nuclei caused by oxy radicals could be involved in glycerol-enhanced lung tumorigenesis in ddY mice treated with 4-nitroquinoline 1-oxide (4NQO). This study was undertaken to estimate if dietary iron could act as a stimulating factor on lung tumorigenesis in mice treated with 4NQO plus glycerol. Feeding excessive iron to mice treated with these agents significantly increased nuclear thiobarbituric acid reactive substances (TBARS) and DNA single strand breaks (DNA-SSB) in the lungs as compared with mice fed adequate iron 4 weeks after 4NQO injection. Nuclear non-haem iron level in mice fed excessive iron was also higher than the level in mice fed adequate iron. Twenty-three weeks after 4NQO injection (at the end of this experiment) the supply of excessive iron for 4 and 23 weeks after 4NQO injection stimulated the development of lung tumors in mice treated with 4NQO plus glycerol. These results suggest that a high dietary iron level acts as a stimulating factor on lung tumorigenesis in mice treated with 4NQO plus glycerol.

4-Nitroquinoline-1-oxide↗

Effect of vitamin E on 4-nitroquinoline 1-oxide-induced lung tumorigenesis in mice.

Oxidative stress may play a partial role in chemically induced tumorigenesis in mice. Herein, we investigated the preventive effect of vitamin E on 4-nitroquinoline 1-oxide (4NQO)-induced oxidative damage on pulmonary nuclei and lung tumorigenesis in mice. At 4 weeks after 4NQO injection, the levels of nuclear thiobarbituric acid substances (TBARS) and DNA single strand breaks (DNA-SSB) in the lungs of mice treated with 4NQO were significantly higher than those in the control mice. The 4NQO-induced oxidative stress on the nuclei and DNA-SSB were significantly inhibited by vitamin E treatment. The nuclear alpha-tocopherol level in the 4NQO-treated group was significantly lower than that in the control, but the plasma alpha-tocopherol level in the former was slightly lower than that in the latter. Vitamin E feeding compensated the decrease of the level in the nuclei and plasma. The feeding on excessive vitamin E for 23 weeks after 4NQO injection could partly reduce the lung tumor incidence as well as lung tumor multiplicity in mice. These findings suggest that vitamin E could partly suppress 4NQO-induced lung tumorigenesis in mice, probably through the inhibition of 4NQO-induced oxidative damage on the nuclei.

4-Nitroquinoline-1-oxide↗

Prediction of skin permeabilities of diclofenac and propranolol from theoretical partition coefficients determined from cohesion parameters.

The cohesion parameters of diclofenac and propranolol were determined experimentally. The theoretical partition coefficient (Ps,v) was calculated from the activity coefficient (gamma) and the cohesion parameters of the solvent (delta 1 = delta v), solute (delta 2), and skin (delta s). By using the extended Hildebrand solubility equation, the potential energy of solute-solvent interaction in a given solution was considered to have the gamma value derived from solubility data of diclofenac and propranolol in ethanol-aqueous buffer. Values for experimental permeability coefficients (Kp), which were determined from flux and solubility, were compared with values for the respective Ps,v. For a solvent that consists of ethanol-aqueous buffer exhibiting cohesion parameters in the range of delta v = 18-24 (cal/cm3)1/2, the fluxes increased and the Kp decreased because of the similarity in cohesion parameters of these solvents to the solute. The difference between Ps,v and experimental Kp suggests that ethanol in the solvent affects the membrane and diclofenac and propranolol penetrate through the membrane, possibly solvated by ethanol.

Animals↗

Isolation and characterization of mouse CD7 cDNA.

The human CD7 antigen is a glycoprotein, M(r) 40,000, expressed on the surface of peripheral blood T-lymphocytes and thymocytes, and is the earliest surface antigen to appear on T-cell lineage cells. In this study, putative mouse CD7 cDNA was identified based on its similarities with human CD7. Five independent clones originating from the same mRNA species were isolated (designated as mCD7) by screening a mouse thymocyte cDNA library with human CD7 cDNA, J61, under moderate stringency. The longest insert of a 995 base pair had an open reading frame of 210 amino acids. Northern blot analysis using the mouse CD7 cDNA probe demonstrated a single 1.2 kilobase mRNA in the thymus, spleen, bone marrow, and small intestine. The protein deduced from mCD7 cDNA consisted of the leader, extracellular, transmembrane, and cytoplasmic domains of 24, 126, 21, and 39 amino acids, respectively, based on the hydrophobicity plot and the structure of human CD7. The extracellular domain contained three potential N-glycosilation sites, while the cytoplasmic domain contained one potential protein kinase C phosphorylation site. The amino acid sequence had 45.5% similarity with human CD7, while the similarities for the individual domains ranged from 49.2% to 63.2%. The six highly conserved regions, which may possibly be involved with still unknown CD7-mediated functions, were located in the extracellular and cytoplasmic domains.

Amino Acid Sequence↗

Effect of pretreatment of skin with cyclic monoterpenes on permeation of diclofenac in hairless rat.

The promoting effect of d-limonene and l-menthol on the percutaneous absorption of nonionized and ionized diclofenac (DF) was investigated employing a pretreatment method. After the pretreatment of hairless rat skin with an ethanol buffer solution containing terpenes, the permeation study was performed in vitro. The permeability coefficients of nonionized (Pn) and ionized diclofenac (Pi) were calculated under the assumption that the total flux was composed of individual fluxes of nonionized and ionized DF. In the case of pretreatment with d-limonene, both Pn and Pi values were increased dramatically. However, the promoting magnitude was not affected by an extension of the pretreatment period. In contrast, when the skin was pretreated with l-menthol, the Pn and Pi values increased gradually as the pretreatment period increased. Based on the measurement of the solubility of terpenes in the pretreatment solution, the difference in promoting efficiency could arise from the difference in thermodynamic activity of the terpenes.

Animals↗

Non-specific immunological abnormalities and association of autoimmune diseases in idiopathic portal hypertension. A study by questionnaire.

A large survey by questionnaire of idiopathic portal hypertension (IPH) in Japan disclosed that 11.9% of 160 cases were associated with one or two autoimmune diseases, and 26.3% of them disclosed hypergammaglobulinemia. Patients with IPH also frequently showed one or more autoantibodies in the serum, such as antinuclear or anti-smooth muscle antibodies. These findings overlapped frequently in the same patient. These data imply that immunological disturbance and/or chronic antigenic stimulation are related to the pathogenesis of IPH, though the exact immunological mechanisms remain unclear. It will be necessary to study more specific immunological reactions in IPH.

Autoantibodies↗

A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Phenotypic and genotypic findings were correlated and compared for 35 specimens taken from 34 patients with three specific types of low-grade peripheral T-cell lymphoma: lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphoma. Frozen sections were stained by the double immunoenzymatic method using a combination of the monoclonal antibody Ki-67 for proliferating nuclei and those against lymphocyte surface antigens. Data were correlated by observing clonal rearrangements in the genes of the T-cell receptor beta chain (TCR beta). Of the 35 specimens studied, 32 (91%) were of predominantly CD4+ helper cell proliferation, and 21 (60%) showed the TCR beta gene rearrangement. There were 15 cases of AILD and TzL with predominantly helper cell proliferation, which contained a minimum of 21% CD4+Ki-67+ cells based on the total number of cells present in the specimen. Of these, 13 (87%) showed TCR beta rearrangement. In eight cases, containing a maximum of 20% CD4+Ki-67+ cells, only one (13%) showed any rearrangement. In addition, TCR beta rearrangement was observed in five of the nine cases of LeL, including two cases with only 12% CD4+Ki-67+ cells. For each of the three types, the proportion of CD4+ cells among the Ki-67+ population showed a relatively good correlation with the clonal TCR beta gene rearrangement. Moreover, there was a significant difference (P less than 0.05) in survival curves between groups with and without TCR beta rearrangement, although no obvious plateau was seen. These results suggest that the paucity of tumor cells in these lesions may account for the absence of a detectable band of rearrangements in some patients with one of these three specific types of low-grade peripheral T-cell lymphoma.

Antigens, CD↗