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Biomedical subjects

Y Nakajima

Publications and source records attributed to Y Nakajima.

At least 19 recordsLinked to original sources
PubMed2006

Surgical techniques and long-term outcomes of living donor liver transplantation for Budd-Chiari syndrome.

We have developed the surgical techniques of living donor liver transplantation (LDLT) for Budd-Chiari syndrome (BCS) and evaluated long-term outcomes including specific complications. BCS is characterized by hepatic outflow obstruction. Liver transplantation from living donors poses a unique challenge as liver replacement therapy does not replace the retrohepatic segment of inferior vena cava (IVC). We have performed 1105 LDLTs in 1055 patients from January 1990 to March 2005. Of these, nine patients (eight males and one female) underwent LDLT for BCS. Five out of nine patients underwent LDLT as a primary procedure and four patients had received other treatments before transplantation. Eight patients presented with chronic and one with fulminant liver failure. Predisposing factors were identified in three patients. IVC reconstruction without patch plasty was performed on four patients. Five patients needed cavoplasty using a replacement vein graft. Of the nine patients, seven are alive at a median follow-up of 58 months (range 1 month to 15.2 years) with two patients developing recurrent hepatic vein stenosis which were treated successfully with metallic stent placement. Two patients died: one from multiorgan failure and the other from pulmonary embolism secondary to disease recurrence. LDLT for BCS is highly effective by using modified cavoplasty and provides good long-term survival which may be obtained by life-long anticoagulant treatment and nonsurgical interventions.

Adolescent↗
PubMed2006

A novel CCR5/CXCR3 antagonist protects intestinal ischemia/reperfusion injury.

Chemokines and chemokine receptors have been demonstrated to be critical regulators in a variety of physiologic and pathologic immune responses. In particular, CCR5 and CXCR3 have been reported to play important roles in the alloimmune response. In this study, we investigated the therapeutic efficacy of a novel small-molecule compound, TAK779, an antagonist targeting both CCR5 and CXCR3 in intestinal ischemia/reperfusion (I/R) injury. We utilized an established murine intestinal I/R injury model. TAK779 treatment significantly improved mouse survival after 60 minutes of intestinal ischemia. We then examined the local intestinal expression of several cytokines and chemokines at 2 hours after reperfusion using real-time PCR. TAK779 treatment downregulated the expression of several cytokines, including TNF-alpha, IFN-gamma, and IL-4, suggesting that the beneficial effect of TAK779 was associated with inhibition of local immune activation. We further examined the systemic response after TAK779 treatment. Lung tissue damage was significantly prevented by the treatment, as determined by lung wet-to-dry weight ratios at 4 hours after intestinal I/R injury. In addition, we observed that CCR5 expression in the lung was significantly downregulated by the treatment, suggesting that TAK779 inhibited the infiltration of CCR5-positive cells into the remote organ. Our data suggest the critical role of CCR5 and CXCR3 in intestinal I/R injury and therapeutic efficacy of a novel small compound, TAK779, for protection against the intestinal I/R injury.

Amides↗
PubMed2006

Protective effect of prostaglandin E2 receptors EP2 and EP4 in alloimmune response in vivo.

Prostaglandin E2 (PGE2) is produced during inflammatory responses mediating a variety of both innate and adaptive immune responses through 4 distinct receptors: EP1 to EP4. The use of gene-targeted mice and selective agonists/antagonists responsible for each receptor has gradually revealed that each receptor plays a unique and important role in various disease conditions. In addition, PGE2 is known to have some immunosuppressive properties. In this study, we investigated the role of PGE2 receptors by examining the therapeutic efficacy of highly selective receptor agonists on the alloimmune response in vivo. We used a fully major histocompatibility complex (MHC)-mismatched murine cardiac transplantation model. C57BL/6 cardiac allografts were heterotopically transplanted into BALB/c recipients. We treated mice with a highly selective agonist for each EP receptor. EP2 and EP4 agonists significantly prolonged allograft survival compared with controls. In particular, the EP4 agonist was more effective than the EP2 agonist in the inhibition of acute allograft rejection. In conclusion, PGE2 receptors merit further study as novel therapeutics for clinical transplantation.

Animals↗
PubMed2006

Small interfering RNA expression vector targeting hypoxia-inducible factor 1 alpha inhibits tumor growth in hepatobiliary and pancreatic cancers.

Hepatobiliary and pancreatic carcinomas are hypovascular tumors that can proliferate under hypoxic conditions. Recent reports have demonstrated that hypoxia-inducible factor 1 alpha (HIF1alpha) plays an important role in the survival of these cancers. Given these findings, the inhibition of the HIF1alpha pathway might prove to be a powerful tool in the treatment of these cancers. To inhibit HIF1alpha expression, we used small interference RNA (siRNA) expression vectors in this study. The transient transfection of siRNA expression vectors significantly reduced both HIF1alpha mRNA levels (13% of control) and protein levels (41% of control) and significantly inhibited the growth of cancer cell lines (P<0.05). VEGF, Glut1, and aldorase A expressions were also significantly reduced by transfection with these vectors (P<0.05), and we found that these vectors induced apoptosis but not cell cycle arrest. In a subcutaneous tumor model using nude mice, transfected MIA PaCa-2 cells, stably expressing siRNAs, barely formed tumors compared to control (P<0.05). This study thus demonstrates the usefulness of siRNA expression vector in targeting HIF1alpha and points to a potential clinical role in the treatment of pancreatic and hepatobiliary carcinomas.

Animals↗
PubMed2006

Allergen-specific helper T cell response in patients with cow's milk allergy: Simultaneous analysis of proliferation and cytokine production by carboxyfluorescein succinimidyl ester dilution assay.

BACKGROUND: The role of antigen-specific T cells in the allergic reaction to cow's milk or in tolerance induction is not yet fully understood. OBJECTIVE: This study was designed to analyse both cow's milk protein (CMP)-specific T cell proliferation and cytokine production simultaneously in children with cow's milk allergy (CMA) in comparison with subjects with various allergic backgrounds. METHODS: Carboxyfluorescein succinimidyl ester was used to detect cow's milk-specific T cells by flow cytometry. The intra-cytoplasmic cytokine production of these antigen-specific T cells was also analysed. RESULTS: Significant differences of both CMP-specific CD4+ cell proliferation and cytokine production between CMA and non-allergic children were observed. While the proliferative responses of children who recently outgrew CMA were not significantly different from those of patients, the patterns of cytokine production were similar to those of non-allergic children. CONCLUSION: These results suggest that the presence of CMP-specific T cell clones per se does not produce CMA, but that the T-helper type 2-skewed pattern of those T cells is associated with adverse reactions. Although it is not possible to distinguish between individual patients with and without CMA on the basis of CFSE assays, these results contribute to the understanding of the pathogenesis and tolerance induction of CMA.

Allergens↗
PubMed2006

A case of suspected lysosomal storage disease in a neonatal Japanese black calf.

A 5-day-old Japanese black calf was necropsied and intracytoplasmic vacuolations were histologically observed in many tissues. In the central nervous system, intracytoplasmic inclusions and vacuoles were found in neuronal cells. Intracytoplasmic inclusions were more conspicuous in the nuclei containing large nerve cells, especially in the brain stem and spinal cord. These inclusions were stained weak positive to positive with alcian blue, Giemsa, Luxol fast blue and periodic acid-Schiff stains but not with oil red O. Ultrastructurally, neuronal inclusions were observed in lysosomes and consisted of an amorphous electron-dense substance and occasional membranous structures. These findings seem to differ from the cases of bovine lysosomal diseases that have been reported, and this case may be another type of lysosomal storage disease.

Animals↗
PubMed2006

In vivo engineering of metabolically active hepatic tissues in a neovascularized subcutaneous cavity.

Recent success in clinical hepatocyte transplantation therapy has encouraged further investigation into bioengineering hepatic tissues in vivo. Engineering tissues in the subcutaneous space is an attractive method; however, hepatocyte survival has been transient due to insufficient vascular network formation. To establish a vascularized cavity, we created a polyethylene terephthalate mesh device coated with poly(vinylalcohol) that allowed for the gradual release of basic fibroblast growth factor (bFGF), a potent angiogenic factor. The efficacy of the bFGF-releasing device in inducing vascular network formation in the subcutaneous space was observed in mouse and rat studies. Isolated mouse hepatocytes transplanted into newly vascularized subcutaneous cavities allowed for persistent survival up to 120 days. In the absence of a vascularized compartment, the survival of the transplanted hepatocytes was markedly diminished. Functional maintenance of the engineered hepatic tissues was confirmed by high expression of liver-specific mRNAs and proteins. These engineered hepatic tissues have the ability to take up inoculated compounds and express strong induction of drug-metabolizing enzymes, demonstrating functional relevance as a metabolic tissue. In conclusion, we have created a novel technology to engineer functionally active hepatic tissues in the subcutaneous space, which will likely facilitate hepatocyte-based therapies.

Animals↗
PubMed2006

Cyclin B1 is useful to predict occult cervical lymph node metastases in tongue carcinoma.

Cyclin B1 plays an important role in regulating the G2-M transition of the cell cycle. In this study, we evaluated the immunohistochemical expression of cyclin B1 in a series of 40 oral tongue squamous cell carcinomas and analyzed the findings in relation to both clinicopathological variables and the Ki-67 labeling index. In normal squamous epithelium, cyclin B1 was localized in the nucleus and was expressed only in several cells of the basal and parabasal layers. By contrast, in dysplastic epithelium, cyclin B1 was localized in the cytoplasm and nuclei, and the numbers of cyclin B1 positive cells increased compared with normal epithelium. In tumor tissues, cyclin B1 expression was observed mainly in the cytoplasm, and the cyclin B1 labeling index ranged from 2 to 21%, with a mean of 11%. Cyclin B1 overexpression was positively correlated with occult cervical lymph node metastases and the number of mitotic cells. In addition, there was a positive relationship between labeling indices of cyclin B1 and Ki-67. These findings indicate that cyclin B1 could be a useful prognostic marker of occult cervical lymph node metastases in tongue carcinoma.

Adult↗
PubMed2005

Thermal transport in the hidden-order state of URu2Si2.

We present a study of thermal conductivity in the normal state of the heavy-fermion superconductor URu2Si2. Ordering at 18 K leads to a steep increase in thermal conductivity and (in contrast with all other cases of magnetic ordering in heavy-fermion compounds) to an enhancement of the Lorenz number. By linking this observation to several other previously reported features, we conclude that most of the carriers disappear in the ordered state and this leads to a drastic increase in both the phononic and electronic mean free path.

Journal Article↗
PubMed2005

Clonidine produces a dose-dependent impairment of baroreflex-mediated thermoregulatory responses to positive end-expiratory pressure in anaesthetized humans.

BACKGROUND: Perioperative hypothermia is common and results from anaesthesia-induced inhibition of thermoregulatory control. Hypothermia is blunted by baroreceptor unloading caused by positive end-expiratory pressure (PEEP), and is mediated by an increase in the vasoconstriction threshold. Premedication with clonidine impairs normal thermoregulatory control. We therefore determined the effect of clonidine on PEEP-induced hypothermia protection. METHODS: Core temperature was evaluated in patients undergoing combined general and epidural anaesthesia for lower abdominal surgery. They were assigned to an end-expiratory pressure of zero (ZEEP) or 10 cm H(2)O PEEP. The PEEP group was divided into three blinded subgroups that received placebo (Cl-0), clonidine 150 microg (Cl-150) and clonidine 300 microg (Cl-300) respectively. Placebo or clonidine was given orally 30 min before surgery. We evaluated core temperature and thermoregulatory vasoconstriction. We also determined plasma epinephrine, norepinephrine, angiotensin II concentrations and plasma renin activity. RESULTS: Core temperature after 180 min of anaesthesia was 35.1 (0.4) degrees C in the ZEEP group. PEEP significantly increased final core temperature to 35.8 (0.5) degrees C (Cl-0 group). Clonidine produced a linear, dose-dependent impairment of PEEP-induced hypothermia protection: final core temperatures were 35.4 (0.3) degrees C in the Cl-150 group and 35.0 (0.6) degrees C in the Cl-300 group. Similarly, clonidine produced a linear and dose-dependent reduction in vasoconstriction threshold: Cl-0, 36.4 (0.3) degrees C; Cl-150, 35.8 (0.3) degrees C; Cl-300, 35.4 (0.6) degrees C. Plasma norepinephrine, angiotensin II concentrations and renin activity were consistent with the thermoregulatory responses. CONCLUSION: Baroreceptor unloading by PEEP normally moderates perioperative hypothermia. However, clonidine premedication produces a linear, dose-dependent reduction in this benefit.

Adrenergic alpha-Agonists↗
PubMed2005

Analysis of risk factors for the development of gallstones after gastrectomy.

BACKGROUND: The incidence of gallstones is higher in people who have undergone gastrectomy than in the general population, but the cause of this is unknown. METHODS: Between January 1992 and January 2003, 749 patients underwent ultrasonography of the gallbladder after gastrectomy for gastric cancer. A total of 2327 examinations were carried out. The incidence of gallstones was compared in subgroups of patients classified according to the type of reconstruction, extent of gastrectomy, whether the duodenum was excluded and type of lymph node dissection. RESULTS: The incidence of gallstones was significantly higher after total compared with partial gastrectomy (27.9 versus 7.8 per cent at 5 years; P < 0.001). Reconstruction with duodenal exclusion was associated with a significantly higher incidence than non-exclusion (25.1 versus 8.2 per cent at 5 years; P < 0.001). Patients who had lymph node dissection in the hepatoduodenal ligament had a significantly higher incidence of gallstones than those who did not (28.2 versus 7.5 per cent at 5 years; P < 0.001). In multivariate analysis that included type of reconstruction and lymph node dissection, lymph node dissection in the hepatoduodenal ligament was identified as the most significant risk factor for gallstone development (odds ratio 3.66 (95 per cent confidence interval 2.16 to 6.22); P < 0.001). CONCLUSION: Lymph node dissection in the hepatoduodenal ligament, total gastrectomy and exclusion of the duodenum are risk factors for gallstones after gastrectomy.

Adult↗
PubMed2005

Development of the needle insertion robot for percutaneous vertebroplasty.

Percutaneous Vertebroplasty (PVP) is an effective and less invasive medical treatment for vertebral osteoporotic compression fractures. However, this operative procedure is quite difficult because an arcus vertebra, which is narrow, is needled with accuracy, and an operator's hand is exposed to X-ray continuously. We have developed a needle insertion robot for Percutaneous Vertebroplasty. Its experimental evaluation on the basic performance of the system and needle insertion accuracy are presented. A needle insertion robot is developed for PVP. This robot can puncture with accuracy and an operator does not need to be exposed to X-ray. The mechanism of the robot is compact in size (350 mm x D 400 mm x H270 mm, weight: 15 kg) so that the robot system can be inserted in the space between C-arm and the patient on the operating table. The robot system is controlled by the surgical navigation system where the appropriate needle trajectory is planned based on pre-operative three-dimensional CT images. The needle holding part of the robot is X-ray lucent so that the needle insertion process can be monitored by fluoroscopy. The position of the needle during insertion process can be continuously monitored. In vitro evaluation of the system showed that average position and orientation errors were less than 1.0 mm and 1.0 degree respectively. Experimental results showed that the safety mechanism called mechanical fuse released the needle holding disk properly when excessive force was applied to the needle. These experimental results demonstrated that the developed system has the satisfactory basic performance as needle insertion robot for PVP.

Bone Cements↗
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

Efficacy of auxiliary partial orthotopic liver transplantation for cure of hemophilia in a canine hemophilia A model.

Metabolic liver disease can be cured by orthotopic liver transplantation. Some successful cases of whole or partial liver transplantation have been reported. Because liver function in these recipients is normal save for the production of the responsive metabolic factor, auxiliary partial orthotopic liver transplantation (APOLT) may produce a benefit. However, no experimental model of APOLT for metabolic liver diseases has been reported. We established a canine APOLT model to evaluate the clinical feasibility and efficacy of APOLT to cure hemophilia. The donor normal beagle dog was used to establish an APOLT model. A left lobe partial liver graft taken from the donor was orthotopically transplanted to the recipient after resection of the native left lobe preserving the native right lobe. Recipients showed no atrophy and comparable blood flow in both the graft and the native liver at the time of exploration after APOLT. Thus, APOLT was performed from a normal donor to a recipient with hemophilia A. In this recipient, blood factor VIII activity markedly increased after APOLT and was maintained for 7 weeks. No episode of bleeding was seen during the observation. In conclusion, a canine APOLT model was successfully established as evidenced by sustained production of factor VIII in a hemophilia recipient. These findings suggest the clinical feasibility and efficacy of APOLT for metabolic liver diseases.

Animals↗
PubMed2005

Heterotopically transplanted hepatocyte survival depends on extracellular matrix components.

The novel approach of tissue engineering to treat many forms of liver diseases using hepatocytes requires sufficient numbers and sustained survival of the transplanted cells. It has been shown that providing extracellular matrix components extracted from Engelbreth-Holm-Swarm cells (EHS-ECMs) to heterotopically transplanted hepatocytes allows significantly greater hepatocyte survival. We investigated the survival and morphology of hepatocytes and EHS-ECMs transplanted under the kidney capsule compared with hepatocytes with growth factor-reduced EHS-ECMs in mice. Both the EHS-ECMs and growth factor-reduced EHS-ECMs showed a large number of surviving hepatocytes under the kidney capsule without any intergroup differences. Histologically, transplanted hepatocytes in both groups retained their characteristic morphologies and formed small liver tissues. These data indicate that extracellular matrix components are the predominant factor in EHS-ECMs required to maintain hepatocytes at heterotopic sites.

Animals↗
PubMed2005

[Evaluation of open window thoracostomy for chronic tuberculous empyema with broncho-pleural fistula; a retrospective analysis of 33 cases].

We report here our 13-year experience treating chronic tuberculous empyema by open window thoracostomy. The subjects were 33 patients (28 males and 5 females) with a median age of 70 (range: 56-83) years who underwent surgery between January 1990 and December 2002. Patients with a history of pulmonary resection or thoracoplasty were excluded. All patients complained of cough and purulent sputum related to the presence of bronchopleural fistula. Previous illnesses included pulmonary tuberculosis (n = 20) and tuberculous pleurisy (n = 14) treated by artificial pneumothorax (n = 1) or chemotherapy (n = 22). Median duration from the initial episode of tuberculosis to surgery was 44 (range: 1-60) years. Mycobacterium tuberculosis (n = 9), Aspergillus fumigatus (n = 6), methicillin-resistant Staphylococcus aureus (MRSA) [n = 5], and Pseudomonas aeruginosa (n = 5) were representative microorganisms isolated from empyema. Preoperative mean %VC was 48 (range: 31-74)%. Mean follow-up was 34 (range: 1-131) months. Seven patients died of empyema-related disease within 6 months postoperatively. Nine patients underwent curative surgery to close the thoracostomy, including extrapleural pneumonectomy (n = 5), muscular transposition with thoracoplasty (n = 3), and lobectomy with muscular transposition and thoracoplasty (n = 1). In 17 patients, the thoracostomy was left open throughout the observation period because of severe impairment of pulmonary function. In elderly patients with severely impairment of pulmonary function, open window thoracostomy does not control empyema well and has a high rate of mortality.

Aged↗
PubMed2005

[Concomitant off-pump coronary artery bypass and left lower lobectomy for lung cancer with pneumoconiosis].

Surgical strategy for patients for lung cancer with coronary disease remains controversial. We performed concomitant off-pump coronary artery bypass grafting (off-pump CABG: OPCAB) and left lower lobectomy with ND 2a lymph nodes dissection for lung cancer with pneumoconiosis. After CABG, due to fixed adhesion of peribronchial lymph node, left lower lobectomy was hard to carry out. Postoperative management was done with much difficulty for massive sputum and pneumonia caused by chronic inflammatory lung disease. As a result, postoperative course has been uneventful for 2 years after operation. In the concomitant OPCAB and lung resection with chronic inflammatory lung disease, whether the synchronous or 2 periods operation was appropriate was still unknown. We think that careful pre- and intraoperative assessment for this disease is important.

Aged↗