[Diagnosis of magnesium metabolism disorders].
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Diagnosis, Differential↗
Biomedical subjects
K Kikuchi
Publications and source records attributed to K Kikuchi.
Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells.
Angiotensin II activates p21ras, and mediates cardiac hypertrophic growth through the type 1 angiotensin II receptor in cardiac myocytes. An inhibitor of 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) reductase has been shown to block the post-translational farnesylation of p21ras and inhibit protein synthesis in several cell types. Primary cultures of neonatal cardiac myocytes were used to determine whether HMG-CoA reductase inhibitors, lovastatin, simvastatin and pravastatin inhibit the angiotensin II-induced hypertrophic growth. Angiotensin II (10(-6) M) significantly increased protein-DNA ratio, RNA-DNA ratio, ratios of protein synthesis and mitogen-activated protein (MAP) kinase activity. Lipid-soluble HMG-CoA reductase inhibitors, lovastatin (10(-6) M) and simvastatin (10(-6) M) partially and significantly inhibited the angiotensin II-induced increases in these parameters, but a water-soluble HMG-CoA reductase inhibitor, pravastatin (10(-6) M) did not. Mevalonate (10(-4) M) overcame the inhibitory effects of lovastatin and simvastatin on angiotensin II-induced increases in these parameters. A selective protein kinase C inhibitor, calphostin C (10(-6) M) partially and significantly prevented angiotensin II-induced increases in these parameters, and treatment with both lovastatin and calphostin C inhibited completely. Angiotensin II increased p21ras activity and membrane association, and lovastatin inhibited them. These studies demonstrate that a lipid-soluble HMG-CoA reductase inhibitor, lovastatin, may prevent angiotensin II-induced cardiac hypertrophy, at least in part, through p21ras/MAP kinase pathway, which is linked to mevalonate metabolism.
Angiotensin II↗
Effects of hormones and osmolarity in the culture medium on germinal vesicle breakdown of porcine oocytes.
The present study was conducted to examine effects of hormones and osmolarity on germinal vesicle breakdown (GVBD) and histone H1 kinase (H1K) activity in porcine oocytes cultured in vitro. The basic medium used for culture of oocytes was modified Tyrode's solution in which the osmolarity was adjusted to 134 to 495 mOsm by changing the concentration of sodium chloride (NaCl). When the hormones were present, osmolarity of medium that allows GVBD of oocytes was less than 400 mOsm. However, the range of osmolarity of medium that allows meiotic maturation of oocytes was 210 to 362 mOsm. On the other hand, without hormonal supplement, the incidence of GVBD in oocytes decreased as the osmolarity of the medium increased in the rage of 210 to 362 mOsm. By increasing the osmolarity of the medium from 210 to 362 mOsm by addition with sorbitol instead of NaCl, the incidence decreased from 89.1% to 13.3%. In oocytes cultured in medium of 210 mOsm without hormones, the percentage of oocytes that underwent GVBD and had increased H1K activity 20 h after culture was significantly higher (P < 0.05) than those of oocytes cultured in the same medium supplemented with hormones or medium of 362 mOsm. These results indicate that in vitro induction of GVBD in porcine oocytes is strongly affected by osmolarity of the medium in the absence of hormones. The results also suggest that, under low osmolarity (210 mOsm), GVBD is accelerated with rapid increase of H1K activity.
Animals↗
Imaging of caspase-3 activation in HeLa cells stimulated with etoposide using a novel fluorescent probe.
Microscopic visualization of intracellular enzyme activity can provide information about the physiological role of the enzyme. Caspases are cysteine proteases that have critical roles in the execution of apoptosis. General fluorometric substrates of caspase-3, such as DEVD-MCA, are unsuitable for imaging because they are excited at short wavelength, so we designed and synthesized novel fluorescent probes that are excited at suitable wavelengths for detecting caspase-3 activity in living cells. Using one of these probes, we succeeded in microscopic visualization of caspase-3-like activity within HeLa cells treated with etoposide. The caspase-3-like activity was increased in the cytosol at first, then expanded to the whole cell.
Apoptosis↗
Synthesis and evaluation of 1-position-modified inositol 1,4,5-trisphosphate analogs.
IP3 analogs were synthesized by the modification of phosphate at the 1-position, and their affinity for the IP3 receptor was analyzed by means of surface plasmon resonance measurements. Our results suggest that a hydrophobic and charged moiety linked to this position enhances the affinity for the IP3 receptor.
Binding, Competitive↗
Identification of a novel gene, DAM1, amplified at chromosome 1p13.3-21 region in human breast cancer cell lines.
Screening for differentially expressed genes in cancer cell lines by the RNA differential display (DD) technique identified a novel mRNA that encodes a 26-kDa protein and is up-regulated in MCF-7 and BT-20 breast cancer cells. The predicted amino acid sequence showed 38% homology to Caenorhabditis elegans T12A2.7 protein, indicating that this is a possible human homologue for C. elegans T12A2.7 protein. The mRNA, designated DAM1 (DNA amplified in mammary carcinoma), was mapped at the 1p13.3-21 region, which is frequently altered in human breast cancer. By Southern blot analysis, we confirmed that the up-regulation of this novel gene is associated with gene amplification in MCF-7 (10-fold) and BT-20 (5-fold) cells. Our findings suggest that the DAM1 gene is a novel gene up-regulated by amplification in human breast cancer cell lines.
Amino Acid Sequence↗
[A family of hereditary motor and sensory neuropathy type 1B showing a marked difference of neurological disability score among affected family members].
The proband was a 22-year-old man with a complaint of progressive weakness in his lower limbs. His clinical diagnosis of hereditary motor and sensory neuropathy (HMSN) type 1 was made based on the neurological findings and the results of peripheral nerve conduction studies and of histological studies of the sural nerve obtained on biopsy. The molecular genetic studies revealed arginine-to-histidine substitution at amino acid 98 of the Po protein in the proband. Therefore, the final diagnosis of HMSN type 1B was made. The same mutation was found in his mother and his two sisters. The neurological disability score of the proband was 69. It was 24 for his affected mother. The scores were 16 and 20 for the two affected sisters. The reason why the proband showed the highest score was considered to be the presence of the marked muscle weakness in the lower limbs found only in the proband. Therefore, it was concluded that the neurological disability score differs greatly among the affected members even with the same genetic abnormality in the same generation of the same family with HMSN type 1B. The affected family member with a low neurological disability score may be clinically undiagnosed.
Adolescent↗
Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney.
BACKGROUND: Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown. METHODS AND RESULTS: We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of </=10(-10) mol/L reduced renal perfusion pressure in Dahl salt-resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive (S) rats (10(-10) mol/L: -10.3+/-0. 6% versus 11.2+/-1.5%, R versus S; P<0.01). BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the level of NO release in S rats was lower, as detected by chemiluminescence (10(-10) mol/L: 10.7+/-0.7 versus 3.1+/-0.4 fmol/min per gram of kidney, R versus S; P<0.01). Similar effects of BQ-3020 were observed in streptozotocin-induced diabetic rats and diet-induced hypercholesterolemic rats. Expression of endothelial NO synthase decreased in S rats but not in diabetic or hypercholesterolemic rats. In contrast, expression of ETBR in the endothelium was decreased in all 3 disease models compared with that in the vascular smooth muscle cell. CONCLUSIONS: These results suggest that impaired NO release in response to stimulation of ETBR is due, at least in part, to a decrease in endothelial ETBR and may play a role in vascular dysfunction usually associated with arteriosclerosis-related diseases.
Animals↗
Characterization of the carp myosin heavy chain multigene family.
We isolated partial coding sequences for 29 carp myosin heavy chain genes (MyoHCs) and determined the nucleotide sequences around the region encoding the loop 2 of the myosin molecule. The predicted amino acid sequences from the isolated genes all showed very high similarity to those of skeletal and cardiac muscles from higher vertebrates, but not to those of smooth and non-muscle counterparts. Among all clones isolated, carp MyoHC10, MyoHCI-1-3 and MyoHC30 showed exon-nucleotide sequences identical to those of cDNAs encoding the loop 2 region of the 10 degrees C-, intermediate- and 30 degrees C-type fast skeletal isoforms [Hirayama and Watabe, Euro. J. Biochem. 246 (1997) 380-387]. The loop 2 of 28 types of carp MyoHCs was encoded by two exons separated by an intron corresponding to that of the 16th in higher vertebrate MyoHCs, whilst this intron was not found in carp MyoHC30. Although carp MyoHC30 had a gene organization different from those of higher vertebrates and other carp MyoHCs, its predicted amino acid sequence for loop 2 showed the highest homology to those of higher vertebrates among carp MyoHCs. In the 28 carp MyoHCs containing the intron, a combination of different nucleotide sequences for the two resulted in 14 distinct series for the combined coding sequence. These different nucleotide sequences encoded nine distinct amino acid sequences. Phylogenetic analysis for the present loop 2 and light meromyosin previously reported for carp MyoHCs [Imai et al., J. Exp. Biol. 200 (1997) 27-34] revealed that carp MyoHCs have recently diverged and are more closely related to each other than to MyoHCs from other species.
Amino Acid Sequence↗
Cloning, expression, and genetic mapping of Sema W, a member of the semaphorin family.
The semaphorins comprise a large family of membrane-bound and secreted proteins, some of which have been shown to function in axon guidance. We have cloned a transmembrane semaphorin, Sema W, that belongs to the class IV subgroup of the semaphorin family. The mouse and rat forms of Sema W show 97% amino acid sequence identity with each other, and each shows about 91% identity with the human form. The gene for Sema W is divided into 15 exons, up to 4 of which are absent in the human cDNAs that we sequenced. Unlike many other semaphorins, Sema W is expressed at low levels in the developing embryo but was found to be expressed at high levels in the adult central nervous system and lung. Functional studies with purified membrane fractions from COS7 cells transfected with a Sema W expression plasmid showed that Sema W has growth-cone collapse activity against retinal ganglion-cell axons, indicating that vertebrate transmembrane semaphorins, like secreted semaphorins, can collapse growth cones. Genetic mapping of human SEMAW with human/hamster radiation hybrids localized the gene to chromosome 2p13. Genetic mapping of mouse Semaw with mouse/hamster radiation hybrids localized the gene to chromosome 6, and physical mapping placed the gene on bacteria artificial chromosomes carrying microsatellite markers D6Mit70 and D6Mit189. This localization places Semaw within the locus for motor neuron degeneration 2, making it an attractive candidate gene for this disease.
Amino Acid Sequence↗
[A message from JNCVI (Joint National Committee-VI) on the treatment of hypertension].
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Humans↗
Quantitative determination of E5880 in rat plasma by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
A simple and sensitive method is described for the determination of E5880 in rat plasma. The method is based on high-performance liquid chromatography/electrospray ionization mass spectrometry, using deuterated E5880 as an internal standard. Selected reaction monitoring is employed for selectivity and sensitivity, this in turn enables quantification in a short period of time (within 7 minutes) over the extended range of 0.1-1000 ng/ml with acceptable precision and accuracy. The method demonstrated to be suitable for the quantitative analysis of E5880 in rat plasma. The pharmacokinetic profile of E5880 after a single intravenous administration of E5880 was elucidated.
Animals↗
A series of protein phosphatase gene disruptants in Saccharomyces cerevisiae.
Thirty-two protein phosphatase (PPase) genes were identified in the genome nucleotide sequence of Saccharomyces cerevisiae. We constructed S. cerevisiae disruptants for each of the PPase genes and examined their growth under various conditions. The disruptants of six putative PPase genes, i.e. of YBR125c, YCR079w, YIL113w, YJR110w, YNR022c and YOR090c, were created for the first time in this study. The glc7, sit4 and cdc14 disruptants were lethal in our strain background. The remaining 29 PPase gene disruptants were viable at 30 degrees C and 37 degrees C, but only one disruptant, yvh1, showed intrinsic cold-sensitive growth at 13 degrees C. Transcription of the YVH1 gene was induced at 13 degrees C, consistent with an idea that Yvh1p has a specific role for growth at a low temperature. The viable disruptants grew normally on nutrient medium containing sucrose, galactose, maltose or glycerol as carbon sources. The ppz1 disruptant was tolerant to NaCl and LiCl, while the cmp2 disruptant was sensitive to these salts, as reported previously, and none of the other viable PPase disruptants exhibited the salt sensitivity. When the viable disruptants were tested for sensitivity to drugs, i.e. benomyl, caffeine and hydroxyurea, ppz1 and ycr079w disruptants exhibited sensitivity to caffeine.
Benomyl↗
Urotensin II is the endogenous ligand of a G-protein-coupled orphan receptor, SENR (GPR14).
Two molecular species of urotensin II (UII) were isolated from porcine spinal cords and identified as the endogenous ligands of a G-protein-coupled orphan receptor, SENR (sensory epithelium neuropeptide-like receptor), which is identical to GPR14. We established a CHO cell line stably expressing the rat SENR and investigated several tissue extracts to evoke the response mediated by the SENR. Extract from porcine spinal cords showed an activity of arachidonic acid metabolites release from SENR-expressing cells and was purified using HPLC. Two active substances were isolated and their sequences were determined as GPTSECFWKYCV and GPPSECFWKYCV, which were revealed to be porcine UII. Synthetic UII peptides caused arachidonic acid metabolites release activity in the rat SENR-expressing cells with an EC(50) value of 1 nM. Three cDNAs encoding the precursor proteins of porcine UII were cloned from a porcine spinal cord cDNA library; 2 consist of 121 amino acid residues and the other, which seemed to be a splicing variant, consist of 85 residues.
Amino Acid Sequence↗
Cloning and phylogenetic relationship of red drum somatolactin cDNA and effects of light on pituitary somatolactin mRNA expression.
The nucleotide sequence for red drum somatolactin (SL) cDNA was determined and the expression of pituitary SL mRNA was examined in red drum kept under various light conditions. A full length of SL cDNA (1629 bp) was isolated and characterized from a red drum pituitary cDNA library. The SL cDNA has an open reading frame of 696 nucleotides which encodes a 24-amino-acid signal peptide and a 207-amino-acid mature peptide. Red drum SL shares 58-87% amino acid sequence identity and 56-85% nucleotide sequence identity with other teleost SLs. The characteristic seven cysteine residues and one N-glycosylation site of SL are well conserved in the red drum SL mature peptide. Phylogenetic analysis shows that red drum SL is closely related to seabream SL and is also closely related to lumpfish, flounder, halibut, and sole SLs, whereas SLs of Atlantic cod, chum salmon, rainbow trout, and eel are more distantly related to those of the more advanced teleosts. Two SL transcripts, designated as SL I at 1.8 kb and SL II at 1.3 kb, are expressed in red drum pituitaries and correspond to two polyadenylation signal sites in red drum SL cDNA at nucleotide positions 1554 and 1270. Levels of the SL I mRNA were 2- to 4-fold higher in pituitaries of blind red drum and intact fish kept under constant darkness for 1 week than those in control fish sampled during the light phase of the light-dark cycle. Similarly, pituitary levels of SL II mRNA were 9-fold higher in blind fish and 1.6- to 4-fold higher in intact fish kept under constant darkness than in the control fish. Furthermore, these changes in mRNA levels in pituitaries were accompanied by more than 10-fold increases in SL protein concentrations in plasma. The finding that the absence of light perception for extended periods leads to dramatic increases in SL mRNA expression as well as SL secretion in red drum provides further evidence that illumination levels and SL physiology are intimately related in this species.
Amino Acid Sequence↗
Cloning and characterization of a novel class VI semaphorin, semaphorin Y.
Semaphorins comprise a large family of proteins implicated in axonal guidance. We cloned a novel transmembrane semaphorin, semaphorin Y (Sema Y), which has a class VI sema domain. Sema Y shows growth cone collapsing activity on DRG neurons in vitro, and the target regions of the DRG neurons express sema Y mRNA during development. Sema Y may be a stop signal for these neurons in their target areas. Interestingly, sema Y mRNA was also detected in other neurons and their targets. Two isoforms of Sema Y derived from alternative splicing were identified and their expression was found to be regulated in a tissue- and age-dependent manner. Distribution of sema Y mRNA suggests that Sema Y might also be important during maintenance of axonal connections and/or differentiation and migration of cells. Sequence comparison among class VI semaphorins revealed two short conserved sequence stretches in their cytoplasmic domains, suggesting interaction of these semaphorins with a common intracellular component(s).
Alternative Splicing↗
Surgical management of idiopathic tracheal stenosis.
Most nonmalignant upper tracheal stenoses are caused by prolonged endotracheal intubation or tracheostomy, and idiopathic stenosis is uncommon. A 43-year-old woman complained of increasing shortness of breath during exercise over a year prior to admission. She had no significant past medical history, including endotracheal intubation. Bronchoscopy and tracheal tomography revealed nonmalignant circumferential upper tracheal stenosis 20 mm long. Single-stage surgical resection with cricotracheal anastomosis completely relieved her respiratory symptoms. Idiopathic tracheal stenosis is extremely rare, and the treatment of choice is surgery.
Adult↗
A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy.
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum.
Female↗