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Biomedical subjects

Y Kubo

Publications and source records attributed to Y Kubo.

At least 199 records · Page 11Linked to original sources

[DNA content analysis and expression of human leucocyte antigen on esophageal cancer].

To examine the usefulness of DNA analysis of cancer cells in estimating the prognosis of the patients with cancer, we measured the DNA content of cancer cells using flow cytometry in 82 patients bearing esophageal cancer. Although neither DNA content nor DNA ploidy alone was a prognostic factor, the aneuploid pattern with a DNA index greater than 1.3 was an indicator of poor prognosis. In addition, we studied the HLA class I expression in the same patient group using immunochemical staining (anti-HLA class I monoclonal antibody; w6/32). Forty-four cases (53.7%) were HLA class I positive and 38 (46.3%) were negative. Pathological lymph node metastasis was found more frequently in HLA class I negative patients than positive patients with statistical significance (p < 0.05). The tumors with positive HLA expression induced significantly more TILs around them (p < 0.05). The patients with the aneuploid pattern and negative HLA class I appeared to have the poorest prognosis from the survival curve study, although the difference was not statistically significant. These findings suggest that the expression of HLA class I on tumors is an important prognostic factor in patients with esophageal cancer.

DNA, Neoplasm↗

[Alteration of serum levels of endotoxin, polymorphonuclear leukocyte elastase, and the molecular markers of the coagulation and fibrinolytic system in the patients with esophageal cancer and lung cancer before and following operation].

The serum levels of endotoxin, polymorphonuclear leukocyte elastase (PMN-E), and the coagulation and fibrinolytic markers (D-dimer, TAT) were measured in the patients with esophageal cancer, lung cancer, and benign pulmonary tumors before and after the operation; on the day of operation, and the 1st, 3rd, and 7th postoperative day. The biological responses of the patients under surgical stress were evaluated. In the patients without complications, the endotoxin levels measured by the Toxicolor method and the PMN-E levels did show any significant increase in the early postoperative period, and they returned to the normal levels by the 7th postoperative day. On the contrary, in the patients with postoperative complications, they continued to increase throughout the study period. The endotoxin levels measured by the Endospacy test did not show any significant changes postoperatively. The D-dimer and TAT levels showed their highest values on the first postoperative day. The serum levels of endotoxin, PMN-E, and molecular markers of the coagulation and fibrinolytic system in the patients under surgical stress may be useful factors in predicting the postoperative outcome.

Aged↗

[Experimental evaluation of a new gelatin-impregnated woven Dacron vascular prosthesis (CL301)].

We investigated the biological response and biodegradation of CL301, a presealed woven Dacron prosthesis (UBE woven) with glutaraldehyde stabilized gelatin. The sealant does not affect its handling characteristics because of the glycerin treatment. The total content of endotoxin in the CL301 was 5.3 +/- 0.5 pg/mg of sealant material (1.7 +/- 0.2 pg/cm2), which was 1/5 and 1/6 of that found in Hemashield and Gelseal, respectively. The pyrogen test was negative and the content was estimated below the minimum pyrogenic doses for thoracic aortic surgery. Five cm-long grafts with a diameter of 10 mm were implanted into the descending thoracic aorta of dogs weighing 10-16 kg. These grafts were retrieved 2 hours, 7, 10 days, 5, 8 and 10 weeks after implantation. Thrombus-free surfaces were 28%, 77%, at 5 and 10 weeks and there was no excessive inflammatory response to the sealant. The total, and the effective sealant remaining were 80.6%, 56.5% at 5 weeks, 60.8%, 38.3% at 10 weeks, respectively. The sealant was removed more rapidly from the inner surface than from the outer. In half of the graft area, the sealant was removed or detached from the Dacron surface 5 weeks after implantation, indicating that delayed resorption of the sealant substantially did not affect the healing process. We conclude that because of the harmless amount of endotoxin and effective sealing for 5 weeks, followed by an acceptable healing process experimentally, CL301 is the presealed Dacron graft of choice for thoracic aortic surgery.

Animals↗

[Malignant mediastinal lesions with invasion to the superior vena cava].

Four patients underwent resection of mediastinal malignant tumors with invasion to the superior vena cava. Two patients had invasive thymoma, one seminoma, and one metastatic mediastinal lymph nodes of unknown origin. Prior to resection of the tumor, an ePTFE graft was anastomosed between the innominate vein and the right atrium to maintain the venous drainage from the brain and the upper extremities. In two patients, the superior vena cava was reconstructed by patch angioplasty after the tumor with a part of the vena cava was safely resected. One patient died of acute respiratory failure, but the other three are alive and well without any evidence of graft obstruction. This safe and useful method in order to prevent cerebral congestion during and after resection of the tumor.

Adult↗

Functional characterization and localization of a cardiac-type inwardly rectifying K+ channel.

We cloned inwardly rectifying K+ channel cDNAs from porcine, rat and human, which were structurally almost identical with recently reported CIR(cKATP-1). The expression of CIR alone was low and unstable in Xenopus oocytes. The CIR/GIRK1 co-expression showed an increased current amplitude. Both the CIR and CIR/GIRK1 currents increased by coexpressing G beta gamma. The CIR and CIR/GIRK1 currents displayed two qualitative differences. (1) The conductance of the CIR channel did not saturate, but that of the CIR/GIRK1 channel showed saturation at hyperpolarized potential. (2) The CIR current showed instantaneous activation upon hyperpolarization, whereas the CIR/GIRK1 current exhibited slow activation, which was fitted by the sum of two exponentials. The CIR/GIRK1 current was also different from the GIRK1 current. The activation of the CIR/GIRK1 current was approximately ten times faster than that of the GIRK1 current. The increase in current amplitude and the qualitative differences imply the formation of functional heteromultimer. The CIR/GIRK1 channel showed differences from the native muscarinic K+ channel in that the basal level before m2 receptor activation is significantly large, and that the activation kinetics are much faster. Using anti-CIR antiserum, the CIR was detected in myocardial cells of the atrium and the ventricular subendocardial layer, and in the cardiac ganglion.

Amino Acid Sequence↗

A novel cancer predisposition syndrome in the Eker rat model.

Hereditary renal carcinomas (RCs) develop in virtually all Eker rats by the age of one year. Investigation of extrarenal primary tumors occurring in Eker rats late in life (at 2 years) additionally revealed pituitary adenomas (17/31 = 54.8% (carrier) vs 7/32 = 21.9% (non-carrier siblings of affected animals), P < 0.01), sarcomas of the spleen (21/31 = 67.7% vs. 0/32 = 0%, P < 0.001) and sarcomas (of probable stromal origin) of the uterus (8/17 = 47.1% vs. 0/15 = 0%, P < 0.01). Thus, the Eker rat might provide a novel animal model of cancer predisposition syndromes.

Animals↗

Allelic loss at the predisposing gene locus in spontaneous and chemically induced renal cell carcinomas in the Eker rat.

Hereditary renal carcinoma (RC) in the rat, originally reported by Eker in 1954, is an example of a Mendelian dominant predisposition to a specific cancer in an experimental animal. We previously reported that ionizing radiation induces additional tumors in a linear dose-response relationship, suggesting that in heterozygotes two events (one inherited, one somatic) are necessary to produce tumors. Recently, the predisposing gene has been mapped to rat chromosome 10. This study was designed to examine loss of heterozygosity (LOH) at chromosome 10 in the RCs developed from hybrid F1 rats carrying Eker mutation. In spontaneous RCs, 6 of 10 (60%) showed loss of the wild-type allele covering over 30 cM, consistent with two-hit hypothesis. Individual tumors have different patterns of LOH even from the same kidney, showing independent clonal origins of RCs. In contrast, none of N-ethyl-N-nitrosourea-induced RCs had allelic loss (0 of 9 = 0%, P < 0.01). Thus, the nature of the second event differs between spontaneous and chemically induced tumors in the Eker rat. These results suggest that chemically induced tumors in experimental animals involve intragenic mutations and so do not cause LOH of syntenic markers. Interestingly, 1 of 5 spontaneous pituitary tumors that developed in the Eker rat showed LOH for chromosome 10 markers.

Alleles↗

Secondary infection with rescued M-MSV is requisite for focus formation of S+L- mink cells by murine leukemia virus.

Whether the foci on S+L- mink cells transformed by the superinfection of MuLV were induced by the secondary infection of M-MSV pseudotype generated in the cells or by the secondary infection of MuLV has remained unresolved since the requirement of secondary infection was first reported (A. Ishimoto, J. Virol. 36, 18-21, 1980). Here, we show that infection with ecotropic MuLV of S+L- mink cells transfected with the receptor gene for ecotropic MuLV induced transformed foci resembling those induced by xenotropic and amphotropic viruses. This observation and our previous results (A. Ishimoto, J. Virol. 36, 18-21, 1980) that clonal lines of S+L- mink cells chronically infected with ecotropic MuLV are morphologically indistinguishable from normal S+L- mink cells suggest that the focus formation of S+L- mink cells by superinfection with MuLV is not due to secondary spread of helper virus which transactivates the expression of the v-mos oncogene by the MuLV, but is due to the secondary infection of the defective M-MSV genome. A new S+L- mink cell line with a receptor gene for ecotropic MuLV, designated ID cells, provided a new method for titrating the ecotropic MuLV that develop few XC foci and to simultaneously detect viruses in various host ranges.

Animals↗

Restoration of pathogenicity of a penetration-deficient mutant of Collectotrichum lagenarium by DNA complementation.

Infection by Colletotrichum lagenarium requires formation of an appressorium and of a penetration peg. A mutant, 83,348, defective in morphogenesis of the penetration peg was unable to penetrate into cellulose membranes or infect cucumber leaves. DNA transformation using a wild-type genomic library constructed in pKVB resulted in two transformants, Ppr1 and Ppr2, with restored penetration peg formation, from 2,000 benomyl-resistant transformants. However, penetration into cellulose membranes by these transformants ranged from 30 to 40% compared to greater than 90% by wild-type. Southern-blot hybridization showed that a single copy of a cosmid clone had integrated into the genome of the transformants. A 12.0-kbp fragment of the cosmid vector with the flanking region of wild-type genomic DNA was recovered by plasmid rescue from Ppr1. Using the flanking DNA sequences as a probe for colony blot hybridization, a genomic clone was identified and designated pRP46. Transformants obtained following transformation with pRP46 were able to penetrate cellulose membranes. The penetration frequency of pRP46 transformants ranged from 25 to 65%. Transformants were also pathogenic on cucumber.

Cloning, Molecular↗

The superiority of UW solution for maintaining ATP concentrations during pulmonary preservation.

We evaluated three solutions used for preserving lungs, namely, University of Wisconsin (UW), Euro-Collins (E-C), and low potassium dextran (LPD), by measuring the high energy phosphates in the preserved lung tissue. The left lungs of Sprague-Dawley rats were excised and flushed with 5 ml of one of the solutions at 10 degrees C through the pulmonary artery, after which they were deflated and immersed in the solution at 10 degrees C for 24 h. The tissue adenosine triphosphate (ATP) concentration in mumol/g tissue wet weight after 24 h of storage was 2.55 +/- 0.48 (n = 7) in the UW lungs, 1.98 +/- 0.25 (n = 6) in the E-C lungs, and 1.53 +/- 0.32 (n = 4) in the LPD lungs, being significantly higher in the UW lungs than in either the E-C or LPD lungs (P < 0.05). The histopathological findings of the E-C lungs were more deteriorated, with marked interstitial edema, septal hypertrophy, and perivascular hyaline degeneration, than either the UW or LPD lungs. Thus, the findings of this study indicate the superiority of UW solution for lung preservation.

Adenine Nucleotides↗

Plantar or dorsalis pedis artery bypass in Buerger's disease.

The peripheral type of Buerger's disease is unresponsive to conservative therapy when accompanied by multisegmental occlusion at the level of the ankle. Between November 1983 and April 1993, we performed 15 bypasses below the ankle for this type of thromboangiitis obliterans in 13 patients (mean age 45.7 years), including four females. Ten patients had intractable toe ulcers with severe pain, and five had foot-threatening ischemia or disabling foot claudication. Eleven patients were heavy smokers, two were passive smokers, and six had a history of sympathectomy. All patients had occlusion of the three main crural arteries or both of the tibial arteries at the ankle. Of the 15 bypasses, 10 were to the medial or lateral plantar arteries, two were to the common plantar artery, and three were to the dorsalis pedis artery. There were three early and three late graft failures. The causes of early graft failure were thrombosis at the site of cross-clamping, anastomosis to a diseased segment, and arterial spasm. The three late failures (> 3 months) were due to disease progression in patients who continued to smoke, whereas all grafts remained patent and functioned well in patients who stopped smoking. Because patients with thromboangiitis obliterans are relatively young and active, early healing of ulcers and restoration of normal limb function are important objectives in their treatment. Bypass to the foot arteries can provide an excellent outcome, although special techniques and postoperative cessation of smoking are essential for success.

Adult↗