All-trans retinoic acid-induced multiple mononeuropathies.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S Motomura
Publications and source records attributed to S Motomura.
Modulation of AV nodal and Hisian conduction by changes in extracellular space.
Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block (n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block (n = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5-10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.
Acetylcholine↗
Primary esophageal T cell lymphoma.
A 60 year-old woman with primary esophageal T-cell lymphoma in clinical stage I(E)B is presented. Immunohistologic examination showed tumor cells to be positive for anti-LCA, anti-UCHL-1, anti-MT-1, anti-CD3 antibodies, and negative for anti-L26 antibody. Disappearance of dysphagia and improvement in esophageal findings were noted after 65 Gy of irradiation, and biopsy specimens from the esophagus revealed no malignancy. Primary esophageal lymphoma is extremely rare, and this T-cell lymphoma is only the fourth case reported in the literature.
Antineoplastic Combined Chemotherapy Protocols↗
[Donor leukocyte transfusion in a patient with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation: analysis of natural killer cell activity and T-cell receptor repertoire in bone marrow T cells that exhibited graft-versus-leukemia activity].
Hematologic relapse of chronic myeloid leukemia developed in 37-year-old man 255 days after allogeneic bone marrow transplantation. The patient received a donor lymphocyte transfusion (DLT) twice at a dose of 5 x 10(6)/kg T cells. He achieved complete cytogenetic response (CCR) 14 weeks after DLT, and has remained in a CCR state for 17 months. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. Natural killer (NK) cell activity was elevated. Also, analysis of the T cell receptor (TCR) repertoire disclosed oligoclonal expansion of T cells of the TCR V beta and J beta subfamilies. These observations provide evidence for the clonal expansion of allogeneic T cells that are capable of mediating antileukemic activity without causing GVHD.
Adult↗
Heterogeneity of glucose metabolism in corticobasal degeneration.
A positron emission tomography (PET) study on the regional cerebral glucose metabolism (rCMRglc) was performed in six patients with corticobasal degeneration (CBD). The clinical features included asymmetrical parkinsonism with apraxia, were related to the cerebral cortical and basal ganglionic dysfunction. An MRI study showed all cases to have asymmetrical atrophy in the front-parietal cortex contralateral to the dominantly affected limb; however, no case was pathologically verified. A PET study revealed three cases to have asymmetrical glucose hypometabolism in the parietal lobe and thalamus, which was compatible with the results of previous reports. However, two patients demonstrated symmetrical glucose hypometabolism in the frontal lobe, striatum and parietal lobe while one case had a diffuse hypometabolism, in spite of a marked asymmetry of the neurological findings. These results therefore suggest the heterogeneity of the glucose hypometabolism in CBD based on the PET findings.
Aged↗
Clinical significance of inhibitors in acquired von Willebrand syndrome.
Of 260 patients enrolled, 25 patients (9.6%) were associated with acquired von Willebrand syndrome (AvWS). We studied 25 patients with AvWS, retrospectively. AvWS was diagnosed by reduced levels of von Willebrand factor (vWF) (decrease of von Willebrand factor antigen [vWF:Ag] and von Willebrand ristocetin cofactor [vWF:RCoF]), a decrease of ristocetin-induced platelet agglutination (RIPA), sometimes decreased high-molecular-weight multimers, and prolonged bleeding time with neither prior nor family histories of bleeding problems and the evidence of normal vWF:RCoF in their families. The inhibitor of vWF was determined by mixing patient plasma with pooled normal plasma. Eight patients in this study had the inhibitors to vWF that were of the IgG class; the subclasses were IgG1 (7 cases) and IgG2 (1 case). Multimeric analysis of vWF showed selective loss of large multimers in most patients with AvWS similar to that of congenital type-2 von Willebrand disease (vWD). All inhibitors blocked ristocetin-mediated vWF binding to platelets. Five out of 6 IgGs evaluated here recognized the 39/34-kD fragment (residues 480/481-718) and Fragment III (residues 1-1365) that implied binding domain of glycoprotein Ib (GPIb), whereas 1 recognized Fragment I (residues 911-1365). A close relationship was found between the presence of the inhibitor and bleeding tendency. Of the 7 patients with inhibitors, 6 patients (86%) had a bleeding tendency, as well as 1 of the 15 patients without inhibitors (6%). The efficacy of treatment of underlying diseases and/or therapy with deamino D-arginine vasopressin (DDAVP) for the treatment of AvWS also depends on the presence of an inhibitor. Four of 8 patients with inhibitors (50%) had poor response to treatment of the underlying disease and/or therapy with DDAVP, as well as 1 of the 16 patients without inhibitors (6%). These results indicate that patients with AvWS developing inhibitors to vWF are likely to have bleeding problems and might be resistant to treatment of underlying diseases and/or therapy with DDAVP for bleeding to AvWS. We also showed evidence that intravenous immunoglobulin therapy (0.3 g/kg, 3 days) was effective to correct a hemostatic defect and manage severe bleeding in a patient with AvWS developing inhibitors. We might consider an additional treatment including expensive high-dose immunoglobulin therapy when uncontrollable bleeding is continued after the treatment of the underlying diseases and/or therapy with DDAVP.
Adult↗
Inhibition of P-glycoprotein and recovery of drug sensitivity of human acute leukemic blast cells by multidrug resistance gene (mdr1) antisense oligonucleotides.
To overcome the problem of multidrug resistance, we investigated the effectiveness of phosphrothioate antisense oligonucleotides (MDR1-AS) in suppressing multidrug resistance gene (mdr1) expression in drug-resistant acute myelogenous leukemia (AML) blast cells and the K562 adriamycin-resistant cell line K562/ADM. The percentage of cells with the mdr1 gene product P-glycoprotein (P-gp) was decreased from 100% to 26% by 20 micromol/L MDR1-AS in the K562/ADM cells, and from 48.1% to 10.2% by 2.5 micromol/L MDR1-AS in the AML blast cells. Western blot analysis also showed a decrease in the amount of P-gp in the MDR1-AS-treated K562/ADM cells. This effect was specific to MDR1-AS, and not observed with sense or random control oligonucleotides. The expression of mdr1 mRNA in K562/ADM and AML blast cells treated with MDR1-AS was decreased compared with the random control. Intracellular rhodamine retention and [3H]daunorubicin also increased after antisense treatment. Chemosensitivity to daunorubicin increased in MDR1-AS-treated blast cells up to 5.9-fold in the K562/ADM cells and 3.0- to 6.4-fold in the AML blast cells. The expression of mdr1 mRNA derived from colony cells decreased in the MDR1-AS-treated groups. No inhibitory effect of the oligonucleotides on normal bone marrow progenitors was observed. These findings suggest that MDR1-AS is useful to overcome multidrug resistance in the treatment of leukemia.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Unusual leukocytosis with eosinophilia by an allergic disease.
Explore the source record for details and available documents.
Adult↗
Progression of a myelodysplastic syndrome with trisomy 8 to acute lymphoblastic leukemia.
Explore the source record for details and available documents.
Adult↗
Isolated extramedullary relapse in knee joint after allogeneic bone marrow transplantation for Ph ALL.
We report a patient who relapsed in a patella and knee joint after allogeneic bone marrow transplantation (BMT) for Ph chromosome-positive acute lymphoblastic leukemia. The patient complained of pain and swelling of knee joint 14 months post-BMT. Fluid from the knee joint included leukemic cells consistent with the immunophenotype of blasts prior to BMT and also revealed the bcr/abl transcript by reverse-transcriptase polymerase chain reaction. Magnetic resonance imaging demonstrated an abnormal signal in the patella. Radiotherapy to the localized extramedullary lesion was successful and no bone marrow relapse has been detected cytologically and cytogenetically to date. This case suggests that the physician should be aware of unusual relapse sites of leukemia post-BMT.
Adult↗
Time course of a new ultrashort-acting beta-adrenoceptor-blocking drug, ONO-1101: comparison with those of esmolol and propranolol by using the canine isolated, blood-perfused heart preparations.
Time courses of beta-adrenoceptor-blocking actions of ONO-1101, a new cardioselective beta-blocker, were compared with those of esmolol and propranolol by using the isolated, blood-perfused sinoatrial node (SAN) and papillary muscle (PM) preparations of dogs. ONO-1101 per se given intraarterially (i.a.) in each nutrient artery did not affect basal sinoatrial rates (SARs; 99 +/- 2 beats/min, n = 7) in the SAN and developed tension (DT; 3.2 +/- 0.7 g, n = 7) of the PM preparations. Norepinephrine (NE) injected i.a. into the each artery induced increases in SAR (42 +/- 6 beats/min at 0.051 +/- 0.014 microg) and PMDT (2.9 +/- 0.4 g at 0.048 +/- 0.011 microg). The i.a. injections of NE were repeated every 3 min after i.v. bolus injections of ONO- 1101 into the support dog. NE-induced increases in SAR and PMDT were maximally inhibited 3 to 6 min after the i.v. injections of ONO-1101. Maximal percentage inhibitions by ONO-1101 of NE-induced increases in SAR were 54 +/- 6, 78 +/- 3, and 96 +/- 2% at 0.01, 0.1, and 1 mg/kg of the drug, respectively. Similarly, maximal percentage inhibitions by ONO-1101 of NE-induced increases in PMDT were 50 +/- 12, 93 +/- 2, and 100% +/- 0, respectively. The inhibition was quickly recovered; times required for 50% recovery (RT1/2) were 12 +/- 3. 17 +/- 3, and 32 +/- 10 min in the SAN preparation, and 13 +/- 3, 16 +/- 2, and 39 +/- 11 min in the PM preparations, after i.v. injections of 0.01, 0.1, and 1 mg/kg of ONO-1101, respectively. In comparison, maximal percentage inhibitions by esmolol of NE-induced increases in SAR were 45 +/- 5, 79 +/- 6, and 96 +/- 2%, and those in PMDT were 34 +/- 4, 75 +/- 5, and 97 +/- 1%, whereas the RT1/2 values were 11 +/- 2, 15 +/- 4, and 40 +/- 12 min in the SAN preparation, and 10 +/- 2, 16 +/- 7, and 27 +/- 6 min in the PM preparations, after i.v. injections of 0.01, 0.1, and 1 mg/kg of esmolol, respectively. In contrast, the maximal percentage inhibitions by an i.v. bolus injection of 0.1 mg/kg of propranolol of NE-induced increases in SAR and PMDT were 77 +/- 18% and 87 +/- 13% (n = 4). respectively. The maximal inhibitions were obtained 6-15 min after injections of propranolol and then slowly recovered only by 21% in the SAN and 8% in the PM preparations, even after 60 min. These results clearly demonstrate that ONO-1101 is an ultrashort-acting beta-blocker, but the recovery time is dose dependent, and that the beta-blocking action of ONO-1101 is almost similar to or slightly more potent (or both) than esmolol.
Adrenergic beta-Antagonists↗
A new approach to Pneumatosis cystoides intestinalis by target air-enema CT.
A 48-yr-old man was admitted to our hospital with abdominal discomfort and distension. A barium enema showed multiple radiolucent filling defects in the wall of the ascending colon. Colonic endoscopy revealed numerous round, polypoid masses covered with normal mucosa. These findings suggested Pneumatosis cystoides intestinalis. Target air-enema computed tomography was performed to make a final diagnosis, and demonstrated several gas collections covered with soft tissue in the wall of the ascending colon. This is the first reported case of Pneumatosis cystoides intestinalis in which multiple gas-filled cysts could be recognized by target air-enema computed tomography.
Abdominal Pain↗
Pharmacological properties of pteleprenine, a quinoline alkaloid extracted from Orixa japonica, on guinea-pig ileum and canine left atrium.
We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium. Although pteleprenine (0.1-1 microM) had no effect on the contraction of the ileum induced by acetylcholine at 10 microM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0.1-10 microM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 microM. From Schild analysis the pA2 of pteleprenine on the guinea-pig ileum was found to be 6.6. The contraction of the ileum induced by 10 microM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine receptors, was concentration-dependently suppressed by 10 nM-10 microM pteleprenine. In contrast, 0.1-10 microM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.
Acetylcholine↗
Induction of apoptosis in ovarian carcinoma cell line by gonadotropin-releasing hormone agonist.
Gonadotropin releasing hormone (GnRH) agonist suppresses the growth of the cancer cells in vitro. To evaluate the effect of a GnRH agonist (GnRHA) in ovarian carcinomas, we investigated the interactions of GnRHA with the KOC-2s human ovarian cancer cells. The addition of GnRHA (10(-8)-10(-6)M) produced an increase 20-30% in the number of cells (p < 0.05). GnRHA (10(-5) M) produced a slight, statistically insignificant decrease of < 10% in the cell count. No DNA fragmentation was produced by GnRHA (10(-8)-10(-6)M). However, GnRHA (10(-5)M) produced internucleosomal cleavage of DNA into fragments with multiples of 180 to 200 bp. This DNA "ladder" pattern is characteristic of apoptosis. The amount of Fas antigen was reduced by each concentration of GnRHa. The addition of GnRHA (10(-6)M and 10(-5)M) significantly increased the secretion of TNF-alpha (p < 0.001). The time- and dose-dependent effects of GnRHA might be confined to the KOC-2s cells as demonstrated by growth inhibitions and characteristic internucleosomal DNA fragmentation. However, the effects of GnRHA on secretion of TNF-alpha and the expression of Fas antigen differed. The present results provide a basis for future studies on the mechanism of apoptotic effect of GnRHA.
Apoptosis↗
Residual leukemic cell counts in the bone marrow at the end point of intensive induction therapy may be a prognostic factor for acute myeloblastic leukemia in adults.
Between January 1990 and May 1994, 59 previously untreated adult patients with acute myeloblastic leukemia (AML) were treated with a combination of behenoyl-cytosine-arabinoside (BHAC), daunorubicin (DNR), 6-mercaptopurine (6-MP) and prednisolone (PSL). Forty one patients (69.5%) achieved complete remission (CR). The Kaplan-Meier analysis revealed an actuarial probability for remaining in remission of 36% in patients who achieved remission and a survival of 29% in all patients at 5 years. A favorable factor relative to achieving CR was performance status (P=0.04). In addition the presence of 300 cells/microl or less of residual leukemic cell counts in the bone marrow at the end point of induction therapy tended to favor remission (P=0.06) using the multivariate analysis with a multiple logistic regression model. In addition the residual leukemic cells counts of less than 300/microl in the bone marrow at the end point of induction therapy was the most significant factor for durable remission (P=0.05) by the Cox's proportional hazard model. We concluded that residual leukemic cells counts in the bone marrow at the end point of intensive induction therapy is a valuable prognostic factor for adults receiving response-oriented individualized induction therapy for AML.
Adolescent↗
[Chronic myelogenous leukemia with long-term hypoplasia induced by alpha-interferon and hydroxyurea].
A 48-year-old woman was admitted with chronic myelogenous leukemia in November, 1996 and was treated with hydroxyurea (HU), because of marked leukocytosis; WBC 404,000/microliter. On January 29, 1997, administration of HU was stopped, and treatment of alpha-interferon (IFN alpha) was started with 6x 10(6)U, every day. However, the WBC count rose from 19,600/microliter to 56,800/microliter, and the combination of IFN and 2,000 mg of HU was started on February 4. The dose of HU was reduced to 500 mg on February 27, and the IFN administration was reduced to 3 times a week from April 4, because the WBC count was less than 10,000/microliter. Pancytopenia was revealed in May. The bone marrow biopsy specimen demonstrated marked hypoplastic changes, and chromosome analysis of bone marrow cells showed Philadelphia chromosome in all 20 metaphases. Treatment was interrupted for 7 months, but hematologic parameters did not recover. There were 9 cases reported in detail with bone marrow hypoplasia induced by IFN. One patient received IFN alone and 8 patients received anti-cancer drugs before treatment of IFN. We concluded that great care must be taken for IFN treatment of CML.
Antineoplastic Agents↗
[A case of severe hypernatremia complicated with rhabdomyolysis].
We report a 45-year-old male patient with severe hypernatremia followed by rhabdomyolysis and acute renal failure. He had developed hypernatremia for two years after a surgery for an intraventricular AVM involving the hypothalamic area, which was fed by the anterior cerebral artery. He was admitted to our hospital because of progressive muscle weakness. Because of loss of water intake due to impaired thirst sensation, he developed severe hypernatremia (191mEq/l) and marked rhabdomyolysis (CK 17,772 IU/l). He was treated with fluid supplement and hemodialysis for acute renal insufficiency. He had no thirst feeling. Blood studies revealed hyporeactivity to ADH in spite of marked hypernatremia and hyperosmorality. Therefore his condition was considered as adipsic hypernatremia. We concluded that rhabdomyolysis of this case was caused by severe hypernatremia. On reviewing the literature, only a few cases of rhabdomyolysis due to hypernatremia have been reported.
Acute Kidney Injury↗