Biomedical subjects

Masayoshi Minegishi

Publications and source records attributed to Masayoshi Minegishi.

8 recordsLinked to original sources

PubMed2006

A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient.

Wiskott-Aldrich syndrome (WAS) is caused by mutations in the gene encoding WAS protein (WASP ). Recently, somatic mosaicism caused by reversions or second-site mutations has been reported in some inherited disorders including WAS. In this article, we describe somatic mosaicism in a 15-year-old WAS patient due to a second-hit mutation in the initiation codon. The patient originally had a single-base deletion (c.11delG; p.G4fsX40) in the WAS (WASP) gene, which resulted in a frameshift and abrogated protein expression. Subsequently, a fraction of T and natural killer (NK) cells expressed a smaller WASP, which binds to its cellular partner WASP-interacting protein (WIP). The T and NK cells were found to have an additional mutation in the initiation codon (c.1A>T; p.M1_P5del). The results strongly suggest that the smaller WASP is translated from the second ATG downstream of the original mutation, and not only T cells but also NK cells carrying the second mutation acquired a growth advantage over WASP negative counterparts. To our knowledge, this is the first report describing somatic mosaicism due to a second-site mutation in the initiation codon of any inherited disorders.

Adolescent↗

PubMed2006

Predictive value of the original content of CD34(+) cells for enrichment of hematopoietic progenitor cells from bone marrow harvests by the apheresis procedure.

We retrospectively investigated the feasibility of the apheresis procedure for red blood cell (RBC) reduction with a closed-bag system. We also sought to determine the optimal processing volume for the maximal recovery of hematopoietic progenitor cells (HPC). Twelve bone marrow (BM) harvests were processed for major ABO-incompatible allogeneic transplantation and one BM harvest was processed for autologous transplantation. The processing was performed through seven apheresis cycles with a two-bag system using COBE Spectra Version 6.1. The mean recovery rates were compared in the products after four cycles and seven cycles of BM processing. Mean cell recovery rates were 79.2% (67.6-97.5%) and 87.3% (68.9-111.9%) for the mononuclear cells (MNC) and 84.5% (69.4-109.5%) and 92.0% (79.0-107.7%) for the CD34(+) cells after four and seven cycles, respectively. A mean of 96.3% (93.0-98.1%) of the RBCs were finally removed. The yield of CD34(+) cells after seven cycles of processing (median: 10.35 x 10(7) cells) was 7.9% greater than that after four cycles of processing (median: 9.65 x 10(7) cells), exhibiting a less-than-significant enhancement in yield. The CD34(+) cell contents recovered in the concentrates up to four cycles (r = 0.989) and up to seven cycles (r = 0.993) were strongly correlated with the original content of the CD34(+) cells. Engraftment was obtained in all patients except one patient infused with purified CD34(+) cells. This latter result confirmed the hematopoietic potential of the cell populations recovered. Granulocyte recovery (defined as an absolute neutrophil cell count > or = 500/microL for a period of three consecutive days) ranged from 8 to 25 days (median: 16 days) post-transplantation. No hemolytic reaction was observed in any of the patients. Our results confirmed the efficacy of BM processing cycles with the COBE Spectra device. However, we could not conclude that the large-volume apheresis for BM processing significantly enhanced the yields of HPC. The final recovery of CD34(+) cells after processing could be predicted from the CD34(+) cell content of the original collected marrow.

ABO Blood-Group System↗

PubMed2006

The first infant case with hepatosplenic gammadelta T-cell lymphoma after acute disseminated encephalomyelitis (ADEM)-like exacerbation.

We report the first infant case with hepatosplenic gammadelta T-cell lymphoma after recurrent acute disseminated encephalomyelitis-like, which were rapidly resolved with steroid pulse therapy. The patient had a history of recurrent bronchitis, intractable diarrhea, and failure to thrive since 4 months of age. Immunologic analysis revealed higher percentage of circulating gammadelta T-cells with markedly reduced numbers of CD3TCRalphabetaCD8 T-cells. The patient developed gammadelta T-cell lymphoma at the age of 15 months. Clinical course of the patient suggests the importance of immunological background for the development of hepatosplenic gammadelta T-cell lymphoma.

Encephalomyelitis, Acute Disseminated↗

PubMed2006

Prophylaxis of mucosal toxicity by oral propantheline and cryotherapy in children with malignancies undergoing myeloablative chemo-radiotherapy.

Mucosal toxicity is an incapacitating complication of intensive chemo-radiotherapy for children with malignant disorders, and is physically and psychologically distressful. It is therefore important to minimize mucosal toxicity in those patients. In this report, the effects of the combined prophylaxis of oral cooling (cryotherapy) and administration of propantheline, an anticholinergic drug, were studied in patients (aged 2-16 year) with acute leukemias or solid tumors, who underwent myeloablative chemo-radiotherapy and autologous peripheral blood stem cell rescue from 1993 to 1997. Patients were pretreated with the combined prophylaxis (n = 12) or single prophylaxis (n = 5), or left untreated (n = 7). The combined prophylaxis significantly reduced the severe mucositis (combined, 8.3%; single, 20.0%; and untreated, 42.9%) and severe diarrhea (combined, 16.7%; single, 60.0%; and untreated, 57.1%). Moreover, the combined prophylaxis tended to shorten the periods of febrile episodes defined as temperature > 38 degrees C (combined, 3.8 days; single, 4.6 days; and untreated, 5.6 days). Therefore, the combination of propantheline and oral cryotherapy may be feasible and effective for reduction of mucosal toxicity in patients with malignancy who undergo high-dose chemotherapy.

Administration, Oral↗

PubMed2005

Evaluation of hematological reconstitution potential of autologous peripheral blood progenitor cells cryopreserved by a simple controlled-rate freezing method.

A novel and simple procedure for the controlled-rate cryopreservation of peripheral blood progenitor cells (PBPCs) was introduced. A freezing bag housed in a protective aluminum canister was placed on top of a styrene foam box in the -85 degrees C electric freezer. A second set of samples was kept in cryotubes placed in a double styrene foam box in the same electric freezer. Measurement of the freezing rate in the PB bags and cryotubes demonstrated that this simple method for PBPC cryopreservation provided optimal conditions for both large-scale and small-scale cryopreservation. Within several days after autologous peripheral blood stem cell transplantation, we thawed the cells in the small sample tubes and evaluated the cell viability, the cell recovery, and the recovery rates of hematopoietic progenitor cells (HPCs), such as CD34+ cells and colony-forming unit-granulocyte/macrophage (CFU-GM) colonies. The median duration of cryopreservation was 59 days (range, 14-365 days). According to our analysis, infusions of more than 2 x 10(6) CD34+ cells/kg body weight and 0.5 x 10(6) CFU-GM colonies/kg body weight after thawing had favorable influences on the neutrophil engraftment. We have therefore established a simple freezing method for cryopreservation of human PBPCs, which ensures the transplantability of hematopoietic progenitors even after thawing. In vitro HPC assay after thawing is important to evaluate the quality of cryopreservation procedures.

Adolescent↗

PubMed2004

Fludarabine- and cyclophosphamide-based nonmyeloablative conditioning regimen for transplantation of chronic granulomatous disease: possible correlation with prolonged pure red cell aplasia.

An 18-year-old patient with chronic granulomatous disease who had had at least 2 episodes of life-threatening Aspergillus pneumonia was treated with nonmyeloablative allogeneic stem cell transplantation (NSCT) from an HLA-identical and major ABO-incompatible sibling. The conditioning regimen consisted of cyclophosphamide at a dose of 60 mg/kg (days -5, -4) and fludarabine at a dose of 30 mg/m2 (days -5, -4, -3, -2, -1). Full donor T-cell engraftment was attained on day 28, and full myeloid engraftment was established by day 150 after tacrolimus withdrawal. The bacteriocidal activity of neutrophils, as indicated by flow cytometry with the use of a dichlorofluorescein diacetate oxidation assay, remained low until 150 days after transplantation, but no infection was detected, a finding that suggests mixed chimerism of granulocytes controlled infection. Graft-versus-host disease and severe regimen-related toxicity (grade 3 or greater) were not observed. This patient developed prolonged pure red cell aplasia, possibly caused by persistent antidonor isohemagglutinin produced by the residual host B-cells. The aplasia resolved with the combination of erythropoietin, double filtration plasmapheresis, and rituximab. In the setting of major ABO-incompatible NSCT, a fludarabine- and cyclophosphamide-based conditioning regimen may lead to prolonged PRCA.

ABO Blood-Group System↗

PubMed2003

A simple controlled-rate freezing method without a rate-controlled programmed freezer provides optimal conditions for both large-scale and small-scale cryopreservation of umbilical cord blood cells.

BACKGROUND: Umbilical cord blood (CB) is being used as a source of alternative HPCs for transplantation with increasing frequency. The goal of CB banks for unrelated transplantation is to provide good quality-controlled CB units that can be transplanted for HPCs into the largest possible number of patients. STUDY DESIGN AND METHODS: Large CB samples in freezing bags wrapped with insulators and small samples in cryotubes placed into double styrene-foam boxes were cryopreserved at -85 degrees C without a rate-controlled freezing machine, followed by storage in the liquid phase of nitrogen. After thawing these cells, the viability and recovery of cells, as well as the recovery rate of HPCs such as CD34+ cells, CFU-GM, and total CFU were evaluated. RESULTS: Measurement of the freezing rate in CB bags and cryotubes demonstrated that this simple method for cryopreservation of CB cells provided optimal conditions for both large-scale and small-scale cryopreservation. Recovery of CB progenitor cells after cryopreservation was also shown to be potentially acceptable when evaluated with CD34+ cells, CFU-GM, and total CFU. These results were comparable to the method using a rate-controlled programmed freezer. CONCLUSIONS: A simple method for cryopreservation of CB cells without a rate-controlled programmed freezer could provide a sufficient-enough potential for the transplantability of HPCs after thawing.

Blood Banks↗

PubMed2003

The absolute number of peripheral blood CD34+ cells predicts a timing for apheresis and progenitor cell yield in patients with hematologic malignancies and solid tumors.

Retrospective analysis was conducted in 51 autologous peripheral blood progenitor cell (PBPC) collections using the Spectra AutoPBSC System from patients with hematologic malignancies and solid tumors to study the predictive value of CD34+ cell counts in the peripheral blood for the yield of CD34+ cells in the apheresis product. The correlation coefficients for CD34+ cells microL(-1) of peripheral blood with CD34+ cell yield (x 10(6) kg(-1) of body weight and x 10(5) kg(-1) of body weight L(-1) of blood processed) were 0.903 and 0.778 (n=51 collections), respectively. Products collected from patients with CD34+ cell counts below 15 microL(-1) in the peripheral blood contained a median of 0.49 x 10(6) CD34+ cells kg(-1) (range: 0.05-2.55), whereas those with CD34+ cell counts more than 15 microL(-1) contained a median of 3.72 x 10(6) CD34+ cells kg(-1) (range: 1.06-37.57). From these results, a number of at least 15 CD34+ cells microL(-1) in the peripheral blood ensured a minimum yield of 1 x 10(6) CD34+ cells kg(-1) as obtained by a single apheresis procedure. The number of CD34+ cells in the peripheral blood can be used as a good predictor for timing of apheresis and estimating PBPC yield. With regard to our results, apheresis with a possibly poor efficiency should be avoided because the collection procedure is time-consuming and expensive.

Adolescent↗