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Biomedical subjects

Shinichiro Okamoto

Publications and source records attributed to Shinichiro Okamoto.

At least 73 records · Page 4Linked to original sources
PubMed2003

Successful treatment of extramedullary blast crisis of chronic myelogenous leukemia with imatinib mesylate (STI571).

We describe a patient with chronic myelogenous leukemia (CML) who developed extramedullary blast crisis, and was successfully treated with imatinib mesylate (STI571). A 42-year-old man had been diagnosed with chronic phase Philadelphia chromosome (Ph)-positive CML and treated with interferon-alpha. He achieved partial cytogenetic response. Two years after the diagnosis, he presented with superficial lymphadenopathy in his neck and supraclavicular regions. Lymph node biopsy disclosed the infiltration of myeloblasts. Although the patient's bone marrow was without increasing blasts at that time, cytogenetic response was no longer observed. STI571 at a dose of 600 mg/day was initiated, and led to the complete disappearance of lymphadenopathy within a month and also to major cytogenetic response in the bone marrow (90% Ph-negative metaphases). Subsequently, the patient underwent allogeneic bone marrow transplantation from an HLA-matched unrelated donor and was in complete remission without evidence of extramedullary disease 12 months after transplantation.

Adult↗
PubMed2003

Hemophagocytic syndrome associated with fulminant hepatitis A: a case report.

A 37-year-old man had a sore throat and pyrexia since January 1999. He was treated at a nearby hospital, but not improved. Jaundice was indicated there, and the patient was referred transferred to our hospital, where he was admitted for treatment with a diagnosis of severe acute hepatitis with acute renal failure. Thereafter the patient was revealed to have had a past history of heavy drinking, and he underwent the treatment with a diagnosis of acute fulminant hepatitis due to hepatitis A virus (HAV). He showed a tendency toward improvement. During the course, however, viral associated hemophagocytic syndrome (VAHS) developed. Various treatments were conducted, but it was not improved, and the patient died on Hospital Day 66. On pathologic autopsy, remarkable hepatosplenomegaly associated with marked bone marrow abnormalities compatible with VAHS was observed. Aspergillus abscesses were also observed in many organs, and they were considered as an adverse reaction to potent immunosuppressive therapy. Since there have been only a few reports on HAV-related VAHS, discussing VAHS related to HAV, the present case was considered valuable.

Adult↗
PubMed2003

[Improvement of diabetes insipidus after allogeneic bone marrow transplantation in a patient with myelodysplastic syndrome].

A 45-year-old male was diagnosed as having myelodysplastic syndrome (RAEB) in March 2001. He was admitted to our hospital because of cellulitis in his left lower limb in May. The blood cell count showed pancytopenia and immature myeloid cells were seen in the peripheral blood. Bone marrow aspiration showed the proliferation of myeloblasts (11.2%) and complex karyotypic abnormalities were detected including the long arm deletion of chromosome 7. The patient developed polyuria and polydipsia after admission and was diagnosed as having central diabetes insipidus. He was treated with DDAVP and the polyuria disappeared. In November, he underwent unrelated allogeneic bone marrow transplantation after conditioning with total body irradiation and cytarabine. After transplantation DDAVP was no longer required. Central diabetes insipidus has been reported as a rare complication of leukemia or myelodysplastic syndrome, but the underlying mechanism remains unclear. The complete remission of diabetes insipidus after bone marrow transplantation suggests that the infiltration of leukemic cells into the pituitary gland caused the diabetes insipidus in this case.

Bone Marrow Transplantation↗
PubMed2003

[Measurement of plasma von Willebrand factor cleaving protease in patients with varied thrombotic microangiopathy].

Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma of patients with TTP has been shown to contain unusually large von Willebrand factor(vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP. We examined the activity of the vWF-cleaving protease(vWF-CP), by modified Furlan's method, in plasma from patients with a familial TTP, 3 acquired TTP, 4 thrombotic microangiopathy(TMA) and 2 veno-occlusive disease(VOD) associated after allo-BMT. Diluted plasma samples of patients were incubated with protease-free vWF purified from normal human plasma, in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in SDS-agarose gels and immunoblotting. Activity of vWF-CP from 12 normal plasma have been shown as 77-180%(average 115%), whereas, no vWF-CP(below 5%) was observed in plasma from familial TTP, before and after plasma exchange, although FFP infusion therapy has been effective for this patient to recover thrombocytopenia. In 3 acquired TTP, 2 patients showed lack of vWF-CP activity in plasma, and inhibitors against vWF-CP have been elucidated by plasma cross-mixing test. After extensive plasma exchange and FFP infusion followed by corticosteroid therapy, normal vWF-CP was recovered in plasma from 2 acquired TTP patients. Among BMT patients, plasma from 4 BMT-TMA showed normal vWF-CP activities as 55-111%, whereas plasma from 2 BMT-VOD revealed low vWF-CP activity, as 24% and 37%, respectively. Thus, measurement of vWF-CP is crucial to predict differentiation of primary forms of TMA to establish the pathogenesis in varied endothelial dysfunction.

ADAM Proteins↗
PubMed2003

[Chronic myelogenous leukemia in a lymphoblastic crisis complicated with deep venous thrombosis successfully treated by thromboembolectomy].

A 20-year-old man was referred to our hospital because of leukocytosis and was diagnosed as having chronic myelogenous leukemia in lymphoblastic crisis. His left leg began to swell soon after the beginning of induction chemotherapy and deep vein thrombosis (DVT) was confirmed by doppler echography, which progressed to compartment syndrome next day. After placing a venous filter in the inferior vena cava, the patient successfully underwent thromboembolectomy. Venous congestion due to massive lymphadenopathy enlarged kidneys, and a hypercoagulable condition due to the rapid destruction of leukemic cells may have contributed to the formation of the thrombus. This case demonstrates the importance of aggressive surgical intervention for severe DVT in patients with leukemia.

Adult↗
PubMed2002

Damaged epithelia regenerated by bone marrow-derived cells in the human gastrointestinal tract.

Studies have shown that bone marrow cells have the potential to differentiate into a variety of cell types. Here we show that bone marrow cells can repopulate the epithelia of the human gastrointestinal tract. Epithelial cells of male donor origin were distributed in every part of the gastrointestinal tract of female bone marrow transplant recipients. Donor-derived epithelial cells substantially repopulated the gastrointestinal tract during epithelial regeneration after graft-versus-host disease or ulcer formation. Regeneration of gastrointestinal epithelia with donor-derived cells in humans shows a potential clinical application of bone marrow-derived cells for repairing severely damaged epithelia, not only in the gastrointestinal tract but also in other tissues.

Adult↗
PubMed2002

Multiple sclerosis associated with interferon-alpha therapy for chronic myelogenous leukemia.

We report a chronic myelogenous leukemia (CML) patient in chronic phase (CP) who developed multiple sclerosis (MS) in association with interferon-alpha (IFN-alpha) administration. In our patient, recombinant IFN-alpha2b therapy induced hematologically complete and cytogenetically major partial response for CML first, and sequential central nervous system dysfunction evolved, which subsided shortly after the cessation of its administration. Restarting IFN-alpha therapy by changing to a natural type of IFN-alpha resulted in rapid exacerbation of MS. The patient's neurological symptoms progressed gradually, but partial hematologic response persisted without any IFN-alpha derivatives or anti-cancer agents until a matched unrelated donor transplant procedure was performed. Myeloablative therapy led to lasting stable state of MS and finally to complete cytogenetic remission of CML. This patient's presenting clinical course and laboratory data suggest that both exertion of anti-leukemic activity and autoimmune process of MS might be mediated by mutual mechanisms, such as enhancement of specific cellular immunity induced by IFN-alpha.

Adult↗
PubMed2002

Long-term follow-up of allogeneic bone marrow transplantation after reduced-intensity conditioning in patients with chronic myelogenous leukemia in the chronic phase.

Although allogeneic transplantation is a curative therapy for chronic myelogenous leukemia (CML), treatment-related mortality is still a major cause of death after transplantation, especially in older patients. We investigated the safety and efficacy of reduced-intensity conditioning consisting of low-dose (600 cGy) total body irradiation and cytosine arabinoside (1 g/m2) together with a continuous infusion of granulocyte colony-stimulating factor and cyclophosphamide (120 mg/kg) in patients with CML in the chronic phase. Fractionated splenic irradiation (5 Gy) was also administered as part of the conditioning treatment. Eight patients older than 40 years underwent allogeneic bone marrow transplantation from an HLA-matched sibling following this conditioning. Regimen-related toxicities (equal to or greater than grade III) were not observed. Rapid restoration of 100% donor chimerism was confirmed by fluorescence in situ hybridization methods in 5 sex-mismatched transplant recipients. One patient died from severe acute graft-versus-host disease and another from Pneumocystis carinii pneumonia early in the course of transplantation. A sustained engraftment was achieved in 5 long-term survivors; in 1 case, the graft was rejected but the Philadelphia chromosome and BCR/ABL-negative autologous hemopoiesis were restored. After a minimum follow-up period of 60 months, 6 patients, including the patient with restored autologous hemopoiesis, were still alive and in remission with 100% donor chimerism. Six years after the transplantation, 1 patient experienced a cytogenetic relapse, which was successfully treated with donor lymphocyte infusions. In summary, this reduced-intensity conditioning resulted in a cure with markedly reduced regimen-related toxicities in this relatively older cohort of patients with CML.

Adult↗
PubMed2002

Current status of Japan marrow donor program (JMDP) and its roles in international cooperation.

Transplants for patients lacking an HLA identical sibling donor have become possible, and thank to the establishment of large registries of HLA typed volunteers. Japan Marrow Donor Program (JMDP) now stands at about 152,339 volunteer donors, and have provided 4,013 marrows nationally and internationally. Advancements in HLA typing technology and greater precision in donor recipient matching have greatly increased the safety of unrelated donor transplants. In the JMDP retrospective study the strongest risk factor for acute GVHD and mortality was found to be mismatching for the BLA-A locus. Better matching criteria using molecular typing, however, will reduce the likelihood of identification of donors, especially in minorities. The chance of finding a matched unrelated donor is likely to be higher in the registries which share the same ethnic background of a recipient. There are five marrow donor registries have been established in Asia and are actively functioning. The expansion of volunteer donor pool of those registries and their efficient collaboration is very important to increase the probability of finding a match. The identification of permissive antigens may increase flexibility in donor-recipient pair matching may also be achieved through integration of international efforts and the creation of larger HLA data base.

Bone Marrow Transplantation↗
PubMed2002

Elevated level of plasma basic fibroblast growth factor in multiple myeloma correlates with increased disease activity.

Recent reports that bone marrow angiogenesis is increased in multiple myeloma prompted us to examine plasma concentrations of angiogenic growth factors and to elucidate their clinical and biological significance. In 45 cases including 36 cases of multiple myeloma and 9 cases of monoclonal gammopathies of undetermined significance (MGUS), plasma concentrations of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) were evaluated. FGF-2 was significantly elevated in 25 out of 45 (56%) of the patients with multiple myeloma compared with control subjects (median 9.01 pg ml vs. 1.58 pg/ml, P < 0.0001). The 25 cases were all active multiple myeloma, and none of the non-active myeloma and MGUS patients showed a high FGF-2 level. VEGF level was also elevated in 26 out of 45 patients (58%) compared with control subjects (median 42.0 pg/ml vs. 15.8 pg/ml, P < 0.0001 for VEGF). VEGF concentration was high in 20 active myelomas, but also in one non-active myeloma and five MGUS. Elevation of FGF-2 level was associated with beta2-microglobulin level, anemia and bone marrow plasma cell percentage, which represent disease activity. Interestingly, none of five Bence-Jones type myelomas, including four clinically active cases, revealed a high plasma FGF-2 level, while all of them showed a high VEGF level. In all five responders, the plasma FGF-2 levels were significantly decreased after chemotherapy. FGF-2 was immunohistochemically detected in the bone marrow myeloma cells of the patients with high plasma FGF-2 level. We conclude that plasma concentration of FGF-2 can be a useful indicator of disease activity.

Aged↗
PubMed2002

Thalidomide for the treatment of refractory multiple myeloma: association of plasma concentrations of thalidomide and angiogenic growth factors with clinical outcome.

Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2 - 4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (2.0 microg/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P = 0.025), but not in non-responders (P = 0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide.

Adult↗
PubMed2002

Role of nitric oxide in host defense in murine salmonellosis as a function of its antibacterial and antiapoptotic activities.

Host defense functions of nitric oxide (NO) are known for many bacterial infections. In this study, we investigated the antimicrobial effect of NO in murine salmonellosis by using inducible NO synthase (iNOS)-deficient mice infected with an avirulent or virulent Salmonella enterica serovar Typhimurium strain. All iNOS-deficient mice died of severe septicemia within 6 days after intraperitoneal injection with an avirulent strain (LT2) to which wild-type mice were highly resistant; 50% lethal doses (LD(50)s) of the LT2 strain for iNOS-deficient and wild-type mice were 30 CFU and 7 x 10(4) CFU, respectively. Lack of NO production in iNOS-deficient mice was verified directly by electron spin resonance spectroscopy. Bacterial yields in liver and blood were much higher in iNOS-deficient mice than in wild-type mice throughout the course of infection. Very small amounts of a virulent strain of serovar Typhimurium (a clinical isolate, strain Gifu 12142; LD(50), 50 CFU) given orally caused severe septicemia in iNOS-deficient animals; wild-type mice tolerated higher doses (LD(50), 6 x 10(2) CFU). Histopathology of livers from infected iNOS-deficient mice revealed extensive damage, such as diffuse hepatocellular apoptosis and increased neutrophil infiltration, but livers from infected wild-type mice showed a limited number of microabscesses, consisting of polymorphonuclear cells and macrophages and low levels of apoptotic change. The LT2 strain was much more susceptible to the bactericidal effect of peroxynitrite than the Gifu strain, suggesting that peroxynitrite resistance may contribute to Salmonella pathogenicity. These results indicate that NO has significant host defense functions in Salmonella infections not only because of its direct antimicrobial effect but also via cytoprotective actions for infected host cells, possibly through its antiapoptotic effect.

Animals↗
PubMed2002

[Craniotomy side for neck clipping of the anterior communicating aneurysm via the pterional approach].

The safety and reliability of neck clipping of the anterior communicating artery (Acom) aneurysm via the pterional approach was evaluated in terms of craniotomy side in 39 consecutive cases operated on by the senior surgeon from April 1991 through March 2000. These aneurysms were approached in principle via the side where the proximal A2 portion of the anterior cerebral artery was located posteriorly, for the purpose of easier identification of all five arteries involved, i.e., A1 and A2 portions of the anterior cerebral arteries of both sides and Acom. All aneurysms were clipped safely irrespective of the approach side because it was possible prior to aneurysmal dissection to prepare both A1 portions of the anterior cerebral arteries for temporary clipping, but not as far as the place where the aneurysm projects inferiorly and its fundus adheres firmly to the optic chiasm. The security of perforating arteries, however, could not be confirmed even after the completion of neck clipping in 9 cases. Clipping was impossible in the other 2 cases. In 2 of these 11 aneurysms the difficulty in clipping was not based on what side was used for craniotomy but on their large size. In the remaining 9 aneurysms, the necks of which were all situated on the posterior wall of the Acom, the craniotomy side turned out to be inappropriate when they were approached via the side where the proximal A2 portion of the anterior cerebral artery was located posteriorly. It was concluded that the craniotomy side should be selected so that the surgeon can observe directly the neck of the aneurysm.

Adult↗