Biomedical subjects

Shigeki Miyata

Publications and source records attributed to Shigeki Miyata.

10 recordsLinked to original sources

PubMed2006

Unblinded pilot study of autologous transplantation of bone marrow mononuclear cells in patients with thromboangiitis obliterans.

BACKGROUND: The short-term clinical benefits of bone marrow mononuclear cell transplantation have been shown in patients with critical limb ischemia. The purpose of this study was to assess the long-term safety and efficacy of bone marrow mononuclear cell transplantation in patients with thromboangiitis obliterans. METHODS AND RESULTS: Eleven limbs (3 with rest pain and 8 with an ischemic ulcer) of 8 patients were treated by bone marrow mononuclear cell transplantation. The patients were followed up for clinical events for a mean of 684+/-549 days (range 103 to 1466 days). At 4 weeks, improvement in pain was observed in all 11 limbs, with complete relief in 4 (36%). Pain scale (visual analog scale) score decreased from 5.1+/-0.7 to 1.5+/-1.3. An improvement in skin ulcers was observed in all 8 limbs with an ischemic ulcer, with complete healing in 7 (88%). During the follow-up, however, clinical events occurred in 4 of the 8 patients. The first patient suffered sudden death at 20 months after transplantation at 30 years of age. The second patient with an incomplete healing of a skin ulcer showed worsening of the lesion at 4 months. The third patient showed worsening of rest pain at 8 months. The last patient developed an arteriovenous shunt in the foot at 7 months, which spontaneously regressed by 1 year. CONCLUSIONS: In the present unblinded and uncontrolled pilot study, long-term adverse events, including death and unfavorable angiogenesis, were observed in half of the patients receiving bone marrow mononuclear cell transplantation. Given the current incomplete knowledge of the safety and efficacy of this strategy, careful long-term monitoring is required for future patients receiving this treatment.

Adult↗

PubMed2006

Successful treatment of extremely severe fetal anemia due to anti-Jra alloimmunization.

BACKGROUND: Although Jr(a) hemolytic disease of the newborn (HDN) is generally considered to be mild, we encountered a case of anti-Jr(a) alloimmunization hydrops fetalis due to extremely severe fetal anemia that required aggressive intrauterine treatment. CASE REPORT: A Japanese woman developed hydrops fetalis at the 29th week of gestation. Blood examination was highly positive for anti-Jr(a) antibodies. Cordocentesis demonstrated that the fetus had anti-Jr(a) antibodies and the lowest fetal hemoglobin concentration was 2.3 g/dl. After a total of four intravascular transfusions, fetal hydrops improved and a healthy girl of 2,120 g was delivered at the 35th week of gestation. The initial neonatal hemoglobin concentration at birth was 7.2 g/dl. After two straight transfusions, the infant's anemia did not worsen. Anti-Jr(a) antibodies became negative without developing hyperbilirubinemia. CONCLUSION: The incidence of Jr(a) negativity can lead to underestimation of the risk of Jr(a) alloimmunization. This case shows that anti-Jr(a) alloimmunization may cause HDN and hydrops fetalis.

Adult↗

PubMed2006

[A case of heparin-induced thrombocytopenia associated with unexpected excessive argatroban anticoagulation after abdominal aortic aneurysm resection].

We experienced excessive anticoagulation induced by argatroban for the treatment of heparin-induced thrombocytopenia (HIT). A 74-year-old man was scheduled for elective abdominal aortic aneurysm resection. During the surgery, both femoral arteries were found non-pulsatile requiring thrombectomy. The next day, second laparotomy was needed because of superior mesenteric artery occlusion. After the surgery, acute renal failure and hypoxemia continued with progressive thrombocytopenia necessitating frequent administration of platelet concentrates. Considering possibility of HIT, we stopped heparin and began argatroban. Due to his mild liver dysfunction, we initiated argatroban at 0.5 microg x kg(-1) x min(-1) one-fourth of standard initial dose, according to its drug information approved by FDA. Although expected APTT level was from 50 to 60 sec, it increased immediately up to 93 sec. Excessive anticoagulation continued more than 24 hours after cessation of argatroban and bleeding occurred from the tracheostomy site. When APTT decreased to the target range, we restarted argatroban and found the adequate dosage at 0.08 microg x kg(-1) x min(-1). After argatroban treatment, platelet count recovered immediately and no thromboembolism was observed. We recommend that argatroban should be initiated at a lower dosage than the dose shown in its drug information for HIT patients after cardiovascular surgery with frequent monitoring of APTT.

Aged↗

PubMed2005

Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura.

ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation through cleavage of von Willebrand factor (VWF) multimers. In humans, genetic or acquired deficiency in ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi. In this study, we report characterization of mice bearing a targeted disruption of the Adamts13 gene. ADAMTS13-deficient mice were born in the expected mendelian distribution; homozygous mice were viable and fertile. Hematologic and histologic analyses failed to detect any evidence of thrombocytopenia, hemolytic anemia, or microvascular thrombosis. However, unusually large VWF multimers were observed in plasma of homozygotes. Thrombus formation on immobilized collagen under flow was significantly elevated in homozygotes in comparison with wild-type mice. Thrombocytopenia was more severely induced in homozygotes than in wild-type mice after intravenous injection of a mixture of collagen and epinephrine. Thus, a complete lack of ADAMTS13 in mice was a prothrombotic state, but it alone was not sufficient to cause TTP-like symptoms. The phenotypic differences of ADAMTS13 deficiencies between humans and mice may reflect differences in hemostatic system functioning in these species. Alternatively, factors in addition to ADAMTS13 deficiency may be necessary for development of TTP.

ADAMTS13 Protein↗

PubMed2005

Adiponectin acts as an endogenous antithrombotic factor.

OBJECTIVE: Obesity is a common risk factor in insulin resistance and cardiovascular diseases. Although hypoadiponectinemia is associated with obesity-related metabolic and vascular diseases, the role of adiponectin in thrombosis remains elusive. METHODS AND RESULTS: We investigated platelet thrombus formation in adiponectin knockout (APN-KO) male mice (8 to 12 weeks old) fed on a normal diet. There was no significant difference in platelet counts or coagulation parameters between wild-type (WT) and APN-KO mice. However, APN-KO mice showed an accelerated thrombus formation on carotid arterial injury with a He-Ne laser (total thrombus volume: 13.36+/-4.25 x 10(7) arbitrary units for APN-KO and 6.74+/-2.87x10(7) arbitrary units for WT; n=10; P<0.01). Adenovirus-mediated supplementation of adiponectin attenuated the enhanced thrombus formation. In vitro thrombus formation on a type I collagen at a shear rate of 250 s(-1), as well as platelet aggregation induced by low concentrations of agonists, was enhanced in APN-KO mice, and recombinant adiponectin inhibited the enhanced platelet aggregation. In WT mice, adenovirus-mediated overexpression of adiponectin additionally attenuated thrombus formation. CONCLUSIONS: Adiponectin deficiency leads to enhanced thrombus formation and platelet aggregation. The present study reveals a new role of adiponectin as an endogenous antithrombotic factor.

Adenoviridae↗

PubMed2004

Network computer-assisted transfusion-management system for accurate blood component-recipient identification at the bedside.

BACKGROUND: ABO-mismatched transfusions caused by human error are among the most serious problems in transfusion therapy. The major cause is misidentification of a recipient or a blood component at the bedside. STUDY DESIGN AND METHODS: A network computer-assisted transfusion-management system has been developed with bar coding as a fail-safe/fool-proof system for accurate component-recipient identification at the bedside, which allows us to monitor the usage of blood components in real time. The efficacy of this system was evaluated to prevent human errors by monitoring the transfusion process via the network and analyzing voluntary and mandatory reports with regard to transfusion errors over a 3-year period. The crossmatch-to-transfusion ratio for operations and outdate rate of RBCs were calculated to assess economic benefit. RESULTS: More than 60,000 blood components have been transfused perfectly to the intended recipients via the network, and one human error was prevented by the system. After establishment of the network system, the crossmatch-to-transfusion ratio for operations and outdate rate of RBCs have been gradually reduced from around 2.5 to 1.8 and from 3.9 to 0.32 percent, respectively. CONCLUSION: The network computer-assisted management system greatly contributes to safe and efficient transfusion therapy.

ABO Blood-Group System↗

PubMed2002

Mural thrombus generation in type 2A and 2B von Willebrand disease under flow conditions.

To explore the mechanisms that underlie the bleeding tendency in type 2A and 2B von Willebrand disease (VWD), we analyzed the mural thrombus generation process on a collagen surface under physiologic blood flow in a perfusion chamber using whole blood from these VWD patients. At a low shear rate (50 s(-1)), thrombus generation in all type 2A and 2B VWD patients was comparable to that of healthy controls. At a high shear rate (1500 s(-1)), thrombus generation was impaired in all type 2A patients, whereas that in type 2B VWD patients varied from normal to significantly defective, as judged by epifluorescence microscopy of thrombus surface coverage. However, in type 2B patients who showed normal thrombus generation at 1500 s(-1), the height and volume of thrombi was significantly reduced, albeit with the normal surface coverage, compared with control thrombi, and von Willebrand factor (VWF) was poorly distributed within the type 2B thrombus mass when analyzed in detail by confocal laser scanning microscopy. Addition of purified VWF to patient blood completely reversed the defective spatial thrombus growth in type 2B VWD. Thus, our results confirm the impaired thrombus generation in type 2B VWD, which has never been demonstrable in previous in vitro soluble-phase platelet aggregation assays, and point to the critical function of larger VWF multimers in the proper spatial growth of mural thrombi under high shear rate conditions.

Blood Coagulation↗

PubMed2002

Distinct and concerted functions of von Willebrand factor and fibrinogen in mural thrombus growth under high shear flow.

Using a perfusion chamber and confocal laser scanning microscopy, we analyzed the interplay of von Willebrand factor (VWF) and fibrinogen during thrombus growth on a collagen surface under physiologic high shear rate conditions. During initial thrombogenesis, platelet thrombi were constructed totally by VWF, not by fibrinogen. Fibrinogen accumulated predominantly inside the growing thrombi as a function of time, whereas the thrombus surfaces directly exposed to flow were occupied constantly by VWF throughout the observation period. In perfusion of afibrinogenemia (AF) blood lacking both plasma and platelet fibrinogen, the final height and volume of thrombi were significantly reduced compared with controls, albeit the area of surface coverage was normal. The impaired thrombus growth in AF was only partially corrected by the addition of purified fibrinogen to AF blood, whereas the addition of purified VWF to blood of severe von Willebrand disease (VWD) completely normalized the defective thrombus growth in this disease. Thus, the initial 2-dimensional thrombus expansion involves only VWF, whereas the time-dependent accumulation of fibrinogen, released from activated platelets, acts as a core adhesive ligand, increasing thrombus strength and height and resulting in 3-dimensional thrombus development against rapid blood flow.

Afibrinogenemia↗

PubMed2002

Platelet shape changes and adhesion under high shear flow.

Recent studies have revealed that the platelet adhesive process under flow is tightly regulated by multiple ligand-receptor interactions. However, platelet morphological changes during this process, particularly its physiological relevance, remain unknown under blood flow conditions. Using epifluorescence and scanning electron microscopy, we evaluated the real-time changes in platelet morphology during a platelet adhesive process on a von Willebrand factor-coated surface under physiological high shear flow in a perfusion chamber. Here, we show that dynamic platelet shape changes occurring during distinct phases of the adhesive process are precisely regulated by "inside-out" and "outside-in" integrin signals and are also a key regulatory element in successful platelet thrombogenesis opposing rapid blood flow in vivo.

Androstadienes↗

PubMed2002

Functional property of von Willebrand factor under flowing blood.

von Willebrand factor (vWF) is produced in megakaryocytes and endothelial cells, is stored in the alpha-granule of platelets and in the Weibel-Palade body of endothelial cells, and is present in plasma and vascular subendothelium. This huge protein with a unique multimeric structure plays a pivotal role in both hemostasis and pathological intravascular thrombosis, in which vWF contributes to both platelet adhesion/aggregation and blood coagulation through its multiple adhesive functions for the platelet membrane receptors, glycoprotein Ib-IX-V complex, integrin alphaIIbbeta3, heparin, various types of collagen, and coagulation factor VIII. Among various functions, the most characteristic feature of vWF is its determinant role on platelet thrombus formation under high-shear-rate conditions. Indeed, at in vivo rheological situations where platelets are flowing with high speed in the bloodstream, the only reaction that can initiate mural thrombogenesis is the interaction of vWF with platelet glycoprotein Ibalpha. The recent x-ray analysis of the crystal structure of various functional domains and functional studies of this protein under experimental flow conditions have rapidly advanced and revised our knowledge of the structure-function relationships of vWF, a key protein for hemostasis and arterial thrombosis.

Animals↗