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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 559 records · Page 31Linked to original sources

[A case of chronic empyema due to tuberculosis with bronchopleural fistulae treated successfully by extraperiosteal air plombage thoracoplasty and omentoplasty].

A 63-year-old man, who had undergone induction of artificial pneumothorax at 20 years of age as a treatment for right tuberculosis, developed fever and cough. A chest X-ray film showed marked pleural effusion in the right chest. Examination of sputum and the pleural effusion revealed tubercle bacillus, and right tuberculous empyema was diagnosed. At surgery, the right thoracic cavity was occupied by empyema, and multiple bronchopleural fistulae were observed. Because of the presence of tubercle bacilli in the empyema cavity, extraperiosteal air plombage thoracoplasty was insufficient for control of the empyema. Therefore, omentoplasty was added. Two months after the operation, the patient was discharged in good condition. He has been doing well without any sign of recurrence of empyema for the last two years. Although extraperiosteal air plombage thoracoplasty is a considerably effective therapy for empyema, its curability rate is lower in cases like the present one in which bronchopleural fistulae and bacteria are present in empyema cavity, such as our case. We consider that our method, extrapriosteal air plombage thoracoplasty with omentoplasty, is a reliable one for control of empyema, in patient with high risk factors for recurrence, such as bronchopleural fistulae and bacteria in the cavity.

Bronchial Fistula↗

Prolongation of kidney graft survival by cyclophosphamide-induced tolerance in rats.

In this study, we have extended a cyclophosphamide (CP)-induced tolerance system to kidney transplantation in rats to examine whether or not we can overcome fully allogeneic (major histocompatibility complex plus minor histocompatibility) antigen barriers in organ transplantation. In the recipient Lewis (LEW, RT1(1)) rats that were primed intravenously with 4 x 10(8) spleen cells plus 2 x 10(8) bone marrow cells from Brown-Norway (BN, RT1n) rats and treated intraperitoneally with 100 mg./kg. of cyclophosphamide (CP) 2 days later, the survival of kidney allografts, but not skin allografts, from BN was prolonged as compared with that in the untreated LEW rats. Some of the kidney allografts survived for more than 100 days without further immunosuppressants. The tolerant state induced was tolerogen specific, and the suppression of tissue damage of the grafted kidney in such tolerant rats was also confirmed by the histopathological findings of the grafted kidney. These results indicate that considerable levels of tolerance can be induced, at least in organ transplantation, across fully allogeneic antigen barriers in rats by a CP-induced tolerance system. We believe that the present study is the first step in applying our CP-induced tolerance system using skin grafting in the murine model to clinical organ transplantation.

Animals↗

The relative significance of repopulation and hypoxic clonogens in the fractionated radiotherapy of a mouse tumor.

The aim of this study was to analyze the significance of the repopulation of tumor cell clonogens, reoxygenation and hypoxic cells for the outcome of fractionated radiotherapy. Our previous fractionation study using a murine tumor was used for the analysis (Nishimura and Urano, Int. J. Radiat. Oncol. Biol. Phys. 29, 141-148, 1994). In the previous study, single cell suspensions were prepared from the early-generation isotransplants of a spontaneous fibrosarcoma, FSa-II, in a C3Hf/Sed mouse and transplanted into the foot of C3Hf/Sed mice. Fractionation schedules consisted of equal graded daily doses (1-20 fractions) given in air or under hypoxic conditions with 137Cs. Treatment was initiated when tumors reached an average diameter of 4 mm. A twice-a-day (b.i.d.) irradiation was tested for 20 doses. Tumor control was the end point, and the TCD50 (50% tumor control dose) was obtained. The surviving fractions resulting from these TCD50 doses were calculated using the alpha and beta values for the FSa-II cells, assuming that these values were constant throughout the fractionation period. These surviving fractions were used to calculate the clonogen repopulation and the reoxygenation of the hypoxic cells. Tumor clonogens repopulated rapidly and the hypoxic cells appeared to reoxygenate substantially during 10-20 doses. In the fractionation regimens consisting of more than 5 doses, the repopulation became significant. This rapid repopulation was reflected as a small alpha/beta ratio on the Fe plot. During 20 daily doses given under hypoxic conditions, clonogens (including both oxygenated and hypoxic) repopulated by a factor of 1.9 x 10(6). The hypoxic clonogens (based on the TCD50 after doses in air) repopulated to a much lesser extent than did the total clonogens. Reoxygenation was not substantial up to 5 daily doses but appeared to become significant during 10 to 20 doses. The magnitude of reoxygenation appeared to be substantially greater during 20 daily doses than during 20 b.i.d. doses. The significance of the hypoxic cells appeared to be less with increasing fractionation for the tumor control, but still remained critical in 20 daily doses. This study also suggested that the inhibition of clonogen repopulation could improve the outcome of radiotherapy, but this inhibition should be accompanied by further reoxygenation as long as hypoxic clonogens remain critical for the tumor control.

Animals↗

[Clinical usefulness of polyamino acid particle agglutination test for detection of anti-HTLV-I antibody].

A new artificial carrier particle agglutination test using polyamino acid (polyamino PA) was developed for anti HTLV-I assay. We carried out the comparative study on anti-HTLV-I among polyamino PA, gelatin PA, EIA and WB methods. All of 76 ATL, 20 HAM/TSP, 53 patients with uveitis and 50 HTLV-I carriers were seropositive and 50 HTLV-I non carriers were seronegative with four methods. Eighteen of 503 patients include autoimmune diseases showed seropositive by polyamino PA and gelatin PA. One of 19 seropositives by EIA was false positive. All of 25 sera showed non-specific reaction by the gelatin PA were clearly negative by the polyamino PA. This is due to the fact that the polyamino acid particle has a greater specific gravity as carrier. The final judgement was got within 45 minutes. It was earlier more 30 minutes than the gelatin PA. The polyamino PA is a simple, rapid, sensitive and specific method. Therefore, it is useful for mass screening and clinical diagnosis.

Agglutination Tests↗

[Bone mineral content in patients with bronchial asthma].

To study the factors related to bone mineral content (BMC) in patients with bronchial asthma (BA), we measured BMC of the whole body, bone mineral density (BMD) in the second, third, and fourth lumbar vertebrae (by dual energy X-ray absorptiometry, DXA XR-26, Norland), and pulmonary function in patients with BA. Subjects were 103 patients with BA and 194 age-matched normal controls. There was no significant difference in BMC or BMD between patients with BA and controls. In patients with BA, there was no significant difference in BMC or BMD between those who were taking steroids and those who were not. BMC and BMD were significantly correlated with age, body weight, VC, %VC, and FEV1, but not with the duration of steroid administration or the total steroid dose administered. These results suggest that patients with BA have normal BMC and that steroid administration does not affect bone mineral loss in such patients.

Asthma↗

The effects of inhibitors and substrates of different types of cytochrome P450 isozymes on serum dimethadione/trimethadione ratio in rats in vivo.

Trimethadione(TMO) is regarded as a model drug for estimating the hepatic drug oxidative capacity in vivo. However, the P450 isozymes that are responsible for TMO N-demethylation have not been identified clearly yet. This study was designed to determine these P450 isozymes that participate in the TMO N-demethylation in vivo by employing several typical P450 inhibitors and substrates. Male Sprague-Dawley(SD) rats were pretreated with P450 inhibitors or substrates before TMO(100mg/kg, p.o.) treatment. Serum dimethadione(DMO)/TMO ratios were employed for the assessment of metabolic capacity toward TMO. Pretreatment with imidazole and acetone significantly decreased the DMO/TMO ratios in a dose related manner. Weaker inhibitory effects were observed with SKF525A. However, pretreatment with alpha-naphthoflavone, quinine, debrisoquine, triacetyloleandomycin and lauric acid did not affect the ratios. These results suggest that various forms of P450 are involved in TMO metabolism to some extent and that CYP2E1 is attributed to major P450 isozyme for TMO N-demethylation in vivo.

Animals↗

[Surgical treatment of interrupted aortic arch with aorticopulmonary window].

From January, 1988, through September, 1993, 3 neonates underwent one-stage repair for interrupted aortic arch (IAA) with aorticopulmonary window (APW). Their mean weight was 3.0 kg (2.7-3.3 kg). IAA was Celloria-Patton classification type B in two patients and type A in the other. In all cases, APW was Mori's classification type II. Two patients took a sudden turn for worse during the stay of our hospital and underwent emergency operation. Surgical procedures were as follows; In the first patient, aortic arch reconstruction was performed with phi 8 mm Golaski graft, under extracorporeal circulation for only upper body under moderate hypothermia. After distal anastomosis, perfusion for lower body was restarted through the graft branch, then proximal anastomosis was done. In the other two patients, arch reconstruction was performed by end to side direct anastomosis under total circulatory arrest and deep hypothermia, and APW was divided during recirculation, rewarming period. In the first patient, graft was anastomosed to the defect of the ascending aorta. In the other two patients the defect of the aorta was directly closed. The defect of the pulmonary artery was closed directly in two patients and with autopericardium in the other. There was no operative deaths. Two cases who underwent emergency operation due to sudden turn for worse didn't become well soon. Thus, we concluded that surgical intervention should be done as soon as possible before patient became critically ill and one-stage repair should be recommended because of the difficulty of palliation such as PA banding in this disease.

Anastomosis, Surgical↗

Quantification of immunohistochemistry using an image analyser: correlation with hormone concentrations in pituitary adenomas.

The usefulness of immunohistochemistry is usually confined to qualitative analysis. Quantitative evaluation is not performed. At best, the number of immunopositive cells and the immunointensities are recorded as several grades, to which a strict categorization may be applied by individual examiners, but these categorizations are not standardized. We have attempted to quantify immunohistochemical observations using an image analyser. Sections from rat pituitary adenomas secreting prolactin and growth hormone were immunostained for these hormones with either immunogold silver or avidin-biotinylated peroxidase complex (ABC) methods. The number of immunopositive cells were counted by eye on specimens stained with the ABC method. In sections stained by an immunogold-silver technique, an immunopositive area was measured at several immunointensity ranges, to which certain points were allotted. Immunohistochemical values obtained by summing the products of the immunopositive area and intensity points at each range were correlated with concentrations of hormones in adenoma tissues measured by radioimmunoassay. A high correlation between the immunohistochemical values and hormone concentrations were shown for both prolactin and growth hormone, in contrast to a low correlation between the number of immunopositive cells counted by eye and the hormone concentrations. These findings indicate that the immunohistochemical observations can be quantified using the image analyser to the extent that they can be substituted, albeit roughly, for the hormone concentrations measured biochemically.

Adenoma↗

Conformational changes of purine repressor DNA-binding domain upon complexation with DNA.

The purine repressor (PurR) consists of two functional domains: an N-terminal DNA-binding domain and a C-terminal corepressor-binding domain. Recently, the structure of PurR-corepressor-operator ternary complex was determined by X-ray crystallography. In the complex the DNA-binding domain, consisting of 56 amino acids, was composed of four helices. Here, we have determined the solution structure of the DNA-binding domain in its DNA free state by NMR. It consists of three helices and the fourth helix (the hinge helix) region is diordered. The architecture of the first three helices of its DNA free state is very similar to that of its DNA-bound form. The hinge helix is induced by the specific DNA binding and by the dimerization of PurR which is provided by the corepressor-binding domain.

Bacterial Proteins↗

Esophageal cancer treated with radiotherapy: impact of total treatment time and fractionation.

PURPOSE: Local control rate and survival rate of esophageal cancer treated with radical radiation therapy (RT) were analyzed with special respect to total treatment time and fractionation. METHODS AND MATERIALS: Between 1979 and 1992, 88 patients with Stages I-III esophageal cancer were treated radically with RT at Kyoto University Hospital and Wakayama Red Cross Hospital. Of the 88 patients, 52 patients were treated with conventional fractionation (1.7-2.0 Gy/day, five times/week), and the remaining 36 patients were treated with accelerated hyperfractionation (AHF). In 1989, we started AHF regimen for esophageal cancer. Daily fractionations were 2.0 Gy and 1.2 Gy (field-in-field), or 1.5 Gy and 1.5 Gy at 5- to 6-h interval. Most of the patients treated with AHF received the total radiation dose of 64-68 Gy. Twenty-seven patients were treated with intraluminal brachytherapy (IBT) as boost therapy following external RT. Fourteen patients were treated with IBT following AHF. RESULTS: The median of treatment time of AHF was approximately 2 weeks shorter than that of conventional fractionation. Local control rate at 1 year were 47% for AHF, which was significantly higher than that for conventional fractionation (22%, p < 0.05). The improvement of local control by AHF was responsible for a trend to an improved cause-specific survival (p = 0.07). Local control rates at 1 year were plotted as a function of total treatment time. The slope of the linear regression line was -2.3 +/- 0.5% per day (p < 0.025) for patients treated with external RT alone, indicating a 2.3% per day loss in local control. Pretreatment and treatment parameters were evaluated in a multivariate analysis for the end point of local control. T stage (T1, 2 vs. T3, 4; p = 0.003) and fractionation schedule (p = 0.03) were independent of prognostic significance. Patients could tolerate the AHF well, although esophageal stenosis was noted frequently as a late toxicity. CONCLUSION: Accelerated hyperfractionation was the most important treatment-related variable in this patient population. Total treatment time may have a significant impact on the treatment outcome for esophageal cancer.

Adenocarcinoma↗

Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices.

The DNA-binding region of Myb consists of three imperfect tandem repeats (R1, R2, and R3). We have determined the solution structure of a specific DNA complex of the minimum DNA-binding domain (R2R3) by heteronuclear multidimensional NMR. Both R2 and R3 contain three helices, and the third helix in each is found to be a recognition helix. R2 and R3 are closely packed in the major groove, so that the two recognition helices contact each other directly to bind to the specific base sequence, AACNG cooperatively; this is a significant arrangement of recognition helices. The three key base pairs in this sequence are specifically recognized by Asn-183 (R3), Lys-182 (R3), and Lys-128 (R2). In contrast, R1 has no specific interactions with DNA from our NMR study of the DNA complex of the full DNA-binding domain (R1R2R3).

Amino Acid Sequence↗

Three-dimensional treatment planning for maxillary cancer using a CT simulator.

PURPOSE: The results of three-dimensional treatment planning using a computed tomography simulator were evaluated in patients with maxillary cancer. METHODS AND MATERIALS: Treatment planning was done in 25 patients using an x-ray simulator and plain x-ray films (1979-1982, group 1) in 34 patients using an x-ray simulator and computed tomography films (1983-1987, group 2), in 24 patients using a computed tomography simulator (1988-1992, group 3). The number of patients with Stage IV disease increased in the order of group 1 to group 3. RESULTS: The average radiation field was smallest in group 3 (66.5 cm2) followed by group 2 (67.4 cm2) and group 1 (72.9 cm2). A radiation dose of more than 30 Gy to the lens of the effected side was delivered to 13% of group 3, 44% of group 2, and 44% of group 1. The dose to the lens on the uneffected side was zero in 56% of group 1, 74% of group 2, and 96% of group 3. A long-term decrease in visual activity on the effected side occurred in 11% of group 3, 32% of group 2, and 44% of group 1. However, a significant increase in survival was only noted between groups 1 and 2, because the three population of patients were different. CONCLUSION: The three-dimensional treatment planning results in a better treatment than two-dimensional treatment planning as measured by complication rates and field sizes.

Aged↗

Amelioration of acute graft-versus-host disease and re-establishment of tolerance by short-term treatment with an anti-TCR antibody.

We investigated whether tolerance can be re-established in mice with graft-vs-host disease (GVHD) by using a short-term, T cell-depleting treatment with an anti-TCR-alpha beta mAb. GVHD was induced in 950-rad-irradiated AKR mice (H-2k, Mls-1a) by injecting 5 x 10(6) T cell-depleted bone marrow cells together with either 10(7) or 2 x 10(6) lymph node (LN) cells from BALB/c mice (H-2d, and Mls-1b). AKR mice that received 10(7) LN cells exhibited a severe form of acute GVHD, in which all mice died by day 60. In this severe form of GVHD, treatment with anti-TCR-alpha beta mAb completely ameliorated the induction of GVHD when initiated on day 0 (a total of 800 micrograms/mouse administered on days 0,5, and 10). When the same protocol was begun on day 10, it had no therapeutic effect. However, this delayed treatment with anti-TCR-alpha beta mAb was very effective in reversing a less severe form of GVHD that was induced by the injection of 2 x 10(6) donor LN cells. Recipient mice given prophylactic anti-TCR-alpha beta treatment achieved host-specific tolerance in association with clonal deletion of host Mls-1a-reactive V beta 6+ T cells. In contrast, spleen cells from recipient mice that recovered from the mild form of GVHD as a result of the delayed anti-TCR-alpha beta treatment contained a considerable proportion of the V beta 6+ T cells, despite the healthy appearance of these mice. A MLR assay revealed that the spleen cells from these mice responded well to Mls-1a Ag but not to H-2k Ag, in contrast with the apparent responses of spleen cells from untreated GVHD controls to both Ags. In addition, cells from the anti-TCR-alpha beta-treated mice exhibited a specific reduction in cytotoxicity against AKR blasts. Collectively, these data indicate that a short-term treatment of mice having GVHD with an anti-TCR-alpha beta mAb, starting even after disease onset, can re-establish host-specific tolerance, at least to the host-histo-compatibility Ag.

Acute Disease↗

Energy migration in allophycocyanin-B trimer with a linker polypeptide: analysis by the principal multi-component spectral estimation (PMSE) method.

Energy migration processes in allophycocyanin-B trimer with a linker polypeptide were analyzed using the principal multi-component spectral estimation (PMSE) method, which does not require assumption of component number, decay function, or the spectral band shape. We determined the number of spectral components showing independent kinetic behavior by the eigen-value of an auto-correlation matrix, and further the spectra of the components and their rise and decay curves. Two decay components were resolved at 20 degrees C: one corresponded to the decay of one type of beta-84 chromophore, and the other to the decay from the thermally equilibrated state between another type of beta-84 chromophore and the alpha-allophycocyanin B chromophore. An additional slow decay process was resolved at -196 degrees C. We also compared the component spectra obtained using the PMSE method with the decay-associated spectra obtained using the global analysis.

Cyanobacteria↗

Allele specificity of structural requirement for peptides bound to HLA-DRB1*0405 and -DRB1*0406 complexes: implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome.

Self-peptides bound to HLA-DR4 (DRA-DRB1*0405 complex) were eluted from the purified DR4 complex, fractionated on reverse-phase HPLC, and subjected to NH2-terminal sequencing. Seven independent sequences were obtained, and all putative peptides synthesized bound to DRB1*0405 as well as DRB1*0406 complex, which differ only at DR beta residues 37, 57, 74, and 86. Binding assay using analogue peptides of a DR4 binder GSTVFDNLPNPE revealed that FxxLxN is an important anchor motif necessary for binding (where x is any amino acid), which was common to DRB1*0405 and 0406. Determination of the binding affinity of 60 synthetic AAFAALANAA-based analogue peptides showed that substituting F to W or C; L to F, W, or Y; and N to Q or S on AAFAALANAA changed the affinity substantially between DRB1*0405 and DRB1*0406. It is noteworthy that all patients with methimazole-induced insulin autoimmune syndrome are positive for DRB1*0406 and negative for DRB1*0405. Interestingly, the quantitative structural motif identified in this study predicted that 8TSICSLYQLE17 of human insulin alpha chain may bind specifically to DRB1*0406 using its 10IxxLxQ15 motif. Indeed, DRB1*0406 complex bound 8TSICSLYQLE17 with a high affinity, and in striking contrast, DRB1*0405 complex did not. Furthermore, a short-term T cell line specific to human insulin established from a DRB1*0406-bearing individual did show reactivity with a peptide fragment containing the 10IxxLxQ15 motif. Although this fragment probably exists at a very low level under normal physiological conditions due to the disulfide bond between flanking cysteine residues (6Cys-11Cys), a reducing compound such as methimazole may cleave the disulfide bond in vivo and allow DR alpha-DRB1*0406 complex on antigen-presenting cells to bind much of the linear fragment of insulin alpha chain, which may lead to the activation of self-insulin-specific T-helper cells.

Alleles↗

Cytotoxicity of fresh NK1.1+ T cell receptor alpha/beta+ thymocytes against a CD4+8+ thymocyte population associated with intact Fas antigen expression on the target.

Recent studies have revealed that 10-20% of CD4+8- or CD4-8- thymocyte populations contain NK1.1+ T cell receptor (TCR)-alpha/beta+ cells. This subpopulation shows characteristics that are different from NK1.1- CD4+ or NK1.1- CD8+ T cells and seems to have developed in a manner different from NK1.1- T cells. Although extensive studies have been performed on the NK1.1+ TCR-alpha/beta+ thymocytes, the physiological role of the NK1.1+ TCR-alpha/beta+ thymocytes has been totally unclear. In the present study, we found that freshly isolated NK1.1+ TCR-alpha/beta+ thymocytes, but neither whole thymocytes nor lymph node T cells, directly killed CD4+8+ thymocytes from normal syngeneic or allogeneic mice by using a long-term cytotoxic assay in which flow cytometry was used to detect the cytotoxicity. However, only weak cytotoxicity was detected against thymocytes from lpr mice on which the Fas antigen that transduces signals for apoptosis into the cells is not expressed. Furthermore, the NK1.1+ TCR-alpha/beta+ thymocytes exhibited high cytotoxicity against T lymphoma targets transfected with fas genes as compared with the parental T lymphoma targets or target cells transfected with mutated fas genes, which lack the function of transducing signals. On the other hand, NK1.1+ effector thymocytes from gld mice that carry a point mutation in Fas ligand did not kill thymocyte targets from normal mice. The present findings, thus, consistently suggest that the NK1.1+ TCR-alpha/beta+ thymocytes kill a subpopulation among CD4+8+ thymocytes via Fas antigen and in this way regulate generation of T lineage cells in the thymus.

Animals↗

The identification of Escherichia coli ispB (cel) gene encoding the octaprenyl diphosphate synthase.

The gene located upstream of the nlp gene at min 69 on the chromosome of Escherichia coli was cloned from the plasmid pLC7-42 constructed by Clarke and Carbon. The extract of the strain harboring the plasmid containing this gene showed increased activity of the prenyltransferase. The product of the enzyme reaction was analyzed by two systems of the thin-layer chromatography and shown to be the phosphate ester of all-E-octaprenol. These results suggested that the gene was the structural gene for the octaprenyl diphosphate synthase which supplied the precursor of the side chain of the isoprenoid quinones.

Alkyl and Aryl Transferases↗