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Biomedical subjects

Hiroyuki Tsutsumi

Publications and source records attributed to Hiroyuki Tsutsumi.

At least 19 recordsLinked to original sources

Development of a reexpandable covered stent for children.

The use of covered stents in children is limited by the need for a large long sheath for delivery and the impossibility of redilation once implanted. The authors developed a reexpandable covered stent implantable in children through a small sheath and evaluated its clinical feasibility in mini piglets. An original Palmaz stent was covered with a polyurethane membrane that could be stretched up to 700%. Under general anesthesia, the authors implanted the covered stents in six mini piglets using a long sheath with a diameter approximately 1 French larger than the recommended size required to deliver an uncovered Palmaz stent. The implantation technique was similar to conventional stent implantation. In six piglets, the stent could be redilated from 7.5 to 8.7 mm 28-70 days after implantation. Macroscopic and microscopic examination showed intimal coverage of the coating with minimal inflammatory reaction around the stent. Our newly designed reexpandable stent covered with a polyurethane membrane is promising for use in children.

Angioplasty, Balloon↗

Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections.

The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS-CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS-CoV infection. Therefore, SARS-CoV replication was suppressed by pretreatment with IFN. SARS-CoV and RSV induced high levels of IL-6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling-3 (SOCS3) by SARS-CoV was significantly lower than that by RSV in spite of the significant production of IL-6. Toll-like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS-CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with "severe" inflammation in SARS.

Caco-2 Cells↗

Screening for vaginal shedding of cytomegalovirus in healthy pregnant women using real-time PCR: correlation of CMV in the vagina and adverse outcome of pregnancy.

The impact of cytomegalovirus (CMV) infection of the genital tract during pregnancy on adverse pregnancy outcomes is not understood fully. A real-time PCR assay was used to determine vaginal shedding of CMV in 993 healthy pregnant Japanese women and the results were compared with the outcome of pregnancy. CMV DNA was detected in 76 (7.7%) of the women. The outcome of pregnancy could be determined finally in 848 women, of whom 60 (7.1%) were CMV positive. The carriers of CMV had an increased miscarriage rate (RR 6.96, 95% CI 2.04-23.84, P < 0.01). These findings suggest that latent genital tract CMV infection predisposes to adverse pregnancy outcomes.

Abortion, Spontaneous↗

Relapse of T-cell all after stem cell transplant presenting as hypertrophic cardiomyopathy: the value of non-invasive diagnostic imaging in detecting cardiac leukemia.

We describe a 14-year-old female with acute lymphoblastic leukemia (ALL) with a mediastinal mass at diagnosis who developed hypertrophic cardiomyopathy (HC) after stem cell transplantation (SCT). During refractory relapse after SCT using bone marrow from her HLA-matched sibling, she underwent whole thorax irradiation because of pleural effusion and a recurrent mediastinal mass. After a second SCT using peripheral blood from the same donor, she developed HC suspected to be related to tacrolimus. However, isolated cardiac relapse was finally diagnosed by several non-invasive imaging techniques. Cardiac irradiation resolved her cardiac failure, though she eventually developed progressive and fatal hematological disease.

Adolescent↗

Induction of autologous CD4- and CD8-mediated T-cell responses against acute lymphocytic leukemia cell line using apoptotic tumor cell-loaded dendritic cells.

OBJECTIVE: Several studies have demonstrated that dendritic cells (DCs) pulsed with tumor lysate or apoptotic tumor cells can elicit effective T-cell responses. This technique does not require the identification of the tumor antigen or HLA haplotype of the patient. We applied this approach to induce HLA class I- and class II-restricted T-cell responses directed against autologous acute lymphocytic leukemia (B-ALL) cell line NH-1. METHODS: Autologous T cells were stimulated by apoptotic tumor cell-loaded DCs generated from a patient with ALL. The stimulated and expanded T cells were isolated into CD8(+) T-cell line and CD4(+) T-cell line, and each of them was examined as to their functions. RESULTS: Both CD8(+) and CD4(+) T-cell lines demonstrated cytotoxicity against NH-1 in an major histocompatibility complex-dependent manner. Finally, we established two independent CD4(+) T-cell clones restricted to HLA-DR. The CD4(+) T-cell line responded strongly to autologous Epstein-Barr virus-transformed lymphoblastoid cell lines (EBV-LCL) but not to autologous normal cells. Furthermore, the T-cell clones also responded to allogeneic EBV-LCLs and B-ALL cell lines in the context of the HLA-DRB1( *)04051 molecule. Interestingly, 293T and COS-7 cells, which had been transfected with the HLA-DRB1( *)04051, were also recognized by T-cell clones. CONCLUSION: These findings indicate that B-ALL has shared and strong immunogenic epitopes expressed on HLA class II molecules, the expression of which is limited to immortalized cells. These data suggest that vaccinations using DCs loaded with apoptotic tumor cells might be a potent strategy in the treatment of B-ALL.

Apoptosis↗

Detection of BK virus and adenovirus in the urine from children after allogeneic stem cell transplantation.

The development of hemorrhagic cystitis (HC) and urinary excretion of polyoma BK virus (BKV) and adenovirus (ADV) was investigated by polymerase chain reaction in 20 children undergoing allogeneic stem cell transplantation. Five children developed HC, and all of them excreted BKV; however, only 1 excreted ADV, suggesting that BKV is more significant cause of HC than ADV in children undergoing stem cell transplantation.

Adenoviridae↗

Treatment of stage IV malignant rhabdoid tumor of the kidney (MRTK) with ICE and VDCy: a case report.

The prognosis of stage IV malignant rhabdoid tumor of the kidney (MRTK) has been extremely poor. However, a combination of ICE (ifosfamide, carboplatin, and etoposide) and VDCy (vincristine, doxorubicin, and cyclophosphamide) was recently reported to be effective for metastatic MRTK. We describe a 21-month-old girl with stage IV MRTK who was successfully treated with ICE, VDCy, and radiotherapy. She remained well, without recurrence, 24 months after diagnosis. Alternating therapy with ICE and VDCy might become a standard regimen for stage IV MRTK, although further study is required to confirm its effectiveness.

Antineoplastic Combined Chemotherapy Protocols↗

Intractable colitis associated with chronic granulomatous disease.

The case of a 20-year-old Japanese man, diagnosed as having autosomal recessive chronic granulomatous disease (CGD), who was being treated with corticosteroids for intractable unclassified colitis, is described. He died from multiple organ failure following disseminated intravascular coagulation secondary to disseminated varicella-zoster virus (VZV) infection. He was diagnosed as an index case of CGD when 2 years old, was inoculated against VZV at the age of 5 years and had had an unremarkable course for 19 years. He was admitted to hospital because of a third episode of recurrent bloody diarrhoea. Clinical remission for each episode was achieved by intravenous corticosteroid therapy. Unclassified colitis associated with CGD was diagnosed based on a colonic biopsy demonstrating characteristic macrophages with lipofuscin deposits. From a treatment viewpoint, idiopathic inflammatory bowel disease (IBD) should be differentiated from secondary IBD occurring in CGD, in which immunosuppressive drugs including corticosteroids, still the mainstay of IBD treatment, should be avoided.

Adult↗

Virological, serological, and clinical features of an outbreak of acute gastroenteritis due to recombinant genogroup II norovirus in an infant home.

Norovirus (NV) is an important cause of acute nonbacterial gastroenteritis worldwide. Recently, several sporadic cases due to naturally occurring recombinant NVs have been reported. In January 2000, there was an outbreak of gastroenteritis in an infant home in Sapporo, Japan. Of 34 residents of the home that were less than 2 years old, 23 developed gastrointestinal symptoms and NV infection was confirmed by conventional reverse transcription-PCR to detect the RNA polymerase region of genogroup II NV. In this virus, the RNA polymerase region shared 86% nucleotide identity with Hawaii virus but only 77% with Mexico virus; however, its capsid region shared only 70% identity with Hawaii virus but 90% with Mexico virus. On the other hand, both regions shared a higher 96% nucleotide identity with Arg320 virus, which was found in Mendoza, Argentina, in 1995 and considered to be a recombinant of Hawaii and Mexico viruses. The findings indicate that the virus involved in the outbreak was similar and may have evolved from the Arg320 virus. Clinically the cases were more severe than those of previously reported sporadic or outbreak cases of NV infection.

Acute Disease↗

Coil occlusion of patent ductus arteriosus.

BACKGROUND: Coils are the only devices available for transcatheter occlusion of patent ductus arteriosus (PDA) in Japan. Since April 1999, we have introduced a 0.052-inch Gianturco coil (0.052-inch coil) to close PDA >or=2.5 mm. METHODS AND RESULTS: A retrospective survey of the outcome of coil occlusions for PDA >or=2.5 mm before and after the 0.052-inch coil became available found that (1) the frequency of PDA >or=2.5 mm among all candidates for coil occlusion significantly increased after the availability of a 0.052-inch coil (p<0.01); (2) deployment complicated by migration (p<0.01), and prolonged procedure time (p<0.05) were significantly decreased after the introduction of the 0.052-inch coil. In a multivariate logistic regression model for uneventful deployment adjusted for age, pulmonary to systemic flow ratio, and use of a 0.052-inch coil, use of the 0.052-inch coil significantly decreased eventful deployment (p<0.05); and (3) successful deployment of a coil for PDA >or=4 mm significantly increased with the 0.052-inch coil (p<0.01). Complete occlusion was achieved once deployment was successful. CONCLUSION: Introduction of the 0.052-inch coil decreased complicated coil occlusion deployment for PDA >or=2.5 mm, and contributed to a better likelihood of coil occlusion for PDA >or=4 mm.

Balloon Occlusion↗

Late distortion of the original Palmaz stent implanted in postoperative lesions associated with congenital heart disease.

The objective of this study was to report late distortion of a Palmaz stent. Late distortion of an original Palmaz stent, implanted in an extracardiac lesion, is rare. We completed a 1-year follow-up of 54 patients who had been implanted with 80 Palmaz stents in extracardiac lesions. Distortion of two stents was detected in two patients. For case 1, we implanted a P188 stent for supravalvar pulmonary stenosis complicating an arterial switch operation in a 14-year-old girl. Seven months later, we found compression of the stent. Although we implanted two P308 stents anterior to the distorted stent, distortion of both stents developed after 1 month. Two more P308 stents placed inside each stent were gradually recompressed. A CAT scan showed compression of the stent by a dilated sinus of valsalva. For case 2, we implanted a P308 stent for stenosis of the superior vena cava after Williams operation in an 11-year-old boy. A chest X-ray documented longitudinal compression of the stent 27 months after implantation and a CAT scan showed the ascending aorta was in contact with the stent. A Palmaz stent may be distorted when implanted in a lesion adjacent to a pulsating aorta.

Adolescent↗

A phylogenetic study of human respiratory syncytial viruses group A and B strains isolated in two cities in Japan from 1980-2002.

The circulation pattern and genetic evolution of respiratory syncytial virus (RSV) in Japan were examined based on 109 RSV field strains isolated over 20 seasons (1980-2002) in two cities, Sapporo and Tokyo. The second hypervariable region of the large glycoprotein (G) gene was amplified by RT-PCR and the products sequenced directly. The nucleotide sequences were compared to those representatives of RSV genotypes identified previously. Japanese group A and B isolates clustered into five and four genotypes defined previously, respectively. Another one group A and one group B genotypes, which could not be assigned to previous genotypes, were also identified. Although different genotypes usually co-circulated in each season, the isolates in proximate seasons from two communities were usually located in the same branches. Moreover, the strains with genotypes defined previously were usually isolated at the same time as each reference strain of Western countries. Several mutant group B strains with 1-20 longer amino acid G proteins were newly identified in Sapporo. These findings suggest that Japanese RSV strains underwent geographical and also temporal clustering while participating in RSV genetic evolution in a global setting. In addition, Japanese strains, especially group B, might have evolved individually in each community, sometimes changing the length of the G protein.

Amino Acid Sequence↗

Human cytomegalovirus genetic variability in strains isolated from Japanese children during 1983-2003.

The genetic variability of 74 human cytomegalovirus (HCMV) clinical isolates from 60 Japanese infants and children during 1983-2003 was investigated, and the relevance to their clinical course was studied. The patients consisted of 10 asymptomatic congenitally infected babies, 45 infected perinatally or postnatally resulting in HCMV mononucleosis/hepatitis and 5 immunocompromised hosts. The hypervariable region of the HCMV genome, that is the a sequence and UL144 region was analyzed using the polymerase chain reaction (PCR) and unrooted phylogenetic trees. HCMV glycoprotein B (gB) polymorphism was also studied. Unrooted phylogenetic trees of a sequence and UL144 allowed the isolates to be grouped to 5 and 3 clades, respectively. Three gB genotypes were also determined. However, there was no correlation between specific genotypes of these three genes and clinical forms, except for congenital infection which fell into one of three clades of the UL144 gene. In addition, the variability of the three genes had no correlation with each other. This implies that study of a single gene is insufficient for investigating the molecular epidemiology of HCMV. This study provides basic data on the genetic variability of HCMV in an Asian population and should help to determine the strains for vaccine candidates.

Adolescent↗

Gastric antral vascular ectasia in 2-yr-old girl undergoing unrelated cord blood stem cell transplantation.

Gastrointestinal bleeding is a common complication after hematopoietic stem cell transplantation (HSCT) and is often related to acute graft-vs.-host disease (aGVHD). Gastric antral vascular ectasia (GAVE), recently recognized as a complication after HSCT, is a rare cause of severe gastrointestinal bleeding, which has only been reported in adult patients so far. We report a 2-yr-old girl who developed GAVE after unrelated cord blood stem cell transplantation (CBSCT) as treatment of intractable Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Her conditioning regimen for CBSCT consisted of etoposide, busulfan, and cyclophosphamide. She was doing well after CBSCT without recurrence and developed only grade I aGVHD. She suddenly developed coffee ground emesis, tarry stools and severe anemia 76 days after CBSCT. As antacids were ineffective, esophagogastroduodenoscopy was performed and revealed GAVE on day 97. Endoscopic coagulation therapy was performed twice; subsequently, she needed no further transfusions and there was no clinical recurrence of GAVE.

Adolescent↗

[Respiratory syncytial virus infection].

Human respiratory syncytial virus (RSV) is the most common worldwide cause of lower respiratory tract infections (LRI) in infants less than 12 months of age. RSV isolates can be divided into group A and B. In addition, there were many genotypes within each group, and these genotypes have evolved global setting with temporal and geographic clustering. Many cellular genes encoding cytokines and chemokines which are activated by RSV infection has now been focused for the elucidation of pathophysiology of RSV LRI. The prophylaxis against RSV infection by vaccination has been unsuccessful because of its adverse effects. No valuable anti-RSV drugs for clinical use have been yet developed. Therefore RSV LRI has been treated mainly symptomatically. Recently humanized anti-RSV F protein monoclonal antibody was developed and prescribed for prevention in high-risk infants such as premature ones and those with chronic lung and congenital heart diseases. It reduced the incidence of hospitalization significantly.

Animals↗

Coil occlusion for patent ductus arteriosus larger than 3 mm.

BACKGROUND: Coil occlusion of patent ductus arteriosus (PDA) is now widely accepted as the first-line treatment, but there are few reports of age-dependent differences in the complications associated with this technique. METHODS AND RESULTS: Sixteen patients (11 adults, 5 children) with a PDA larger than 3 mm, who underwent coil occlusion at Sapporo Medical University Hospital between September 1995 and August 2004, were enrolled. Immediate and intermediate outcomes and complications were analyzed. Procedural success rate was 72.7% (8/11) in the children and 100% (5/5) in the adults. Coil migration occurred in 4 children and 1 adult, and 3 adult patients had hemolysis. CONCLUSION: Hemolysis was more frequent in adults than in children even though the residual shunt was trivial.

Aged↗

[Respiratory syncytial virus].

Human respiratory syncytial virus (RSV) is the most common worldwide cause of lower respiratory tract infections (LRI) in infants less than 6 months of age. The prophylaxis against RSV infection by vaccination has been unsuccessful because of its adverse effects. As antiviral drug, ribavirin spray (aerosol) had been used clinically and reduces the amount of virus load, without reducing the necessity of symptomatic therapy and the duration of hospitalization. Therefore RSV LRI has been treated mainly symptomatically. Recently humanized anti-RSV F protein monoclonal antibody was developed and prescribed for prevention in high-risk infants such as premature ones and those with chronic lung and congenital heart diseases. It reduced the incidence of hospitalization significantly. It has been introduced in clinical use in Japan following to Western countries. On the other hand, a number of anti-RSV drugs have now been investigation; however, no valuable drugs for clinical use have been yet developed.

Animals↗