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T Miki

Publications and source records attributed to T Miki.

At least 271 records · Page 15Linked to original sources
PubMed1998

Molecular analysis of two pre-mutations in myotonic dystrophy.

Here we report two families with myotonic dystrophy (DM) in which the asymptomatic parent proved to be in a pre-mutation state. Polymerase chain reaction (PCR) analysis of the region spanning the CTG expansion demonstrated that one father of the proband possessed (CTG)n repeats of n = 12 and 44 copies and the other of 15 and 47. Clinical examination showed no definite signs of DM in these two men. Haplotype analysis of DNA markers close to the DM protein kinase (DMPK) gene suggested a common ancestral DM mutation. A continuous gradient of repeat sizes from normal to abnormal range can explain this phenomenon.

Adult↗
PubMed1998

Detection of chimaeric transcripts of the immunoglobulin heavy chain and BCL6 genes by reverse-transcriptase polymerase chain reaction in B-cell non-Hodgkin's lymphomas.

T(3;14)(q27;q32) is frequently detected in B-cell non-Hodgkin's lymphomas, especially the diffuse large cell type and the follicular type. The BCL6 gene encoding a putative transcriptional factor which resides on 3q27 rearranges to the immunoglobulin heavy chain (IgH) gene on 14q32 in this chromosomal translocation. The upstream regulatory region of the BCL6 gene is replaced by the IgH gene. Deregulation of the BCL6 gene may contribute to tumourigenesis of these diseases. The rearrangement between the IgH and BCL6 genes generates chimaeric transcripts in which the joining (J) region of the IgH gene fuses to exon 3 of the BCL6 gene. We established a method to detect these chimaeric transcripts by reverse transcriptase polymerase chain reaction (RT-PCR) using the consensus sequence of the J region and the sequence of exon 3 of the BCL6 gene as primers. Using the semi-nested RT-PCR method and a cell line carrying t(3;14)(q27;q32), we detected one lymphoma cell among 10,000 background cells. We detected these chimaeric transcripts in two out of 13 clinical samples by this method. This method can detect t(3;14)(q27;q32) easily, whereas this alteration is frequently overlooked by routine karyotype analysis. Since this technique is sensitive enough to detect a small number of lymphoma cells with this genetic abnormality, it could be employed to detect contaminating lymphoma cells in bone marrow and peripheral blood and minimal residual diseases.

Base Sequence↗
PubMed1998

Two M-components in a single cell lineage in a patient with a dual isotype secretory B-cell tumour.

We describe a case of Waldenström's macroglobulinaemia with two M-components (IgM and IgG) with the same lambda light chain. Southern blot analysis of bone marrow cells showed rearrangements of immunoglobulin heavy and lambda light chain genes. Sequencing of the complementarity determining region 3 of the two lambda and mu transcripts showed 100% homology. Immunofluorescence study showed that most cells stained for both IgG and IgM. These findings indicated that a single population of cells was expressing two isotypic variants of IgG and IgM, as the genes responsible for production of both components had the same origin.

Base Sequence↗
PubMed1998

Lymphotactin: a key regulator of lymphocyte trafficking during acute graft rejection.

The attraction of leucocytes to allografts is essential for rejection. The process is controlled by chemokines. In order to clarify the role of lymphotactin (a cytokine that represents a novel branch of the chemokine superfamily) in regulating leucocyte trafficking during graft rejection, we used rat renal transplantation models to examine its gene expression and the distribution of lymphotactin-expressing cells in renal grafts. Lymphotactin mRNA was upregulated strongly in acutely rejecting renal allografts. The mRNA was undetectable in isografts, chronically rejecting renal allografts or normal kidney. Once lymphotactin was expressed, large numbers of infiltrating lymphocytes were seen. Moreover extended studies demonstrated that in cultured rat spleen cells the expression of lymphotactin mRNA was markedly induced by phytohaemagglutinin (PHA) or phorbol myristate acetate (PMA), and such induction was inhibited by the immunosuppressive drugs FK506 and cyclosporin. Collectively, these observations provide new evidence demonstrating that lymphotactin is a key regulator of lymphocyte motility and adhesiveness during acute allograft rejection. FK506 and cyclosporin inhibition of lymphotactin expression is likely to represent an important molecular mechanism of the action of the drugs.

Acute Disease↗
PubMed1998

Comparison of clinical outcomes of laparoscopic and conventional open adrenalectomy.

From September 1992 to November 1996, 28 patients underwent laparoscopic adrenalectomy at Osaka University Medical Hospital. They were compared with 25 instances of conventional open surgery performed between May 1990 and April 1996 at the same institution. Laparoscopic adrenalectomy was performed via either a transperitoneal or a retroperitoneal approach. The mean operative time of 375 minutes for laparoscopic adrenalectomy was significantly longer than that of 133 minutes for open surgery. The average hospital stay for laparoscopic surgery was significantly shorter than that of conventional open adrenalectomy. The convalescent period was also significantly shorter in the patients who had laparoscopic adrenalectomy. There was no statistical difference in blood loss during the operation or the number of doses of analgesics administered after operation in the two groups. We conclude that laparoscopic adrenalectomy is one of the options to be selected in surgically managing adrenal tumors. Laparoscopic adrenalectomy could become a standard operative procedure as instruments and techniques of laparoscopy improve significantly.

Adolescent↗
PubMed1998

Further characterization of hydrogen peroxide-dependent fatty acid alpha-hydroxylase from Sphingomonas paucimobilis.

Although fatty acid alpha-hydroxylase (FAAH) activity has been detected in various species, FAAH has not been sufficiently characterized. In this report, we describe the properties of FAAH highly purified from Sphingomonas paucimobilis. The FAAH was purified by about 5,200-fold. Blotting analysis with a specific antibody against the FAAH showed that its apparent molecular mass was approximately 43 kDa. FAAH showed alpha-hydroxylation activity in the presence of H2O2, but little if any activity with cumene hydroperoxide, t-butyl hydroperoxide, or t-butyl peroxybenzonate. The Km value for H2O2 was 72 microM. Highly purified FAAH oxidized various non-esterified saturated and unsaturated fatty acids including myristic acid, but not myristoyl-CoA. Potassium cyanide and sodium azide inhibited the FAAH activity in a concentration-dependent manner. Other respiratory chain inhibitors such as rotenone and antimycin A did not inhibit the activity. Among cytochrome P450 inhibitors, SKF-525A markedly inhibited the activity at the concentration of 2 mM, but CO did not. Imidazole, an inhibitor of plant alpha-oxidation, showed no inhibitory effect at 1 mM.

Catalysis↗
PubMed1998

Infarct-size limitation by preconditioning is enhanced by dipyridamole administered before but not after preconditioning: evidence for the role of interstitial adenosine level during preconditioning as a primary determinant of cardioprotection.

Although the importance of adenosine (Ado)-receptor activation in preconditioning (PC) has been established, it is unclear whether cardioprotection afforded by PC is determined by the Ado level during PC ischemia or by that during sustained ischemia. Accordingly, we tested whether the PC effect is modified by augmenting the increase in the interstitial Ado level during PC or by that during sustained ischemia. In the first series of experiments, the effect of 0.25 mg/kg dipyridamole (DIP) on the interstitial Ado level was assessed by in vivo microdialysis in the rabbit heart. Dialysate Ado during 2-min ischemia was 70% higher in the heart pretreated with 0.25 mg/kg of DIP than in the untreated controls, indicating that DIP was capable of enhancing an ischemia-induced increase of interstitial Ado. In the second series of experiments, myocardial infarction was induced in the rabbit by 30-min coronary artery occlusion and 3-h reperfusion. Infarct size was determined by tetrazolium staining and expressed as percentage of area at risk (%IS/AR). Rabbits were subjected to one of nine treatments before the 30-min ischemia: no treatment, DIP (0.25 mg/kg, i.v.), PC with 2-min ischemia, DIP before 2-min PC, DIP after 2-min PC, PC with 3-min ischemia, DIP before 3-min PC, DIP after 3-min PC, or 8-sulfophenyltheophylline (SPT) after 3-min PC. DIP alone did not modify %IS/AR (38.8 +/- 5.8% vs. 41.2 +/- 4.7%), but administration of DIP before 2-min PC significantly enhanced the infarct size-limiting effect (14.6 +/- 2.1% with DIP vs. 32.1 +/- 4.7% without DIP). Although the 3-min PC per se could achieve significant infarct limitation, the effect of DIP on 3-min PC was not significant (14.7 +/- 1.9% with DIP vs. 20.5 +/- 1.8% without DIP). On the other hand, the effect of DIP administered after PC was very slight (only 7% reduction of %IS/AR) and statistically insignificant, regardless of the duration of PC ischemia. However, infarct limitation by 3-min PC was inhibited by SPT given after the PC (%IS/AR = 34.5 +/- 3.2), as reported previously. These results suggest that the interstitial Ado level during PC ischemia, not the level during sustained ischemia, is a primary determinant of the extent of cardioprotection by PC and that the threshold for Ado-receptor activation required during sustained ischemia is much lower than that for triggering PC.

Adenosine↗
PubMed1998

Prevention by synthetic phenolic antioxidants of 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)- or activated MeIQx-induced mutagenesis and MeIQx-induced rat hepatocarcinogenesis, and role of antioxidant activity in the prevention of carcinogenesis.

Effects of synthetic phenolic antioxidants 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butylhydroquinone (TBHQ) and propyl gallate (PG) on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)- or activated MeIQx-induced mutagenesis and rat hepatocarcinogenesis were compared, and the association between antioxidative activity and inhibition of carcinogenesis was examined. When the antimutagenic activity of five antioxidants against MeIQx- or activated MeIQx-induced mutagenesis was compared in the Ames assay using the Salmonella strain TA 98, HTHQ showed the greatest effect, followed by BHA, BHT, PG and TBHQ, in that order. In a rat hepatocarcinogenesis study, 6-week-old male F344 rats were given a single i.p. injection of 200 mg/kg bw of diethylnitrosamine (DEN) and starting 2 weeks later, groups of 15 animals received a diet containing 0.03% MeIQx alone, MeIQx together with each antioxidant at a dietary dose of 0.25%, each antioxidant alone, or basal diet alone for 6 weeks. Three weeks after the DEN injection, animals were subjected to 2/3 partial hepatectomy. Liver tissues obtained at partial hepatectomy were processed for the measurement of 8-hydroxydeoxyguanine (8-OHdG) and lipid peroxidation. The average number and areas of glutathione S-transferase placental form (GST-P) positive foci were increased by the treatment with MeIQx (27.2 +/- 6.5 per cm2 and 3.17 +/- 0.96 mm2/cm2, respectively). A significant decrease in these parameters was found with the simultaneous antioxidant treatment, HTHQ demonstrating the greatest effect, followed by BHA, BHT and TBHQ, and PG. Without MeIQx, a weak increase in the number of foci was observed in the BHT treatment case. Examination of 8-OHdG levels in liver DNA, as well as malondialdehyde (MDA) and 4-hydroxyalkenals, did not reveal any inter-group variation. These results indicate that antimutagenic activity of antioxidants against MeIQx roughly parallels their anticarcinogenic activity, with HTHQ as the most powerful chemopreventor, but that oxidative stress and antioxidative activity may not be responsible for MeIQx-induced hepatocarcinogenesis and its inhibition, respectively.

Animals↗
PubMed1998

Dose dependence of 1-O-hexyl-2,3,5-trimethylhydroquinone promotion of forestomach carcinogenesis in rats pretreated with N-ethylnitrosourethane.

Post-initiation dose-dependent effects of the chemopreventive antioxidant 1-O-hexyl-2, 3, 5-trimethylhydroquinone (HTHQ), a potent inhibitor of heterocyclic amine-induced mutagenesis and carcinogenesis, on the development of forestomach and tongue tumors were investigated in male F344 rats. Groups of 22 rats were treated with 0.01% ethylnitrosourethane (ENUR) as an initiator in the drinking water for 4 weeks, then placed on diet containing 1.0%, 0.5%, 0.25% or 0.125% HTHQ, or basal diet alone for 36 weeks. Further group of 12 rats each were similarly treated with the different doses of HTHQ or given basal diet alone for 36 weeks without prior ENUR treatment. All animals were killed at week 40. Tongue papillary hyperplasia and papillomas tended to be increased in the groups treated with ENUR followed by 0.5-0.125% HTHQ, though there was no effect at the highest dose, in line with increased bromodeoxyuridine labeling indices. In the forestomach, the incidences of papillomas and carcinomas were also significantly elevated only in the group treated with ENUR followed by 0.125% HTHQ. Without ENUR pretreatment, papillary hyperplasia was found in the 1-0.125% HTHQ groups and the labeling index was also increased, though without clear dose dependence. The results indicate that HTHQ may have very weak or weak promotion potential for tongue and forestomach carcinogenesis, but that both minimum and maximum thresholds for active dose levels may exist.

Animals↗
PubMed1998

Long-term results of adjuvant irradiation or surveillance in stage I testicular seminoma.

BACKGROUND: Excellent treatment results are obtained for stage I testicular seminoma treated with orchiectomy and prophylactic radiotherapy. In patients with stage I nonseminomatous testicular tumors, surveillance alone is successful, however, this treatment option for stage I testicular seminomas is controversial. There have been few reports of long-term follow-up of surveillance alone for patients with stage I testicular seminoma. METHODS: To assess the appropriateness of th is treatment option, a retrospective survey of stage I testicular seminoma was undertaken. Twenty-seven patients who underwent prophylactic radiation therapy (RT group) and 41 patients followed only by surveillance (S group) after high orchiectomy were evaluated. Their follow-up consisted of frequent clinical examinations, abdominal CT scans, chest x-rays and serum tumor markers. RESULTS: In the RT group, with a median follow-up period of 15 years, 1 patient (3.6%) had a recurrence in the lung at 4 months after orchiectomy and died, but the remaining 26 are alive with no evidence of disease (NED). In the S group, with a median follow-up period of 7.3 years, 5 (12.2%) relapsed in the retroperitoneal lymph nodes, but all are alive with NED following chemotherapy. The remaining 36 are all alive without recurrence (follow-up period, 38 to 132 months). Although the relapse rate in the S group was relatively higher than in the RT group, there was no significant difference between the 2 groups. CONCLUSION: If a frequent follow-up protocol is administered and followed by the patient, surveillance alone may be a recommended management for stage I testicular seminoma.

Adult↗
PubMed1998

Antitumor effect of irinotecan hydrochloride (CPT-11) on human renal tumors heterotransplanted in nude mice.

BACKGROUND: There has been a paucity of antitumor drugs that are active against renal tumors. Irinotecan hydrochloride (CPT-11), a DNA topoisomerase type 1 inhibitor, has demonstrated antitumor activity against human tumors, however, no antitumor effect of CPT-11 on renal tumors has been reported. The antitumor effect of CPT-11 was investigated on 2 human renal tumors (OUR-10 and OUR-20) heterotransplanted into nude mice. METHODS: Tumor-bearing nude mice were given daily intraperitoneal injections of multiple anticancer drugs suspended in 0.2 mL of phosphate-buffered saline (PBS) 3 times at 3-day intervals. Control mice were injected with 0.2 mL of PBS. The antitumor effects were evaluated by calculating the T/C ratio (treated tumors/controls) of the tumor volume. RESULTS: Among the 10 anticancer drugs tested, 50 mg/kg of CPT-11 showed an active antitumor effect on OUR-20 (T/C ratio 34). However, all drugs tested on OUR-10 failed to show antitumor activity. CONCLUSION: Since CPT-11 was effective in 1 of 2 renal tumors examined without severe toxicity, this drug could be a candidate for chemotherapy of renal cell carcinoma.

Animals↗
PubMed1998

Utility of immunohistochemical detection of high molecular weight cytokeratin for differential diagnosis of proliferative conditions of the prostate.

BACKGROUND: Differential diagnosis of adenocarcinoma from other proliferative conditions in the prostate is often problematic. Immunohistochemistry using an antibody (34 beta E12) to high molecular weight cytokeratin, specifically present in basal cells of the prostate, could clearly demonstrate the presence or absence of these cells in the proliferating glands and thus provide an important clue in cancer diagnosis. METHODS: To examine the utility of immunostaining using 34 beta E12, we examined 88 equivocal lesions. Twenty lesions with apparently benign and malignant features were added as controls. We compared the morphologic features of these lesions with their immunoreactivities toward 34 beta E12 on a personal computer display following storage on the MICROPHOT-FXA system. RESULTS: Proliferating glands in all 20 benign lesions had 34 beta E12-reactive basal cells, but none of the malignant lesions did. The equivocal lesions were categorized on morphologic grounds into 2 groups: possibly benign and possibly malignant. Forty-five (51.1%) of the 88 equivocal lesions, were positive for 34 beta E12. These included 35 of the 45 (77.8%) possibly benign lesions and 10 of the 43 (23.3%) possibly malignant lesions. Among the equivocal lesions, 10 considered possibly benign on morphologic grounds showed negative reactivities, and 10 considered possibly malignant showed positive reactivities. Even through comparison on the computer display, no difference in morphology could be discovered between the negative and positive lesions in either group. CONCLUSION: Immunohistochemical procedures using 34 beta E12 are indispensable in the diagnosis of equivocal prostate lesions.

Adenocarcinoma↗
PubMed1998

Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor.

BACKGROUND: The growth and progression of prostate cancer depends on the stromal-epithelial interaction which is under paracrine control. Hepatocyte growth factor (HGF), produced by mesenchymal cells, is a multifunctional growth factor stimulating the movement and growth of epithelial cells including cancer cells. We therefore assessed the relationship between the invasive potential of prostate cancer and HGF in vitro. METHODS: Three human prostate cancer cell lines were used including PC-3 and DU145 (androgen-independent), and LNCaP (androgen-dependent). We studied the expression of the HGF receptor c-met proto-oncogene (c-met) by Western blot analysis, and also determined the effects of HGF on cell scattering, and the mechanisms of invasion and proliferation, by microscopic observation, the matrigel invasion chamber assay, and the MTT assay. RESULTS: c-met was detected in PC-3 and DU145 cells, but not in the LNCaP cells. There was increased cell motility in the scatter assay and an increased cell invasive potential in the matrigel invasion chamber assay by stimulation with HGF only with DU145 cells. CONCLUSION: HGF plays an important role in the invasion and metastasis of the DU145 cell line through a paracrine mechanism mediated by the c-metreceptor. In the PC-3 cell line, the lack of downstream signal transduction after the c-met receptor is suggested.

Biocompatible Materials↗
PubMed1998

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

BACKGROUND: Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. METHODS: ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. RESULTS: There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. CONCLUSIONS: The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

Analysis of Variance↗
PubMed1998

Ecto-5'-nucleotidase is not required for ischemic preconditioning in rabbit myocardium in situ.

This study tested the hypothesis that cardiac ecto-5'-nucleotidase (ecto-5'-NT) activity during ischemic preconditioning (PC) contributes to augmented tolerance against ischemia, thereby reducing infarct size in the rabbit heart in situ. The effects of alpha,beta-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5'-NT, on cardiovascular responses to AMP were measured to establish in vivo activities of the enzyme and its inhibitor. Left atrial infusion of AOPCP (0.75 mg . kg-1 . min-1) raised AOPCP plasma levels to 138 microM; under these conditions negative chronotropic and inotropic effects of AMP were blocked, demonstrating essentially full inhibition of ecto-5'-NT in the heart in situ. This AOPCP-blocked heart in situ model was used to examine the proposed contribution of ecto-5'-NT in ischemic PC. Myocardial infarction caused by 30-min ischemia was followed by 3-h reperfusion. Infarct size (IS) was measured and expressed as a percentage of the size of the area at risk (%IS/AR). In untreated controls, %IS/AR was 38.1 +/- 3.8%; PC (5-min ischemia, 5-min reperfusion) markedly reduced %IS/AR to 10.0 +/- 2.0%. Essentially identical IS reductions by PC were observed in AOPCP-blocked animals (%IS/AR = 13.8 +/- 2.2 and 13.3 +/- 1.8% in rabbits receiving AOPCP at 0.75 and 1.50 mg . kg-1 . min-1, respectively); here plasma AOPCP levels were established before and during PC but not during the subsequent prolonged ischemia. As expected, AOPCP also did not affect %IS/AR in non-PC controls (%IS/AR = 35.5 +/- 3.7%). In contrast but as predicted, adenosine-receptor blockade by 8-phenyltheophylline (10 mg/kg iv) substantially attenuated IS reduction by PC in both AOPCP-blocked and control hearts (%IS/AR = 25.2 +/- 4.3 and 21.8 +/- 2.2%, respectively; P < 0.05 vs. PC alone). The results demonstrate that cardiac ecto-5'-NT is not required for ischemic PC against infarction in the rabbit.

5'-Nucleotidase↗