Supersymmetry algebra in N=1 chiral supergravity.
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Journal Article↗
Biomedical subjects
M Tsuda
Publications and source records attributed to M Tsuda.
A resonance Raman study of the C=N configurations of octopus rhodopsin, bathorhodopsin, and isorhodopsin.
The resonance Raman spectra of octopus rhodopsin, bathorhodopsin, and isorhodopsin at 120 K have been obtained as well as those of pigments regenerated with isotopically labeled retinals near the C14-C15 bond. Deuteration of the Schiff base nitrogen induces relatively large changes in the C-C stretch region between 1100 and 1300 cm-1, including a large frequency shift of the C14-C15 stretch mode located at 1206-1227 cm-1 in the three octopus species, as revealed by the Raman spectra of their 14,15-(13)C2 derivatives. Such results are different compared to those of the bovine pigments, in which no significant frequency shift of the C14-C15 stretch mode was observed upon Schiff base N deuteration. In an earlier Raman study of a Schiff base model compound which contained only one single bond adjacent to two double bonds, we have found that the stretch mode of this C-C single bond at 1232 cm-1 shifts up by 15 cm-1 and its intensity is also greatly reduced upon Schiff base N deuteration when the C=N configuration is anti [Deng et al., (1994) J. Phys. Chem. 98, 4776-4779]. The same study has also shown that when the C=N configuration is syn, the C-C stretch mode should be at about 1150 cm-1. Since the C14-C15 stretch mode frequency is relatively high in the spectra of octopus rhodopsin and bathorhodopsin (> 1200 cm-1) and since the normal mode pattern near the Schiff base is similar to the model, we suggest that the C=N configuration in these two species is anti. The different responses of the C14-C15 stretch mode to the Schiff base nitrogen deuteration in bovine and octopus pigments are due to the fact that the coupled C14-C15 stretch and the C12-C13 stretch motions in the model compound or in bovine rhodopsin are altered in octopus rhodopsin so that the stretch motion of the C14-15 bond is more localized, similar to the C-C stretch motion in the small Schiff base model compound. In clear contrast with the bovine rhodopsin Raman spectrum, which is very similar to that for the 11-cis-retinal Schiff base, the drastically different octopus rhodopsin spectrum indicates large protein perturbations on the C11=C12-C13 moiety, either by steric or by electrostatic interactions. Further studies are required to determine if such spectral differences indicate a difference of the energy conversion mechanism in the primary photochemical event of these two pigments.
Animals↗
Involvement of the opioid system in the anxiolytic effect of diazepam in mice.
In the present study, the anticonflict effect of diazepam was significantly abolished by pretreatment with naloxone, beta-funaltrexamine or nor-binaltorphimine but not naltrindole, using a Vogel-type conflict paradigm in mice. However, naloxone alone had a significant proconflict effect, and beta-funaltrexamine alone tended to produce a proconflict effect. Spontaneous drinking behavior was not affected by treatment with diazepam and nor-binaltorphimine. In addition, nor-binaltorphimine had no effect on diazepam-induced motor incoordination, hypothermia or anticonvulsant action, respectively. Moreover, the stable dynorphin analog E2078 ([N-methyl-Tyr1, N-alpha-methyl-Arg7-D-Leu8]dynorphin A-(1-8) ethylamide) and the highly selective kappa-opioid receptor agonist U50,488H (trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)cyclohexyl)benzenacetamide++ + methanesulfonate hydrochloride) produced a significant anticonflict effect, which was completely antagonized by pretreatment with nor-binaltorphimine. These findings suggested that the kappa-opioid system may play an important role in the anxiolytic effect of benzodiazepine and the regulation of anxiety.
Analgesics, Non-Narcotic↗
Cloning and sequencing of the gene for Na+/H+ antiporter of Vibrio parahaemolyticus.
A gene encoding an Na+/H+ antiporter was cloned from vibrio parahaemolyticus into the plasmid pBR322 and expressed in Escherichia coli cells. The gene enabled mutant E. coli cells to grow in the presence of 0.2 M NaCl (or 10 mM LiCl). These cells were originally unable to grow under such conditions because of the lack of major Na+(Li+)/H+ antiporters. We detected Na+/H+ antiporter activity due to the gene in membrane vesicles. The gene was sequenced and the deduced amino acid sequence was found to be 72% identical to the NhaB Na+/H+ antiporter of E. coli.
Amino Acid Sequence↗
Sequence of a Na+/glucose symporter gene and its flanking regions of Vibrio parahaemolyticus.
The nucleotide sequence of an approximately 6 kbp segment of chromosomal DNA of Vibrio parahaemolyticus was determined. The nucleotide sequence revealed four open reading frames (ORFs) in this region. Hydropathy profiles of the deduced amino acid sequence of the ORFs indicate that ORF1 encodes a hydrophobic polypeptide with typical characteristics of a membrane transport protein. All other ORFs encode hydrophilic polypeptides. ORF1 showed significant amino acid sequence similarity to proteins of the SGLT (Na+/glucose symporter) family, and the amino acid sequence of ORF4 showed very high similarity to several bacterial transcriptional repressor proteins (GalR-LacI family). We observed elevated glucose transport activity in cells harboring a plasmid carrying the DNA region corresponding to ORF1, and the glucose transport was greatly stimulated by Na+. Thus, we believe that ORF1 encodes a Na+/glucose symporter.
Amino Acid Sequence↗
Properties of a Na+/galactose (glucose) symport system in Vibrio parahaemolyticus.
We have investigated galactose transport in a mutant strain of Vibrio parahaemolyticus that lacks a glucose-PTS (phosphoenolpyruvate:carbohydrate phosphotransferase system) and a trehalose-PTS. Cells of the V. parahaemolyticus actively transported D-galactose and Na+ greatly stimulated the transport. Maximum stimulation of D-galactose transport activity was observed at 10mM NaCl, and Na+ could be replaced with Li+. Addition of galactose to the cell suspension under anaerobic conditions elicited Na+ uptake. Therefore, we conclude that this organism accomplishes galactose transport by a Na+/solute symport mechanism. Judging from inhibition results, D-galactose, D-glucose and to a lesser extent alpha-D-fucose are substrates of this transport system. The Na+/galactose symport system exhibited a high affinity for D-galactose (Km: 40 microM) and showed a relatively lower affinity for D-glucose (Km: 420 microM), but the maximum velocities for galactose and glucose transport were almost same (about 52 nmol/min per mg protein). The Na+/D-galactose symport system was induced by either D-galactose or alpha-D-fucose, and repressed by D-glucose.
Biological Transport↗
The defective secretion of a naturally occurring alpha-1-antichymotrypsin variant with a frameshift mutation.
A newly found variant alpha-1-antichymotrypsin (ACT), ACT Isehara-2, has a deletion of two bases (AA) at codon 391 near the carboxyl terminus. This frameshift mutation caused a change in the amino acid sequence and generated 10 extra amino acids (408 amino acids total) [Tsuda, M., Sei, Y., Matsumoto, M., Kamiguchi, H., Yamamoto, Y., Shinohara, Y., Igarashi, T. & Yamamura, M. (1992) Hum. Genet. 91. 467-468]. The serum ACT levels in three unrelated heterozygotes with this mutant ACT gene were 37% 49% and 54% that of the normal individuals. To examine the reduced serum levels, the normal ACT and the mutant ACT created by site-directed mutagenesis were transfected into COS-7 cells for comparison. The value for the retention rate (intracellular ACT/total ACT) was apparently higher in the cells expressing mutant ACT Isehara-2 than those bearing the normal gene. In the pulse-chase experiments, the secretion of the synthesized mutant ACT into the medium was not observed, whereas the normal ACT was mostly secreted as a 64-kDa form. The endoglycosidase H digestion and an electron microscopic analysis indicated that the retained mutant ACT was present in the endoplasmic reticulum. These results provide the biochemical basis for the decreased serum ACT level of individuals with ACT Isehara-2, and suggest the importance of the carboxyl-terminal region for its secretion.
Amino Acid Sequence↗
A new type of major aminopeptidase in bovine brain.
A new type of major aminopeptidase was purified from bovine brain by ammonium sulfate fractionation and TMAE-fractogel (anion exchange), arginine-Sepharose 4B, Sephadex G-150, and Sephadex G-100 column chromatography. The purified enzyme showed a maximum activity at pH 7.2, and its molecular size was estimated to be 98,000 by gel filtration and 104,000 by SDS-PAGE with or without 2-mercaptoethanol. Further properties were activation by thiol reagents; inhibition by EDTA, puromycin, bestatin, amastatin, actinonin, leuhistin and probestin; and very low concentrations of Cu2+, Cd2+, Pb2+, Al3+, Fe3+, and Zn2+ inhibited activity. The enzyme hydrolyzed several amino acyl-7-amido-4-methylcoumalin derivatives (amino acid-MCA). The order of MCA-substrate specificity expressed as kcat/Km is Lys-MCA > Arg-MCA > Leu-MCA > Met-MCA > Phe-MCA > Tyr-MCA > Ala-MCA >> Gly-MCA, Pro-MCA, Ser-MCA, Asn-MCA. Immunoreactivity of the antibody against the purified aminopeptidase was observed in human brain and most rat tissues examined including brain, liver, kidney, lung, heart, and skeletal muscle at the same molecular size as in bovine brain aminopeptidase. Most of the Lys-, Leu-, Met-, and Phe-MCA degrading activity in crude bovine and human brain extracts was absorbed by the aminopeptidase IgG, suggesting that this aminopeptidase is a major enzyme, sharing at least Lys-, Leu-, Met-, and Phe-MCA degrading aminopeptidase activities in the brains.
Amino Acids↗
Increase in femoral bone mass by ipriflavone alone and in combination with 1 alpha-hydroxyvitamin D3 in growing rats with skeletal unloading.
We assessed the possibility that ipriflavone treatment might result in bone restoration in immobilized rats. We also investigated the effect of combined treatment with ipriflavone and vitamin D3 on the bone. Male Sprague-Dawley rats, 6 weeks of age, were subjected to unilateral sciatic neurectomy. Three weeks after the operation, ipriflavone (100 mg/kg), 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3, 25 ng/kg], or both ipriflavone and 1 alpha (OH)D3 were orally administered every day for 12 or 24 weeks. After 12 weeks of treatment, only the group receiving combined treatment with ipriflavone and 1 alpha (OH)D3 showed increases in total femur calcium content (+16.4%, compared with the control). After 24 weeks, both animals treated with ipriflavone alone and those that had received the combination of ipriflavone and 1 alpha (OH)D3 showed significant increases in femur calcium content (+18.0% and +23.8%, respectively). In these treatment groups, X-ray analysis revealed an increase in bone mineral density over the entire length of the femur, and an increase in cortical diameter at the midshaft without affecting medullary width. Administration of 1 alpha (OH)D3 (25 ng/kg) alone had no effect. Body weight, femur length, and serum markers of calcium and bone metabolism were not affected in any group. We evaluated the relationship between ipriflavone and vitamin D3 in bone cells in a culture system using rat bone marrow stromal cells in which the cells subsequently form mineralized bone-like tissue. Continuous treatment with ipriflavone (10(-5) M) for 21 days resulted in an increase in osteocalcin secretion, and enhanced its response to 1 alpha, 25-dihydroxyvitamin D3 (10(-11) M-10(-8 M)). These findings indicate that ipriflavone treatment increases the femoral bone mass in immobilized rats. In addition, a low dose of 1 alpha (OH)D3, which did not induce hypercalcemia, in combination with ipriflavone, augmented the stimulatory effect of ipriflavone alone on the bone mass, possibly due to a direct effect of each agent on osteoblastic cells.
Animals↗
Diazepam pretreatment suppresses morphine withdrawal signs in the mouse.
The effect of diazepam on the development of physical dependence on morphine and on the naloxone-precipitated increase in cortical NA turnover were investigated in mice. Co-administration of diazepam (1-4 mg/kg, i.p.) during chronic morphine treatment suppressed the expression of naloxone (3 mg/kg, s.c.)-precipitated withdrawal signs (jumping, exploratory rearing and weight loss). However, a single injection of diazepam (4 mg/kg, i.p.) in morphine-dependent mice did not affect the expression of naloxone-precipitated withdrawal signs. The 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) level and noradrenaline (NA) turnover (MHPG/NA) in the cerebral cortex were increased by naloxone (3 mg/kg) challenge. These increases in the cortical MHPG level and NA turnover were significantly prevented by co-administration of diazepam (4 mg/kg, i.p.) during chronic morphine treatment. These findings suggest that the co-administration of diazepam during chronic morphine treatment may prevent some neurochemical changes in the central noradrenergic system during chronic morphine treatment, and may suppress the development of physical dependence on morphine. Therefore, the inhibitory action of GABA via benzodiazepine binding sites may play an important role in the development of physical dependence on morphine.
Adrenergic alpha-Agonists↗
Induction of SPI-3 mRNA, encoding a serine protease inhibitor, in gerbil hippocampus after transient forebrain ischemia.
We cloned genes the expression of which is induced in the Mongolian gerbil (Meriones unguiculatus) hippocampus after transient forebrain ischemia by a differential display technique. Among these genes, a rat serine protease inhibitor SPI-3 homologue was isolated. Present analyses suggested that the expression of gerbil SPI-3 mRNA was closely associated with delayed neuronal death and may block activities of proteases leaking from degenerating neurons or may support neuronal survival.
Amino Acid Sequence↗
Cascade of gene expression induced by Ca2+ signals in neurons.
To understand the cellular processes involved in learning and memory, the cellular responses of neurons to calcium (Ca2+) signals, which can be evoked via synaptic activity, should be examined. A series of investigations in primary cultures of neurons revealed that the regulation of brain-derived neurotrophic factor (BDNF) mRNA expression is mediated by almost the same Ca2+ signaling pathways as that of c-fos mRNA expression. Such early co-activation of both genes in response to Ca2+ signals further suggests that sets of calcium-responsive genes (CaRGs) are concurrently activated by Ca2+ signals. The products encoded by CaRGs should then evoke a variety of physiological responses in neurons with the expression of another set of genes, the products of which are directly involved in the outcomes of neuronal functions. Thus, a cascade of gene expression can be induced by Ca2+ signals evoked via synaptic activity. It is of particular interest to identify the CaRGs and investigate the regulational mechanisms of their expression. A cellular approach using primary cultures of neurons would therefore lead to a better understanding of the intracellular processes involved in learning and memory.
Animals↗
Differential axonal transport of soluble and insoluble tau in the rat sciatic nerve.
Axonal transport of microtubule-associated protein tau was studied in the motor fibers of the rat sciatic nerve 1-4 weeks after labeling of the spinal cord with [35S]methionine. As 60-70% of low molecular weight tau in this system was found to be insoluble in 1% Triton-containing buffer, labeled proteins in 6-mm consecutive nerve segments were first separated into Triton-soluble and insoluble fractions. Two-dimensional gel electrophoresis and immunoblotting with anti-tau antibody confirmed the presence of tau among labeled, transported proteins in both fractions. Isoform composition of labeled tau was similar to that of bulk axonal tau, the most acidic species with apparent molecular mass of 66 kDa being the major component. Transport profiles obtained by measuring radioactivities associated with this major isoform showed that soluble and insoluble tau were transported at different rates. Insoluble tau, which contained the majority of tau-associated radioactivity, was transported at 1.7 mm/day in slow component a (SCa), whereas soluble tau was transported faster, at 3 mm/day, corresponding to the rate of slow component b (SCb). Cotransport of insoluble tau with insoluble tubulin in SCa suggests its association with stable microtubules.
Animals↗
Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection.
Infection with the liver fluke, Opisthorchis viverrini, is a causative agent of cholangiocarcinoma. One possible contributing factor in this carcinogenesis is the chronic, local generation of nitric oxide by inflammatory cells expressing inducible nitric oxide synthase and the production of N-nitroso compounds via the reaction between amines and nitrosating agents derived from nitric oxide. Our previous studies provided evidence that nitric oxide synthesis is elevated during human liver fluke infection. Here we present data on the same sample of men which definitively demonstrates increased nitrosation of proline and thioproline (thiazolidine-4-carboxylic acid) among infected men compared to uninfected control subjects on a low nitrate diet. This difference was specifically abolished by co-administration of ascorbic acid with proline and by elimination of parasites by praziquantel treatment. Multivariate statistical models demonstrate the importance of salivary thiocyanate levels to variation in the nitrosation of proline among uninfected individuals, but not among those with current fluke infection. This suggests that considerable generation of nitrosating agents (N203/N204) in infected people may be occurring via oxidation of arginine by nitric oxide synthase in inflamed tissue which is thiocyanate insensitive. Analyses revealed positive associations between N-nitrosoproline excretion and nitrate/nitrite levels in urine, plasma and saliva and with usual alcohol intake; with variation in these trends between groups. In conclusion, we have confirmed the relationship between O.viverrini infection and enhanced endogenous nitrosation, showing evidence of its extragastric site. New information is also provided on the determinants of N-nitrosamino acid excretion in men on a controlled low nitrate diet without smoking, conditions which reduce exogenous sources of nitrosating agents.
Adult↗
The thiJ locus and its relation to phosphorylation of hydroxymethylpyrimidine in Escherichia coli.
Extracts from Escherichia coli K-12 contained two distinct enzymes capable of catalysing the phosphorylation of hydroxymethylpyrimidine (HMP) to HMP monophosphate: pyridoxine kinase (EC 2.7.1.35) and an enzyme that has not previously been genetically analysed, HMP kinase (EC 2.7.1.49). Two distinct genes, pdxL and thiJ, specify the activities of the former and latter enzymes, respectively. The inactivation of both genes by independent mutations in the same cell resulted in the complete loss of HMP kinase activity. Experiments with a series of strains that carry mutations in thiC, thiC pdxB, thiC pdxB pdxL and thiC pdxB pdxL thiJ revealed that the ability of the double mutant (pdxL thiJ) to utilize HMP in thiamin pyrophosphate biosynthesis was restored by introducing the wild-type allele corresponding to the thiJ mutation. The thiJ locus was mapped on the chromosome near the thiD and thiM loci, which govern the activities of phosphomethylpyrimidine kinase (EC 2.7.4.7) and hydroxyethylthiazole kinase (EC 2.7.1.50), respectively.
Chromosome Mapping↗
A newly identified exonic mutation of the WT1 gene in a patient with Denys-Drash syndrome.
An 11 month old boy with hypospadias and bilateral undescended testes developed renal failure. Denys-Drash syndrome was suspected and molecular analysis of the WT1 gene was performed, although no Wilms' tumor was identified. Direct sequencing analysis of genomic DNA from this patient revealed a G to A transition resulting in 366Arg to Leu substitution in exon 8 which has hitherto not been described. This newly identified mutation will help in the understanding of functional domains and in making a diagnosis of Denys-Drash syndrome.
DNA Mutational Analysis↗
A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion.
Protein tyrosine phosphatases (PTPases), such as SHP-1 and SHP-2, that contain Src homology 2 (SH2) domains play important roles in growth factor and cytokine signal transduction pathways. A protein of approximately 115 to 120 kDa that interacts with SHP-1 and SHP-2 was purified from v-src-transformed rat fibroblasts (SR-3Y1 cells), and the corresponding cDNA was cloned. The predicted amino acid sequence of the encoded protein, termed SHPS-1 (SHP substrate 1), suggests that it is a glycosylated receptor-like protein with three immunoglobulin-like domains in its extracellular region and four YXX(L/V/I) motifs, potential tyrosine phosphorylation and SH2-domain binding sites, in its cytoplasmic region. Various mitogens, including serum, insulin, and lysophosphatidic acid, or cell adhesion induced tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2 in cultured cells. Thus, SHPS-1 may be a direct substrate for both tyrosine kinases, such as the insulin receptor kinase or Src, and a specific docking protein for SH2-domain-containing PTPases. In addition, we suggest that SHPS-1 may be a potential substrate for SHP-2 and may function in both growth factor- and cell adhesion-induced cell signaling.
Amino Acid Sequence↗
Acute-phase plasma proteins in gastric cancer: association with metastatic potential and prognosis.
We evaluated the possibility that acute-phase plasma proteins such as alpha 1-antichymotrypsin (ACT) and immunosuppressive acidic protein (IAP) might be useful predictors of lymph node metastasis and prognosis in patients with gastric cancer. Both ACT and IAP levels generally increased according to the pTNM stage. Patients with both abnormal IAP and ACT levels showed a high risk of lymphatic and hepatic metastasis as well as peritoneal dissemination, with a resultant poor prognosis. Patients who had abnormal IAP levels with or without abnormal ACT levels had a significantly higher risk of lymph node metastasis, as well as more invasive tumors and a worse prognosis than those who had normal IAP levels with or without abnormal ACT levels. In combination group 4 [IAP(+) ACT(-) vs. IAP(-) ACT(+)] lymphatic metastasis was seen more often with isolated IAP(+) (76.4%) than with ACT(+) (52.9%) (p < 0.0045), especially in the subgroup of poorly differentiated adenocarcinoma (POR; p < 0.0177). However, this does not demonstrate that ACT(+) is a protective factor against lymphatic invasion, because the results of combination group 6 [IAP(-) ACT(+) vs. IAP(-) ACT(-)] show that isolated ACT(+) is also significantly related to lymphatic metastasis (p < 0.001). The same is true for the subgroup of signet ring cell carcinomas (p = 0.038), but it has not been tested versus the POR subgroup.
Acute-Phase Proteins↗