Search PubMed⌕ Search

Biomedical subjects

M Hino

Publications and source records attributed to M Hino.

At least 109 records · Page 6Linked to original sources

[Total hematological analysis system as a screening test for hematological malignancy].

Measurement of complete blood cell count and white blood cell differentiation is an essential laboratory test and the most important screening test for hematological malignancy. Recently, several automated blood cell analyzers have been developed to improve accuracy and precision. When flag messages generated in the presence of morphological abnormalities of the samples are displayed, manual revision is necessary. In our laboratory, the manual revision rate has been 35-40%. Therefore blood cell analyzers are useful in screening for abnormalities as well as greatly reducing expensive and time-consuming manual differential procedures. In addition, automated blood cell analyzers can provide several types of useful information including the leukocyte distribution scattergram. However, most such information is not utilized in the clinical field. In the future, a total hematological analysis system will be constructed so that all information provided by automated blood cell analyzer and by manual methods are available.

Blood Cell Count↗

[Mycosis fungoides terminating in acute myelocytic leukemia].

A 57-year-old woman was admitted to our hospital with suspected leukemia in September 1999. In 1990, systemic erythema had occurred, and mycosis fungoides (MF) had been diagnosed by skin biopsy. Interferon-gamma therapy had not been effective, and the erythema had disappeared after treatment with psoralen and ultraviolet A (PUVA) therapy (1.46 J/cm2). The patient had subsequently done well with a course of topical steroids. On admission this time, the WBC count was 1,600/microliter with 6% blasts. The total nucleated cell count in a bone marrow aspirate was 43.1 x 10(4)/microliter, of which 86.2% were peroxidase-positive blasts. Acute myelocytic leukemia (AML) was diagnosed. Chromosomal analysis demonstrated abnormalities of 48, XX, +4, +8, +add(10)(p11), add(11)(q23) in 10 of 20 cells, and 51, idem, +6, +8, +21, +mar in 8 cells with mixed-lineage leukemia gene rearrangement. Therapies (radiation, chemotherapy and PUVA) for MF, and the altered immune response seen in patients with this disease, especially in the more advanced stages, collectively termed cutaneous T-cell lymphoma (CTCL), suggest that such patients may be at increased risk of a second primary malignancy. To our knowledge, AML has been reported in 8 MF patients including the present one. Attention should be given to the possibility of MF terminating in AML.

Female↗

[B precursor lymphoblastic leukemia/lymphoma manifested at onset as hemophagocytic syndrome].

A 20 year-old male patient was admitted to our department for the treatment of recurrence of fever and pancytopenia developed despite of temporal remission of hemophagocytosis syndrome that had been treated with large doses of methylprednisolone in our hospital. Superficial lymph nodes were not palpable. CT scan and echography revealed neither findings of splenohepatomegalia or enlargement of intraabdominal lymph nodes. Bone marrow aspiration showed an increase of histiocytes, the cells phagocytizing erythrocytes and platelets, and a negative test for peroxidase stain. Analysis of surface antigens showed that 11.3% of cells were blast cells positive for CD10, CD19, CD20, CD34 and TdT. Bone marrow biopsy revealed a localized increase in tumor cells positive for L26, CD10 and negative for UCHL-1. Because of the absence of detectable tumor masses and the difficulty in differentiating between malignant lymphoma and lymphatic leukemia, we diagnosed the condition as B precursor lymphoblastic leukemia/lymphoma. If diagnosed with malignant lymphoma preceded by hemophagocytic syndrome(LAHS), he might have a rare type of LAHS-associated malignant lymphoma since histological examination did not reveal diffuse large cell lymphoma, a condition found in most patients with LAHS-associated malignant lymphoma. Whereas if diagnosed as ALL, he was the first adult patient with ALL with HPS at onset as far as we know. In any of these possibilities, the case was considered rare.

Adult↗

[Clinical cases of acquired coagulation inhibitors].

The acquired coagulation factor inhibitors are classified into alloantibodies, which appear in association with supplementary treatment for congenital coagulation factor deficiency, and autoantibodies, which are spontaneously produced. We report here 2 cases of acquired factor VIII inhibitor and 1 case of factor V inhibitor. Case 1: A 52-year-old woman noted swelling of the right parotid region in March 1988. Though contrast examination was scheduled, she was admitted for detailed examination due to a markedly prolonged coagulation time. An APTT correction test suggested that decreased factor VIII activity was due to the presence of an inhibitor. Since antinuclear antibody and SS-A antibody were positive and infiltration by lymphocytes in the salivary gland acini in a lip biopsy specimen was detected, Sjögren's syndrome was diagnosed. Case 2: A 33-year-old woman had normal delivery of her second child in February 1998. In June 1998, she suffered slight contusion in the left lower limb. The affected site became swollen and painful, making walking difficult. Since both upper limbs became markedly swollen after 1 week, she visited our hospital. Prolonged APTT and a marked decrease in factor VIII activity were observed. Factor VIII inhibitor titer was high at 19 Bethesda units. Case 3: A 64-year-old man had had asymptomatic macroscopic hematuria since the beginning of August 1998 but was placed under observation since no abnormal findings were observed on various imaging tests. However, he was admitted to Osaka City General Medical Center because of vesicular tamponade. Factor V activity was markedly decreased to 1.0%. PT correction test suggested that decreased factor V activity was due to the presence of an inhibitor. The underlying disease could not be determined in this case. In patients with acquired coagulation inhibitors, bleeding symptoms are reported to be mild in many cases, and severe bleeding is rare. However, cases of death without severe bleeding or underlying disease have also been reported, indicating that the prompt diagnosis and treatment of this condition are necessary.

Adult↗

HLA class II alleles in Japanese patients with non-Hodgkin's lymphoma.

The distribution of HLA-DRB1 alleles and DQB1 alleles in 30 Japanese patients with non-Hodgkin's lymphoma (NHL) was analyzed using polymerase chain reaction with the sequence-specific primer (PCR-SSP) method, and the association between the disease and the presence of certain HLA class II alleles was investigated. The frequencies of HLA-DRB1*0803, DRB1*0802 and DRB1*1502 were increased while those of DRB1*1501 and DRB1*0405 were decreased. On the other hand, the incidence of HLA-DQB1 alleles was similar to that in the normal population. However, none of these HLA class II alleles showed significant positive or negative associations with NHL. In addition, when allele frequencies of NHL Japanese patients were compared to Thai patients, only DRB1*0803 was significantly increased in Japanese patients. These results indicate that DRB1*0803 may not contribute to NHL susceptibility in the Japanese population. However, further studies with larger numbers of NHL Japanese patients are needed to confirm our preliminary findings.

Adolescent↗

Cytokine-specific activation of distinct mitogen-activated protein kinase subtype cascades in human neutrophils stimulated by granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha.

To clarify the differences of the signaling pathways used by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor- (TNF), we investigated activation of mitogen-activated protein kinase (MAPK) subtype cascades in human neutrophils stimulated by these cytokines. G-CSF exclusively tyrosine-phosphorylated extracellular signal-regulated kinase (ERK). GM-CSF tyrosine-phosphorylated ERK strongly and p38 MAPK weakly, whereas TNF tyrosine-phosphorylated p38 MAPK strongly and ERK weakly. Consistent with these findings, MEK, an upstream kinase of ERK, was phosphorylated by G-CSF, GM-CSF, and TNF, whereas MKK3/MKK6, an upstream kinase of p38 MAPK, was phosphorylated by GM-CSF and TNF, but not by G-CSF. The potency of these cytokines to phosphorylate ERK and MEK was GM-CSF > G-CSF > TNF, whereas that to phosphorylate p38 MAPK and MKK3/MKK6 was TNF > GM-CSF. C-Jun amino-terminal kinase (JNK) was not tyrosine-phosphorylated by any cytokine despite the existence of JNK proteins in human neutrophils, whereas it was tyrosine-phosphorylated by TNF in undifferentiated and all-trans retinoic acid-differentiated HL-60 cells. Increased phosphorylation of ERK or p38 MAPK was detected within 1 to 5 minutes after stimulation with each cytokine and was dependent on the concentrations of cytokines used. MEK inhibitor (PD98059) reduced tyrosine phosphorylation of ERK, but not p38 MAPK, induced by G-CSF, GM-CSF, or TNF. GM-CSF- or TNF-induced superoxide (O2-) release was inhibited by p38 MAPK inhibitor (SB203580) in a dose-dependent manner, suggesting the possible involvement of p38 MAPK in GM-CSF- or TNF-induced O2- release. The results indicate that G-CSF, GM-CSF, and TNF activate the overlapping but distinct MAPK subtype cascades in human neutrophils and suggest that the differential activation of ERK and p38 MAPK cascades may explain the differences of the effects of these cytokines on human neutrophil functions.

Calcium-Calmodulin-Dependent Protein Kinases↗

HLA class II polymorphism in Thai patients with non-Hodgkin's lymphoma.

The distribution of HLA-DRB1 alleles and DQB1 alleles in 100 Thai patients with non-Hodgkin's lymphoma (NHL) was analysed using the polymerase chain reaction with sequence-specific primer (PCR-SSP) method, and the association between the disease and the presence of certain HLA class II alleles was investigated. The frequencies of HLA-DRB1*1502 and DRB1*09012 were increased while those of DRB1*0404, DRB1*0803 and DRB1*1106 were decreased. On the other hand, the incidence of HLA-DQB1 alleles was similar to that in the normal population. Interestingly, only HLA-DRB1*1502 showed a significant positive association with NHL, especially in patients < or / = 45 years and in male patients. It is concluded that the DRB1*1502 allele may contribute to NHL susceptibility in the Thai population. However, further studies on the functional roles of the HLA class II alleles are necessary to elucidate NHL susceptibility.

Adult↗

Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 1st communication: phosphodiesterase III inhibitory effect and class III antiarrhythmic effect in guinea-pig heart.

In order to clarify the mechanism of action of 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5,6- tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013), a novel cardiotonic agent with Ca++ sensitizing action, its effects on contractile force, atrial rate and action potential, and on the activity of Na+, K(+)-ATPase and phosphodiesterase (PDE) I-IV were studied in the guinea-pig heart. SCH00013 exerted a positive inotropic effect (PIE) on isolated right ventricular papillary muscles in a concentration-dependent manner (EC50 = 9.2 mumol/l): the relative potency was milrinone > SCH00013 > vesnarinone. The PIE of SCH00013 was not influenced by propranolol, a beta-blocker, and SCH00013 did not affect the activity of cardiac Na+, K(+)-ATPase. The PIE of SCH00013 was partially inhibited by carbachol, a muscarinic receptor agonist, which implies a partial contribution of the cAMP-dependent mechanism to the PIE. SCH00013 inhibited the activity of PDE III selectively, but the potency was weak: the IC50 value was 64.9 mumol/l, which was 46 and 3.9 times less potent than those of milrinone and vesnarinone, respectively. SCH00013 and vesnarinone elicited a moderate decrease in the rate of beating of isolated right atria, while milrinone increased it. SCH00013 markedly prolonged the action potential duration and the effective refractory period with no change in the resting membrane potential and dV/dtmax, an indication that SCH00013 may suppress the activity of delayed rectifying K+ channels. These results indicate that SCH00013, that primarily acts as a Ca++ sensitizer, possesses a weak selective PDE III inhibitory effect. The potential positive chronotropic effect of SCH00013 due to PDE III inhibition may be offset by its effect on K+ channels.

Action Potentials↗

Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 2nd communication: in vivo cardiovascular effects and bioavailability in dogs.

In vivo cardiovascular effects and bioavailability of 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]-1,2,5,6- tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013), a novel cardiotonic agent, were investigated. In anesthetized dogs, intravenous administration of SCH00013 (0.3-10 mg/kg) increased maximum rate of rise in left ventricular pressure (LVdP/dtmax) in a dose-dependent manner with no change in heart rate (HR) and, at the dose of 3 mg/kg or higher, at which the increase in LVdP/dtmax reached the maximum, it decreased blood pressure. In conscious dogs, oral administration of SCH00013 (1-10 mg/kg) also increased LVdP/dtmax dose-dependently with no change in HR. The increase in the plasma concentration of orally administered SCH00013 (3 mg/kg) was parallel to the increase in LVdP/dtmax. The areas under the plasma concentration versus time curve (AUC0-24 h) after oral and intravenous administration of SCH00013 (3 mg/kg) were essentially identical (15.3 +/- 2.0 micrograms.h/ml and 16.5 +/- 2.1 micrograms.h/ml, respectively). These results suggest that oral bioavailability of SCH00013 is notably high. In conclusion, the positive inotropic effect of SCH00013 with neither elevation of HR nor excessive hypotension, as well as the high oral bioavailability of this compound, may provide a beneficial pharmacological treatment of the patients with congestive heart failure.

Administration, Oral↗

Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 3rd communication: stereoselectivity of the enantiomers in cardiovascular effects.

The cardiovascular effects of the enantiomers, (+)-SCH00013 and (-)-SCH00013, of a novel cardiotonic agent 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]- 1,2,5,6-tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013) were investigated in vitro and in vivo. The enantiomers of SCH00013 elicited an equipotent positive inotropic effect in isolated guinea-pig papillary muscles. Both of the enantiomers had a modest negative chronotropic effect in isolated guinea-pig right atria and the difference in the chronotropic effects of the enantiomers was not significant. In anesthetized dogs, both enantiomers increased LVdP/dtmax without change in heart rate and slightly decreased blood pressure. These hemodynamic effects of the enantiomers were not significantly different from each other. (+)-SCH00013 and (-)-SCH00013 increased the extent of cell shortening in association with only a small increase in the Ca++ transients in indo-1-loaded rabbit cardiomyocytes, and both the increases in cell shortening and Ca++ transients were not significantly different between the enantiomers. Both isomers equally shifted the relationships between the increases in the cell shortening and Ca++ transients to the left and upward as compared with the relationships for the elevation of extracellular Ca++ concentration and isoproterenol, which indicates that the effectiveness of the Ca++ sensitizing effects of the enantiomers are almost equivalent. The enantiomers of SCH00013 showed equipotent inhibitory effect on the phosphodiesterase (PDE) III activity. The maximal extent and the potency of prolonging effect of the two enantiomers on the effective refractory period were also the same. Thus, the efficacy and potency of the effects on the cardiovascular parameters such as myofibrillar Ca++ sensitivity, PDE III activity and the effective refractory period for the both enantiomers of SCH00013 are equivalent, indicating that the cardiovascular effects of SCH00013 may be due to equal contribution of both enantiomers.

Anesthesia↗

Investigation on SCH00013, a novel cardiotonic agent with Ca++ sensitizing action. 4th communication: influence on experimentally induced ventricular arrhythmia in dogs.

Influence of 4,5-dihydro-6-[1-[2-hydroxy-2-(4-cyanophenyl)ethyl]- 1,2,5,6,-tetrahydropyrido-4-yl]pyridazin-3(2H)-one (SCH00013) and vesnarinone (CAS 81840-15-5) on the arrhythmia experimentally induced by three different methods was investigated in dogs. In digitalis-induced arrhythmia, SCH00013 (3 mg/kg i.v.) showed a tendency to improve the arrhythmia with a decrease in the arrhythmic ratio and an increase in the conducted beats (CB), though these changes did not reach a significant level; it decreased significantly the blood pressure (BP) with no change in the total heart rate (THR) and atrial rate (AR). Vesnarinone (3 mg/kg i.v.) did not affect these parameters except for BP that was decreased significantly. In two-stage coronary ligation-induced arrhythmia, SCH00013 (1 and 3 mg/kg i.v.) did not change the arrhythmic ratio, CB, AR and BP, while the THR being slightly decreased; the arrhythmic ratio showed a tendency to decrease with SCH00013 when examined at 24 h after coronary ligation. Vesnarinone (3 mg/kg i.v.) did not affect these parameters at 24 and 48 h after ligation. In epinephrine (adrenaline)-induced arrhythmia, both SCH00013 and vesnarinone showed exacerbation of arrhythmia. SCH00013 at 1 mg/kg i.v. did not elicit ventricular fibrillation (VF) in five dogs examined, but at 3 mg/kg i.v. it elicited VF in two of three dogs. Vesnarinone at 1 mg/kg i.v. induced VF in all of three dogs examined. Incidence of VF induced by optical isomers of SCH00013 was not significantly different from each other: both isomers elicited VF in two of six dogs at 1 mg/kg i.v. and at 3 mg/kg i.v. each of them induced VF in two dogs examined. The present results indicate that SCH00013 is a cardiotonic agent that is equivalent to or less arrhythmogenic than vesnarinone in animal models of arrhythmia, such as adrenaline- and digitalis-induced arrhythmia and the two-stage coronary ligation-induced arrhythmia. Optical isomers of SCH00013 were essentially equieffective in eliciting exacerbation of adrenaline-induced arrhythmia in the dog.

Animals↗

Pathophysiological significance of simultaneous measurement of reticulated platelets, large platelets and serum thrombopoietin in non-neoplastic thrombocytopenic disorders.

An automated reticulocyte counter using flowcytometric analysis, the R-3000 (Sysmex Inc. Kobe, Japan), has recently been modified to determine reticulated platelets (RPs) and large platelets (LPs). We measured frequencies of RPs, LPs in total platelet count and serum thrombopoietin concentration comprehensively in non-neoplastic thrombocytopenic patients with immune thrombocytopenic purpura (ITP, n = 23), aplastic anemia (AA, n = 21), liver cirrhosis (LC, n= 17), and hematologically normal subjects (control, n = 151). ITP was characterized as high frequencies of both RP and LP, AA as high RP frequency and elevated thrombopoietin concentration, and LC as no difference compared with control. Interestingly, the frequency of RP appeared to depend on total platelet count rather than the cause of thrombocytopenia, while the frequency of LP appeared to depend much less on total platelet count. Furthermore, significant positive correlations were observed between frequencies of RP and LP in control, ITP and LC subjects, in whom bone marrow stem cells are intrinsically normal. However, there was no such correlation in AA patients with stem cell deficiency, suggesting that this correlation might be a useful new parameter for detecting qualitatively abnormal platelets. Measurement of RP and LP is thus useful for elucidating the pathophysiology of thrombocytopenic disorders.

Adolescent↗

[Parvovirus B19 infection-induced anemia and leukocytopenia after myomectomy].

A 38-year woman was hospitalized because of myoma uteri. She underwent myomectomy on September 30, 1997 with 2,000 ml blood loss. No blood transfusion was required, but she received a plasma protein product. On the 14th postoperative day, a complete blood count revealed anemia (Hb 9.3 g/dl) and leukocytopenia (1,600/ul). But it did not reveal anemia before the operation. Bone marrow smears showed erythroblastopenia with giant proerythroblasts. Anti-parvovirus B19 IgM antibody were positive in the serum and parvovirus B19 DNA was detected in the bone marrow cells by polymerase chain reaction. From the results, the patient was diagnosed as the anemia and leukocytopenia secondary to parvovirus B19 infection. Parvovirus B19 was not detected in the samples of the plasma protein product received on the myomectomy. The reticulocyte gradually decreased to 1/1000 on the 20th postoperative day. The anemia and leukocytopenia gradually improved. This case shows that parvovirus B19 infection could cause hematological disorders in the normal person under acute blood loss. This report warns that a careful observation is necessary for the patients who have received operations with acute blood loss.

Adult↗

Automated enumeration of cellular composition in bone marrow aspirate with the CELL-DYN 4000 automated hematology analyzer.

The present study was designed to evaluate the automated analysis of bone marrow aspirates with the CELL-DYN 4000 (CD4000) hematology analyzer. Bone marrow aspirates were diluted twice with phosphate-buffered saline and assayed with the CD4000. The percentages of subpopulations including lymphocytes, neutrophils, and erythroblasts were obtained with the CD4000, and as a reference, differential counts by microscopic observation of May-Grünwald-Giemsa-stained films of bone marrow aspirate were performed (n = 48). Significant correlations (p < 0.0001) between the results with the two methods were obtained for total nucleated cell count, lymphocytes, neutrophils, erythroid cells, and the myeloid/erythroid ratio. The present method can provide quantitative data of bone marrow aspirate and will be useful in bone marrow screening.

Biopsy, Needle↗

WF14861, a new cathepsins B and L inhibitor produced by Colletotrichum sp. II. Biological properties.

WF14861, 3-(N-(1-(N-(4-aminobutyl)-N-(3-aminopropyl)carbamoyl)-2-(4-hydroxyphenyl )ethyl)carbamoyl)oxirane-2-carboxylic acid, was obtained from the culture mycelium of Colletotrichum sp. as a novel cathepsins B and L inhibitor. WF14861 also showed inhibitory activities against bone derived crude protease and other cysteine proteases in vitro. The compound ameliorated the tissue damage and the bone destruction models of low-calcium-diet-fed mouse and adjuvant arthritis rat model.

Animals↗

[Human parvovirus B19-induced aplastic crisis in a patient treated with fibrin sealant].

A 42-year-old woman underwent a myomectomy on March 31, 1998. On the 10th postoperative day, leukopenia and reticulocytopenia were observed. Bone marrow aspiration revealed severe erythroblastopenia with giant proerythroblasts, suggesting a recent parvovirus infection. Both anti-parvovirus B19 IgM antibody and IgG antibody seroconversion was observed, and human parvovirus B19 DNA was detected by polymerase chain reaction (PCR) methods. The hematologic data on the patient rapidly improved thereafter. It was determined that acute-phase serum had inhibited CFU-E and BFU-E derived colony formation. Based on these findings, parvovirus B19-induced aplastic crisis was diagnosed. Fibrin sealant, which is a typical hemostatic agent produced from blood, had been during the operation. Human parvovirus B19 DNA was detected in the fibrin sealant by PCR. Our case report documents the transmission of human parvovirus B19 by fibrin sealant.

Acute Disease↗

[Detection of anti-IgA alloantibody in a case of non-hemolytic transfusion reaction].

A 59-year-old man with myelodysplastic syndrome exhibited unticaria, dyspnea, fever, and hypotension immediately after the start of platelet concentrate (PC) transfusion on the 15th day of hospitalization. On the 17th and 21st day of hospitalization, the patient exhibited severe unticaria resembling that of erythroderma after the start of PC transfusion. Anti-IgA IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA) on the 28th day of hospitalization. Anti-IgA (purified from pooled human plasma) was detected by Western blotting. The patient's IgA level was normal. No antibodies against HLA or platelet-specific antigens were detected in serum. The patient had no reaction to administration of washed PC. These findings suggest that anti-IgA antibody might have been responsible for the nonhemolytic transfusion reaction in this patient.

Antibodies, Anti-Idiotypic↗