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T Nakatani

Publications and source records attributed to T Nakatani.

At least 37 records · Page 2Linked to original sources
PubMed2002

Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma.

As regulators of malignant cell behaviour and communication with stroma, cytokines have proved useful in understanding cancer biology and developing novel therapies. In renal cell carcinoma, patients with inflammatory reactions are known to have poor prognosis. In order to elucidate the relation between renal cell carcinoma and the host, serum levels of inflammatory cytokines, interleukin-6, tumour necrosis factor alpha, interleukin-1beta, were measured. One hundred and twenty-two patients with renal cell carcinoma and 21 healthy control subjects were studied, and serum cytokine levels were measured using a highly sensitive ELISA kit. As a result, in the control group, interleukin-6, tumour necrosis factor alpha and interleukin-1beta levels were 1.79+/-2.03, 2.74+/-0.94 and 0.16+/-0.17 pg ml(-1), respectively. In the renal cell carcinoma patients, they were 8.91+/-13.12, 8.44+/-4.15 and 0.53+/-0.57 pg ml(-1), respectively, and significantly higher. In the comparison of stage, interleukin-6 level was significantly higher in the stage IV group compared to the other stage groups including the control group, while tumour necrosis factor alpha level was significantly higher in each stage group compared to the control group. As for grade, interleukin-6 level was significantly higher in the grade 3 group compared to the control, grade 1 and grade 2 groups, while tumour necrosis factor alpha level was significantly higher in each grade group compared to the control group. All cytokines had a positive correlation with tumour size. In regard to the correlation with CRP, all cytokines had a positive correlation with CRP, while interleukin-6 had a particularly strong correlation. In conclusion, interleukin-6 may be one of the factors for the poor prognosis of patients with renal cell carcinoma. In addition, tumour necrosis factor alpha may be useful in the early diagnosis of renal cell carcinoma and post-operative follow-up.

Biomarkers, Tumor↗
PubMed2002

Susceptibility locus for non-obstructive azoospermia is localized within the HLA-DR/DQ subregion: primary role of DQB1*0604.

Non-obstructive azoospermia is a male infertility characterized by no or little sperm in semen as a result of a congenital dysfunction in spermatogenesis. Previous studies have reported a higher prevalence of particular human leukocyte antigen (HLA) antigens in non-obstructive azoospermia. As the expression of the RING3 gene located in the HLA class II region was predominant in the testis, mainly around spermatids and pachytene spermatocytes, it is tempting to speculate that RING3 is one of the strong candidate genes responsible for the pathogenesis of the disease. In this study, the genetic polymorphism in the RING3 gene was investigated by the direct sequencing technique. As a result, a total of 14 single nucleotide polymorphisms were identified. Among them, six were localized in the coding region but none of them was accompanied by an amino-acid substitution. No significant difference in the allelic distribution at these 14 polymorphic sites was observed between the patients and healthy controls, suggesting that the susceptible gene for non-obstructive azoospermia is not the RING3 gene. Then, in order to map the susceptibility locus for non-obstructive azoospermia precisely within the HLA region, 11 polymorphic microsatellite markers distributed from the SACM2L gene just outside the HLA class II region (187 kb telomeric of the DPB1 gene) to the OTF3 gene in the HLA class I region were subjected to association analysis in the patients. Statistical analysis of distribution in the allelic frequency at each microsatellite locus demonstrated that the pathogenic gene for non-obstructive azoospermia is located within the HLA-DR/DQ subregion. In fact, DRB1*1302 and DQB1*0604 were found to be strongly associated with non-obstructive azoospermia by polymerase chain reaction-based DNA typing. Further, haplotype analysis suggested that the DQB1*0604 allele may play a decisive role in the pathogenesis of non-obstructive azoospermia.

Alleles↗
PubMed2001

The copper-chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells.

Angiogenesis is now recognized as a crucial process in tumor development, including hepatocellular carcinoma (HCC). Since HCC is known as a hypervascular tumor, anti-angiogenesis is a promising approach to inhibit the HCC development. Trientine dihydrochloride (trientine) is used in clinical practice as an alternative copper (Cu)-chelating agent for patients with Wilson's disease of penicillamine intolerance. In our study, we examined the effect of Cu-chelating agents on tumor development and angiogenesis in the murine HCC xenograft model. Although both trientine and penicillamine in the drinking water suppressed the tumor development, trientine exerted a more potent inhibitory effect than penicillamine. In combination with a Cu-deficient diet, both trientine and penicillamine almost abolished the HCC development. Trientine treatment resulted in a marked suppression of neovascularization and increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. In vitro studies also exhibited that trientine is not cytotoxic for the tumor cells. On the other hand, it significantly suppressed the endothelial cell proliferation. These results suggested that Cu plays a pivotal role in tumor development and angiogenesis in the murine HCC cells, and Cu-chelators, especially trientine, could inhibit angiogenesis and enhance apoptosis in the tumor with consequent suppression of the tumor growth in vivo. Since trientine is already used in clinical practice without any serious side effects as compared to penicillamine, it may be an effective new strategy for future HCC therapy.

Animals↗
PubMed2001

Microbial glycosyltransferases for carbohydrate synthesis: alpha-2,3-sialyltransferase from Neisseria gonorrheae.

The alpha-2,3-sialyltransferase from Neisseria gonorrheae was overproduced in E. coli for exploitation of its substrate specificity and synthetic utility. Several potential acceptor substrates were synthesized in this study, including mono- and oligosaccharides, glycolipids, and glycopeptides and their sulfate derivatives. Some CMP-sialic acid derivatives with modification at the C-5 position were also prepared for evaluation as donor substrates. It was found that the enzyme exhibits a broader acceptor substrate specificity when compared to other sialyltransferases, though the donor specificity is quite limited. Application of the enzyme to the preparative synthesis of representative sialyl glycoconjugates has been demonstrated. On the basis of this work and the work of others, this enzyme is the most versatile and synthetically useful among all sialyltransferases known to date, especially for the synthesis of sulfate-containing glycoconjugates.

Carbohydrates↗
PubMed2001

Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction.

Significant sex differences exist among cases of bladder cancer in humans as well as in experimental animals such as rats. Aromatic amines such as benzidine and 2-naphthylamine are known to induce bladder cancer. These carcinogenic amines are activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate sex difference in bladder carcinogenesis. Competitive reverse transcription-polymerase chain reaction was used to investigate the expression of rat CYP4B1 mRNA occurring in small amounts of tissue such as bladder tissue. Expression of CYP4B1 in the bladder of male rats increased with development but not in that of female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in the bladder than did mature female rats. Castration of male rats decreased CYP4B1 levels and treatment with testosterone led to a partial recovery of CYP4B1 levels. These results indicate that CYP4B1 levels in the rat bladder are partly regulated by androgens. Furthermore, the present findings suggest that the sex difference observed in bladder carcinogenesis was due to sex-different expression of CYP4B1 in bladder tissue.

Age Factors↗
PubMed2001

Soft x-ray absorption spectra of ilmenite family.

We have carried out soft x-ray absorption spectroscopy to study the electronic structure of ilmenite family, such as MnTiO3, FeTiO3, and CoTiO3 at the soft x-ray beamline, BL23SU, at the SPring-8. The Ti and M L2,3 absorption spectra of MTiO3 (M=Mn, Fe, and Co) show spectra of Ti4+ and M2+ electron configurations, respectively. Except the Fe L2,3 spectrum, those spectra were understood within the O(h) symmetry around the transition metal ions. The Fe L3-edge spectrum clearly shows a doublet peak at the L3 edge, which is attributed to Fe2+ state, moreover the very high-resolution the L-edge spectra of transition metals show fine structures. The spectra of those ilmenites are compared.

Journal Article↗
PubMed2001

Severely reduced production of klotho in human chronic renal failure kidney.

We recently identified a novel gene, termed klotho (kl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the kl gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short life-span and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in kl mutant mice. Furthermore, the kl gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of kl mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in kl gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients.

Adult↗
PubMed2001

Modification of bicaval anastomosis technique for orthotopic heart transplantation.

A modified bicaval anastomosis technique was utilized for 4 consecutive patients undergoing heart transplantation. Instead of transecting the superior and inferior vena cavae, a strip of the posterior right atrial wall was left undivided as a bridge connecting the superior and inferior vena cavae. This minor modification perfectly prevented shrinkage and retraction of the caval tissue, thus providing easier anastomotic orientation and better estimation of the appropriate tissue length that fits well, particularly when a small donor heart was available.

Adolescent↗
PubMed2001

Susceptibility to vesicoureteral reflux in Japanese is linked to HLA-DR antigen.

OBJECTIVES: To determine whether vesicoureteral reflux is associated with the human leukocyte antigen (HLA) genes. METHODS: We evaluated 40 Japanese patients (27 males and 13 females) with reflux. HLA-DR low-resolution genotyping and high-resolution typing of HLA-DRB1 alleles were performed. The frequencies of the HLAs and alleles were calculated and compared with those previously reported in 493 healthy Japanese. RESULTS: Low-resolution typing showed that the frequency of the HLA-DR11 antigen was significantly higher in the patients with reflux than in the control group. High-resolution typing revealed that the frequencies of HLA-DRB1*1101 and 1502 alleles were significantly higher in the patients with reflux than in the control group. In the patients with and without renal scarring, the frequencies of the HLA-DR11 antigens and HLA-DRB1*1101 alleles were significantly lower in those with renal scarring. In the patients with and without the chief complaint of urinary tract infection symptoms, the frequencies of HLA-DR13 antigens and HLA-DRB1*1302 alleles were significantly lower in those with that chief complaint. CONCLUSIONS: The susceptibility to reflux is, in part, controlled by HLA genes themselves or an unknown gene or genes, the locus for which is located close to the DRB1 gene. The lack of a HLA-DRB1*1101 allele and DRB1*1302 allele in patients with reflux might be connected with renal scarring and urinary tract infection, respectively.

Adolescent↗
PubMed2001

Gene therapy for hepatocellular carcinoma based on tumour-selective suicide gene expression using the alpha-fetoprotein (AFP) enhancer and a housekeeping gene promoter.

The aim of this study was to examine whether the human alpha-fetoprotein (AFP) enhancer could be used to induce hepatocellular carcinoma (HCC)-selective expression of the herpes simplex virus thymidine kinase (HSV-tk) gene which is under the control of the phosphoglycerate kinase (pgk) promotor. The human AFP enhancer was linked with the non-tissue-specific, human housekeeping pgk promoter in a retroviral vector. AFP-producing HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter were much more susceptible to the prodrug, ganciclovir (GCV), than those infected with the same retroviruses without the AFP enhancer. Non-HCC cells infected with retroviruses carrying the HSV-tk gene under the control of the AFP enhancer/pgk promoter exhibited profoundly increased resistance to GCV compared with those infected with the same retroviruses without the AFP enhancer. Northern blot analysis revealed that the AFP enhancer caused enhanced HSV-tk expression in AFP-producing HCC cells and suppressed HSV-tk expression in non-HCC cells. Our results indicate that the AFP enhancer could give HCC selectivity to the pgk promoter, and that this novel strategy may be useful for HCC-selective cancer gene therapy.

Blotting, Northern↗
PubMed2001

Establishment and characterization of cell line TNMY1 derived from human malignant fibrous histiocytoma.

Although malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas, its pathogenesis remains unclear. In this study, a cell line derived from human MFH, TNMY1, was established from a metastatic chest-wall lesion of a 60-year-old woman with MFH. The TNMY1 cell line was passaged 95 times, and it still retained the biological characteristics of the original tumor. TNMY1 consists of spindle-shaped cells and pleomorphic cells associated with multinucleated giant cells. Immunohistochemical studies showed that the spindle-shaped and pleomorphic cells were positive for vimentin, CD68 and alpha-smooth muscle actin, but negative for epithelial membrane antigen, desmin, muscle actin, alpha-sarcomeric actin, myoglobin, lysozyme and S-100 protein. The cells expressed collagen types I, III and V. These results indicate that MFH may originate from mesenchymal stem cells with the potential to differentiate into either fibroblasts or histiocytes. An elevated level of collagen type V mRNA expression is considered to support a diagnosis of MFH.

Animals↗
PubMed2001

Renal transplantation with aged donors.

Research indicates that aged heart-beating cadaveric donors cause greater risk factors in kidney transplantation. The influence of age on the outcome of non-heart-beating (NHB) cadaveric renal transplantations has not yet been clarified. From July 1986 to May 1999, 63 patients who received cadaveric renal transplantation at Osaka City University Hospital and Osaka City General Hospital were divided into two groups according to their age. Renal function and graft-survival rates of the two groups were compared. The mean values of nadir donor serum creatinine were significantly worse (P < 0.05) in the aged donor group. In the aged donor group the percentage of immediately functioning grafts was lower and the percentage of non-functioning grafts was higher. During the first 10 years post-transplant, graft survival in the aged donor group was significantly lower than that in the younger donor group. We conclude that cadaveric renal transplantation from NHB aged donors can be to the detriment of renal function and graft survival rates compared to transplantation from younger donors.

Age Factors↗
PubMed2001

The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model.

The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation.

Animals↗
PubMed2001

Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats.

The renin-angiotensin system (RAS) is frequently activated in patients with chronic liver diseases. Angiotensin-II (AT-II) has been suggested to play an important role in liver fibrogenesis. It induces hepatic stellate cell (HSC) proliferation and up-regulates the transforming growth factor beta(1) (TGF-beta(1)) expression via AT-II type 1 receptor (AT(1)-R) in vitro. The aim of the present study was to examine the in vivo effect of candesartan (CA), a clinically used AT(1)-R blocker (ARB), and perindopril (PE), an angiotensin-converting enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development in rats. The clinically available comparable doses of CA and PE significantly attenuated the fibrosis development. These inhibitory effects of PE and CA were also found in the on-going liver fibrosis model. The hepatic hydroxyproline and serum fibrosis markers were significantly suppressed by CA and PE treatment. Furthermore, the alpha smooth muscle actin (alpha-SMA) positive cells in number were markedly suppressed by CA and PE treatment. Similarly, the hepatic TGF-beta(1) protein and messenger RNA (mRNA) levels were significantly suppressed. Our in vitro study showed that AT-II increased the TGF-beta(1) mRNA expression in the activated HSCs, and this effect was totally blocked by CA. These results suggested that the RAS, especially AT-II and AT(1)-R interaction plays a pivotal role in liver fibrosis development through HSC activation. Because both CA and PE are widely used in clinical practice without serious side effects, these drugs may provide an effective new strategy for anti-liver fibrosis therapy.

Angiotensin II↗