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J Hata

Publications and source records attributed to J Hata.

At least 37 records · Page 2Linked to original sources
PubMed2002

Evaluation of gastric emptying measured with the 13C-octanoic acid breath test in patients with functional dyspepsia: comparison with ultrasonography.

BACKGROUND: As a non-invasive modality by which to evaluate the gastric emptying of a solid meal, the 13C-octanoic acid breath test has recently become more widely used. Previously, we reported that ultrasonography was another non-invasive and reliable method for assessing gastric motility. The aim of this study was to compare the reliability of these two methods. METHODS: Seventeen patients with functional dyspepsia and 10 healthy volunteers were studied. The solid test meal consisted of a scrambled egg labeled with 13C-octanoic acid (100 mg) and served with a bowl of rice and boiled chicken (total 424 kcal). After ingestion of the test meal, all subjects were examined in the sitting position. Ultrasonography images were obtained every 15 min for 3 h. Breath sampling followed the same time schedule as for the ultrasonography, with an additional 3 h of sampling at 30-min intervals. We investigated the half emptying time (T1/2) and the lag phase with both methods. RESULTS: The T1/2 by the ultrasonography method and the breath test were positively correlated (r2 = 0.638); however, there was no significant agreement between the study groups. Both the T1/2 and the lag phase were prolonged in the functional dyspepsia patients compared with the healthy volunteers, regardless of the method of measurement. The lag phase was significantly correlated (r2=0.864) with the T1/2 by the breath test. CONCLUSIONS: Although the 13C-octanoic acid breath test cannot assess the gastric emptying of solids as reliably as ultrasonography, both tests are useful for evaluating functional dyspepsia patients with delayed gastric emptying.

Adolescent↗
PubMed2002

Preoperative assessment of gastric cancer vascularity by flash echo imaging.

BACKGROUND: Tumor vascularity as indicated by immunohistochemical staining is a significant prognostic factor in gastric and other cancers. Non-invasive preoperative assessment of the vascularity of gastric cancers has not been possible. We aim to determine the reliability of harmonic flash echo imaging (FEI) for assessment of vascularity of gastric cancers by comparison with CD34 staining of resected specimens. METHODS: Twelve patients undergoing surgical resection of advanced gastric cancer were studied. An ultrasound system transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second harmonic image) was used for harmonic FEI. Approximately 30 s after intravenous injection of ultrasonic contrast medium (SHU 508A, Levovist), second harmonics (4.6 MHz) emitted from microbubbles were obtained to enhance the B-mode images. Using the tumor image showing strongest enhancement in each FEI series, regions of interest were determined to measure mean echo intensity in the tumor. Immunohistochemistry using antibodies against CD34 was carried out in resected specimens. Tumor vascularity was determined by counting stained microvessels. RESULTS: A significant positive correlation was noted between sonographic amplitude determined preoperatively by FEI analysis and number of CD34-stained microvessels in tumor specimens (r = 0.869, P = 0.004). CONCLUSION: Vascularity of gastric cancers now can be evaluated non-invasively by harmonic FEI.

Antigens, CD34↗
PubMed2002

Warm autoimmune hemolytic anemia with mimicking anti-c and -E specificities.

An 18-month-old male was admitted to a hospital with a hemoglobin of 4.1 g/dL and a reticulocyte count of 53 percent. There was no history of prior transfusion. Serologic evaluation revealed the presence of both a positive direct antiglobulin test (DAT) and an indirect antiglobulin test (IAT). The patient's red blood cells (RBCs) typed as group A, C-D-E-c+e+ (cde/cde). Evaluation of the IAT revealed the presence of anti-c and anti-E. All other major antibodies were ruled out. Upon adsorption of the patient's serum with ficin-treated Cde/Cde RBCs, both antibody specificities were adsorbed; however, the antibodies were not adsorbed with native (untreated) Cde/Cde RBCs. Furthermore, the autoantibody was not adsorbed by Rhnull cells, thereby suggesting Rh specificity. The serum was incompatible with cde/cde RBCs and compatible with Cde/Cde RBCs. The patient was successfully transfused with Cde/Cde RBCs followed by resolution of his anemia, as evidenced by an increased and stable hemoglobin. It was concluded that the autoantibody had mimicking anti-c and -E specificities. This is a report of an unusual case of autoimmune hemolytic anemia because the Rh autoantibody appeared to have dual mimicking specificities, and the patient's RBCs were antigen negative for one of the antibody specificities, i.e., anti-E.

Journal Article↗
PubMed2001

EAT/mcl-1 expression in the human embryonal carcinoma cells undergoing differentiation or apoptosis.

Differentiation and apoptosis are precisely regulated events in early embryogenesis. Retinoic acid-induced differentiation in the embryonal carcinoma (EC) cell line NCR-G3 triggers concurrent induction of apoptosis. Using this system, which serves as a model of early embryogenesis, the expression of various bcl-2-related genes was analyzed as these genes display either positive or negative regulatory effects on apoptosis. EAT/mcl-1, an antiapoptotic bcl-2-related gene and immediate early gene, was dramatically expressed at an early stage of NCR-G3 differentiation. Bcl-xL, another antiapoptotic gene, was induced at a middle stage of differentiation and then gradually decreased to basal level. Expression of Bax, a proapoptotic molecule, was detected at a high level and remained relatively constant. Meanwhile, Bcl-2 and Bcl-xS were below detectable levels throughout the various stages of differentiation. As the balance of bcl-2 genes is a crucial regulatory step in apoptosis, the results suggest that EAT and Bax likely regulate apoptosis in the early stages of differentiation. In later stages of differentiation, down-regulation of EAT was found to coincide with a gradual increase in apoptosis of NCR-G3 cells. Furthermore, use of the monoclonal antibody (3A2) specific to EAT revealed that EAT is localized to the outer mitochondrial membrane in human EC cells. In addition, EAT immunoreactivity was not detected in apoptotic NCR-G3 cells while it was observed in nearly all viable cells. The findings suggest that rapid induction of EAT may prevent NCR-G3 cells from undergoing apoptosis, thereby supporting viability at the early stage of differentiation.

Antineoplastic Agents↗
PubMed2001

Epigenetic mark sequence of the H19 gene in human sperm.

We have investigated the epigenetic mark in the human H19 gene. The H19 promoter is methylation-free in human sperm, but it is methylated in the paternally derived allele of most adult tissues. Consequently, the H19 gene is exclusively transcribed from the maternal allele. It was demonstrated that the differentially methylated region (DMR) located 2 kb upstream from mouse H19 is essential for the imprinting of H19. A 39 bp sequence in DMR has a high degree of similarity between humans, mice and rats. The highly conserved 15 bp core region of the consensus sequence contains four methylatable sites, and thus has been proposed as a potential imprinting mark region. In this study, fine epigenetic sequencing analysis was performed on the sperm DNA in comparison with other adult organs. Interestingly, the conserved sequence of the potential mark region was methylated in almost all the sperm genomes analyzed. Furthermore, the single dinucleotide CpG, whose methylation affects the accessibility of the element to CTCF, was methylated in the conserved core in the human sperm. These results suggest that the human core sequences may act as an imprinting center in the reciprocal monoallelic expression of H19.

Adult↗
PubMed2001

Augmentation of megakaryocytopoiesis within the hematopoietic microenvironment of human granulocyte colony-stimulating factor transgenic mice.

OBJECTIVE: Megakaryocytopoiesis was dramatically augmented in human granulocyte colony-stimulating factor transgenic mice (G-Tg) compared to littermates. We examined the characteristics of megakaryocytes and megakaryocyte progenitor cells in these mice. MATERIALS AND METHODS: The numbers of colony-forming unit megakaryocytes (CFU-MK) and megakaryocytes in hematopoietic organs were counted. The megakaryocytes of G-Tg were examined ultrastructurally, and bone marrow transplantation studies using congenic G-Tg (Ly5.2) and C57BL/6 (Ly5.1) were performed. The number of day-14 colony-forming unit spleen (CFU-S) that contained megakaryocytes in [Ly5.1 > G-Tg] and [G-Tg > Ly5.1] mice also was counted. RESULTS: The number of CFU-MK increased markedly in the spleen, bone marrow, and peripheral blood. The number of megakaryocytes in the spleen and bone marrow also were increased in G-Tg mice. Ultrastructural analyses revealed that megakaryocytes in G-Tg mice were immature. Bone marrow transplantation studies of [Ly5.1 > G-Tg] mice resulted in a significantly increased number of megakaryocytes compared to [G-Tg > Ly5.1] mice. The number of day-14 CFU-S that contained megakaryocytes was increased markedly in [Ly5.1 > G-Tg] mice compared to [G-Tg > Ly5.1] mice. In vitro differentiation of megakaryocytes in [Ly5.1 > G-Tg] mice was induced by interleukin-11 and thrombopoietin. CONCLUSION: The results showed that the hematopoietic marrow microenvironment of G-Tg is important in augmenting megakaryocytopoiesis. [Ly5.1 > G-Tg] mice are potentially useful as a source of murine megakaryocytes and their progenitors.

Animals↗
PubMed2001

A novel differentiation-inducing therapy for acute promyelocytic leukemia with a combination of arsenic trioxide and GM-CSF.

Arsenic trioxide (As2O3) effectively induces clinical remission via apoptosis in relapsed acute promyelocytic leukemia (APL). However, because this new anti-leukemic drug is also considered to be a poison, its possible adverse effects are a highly important issue related to its clinical use. We here investigated, both in vitro and in vivo, the effects of a combination of As2O3 and GM-CSF as a novel therapeutic approach for the treatment of APL. Treatment of both retinoic acid (RA)-sensitive and -resistant APL cell lines (NB4 and UF-1 cells, respectively), as well as primary APL cells with a combination of As2O3 and GM-CSF for 4 days resulted in inducing differentiation, but not apoptosis, to mature granulocytes. In addition, a combination of both agents induced degradation of the PML/RARalpha protein. GM-CSF was found to be associated with increased tyrosine phosphorylation of Jak2 kinase in both NB4 and UF-1 cells, and a specific inhibitor of Jak2, AG490, completely blocked the ability of GM-CSF to prevent apoptosis and induce differentiation of As2O3-treated UF-1 cells. In in vivo analysis, As2O3 induced differentiation of APL cells in a RA-resistant APL model of human GM-CSF-producing transgenic SCID mice that had a high level of human GM-CSF in their sera. In contrast, As2O3 alone diminished tumors in UF-1 cells transplanted into NOD/SCID mice via induction of apoptosis. In conclusion, a combination of As2O3 and GM-CSF appears to be a novel differentiation-inducing therapy in patients with APL, including relapsed or RA-resistant cases.

Animals↗
PubMed2001

Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function.

BACKGROUND: Duodenogastric reflux has been implicated in the pathogenesis of gastric ulcer and gastritis. Duodenogastric reflux after cholecystectomy is also a possible cause of post-cholecystectomy syndrome. AIM: To investigate the role of antroduodenal motor function in increased duodenogastric reflux following cholecystectomy and the effect of trimebutine maleate (trimebutine) on the duodenogastric reflux in conscious dogs. METHODS: Antropyloric and duodenal motility and bile acids content in the gastric juice were measured for 3 h during the inter-digestive state in dogs with or without cholecystectomy. RESULTS: Bile acids content in the gastric juice of cholecystectomized dogs was significantly higher than that of non-cholecystectomized dogs. The frequency of pyloric relaxation during phase II of the migrating motor complex was significantly increased following cholecystectomy. Intravenous infusion of trimebutine inhibited both the increased duodenogastric reflux and the frequency of pyloric relaxation in the cholecystectomized dog. CONCLUSION: Duodenogastric reflux and frequency of pyloric relaxations were increased in cholecystectomized dogs and trimebutine suppressed both of them. These findings suggest that the increased frequency of pyloric relaxation contributes to the duodenogastric reflux following cholecystectomy.

Animals↗
PubMed2001

Brain from bone: efficient "meta-differentiation" of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent.

Bone marrow stromal cells are able to differentiate into adipogenic, chondrogenic, myogenic, osteogenic, and cardiomyogenic lineages, all of which are limited to a mesoderm-derived origin. In this study, we showed that neurons, which are of an ectoderm-origin, could be generated from marrow-derived stromal cells by specific inducers, fibronectin/ornithine coating, and neurosphere formation. The neurons generated from marrow stroma formed neurites, expressed neuron-specific markers and genes, and started to respond to depolarizing stimuli as functional mature neurons. Among stromal cells, isolated mature osteoblasts which had strong in vivo osteogenic activity could be efficiently converted into functional neurons. This transdifferentiation or meta-differentiation was enhanced by Noggin, an inhibitor of bone morphogenetic proteins, in comparison with 5-azacytidine, a demethylating agent capable of altering the gene expression pattern. Marrow stroma is therefore a potential source of cells for neural cell transplantation.

Animals↗
PubMed2001

Isolated diffuse mesangial sclerosis and Wilms tumor suppressor gene.

Diffuse mesangial sclerosis is a rare renal disease, occurring either in isolation or as part of Denys-Drash syndrome. Denys-Drash syndrome originates from mutations of the Wilms tumor suppressor gene (WT1 ). We describe the presence of WT1 mutations in 7 Japanese children with isolated diffuse mesangial sclerosis.

Female↗
PubMed2001

Extracorporeal ultrasound is an effective diagnostic alternative to endoscopic ultrasound for gastric submucosal tumours.

BACKGROUND: Although endoscopic ultrasonography (EUS) is the best modality in the diagnosis of gastric submucosal tumours (G-SMT), it is still invasive and expensive. We evaluated the usefulness of transabdominal ultrasonography (US) as an alternative to EUS in the assessment and clinical management of G-SMT. METHODS: This is a prospective study of 156 successive patients who had been diagnosed with G-SMT by direct endoscopic visualization. For each patient, US was performed prior to EUS by an examiner who had not been informed about the site or the size of the patient's G-SMT beforehand. US diagnoses were compared with those ascertained by EUS. Diagnostic grade by US was divided into three groups: diagnosed (G-SMT was clearly demonstrated including location, site and type), detected (G-SMT was demonstrable but the type was not clear) and undetected (G-SMT was not demonstrated by US). RESULTS: We found that US can be an alternative to EUS for: 1) diagnosis of extramural compression, 2) diagnosis of G-SMT with size >30 mm in diameter, 3) detection and measurement of the size of a G-SMT from 21 to 30 mm in diameter, and 4) detection and measurement of the size of a G-SMT at both the gastric angle and cardia, regardless of the size of the tumour. Overall sensitivity and specificity for the detection of G-SMT were 82.5% and 100%, respectively. The diagnostic rates of G-SMT in each group were 60.1% (86/143) for diagnosed, 22.4% (32/143) for detected and 17.5% (25/143) for undetected. Approximate 95% (21/22) of G-SMT over 20 mm in diameter were at least detected, and 97% (30/31) of G-SMT over 30 mm in diameter were diagnosed by US. CONCLUSION: US can be an alternative method in the assessment of G-SMT, especially in the follow-up of patients already diagnosed.

Adolescent↗
PubMed2001

Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene.

BACKGROUND/AIM: EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. METHODS: EAT transgenic mice incorporating the EF-1alpha promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. RESULTS: The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (p<0.01). Although the differences between the two survival curves did not reach statistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95% confidence interval (CI) 0.0347-0.0500) than in littermates (0. 0199/mouse/week; 95% CI 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI 0-0.0120) and 0.0419/mouse/week in the EAT mice (95% CI 0.0286-0.0500). CONCLUSION: Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.

Animals↗
PubMed2001

Specific accumulation and elimination kinetics of tris(4-chlorophenyl)methane, tris(4-chlorophenyl)methanol, and other persistent organochlorines in humans from Japan.

We examined human adipose tissue, liver, and bile from humans in Japan to understand the contamination status, specific accumulation, and elimination of two newly identified environmental contaminants, tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and other persistent organochlorines such as polychlorinated biphenyls (PCBs), DDT and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), and chlordane compounds (CHLs). TCPMe and TCPMOH concentrations in Japanese human adipose tissue were slightly higher than those reported previously, indicating widespread exposure to these compounds in humans. Elevated residues of PCBs and DDTs are found in adipose tissue and liver. Concentrations in bile strongly correlated with concentrations in adipose fat and liver, which may suggest an equilibration in adipose fat/bile and liver/bile and possible biliary excretion of persistent organochlorines in humans. Composition of the organochlorines accumulated further indicates a metabolic capacity in humans higher than that of marine mammals. We observed age-dependent accumulation for TCPMe, TCPMOH, and other organochlorines, but there were no significant gender differences. p,p'-DDE and TCPMe were estimated to have low biliary excretion rate. Elimination potential of persistent organochlorines may be related to their octanol-water partition coefficient. The relationship between excretion rate and octanol-water partition coefficient may be used to predict the biliary excretion potential of some other lipophilic organochlorines such as dioxins and dibenzofurans in humans. The presence of organochlorines in bile suggests that the hepatic excretory system plays a major role in the elimination of xenobiotics in humans. To our knowledge, this is the first study of accumulation and elimination of TCPMe and TCPMOH in humans.

Adipose Tissue↗
PubMed2001

Dioxins in bile in relation to those in the human liver and blood.

The levels of 20 dioxin congeners, 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and three coplanar polychlorinated biphenyls (Co-PCBs), in bile were examined in comparison with those in the blood and liver, in 27 autopsy cases. Total-TEQ values were the same in the bile (43.2 +/- 30.9 pg TEQ/g lipid) and blood (43.1 +/- 24.2 pg TEQ/g lipid), and three times higher in the liver (127.8 +/- 57.4 pg TEQ/g lipid). Highly chlorinated PCDDs and PCDFs have a tendency to accumulate in the liver, and their levels in bile and blood were relatively low compared with those in the liver, with 1,2,3,4,6,7,8-heptachlorodibenzofuran having the highest tendency among the 20 congeners. Daily excretion in bile was calculated to be 54 pg TEQ at age 65, by assuming that daily bile secretion is 750 ml and is concentrated 7.5-fold in the gallbladder. The correlation between bile and blood total-TEQ was high, with a correlation coefficient of 0.89 among the 27 autopsy cases. Thus, the regression equation of y = 1.14x - 6.02 will provide us levels in bile (total TEQ per g lipid), knowing the blood total-TEQ level, where x is total-TEQ per g lipid of the blood. Furthermore, accumulation of dioxins was estimated to be 0.99, 0.70 and 1.91 pg TEQ/g lipid/year in bile, blood and liver, respectively.

Age Factors↗
PubMed2001

A case of generalized Hailey-Hailey disease with fatal liver injury.

We report a case of a 59-year-old man with a severe generalized form of Hailey-Hailey disease that was complicated by fatal liver injury. Erosive lesions were first noted in the axillary and perianal regions at 15 year of age, and Hailey-Hailey disease was diagnosed based on the clinical features and histologic findings in skin biopsy specimens. The patient was treated with at first topical steroids and later a low dose of a corticosteroid, but the skin lesions gradually became generalized. At 45 years of age liver dysfunction was detected after azathioprine and vinblastine treatment for the generalized skin lesions. The liver injury gradually progressed and finally the patient died. The gene responsible for Hailey-Hailey disease was recently identified as ATP2C1, and it encodes a Ca(2+)-transport ATPase with broad expression, including in skin and liver. This finding suggests that mutation of the ATP2C1 gene may give rise to an extracutaneous phenotype, such as the liver dysfunction observed in severe cases, including our own. Further accumulation of cases is necessary to determine whether this is true.

Calcium-Transporting ATPases↗
PubMed2000

Diabetes and tumor formation in transgenic mice expressing Reg I.

To examine the effect of overexpressed regenerating gene (Reg) I on pancreatic beta-cells, we generated transgenic mice expressing Reg I in islets (Reg-Tg mice). Three lines of Reg-Tg mice were established. In line-1 Reg-Tg mice, the expression level of Reg I mRNA in islets was 7 times higher than those in lines 2 and 3 of Reg-Tg mice, and line 1 mice developed diabetes by apoptosis of beta-cells, as well as various malignant tumors. In addition to the decrease in beta-cells, compensatory islet regeneration and proliferation of ductal epithelial cells were observed in line-1 Reg-Tg mice. Because Reg I protein was secreted primarily into pancreatic ducts from acinar cells, it may primarily stimulate the proliferation of ductal epithelial cells, and not beta-cells, and their differentiation into islets. Moreover, the tumor-promoting activity of Reg I protein should be considered for its possible clinical applications.

Animals↗
PubMed2000

Involvement of EAT/mcl-1, an anti-apoptotic bcl-2-related gene, in murine embryogenesis and human development.

Apoptosis plays an important regulatory role in mammalian embryogenesis and development. EAT/mcl-1 (EAT), an anti-apoptotic bcl-2-related gene, was isolated during the early differentiation of a human embryonal carcinoma cell line, an event which serves as a model of early embryogenesis. EAT is involved in apoptotic regulation and is believed to also function as an immediate-early gene. Thus it was hypothesized that EAT would be expressed during early embryogenesis and would be involved in the regulation of apoptosis during this critical period. To clarify this early expression, two antibodies to EAT were generated by use of immunizing oligopeptide (aa 37-55) and recombinant protein (aa 31-229) for use in immunohistochemistry and immunoblotting, respectively. With these antibodies, we then determined EAT expression during murine embryogenesis and in human development, using human fetal tissue of 6 to 23 gestational weeks. During murine embryogenesis, the EAT protein was found to be rapidly induced after fertilization, to peak at the 2-cell stage, to remain constant until the 8-cell stage, and then to decrease to below unfertilized egg levels in blastocysts. EAT expression patterns in early human development were found to essentially overlap those observed in adult tissues which suggest that EAT expression continues until adulthood in terminally differentiated tissues. Among tissues distinct to fetal development, EAT was detected in the mesonephric (Wolffian) duct and paramesonephric (Müllerian) duct. It is also noteworthy that prominent EAT immunoreactivity was also observed in large primary oocytes in 21-week fetal ovary, but was not detected in primordial germ cells in 23-week fetal testis. In summary, EAT expression was detected in hematopoietic, epithelial, neural, endocrine, and urogenital cells; this provides evidence that EAT, as an anti-apoptotic molecule, possibly functions to regulate apoptosis during development in these systems.

Amino Acid Sequence↗