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Biomedical subjects

M Yabe

Publications and source records attributed to M Yabe.

At least 19 recordsLinked to original sources

Comparison of PCR-amplified JC virus control region sequences from multiple brain regions in PML.

The authors report a 14-year-old boy with Wiskott-Aldrich syndrome complicated by progressive multifocal leukoencephalopathy after allogeneic bone marrow transplantation. Several therapeutic approaches were attempted, but there was no response. The patient died 2 months after the onset of neurologic symptoms. We detected three distinct, rearranged regions of JC virus in the cerebellum, occipital lobe, and brainstem. These findings suggest that the brain lesions had three independent origins.

Adolescent↗

Multivariate analysis of risk factors for hemorrhagic cystitis after hematopoietic stem cell transplantation.

To establish the most appropriate prophylactic therapy and risk factors for predicting hemorrhagic cystitis (HC) after stem cell transplantation (SCT), we retrospectively analyzed the clinical records of 450 transplant patients treated from 1982 to 2002. In all, 81 patients developed early- and/or late-onset HC (early=29, late=48, both=4). For the incidence of early-onset HC, administration of cyclophosphamide (CY) (p=0.0079, odds ratio (OD)=5.109, 95% confidence interval (CI)=1.533-17.030), busulfan (BU) (p=0.0015, OD=3.336, 95% CI=1.584-7.027), BU+CY (p=0.0001, OD=4.369, 95% CI=2.055-9.292), antithymocyte globulin (p=0.0009, OD=3.368, 95% CI=1.642-6.911), nonradiation (p=0.0163, OD=2.564, 95% CI=0.181-0.841), 2-mercaptoethane sodium sulfonate (Mesna) (p=0.0001, OD=7.519, 95% CI=2.847-19.858), and bladder irrigation (p=0.0001, OD=4.950, 95% CI=2.328-10.523) were risk factors. By Fisher's exact test, the combination of BU and Mesna was a more significant risk factor (P<0.001) than Mesna alone (p=0.008) compared to the administration of neither agent. By multivariate analysis, prophylactic administration of Mesna (p=0.0105, OD=5.301, 95% CI=1.477-19.026) and bladder irrigation (p=0.0001, OD=9.469, 95% CI=3.872-23.156) were significant risk factors of early-onset HC. We conclude that (i). high-dose BU as well as CY is a cause of HC, (ii). protective bladder irrigation has an opposite effect, and (iii). Mesna possibly has a toxic effect on bladder mucosa.

Adolescent↗

Huge cystic lymphangioma of the pancreas: report of a case.

We report herein the case of a 33-year-old woman who presented with palpable abdominal swelling found to be caused by a huge lymphangioma of the pancreas. An abdominal computed tomographic (CT) scan showed a large multilocular cystic mass with water-dense contents, which was derived from the pancreatic head. A pancreaticoduodenectomy (PD) was performed because the tumor had invaded the duodenum. The resected tumor, which was 23 x 12 x 23 cm in size with 21 of serous fluid, was pathologically diagnosed as a cystic lymphangioma. The endothelial cells lining the internal surface of the cystic spaces were immunohistochemically positive for factor VIII-R antigen and CD31. Our review of the literature revealed 45 reports of lymphangioma of the pancreas, including this one, but to the best of our knowledge this is only the fifth case that required a PD. Nevertheless, we recommend that a complete resection be performed to reduce the risk of recurrence.

Adult↗

Injection of CD4(+) and CD8(+) cells with donor or host accessory cells induces acute graft-vs-host disease in human skin in immunodeficient mice.

OBJECTIVE: We examined cell subsets with respect to cutaneous graft-vs-host disease by cell sorting selection of subsets of human mononuclear cells and injecting the subsets subcutaneously in a mouse model. MATERIALS AND METHODS: Cell suspensions containing cultured human epidermal cells and dermal fibroblasts from a single donor mixed with lymphoid cell subsets positively selected using the FACSVantage cell sorting instrument and/or MACS cell isolation kits from unrelated individuals were injected into immunodeficient mice. This model is known to generate human skin with histologic findings similar to human graft-vs-host disease. RESULTS: Donor T-cell subsets CD4(+) and CD8(+) plus either host or donor CD14(+) cells were necessary to cause acute cutaneous graft-vs-host disease. Although graft-vs-host disease can result from recognition of class I antigens expressed on human cutaneous cells by donor peripheral blood mononuclear cells, additional recognition of class II antigens expressed on host mononuclear cells resulted in more severe histologic manifestations. Dendritic cells that differentiated from donor and host monocytes also showed competent accessory cell function in this system. CONCLUSIONS: Based on this model, human cutaneous graft-vs-host disease was caused by donor CD4(+) cells and CD8(+) cells activated through recognition of host antigens, including class I and class II antigens presented by either donor or host CD14(+) cells or dendritic cells.

Animals↗

Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.

Bone Marrow Transplantation↗

Absence of a CD34- hematopoietic precursor population in recipients of CD34+ stem cell transplantation.

The purified CD34(+) cell fraction has been used for hematopoietic stem cell transplantation since they were demonstrated to have long-term reconstituting ability. Therefore, the potential effects of CD34(-) stem cells on the clinical course have been a major concern in recipients of CD34(+)-selected transplantation. To address this concern, we used an in vitro assay to determine whether transplant recipients have CD34(-)precursor population. Lin(-)CD34(-) cells were isolated from bone marrow cells in 11 transplant recipients including four CD34-selected transplantations, six standard bone marrow transplantations, and one T cell-depleted marrow transplantation. The frequency of the Lin(-)CD34(-) population in four CD34-enriched transplantation recipients was not different from those of normal donors or recipients of other modes of transplantation: 0.96 +/- 1.01% (mean +/- s.d., n = 4), 0.45 +/- 0.16% (n = 6), and 0.66 +/- 0.59% (n = 7), respectively. However, the Lin(-)CD34(-)population obtained from the recipients of CD34-enriched transplantation acquired neither CD34 expression nor colony-forming activity after 7 days of culture, whereas the cells from all the normal individuals and standard BMT recipients were able to differentiate into CD34(+) cells accompanied by the emergence of colony-forming activity.We conclude that recipients of CD34-enriched transplantation appear to have defects in their CD34(-) precursor population. The clinical significance of these defects will be determined in a life-long follow-up of these patients.

Adolescent↗

Final height and growth hormone secretion after bone marrow transplantation in children.

Growth hormone (GH) deficiency has been regarded as a principal determinant for growth failure following bone marrow transplantation (BMT). We herein analyzed final height and GH secretion in the patients who received BMT during childhood. The study on final height in 30 patients (23 males; 19 with malignant disease) who underwent BMT before or at the onset of puberty showed the following findings: (1) Final height SD score (SDS) significantly decreased compared to pretreatment height SDS. (2) Patients who underwent BMT before the age of 10 years showed significantly greater reduction in height SDS compared to those who received after the age of 10 years. (3) The type of disease or a difference in preconditioning regimen did not influence the outcome of growth. (4) No patient showed GH deficiency. The study on GH secretion included 71 patients who had been followed for more than 5 years and who underwent insulin tolerance test more than twice following BMT. Thirteen patients experienced poor GH response at least once. Two of these patients had poor GH response repeatedly. In conclusion, children who undergo BMT at younger age have a higher risk of growth failure, and GH deficiency is not a major contributing factor for growth impairment following BMT.

Adolescent↗

Differentiation of mouse hepatitis viruses in animal facilities in Japan by use of nucleotide analysis of the nucleocapsid gene.

The nucleotide sequences of the coding region of the nucleocapsid (N) gene of 12 mouse hepatitis virus (MHV) strains recently found in animal facilities in Japan were analyzed. Nucleotide sequencing was performed directly on polymerase chain reaction (PCR) products amplified by reverse transcription (RT) and polymerase chain reaction (RT-PCR) analysis from fecal samples or isolated viruses. Phylogenetic analysis of these MHV strains along with those reported previously indicated that sequence analysis of the N gene was a useful tool for differentiation of MHV strains,although most MHV strains in Japanese facilities were phylogenetically close. Results suggested that interchange of mice infected with MHV among facilities provided opportunities of introduction of MHV into otherwise MHV-free facilities and that the source of MHV infection could be traced by use of nucleotide analysis of the N gene.

Animals↗

The IVS4 + 4 A to T mutation of the fanconi anemia gene FANCC is not associated with a severe phenotype in Japanese patients.

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and a susceptibility to leukemia. There are at least 8 complementation groups (A through H). Extensive analyses of the FA group C gene FANCC in Western countries revealed that 10% to 15% of FA patients have mutations of this gene. The most common mutation is IVS4 + 4 A to T (IVS4), a splice mutation in intron 4, which has been found only in patients of Ashkenazi Jewish ancestry. When we screened 29 Japanese patients (20 unrelated patients and 4 families) using polymerase chain reaction-single strand conformation polymorphism, we found 8 unrelated patients homozygous for IVS4. This is apparently the first non-Ashkenazi-Jewish population for whom this mutation has been detected. The Ashkenazi Jewish patients homozygous for IVS4 have a severe phenotype, in comparison with other FA patients. Our analyses of Japanese patients indicate no significant difference between IVS4 homozygotes and other patients with regard to severity of a clinical phenotype. Thus, ethnic background may have a significant effect on a clinical phenotype in FA patients carrying the same mutation. (Blood. 2000;95:1493-1498)

Adolescent↗

Unique N-linked glycosylation of murine coronavirus MHV-2 membrane protein at the conserved O-linked glycosylation site.

The membrane (M) proteins of murine coronavirus (MHV) strains have been reported to contain only O-linked oligosaccharides. The predicted O-glycosylation site consisting of four amino acid residues of Ser-Ser-Thr-Thr is located immediately adjacent to the initiator Met and is well conserved among MHV strains investigated so far. We analyzed the nucleotide sequence of a highly virulent strain MHV-2 M-coding region and demonstrated that MHV-2 had a unique amino acid, Asn, at position 2 at the conserved O-glycosylation site. We also demonstrated that this substitution added N-linked glycans to MHV-2 M protein resulting in increment of molecular mass of MHV-2 M protein compared with JHM strain having only O-linked glycans.

Amino Acid Sequence↗

Sequence analysis of major structural proteins of newly isolated mouse hepatitis virus.

We have isolated the virus from a fecal pellet in the colon of a BALB/c mouse with X-linked immunodeficiency (xid) housed in a room in which there has recently been an epidemic due to mouse hepatitis virus (MHV) and designated it as the MHV-TY strain. Sequence analysis of the MHV-TY strain was performed on major structural, spike (S), membrane (M) and nucleocapsid (N), proteins directly from PCR products. The comparison of nucleotide sequences of MHV-TY with other strains investigated so far revealed that all three structural proteins of the TY strain had some unique amino acid sequences among MHV strains which can be used as markers of this strain.

Amino Acid Sequence↗

An in vivo model of human skin acute graft-versus-host disease: transplantation of cultured human epidermal cells and dermal fibroblasts with human lymphocytes into SCID mice.

The ability of mixed epidermal cell-lymphocyte reactions to detect allogeneic reactivities in an in vivo model was investigated by developing an in vivo model of acute graft-versus-host disease (GVHD), using SCID mice with a C.B-17 background in which human skin structures were generated by transplantation of cultured human epidermal cells (HEC) with dermal fibroblasts (HDFC). Suspensions containing cultured HEC and HDFC from a single donor were mixed with autologous peripheral blood mononuclear cells (PBMNC) or with PBMNC from unrelated individuals, and were injected into the flanks of C.B-17-SCID mice. Ten and 21 days after injection, subcutaneous nodules generated in the mice were examined histologically and immunohistochemically. Cystic structures developing after injection of HEC and HDFC without human PBMNC showed normal epidermislike tissue. Human skin generated in SCID mice injected with HEC and HDFC with auto-PBMNC showed no graft-versus-host reaction (GVHR) histologically, whereas those mice injected with PBMNC from siblings that shared an HLA haplotype showed mild GVHR. Human skin in SCID mice injected with HEC and HDFC with histoincompatible unrelated PBMNC showed moderate to severe GVHR. The severity of GVHR paralleled the dose of unrelated PBMNC, and GVHR was prevented by peroral treatment with cyclosporine A. Immunohistochemically, inflammatory cells infiltrating human cutaneous tissue formed in the SCID mice were stained by an anti-human CD45RO antibody that reacts with human T cells but not with murine lymphocytes, and most T cells were stained by an anti-human CD8 antibody recognizing HLA class I antigens. These findings are similar to those in clinical skin graft-versus host disease (GVHD) observed in patients undergoing allogeneic bone marrow transplantation. This experimental system should be useful as an in vivo model of human skin GVHD.

Animals↗

Role of interleukin-12 in the development of acute graft-versus-host disease in bone marrow transplant patients.

Interleukin-12 (IL-12) is a crucial cytokine regulating cell-mediated immunity, and may contribute to the development of graft-versus-host disease (GVHD). We investigated serum IL-12 concentrations, interferon gamma (IFN-gamma) production by peripheral blood lymphocytes (PBL) from allogeneic stem cell recipients after IL-12 plus anti-CD3 monoclonal antibody (mAb) stimulation. We also investigated IL-12 production by peripheral macrophages (Mphi) after lipopolysaccharide (LPS) stimulation from allogeneic stem cell recipients and patients receiving donor leukocyte transfusions (DLT) for treatment or prophylaxis of leukemia relapse and Epstein-Barr virus (EBV) lymphoproliferative disease (LPD). PBL from acute GVHD patients produced high IFN-gamma levels after IL-12 plus anti-CD3 mAb stimulation, whereas PBL from patients without acute GVHD produced low levels of IFN-gamma. However, serum IL-12 concentrations were low in both groups. Peripheral Mphi IL-12 production increased in patients who developed acute GVHD compared to patients without acute GVHD. Five patients receiving DLT for treatment or prophylaxis of leukemia relapse developed acute GVHD. IFN-gamma production by PBL stimulated by IL-12 plus anti-CD3 mAb increased, while IL-12 production by peripheral Mphi stimulated by LPS was very high after the development of acute GVHD. However, serum IL-12 concentration remained low. Three patients receiving DLT for EBV-LPD did not develop acute GVHD with no increase of IFN-gamma and IL-12 production. These results indicate that IL-12 may play an important role in the development of acute GVHD after allogeneic stem cell grafting or DLT, and increased IL-12 production by Mphi occurs with various stimuli, including LPS.

Acute Disease↗

Ovarian function after bone marrow transplantation performed before menarche.

AIM: To examine the long term effect of bone marrow transplantation (BMT) on ovarian function in girls. METHODS: Eighteen girls who underwent BMT before menarche, had been disease free for more than six years, and were over 14 years of age at the time of study were investigated. The preparative regimen consisted of irradiation and chemotherapy. The occurrence of menarche and changes in basal serum follicle stimulating hormone (FSH) concentrations were studied. RESULTS: Twelve patients achieved menarche at a median age of 12.8 years. Age at transplant was significantly younger in patients who achieved menarche than in those who did not (mean (SD), 7.2 (0.5) v 11.1 (1.7) years). Basal FSH began to rise to menopausal concentrations after 10 years of age, and the girls who did not experience menarche had a sustained rise in FSH concentrations. Among those with raised FSH concentrations, five girls experienced menarche while serum FSH values were decreasing and four achieved menarche while FSH remained raised. CONCLUSIONS: The high incidence of menarche suggests a favourable outcome of ovarian function in girls who undergo BMT at a young age.

Adolescent↗

11p15 translocations involving the NUP98 gene in childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome.

In a survey of childhood therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) in Japan, we found 11p15 translocations in 5 (6%) of 81 children with t-AML/MDS. t(11;17)(p15;q21), t(11;12)(p15;q13), t(7;11)(p15;p15), inv(11)(p15q22), and add(11)(p15) were each found in one patient. Southern blotting and/or RT-PCR analyses revealed rearrangements of the NUP98 gene in tumor samples of all five patients. Rearrangements of DDX10 were detected in t-AML/MDS cells with inv(11), and rearrangements of HOXA9 were detected in t-AML cells with t(7;11). The 17q21 breakpoint of t(11;17) and the 12q13 breakpoint of t(11;12)(p15;q13) coincided with the loci of the HOXB and HOXC gene families, respectively. Therefore, it is reasonable to speculate that one of the HOXB genes and one of the HOXC genes were fused to NUP98 by t(11;17) and t(11;12), respectively, in t-AML/MDS cells. We propose that NUP98 may be a target gene for t-AML/MDS, and that t-AML/MDS with a fusion of NUP98 and HOX or DDX10 genes may be more frequent in children than in patients of other age groups.

Acute Disease↗

Requirement of proteolytic cleavage of the murine coronavirus MHV-2 spike protein for fusion activity.

The spike (S) protein of a non-fusogenic murine coronavirus, MHV-2, was compared to that of a variant, MHV-2f, with fusion activity. Two amino acids differed between The S proteins of these viruses; one was located in the signal sequence (amino acid 12) and the other in the putative cleavage site (amino acid 757). To determine which one of these amino acid changes is important for the alteration of fusogenicity, chimeric S proteins between MHV-2 and -2f were constructed and expressed in DBT cells by a vaccinia virus expression system. The results revealed that one amino acid change (Ser to Arg) at position 757 is responsible for the acquisition of fusogenicity of the MHV-2f S protein. This change also altered the susceptibility to proteolytic cleavage of the MHV-2 S protein which was originally uncleavable. We concluded that the non-fusogenic activity of MHV-2 results from the lack of cleavage of its S protein.

Animals↗

Myeloproliferative disease in a calf.

A myeloproliferative disease was found in a 128-day-old Holstein female calf. The tumour consisted chiefly of primitive cells, and more mature cells, many of which were positive for haemoglobin, were admixed with them. Binucleated cells at various stages of maturation were occasionally seen, and siderosomes were confirmed in both primitive cells and more mature cells by electron microscopy. The primitive cells resembled proerythroblasts, and this tumour, thought to be an acute type neoplasm of the erythroid system, was distinguishable from chronic erythremic myelosis and polycythemia vera.

Animals↗