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Biomedical subjects

K Yamato

Publications and source records attributed to K Yamato.

At least 73 records · Page 4Linked to original sources

Thrombocytopenic purpura in a patient with lupus anticoagulant: requirement of both immunosuppressive and antithrombotic therapies.

A 33 year old woman with severe thrombocytopenic purpura complicated by typical lupus anticoagulant developed repeated spontaneous abortion, deep venous thrombosis, and cerebral thrombosis. The platelet count fluctuated from 4,000 to 400,000/mm3 during the 13 year clinical course. The physical and laboratory findings at the time of severe thrombocytopenic purpura were compatible with the criteria of idiopathic thrombocytopenic purpura except for positive lupus anticoagulant. Both immunosuppressive therapy with prednisolone and antithrombotic therapy with warfarin and aspirin were necessary for the control of bleeding and venous and arterial thrombosis.

Adult↗

Modulation of interleukin-1 beta RNA in monocytic cells infected with human immunodeficiency virus-1.

The effect of HIV-1 infection on cytokine levels was studied in monocytic cells by using Northern blotting analysis. Monoblasts (THP-1, U937) did not express IL-1 beta RNA even if the cells were infected with HIV-1. After exposure to LPS (10 micrograms/ml) and 12-O-tetradecanoylphorbol-13-acetate (TPA, 100 nM) for 12 h, these HIV-1-infected monoblasts accumulated 8-15-fold greater levels of IL-1 beta RNA as compared with their HIV-1-uninfected counterparts that were similarly stimulated. In contrast, levels of RNAs coding for monocyte-colony-stimulating factor (M-CSF) and tumor necrosis factor-alpha (TNF alpha) were elevated less than twofold in the HIV-1-infected cells as compared with HIV-1-uninfected cells after their stimulation with LPS and TPA. Inhibition of new protein synthesis did not block the marked accumulation of IL-1 beta RNA produced by exposure to LPS and TPA in the HIV-1-infected cells. Time-course experiments showed that the maximal levels of IL-1 beta RNA occurred at 12 and 24 h after LPS and TPA stimulation of the HIV-1-infected and uninfected U937 cells, respectively. Studies of stability of RNA using actinomycin D showed that IL-1 beta RNA was equally stable in infected and uninfected U937 cells after their stimulation with TPA and LPS. Taken together, our data show that HIV-1 infection markedly augments IL-1 beta RNA accumulation in stimulated monocytic cells, probably through increasing rate of transcription of IL-1 beta.

Cell Line↗

[Acute myelomonocytic leukemia with Inv(16) (p13 q22) relapsed in transverse myelopathy].

We report a case of AML (M 4) with eosinophilia who developed meningeal relapse and transverse myelopathy. A 37-year-old woman was admitted to our hospital because of lymphadenopathy and ecchymosis. One week prior to admission, she noticed swelling of the cervical lymph nodes and bleeding tendency. On admission, low-grade fever, gingival swelling, generalized lymphadenopathy, and ecchymosis on the lower legs were found. A white blood cell count was 93,900/microliters with 82% blast cells, and a platelet count was 24,000/microliters. A bone marrow was composed of 45.3% myeloblasts, 27% monocytes and 7.1% eosinophils. Chromosome analysis revealed inv(16). The diagnosis of M4Eo was made. About one year after she gained complete remission, she was readmitted because of disturbance of urination. There was a sign of transverse myelopathy at the seventh vertebral level, and blast cells were detected in the cerebrospinal fluid. Despite of radiation and chemotherapy, paresis of lower extremities and sensory disturbance were persistent, and the patient died on 52th hospital day.

Adult↗

Regulation of levels of IL-1 mRNA in human fibroblasts.

Interleukin-1 (IL-1) has a crucial role in host defenses, inflammatory processes, and tissue homeostasis. A wide variety of cells produce this protein in response to a number of extracellular stimuli including microorganisms, antigenic stimuli, and products from other cells. Regulation of IL-1 production at the molecular level is poorly understood. We studied expression, intracellular signals, and posttranscriptional regulation of IL-1 mRNA in human mesenchymal cells by using Northern blot analysis. Tumor necrosis factor alpha (TNF alpha) and activators of protein kinase C including 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin induced the accumulation of IL-1 beta mRNA in human fibroblasts (WI-38). Effect of TNF alpha was not blocked by inhibitors of either protein synthesis (cycloheximide) or protein kinase C activity. Accumulation of IL-1 beta mRNA was also increased by a calcium ionophore (A23187) and an inhibitor of the Na+/K+ pump (ouabain); both compounds are known to increase cytoplasmic levels of Ca++. Stability of IL-1 beta mRNA in fibroblasts exposed to TPA was more than fourfold greater than after fibroblasts were exposed to either TNF alpha or cycloheximide. This suggests that posttranscriptional stabilization of IL-1 beta mRNA is a major mechanism leading to accumulation of IL-1 beta mRNA after activation of PKC in fibroblasts. Fibroblasts did not express IL-1 alpha mRNA after exposure to stimuli which induced the accumulation of IL-1 beta mRNA. In summary, several different pathways regulate levels of IL-1 beta mRNA in human mesenchymal cells.

Calcimycin↗

Granulocyte-macrophage colony-stimulating factor: signals for its mRNA accumulation.

Granulocyte-monocyte colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor. Mesenchymal cells produce abundant GM-CSF in response to tumor necrosis factor alpha (TNF). We wished to determine (1) what cellular pathways enhanced levels of GM-CSF mRNA, and (2) if TNF used any of these pathways. Modulation in levels of GM-CSF mRNA in human fibroblasts (WI-38) was studied by using Northern blot analysis. Markedly increased levels of GM-CSF mRNA occurred in these cells after exposure to sodium fluoride (NaF) and the effect of NaF was slightly enhanced by aluminum chloride; these results suggest that accumulation of GM-CSF mRNA can occur by activating a G-binding protein. Stimulators of protein kinase C dramatically increased levels of GM-CSF mRNA; however, blockade of protein kinase C activity did not attenuate accumulation of GM-CSF mRNA stimulated by TNF and NaF. Exposure to ouabain increased levels of GM-CSF mRNA and this effect was prominently enhanced in the presence of low concentrations of extracellular K+ and was almost abolished in high concentrations of extracellular K+. A monovalent ionophore (monensin) also increased levels of GM-CSF mRNA. Both ouabain and monensin can increase intracellular Ca++ concentration (Cai++) through Na+-Ca++ exchange. A calcium channel blocker (diltiazem) blocked the increased levels of GM-CSF mRNA mediated by ouabain, but could not block the stimulation mediated by TNF alpha. Ca++ ionophores also increased levels of GM-CSF mRNA and rapidly increased levels of Cai++. TNF did not increase Cai++ and, moreover, was able to stimulate accumulation of GM-CSF mRNA in the absence of extracellular Ca++. Taken together, we have found that several different cellular pathways can lead to prominent accumulation of GM-CSF mRNA in mesenchymal cells including (1) activation of protein kinase C, (2) increase in Cai++, and (3) stimulation of G-binding protein. Our studies show that TNF appears to increase levels of GM-CSF mRNA independent of protein kinase C activity or levels of Cai++.

Aluminum↗

[Acute myelofibrosis terminating in acute myelomegakaryoblastic leukemia].

We report a case of acute myelofibrosis (AMF) developing into acute myelomegakaryoblastic leukemia. A 33-year-old woman was admitted to our hospital because of fever and chest pain. On physical examination, hepatosplenomegaly was not noticed. Pancytopenia and a small number of blast cells were observed in the peripheral blood. Poikilocytosis was not detected. Bone marrow examination revealed dry tap on aspiration, and moderate increase in reticulin fiber on biopsy. The diagnosis of AMF was made. Eight months later, blast cells markedly increased. Surface marker was investigated and MCS-2 (CD13), C17 (CDw41) and P2 (CDw41) were found to be positive. Electron microscopic examination revealed that blast cells were composed of PPO-positive cells and MPO-positive cells. Based on these findings, it was considered that the patient developed acute myelomegakaryoblastic leukemia. Recently AMF is thought to be a state to have the ability to develop into various types of acute leukemia. Adequate therapy may be required before the development of leukemia.

Acute Disease↗

Transmission and genetic shift of human immunodeficiency virus (HIV) in vivo.

HIVYU-6 and HIVYU-7 were isolated from an acquired immune deficiency syndrome patient (MK) and his asymptomatic sexual partner (MM), respectively. YU-6 readily infected not only peripheral lymphocytes from normal individuals but also human T-cell lines such as H9, HUT-78, MOLT-4 and MT-4; YU-7, on the other hand, could not infect H9 and MT-4 cells. Furthermore, although autologous serum failed to neutralize YU-6, it was neutralized by the heterologous serum from the partner. Restriction endonuclease analysis of YU-6 demonstrated that it was a mixture of viruses. We have isolated two clones from YU-6 (YU-6-a and YU-6-b) by a plaque assay method and showed that YU-6-a had one more KpnI site than YU-6-b. It was also evident that YU-7 derived from YU-6-a, but had already shifted genetically from YU-6-a. Transmission of human immunodeficiency virus through heterosexual contact and a possible genetic shift of YU-6-a, b and YU-7 from a common progenitor virus in vivo is discussed.

Acquired Immunodeficiency Syndrome↗

Serial transmission of human T-cell leukemia virus type I by blood transfusion in rabbits and its prevention by use of X-irradiated stored blood.

Human T-cell leukemia virus type I (HTLV-I) was serially transmitted for 5 passages from rabbit to rabbit by blood transfusion. The virus could be transmitted with 20 ml of whole blood or washed blood cell suspension (fresh or stored for 1-2 weeks at 4 degrees C) but not with cell-free plasma from seroconverted rabbits. Seroconversion occurred 2-4 weeks after blood transfusion and serum anti-HTLV-I titers ranged from 1:20 to 1:640 with the immunofluorescence assay. From transfusion recipients of the 1st to 4th passages, virus-producing cell lines were established by culturing lymphocytes in the presence of T-cell growth factor (TCGF). Three of the 4 cell lines became TCGF-independent after 2-12 months of continuous culture. Blood was transfused between rabbits of opposite sexes and the recipient origin of each cell line was determined by chromosome analysis. We also investigated the effect of X-irradiation (6,000 rad) on blood from seropositive rabbits. Seroconversion likewise occurred in rabbits transfused with blood that had been irradiated immediately before transfusion but not in rabbits transfused with blood that had been irradiated and stored for 1-2 weeks at 4 degrees C. Thus, our rabbit model shows that HTLV-I is serially transmissible by blood transfusion and that this can be prevented by irradiation of blood. The same procedure, therefore, may be useful for the prevention of transfusion-related transmission of HTLV-I in humans.

Animals↗

Inactivation of lymphocyte-transforming activity of human T-cell leukemia virus type I by heat.

Peripheral blood lymphocytes from 2 normal individuals seronegative for human T-cell leukemia virus type I (HTLV-I) were co-cultured with HTLV-I-producing MT-2 cells that had been heated at 56 degrees for 30 min or exposed to 10,000 rad of X-irradiation. HTLV-I-induced lymphocyte transformation was consistently achieved by co-culture with irradiated MT-2 cells but not by co-culture with heated MT-2 cells. The heat treatment was found to be lethal to both MT-2 cells and the virus. These findings are discussed in terms of their potential clinical application for preventing the transmission of HTLV-I.

Breast Feeding↗

Infectious transmission of human T-cell leukemia virus to rabbits.

A rabbit lymphoid cell line (Ra-1) was established by co-cultivation with a human T-cell line (MT-2) carrying human T-cell leukemia virus (HTLV). The Ra-1 cell line is chromosomally male and is persistently infected with HTLV. Ra-1 cells, with or without mitomycin C treatment, were inoculated intravenously (i.v.) into 3 female rabbits. All 3 animals responded with the production of antibodies to HTLV antigens. Lymphocytes from one of these seroconverters were cultured in the presence of T-cell growth factor (TCGF) and HTLV particles were detected in the TCGF-grown lymphocytes which were chromosomally female. Co-cultivation of lymphocytes from the 2 other seroconverters with lymphocytes from 2 anti-HTLV-negative healthy men gave rise to the establishment of an HTLV-producing T-cell line derived from each individual. Blood transfusion from one of the HTLV-infected rabbits into 2 female rabbits also resulted in the seroconversion of both recipients. An HTLV-carrying lymphoid cell line (Ra-2) was established from one of the transfusion-related seroconverters. The Ra-2 cell line was initially TCGF-dependent but later became TCGF-independent. There results indicate that HTLV can be transmitted to rabbits. These animals may provide a suitable model system for studying the mode of transmission and pathogenicity of HTLV.

Adult↗

[Clinical evaluation of cefmenoxime in chronic complicated urinary tract infection].

The efficacy of cefmenoxime (CMX), which is a third generation, beta-lactamase-resistant cephem with a broad antibacterial spectrum, was examined in 43 patients with chronic complicated urinary tract infections. The usual dosage regimen was given 2 approximately 4 g/day of CMX by intravenous drip infusion over 1 hour. The duration of treatment was 5 days. Fifteen patients were cured and 21 improved, and the effective rate was 83.7%. Bacterial eradication rate in these cases was 88.2%, especially eradication of the original pathogens such as Serratia marcescens, Proteus species and Klebsiella species, occurred in high frequency. Laboratory abnormalities were slight elevation of serum GOT and GPT in 2 cases. From these findings, CMX was considered to be very effective in complicated urinary tract infections.

Adolescent↗

Amino acid sequence of the active site of human pseudocholinesterase.

The usual E1u and atypical E1a human pseudocholinesterases (acylcholine acylhydrolase, EC 3.1.1.8) were purified to homogeneity. The active-site serine residue was conjugated with diisopropyl fluorophosphate and digested with trypsin. The tryptic peptide containing the active site was isolated by gel filtration followed by two-dimensional paper chromatography and electrophoresis. The amino acid sequence of the active site peptide obtained from the usual E1u enzyme was found to be Gly-Glu-Ser-Ala-Gly-Ala-Ser-Ala-Val-Ser-Leu. A remarkable structural homology exists between the human and the horse enzymes in their active sites. From the difference in electrophoretic mobility of the active-site peptides obtained from the usual and atypical enzymes, the probable structure of the atypical human enzyme was deduced as Gly-His-Ser-Ala-Gly-Ala-Ser-Ala-Val-Ser-Leu.

Amino Acid Sequence↗