Serum IL-18 levels in patients with various hematological disorders.
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Adult↗
Biomedical subjects
T Takubo
Publications and source records attributed to T Takubo.
Effect of trimethoprim on the renal clearance of lamivudine in rats.
Lamivudine undergoes minimal metabolism and renal clearance of the unchanged drug is the predominant mechanism of clearance. The effect of trimethoprim on the renal clearance of lamivudine was investigated in rats in-vivo. Total renal clearance of lamivudine was about three times higher than the glomerular filtration rate in rats receiving an infusion of tritium-labelled lamivudine. Concomitant infusion of trimethoprim reduced the renal clearance of lamivudine to about half, but did not affect the level of radioactivity in the renal cortex. When rats received an infusion of lamivudine with probenecid, cimetidine or quinidine, the renal clearance of lamivudine was only significantly reduced by co-administration of cimetidine. These findings suggest that secretion in the renal proximal tubule takes an active part in the total renal clearance of lamivudine, and that cationic drugs such as trimethoprim and cimetidine may inhibit the secretion of lamivudine without greatly affecting the concentration of lamivudine in the renal cortex.
Animals↗
Effect of lamivudine on uptake of organic cations by rat renal brush-border and basolateral membrane vesicles.
The effect of lamivudine on uptake of a representative organic cation, tetraethylammonium (TEA), by rat renal brush-border membrane vesicles (BBMV) and basolateral membrane vesicles (BLMV) has been investigated. The pH-driven uptake of TEA by BBMV (pHin = 6.0, pHout = 7.5) was inhibited by lamivudine. The IC50 value (concentration resulting in 50% inhibition) for the concentration-dependent effect of lamivudine on TEA uptake by BBMV after 30 s was 2668 microM whereas IC50 values for cimetidine and trimethoprim were < 2.5 microM and < 25 microM, respectively. The early uptake of TEA by BLMV was also reduced significantly by lamivudine. The IC50 value for the concentration-dependent effect of lamivudine on uptake of TEA by BLMV at 30 s was > 25 mM, whereas the IC50 values for cimetidine and trimethoprim were 2116 microM and 445 microM, respectively. These findings suggest that compared with other cationic drugs, such as trimethoprim and cimetidine, lamivudine is a weak inhibitor of organic cation transport into the tubules by the brush-border and basolateral membranes of renal epithelial cells. It is unlikely lamivudine will have any significant effect on the excretion of co-administered cationic drugs by the renal tubules.
Animals↗
Leptin receptor and leukemia.
The receptor for leptin, the gene product of the obese gene, is expressed in hematopoietic stem cells. Leptin stimulates normal myeloid and erythroid development, and is secreted from bone marrow adipocytes, which occupy most of the marrow cavity in humans. Leptin might thus play an important role in the control of the expansion and differentiation of primitive hematopoietic cells through paracrine interaction in the bone marrow microenvironment. Leukemic cells of some patients with acute myeloblastic leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia (CML) also express the leptin receptor. In cases of CML, higher expression of leptin receptor is observed during blast crisis than in chronic phase. Leptin alone and in combination with other cytokines has stimulative effects on proliferation of leukemia cells as well as anti-apoptotic effects. These findings suggest the possibility that leptin plays roles in the pathophysiology of leukemia.
Carrier Proteins↗
[Reference values for hematologic laboratory tests and hematologic disorders in the aged].
The establishment of reference values in the complete blood count and lymphocyte subsets for the aged is necessary for diagnosis and therapy since the number of the aged is increasing rapidly in recent years. However, it is problematical to define the healthy aged because of physiological changes with aging, compared with the healthy adults. Red blood cell count, hemoglobin concentration(Hb) and hematocrit for the healthy aged showed the tendency of moderate decreasing with aging. These phenomena become more obvious by dividing the healthy aged into three groups, 65-74 years, 75-84 years and over 85 years. The mean corpuscular volume(MCV) for the healthy aged showed the tendency of increasing with aging, while mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration for the healthy aged showed no tendency with aging. No changes for the healthy aged were observed in the leukocyte differential, white blood cell count and platelet count with aging. Results of lymphocyte subsets(CD3, CD4, CD8, CD19 and CD4/CD8 ratio) for the healthy aged are not coincident among reporters at present because the healthy aged population is different and the determination of lymphocyte subsets is not standardized. It is important to diagnose as anemia below Hb 11.0 g/dL between 65 and 74 years, Hb 10.0 g/dL over 75 years using Hb level with high accuracy. Most of hematologic disorders in the aged are the secondary anemia based on malignant tumor. In the aged between MCV 95 and 120 fL or over MCV 120 fL, myelodysplastic syndrome or vitamin B12 deficiency is considered, respectively. In the future, more vertical study in the aged population is needed to establish the reference values for the aged.
Adult↗
[Sleep medicine in USA and European countries--now and then].
In looking to the future in a field such as sleep medicine, there seems to be two general areas: (1) the scientific accomplishments that are likely to transpire in the years ahead and (2) how sleep medicine will be practiced in our evolving medical system. As the care of apnea patients becomes more standardized and effective, sleep medicine must be expanded scientifically and clinically, thereby becoming a complete and mature field. Advancing basic science and technology is likely to improve the well-being of patients with sleep disorders.
Academic Medical Centers↗
Low-molecular-weight heparin as a multipurpose anticoagulant for laboratory testing.
The availability of low-molecular-weight heparin (LMWH) for use as an anti-coagulant for laboratory testing was studied. Hematology and chemistry tests were performed with an automated hematology analyzer and an automated chemistry analyzer, respectively. The results of hematology tests of LMWH-treated blood were similar to those obtained for blood treated with ethylenediaminetetraacetic acid (EDTA)-2K, except for platelet count. The platelet count of LMWH-treated blood was lower than that of EDTA-treated blood, and the decrease in platelet count in the former was due to platelet aggregation. Prothrombin time tests could be performed with plasma prepared from LMWH-treated blood, although with such blood the prothrombin time was prolonged. Chemistry tests could be performed for all 18 parameters. These results suggest that LMWH is a candidate for use for hematology testing (with the exception of platelet count), coagulation testing, and chemistry tests.
Anticoagulants↗
Analogues of ethylenediaminetetraacetic acid and sodium fluoride as anticoagulants.
Three analogues of ethylenediaminetetraacetic acid (EDTA), ethyleneglycoltetraacetic acid (EGTA), ethylendiaminedipropionic acid (EDDP), and hexamethylenediaminetetraacetic acid (HDTA), and sodium fluoride (NaF) were evaluated as anticoagulants used for rapid and multi-parametric analysis with minimal amounts of blood. EDDP and HDTA induced rapid blood coagulation (< 30 min), while NaF was not useful for coagulation tests because no coagulation was observed by addition of PT- or APTT-reagents. EGTA could be used for hematology and coagulation tests, although platelet count was significantly decreased in comparison with EDTA treated blood due to platelet aggregation, although prothrombin time was prolonged with EGTA-treated blood. Platelet aggregation could be prevented by addition of kanamycin. In chemistry tests, correlations between serum values and EGTA and kanamycin treated plasma values were good for all items. Based on these findings, we concluded that EGTA could be used for hematology, coagulation, and chemistry tests, although with some limitations.
Adult↗
[High-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of non-Hodgkin's lymphoma].
Findings for 41 patients with non-Hodgkin's lymphoma (NHL) treated with high-dose chemotherapy (HDC) and/or autologous peripheral blood stem cell transplantation (PBSCT) are reported. Two of the 41 patients were treated with HDC alone without PBSCT. At transplant, 20 patients were in complete remission, while 19 had resistant NHL and had failed to achieve a complete remission (CR) after several courses of conventional chemotherapy. The conditioning regimens used were mainly ACE (cytarabine, cyclophosphamide, etoposide) and MEAC (MCNU, etoposide, cytarabine, cyclophosphamide). The treatment-related mortality rate was 4.9%. Two patients treated with MEAC died from intractable congestive heart failure. Nine of the 19 patients with resistant NHL achieved CR, and at a median follow-up of 26 months (range, 3 to 93 months) the estimated two-year disease-free survival rate for these patients was 44.4%. Four patients in CR at present were in partial remission before HDC and PBSCT. Fifteen of the 20 patients in CR before HDC were transplanted in first CR and 5 in 2nd CR. At a median follow-up of 49 months (range, 3 to 96 months), the estimated 3-year DFS for the group of all patients was 73.7%. Five relapses occurred between 5 and 35 months post-transplantation. In conclusion, HDC and PBSCT as induction therapy was only effective for patients with resistant NHL who responded to conventional chemotherapy, and may improve the survival of patients in CR as consolidation therapy.
Adolescent↗
[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↗
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↗
[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↗
Relative distribution of myosin, actin, and alpha-actinin in adherent monocytes.
The characteristic amoeboid movement of human leucocytes uses mechanical energy derived from the hydrolysis of adenosine triphosphate through a mechanochemical system of the contractile proteins myosin, actin, and the actin-associated protein alpha-actinin. We observed the relative distribution of myosin, actin, and alpha-actinin in adherent monocytes during movement by a double-fluorescence staining procedure. The results indicate that myosin and alpha-actinin are closely associated with the actin cable network, and that alpha-actinin is in close association with the plasma membrane and anchors filamentous actin (F-actin) beneath the plasma membrane; F-actin and alpha-actinin play an important role at the leading edge during the formation of lamellipodia. These findings should be helpful in clarifying the mechanism of leucocyte movement from a morphologic standpoint.
Actinin↗
Microscopic co-distributions of myosin, actin, alpha-actinin and vinculin in human neutrophils during movement.
Human neutrophils initiate their characteristic ameboid movement in response to external stimuli via a mechanochemical system of contractile proteins using mechanical energy derived from hydrolysis of adenosine triphosphate. We have visualized contractile proteins, including myosin, filamentous actin (F-actin), alpha-actinin, tropomyosin, and vinculin in human neutrophils during movement by fluorescence microscopy using double immunofluorescence staining procedures of fluorescein isothiocyanate-labeled antibodies, rhodamine-labeled antibodies, or rhodamine-conjugated phalloidin. From dual color images, both myosin and F-actin, both alpha-actinin and F-actin, both vinculin and F-actin showed co-localization, both myosin and alpha-actinin showed a partial co-localization, at the leading edge in the lamellipodia, and both vinculin and alpha-actinin were co-localized at the leading edge and appeared reciprocally at regular intervals in the lamellipodia. Our observations indicate that most of myosin, F-actin, alpha-actinin, and vinculin are focused in order to reorganize dynamically at the leading edge in the lamellipodia, and a motile apparatus is reconstituted there, when neutrophils start to move toward external substances.
Actinin↗
[Recurrent hemolytic uremic syndrome induced by pranoprofen].
A 25-year-old woman was admitted to our hospital because of dark red urine in 1993. A diagnosis of hemolytic uremic syndrome (HUS) because of findings of hemolytic anemia with fragmented erythrocytes, thrombocytopenia, and renal dysfunction. The patient achieved remission with steroids and diuretics. In 1998 she caught a cold and happened to take the nonsteroidal anti-inflammatory drug, pranoprofen. Six hours later, she was rehospitalized because of dark red urine. Hemolytic anemia, fragmented erythrocytes, thrombocytopenia and renal dysfunction were observed again, also. A diagnosis of HUS was made. The patient was treated with steroid pulse therapy, infusion of fresh plasma, and plasma exchange transfusion. She recovered completely. In 1993 she had taker pranoprofen just prior to her first HUS episode. This was a recurrent case of HUS induced by pranoprofen.
Adult↗
[Non-hemophilic patient with inhibitor against factor VIII produced after the second delivery].
A 33-year-old woman who had been healthy and had no history of abnormal bleeding developed widespread ecchymoses and intramuscular bleeding 4 months after her second delivery. On admission, laboratory examination data revealed that factor VIII activity was markedly reduced (4%) and APTT was prolonged (119.7s). Factor VIII inhibitor titer was high, at 19 Bethesda units. Her chemical and serological data were normal. No antinuclear antibodies were detected. We concluded that factor VIII inhibitor had been spontaneously produced after the second delivery and was responsible for her bleeding tendency. Prednisolone (60 mg/day) and factor VIII concentrates were administered to stop the bleeding, but factor VIII activity did not increase while factor VIII inhibitor titer increased to 29 Bethesda units. Therefore, treatment with factor VIII concentrate (was stopped while prednisolone was continued resulting in reduction of factor VIII inhibitor titer and improvement of her bleeding tendency. At 8 months after admission, factor VIII inhibitor titer was not detected by the Bethesda method and factor VIII activity and APTT were normal.
Adult↗
Successful treatment using peroral itraconazole in a patient with acute promyelocytic leukemia complicated with splenic candidiasis.
A 57-year-old female with acute promyelocytic leukemia was admitted to our hospital. The PML-RAR alpha fusion transcript was reverse transcription polymerase chain reaction. Complete remission was achieved with intensive induction chemotherapy. Then a high fever unresponsive to antibiotics with increased C-reactive protein continued. Abdominal computed tomography revealed multiple low-density lesions in the spleen. Splenic candidiasis was suspected and peroral treatment with itraconazole (200 mg/day) was begun. After the fungal infection was confirmed to be inactive, splenectomy was performed. The splenic tissue showed multiple white or yellow nodules and methenamine silver stain revealed fungal hyphae characteristic to Candida. There was no evidence of relapse of Candida infection. She has been in complete remission for these two years and free of fungal infection. It is indicated from our case that splenic candidiasis in patients with acute myeloid leukemia can be successfully treated with oral administration of itraconazole and subsequent splenectomy, when it is confined in the spleen.
Antifungal Agents↗