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Biomedical subjects

Y Nishimura

Publications and source records attributed to Y Nishimura.

At least 793 records · Page 44Linked to original sources

[A case of carcinoma of the esophagus involving the trachea undergoing anterior mediastinal tracheostomy with pedicled omental wrapping].

A 62-year-old male who complained of dysphagia, body weight loss and hoarseness was admitted to our hospital. Chest x-ray film disclosed right superior mediastinal mass compressing membranous portion of trachea. Esophageal fiberscope revealed carcinoma of cervical esophagus. Bronchofiberscope revealed the paralysis of right recurrent laryngeal nerve and the invasion of esophageal cancer to tracheal membranous portion from the 5th tracheal ring to the 12th. The cancer also invaded the right lobe of thyroid which was shown by echogram. Operation was performed. On dissecting the cervical region, it was found that the tumor invaded both sides of the trachea so that tracheal reconstruction could not be done without injuring left recurrent laryngeal nerve. Sternotomy was added. Anterior mediastinal tracheostomy was done after laryngeal resection with total thoracic esophagectomy and tracheal resection leaving 5 rings long cartilage from carina. The trachea was wrapped with pedicled omentum. Post-operative course was uneventful. This procedure helps to increase blood supply to the tracheal anastomosis and turns to advantage in preventing infectious extension around trachea to mediastinum as well as tracheal compression to major vessels.

Esophageal Neoplasms↗

Evidence for involvement of clonal anergy in MHC class I and class II disparate skin allograft tolerance after the termination of intrathymic clonal deletion.

Mechanisms of cyclophosphamide (CP)-induced tolerance to class I (D) and class II (IE) alloantigens were studied. Transplantation tolerance across H-2D plus IE Ag-barriers has been achieved when B10.Thy-1.1 (Kb,IAb,IE-,Db; Thy-1.1) mice were primed i.v. with 9 x 10(7) spleen cells plus 3 x 10(7) bone marrow cells from B10.A(5R) mice (5R; kb,IAb,IEb,Dd; Thy-1.2) and treated i.p. with 200 mg/kg of CP 2 days later. The tolerant state in the early and the late stage was confirmed by prolonged acceptance of donor-type skin grafts, and in vitro unresponsiveness to donor Ag. In the tolerant B10.Thy-1.1 mice treated with 5R cells 28 days earlier and followed by CP, intrathymic clonal deletion of V beta 11+ T cells reactive to IE-encoded antigens was observed in association with intrathymic mixed chimerism. 5R skin survived, however, even after the clonal deletion of V beta 11+ T cells terminated by 180 days after tolerance induction. V beta 11+ T cells, which reappeared in the periphery of the recipient B10.Thy-1.1 mice bearing 5R skin at this stage, were not capable of proliferating in response to receptor cross-linking with V beta 11-specific mAb. Furthermore, the CTL activity against class I (Dd) alloantigens of spleen cells from these tolerant mice was restored by the addition of IL-2 to MLC. Thus, our experiments provide direct evidence that tolerance to both class I (Dd) and class II (IEb) alloantigens by clonal allergy occurs during the termination of intrathymic clonal deletion. These results clearly show practical hierarchy of the mechanisms of transplantation tolerance.

Animals↗

The tryptophan cluster: a hypothetical structure of the DNA-binding domain of the myb protooncogene product.

In the DNA-binding domain of the c-myb protooncogene product (c-Myb) which consists of three repeats of 51-52 amino acids, there are 3 perfectly conserved tryptophans in each repeat. Site-directed mutagenesis of these tryptophans showed that any single or multiple mutations of tryptophan to hydrophilic residues or alanine abolished or greatly reduced the sequence-specific DNA-binding activity, but mutations to hydrophobic amino acids retained considerable activity. Raman spectroscopic study showed that these tryptophans were buried in the protein core. These 3 tryptophans are proposed to form a cluster in the hydrophobic core in each repeat. This hypothetical structure is referred to as the "tryptophan cluster," and it may represent a characteristic property of a group of DNA-binding proteins including the myb- and ets-related proteins.

Animals↗

Simultaneous determination of ampicillin and sulbactam by liquid chromatography: post-column reaction with sodium hydroxide and sodium hypochlorite using an active hollow-fibre membrane reactor.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of ampicillin (ABPC) and sulbactam (SBT) in serum and urine. The method involves separation of ABPC and SBT from the background components of serum and urine on a C18 column, post-column reaction with sodium hydroxide and sodium hypochlorite using an active hollow-fibre membrane reactor, and detection at 270 nm. At ABPC and SBT concentrations of 10 and 5 micrograms/ml in urine and serum samples, the precisions (relative standard deviations) were 0.9-2.5% (n = 8). The detection limits were 20 and 5 ng for ABPC and SBT, respectively, at a signal-to-noise ratio of 3.

Ampicillin↗

[Serum levels of beta-seminoprotein (beta-Sm) in patients with breast cancer].

Serum levels of beta-Sm (a component of human seminal plasma) were measured in patients with breast cancer or mastopathy by RIA method. 9.4 +/- 9.5 ng/ml in control healthy adult women and 11.7 +/- 15.7 ng/ml in 8 patients with mastopathy were observed. Whereas, in 30 patients with breast cancer including 28 pre-operation and 2 recurrence 64.5 +/- 52.3 ng/ml were observed. Especially, high levels of beta-Sm (135.8 and 182.3 ng/ml) in the recurrence were detected. Each case of 8 post-operation was below 50 ng/ml. Fifty-seven percent of patients with breast cancer including pre-operation and recurrence were showed over 50 ng/ml. In histological typing, the beta-Sm levels of papillotubular carcinoma were higher than that of scirrhous carcinoma. In tubular carcinoma, 45% of stage I, 67% of stage II and 100% of stage III, IV and recurrence cases were over 50 ng/ml. The evidence suggests that serum levels of beta-Sm is useful for the diagnosis of breast cancer.

Adenocarcinoma↗

New topoisomerase essential for chromosome segregation in E. coli.

The nucleotide sequence of the parC gene essential for chromosome partition in E. coli was determined. The deduced amino acid sequence was homologous to that of the A subunit of gyrase. We found another new gene coding for about 70 kd protein. The gene was sequenced, and the deduced amino acid sequence revealed that the gene product was homologous to the gyrase B subunit. Mutants of this gene were isolated and showed the typical Par phenotype at nonpermissive temperature; thus the gene was named parE. Enhanced relaxation activity of supercoiled plasmid molecules was detected in the combined crude cell lysates prepared from the ParC and ParE overproducers. A topA mutation defective in topoisomerase I could be compensated by increasing both the parC and the parE gene dosage. It is suggested that the parC and parE genes code for the subunits of a new topoisomerase, named topo IV.

Amino Acid Sequence↗

[Fundamental studies on efficacy of intraoperative radiotherapy on pancreatic carcinomas transplanted into the pancreas of hamsters].

Efficacy of intraoperative electron beam radiotherapy (IOER) on N-nitrosobis (2-hydroxypropyl) amine (BHP) induced pancreatic carcinomas transplanted into the pancreas of the Syrian golden hamsters were studied and the following results were obtained. 1. Selective electron beam application to the carcinoma transplanted into the pancreas of hamsters was accomplished using an electron beam collimator. 2. Intra-pancreatic transplantability of BHP-induced serially transplantable subcutaneous pancreatic carcinomas was 100%. 3. Intra-pancreatic transplanted pancreatic carcinomas disappeared in 2 out of 19 hamsters (11%) by 10 Gy irradiation and 7 out of 15 (47%) by 20 Gy irradiation given 2 weeks after intra-pancreatic transplantation. 4. In contrast to the linear growth of tumor size in the non-irradiated group, the tumor size showed an electron dose-dependent reduction in the irradiated group. 5. Histologically, marked necrosis was noted in the irradiated group, and the intensity of necrosis differed between the 10 Gy and 20 Gy groups. 6. Direct invasion of tumor to the stomach, small intestine, large intestine, liver and abdominal wall was noted. Its incidence tended to decrease as the electron dose increased (5/19 or 26% for the control group, 4/19 or 21% for the 10 Gy group, and 1/17 or 6% for the 20 Gy group), although the difference was not statistically significant. 7. The incidences of liver and lymph node metastasis were not different between the non-irradiated and the irradiated groups. These results suggest that selective IOER on BHP-induced pancreatic carcinomas has an effectiveness to kill cancer cells in hamsters.

Animals↗

Sequential mechanisms of cyclophosphamide-induced skin allograft tolerance including the intrathymic clonal deletion followed by late breakdown of the clonal deletion.

The cellular basis of the transplantation tolerance in a model system of BALB/c (Mls-1b) mice rendered cyclophosphamide (CP)-induced tolerant to DBA/2 (Mls-1a) skin allograft was investigated by assessing V beta 6+ T cells. From our results, three major mechanisms that are essential to the CP-induced skin allograft tolerance were sequentially elucidated. The first mechanism was destruction of donor-Ag-stimulated T cells in the periphery by CP treatment. The second mechanism was intrathymic clonal deletion of donor-reactive T cells, such as V beta 6+ T cells, correlating strongly with intrathymic mixed chimerism. The clonal deletion, however, was not always essential for the maintenance of the skin allografts, because DBA/2 skin survived even after the clonal deletion terminated and V beta 6+ T cells reappeared in the periphery of the recipient BALB/c mice. The third mechanism was generation of tolerogen-specific suppressor T cells, especially in the late stage of the tolerance. In contrast, the clonal anergy that is evidenced by the specific suppression of mixed lymphocyte reaction in the recipient BALB/c mice after injecting with DBA/2 spleen cells alone was not considered as a significant mechanism in prolonging skin allograft survival because such anergic mice showed accelerated rejection of the skin allografts. These results may suggest practical hierarchy of the mechanisms of CP-induced allograft tolerance.

Animals↗

[Clinical research on hyperthermia of cancer using microwave heating equipment of lens applicator type].

Ninety cases with 96 tumors were treated by the 430 MHz microwave heating systems, HTS-100, at Tokyo Metropolitan Komagome Hospital, Kyoto University and Aichi Cancer Center. The results of treatment were analyzed, and the following have been clarified. Three cases are demonstrated showing feature of HTS-100. 1) The results of 383 sessions of heating by HTS-100 were analyzed, and it has been clarified that even the larger tumors, more than 5 cm both in size and depth, can be heated satisfactorily to temperatures higher than 42 degrees C. This system is capable of heating remarkably wider areas compared with the conventional microwave heating systems. 2) Hyperthermia by HTS-100 and radiotherapy were combined for treatment. The success rate (total percentage of CR plus PRa) of 89 cases analyzed was as high as 66.3%. Furthermore, local heating was successful for 60.7% of tumors, larger than 5 cm and deeper than 4 cm. 3) Combination of microwave heating and RF wave heating is a new method which is helpful for expansion of indications. 4) The frequencies of side effects of HTS-100 heating were: pain, 15.6%; sensation of heat, 6.3%; burns, 3.6%. Most of side effects were transient and slight. The higher frequency of pain than the conventional microwave heating is attributable to expansion of heating area.

Adenocarcinoma↗

Expression of the human MHC, HLA-DQW6 genes alters the immune response in C57BL/6 mice.

In an attempt to obtain direct evidence for the critical role of HLA class II molecules in regulating the immune response, genomic genes for alpha- and beta-chains of HLA-DQw6 from HLA-Dw12 haplotype were introduced into the C57BL/6 (B6) strain of mouse and a line of HLA-DQw6 transgenic mouse was obtained. Tissue specificity of the expression of the transgenes was much the same as that of murine I-Ab genes. DQw6 molecules were expressed on B cells and macrophages in spleen cells and about 30 to 40% of the I-Ab+ spleen cells were positive for DQw6. The HLA-DQw6 transgenic B6 mouse became tolerant to the DQw6 molecules, as evidenced by the MLR and antibody production specific to the DQw6 molecules. The HLA-DQw6 transgenic B6 mouse showed a strong immune response to streptococcal cell wall antigen (SCW), whereas the B6 mouse was a low responder to SCW. The SCW-specific T cell line was established from the transgenic mouse and this T cell line recognized SCW in the context of HLA-DQw6 molecules expressed on the mouse L cell transfectant or on human monocytes. The proliferative response to SCW of primed lymph node T cells and the SCW-specific T cell line derived from the transgenic mice was inhibited by anti-HLA-DQ mAb. Thus, it is clear that the HLA-DQw6 genes acted as major histocompatibility genes in these transgenic mice.

Animals↗

[Aspects of parasternal lymphnode dissection in radical mastectomy for breast cancer].

In order to clarify the surgical aspects for parasternal lymphnode dissection to improve prognosis in patients with breast cancer, we have retrospectively investigated a total of 319 patients with breast cancer who underwent radical mastectomy with parasternal lymphnode dissection. During the 13 years from 1974 to 1986, 418 patients with breast cancer underwent radical mastectomy. Of these, 319 underwent combined dissection of the parasternal lymphnodes. Among these 319 cases, 36 (11.3%) showed pathologically-confirmed positive lymphnode metastasis. In those cases involving a tumor of diameter greater than 5 cm and more than 4 positive metastatic axillar lymphnodes, then the positive parasternal lymphnode metastasis was higher than 30%. The 5-year survival rate was 88.9% for negative parasternal lymphnode metastasis and 44.7% for positive cases (p less than 0.01 logrank test). The standard adjuvant chemotherapy, chemo-endocrine therapy and radiation therapy, each did not significantly affect or improve prognosis. We conclude that parasternal lymphnode positivity is an important factor in radical mastectomy affecting prognosis and a more powerful adjuvant chemotherapy must be developed to improve prognosis.

Breast Neoplasms↗

pp60c-src protein kinase activity in human gastric carcinomas.

We examined pp60c-src protein kinase activity in human gastric carcinoma cell lines and gastric carcinoma tissues as well as normal mucosa. pp60c-src kinase activity was detected in all 5 carcinoma cell lines at various levels. Of 16 gastric carcinoma tissues, 8 showed higher pp60c-src kinase activity in tumor tissues than in corresponding normal mucosa. However, the levels of expression of pp60c-src detected by Western blotting were not always consistent with the activities of pp60c-src protein kinase. These findings suggest that the increase in pp60c-src protein kinase activity might be brought about by post-translational changes.

Blotting, Northern↗

Augmented excretion of procathepsin L of a fos-transferred highly metastatic rat cell line.

We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line (SR-3Y1-2) enhanced lung metastasis accompanied with an increase in invasiveness. When analyzing factors relating to the high invasiveness, with special reference to typical lysosomal proteases (cathepsins), involving degradation of stroma, we found that the excretion of procathepsin L was significantly larger in the fos-transferred highly metastatic cell line (fos-SR-3Y1-202) than that in the recipient cell lines. The cathepsin D-induced enzyme activity of the excreted procathepsin L in fos-SR-3Y1-202 was about 4 and 13 fold that of SR-3Y1-2 and 3Y1, respectively. The increase in the excretion of procathepsin L from fos-SR-3Y1-202 may play a role in the high invasiveness induced by transfer with the v-fos oncogene.

Animals↗

Radiofrequency thermotherapy for malignant liver tumors.

Inoperable malignant liver tumors have been treated by radiofrequency hyperthermia at Kyoto University Hospital since 1983. In this study, clinical hyperthermia for malignant liver tumor was evaluated for 67 tumors in which we could measure intratumor temperatures. Of the 67 tumors, 41 were hepatocellular carcinomas (HCC), six cholangiocarcinomas, and 20 metastatic tumors. Cholangiocarcinoma and metastatic tumors were more susceptible to this treatment than HCC. Of the three types of HCC, higher intratumor temperatures were achieved in the diffuse type than in the nodular or massive types. The minimum tumor temperature of HCC stayed below 40 degrees C in 46% of cases, especially in larger tumors. The local response rates (complete remission plus partial remission/all) were 28% and 11% for HCC and non-HCC, respectively, for thermochemotherapy; 86% and 33%, for thermoradiotherapy; and 33% and 89%, for thermotherapy with embolization. No apparent relationship was observed between the intratumor temperatures and local response rate.

Adenoma, Bile Duct↗

[Intraarterial urokinase infusion therapy for arterial occlusive disease of the pelvis and extremities with special reference to short-term high dose infusion].

Thirty-five complete arterial occlusions of pelvis and extremity in 29 patients were treated with intraarterial urokinase infusion therapy. In 28 limbs, the occlusions were due to arteriosclerotic change and in 7 lesions, the occlusions were due to Burger's disease. The patients with arteriosclerotic change ranged in age from 52 to 84 years with a mean age of 68 years, and the patients with Burger's disease ranged in age from 35 to 47 years with a mean age of 43 years. There were 24 men and 5 women. The estimated duration of the occlusion was from 5 days to 5 years with a mean duration of 11 months. The length of the occluded segments ranged from 1 to 45 cm with a mean length of 13.9 cm. The occlusion was located in the iliac artery in 13 patients, the femoral artery in 11 patients, both the iliac and the femoral artery in 2 patients, the popliteal artery in 5 patients, the femoro-popliteal artery in 1 patient, the brachial artery in 2 patients and the radial artery in 1 patient. The infusion catheter was gently advanced into the proximal portion of the clot over a flexible guide wire, and urokinase was infused at a rate of 5000-10000 IU/min, as a short term high dose infusion (SHI), until antegrade blood flow was reestablished. The catheter was then withdrawn to a point proximal to all of the remaining clot, and the infusion rate was reduced to 10000-20000 IU/h as a continuous low dose infusion (CLI). After thrombolytic recanalization, a percutaneous transluminal angioplasty (PTA) was performed in those cases which demonstrated a residual narrowing of the lumen. The initial success rate was 86%. Reocclusions were observed in 5 lesions (17%) and a second recanalization was successful in 2 of 3 patients. The 1-year cumulative patency rate following recanalization was 88.4% and the 2-year patency rate was 78.6%. No significant complications directly related to the procedure were observed. SHI combined with CLI and PTA appears to be an effective and safe therapy for chronic long segmental arterial occlusion.

Adult↗

A monoclonal antibody 5E5 recognizes an intranuclear antigen selectively present in a subpopulation of the neurons.

Monoclonal antibody 5E5 labeled the nuclear antigen of the neurons in the guinea pig and rat central nervous systems including the cerebrum, cerebellum, spinal cord and retina. This antibody could discriminate neurons even among the same cell class. In in vitro study, only 10% of dividing PC12 cells was labeled with this antibody. An electron microscopic immunohistochemical study also revealed that this antibody selectively labeled heterochromatins in the neurons. Although we could not obtain any positive result by an immunoblot study, the antigenicity was remarkably diminished by the DNase I or S1 nuclease treatment on the tissue sections whereas RNase and trypsin was ineffective. These results suggested that this antigen might be a single-stranded DNA-protein complex resistant to proteolytic procedures, and possibly related to cell function or state of differentiation.

Animals↗