[Case of glycogen storage disease with accentuated myocardial hypertrophy and characteristic ECG changes in a 19-old man].
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Adult↗
Biomedical subjects
H Ohashi
Publications and source records attributed to H Ohashi.
Evidence for nonclonal hematopoietic progenitor cell populations in bone marrow of patients with myelodysplastic syndromes.
Clonality of marrow hematopoietic progenitor cells in myelodysplastic syndromes (MDS) was analyzed by X-chromosome inactivation pattern using polymerase chain reaction (PCR). Five female patients were included in this study; two with refractory anemia (RA) and three with RA with excess blasts (RAEB). They were heterozygous for BstXI restriction fragment length polymorphisms (RFLP) of the X-chromosome-linked phosphoglycerate kinase (PGK) gene. In each patient, erythroid and nonerythroid colonies, grown in the presence of erythropoietin and granulocyte-macrophage colony-stimulating factor (GM-CSF), exhibited no remarkable difference in clonal constitution. Two patients showed only one methylation pattern, suggesting the monoclonal origin of hematopoietic progenitor cells. Colonies of two other patients exhibited predominant and minor methylation patterns in PGK gene, indicating that nonclonal progenitor cells remain a minor population. The bone marrow of one patient appeared to contain a greater proportion of nonclonal progenitors. Stem cell factor (SCF), a potent colony-stimulating factor, enhanced both erythroid and nonerythroid colony formation. However, it did not notably alter the clonal constitutions. We conclude that nonclonal hematopoietic progenitor cells can persist in a substantial number of MDS patients.
Aged↗
Another family with tricho-rhino-phalangeal syndrome type III (Sugio-Kajii syndrome).
Tricho-rhino-phalangeal syndrome Type III (TRPS III) is a newly defined genetic entity. Only 9 patients in a family and one sporadic patient have been reported. We add another family in which 4 individuals in 3 generations are affected with this autosomal dominant trait. Although they manifested short stature, sparse hair, "pear-shaped" nose, and cone-shaped epiphyses, sharing these findings with TRPS Type I, the presence of a severe form of generalized shortness of all phalanges and metacarpals, and the absences of mental deficiency and exostoses in this family distinguish the disorder from the TRPS Types I and II. Their manifestations are quite similar to those of the patients reported as TRPS III (Sugio-Kajii syndrome).
Abnormalities, Multiple↗
Peripheral blood cells are predominantly chimeric of affected and normal cells in patients with paroxysmal nocturnal hemoglobinuria: simultaneous investigation on clonality and expression of glycophosphatidylinositol-anchored proteins.
To investigate clonal compositions of hematologic cells in paroxysmal nocturnal hemoglobinuria (PNH), we analyzed peripheral blood (PB) cells of 12 female patients with PNH, by clonality analysis using X-chromosome inactivation and assessment of expression of glycophosphatidylinositol-anchored proteins (GPI-APs) by flow cytometry. Southern hybridization showed that granulocytes were monoclonal in three and polyclonal in eight patients, respectively, whereas lymphocytes were polyclonal in all nine patients examined. Expressions of CD16 and CD59 on granulocytes varied greatly in seven patients examined. Clonality analysis of granulocytes by the polymerase chain reaction showed that CD59- and CD59low+ cells were monoclonal, whereas CD59+ cells were polyclonal. It was shown that PB cells are predominantly chimeric of clonal (GPI-AP- or GPI-APlow+) and nonclonal (GPI-AP+) cells in PNH, and that degrees of chimerism differ greatly from patient to patient.
Adolescent↗
Ligand-induced activation of chimeric receptors between the erythropoietin receptor and receptor tyrosine kinases.
Ligand-induced dimerization is a key step in the activation of receptor tyrosine kinases, including the epidermal growth factor receptor, stem cell factor receptor (c-kit), and colony-stimulating factor 1 receptor (c-fms). The erythropoietin receptor (EPOR), a member of the cytokine receptor family, contains no kinase motif and its activation mechanism remains unclear. Here we show that chimeric receptors carrying the extracellular domain of the epidermal growth factor receptor or c-kit linked to the cytoplasmic domain of the EPOR, transmitted epidermal growth factor or stem cell factor-dependent proliferation signals in an interleukin 3-dependent cell line. The chimeric receptors as well as the wild-type EPOR also mediated the ligand-induced tyrosine phosphorylation of a set of similar proteins. Moreover, erythropoietin triggered mitogenic signals of chimeric receptors carrying the extracellular domain of the EPOR linked to the tyrosine kinase of c-fms. These data demonstrate the interchangeability of domains between two distinct receptor families and suggest that ligand-induced dimerization is a key step in activating the EPOR.
Amino Acid Sequence↗
High-yield production of human big endothelin-1 by a combination of chemical modification and proteolysis of a fusion protein in Escherichia coli.
A protein modification method has been developed for the production of human big endothelin (ET)-1. Production of a large quantity of big ET-1 by the method described here is expected to facilitate future experiments such as X-ray crystallography and nuclear magnetic resonance studies, aimed at understanding the tertiary structure of big ET-1 and its dynamics. The plasmid pETB-50 used for the synthesis carries the gene for a fusion protein consisting of 34-amino acid (aa) residues of an N-terminal portion of beta-galactosidase and the 38-aa residues of big ET-1. The fusion protein ETB-50P contains an arginine residue in the big ET-1 portion at its second C-terminal site and three lysine residues including the C-terminal site in the beta-galactosidase portion, all of which are susceptible to trypsin. Tryptic digestion of the fusion protein quantitatively produced big ET-1 (1-37), which is depleted in the C-terminal serine. However, a treatment of the fusion protein with 1,2-cyclohexanedione prior to tryptic digestion gave full-length big ET-1 with N7, -N8-(1,2-dihydroxycyclohex-1,2- ylene)-arginine. This modification was reversed to the intact arginine residue when the modified big ET-1 was incubated in 0.5 M TRIS-HCl buffer, pH 8.0. Consequently, a combination of such a reversible protein modification and tryptic digestion gave 1.74 mg of recombinant big ET-1 from 2.01 of culture broth. The procedure described here may be applied to produce other arginine-containing peptides from fusion proteins.
Amino Acid Sequence↗
Ras oncogene enhances the production of a recombinant protein regulated by the cytomegalovirus promoter in BHK-21 cells.
In order to enhance recombinant protein productivity in animal cells, we developed the oncogene activated production (OAP) system. The OAP system is based on the premise that oncogenes are able to enhance promoter activity. To this end, we constructed reported plasmids by fusing various promoters to the human interleukin-6 (hIL-6) cDNA, and the effector plasmids by inserting individual oncogenes, for example c-myc, c-fos, v-jun, v-myb and c-Ha-ras, downstream from the human cytomegalovirus immediate early (CMV) promoter. Results of transient expression experiments with BHK-21 cells suggest that the CMV promoter is the most potent promoter examined and that the ras product is able to transactivate the beta-actin, CMV and SR alpha promoters. Recombinant BHK-21 cells producing hIL-6 under the control of the CMV promoter were contransfected with the ras oncogene and dihydrofolate reductase gene, then selected with 50 nM methotrexate to coamplify the ras oncogene. We were able to rapidly establish a stable and highly productive clone which exhibited a 35-times higher production rate as compared to the control value.
Actins↗
The c-kit receptor transduces the stem cell factor-triggered growth signal in murine interleukin-3-dependent cell line.
The stem cell factor is a glycoprotein hormone which regulates the proliferation and differentiation of primitive hematopoietic cells through its interaction with a tyrosine kinase transmembrane receptor which is encoded by the c-kit proto-oncogene. To examine whether a murine c-kit receptor can be functional in murine interleukin-3 (mIL-3)-dependent hematopoietic cell line, we introduced the murine c-kit cDNA into mIL-3-dependent pro-B cell line Ba/F3. One of the resulting clones, Ba/F3 clone BF-K96, expressed the 140 kDa protein recognized by anti-c-kit monoclonal antibody and the expressed c-kit receptor protein on the cell surface bound to a radiolabeled soluble form of murine stem cell factor (mSCF) with high affinity. BF-K96 clone expressing the c-kit receptor could proliferate in response to mSCF in the absence of mIL-3. The cell clone could also grow in co-culture with mouse 3T3 cells which are endogeneously expressing a membrane-associated type of mSCF on their cell surfaces. These findings demonstrate that the c-kit receptor expressed on mIL-3-dependent hematopoietic cell line Ba/F3 transduce the mSCF-dependent growth signal, indicating that established cell clone will provide a unique cellular system for the study of SCF/c-kit signal transduction mechanism.
Animals↗
Thermal lattice Bhatnagar-Gross-Krook model without nonlinear deviations in macrodynamic equations.
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Journal Article↗
Currarino triad (anorectal malformation, sacral bony abnormality and presacral mass) with partial trisomy of chromosomes 13q and 20p.
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Abnormalities, Multiple↗
Mechanical and current responses to neurotensin in the smooth muscle of guinea-pig intestine.
1. The effects of neurotensin (NT) on the mechanical activity of the smooth muscle and membrane currents of enzymatically-dispersed single smooth muscle cells of guinea-pig intestine were investigated by the isometric tension recording method and the whole-cell patch clamp technique, respectively. 2. NT (0.3-670 nM) produced an initial relaxation followed by a contraction in segment preparations of the jejunum and ileum. Atropine (0.2 microM) abolished the contraction. In 30% of ileal segments, NT produced a slowly-developed contraction in the presence of atropine. The atropine-resistant contraction was insensitive to tetrodotoxin (TTX, 0.2 microM). The relaxant effect of NT was unaffected by TTX (0.2 microM) and guanethidine (2 microM), but markedly reduced or abolished by apamin (67 nM). 3. In segment preparations of the colon and rectum, NT produced a biphasic response, similar to that in the small intestine, or a triphasic one (relaxation, contraction and relaxation). The contractile effect of NT was affected neither by atropine (0.2 microM) nor by TTX (0.2 microM). The first relaxation in response to NT was similar in pharmacological properties to that in the small intestine. 4. Responses to NT in longitudinal muscle strips were similar to those in segment preparations. The taenia caecum responded to NT with a contraction alone and the effect was unaffected by atropine (0.2 microM) and TTX (0.2 microM). 5. NT had little or no effect on the mechanical activity in the circular muscle of the small intestine. In the circular muscle of the large intestine, NT had a weak inhibitory effect on the spontaneous activity which was followed by a small rise in muscle tone. Apamin (67 nM) converted the biphasic response to a contraction. 6. In cells dialysed with a KCl-based solution under voltage clamp at 0 mV, NT (5 microM) produced a brief, outward current in a very small fraction of cells (4 out of 40 cells). When cells were dialysed with a CsCl-based solution under voltage clamp at -50 or -60 mV, no current response to NT (5 microM) was observed in all 37 cells, but NT increased inward Ca2+ currents evoked upon depolarization. 7. From these results, it appears that there is a regional difference in the mode of action of NT to contract and relax the smooth muscle of guinea-pig intestine, and NT acts on its receptors on the smooth muscle to enhance activation of voltage-dependent Ca2+ channels, which underlies the slow contraction in the longitudinal muscle of the intestine.
Adenosine Triphosphate↗
Effect of trimebutine on contractile responses in skinned ileal smooth muscle.
The effects of trimebutine on Ca2+ release and modulation of Ca2+ sensitivity of contractile elements induced by carbachol (CCh) were investigated using a tension measuring method in beta-escin-treated skinned smooth muscle of the longitudinal muscle layer of guinea pig ileum. Trimebutine (10-100 microM) concentration-dependently inhibited tension development brought about by Ca2+ release from intracellular stores induced by CCh (10 microM), but did not affect those induced by inositol 1,4,5-trisphosphate (IP3, 25 microM) or caffeine (5 mM). The inhibitory effect was reversible. Trimebutine (100 microM) neither altered the Ca2+ sensitivity of the contractile elements nor affected the effects of GTP gamma S (50 microM) and CCh (100 microM) in potentiating Ca2+ sensitivity of the contractile elements after the Ca2+ storage function had been eliminated by A23187. These results suggest that trimebutine inhibits CCh-induced Ca2+ release by acting at some point during the coupling of muscarinic receptors through a G-protein to phospholipase C and thus reducing the accumulation of IP3.
Animals↗
Efficient expression of a transfected foreign gene by Cos1 cells in serum-free medium.
In this report, we have found that fatty acid-free bovine serum albumin stimulated the expression of a transfected foreign gene in Cos1 cells in serum-free medium and that its activity was as same as that of fetal calf serum. This will simplify the purification of the gene product from the culture medium.
Animals↗
[A case report of coronary artery bypass grafting surgery with aprotinin in a patient undergoing chronic haemodialysis].
A 61-year-old patient who was receiving haemodialysis because of chronic renal failure developed unstable angina pectoris with three vessel disease. We performed successful coronary artery bypass grafting, using aprotinin to reduce blood loss. Blood loss during the operation was 750 ml, and during a 6 hour period after the operation it was 150 ml. This amount seemed to be small. No adverse clinical effects attributable to aprotinin were seen, and urine volume and plasma creatinine were not different before and after the operation. In summary, aprotinin is useful adjunct to open heart surgery in chronic haemodialysis patients.
Aprotinin↗
Effects of thyroid hormones on the lymphocyte phenotypes in rats: changes in lymphocyte subsets related to thyroid function.
The effects of hyperthyroidism and hypothyroidism on the immune function were assessed in rats by the changes in lymphocyte subsets in peripheral blood and spleen. Hyperthyroidism was induced in rats by intraperitoneal injection of large doses of T4. Hypothyroid rats were prepared by total thyroidectomy followed by 131I administration. In the hyperthyroid rats, the peripheral blood helper/suppressor T cell ratio was decreased, while in hypothyroidism this ratio was increased. However, in spleen cells, this ratio was increased in hypothyroid rats as compared to normal controls. The most striking finding was an augmentation of activated T cells (transferrin receptor positive lymphocytes) in both peripheral blood and spleen cells in the hypothyroid rat. These results suggested that thyroid hormone suppressed the immune response and that a deficiency of this hormone was associated with an increase of activated T cells. These effects of thyroid hormone on the lymphocyte subsets in rats were at variance with the abnormalities that have been observed in humans with such autoimmune thyroid disease as Graves' disease.
Animals↗
Recovery of polyclonal hematopoiesis in patients with myelodysplastic syndromes following successful chemotherapy.
We performed X-linked restriction fragment length polymorphism (RFLP)-methylation analysis to study the clonality of hematopoiesis in five patients with myelodysplastic syndromes (MDS), who had responded to chemotherapy. Two patients had MDS in blast crisis, two had refractory anemia with an excess of blasts in transformation (RAEB-T), and one had acute myelogenous leukemia with trilineage myelodysplasia (AML-TMDS). Following the administration of low-dose cytarabine therapy or of conventional intensive chemotherapy, we observed a reversion to polyclonal hematopoiesis in three patients who achieved a complete remission (CR). Polyclonal hematopoiesis persisted in one patient in CR, and monoclonal hematopoiesis persisted in another patient of minor response. These results indicate that polyclonal hematopoiesis can be restored in some MDS patients who achieved CR. We are encouraged, therefore, to administer intensive consolidation chemotherapy to prolong the duration of remission.
Adult↗
[Severe ascending aortic stenosis after one-stage repair of aortopulmonary window and interrupted aortic arch].
A 33-day-old girl was transferred to our hospital because of severe cyanosis and tachypnea. The diagnosis of aortopulmonary window and interrupted aortic arch was established by echocardiogram and cineangiocardiogram. Reconstruction of aortic arch by extended direct anastomosis and simple patch closure of aortopulmonary window were performed by means of profound hypothermia and circulatory arrest on 36 days of age. Her postoperative clinical course was uneventful, but at 2 months after operation, stenosis of the ascending aorta was noticed by echocardiographic examination. As her physical growth had been satisfactory, she was managed under close observation at outpatient clinic. At seven months after operations, she fell into progressive left heart failure, and emergency operation was carried out for the relief of stenosis of the ascending aorta, but she could not come off bypass. A stenosis of the ascending aorta is a fatal complication that may occur after one-stage repair of interrupted aortic arch with aortopulmonary window consisting of extended direct anastomosis and simple patch closure. We now consider that division of ascending aorta and pulmonary artery and repair of both of the defect is indispensable for the correction of aortopulmonary window, especially in neonate and small infant with this lesion associated with interrupted aortic arch.
Aorta↗
A stable acentric marker chromosome: possible existence of an intercalary ancient centromere at distal 8p.
A centromere is considered to be an essential chromosomal component where microtubule-kinetochore interaction occurs to segregate sister chromatids faithfully and acentric chromosomes are unstable and lost through cell divisions. We report a novel marker chromosome that was acentric but stable through cell divisions. The patient was a 2-year-old girl with mental retardation, patent ductus arteriosus, and mild dysmorphic features. G-banded chromosome analysis revealed that an additional small marker chromosome was observed in all 100 cells examined. By the reverse-chromosome-painting method, the marker was found to originate from the distal region of 8p, and a subsequent two-color FISH analysis with cosmid probes around the region revealed that the marker was an inverted duplication interpreted as 8pter-->p23.1::p23.1-->8pter. No centromeric region was involved in the marker. By FISH, no alpha-satellite sequence was detected on the marker, while a telomere sequence was detected at each end. Anti-kinetochore immunostaining, using a serum from a patient with CREST (calcinosis, Raynaud syndrome, esophageal dismotility, sclerodactyly, and telangiectasia) syndrome, showed a pair of signals on the marker, which indicated that a functional kinetochore was present on the marker. The analysis of this patient might suggest the possibility that an ancient centromere sequence exists at distal 8p (8p23.1-pter) and was activated through the chromosome rearrangement in the patient.
Abnormalities, Multiple↗