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Biomedical subjects

N Shimizu

Publications and source records attributed to N Shimizu.

At least 19 recordsLinked to original sources
PubMed2006

Surgical outcomes after treatment of fractures in femur and tibia in pycnodysostosis.

Pycnodysostosis is a rare hereditary disease, characterized by systemic bone sclerosis. The most important orthopedic problem in this condition is the recurrent pathological fracture of long bones. In this paper, the surgical results for fractures of six limbs (three femurs and three tibias) in five cases of pycnodysostosis are reported. Five limbs achieved fracture union and union is developing in one tibia after intramedullary nail (IM) nailing or Ilizarov external fixation (IEF), although fracture line tends to persist for longer periods of time. One femoral fracture was treated by IM nailing, and one femoral and one tibial fracture were treated by IEF leading to final bone union. One femoral and one tibial fracture were initially treated by IEF, and were treated by IM nailing after re-fracture. One tibial fracture was initially treated by IEF leading to a failure of union, and was converted to IM nailing. All cases are able to walk; one case requires a single crutch. Infection was noted in two limbs after IM nailing following IEF. Fixation with IM nail was effective in preventing re-fracture as well as in alignment correction. Although the surgical technique is more difficult, IM nailing in the initial surgery may be a better choice for achieving successful union while reducing the risk of re-fracture or infection.

Adult↗
PubMed2006

A multicenter study on laparoscopic surgery for colorectal cancer in Japan.

BACKGROUND: Laparoscopic colectomy for malignant disease technically is feasible but not widely accepted because there are no large-series studies or data on long-term outcomes. A retrospective, multicenter study investigating a large series of patients was conducted in Japan to evaluate preliminary long-term results of laparoscopic surgery for colorectal cancer. METHODS: The study group comprised 2,036 patients who underwent laparoscopic colorectal resection April 1993 to August 2002 in 12 participating surgical units (Japanese Laparoscopic Surgery Study Group). RESULTS: Of the 1,495 patients with colon cancer, 781 (59%) had International Union Against Cancer (UICC) stage I, 248 (19%) had stage II, and 284 (22%) had stage III disease. Cancer recurred for 61 (4.1%) of 1,367 curatively treated patients (median follow-up period, 32 months; range, 6-125 months). The 5-year survival rate was 96.7% for stage I, 94.8% for stage II, and 79.6% for stage III disease. Of the 541 patients with rectal cancer, 220 (56%) had stage I, 62 had (16%) stage II, and 108 (28%) had stage III disease. Cancer recurred for 30 (5.6%) of 476 curatively treated patients (median follow-up period, 25 months; range 6-102 months). The 5-year survival rate was 95.2% for stage I, 85.2% for stage II, and 80.8% for stage III disease. CONCLUSIONS: The findings indicate that laparoscopic surgery for colorectal cancer yields an oncological outcome as good as that reported for conventional open surgery in the Japanese Registry for all disease stages.

Colonic Neoplasms↗
PubMed2006

Suppression of replication fork progression in low-dose-specific p53-dependent S-phase DNA damage checkpoint.

The S-phase DNA damage checkpoint is activated by DNA damage to delay DNA synthesis allowing time to resolve the replication block. We previously discovered the p53-dependent S-phase DNA damage checkpoint in mouse zygotes fertilized with irradiated sperm. Here, we report that the same p53 dependency holds in mouse embryonic fibroblasts (MEFs) at low doses of irradiation. DNA synthesis in p53 wild-type (WT) MEFs was suppressed in a biphasic manner in which a sharp decrease below 2.5 Gy was followed by a more moderate decrease up to 10 Gy. In contrast, p53-/- MEFs exhibited radioresistant DNA synthesis below 2.5 Gy whereas the cells retained the moderate suppression above 5 Gy. DNA fiber analysis revealed that 1 Gy irradiation suppressed replication fork progression in p53 WT MEFs, but not in p53-/- MEFs. Proliferating cell nuclear antigen (PCNA), clamp loader of DNA polymerase, was phosphorylated in WT MEFs after 1 Gy irradiation and redistributed to form foci in the nuclei. In contrast, PCNA was not phosphorylated and dissociated from chromatin in 1 Gy-irradiated p53-/- MEFs. These results demonstrate that the novel low-dose-specific p53-dependent S-phase DNA damage checkpoint is likely to regulate the replication fork movement through phosphorylation of PCNA.

Animals↗
PubMed2006

Protocadherin 15 (PCDH15): a new secreted isoform and a potential marker for NK/T cell lymphomas.

Natural killer cells are well known to play an important role in immune defense against tumor development and viral infections. To further characterize new functionally relevant structures in these cells, we studied a series of monoclonal antibodies that we have raised against the NK cell line YT. One of these antibodies previously described as AY19, recognizes a 85 kD surface glycoprotein. Here we report the identification of a new secreted isoform of protocadherin 15, PCDH15C, which represents a potential associated protein for p85. Importantly, whereas protocadherins are absent from the surface of normal hematopoietic cells, we describe, for the first time, that PCDH15 is expressed in cytotoxic tumor-derived T- and NK-cell lines as well as in biopsies of nasal NK/T-cell lymphomas.

Animals↗
PubMed2006

Transcriptional profiling of Epstein-Barr virus (EBV) genes and host cellular genes in nasal NK/T-cell lymphoma and chronic active EBV infection.

Nasal NK/T-cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma (NHL) that is closely associated with Epstein-Barr virus (EBV). The clonal expansion of EBV-infected NK or T cells is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might share a partially similar mechanism by which EBV affects host cellular gene expression. To understand the pathogenesis of EBV-associated NK/T-cell lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in six cell lines established from EBV-associated NK/T-cell LPD. We found that expression of BZLF1, which encodes the immediate-early gene product Zta, was expressed in SNK/T cells and the expression levels were preferentially high in cell lines from CAEBV infection. We also analyzed the gene expression patterns of host cellular genes using a human oligonucleotide DNA microarray. We identified a subset of pathogenically and clinically relevant host cellular genes, including TNFRSF10D, CDK2, HSPCA, IL12A as a common molecular biological properties of EBV-associated NK/T-cell LPD and a subset of genes, such as PDCD4 as a putative contributor for disease progression. This study describes a novel approach from the aspects of viral and host gene expression, which could identify novel therapeutic targets in EBV-associated NK/T-cell LPD.

Chronic Disease↗
PubMed2006

PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer.

Trastuzumab is the only HER2/neu-directed therapy to have received Food and Drug Administration approval for the treatment of patients with metastatic breast cancer. The efficacy of trastuzumab depends on the HER2/neu status of the tumour and the patient's prior treatment, but even when patients are selected on the basis of HER2/neu gene amplification, the single-agent response rate ranges from 12 to 30% and few patients respond to trastuzumab monotherapy. Here, we propose PTEN as a predictive biomarker for trastuzumab efficacy. Human breast cancer SKBR3 and drug-resistant SKBR3/R cells were investigated. We also examined clinical samples from patients who had been treated with trastuzumab and analysed the relationship between trastuzumab efficacy and PTEN level. The PI3K/Akt signalling pathway was observed to be highly active in the drug-resistant cells, and their level of PTEN was low. Delivery of antisense PTEN duplex siRNA significantly decreased the trastuzumab chemosensitivity of parental SKBR3 cells, and marked activation of Akt signalling pathway was also recognised. Moreover, immunohistochemical investigation revealed that trastuzumab treatment was remarkably successful in cells with elevated PTEN expression. Along with the immune-system-associated cytotoxic mechanism, several mechanisms have been proposed for the effect of trastuzumab. PTEN activity might play an important and major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful biomarker for predicting the efficacy of trastuzumab in the treatment of breast cancer.

Antibodies, Monoclonal↗
PubMed2006

Manipulation of the small intestine as a cause of the increased inflammatory response after open compared with laparoscopic surgery.

BACKGROUND: Laparoscopic surgery of the gastrointestinal tract involves a reduced immune response compared with open surgery. The aim of this study was to assess manual handling of the gut in open procedures as the principal cause of the enhanced immune response. METHODS: Eighteen Landrace pigs underwent gastrectomy by three different methods: conventional open wound with bowel manipulation, laparoscopically assisted gastrectomy, and gastrectomy without manipulation using a combination of open wound and laparoscopic surgical devices. Local inflammatory changes were assessed by ascites formation, intestinal adhesion development and intestinal inflammatory gene expression. Associated systemic inflammatory changes were determined by measuring portal and systemic plasma endotoxin levels, plasma inflammatory cytokine levels, liver inflammatory gene expression and transaminase levels. RESULTS: Significantly more postoperative intra-abdominal fluid and adhesions were seen in the open group. The expression of inflammatory cytokines was significantly greater in the intestine and liver in the open group. Portal and systemic levels of endotoxin, inflammatory cytokines and transaminases were also higher. CONCLUSION: Manual handling of organs during gastrectomy is an important contributor to the molecular and humoral inflammatory response to surgery, supporting the use of minimally invasive techniques in gastrointestinal surgery.

Animals↗
PubMed2005

Correction of severe post-traumatic deformities in the distal femur by distraction osteogenesis using Taylor Spatial Frame: a case report.

A case of deformity and shortening after post-traumatic growth arrest treated using the Taylor Spatial Frame (Smith & Nephew, Tennessee, USA) is presented. This is the first report showing the application of the frame for post-traumatic deformity in the distal femur, and successful outcomes promise utilization of the frame even for correction of severe deformity in the distal femur.

Adult↗
PubMed2005

Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in gastrointestinal tumour.

The human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumour-suppressor gene inactivated by methylation in several cancers. In this study, we analysed the methylation and expression status of hDAB2IP in gastrointestinal tumours. The promoter region of hDAB2IP was divided into two regions (m2a and m2b) based on our previous report, and the methylation status was determined by bisulphite DNA sequencing in gastric cancer cell lines. The gene expression was semiquantified by real-time RT-PCR, and the results indicated that the m2b promoter region might be an authentic methylation-mediated key regulator of the gene expression. Based on the sequence data, we developed a methylation-specific PCR (MSP) for the m2a and m2b regions and applied it to the samples. Methylation-specific PCR revealed aberrant methylation in the m2a region in eight of 12 gastric cancer cell lines (67%), 16 of 35 gastric cancer tissues (46%) and 29 of 60 colorectal cancer tissues (48%), and in the m2b region in eight of 12 cell lines (67%), 15 of 35 gastric cancer tissues (43%) and 28 of 60 colorectal cancer tissues (47%). On the other hand, seven (12%) and 11 (19%) of 59 gastrointestinal nonmalignant mucosal specimens showed methylation in the m2a and m2b regions, respectively, suggesting that hDAB2IP methylation might play a causative role in carcinogenesis. The 5-aza-2'-deoxycytidine treatment restored the gene expression in the m2b-methylated cell lines, confirming that the methylation caused gene downregulation. We also examined the relationship between hDAB2IP methylation and the clinicopathological features in patients with primary tumours, and determined that methylation in the m2b region was associated with location of the tumour in the stomach. In summary, our results demonstrated that hDAB2IP methylation is frequently present in gastrointestinal tumours and that the resulting gene silencing plays an important role in gastrointestinal carcinogenesis.

Azacitidine↗
PubMed2005

Novel rearrangement of chromosome band 22q11.2 causing 22q11 microdeletion syndrome-like phenotype and rhabdoid tumor of the kidney.

The 22q11.2 microdeletion syndrome is the most frequent microdeletion syndrome in humans, yet its genetic basis is complex and is still not fully understood. Most patients harbor a 3-Mb deletion (typically deleted region [TDR]), but occasionally patients with atypical deletions, some of which do not overlap with each other and/or the TDR, have been described. Microduplication of the TDR leads to a phenotype similar, albeit not identical, to the deletion of this region. Here we present a child initially suspected of having 22q11 microdeletion syndrome, who in addition developed a fatal malignant rhabdoid tumor of the kidney. Detailed cytogenetic and molecular analyses revealed a complex de novo rearrangement of band q11 of the paternally derived chromosome 22. This aberration exhibited two novel features. First, a microduplication of the 22q11 TDR was associated with an atypical 22q11 microdeletion immediately telomeric of the duplicated region. Second, this deletion was considerably larger than previously reported atypical 22q11 deletions, spanning 2.8 Mb and extending beyond the SMARCB1/SNF5/INI1 tumor suppressor gene, whose second allele harbored a somatic frameshift-causing sequence alteration in the patient's tumor. Two nonallelic homologous recombination events between low-copy repeats (LCRs) could explain the emergence of this novel and complex mutation associated with the phenotype of 22q11 microdeletion syndrome.

Chromosome Deletion↗
PubMed2005

Assessment of talus deformity by three-dimensional MRI in congenital clubfoot.

PURPOSE: To evaluate the morphological deformity of talus in congenital clubfoot by three-dimensional MRI. MATERIAL AND METHOD: Subjects were five patients (two male, three female, mean age 5 months) with unilateral congenital clubfoot. Magnetic resonance imaging was performed of both feet using 1.5 T magnet. Based on the resulting magnetic resonance imaging volume data, a three-dimensional surface bone model was reconstructed by the Marching Cubes method. The long axis of the reconstructed model was determined, and in relation to the standard planes including this axis, the degree of talar head and neck deviation, and the relative positioning of the talus and navicular in the talonavicular joint were compared between normal foot and clubfoot. RESULT: The talar head and neck angle in relation to the talus exhibited significant medial deviation in the clubfoot, but the degree of plantar deviation of the talar head and neck did not show significance. The navicular was located more medially in clubfoot than in normal foot. The volume of the total talar and of the ossific nucleus for the clubfoot was smaller than that for the normal foot. CONCLUSION: The assessment technique presented herein was shown to be useful in ascertaining the various pathological characteristics associated with clubfoot.

Ankle Joint↗
PubMed2005

Relationship between anti-ABO antibody production and hemolytic anemia after minor ABO-mismatched living-donor lobar lung transplantation.

With the shortage of lung donors, we have performed 28 living donor lobar lung transplantations (LDLLTs) since October 1998. Although lungs from ABO-identical donors were used if available, lungs were transplanted from donors showing minor ABO mismatches when suitable ABO-identical donors were not found. The aim of this study was to evaluate the relationship between anti-ABO antibody (Ab) production and the outcomes of lung transplantation with ABO-mismatched living donor lungs. We reviewed 28 patients (28 recipients with 55 donors) who underwent LDLLT between October 1998 and March 2004. In this patient population, 13 patients (46.4%) received minor ABO-mismatched transplants. Anti-A or B-IgG or IgM antibodies (Abs) in the serum and red cell elutes were examined. All 28 patients are alive and well at a mean observation period of 28.0 months (ranging from 5 to 70 months). Anti-A or B-IgG or IgM Abs were detected in 5 out of 13 minor ABO-mismatched patients (38.5%) after transplantation, but only one of them showed evidence of severe hemolytic anemia due to donor-derived antibodies. The titer of that patient's Abs was higher than that of the other recipients. Anti-ABO antibody production and anemia were not associated with gender, age, relationship between donors and recipients, and HLA matching. We conclude that LDLLT across ABO mismatches is an acceptable treatment for end-stage lung disease.

ABO Blood-Group System↗
PubMed2005

Peripheral lung volume reduction improved early graft function in severe size mismatched living donor lobar lung transplantation.

BACKGROUND: Lung transplantation from adults to infants or small children is still challenging because of concerns related to size disparity. Peripheral lung volume reduction for size disparity in cadaveric donor lung transplantation has been widely performed; however, little is known about the efficacy and the functional outcomes of downsizing the implanted lobes for severe size disparity in living donor lobar lung transplantation. METHODS: Thirteen size-mismatched (donor/recipient lung volume ratio > 2.82) bilateral living donor lobar lung transplants were performed with (reduction group, n = 6) or without (no-reduction group, n = 7) peripheral lung volume reduction. RESULTS: On spontaneous respiration, PaO2 in the reduction group was significantly higher than that in the no-reduction group (P < .01) and PaCO2 in the reduction group was significantly lower than that in the no-reduction group (P < .001). Pulmonary vascular resistance in the reduction group remained significantly lower than that in the no-reduction group throughout the assessment periods after chest closure (P < .05). Peak airway pressure in the no-reduction group increased significantly at the time of chest closure (P < .001) and remained significantly higher than that in the reduction group throughout the assessment period on mechanical ventilation (P < .01). The percentage of weight reduced from implanted grafts significantly correlated with donor/recipient lung volume ratio (r = 0.82, P < .05). CONCLUSIONS: Peripheral lung volume reduction is useful to improve early graft function in severe size mismatched experimental living donor lobar lung transplantation. The technique might allow for further flexibility in donor size and for increasing the donor pool for small recipients.

Adult↗
PubMed2005

Associations of menstrual pain with intakes of soy, fat and dietary fiber in Japanese women.

OBJECTIVE: Intakes of soy, fat, and dietary fiber may be associated with the symptoms of dysmenorrhea through their biological effects on estrogens or prostaglandin production. The present study was to examine the relationships between intakes of soy, fat, and dietary fiber and the severity of menstrual pain. DESIGN: Cross-sectional study. SETTING: Three colleges and two nursing schools. SUBJECTS: A total of 276 Japanese women aged 19-24 y. METHODS: Intakes of nutrients and foods including soy products, isoflavones, fats and dietary fiber were estimated by a validated semiquantitative food frequency questionnaire. Severity of menstrual pain was assessed by the multidimensional scoring system reported by Andersch and Milson. RESULTS: Intake of dietary fiber was significantly inversely correlated with the menstrual pain scale (r=-0.12, P=0.04) after controlling for age, smoking status, age at menarche and total energy intake. Neither soy nor fat intake was significantly correlated with menstrual pain after controlling for the covariates. CONCLUSIONS: The cross-sectional difference in dietary fiber intake across the level of menstrual pain was small in magnitude but warrants further studies.

Adult↗
PubMed2005

[Lobar torsion after pulmonary resection for lung cancer].

We reviewed our experience on postoperative lobar torsion. From January 1994 to December 2003, 1002 patients underwent lobectomy for lung cancer. Two (0.2%) patients with postoperative lobar torsion required surgical reintervention. The first case was that of a 79-year-old man who underwent left lower lobectomy for pulmonary adenocarcinoma. Based on the postoperative course, lobar torsion was highly suspected with progressive respiratory dysfunction and the chest X-ray showed complete opacification of the residual lobe. Rethoracotomy was performed on postoperative day 4. The left upper lobe was rotated clockwise, and completion pneumonectomy was carried out. The patient died 16 days after the second surgery because of respiratory failure due to severe pneumonia. The second case was that of a 24-year-old man with a diagnosis of metastatic lung cancer in the right upper lobe arising from pharyngeal cancer. The patient underwent right upper lobectomy and developed hemoptysis and persistent high fever. A chest computed tomography (CT) and bronchoscopy findings revealed lobar torsion of the middle lobe, and a reoperation was performed. The middle lobe was resected and the patient was discharged 8 days after the rethoracotomy. Pulmonary lobar torsion poses a difficult diagnostic dilemma in the early postoperative period after the pulmonary resection. Since late reoperation for postoperative lobar torsion sometimes results in poor prognosis, careful observation with bronchial fiberscopy as well as chest radiography is necessary for accurate diagnosis. Rethoracotomy should be carried out without any delay in cases of lobar torsion following pulmonary resection.

Adenocarcinoma↗