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Y Nakano

Publications and source records attributed to Y Nakano.

At least 109 records · Page 6Linked to original sources
PubMed2001

[Significant role of cisplatin and 5-FU combination chemotherapy for first-line intensive treatment for advanced esophageal cancer].

We evaluated the efficacy of first-line chemotherapy consisting of cisplatin and 5-fluorouracil combination therapy (in the following, FP) in intensive treatment for esophageal cancer. This first-line chemotherapy was administered to 18 patients with squamous cell carcinoma. Three patients had T2 tumor, 10 had T3 and 5 had T4. Lymph node metastasis was detected in 10 patients and not detected in 8 patients. Five patients had distant metastasis. Ten patients showed a partial response and the response rate was 55.6%. Of these 10 patients, 5 were followed with surgery, 3 of whom survived without recurrence of the disease. Five patients were treated by FP, radiation therapy or combination of FP and radiation. Of these 5 patients, 2 showed a complete response. On the other hand, 8 nonresponders died from progressive disease, despite following intensive treatment. These results suggest that first-line chemotherapy by FP, which requires following intensive treatment, improves the overall long-term survival of advanced esophageal cancer patient.

Aged↗
PubMed2001

[Usefulness of hepatic arterial infusion chemotherapy for liver metastasis in gastric cancer].

UNLABELLED: We have performed intra-hepatic arterial chemotherapy for 9 patients with liver metastasis arising from gastric cancer. We mainly used 5-FU and CDDP as antineoplastic drugs. RESULTS: The median survival after gastrectomy was 600 days. Of 9 cases, 2 showed CR, 4 PR, 2 NC, 1 PD. The response rate was 67%. The 9 cases were classified into 2 groups. One group, the short-term survival group, concised of 5 patients that had no more than 2 years survival and the other, the long-term survival group, consisted 4 patients that had more than 2 years survival. We compared these 2 groups and found no difference in the primary lesions between the 2 groups. The patients in the long-term survival group had fewer and smaller metastatic lesions in the liver than the patients of the short-term survival group. The patients in the long-term survival group had no unresectable lesions except liver metastasis when gastrectomy was performed. However, 2 patients in the short term survival group had unresectable lymphatic involvement at the time gastrectomy was performed. Of 9 patients, 6 died from the extrahepatic lesion. CONCLUSION: The intra-arterial chemotherapy was effective and useful for liver metastasis arising from gastric cancer. However, the majority of patients died from extrahepatic lesions. We should therefore consider the use of systemic chemotherapy with intra-arterial chemotherapy.

Aged↗
PubMed2000

Genetic analysis of the gene cluster for the synthesis of serotype a-specific polysaccharide antigen in Aactinobacillus actinomycetemcomitans.

The serotype a-specific polysaccharide antigen (SPA) of Actinobacillus actinomycetemcomitans consists of 6-deoxy-D-talose. A gene cluster associated with the biosynthesis of SPA was cloned and sequenced from the chromosomal DNA of A. actinomycetemcomitans SUNYaB 75 (serotype a). This cluster consisted of 14 open reading frames. Insertional inactivation of eight genes in this cluster resulted in loss of the ability of A. actinomycetemcomitans SUNYaB 75 cells to produce the polysaccharide. A protein database search revealed that the 11 sequential genes containing these eight genes were not found in SPA-associated gene clusters of the other serotypes of A. actinomycetemcomitans. These results suggest that the gene cluster is unique to serotype a and is essential to the synthesis of the SPA.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Patched represses the Hedgehog signalling pathway by promoting modification of the Smoothened protein.

Hedgehog (Hh) signalling plays a central role in many developmental processes in both vertebrates and invertebrates [1]. The multipass membrane-spanning proteins Patched (Ptc) [2-4] and Smoothened (Smo) [5-7] have been proposed to act as subunits of a putative Hh receptor complex. According to this view, Smo functions as the transducing subunit, the activity of which is blocked by a direct interaction with the ligand-binding subunit, Ptc [8]. Activation of the intracellular signalling pathway occurs when Hh binds to Ptc [8-11], an event assumed to release Smo from Ptc-mediated inhibition. Evidence for a physical interaction between Smo and Ptc is so far limited to studies of the vertebrate versions of these proteins when overexpressed in tissue culture systems [8,12]. To test this model, we have overexpressed the Drosophila Smo protein in vivo and found that increasing the levels of Smo protein per se was not sufficient for activation of the pathway. Immunohistochemical staining of wild-type and transgenic embryos revealed distinct patterns of Smo distribution, depending on which region of the protein was detected by the antibody. Our findings suggest that Smo is modified to yield a non-functional form and this modification is promoted by Ptc in a non-stoichiometric manner.

Animals↗
PubMed2000

Structural characterization and formation mechanism of sitting-atop (SAT) complexes of 5,10,15,20-tetraphenylporphyrin with divalent metal ions. Structure of the Cu(II)-SAT complex as determined by fluorescent extended X-ray absorption fine structure.

The UV-vis absorption spectra and the formation kinetics of sitting-atop (SAT) complexes (M(H2tpp)2+) of 5,10,15,20-tetraphenylporphyrin (H2tpp) with a series of divalent metal ions (M2+ = Mn2+, Fe2+, Co2+, Ni2+, Cu2+, and Zn2+) in acetonitrile have been investigated. The structural characteristics of the SAT complexes for a series of M2+ ions are discussed on the basis of the UV-vis absorption spectra. The structure parameters around Cu2+ in the Cu(II)-SAT complex were determined by a fluorescent EXAFS method: the coordination number is 6 with three kinds of Cu-N interactions having bond lengths of 2.05, 1.98, and 2.32 A for pyrrolenine nitrogens of H2tpp, acetonitrile nitrogens at equatorial sites, and acetonitrile nitrogens at axial sites, respectively. The rate constants at 25 degrees C for the formation of the SAT complex in acetonitrile are as follows: kf/mol-1 kg s-1 = 3.4 x 10(2) for Mn2+, 0.18 for Co2+, 1.6 x 10(-3) for Ni2+, and 61 for Zn2+. The finding that the variation trends in the rate constants for a series of M2+ ions for the SAT complex formation and the solvent exchange reaction in various solvents are very similar indicates that the rate-determining step for the SAT complex formation is the interchange between the coordinating nitrogen of a bound acetonitrile and the pyrrolenine nitrogen of H2tpp. The fact that the values of kf are smaller by 4-6 orders of magnitude in comparison with those of the solvent exchange suggests that there is a large energetic loss due to the fast preequilibria prior to the rate-determining step, such as deformation of a porphyrin ring and outer-sphere encounter formation due to an electrostatic interaction between M2+ and the local negative charge on the pyrrolenine nitrogens. We observed the subsequent formation of the corresponding metalloporphyrins by deprotonation of the SAT complex and oxidation of the M2+ center, of which the dynamic behavior was significantly different for the different M2+ ions.

Journal Article↗
PubMed2000

A gene cluster for the synthesis of serotype d-specific polysaccharide antigen in Actinobacillus actinomycetemcomitans.

The serotype d antigen of Actinobacillus actinomycetemcomitans consists of D-glucose, D-mannose, and L-rhamnose in a molar ratio of 1:2:1. A gene cluster involved in the synthesis of serotype-specific polysaccharide antigen was cloned from the chromosomal DNA of A. actinomycetemcomitans IDH 781 (serotype d). This cluster consisted of 12 open reading frames. Insertional inactivation of six genes in this cluster resulted in loss of ability of A. actinomycetemcomitans IDH 781 cells to produce the polysaccharide. Comparing the structure of the gene cluster with similar clusters from other serotypes of A. actinomycetemcomitans, showed that eight genes are unique to serotype d; the other four genes are involved in the biosynthesis of dTDP-L-rhamnose. These results suggest that the synthesis and structure of serotype d-specific polysaccharide of A. actinomycetemcomitans is quite different from those of other serotype strains.

Actinobacillus↗
PubMed2000

Thymidine diphosphate-6-deoxy-L-lyxo-4-hexulose reductase synthesizing dTDP-6-deoxy-L-talose from Actinobacillus actinomycetemcomitans.

The serotype c-specific polysaccharide antigen of Actinobacillus actinomycetemcomitans NCTC 9710 contains an unusual sugar, 6-deoxy-L-talose, which has been identified as a constituent of cell wall components in some bacteria. Two genes coding for thymidine diphosphate (dTDP)-6-deoxy-L-lyxo-4-hexulose reductases were identified in the gene cluster required for biosynthesis of serotype c-specific polysaccharide. Both dTDP-6-deoxy-L-lyxo-4-hexulose reductases were overproduced and purified from Escherichia coli transformed with the plasmids containing these genes. The sugar nucleotides converted by both reductases were purified by reversed-phase high performance liquid chromatography and identified by (1)H nuclear magnetic resonance and gas-liquid chromatography. The results indicated that one of two reductases produced dTDP-6-deoxy-L-talose and the other produced dTDP-L-rhamnose (dTDP-6-deoxy-L-mannose). The amino acid sequence of the dTDP-6-deoxy-L-lyxo-4-hexulose reductase forming dTDP-6-deoxy-L-talose shared only weak homology with that forming dTDP-L-rhamnose, despite the fact that these two enzymes catalyze the reduction of the same substrate and the products are determined by the stereospecificity of the reductase activity. Neither the gene for dTDP-6-deoxy-L-talose biosynthesis nor its corresponding protein product has been found in other bacteria; this biosynthetic pathway is identified here for the first time.

Aggregatibacter actinomycetemcomitans↗
PubMed2000

Attachment of Moraxella catarrhalis occurs to the positively charged domains of pharyngeal epithelial cells.

Attachment of bacteria to host cells is the initial step in the pathogenesis of infection. Several factors, such as hydrophobicity, surface electric charge, and van der Waals force, are considered to be responsible for the attachment step. However, it is not clear why bacteria and epithelial cells, both of which possess a negative surface charge, do not repel one another. In the present study, we used Moraxella catarrhalis and pharyngeal epithelial cells to study the surface charges of structures involved in the attachment. By atomic force microscopy (AFM) equipped with surface potential spectroscopy, it was found that the cell surface microplicae have a positive charge of 30.1+/-3.6 mV (mean+/-SE). The depressions between the microplicae have a negative surface charge of 43.5+/-4.0 mV. Using cationic ferritin and electron microscopy (EM) we confirmed that the depressions between the microplicae have a negative charge. By AFM and by using cationic ferritin with EM, it was found that the net surface charge of the bacterial cells is negative. By both AFM and EM, it was found that the bacterial cells attach to the microplicae of the pharyngeal epithelial cell. Our work confirmed the general belief that both kinds of cells do have a net negative charge. We conclude that there are positively and negatively charged domains on the surface of human pharyngeal epithelial cells. M. catarrhalis evidently attaches to the positively charged domain (i.e. microplicae) of pharyngeal epithelial cells.

Adult↗
PubMed2000

Vitamin D receptor gene polymorphism is associated with serum total and ionized calcium concentration.

Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5+/-0.3 vs. 4.5+/-0.4 vs. 4.4+/-0.5 mmol/l in normotensives and 4.6+/-0.3 vs. 4.6+/-0.4 vs. 4.4+/-0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17+/-0.04 vs. 1.16+/-0.04 vs. 1.15+/-0.04 mmol/l in normotensives and 1.16+/-0.04 vs. 1.16+/-0.04 vs. 1.14+/-0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects.

Adult↗
PubMed2000

The usefulness, indications, and complications of laparoscopy-assisted colectomy in comparison with those of open colectomy for colorectal carcinoma.

The technique of laparoscopy-assisted colectomy (LAC) was developed for benign and malignant diseases of the colon and rectum; however, its feasibility and the associated clinical outcome remain unclear. We reviewed 45 patients who underwent LAC (LAC group) and 62 patients who underwent traditional open surgery (Open group) for colorectal carcinoma in our hospital, and compared the clinical data between the two groups in an effort to determine whether LAC is really minimally invasive and if it enhances the quality of life. So that the backgrounds of the patients in both groups were almost the same, we only compared data of patients with colorectal carcinoma of stages 0, I, and II. The duration of surgery in the Open group was significantly shorter for all procedures except sigmoid resection, but the blood loss was not significantly different between any of the procedures except for right colectomy. The time to the first passing of flatus and restarting oral intake, length of hospital stay, and duration of epidural analgesia were significantly shorter in the LAC group. The morbidity and mortality rates in the LAC group were almost the same as those in the Open group at 29.5% and 3.3% versus 22.6% and 1.6%, respectively. However, five major complications of LAC for advanced colorectal carcinomas might be prevented by performing an open procedure. In conclusion, LAC is a safe and minimally invasive surgical technique following which we can expect a faster recovery; however, patients with advanced colorectal carcinomas must be carefully selected for this operation.

Adenocarcinoma↗
PubMed2000

Dietary docosahexaenoic acid suppresses inflammation and immunoresponses in contact hypersensitivity reaction in mice.

This study was designed to examine the immunomodulatory effects of dietary docosahexaenoic acid (DHA) in the absence of eicosapentaenoic acid (EPA). We investigated the effects of feeding dietary DHA ethyl ester (DHA-Et) (97% pure) at levels of 4.8 wt% of the total diet and of feeding EPA ethyl ester (EPA-Et) (99% pure) at 4.8 wt% on the inflammatory response in the challenge phase of the contact hypersensitivity reaction (CHR) in the ears of mice sensitized with 2,4-dinitro-1-fluorobenzene (DNFB). The effect of DHA-Et on T lymphocytes at the CHR site was examined using anti-CD4 antibodies. Furthermore, we examined the cytokines formed at the CHR site on the mRNA level. It was found that 24 h after the challenge, DHA-Et but not EPA-Et reduced the ear swelling. Infiltration of inflammatory cells, in particular, CD4-positive T lymphocytes, into the ears in the challenge phase of CHR was observed. DHA-Et reduced the infiltration of CD4-positive T lymphocytes into the ears. DHA-Et also decreased the expression of interferon-gamma, interleukin (IL)-6, IL-1beta, and IL-2 mRNA in ears. These observations suggest that DHA, but not EPA, may exert an antiinflammatory and immunosuppressive effect. The immunosuppressive effectiveness of fish oil may be attributed mainly to DHA.

Animals↗
PubMed2000

Habituation of event-related potentials in patients with Parkinson's disease.

Auditory event-related potential (ERP) was studied in idiopathic Parkinson's disease (PD) using our new procedures. We examined 12 non-demented patients with PD, and 9 age-matched control subjects. Ninety responses induced by rare stimulation were continuously recorded from Fz, Cz, Pz referred to linked earlobe electrode (A1A2), and were divided into nine blocks (one block = 10 responses) for statistical analysis. We assessed the habituation of auditory ERP to detect delicate changes related to the information processing in PD. N100 and P300 latencies were significantly longer in PD than in control subjects (p<0.05). P300 latency gradually increased with progression of recording blocks in both PD and control subjects, whereas N100 latency increased only in PD. Three way analysis of variance for P300 amplitude revealed significant effects of subject group, recording electrode site, and trial block. P300 amplitude was smaller in PD than in control subjects. Significant negative correlation between P300 amplitudes and block numbers were observed at Cz and Pz in PD, and at Fz in the control group. Previous reports as well as present results suggest that prolongation of N100 latency might be related to frontal lobe dysfunction, and abnormality of P300 to dysfunction in both the frontal lobe and hippocampus in PD.

Aged↗
PubMed2000

Poor clinical significance of p53 gene polymorphism in acute myeloid leukemia.

The cancer susceptibility according to the p53 polymorphism at codon 72 has been in controversy. In this study, the clinical significance of p53 polymorphism in de novo acute myeloid leukemia (AML) was examined. Although the allelic frequency of Arg in 200 patients with AML (64.3%) tended to be greater than that in normal controls (56. 6%), these frequencies were within the normal range according to the previous data in Japan (from 59.9 to 65.3%). p53 mutations, found in nine (4.5%) of the 200 patients, were not related to the polymorphism. Six of 93 patients showing heterozygosity at codon 72 had allelic imbalance according to the polymerase chain reaction assay, which occurred in either allele and was associated with p53 mutation and poor prognosis (P=0.01). However, the p53 polymorphism was not associated with clinical features, complete remission rates or prognosis of AML. These results indicate that the p53 genotype at codon 72 is useful to detect loss of heterozygosity but not associated with risk, pathophysiology or therapeutic response of AML.

Female↗
PubMed2000

Measurement of the concentrations of glucose and lactic acid in peritoneal dialysis solutions using near-infrared spectroscopy.

Near-infrared spectroscopy (NIR), a nondestructive analytical technique, was employed for the simultaneous determination of the concentrations of glucose and lactic acid in peritoneal dialysis solutions. Solutions were placed in a near-infrared spectrophotometer and the absorbance at wavelengths between 400 and 2500 nm was measured at 2 nm intervals. To obtain calibration equations, multiple linear regression (MLR) was carried out on the NIR spectral data and on the glucose and lactic acid concentrations obtained by enzymatic methods using a calibration sample set. The value of the simple correlation coefficient (r) was 0.996 when using a wavelength of 2270 nm for glucose. The value of the multiple correlation coefficient (R) for lactic acid was 0.997 when using wavelengths of 1688 and 1268 nm. To validate the calibration equations obtained, glucose and lactic acid concentrations in a prediction sample set which was not used for calibration were calculated using the calibration equation and compared with the concentrations measured by the enzymatic method. Excellent agreement between the results of the enzymatic method and of NIR was observed for both constituents. Concentrations of glucose and lactic acid in the peritoneal dialysis solutions were analyzed simultaneously by NIR. The procedure for NIR was simple, and the operation time required to determine the concentrations was a few minutes. These results indicate that NIR may be a useful method for monitoring of the production of peritoneal dialysis solutions.

Journal Article↗
PubMed2000

Inhibition of rare earth catalytic activity by proteins.

Catalytic action of rare earth element, Ce(IV) to hydrolyze phosphomonoester bonds was confirmed. This effect was considered to suppress abiotic synthesis of nucleotides and nucleic acids in the primitive sea, and hence the origin of life. However, we found that the presence of proteins, especially albumin, strongly inhibited the catalytic action of Ce(IV). This finding was supported by preferential binding of rare earth elements (REEs) to proteins which was revealed using the radioisotopes of these REEs. Consequently, if a large amount of proteins was synthesized in the primitive sea, abiotic synthesis of phosphomonoester compounds, and hence nucleic acids, might have been possible.

Catalysis↗
PubMed2000

Prognostic value of p53 gene mutations and the product expression in de novo acute myeloid leukemia.

In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent but associated with a poor prognosis. The majority of mutations are missense mutations, which generally lead to accumulation of nuclear p53 protein. However, the prognostic significance of the accumulation remains unknown in AML. In this study, we compared the prognostic value of p53 mutations versus accumulation of the product. p53 mutations were found in 9 (4.5%) of 200 patients with de novo AML. The p53 mutation detectable (mutation+) group had a worse prognosis (p = 0.0009) than the mutation not detectable (mutation-) group. Multivariate analysis showed that the p53 mutation was an independent factor (p = 0.005) for short overall survival as well as 60 yr or older (p = 0.001) and unfavorable karyotypes (p = 0.001). In 79 of the 200 patients, the expression of p53 was studied by immunocytochemistry (ICC) using anti-p53 monoclonal antibody (DO-7). All samples carrying missense mutations (N = 6) were positive for ICC in over 15% of nuclei of each sample, chosen as the optimized cutoff value of p53 accumulation. Accumulation was thus found in 14 of the 79 patients. However, there was no prognostic difference according to the accumulation, because the mutation-/accumulation+ group (N = 8) tended to have a good prognosis. These findings indicate that molecular detection of p53 mutations yields better prognostic information than ICC. In a subset of AML, p53 protein might be accumulated without mutation presumably due to upstream signals of p53.

Acute Disease↗
PubMed2000

Gene gun-mediated delivery of an interleukin-12 expression plasmid protects against infections with the intracellular protozoan parasites Leishmania major and Trypanosoma cruzi in mice.

An interleukin-12 (IL-12) expression plasmid was transferred, using a gene gun, to mice infected with Leishmania major or Trypanosoma cruzi. Transfer of the IL-12 gene to susceptible BALB/c mice resulted in regression of lesion size and reduced the number of parasites in draining lymph nodes (LN) at the site of L. major infection. Coincident with these protective effects, the T-helper type (Th) response shifted towards Th1, as evaluated by cytokine production in vitro and L. major-specific antibody responses. Protective effects of the IL-12 gene were also observed in T. cruzi infection. Treatment of BALB/c mice infected with T. cruzi enhanced the production of interferon-gamma (IFN-gamma) by spleen cells, while suppressed production of interleukin-10 (IL-10) compared with control mice. Administration of anti-CD4 or anti-CD8 monoclonal antibody (mAb) abolished the protective immunity against T. cruzi infection, and treatment with the IL-12 gene could not restore the resistance in these mice. Mice depleted of natural killer (NK) cells with anti-asialo GM1 also became susceptible to infection, while the resistance was restored when these mice were treated with the IL-12 gene. Thus, target cells for the treatment appear to be CD4+ and CD8+ T cells, which are ordinarily activated by NK cells. These results suggest that the transfer of cytokine genes using a gene gun is an effective method for investigating the roles of cytokines and gene therapy in infectious diseases.

Animals↗