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Biomedical subjects

Y Kojima

Publications and source records attributed to Y Kojima.

At least 19 recordsLinked to original sources
PubMed2006

Accelerated onsets of gastric hamartomas and hepatic adenomas/carcinomas in Lkb1+/-p53-/- compound mutant mice.

Germline mutations in the LKB1 gene are responsible for Peutz-Jeghers syndrome (PJS), which is characterized by gastrointestinal hamartomas and increasing risk of cancer. Mice with Lkb1(+/-) mutation develop gastric hamartomas after >20 weeks of age, and hepatocellular adenomas and carcinomas >30 weeks. It has been reported that, in PJS patients, carcinomas progressed from hamartomas contain p53 mutations, and that LKB1 regulates p53-dependent apoptosis. To investigate the roles of LKB1 and p53 mutations in tumorigenesis, we constructed compound mutant mice of Lkb1 and p53 genes. In the Lkb1(+/-)p53(-/-) mice, formation of gastric hamartomas and hepatic tumors was accelerated. However, histopathology of hamartomas was similar between Lkb1(+/-)p53(-/-) and Lkb1(+/-) mice, and Lkb1 genotype remained heterozygous, suggesting that the p53 mutation affected hamartoma initiation. Contrary to the heterozygous hamartomas in the stomach and duodenum, the hepatic adenomas in Lkb1(+/-)p53(-/-) mice showed loss of Lkb1 heterozygosity (LOH), suggesting that lack of p53 stimulated Lkb1 LOH and tumor initiation in the liver. Taken together, these results indicate that lack of p53 causes earlier onsets of gastric hamartomas and hepatic tumors in Lkb1(+/-)p53(-/-) mice.

AMP-Activated Protein Kinases↗
PubMed2006

Endoscopic ultrasound-guided fine-needle aspiration biopsy for lymphadenopathy of unknown origin.

BACKGROUND AND STUDY AIMS: The diagnosis of mediastinal and intra-abdominal lymphadenopathy is sometimes difficult, especially in patients who have no other primary lesions. Lymphoma is one of the main causes of this condition. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe and accurate diagnostic procedure for lesions surrounding the gastrointestinal tract. However, diagnosing lymphoma using the EUS-FNA technique remains a diagnostic challenge, due to limitations in the amount of material sampled. The aim of the present study was to evaluate the yield of EUS-FNA biopsy (EUS-FNAB) using a large-gauge needle in patients with mediastinal and intra-abdominal lymphadenopathy of unknown origin, especially in relation to subclassification of the lymphomas. PATIENTS AND METHODS: Consecutive patients with mediastinal and intra-abdominal lymphadenopathy of unknown origin who were referred between October 2003 and March 2005 were enrolled in the study. EUS-FNAB was carried out using a 19-gauge needle, passing through the esophageal, gastric, and duodenal walls. Pathological diagnoses were made on the basis of histological findings, including immunopathological staining. RESULTS: A total of 104 patients were included in the study. The locations of the lymph nodes were mediastinal in 50 patients, intra-abdominal in 48 patients, and both mediastinal and intra-abdominal in six patients. The diagnoses made using EUS-FNAB were lymphoma (n = 48), metastasis (n = 16), and benign/reactive (n = 40). The overall accuracy of EUS-FNAB for unknown lymphadenopathy was 98 %, and it was possible to classify the lymphomas in accordance with the World Health Organization classifications in 88 % of cases. No serious complications occurred with the procedure. CONCLUSIONS: Open thoracic surgery, laparotomy, and other invasive diagnostic procedures such as mediastinoscopy and laparoscopy can now be avoided, as EUS-FNAB is potentially a safe and accurate tool for diagnosing unknown lymphadenopathy, including lymphoma.

Adult↗
PubMed2006

Simultaneous five cell-lineage flow cytometric analysis system for detection of leucocyte antibodies.

Although flow cytometric (FCM) analysis is one of the most widely used approaches to screen the presence of leucocyte antibodies, it has several drawbacks. First, neutrophils and, especially, monocytes exhibit high background reactivity. Second, to determine antibody specificity, it is often necessary to examine not only neutrophils and monocytes but also other lineage cells including T cells, B cells and platelets. Therefore, we attempted to establish an FCM analysis system in which four lineages of leucocytes and platelets are simultaneously tested with low background. FCM analysis was performed using ethylene diamine tetraacetic acid-anticoagulated whole blood as cell sample without any cell preparation. Discrimination of five cell lineages was carried out based on the differences in forward vs. side scatter distribution and in the expression of CD4, CD20 and CD14. When anti-HNA (human neutrophil antigen) 1b antiserum was applied to HNA 1b-positive blood samples, only neutrophils were unambiguously positive. When anti-Naka (anti-CD36) antiserum was applied, only platelets and monocytes were positive. The background reactivity of neutrophils and monocytes was low enough. When anti-human leucocyte antigen (HLA) class II antiserum was tested, only B-lymphocytes and monocytes were positive. When anti-HLA class I antiserum was tested, all the five-lineage cells were positive.

Antibodies↗
PubMed2006

Postoperative outcome among elderly patients after general anesthesia.

BACKGROUND: Preoperative decision-making for elderly patients requires a long-term perspective. The aim of this study was to identify preoperative risk factors for decreased 1- to 5-year survival rates and to compare the survival rates of stratified risk groups with those of the sex- and age-matched general population. METHODS: Subjects were 406 patients, aged 80 years or older, who underwent surgery with general anesthesia. Higher age, male sex, dependency in daily living, low serum albumin level, malignancy, abdominal surgery, emergency surgery and high ASA class were analyzed for survival using univariate and multivariate analysis with Cox's proportional hazard model. One- to 5-year survival rates were estimated using life table analysis for patients divided by risk factors. The survival data were also compared with the cumulative survival rates of the sex- and age-matched general population. RESULTS: Multivariate analysis identified three factors that were significantly associated with decreased survival rates: male sex, dependency in daily living and abdominal surgery. Long-term survival among patients older than 90 years was comparable to those of the general population. Although improved in recent years, overall survival rates were much lower than expected due to poor outcome among patients dependent in daily living and those who underwent abdominal surgery. CONCLUSIONS: In patients 80 years or older who underwent surgery with general anesthesia, independent risk factors for decreased survival are male sex, dependency in daily living and abdominal surgery. Only patients independent in daily living who underwent non-abdominal surgery had survival rates comparable to those of the general population.

Abdomen↗
PubMed2006

[Pulmonary pleomorphic carcinoma; report of 2 cases].

The 1st case was a 74-year-old male diagnosed as femoral neck fracture. Biopsy of the bone revealed metastatic adenocarcinoma. Chest computed tomography (CT) showed a mass lesion located in the right lower lobe. With a diagnosis of primary lung cancer (cT2N1M1), two-staged operation was performed. Pathological diagnosis was pleomorphic carcinoma [pT2N1M1 (OSS), stage IV]. He died 8 months after surgery due to metastasis to the thoracic spine. The 2nd case was a 80-year-old female who complained of lateral chest pain. Chest CT revealed a tumor in the right hilar region, which was diagnosed as adenocarcinoma by transbronchial lung biopsy. Only thoracic drainage was performed since metastases to the brain and the rib were demonstrated. She died 2 months after admission. Autopsy revealed pleomorphic carcinoma of the lung with metastasis to the brain, costa and mediastinal lymph nodes.

Adenocarcinoma↗
PubMed2005

CD16+CD57- natural killer cells in multifocal motor neuropathy.

We analyzed the CD16+CD57- lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57- NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57- NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.

Adult↗
PubMed2005

Observation of the effects of radially sheared electric fields on the suppression of turbulent vortex structures and the associated transverse loss in GAMMA 10.

Vortexlike turbulent structures in hot-ion mode plasmas with several keV are observed in the case with a radially produced weak shear of electric fields E(r). However, a strong E(r) shear formation due to a high ion-confining potential phi(c) production clears up these vortices together with plasma-confinement improvement and disappearance of both drift-wave and turbulencelike Fourier spectral signals. These findings are based on three-time progress in phi(c) in comparison to phi(c) attained 1992-2002. The significant advance of phi(c) is well extended in line with proposed potential-formation physics scalings.

Journal Article↗
PubMed2005

Novel method of inactivation of human immunodeficiency virus type 1 by the freeze pressure generation method.

It has been reported that high-pressure (over 600 MPa) treatment at room temperature inactivates human immunodeficiency virus type 1 (HIV-1), and it has recently been shown that the high pressure generated by the expansion of water due to freezing (freeze pressure generation method, or FPGM) has an inactivating effect on bacteria and fungi. In this study, we examined the effects of treatment by FPGM on HIV-1. A sturdy vessel filled with water and securely closed with a lid was kept at 0 degrees C to -30 degrees C. High pressures of 200 MPa and 250 MPa were generated at -20 degrees C and -30 degrees C, respectively. When T-cell-tropic and macrophage-tropic laboratory strains of HIV-1 were kept at -10 degrees C, the virus infectivity decreased to approximately 1/100, and was completely lost at -20 degrees C and -30 degrees C. Four T-cell-tropic and four macrophage-tropic laboratory strains and clinical isolates of HIV-1 became completely inactivated at -30 degrees C. Treatment by FPGM at -20 degrees C to -30 degrees C reduced HIV-1 reverse transcriptase activity to approximately one tenth. In addition, treatment by FPGM at -20 degrees C was found to destroy the ability of HIV-1 to bind to CD4+ cells. In conclusion, this study showed that treatment by FPGM at -20 degrees C to -30 degrees C destroyed the infectivity of a wide range of HIV-1 strains, and suggested that the mechanisms of HIV-1 inactivation were the reduction in viral enzyme activity and the loss of the cell-binding ability of a viral envelope protein.

Cell Line, Tumor↗
PubMed2005

Root fracture in immature anterior teeth followed for 15 years.

We report a case of injury to an immature tooth, observed over a period of 15 years. In 1987, a 9-year-old boy fell down in a schoolyard. The right central incisor demonstrated palato-version and radiographic observations revealed that the roots of both central incisors were incomplete. Further, a root fracture in the apical region of the central incisors was observed. During the first treatment visit, the right central incisor was repositioned and both teeth splinted. After confirming that the line of fracture was aligned, the fixation was continued for 2 months. The teeth were examined periodically for the next 15 years. Both teeth had favorable outcomes with continued root development of both the apical and coronal segments with good apposition of the fracture lines.

Child↗
PubMed2005

Eruption sequestrum: x-ray microanalysis and microscopic findings.

A 12 year-old girl with eruption sequestrum of the mandibular left second molars is reported. Intraoral findings revealed that a small hard tissue fragment white in color and with bone-like hardness on the occlusal surface of the mandibular second molar which was erupting. Histopathologically, the fragments consisted of necrotized cortical bone. Chronic inflammatory alterations were also observed in the gingiva in the area of contact with the osseous tissue. X-ray microanalyzer findings revealed the percentages of calcium and phosphorous (by weight) as 78.41% and 21.59%, respectively, for a calcium to phosphorous ratio of 3.63, which was higher than that seen in normal osseous tissue.

Bone and Bones↗
PubMed2005

Mechanical assessment of effects of grape seed proanthocyanidins extract on tibial bone diaphysis in rats.

We studied the effects of grape seed proanthocyanidins extract (GSPE) given as a ratio of 3 mg in 100 g in a standard diet, on the tibial bone diaphysis in low-calcium fed rats. Measurements of bone density, mineral content, geometry, and bone strength using peripheral quantitative computed tomography (pQCT). Further, the whole tibia bones were tested for mechanical resistance using a material-testing machine, and mineral elements were also determined. Forty male Wistar rats, 5 weeks old, were divided into control (Co), low-calcium diet (LC), low-calcium diet . standard diet (LCS), and low-calcium diet . standard diet with supplementary GSPE (LCSG) groups. We found no significant differences in body weight among the 4 groups, whereas all of the bone parameters in LC were significantly lower than those in Co (p<0.01, except in periosteal perimeter (Peri) p<0.05). The cortical bone mineral content (CtBMC), cortical bone density (CtvBMD) and Peri in LCSG were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05, respectively). All bone parameters in LCSG were significantly higher than those in LC (p<0.01, except in Peri, and stress strain index to reference axis x (xSSI) p<0.05)). In addition, Ca, P, and Zn contents in LCSG were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05, respectively). Our results suggest that GSPE included in a diet mixture with calcium has a beneficial effect on bone formation and bone strength for the treatment of bone debility caused by a low level of calcium.

Animals↗
PubMed2004

Investigation of the pharmacokinetics of cyclosporine in patients following long-term administration after a kidney transplant: comparison of Neoral and Sandimmune.

A crossover administration of Neoral and Sandimmune was performed in 43 renal allograft recipients who had been on cyclosporine maintenance therapy for 2 to 19 years posttransplant to investigate the pharmacokinetics of cyclosporine. Although there was no difference in C0 values (trough values) when Neoral and Sandimmune were administered at the same doses, AUC(0-4) and AUC(0-12) values of Neoral were 1.57- and 1.36-fold greater than those of Sandimmune, respectively. For both Neoral and Sandimmune, there was a high correlation between the C2 value and AUC(0-4). The Pearson's product-moment coefficient for the correlation between the C2 value and AUC(0-4) was R=0.91642. On the other hand, the correlation with the C0 value (trough value) was low (R=0.53181). During the period of the study, there was no acute rejection episode, onset of adverse drug reaction symptoms, or marked change in laboratory test values.

Adult↗
PubMed2004

Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis.

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

Adult↗
PubMed2004

Promoter polymorphism of SLC11A1 (formerly NRAMP1) confers susceptibility to autoimmune type 1 diabetes mellitus in Japanese.

Defective function of antigen-presenting cells has been postulated to be one of the non-HLA-linked susceptibility factors for type 1 diabetes mellitus, though the underlying genetic factors remain unclear. SLC11A1 (formerly NRAMP1), a divalent cation transporter, plays a crucial role in macrophage activation. We performed a case-control study in 224 healthy and 95 type 1 diabetic Japanese subjects, examining the length polymorphisms in the promoter region (-377 to -222) of SLC11A1, which may influence transcriptional activity. Alleles designated 2, 3, and 7 have been identified in Japanese subjects. The frequency of allele 7 was significantly higher in subjects with type 1 diabetes (9.47%) than in the healthy controls (4.46%). The difference is more marked in the subpopulation of Japanese subjects with type 1 diabetes; diabetic subjects with at least one protective HLA class II allele and those without any susceptibility HLA class II haplotypes, DR4-DQ4 or DR9-DQ9, had a much higher allele 7 frequency than controls. These findings suggest that the novel promoter polymorphism of SLC11A1 influences the susceptibility to type 1 diabetes in Japanese subjects.

Adolescent↗
PubMed2004

Relationship between temporomandibular joint (TMJ)-related pain and morphological changes of the TMJ condyle in patients with temporomandibular disorders.

OBJECTIVES: The purpose of this study was to analyse the relationship between temporomandibular joint (TMJ)-related pain and morphological change of the TMJ condyle in patients with temporomandibular disorders. METHODS: Data were obtained from 178 joints in 89 patients. The joints were clinically assessed for pain on mandibular function and on lateral palpation of the TMJ. They were also assessed for radiographic evidence of bone change at the articular surface (OAAS) and resorption of the lateral part of the condyle (RLC). RESULTS: A higher prevalence of joint pain on function was observed in joints with OAAS than in those without OAAS (Chi-square test of independence, P < 0.05). Significant relationships were found between palpation pain and OAAS and between palpation pain and RLC (Chi-square test of independence, P < 0.05). In addition, patients with RLC showed a significantly lower pain threshold for external mechanical stimuli than those without RLC (Welch's t-test, P < 0.05). CONCLUSIONS: These results suggest a possible relationship between pain on function and OAAS as well as a relationship between palpation pain and RLC. Pain on lateral palpation may be related to the pathological conditions that induce RLC.

Adolescent↗