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H Okawa

Publications and source records attributed to H Okawa.

At least 37 records · Page 2Linked to original sources

Comparison of initial distribution volume of glucose and plasma volume in thoracic fluid-accumulated patients.

OBJECTIVE: We have reported that initial distribution volume of glucose indicates the central extracellular fluid volume in the presence of fluid gain or loss. The purpose of this study was to describe changes in initial distribution volume of glucose, plasma volume determined by the indocyanine green dilution method (PV-ICG), and thoracic fluid content by thoracic electrical bioimpedance in patients with or without apparent thoracic fluid accumulation in the absence of pleural effusion. We also sought to test whether initial distribution volume of glucose rather than PV-ICG mirrors thoracic fluid content. DESIGN: Prospective, clinical study. SETTING: General intensive care unit. PATIENTS: Eleven consecutive patients with apparent thoracic fluid accumulation as judged by thoracic fluid content >0.05/ohm and underlying pathology and 20 consecutive acute myocardial infarction patients within 24 hrs after its onset were selected for study. None of the acute myocardial infarction patients had thoracic fluid content >0.05/ohm. INTERVENTIONS: Five grams of glucose and 25 mg of indocyanine green were administered simultaneously to calculate initial distribution volume of glucose and PV-ICG daily for the fluid-accumulated patients, and the same dosages were administered to the acute myocardial infarction patients immediately after their admission to the intensive care unit after percutaneous coronary angioplasty. Only the data on the day of the maximal and minimal thoracic fluid content in the fluid-accumulated patients were used for the study. The relationship between these two fluid volumes and thoracic fluid content was evaluated in the two patient groups. MEASUREMENTS AND MAIN RESULTS: Initial distribution volume of glucose and thoracic fluid content rather than PV-ICG and thoracic fluid content moved together in the same direction in each fluid-accumulated patient. Neither pulmonary artery occlusion pressure, central venous pressure, nor PV-ICG produced a better correlation with cardiac index when compared with initial distribution volume of glucose in patients with or without thoracic fluid accumulation. CONCLUSIONS: We suggest that initial distribution volume of glucose rather than PV-ICG is a better indicator of the intrathoracic blood volume status, even although intravenously administered glucose cannot stay in the intravascular compartment.

APACHE↗

[Early detection of hypoxia with BIS monitoring during percutaneous cardiopulmonary support].

We report a patient in whom hypoxia developed during percutaneous cardiopulmonary bypass (PCPS) and was detected with the lowering of the bispectral index (BIS) values. A 7-yr-old boy was managed with PCPS for the treatment of cardiogenic shock after cardiac surgery. His circulation was dependent on PCPS and pulse pressure was nearly zero. Signals by pulse oxymetry were undetectable and periodical blood gas analysis was performed to confirm proper oxygenation. BIS was monitored, and a gradual decrease in the value was observed. Careful observation also revealed darkening of the blood in the PCPS circuit and blood gas analysis showed severe hypoxia. Oxygen concentration of the gas to a PCPS oxygenator was increased immediately and new PCPS circuit was prepared. It took almost two minutes to exchange the circuit. Near circulatory arrest might have occurred during the procedure and BIS and suppression ratio (SR) became below 10 and above 90, respectively. Both returned to the previous values 30 min after the replacement of the circuit. Severe hypoxia, otherwise overlooked, was detected with BIS monitoring and BIS reflected the circulatory status of the patient, especially of the brain. This monitoring is useful to confirm proper oxygenation during PCPS.

Cardiopulmonary Bypass↗

A Cu(II)-mediated C-H oxygenation of sterically hindered tripyridine ligands to form triangular Cu(II)3 complexes.

Two sterically hindered tris-pyridyl methane ligands, tris(6-methyl-2-pyridyl)methane (L1) and bis(6-methyl-2-pyridyl)pyridylmethane (L2), are newly synthesized. Under aerobic conditions, Ln (n = 1 or 2) reacts with CuX2 (X = Cl or Br), oxygenated at the methine position to LnOH or LnOMe. The former alcoholate ligand creates trinuclear Cu(II) complexes [Cu3(X)(LnO)3](PF6)2 [(X, n) = (Br, 1) 1, (C1, 1) 2, (Br, 2) 3, or (C1, 2) 4] in which the alkoxide oxygen atoms bridge copper centers. The crystal structures of 1-4 are presented along with their magnetic susceptibility data. The weak antiferromagnetic coupling between the Cu(II) centers in this trinuclear arrangement is due to weak interaction of the magnetic orbitals (dz2) which are oriented along three alternate sides in a hexagon of the Cu3O3 core in 1-4. Under anaerobic conditions, L1 reacts with CuBr2 to form a square pyramidal complex [CuL1Br2] (9) with the ligand facially capping. [Cu(Br)2(L1OMe)] (10) was obtained after the suspension of 9 in MeOH was stirred under air for 48 h. In the presence of cyclohexene, 9 is converted to [Cu(Br)(L1)]m (m = 1 or 2) 5 quantitatively to give trans- 1,2-dibromocyclohexane, indicating that Br2 is generated during the reaction. The FAB MS spectrum of [18O]-1 prepared by the reaction of L1 with CuBr2 under 18O2 shows that the ligand of [18O]-1 is L1(18O-.) L1(18OH), L1OCD3, and bis(6-methyl-2-pyridyl) ketone were obtained from reaction of L1 with CuBr2 in CD3OD under 18O2. These results indicate that the origins of the O atom in L1OH and L1OMe are O2 and MeOH, respectively. On the basis of these results, a mechanism of the oxygenation of L1 in the present system will be proposed.

Journal Article↗

The initial distribution volume of glucose rather than indocyanine green derived plasma volume is correlated with cardiac output following major surgery.

OBJECTIVES: To determine whether the initial distribution volume of glucose (IDVG) rather than plasma volume or blood volume is correlated better with cardiac output during the 4 days following major surgery. DESIGN AND SETTING: Prospective clinical investigation in the general intensive care unit of a university hospital. PATIENTS AND METHODS: 31 consecutive patients who underwent radical surgery for esophageal carcinoma were enrolled. Continuous thermodilution cardiac output monitor was placed in the operating room. Indocyanine green (ICG; 25 mg) and glucose (5 g) were administered simultaneously to calculate IDVG and plasma volume determined using the ICG dilution method. Blood volume was also calculated from plasma volume ICG and hematocrit. Those volumes were measured on admission to the ICU and daily on the first 3 postoperative days. The relationships between each volume and cardiac index (CI), and between routine clinical variables and CI were evaluated. RESULTS: IDVG had a linear correlation with CI in the early postoperative days (r = 0.71, n = 124, p < 0.000001). Measurements of neither the plasma volume nor the blood volume yielded a better correlation with CI than did IDVG (r = 0.45, n = 124, p < 0.000001, and r = 0.23, n = 124, p < 0.01, respectively). No correlation was found between pulmonary artery wedge pressure and CI or between central venous pressure and CI. CONCLUSIONS: Our results indicate that IDVG rather than intravascular volume is correlated with cardiac output. We suggest that IDVG has potential as an alternative indicator of cardiac preload following major surgery.

Adult↗

Characterization of [Nphe(1)]nociceptin(1-13)NH(2), a new selective nociceptin receptor antagonist.

1.. Nociceptin (orphanin FQ) is a novel neuropeptide capable of inducing a variety of biological actions via activation of a specific G-protein coupled receptor. However, the lack of a selective nociceptin receptor antagonist has hampered our understanding of nociceptin actions and the role of this peptide in pathophysiological states. As part of a broader programme of research, geared to the identification and characterization of nociceptin receptor ligands, we report that the novel peptide [Nphe(1)]nociceptin(1-13)NH(2) acts as the first truly selective and competitive nociceptin receptor antagonist and is devoid of any residual agonist activity. 2. [Nphe(1)]nociceptin(1-13)NH(2) binds selectively to recombinant nociceptin receptors expressed in Chinese hamster ovary (CHO) cells (pK(i) 8.4) and competitively antagonizes the inhibitory effects of nociceptin (i) on cyclic AMP accumulation in CHO cells (pA(2) 6.0) and (ii) on electrically evoked contractions in isolated tissues of the mouse, rat and guinea-pig with pA(2) values ranging from 6.0 to 6.4. 3. [Nphe(1)]nociceptin(1-13)NH(2) is also active in vivo, where it prevents the pronociceptive and antimorphine actions of intracerebroventricularly applied nociceptin, measured in the mouse tail withdrawal assay. Moreover, [Nphe(1)]nociceptin(1-13)NH(2) produces per se a dose dependent, naloxone resistant antinociceptive action and, at relatively low doses, potentiates morphine-induced analgesia. 4. Collectively our data indicate that [Nphe(1)]nociceptin(1-13)NH(2), acting as a nociceptin receptor antagonist, may be the prototype of a new class of analgesics.

Analgesics, Opioid↗

Interaction of local anaesthetics with recombinant mu, kappa, and delta-opioid receptors expressed in Chinese hamster ovary cells.

Local anaesthetics potentiate epidural or intrathecal opioid analgesia via a poorly defined mechanism. In this study, we have examined the interaction of local anaesthetics (lidocaine, bupivacaine and its optical isomers, tetracaine, procaine and prilocaine) with recombinant mu-, kappa-, and delta-opioid receptors expressed in Chinese hamster ovary cells (CHO-mu, kappa, and delta, respectively). Lidocaine produced a concentration-dependent displacement of radiolabelled opioid antagonist [3H]diprenorphine ([3H]DPN) binding with the following rank order of inhibitor constant (Ki): kappa (210 microM) > mu (552 microM) > delta (1810 microM). Procaine, prilocaine, tetracaine and bupivacaine also displaced [3H]DPN binding in CHO-mu with Ki values of 244, 204, 43 and 161 microM respectively. Lidocaine produced a concentration-dependent and naloxone-insensitive inhibition of cAMP formation in all cell lines including untransfected cells. Concentration producing 50% inhibition of maximum was mu, 1.32 mM; kappa, 2.41 mM; delta, 1.27 mM; untransfected, 2.78 mM. When lidocaine (300 microM) was co-incubated with spiradoline (kappa-selective) and [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO mu-selective) in CHO-kappa and mu cells we did not observe an additive interaction for cAMP formation. In contrast, there was an apparent inhibitory action of the combination at the kappa receptor. This study suggests that clinical concentrations of local anaesthetics interact with mu and kappa but not delta opioid receptors. As there was no synergism between local anaesthetics and opioids we suggest that the interaction of these agents in the clinical setting does not occur at the cellular level.

Anesthetics, Local↗

Smoking decreases alveolar macrophage function during anesthesia and surgery.

BACKGROUND: Smoking changes numerous alveolar macrophage functions and is one of the most important risk factors for postoperative pulmonary complications. The current study tested the hypothesis that smoking impairs antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery. METHOD: The authors studied 30 smoking and 30 nonsmoking patients during propofol-fentanyl general anesthesia. Alveolar immune cells were harvested by bronchoalveolar lavage immediately and 2, 4, and 6 h after induction of anesthesia and at the end of surgery. The types of alveolar immune cell and macrophage aggregation were determined. The authors measured opsonized and unopsonized phagocytosis. Microbicidal activity was determined as the ability of the macrophages to kill Listeriamonocytogenes directly. Finally, RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin 1beta, 6, and 8, interferon gamma, and tumor necrosis factor alpha were measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. RESULTS: The fraction of aggregated macrophages increased significantly over time in both groups, whereas phagocytosis of opsonized and nonopsonized particles and microbicidal activity of alveolar macrophages decreased significantly. The changes, though, were nearly twice as great as in patients who smoked. Gene expression of all proinflammatory cytokines in alveolar immune cells except interleukin 6 increased 2- to 20-fold over time in both groups. The expression of interleukin 1beta, interferon gamma, and tumor necrosis factor alpha, however, increased only half as much in smokers as in nonsmokers. CONCLUSION: Smoking was associated with macrophage aggregation but markedly reduced phagocytic and microbicidal activity-possibly because expression of proinflammatory cytokines was reduced in these patients. Our data thus suggest that smokers may have a limited ability to mount an effective pulmonary immune defense after anesthesia and surgery.

Anesthesia, General↗

Mutations of the WASP gene in 10 Japanese patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia.

Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency, and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study, we identified mutations of the WASP gene in 10 Japanese patients from 9 unrelated families with WAS/XLT. All XLT patients (n = 3) and one WAS patient had a missense mutation at the PH domain of WASP. Two WAS patients had nonsense mutations. One WAS patient had exon 8 skipping caused by one nucleotide deletion at the acceptor site of intron 7. Three WAS patients had genomic deletions; one of the three had a large genomic deletion involving exons 3 to 7. Codons 45 and 86 seem to be the hot spots of the WASP mutation, because missense mutations in these codons have been reported previously in several WAS/XLT patients in addition to the patients in this report, and patients with the same mutation show a similar clinical phenotype. All other mutations are novel, indicating that the mutations of WASP are heterogeneous. EB virus-transformed cell lines from XLT patients expressed nearly normal amounts of WASP, whereas those from typical WAS patients expressed almost undetectable amounts of WASP. We conclude that the analysis of gene mutation and protein expression of WASP are useful together in assessing the severity of WAS.

Adult↗

Isokinetic strength of elbow extensor muscles correlates with race time in wheelchair half marathon racers.

It has been reported that grasping power and isometric muscle strength of elbow extensors in fine wheelchair racers were greater than the poor racers in the wheelchair full marathon. The purpose of the present study was to investigate the relationship between muscle strength of elbow extensors and flexors and the race time in wheelchair half marathon race. Four wheelchair half marathon racers who completed the half marathon division of the 16th Oita International Wheelchair Marathon (OIWM) in 1996 participated in the present study. The day before the race, all subjects reported to the training room and the isokinetic muscle strength of elbow extensor and flexor muscle groups was measured at angular speeds of 60 degrees, 120 degrees and 240 degrees/sec using the isokinetic dynamometer. There was a significant correlation between race time and isokinetic muscle strength of the elbow extensors at 60 degrees, 120 degrees and 240 degrees/sec, but not flexor muscles. Our findings suggest that increased muscle strength of elbow extensors may improve the race time in wheelchair half marathon race.

Adult↗

Static exercise-induced increase in blood pressure in individuals with cervical spinal cord injury.

OBJECTIVE: To compare the pressor response to static exercise in subjects with cervical spinal cord injury (SCI) at the C6 to C8 level with that in able-bodied control subjects. In these SCI subjects, the descending supraspinal sympathetic neurons and afferent pathways from the contracting muscles to peripheral vessels via the medullary cardiovascular center are damaged. DESIGN: Mean arterial blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, renin activity, vasopressin, aldosterone, and human atrial natriuretic peptide were measured during a 2-minute period of sustained contraction of elbow flexor group muscle in 7 SCI subjects and 7 age-matched able-bodied control subjects. RESULTS: Static exercise resulted in a significant increase in mean blood pressure (p<.05) in both SCI subjects (pre-exercise. 74.7+/-2.2 mm Hg; static exercise, 81.9+/-4.1 mm Hg) and control subjects (pre-exercise, 101.0+/-4.2 mm Hg; static exercise, 117.0+/-4.9 mm Hg). In SCI subjects, there was no change in heart rate during exercise, whereas in control subjects heart rate increased during exercise (p<.05) (pre-exercise, 8.7+/-3.8 beats/min: static exercise, 76.0+/-3.1 beats/min). There were no significant changes in the hormone levels in the SCI subjects throughout the experiment. CONCLUSION: The significant increase in mean blood pressure observed in the present study indicates the presence of peripheral control from muscle receptors and evoked pressor response during static exercise in SCI subjects.

Adult↗

EBV infection induced transformation of benign T lymphoproliferative state in patient with chronic active EBV infection into malignant lymphoma: implication of EBV infection as additive oncogenic factor in tumorigenesis.

An 11-year-old girl with chronic EBV (Epstein-Barr virus) infection, who later developed malignant lymphoma in the lung, is reported. She had an increased number of V alpha2, V beta8, CD3, CD4, and HLADR positive activated lymphocytes (20-30% of total lymphocytes) in peripheral blood. One year later, she developed lymphoma in the lung, which was V alpha2, V beta8, CD3, CD4, HLADR and IL2Rbeta positive. At that time, the population in the peripheral blood increased up to 40%, but there was no evidence of lymphoma in the bone marrow. In situ hybridization revealed lymphoma cells were EBER-1 positive but gp350/220 and LMP mRNA negative. The EBV genome was detected in the tumor, but not in the peripheral T cells. Clonal analysis of the lymphoma cells revealed monoclonal rearrangement of the TcRbeta and gamma gene, however, investigation of the terminal repeat of EBV gene did not show the monoclonal pattern. These results indicate that infection of EBV into clonally activated T cells was related with transformation from benign lymphoproliferative disease to malignant lymphoma in this patient.

Child↗

Comparison of the effects of [Phe1psi(CH2-NH)Gly2]nociceptin(1-13)NH2 in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors.

Nociceptin(NC) is the endogenous ligand for the opioid receptor like-1 receptor (NC-receptor). [Phe1(psi)(CH2-NH)Gly2]Nociceptin(1-13)NH2 ([F/G]NC(1-13)NH2) has been reported to antagonize NC actions in peripheral guinea-pig and mouse tissues. In this study, we investigated the effects of a range of NC C-terminal truncated fragments and [F/G]NC(1-13)NH2 on NC receptor binding, glutamate release from rat cerebrocortical slices (rCX), inhibition of cyclic AMP accumulation in CHO cells expressing the NC receptor (CHO(NCR)) and electrically evoked contractions of the rat vas deferens (rVD). In radioligand binding assays, a range of ligands inhibited [125I]-Tyr14-NC binding in membranes from rCX and CHO(NCR) cells. As the peptide was truncated there was a general decline in pKi. [F/G]NC(1-13)NH2 was as potent as NC(1-13)NH2. The order of potency for NC fragments to inhibit cyclic AMP accumulation in whole CHO(NCR) cells was NCNH2> or =NC=NC(1-13)NH2>NC(1-12)NH2> >NC(1-11)NH2. [F/G]NC(1-13)NH2 was a full agonist with a pEC50 value of 8.65. NCNH2 and [F/G]NC(1-13)NH2 both inhibited K+ evoked glutamate release from rCX with pEC50 and maximum inhibition of 8.16, 48.5+/-4.9% and 7.39, 58.9+/-6.8% respectively. In rVD NC inhibited electrically evoked contractions with a pEC50 of 6.63. Although [F/G]NC(1-13)NH2, displayed a small (instrinsic activity alpha = 0.19) but consistent residual agonist activity, it acted as a competitive antagonist (pA2 6.76) in the rVD. The differences between [F/G]NC(1-13)NH2 action on central and peripheral NC signalling could be explained if [F/G]NC(1-13)NH2 was a partial agonist with high strength of coupling in the CNS and low in the periphery. An alternative explanation could be the existence of central and peripheral receptor isoforms.

Animals↗

Kinetic factors determining wheelchair propulsion in marathon racers with paraplegia.

OBJECTIVE: To assess the different factors that determine the propulsion of wheelchair in long distance racers with spinal cord injuries. DESIGN AND METHODS: Nine highly handicapped men who competed at the Oita International Wheelchair Marathon in 1995, participated in this study. Subjects performed steady and exhaustive wheelchair propulsion at their optimal speed on wheelchair rollers in a laboratory setting during a 5-min period. Movements of the trunk and arms were filmed by a video camera then analyzed kinetically using a two-dimensional analysis system. In order to determine the actual pushing time and angle of wheelchair, we measured the duration between hand contact and hand release from handrim. SETTING: Department of Rehabilitation Medicine University of Occupational and Environmental Health, Japan. RESULTS: The push time, cycle time, total push time, and angular velocity did not relate with the race time or wheelchair velocity. However, the total push angle correlated significantly (P<0.01) with the race time and wheelchair velocity. Improvement of the pushing angular velocity and pushing duration did not contribute to the race time. CONCLUSION: The skilful wheelchair propulsion in long distance racing depends on the total push angle. Improvement of the total push angle should be achieved by both prolongation of the total push time and increased pushing angular velocity.

Adult↗

WASP is involved in proliferation and differentiation of human haemopoietic progenitors in vitro.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, immunodeficiency and eczema. X-linked thrombocytopenia (XLT) is a mild form of WAS with isolated thrombocytopenia. Both phenotypes are caused by mutation of the Wiskott-Aldrich syndrome protein (WASP) gene. In this study we investigated the role of WASP in the differentiation of CD34-positive (CD34+) cells isolated from the bone marrow of patients with WAS (n = 5) or with XLT (n = 4). Megakaryocyte colony formation was significantly decreased in patients with WAS when compared with normal controls. The formation of granulocyte-macrophage colonies and erythroid bursts were also decreased in WAS patinets. In contrast, in XLT patients, formation of all these colonies was normal. However, in vitro proplatelet formation of megakaryocytes induced by thrombopoietin was markedly decreased in both XLT and WAS. Electron microscopic examination revealed that megakaryocytes obtained from WAS or XLT patients grown in vitro had abnormal morphologic features, which seemed to be caused by defective actin cytoskeletal organization, including labyrinth-like structures of the demarcation membrane system and deviated distribution of the alpha-granules and demarcation membrane system. These observations indicate that WASP is involved in the proliferation and differentiation of CD34+ haemopoietic progenitor cells probably by its participation in signal transduction and in the regulation of the cytoskeleton.

Blood Platelets↗

Stereoselective interaction of ketamine with recombinant mu, kappa, and delta opioid receptors expressed in Chinese hamster ovary cells.

BACKGROUND: The authors examined the interaction of ketamine with recombinant mu, kappa, and delta opioid receptors and recombinant orphan opioid receptors expressed in Chinese hamster ovary cells (CHO-mu, CHO-kappa, CHO-delta, and CHO(ORL1), respectively). METHODS: CHO-mu, CHO-kappa, and CHO-delta membranes were incubated with the opioid receptor radioligand [3H]diprenorphine at room temperature. Ketamine (racemic, R(-) and S(+)) was included at concentrations covering the clinical range. CHO(ORL1) membranes were incubated with [125I]Tyr(14)nociceptin and racemic ketamine at room temperature. The effects of racemic ketamine and selective opioid receptor agonists (mu: [D-Ala2, MePhe4, Gly(ol)5] enkephalin (DAMGO); kappa: spiradoline or delta: [D-pen2, D-pen5] enkephalin (DPDPE)) on forskolin-stimulated cyclic adenosine monophosphate formation also were examined. Data are mean +/- SEM. RESULTS: Racemic ketamine increased the radioligand equilibrium dissociation constant for [3H]diprenorphine from 85+/-5 to 273+/-11, 91+/-6 to 154+/-16, and 372+/-15 to 855+/-42 pM in CHO-mu, CHO-kappa, and CHO-delta, respectively. The concentration of radioligand bound at saturation was unaffected. In CHO-mu and CHO-kappa cells, racemic ketamine did not slow the rate of naloxone-induced [3H]diprenorphine dissociation. Ketamine and its isomers also displaced [3H]diprenorphine binding to mu, kappa, and delta receptors in a dose-dependent manner, with pKi values for racemic ketamine of 4.38+/-0.02, 4.55+/-0.04, and 3.57+/-0.02, respectively. S(+)-ketamine was two to three times more potent than R(-)-ketamine at mu and kappa receptors. Racemic ketamine displaced [125I]Tyr(14)nociceptin with an estimated affinity constant of 0.5 mM. Racemic ketamine inhibited the formation of cyclic adenosine monophosphate (naloxone insensitive) in a dose-dependent manner (concentration producing 50% inhibition approximately 2 mM) in all cell lines, including untransfected CHO cells. Ketamine (100 microM) reversed DAMGO (mu) and spiradoline (kappa) inhibition of formation of cyclic adenosine monophosphate. CONCLUSIONS: Ketamine interacts stereoselectively with recombinant mu and kappa opioid receptors.

Animals↗

Clinical and biological aspects of acute lymphoblastic leukemia in 62 infants: retrospective analysis of the Tokyo Children's Cancer Study Group.

BACKGROUND: As a first step to formulate a new treatment strategy for refractory acute lymphoblastic leukemia (ALL) in infants, clinical results and immunophenotypic and cytogenetic data were analyzed and compared with those from overseas. METHODS: There were 62 infants with ALL who were treated between 1977 and 1995 at 30 institutions affiliated with the Tokyo Children's Cancer Study Group. Clinical and laboratory data obtained from these infants (all under 1 year of age) were retrospectively studied. RESULTS: The morphological diagnoses were FAB-L1 for 51 patients (82.2%) and FAB-L2 for 11 patients (17.8%). Hepatomegaly and splenomegaly were found in 40 (70.0%) and 40 patients (68.3%), respectively. The mean (+/- SEM) leukocyte count at diagnosis was 205,900 +/- 35,700/microL. The involvement of the central nervous system was evident in nine of 36 patients who were subjected to lumbar puncture, while three of these nine patients were free of neurological symptoms at diagnosis. Thirty-one patients (55.4%) were CD10 negative and 14 (25.0%) were CD10 positive. Thirty-one of 47 patients (65.9%) exhibited chromosomal abnormalities, including 28 patients (59.6%) with 11q23 abnormalities. Rearrangements in the MLL gene were found in nine of 13 infants (69.2%) examined. Translocation of 11q23 and/or MLL gene rearrangement (11q23/MLL) was significantly associated with the absence of the CD10 antigen. Hyperleukocytosis of more than 50,000/microL and 11q23/MLL gene rearrangements were related to a poor prognosis. The probability of an event-free survival in 62 infants was 13.1 +/- 4.8% at 48 months. CONCLUSIONS: New therapeutic strategies and large-scale cooperative prospective trials are needed to improve the prognosis of ALL in infants.

Chromosomes, Human, Pair 11↗

Rat central ORL-1 receptor uncouples from adenylyl cyclase during membrane preparation.

Nociceptin/orphanin FQ is the endogenous agonist of the orphan receptor ORL-1. In this study, we sought to examine any possible regional differences of nociceptin binding using [125I]Tyr14-nociceptin, and of agonist induced inhibition of cAMP formation in membranes prepared from cerebrocortex, cerebellum and brainstem. The binding of [125I]Tyr14-nociceptin was concentration-dependent and saturable, with Bmax and pKd (pM) values of 179.7+/-15.3 fmol/mg protein and 10.26+/-0.09 (60.0), 12.4+/-1.8 fmol/mg protein and 10.44+/-0.07 (37.0), 52.3+/-0.8 fmol/mg protein and 10.16+/-0.08 (74.0) in cerebrocortical, cerebella and brainstem membranes, respectively. In all preparations, nociceptin up to 1 microM failed to inhibit basal and forskolin stimulated cAMP formation. In all tissues forskolin stimulated and nabilone (acting at the central cannabinoid receptor) inhibited cAMP formation. Collectively these data report regional differences in ORL-1 receptor expression and that these receptors uncouple during membrane preparation.

Animals↗