Biomedical subjects

S Hattori

Publications and source records attributed to S Hattori.

At least 37 records · Page 2Linked to original sources

PubMed2001

Signal transduction pathways through TRK-A and TRK-B receptors in human neuroblastoma cells.

Little is known about the signal transduction pathways of TRK family receptors in neuroblastoma (NB) cells. In this study, an NB cell line, designated MP-N-TS, was established from an adrenal tumor taken from a 2-year-old boy. This cell line expressed both TRK-A and TRK-B receptors, which is rare in a single NB cell line. Therefore, the MP-N-TS cell line was used to determine whether the signal transduction through these constitutive receptors is functional. Three neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-4 / 5 (NT-4 / 5), induced tyrosine phosphorylation of panTRK, and BDNF and NT-4 / 5 induced tyrosine phosphorylation of TRK-B. Tyrosine phosphorylation of panTRK and / or TRK-B by the neurotrophins was inhibited in the presence of a tyrosine kinase inhibitor K252a. Tyrosine phosphorylation of Src homologous and collagen (Shc), extracellular signal-regulated kinase (ERK)-1 and ERK-2, and phospholipase C-gamma1 (PLC-gamma1) was increased by the three neurotrophins and the increase was inhibited in the presence of K252a. Activation of Ras, detected as the GTP-bound form of Ras, was induced by the three neurotrophins. The neurotrophins did not modulate the expressions of TRK-A or TRK-B mRNA, but they did induce the expression of c-fos mRNA. Exogenous NGF induced weak neurite outgrowth, whereas exogenous BDNF and NT-4 / 5 induced distinct neurite outgrowth. Exogenous BDNF and NT-4 / 5 increased the number of viable cells, while NGF did not. Our results demonstrate that the signal transduction pathways through TRK-A and TRK-B in MP-N-TS cells are functional and similar, and the main downstream signaling pathways from the three neurotrophins are mitogen-activated protein kinase (MAPK) cascades through Shc, activated Ras, ERK-1 and ERK-2, and the transduction pathway through PLC-gamma1. Further, BDNF and NT-4 / 5 increased cell viability. The MP-N-TS cell line should be useful for clarifying the TRK-A and TRK-B signaling pathways responsible for the different prognoses in patients with NB.

Adrenal Gland Neoplasms↗

PubMed2001

The McGill Pain Questionnaire, Japanese version, reconsidered: confirming the theoretical structure.

BACKGROUND: Based on a tripartite theoretical model of pain, the Pain Rating Index (PRI) of the McGill Pain Questionnaire (MPQ) continues to be one of the most frequently used instruments to measure clinical pain. However, language and cultural barriers have hindered its wide use and standardization in Japan. Although a number of exploratory factor analysis studies have failed to support consistently the theoretical structure of the MPQ, a few previous confirmatory factor analysis studies did statistically support the a priori model. OBJECTIVE: To test, through confirmatory factor analysis (CFA), the theoretical structure of a Japanese version of the MPQ (JMPQ), which followed a format similar to that of the original MPQ. DESIGN: This study used CFA on prospectively collected data from 199 consecutive outpatients with chronic pain at a university hospital to test the theoretical structure of the JMPQ. RESULTS AND CONCLUSIONS: CFA was completed on the first 16 PRI subclass scores; this process yielded a well fitting final model that explained 92% of the covariance in the observed data. The results supported the hypothesis that the sensory, affective and evaluative subscales of the PRI are representative of the multidimensionality of the pain experience, with minimal overlap. It is suggested that the theoretical structure of the MPQ is maintained in the JMPQ used in this study. Therefore, this study is the first step toward standardization of the JMPQ, serving as a cultural bridge in the field of pain medicine between Japan and English-speaking nations such as Canada.

Adult↗

PubMed2001

4-hydroxynonenal prevents NO production in vascular smooth muscle cells by inhibiting nuclear factor-kappaB-dependent transcriptional activation of inducible NO synthase.

The role of lipid peroxidation products in atherogenesis was studied. We investigated whether 4-hydroxy-2-nonenal (HNE) modulates activation of the nuclear factor (NF)-kappaB system or alters expression of the NF-kappaB target gene product, inducible NO synthase (iNOS), in vascular smooth muscle cells (VSMCs) stimulated by lipopolysaccharide (LPS) in combination with interferon (IFN)-gamma (LPS/IFN). NO production induced by LPS/IFN was dose-dependently inhibited by HNE. NF-kappaB activation by LPS/IFN was inhibited by HNE in a dose-dependent manner. HNE significantly decreased LPS/IFN-stimulated proteolysis of IkappaB-alpha. iNOS promoter activity stimulated by LPS/IFN was also decreased by HNE dose-dependently. The treatment of VSMCs with LPS/IFN strongly stimulated iNOS mRNA and protein expression. The LPS/IFN-induced increases in iNOS mRNA and protein levels were dose-dependently decreased by HNE. Our data suggest that treatment with HNE blocks signaling events required for IkappaB-alpha degradation, thereby preventing NF-kappaB activation. Inhibition of NF-kappaB-regulated gene expression, especially modulation of NO production, may contribute to atherogenesis.

Aldehydes↗

PubMed2001

Type V collagen distribution in liver is reconstructed in coculture system of hepatocytes and stellate cells; the possible functions of type V collagen in liver under normal and pathological conditions.

The contents of type I, type III and type V collagen and the collagen type specific distributions in liver under normal and cirrhotic conditions were examined. In CCl4 injected rat, the increasing amount of type V collagen was a specific event during the progression of cirrhosis. In normal liver, immunohistochemical observation showed that type V collagen was localized on the fine fibrils, while type I was localized on the thick fibril. Type V collagen was partially colocalized with type IV collagen. In the cirrhotic liver, type V collagen was localized on the margin of the thick fibrous septa along with type IV collagen. Type I collagen existed in the core region of fibrous septa where the stellate cells were prominent. To elucidate the mechanism of the type specific deposition of collagen in the liver, we constructed a coculture system using both stellate cells and hepatocytes. In this system, type V collagen was mainly deposited on hepatocyte colonies not on stellate cells, while type I collagen fibrils were localized on stellate cells. The spatial positioning of type I and type V collagens in vitro was similar to that in the liver. In the cell adhesion assay, the adhesion of stellate cells to type V collagen was poorer than that of the hepatocytes. The collagen type-specific affinity of the stellate cells and hepatocytes may explain the specific localization of type V collagen in the liver and coculture system. These results suggested that the functions of type V collagen are not only to connect type IV collagen with type I collagen fibril, but also to protect the parenchyma from excess type I collagen deposition produced by stellate cells under pathological conditions.

Animals↗

PubMed2001

Involvement of formate as an interspecies electron carrier in a syntrophic acetate-oxidizing anaerobic microorganism in coculture with methanogens.

To determine whether formate is involved in interspecies electron transfer between substrate-oxidizing bacteria and hydrogenotrophic microorganisms under anaerobic conditions, a syntrophic acetate-oxidizing bacterium Thermacetogenium phaeum strain PB was cocultured either with a formate /H2-utilizing methanogen strain TM (designated as PB/TM coculture), or an H2-utilizing methanogen strain deltaH (designated as PB/deltaH coculture). Acetate oxidation and subsequent methanogenesis in PB/TM coculture were found to be significantly faster than in PB/deltaH coculture. Formate dehydrogenase and hydrogenase were both detected in strains PB and TM. H2 partial pressures in the PB/TM coculture were kept lower (20 to 40 Pa) than those of the PB/deltaH coculture (40 to 60 Pa) during the exponential growth phase. Formate was also detected in both PB/TM and PB/deltaH cocultures, and the concentration of formate was maintained at a lower level in the PB/TM coculture (5 to 9 microM) than in the PB/deltaH coculture. Thermodynamic calculations revealed that the concentrations of both H2 and formate severely affect the syntrophic oxidation of acetate. These results strongly indicate that not only H2 but also formate may be involved in interspecies electron transfer.

Journal Article↗

PubMed2001

Horizontal transmission of Toxoplasma gondii in squirrel monkeys (Saimiri sciureus).

The possibility of horizontal transmission of T. gondii was examined in squirrel monkeys. After three monkeys were inoculated perorally with 1.1-2.1 x 10(3) cysts of the T. gondii ME49, the animals were divided into two cages and maintained with one normal monkey for each cage as a cagemate. Two out of the three T. gondii-inoculated monkeys died, and the remaining one monkey was sacrificed in a moribund state one week after infection because of acute toxoplasmosis. Many T. gondii tachyzoites were recovered from broncho-alveolar lavages and were also found histopathologically in the lung, liver, spleen, kidney and lymph nodes and impression smears of tissues from the three T. gondii-inoculated monkeys by Giemsa staining. Anti-T. gondii antibody was examined by immunoblot assay in these animals, and the antibody to T. gondii major surface membrane protein (p30) could be detected after the start of experiment. Furthermore, a specific band of T. gondii NTPase gene was observed by PCR in the liver and lung of infected and cagemate monkeys, and the sequence of the second PCR products obtained from the cagemates, which were clinically normal but gave a positive result in immunoblotting assay, was exactly the same as the sequence of the NTPase gene of T. gondii ME49. These findings suggested that transmission of T. gondii from the infected monkeys to cagemates occurred easily, and since many T. gondii tachyzoites were recovered from the bronchoalveolar lavages of the three T. gondii-inoculated monkeys, we suggest that aerosol infection plays an important role for the enzootic toxoplasmosis in colonies of squirrel monkeys.

Aerosols↗

PubMed2001

Tripropeptins, novel antimicrobial agents produced by Lysobacter sp. I. Taxonomy, isolation and biological activities.

Peptide antibiotics tripropeptins A, B, C, D and Z were isolated from cultured cells and broth of Lysobacter sp. The differences among these components are in the lengths of the alkyl side chain. Tripropeptins are active against Gram-positive bacteria including MRSA in vitro. Bactericidal activity of tripropeptin C disappeared in the simultaneous presence of chloramphenicol, a bacteriostatic agent.

Anti-Bacterial Agents↗

PubMed2001

Analgesic effects of flecainide on postherpetic neuralgia.

Sodium channel blockers have been reported to be effective in relieving neuropathic pain. However, although intravenous lidocaine has proved to be effective, in some patients oral mexiletine fails to produce adequate pain relief. In this study, we investigated the analgesic effect of flecainide, a long-lasting antitachyarrhythmic drug, on postherpetic neuralgia. Twenty patients with postherpetic neuralgia received an intravenous infusion of flecainide and 15 (75%) of those who achieved pain relief subsequently received oral flecainide. The patients were assessed using a 100 mm visual analog scale 1 month after treatment. Significant improvement compared with the pretreatment reading was found. This study suggests that the action of flecainide in blocking the sodium channel is potent and long-lasting and that, like the intravenous formulation, the oral formulation has a stable analgesic effect on postherpetic neuralgia.

Aged↗

PubMed2001

[A study on contamination from Legionella spp. at a home for the elderly in Toyohashi City].

OBJECTIVE: Legionnaires disease has been attributed to Legionella spp. in the water distribution systems of buildings. However, recently cases due to contamination of thermal-bath water have been reported in Japan. In this investigation, we examined the supervision of baths and the presence of Legionella spp. in thermal-bath water of homes for the elderly in Toyohashi city. METHODS: The research was conducted through questionnaires on bathing facilities at 50 sites. Thermal baths were found to be installed at 14 of the sites. We then tested 22 samples from the 14 sites for Legionella spp. and other materials. RESULTS: From the genus Legionella, only Legionella pneumophila was detected, in 8 samples from 4 sites. Coliforms were also detected. Moreover, disinfectant was not detected in any of the Legionella positive samples of bath water. Legionella positive sites had, however, been replacing their water once a day. CONCLUSIONS: These findings indicate that the use of disinfectant and the proper supervision of bathing facilities are important in controlling Legionella spp. Legionnaires disease can be averted in homes for the elderly through appropriate measures.

Aged↗

PubMed2000

Possible involvement of aminotelopeptide in self-assembly and thermal stability of collagen I as revealed by its removal with proteases.

The functions of aminotelopeptide and N-terminal cross-linking of collagen I were examined. Acetic acid-soluble collagen I (ASC) was purified from neonatal bovine skin and treated with three kinds of proteases. The amino acid sequencing analysis of the N terminus showed that ASC contained a full-length aminotelopeptide. Pepsin and papain cleaved the aminotelopeptide of the alpha1 chain at the same site and the aminotelopeptide of the alpha2 chain at different sites. Proctase-treated ASC lost the whole aminotelopeptide, and the N-terminal sequence began from the tenth residue inside the triple helical region. The rates of fibril formation of pepsin-treated ASC and proctase-treated ASC were the same and were slower than that of ASC. The denaturation temperatures, monitored by CD ellipticity at 221 nm, of ASC, pepsin-treated, or papain-treated collagens were the same at 41.8 degrees C. Proctase-treated ASC showed a lower denaturation temperature of 39.9 degrees C. We also observed the morphology of the collagen fibrils under an electron microscope. The ASC fibrils were straight and thin, whereas the fibrils of pepsin-treated ASC were slightly twisted, and the fibrils from papain- and proctase-treated ASC were highly twisted and thick. When the collagen gel strength was examined by a modified method of viscosity-measurement, ASC was the strongest, followed by pepsin-treated ASC, and papain- and proctase-treated ASCs were the weakest. These results suggest that the aminotelopeptide plays important roles in fibril formation and thermal stability. In addition, the functions of intermolecular cross-linking in aminotelopeptides may contribute to the formation of fibrils in the correct staggered pattern and to strengthening the collagen gel.

Acetic Acid↗

PubMed2000

Regulatory proteins of R-Ras, TC21/R-Ras2, and M-Ras/R-Ras3.

We studied the regulation of three closely related members of Ras family G proteins, R-Ras, TC21 (also known as R-Ras2), and M-Ras (R-Ras3). Guanine nucleotide exchange of R-Ras and TC21 was promoted by RasGRF, C3G, CalDAG-GEFI, CalDAG-GEFII (RasGRP), and CalDAG-GEFIII both in 293T cells and in vitro. By contrast, guanine nucleotide exchange of M-Ras was promoted by the guanine nucleotide exchange factors (GEFs) for the classical Ras (Ha-, K-, and N-), including mSos, RasGRF, CalDAG-GEFII, and CalDAG-GEFIII. GTPase-activating proteins (GAPs) for Ras, Gap1(m), p120 GAP, and NF-1 stimulated all of the R-Ras, TC21, and M-Ras proteins, whereas R-Ras GAP stimulated R-Ras and TC21 but not M-Ras. We did not find any remarkable difference in the subcellular localization of R-Ras, TC21, or M-Ras when these were expressed with a green fluorescent protein tag in 293T cells and MDCK cells. In conclusion, TC21 and R-Ras were regulated by the same GEFs and GAPs, whereas M-Ras was regulated as the classical Ras.

Amino Acid Sequence↗

PubMed2000

Protein-tyrosine kinase Pyk2 is involved in interleukin-2 production by Jurkat T cells via its tyrosine 402.

We established Jurkat transfectants that overexpress Pyk2 or its mutants, K457A (lysine 457 was mutated to alanine), Pyk2-Y402F (tyrosine 402 to phenylalanine), and Pyk2-Y881F to investigate the role of Pyk2 in T cell activation. Pyk2 as well as kinase-inactive Pyk2-K457A, was phosphorylated at tyrosine residues 402, 580, and 881 upon T cell antigen receptor cross-linking, indicating that these residues are phosphorylated by other tyrosine kinase(s). However, no tyrosine phosphorylation of Pyk2-Y402F was detected while more than 60% of the tyrosine phosphorylation was observed in Pyk2-Y881F. Pyk2-Y402F inhibited the activation of endogenous Pyk2. The degree of activation of both c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase but not extracellular signal-regulated protein kinase after concurrent ligation of T cell antigen receptor and CD28 was reduced by more than 50% in the clones expressing Pyk2-Y402F. Consistent with this inhibition, IL-2 production was significantly diminished in the Pyk2-Y402F-expressing clones. Furthermore, we found that Pyk2, when overexpressed, associates with Zap70 and Vav. Taken together, these findings suggest that Pyk2 is involved in the activation of T cells through its tyrosine 402.

CD28 Antigens↗

PubMed2000

Role of the von Hippel-Lindau tumor suppressor protein during neuronal differentiation.

The von Hippel-Lindau (VHL) tumor suppressor protein down-regulates transcription by transcriptional elongation enhanced by antagonizing elongin B and C. Transcriptional regulation is an important control mechanism for embryogenesis and tumorigenesis. The VHL gene and protein are expressed in neuronal cells of the fetal and adult brain. However, the role of the VHL gene in the central nervous system (CNS) has not been elucidated. The VHL gene might modify the expression of various genes during embryogenesis and tumorigenesis in CNS. We investigated the role of the VHL gene in CNS development using rodent CNS progenitor cells. Here we show that expression of the VHL protein is correlated with neuronal differentiation but not with glial differentiation in CNS progenitor cells, and we also show that VHL gene transduction induces neuronal differentiation. In addition, a VHL mRNA antisense oligonucleotide inhibits differentiation of CNS progenitor cells and up-regulates their cell cycle. In conclusion, the VHL gene plays an essential role in neuronal differentiation as well as transcription.

Animals↗

PubMed2000

Therapeutic efficiency of IL-2 gene transduced tumor vaccine for head and neck carcinoma.

Transduction of the human interleukin-2 (IL-2) gene into tumor cells was carried out in order to develop a new immunotherapy for advanced head and neck carcinomas with a poor outcome. We transduced the IL-2 gene into KB cells, a head and neck squamous cell carcinoma cell line, using a defective herpes simplex viral (HSV) amplicon vector as a gene transfer vehicle. A high level of IL-2 was secreted by IL-2 gene-transduced KB cells (KB/IL-2). The IL-2 producibility of irradiated KB/IL-2 cells was almost the same as that of non-irradiated cells. In the tumor establishment model in nude mice, IL-2 and interferon-gamma (IFN-gamma) at high concentrations were detected in the sera of mice transplanted with KB/IL-2 cells. The spleen cells of nude mice transplanted with KB/IL-2 cells exhibited high cytotoxic activity compared to those from mice transplanted with KB cells and from untreated mice. Three of five mice transplanted with KB/IL-2 cells rejected tumors. In the treatment of established tumors, therapeutic effects due to irradiated KB/IL-2 were dose-dependent. The suppressive effects on tumor growth were blocked by anti-asialo GM1, anti-human IL-2 and anti-IFN-gamma antibodies. Immunohistochemical observation revealed the presence of asialo GM1(+) cells among the KB/IL-2 cells in tumors transplanted into nude mice.

Animals↗

PubMed2000

Regional evolution of venom-gland phospholipase A2 isoenzymes of Trimeresurus flavoviridis snakes in the southwestern islands of Japan.

Conventional chromatographic analysis showed that phospholipase A(2) (PLA(2)) isoenzymes of the venom of Trimeresurus flavoviridis (Habu snake) of Okinawa island are profoundly different in composition from those of T. flavoviridis of Amami-Oshima and Tokunoshima islands. The most striking feature was that myotoxic [Lys(49)]PLA(2) isoenzymes, called BPI and BPII, which are expressed abundantly in the venoms of Amami-Oshima and Tokunoshima T. flavoviridis, are missing from the venom of Okinawa T. flavoviridis. Northern blot analysis of Okinawa T. flavoviridis venom-gland mRNA species showed the absence of BPI and BPII mRNA species. Analysis by single-stranded conformational polymorphism-PCR of venom-gland mRNA species of T. flavoviridis from three islands, with reference to five DNA species each encoding different PLA(2) isoenzymes from Tokunoshima T. flavoviridis venom gland, also suggested that BPI and BPII mRNA species are not expressed in Okinawa T. flavoviridis venom gland. In contrast, genomic Southern blot analysis with a variety of probes showed that only the bands corresponding to the upstream and downstream regions of the genes for BPI and/or BPII can be detected in Okinawa T. flavoviridis. These results suggested that the genes for BPI and BPII in Okinawa T. flavoviridis genome had been inactivated to form pseudogenes. Differently from Amami-Oshima and Tokunoshima T. flavovirdis genomic DNAs, PCR amplification of the segments of BPI and BPII genes between the 5' moiety of second exon and the middle portion of second intron failed for Okinawa T. flavoviridis genomic DNAs. In sequence analysis of the two segments involving polymorphism between BPI and BPII genes, which are located in first exon and third exon, respectively, only one base was detected at the polymorphic positions for pseudogene in Okinawa T. flavoviridis genome. Based on these facts, it became evident for pseudogene that the upstream region of BPI gene down to the 5' moiety of second exon and the downstream region of BPII gene starting from the middle portion of second intron are in a linked form with a possible insertion. Such observations suggest that venom-gland genes for PLA(2) isoenzymes in T. flavoviridis snakes isolated for one to two million years have evolved independently. Their evolution is regional and seems, from several lines of consideration and observation, to be adaptive to the environment.

Animals↗

PubMed2000

In vivo gene gun-mediated DNA delivery into rodent brain tissue.

Various types of gene transfer into live tissues have been tried. However, in vivo gene transfer into brain tissue or neuronal cells without virus vector has required a great effort. Particle-mediated gene transfer into live brain tissue was thought to be impossible because of its fragility and the mechanical problem of a previous type of gene gun. In addition, particle-mediated DNA transfer into monolayer-cultured cells without mechanical damage has been difficult. We successfully transferred DNA into rodent live brain tissue and also into monolayer-cultured cells without mechanical damage by using a new type of gene gun and also confirmed gene expression in the brain. This new method represents another variation of gene transfer into the brain.

Animals↗

PubMed2000

Chat, a Cas/HEF1-associated adaptor protein that integrates multiple signaling pathways.

Cas (Crk-associated substrate) and HEF1 (human enhancer of filamentation) are related adaptor proteins that function in integrin-mediated cell adhesion and antigen receptor signaling pathways. We report here a molecular cloning of Chat (Cas/HEF1-associated signal transducer) that associates with Cas and HEF1. Chat is a 78-kDa signaling molecule with an N-terminal SH2 domain and is expressed in a wide range of tissues. In hematopoietic cells, a 115-kDa isoform of Chat (Chat-H) was specifically expressed. Chat is associated with Cas in brain, and Chat-H is associated with HEF1 in splenocytes. Deletion analyses revealed that Chat and Cas are associated with each other by their C-terminal domains. Treatment of PC12 cells with epidermal growth factor or nerve growth factor increased the phosphorylation level of Chat. This increase was suppressed by an inhibitor of mitogen-activated protein (MAP) kinase kinase, PD98059, suggesting the phosphorylation of Chat by MAP kinase. In Chat-overexpressed COS7 cells, the activity of c-Jun N-terminal kinase was up-regulated. After the epidermal growth factor stimulation, Chat and Cas were colocalized with actin filaments at ruffling membranes. These findings suggest that Chat transduces signals of tyrosine kinases and MAP kinase to Cas signaling pathway.

Actins↗

PubMed2000

High-glucose-induced nuclear factor kappaB activation in vascular smooth muscle cells.

OBJECTIVE: Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy. This dysfunction may be caused or exacerbated by expression of many of genes potently activated by the transcriptional factor nuclear factor kappaB (NF-kappaB). We have examined whether culture of VSMCs under high glucose conditions to stimulate the diabetic state can lead to the activation of NF-kappaB. METHODS: NF-kappaB activation was assessed in VSMCs stably transfected with a cis-reporter plasmid containing the NF-kappaB binding sites. RESULTS: Within 3-h incubation, high glucose (27.5 or 55 mmol/l) alone induced an increase in NF-kappaB activity in VSMCs; this increase was mimicked by mannitol given to deliver the same osmolar stress to the cells. High glucose or mannitol also enhanced TNFalpha-stimulated NF-kappaB activity. Incubation with high glucose for 48 h followed by stimulation with TNFalpha led to a marked potentiation of NF-kappaB activation compared with normoglycemic (5.5 mmol/l) VSMCs exposed to TNFalpha, while mannitol attenuated this effect. A 48-h incubation with high glucose substantially reduced glutathione (GSH) levels compared with normoglycemic VSMCs, whereas mannitol significantly increased GSH levels. An antioxidant N-acetyl-L-cysteine and a selective protein kinase C (PKC) inhibitor GF109203X significantly suppressed the TNFalpha-induced NF-kappaB activation, and abrogated potentiation of TNFalpha-induced NF-kappaB activity caused by high glucose (27.5 mmol/l). CONCLUSION: These results suggest that acutely high glucose causes alterations in osmolarity leading to activation of NF-kappaB, but that exposure to high glucose for more prolonged times causes changes in antioxidant defences and activation of PKC, which potentiates cytokine activation of NF-kappaB. Further definition of these pathways will help to delineate important signals mediating the aberrant behavior of VSMCs under hyperglycemic/diabetic conditions.

Acetylcysteine↗