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Biomedical subjects

N Suzuki

Publications and source records attributed to N Suzuki.

At least 55 records · Page 3Linked to original sources
PubMed2004

The prevalence of small, flat colorectal cancers in a western population.

OBJECTIVE: Small, flat colorectal cancers have been widely reported in the Japanese literature but are thought to occur rarely outside Japan. The aim of this retrospective cohort study was to clarify the prevalence of flat colorectal cancer in a Western population. METHODS: One thousand and twenty-six consecutive colonoscopies performed by a single experienced endoscopist were retrospectively analysed over a two-year period. The morphology, site and histological appearance of all documented colorectal cancers (CRC) were recorded. RESULTS: Forty-seven cases of CRC were detected, five of which (10%) demonstrated flat configuration. Flat cancers varied between 8 and 15 mm in diameter (mean 11 mm). Histologically, all flat lesions were moderately differentiated Dukes A adenocarcinomas. Two of these cancers contained no adenomatous component. CONCLUSION: This study confirms that small, flat colorectal cancers are not an uncommon finding at colonoscopy in Western patients. Compared to polypoid neoplastic lesions, flat cancers appear to undergo malignant change at a smaller size.

Adenocarcinoma↗
PubMed2004

Identification of novel MUNC13-4 mutations in familial haemophagocytic lymphohistiocytosis and functional analysis of MUNC13-4-deficient cytotoxic T lymphocytes.

BACKGROUND: Familial haemophagocytic lymphohistiocytosis (FHL) has an autosomal recessive mode of inheritance and consists of at least three subtypes. FHL2 subtype with perforin (PRF1) mutation accounts for 30% of all FHL cases, while FHL with MUNC13-4 mutation was recently identified and designated as FHL3 subtype. OBJECTIVE: To examine MUNC13-4 mutations and the cytotoxic function of MUNC13-4 deficient T lymphocytes in Japanese FHL patients METHODS: Mutations of MUNC13-4 and the cytotoxicity of MUNC13-4-deficient cytotoxic T lymphocytes (CTL) were analysed in 16 Japanese families with non-FHL2 subtype. RESULTS: Five new mutations of the MUNC13-4 gene were identified in six families. The mutations were in the introns 4, 9, and 18, and exons 8 and 19. Two families had homozygous mutations, while the remaining four had compound heterozygous mutations. Cytotoxicity of MUNC13-4 deficient CTL was low compared with control CTL, but was still present. Clinically, the onset of disease tended to occur late; moreover, natural killer cell activity was not deficient in some FHL3 patients. CONCLUSIONS: MUNC13-4 mutations play a role in the development of FHL3 through a defective cytotoxic pathway.

Age of Onset↗
PubMed2004

SAG1 is a host-targeted antigen for protection against toxoplasma gondii infection.

We previously reported that SAG1 transgenic (tg) mice have an elevated susceptibility resulting from their inability to elicit strong Th1-based protection against Toxoplasma gondii infection. Here, we demonstrate that SAG1 tg mice were protected against T. gondii infection, characterized by a decline in IFN-gamma levels, following administration of a lethal dose of T. gondii. Moreover, immunization with T. gondii homogenate conferred protection and induced production of IgG, with IgG1 and IgG2a subclasses driven by Th2 and Th1 responses, respectively, in both SAG1 tg and wild-type (wt) mice. IgG titers were significantly higher from day 10 after immunization in wt mice compared to those in SAG1 tg mice. There were no significant differences observed in levels of IgG1 in both groups. However, significantly lower IgG2a titers were measured in the sera from SAG1 tg mice on days 10, 15 and 20. IFN-gamma levels in sera were significantly lower in SAG1 tg mice compared to those in wt mice on day 20 after immunization. When challenged with a lethal dose of the Beverley strain of T. gondii, 80 and 100% survival rates were observed in SAG1 tg and wt mice, respectively, indicating that SAG1 tg mice were protected to a lesser extent from challenge due to the decrease in protective immunity. These results suggest that SAG1 plays a critical role in eliciting protection, hence a target antigen for the development of protective Th1-based responses against T. gondii infection in mice.

Animals↗
PubMed2004

An economic evaluation of recombinant bovine somatotropin approval in Japan.

A comprehensive econometric model was developed to evaluate potential impacts of recombinant bovine somatotropin (rbST) approval in Japan. Three novel features of the analyses include 1) investigation of impact of rbST on herd-size structure, 2) determination of economic feasibilities of rbST adoption by herd size, and 3) evaluation of policies to mitigate negative effects of rbST approval. Simulation analysis was conducted over a 10-yr projected period assuming rbST was approved in Japan in 2001. Nine hypothetical scenarios were simulated to examine sensitivity of simulation results. Simulation results indicate that rbST approval would accelerate structural change in Japan's dairy industry toward fewer, larger farms. Negative effects of rbST on farm income are projected to be more severe for smaller farms, because of higher costs, lower profit-earning ability, lower milk yields, and lower adoption rates of rbST. Larger farms benefit from rbST adoption if milk demand is maintained. However, if concerns about rbST induce significant milk demand decreases, even the largest farms' income and cow numbers will decrease. Thus, Japan's dairy industry could be caught in a double downward spiral of declining milk prices and production. Assuming rbST is approved, small farms would benefit by using the technology, but they fare best if rbST is not approved. Two policies could be effective in mitigating possible farm income losses. First, lost farm income can be offset if dairy cooperatives can exercise greater market power to control fluid milk marketings. Second, because generic milk advertising has positive effects on both milk demand and farm income, increasing check-off rates to fund more advertising could ease farm income losses.

Animals↗
PubMed2003

Video-assisted bullectomy using needlescopic instruments for spontaneous pneumothorax.

Patients with spontaneous pneumothorax require immediate insertion of a chest drain to evacuate the intrathoracic air. During video-assisted bullectomy, we made use of an existing chest drain hole to insert a thoracoscope or an endoscopic linear stapler. Video-assisted bullectomy was performed through three ports-two 2-mm ports and the existing chest drain hole. Therefore, no new skin incisions were required for the insertion of the 2-mm ports. A chest drain was again inserted via the existing chest drain hole after bullectomy. This procedure was used on 8 of 10 patients with spontaneous pneumothorax. There were no postoperative complications or recurrences. Thoracoscopic bullectomy using needlescopic instruments is technically feasible, safe, and effective. Currently, the procedure is indicated only for simple cases and not for the lysis of adhesions.

Endoscopes↗
PubMed2003

Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats.

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.

Alkaline Phosphatase↗
PubMed2003

Distribution of Actinobacillus actinomycetemcomitans serotypes and Porphyromonas gingivalis in Japanese adults.

Strains of the bacterium Actinobacillus actinomycetemcomitans found in the human oral cavity are divided into five serotypes, a, b, c, d, and e. In this study, A. actinomycetemcomitans serotypes and Porphyromonas gingivalis were isolated from 656 subgingival sites in systemically healthy Japanese adults. A. actinomycetemcomitans was detected in 19.5% of 328 Japanese subjects, while 27.1% of subjects were positive for P. gingivalis. Of 75 A. actinomycetemcomitans-positive sites, only one serotype was detected in 39 sites (52.0%). The numbers of sites in which two different serotypes and three different serotypes were detected were 18 (25.0%) and 7 (9.3%), respectively. A. actinomycetemcomitans serotype c was detected more frequently in sites that were positive for both P. gingivalis and A. actinomycetemcomitans (76.9%) than in sites that were P. gingivalis-negative and A. actinomycetemcomitans-positive (33.9%). In addition, serotype c was detected much more frequently than the other serotypes (<16%) in sites that were positive for both P. gingivalis and A. actinomycetemcomitans. These findings suggest that the characteristics of serotype c may differ from those of the other serotypes. This report is the first to use PCR to describe the distribution of A. actinomycetemcomitans serotypes in humans and to examine the association between the distribution of A. actinomycetemcomitans serotypes and the presence of P. gingivalis.

Adult↗
PubMed2003

Clinical features associated with recurrence of tumours of the spinal cord and cauda equina.

STUDY DESIGN: Retrospective review of consecutive cases of recurrent spinal cord and cauda equina tumours. OBJECTIVES: We sought to identify factors and conditions resulting in re-operation to treat recurrences of spinal cord and cauda equina tumours. SETTING: Keio University Hospital, Tokyo, Japan. METHODS: Re-operation was performed in 39 patients with spinal cord and cauda equina tumours. Times of operation, interval between operations, affected spinal level, tumour site on cross section, configurations among dumb-bell tumours, and pathologic diagnoses were analysed. Recurrence rates were defined in terms of the number of cases with re-operation due to tumour recurrence relative to the total number of surgical cases for the same period at our institution. RESULTS: Recurrence rates were relatively high for intradural, extramedullary tumours and for tumours located anteriorly rather than laterally. Of patients with intradural, extramedullary plus extradural tumours who underwent initial surgery at our hospital, 75% (9/12) recurred; all tumours had dumb-bell-type configurations. The overall rate of re-operation due to tumour recurrence in 249 cases was 7.2% at our institution. By tumour types, 40% of malignant schwannomas recurred (2/5), as did 35.7% of neurofibromas (5/14), and 33.3% of ependymomas (6/18). CONCLUSION: Risk factors for tumour recurrence were anterior location, an intradural, extramedullary plus extradural site, extensive dumb-bell tumours, and pathologic diagnoses of neurofibroma, ependymoma, or malignant schwannoma.

Adolescent↗
PubMed2003

The production of 6-deoxy-L-talan from Actinobacillus actinomycetemcomitans via bacterial coupling in vitro.

A method of producing 6-deoxy-L-talan, the serotype c-specific polysaccharide antigen (SPA) from Actinobacillus actinomycetemcomitans,was established using a whole-cell reaction with two recombinant Escherichia coli strains. The production of serotype c-SPA was investigated using the dot blot assay with anti-A. actinomycetemcomitans NCTC 9710 serum after an 18-h reaction, starting with a solution containing the recombinant E. coli cells, alpha-d-glucose-1-phosphate, and dTTP. Moreover, examination of the time course for 6-deoxy-L-talan production proved that this system ran satisfactorily. This paper is the first report of a convenient method to readily produce the exopolysaccharide from A. actinomycetemcomitans in vitro.

Aggregatibacter actinomycetemcomitans↗
PubMed2003

Morphological and biochemical studies of human beta-mannosidosis: identification of a novel beta-mannosidase gene mutation.

BACKGROUND: There are seven well-known lysosomal storage diseases that produce angiokeratoma corporis diffusum clinically. beta-Mannosidosis (MANB1; OMIM248510), first reported in humans in 1986, is a rare hereditary lysosomal storage disease caused by a deficiency of the enzyme beta-mannosidase. Since then, 13 cases of beta-mannosidase deficiency in ten families have been described. A human beta-mannosidase mutation has been reported only by Alkhayat et al. in 1998. OBJECTIVES: To clarify its pathogenesis we did electron microscopic, biochemical and molecular biological investigations of a Japanese patient with beta-mannosidosis. METHODS: Ultrastructural analyses, enzyme assays, cell culture and mRNA and genomic DNA were sequenced to find mutations in the beta-mannosidase gene. RESULTS: Electron microscopy of skin biopsy specimens from the patient showed cytoplasmic vacuolation of lysosomes in blood and lymph vessels, endothelial cells, fibroblasts, secretory portions of eccrine sweat glands, neural cells and basal keratinocytes in the epidermis. This vacuolation was also observed in cultured keratinocytes and fibroblasts. Assays of seven enzyme activities in plasma and cultured skin fibroblasts showed a marked decrease of beta-mannosidase activity. Sequencing the beta-mannosidase cDNA revealed a four-base (ATAA) insertion between exons 7 and 8, resulting in a frameshift at codon 321 and termination at codon 325. Analysis of the patient's genomic DNA revealed a novel homozygous A(+1)-->G splice site mutation in intron 7. CONCLUSIONS: To our knowledge, this is the first case of beta-mannosidosis reported in Japan and the second report in which a gene mutation is identified. The biological importance of beta-mannose moieties in glycoproteins in basal keratinocytes is suggested.

Cells, Cultured↗
PubMed2003

Successful induction of immune tolerance in a patient with haemophilia B with inhibitor.

We describe successful induction of immune tolerance (IT) in a 10-month-old boy with severe haemophilia B. Urticaria developed soon after starting prophylactic treatment and was associated with an inhibitor at 7 Bethesda units mL(-1). Initially, we tried low dose factor IX therapy to induce IT with only a transient effect. The patient experienced an intracranial haemorrhage. A simple bolus dose of FIX eradicated the inhibitor. Thereafter he has been free from inhibitor and nephrotic syndrome for more than 5 years, although he receives FIX three times a week.

Drug Administration Schedule↗
PubMed2003

Difference in the heat sensitivity of DNA-dependent protein kinase activity among mouse, hamster and human cells.

PURPOSE: To examine the heat sensitivity of DNA-dependent protein kinase (DNA-PK) activity in a variety of cultured mouse, hamster and human cell lines. MATERIALS AND METHODS: Eight cell lines, which have been routinely used in our laboratory, were examined. Cells were heated at 44.0 +/- 0.05 degrees C and DNA-PK activity was measured by a DNA-pull-down assay followed by gel-electrophoresis. Cellular sensitivity to hyperthermia and/or X-ray was evaluated by a colony formation assay. RESULTS: In mouse FSA1233 and FM3A cells, DNA-PK activity dropped to 15-16% of unheated control after 20 min of heating. In Chinese hamster V79 and CHO-K1 cells, kinase activity did not change appreciably after 20 min treatment but decreased to 60-70 and 22-23% after 40 or 60 min treatment, respectively. However, even after 180 min treatment, DNA-PK activity remained almost intact in human MOLT-4, MKN45 and A7 cells, and decreased only slightly in U937 cells. Hyperthermic radiosensitization was seen even in human cells but, as a trend, it was small compared with rodent cells. CONCLUSIONS: The heat sensitivity of DNA-PK was clearly different among mouse, hamster and human cells. The results suggested a possibility that the role of DNA-PK inactivation in hyperthermic radiosensitization might be variable, depending on cells, and would reinforce the warning that the direct extrapolation of data from rodent cells might lead to overestimation of the effectiveness of hyperthermia on human cancer.

Animals↗
PubMed2003

Decreased c-Myc expression and its involvement in X-ray-induced apoptotic cell death of human T-cell leukaemia cell line MOLT-4.

PURPOSE: To investigate the possible involvement of c-Myc and ceramide-c-Jun N-terminal kinase (JNK) pathway in X-ray-induced apoptotic cell death of MOLT-4 cells. MATERIALS AND METHODS: The expressions of c-Myc protein and c-myc mRNA after X-irradiation were analysed by Western blotting and RT-PCR between radiosensitive MOLT-4 and radioresistant variant Rh-1a cells with less JNK activation than the parental cells. Apoptotic cell death was determined by a dye exclusion test, the appearance of chromatin condensation and DNA fragmentation. The effect of a JNK activator anisomycin or c-Myc inhibitor peptides (Int-H1-S6A, F8A) on the amount of c-Myc protein and on the induction of apoptosis was investigated, respectively. RESULTS: In X-irradiated MOLT-4 cells, amounts of both c-myc mRNA and c-Myc protein rapidly decreased, which was followed by apoptotic cell death, while little change or limited reduction of c-Myc protein was observed in X-irradiated Rh-1a cells with accompanying higher cell viability. Exposure of MOLT-4 and Rh-1a cells to c-Myc inhibitor peptides similarly induced apoptotic cell death with decreases of c-Myc protein. Anisomycin rapidly induced JNK activation and a subsequent decrease of c-Myc protein, causing cell death in MOLT-4 cells. On the other hand, Rh-1a cells were more resistant to anisomycin than parental MOLT-4 cells, showing less JNK activation and a delayed decrease of c-Myc protein. CONCLUSION: A decrease of c-Myc protein was considered important in X-ray-induced apoptotic cell death of MOLT-4 cells; activation of the JNK pathway caused reduction in the amounts of c-myc mRNA and c-Myc protein, and finally induced apoptotic cell death.

Anisomycin↗
PubMed2003

Retinal findings in systemic sclerosis: a comparison with nailfold capillaroscopic patterns.

OBJECTIVE: To determine the prevalence of retinal disease in systemic sclerosis (SSc) and to characterise the findings of retinopathy. Additionally, to analyse the association of retinal disease with other clinical/laboratory findings, particularly the findings of nailfold capillaries in patients with SSc. METHODS: Photographs of the ocular fundi were taken and were evaluated by an ophthalmologist who was unaware of the SSc status of the patients. The nailfold capillaries were analysed with a dermatoscope. Patients were divided into two groups according to the presence (group A) or absence (group B) of retinal disease. RESULTS: Retinal findings of the patients with SSc consisted of hard exudates, vascular tortuosity, microhaemorrhage, and macular degeneration. The prevalence of retinal disease among the patients with SSc was 34% (10/29), compared with 8%(3/38) among the controls (p=0.011). The mean systolic blood pressure and the age of the patients in group A were significantly higher than those in group B. However, there was no significant difference in the nailfold capillary damage between groups A and B. CONCLUSION: Retinal abnormalities are often seen in patients with SSc and they may reflect the vascular changes characteristic of SSc. However, retinal changes may differ in quality from the changes of nailfold capillaries.

Capillaries↗