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K Noda

Publications and source records attributed to K Noda.

At least 127 records · Page 7Linked to original sources
PubMed1998

High expression of alpha-1-6 fucosyltransferase during rat hepatocarcinogenesis.

Alpha-1-6 fucosylated alpha-fetoprotein (AFP) is known to be elevated in patients with primary hepatoma and has been suggested as being useful as an early indicator and predictor of the poor prognosis for hepatoma. Although GDP-L-fucosyl-N-acetyl-beta-D-glucosaminide alpha-1-6 fucosyltransferase (alpha-1-6 FucT), is the key enzyme involved in alpha-1-6 fucosylation of AFP, when and how the expression of alpha-1-6 FucT is enhanced during hepatocarcinogenesis is unknown. Recently, we established a convenient assay method for this enzyme and were successful in the purification and cDNA cloning of alpha-1-6 FucT from human gastric cancer, as well as from porcine brain. In the present study, levels of alpha-1-6 FucT activity and mRNA expression have been determined during hepatocarcinogenesis in LEC rats which spontaneously develop hereditary hepatitis and hepatoma. The fetal liver contained the highest enzymatic activity, which tended to increase in inverse proportion to gestation. The enzymatic activity was significantly increased in hepatoma tissues as compared with uninvolved adjacent tissues. Northern-blot analysis revealed high expression of alpha-1-6 FucT mRNA in hepatoma tissues, whereas the expression was fairly low in normal, hepatitis and uninvolved adjacent liver tissues. While the fetal liver had the highest enzymatic activity, the expression of alpha-1-6 FucT mRNA was low, suggesting that another alpha-1-6 FucT is induced in fetal liver or that post-translational modification occurs. High expression of alpha-1-6 FucT was also observed in 3'-MeDAB-induced rat hepatomas and some rat hepatoma cell lines. Collectively, alpha-1-6 FucT was strongly enhanced from an early stage of hepatocarcinogenesis and was maintained at a high level in rat hepatomas.

Aging↗
PubMed1998

Suppressive effects of low-power laser irradiation on bradykinin evoked action potentials in cultured murine dorsal root ganglion cells.

The effects of Ga-Al-As diode laser (830 nm, 16.2 mW) irradiation on the distal portion of the processes of cultured murine dorsal root ganglion (DRG) neurons associated with C-fibers were studied by patch-clamp whole-cell recording of membrane potentials at the cell body. The chemical as well as laser light stimulations were limited to the processes of the neuron isolated from the cell body with a separator. The action potentials elicited by bradykinin (BK) in the cell body were reversibly suppressed by the irradiation of laser light. The laser irradiation may block the conduction of nociceptive signals in primary afferent neurons. The present experimental method offers a simple and easy to use procedure for studying the pain relief effects by laser irradiation.

Action Potentials↗
PubMed1998

Gene expression of alpha1-6 fucosyltransferase in human hepatoma tissues: a possible implication for increased fucosylation of alpha-fetoprotein.

The 1-6 fucosylated -fetoprotein (AFP) present in serum of patients with hepatocellular carcinoma (HCC) has been employed for the differential clinical diagnosis of HCC from chronic liver diseases. The molecular mechanism by which this alteration occurs, however, remains largely unknown. To address this issue, we purified GDP-L-Fuc:N-acetyl-beta-D-glucosaminide 1-6 fucosyltransferase (1-6 FucT), an enzyme involved in the 1-6 fucosylation of N-glycans from porcine brain, as well as from a human gastric cancer cell line, and cloned their genes. In this study, levels of 1-6 FucT mRNA expression and the activity of this enzyme for 12 human HCC tissues were examined and compared with that in surrounding tissues and normal livers. The mean +/- SD for 1-6 FucT activity was 78 +/- 41 pmol/h/mg in normal control liver, 202 +/- 127 pmol/h/mg in adjacent uninvolved liver tissues (chronic hepatitis: 181 +/- 106 pmol/h/mg; liver cirrhosis: 233 +/- 164 pmol/h/mg), and 195 +/- 72 pmol/h/mg in HCC tissues. The mRNA expression of 1-6 FucT was also enhanced in proportion to enzymatic activity except for a few cases, suggesting that 1-6 FucT expression is increased in chronic liver diseases, especially liver cirrhosis. Transfection of 1-6 FucT gene into cultured rat hepatocytes markedly increased 1-6 FucT activity and led to an increase in lens culinaris agglutinin (LCA) binding proteins in both cell lysates and condition media. When the 1-6 FucT gene was transfected into a human HCC cell line, Hep3B, which originally showed low levels of 1-6 FucT expression, 1-6-fucosylated AFP was dramatically increased in the condition media. Collectively, these results suggest that the enhancement of 1-6 FucT expression increased the fucosylation of several proteins, including AFP, and that the level of 1-6-fucosylated AFP in patients with HCC was in part caused by up-regulation of the 1-6 FucT gene expression.

Adult↗
PubMed1998

Interrelationship between alcohol intake, hepatitis C, liver cirrhosis, and hepatocellular carcinoma.

The discovery of a cDNA clone of hepatitis C virus (HCV) genome in 1989 has resulted in numerous reports of high rates of the prevalence of HCV antibody in patients with alcoholic liver disease, in particular, alcoholic liver cirrhosis and hepatocellular carcinoma. Thus, the interaction between alcohol intake and HCV infection has become of great importance. In terms of the effect of alcohol on HCV-RNA levels, the data are controversial; in some reports, alcohol increases HCV-RNA levels, and in the other reports it does not. There are several reports suggesting the possibility of an elevated quasi-species of hypervariable region 1 in the HCV genome caused by alcohol drinking. Recent studies have documented that alcohol intake exaggerates the responsiveness of interferon therapy for chronic hepatitis C; however, its mechanism is still obscure. Several studies have suggested the promoting effect of alcohol on the development of hepatocellular carcinoma in type C liver cirrhosis, which has been similarly observed in type B chronic liver disease, whereas its mechanism is limited to speculations.

Alcohol Drinking↗
PubMed1998

A novel glycoprotein obtained from Chlorella vulgaris strain CK22 shows antimetastatic immunopotentiation.

A glycoprotein extract (CVS), derived from the unicellular green alga Chlorella vulgaris, strain CK22, exhibited a pronounced antitumor effect against both spontaneous and experimentally induced metastasis in mice. Inhibition of tumor metastasis was enhanced when intratumor administration of CVS was followed by s.c. injection of CVS. Anti-metastatic immunopotentiation was observed in euthymic mice, but not in athymic nude mice. The antitumor activity of CVS was reflected in antigen-specific, T-cell-mediated immunity. Both CD4 and CD8 T cells contributed to the antimetastatic effects, as shown by in vivo depletion experiments with anti-T-cell subset antibodies. Furthermore, CVS caused the recruitment of T cells to the regional lymph nodes and their proliferation in these organs. The CD4-positive population, following CVS injection at the time of tumor rechallenge, displayed a pronounced increase in the proportion of T cells that were CD18 bright, CD44 bright, CD25+, CD54+, CD69+ or CD71+ in the lymph nodes. Thus, CVS induces T cell activation in peripheral lymph nodes in tumor-bearing mice. We conclude that CVS augments antimetastatic immunity through T cell activation in lymphoid organs and enhances recruitment of these cells to the tumor sites. Presurgical treatment with CVS might prevent metastasis or tumor progression.

Animals↗
PubMed1998

Phase I study of E7010.

E7010 is a novel sulfonamide which was discovered using slow-growing colon 38 carcinoma cells as a screening model. E7010 exhibits a broad spectrum of antitumor activity against human tumor xenografts. The mechanism of action is by arresting the progression of cells in M phase of the cell cycle by inhibiting tubulin polymerization. The objective of this phase I study was to determine the maximum allowable dose (MAD), toxicity, and pharmacokinetics of single or 5-day repeated doses of E7010. In the single-dose study, E7010 was administered orally to 16 patients at doses ranging from 80 to 480 mg/m2. The dose-limiting toxicity was peripheral neuropathy at a dose of 480 mg/m2. Hematological and gastrointestinal toxicities were mild. In the 5-day repeated-dose study, 41 patients were given E7010 at doses ranging from 30 to 240 mg/m2 per day. The dose-limiting toxicities were peripheral neuropathy and intestinal paralysis. Gastrointestinal toxicity was dose-dependent but not severe. Hematological toxicity was not dose-dependent. Pharmacokinetic analysis in the single-dose study showed a rapid increase in the plasma levels of the drug after administration, followed by disappearance with a t1/2 of 4.4-16.6 h. The variation in area under the plasma concentration-time curve (AUC) between the patients was small and increased in a dose-dependent manner. Total drug recovery in urine 72 h after administration was 77.8+/-11.4%, indicating that E7010 has favorable absorption and elimination profiles. The changes in the plasma levels of E7010 on day 5 in the 5-day repeated-dose study were almost the same as those on day 1, indicating that the drug did not accumulate. In the single-dose study, spinal cord metastasis exhibited a 74% reduction in a patient with uterine sarcoma and a minor response (MR) was observed in a pulmonary adenocarcinoma patient. In the 5-day repeated-dose study decreases in the tumor markers carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC) were observed in a patient with stomach cancer and in a patient with recurrent uterine cervical carcinoma, respectively. The recommended phase II doses are 320 mg/m2 for a single-dose study and 200 mg/m2 per day for a 5-day repeated-dose study. Since the activity of E7010 is time-dependent, i.e. a certain concentration of E7010 is required for more than 12 h to suppress the growth of P388 leukemia cells, it is recommended that subsequent phase I/II studies be conducted using a divided dose schedule in order to maintain the blood level of E7010.

Adult↗
PubMed1998

Separation of a process from the neuronal cell body using a thin aluminum foil separator.

A new technique using a simple-structured separator is described to separate the end of the process from the cell body (soma) of cultured cells. By this method, stimulation limited to neuronal processes is experimentally possible. The separator is of an oblong shape and consists of two parts: a square bracket-shaped frame made of Teflon and a thin aluminum foil which is stuck on both free ends of frame (bracket) coated with epoxy-resin. The separator is horizontally placed on the dish under microscope to divide the process on the way, so that the free end of the process is outside the oblong separator. This separator is simple and low cost, and does not need a long process, unlike other methods requiring a special culture dish with a micro-groove for growth of the neuronal process (neurite). The new technique could be useful in basic pain research and neurophysiology.

Aluminum↗
PubMed1998

Neuromuscular toxicities of paclitaxel 210 mg m(-2) by 3-hour infusion.

We retrospectively analysed neuromuscular toxicity associated with paclitaxel 210 mg m(-2) given by 3-h infusion in 247 patients. The severity correlated significantly with total cumulative dose, but could not be predicted by the pretreatment clinical variables or by pharmacokinetic parameters. The toxicity tended to occur in early treatment cycles.

Adult↗
PubMed1998

Dose-finding study of irinotecan and cisplatin plus concurrent radiotherapy for unresectable stage III non-small-cell lung cancer [seecomments].

Irinotecan hydrochloride (CPT-11) shows marked anti-tumour activity alone and in combination with cisplatin in non-small-cell lung cancer (NSCLC). It is necessary to investigate combined-modality therapy including novel effective anti-cancer agents to improve long-term survival of patients with unresectable stage III NSCLC. A phase I/II study of concurrent chemoradiotherapy with CPT-11 and cisplatin was conducted to determine the maximum tolerated dose (MTD) and efficacy in this group of patients. Thirteen previously untreated patients with unresectable stage IIIA/B NSCLC were enrolled and efficacy and toxicity was evaluated in 12 of them; one patient was ineligible. Chemotherapy was repeated every 4 weeks for three courses. Radiation therapy was started on day 2 of the first course of chemotherapy and 60 Gy in 30 fractions was given over 6 weeks. Four of six patients enrolled at level 1 completed the scheduled treatment. Another two received only one and two courses of chemotherapy as a result of persistent leucopenia and neutropenic fever respectively. Three of six patients given level 2 therapy completed the scheduled treatment. Another three received only one and two courses of chemotherapy, two refused treatment because of diarrhoea and one died of pneumonia. Radiation therapy was inadequate in these three patients. As the CPT-11 dose intensity in this trial was low, because of the necessity of omitting CPT-11 administration on days 8 and/or 15 as a result of leucopenia or diarrhoea, and the low radiation therapy completion rate, the trial was discontinued at level 2. Five patients at level 1 and three at level 2 showed partial responses, an overall response rate of 67%. Although neither MTD nor dose-limiting toxicity could be identified, chemotherapy with CPT-11 and cisplatin plus concurrent radiation therapy was deemed unacceptable. We are now conducting a phase I/II study of chemotherapy using CPT-11 as a single agent in combination with radiation therapy.

Adult↗
PubMed1998

Argyrophilic structures stimulate glial reactions in neurofibrillary tangles and senile plaques.

Neurofibrillary tangles (NFT) and senile plaques (SP) contain various pathological structures, and the majority of these pathological structures are argyrophilic. To investigate the glial reactions of the argyrophilic substance, we performed immunohistochemistry for microglia or for astroglia after Gallyas-Braak staining, which is one of the most sensitive silver impregnation techniques detecting argyrophilic structures in NFT and SP. We found that extracellular argyrophilic structures in NFT and SP showed glial reactions, and we observed reactive microglia in the center of NFT and SP in contrast to astroglia, which were situated in the periphery. These findings suggest that the exposed argyrophilic components in the extracellular space stimulate both glial reactions, but that there is a striking difference in localization between microglia and astroglia.

Alzheimer Disease↗
PubMed1998

Genetic analysis of the epithelial sodium channel in Liddle's syndrome.

BACKGROUND: Liddle's syndrome is an autosomal inheritable disorder that causes hypertension due to excess function of sodium channel. OBJECTIVE: To analyze the DNA sequence of the amiloride-sensitive epithelial sodium channel (ENaC) in three patients who had low-renin hypertension with hypokalemia. The patients included a 24-year-old woman and her 20-year-old brother whose mother was hypertensive. The third patient was a 15-year-old girl with no family history of hypertension. METHODS: The DNA sequence of the ENaC was analyzed as follows. Venous blood samples were collected from the patients and total genomic DNA was prepared by standard methods. Specific primers were used for direct polymerase chain reaction; one set of primers for amplifying the C terminus (codon 523-638) of the , subunit of ENaC, and two sets of primers for amplifying the C terminus (codons 525-587 and 568-650) of the y subunit of ENaC. Polymerase chain reaction products were purified and subjected to direct DNA sequence analysis. RESULTS: Direct sequence analysis demonstrated the presence of a single-base substitution in one segment of the 0 subunit of ENaC, a C-T transition that changed the encoded Pro (CCC) at codon 616 to Ser (TCC) in the siblings (cases 1 and 2). In case 3, we found a missense mutation of Pro (CCC) to Leu (CTC) at codon 616. Case 3 is considered to be sporadic, since DNA sequencing of the PY motif of her parents gave normal results. CONCLUSIONS: The DNA sequences of the ENaC in three patients with Liddle's syndrome were analyzed. In one family case, we found a new missense mutation of Pro (CCC) to Ser (TCC) at codon 616 in the 0 subunit of ENaC. A genetic analysis of the amiloride-sensitive epithelial sodium channel is recommended in assessing patients with low-renin, salt-sensitive hypertension whose blood pressure is not responsive to spironolactone treatment.

Adolescent↗
PubMed1998

Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. The Japan Clinical Oncology Group.

PURPOSE: To evaluate the therapeutic significance of cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus granulocyte colony-stimulating factor (G-CSF) compared with cyclophosphamide, doxorubicin, and vincristine, alternating with cisplatin and etoposide (CAV/PE) for extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Two hundred twenty-seven patients were randomized. CODE consisted of cisplatin 25 mg/m2 weekly for 9 weeks; vincristine 1 mg/m2 on weeks 1, 2, 4, and 6; and doxorubicin 40 mg/m2 and etoposide 80 mg/m2 for 3 days on weeks 1, 3, 5, 7, and 9. G-CSF 50 micrograms/m2 was administered on the days when chemotherapy was not administered. CAV/PE consisted of cyclophosphamide 800 mg/m2; doxorubicin 50 mg/m2; and vincristine 1.4 mg/m2 on day 1, which alternated every 3 weeks with cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 3. RESULTS: Overall response rates were 77% for the CAV/PE arm and 84% for the CODE arm respectively (15% complete response in both arms). The median survival times were 10.9 months in the CAV/PE arm and 11.6 months in the CODE arm (P = .1034). The achieved dose-intensity for CODE was approximately twice that for CAV/PE for those drugs common to both arms. The incidence of leukopenia did not differ between the two arms, but anemia and thrombocytopenia had a significantly higher incidence in the CODE arm. Four treatment-related deaths from neutropenic fever occurred in the CODE arm. CONCLUSION: The CODE group had a similar median survival to the CAV/PE group. It does not appear that CODE is a useful approach to improve survival in ED SCLC.

Adult↗
PubMed1998

Angiographic evaluation of culprit lesions in acute coronary syndrome: relation to the original site on previous coronary angiography.

Culprit lesions in acute coronary syndrome [acute myocardial infarction (AMI) and unstable angina pectoris (UAP)] were examined angiographically in 222 patients who had previously undergone coronary angiography (CAG). The observation period lasted 5 years after primary CAG in medically treated patients (group M, 127 cases) and after final follow-up CAG in patients treated by percutaneous transluminal coronary angioplasty (PTCA) (group B, 95 cases). There were 33 AMIs, including 5 deaths (22/127, 17.3%, in group M vs 11/95, 11.6%, in group B; p<0.01) and 189 UAPs (105/127, 82.7%, in group M vs 84/95, 88.4%, in group B; NS). High-grade stenoses (>75%) were found in 76 (59.8%) patients in group M, of which 41 lesions (54%) resulted in acute coronary syndromes (ACSs). In group M, ACSs resulted from insignificant stenosis (< or =50%) in 67 (53%) patients and from significant stenosis (>50%) in 60 (47%) patients. In group B, ACSs resulted from insignificant stenosis in 78 (82%) patients and from significant stenosis in 17 (18%) patients. Out of 95 PTCA sites, high-grade restenosis occurred in 3 lesions and ACSs (2 AMI, 14 UAP) in 16 (16.8%). We conclude that ACSs are more likely to develop from insignificant lesions than from significant lesions. High-grade stenoses are prone to become occlusive lesions and PTCA reduces this potential risk. Most target sites of PTCA that escaped restenosis were stable in the long term.

Aged↗
PubMed1998

[A case of metastasis to the seminal vesicle of renal cell carcinoma].

A case of metastasis to the seminal vesicle of renal cell carcinoma is reported. A 60-year-old man was referred to our department for evaluation of intermittent hematospermia and asymptomatic macrohematuria for about 2 years. He had a left radical nephrectomy for localized renal cell carcinoma 5 years ago. Panendscopy showed a little bleeding of posterior urethra, but there were no abnormal images of upper urinary tracts. Two years later he had asymptomatic macrohematuria again and panendscopy showed swelling and bleeding of verumontanum. Transurethral resection of verumontanum revealed clear cell carcinoma histopathologically and CT revealed seminal vesicle or prostate tumor, then total cystectomy was performed. Pathological examination indicated metastasis to siminal vesicle of renal cell ccarcinoma. There has been no report of metastasis to seminal vesicle of renal cell carcinoma in literature. This is the first case in the world.

Carcinoma, Renal Cell↗
PubMed1998

Finding Genetic Network from Experiments by Weighted Network Model.

We study the problem of finding a genetic network from data obtained by multiple gene disruptions and overexpressions. We define a genetic network as a weighted graph, and analyze the computational complexity of the problem. We show that if there exists a weighted network which is consistent with given data, we can find it in polynomial time. Moreover, we also consider the optimization problem, where we try to find an optimally consistent weighted network with given data. We show that the problem is NP-hard. On the other hand, we give a polynomial-time approximation algorithm to solve it with approximation ratio 2. We report some simulation results on experiments.

Journal Article↗