Acute attacks and brain stem signs in a patient with glutamic acid decarboxylase autoantibodies.
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Acute Disease↗
Biomedical subjects
M Nakajima
Publications and source records attributed to M Nakajima.
Bonding of self-etch and total-etch adhesives to carious dentin.
Carious dentin is partially demineralized and contains mineral crystals in the tubules. This may permit the deeper etching of intertubular dentin but prevent resin tag formation during bonding. We hypothesize that resin adhesives will produce lower bond strengths to caries-infected and caries-affected dentin compared with normal dentin. We tested this by measuring the microtensile bond strength of a total-etch adhesive and an experimental self-etching adhesive (ABF) to caries-infected, caries-affected, and sound dentin and by correlating those results with ultrastructural observations. The bond strengths of both adhesives to sound dentin were significantly (p < 0.05) higher than those to caries-affected dentin, which, in turn were significantly (p < 0.05) higher than those to caries-infected dentin. For both adhesives, hybrid layers in caries-affected dentin were thicker but more porous than those in sound dentin. The lower bond strengths may be due to the lower tensile strength of caries-affected dentin. Clinically, this may not be a problem, since such lesions are normally surrounded by normal dentin or enamel.
Acid Etching, Dental↗
[A study of isolated tricuspid valve surgery late after left heart valve operation].
Management of severe tricuspid regurgitation late after left heart valve operation is controversial. There has been reluctance to the operation due to the high risk of repeat operation, coexistent right ventricular dysfunction and pulmonary hypertension. We investigated 6 cases of isolated tricuspid valve surgery (tricuspid valve replacement: 2, tricuspid valve plasty: 4) late after left heart valve operation. Before operation, these patients showed poor general condition (4 cases were NYHA III or IV) but good left ventricular function [mean ejection fraction (EF) 66 +/- 9.6%]. Hospital mortality was 0% and the mean mid-term actual event-free survival over 2 +/- 1.8 years was 80%. Most of patients demonstrated NYHA I and improvement of hepatomegaly after operation. There were many complications in 2 cases that had been performed previous operation more than 20 years before. In summary, the patient who complained symptoms due to right heart ventricular failure and showed good left ventricular function after left heart valve surgery should be considered to undergo tricuspid valve operation before the occurrence of other complications.
Aged↗
Cytotoxicity and apoptosis produced by troglitazone in human hepatoma cells.
Troglitazone is an antidiabetic agent that increases the insulin sensitivity of target tissues in non-insulin-dependent diabetes mellitus. It has been reported that troglitazone causes severe hepatic injury in certain individuals. In the present study, the mechanism for the hepatic injury by troglitazone was investigated with human hepatoma cell lines. HepG2 cells were incubated with troglitazone, its metabolites M-1 (sulfate), M-2 (gulucronide), M-3 (quinone), and other thiazolidinediones (pioglitazone and rosiglitazone). Troglitazone exhibited time- and concentration-dependent cytotoxicity and M-3 also exhibited weak cytotoxicity. Troglitazone induced apoptotic cell death characterized by internucleosomal DNA fragmentation and nuclear condensation. As other thiazolidinediones, pioglitazone and rosiglitazone, did not induce cell death and apoptosis in the present study, the affinity to PPARgamma may not affect the induction of apoptosis by troglitazone. These results suggest that troglitazone induces apoptotic hepatocyte death which it may be one of the factors of liver injury in humans.
Apoptosis↗
A stereoselective synthesis of the C10-C31 (BCDEF ring) portion of pinnatoxin A.
[reaction: see text] An efficient synthesis of the C10-C31 (BCDEF ring) portion of pinnatoxin A has been achieved. The key step is a highly stereoselective construction of the dispiroketal (BCD ring) system employing an intramolecular hetero-Michael reaction of a reversibly formed hemiketal alkoxide through the use of LiOMe.
Alkaloids↗
Antisense-mediated suppression of human heparanase gene expression inhibits pleural dissemination of human cancer cells.
Heparan sulfate proteoglycans is a major component of the cell surface and extracellular matrix and functions as a barrier against cationic molecules and macromolecules. Heparanase is an endoglucuronidase capable of specifically degrading heparan sulfate, and its activity is associated with the metastatic potential of tumor cells. To inhibit human heparanase expression in human cancer cells, we constructed an adenoviral vector carrying a full-length human heparanase cDNA in an antisense orientation (Ad-AS/hep). Increased heparanase expression in T.Tn human esophageal cancer cells and A549 human lung cancer cells after infection with an adenovirus vector expressing the human heparanase gene (Ad-S/hep) was specifically inhibited by simultaneous infection with Ad-AS/hep in a dose-dependent manner. A modified Boyden chamber assay demonstrated that infection with Ad-AS/hep significantly inhibited in vitro invasion of A549 cells after Ad-S/hep infection. Moreover, intrathoracic administration of Ad-AS/hep reduced the number and size of heparanase-expressing A549 tumors implanted intrathoracically into BALB/c-nu/nu mice. Our results suggest that heparanase contributes to the invasive phenotype of tumor cells, and that antisense-mediated inhibition of heparanase activity may be efficacious in the prevention of pleural dissemination.
Adenoviridae↗
Mechanism of bovine serum albumin aggregation during ultrafiltration.
Protein fouling is a critical problem for ultrafiltration. In this study, we adopted bovine serum albumin (BSA) as a model protein and polysulfone membrane as a typical ultrafiltration membrane. We then investigated the factors of the protein denaturation and aggregation, such as stirring shear stress and intermolecular exchange of disulfide during ultrafiltration, and discussed the BSA fouling mechanism. Fourier transform-infrared analysis revealed that magnetic stirring did not cause any difference in the secondary structural change of BSA gel-like deposits on the ultrafiltration membrane. BSA aggregates were collected from BSA gel-like deposits on the ultrafiltration membrane by centrifugation. Polyacrylamide gel electrophoresis in SDS analysis of BSA aggregates proved that the major binding of the BSA aggregates involved intermolecular disulfhydryl binding and that capping the free thiol group in BSA molecules with cysteine induced a remarkable decrease in the amount of the BSA aggregates during ultrafiltration. We concluded that one of the main factors in the BSA aggregation during ultrafiltration is the intermolecular exchange of disulfide through cysteinyl residue. We also found that the BSA aggregation caused a decrease in alpha-helix from 66% to 50% and an increase in beta-sheet from 20% to 36%, which was presumably because the cysteine residues associated with the intermolecular disulfide bonds had been located in alpha-helices.
Animals↗
Metabolic activation of carcinogenic 1-nitropyrene by human cytochrome P450 1B1 in Salmonella typhimurium strain expressing an O-acetyltransferase in SOS/umu assay.
Metabolic activation of 1-nitropyrene (1-NP) by human cytochrome P450 (P450) family 1 enzymes co-expressed with NADPH-cytochrome P450 reductase (NPR) in Escherichia coli membranes was investigated. 1-NP induced umu gene expression in Salmonella typhimurium TA1535/pSK1002 in the absence of any P450 system, but the activities were influenced by the levels of bacterial O-acetyltransferase (OAT) and nitroreductase. Metabolic activation of 1-NP by human P450 1B1/NPR membranes was observed and was influenced by the levels of OAT levels in tester strains. Metabolic activation of 1-NP (0.3microM) by P450 1B1 was 750 umu units/min/nmol P450 1B1 in an OAT-overexpressing strain NM2009. The metabolic activation of 1-NP (3-30microM) was similar (approximately 300 umu units/min/nmol P450 1B1) using TA1535/pSK1002 or OAT-deficient strain NM2000. P450 1B1 had the highest catalytic activities among P450 family 1 enzymes for the activation of 1-aminopyrene (1-AP) in the OAT-overexpressing strain NM2009, suggesting nitrenium ion formation via N-hydroxylation/O-acetylation. High-performance liquid chromatography (HPLC) analyses revealed the formation of 1-nitropyrene-6-ol and also 1-nitropyrene-3-ol, 1-nitropyrene-8-ol, and trans-4,5-dihydroxy-4,5-diol-1-nitropyrene from 1-NP (10microM), catalyzed by P450 1B1. These results indicate that 1-NP can be activated by human P450 1B1 to a genotoxic agent by nitroreduction/O-acetylation at low substrate concentrations and probably by epoxidation (independent of OAT) at high concentrations.
Acetyltransferases↗
Expression of three extracellular matrix degradative enzymes in bladder cancer.
The relationship between expression of extracellular matrix degradative enzymes, angiogenesis and survival of multistage bladder cancer was determined. Expression of 3 extracellular matrix degradative enzymes (metalloproteinase-2, -9 and heparanase) and microvessel formation were examined in 40 resected bladder cancer specimens by immunohistostochemic staining, and then the association of the enzyme expression with angiogenesis and various stages of cancer was investigated. Heparanase protein expression in muscular invasive or lymph-node metastatic cancer was significantly higher than in superficial or nonmetastatic cancer, respectively (69% vs. 8%, p < 0.001, and 80% vs. 40%, p = 0.028, respectively). Interestingly, heparanase was expressed at much higher levels than matrix metalloproteinase-2 and -9. The mean microvessel count in cancers with heparanase expression was significantly higher than that in cancers without heparanase expression (32.3 +/- 18.2 vs. 5.5 +/- 6.1, p = 0.0008). The microvessel formation was not associated with the expression of matrix metalloproteinase-2 and -9. The cancer-specific and overall survival rates of patients with heparanase expression were significantly lower than those of patients without it (p = 0.0001 and p = 0.0008, respectively). Multivariate analysis showed that heparanase expression was a significantly independent prognostic factor for both cancer-specific (p = 0.0047) and overall survival (p = 0.0200). Our study suggested that heparanase plays important roles in invasion, angiogenesis and metastasis of bladder cancer, and thus, this molecule could be a new molecule to inhibit invasion, angiogenesis and metastasis of bladder cancer. Moreover, our results indicate that expression of heparanase could be a new prognostic factor of this disease.
Adult↗
Catalytic asymmetric synthesis of 1,1'-spirobi[indan-3,3'-dione] via a double intramolecular C-H insertion process.
A highly efficient one-pot construction of optically active 1,1'-spirobi[indan-3,3'-dione] derivative (up to 80% ee) has been achieved by exploiting the double intramolecular C-H insertion reaction of dimethyl 2,2'-methylenebis(alpha-diazo-beta-oxobenzenepropanoate) under the influence of dirhodium(II) tetrakis[N-phthaloyl-(R or S)-tert-leucinate] as a catalyst.
Journal Article↗
Enantioselective Michael addition of beta-keto esters to methyl vinyl ketone employing a chiral N,N'-dioxide-scandium trifluoromethanesulfonate complex as a catalyst.
An enantioselective Michael addition of beta-keto esters to methyl vinyl ketone exploiting a chiral N,N'-dioxide-scandium trifluoromethanesulfonate complex as a catalyst affords the corresponding Michael adducts in high yields and with enantioselectivities of up to 80% ee.
Journal Article↗
cDNA cloning, characterization and vaccine effect analysis of Haemaphysalis longicornis tick saliva proteins.
Immunological control of ticks is currently the only sustainable and practical alternative method to the current use of acaricides which has serious limitations. The success of this method is dependent upon identification and cloning of potential tick vaccine antigens. We used a combination of immuno-screening of an adult tick cDNA library as well as the 3 and 5 rapid amplification of cDNA ends to clone two cDNAs, encoding tick saliva proteins from Haemaphysalis longicornis. The two cDNAs herein named HL 34 and 35 are 1000 bp each and encode polypeptides with 292 and 321 amino acid residues respectively. Northern blotting analysis of total RNA from ticks at different feeding stages revealed that expression of both HL 34 and HL35 mRNAs is induced during the slow feeding phase. We speculate that the functions of both genes are closely associated with blood feeding. Expression analysis by RT-PCR showed that both genes are expressed in other tick organs in addition to salivary glands. Recombinant HL 34 was successfully expressed in Escherichia coli and its suitability as a tick vaccine antigen was analyzed in rabbits. We propose that rHL34 could be a useful component of a cocktail tick vaccine.
Amino Acid Sequence↗
Inhibition of serine proteases: activity of 1,3-diazetidine-2,4-diones.
The present work demonstrates that the 1,3-diazetidine-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and alpha-chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase.
Azetidines↗
Total synthesis of human chymase inhibitor methyllinderone and structure--activity relationships of its derivatives.
Total synthesis of human chymase inhibitor methyllinderone has been achieved in only four steps with an overall yield of 21% from dimethyl squarate. We developed an efficient synthetic method for obtaining methyllinderone derivatives and found the active compound. In addition, we propose the inhibition mechanism of the active compound against human chymase using calculations.
Alkenes↗
Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat.
1. The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated. 2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N (G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOS) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect. 3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation. 4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 micromol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations. 5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations. 6. Intracerebroventricular (I.C.V.) administration of NPY (0.03--3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] NPY (0.03--3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner. 7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 microl) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation. 8. Taken together, these findings suggest that gastric distension-induced pyloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.
Acute Disease↗
p21Cip-1/SDI-1/WAF-1 gene is involved in chondrogenic differentiation of ATDC5 cells in vitro.
Development of skeletal cartilage is characterized with coupling growth arrest and cell differentiation. Here, to understand the cyclin-dependent kinase inhibitors involved in the progression of chondrogenic differentiation, we examined changes in the expression levels of cyclin-dependent kinase inhibitor members using mouse ATDC5 prechondrocytes as a widely used in vitro model of cartilage differentiation. Up-regulation of p21 and p27 mRNA was observed following a decrease in growth rate of prechondrocytes, and both transcripts subsequently accumulated during chondrogenic differentiation; p15, p18, and p19 mRNA, in contrast, did not change during differentiation. Only the up-regulation of p21 mRNA during differentiation was prevented by the continuous treatment of early chondrogenic inhibitor, parathyroid hormone, indicating a close correlation between differentiation and p21 induction in ATDC5 cells. Therefore, to examine the role of p21 during chondrogenesis, we established stable cell lines overexpressing full-length p21 antisense RNA in ATDC5. The reduction of endogenous p21 in these cell lines caused inhibition of early chondrogenic differentiation in ATDC5, indicating that p21 gene plays an important role in this process of the cells in vitro. Furthermore, the level of p21 protein and p21.CDK2 complexes transiently increased during differentiation, but not in undifferentiated cells, leading to a decrease in CDK2-associated kinase. However, differentiation-dependent expressed p21 protein was degraded by a proteasome-dependent pathway. Thus, the progression of chondrogenic differentiation requires down-regulation of CDK2-associated kinase with an increase in p21 protein and subsequent degradation of this protein by a proteasomal pathway.
Animals↗
Expression of p53 protein related to smoking and alcoholic beverage drinking habits in patients with esophageal cancers.
In esophageal squamous cell carcinoma (SCC), we used immunohistochemical analysis to further elucidate the correlation of p53 protein expression with clinicopathological factors, as well as with risk factors, such as tobacco smoking, alcohol consumption and a family history of cancer, using odds ratios (ORs). The expression of p53 protein was demonstrated in 55.1% of 89 esophageal SCC cases examined by immunohistochemistry. The expression of p53 protein did not correlate with gender, age, histological grading, lymph node metastasis, or TNM stage. The prevalence of p53 expression was significantly higher in patients with multiple primary esophageal cancers (P<0.05). p53 expression did not correlate with prognosis in univariate survival analysis. The esophageal SCC in either smokers or alcohol users was 4.67-5.83 times more likely to express p53 protein, while the likelihood of p53 expression in patients who use both tobacco and alcohol was more than 14.0 times. However, a significant association was not found between p53 expression and a family history of cancer, this having an OR as low as 1.85. The expression of p53 protein did not correlate with clinicopathological factors and prognosis in univariate and multivariate survival analyses. In contrast, tobacco smoking and alcohol consumption were shown to be strongly associated with p53 mutations in esophageal carcinogenesis.
Adult↗
The effect of calcitonin gene-related peptide on pancreatic blood flow and secretion in conscious dogs.
The effects of human alpha-calcitonin gene-related peptide (alpha-CGRP) and beta-CGRP on pancreatic arterial (PA), superior mesenteric (SMA) and left gastric arterial (LGA) blood flows were studied by ultrasound transit-time blood flow meters in five conscious dogs. Intravenous injections of alpha-CGRP and beta-CGRP (5-200 pmol/kg) induced a dose-related increase in PA flow and a dose-related decrease in its resistance. At lower doses, alpha-CGRP was more potent than beta-CGRP, but their maximal responses were similar. The blood flow responses to alpha-CGRP (200 pmol/kg) were 153% of the basal flow in LGA, 313% in PA, and 534% in SMA, while those to VIP (100 pmol/kg) were 467% in LGA, 953% in PA and 163% in SMA. Somatostatin reduced blood flow in all arteries. alpha-CGRP, but not beta-CGRP, at higher doses induced gastric contractions and pancreatic protein-rich secretion, which were blocked by atropine. These results suggest that CGRP in perivascular nerves in the pancreas may regulate pancreatic blood flow in dogs but its physiological function remains to be studied.
Animals↗