Treatment with recombinant IL-2 for recurrent respiratory infection in a case of cartilage-hair hypoplasia with autoimmune hemolytic anemia.
Explore the source record for details and available documents.
Anemia, Hemolytic, Autoimmune↗
Biomedical subjects
J Hara
Publications and source records attributed to J Hara.
Prediction of short-term outcome for patients with active ulcerative colitis.
We report results of a retrospective chart review to evaluate factors predicting short-term outcome of patients with ulcerative colitis treated by corticosteroids. Between January 1992 and December 1997, we treated 71 patients with ulcerative colitis (44 with severe and 27 with moderately severe disease). Forty-nine patients were treated by conventional prednisolone therapy and 22 patients by steroid pulse therapy. There were no differences in clinical or endoscopic improvement between the two treatments. Clinical examination showed that 41 patients entered remission, 17 patients improved, and 13 patients did not respond. Endoscopically, 26 patients entered remission, 30 patients improved, and 15 patients did not respond. Extent of disease, type of disease (first attack, relapsing, or chronic active type), and endoscopic findings were factors useful in predicting short-term outcome of medical treatment.
Adolescent↗
Juvenile myelomonocytic leukemia relapsing after allogeneic bone marrow transplantation successfully treated with interferon-alpha.
We report a 5-year-old boy with juvenile myelomonocytic leukemia (JMML) which relapsed after an allogeneic bone marrow transplant who was successfully treated with interferon-alpha (IFN-alpha). One year after starting the therapy, he remains clinically well and in complete remission while continuing treatment with IFN-alpha and bestatin. Although the precise mechanism by which remission was induced is uncertain, a GVL effect combined with a direct antileukemia effect of IFN-alpha may be responsible. Further assessment of the role of IFN-alpha in relapsed JMLL patients is warranted.
Antineoplastic Agents↗
Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease.
BACKGROUND: Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn's disease. We determined serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease. METHODS AND RESULTS: Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn's disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn's disease than in controls, and was significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn's disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn's disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level. CONCLUSIONS: The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition.
Adult↗
High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis.
We have previously demonstrated that there is abnormal expression of sphingomyelin (SM) deacylase-like enzyme in the epidermis of patients with atopic dermatitis (AD), which results in decreased levels of ceramides in their involved and uninvolved stratum corneum. For quantitation of the expression of SM deacylase in AD, we synthesized 16-(9-anthroyloxy) hexadecanoylsphingosylphosphorylcholine or [palmitic acid-14C] SM and used them as substrates to directly measure the activity of SM deacylase by detecting the release of labeled free fatty acid. Direct enzymatic measurements demonstrated that stratum corneum from lesional forearm skin (volar side) of AD patients has an extremely high SM deacylase activity that is at least five times higher than in the stratum corneum from healthy controls. In stratum corneum from nonlesional skin of AD patients, SM deacylase activity is still at least three times higher than in healthy controls. In contrast, stratum corneum from contact dermatitis patients shows levels of SM deacylase similar to healthy controls. In extracts of whole epidermis biopsies from AD patients, SM deacylase activities are significantly (3-fold) increased over healthy controls in the particulate fraction, whereas there is no significant difference in the activity of sphingomyelinase between AD and healthy control. In peripheral blood lymphocytes of AD patients, there is no increase in activity compared with healthy controls, indicating a possibility that the high expression of SM deacylase is highly associated with the skin of AD patients. These findings suggest that, in contrast to changes in sphingolipid metabolism due to aging, the hitherto undiscovered enzyme SM deacylase, is highly expressed in the epidermis of AD patients, and competes with sphingomyelinase or beta-glucocerebrosidase for the common substrate SM or glucosylceramide, which leads to the ceramide deficiency of the stratum corneum in AD.
Adolescent↗
Prediction of non-responsiveness to intravenous high-dose gamma-globulin therapy in patients with Kawasaki disease at onset.
Children with Kawasaki disease (n = 82), treated with intravenous immune globulin (IVIG) at a high dose, were classified as IVIG-responsive (defervescence within 5 days of starting IVIG, n = 69) or IVIG-non-responsive (consistent fever over a 6-day period since starting IVIG, n = 13). One patient in the IVIG-responsive group had a coronary artery abnormality during the acute phase (1. 4%) versus 5 in the IVIG-non-responsive group (38.5%). Age, duration of fever before the initiation of IVIG therapy, and laboratory data obtained on admission were tested by the Mann-Whitney U test. Serum levels of C-reactive protein, total bilirubin, lactate dehydrogenase, and gamma-glutamyltranspeptidase were significantly higher (P =.002, P <.001, P <.034, and P <.038, respectively), and the hemoglobin value was significantly lower (P =.025) in patients in the non-responsive group. A multivariate analysis showed that serum levels of C-reactive protein (P =.006), lactate dehydrogenase (P =. 035), and total bilirubin (P =.046) on admission were independent correlates of the success of IVIG therapy. By defining the predictive values, patients with a C-reactive protein level >10 mg/dL, LDH level >590 IU/L, and/or hemoglobin value <10 g/dL are considered non-responsive to IVIG. Additional therapy at an early stage of the disease should be considered for patients who are predicted to be IVIG-non-responsive.
Bilirubin↗
Role of the beta isoform of 14-3-3 proteins in cellular proliferation and oncogenic transformation.
The 14-3-3 proteins are associated with proto-oncogene and oncogene products. Here, we generated NIH 3T3 cells overexpressing the beta isoform of the 14-3-3 proteins (14-3-3 beta) to examine the function of this isoform in cellular proliferation and oncogenic transformation. Overexpression of 14-3-3 beta in NIH 3T3 cells stimulated cell growth and supported anchorage-independent growth in soft agar medium and tumor formation in nude mice. To elucidate the molecular mechanisms of 14-3-3 beta-mediated NIH 3T3 transformation, we examined the activity of mitogen-activated protein kinase (MAPK) after serum stimulation. Overexpression of 14-3-3 beta augmented MAPK activity after serum stimulation, and MAPK activity correlated well with the amount of 14-3-3 beta expression. The colony-forming ability of NIH 3T3 cells overexpressing 14-3-3 beta in soft agar medium was efficiently abolished by exogenous expression of a dominant-negative mutant of MEK1 and 14-3-3 beta physically interacted with Raf-1 in these cells. These findings indicate that 14-3-3 beta has oncogenic potential, mainly through enhancement of Raf-1 activation and resultant augmentation of signaling in the MAPK cascade.
14-3-3 Proteins↗
Hypotensive effect of endothelin-1 via endothelin-B-receptor pathway on pulmonary circulation is enhanced in rats with pulmonary hypertension.
The pharmacological characterization of endothelin-1 (ET-1) in the pulmonary circulation in pulmonary hypertension (PH) is not known precisely. We investigated the effect of intravenous injection of ET-1 (1000 pmol/kg) on right ventricular systolic pressure (RVSP) (which is equal to systolic pulmonary arterial pressure) in rats with monocrotaline-induced PH. ET-1 decreased RVSP in PH rats; however, ET-1 did not alter RVSP in control rats, suggesting that ET-1 causes dilatation of the pulmonary artery in PH rats. Under pretreatment with the endothelin-A- (ET(A)) receptor antagonist BMS 193884, ET-1 decreased RVSP in PH rats more than in control rats, suggesting that pulmonary vasodilator action of ET-I mediated via the ET(B)-receptor pathway is augmented in PH rats. Under pretreatment with the ET(A/B)-receptor antagonist SB 209670, the effect of ET-1 in lowering pulmonary arterial pressure was abolished in both groups of rats. These results suggest that the hypotensive effect of ET-1 on pulmonary circulation mediated via the ET(B)-receptor pathway is enhanced in PH rats compared with control normal rats. It is considered that the blockade of only the ET(A)-receptor pathway is preferable to the blockade of both the ET(A)- and ET(B)-receptor pathways in the treatment of PH.
Animals↗
Relationship of two ribonucleases with molecular masses of 45 kDa and 37 kDa from the culture medium of Lentinus edodes.
Lentinus edodes (shiitake) produces three base non- specific and acid ribonucleases, RNase Le2, RNase Le37 and RNase Le45. The primary structures of the former two RNases, having molecular masses about 24 and 37 kDa, respectively, have been elucidated to be members of the RNase T2 family. The latter two are excreted from mycelia into the medium. In this report, we estimated the primary structure of RNase Le45 using the following experimental evidence. (i) The partial amino acid sequence of RNase Le45 determined that up to about 60% of total protein was identical with that of RNase Le37. (ii) The amino acid composition of RNase Le45 was identical to that of RNase Le37. (iii) The elution profiles on HPLC of lysylendopeptidase and Staphylococcus aureus V8 protease digests of RCM-RNase Le45 (reduced and S-carboxymethylated RNase Le45) were very similar to those of RNase Le37, except for the absence of C-terminus peptide which contained O-glycosylated peptides. However, RNase Le45 contained about 70 residues of mannose and 4 residues of hexosamine. These values were more than twice those of RNase Le37. (iv) RNase Le45 was immunologically indistinguishable from RNase Le37. (v) After treatment with both glycosidase EndoH and alpha-mannosidase, RNases Le37 and Le45 gave complex bands by slab-gel electrophoresis. However, one of the major bands with the highest mobility from RNase Le45 and Le37 showed the molecular mass of 29 kDa in common, which is slightly larger than that of RNase Le2 containing no carbohydrate. These results indicated that RNase Le45 is an enzyme which is a heavily glycosylated species of RNase Le37.
Amino Acid Sequence↗
Amino acid sequence of an unique ribonuclease with a C-terminus rich in O-glycosylated serine and threonine from culture medium of Lentinus edodes.
The mushroom Lentinus edodes produces three base-non-specific and acid ribonucleases, RNases Le2, Le37, and Le45. The latter two are excreted from mycelia into the medium. The primary structure of RNase Le37, which had a molecular mass of 37 kDa, was sequenced. It was a member of the RNase T2 family, as is RNase Le2. RNase Le37 was some 30 amino acid residues longer at the C-terminal end than RNase Le2. The C-terminal region of RNase LE37 was rich in O-glycosylated serine and threonine. In fungal glucoamylases and chitinases, which hydrolyze raw-starch and chitin, respectively, have structures resembling the structure of the C-terminal of RNase Le37.
Agaricales↗
Structure and chromosomal localization of the RAE28/HPH1 gene, a human homologue of the polyhomeotic gene.
The Polycomb group of (Pc-G) genes and trithorax group of genes are known to play a crucial role in the maintenance of the transcriptional repression state of Hox genes, probably through modification of the chromatin configuration. The rae28/mph1 gene is a mammalian homologue of the Drosophila polyhomeotic gene, which belongs to the Pc-G genes. As reported previously, we established mice deficient in the rae28/mph1 gene and showed that these homozygous animals displayed the developmental defects compatible with a human congenital disorder, CATCH22 syndrome. In this study we analyzed the structural organization of the human counterpart of the rae28/mph1 gene (RAE28/HPH1) and its processed pseudogene (psiPH), which are located on, respectively, human chromosome 12p13 and 12q13. The HPH1 gene consists of 15 exons spanning approximately 26 kb and its structural organization is well conserved between mouse and human. These genetic information of the RAE28/HPH1 gene may provide an important clue for further examination of its involvement in human congenital disorders related to CATCH22 syndrome.
Animals↗
Homozygous Pro74-->Arg mutation in the platelet glycoprotein Ibbeta gene associated with Bernard-Soulier syndrome.
Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbalpha, GPIbbeta, GPIX and GPV. We describe here the genetic basis of the disorder in a patient with BSS. Flow cytometric analysis of the patient's platelets showed greatly reduced GPIbalpha and GPIX surface expression. Immunoblot analysis disclosed absence of GPIbalpha, GPIbbeta and GPIX in the platelets. DNA sequencing analysis revealed a novel missense mutation in the GPIbbeta gene that converts Pro (CCG) to Arg (CGG) at residue 74. Homozygosity of the mutation was confirmed by allele-specific restriction analysis, chromosome 22 microsatellite analysis and quantitative Southern blotting. The mutant GPIbbeta was normally transcribed. Transient transfection studies confirmed that mutant GPIbbeta impairs surface expression of GPIb/IX, showing that the mutation is responsible for a BSS phenotype observed in the patient.
Amino Acid Substitution↗
Prognostic factors in childhood acute lymphoblastic leukemia in Japan. Japan Association of Childhood Leukemia Study.
A retrospective analysis of children with acute lymphoblastic leukemia (ALL) was performed to evaluate the current status of diagnosis and treatment of ALL in Japanese children. Clinical records of 670 children with ALL were collected and analyzed; these children had been diagnosed between 1991 and 1995 at the 53 institutions in 4 areas participating in the Japan Association of Childhood Leukemia Study. It was found that T-cell ALL was significantly less frequent in Tokai and Hokkaido than in Kansai and Chu-Shikoku. The overall induction rate was 92.4%. The estimated 7-year overall survival rate and event-free survival (EFS) rate were 76.0% +/- 1.9% and 61.4% +/- 2.1%, respectively. EFS rates were significantly different among the geographic areas. In female patients with B-cell precursor (B-pre) ALL and white blood cell counts at diagnosis (WBCsdiag) below 50.0 x 10(9)/L, favorable outcomes were significant. Favorable outcomes were not significant in B-pre ALL patients with a WBCdiag above 50.0 x 10(9)/L or in T-cell ALL patients. The EFS rate for infants was significantly worse than that for patients over 1 year of age. In B-pre ALL, but not in T-cell ALL, it was found that the higher the WBCdiag, the worse the EFS rate. Multivariate analysis showed that the following factors were significantly unfavorable for EFS: the Philadelphia chromosome, an translocations associated with chromosome 11q23, an acute unclassified leukemia, mixed-lineage leukemia, a WBCdiag above 100.0 x 10(9)/L, and male gender. Hyperdiploidy (> 50 chromosomes) was significantly favorable for EFS. For further tailoring of treatment and to improve the outcome in childhood ALL, a prospective large-scale study should be undertaken in Japan.
Age Factors↗
Expression of adhesion molecules in childhood B-lineage-cell neoplasms.
We analyzed the expression pattern of adhesion molecules including beta 1-integrins (CD49c, CD49d, CD49e, CD49f), beta 2-integrins (CD11a, CD11b, CD11c), CD44, and CD54 in 141 children with B-cell precursor acute lymphoblastic leukemia (pre-B ALL) and in 21 children with B-cell ALL/non-Hodgkin's lymphoma (B-ALL/NHL). The frequencies of CD11a, CD49f, and CD44 expression were significantly higher in CD34+ pre-B ALL than in CD34- pre-B ALL. Although CD49d, CD49e, and CD44 were less frequently expressed in B-ALL/NHL than in pre-B ALL, the expression of CD11a and CD54 were more frequent in B-ALL/NHL. In pre-B ALL, expression of CD11a positively correlated with that of CD11b (P < .05) and CD54 (P < .01), and CD49c positively correlated with CD49f (P < .01). Of the clinical parameters of patients with pre-B ALL, expression of CD11a was associated with a low leukocyte count (P < .05). The presence of CD54 on the cell surface was an independent factor indicating a poor prognosis. The estimated 5-year event-free survival was 42.3% for CD54+ (n = 31) compared with 70.3% for CD54- patients (n = 38) (P < .05). These findings demonstrated that expression of adhesion molecules is dependent on the phenotype of B-lineage cells and that the expression of some of these molecules has clinical significance.
Antigens, CD↗
Polycomb-group genes and hematopoiesis.
Although long-range chromatin organization during cell differentiation has not yet been determined, considerable evidence suggests that regulation of the chromatin structure may play a crucial part in transcriptional regulation. Drosophila genetics has introduced a unique system that can maintain genes in the on or off state after the initial gene expression decision has been established. This maintenance system is known to be mediated through the trithorax-group (trxG) and Polycomb-group (PcG) genes. The products from these 2 genes individually form multimeric complexes in the chromatin. The trxG genes are known to maintain the transcriptionally active states of the chromatin, and the PcG genes are thought to maintain the repressive states. The function of the PcG genes is defined in terms of anteroposterior patterning not only in Drosophila but also in mammals, whereas mammalian PcG genes have additional functions in higher order biological functions All PcG gene-deficient mice have provided evidence that these genes play a crucial role in hematopoiesis These findings should help shed new light on the roles of the chromatin regulatory system in hematopoiesis.
Animals↗
Lineage switch in childhood leukemia with monosomy 7 and reverse of lineage switch in severe combined immunodeficient mice.
Morphophenotypic lineage switches occur in a small percentage of those with acute leukemia, and the underlying mechanisms are not clear. In this study, we attempted to induce a lineage switch in acute myelocytic leukemia (AML) with monosomy 7, whose lineage had switched from acute T-lymphocytic leukemia (T-ALL) during chemotherapy, in severe combined immunodeficient (SCID) mice. Although the transplanted myeloid cells were engrafted in SCID mice without cytokine administration, T-ALL developed in SCID mice treated with recombinant human granulocyte-macrophage colony-stimulating factor or recombinant human interleukin 3. Analysis of the nucleotide sequences of the rearranged T-cell receptor gamma-chain (TCR-gamma) gene revealed that this lineage switch resulted from the selection of the T-lineage subclone in SCID mice, which had expanded at onset. In addition, we found that the T-lineage and myeloid cells belonged to the distinct subclones, which were different in TCR-gamma gene rearrangements, but were derived from a common clone with an identical N-ras gene mutation for both subclones. In in vitro cultures, only the myeloid subclone grew; the T-lineage subclone failed to grow even in the presence of recombinant human granulocyte-macrophage colony-stimulating factor or recombinant human interleukin 3. These results suggested that the initial diagnostic T-lymphoid subclone, whose growth was dependent on these cytokines and the hematopoietic microenvironment, emerged from a bipotential T-lymphoid/myeloid leukemic stem cell, and further genetic event(s) induced the myeloid subclone, which grew independently of these cytokines and the microenvironment.
Acute Disease↗
Thrombotic microangiopathy associated with reactivation of human herpesvirus-6 following high-dose chemotherapy with autologous bone marrow transplantation in young children.
Thrombotic microangiopathy (TMA) is a serious complication of BMT. Several factors are important in the etiology of TMA, such as cyclosporin A, GVHD, irradiation, intensive conditioning chemotherapy and infection, which cause damage to vascular endothelial cells leading to activation of these cells. We describe two young children with TMA following high-dose chemotherapy with autologous BMT. Development of TMA was accompanied by reactivation of HHV-6, which was identified by both an increase in the copy number of HHV-6 DNA in the peripheral blood and a significant increase in antibody titers to HHV-6. Thus, it was suggested that reactivation of HHV-6 together with high-dose chemotherapy played an important role in the pathogenesis of TMA in these patients. Since HHV-6 is known to infect vascular endothelial cells, and CMV which is virologically closely related to HHV-6, has been reported to be a pathogen that causes TMA, infection with HHV-6 of vascular endothelial cells may induce TMA via damage and activation of these cells.
Bone Marrow Transplantation↗
Approximating dipoles from human EEG activity: the effect of dipole source configuration on dipolarity using single dipole models.
Dipolarity is the goodness-of-fit of the observed potential distribution with one calculated using specific assumptions about the source of the electrical potential distribution. We used computer simulations to examine the effect of different distributions of sources on their resulting dipolarity values. Electric dipoles were placed in a head-shaped model with uniform conductivity using four different dipole configurations (randomly oriented dipoles, a uniform dipole disk layer, a dipole disk layer with uniformly distributed holes, or one with randomly oriented dipoles). The best-fitting single dipole for each configuration was calculated and the dipolarity was computed as the mean squared error of the electrical potential distributions generated by the actual dipole configuration and by the best-fitting single dipole. The simulations show that: 1) a smooth dipole layer with or without holes gives dipolarities above 99.5% even when extended over areas as large as 1256 mm2; 2) randomly oriented dipoles under a smooth dipole layer also give dipolarities above 99.5%; and 3) randomly oriented and distributed dipoles, even if contained in a small portion of the total area, give dipolarities below 93.0%. These simulations show that inhomogeneity (holes) within a dipole disk layer per se do not lower dipolarity; rather, it is the random orientation and distribution of these dipoles which lowers dipolarity. Furthermore, dipolarity is not lowered by such randomly oriented and distributed dipoles when they are beneath a dipole disk layer.
Brain↗