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Biomedical subjects

K Noda

Publications and source records attributed to K Noda.

At least 19 recordsLinked to original sources

VLA-4 blockade suppresses endotoxin-induced uveitis: in vivo evidence for functional integrin up-regulation.

Leukocyte adhesion to the vascular wall is a critical early step in the pathogenesis of inflammatory diseases and is mediated in part by the leukocyte integrin, VLA-4, which binds to endothelial vascular cell adhesion molecule (VCAM) -1. Here, we investigate VLA-4's role in endotoxin-induced uveitis (EIU). At various time points (6-48 h) after EIU induction, the severity of the inflammation was evaluated by quantifying cell and protein content in the aqueous fluid, firm leukocyte adhesion in the retinal vessels, and the number of extravasated leukocytes into the vitreous. Functional activation of VLA-4 in vivo was investigated in our previously introduced autoperfused micro flow chamber assay. Firm adhesion of EIU leukocytes to immobilized VCAM-1 under physiological blood flow conditions was significantly increased compared with normal controls (P<0.05), suggesting an important role for VLA-4 in EIU. VLA-4 blockade in vivo significantly suppressed all uveitis-related inflammatory parameters studied, decreasing the clinical score by 45% (P<0.01), protein content in the aqueous fluid by 21% (P<0.01), retinal leukostasis by 68% (P<0.01), and leukocyte accumulation in the vitreous by 75% (P<0.01). Our data provide novel evidence for functional up-regulation of VLA-4 during EIU and suggest VLA-4 blockade as a promising therapeutic strategy for treatment of acute inflammatory eye diseases.

Animals↗

Molecular mechanisms of nigral neurodegeneration in Park2 and regulation of parkin protein by other proteins.

Most of the patients with Parkinson's disease (PD) are sporadic. However, Since identification of monogenic forms of PD, the contribution of genetic factors to the pathogenesis of sporadic PD is proposed as one of major risk factors. Indeed, this is supported by the demonstration of the high concordance in twins, increased risk among relatives of PD patients in case control and family studies. Thus, the functional analysis for the gene products for familial PD provides us a good hint to elucidate the pathogenesis of nigral degeneration. For example, although alpha-synuclein is involved in a rare dominant form of familial PD with dopa responsive parkinsonian features, this molecule is a major component of and Lewy bodies (LBs). In contrast, Park2 (parkin-related disease) is the most frequent form among patients with young-onset PD. However, Park2 brains generally lack the formation of LBs. In the other word, parkin responsible for Park2 is essential for the formation of LBs. Thus, both alpha-synuclein and parkin are speculated to share a common pathway. Here, we reviewed the parkin function and molecular mechanisms of Park2.

Gene Expression Regulation↗

A method for discriminating a Japanese chicken, the Nagoya breed, using microsatellite markers.

The Nagoya breed native to Japan is popular as a dual-purpose breed for eggs and meat. The current study describes a method to discriminate between the Nagoya breed and other breeds and commercial stocks of chicken. Four strains of the Nagoya breed established at the Aichi-ken Agricultural Research Center were analyzed using 25 microsatellite markers. In these strains, 5 of the markers (ABR0015, ABR0257, ABR0417, ABR0495, and ADL0262) had a single allele. Other chicken samples (448) of various breeds and hybrids were analyzed using the same 5 markers. None of these chicken samples had the same allele combination as the Nagoya breed strains. These 5 microsatellite markers provide a practical method to accurately discriminate the Nagoya breed from other chicken breeds.

Animals↗

Phase II trial of docetaxel in advanced or metastatic endometrial cancer: a Japanese Cooperative Study.

The purpose of this study was to determine whether docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma. Chemotherapy-naïve or previously treated patients (one regimen) with histopathologically documented endometrial carcinoma and Eastern Cooperative Oncology Group performance status </=2 entered the study. Docetaxel 70 mg m(-2) was administered intravenously on day 1 of a 3-week cycle up to a maximum of six cycles. If patients responded well to docetaxel, additional cycles were administered until progressive disease or unacceptable toxicity occurred. Of 33 patients with a median age of 59 years (range, 39-74 years) who entered the study, 14 patients (42%) had received one prior chemotherapy regimen. In all, 32 patients were evaluable for efficacy, yielding an overall response rate of 31% (95% confidence interval, 16.1-50.0%); complete response and partial response (PR) were 3 and 28%, respectively. Of 13 pretreated patients, three (23%) had a PR. The median duration of response was 1.8 months. The median time to progression was 3.9 months. The predominant toxicity was grade 3-4 neutropenia, occurring in 94% of the patients, although febrile neutropenia arose in 9% of the patients. Oedema was mild and infrequent. Docetaxel has antitumour activity in patients with advanced or recurrent endometrial carcinoma, including those previously treated with chemotherapy; however, the effect was transient and accompanied by pronounced neutropenia in most patients.

Adenocarcinoma↗

Impaired glucose tolerance is accompanied by decreased insulin sensitivity in tissues of mice implanted with cells that overexpress resistin.

AIM/HYPOTHESIS: Resistin, the expression of which is suppressed by thiazolidinedione treatment in adipocytes, is one of the key molecules for the tight link between adiposity and insulin resistance. Here, we show the in vivo effects of resistin on insulin sensitivity in mature mice using a cell implantation method. METHODS: Resistin cDNA was transfected into 3T3-L1 pre-adipocytes, which were then implanted into subcutaneous areas of nude mice. Metabolic analyses were performed 4 or 6 weeks after implantation. RESULTS: The mice implanted with 3T3-L1 cells overexpressing resistin (R-mice) showed significantly (p<0.05) increased plasma resistin levels. After a glucose load plasma insulin levels were significantly greater in R-mice than in mice implanted with mock-transfected cells (M-mice). The AUC of insulin after glucose loading was positively correlated with circulating resistin levels. Significantly decreased glucose responses after insulin injection were observed in R-mice, compared to M-mice. The insulin-induced phosphorylation level of IRS-1 was significantly lower in muscles of R-mice than M-mice. The expression of TNF-alpha mRNA in intra-peritoneal fat tissues was significantly greater in R-mice than in M-mice, but there was no difference between the two groups with regard to subcutaneous fat tissues. The concentration of TNF-alpha in plasma was positively correlated with resistin levels in R-mice. CONCLUSIONS/INTERPRETATION: Resistin, when actually secreted from cells in mature mice, causes disturbed glucose metabolism, possibly based on decreased insulin sensitivity in muscle. The in vivo effects of resistin on insulin sensitivity might be in part mediated by increased TNF-alpha expression in visceral fat tissues.

3T3 Cells↗

Regular threshold-energy increase with charge for neutral-particle emission in collisions of electrons with oligonucleotide anions.

Electron-DNA anion collisions were studied using an electrostatic storage ring with a merging electron-beam technique. The rate of neutral particles emitted in collisions started to increase from definite threshold energies, which increased regularly with ion charges in steps of about 10 eV. These threshold energies were almost independent of the length and sequence of DNA, but depended strongly on the ion charges. Neutral particles came from breaks of DNAs, rather than electron detachment. The step of the threshold energy increase approximately agreed with the plasmon excitation energy. It is deduced that plasmon excitation is closely related to the reaction mechanism.

Anions↗

Resonant neutral-particle emission in collisions of electrons with peptide ions in a storage ring.

Electron-biomolecular ion collisions were studied using an electrostatic storage ring with a merging beam technique for singly protonated peptides (angiotensin I, II, and III). A strong neutral-particle emission at around 6.5 eV was found in addition to neutrals from recombination at low energies. The rates of the high-energy peak greatly decreased with a slight decrease in the number of amino-acid residues from angiotensin I to III. These results suggest that some peptide bonds were selectively cleaved.

Angiotensins↗

Relaxing intraoperative natural sound blunts haemodynamic change at the emergence from propofol general anaesthesia and increases the acceptability of anaesthesia to the patient.

BACKGROUND: It is known that auditory input, such as comforting music or sound, blunts the human response to surgical stress in conscious patients under regional anaesthesia. As auditory perception has been demonstrated to remain active under general anaesthesia, playing comforting sounds to patients under general anaesthesia might also modulate the response of these patients to surgical stress. METHODS: Fifty-nine patients scheduled for laparoscopic cholecystectomy were anaesthetized with propofol general anaesthesia in combination with epidural anaesthesia. Natural sounds, chosen preoperatively by each patient as being comforting, were played to 29 patients using headphones during surgery (S group) and the remainder of the patients (n = 30) were fitted with dummy open-type headphones (N group). We compared the haemodynamic change during anaesthesia and the acceptability of anaesthetic practice between the two groups in a randomized double-blind design. RESULTS: There were no differences in haemodynamics between the S and N groups during surgery. During the emergence from anaesthesia, the mean blood pressure and heart rate gradually increased; both parameters were significantly higher in the N group than in the S group. Postoperatively, patients in the S group perceived the experience of anaesthesia as significantly more acceptable than did those in the N group. CONCLUSION: These findings indicate that allowing patients comforting background sounds during general anaesthesia may blunt haemodynamic changes upon emergence from general anaesthesia and increase the acceptability of the experience of anaesthesia.

Aged↗

Isolation and characterization of a transposon mutant of Pseudomonas aeruginosa affecting uptake of dibenzothiophene in n-tetradecane.

AIMS: Isolation and characterization of a transposon mutant of Pseudomonas aeruginosa affecting the uptake of dibenzothiophene (DBT) in n-tetradecane (n-TD). METHODS AND RESULTS: The dsz desulphurization gene cluster from Rhodococcus erythropolis KA2-5-1 was transferred to the chromosome of P. aeruginosa NCIMB9571 using a transposon vector. A recombinant (named PARM1) was obtained which was able to desulphurize DBT in water, but not in n-TD. CONCLUSIONS: PARM1 is a mutant deficient in a DBT transport system operational in n-TD. This transport system is independent of rhamnolipids and of the n-alkane transport system. SIGNIFICANCE AND IMPACT OF THE STUDY: Pseudomonas aeruginosa NCIMB9571 seems to have a specific system of transporting hydrophobic compounds such as DBT in oil.

Alkanes↗

Magnetic resonance imaging in the evaluating of double uterus and associated urinary tract anomalies: a report of five cases.

Uterine anomalies are associated with unilateral renal aplasia. We present the MR features of five cases with 'double' uteri. The anomalies consisted of four cases of uterus didelphys and one of a complete septate uterus. All the cases with uterus didelphys also had a longitudinal vaginal septum. The MR diagnoses were confirmed with hysterosalpingography and with laparoscopy. In one case of didelphic uterus, MR images predicted the (three-dimensional helical) computer tomography (CT)-pyelographic diagnosis of renal aplasia in which the single kidney was normal. The study shows that MR is a valuable tool for the diagnosis of not only uterine anomalies but also associated anomalies in other systems.

Abnormalities, Multiple↗

Randomized phase II study of cisplatin, irinotecan and etoposide combinations administered weekly or every 4 weeks for extensive small-cell lung cancer (JCOG9902-DI).

BACKGROUND: The purpose of this study was to evaluate the toxicity and antitumor effect of cisplatin, irinotecan and etoposide combinations on two schedules, arms A and B, for previously untreated extensive small-cell lung cancer (E-SCLC), and to select the right arm for phase III trials. PATIENTS AND METHODS: Sixty patients were randomized to receive either arm A (cisplatin 25 mg/m(2) day 1, weekly for 9 weeks, irinotecan 90 mg/m(2) day 1, on weeks 1, 3, 5, 7 and 9, and etoposide 60 mg/m(2) days 1-3, on weeks 2, 4, 6, 8), or arm B (cisplatin 60 mg/m(2) day 1, irinotecan 60 mg/m(2) days 1, 8, 15, and etoposide 50 mg/m(2) days 1-3, every 4 weeks for four cycles). Prophylactic granulocyte colony-stimulating factor support was provided in both arms. RESULTS: Full cycles were delivered to 73% and 70% of patients in arms A and B, respectively. Incidences of grade 3-4 neutropenia, anemia, thrombocytopenia, infection and diarrhea were 57, 43, 27, 7 and 7%, respectively, in arm A, and 87, 47, 10, 13 and 10%, respectively, in arm B. A treatment-related death developed in one patient in arm A. Complete and partial response rates were 7% and 77%, respectively, in arm A, and 17% and 60%, respectively, in arm B. Median survival time was 8.9 months in arm A, and 12.9 months in arm B. CONCLUSIONS: Arm B showed a promising complete response rate and median survival with acceptable toxicity in patients with E-SCLC, and should be selected for the investigational arm in phase III trials.

Aged↗

[Liposarcoma of the pleural cavity; report of a case].

A 43-year-old-woman who had sever anterior chest pain visited our hospital on April 3, 2000. A well-defined abnormal shadow was seen in the middle and lower field of the right lung on chest X-ray. Computed tomography showed a large fat density mass in the right pleural cavity with a septum enhanced by contrast medium. Percutaneous needle biopsy revealed lipoma or liposarcoma. Complete resection could be done with combined resection of right lung, lpericardium, parietal pleura and diaphragm. Final histologic diagnosis was well differentiated liposarcoma. There are few reports of liposarcoma arising in the thoracic cavity, we present our case and review the 23 cases reported from the Japanese literatures.

Adult↗

Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat thymocytes: a possibility of aspartame toxicity.

Aspartame is a widely used artificial sweetener added to many soft beverages and its usage is increasing in health-conscious societies. Upon ingestion, this artificial sweetener produces methanol as a metabolite. In order to examine the possibility of aspartame toxicity, the effects of methanol and its metabolites (formaldehyde and formate) on dissociated rat thymocytes were studied by flow cytometry. While methanol and formate did not affect cell viability in the physiological pH range, formaldehyde at 1-3 mmol/L started to induce cell death. Further increase in formaldehyde concentration produced a dose-dependent decrease in cell viability. Formaldehyde at 1 mmol/L or more greatly reduced cellular content of glutathione, possibly increasing cell vulnerability to oxidative stress. Furthermore, formaldehyde at 3 mmol/L or more significantly increased intracellular concentration of Ca2+ ([Ca2+]i) in a dose-dependent manner. Threshold concentrations of formaldehyde, a metabolite of methanol, that affected the [Ca2+]i and cellular glutathione content were slightly higher than the blood concentrations of methanol previously reported in subjects administered abuse doses of aspartame. It is suggested that aspartame at abuse doses is harmless to humans.

Animals↗

Selection of peptides that bind to the core oligosaccharide of R-form LPS from a phage-displayed heptapeptide library.

To characterize common sites within the core oligosaccharide of the R-form lipopolysaccharide (LPS), we screened peptides from a phage-displayed heptapeptide library by using the most truncated form of R-LPS, Re-LPS (S. Typhimurium SL1165) as a ligand. After three rounds of biopanning/amplification and subsequent screening by phagemid enzyme-linked immunosorbent assay (ELISA), we selected three distinct clones that bind to the ligand LPS. We characterized the binding sites of the three clones by ELISA and thin-layer chromatography immunostaining and found that the three clones bind the two Re-LPSs (SL1165 and S. Minnesota Re595) and Rb2-LPS. In addition, one of the clones also bound to S-form LPS (S. Enteritidis). Current data show that those clones bind to common carbohydrate structure(s) expressed in the core oligosaccharides of those LPS samples.

Ligands↗

A change in microsatellite instability caused by cisplatin-based chemotherapy of ovarian cancer.

To clarify the mechanism of acquired CDDP resistance in ovarian cancer, we compared the microsatellite instability (MSI) by the amplification of 10 microsatellite loci and immunohistochemical detection of hMSH2 and hMLH1 expression between the primary resected tumours and the secondary resected residual tumours after 5 or 6 courses of CDDP-based chemotherapy in the 24 cases of ovarian cancer. Of the 24 primary resected tumours, 9 (37.5%) showed MSI (7 cases of MSI-L, 2 cases of MSI-H), while 15 (72.5%) were microsatellite stable tumours (MSS). The primary tumours also had MSI in the residual tumours after CDDP-based chemotherapy. However, all of the cases with MSS in the primary resected tumours exhibited MSI (2 cases were MSI-L, and 13 cases were MSI-H) in the residual tumours after CDDP-based chemotherapy (P< 0.001). Furthermore, 11 (73.3%) of these cases which changed from MSS to MSI also had a change in the expression of hMLH1 from positive to undetectable (P< 0.001). Our data suggest that tumour MSI changes during CDDP-based chemotherapy, and that the loss of hMLH1 expression is one of the factors that has the greatest effect on this transformation.

Adult↗

Sweet's syndrome associated with encephalitis.

The involvement of the central nervous system (CNS) in Sweet's syndrome (acute febrile neutrophilic dermatosis) is rare. We report a 47-year-old woman who presented with acute encephalitis and was subsequently diagnosed as having Sweet's syndrome. She developed altered consciousness following fever and erythematous skin plaques in the extremities. Cerebrospinal fluid (CSF) examination disclosed neutrophilic pleocytosis without decreased glucose level. Brain magnetic resonance imaging (MRI) showed abnormal signal intensity lesions in the basal ganglia and the hippocampus. Skin biopsy revealed a dense dermal infiltration of neutrophils, which is compatible with Sweet's syndrome. Treatment with acyclovir and antibiotics failed, but the subsequent corticosteroid therapy was effective. Awareness of neurological complication in Sweet's syndrome may avoid unnecessary empiric therapy for meningoencephalitis and will lead to a successful treatment with corticosteroids.

Adrenal Cortex Hormones↗