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M Migita

Publications and source records attributed to M Migita.

At least 19 recordsLinked to original sources
PubMed2003

Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells.

AIMS/HYPOTHESIS: Bone marrow cells contain at least two distinct types of stem cells which are haematopoietic stem cells and mesenchymal stem cells. Both cells have the ability to differentiate into a variety of cell types derived from all three germ layers. Thus, bone marrow stem cells could possibly be used to generate new pancreatic beta cells for the treatment of diabetes. In this study, we investigated the feasibility of bone marrow-derived cells to differentiate into beta cells in pancreas. METHODS: Using green fluorescent protein transgenic mice as donors, the distribution of haematogenous cells in the pancreas was studied after bone marrow transplantation. RESULTS: In the pancreas of green fluorescent protein chimeric mice, green fluorescent protein-positive cells were found in the islets, but none of these cells expressed insulin. Previous data has suggested that tissue injury can recruit haematopoietic stem cells or their progeny to a non-haematopietic cell fate. Therefore, low-dose streptozotocin (30 or 50 mg/kg on five consecutive days) was injected into the mice 5 weeks after bone marrow transplantation, but no green fluorescent protein-positive cells expressing insulin were seen in the islets or around the ducts of the pancreas. CONCLUSIONS/INTERPRETATION: Our data suggests that bone marrow-derived cells are a distinct cell population from islet cells and that transdifferentiation from bone marrow-derived cells to pancreatic beta cells is rarely observed.

Animals↗
PubMed2003

Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia.

Brain ischemia induces a marked response of resident microglia and hematopoietic cells including monocytes/macrophages. The present study was designed to assess the distribution of microglia/macrophages in cerebral ischemia using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). At 24 h after middle cerebral artery occlusion (MCAO), many round-shaped EGFP-positive cells migrated to the ischemic core and peri-infarct area. At 48-72 h after MCAO, irregular round- or oval-shaped EGFP/ionized calcium-binding adapter molecule 1 (Iba 1)-positive cells increased in the transition zone, while many amoeboid-shaped or large-cell-body EGFP/Iba 1-positive cells were increased in number in the innermost area of ischemia. At 7 days after MCAO, many process-bearing ramified shaped EGFP/Iba 1-positive cells were detected in the transition to the peri-infarct area, while phagocytic cells were distributed in the transition to the core area of the infarction. The distribution of these morphologically variable EGFP/Iba 1-positive cells was similar up to 14 days from MCAO. The present study directly showed the migration and distribution of bone marrow-derived monocytes/macrophages and the relationship between resident microglia and infiltrated hematogenous element in ischemic mouse brain. It is important to study the distribution of intrinsic and extrinsic microglia/macrophage in ischemic brain, since such findings may allow the design of appropriate gene-delivery system using exogenous microglia/macrophages to the ischemic brain area.

Animals↗
PubMed2003

Congenital fibrosarcoma of the jejunum in a premature infant with meconium peritonitis.

We report an unusual case of perforation of a congenital fibrosarcoma of the jejunum in utero and secondary meconium peritonitis. Prenatal ultrasound showed polyhydramnios and fetal ascites from 25 gestational weeks in the absence of other fetal congenital anomalies. A 2200 g baby girl was born at 34 weeks gestation, presenting with severe generalized edema and respiratory distress immediately after birth. Plain radiography revealed progressive abdominal distension and pneumoperitoneum. The baby subsequently underwent surgery at the age of one day. A perforation of the upper jejunum, which had resulted in meconium peritonitis, was discovered intraoperatively and the perforated section of the intestine was resected and anastomosed successfully. The postoperative course was uneventful. Pathological examination confirmed that the perforation was caused by rupture of a congenital fibrosarcoma originating from the jejunum. Rupture of a malignant tumor is an extremely rare cause of peritonitis in the fetus and neonate.

Female↗
PubMed2001

An AAV-derived Apaf-1 dominant negative inhibitor prevents MPTP toxicity as antiapoptotic gene therapy for Parkinson's disease.

Adeno-associated virus (AAV) vector delivery of an Apaf-1-dominant negative inhibitor was tested for its antiapoptotic effect on degenerating nigrostriatal neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. The wild-type caspase recruitment domain of Apaf-1 was used as a dominant negative inhibitor of Apaf-1 (rAAV-Apaf-1-DN-EGFP). An AAV virus vector was used to deliver it into the striatum of C57 black mice, and the animals were treated with MPTP. The number of tyrosine hydroxylase-positive neurons in the substantia nigra was not changed on the rAAV-Apaf-1-DN-EGFP injected side compared with the noninjected side. We also examined the effect of a caspase 1 C285G mutant as a dominant negative inhibitor of caspase 1 (rAAV-caspase-1-DN-EGFP) in the same model. However, there was no difference in the number of tyrosine hydroxylase-positive neurons between the rAAV-caspase-1-DN-EGFP injected side and the noninjected side. These results indicate that delivery of Apaf-1-DN by using an AAV vector system can prevent nigrostriatal degeneration in MPTP mice, suggesting that it could be a promising therapeutic strategy for patients with Parkinson's disease. The major mechanism of dopaminergic neuronal death triggered by MPTP seems to be the mitochondrial apoptotic pathway.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Differentiation of transplanted bone marrow cells in the adult mouse brain.

BACKGROUND: Bone marrow transplantation is reportedly effective in preventing the progression of neurological deterioration in lysosomal storage disorders, although the mechanism underlying the therapeutic effects remains to be elucidated. Recent research on stem cell biology suggests that bone marrow cells contain nonhematopoietic stem cells, including brain precursor cells. To evaluate the contribution of bone marrow cells as carriers for cell and gene therapy of neurological disorders, we studied the fate of transplanted bone marrow cells in the adult mouse brain. METHODS: Bone marrow cells were genetically marked with a retroviral vector containing the green fluorescence protein gene and then transplanted into irradiated mice by either systemic infusion or direct injection. To identify cell types, brain sections were stained with specific antibodies against neuronal cell markers-neuron specific enolase for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1 (Iba1) for microglia-and then examined under a confocal microscope. RESULTS: Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but none of the other brain cell markers. Conversely, 12 weeks after direct injection, transplanted cells were stained with antibodies against GFAP, CAII, and Iba1. CONCLUSIONS: Bone marrow contains cells capable of differentiating into oligodendrocytes, astrocytes, and microglia when exposed to the brain microenvironment. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for lysosomal disorders with neurological symptoms.

Animals↗
PubMed2001

Two cases of influenza with impaired ocular movement.

Complications of influenza include respiratory disorders (pneumonia, bronchitis and croup) and occasionally myocarditis, myositis, encephalitis, encephalopathy and Reye's syndrome, which may be life-threatening and cause various sequelae. We report two patients who developed unusual complications of influenza infection: one had ptosis and impaired ocular movement, and the other suffered from Guillain-Barré syndrome with paralysis of the extraocular muscles.

Blepharoptosis↗
PubMed2001

Usefulness of bronchoalveolar lavage for the diagnosis and treatment of refractory pneumonia in a patient with Kostmann syndrome, a severe congenital neutropenia.

UNLABELLED: An 11-year-old girl with Kostmann syndrome developed refractory pneumonia. Culture of oral discharge, throat-swab specimens, and blood could not identity the causative organism, and systemic antimicrobial therapy failed to achieve improvement. We then performed diagnostic bronchoalveolar lavage (BAL) and culture of BAL fluid (BALF) yielded Pseudomonas aeruginosa. Therapeutic BAL using gentamicin produced a striking improvement of her pneumonia. CONCLUSION: In immunocompromised children with pneumonia, BAL helps to identify the causative organism. If the patient is unresponsive to systemic antimicrobial therapy, BAL using antimicrobial agents is also worth trying.

Bronchoalveolar Lavage↗
PubMed2000

Temporal criterion for behavior: orientation of the young Japanese flounder Paralichthys olivaceus.

When considering a behavioral pattern as a specific type of mechanism, an inherent problem is that it is difficult to determine to what extent the mechanism is programmed to behave selectively in individual situations. To probe this question further, we investigated the orientation of the body axis of the young Japanese flounder Paralichthys olivaceus. The pattern of the substrate and the orientation of neighboring fish were recognized as the determining factors for orientation in P. olivaceus. It was expected, therefore, that a group of individuals would exhibit a definite orientation pattern with respect to the striped pattern. However, the global orientation patterns on the striped substrate based on ten individuals could be classified into two categories: perpendicular and cross to the stripe pattern. This suggests that the substrate pattern and the surrounding individuals operated as distinct temporal criteria as stimuli for orientation. Analysis based on the local and global viewpoints reveals the temporality quantitatively.

Journal Article↗
PubMed2000

Transduction of fibroblasts and CD34+ progenitors using a selectable retroviral vector containing cDNAs encoding arylsulfatase A and CD24.

Metachromatic leukodystrophy (MLD) is an autosomal recessive, inherited, lysosomal storage disease caused by a deficiency in arylsulfatase A (ASA). This disease is characterized by progressive demyelination leading to severe neurological symptoms. Allogenic bone marrow transplantation at an early stage of clinical course is only effective treatment currently available. Accordingly the corrective transfer of the ASA gene into hematopoietic stem cells is thought to be an important option for curative treatment for MLD. We have recently developed a selectable vector system based on ex vivo sorting of transduced cells (Migita et al. 1995). In this study, we applied this selectable system for development of MLD gene therapy. A bicistronic retroviral vector containing ASA cDNA and CD24 cDNA as a selectable marker gene was constructed. This vector was successfully transduced on fibroblasts from MLD patients, ASA activity was increased 7-fold compared to normal untransduced cells. PCR Southern analysis of hematopoietic colonies showed that transduction efficiency of CD34+ cells was 11-22%. However, after fluorescence-activated cell sorting using anti-CD24 antibody, 75-100% of colonies became vector positive. The sorting raised the ASA activity several fold compared to untransduced CD34+ progenitors. These results suggest that a bicistronic ASA vector containing a CD24 selectable marker could be a useful component of gene therapy for MLD.

Antigens, CD↗
PubMed1999

Learning process by goldfish and its use of a local site as a map.

The issue we address is whether an animal knows or understands the significance of learning. We constructed an animal's own conceptualization via resolving a paradox underlying the process of learning. We found a kind of self-similar pattern in the behavior of goldfish resolving a paradoxical experimental problem. The pattern can be considered as a solution to the paradox in the experiment. An animal's own learning should be revised through solving paradoxes. The dualism of mechanistic thinking and vitalism can thus be avoided.

Animals↗
PubMed1998

A simple and efficient purification of transduced cells by using green fluorescent protein gene as a selection marker.

BACKGROUND: Simple and efficient method for the selection of transduced cells would greatly facilitate the clinical utilization of retrovirus vectors. We developed a therapeutic bicistronic retrovirus vector for Gaucher disease, MFG-GC-GFP, which contains the human glucocerebrosidase (GC) gene and the green fluorescent protein (GFP) gene of the jellyfish Aequorea victoria as a vital selection marker, and investigated its applicability as gene therapy for Gaucher disease. METHODS AND RESULTS: A packaging cell line, GP + envAM12, was transfected with MFG-GC-GFP and, thus, produced a high titer recombinant virus (1.0 x 10(6) c.f.u./mL) in the culture supernatant. The expression level of GFP was correlated with the virus production in cells. The recombinant virus infected skin fibroblasts from a Gaucher patient and a sorted fraction of the cells expressing GFP by flow cytometry exhibited almost a six-fold higher activity of GC than normal fibroblasts. CONCLUSIONS: These data indicate that MFG-GC-GFP enables the one-step purification of a transduced fraction of target cells and is, therefore, considered to be a useful therapeutic vector for the experimental gene therapy of Gaucher disease.

Animals↗
PubMed1998

[Hemophilia B].

Explore the source record for details and available documents.

Animals↗
PubMed1997

Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by alpha-tocopherol supplementation.

UNLABELLED: Natural Killer (NK) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by 51Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral alpha-tocopherol (alpha-Toc) supplementation (100 mg/day), NK cell activity had normalised. When alpha-Toc supplementation was interrupted for 16 weeks. NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16+ CD 56- fraction, which has the most potent NK cell activity. Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of alpha-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. CONCLUSION: These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16+ CD56- NK cells and that this abnormality is reversible with alpha-Toc supplementation.

Adolescent↗
PubMed1997

Mutation of RET proto-oncogene in Japanese patients with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma.

To determine whether patients with medullary thyroid carcinoma (MTC) develop other endocrine neoplasms or their relatives develop MTC, we investigated the mutations in the RET proto-oncogene in patients with multiple endocrine neoplasia type 2B (MEN 2B, N = 1) and sporadic MTC (N = 6). DNA from MTC tissue and the peripheral blood was screened by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis of exons 10 and 11. PCR products of exons 13 and 16 were also analyzed by AluI and FokI restriction enzyme digestion methods, respectively, and then sequenced. We did not find structural abnormalities in exon 10 or 11, or at codon 768 in exon 13, but a mutation at codon 918, ATG to ACG, was found in the peripheral blood and the MTC tissue from a patient with MEN 2B. The same mutation was also found in tumor tissue from 2 of 6 patients with sporadic MTC, but not in their peripheral blood.

Adult↗
PubMed1996

A bicistronic therapeutic retroviral vector enables sorting of transduced CD34+ cells and corrects the enzyme deficiency in cells from Gaucher patients.

Corrective gene transfer for therapeutic intervention in metabolic and hematopoietic disorders has been hampered by the relatively inefficient transduction of human hematopoietic stem cells. To overcome this, a bicistronic recombinant retrovirus has been generated that delivers both a therapeutic glucocerebrosidase (GC) cDNA for the treatment of Gaucher disease, and a small murine cell surface antigen (heat-stable antigen [HSA]) as a selectable marker. An amphotropic retroviral-producing cell clone was created, and filtered supernatant was used to transduce NIH 3T3 cells. Sorting of transduced cells by flow cytometry enabled separation into populations based on cell surface fluorescence intensity derived from the expressed HSA. Significant increases in GC enzyme activity were seen for the transduced and especially the transduced and sorted cells. Similarly, increases in GC specific activity were seen in transduced and sorted skin fibroblasts from a patient with Gaucher disease. To streamline future transfer and sorting protocols for hematopoietic cells, transformed B-cell lines from Gaucher patients were created. Type I B cells were transduced and sorted, and large increases in GC specific activity occurred with concomitant increases in integrated retroviral copy numbers. In addition, toward the goal of using this selectable approach for corrective gene transfer to bone marrow stem cells, CD34+ cells were isolated from normal BM donors, transduced, and sorted based on cell surface expression of HSA. Proviral DNA was detected in approximately 40% of clonogenic progenitor colonies derived from unsorted, transduced CD34+ cells, demonstrating the high titer of the vector. However, after sorting, 100% of the colonies had the corrective GC cDNA, demonstrating the efficiency of this selective system for human hematopoietic progenitors. It is expected that strategies based on this approach will allow sorting of transduced cells of many types before implantation of transduced cells to animals or patients. This vector system may also be used to simplify manipulations and studies on retroviral-mediated gene delivery in vitro and for in vivo models.

3T3 Cells↗
PubMed1996

Tree and loop as moments for measurement.

Biologically motivated computing presents us with a measurement process in science. It triggers an epistemological shift from state-oriented physics to measurement-oriented physics, in which we can find a parallelism with Wittgenstein's shift from rule following to a language game. We argue here that an approximation or computing process can be viewed as a language game and propose an idea of proto-computing which is metaphorically formalized through disequilibration between tree- and loop-program, as a model for measurement-oriented computing.

Computer Simulation↗