Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY.
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Adult↗
Biomedical subjects
Y Horikawa
Publications and source records attributed to Y Horikawa.
Hemorrhagic and nonhemorrhagic stroke: diagnosis with diffusion-weighted and T2-weighted echo-planar MR imaging.
PURPOSE: To determine if diffusion- and T2-weighted echo-planar magnetic resonance (MR) imaging can be used to detect acute hemorrhagic stroke and to differentiate hemorrhagic from nonhemorrhagic stroke. MATERIALS AND METHODS: A total of 118 examinations (diffusion- and T2-weighted MR imaging) in 19 patients with 27 nonhemorrhagic strokes and in six patients with seven hemorrhagic strokes were performed. The ratios of apparent diffusion coefficient and of signal intensity on T2-weighted MR images in lesions to those in contralateral control areas were calculated. RESULTS: Decreased ADC was shown in lesions of acute (0-3 days) hemorrhagic stroke, as well as in lesions of acute nonhemorrhagic stroke. Hypointense areas were seen on T2-weighted MR images in patients with acute hemorrhagic stroke, in contrast to normal to increased signal intensity in those with acute nonhemorrhagic stroke. Apparent diffusion coefficient tended to remain decreased in hemorrhagic stroke lesions even 100 days after onset, in contrast to the increased coefficient in nonhemorrhagic stroke lesions at the late chronic stage (31 days or older). CONCLUSION: Diffusion- and T2-weighted echo-planar MR imaging can be used to detect and distinguish between acute hemorrhagic and nonhemorrhagic stroke.
Acute Disease↗
Atypical clinical presentations of X-linked spinal and bulbar muscular atrophy in patients with mild CAG expansions in androgen receptor gene.
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Aged↗
Atrophy of the cerebellum and brainstem in dentatorubral pallidoluysian atrophy. Influence of CAG repeat size on MRI findings.
To elucidate how the size of the expanded CAG repeat of the gene for dentatorubral pallidoluysian atrophy (DRPLA) and other factors affect the atrophy of the brainstem and cerebellum, and the appearance of high-intensity signals on T2-weighted MRI of the cerebral white matter of patients with DRPLA, we quantitatively analyzed the MRI findings of 26 patients with DRPLA, the diagnosis of which was confirmed by molecular analysis of the DRPLA gene. When we classified the patients into two groups based on the size of the expanded CAG repeat of the DRPLA gene (group 1, number of CAG repeat units > or = 66; group 2, number of CAG repeat units < or = 65), we found strong inverse correlations between the age at MRI and the areas of midsagittal structures of the cerebellum and brainstem in group 1 but not in group 2. Multiple regression analysis, however, revealed that both the patient's age at MRI and the size of the expanded CAG repeat correlated with the areas of midsagittal structures. Involvement of the cerebral white matter as detected on T2-weighted images was observed more frequently in patients belonging to group 2 than in group 1 patients. Furthermore it was demonstrated that high-intensity signals can be detected on T2-weighted images of the cerebral white matter of patients with a largely expanded CAG repeat (group 1) in their thirties. These results suggest that patient age as well as the size of the expanded CAG repeat are related to the degree of atrophy of the brainstem and cerebellum, and the white matter changes in patients with DRPLA.
Adolescent↗
Preoperative detection of the composition of atherosclerotic plaque in the carotid artery using ultrasonography and magnetic resonance imaging.
Preoperative identification of the components of atherosclerotic plaque was attempted using ultrasonography in five patients and magnetic resonance (MR) imaging in three patients before carotid endarterectomy. The correlation between surgical and histological findings, and preoperative ultrasonography and MR imaging was evaluated. Plaque consisting predominantly of calcification appeared as bright echo on ultrasonography and was tough. Plaque consisting predominantly of hemorrhage was echolucent, appeared as low intensity on T2-weighted MR images and was fragile. Such preoperative assessment of plaque composition using ultrasonography and MR imaging is useful for manipulation of atherosclerotic plaque during carotid endarterectomy.
Aged↗
Organization and partial sequence of the hepatocyte nuclear factor-4 alpha/MODY1 gene and identification of a missense mutation, R127W, in a Japanese family with MODY.
Hepatocyte nuclear factor-4 alpha (HNF-4 alpha) is a member of the nuclear receptor superfamily, a class of ligand-activated transcription factors. A nonsense mutation in the gene encoding this transcription factor was recently found in a white family with one form of maturity-onset diabetes of the young, MODY1. Here, we report the exon-intron organization and partial sequence of the human HNF-4 alpha gene. In addition, we have screened the 12 exons, flanking introns and minimal promoter region for mutations in a group of 57 unrelated Japanese subjects with early-onset NIDDM/MODY of unknown cause. Eight nucleotide substitutions were noted, of which one resulted in the mutation of a conserved arginine residue, Arg127 (CGG)-->Trp (TGG) (designated R127W), located in the T-box, a region of the protein that may play a role in HNF-4 alpha dimerization and DNA binding. This mutation was not found in 214 unrelated nondiabetic subjects (53 Japanese, 53 Chinese, 51 white, and 57 African-American). The R127W mutation was only present in three of five diabetic members in this family, indicating that it is not the only cause of diabetes in this family. The remaining seven nucleotide substitutions were located in the proximal promoter region and introns. They are not predicted to affect the transcription of the gene or mRNA processing and represent polymorphisms and rare variants. The results suggest that mutations in the HNF-4 alpha gene may cause early-onset NIDDM/MODY in Japanese but they are less common than mutations in the HNF-1 alpha/MODY3 gene. The information on the sequence of the HNF-4 alpha gene and its promoter region will facilitate the search for mutations in other populations and studies of the role of this gene in determining normal pancreatic beta-cell function.
Alternative Splicing↗
Intracranial vascular stenosis and occlusion: MR angiographic findings.
PURPOSE: To investigate whether obtaining axial source images from three-dimensional Fourier transform (3DFT) time-of-flight MR angiography improves the detection of intracranial vascular stenosis and occlusion if added to maximum-intensity projection (MIP) images. METHODS: The angiograms of 103 patients who had MR angiography for evaluation of possible intracranial vascular disease were reviewed retrospectively in a quantitative and nonquantitative fashion. Diameters of vessels on MR angiograms were measured quantitatively by two reviewers using a magnifying loupe and compared with the results from conventional angiograms. Degrees of stenoocclusive disease were categorized into five classes; an artery with stenosis of 50% or greater was considered to be diseased. Another five observers also reviewed the MIP images with and without source images in a blinded fashion by means of nonquantitative visual inspection. RESULTS: In all, 23 stenoocclusive lesions of 50% or greater were available for review. In the quantitative analysis, with MIP images alone, 14 (78%) of 18 moderate and severe stenoses and four (80%) of five occlusions were identified correctly. The addition of the source images increased the sensitivity to 100% for moderate and severe stenoses and to 100% for occluded vessels. In the visual inspection study, however, no statistically significant differences were found between interpretations of MIP images alone and those of MIP images in combination with source images. CONCLUSION: In the quantitative study, interpretation of source images rather than MIP images reduced the tendency to overestimate stenosis seen with MR angiography and improved the sensitivity for detecting stenosis of 50% or greater. There was a discrepancy between the quantitative study and visual inspection. Experienced observers had a tendency to underestimate the degree of stenosis.
Adult↗
[Influence of preanesthetic medication on the effect of a local anesthetic tape].
We investigated the influence of preanesthetic medication on the pain relieving effect of the lidocaine tape during needle insertion for venous cannulation. Ninety patients scheduled for elective surgery were randomly divided into three groups of 30 each; patients without preanesthetic medication (group N), patients who received 0.1 mg.kg-1 of diazepam (group D) and 5 micrograms.kg-1 of clonidine (group C) as a preanesthetic medication. Ninety minutes before the induction of anesthesia, we applied a lidocaine tape to each patient. The grade of pain at the pinprick test and at the venous puncture was evaluated in the operating room. No significant difference of the pain score was seen between the groups. We concluded that the effect of lidocaine tape was not influenced by the preanesthetic medication.
Adjuvants, Anesthesia↗
Functional role of cation-independent mannose 6-phosphate/insulin-like growth factor II receptor in cell adhesion and proliferation of a human myeloma cell line OPM-2.
The molecular mechanism underlying the interaction between myeloma cells and stromal cells was investigated by using a human myeloma cell line (OPM-2) and human umbilical vein endothelial cells (HUVECs). Adhesion of OPM-2 cells to HUVECs was found to be significantly augmented with treatment of OPM-2 cells with an alpha-glycosidase inhibitor, castanospermine (CSP). The treatment of OPM-2 cells with CSP resulted in alteration of oligosaccharide structures of cell surface glycoproteins particularly at molecular weight of 220 kD (GP220). To determine if GP220 was involved in the adhesion of OPM-2 cells to HUVECs, cell surface glycoproteins of HUVECs were labeled by biotin and were incubated with the PVDF membrane to which cell surface glycoproteins of OPM-2 cells were blotted. The biotinylated glycoproteins at the plasma membrane of HUVECs specifically bound to GP220 of OPM-2 cells. Purification and partial amino acid sequencing of GP220 revealed that GP220 had a structure homologous to cation-independent mannose 6-phosphate/insulin-like growth factor-II (CIM6P/IGF-II) receptor. Furthermore, an antibody against CIM6P/IGF-II receptor was reactive with GP220, indicating that GP220 was a CIM6P/IGF-II receptor. The adhesion of OPM-2 cells to HUVECs was inhibited by mannose 6-phosphate. Moreover, M6P was found to suppress the adhesion of human myeloma cell lines, OPM-2 and RPMI 8226, to bone marrow stromal cells that was established from the patients with multiple myeloma. In addition, proliferation of OPM-2 was stimulated in response to IGF-II. These results suggest that CIM6P/IGF-II receptor may be functional in terms of supporting cell adhesion and proliferation of myeloma cells.
Cell Adhesion↗
The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells.
Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic level in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.
Acute Disease↗
Disaggregation of polyribosomes in the spinal anterior horn cells in a patient with X-linked spinal and bulbar muscular atrophy.
The spinal anterior horn cells (AHCs) in a patient with X-linked spinal and bulbar muscular atrophy (SBMA) were examined by light and electron microscopy, giving special attention to alterations in the rough endoplasmic reticulum (ER). Seven age-matched subjects were used as controls. The patient with SBMA showed a severe decrease of AHCs, but the Nissl substance in the remaining AHCs appeared well preserved on light microscopy. Electron microscopy revealed a relatively well preserved parallel lamellar pattern of ER and marked disaggregation of the polyribosomes surrounding the ER in the remaining AHCs. These findings indicate that the Nissl substance was affected in spite of its light microscopic appearance in SBMA, and that the AHCs degenerate through disaggregation of the polyribosomes of the ER.
Anterior Horn Cells↗
Disordered expression of glycolytic and gluconeogenic liver enzymes of juvenile visceral steatosis mice with systemic carnitine deficiency.
A quantitative study of the effect of carnitine deficiency on expression of glycolytic and gluconeogenic enzymes was performed using juvenile visceral steatosis mice which are systemically deficient in carnitine. The amounts of glucokinase and L-type pyruvate kinase mRNA were reduced in homozygotes, compared to heterozygotes and normal controls at 2 and 8 weeks. Liver-type phosphofructokinase, however, did not differ significantly. The abundance of fructose 1,6-bisphosphatase mRNA was unchanged at 2 and 8 weeks. The level of phosphoenolpyruvate carboxykinase mRNA was increased slightly at 2 weeks, but not at 8 weeks. A part of these changes could not be explained by the plasma glucose or insulin level. Carnitine administration restored the mRNA of these enzymes to normal levels. These results suggest that carnitine deficiency affects the expression of these liver enzymes.
Age Factors↗
Co-ordination of tongue movements and peri-oral muscle activities during nutritive sucking.
A feeding bottle equipped with micro-video-camera and pressure sensor was devised to show the inside of the mouth and record sucking pressure. Activities of the temporal (TM), masseter muscle (MM), orbicular muscle of the mouth (OM) and suprahyoid muscles (SM) of 25 healthy infants were examined. Tongue and jaw movements, EMGs and sucking waves were scanned simultaneously. The tongue movements included elevation of the medial part of the tongue in a backward-moving peristaltic wave; significant correlations were found between jaw motion, tongue movement and sucking pressure. The TM, MM and OM were most active when the sucking pressure became positive and the jaw was closing, the SM showing highest activity in the negative-pressure phase. These findings show that each suckling cycle is biphasic, with sucking pressure, peri-oral muscle activities and jaw motion all closely correlated.
Electromyography↗
Intracranial aneurysms: diagnostic accuracy of MR angiography with evaluation of maximum intensity projection and source images.
PURPOSE: To determine whether evaluation of source images from magnetic resonance (MR) angiography in addition to maximum-intensity projection (MIP) images improves the detection of aneurysms. MATERIALS AND METHODS: Conventional and MR angiography were performed in 193 patients with various intracranial vascular lesions or normal findings. Images were evaluated in a blinded manner. Two readings were performed 6 weeks apart by evaluating MIP images with and without source images. Results were evaluated with receiver operating characteristic analysis. RESULTS: Sensitivity for the detection of aneurysms increased slightly when source images were included. The detection rate of internal carotid artery aneurysms was most improved with the addition of source images. No statistically significant differences in performance were found between the readings with MIP images alone and with source images. CONCLUSION: Sensitivity may improve with combined reading of nonselective MIP and source images.
Case-Control Studies↗
Coexpression of thrombopoietin and c-mpl genes in human acute myeloblastic leukemia cells.
Thrombopoietin (TPO) is a recently identified hematopoietic growth factor that is essential for the growth and development of megakaryocytes. We have previously shown that TPO induces proliferation of acute myeloblastic leukemia (AML) cells in vitro. In this study, we have examined the expression of TPO and its receptor c-mpl in a series of AML cases and human leukemia cell lines. The mRNA transcripts of TPO were detectable in 18 of 50 AML cases and in some myeloid leukemia cell lines (HEL, M07E and CMK) by means of reverse transcriptase polymerase chain reaction (RT-PCR). In addition, TPO transcripts were coexpressed with c-mpl transcripts in 10 of 50 AML cases and in HEL, M07E and CMK cells. With regard to the French-American-British (FAB) classification, coexpression OF TPO and c-mpl was observed with high frequency in AML cases of M7-type. Despite the TPO expression in a substantial fraction of leukemia cells, biological activity of TPO was not found in the conditioned medium that was obtained from cultivation of TPO mRNA-positive leukemia cells. These results suggest that TPO may not commonly participate in the abnormal growth of AML cells as an extracellular autocrine growth factor.
Base Sequence↗
18 years of conformation radiotherapy at Nagoya University Hospital.
Conformation radiotherapy is one of the best techniques for minimizing the radiation dose absorbed by the surrounding normal tissue while delivering a high dose to a cancerous target area. The cases of all patients who underwent external irradiation at Nagoya University Hospital from 1975 to 1992 were reviewed. A total of 5740 patients with 6179 lesions were irradiated during this time, and 3795 treatment plans involved radical intended irradiation. Of the 5740 patients, 1017 had head and neck cancer, 982 had cervical cancer, 506 had lung cancer, 439 had primary brain tumors, 308 had esophageal cancer, 1213 had metastatic tumors, and 1275 had other types of tumors. The total number of treatment plans per year decreased from 442 in 1975 to 292 in 1992. Likewise, the percentage of conformation radiotherapy performed in all patients decreased from 29.4% (130/442) in 1975 to 8.6% (25/292) in 1992. It occupied 14.5% (982/6179) of all intended plans, and 20% (775/3795) of radical treatment plans. The conformation technique was used in cases of cervical cancer (72%), esophageal cancer (65%) and primary brain tumors (25%). Boost Conformation radiotherapy represented 2% of all treatment planning and 29% of the conformation radiotherapy. Boost Conformation radiotherapy has recently become more popular and now represents more than 50% of conformation radiotherapy. With respect to cases of cervical cancer, the rates of local recurrence and late complications in cases treated by conformation radiotherapy were lower than in cases treated by two parallel opposed radiotherapy.
Female↗
Expression and distribution of glucose-6-phosphatase catalytic subunit messenger RNA and its changes in the diabetic state.
Glucose-6-phosphatase (G6Pase) plays a major role in gluconeogenic pathway. To analyze its regulation, we have cloned a full-length cDNA for G6Pase catalytic subunit from the rat liver. In the cloned cDNA, a 492 base insertion, respective to the previously reported sequence, was found in the 3'-noncoding region. In both ends of this insertion, 5'- and 3' 2' splice site motifs were identified. However, spliced mRNA was hardly observed in the rat RNA. Abundant expression was observed in the liver and the kidney by Northern analysis. Expression was also observed in the spleen, adrenal gland and small intestines. Reverse-transcription (RT) polymerase chain reaction (PCR) analysis revealed that G6Pase mRNA was also expressed in a variety of tissues including pancreatic islets. Its expression was increased in the ketotic diabetic mice livers and was corrected by insulin treatment. However, no appreciable changes were observed in kidneys. Broad tissue distribution in expression and the tissue specificity in regulation were thus considered to be the important features of G6Pase gene.
Amino Acid Sequence↗
Hepatocyte nuclear factor-4 alpha gene mutations in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients.
A mutation in the hepatocyte nuclear factor-4 alpha (HNF-4 alpha) gene has been recently reported to cause maturity-onset diabetes of the young (MODY) (Yamagata, Furuta, et al., 1996). The mutation can also be a good candidate for the responsible gene of non-insulin dependent diabetes mellitus (NIDDM). The existence of the mutated allele of Q268X (C to T substitution within the exon 7 of HNF-4 alpha gene) was searched in 514 alleles of Japanese NIDDM patients by polymerase chain reaction-restriction fragment length polymorphism analysis. No mutation was found in these patients. The result showed that the Q268X mutation of HNF-4 alpha gene was not frequent among general NIDDM patients and that it cannot serve as the major diabetogenic gene in the Japanese ethnic group.
Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗