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Biomedical subjects

H Tahara

Publications and source records attributed to H Tahara.

At least 163 records · Page 9Linked to original sources
PubMed1995

[Clinical statistics of 67 cadaveric renal transplantation at the Department of Urology, Kinki University School of Medicine].

A statistic survey was made on the patients undergoing cadaveric renal transplantation between June, 1980 and December, 1993. The total number of patients was sixty-seven. The number of patients per year increased annually. The graft survival rate was 73.8% at 1 year and 63.1% at 5 years. Some transition was seen in immunosuppressive regimens using cyclosporin.

Adolescent↗
PubMed1995

Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions.

Recent evidence indicates that telomerase activity may be necessary for cell immortality, which is required for the sustained and indefinite growth of most malignant cells. We analyzed telomerase activity in gastric and colorectal cancers and in gastric and colorectal precancerous lesions to determine whether malignant progression depends on the activation of telomerase and at what stage of carcinogenesis cells have detectable telomerase activity. Telomerase activity was measured by the telomeric repeat amplification protocol assay and was detected in 17 (85%) of 20 primary gastric carcinoma tissues and in 19 (95%) of 20 primary colorectal carcinomas, regardless of tumor staging and histological types. All nodal metastases, peritoneal metastases, and a recurrent gastric cancer tumor were positive. All cell lines established from gastric and colorectal cancers contained telomerase activity. In precancerous lesions, 10 (100%) of 10 colorectal tubular adenomas were telomerase positive, in addition to 3 (23%) of 13 gastric intestinal metaplasias and 1 (50%) of 2 gastric adenomas, whereas the corresponding gastric normal mucosas as well as colorectal mucosas were negative. These results indicate overall that reactivation of telomerase may occur at an early stage of carcinogenesis and may correlate well with malignant progression of gastric cancer. Telomerase activity thus may serve as a powerful additional tool for cancer diagnosis.

Adenocarcinoma↗
PubMed1994

Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production.

Recent evidence supports the critical and proximate role of IL-12 in regulating both T and NK cell function during inflammation. In these studies, we evaluated the in vivo antitumor activity of murine IL-12 in murine adenocarcinoma and sarcoma models using both systemic and peritumoral administration. Antitumor effects were consistently demonstrated both in models of microdisease, in which IL-12 treatment was initiated soon after tumor inoculation (1 to 5 days), and in animals bearing large established tumors (7 to 14 days). Treatment with IL-12 markedly prolonged survival and, in most cases, caused complete tumor regression. Significant reduction in pulmonary metastases after systemic treatment was observed when treatment was delayed for 10 days after tumor inoculation. Increases in serum IFN-gamma, TNF-alpha, and nitrogen oxides were demonstrated, exceeding those observed with IL-2 treatment. Systemic administration of anti-IFN-gamma Abs before IL-12 treatment nearly completely abrogated the antitumor effect in experiments using subcutaneous tumors or pulmonary metastases. Depletion of the individual T cell subsets CD4 and CD8 by systemic administration of mAbs diminished the effectiveness of IL-12 when administered in combination. An infiltrate composed primarily of CD8+ + cells was demonstrated by using immunohistochemical analysis of tumors after IL-12 treatment. Minimal apparent toxicity was demonstrated at effective doses (0.1 to 1.0 microgram/day) of IL-12. These results indicate that IL-12 is an effective and minimally toxic antitumor agent in murine tumor models and leads to an immune-mediated rejection involving, at least in part, IFN-gamma, CD4+, and CD8+ cells. Human clinical trials of IL-12 for the treatment of malignancy are supported by these studies.

Adenocarcinoma↗
PubMed1994

Preparation of a subtractive cDNA library enriched in cDNAs which expressed at a high level in cultured senescent human fibroblasts.

Subtracted cDNA library was prepared by subtracting [cDNA from young growing SV40-transformed human fibroblasts] from [cDNA from growing SV40-transformed fibroblasts in extended lifespan]. Isolated cDNA clones which expressed at high level in life-extended transformed cells also expressed at high level in normal senescent fibroblasts but did at low level in growing and growth-arrested young cells. Neither fibronectin nor procollagen cDNA was isolated. This cDNA library is useful for isolation of senescent-specific cDNA species which express at high level in normal senescent cells but at low level in growing and growth-arrested young cells, avoiding growth-arrest-specific cDNAs.

Animals↗
PubMed1994

Coronary collateral circulation and diastolic function.

Patients with coronary artery disease reportedly have an impaired left ventricular filling. To evaluate the effects of coronary collaterals on diastolic function in patients with effort-induced angina, resting radionuclide ventriculography was performed in 14 patients with severe isolated (> or = 90% diameter) stenosis of the left anterior descending coronary artery and in seven normal subjects. Contrast ventriculography showed normal wall motion in all patients. Functional indices obtained by radionuclide ventriculography were compared between those patients with collateral vessels, Rentrop classification grades 1 (n = 7) and 3 (n = 1), and those patients without (n = 6) collateral vessels. Global peak filling rate was significantly (P < 0.01) reduced in the patients with collaterals. The septal, apical and lateral peak filling rates were also reduced in patients with collateral vessels, with the reduction in lateral peak filling rate being statistically significant (P < 0.05). The indices of systolic function and the temporal diastolic asynchronous index were similar, irrespective of the presence of collaterals. The exercise tolerance as evaluated by the rate-pressure product at peak treadmill exercise stress testing in 12 patients was significantly (P < 0.01) lower in those with collateral vessels. Angiographically visible collaterals could be a marker for more severe coronary stenosis in patients with effort-induced angina, and an indicator of the severity of deterioration in left ventricular diastolic function.

Aged↗
PubMed1994

Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo.

Interleukin 12 (IL-12), a disulfide-linked heterodimeric cytokine produced primarily by macrophages, is composed of light (p35) and heavy (p40) chains. It binds to a receptor on T-cells and natural killer cells, promoting the induction of primarily a TH1 response in vitro and in vivo. To determine whether paracrine IL-12 secretion can alter tumor cell growth or promote antitumor immunity, we have developed a delivery system using genetically engineered fibroblasts in murine tumor models. NIH3T3 cells were stably transfected to express 100-240 units/10(6) cells/48 h of IL-12 using expression plasmids carrying both the murine p35 and p40 genes of murine IL-12. The effects of paracrine secretion of IL-12 on tumor establishment and vaccination models were examined using the poorly immunogenic murine melanoma cell line (BL-6) in C57BL/6 mice. To determine the effects of IL-12 on tumor formation, nonirradiated BL-6 cells were inoculated s.c. into C57BL/6 mice admixed with NIH3T3 cells transfected with both subunits of mIL-12 (3T3-IL-12) or with cells transfected with only the neomycin phosphotransferase gene (3T3-Neo). Compared to mice given injections of BL-6 alone, the day of emergence of detectable tumors was significantly delayed in mice given injections of BL-6 admixed with 3T3-IL-12, but not in mice with BL-6 admixed with 3T3-Neo. Effectiveness in this system was related to the amount of IL-12 expressed by the 3T3-IL-12. To determine the ability of locally secreted IL-12 at the tumor site to induce antitumor immunity, 10(6) irradiated tumor cells mixed with 3T3-IL-12 or 3T3-Neo were injected as a vaccine, and the response to a tumor challenge was subsequently examined. With a tumor challenge of less than 1 x 10(5) nonirradiated BL-6 cells, significant delay of establishment of tumor was noted with a relatively small amount of IL-12 secretion (1.2 units/5 x 10(5) cells/48 h). Larger amounts of secreted IL-12 provided no additional therapeutic benefit. Histological examination of tumor inoculum with 3T3-IL-12 secreting a high level of IL-12 showed peritumoral accumulation of macrophages, a characteristic capsule around the tumor composed of palisades of fibroblasts, and decreased numbers of CD4+ cells in the tumor. These results suggest that local delivery of IL-12 inhibits tumor growth in a dose dependent manner but leads to the development of an antitumor immune response when IL-12 is expressed at the tumor site at the relatively small amount indicated above.(ABSTRACT TRUNCATED AT 400 WORDS)

3T3 Cells↗
PubMed1994

Construction and characterization of retroviral vectors expressing biologically active human interleukin-12.

Interleukin-12 (IL-12) is a heterodimeric cytokine originally defined by its ability to induce the maturation of cytolytic lymphocytes and by its capacity to effectively synergize with IL-2 in the induction of cytolytic activity. Recent studies in mice have demonstrated the ability of IL-12 to cause tumor regression and stimulate long-term antitumor immunity in treated animals. To examine the antitumor effect of direct gene transfer of IL-12 into tumors, we have developed retroviral vectors that coordinately express both subunits of IL-12. An MFG-based retroviral vector was used to generate a recombinant retrovirus in which a long terminal repeat (LTR)-driven polycistronic transcript encodes both subunits of human IL-12: hp35 and hp40 cDNAs are linked and coexpressed using the internal ribosome entry site (IRES) from the encephalomyocarditis virus (DFG-hIL-12). In addition, two IRES sequences were used to express both subunits of IL-12 and a neomycin resistance (neoR) selectable marker gene from the same polycistronic message (TFG-hIL-12). The amphotropic DFG-hIL-12 and TFG-hIL-12 viruses were used to infect both human and murine cell lines as well as primary tumor cultures. The production of human IL-12 by the nonselected, infected cells was measured in both a PHA blast proliferation bioassay and an ELISA and ranged from 15 to 40 ng/10(6) cells per 24 hr. Following G418 selection of TFG-hIL-12-infected cells, the level of expression of IL-12 was significantly higher (up to 120 ng/10(6) cells per 24 hr). The IL-12 protein secreted by the infected cells exhibited all of the biologic activities of recombinant hIL-12: proliferation of activated natural killer (NK) and T cells, stimulation of interferon-gamma (IFN-gamma) induction by NK and T cells, and enhancement of lymphokine-activated killer (LAK) activity. These retroviral vectors expressing human IL-12 should be useful in evaluating the biological properties of IL-12 as well as for use in clinical trials for gene therapy of patients with cancer.

Animals↗
PubMed1994

Specificity of sialyl-sugar chain mediated recognition by the hemagglutinin of human influenza B virus isolates.

Recognition specificity for sialylsugar chains by the hemagglutinin of influenza B viruses isolated in different years from 1940 through 1990 (B/Lee/40, B/Setagaya/3/56, B/Tokyo/7/66, B/Kagoshima/1/68, B/Gifu/2/73, B/Kanagawa/3/76, B/Ibaraki/2/85, B/Yamagata/16/88, and B/Bangkok/163/90) was studied using 13 gangliosides. Reactivity of the viruses' hemagglutinin binding to gangliosides was determined by using thin-layer chromatography/virus-binding assay, and also by measuring virus binding to erythrocytes modified by incubation with gangliosides in terms of the absorbance of hemoglobin released from the infected cells. Eight strains preferentially recognized a novel ganglioside, carrying lacto-series type I and II sugar chains with the Neu5Ac alpha 2-6Gal linkage. It was found that B/Gifu/2/73 strain binds to lacto-series gangliosides containing Neu5Ac alpha 2-6Gal and Neu5Ac alpha 2-3Gal linkages. Other gangliosides studied, including GM4, GM3(alpha 2-3), GM3(alpha 2-6), GM2, GM1a, GD3, GD1a, GD1b, and GT1b, were poor receptors.

Animals↗
PubMed1994

Heparin suppresses endothelin-1 peptide and mRNA expression in cultured endothelial cells of spontaneously hypertensive rats.

Heparin given sc consistently lowers blood pressure in spontaneously hypertensive rats (SHR). This study was designed to examine heparin's effect on vasoconstrictor endothelin-1 production in cultured aortic endothelial cells (EC). Aortic EC from SHR and normotensive Wistar Kyoto rats (WKY) were cultured and incubated with or without different concentrations of heparin. Heparin suppressed endothelin-1 release and endothelin-1 mRNA expression in a dose- and a time-dependent fashion in both WKY and SHR. The suppressive effects were more augmented in SHR than in WKY: SHR versus WKY--endothelin-1 level at 6 h = 8 +/- 1.8 versus 14 +/- 2.2 pg/10(6) cells (P < 0.01) and mRNA expression--85 versus 52% maximal inhibition by heparin, 10 U/mL (=70 micrograms/mL) (P < 0.01). When heparin was added with transcriptional inhibitor actinomycin D and incubated for 30 min, no further inhibition of endothelin-1 mRNA level measured after another 30 minutes was observed compared with the endothelin-1 mRNA level in cultured EC of SHR treated with just actinomycin D at 30 min. These results suggest that heparin regulates endogenous endothelin-1 production by cultured EC, probably at the transcriptional level, and that this effect is more marked in SHR than in WKY.

Animals↗
PubMed1994

[Phimosis as a pathogenetic factor in urinary tract infection and vesicoureteral reflux].

The present study has been carried out to clarify relationship between phimosis and urinary tract infection or vesicoureteral reflux. The subjects consisted of 654 boys up to 15 years old with phimosis who had been treated at the outpatient division, Fukuoka University Hospital during 13 years from 1974; 393 boys (60%) with false phimosis, 261 boys (40%) with true phimosis. Thirty three cases (5%) had abnormal voiding (weak stream, preputial ballooning, dribbling etc.) Boys with true phimosis without abnormal voiding showed high incidence of urinary tract infection compared with normal subject, and if these boys had abnormal voiding symptoms as well, the incidence of urinary tract infection, particularly in the form of pyelonephritis, was noted to be high. Therefore, we suggest that boys with phimosis should be treated surgically. The incidence of urinary tract infection in boys with false phimosis were similar to normal group. All cases except one of vesicoureteral reflux accompanied by true phimosis was diagnosed as primary reflux cystoscopically. Therefore in most cases of phimosis associated with reflux, phimosis is determined to be only an accessory factor of vesicoureteral reflux. And refluxing patients should be worked up for urinary tract infection after they have had circumcision. Only in one boy with phimosis and reflux, was the reflux thought to be secondary reflux caused by phimotic obstruction.

Adolescent↗
PubMed1994

Disorder in ultrastructure of basement membrane and mechanical junction in human esophageal cancer.

The ultrastructure and clinical significance of the basement membrane (BM) are still unclear in esophageal cancer. In this report, we examined the ultrastructure of the BM and microstructures related intercellular adhesion in squamous cell carcinoma of human esophagus using a transmission electron microscope, and investigated their clinical significance. BM was absent in 38% of the examined cases and the frequency or the presence of the microstructures of cancer cells of the infiltrating margin (CCIM) was negatively related to the presence of BM (BM-P); CCIM of BM-P tumors often had smaller number per cell of desmosomes and cytoplasmic processes. These results indicate that CCIM of BM-P tumor are in an 'inconvenient status' for tumor cells to form a firm group. In the intercellular space between CCIM and BM or surrounding stromal cells, all of the CCIM of BM-P tumors had hemidesmosomes, but not those of BM absent (BM-A) tumors. Though no statistical significant difference was found in our clinical observation between BM-P and BM-A tumors, the present study suggested that a considerable proportion of cancer cells have abnormal intercellular adhesiveness via a mechanical mechanism related to the presence or absence of BM.

Basement Membrane↗