[Study of anti-cancer drug delivery into the organs during resection of esophagus--an experimental study].
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Animals↗
Biomedical subjects
M Osawa
Publications and source records attributed to M Osawa.
[False positive FDP test associated with malignant lymphoma].
We present a man with non-Hodgkin's lymphoma who had false positive FDP test results and who had monoclonal IgM and IgG. At admission, laboratory examinations showed elevated FDP levels and prolonged PT and APTT, which did not improve by anti-coagulation therapy. Although coagulation system data returned to normal levels after steroid pulse therapy, the FDP level increased. Positive pregnancy test and results of dilution analyses on FDP assay yielded a diagnosis of false positive FDP test results due to serum latex agglutinin. The addition of anti-immunoglobulin antibody inhibited latex agglutination by serum. FDP levels positively correlated with serum IgM concentrations. These data suggest that the false positive FDP test in this case was due to latex agglutination by monoclonal IgM.
Connectin↗
Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in mechanically stimulated vascular endothelial cells.
Fluid flow triggers signal transducing events, modulates gene expression, and remodels cytoskeletal structures in vascular endothelial cells (ECs). However, the primary steps of mechanoreception are still unknown. We have recently reported that a glycoprotein is rapidly tyrosine-phosphorylated in bovine ECs exposed to fluid flow or osmotic shock. Here were cloned a 3.4 kb cDNA encoding this protein and found that this was bovine PECAM-1. The tyrosine-phosphorylation level of PECAM-1 immunoprecipitated from mechanically stimulated bovine or human ECs increased. The PECAM-1 phosphorylation was not induced by reagents that triggered Ca2+ mobilization in ECs. An autophosphorylatable band comigrating with c-Src was co-immunoprecipitated with anti-PECAM-1, and c-Src phosphorylated and bound to a GST fusion protein containing the PECAM-1 cytoplasmic domain. A spliced mRNA form lacking amino acid residues 703-721 in the cytoplasmic domain was also expressed in bovine ECs, c-Src neither phosphorylated nor bound to the fusion protein containing the spliced PECAM-1 cytoplasmic domain which lacked one (Tyr 713) of the six tyrosine residues in the PECAM-1 cytoplasmic domain. These results suggest that the YSEI motif containing Tyr 713 is the Src phosphorylation/binding site. Our study is the first demonstration of inducible tyrosine phosphorylation of PECAM-1 and suggests involvement of PECAM-1 and Src family kinases in the sensing/signal transduction of mechanical stimuli in ECs.
Amino Acid Sequence↗
alpha-Galactosylceramide (AGL-517) treatment protects mice from lethal irradiation.
AGL-517 (AGL) has an alpha-galactosylceramide structure and is a derivative of agelasphin-9b, which in turn is isolated from Agelas mauritianus and has immunomodulating activity. When administered before irradiation, AGL has been found to increase survival rates in lethally irradiated mice. In this study, we found that a single injection of AGL administered within 2 hours of lethal irradiation resulted in the long-term survival of mice without bone marrow transplantation. Peripheral blood hematology showed that AGL administration accelerated the recovery of hematopoietic parameters, including reticulocytes and red and white blood cells. Recovery of platelets was moderate. In addition, AGL significantly increased the number of endogenous colony forming units-spleen (E-CFU-S). AGL itself displayed no colony-stimulating activity, but AGL-stimulated spleen cell-conditioned medium (AGL-SCM) promoted the proliferation and differentiation of bone marrow mononuclear cells from normal mice and Lin marrow cells from 5-fluorouracil (5-FU)-treated mice. Using suitable assay systems, we analyzed cytokines in AGL-SCM and found significant increases in stem cell factor (SCF), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-6 levels compared with control SCM. Additionally, using immunoenzymetric assays, we assessed serum levels of these factors in AGL-treated mice after lethal irradiation. The serum concentrations of IL-3, GM-CSF, and IL-6 were substantially elevated, the maximum levels being reached within 2 hours of injection. Despite inducing the in vitro increase in SCF, AGL did not elevate serum SCF levels. However, certain levels of SCF (approximately 5 ng/mL) were detected in mouse serum regardless of irradiation or AGL treatment. When irradiated mice were given a cytokine cocktail composed of recombinant murine (rm) IL-3, rmGM-CSF, and recombinant human (rh) IL-6 three times a day for 6 days (1 microg of each factor per mouse per day) starting 2 hours after irradiation, 60% of the mice achieved 50-day survival. The radioprotective effect of AGL can be attributed, in part, to the cooperative effect of the cytokines induced by AGL in vivo. These findings suggest that AGL may be a useful in treating radiation-induced hematopoietic damage.
Animals↗
Experimental studies on effects of barbiturate on electroencephalogram and auditory brain-stem responses.
The effects of pentobarbital on electroencephalogram (EEG) and auditory brain-stem response (ABR) were evaluated in 13 Japanese white male rabbits, divided into two groups, 7 and 6, respectively. After baseline evoked responses were obtained, pentobarbital was infused intravenously at 60 mg/kg/h in both groups. EEGs and ABR were recorded with 15 min intervals. When the blood concentration of pentobarbital reached therapeutic levels (2.0-5.0 mg/dL), cortical and hippocampal EEGs became isoelectric. Although the appearance of ABR waves was significantly delayed, each wave was clearly observed in spite of isoelectric EEG levels. The rabbits in one group were killed at that time, and their brains were removed to determine the concentration of pentobarbital in the brain tissue. In another group, pentobarbital was additionally infused at the rate of 120 mg/kg/h. Although the waves (II-IV) of the ABR gradually disappeared with increasing dosage, wave I was present until just prior to cardiac arrest. It is considered that the persistency of ABR at high doses of barbiturates is characteristic of patients in deep barbiturate coma. Therefore, at the diagnosis of brain death, there is no necessity to consider the half-life of the barbiturate, even if an excessive amount of barbiturate remains in the brain. In this study, pentobarbital concentration in the brain was nearly equal to the concentration in the blood. However, it is estimated that a large amount of barbiturate is accumulated in the brain of a patient after brain death because the blood flow in the brain is stagnant.
Animals↗
Prenatal diagnosis of Fukuyama type congenital muscular dystrophy by polymorphism analysis.
Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive disorder characterized by a combination of primary muscular dystrophy of early infantile onset and brain malformation (lissencephaly type II). The identification of the FCMD gene locus at 9q31 opened the theoretical possibility of prenatal diagnosis. The authors conducted prenatal diagnosis in two unrelated FCMD families by analysis using nine microsatellite CA-repeat polymorphic markers flanking the FCMD locus, and calculated phenotype probabilities in fetuses with a computer program, LINKAGE. The fetus in family 1 showed a 99% probability of being healthy either as a normal homozygote or a heterozygote carrier and was born without signs of FCMD. In family 2, the fetus was diagnosed to have FCMD with at least 86% probability. The parents of this family decided to terminate the pregnancy and an abortus showed brain malformations characteristic of an FCMD fetus.
Brain↗
Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell.
Hematopoietic stem cells (HSCs) supply all blood cells throughout life by making use of their self-renewal and multilineage differentiation capabilities. A monoclonal antibody raised to the mouse homolog of CD34 (mCD34) was used to purify mouse HSCs to near homogeneity. Unlike in humans, primitive adult mouse bone marrow HSCs were detected in the mCD34 low to negative fraction. Injection of a single mCD34(lo/-), c-Kit+, Sca-1(+), lineage markers negative (Lin-) cell resulted in long-term reconstitution of the lymphohematopoietic system in 21 percent of recipients. Thus, the purified HSC population should enable analysis of the self-renewal and multilineage differentiation of individual HSCs.
Animals↗
In vivo self-renewal of c-Kit+ Sca-1+ Lin(low/-) hemopoietic stem cells.
The long term marrow-repopulating ability of mouse bone marrow c-Kit+ Sca-1+ Lin(low/-) cells was studied. Injection of as few as 100 c-Kit+ Sca-1+ Lin(low/-) cells could rescue a lethally irradiated recipient mouse and reconstitute both myeloid and lymphoid cells in their peripheral blood for at least 10 mo. When limiting dilution analysis was performed in the presence of host-derived rescue cells, as low as five c-Kit+ Sca-1+ Lin(low/-) cells were shown to be capable of repopulating lymphohemopoietic cells. Subsequently, we examined whether c-Kit+ Sca-1+ Lin(low/-) cells had a capacity for self-renewal in vivo. After transplantation of 500 c-Kit+ Sca-1+ Lin(low/-) Ly-5.1+ cells into lethally irradiated Ly-5 congenic mice, the expansion of cells with the same phenotypes as the injected cells was monitored. By day 28 post-transplantation, more than 50,000 donor type c-Kit+ Sca-1+ Lin(low/-) Ly-5.1+ cells were found in the spleen and over 18,000 cells were found in bone marrow. The expansion in spleen, however, was transient in that by day 60 cells of the donor phenotype were found only in bone marrow. The c-Kit+ Sca-1+ Lin(low/-) LY-5.1+ cells expanded in spleen or bone marrow contained as many high proliferative potential colony-forming cells as the originally injected cells. They also contained cells with LTRA, but the frequency appeared to be less compared with naive c-Kit+ Sca-1+ Lin(low/-) cells. These data provide evidence that c-Kit+ Sca-1+ Lin(low/-) cells in bone marrow are capable of multilineage differentiation as well as self-renewal and that spleen is a primary site of stem cell expansion after transplantation.
Animals↗
Serum thrombopoietin level in various hematological diseases.
To investigate the pathophysiological role of thrombopoietin (TPO) in thrombopoiesis, we measured its serum levels in 15 healthy individuals, 84 patients with various hematological diseases and 2 patients with liver cirrhosis using an enzyme immunoassay procedure. The TPO level was 0.84 +/- 0.40 f mol/ml in normal individuals. TPO levels were considerably elevated in patients with myelosuppression after intensification chemotherapy of acute leukemia in complete remission (postchemotherapy group; n = 18; 18.46 +/- 9.70 f mol/ml). When the data of normal individuals and the postchemotherapy group were combined, TPO levels were inversely correlated with the platelet count in this combined group. We compared these data of normal individuals and the postchemotherapy group with various hematological disease states. In aplastic anemia (n = 13; 16.03 +/- 9.44 f mol/ml), acute lymphoblastic leukemia (n = 5; 10.36 +/- 5.57 f mol/ml), malignant lymphoma (n = 6; 2.79 +/- 2.27 f mol/ml), multiple myeloma (n = 3; 3.34 +/- 0.20 f mol/ml) and chronic lymphocytic leukemia (n = 2; 1.71 +/- 3.91 f mol/ml), the relationship of serum TPO levels and platelet counts was almost the same as in the combined group with normal individuals and the postchemotherapy group. However, the TPO levels were slightly higher in myeloproliferative disorders (n = 12; 1.99 +/- 1.47 f mol/ml) and lower in acute myelogenous leukemia (n = 8; 2.27 +/- 1.25 f mol/ml), hypoplastic leukemia (n = 3; 2.76 +/- 2.23 f mol/ml), myelodysplastic syndrome (n = 2; 0.42 +/- 0.60 f mol/ml), liver cirrhosis (n = 2; 1.50 +/- 0.92 f mol/ml) and idiopathic thrombocytopenic purpura (n = 12; 2.08 +/- 1.41 f mol/ml), when compared to the regression line for the combined group with normal individuals and postchemotherapy group. These findings suggest that TPO might play an important role in regulation of the platelet count in normal and pathological conditions.
Adult↗
Surgical outcome for multiple intracranial aneurysms.
The surgical outcome of 221 cases with multiple intracranial aneurysms operated upon during the years 1988 to 1994 were reviewed. The patients were classified into three groups according to the locations of the aneurysms; group 1: multiple aneurysms located unilaterally in the anterior circulation only (147 cases); group 2: multiple aneurysms located bilaterally in the anterior circulation only (44 cases) and group 3: multiple aneurysms located in both anterior and posterior circulation or in the posterior circulation alone (30 cases). In 132 cases of group 1 (89.8%) all aneurysms were treated in one-stage operations. Twenty-eight patients from group 2 (63.6%) received partial treatment, where only the ruptured or the symptomatic aneurysms were treated. In 12 other cases from group 2 (27.3%) all multiple aneurysms were treated in two-stage operations. In group 3 patients, one-stage operations were performed in 18 cases (60%), while 9 patients (30%) received partial treatment only. Of the 221 multiple aneurysm cases, 162 (73.3%) presented with manifestations of subarachnoid haemorrhage (SAH). The remaining 59 multiple aneurysms cases (26.7%) presented with manifestations other than SAH (unruptured aneurysms). In the postoperative follow-up, of the 221 multiple aneurysms cases, 113 (51.1%) were free of neurological deficit (excellent), 48 cases (21.7%) were capable of leading an independent life (good), 32 cases (14.5%) were not independent and needed to be assisted (fair), and 28 patients (12.7%) died. These results were comparable to the results of patients with single aneurysms operated on during the same period. Based on our results, we recommend that whenever possible all multiple aneurysms should be treated in one-stage operations. In unruptured multiple aneurysm cases surgical management is the recommended treatment. In poor grade SAH patients or unruptured multiple aneurysms in old patients, two-stage operations or partial treatment of only the ruptured or the symptomatic aneurysms may be adopted.
Adult↗
The role of vasopressin, somatostatin and GABA in febrile convulsion in rat pups.
In order to further elucidate a possible role of neuropeptides and GABA in the pathogenesis of febrile convulsions, we studied changes of immunoreactive-arginine vasopressin (IR-AVP), IR-somatostatin (IR-SRIF) and gamma-aminobutyric acid (GABA) in the rat brain after febrile convulsions induced by ultra-red light (UR). Male Wistar rats at 16 days of age irradiated with UR developed generalized convulsions after 4.9 +/- 0.5 min irradiation. Six rats were killed by microwave irradiation 3 min after UR irradiation prior to convulsion development, and 29 rats were killed either 0 min, 2 h, 6 h, 24 h or 48 h after febrile convulsions. Non-irradiated rats served as controls. The rat brain was dissected into 4 regions; amygdala, hypothalamus, cortex and hippocampus, and subjected to radioimmunoassays. IR-AVP levels in hypothalamus were increased 3 min after UR and decreased at 2 h and 6 h after the convulsions. IR-SRIF levels were increased in cortex and hippocampus at 3 min after UR and 0 min after the convulsions. The GABA content increased in all regions tested at 2 h and 6 h after the convulsions. These results suggest that AVP, SRIF and GABA may be involved in the pathogenesis of febrile convulsions in different ways.
Animals↗
Extradural extension of glioblastoma multiforme into the oral cavity: case report.
A rare case of glioblastoma multiforme with oral extension is presented in a 41-year-old female. She underwent two surgical treatments and both radiotherapy and chemotherapy for the right temporoparietal glioblastoma multiforme. A follow-up computed tomographic scan and magnetic resonance imaging demonstrated destruction of the temporal base and extradural extension of the tumor into the orbital, nasal, and oral cavities. This is the first report of the oral extension of glioblastoma multiforme. The mechanism for the extradural extension is discussed.
Adult↗
Pharmacokinetics of all-trans-retinoic acid in Japanese patients with acute promyelocytic leukemia.
All-trans-retinoic acid (ATRA) was administered at 45 mg/m2 to 4 Japanese patients with acute promyelocytic leukemia (APL). A pharmacokinetic study revealed that the mean peak plasma concentration was 208 ng/ml and was reached at 150 min after ingestion. The mean area under the concentration x time curve (AUC) was 498 ng.h/ml. Two patients showed a good hematological response to ATRA, and they had higher peak plasma concentrations of ATRA and larger AUCs. In one patient, dose escalation of ATRA (90 mg/m2) increased the plasma concentration markedly. In another patient, the plasma concentration decreased markedly in the fasting state. A larger pharmacokinetic study is necessary to examine the influence of food on the absorption of this agent and an optimum administration schedule of ATRA in Japanese APL cases.
Adult↗
Administration of granulocyte colony-stimulating factor during remission induction therapy with all-trans retinoic acid for acute promyelocytic leukemia.
Granulocyte colony-stimulating factor (G-CSF) enhances the differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA) in vitro. Accordingly, we initiated a pilot study on G-CSF in APL patients who developed neutropenia and severe infection during remission induction therapy with ATRA. Seven out of nine treated patients displayed a marked increase in granulocyte counts without leukemic regrowth, and two displayed a dramatic decrease in leukemic blasts. However, leukemic regrowth occurred in two patients under treatment for post-ATRA relapse. Our findings suggest that administration of G-CSF combined with ATRA can improve the hematological state in APL patients not previously receiving ATRA therapy.
Adult↗
Fatal methamphetamine poisoning in police custody.
A fatal case of methamphetamine poisoning whilst in police custody is described. Drug identification and quantification in postmortem blood, urine, brain and gastric contents was achieved using gas chromatography-mass spectrometry. The blood concentration of methamphetamine was 4.92 micromol/100 g, which is in the lethal range. It is necessary for police officers to have a good knowledge of the toxic effects of abused drugs.
Journal Article↗
Long-term prognosis of Lennox-Gastaut syndrome.
We investigated the long-term prognosis of Lennox-Gastaut syndrome (LGS) in 72 patients followed up for > 10 years. Long-term seizure and intellectual outcomes were poor, as previously reported. The diagnosis of LGS was first made in the age range from 2 to 15 years with peak occurrence at 5 years. Progressive IQ score deterioration with age was apparent. At the last examination, 33% of patients with cryptogenic and 55% with symptomatic LGS had lost the characteristics of LGS, and their seizure disorders were classifiable as symptomatic generalized epilepsies, severe epilepsy with multiple independent spike foci, or localization-related epilepsies. Disabling drop attacks appeared in 46% of patients and tended to occur at older than 10 years. Gait deterioration was recognized in 12 patients and seemed to be due largely to progression of the epileptic encephalopathy. The gait disturbances, as well as increased frequency of violent drop attacks, were disabling in daily life and resulted in some patients being wheelchair bound.
Activities of Daily Living↗
CBFB/MYH11 fusion transcripts in a case of acute myelogenous leukemia (M1) with partial deletion of the long arm of chromosome 16.
Pericentric inversion of chromosome 16 [inv(16)(p13q22)] is seen in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. This inversion juxtaposes the MYH11 gene on p13 and the CBFB gene on q22, resulting in the formation of a chimeric mRNA transcript. We describe a patient with acute myelogenous leukemia (M1), with del(16)(q22), who expressed the chimeric transcript. Reverse transcriptase polymerase chain reaction and the sequencing of its product showed fusion of 5'CBFB at position 495 to 3'MYH11 at position 1201. To our knowledge, this is the first report of an AML (M1) case with del(16) and CBFB/MYH11 rearrangement.
Amino Acid Sequence↗
[Usefulness of functional image of dynamic computed tomography (FID-CT) on acute cerebral ischemic disease: correlation between parameters of dynamic CT and angiographical findings].
We reported the correlation between the angiographical findings and parameters of the functional images of dynamic CT (FID-CT) in ten patients with cerebral ischemic disease. Six of these ten patients with an abnormal area on corrected mean transit time (CM) and time to peak (TP) had complete occlusion of intracerebral main arteries with poor collateral cerebral blood flow or no collateral flow on the angiography. Four patients with prolonged time only in the TP area, but not in the CM area, had stenosis or occlusion of the main trunk with satisfactory anterograde cerebral blood flow on the angiography. FID-CT is easy to apply for clinical use and said to be useful to predict arterial trunk occlusion or infarction volume. It might also be helpful to get further information about the intracerebral circulation disorders in the acute stage of cerebral ischemic disease.
Acute Disease↗