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Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 19 recordsLinked to original sources
PubMed2006

Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer.

Hepatocyte nuclear factor-4alpha (HNF4alpha) exists in multiple isoforms that are generated by alternative promoter (P1 and P2) usage and splicing. Here we establish monoclonal antibodies (mAbs) for detecting P1 and P2 promoter-driven HNF4alpha, and evaluate their expression in normal adult human tissues and surgically resected carcinomas of different origins. Using immunohistochemical analysis, we demonstrate that, while P1 promoter-driven HNF4alpha is expressed in hepatocytes, small intestine, colon, kidney and epididymis, P2 promoter-driven HNF4alpha is expressed in bile duct, pancreas, stomach, small intestine, colon and epididymis. Altered expression patterns of P1 and P2 promoter-driven HNF4alpha were observed in gastric, hepatocellular and colorectal carcinomas. HNF4alpha was expressed in lung metastases from renal cell, hepatocellular and colorectal carcinoma but was not observed in lung tumours. The P1 and P2 promoter-driven HNF4alpha expression pattern of tumour metastases correlated with the primary site of origin. P1 promoter-driven HNF4alpha was also found in intestinal metaplasia of the stomach. These data provide evidence for the tissue distribution of P1 and P2 promoter-driven HNF4alpha at the protein level and suggest that HNF4alpha may be a novel diagnostic marker for metastases of unknown primary. We propose that the dysregulation of alternative promoter usage of HNF4alpha is associated with the pathogenesis of certain cancers.

Animals↗
PubMed2006

Analysis of gene mutations in four cases of dermatofibrosarcoma protuberans.

Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been described in dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have been shown to be involved in the fusion with exon 2 of the PDGFB gene. We examined the breakpoints of the COL1A1 gene using the tumour specimens from four patients with DFSP. The COL1A1-PDGFB fusion transcripts were detected from the cultured tumour cells by reverse transcriptase polymerase chain reaction. Sequence analysis revealed that the ends of exons 23, 25, 26 and 36 in the COL1A1 gene were fused with the start of exon 2 in the PDGFB. This study identified three novel COL1A1 breakpoints: exons 23, 26 and 36 of the COL1A1 gene. In one case, the tumour was composed of two areas that differed in cytological atypia, cellularity and mitotic activity, indicating the dedifferentiation of the tumour. In tumour cells from two different areas the same aberrant fusion transcripts were identified. These results suggest that the dedifferentiation of tumour cells has nothing to do with the specific breakpoints of the COL1A1 gene, but depends on other unknown factors.

Adult↗
PubMed2006

Novel cynomolgus macaque MHC-DPB1 polymorphisms in three South-East Asian populations.

Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or long-tailed macaques, live across a vast range of South-East Asia. These non-human primates have emerged as important animal models in infectious and chronic diseases and transplantation studies, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphic variation or diversity of the Mafa-DPB1 locus is largely limited in comparison with the more commonly studied rhesus macaque DPB1 locus. In this article, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East Asian populations and to investigate how the allele differences between macaques and humans might affect their respective immune responses, we identified 40 alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217 individuals. We also performed evolutionary and population analyses using these sequences to reveal some population-specific alleles and trans-species allelic conservation between the cynomolgus macaques and the rhesus macaques. Of the 40 new alleles, eight belong to a newly identified lineage group not previously found in the rhesus macaque species. This allele information will be useful for medical researchers using the cynomolgus macaques in disease and immunological studies.

Alleles↗
PubMed2006

Tracer clearance in radionuclide cisternography in patients with spontaneous intracranial hypotension.

We semiquantitatively analysed radionuclide cisternography in three patients with spontaneous cerebrospinal fluid (CSF) leakage diagnosed by typical symptoms and magnetic resonance imaging findings before and several months after treatment with epidural blood patch. Radioactivity in the whole CSF space was measured immediately after and at 1, 5, 7 and 24 h after intrathecal injection of (111)In-diethylenetriaminepentaacetic acid (DTPA). Initial findings included the vague appearance of leakage in the thoracic spine in two patients, early bladder filling at 1 h in one and a lack of tracer filling into the high cranial convexity in all three. The radioactivity count rapidly decreased within several hours after injection and reached 20% of the initial value at 24 h. In contrast, no rapid decrease was observed after treatment and more than 50% of tracer remained at 24 h after injection. Semiquantitative analysis of tracer clearance may provide additional information in the diagnosis of CSF leakage, especially with no obvious qualitative findings.

Female↗
PubMed2006

Detection of Lactobacillus gasseri OLL2716 strain administered with yogurt drink in gastric mucus layer in humans.

In animal models and human trials, Lactobacillus gasseri OLL2716 (LG21) strain suppressed Helicobacter pylori colonization in the stomach. The aim of the present study was to clarify whether orally administered LG21 strain can enter the gastric mucus layer. Biopsy samples were taken from the gastric antrum and corpus of two healthy volunteers (H. pylori infected and non-infected) who drank yogurt supplemented with LG21 strains. DNA of LG21 and H. pylori in the mucus layer was detected using the laser-assisted microdissection and non-contact pressure catapulting (LMPC) method and the semi-nested PCR method with primer sets of RNA helicases of superfamily II gene-Insertion sequence for LG21 strain and those of ureA gene for H. pylori. In the volunteer with H. pylori infection, DNA fragments of LG21- and H. pylori-specific regions from both antrum and corpus were amplified, whereas in a non-infected volunteer, only the LG21 DNA from the antrum was amplified. The present study demonstrated that LG21 strains administered through a yogurt drink can enter into the gastric mucus layer. Our novel method may be useful in studying gastric probiotics for H. pylori infection.

Gastric Mucosa↗
PubMed2006

Chronic posterior dislocation of the glenohumeral joint complicated by a fractured proximal humerus: a case report.

A 41-year-old right-handed woman was involved in a traffic accident and landed on the right arm while the right shoulder was in flexion. She experienced pain and severe impairment of right shoulder motion immediately following the accident. She was misdiagnosed with a fractured proximal humerus with no displacement and was treated conservatively by immobilisation. There was inadequate recovery in range of motion and gradual development of severe pain. Two years and 4 months after the injury, the patient presented to our hospital where a diagnosis of chronic posterior fracture dislocation of the shoulder with split articular surface of the humeral head was made. A humeral head replacement without resection of the greater tuberosity or the coracoid process was performed. Postoperative recovery was uneventful. The patient returned to work as a cook one year later. At 20-month follow-up, the patient had no pain, and her shoulder range of motion was forward flexion 160 degrees, abduction 140 degrees, external rotation 40 degrees, and internal rotation L3.

Adult↗
PubMed2006

Variation of microvascular blood flow augmentation--supercharge in esophageal and pharyngeal reconstruction.

AIM OF THE STUDY: A gastric tube is commonly used in thoracic esophageal reconstruction. When a gastric tube is not available, pedicled jejunum transfer and colonic interposition are alternative methods. Oral end of the reconstructed esophagus occasionally has poor blood flow and may result in partial necrosis of the oral segment. We performed additional microvascular blood flow augmentation, the "supercharge" technique, to improve a blood flow circulation in the oral segment of the reconstructed esophagus. METHODS: A series of 86 esophageal reconstructions with microvascular blood flow augmentation using the "supercharge" technique were performed. Reconstructive methods included a gastric tube in five patients, a gastric tube combined with a free jejunual graft in one, an elongated gastric tube in eight, a pedicled colonic interposition in 22, and a pedicled jejunum in 50. Recipient vessels were used in neck or chest region. RESULTS: The color and blood flow of the transferred intestine appeared greatly improved after microvascular blood flow augmentation. Thrombosis was noticed in three patients during the surgery, and all thrombosies were salvaged by re-anastomosis. There were only three patients with partial graft necrosis of oral segment, two patients with anastomotic leakage, one anastomotic stricture. CONCLUSIONS: Augmentation of microvascular blood flow by this "supercharge" technique can be expected to reduce the risk of leakage and partial necrosis of the transferred intestine. This technique contributes to the successful reconstruction of esophageal defect.

Adult↗
PubMed2005

Lateral gaze disturbance due to cerebral microbleed in the medial lemniscus in the mid-pontine region: a case report.

A 72-year-old man who was attending the outpatients clinic in our hospital because of multiple lacunar cerebral infarctions and mild mental disturbance developed an inability to gaze to the left side voluntarily. MR imaging revealed a new cerebral microbleed in the medial lemniscus of the right side in the mid-pontine region. The finding in this case suggests that the pathways from the frontal eye field descend at least to the level of the mid-pontine region ipsilaterally, and that the pathways then contralaterally decussate and terminate in the paramedian pontine reticular formation. Cerebral microbleeds can be symptomatic depending on the neuro-anatomical structures involved.

Aged↗
PubMed2005

Intramedullary spinal cord germinoma expresses the protooncogene c-kit.

A 33-year-old woman first noticed numbness in the both lower extremities and the numbness gradually extended up to the thorax. Magnetic resonance (MR) imaging demonstrated a mass with moderate and heterogeneous enhancement and peritumoural intramedullary cysts in the spinal cord at the T-1 to T-3 levels. The tumour was explored partially and intra-operative pathological examination demonstrated the so-called "two-cell pattern" typical of germinoma. The margin of the tumour was not clear. Histological examination showed germinoma with strong c-kit protein expression on the tumour cell surface. Chemotherapy and radiation therapy were given following surgery. Her neurological deficits were improved but not resolved.

Adult↗
PubMed2005

Successful treatment of a patient with a 13-year history of post-traumatic rhinorrhea due to malabsorption of cerebrospinal fluid.

Chronic cerebrospinal fluid (CSF) leaks associated with skull base fractures are rare but intractable and patients may be subjected to numerous operations. We present a 30-year-old man with a 13-year history of chronic CSF rhinorrhea following a cranial trauma. Computed tomography (CT) showed a bone defect in the planum sphenoidale. CT cisternography revealed a leak from the defect and CSF malabsorption. The absence of symptoms of CSF malabsorption may be attributable to external leakage of excess CSF. After closing the leak via the extended transsphenoidal approach we placed a ventriculoperitoneal shunt for occult hydrocephalus. We discuss the clinical symptoms of chronic CSF leakage and present therapeutic strategies dictated by the mechanisms underlying the leak.

Adult↗
PubMed2005

Aspergillus mycotoxins and their effect on the host.

Aspergillus fumigatus is known to produce various immunosuppressive mycotoxins including gliotoxin. However, none of these mycotoxins has been confirmed as being directly related to the pathogenesis of aspergilli. Recent studies have made substantial progress in the determination of mycotoxins as virulence factors. Gliotoxin was found to be produced much faster than previously believed under certain culture conditions, such as at 37 degrees C and under high oxygen content, which is close to the environment in the host. Gliotoxin was also found to be detectable in the sera of aspergillosis mice and of aspergillosis patients. Based on these findings, it is becoming evident that gliotoxin is produced in the infected organs of patients of aspergillosis at a significant level. In addition to these known mycotoxins, A. fumigatus produces many mycotoxins apparently different from known toxins. From the aspect of gene analysis, the deletion of laeA was found to block the expression of metabolic gene clusters such as sterigmatocystin, and the gene is also expected to be related to the production of gliotoxin. The significance of mycotoxins as virulence factors will hopefully be clarified in the near future.

Animals↗
PubMed2005

Adoptive transfer of T-helper cell type 1 clones attenuates an asthmatic phenotype in mice.

T-helper cell type 1 (Th1) cells have been postulated to have a significant role in protective immunity against allergic diseases. However, recent studies using polarised Th1 cells showed conflicting effects on both airway responsiveness and eosinophilic inflammation in a mouse asthma model. The current study explored the effects of adoptive transfer of established Th1 clones on a murine model of atopic asthma. Mice (BALB/c) were sensitised with ovalbumin (OVA) and challenged with aerosolised OVA (5%, 20 min) for 5 days. Just before starting the first challenge, Th1 clones (5x10(6) x body(-1)) or PBS alone were injected via the tail vein. After assessment of airway responsiveness to methacholine, bronchoalveolar lavage fluid (BALF) was obtained. Histological examination, including morphometric analysis, measurement of cytokines in the BALF and Northern blotting of lung chemokines, was also performed. Adoptive transfer of Th1 clones showed a significantly increased total number of cells, whereas significantly decreased eosinophils were found in the BALF, when compared with mice with injection of vehicle alone or splenic mononuclear cells. Administration of Th1 clones significantly decreased the infiltration of eosinophils but increased mononuclear cells in the peribronchial area. Goblet cell hyperplasia and peribronchial fibrosis were also suppressed by Th1 clones. The transfer of Th1 cells significantly decreased airway responsiveness. Th1 injection significantly increased interferon gamma in the BALF, but significantly decreased interleukin (IL)-5 and IL-13. Eotaxin mRNA was predominantly expressed in the lungs of asthma model mice, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) predominates in such mice with Th1 transfer. In conclusion, results suggest that the adoptive transfer of T-helper cell type 1 clones can suppress both lung eosinophilia and airway responsiveness, but increase noneosinophilic inflammation in a mouse model of asthma.

Adoptive Transfer↗
PubMed2005

[Pulmonary metastasis from colorectal cancer with hepatic metastasis].

We have investigated cases where pulmonary metastasis from colorectal cancer was resected during the last 15 years, comparing a group with liver metastasis [LM (+)] to a group without liver metastasis [LM (-)]. The following are the characteristics of the LM (+) versus LM (-) groups. Gender: male 6, female 5 versus male 9, female 11, age: 61.4+/-11.4 versus 63.9+/-9.4 years, number of lung metastasis: 1.42 versus 1.29, duration of primary-lung metastasis: 1.59+/-1.02 versus 2.55+/-1.46 years, preoperative CEA: 69.3+/-71.1 versus 8.64+/-5.63 ng/ml, ratio of bilateral lung metastasis: 23.0 versus 4.8%, more than 1 ratio of pulmonary metastasis: 38 versus 19%, complete resection ratio of pulmonary metastasis: 84.6 versus 100%, ratio of thoracoscopic surgery: 69.2 versus 66.7%, and 2-year survival ratio: 63 versus 78%. There were no statistically significant differences in these values between the LM (+) and LM (-) group. A larger number of cases and follow-up duration will be required in the future; we think that the resection of pulmonary metastasis from colorectal cancer with liver metastasis can be supported for the present.

Aged↗
PubMed2004

CT findings of bilateral congenital absence of the long process of the incus.

Bilateral conductive deafness due to congenital absence of the long process of the incus (CALPI) is rare. The authors present the case of a patient with bilateral CALPI. To the best of our knowledge, this is the first reported case preoperatively diagnosed as bilateral CALPI by computed tomography. Multislice computed tomography is very useful for the diagnosis of minute abnormalities of the ossicles.

Child↗
PubMed2004

Near-triploidy and near-tetraploidy in hematological malignancies and mutation of the p53 gene.

Hyperdiploidy of > or =58 chromosomes is reported in 0.5-3% of hematological malignancies, but reports of near-triploidy (58-80 chromosomes) and near-tetraploidy (81-103 chromosomes), are few. We examined these chromosome abnormalities and analyzed the relationship with the mutation of the p53 gene. Thirty-one of 979 adult patients (3.2%) with hematological malignancies were identified as having near-triploid or near-tetraploid (tri-/tetraploid) chromosomes. These included 11 with B-cell neoplasms, seven with Hodgkin's lymphoma, five with T-cell neoplasms, four with myelodysplastic syndromes and four with acute myeloid leukemias. All patients had concurrent complex chromosome aberrations. Deletion of one allele of the p53 gene was found in two patients and a point mutation of the p53 gene was detected in five patients. Although abnormalities of the p53 gene have been reported in about 10% of hematological malignancies, these were found in seven of 31 (23%) patients with tri-/tetraploidy. These findings suggest that the abnormality of the p53 gene may be closely related with tri-/tetraploidy. The four myelodysplastic syndrome (MDS) patients with tri-/tetraploidy had a significantly worse prognosis than those with diploid cytogenetics (n = 35; P < 0.002). In B-cell neoplasms (n = 3), triploidy was associated with a worse prognosis than tetraploidy (n = 8) and diploidy (n = 130; P < 0.02).

Adult↗
PubMed2004

A case of secondary diabetes mellitus with acromegaly improved by pioglitazone.

AIM: The acromegaly patient was diagnosed with Type 2 diabetes mellitus. His HbA1c was 10.6% and fasting blood glucose (FBG) 15.3 mmol/l. We prescribed glibenclamide (10 mg/day), but his HbA1c and FBG remained high. At this stage, treatment with short-acting insulin was instigated at a dose of 20 U/day. However, the patient's blood glucose level remained unsatisfactory. We tried using pioglitazone. METHOD: Pioglitazone was prescribed at 30 mg/day in combination with the insulin. RESULTS: The FBG and HbA1c value decreased to 7.2 mmol/l and 7.3%, respectively, within 2 months and insulin was discontinued. Pioglitazone alone was able to control the FBG level. CONCLUSIONS: Pioglitazone treatment might be considered as a choice for similar cases of diabetes secondary to acromegaly.

Acromegaly↗
PubMed2004

[Strategy for surgical treatment for small peripheral carcinoma of the lung especially on systemic nodal dissection].

The diagnosis of small-sized (< or = 2 cm) non-small cell lung cancer (NSCLC) has increased with the development of computed tomography (CT), whereas unexpected extensive mediastinal involvement has been occasionally detected in such a small-sized lung cancer. We retrospectively analyzed the clinicopathological features to determinate the predictors for lymph node involvement in patients with a small-sized adenocarcinoma. One hundred and eighty one patients who underwent pulmonary resection and systematic nodal dissection for a peripheral small-sized adeno-carcinoma were reviewed. Of these, 24 patients (13.3%) had lymph node involvement. These patients were divided into 2 groups according to the existence of lymph node involvement, and the predictors for lymph node involvement were determined using univariate analysis and multivariate regression analysis. Univariate analysis revealed GGOR (ground glass opacity area/tumor area at the level of the greatest dimension of the lesion on chest computer tomography) > or = 25% (p = 0.0137) and pleural lavage fluid involvement (p = 0.0467) as predictors for lymph node involvement. No patients had lymph node involvement if their GGOR was higher than 50%. Multivariate regression analysis revealed GGOR > or = 25% (p = 0.0274), pleural tags on the lesion on chest CT (p = 0.0138) and pleural lavage fluid involvement (p = 0.0415) as predictors. We recommend performing systemic nodal dissection even if small peripheral adeno-carcinoma's maximal diameter is 20 mm or less. Systemic nodal dissection is unnecessary if the patients' GGOR > or = 50% or they do not have pleural tags or pleural lavage fluid involvement.

Aged↗