Resolution of atopic dermatitis following allogeneic bone marrow transplantation for chronic myelogenous leukemia.
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Adult↗
Biomedical subjects
J Taguchi
Publications and source records attributed to J Taguchi.
Human herpesvirus-6 encephalitis after unrelated cord blood transplantation.
Here we describe 2 patients with acute leukemia in whom human herpesvirus-6 (HHV-6) encephalitis developed after cord blood transplantation. In patients 1 and 2, generalized seizure and coma developed on day 62 and day 15, respectively, after cord blood transplantation, which failed to engraft in patient 1. Magnetic resonance imaging (MRI) of patient 1's brain showed low-intensity signals at the gyri of the bilateral lateral lobes on T1-weighted images and high-intensity signals on T2-weighted images. MRI of patient 2's brain showed high-intensity signals in bilateral white matter on T2-weighted images and on fluid-attenuated inversion recovery (FLAIR) images. Cerebrospinal fluid examination revealed an increased protein level with pleocytosis in patient 1 and a normal protein level without pleocytosis in patient 2. Polymerase chain reaction analysis detected HHV-6 DNA in the cerebrospinal fluid of both patients. Patient 1 recovered after administration of gancyclovir for 3 weeks. However, she again suffered from encephalitis after discontinuation of gancyclovir, and died of sepsis. Patient 2 died from an anoxic brain caused by generalized seizure. When neurological symptoms and signs appear in hematopoietic stem cell transplantation recipients, we should consider HHV-6 encephalitis and promptly and empirically treat them with gancyclovir or foscarnet.
Adult↗
Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome.
In all, 18 patients (30-56 years; median 49) with MDS underwent allogeneic HSCT from related (n=12) or unrelated (n=6) donors after a conditioning regimen comprising thiotepa, cyclophosphamide, and TBI. GVHD prophylaxis consisted of cyclosporine (n=15) or tacrolimus (n=3) with short-course methotrexate. Four patients had low-risk disease (refractory anemia or complete remission after chemotherapy) and 14 patients had high-risk disease (RAEB, RAEB-t, or AML). Grade II-IV acute GVHD developed in six patients and chronic GVHD in 10. With a median follow-up of 31 months, the 2-year survival probability is 75% for low-risk patients and 57% for high-risk patients. One patient died of leukemia and six of treatment-related causes. This conditioning regimen requires further study in patients with MDS.
Adult↗
Neuroleptic malignant syndrome following BMT.
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Bone Marrow Transplantation↗
Lecithinized Cu, Zn-superoxide dismutase limits the infarct size following ischemia-reperfusion injury in rat hearts in vivo.
Covalent binding of 4 molecules of phosphatidylcholine palmitoyl to human recombinant superoxide dismutase (SOD) results in a compound (lecithinized SOD) that has a longer half-life and greater affinity to the cell membrane than unmodified SOD. We investigated whether lecithinized SOD played a protective role against myocardial ischemia-reperfusion injuries in rats. Rats underwent 45 min of myocardial ischemia by occluding the left coronary artery followed by 120 min of reperfusion. They were randomly assigned to receive either lecithinized SOD, polyethylene glycol conjugated SOD (PEG-SOD), unmodified SOD, free lecithin derivative, or PBS intravenously at 5 min prior to reperfusion. Myocardial infarct area assessed by TTC staining was smaller in lecithinized SOD group than PEG-SOD, unmodified SOD, free lecithin derivative or control group. Blood pressure and heart rate was similar in each group. ELISA demonstrated SOD level in the heart was significantly high in lecithinized SOD group, especially in the heart of ischemia at risk. Although serum SOD level of PEG-SOD was as high as lecithinized SOD, SOD level of the heart was low. These data suggested lecithinized SOD had a protective effect in myocardial ischemia-reperfusion injuries through its increased bioavailability.
Animals↗
Lecithinized copper, zinc-superoxide dismutase ameliorates ischemia-induced myocardial damage.
We have reported that lecithin-conjugated recombinant human Cu, Zn-superoxide dismutase (lecithinized SOD) has greater pharmacological potency than unmodified SOD through an increase in cell membrane affinity and half-life in plasma. Recently, ischemia or hypoxia alone has been suggested to result in increased superoxide anions, which lead to apoptosis in cardiomyocytes. We tested the effect of lecithinized SOD in reducing the infarct size following prolonged myocardial ischemia without reperfusion. Rats were subjected to a 24-h left coronary occlusion. Lecithinized SOD, unmodified SOD, free lecithin derivative or PBS was administered intravenously 30 min before coronary occlusion. SOD concentration of the heart, measured by ELISA, was higher in the lecithinized SOD-treated group than in the other groups 24 h after administration. The infarct area ratio of the heart, assessed by TTC staining, in the lecithinized SOD-treated group was significantly smaller than those of the other groups. Both TUNEL-positive cardiomyocytes and DNA laddering were attenuated in the ischemic area of the heart treated with lecithinized SOD. Single bolus administration of lecithinized SOD had a cardioprotective effect against ischemia without reperfusion in the rat model of acute myocardial infarction, possibly due to its sustained high tissue concentration.
Animals↗
The interleukin-13 receptor alpha2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway.
The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13Ralpha1 (also known as IL-13Ralpha') and IL-13Ralpha2 (also known as IL-13Ralpha). For a functional IL-13 receptor, the IL-13Ralpha1 chain forms a productive complex with the primary IL-4 binding protein (IL-4Ralpha also known as IL-4Rbeta). However, the function of the IL-13Ralpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13Ralpha2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of (125)I-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ralpha2 chain; (2) a recombinant chimeric fusion protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13Ralpha2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13Ralpha2-transfected cells. IL-13 efficiently caused activation of STAT6 protein in cells transfected with the IL-13Ralpha1 and IL-4Ralpha chains, and IL-13Ralpha2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13Ralpha2 is signal independent and that this property of IL-13Ralpha2 can be exploited for receptor-directed cancer therapy.
Animals↗
The CDCREL1 gene fused to MLL in de novo acute myeloid leukemia with t(11;22)(q23;q11.2) and its frequent expression in myeloid leukemia cell lines.
We report on an adult patient with de novo acute myeloid leukemia (AML) with a t(11;22)(q23;q11.2) involving CDCREL1 and MLL genes. Reverse transcriptase (RT)-polymerase chain reaction (PCR) followed by direct sequencing analysis revealed the MLL-CDCREL1 fusion transcript in his leukemic cells. Analysis of the fusion transcript showed that exon 6 of MLL was fused to exon 4 of CDCREL1, which contains an AT-hook domain of MLL and a GTP binding domain of CDCREL1. To investigate the roles of CDCREL1 further, we examined the expression of the CDCREL1 gene in various cell lines. Expression of CDCREL1 was detected in 11 (85%) of 13 AML cell lines and 3 (21%) of 14 acute lymphoblastic leukemia (ALL) cell lines, but none of 11 EB virus transformed B-cell lines by RT-PCR. The expression rate of CDCREL1 was significantly higher in AML cell lines than in ALL cell lines (P = 0.0035). Platelet glycoprotein 1B beta (GP1B beta), which is located downstream of CDCREL1 and is cotranscribed with CDCREL1 due to a nonconsensus polyadenylation sequence, was expressed in all these cell lines. The higher expression rate of CDCREL1 in AML cell lines than in ALL cell lines suggests that this gene may play some role in myeloid leukemogenesis.
Adult↗
De novo acute myeloid leukemia in the elderly; a consistent fraction of long-term survivors by standard-dose chemotherapy.
To clarify the characteristics of de novo acute myeloid leukemia (AML) among the elderly, we reviewed 112 patients over 60 years old (median age 72 years) who were treated at hospitals in Nagasaki Prefecture with a population of 1.5 million between 1987 and 1994. Reclassification of morphological diagnosis revealed that the proportion of M3 was lower but that of M6 and the incidence of cases with trilineage dysplasia (TLD), known as poor prognostic features, were higher in the elderly than in patients less than 60 years old. Similarly, chromosomal data showed a lower frequency of favorable karyotypes such as t(8;21) and t(15;17) in the elderly. The overall survival of all 112 patients was 10.3% at 5 years. Multivariate analysis indicated that good performance status (PS), low WBC at diagnosis, standard dose multi-drug chemotherapy and all-trans retinoic acid (ATRA) treatment for M3 patients, and morphological findings without TLD were significantly correlated with longer survival. Most of the long-term survivors were found among those who received standard dose therapy in this series, although no consensus has been established how to treat elderly AML patients. We propose that a prospective controlled trial is necessary to confirm the role of standard dose chemotherapy for elderly patients with de novo AML.
Acute Disease↗
Directed mutagenesis studies of the C-terminal fingerprint region of Bacillus subtilis pyrophosphatase.
The sequence SRKKQxxP near the C-terminus is conserved in pyrophosphatases of the recently discovered family II and includes a triplet of positively charged residues, two of which (Arg295 and Lys296 in Bacillus subtilis pyrophosphatase) are part of the active site and one (Lys297) is not. The importance of this triplet for catalysis by B. subtilis pyrophosphatase has been estimated by mutational analysis. R295K and K296R substitutions were found to decrease the catalytic constant 650- and 280-fold, respectively, and decrease the pK(a) of the essential acidic group by 1.1 and 0.5, respectively. K297R substitution was found to increase the catalytic constant 4.7-fold and to markedly change the protein circular dichroism spectrum in the range 250-300 nm. These results, together with the results of theoretical modelling of the enzyme-substrate complex, provide support for the direct involvement of Arg295 and Lys296 in substrate binding in family II pyrophosphatases.
Amino Acid Sequence↗
Primary carcinoid of the testis associated with carcinoid syndrome.
Testicular carcinoid is a rare disease accounting for less than 1% of all testicular neoplasms. It rarely manifests symptoms of carcinoid syndrome. Recent reports have noted that only 1.1-3.1% of testicular carcinoid tumors are complicated by carcinoid syndrome. In general, large tumor size and the presence of carcinoid syndrome are features associated with a malignant course. In the present case, pathological findings revealed pure carcinoid of the testis without metastasis. Moreover, watery diarrhea due to carcinoid syndrome disappeared and the serum serotonin level normalized following orchiectomy. The patient was followed up for 12 months with whole body computed tomography scan and assessment of serotonin levels. To date, there is no evidence of tumor recurrence. These findings suggest that monitoring serum serotonin levels may be useful as a marker during follow up of this type of tumor.
Adult↗
Different effects of angiotensin II and catecholamine on renal cell apoptosis and proliferation in rats.
BACKGROUND: We have recently found that chronic infusion of angiotensin II (Ang II) into rats resulted in an impairment of renal function, whereas norepinephrine (NE) infusion did not. We investigated whether chronic infusion of Ang II and NE caused different degrees of renal cell apoptosis and proliferation. METHODS: Rats were made hypertensive via continuous infusion of either Ang II or NE for up to seven days. Renal cell apoptosis and proliferation were analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and staining with antibody against proliferating cell nuclear antigen (PCNA), respectively. In some experiments, an inducer or inhibitor of heme oxygenase-1 (HO-1) was administered to investigate the possible role of HO-1 in renal cell homeostasis. RESULTS: Infusion of Ang II, but not NE, resulted in approximately a sevenfold increase in bax protein at seven days of infusion. The TUNEL assay revealed that Ang II infusion significantly increased the number of apoptotic cells, whereas NE infusion did not. TUNEL- and PCNA-positive cells were mainly seen in the tubulointerstitial region of Ang II-infused rats. Ang II induced increased positivity of TUNEL, and PCNA was blocked completely by losartan, but only partially by hydralazine. Induction of HO-1 reduced and inhibition of HO increased Ang II-induced cell proliferation. CONCLUSIONS: These data suggest that Ang II plays a pivotal role in the development of renal cell proliferation and apoptosis in the setting of hypertension. The renal HO system may modulate proliferative and pro-apoptotic effects of Ang II.
Angiotensin II↗
Subcutaneous extramedullary hematopoiesis in a patient with secondary myelofibrosis following polycythemia vera.
We describe the case of a 73-year-old woman with secondary myelofibrosis who developed subcutaneous extramedullary hematopoiesis. Although extramedullary hematopoiesis has been generally observed in primary myelofibrosis, in this case it was seen in myelofibrosis secondary to polycythemia vera. Histological examination of the subcutaneous nodule revealed that the lesion included cells from the myeloid and megakaryocytic series. The skin lesion almost disappeared after treatment with hydroxyurea. We report here this rare manifestation in secondary myelofibrosis including a review of literature.
Aged↗
Primary splenic Hodgkin's disease with remarkable granulomatous reaction.
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Aged↗
[Successful second transplant from one-locus HLA-mismatched unrelated donor for graft rejection following initial transplant from another unrelated donor in a patient with chronic myelogenous leukemia].
We report a patient with chronic myelogenous leukemia who received a second transplant from a one-locus HLA-mismatched unrelated donor after rejection of an initial bone marrow graft. For the first transplant, HLAs were fully matched, conditioning with busulfan + cyclophosphamide (CY) was applied, and cyclosporin A + short-term methotrexate (sMTX) was used for prophylaxis against GVHD. A complete chimera was not obtained, and the graft was rejected on day 122. For the second transplant, there was a one-HLA locus (DR) mismatch, conditioning was done with total body irradiation + cytarabine + CY, and GVHD prophylaxis consisted of FK506 + sMTX. Engraftment was obtained on day 27, and no graft failure was occurred at the time of writing. This case suggests that strong immunosuppression may have prevented rejection of the second bone marrow graft.
Adult↗
Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo.
Enhanced production of reactive oxygen species plays a role in myocardial injury following ischemia/reperfusion. Heme oxygenase-1 (HO-1) is a heme-catabolizing enzyme that is induced by and acts against oxidant-induced tissue injury. We examined whether HO-1 expression was regulated following ischemia and reperfusion in the rat heart. HO-1 expression increased as early as 24 h after reperfusion. Strong HO-1 expression was seen in monocytes/macrophages and myofibroblasts. Next, we examined whether the induction of HO-1 could ameliorate cardiac injury following ischemia/reperfusion. Intraperitoneal hemin injection (30 mg/kg/day) for 2 days prior to the operation resulted in an about 2.8-fold increase in HO-1 expression in the rat heart. Hemin treatment significantly decreased infarct area (6 +/- 2%) compared to the control (21 +/- 2%), which was reversed by the coadministration of an HO inhibitor in a dose-dependent manner. Our data suggest that induction of HO-1 can reduce the cardiac injury in vivo following ischemia/reperfusion.
Animals↗
Application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer into rabbit aortas.
We investigated whether application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer into rabbit aortas. Assay of beta-galactosidase activity was performed in the aortas subjected to adenovirus encoding LacZ gene (Ad-LacZ) transfer. Application of hydrostatic pressure at 8 atmospheres during Ad-LacZ gene transfer (10(10) pfu/mL, 10 min) to aortic segments resulted in an approximately 4.5-fold increase in transgene efficiency. X-Gal staining showed predominant beta-galactosidase activity in the endothelial and the adventitial cells in the aorta subjected to pressure-supported Ad-LacZ gene transfer. Then we examined the effect of heme oxygenase-1 (HO-1), which catabolizes heme to carbon monoxide and biliverdin, by transferring adenovirus encoding HO-1 (Ad-HO-1) into rabbit aortas using this pressurization system. The Ad-HO-1-infected aortic segment showed a significantly decreased contractile response to phenylephrine compared to the Ad-LacZ-infected aortic segment. Pressure-supported adenovirus gene transfer may increase the feasibility of exploiting intraoperative adenovirus-mediated gene transfer.
Acetylcholine↗
Lecithinized copper, zinc-superoxide dismutase ameliorates prolonged hypoxia-induced injury of cardiomyocytes.
Recent studies have suggested that prolonged hypoxia results in increased production of reactive oxygen species in cardiomyocytes, which leads to apoptosis of these cells. We previously showed that lecithinized recombinant human copper, zinc-superoxide dismutase (rhSOD) showed increased bioavailability through greater membrane affinity and a longer half-life than unmodified SOD. The purpose of this study was to investigate whether lecithinized SOD plays a protective role against hypoxic injury in cardiomyocytes. Cultured rat cardiomyocytes incubated with lecithinized SOD (100 U/ml), unmodified SOD (100 U/ml), or vehicle alone were subjected to hypoxia for up to 72 h. Lecithinized SOD, but not unmodified SOD, was successfully delivered intracellularly, which was verified by Western blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized SOD significantly suppressed hypoxia-induced cell damage. Since lecithinized SOD also suppressed hypoxia-induced DNA fragmentation, the improved cell survival provided by lecithinized SOD is thought to be mediated by its antiapoptotic effect. In summary, lecithinization resulted in a facilitated rhSOD delivery into cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to prolonged hypoxia.
Animals↗