[Cardiogenic brain embolism].
Explore the source record for details and available documents.
Heart Diseases↗
Biomedical subjects
Y Akatsuka
Publications and source records attributed to Y Akatsuka.
Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, attenuates metabolic coronary vasodilatation induced by pacing tachycardia in dogs.
BACKGROUND: We previously reported that glibenclamide (a selective inhibitor of ATP-sensitive K+ channels [K+ATP channels]) inhibited metabolic coronary vasodilatation induced by beta 1-adrenoceptor stimulation. However, the role of K+ATP channels in metabolic coronary vasodilatation induced by tachycardia is still unknown. This study aimed to determine whether glibenclamide attenuates metabolic coronary vasodilatation induced by pacing-induced tachycardia. METHODS AND RESULTS: In anesthetized dogs, increasing heart rate from 103 +/- 1 to 160 beats per minute with atrial pacing increased coronary blood flow without altering arterial pressure and left ventricular pressure. Intracoronary infusion of glibenclamide at 1.5 and 5.0 micrograms.kg-1.min-1 did not alter basal coronary blood flow but significantly attenuated (P < .01) the tachycardia-induced coronary vasodilatation without altering the tachycardia-induced increase in myocardial oxygen consumption (MVO2). In conscious dogs, intracoronary glibenclamide at 5.0 micrograms.kg-1.min-1 attenuated (P < .05) coronary vasodilatation induced by ventricular pacing from 85 +/- 6 to 150 beats per minute. Glibenclamide markedly attenuated coronary vasodilation evoked with the K+ATP channel opener pinacidil. CONCLUSIONS: These data indicate that blockade of coronary vascular K+ATP channels with glibenclamide inhibited metabolic coronary vasodilatation induced by pacing tachycardia in dogs, suggesting that K+ATP channels are involved in the mechanism mediating metabolic coronary vasodilatation associated with pacing tachycardia.
Adenosine Triphosphate↗
Endothelium-derived nitric oxide does not modulate metabolic coronary vasodilation induced by tachycardia in dogs.
Endothelium-derived nitric oxide (EDNO) has been implicated in the modulation of coronary arterial tone. The aim of this study was to determine if metabolic coronary vasodilation induced by pacing tachycardia is altered by the inhibition of EDNO synthesis. Before and after the intracoronary infusion of an inhibitor of EDNO synthesis (N omega-nitro-L-arginine-methyl-ester, L-NAME), changes in coronary blood flow (CBF), regional myocardial blood flow (MBF), and myocardial oxygen consumption (MVO2) were measured in anesthetized dogs in response to atrial pacing tachycardia. Increasing the heart rate from 109 +/- 10 to 160 beats/min by pacing produced significant increases in CBF (p < 0.05), MVO2 (p < 0.05), and MBF in each sublayer of the myocardium (p < 0.05). L-NAME did not alter the pacing-induced increases in CBF, MVO2, or regional MBF. In addition, the ratio of the tachycardia-induced increase in CBF to the increase in MVO2 was not changed by L-NAME. The coronary vasodilation evoked by acetylcholine was attenuated by L-NAME (p < 0.05). However, the response to sodium nitroprusside was not altered. These results suggest that EDNO does not play a primary role in the mechanism mediating metabolic coronary vasodilation induced by pacing tachycardia in dogs.
Analysis of Variance↗
ATP sensitive potassium channels are involved in adenosine A2 receptor mediated coronary vasodilatation in the dog.
OBJECTIVE: The aim was to determine a role of ATP sensitive potassium (KATP) channels in adenosine A2 receptor mediated coronary vasodilatation in anaesthetised dogs in vivo. METHODS: Coronary blood flow in the left circumflex coronary artery, aortic pressure, and left ventricular pressure were measured during intracoronary infusions of the drugs into the left circumflex artery. RESULTS: A non-selective A2 receptor agonist NECA (5'-N-ethylcarboxamidoadenosine) at 10(-10)-10(-8) mol.min-1 before and after an A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) increased coronary blood flow in a dose dependent manner, without affecting other haemodynamic variables. Glibenclamide at 10 micrograms.kg-1.min-1, which did not alter baseline haemodynamic variables, markedly inhibited the increases in coronary blood flow caused by NECA alone and after DPCPX (p < 0.01). A non-selective adenosine receptor antagonist 8-phenyltheophylline abolished the NECA induced increases in coronary blood flow after DPCPX. These results suggest that A2 receptor mediated coronary vasodilatation was mediated largely by opening of KATP channels. Glibenclamide did not alter the increase in coronary blood flow evoked by forskolin or acetylcholine, suggesting that KATP channels may not be involved in coronary vasodilatation induced by activation of adenylate cyclase or guanylate cyclase. Furthermore, DPCPX increased basal coronary blood flow, which was blocked by 8-phenyltheophylline and by glibenclamide, suggesting that it may have unmasked A2 receptor mediated coronary vasodilatation by inhibiting the A1 receptor mediated vasoconstricting action of endogenous adenosine. CONCLUSIONS: Opening of KATP channels may be involved importantly in adenosine A2 receptor mediated coronary vasodilatation in canine hearts.
Acetylcholine↗
Glibenclamide prevents coronary vasodilation induced by beta 1-adrenoceptor stimulation in dogs.
This study aimed to determine whether a putative ATP-sensitive K(+)-channel blocker, glibenclamide (Glb), prevents metabolic coronary vasodilation associated with increased myocardial oxygen consumption (MVO2) caused by beta 1-adrenoceptor stimulation in anesthetized open-chest dogs. Isoproterenol (Iso) was infused selectively into the left circumflex coronary artery before and after Glb. Coronary blood flow (CBF) by an electromagnetic flowmeter, regional myocardial function by sonomicrometers, and left ventricular and arterial pressures were continuously measured. An intracoronary infusion of Iso (10 ng.kg-1 x min-1) resulted in the sustained increase in CBF as well as in the myocardial inotropic and chronotropic state. Glb (10, 30, and 100 micrograms/min ic) attenuated the Iso-induced increase in CBF in a dose-dependent manner, whereas inotropic and chronotropic responses to Iso were not affected by Glb. After beta 1-blockade with bisoprolol (0.3 mg/kg), which completely inhibited inotropic and chronotropic responses to Iso, the Iso-induced increase in CBF, presumably mediated by vascular beta 2-receptor stimulation, was not affected by Glb. Intracoronary denopamine (0.1 microgram.kg-1 x min-1), a beta 1-selective agonist, increased CBF, which was almost completely abolished by Glb. The increases in MVO2 induced by Iso or denopamine were similar before and after Glb, indicating that attenuation of the Iso- or denopamine-induced increase in CBF by Glb did not result from the decrease in MVO2. These results indicate that Glb prevented the increase in CBF associated with increased MVO2 caused by beta 1-adrenoceptor stimulation. It is suggested that ATP-sensitive K+ channels may play an important role in metabolic coronary vasodilation in dogs.
Adenosine Triphosphate↗
Retrovirus-mediated transfer of a hygromycin phosphotransferase-thymidine kinase fusion gene into human CD34+ bone marrow cells.
Retrovirus-mediated gene transfer into human hematopoietic stem cells has been proposed as a means of therapy for various inherited diseases and as a method of gene marking. The transduction efficiency of an amphotropic retroviral vector (PA317/HyTK) containing a hygromycin phosphotransferase-thymidine kinase fusion gene was examined with human CD34+ bone marrow cells in the presence of interleukin-3 (IL-3), interleukin-6 (IL-6), and stem cell factor. Transduction efficiencies determined from the ability of transduced granulocyte-macrophage colony forming units (CFU-GM) to grow in hygromycin B and from polymerase chain reaction analysis of individual transduced CFU-GM growing in the presence of hygromycin B were 0.3-3.0% (mean +/- S.D., 1.1 +/- 0.9%) and 0.1-1.2% (mean +/- S.D., 0.5 +/- 0.4%), respectively. Ganciclovir at a dose of approximately 1 microM reduced the number of CFU-GM derived from vector-infected CD34+ cells by 50%. These findings demonstrate that human hematopoietic stem cells infected with this retroviral vector are susceptible to ganciclovir, offering the potential to control transduced gene expression in vivo.
Antigens, CD↗
Follow-up laparoscopy in patients with ovarian cancer.
Between 1982 and 1990, two hundred and fourteen consecutive laparoscopies were performed on 75 patients with epithelial ovarian cancer when the disease appeared to be clinically in complete remission according to simultaneous CT scan or ultrasonography. Evaluation were based on macroscopic findings through the laparoscope, by cytologic examination of ascitic and peritoneal washings and by intraperitoneal biopsy. The results were positive in 34 laparoscopies for 19 patients, suspicious in 15 laparoscopies for 13 patients and negative in 164 laparoscopies. the intraperitoneal recurrence rate after negative second-look laparoscopy was 14.0% as a whole, and 4.5% in cases with more than two consecutive negative evaluations. Serum CA-125 levels exhibited and elevation in 28 of 34 positive laparoscopies before treatment and remained within the normal range in 22 (78.6%) of the 28 cases after treatment despite positive follow-up laparoscopies. The repeated laparoscopies offer the advantage of lowering the false negative rate. This will enable early detection of intraperitoneal recurrence, better prognoses and reduction of unnecessary laparotomies.
Female↗
[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].
One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.
Adolescent↗
[Phase I study of paclitaxel].
Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.
Adolescent↗
[Allogeneic cryopreserved marrow transplantation in a patient with chronic myelogenous leukemia].
A 45-year-old male with chronic myelogenous leukemia received cryopreserved allogeneic bone marrow from his HLA-identical sister. Bone marrow was harvested and cryopreserved prior to chemoradiotherapy since the donor had neurotic tendencies. The preconditioning regimen consisted of standard dosage of busulfan plus cyclophosphamide and total lymphoid irradiation (5Gy). A total of 3.1 x 10(7)/kg marrow mononuclear cells, containing 4.7 x 10(5) CD34+ cells/kg, and 8.0 x 10(6)/kg buffy coat cells collected from the donor at day 0 was infused. Marrow engraftment occurred by day 38 although hematological recovery was delayed and subsequent administration of GM-CSF, methylprednisolone and donor buffy coat cells were required. Mononuclear cells obtained from the patient's blood at day 28 had an inhibitory effect on CFU-GM formation of the donor's bone marrow mononuclear cells. We considered that this case suffered from a transient myelosuppression due to residual host cells after bone marrow transplantation.
Bone Marrow↗
Acute renal failure and degenerative tubular lesions associated with in situ formation of adenovirus immune complexes in a patient with allogeneic bone marrow transplantation.
We describe the development of acute renal failure and degenerative tubular lesions associated with local immune deposits in a patient with allogeneic bone marrow transplantation. A 21-year-old man with an acute myelocytic leukemia received a bone marrow graft from a cousin mismatched for a single HLA-DR locus antigen. Hemorrhagic cystitis due to adenovirus type 11 infection occurred 26 days after transplantation, and 17 days later the patients developed acute renal failure. A study of renal tissue obtained by needle biopsy showed degenerative and necrotic lesions, especially in the distal part of the nephron. By electron microscopy adenovirus type 11 particles were found in the nuclei of tubular cells and in cellular debris in tubular lumina. By immunofluorescence technique, granular immune deposits containing adenovirus type 11 related antigen(s), immunoglobulins, C3, and membrane attack complex (MAC) C5b-9 of the complement system were detected along the tubular basement membranes but not in glomeruli. The patient's IgG did not bind to normal human kidneys. These findings suggest that adenovirus type 11 directly induced acute tubular damage, and that the tubular immune deposits were formed "in situ" by viral antigens and circulating viral antibody.
Acute Kidney Injury↗
Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia.
We have screened mutations of the N-ras gene at codons 12, 13, and 61 in leukemia cells obtained from 100 patients with acute myeloid leukemia (AML), and found mutated N-ras alleles in 9 patients. We further analyzed the polyclonality of multiple N-ras gene mutations in 4 AML patients. One patient, who had the monoclonal karyotype, t(11;17), had two types of double missense mutations at codons 13 and 61 in the same allele. Each of the remaining three patients, one of whom had t(15;17) with a monoclonal rearrangement of the retinoic acid receptor alpha and PML genes, carried two missense mutations in a relatively small population of leukemia cells. We have demonstrated that multiple clonality of the N-ras gene is occasionally observed in leukemia with a monoclonal karyotype. These findings indicate that the N-ras mutations may not always be characterized simply by an accumulative process and that the activated N-ras gene alone is not sufficient to cause leukemia.
Acute Disease↗
Glibenclamide, a putative ATP-sensitive K+ channel blocker, inhibits coronary autoregulation in anesthetized dogs.
We tested the hypothesis that ATP-sensitive K+ channels are involved in the mechanism mediating coronary autoregulation in open-chest dogs. We perfused the left anterior descending coronary artery with arterial blood from an extracorporeal circuit and measured steady-state coronary blood flow (CBF) with stepwise changes in coronary perfusion pressure (CPP) between 50 and 150 mm Hg during an intracoronary infusion of vehicle or glibenclamide (a putative blocker of ATP-sensitive K+ channels). CBF was relatively stable over CPP between 50 and 110 mm Hg during vehicle infusion, indicating the presence of autoregulation at the CPP range. During glibenclamide infusion (10 micrograms.min-1 x kg-1), CBF progressively decreased with reduction in CPP below 110 mm Hg, whereas the CPP-CBF relation at CPP above 110 mm Hg was not altered by glibenclamide. The autoregulation index [1-(delta F/F)/(delta P/P), where F indicates CBF and P indicates CPP] was greater than 0 over the CPP range between 50 and 100 mm Hg during vehicle infusion and was less than 0 during glibenclamide infusion. Glibenclamide did not alter systemic arterial pressure, heart rate, left ventricular pressure, and changes in regional myocardial oxygen consumption associated with changes in CPP. In the absence of glibenclamide, the CPP-CBF relation was reproducible in the repeated studies for time control. These results suggest that ATP-sensitive K+ channels play an important role in mediating coronary autoregulation at the lower range of CPP in the blood-perfused dog heart.
Adenosine Triphosphate↗
[Analysis of chronic graft-versus-host disease in patients after bone marrow transplantation from HLA-identical siblings].
The incidence of chronic GVHD, involved organs, and outcome were evaluated in 59 patients aged 15 years or more who survived for 2 months or more after HLA-matched bone marrow transplantation. The incidence of chronic GVHD was 65.3%. The incidence was not correlated with the age at the time of transplantation, underlying disease, or the method to prevent GVHD (group treated with MTX alone and CSP-treated group). Concerning the degree of organ involvement, the CSP-treated group more frequently showed slight involvement and, especially a significantly lower incidence of dryness of the eyeballs. According to organs, the oral cavity was most frequently involved (87%), followed in order by the liver (74%), skin (52%), and the eyes (30%). The oral cavity alone was involved in 6 patients, and the outcome was generally good. The outcome of multi-organ involvement of chronic GVHD was poor, and the major causes of death were interstitial pneumonia and sepsis. Even of patients who did not develop chronic GVHD, 25% showed dryness of the eyeballs and oral cavity. Biopsy and careful observation of the clinical course are needed for diagnosing GVHD.
Adolescent↗
Bone marrow transplantation for chronic myelogenous leukemia in blastic phase using a phenotypically identical unrelated volunteer donor. Nagoya Bone Marrow Transplantation Group (NBMTG), Tokai Marrow Donor Bank (TMDB).
A 26-year-old male with chronic myelogenous leukemia in lymphoid blast crisis received a bone marrow transplant (BMT) from a phenotypically identical, mixed lymphocyte reaction (MLR)-weakly positive unrelated male volunteer donor. The volunteer was obtained from the Tokai Marrow Donor Bank (TMDB), which was established in Japan in 1989. This donor was selected from volunteer donors who were identical with our patient at the HLA-A,B loci, followed by matching at HLA-DQ, DR loci. On MLR testing, the donor's cells showed no response, but the patient's cells showed a low response to the donor's cells (relative response index 0.29). The patient showed rapid hemopoietic engraftment. He developed acute graft-versus-host disease (GVHD) with vesicle formation on palms and soles and mild liver damage, which were successfully treated with intravenous prednisolone 1 mg/kg per day. Although he also suffered from interstitial pneumonitis on day 64 and localized varicella-zoster infection on day 87, and has suffered from moderate stomatitis and dry skin characteristic of chronic GVHD, he is currently 22 months post-transplant with hematological remission and has a normal daily social life.
Adult↗
[A case report of multiple-transfused aplastic anemia complicated by hemolysis and delayed neutrophil recovery after bone marrow transplantation].
The authors report an 18-year-old female who developed severe hemolytic reaction and delayed neutrophil recovery after bone marrow transplantation (BMT) for aplastic anemia from her HLA-identical sibling. She had received much transfusion (61 units of red blood cells including 4 units of fresh whole blood from her parents and 350 units of platelets) for 12 years before BMT. To prevent graft rejection, she received an intensified preparative regimen consisted of cyclophosphamide 200 mg/kg followed by 5 Gy total body irradiation and 5 Gy total lymphoid irradiation. Prophylaxis for GVHD was short term methotrexate and cyclosporin-A. Despite of the removal of the red cells from the marrow, marked hemolytic reaction caused by antibodies directed to rh" (E) and hr' (c) red cell antigens was observed when rh" (E) and hr' (c) positive donor erythroid began to recover. The recovery of neutrophils, especially the fraction of segmented cells was also delayed. Flow cytometry showed that the serially collected patient's sera reacted to neutrophils derived from both patient's blood on the 64th post-transplant day and the donor's blood. The reactivity was strongest in pre-BMT sera. We conclude that residual antibodies sensitized before BMT are a major cause of these hematological problems.
Adolescent↗
[High-dose chemotherapy with autologous bone marrow transplantation as treatment for relapsing testicular cancer].
In testicular cancer the tumor shows a high response rate to chemotherapy with dose responsiveness. However, when it is treated with high-dose chemotherapy, myelosuppression is severe. To overcome this problem, autologous bone marrow transplantation has been attempted. This is a report of an 18-year-old man with advanced nonseminomatous testicular cancer (stage IIB, embryonal carcinoma and teratoma) with relapse after first course of therapy. He was treated with high-dose chemotherapy (etoposide 1,750 mg/m2, cisplatin 200 mg/m2, cyclophosphamide 60 mg/kg) and with autologous bone marrow transplantation. This patient has been in complete remission for more than 15 months without severe side effects or complications. We consider this a striking response to treatment in an early phase of relapsing testicular cancer.
Adolescent↗
[Delay in red blood cell recovery after major ABO incompatible bone marrow transplantation].
In 6 of 27 patients in whom major ABO incompatible marrow was transplanted, the recovery of red blood cells (reticulocyte count greater than or equal to 1%) required more than 50 days after the transplantation. In 3 of them, more than 100 days were required. High titers of pre-transplant anti-A or anti-B agglutinin correlated with the delay in red blood cell recovery (IgM: p less than 0.01, IgG: p less than 0.05). In all of the patients whose pre-transplant IgM titers were 4 or less, and whose IgG titers were 32 or less, the red blood cells recovered within 50 days. Administration of cyclosporine did not correlate with the delay in red blood cell recovery. All the patients finally developed red cell production within 8 months without any treatment.
ABO Blood-Group System↗