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Biomedical subjects

M Nakamura

Publications and source records attributed to M Nakamura.

At least 91 records · Page 5Linked to original sources
PubMed2005

Induction of mononuclear cell infiltration into liver by Japanese herbal medicine.

Juzen-Taiho-To (JTT) is a Japanese herbal medicine that has been administered mainly to patients weakened by long illness. Currently, it has also been used for cancer patients and showed antitumor effects that have been reported as phagocytosis enhancement, cytokine induction and antibody production. In this study, we examined the effect of oral administration of JTT in mice on the immunological restoration of the liver, especially focused on natural killer (NK) T-cell induction. Mice were grouped to receive JTT or placebo orally for a period of 1, 3 and 7 days. After sacrifice, the liver tissue was fixed, embedded and stained with hematoxylineosin and some antibodies by common staining methods. Transmission electron microscope (TEM) observation was also carried out. Although the JTT-treated mice had the same appearance as the non-JTT-treated mice, their livers were infiltrated by massive mononuclear cells, some of which were aggregated in clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of interleukin (IL)-12 and massive infiltration of mononuclear cells with large granules in the liver of JTT-treated mice. Oral administration of JTT may induce the expression of IL-12 and be followed by immunological restoration such as NK T-cell induction in liver

Animals↗
PubMed2004

Urine diacetylspermine as a novel tumour maker for pancreatobiliary carcinomas.

BACKGROUND: Serum carcinoembryonic antigen (highly specific) and carbohydrate antigen 19-9 (highly sensitive) have been used as tumour markers for pancreatobiliary cancers. A novel urine tumour marker, diacetylspermine, was compared with the two conventional serum tumour markers in 125 patients with pancreatobiliary diseases. RESULTS: When the diagnosis of benign or malignant condition was examined, the sensitivity of urine diacetylspermine (75%) was higher than that of serum carcinoembryonic antigen (44%; P=0.048) and the same as that of serum carbohydrate antigen 19-9 (75%). The specificity of urine diacetylspermine (81%) was lower than that of serum CEA (92%) and as high as that of serum carbohydrate antigen 19-9 (80%). The efficiency of urine diacetylspermine (79%) was higher than that of serum carcinoembryonic antigen (74%) and the same as that of serum carbohydrate antigen 19-9 (79%). CONCLUSION: These results suggest that urine diacetylspermine is a marker for pancreatobiliary carcinoma, which is as highly sensitive and specific as serum carbohydrate antigen 19-9.

Adult↗
PubMed2004

A novel antigenic variant of Canine parvovirus from a Vietnamese dog.

Nine isolates of Canine parvovirus (CPV) were obtained from Vietnamese dogs and cats. One canine isolate showed a unique antigenic property which indicates a novel antigenic variant of CPV-2b when examined with hemagglutination inhibition tests using our monoclonal antibodies, 21C3 and 19D7, which were recently developed. This isolate had an amino acid substitution of residue 426, Asp to Glu, and the same substitution has recently been found in CPV from Italian dogs. This study first showed that such substitution caused an antigenic difference demonstrable by monoclonal antibodies and that a similar evolution may have occurred in CPV in Vietnam.

Animals↗
PubMed2004

Near-infrared spectrophotoscopy of finger venules in assessment of autonomic dysfunction.

The authors evaluated morphologic changes in the venules of the finger using near-infrared spectrophotoscopy in patients with autonomic dysfunction, such as familial amyloidotic polyneuropathy and multiple-system atrophy. Abnormalities of the venules, such as tortuosity, irregular venous caliber, and microaneurysm-like change, and a linear negative correlation between the degree of orthostatic hypotension and the degree of vasoconstriction of the venules were observed.

Adult↗
PubMed2004

Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury.

Endogenous neural stem/progenitor cells (NSPCs) have recently been shown to differentiate exclusively into astrocytes, the cells that are involved in glial scar formation after spinal cord injury (SCI). The microenvironment of the spinal cord, especially the inflammatory cytokines that dramatically increase in the acute phase at the injury site, is considered to be an important cause of inhibitory mechanism of neuronal differentiation following SCI. Interleukin-6 (IL-6), which has been demonstrated to induce NSPCs to undergo astrocytic differentiation selectively through the JAK/STAT pathway in vitro, has also been demonstrated to play a critical role as a proinflammatory cytokine and to be associated with secondary tissue damage in SCI. In this study, we assessed the efficacy of rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) in the treatment of acute SCI in mice. Immediately after contusive SCI with a modified NYU impactor, mice were intraperitoneally injected with a single dose of MR16-1 (100 microg/g body weight), the lesions were assessed histologically, and the functional recovery was evaluated. MR16-1 not only suppressed the astrocytic diffentiation-promoting effect of IL-6 signaling in vitro but inhibited the development of astrogliosis after SCI in vivo. MR16-1 also decreased the number of invading inflammatory cells and the severity of connective tissue scar formation. In addition, we observed significant functional recovery in the mice treated with MR16-1 compared with control mice. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI represents an attractive option for the treatment of SCI.

Analysis of Variance↗
PubMed2004

Effect of flow disturbances remaining at the beginning of diastole on intraventricular diastolic flow and colour M-mode Doppler echocardiograms.

A computational model of the fluid dynamics of intraventricular flow was used to investigate the importance of the effects of flow disturbances existing within the left ventricle (LV) at the onset of diastole on a diastolic flow field. The simulation started with a quiescent flow state; it continued for a number of cardiac cycles to obtain a cyclically repeatable flow. After the flow became periodic, the initial diastolic flow was not quiescent: flow disturbances, remnants of a systolic flow, were present within the LV. Nevertheless, they faded away during an acceleration phase of diastole and almost ceased by the end of this phase. Consequently, a flow field during a deceleration phase of diastole, characterised by the formation of a vortex ring, was hardly affected by the initial flow disturbances. The propagation velocity of a colour M-mode Doppler echocardiogram obtained by scanning velocity along the LV long axis was 0.58 m s(-1) in the case where diastolic flow was initially quiescent and 0.56 m s(-1) in the case where flow disturbances existed at the beginning of diastole. These results indicated that the colour M-mode Doppler echocardiographic technique captures flow dynamics produced purely by ventricular expansion, with little influence from initial diastolic flow disturbances.

Computer Simulation↗
PubMed2004

Plasma eotaxin level and severity of asthma treated with corticosteroid.

Our understanding of asthma severity was advanced by the identification of biomarkers which account for differences in lung function impairment. We tried to examine the effects of corticosteroid treatment on known correlates of asthma severity including peripheral eosinophil counts, total IgE, IL-5, and eotaxin Levels in plasma. We compared these biomarkers among groups of stable asthmatics categorized by the dose of corticosteroid (N: steroid-free, n = 25; L: low-dose inhaled, n = 27; MH: medium or high-dose inhaled, n= 19; O: inhaled plus oral, n= 8). Next we compared these markers and peak expiratory flow rate (PEFR) in unstable asthmatics before and after treatment with steroids (n = 22). Eotaxin levels in the O group were higher than those in the N and MH groups (P < 0.05). Logistic regression analysis demonstrated that plasma eotaxin level was correlated with the severity of asthma defined by treatment intensity (P = 0.01) and % FEV1 (P = 0.04) while the other markers were not. Eotaxin levels did not change after steroid treatment in unstable patients, whereas eosinophil counts decreased in parallel with PEFR. Among biomarkers of asthma severity studied, plasma eotaxin level was not significantly affected by corticosteroid treatment, and was associated with the severity even in the presence of steroid therapy.

Administration, Inhalation↗
PubMed2004

Real-time monitoring for detecting rejection using strain gauge force transducers in porcine small bowel transplantation.

PURPOSE: The clinical results of small bowel transplantation (SBT) have not been satisfactory mainly because of the immunological barrier. It is important to detect the presence of and to perform adequate treatment of rejection as early as possible to improve graft survival. Therefore, we have established a pig model to monitor graft motility as a means to detect rejection in real time. METHODS: Orthotropic SBT was performed in 25 pigs using FK-506 (0.05 to 0.1 mg/kg/d) immunosuppression. The interdigestive motor patterns were evaluated using strain gauge force transducers (SG). Seven pigs without SBT were treated as controls (C). Animals that displayed migrating motor complex (MMC) activity as evidenced by duration, amplitude, and interval in the graft were alive more than 10 days with adequate oral feeding: the functional graft (FG) group. In contrast the rejection (R) group did not show these activities on data recorded within 10 days before death due to rejection. RESULTS: The FG group showed MMC propagated throughout the graft with all parameters almost the same as the control group except for the duration. In contrast, all parameters in the group R were significantly lower than those in group FG, suggesting that group R motility was obviously impaired by rejection. CONCLUSIONS: The SG method may afford real-time monitoring of transplanted bowel motility that could be useful to detect rejection after SBT.

Animals↗
PubMed2004

Hand-assisted laparoscopic live donor nephrectomy: report of 100 cases.

INTRODUCTION: Laparoscopic live donor nephrectomy is not yet widespread in Japan. After our first hand-assisted laparoscopic live donor nephrectomy (HALapNx) in 2001, we report our 100 cases and examine the possibility of making this technique widely available in Japan. METHODS: HALapNx was performed in 100 cases (44 males and 56 females) from February 2001 through July 2003. The operative procedure for HALapNx was briefly described here. First, 2 12-mm ports were placed in the midaxillary line at the superior and inferior level of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system was fitted through the abdominal incision. After 10 mm Hg pneumoperitoneum, HALapNx begins with mobilization of the left colon. RESULTS: HALapNx was completed successfully in all cases and no patients required conversion to laparotomy. The estimated blood loss was 33.5 +/- 40.3 g and no patient required blood transfusion. The mean operative time was 168.8 +/- 47.6 minutes, and there was no major complication in a donor. CONCLUSIONS: HALapNx is technically feasible and may offer several advantages over open donor nephrectomy in terms of less blood loss, less postoperative pain, and minimal cosmetic disfigurement. In Japan, laparoscopic donor nephrectomy is not yet widespread, possibly due to the need for surgical laparoscopic skills. We believe that the best way to make laparoscopic donor naphrectomy widely available is through hand-assisted laparoscopic surgery.

Adult↗
PubMed2004

Efficacy of basiliximab induction therapy in ABO-incompatible kidney transplantation: a rapid steroid withdrawal protocol.

INTRODUCTION: We have performed ABO-incompatible (ABO-i) kidney transplantation (KT) to alleviate the severe organ shortage in our country. Induction therapy with basiliximab, a monoclonal anti-interleukin-2 receptor antibody, is known to be effective in reducing the incidence of acute rejection (AR) after ABO-compatible KT. However, the efficacy of basiliximab in ABO-i KT is still unknown. In this study, we evaluated the effect of basiliximab to decrease overall maintenance immunosuppression (a steroid withdrawal protocol) and to improve the outcome of ABO-i KT. PATIENTS AND METHODS: Between April 2002 and May 2003, 14 adult patients underwent ABO-i KT from living donors with cyclosporine (CsA)-based immunosuppression. There were seven men and seven women of mean age 48 +/- 10 years. Three of the 12 cases were second KT. Three sessions of plasmapheresis were performed to remove anti-AB antibodies before KT. Splenectomy was performed in all patients. Immunosuppression consisted of methylprednisolone (MP), CsA, and mycophenolate mofetil, in addition to antibody induction with basiliximab. MP was completely withdrawn on postoperative day 14. RESULTS: In 3 of 14 recipients, MP was restarted because of AR or a suspicion of AR. Both patient and graft survivals were 100%. The incidence of biopsy-proven AR was 14% (2/14). There was no adverse effect related to the antibody therapy. CONCLUSION: The use of basiliximab induction therapy may eliminate the need for steroid maintenance therapy without increasing AR risk, even among ABO-i KT recipients. We conclude that basiliximab provides safe and effective induction immunosuppression in ABO-i KT recipients.

ABO Blood-Group System↗
PubMed2004

Living related liver transplantation for biliary atresia with portopulmonary hypertension: case report.

Portopulmonary hypertension is a complication of end-stage liver disease that adversely affects the outcome of liver transplantation (LT). We report a case of living related LT who developed severe pulmonary hypertension during and after LT. This 16-year-old girl suffered from biliary atresia, having undergone a portoenterostomy at 60 days of age, at the time of discovery of liver cirrhosis. She had been admitted to a local hospital several times for episodes of esophageal variceal bleeding. Neither dyspnea nor cyanosis was discerned until LT. Although pulmonary hypertension (PH) was disclosed by echocardiogram upon preoperative evaluation, we did not consider this a contraindication for LT, because the PH was mild. She underwent living LT from her father (graft volume/recipient body weight ratio: 0.99%). After induction of anesthesia for LT, a pulmonary flotation catheterization showed severe PH (>40 mm Hg). The pulmonary artery pressure continued to be elevated during surgery, although it was possible that her severe scoliosis affected the data. Hyperbilirubinemia was observed after LT, despite good liver function tests. On postoperative day 12, a portal vein thrombosis was detected requiring emergency thrombectomy and splenectomy. Her general condition worsened after the second surgery. She died due to cardiopulmonary failure. Autopsy showed marked hypertrophy of the right ventricle with intimal thickening in the pulmonary artery. In this case, the underestimated PH might have resulted in the unfortunate outcome. Before LT, PH should be carefully evaluated by measures including invasive assessment.

Adolescent↗
PubMed2004

Results of kidney transplantation in patients receiving MMF- or MMF and basiliximab-containing immunosuppression.

UNLABELLED: Mycophenolate mofetil (MMF) is a more potent immunosuppressive drug than azathioprine or mizoribine in combination with cyclosporine (CsA) and steroids. Recently, basiliximab (BA), an interleukin-2 receptor antagonist, has become available in Japan. The purpose of this study was to evaluate the efficacy of an extremely low CsA dose immunosuppressive protocol with MMF versus MMF plus BA after renal transplantation (RTx). PATIENTS: Between September 2001 and March 2003, we performed 79 RTx with CsA-based immunosuppression, including nine from cadavers and 70 from living donors with 15 ABO-incompatible RTx. Immunosuppression consisted of methylprednisolone (MP), CsA and MMF (group 1; n = 24) versus added BA during the induction phase (group 2; n = 55). In group 2, MP was withdrawn on postoperative day 14. Supplementary MP, muromonab-CD3, or gusperimus was administered if rejection was suspected clinically or diagnosed by biopsy. RESULTS: The incidence of biopsy-proven acute rejection (AR) was significantly higher among group 1 than group 2 patients (P < .05). CsA C2 levels in group 1 were significantly higher than group 2 at each time (P < .01). The incidence of infection was comparable. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 98% and 98%, respectively. CONCLUSION: The short-term results of RTx were favorable in both the MMF, and the MMF plus BA immunosuppression. In addition, BA significantly reduced the number of AR episodes. Early steroid withdrawal in recipients receiving BA induction was not associated with an increased risk of AR.

Adult↗
PubMed2004

An intraoperative fluorescent imaging system in organ transplantation.

UNLABELLED: An intraoperative fluorescent imaging system (SPY system; Novadaq Technologies, Inc, Concord, Ontario, Canada) that enables vascular surgeons to confirm the location and states of the reconstructed vessels during surgery, has been developed in the field of open heart surgery. In this paper, we evaluated the usefulness of the SPY system in kidney and liver transplantation. PATIENTS AND METHODS: SPY system visualizes arteries and grafts intraoperatively, using indocyanine green (ICG) with a portable imaging device. The modality was evaluated in 15 patients undergoing kidney (n = 13) or liver (n = 2) transplantation with respect to safety, feasibility of use, and image quality. Images were generated and acquired with a portable laser diode/infrared camera device after injection of 10 mL of ICG (2.5 mg/mL) intravenously. RESULT: There was no complication associated with ICG injection or the imaging device. The SPY system was easily used during transplant surgery and adequately demonstrated reconstructed arteries and patency in all patients. CONCLUSION: The intraoperative imaging system enables the surgeon to view, record, and replay real-time images of the reconstructed arteries during surgery. The system may provide useful information during surgery such as solid organ transplantation that requires vascular reconstruction.

Fluorescein Angiography↗
PubMed2004

Expression of P450 aromatase protein in developing and in sex-reversed gonads of the XX/XY type of the frog Rana rugosa.

Gonadal differentiation in some species of amphibians is sensitive to steroids. The phenotypic sex of XX/XY-type frogs such as Rana rugosa can be reversed from female to male by injection of testosterone into tadpoles, but little is known about the molecular mechanism of this sex reversal. To elucidate the mechanism of the sex differentiation, we examined the role of P450 aromatase (P450arom), an enzyme that converts testosterone to estrogen, during gonadal differentiation of amphibians. In this study, we first cloned a P450arom cDNA homolog of the frog R. rugosa and analyzed by RT-PCR its expression profile in developing and in female-to-male sex-reversed gonads. P450arom expression was observed in the gonad of tadpoles during ovarian differentiation and became much stronger in the developing ovary in which only immature oocytes were observed. However, its expression declined significantly in the ovary of frogs 2 months after metamorphosis, when oocytes were growing; and it was no longer seen in adult ovaries. By RT-PCR, we also examined the expression of P450arom and SF-1 (steroidogenic factor-1; the orphan nuclear receptor) in the female-to-male sex-reversed gonad. The level of P450arom mRNA was high in the ovary, but it declined rapidly after the injection of testosterone. In contrast, no change in the SF-1 (also known as Ad4BP) expression was observed. Moreover, to identify the type(s) of cells expressing P450arom protein, we performed immunostaining with an antibody against frog P450arom protein. Cells giving positive signals were observed around oocytes in the ovary of frogs 1 month after metamorphosis. They were identified as follicle cells by both light and electron microscopy. The results, taken together, indicate that P450arom protein is synthesized in follicle cells and that P450arom is very much involved in ovarian differentiation in R. rugosa.

Amino Acid Sequence↗
PubMed2004

Targeted conversion of the transthyretin gene in vitro and in vivo.

Familial amyloidotic polyneuropathy (FAP) is the common form of hereditary generalized amyloidosis and is characterized by the accumulation of amyloid fibrils in the peripheral nerves and other organs. Liver transplantation has been utilized as a therapy for FAP, because the variant transthyretin (TTR) is predominantly synthesized by the liver, but this therapy is associated with several problems. Thus, we need to develop a new treatment that prevents the production of the variant TTR in the liver. In this study, we used HepG2 cells to show in vitro conversion of the TTR gene by single-stranded oligonucleotides (SSOs), embedded in atelocollagen, designed to promote endogenous repair of genomic DNA. For the in vivo portion of the study, we used liver from transgenic mice whose intrinsic wild-type TTR gene was replaced by the murine TTR Val30Met gene. The level of gene conversion was determined by real-time RCR combined with mutant-allele-specific amplification. Our results indicated that the level of gene conversion was approximately 11 and 9% of the total TTR gene in HepG2 cells and liver from transgenic mice, respectively. Gene therapy via this method may therefore be a promising alternative to liver transplantation for treatment of FAP.

Amyloid Neuropathies↗
PubMed2004

Endoscopic resection of submucosal esophageal tumors: a prospective case series.

BACKGROUND AND STUDY AIM: The introduction of endoscopic ultrasound (EUS) and endoscopic mucosal resection has offered a new alternative to simple observation or surgical resection for the management of esophageal submucosal tumors. PATIENTS AND METHODS: During a 4-year period, endoscopic resection was attempted in 20 consecutive patients (nine women, 11 men; mean age 52 +/- 10 years) with esophageal submucosal tumors < 4 cm in size, confirmed by endoscopy and miniprobe EUS (20 MHz). The mean tumor diameter was 17 +/- 8 mm (8 - 34 mm). Prior EUS-guided cytological examination revealed benign tumors in 11 patients; however, endoscopic resection was attempted in most patients for diagnostic purposes also. Several patients were symptomatic (retrosternal pain, n = 4; dysphagia, n = 4; recurrent bleeding, n = 2) but most tumors had been detected incidentally. RESULTS: In the majority of patients the tumor was ligated with a rubber band and then resected with a snare (n = 11), and in the others simple snare resection ("lift-and-cut," n = 7) or cap resection (n = 2) was done. A macroscopically complete endoscopic resection was achieved in 19/20 patients, and the remaining patient was managed surgically. Endoscopic hemostasis was necessary (and successful) in eight patients (40 %), but blood transfusion was not required. No other side effects occurred. Histological examination revealed granular cell tumor in 12 patients, leiomyoma in six patients, and a lipoma and stromal tumor in one patient each. Histologically, all tumors were judged to be benign and a microscopically complete resection (R0) was achieved in all patients, with the exception of the one patient with a stromal tumor. Thus, surgical resection was necessary in only two of the 20 patients (10 %). During the median prospective follow-up of 12 months no tumor recurrence was detected in any patient. CONCLUSION: Endoscopic resection of esophageal submucosal tumors is safe and effective. The probability of achieving curative resection (R0 resection, histologically benign) is high especially if the tumors are smaller in size (< 4 cm).

Endoscopy↗
PubMed2004

Flow cytometric detection of cell-associated interleukin-8 in alveolar macrophages in vivo from patients with hypersensitivity pneumonitis and sarcoidosis.

In comparison with neutrophil-mediated lung diseases, such as acute respiratory distress syndrome, the involvement of IL-8 in lymphocyte-mediated lung diseases has not been fully investigated. Several reports have shown a slight increase in bronchoalveolar lavage fluid (BALF) IL-8 in patients with hypersensitivity pneumonitis (HP) and sarcoidosis (SAR), but the source of the IL-8 has not been clarified. In the present study, the in vivo production of IL-8 by alveolar macrophages (AMs) is examined in these patients by analyzing the cell-associated IL-8, using the flow cytometric method adopted previously. The IL-8 levels in the epithelial lining fluid (ELF) were also assessed. Initially, slight, but significant, increased levels of ELF IL-8 in HP and SAR were confirmed. Using flow cytometric analysis, a significant increase was found in the cell-associated IL-8 of the freshly isolated AMs in HP, but not in SAR, indicating in vivo production of IL-8 by AMs in HP. The cell-associated IL-8 of the AMs cultured with or without lipopolysaccharide was also analyzed. However, in contrast to previous findings in patients with idiopathic pulmonary fibrosis, no differences were found between SAR and HP patients and control subjects. Based on these findings, it is speculated that ELF IL-8 levels are slightly increased in HP and SAR, and they may contribute to the accumulation of neutrophils and possibly lymphocytes. However, the source of IL-8 may be different and AMs are the candidate source of IL-8 in HP, but not in SAR. The flow cytometric method may be useful in assessing cytokines production by AMs.

Adult↗