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Biomedical subjects

S Asano

Publications and source records attributed to S Asano.

At least 55 records · Page 3Linked to original sources
PubMed2001

Prompt and durable hematopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anemia.

We describe here the case of an 8-year-old girl with Fanconi anemia (FA) whose hematopoiesis was successfully restored by unrelated umbilical cord blood (UCB) transplantation. The patient became resistant to androgen therapy, and developed intracranial hemorrhage and dyserythropoiesis. Her hematopoietic recovery after the transplantation was excellent and a complete chimerism has been durably maintained. UCB should be considered as a stem cell source for transplantation when a patient with FA does not have an HLA-identical unaffected sibling donor.

Child, Preschool↗
PubMed2001

Inhibitory effect of interleukin 3 on early development of human B-lymphopoiesis.

Interleukin 3 (IL-3) is known as a stimulator of proliferation and differentiation of non-lymphoid cells, but information about the activity of IL-3 in lymphopoiesis is limited. In the present study, we examined the effect of IL-3 on human B-lymphopoiesis using the co-culture system on a murine stromal cell line, MS-5, with stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). Although a large number of CD45+CD19+ B cells were generated in the co-culture of cord blood CD34+ cells, the addition of IL-3 to the co-culture suppressed the B-cell generation in a dose-dependent manner. In the co-culture, CD34+IL-3 receptor alpha-chain (IL-3Ralpha)+ cells, but not IL-3Ralpha- cells, produced B cells, and IL-3 suppressed the B-cell generation from CD34+IL-3Ralpha+ cells, suggesting that IL-3 exerts an inhibitory effect through the binding to IL-3Ralpha on CD34+ cells. Because the delayed addition of IL-3 and the short-term exposure to IL-3 showed that IL-3 acted as an inhibitor at an early stage of B-cell development from CD34+ cells, before the generation of CD19+ B cells, the effect of IL-3 on the early development of B cells from immature CD34+CD38- cells was examined. Individual colonies, produced from clone-sorted CD34+CD38- cells by SCF, thrombopoietin and a complex of IL-6/soluble IL-6R with or without IL-3, were divided into two fractions and analysed for B-cell potential using co-culture on MS-5 with SCF and G-CSF, and haematopoietic potential using methylcellulose clonal culture. Although some colonies cultured without IL-3 showed both B-cell and haematopoietic potential, all the colonies cultured with IL-3 showed only haematopoietic potential. These results indicate that IL-3 has an inhibitory effect on the B-cell generation from human lymphohaematopoietic progenitor cells.

Animals↗
PubMed2001

Unrelated cord blood transplantation for adult patients with myelodysplastic syndrome-related secondary acute myeloid leukaemia.

Seven adult patients with myelodysplastic syndrome (MDS)-related secondary acute myeloid leukaemia (AML) were treated with total body irradiation (TBI), cytosine arabinoside (Ara-C) and cyclophosphamide (CY), followed by unrelated human leucocyte antigen (HLA)-mismatched cord blood transplantation (CBT). Granulocyte colony-stimulating factor (G-CSF) was infused continuously from 12 h before until the end of Ara-C therapy to enhance the antileukaemia effect of Ara-C. Five patients are alive and free of disease at 7-31 months after transplantation. These preliminary results suggest that adult MDS-related secondary AML patients without suitable related or unrelated bone marrow donors should be considered as candidates for CBT.

Acute Disease↗
PubMed2001

Phosphatidylinositol-specific-phospholipase C cleaves urokinase plasminogen activator receptor from the cell surface and leads to inhibition of pemphigus-IgG-induced acantholysis in DJM-1 cells, a squamous cell carcinoma line.

We showed previously that pemphigus IgG enhanced both the activity of urokinase plasminogen activator (uPA) in cultured cells and the expression of its receptor (uPAR) on uPA-binding keratinocytes. In the present study, to clarify whether uPAR and uPA-activated plasmin are actually involved in the blistering process after pemphigus IgG binding to the cell surface, we examined the effects of the following on uPAR expression and on cell-cell detachment in DJM-1 cells, a squamous cell carcinoma line: (i) phosphatidylinositol-specific phospholipase C (PI-PLC) - which releases uPAR from the membrane surface into the culture medium by cleaving the glycosylphosphatidylinositol anchor thus inhibiting uPAR activity, and (ii) uPA inhibitors (tranexamic acid, aprotinin, p-aminobenzonic acid and dexamethasone). Preincubation with PI-PLC decreased dramatically the pemphigus IgG-induced uPAR expression in a dose-dependent manner, and inhibited pemphigus IgG-induced cell-cell detachment at 10 microg/mL. On the other hand, tranexamic acid (15 mM) inhibited pemphigus IgG-induced cell-cell detachment without reduction of uPAR expression, although aprotinin, p-aminobenzonic acid and dexamethasone failed to alter either of these parameters. Although uPAR expression on the pemphigus IgG-bound cell surface and uPA activation may contribute significantly to the pathogenesis of acantholysis in pemphigus, the mechanisms are complicated and should be defined further.

Acantholysis↗
PubMed2001

Coronin forms a stable dimer through its C-terminal coiled coil region: an implicated role in its localization to cell periphery.

BACKGROUND: Coronin is an actin-binding protein, which contains WD (Trp-Asp) repeats and a coiled-coil motif, and plays a role in regulating organization of the actin cytoskeletal network. Coronin localizes to the cell periphery, is involved in lamellipodium extension, and has an implicated role in cytokinesis, cell motility and phagocytosis. RESULTS: Our experiments with two different tagged forms of Xenopus coronin (Xcoronin) have shown that Xcoronin forms an oligomer. This oligomer complex is stable, resistant to 2.4 M NaCl, 0.6 M KI or 2 M urea. Physiochemical analysis of endogenous Xcoronin and the protein expressed in COS7 cells or in bacteria has revealed that the oligomer complex is an Xcoronin dimer. A C-terminal coiled-coil motif of Xcoronin is necessary and sufficient for the dimerization. Mutations in the coiled-coil motif generated dimerization deficient mutants of Xcoronin. Moreover, these mutant forms of Xcoronin failed to localize to the cell periphery, suggesting that dimerization is important for the proper subcellular localization of Xcoronin. CONCLUSION: Xcoronin forms a stable dimer via its C-terminal coiled-coil region. We propose that coronin dimerization is necessary for its proper subcellular localization and function.

Actins↗
PubMed2001

Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: indications and dose escalation.

To clarify the role of dose escalation of donor leukocyte infusion (DLI) in the treatment of relapsed leukemia after allogeneic bone marrow transplant (BMT), data from 100 patients were collected from 46 facilities in Japan and analyzed with respect to indications and infused cell dose. Complete remission (CR) was achieved in 11 of 12 (91%) patients with relapsed chronic myelogenous leukemia (CML) in the chronic phase, 3 of 11 (27%) with CML in the acute phase, 8 of 21 (38%) with acute myelogenous leukemia (AML), 6 of 23 (25%) with acute lymphoblastic leukemia (ALL), and 5 of 11 (45%) with myelodysplastic syndrome (MDS). The probability of remaining in CR at 3 years was 82% in CML patients in the chronic phase, but 0% in those with CML in the acute phase, 7% in those with AML, 0% with ALL, and 33% with MDS. Acute graft-versus-host disease (GVHD) (> or = 2) developed in 31 of 89 (34%) patients with human leukocyte antigen identical related donors and was fatal for 7 (7%). A leukocyte dose of 1 x 10(7)/kg of recipient body weight with CML in the chronic phase, 3 x 10(7)/kg of recipient body weight with MDS, and 1 x 10(8)/kg of recipient body weight with acute leukemia appeared to be optimal as an initial dose of DLI. However, the minimal dose of leukocyte developing fatal GVHD was 7 x 10(7)/kg of recipient body weight. These suggest that a relatively small dose of DLI ranging from 1 x 10(7)/kg to 5 x 10(7)/kg of recipient body weight should be administered initially then the infused escalating dose 2 or 3 months later in patients with CML in the chronic phase and MDS. However, a large number of leukocytes around 1 x 10(8)/kg are needed to induce graft versus leukemia effects in patients with acute leukemia despite a 7% fatality in GVHD.

Adolescent↗
PubMed2001

Is rabbit CLCA1 related to the basolateral Ca2+ -dependent Cl- channel of gastric parietal cells?

An expression of mRNA coding the calcium-activated Cl- channel-1 (CLCA1) in rabbit gastric parietal cells was examined to verify the possibility that the CLCA1 mediates housekeeping Cl- channels in the basolateral membrane. In whole-cell voltage-clamp experiments of rabbit parietal cells, A23187 (2 microM), a Ca2+ ionophore, activated the basolateral Cl- channels. The partial cDNA fragment of rabbit CLCA1 could be amplified from the total RNA of tracheal epithelium. A Northern blot analysis showed that rabbit CLCA1 mRNA of 3.4 kb is highly expressed in the tracheal epithelium, but not in the gastric parietal cells. Even in a more sensitive detection of rabbit CLCA1 mRNA by RT-PCR, no signal could be observed in the gastric parietal cells. These results suggest that the CLCA1 protein may not be a subunit of the housekeeping Ca2+ -dependent Cl- channel in the basolateral membrane of rabbit gastric parietal cells.

Amino Acid Sequence↗
PubMed2001

Dissecting aneurysms at the A1 segment of the anterior cerebral artery--two case reports.

Two rare cases of dissections which involve the anterior cerebral artery (ACA) are reported. A 58-year-old woman presented with a ruptured dissecting aneurysm manifesting as sudden onset of severe headache and consciousness disturbance followed by aphasia, right hemiparesis, paresis of the left lower extremity, and choreoathetotic movements of the upper arms and face. Computed tomography and angiography revealed subarachnoid hemorrhage due to a dissecting aneurysm at the left A1 segment. The dissecting aneurysm was trapped surgically on the day of onset. Her neurological deficits disappeared within a month. A 39-year-old woman experienced continuous dull headache from the day before onset, and then suffered right hemiparesis. Magnetic resonance (MR) imaging revealed cerebral infarction at the left globus pallidus. Angiography and MR imaging revealed a dissecting aneurysm at the left A1 segment and occlusion of the left Heubner's artery. She received conservative treatment and her neurological findings were improved. Dissections or dissecting aneurysms involving the ACA can be classified into three types: Extension of a dissection to the ACA from the internal carotid artery, dissection at the A1 segment, and dissection at the A2-A4 segments. These types of dissection have distinct uniform clinical features.

Aortic Dissection↗
PubMed2001

[Septic shock due to pyonephrosis-calculosa: a case report].

A 69-year-old female was admitted to hospital with the complaint of high-grade fever and clouding of consciousness. Physical examination and laboratory data revealed septic shock, disseminated intravascular coagulation and multiple organ failure. Ultrasonography demonstrated left hydronephrosis and a cystic mass in peri-renal fatty tissue. KUB showed a left ureteral stone. A diagnosis of septic shock due to pyonephrosis-calculosa and peri-renal abscess was considered. A left nephrectomy, endotoxin removal therapy and continuous hemodiafiltration was performed. Thereafter all morbidities improved. A nephrectomy and intensive treatment are the good alternative method for such a case.

Aged↗
PubMed2001

[A case of advanced gastric cancer with Virchow's and paraaortic lymph node metastases successfully resected after combined chemotherapy of low-dose CDDP and 5-FU].

The patient was a 61-year-old woman who had Stage IV advanced gastric cancer with Virchow's and paraaortic lymph node metastases. The lesions were considered surgically incurable, so she was placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 3 courses of chemotherapy, the tumor had decreased remarkably in size and Virchow's metastasis had disappeared. She was considered to have a partial response (PR) and underwent distal gastrectomy. Histopathological examination of the primary tumor revealed that almost all cancer cells existed in the mucosal and submucosal layers; few had infiltrated the serosa. A few paraaortic lymph nodes were positive for metastasis, but a curative resection (Cur B) was performed. The patient received another course of chemotherapy after the operation. Low-dose CDDP and 5-FU therapy was associated with few adverse events in this case, and thought to be effective against advanced gastric cancer.

Adenocarcinoma↗
PubMed2001

[Present status and future problems of clinical laboratory from view points of an anatomical pathologist].

The medical situation surrounding laboratory examinations has changed remarkably. We, the staff of laboratory divisions, must offer the best medical care for patients and operate efficiently. Fertility management service(FMS) and branch laboratory(Branch Lab.) are examples of useful contributions to our hospital from the perspective of economy and personnel expenditure including staff attrition.

Clinical Laboratory Techniques↗
PubMed2001

[Introduction: chronic myelogenous leukemia leading advanced clinical oncology].

Our understanding of the pathological molecular events underlying chronic myelogenous leukemia(CML) has rapidly grown over the past 2 decades. At the same time, new therapeutic modalities for CML which can cure or prolong survival in this formerly incurable disease, including interferon alpha administration and allogeneic hematopoietic stem cell transplantation, have been established. Now, a new molecule-specific drug, a ABL tyrosine kinase inhibitor(STI571), are developing, which is offering new hope for expanded treatment options for patients with CML. Clinical investigators and medical doctors will have responsibility in helping newly diagnosed patients with CML to properly elect treatment planning among the increased options available now. This specific number of JJ CO will be hoped to provide information to many medical oncologists beyond the hematology speciality.

Benzamides↗
PubMed2001

[Umbilical cord blood transplantation].

Umbilical cord blood transplantation(CBT) from HLA-mismatched unrelated donors has been increasingly performed. One of the advantages of unrelated CBT is a low risk of severe acute graft-versus-host disease(aGVHD). The degree of HLA disparities is not strongly associated with the occurrence of severe aGVHD. The disadvantages of CBT include a delayed time of hematopoietic recovery and a high rate of graft failure, which are significantly associated with the lower number of infused cord blood cells. Despite a relatively high rate of early transplant-related mortality, cord blood cells from HLA-mismatched unrelated donors should be considered as an alternative hematopoietic stem source for both children and adults who have no suitable related and unrelated bone marrow donors. Further clinical and laboratory studies are needed to improve the outcome of CBT.

Blood Preservation↗
PubMed2000

US3 protein kinase of herpes simplex virus protects primary afferent neurons from virus-induced apoptosis in ICR mice.

Possible roles of the US3 gene of the herpes simplex virus (HSV) in the interaction between the virus and primary afferent neurons were examined. Neuronal apoptosis was observed in the trigeminal ganglion of mice that were infected with the wild-type (wt) of HSV-2 strain 186 and with US3-deficient mutant virus (L1BR1). In wt virus-infected mice, many HSV-immunoreactive (HSV-ir) cells were seen throughout the trigeminal ganglion, although no apoptotic change was detected. On the other hand, HSV-ir cells in L1BR1-infected mice were found only in the ophthalmic division of the trigeminal ganglions. Examination by HSV-immunohistochemistry combined with the terminal deoxynucleotidal transferase (Tdt)-mediated deoxyuridin 5'-triphosphate (dUTP) nick-end labeling (TUNEL) method showed that DNA fragmentation had occurred in almost all HSV-ir cells in the L1BRI-infected ganglion. Ultrastructurally, many viral particles were detected in apoptotic ganglionic neurons of mice infected with L1BR1. These results indicate that US3 protein kinase (US3pk) played a role in protecting HSV-infected primary afferent neurons from apoptotic cell death. The present study suggests that US3pk plays a role when HSV establishes latent infections in the sensory ganglia.

Animals↗
PubMed2000

Characterization of the yeast Cdc7p/Dbf4p complex purified from insect cells. Its protein kinase activity is regulated by Rad53p.

The yeast Saccharomyces cerevisiae Cdc7p/Dbf4p protein kinase complex was purified to near homogeneity from insect cells. The complex efficiently phosphorylated yeast Mcm2p and less efficiently the remaining Mcm proteins or other replication proteins. Significantly, when pretreated with alkaline phosphatase, Mcm2p became completely inactive as a substrate, suggesting that it must be phosphorylated by other protein kinase(s) to be a substrate for the Cdc7p/Dbf4p complex. Mutant Cdc7p/Dbf4p complexes containing either Cdc7-1p or Dbf4-1 approximately 5p were also partially purified from insect cells and characterized in vitro. Furthermore, the autonomously replicating sequence binding activity of various dbf4 mutants was also analyzed. These studies suggest that the autonomously replicating sequence-binding and Cdc7p protein kinase activation domains of Dbf4p collaborate to form an active Cdc7p/Dbf4p complex and function during S phase in S. cerevisiae. It is shown that Rad53p phosphorylates the Cdc7p/Dbf4p complex in vitro and that this phosphorylation greatly inhibits the kinase activity of Cdc7p/Dbf4p. This result suggests that Rad53p controls the initiation of chromosomal DNA replication by regulating the protein kinase activity associated with the Cdc7p/Dbf4p complex.

Alkaline Phosphatase↗