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Biomedical subjects

Y Eto

Publications and source records attributed to Y Eto.

At least 91 records · Page 5Linked to original sources
PubMed1999

Psychiatric inpatients and chromosome deletions within 22q11.2.

Velocardiofacial syndrome (VCFS) is a congenital disorder characterised by multiple dysmorphisms, cleft palate, cardiac anomalies, and learning disabilities due to a microdeletion of chromosome 22q11.2. Although VCFS is often associated with psychiatric symptoms, its prevalence among psychiatric patients is unknown. A total of 326 patients admitted in September and October 1997 to a Japanese psychiatric hospital were screened for the clinical features of VCFS. Twelve patients with minor facial dysmorphia were identified; chromosomal analysis with fluorescent in situ hybridisation (FISH) was performed in six patients who, further assessment suggested, were most likely to have VCFS. Chromosome 22q11.2 deletion was identified in a 41 year old woman who had symptoms of schizophrenia but no major dysmorphia, such as cardiovascular anomalies and cleft palate. Her behavioural and neuropsychological profiles were similar to those previously reported in VCFS. She was hemizygous for the FISH probe N25 (GDB locus D22S75) and also for probes N72H9 (D22S181), sc11.1a, C443 (D22S941), sc4.1 (D22S134), sc11.1b, N19B3 (D22S264), N122B5 (D22S934), and N77F7 (D22S939). The size of the deletion was about 3 Mb. Our patient had only some features of VCFS including a square nasal root, hypernasal speech, and hypoparathyroidism. She did, however, have the common larger deletion of type A. This finding suggests that psychiatric symptoms in VCFS can occur without major developmental symptoms such as cardiovascular anomalies and cleft palate. Additional patients with schizophrenia may have subtle features of VCFS which are unrecognised on routine medical examinations.

Abnormalities, Multiple↗
PubMed1998

Inflamed site-specific gene delivery using bone marrow-derived CD11b+CD18+ vehicle cells in mice.

We report a novel technique that may allow site-specific gene delivery into inflamed tissues. Bone marrow cells from DBA/2 mice were incubated for 7 days in L-929 cell-conditioned medium containing elements that favor the development of mononuclear cells, such as colony-stimulating factors. Flow cytometric analysis revealed that 99.1 +/- 0.9% of the subcloned cells were positive for CD11b and CD18, both of which are ligands of the intercellular adhesion molecule 1 (ICAM-1). These vehicle cells were labeled with a fluorescent lipophilic probe and returned intravenously to the DBA/2 mice. The mice then received, for 1 week, intraperitoneal injections of either lipopolysaccharide (LPS) to enhance ICAM-1 expression in the glomerulus, or saline as a control. In the LPS-treated mice, labeled vehicle cells were detected within the glomerulus cross-section (gcs) 24 hr after the first injection (0.73 +/- 0.10/gcs). The number of labeled vehicle cells within the glomerulus gradually increased for 1 week (1.47 +/- 0.19/gcs) and decreased after discontinuation of the LPS injections. However, in the saline-treated control group, only a negligible number of vehicle cells could be detected in the glomerulus (0.05 +/- 0.03/gcs). A second administration of LPS 4 weeks after injection of the vehicle cells was also able to promote accumulation in the glomerulus. Furthermore, immunohistochemical analysis revealed that the kinetics of the vehicle cell recruitment into the glomerulus corresponded to the level of ICAM-1 expression. On the assumption that the LPS-induced ICAM-1 expression may regulate the site and timing of the delivery of vehicle cells into the glomerulus, vehicle cells were transduced with human glucocerebrosidase (GC) gene, using an adenovirus vector, and reintroduced into the mice. The basal expression of GC gene in the isolated glomeruli of vehicle cell-treated mice rose by 1.7-fold compared with endogenous activity, whereas the GC activity was enhanced 3.2-fold by LPS treatment. Polymerase chain reaction designed to detect human GC-specific sequence revealed that isolated glomeruli of vehicle cell-treated mice contained exclusively the vehicle cell-oriented GC. This indicates that vehicle cells can be used to carry a certain gene to a specific inflamed site. Injection of vehicle cells, with or without LPS, had small effect on urinary protein excretion or serum creatinine levels. These findings suggest that our novel method allows site-specific gene delivery into inflamed glomeruli through interaction of adhesion molecules.

Animals↗
PubMed1998

Nipradilol inhibits DNA synthesis by regulating nitric oxide synthesis in cultured rat mesangial cells.

To elucidate whether nipradilol modulates mesangial cell function, we assessed the effects of nipradilol on DNA synthesis in the presence and absence of N-nitro-L-arginine methyl ester (L-NAME) in cultured rat mesangial cells stimulated with 1% fetal bovine serum. Nipradilol inhibited [3H]thymidine incorporation into mesangial cells in a dose- and time-dependent manner. In addition, the anti-mitogenic effect of 100 microM nipradilol was significantly inhibited in the presence of 10 microM L-NAME. Moreover, nipradilol increased intracellular cyclic guanosine monophosphate (cGMP). These results suggest that nipradilol exerts its efficacy in the treatment of several types of glomerulonephritis with mesangial cell proliferation by increasing in intracellular cGMP.

Adrenergic beta-Antagonists↗
PubMed1998

Activin A: a commitment factor in erythroid differentiation.

Erythropoietin is known to be an essential hemopoietic growth factor for maturation of erythroid progenitor cells. Like other hemopoietic growth factors, erythropoietin acts as a survival factor that supports maturation of the erythroid progenitor through the suppression of apoptosis. It is unclear whether erythropoietin can also induce differentiation, or if another external regulator is needed to initiate this process. The present study using murine cell lines revealed that maturation of the erythroid lineage requires costimulation by activin A and erythropoietin. Erythropoietin alone dose not induce differentiation and cells stimulated by activin A alone undergo apoptotic death. Costimulation with erythropoietin and activin A, however, rescues the cells from apoptotic death and permits differentiation. Two-step cultivation showed that cells pretreated with activin A no longer need activin A and differentiate in the presence of erythropoietin alone. The action of activin A commits the cell to death or to differentiation, and the presence of erythropoietin enables differentiation through suppression of apoptosis.

Activins↗
PubMed1998

Type 1 Gaucher disease: phenotypic expression and natural history in Japanese patients.

Gaucher disease is caused by a deficiency of glucocerebrosidase, resulting in hepatosplenomegaly, pancytopenia, growth retardation and skeletal involvement. We analyzed data on genotype and key clinical parameters in 35 Japanese patients with Gaucher disease type 1. Our data demonstrated that over 60% of patients had onset of Gaucher disease signs/symptoms at less than 5 years. Sixty percent and 46% of evaluable patients were splenectomized and developed severe bone involvement, respectively. Within mean follow-up periods of 8 years and 4 months, mean relative height and weight, severity score index and platelet count all worsened to a highly significant degree. These data suggest that type 1 Gaucher disease tends to be severe and progressive in Japanese patients, most of whom would be suitable for treatment and might indeed require earlier and more aggressive therapy.

Adult↗
PubMed1998

An autopsy case of fetal Gaucher disease.

BACKGROUND: A case of fetal form of Gaucher disease in a Japanese fetus is presented. RESULTS: A macerated baby showing hydrops fetalis was dissected at 29 weeks of gestation. The fetus was heavier in the body, liver and spleen than a normal fetus at the same gestation period. It also suffered from pericardial effusion and ascites. The diagnosis of Gaucher disease was made by histological and biochemical findings. In microscopical examinations 'Gaucher cells', which were periodic acid-Shiff (PAS)-positive, alcian blue-positive and CD68-positive, existed in the lungs, liver, spleen, thymus, adrenal glands, bone marrow and brain. In thin layer chromatography, a large quantity of glucocerebroside was seen to have accumulated in the patient's organs.

Adult↗
PubMed1998

Efficient and persistent expression of beta-glucuronidase gene in CD34+ cells from human umbilical cord blood by retroviral vector.

We succeeded in efficiently transferring the beta-glucuronidase gene in a retroviral vector to human hematopoietic progenitor cells using a centrifugation enhancement protocol. The transduction efficiency in CFU-GM was highly variable (23-100%) with an average of 66.8%. In the case of BFU-E, efficiency was 83% and 76% in 2 separate experiments. In LTCIC (long-term culture-initiating cell), transduction efficiency were 20% and 50% in 2 experiments. The enzymatic activity of beta-glucuronidase in transduced cells were increased above the control level up to 5 wk. Considering that correction of the enzyme deficiency in a small number of hematopoietic cells can be therapeutic for the Sly disease mouse, our data provide encouragement that human trials of gene therapy based on transferring beta-glucuronidase gene to hematopoietic cells may be efficacious.

Animals↗
PubMed1998

Macrophage inhibition of lymphocyte and tumor cell growth is mediated by 25-hydroxycholesterol in the cell membrane.

We have previously reported that a lipid molecule in the membrane fraction of cloned macrophage hybridomas inhibited the growth of lymphocytes and several tumor cell lines. In this study, the inhibitory lipid molecule in the membrane fraction of macrophages was analyzed by thin-layer chromatography and identified as 25-hydroxycholesterol, a family of oxysterols. This conclusion was confirmed by analysis using gas chromatography-mass spectrometry. In addition, both 25-hydroxycholesterol and the lipid molecule recovered from macrophage cell membrane induced apoptosis of the murine T cell lymphoma, BW-5147. These results suggest that an oxysterol expressed in the macrophage cell membrane may participate in the regulation of cell growth through cell contact.

Animals↗
PubMed1997

Adenovirus-mediated gene transfer and expression of human beta-glucuronidase gene in the liver, spleen, and central nervous system in mucopolysaccharidosis type VII mice.

Mucopolysaccharidosis type VII (Sly syndrome) is a lysosomal storage disease caused by inherited deficiency of the lysosomal enzyme beta-glucuronidase. A murine model of this disorder has been well characterized and used to study a number of forms of experimental therapies, including gene therapy. We produced recombinant adenovirus that expresses human beta-glucuronidase and administered this recombinant adenovirus to beta-glucuronidase-deficient mice intravenously. The beta-glucuronidase activities in liver and spleen were elevated to 40% and 20%, respectively, of the heterozygote enzymatic level at day 16. Expression persisted for at least 35 days. Pathological abnormalities of these tissues were also improved, and the elevated levels of urinary glycosaminoglycans were reduced in treated mice. However, the beta-glucuronidase activity in kidney and brain was not significantly increased. After administration of the recombinant adenovirus directly into the lateral ventricles of mutant mice, the beta-glucuronidase activity in crude brain homogenates increased to 30% of heterozygote activity. Histochemical demonstration of beta-glucuronidase activity in brain revealed that the enzymatic activity was mainly in ependymal cells and choroid. However, in some regions, the adenovirus-mediated gene expression was also evident in brain parenchyma associated with vessels and in the meninges. These results suggest that adenovirus-mediated gene delivery might improve the central nervous system pathology of mucopolysaccharidosis in addition to correcting visceral pathology.

Adenoviridae↗
PubMed1997

Anti-mitogenic effects of sarpogrelate in cultured rat mesangial cells.

We investigated the effects of the new 5-HT2A receptor antagonist, sarpogrelate, on DNA synthesis in renal mesangial cells stimulated with 5-HT in the presence and absence of platelet-derived growth factor (PDGF)-BB. Both 5-HT and PDGF-BB demonstrated a mitogenic effect on these cells. When mesangial cells were incubated in the absence of PDGF-BB, sarpogrelate inhibited DNA synthesis in these cells in a dose-dependent manner. In the presence of PDGF-BB, sarpogrelate had a weaker anti-mitogenic effect in mesangial cells stimulated with 5-HT. Sarpogrelate was cytotoxic at concentrations over 10(-5) M according to the results of LDH release assays, and it reduced the S1 phase in mesangial cells stimulated with 5-HT by a flow cytometry. These findings suggest that sarpogrelate may be effective in the treatment of some glomerulonephritis associated with mesangial cell proliferation.

Animals↗
PubMed1997

Enhanced magnetic resonance imaging of leptomeningeal angiomatosis.

We present two patients with unilateral occipital gyriform calcification and seizures. Gyriform or serpentine calcification as revealed by computed tomography (CT) scan is rare and is a characteristic finding of Sturge-Weber syndrome (SWS) and celiac disease (CD). These patients had neither the facial nevus flammeus or neurological deficits characteristic of SWS, nor the gastrointestinal symptoms characteristic of CD. CD is often accompanied by cerebral occipital calcification indistinguishable from that of SWS. We demonstrate the presence of cerebral leptomeningeal angiomatosis (LA) by Gadolinium-DTPA-enhanced magnetic resonance imaging (MRI) but could not detect LA by either CT scanning or angiography. It has been reported that contrast-enhanced MRI is useful to detect LA in SWS. However, we found no reports of enhanced MRI in patients with SWS without facial angioma. If future studies can demonstrate the absence of cortical enhancement by contrast-enhanced MRI in CD with cerebral calcifications, enhanced MRI would become an important tool for differentiating CD from SWS.

Angiomatosis↗
PubMed1997

Mutation prevalence among 47 unrelated Japanese patients with Gaucher disease: identification of four novel mutations.

Utilizing PCR and PCR-SSCP analysis we investigated the prevalence of glucocerebrosidase gene mutations in 47 unrelated Japanese patients with Gaucher disease. Sixty alleles (63.8%) and 20 alleles (21.3%) were identified by analysis for common mutations and PCR-SSCP analysis, respectively. The L444P and F213I mutations were common, accounting for 41 alleles (43.6%) and 14 alleles (14.9%). R496C, D409H, S366G and 1447-1466 del ins TG mutations were identified in 5, 3, 3 and 3 alleles, respectively. The other mutations were unique. In spite of vigorous screening, 14 alleles (14.9%) could not be identified. Four novel mutations were identified by PCR-SSCP analysis: G189V, S366G, K413Q and R433G. These data indicate that besides the L444P mutation no other frequent mutation is present and there is broad heterogeneity of the glucocerebrosidase gene mutations in Japanese patients with Gaucher disease.

Alleles↗