Myasthenia gravis associated with limited scleroderma (CREST syndrome)
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CREST Syndrome↗
Biomedical subjects
T Yoshimura
Publications and source records attributed to T Yoshimura.
The influence of traditional Chinese herbal drugs on serum 1, 5-anhydroglucitol levels.
The serum concentration of 1,5-anhydroglucitol (1,5-AG), a polyol which originates mainly in the diet, is used in Japan as a new marker for glycemia. To evaluate the potential interference of 1, 5-AG measurements by traditional Chinese medicines (Kampo), we examined the 1,5-AG content in 32 types of concentrated dosage forms of Kampo using high performance liquid chromatography (HPLC). The 32 types of Kampo were the most frequently used in Japan, two of which, Ninjin-yoei-to (7030 microg/g dry weight) and Kami-kihi-to (6700 microg/g dry weight), contained large amounts of 1,5-AG. Six others contained small amounts of 1,5-AG. Both Ninjin-yoei-to and Kami-kihi-to contain the same ingredient, Polygalae radix, which is a crude form of polygalitol (1,5-AG). To confirm the effects of these Kampo medicines on the serum levels of 1,5-AG, we administered Ninjin-yoei-to (7.5 g/day) for 8 weeks to 18 patients with Type 2 diabetes mellitus (Type 2 DM). The serum level of 1,5-AG increased from 9.8+/-8.9 to 28.1+/-17.5 microg/ml by week 8. Hemoglobin A1c (HbA1c) had not changed by week 8. Thus, an abnormal serum 1,5-AG level may be present in patients taking Kampo which contains Polygalae radix.
Aged↗
Analysis of glycosidically bound aroma precursors in tea leaves. 1. Qualitative and quantitative analyses of glycosides with aglycons as aroma compounds.
Twenty-six synthetic glycosides constituting aglycons of the main tea aroma compounds ((Z)-3-hexenol, benzyl alcohol, 2-phenylethanol, methyl salicylate, geraniol, linalool, and four isomers of linalool oxides) were synthesized in our laboratory as authentic compounds. Those compounds were used to carry out a direct qualitative and quantitative determination of the glycosides as aroma precursors in different tea cultivars by capillary gas chromatographic-mass spectrometric (GC-MS) analyses after trifluoroacetyl conversion of the tea glycosidic fractions. Eleven beta-D-glucopyranosides, 10 beta-primeverosides (6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside) with aglycons as the above alcohols, and geranyl beta-vicianoside (6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside) were identified (tentatively identified in the case of methyl salicylate beta-primeveroside) in fresh tea leaves and quantified on the basis of calibration curves that had been established by using the synthetic compounds. Primeverosides were more abundant than glucosides in each cultivar we investigated for making green tea, oolong tea, and black tea. Separation of the diastereoisomers of linalool and four isomers of linalool oxides by GC analyses is also discussed.
Calibration↗
Mapping quantitative trait loci for circadian behavioral rhythms in SMXA recombinant inbred strains.
SM/J and A/J inbred strain of mice have different characteristics in circadian behaviors such as free-running period (tau), phase relationship (psi) between light-dark cycles and activity rhythms, and amount of wheel-running activity. To determine the genes which affect these behaviors, a quantitative trait locus (QTL) analysis using SMXA recombinant inbred strains derived from SM/J and A/J mice was performed. Concerning tau, two regions on chromosomes (Chrs) 7 and 18 surpassed the genome-wide suggestive level. As for psi, one suggestive QTL was detected on Chr 7. The QTLs which affect daily activity counts under light-dark cycles and constant darkness were mapped to the same chromosomal regions on Chrs 1 and 17, respectively. The provisional QTLs detected in the present study might be useful for understanding the complex mechanism regulating circadian behaviors.
Animals↗
Alteration in the responsiveness to tumour necrosis factor-alpha is crucial for maximal expression of monocyte chemoattractant protein-1 in human neutrophils.
We previously reported delayed expression of monocyte chemoattractant protein-1 (MCP-1) in human neutrophils cultured with a cytokine-rich crude supernatant of phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PHA-sup). Tumour necrosis factor-alpha (TNF-alpha) contained in the PHA-sup played a key role in this event, but there appeared to be another factor(s) in the same supernatant that co-operated with TNF-alpha for maximal MCP-1 expression. In the present study, we reduced TNF-alpha concentrations in the PHA-sup to minimal levels using anti-TNF-alpha affinity columns (TNF-depleted-sup) and investigated the co-operation between TNF-alpha and TNF-depleted-sup. Nine hours of preincubation with TNF-depleted-sup altered the responsiveness of neutrophils to TNF-alpha and enabled TNF-alpha to increase the level of MCP-1 expression to a maximal level within 4 hr. The priming effect was not due to the increased expression of cell-surface TNF receptors. However, the activation of primed cells by TNF-alpha was clearly through TNF receptor-p55. Finally, the activity in the TNF-depleted-sup that co-operated with TNF-alpha was eluted at 60 000 MW on high-performance liquid chromatography-gel filtration. Thus, delayed neutrophil expression of MCP-1 is regulated by a cytokine-dependent mechanism that induces neutrophils to enter a 'mature' stage.
Antigens, CD↗
Modulation of activity and substrate specificity by modifying the backbone length of the distant interdomain loop of D-amino acid aminotransferase.
The activity and substrate specificity of D-amino acid aminotransferase (D-AAT) (EC 2.6.1.21) can be rationally modulated by replacing the loop core (P119-R120-P121) with glycine chains of different lengths: 1, 3, or 5 glycines. The mutant enzymes were much more active than the wild-type enzyme in the overall reactions between various amino acids and pyruvate. The presteady-state kinetic analyses of half-reactions revealed that the 5-glycine mutant has the highest affinity (Kd) among all mutant enzymes and the wild-type enzyme towards various amino acids except D-aspartate. The 5-glycine mutant was much more efficient as a catalyst than the wild-type enzyme because the mutant enzyme showed the highest value of specificity constant (kmax/Kd) for all amino acids except D-aspartate and D-glutamate. The kmax/Kd values of the three mutants decreased with decrease in glycine chain length for each amino acid examined. Our findings may provide a new approach to rational modulation of enzymes.
Alanine Transaminase↗
3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase deficiency in a 23-year-old woman.
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3-Hydroxysteroid Dehydrogenases↗
Evaluation of the clinical relevance of the iceA1 gene in patients with Helicobacter pylori infection in Japan.
BACKGROUND: A novel Helicobacter pylori gene, iceA, has two allelic variants, and the iceA1 strain is associated with peptic ulcer disease. The aims of this study were to evaluate whether the possession of iceA1 gene is associated with gastric cancer or the severity of gastritis. METHODS: Ninety-seven subjects (46 patients with early gastric cancer and 51 control subjects) infected with H. pylori were studied. DNA was extracted from isolated H. pylori strains, and the presence of the iceA1 gene was examined by polymerase chain reaction. The features of gastritis were graded in accordance with the updated Sydney System, using gastric biopsy specimens. RESULTS: iceA1 was found in 61% of patients with gastric cancer and 53% of control subjects (NS). The grade of gastritis in iceA1-positive and -negative gastric mucosa was compared. Higher polymorphonuclear cell infiltration was observed in iceA1-positive subjects (P < 0.05). However, no significant difference was observed in the grades of mononuclear cell infiltration, glandular atrophy, and H. pylori density. CONCLUSIONS: Our results suggest that the iceA1 gene is not associated with the development of gastric cancer in Japan, whereas the iceA1-positive strain may induce more enhanced active gastric inflammation in cagA-positive and vacA s1/m1 strains.
Alleles↗
Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy.
Nitric oxide (NO) represents a new paradigm for second messengers in regulation. Despite the numerous physiological and pathophysiological functions of NO, its importance as an endogenous second messenger and a cytostatic and/or cytotoxic agent was unknown until 1987. Recent developments in detection methods for endogenous NO produced directly or indirectly from NO synthases (NOSs) have enabled major advances in our understanding of the role of NO in biological systems. The spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy is a method for analyzing NO production directly both in vivo and in vitro. Iron complexes with dithiocarbamate derivatives are noteworthy among the spin-trapping reagents for NO because NO has a high affinity for iron complexes. The resultant stable nitrosyl iron complexes exhibit an intense three-line signal at room temperature and an axial signal at low temperature. Besides the facility and wide applicability of this method, its outstanding feature is that noninvasive in vivo measurements are available by using a low-frequency EPR spectrometer. In this article, we review on previous and recent developments of in vitro, in vivo, and ex vivo EPR detection and imaging of endogenously produced NO.
Animals↗
Prospective study on the relation of cigarette smoking with cancer of the liver and stomach in an endemic region.
BACKGROUND: Smoking has not been confirmed as a risk factor for cancers of the liver and stomach. The authors examined prospectively the relationship between smoking and these cancers in an endemic region. METHODS: The data used were a cohort study on the relationship between lifestyle and health in the region having the highest liver cancer mortality in Japan. Of the cohort members, 4050 males aged > or =40 years were included in the present analysis with a 9-year mean follow-up. Cox proportional hazards regression was used to estimate relative risks (RR) for cancer of the liver, stomach, smoking-related sites and others, while adjusting for age, residence, and alcohol intake. RESULTS: By the end of the study period, 59 cases of liver cancer and 53 cases of stomach cancer were identified. Current smokers, compared to subjects who had never smoked, had a threefold risk of liver cancer (RR = 3.3; 95% CI: 1.2-9.5) and a twofold risk of stomach cancer (RR = 2.2; 95% CI: 0.8-5.7). Sub-cohort analysis showed that adjustment for history of chronic liver disease did not attenuate the risk of liver cancer. Light/medium smokers had almost the same risk of these cancers as heavy smokers, while they showed a relatively low risk of smoke-related cancers. CONCLUSIONS: The present results indicate that smoking is a risk factor of liver and stomach cancer in a population with a high background risk for these cancers. However, causal inferences should be made cautiously due to a lack of information on known risk factors.
Adult↗
Kinetic and mutational studies of three NifS homologs from Escherichia coli: mechanistic difference between L-cysteine desulfurase and L-selenocysteine lyase reactions.
We have purified three NifS homologs from Escherichia coli, CSD, CsdB, and IscS, that appear to be involved in iron-sulfur cluster formation and/or the biosynthesis of selenophosphate. All three homologs catalyze the elimination of Se and S from L-selenocysteine and L-cysteine, respectively, to form L-alanine. These pyridoxal 5'-phosphate enzymes were inactivated by abortive transamination, yielding pyruvate and a pyridoxamine 5'-phosphate form of the enzyme. The enzymes showed non-Michaelis-Menten behavior for L-selenocysteine and L-cysteine. When pyruvate was added, they showed Michaelis-Menten behavior for L-selenocysteine but not for L-cysteine. Pyruvate significantly enhanced the activity of CSD toward L-selenocysteine. Surprisingly, the enzyme activity toward L-cysteine was not increased as much by pyruvate, suggesting the presence of different rate-limiting steps or reaction mechanisms for L-cysteine desulfurization and the degradation of L-selenocysteine. We substituted Ala for each of Cys358 in CSD, Cys364 in CsdB, and Cys328 in IscS, residues that correspond to the catalytically essential Cys325 of Azotobacter vinelandii NifS. The enzyme activity toward L-cysteine was almost completely abolished by the mutations, whereas the activity toward L-selenocysteine was much less affected. This indicates that the reaction mechanism of L-cysteine desulfurization is different from that of L-selenocysteine decomposition, and that the conserved cysteine residues play a critical role only in L-cysteine desulfurization.
Bacterial Proteins↗
Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli.
4-Amino-4-deoxychorismate lyase (ADCL) is a member of the fold-type IV of PLP dependent enzymes that converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. The crystal structure of ADCL from Escherichia coli has been solved using MIR phases in combination with density modification. The structure has been refined to an R-factor of 20.6% at 2.2 A resolution. The enzyme is a homo dimer with a crystallographic twofold axis, and the polypeptide chain is folded into small and large domains with an interdomain loop. The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. Although the main chain folding of the active site is homologous to those of D-amino acid and L-branched-chain amino acid aminotransferases, no residues in the active site are conserved among them except for Arg59, Lys159, and Glu193, which directly interact with the coenzyme and play critical roles in the catalytic functions. ADC was modeled into the active site of the unliganded enzyme on the basis of the X-ray structures of the unliganded and liganded forms in the D-amino acid and L-branched-chain amino acid aminotransferases. According to this model, the carboxylates of ADC are recognized by Asn256, Arg107, and Lys97, and the cyclohexadiene moiety makes van der Waals contact with the side chain of Leu258. ADC forms a Schiff base with PLP to release the catalytic residue Lys159, which forms a hydrogen bond with Thr38. The neutral amino group of Lys159 eliminates the a-proton of ADC to give a quinonoid intermediate to release a pyruvate in accord with the proton transfer from Thr38 to the olefin moiety of ADC.
Amino Acid Sequence↗
Stereochemistry of the transamination reaction catalyzed by aminodeoxychorismate lyase from Escherichia coli: close relationship between fold type and stereochemistry.
Aminodeoxychorismate lyase is a pyridoxal 5'-phosphate-dependent enzyme that converts 4-aminodeoxychorismate to pyruvate and p-aminobenzoate, a precursor of folic acid in bacteria. The enzyme exhibits significant sequence similarity to two aminotransferases, D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase. In the present study, we have found that aminodeoxychorismate lyase catalyzes the transamination between D-alanine and pyridoxal phosphate to produce pyruvate and pyridoxamine phosphate. L-Alanine and other D- and L-amino acids tested were inert as substrates of transamination. The pro-R hydrogen of C4' of pyridoxamine phosphate was stereospecifically abstracted during the reverse half transamination from pyridoxamine phosphate to pyruvate. Aminodeoxychorismate lyase is identical to D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase in the stereospecificity of the hydrogen abstraction, and differs from all other pyridoxal enzymes that catalyze pro-S hydrogen transfer. Aminodeoxychorismate lyase is the first example of a lyase that catalyzes pro-R-specific hydrogen abstraction. The result is consistent with recent X-ray crystallographic findings showing that the topological relationships between the cofactor and the catalytic residue for hydrogen abstraction are conserved among aminodeoxychorismate lyase, D-amino acid aminotransferase and branched-chain L-amino acid aminotransferase [Nakai, T., Mizutani, H., Miyahara, I., Hirotsu, K., Takeda, S., Jhee, K.-H., Yoshimura, T., and Esaki, N. (2000) J. Biochem. 128, 29-38].
Alanine↗
Gastric mucosal inflammation and epithelial cell turnover are associated with gastric cancer in patients with Helicobacter pylori infection.
BACKGROUND: Infection with a virulent Helicobacter pylori strain is associated with gastric mucosal damage and the increased risk of gastric cancer. AIMS: To examine the characteristics of host gastric mucosal responses in patients with gastric cancer, histological grade of gastritis, gastric epithelial apoptosis, and proliferation were studied. METHODS: Thirty two patients with early gastric cancer and 32 sex and age matched controls were studied. All subjects were infected with a virulent H pylori strain (vacA s1/m1, cagA positive genotype). Biopsy specimens were taken from the antrum and the corpus of the stomach. The grade of gastritis was assessed according to the updated Sydney system. Apoptotic cells were detected using terminal uridine deoxynucleotidyl nick end labelling, and epithelial cell proliferation was determined by means of the Ki-67 labelling index. RESULTS: In patients with gastric cancer, significantly higher grades were observed when glandular atrophy (p < 0.05) and intestinal metaplasia (p < 0.01) were present in the antrum, and when mononuclear cell infiltration was present in the corpus (p < 0.05). The numbers of apoptotic cells were increased in patients with cancer (p < 0.05) and the apoptotic index correlated significantly with the grade of glandular atrophy. Epithelial cell proliferation was more likely to be increased in mucosa where intestinal metaplasia was present. CONCLUSIONS: Infection with H pylori causes increased gastric epithelial apoptosis, resulting in more severe glandular atrophy in patients with gastric cancer. Increased damage of gastric epithelial DNA and the presence of more severe atrophic gastritis might contribute to the development of gastric cancer.
Adult↗
Nitric oxide affects angiotensin II pressor response: possible mechanism of attenuated pressor response during pregnancy and etiology of pregnancy-induced hypertension.
OBJECTIVE: To investigate the mechanism of attenuated pressor responses to several vasoconstrictors during gestation, we sought to characterize the effects of N(G)-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats. METHODS: L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The L-NMMA group received an infusion of L-NMMA (3 mg/day) daily for 13 days, whereas the L-NMMA plus L-Arg group received L-NMMA (3 mg/day) daily for 4 days, followed by L-NMMA plus L-Arg (12 mg/day) daily for 9 days. Sham-operated rats served as controls. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from anesthesia, the pressor response to intravenous bolus doses of angiotensin II (50, 100, 200, and 400 ng/kg) were determined after recovery from anesthesia. RESULTS: While the baseline mean arterial blood pressure was not affected by L-NMMA, with or without L-Arg, the pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group, at doses of 50, 100, and 200 ng/kg. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group. CONCLUSION: Results indicate that the infusion of a nitric oxide synthase inhibitor, at a dose insufficient to produce hypertension, increases the pressor response to angiotensin II.
Angiotensin II↗
Primary vaginal stone in an 11-year-old recumbent girl.
Primary vaginal stones are extremely rare, particularly in young women. We describe the occurrence of a primary vaginal calculus in a severely retarded 11-year-old girl who was not diagnosed until she was examined using computerized tomography. We postulate that the calculus was formed as a consequence of urinary contamination of the vagina in association with incontinence and prolonged maintenance in a recumbent posture.
Calculi↗
Nitric oxide enhances expression and shedding of tumor necrosis factor receptor I (p55) in endothelial cells.
The biological actions of tumor necrosis factor-alpha (TNF-alpha) are mediated by 2 distinct receptors, TNF-RI (p55) and TNF-RII (p75). The extracellular domains of both receptors are shed in soluble form (sTNF-RI and sTNF-RII). The soluble receptors are involved in regulating TNF-alpha activities and may have therapeutic potential as TNF-neutralizing agents. However, it remains unclear as to what kind of physiological molecule can regulate TNF receptors. Nitric oxide (NO) mediates a variety of biological and pathophysiological functions. We hypothesized that NO may modulate the expression and shedding of TNF-RI. An NO donor, diethylamine/NO complex (NOC 5), increased sTNF-RI in the supernatants of ECV304, a human umbilical vein cell line, in a dose-dependent manner. TNF-RI mRNA in these cells was upregulated by NOC 5. 8-Br-cGMP and peroxynitrate had no effect on sTNF-RI release. Genistein and herbimycin A, inhibitors of tyrosine kinase, inhibited sTNF-RI release. Herbimycin A inhibited the levels of TNF-RI mRNA enhanced by NOC 5, which downregulated the surface expression of TNF-RI, indicating that NO is also involved in the shedding process of TNF-RI. The shedding of TNF-RI was abolished by a synthetic inhibitor of matrix metalloproteinase, KB-R8301. In conclusion, NO enhanced the release of sTNF-RI from endothelial cells by a cGMP-independent mechanism. Dual pathways suggested for NO-induced sTNF-RI release include (1) enhanced expression of TNF-RI, at least partially, by a tyrosine kinase-dependent mechanism and (2) increased shedding of TNF-RI by a type of metalloproteinase.
8-Bromo Cyclic Adenosine Monophosphate↗
Molecular analysis of the inhibition of monocyte chemoattractant protein-1 gene expression by estrogens and xenoestrogens in MCF-7 cells.
Xenoestrogens (XEs) are a diverse group of chemicals that mimic estrogenic actions and may have adverse effects on human health. The influence of these compounds on cytokine production or immune system function remains unclear. In this study we have examined the effects of 17beta-estradiol (E2) and XEs on chemoattractant cytokine (chemokine) production and analyzed the molecular mechanism. Monocyte chemoattractant protein-1 (MCP-1), also termed monocyte chemotactic and activating factor, is a member of the chemokine family and attracts mainly blood monocytes. Human mammary tumor cell line MCF-7 cells produce a large quantity of MCP-1 in response to interleukin-1alpha (IL-1alpha). Addition of E2 to MCF-7 cells inhibited MCP-1 production in a dose-dependent manner. XEs, bisphenol A, and NP also inhibited MCP-1 production, although the potency was 3-4 orders of magnitude lower than that of E2. E2, bisphenol A, and NP inhibited MCP-1 messenger RNA expression in MCF-7 cells. Two closely located nuclear factor-kappaB sites, A1 and A2, have been identified in the promoter of the human MCP-1 gene. A luciferase construct containing this enhancer region (pGLM-ENH) was activated by IL-1alpha, and a mutation at either the A1 or A2 site resulted in a loss of IL-1alpha responsiveness. Treatment with E2 or XEs decreased the IL-1alpha-inducible pGLM-ENH luciferase activity significantly. In an electrophoretic mobility shift assay and supershift analysis, we found that treatment with E2 or XEs diminished the IL-1alpha-induced complex formation with both A1 and A2 probes, which was identified immunochemically to consist of nuclear factor-kappaB, p50, and p65. The IL-1alpha-induced p50/c-Rel complex to the A2 probe was also, to a lesser extent, decreased by E2 or XE treatment. The effects of E2 and XEs on the expression of MCP-1 seem to be much more dramatic than the effects of these agents on the promoters used in the luciferase assay, suggesting the involvement of an additional site(s) of the promoter region of the MCP-1 gene or posttranscriptional regulation of MCP-1 gene expression by E2 and XEs. This work represents the first report describing possible regulation of immune system function by XEs through inhibiting chemokine production.
Blotting, Northern↗