Biomedical subjects

Hiroki Otani

Publications and source records attributed to Hiroki Otani.

At least 19 recordsLinked to original sources

PubMed2006

Quantitative analyses of leukemia inhibitory factor in the cerebrospinal fluid in mouse embryos.

Leukemia inhibitory factor contributes to the self-renewal of neural stem cells in the forebrain. Although the existence of endogenous leukemia inhibitory factor in the brain parenchyma has been controversial, the cerebrospinal fluid is known to be another source of leukemia inhibitory factor. No reports of the measurement of leukemia inhibitory factor concentrations in the cerebrospinal fluid, however, exist. In the present study, we determined the leukemia inhibitory factor concentration in cerebrospinal fluid, amniotic fluid, and sera of embryos and dams in mice by enzyme-linked immunosorbent assay. The leukemia inhibitory factor concentrations were found to be constitutively high in the cerebrospinal fluid from embryonic day 11 to embryonic day 17, with a peak on embryonic day 13 and embryonic day 14. These findings correspond to the timing of cortical neuron production in mouse cerebrum.

Age Factors↗

PubMed2006

The role of leptin in the development of the cortical neuron in mouse embryos.

Leptin is an obese gene product that decreases appetite and raises energy expenditure in adults. We previously reported that leptin was detected in the sera of mouse embryos and leptin receptors were expressed in the mouse embryonic cerebrum, suggesting that leptin plays a role in cerebral development. In this study, we injected leptin into the lateral ventricle of the cerebrum in leptin-deficient ob/ob mouse embryos to investigate the function of leptin in cerebral development. When leptin was injected on embryonic day (E) 14, the ratio of the number of cells in the cortical plate (CP) to that in the intermediate zone (IZ) was higher in leptin-injected than in vehicle-injected ob/ob embryos on E16, although there was no significant difference in the number of cells in the ventricular zone (VZ), IZ, or CP between these groups. The number of postmitotic BrdU-positive CP cells was larger in leptin-injected than in vehicle-injected ob/ob embryos on E16 and E17 when BrdU labeling and leptin injection were performed on E14. By in situ hybridization, NPY mRNA expression in CP neurons on E18 was weaker in leptin-injected than in vehicle-injected ob/ob embryos when leptin was injected on E16. These results suggest that leptin promotes the migration of neuronal lineage cells to CP and that the leptin-NPY axis in neurons works in the cerebral cortex on E16.

Age Factors↗

PubMed2006

The relationship between plasma BNP level and the myocardial phosphocreatine/adenosine triphosphate ratio determined by phosphorus-31 magnetic resonance spectroscopy in patients with dilated cardiomyopathy.

The purpose of this study was to evaluate the correlation between the plasma B-type natriuretic peptide (BNP) level and the myocardial phosphocreatine/adenosine triphosphate ratio determined using rapid phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in patients with dilated cardiomyopathy (DCM). Thirteen DCM patients, who had slight or moderate heart failure, were examined. The plasma BNP was measured on a day close to the rapid 31P-MRS study. 31P-MRS measurements were conducted with a 1.5-T MR instrument. The plasma BNP levels tended to be correlated negatively with the myocardial phosphocreatine/adenosine triphosphate, although the correlation did not reach statistical significance (r = -0.54, p = 0.06). By contrast, the log of the plasma BNP levels was correlated negatively with the myocardial phosphocreatine/adenosine triphosphate (r = -0.73, p < 0.01). Our results indicate that the myocardial energy metabolism evaluated using 31P-MRS tends to be correlated with the severity of heart failure and left ventricular dysfunction estimated using the plasma BNP levels in DCM patients. This paper provides additional information regarding the relationship between the BNP and myocardial energy metabolism in DCM patients.

Adenosine Diphosphate↗

PubMed2006

Spatial and temporal patterns of expression of melanocortin type 2 and 5 receptors in the fetal mouse tissues and organs.

In the present study to analyze the role of ACTH in fetal tissues and organs, we observed the expression of melanocortin type 2 (MC2) and 5 (MC5) receptors in ICR mouse embryos from E11.5 to E18.5 by immunohistochemistry. In the adrenal gland and testis, both receptors were expressed from E13.5 to E18.5. In the genital ridge and the ovary, melanocortin type 2 receptors (MC2R) was detected from E11.5 to E12.5 and from E13.5 to E18.5, respectively, while melanocortin type 5 receptors (MC5R) was not detected. In the mesonephros, MC2R and MC5R were expressed from E11.5 to E12.5, and in the metanephros, MC2R and MC5R were expressed from E12.5 to E18.5 and from E14.5 to E18.5, respectively. In the lung, MC2R was expressed from E11.5 to E14.5, but MC5R was not expressed at all. In blood cells, MC5R was detected at all stages examined, while MC2R was detected at none. MC2R was observed in the brain and spinal cord from E11.5 to E13.5, while MC5R was detected only in the telencephalon and only from E16.5 to E18.5. At different temporal patterns, MC2R, but not MC5R, was detected in the choroid plexus, while MC5R, but not MC2R, was expressed in the liver and in the nasal epithelium, and both MC2R and MC5R were expressed in the dorsal root ganglion and the trigeminal ganglion. These findings show the spatio-temporal specific expression patterns of MC2R and MC5R in the mouse embryo and suggest that ACTH may be related to histogenesis and/or prenatal function of various tissues and organs via MC2R and/or MC5R.

Adrenocorticotropic Hormone↗

PubMed2006

Leptin deficiency causes pycnotic change in fetal cingulate cortical cells.

Leptin is an obese gene product, and leptin-deficient ob/ob mice develop hyperphagia and reduced locomotor activity. Leptin is thought to be related to brain development, because leptin receptors are widely expressed in the brain, and because brain weight as well as brain protein and DNA contents were reduced in adult ob/ob mice. In this study, we investigated the effect of leptin on the fetal cingulate cortex, since the leptin receptor is expressed in the neurons of the cingulate cortex, which is involved in emotion as well as in sensory, motor, and cognitive processes. The ob/ob fetuses had more pycnotic cells than wild-type fetuses in the cingulate cortex at embryonic day (E) 18. Many pycnotic cells were observed in the intermediate zone of the cingulate cortex. Most cells observed in this area were neuronal lineage cells, while few undifferentiated cells and oligodendrocyte precursor cells were found. At E18 there was no significant difference in the rostrocaudal length of the corpus callosum, which contains the neuronal projection from the cingulate cortex, between ob/ob and wild-type fetuses. We also showed that the length of the cerebrum was greater and the width of the cerebrum and cerebellum were lesser in ob/ob fetuses than in wild-type at E16. These results suggest an increased cell death in neuronal lineage cells in the intermediate zone of the cingulate cortex in leptin-deficient ob/ob mice. Leptin deficiency may also alter the gross morphology of the brain in development, but not the formation of the corpus callosum.

Animals↗

PubMed2006

Analysis of polyploid cells in mouse embryonic cells cultured under diabetic conditions.

To clarify the cytogenetic effects of glucose and ketone bodies on the pathogenesis of diabetes-associated congenital anomalies, we cultured cells from gestation-day-8 ICR mouse embryos under the diabetic condition. Cells were cultured in the medium with glucose (300 mg/dL) plus DL-2-hydroxybutyric acid (32 mM) (G + B group), glucose alone (G group), or neither of them (C group) for 5 days. At the end of the culture, cells were analyzed for the chromosomes. After 3-4 days culture, when the living cells grew into a mono-layered sheet, cells floating in the medium were observed and showed morphological features of apoptosis. Ratio of the floating cells was significantly higher in the G + B group than in the G or C group (P < 0.05), suggesting the deleterious effect of glucose and ketone body. Polyploidy was observed in the cultured cells more frequently in the G + B group (64.1%) than in the G group (49.0%), which was higher than the C group (20.5%) (G + B vs G: P < 0.05, G vs C: P < 0.001). The higher ratio of the polyploidy, but not of the aneuploidy, in the G + B and G groups suggested the specific effect of glucose and ketone body for inducing polyploidy. These results suggest that diabetic condition causes polyploidy in cultured embryonic cells.

Animals↗

PubMed2006

Relationship between fluoroscopic time, dose-area product, body weight, and maximum radiation skin dose in cardiac interventional procedures.

OBJECTIVE: Real-time maximum dose monitoring of the skin is unavailable on many of the X-ray machines that are used for cardiac intervention procedures. Therefore, some reports have recommended that physicians record the fluoroscopic time for patients undergoing fluoroscopically guided intervention procedures. However, the relationship between the fluoroscopic time and the maximum radiation skin dose is not clear. This article describes the correlation between the maximum radiation skin dose and fluoroscopic time for patients undergoing cardiac intervention procedures. In addition, we examined whether the correlations between maximum radiation skin dose and body weight, fluoroscopic time, and dose-area product (DAP) were useful for estimating the maximum skin dose during cardiac intervention procedures. MATERIALS AND METHODS: Two hundred consecutive cardiac intervention procedures were studied: 172 percutaneous coronary interventions and 28 cardiac radiofrequency catheter ablation (RFCA) procedures. The patient skin dose and DAP were measured using Caregraph with skin-dose-mapping software. RESULTS: For the RFCA procedures, we found a good correlation between the maximum radiation skin dose and fluoroscopic time (r = 0.801, p < 0.0001), whereas we found a poor correlation between the maximum radiation skin dose and fluoroscopic time for the percutaneous coronary intervention procedures (r = 0.628, p < 0.0001). There was a strong correlation between the maximum radiation skin dose and DAP in RFCA procedures (r = 0.942, p < 0.0001). There was also a significant correlation between the maximum radiation skin dose and DAP (r = 0.724, p < 0.0001) and weight-fluoroscopic time product (WFP) (r = 0.709, p < 0.0001) in percutaneous coronary intervention procedures. CONCLUSION: The correlation between the maximum radiation skin dose with DAP is more striking than that with fluoroscopic time in both RFCA and percutaneous coronary intervention procedures. We recommend that physicians record the DAP when it can be monitored and that physicians record the fluoroscopic time when DAP cannot be monitored for estimating the maximum patient skin dose in RFCA procedures. For estimating the maximum patient skin dose in percutaneous coronary intervention procedures, we also recommend that physicians record DAP when it can be monitored and that physicians record WFP when DAP cannot be monitored.

Body Weight↗

PubMed2006

Heavy water inhibiting the expression of transforming growth factor-beta1 and the development of kaolin-induced hydrocephalus in mice.

OBJECT: The authors investigated the effects of heavy water (D2O) on intrameningeal fibrosis and on the expression of cytokine production in mice with kaolin-induced hydrocephalus. METHODS: Mice in which kaolin was injected into the cisterna magna were divided into two groups: 1) Group H, which had free access to H2O as tap water; and 2) Group D, which had free access to 30% D2O as tap water before and after kaolin injection. A distilled water-injected group, which had free access to H2O as tap water was designated the sham-operated group. The authors examined the effects of D2O within 28 days after injection on the development of hydrocephalus and intrameningeal fibrosis, as well as on the expression levels of several inflammatory and fibrogenic cytokines: transforming growth factor-beta1 (TGFbeta1), fibroblast growth factor-2 (FGF2), platelet-derived growth factor (PDGF)-BB, and interleukin (IL)-6. The cerebral ventricles were less expanded, and intrameningeal fibrosis was milder in Group D than in Group H. The proliferation of fibroblasts was assessed by applying the bromodeoxyuridine labeling index, which was lower in Group D than in Group H. Expression of TGFbeta1 in the macrophages, choroid plexus, and meninges was inhibited in Group D but not in Group H. The serum level of total TGFbeta1 was significantly lower in Group D than in Group H on Day 14, whereas the levels of FGF2, PDGF-BB, and IL-6 did not differ significantly among the groups. CONCLUSIONS: Administration of D2O prevented the development of kaolin-induced hydrocephalus in mice and inhibited intrameningeal fibrosis and upregulation of TGFbeta1.

Animals↗

PubMed2005

The role of leptin in the development of the cerebral cortex in mouse embryos.

Leptin is detected in the sera, and leptin receptors are expressed in the cerebrum of mouse embryos, suggesting that leptin plays a role in cerebral development. Compared with the wild type, leptin-deficient (ob/ob) mice had fewer cells at embryonic day (E) 16 and E18 and had fewer 5-bromo-2'-deoxyuridine(+) cells at E14 and E16 in the neuroepithelium. Intracerebroventricular leptin injection in E14 ob/ob embryos increased the number of neuroepithelium cells at E16. In cultured neurosphere cells, leptin treatment increased Hes1 mRNA expression and maintained neural progenitors. Astrocyte differentiation was induced by low-dose (0.1 microg/ml) but not high-dose (1 microg/ml) leptin. High-dose leptin decreased Id mRNA and increased Ngn1 mRNA in neurosphere cells. The neuropeptide Y mRNA level in the cortical plate was lower in ob/ob than the wild type at E16 and E18. These results suggest that leptin maintains neural progenitors and is related to glial and neuronal development in embryos.

Animals↗

PubMed2005

Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol.

OBJECTIVES: We examined whether right ventricular (RV) [(18)F]fluorodeoxyglucose (FDG) accumulation is increased in patients with pulmonary hypertension using gated positron emission tomography (PET) and whether RV FDG accumulation changes after therapy with epoprostenol. BACKGROUND: Myocardial glucose utilization is increased in animal models with ventricular pressure overload. METHODS: We performed gated FDG-PET in 24 patients with pulmonary hypertension. The RV standardized uptake value (SUV) of FDG was corrected for the partial volume effect based on the wall thickness measured by electron-beam computed tomography or magnetic resonance imaging. RESULTS: The corrected RV SUV of FDG was significantly correlated with the pulmonary vascular resistance, mean pulmonary artery pressure, right atrial pressure, RV wall stress, and plasma brain natriuretic peptide levels, but not with the RV wall thickness and mass. After pulmonary vasodilator therapy with epoprostenol for three months, the corrected RV SUV of FDG significantly decreased in the responders, but not in the non-responders, and the percentage change of the corrected RV SUV of FDG was significantly correlated with the percentage change of the pulmonary vascular resistance (r = 0.78; p < 0.01) and RV systolic wall stress (r = 0.76; p < 0.05). CONCLUSIONS: The RV FDG accumulation corrected for the partial volume effect was significantly increased in accordance with the severity of the RV pressure overload (i.e., the RV peak-systolic wall stress) in patients with pulmonary hypertension. Furthermore, the corrected RV FDG accumulation was decreased after the treatment with epoprostenol in accordance with the degree of reduction in the pulmonary vascular resistance and RV peak-systolic wall stress.

Antihypertensive Agents↗

PubMed2005

Maternal environment affects endogenous virus induction in the offspring of type 1 diabetes model non-obese diabetic mice.

Type 1 diabetes results from the destruction of pancreatic b-cells (insulitis). It is a multifactorial disease involving genetic and environmental factors, including the maternal environment. Viruses have also been implicated in the pathogenesis of human type 1 diabetes as well as in its model non-obese diabetic (NOD) mice during the perinatal period, as endogenous viruses and/or as infectious agents vertically transmitted from mothers. However, the role of virus as genetic or environmental factor and its interaction with other maternal factors remain unclear. In a series of experiments, we transplanted preimplantation-stage NOD embryos into the uterus of recipient Institute of Cancer Research (ICR) mice, which are without diabetic genetic predisposition, and NOD mice, which did not exhibit overt diabetes during the experiment, and designated offspring as NOD/ICR and NOD/NOD, respectively. We previously observed that NOD/ICR offspring developed insulitis significantly earlier than NOD/NOD offspring. To assess the role of viruses in the development of insulitis, we examined the appearance of viral particles and expression of retroviruses between NOD/ICR and NOD/NOD. NOD/ICR showed earlier expression of env region of the xenotropic type C retrovirus by polymerase chain reaction analysis than NOD/NOD, while the retrovirus-like particles were observed in the islet b-cells similarly in both groups by electron microscopy. Serum corticosterone level, which is suggested to enhance retroviral induction, was significantly higher in the ICR than in the NOD surrogate mothers. These findings suggest that the observed virus is endogenous and that maternal environmental factors, including hormone levels, affect the induction of endogenous viruses and cause the earlier onset of insulitis.

Animals↗

PubMed2005

Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization.

Insulin-stimulated glucose uptake in adipocytes is mediated by translocation of vesicles containing the glucose transporter GLUT4 from intracellular storage sites to the cell periphery and the subsequent fusion of these vesicles with the plasma membrane, resulting in the externalization of GLUT4. Fusion of the GLUT4-containing vesicles with the plasma membrane is mediated by a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of vesicle-associated membrane protein 2 (VAMP2), 23-kDa synaptosomal-associated protein (SNAP23), and syntaxin4. We have now generated mouse embryos deficient in the syntaxin4 binding protein Munc18c and show that the insulin-induced appearance of GLUT4 at the cell surface is enhanced in adipocytes derived from these Munc18c-/- mice compared with that in Munc18c+/+ cells. Wortmannin, an inhibitor of PI3K, inhibited insulin-stimulated GLUT4 externalization, without affecting GLUT4 translocation to the cell periphery, in Munc18c+/+ adipocytes, but it did not affect GLUT4 externalization in Munc18c-/- cells. Phosphatidylinositol 3-phosphate, which induced GLUT4 translocation to the cell periphery without externalization in Munc18c+/+ cells, elicited GLUT4 externalization in Munc18c-/- cells. These findings demonstrate that Munc18c inhibits insulin-stimulated externalization of GLUT4 in a wortmannin-sensitive manner, and they suggest that disruption of the interaction between syntaxin4 and Munc18c in adipocytes might result in enhancement of insulin-stimulated GLUT4 externalization.

Adipocytes↗

PubMed2005

Maternal factors in a model of type 1 diabetes differentially affect the development of insulitis and overt diabetes in offspring.

Type 1 diabetes, a multifactorial disease involving genetic and environmental factors, results from the destruction of pancreatic beta-cells. The maternal environment has been suggested to be important in the development of diabetes. To assess the role of maternal factors in the development of insulitis and overt diabetes, we transplanted pre-implantation stage embryos of nonobese diabetic (NOD) mice, a model of type 1 diabetes, into the uterus of each recipient. Recipients were ICR and DBA/2J mice without diabetic genetic predisposition and NOD mice not exhibiting overt diabetes during the experiment; offspring were designated as NOD/ICR, NOD/DBA, and NOD/NOD, respectively; unmanipulated NOD offspring were also examined. NOD/ICR and NOD/DBA offspring developed insulitis significantly earlier than NOD/NOD offspring. However, overt diabetes was significantly suppressed in NOD/ICR and NOD/DBA offspring in comparison with NOD/NOD offspring. Insulin autoantibodies (IAAs) were undetectable in ICR and DBA/2J surrogate mothers and in NOD/ICR and NOD/DBA offspring at the onset of insulitis, suggesting that maternal factors other than transmitted IAAs induced the earlier onset. The present study indicates that altered maternal factors modify the immune response to islets, which in turn might affect the pathogenic course from insulitis to overt diabetes.

Animals↗

PubMed2005

Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

UNLABELLED: Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.

Adult↗

PubMed2004

Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinoma.

KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1-expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention.

Adenocarcinoma↗

PubMed2004

Gi2 signaling enhances proliferation of neural progenitor cells in the developing brain.

Our previous study showed that the pertussis toxin-sensitive G protein, Gi2, is selectively localized in the ventricular zone of embryonic brains, where the neuroepithelial cells undergo active proliferation. In order to clarify the role of Gi2 in this site, we first administered pertussis toxin by an exo-utero manipulation method into the lateral ventricle of mouse brain at embryonic day 14.5. Examination at embryonic day 18.5 revealed that pertussis toxin-injected embryos had brains with thinner cerebral cortices, made up of fewer constituent cells. Bromodeoxyuridine labeling revealed fewer numbers of bromodeoxyuridine-positive cells in the cerebral cortices of pertussis toxin-injected embryos, suggesting impaired proliferation of neuroepithelial cells. Next we cultured neural progenitor cells from rat embryonic brains and evaluated the mitogenic effects of agonists for several Gi-coupled receptors that are known to be expressed in the ventricular zone. Among agonists tested, endothelin most effectively stimulated the incorporation of [3H]thymidine in the presence of fibronectin, via the endothelin-B receptor. This was associated with phosphorylation of extracellular signal-regulated kinase, and pertussis toxin partially inhibited both endothelin-stimulated DNA synthesis and phosphorylation of extracellular signal-regulated kinase. Injection of endothelin-3 into the ventricle of embryonic brains increased numbers of bromodeoxyuridine-positive cells in the cerebral cortex, whereas injection of an endothelin-B receptor antagonist decreased them. These findings indicate that Gi2 mediates signaling from receptors such as the endothelin-B receptor to maintain mitogenic activity in the neural progenitor cells of developing brain.

Animals↗

PubMed2004

Glycosyltransferase encoding gene EXTL3 is differentially expressed in the developing and adult mouse cerebral cortex.

Exostosin tumor-like 3 (EXTL3) is a glycosyltransferase involved in heparan sulfate (HS) biosynthesis. HS proteoglycans are critically involved in different steps during brain development. The present in situ hybridization in mice revealed wide EXTL3 expression at different grades in the central and peripheral nervous system components including the neural retina and neural crest-derived structures at embryonic days (E) 11.5, E12.5, E14.5, and E16.5. In the neopallial cortex, an intense EXTL3 expression was observed in the neuroepithelial cells lining the ventricular zone at E11.5 and E12.5. The signal decreased at E14.5 and was further downregulated at E16.5 in the ventricular zone. The pioneer neurons of the preplate at E12.5 differentially expressed the gene. Heavily stained among weakly or negatively stained neurons were observed. At E14.5, the cortical plate cells were moderately and homogeneously stained. In contrast, at E16.5, an upregulated and differential expression pattern was detected. The labeling pattern at E16.5 subdivided the cortical plate cells into a large number of heavily, a moderate number of less intensely, and some negatively stained cell populations. Interestingly, the distinct expression pattern displayed by the three main cell types of the adult cerebral cortex was similar to that of the late corticogenesis stage (E16.5). In the adult, the strongest expression was observed in the pyramidal neurons. The granule-type neurons showed less intense staining while the glia cells were devoid of signals. Our data revealed that EXTL3 expression is developmentally regulated in the mouse nervous system and suggested that it differentially contributes to brain development and corticogenesis.

Animals↗

PubMed2004

Expression of regenerating gene I in gastric adenocarcinomas: correlation with tumor differentiation status and patient survival.

BACKGROUND: Regenerating gene I (REG) was identified as a growth factor for pancreatic islet beta cells. Enhanced REG expression was observed during the healing of gastric mucosa. REG expression was observed in various tumors including gastric carcinoma, but to the authors' knowledge, the correlation between REG expression and clinicopathologic characteristics and patient prognosis have not been evaluated. METHODS: The REG messenger RNA level was analyzed by Northern blot analysis and localization was performed by in situ hybridization and immunohistochemistry in gastric adenocarcinoma specimens. The correlations between REG expression and clinicopathologic features and survival of the patients were analyzed. RESULTS: Of the 68 patients studied, 24 (35%) were positive for REG. There was a significant consistency in the intensity and localization of REG transcript and protein expressions. REG expression was enhanced in advanced T classification tumors and in tumors that were not well differentiated. A significant number of metastatic lymph nodes were present in REG-positive tumors. Overall and disease-free survival were found to be poor for patients with REG-positive tumors. REG expression was reported to be an independent predictor of overall patient survival. CONCLUSIONS: Determination of REG expression may help to identify aggressive gastric tumors and to tailor appropriate therapy for patients with REG-positive tumors.

Adenocarcinoma↗