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Biomedical subjects

L Wu

Publications and source records attributed to L Wu.

At least 217 records · Page 12Linked to original sources
PubMed2000

RecQ family helicases: roles in cancer and aging.

The RecQ family of DNA helicases includes at least three members in humans that are defective in genetic disorders associated with cancer predisposition and/or premature aging. Recent studies have shed light on the roles of RecQ helicases in suppressing 'promiscuous' genetic recombination and in ensuring accurate chromosome segregation. In particular, the biochemical properties of several family members have been characterised and functional interactions with other nuclear proteins have been defined.

Adenosine Triphosphatases↗
PubMed2000

Human herpesvirus 8 glycoprotein K8.1: expression, post-translational modification and localization analyzed by monoclonal antibody.

BACKGROUND: The genome of human herpesvirus 8 (HHV-8) contains at least 84 open reading frames, including the highly immunogenic K8.1. Other studies have determined that K8.1 gene generates at least two spliced transcripts in the HHV-8 infected BCBL-1 cells, termed as glycoprotein (gp)K8.1A and gpK8.1B. OBJECTIVE: To analyze the expression, post-translational modification and localization of HHV-8 gpK8.1 by monoclonal antibody (mAb). STUDY DESIGN: Mabs to HHV-8 produced by conventional hybridization and several clones identified. A mAb was used by various immunological assays to analyze HHV-8 K8.1 proteins in BCBL-1- and Sf9 insect cells. RESULTS: MAb clone 19B4 identified a 0.75-kb insert from the lambdaZAP cDNA expression library of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced BCBL-1 cells. Sequence analysis revealed that the cDNA insert corresponds to the published spliced ORF K8.1 mRNA of HHV-8. By immunofluorescence assay, the mAb stained the cell membrane, cytoplasm and perinuclear region of TPA induced BCBL-1 cells and showed no cross-reactivity with other herpesviruses. By immunoblotting assay, mAb 19B4 reacted with two species polypeptides giving a diffuse band with rMW from 42 to 64 kDa (gpK8.1A) and two closely migrating polypeptides of rMW 35/37 kDa (gpK8.1B). Both species were labeled by [14C]glucosamine, indicating that they are glycosylated and only gpK8.1A was detected in the virions. Expression of the full length K8.1 derived from cDNA in baculovirus system confirmed that these two glycoproteins are encoded by K8.1 gene. Enzymatic deglycosylation with endoF/peptide-N-glycosidase F, led to the reduction of rMW of both polypeptides whereas deglycosylation with O-glycosidase led only the reduction of rMW of K8.1A. CONCLUSION: The mAb 19B4 reacts specifically with BCBL-1 and Sf9 cells infected with recombinant baculovirus containing HHV-8 K8.1 gene. In several assays the mAb reacts with gpK8.1A and gpK8.1B. Only the mature spliced gpK8.1A is incorporated into virion. Enzymatic deglacosylation determined that gpK8.1A is N- and O-glycosylated, whereas gpK8.1B may lack O-glycosylation.

Alternative Splicing↗
PubMed2000

The multifocal electroretinogram in age-related maculopathies.

To measure and compare the multifocal electroretinogram in control group and patients with age-related maculopathies, 17 eyes of control subjects, 9 eyes of wet-form ARMD, 8 eyes of dry-form ARMD and 14 eyes of idiopathic macular hole were tested with VERIS Sciences 4.0. The latencies and average response densities of 6 ring retinal regions in control eyes were compared with those in ARMD and macular hole. The amplitude depression and latency prolongation were found in age-related maculopathies. The changes of multifocal ERG were dramatic in wet-form ARMD and moderate in dry-form ARMD and IMH, which were correspondent with the pathological changes of the diseases. Our results suggest that the multifocal electroretinogram can be used to quantity the visual function in age-related maculopathies.

Aged↗
PubMed2000

MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.

Notch receptors are involved in cell-fate determination in organisms as diverse as flies, frogs and humans. In Drosophila melanogaster , loss-of-function mutations of Notch produce a 'neurogenic' phenotype in which cells destined to become epidermis switch fate and differentiate to neural cells. Upon ligand activation, the intracellular domain of Notch (ICN) translocates to the nucleus, and interacts directly with the DNA-binding protein Suppressor of hairless (Su(H)) in flies, or recombination signal binding protein Jkappa (RBP-Jkappa) in mammals, to activate gene transcription. But the precise mechanisms of Notch-induced gene expression are not completely understood. The gene mastermind has been identified in multiple genetic screens for modifiers of Notch mutations in Drosophila. Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-Jkappa, and amplifies NOTCH-induced transcription of HES1. These studies provide a molecular mechanism to explain the genetic links between mastermind and Notch in Drosophila and indicate that MAML1 functions as a transcriptional co-activator for NOTCH signalling.

3T3 Cells↗
PubMed2000

Role of A(2A)-adenosine receptor activation for ATP-mediated coronary vasodilation in guinea-pig isolated heart.

1. Adenosine-5'-triphosphate (ATP) and adenosine are potent coronary vasodilators. ATP is rapidly converted to adenosine by ectonucleotidases. We examined whether coronary vasodilation caused by exogenous ATP is mediated by P(2) receptor activation or by A(2A)-adenosine receptor activation. 2. Effects of interventions on coronary conductance were determined by measuring coronary perfusion pressure in guinea-pig isolated hearts perfused at a constant flow of 10 ml min(-1). 3. ATP and adenosine both caused sustained, concentration-dependent increases of coronary conductance. Maximal responses to both agonists were equivalent. The values of pD(2) (+/-s.e.mean) for ATP and adenosine were 6.68+/-0.04 and 7.06+/-0.05, respectively. Adenosine was significantly more potent than ATP (P<0. 0001, n=10). 4. The values of pIC(50) for the selective A(2A)-adenosine receptor antagonist SCH58261 to antagonize equivalent responses to ATP and adenosine were 8.28+/-0.08 and 8.28+/-0.06 (P=0.99, n=6), respectively. 5. The non-selective adenosine receptor antagonists xanthine amine congener (XAC) and CGS15943 antagonized similarly the equivalent vasodilations caused by ATP (pIC(50) values 7.48+/-0.04 and 7.45+/-0.06, respectively) and adenosine (pIC(50) values 7. 37+/-0.13 and 7.56+/-0.11). 6. In contrast to ATP and adenosine, the two P(2) agonists 2-methylthio-ATP and uridine-5'-triphosphate failed to cause stable increases of coronary conductance, caused desensitization of vasodilator responses, and were not antagonized by SCH 58261, 8-parasulphophenyltheophylline, or XAC. 7. Glibenclamide attenuated coronary vasodilations caused by ATP and adenosine by 88 and 89%, respectively, but failed to attenuate those caused by 2-methylthio-ATP. 8. These results strongly suggest that sustained, submaximal coronary vasodilation caused by exogenous ATP is entirely mediated by adenosine acting upon A(2A)-adenosine receptors.

Adenosine↗
PubMed2000

A xylem-specific cellulose synthase gene from aspen (Populus tremuloides) is responsive to mechanical stress.

Angiosperm trees accumulate an elevated amount of highly crystalline cellulose with a concomitant decrease in lignin in the cell walls of tension-stressed tissues. To investigate the molecular basis of this tree stress response, we cloned a full-length cellulose synthase (PtCesA) cDNA from developing xylem of aspen (Populus tremuloides). About 90% sequence similarity was found between the predicted PtCesA and cotton GhCesA proteins. Northern blot and in situ hybridization analyses of PtCesA gene transcripts in various aspen tissues, and PtCesA gene promoter-beta-glucuronidase (GUS) fusion analysis in transgenic tobacco, demonstrated conclusively that PtCesA expression is confined to developing xylem cells during normal plant growth. During mechanical stress induced by stem bending, GUS expression remained in xylem and was induced in developing phloem fibers undergoing tension stress, but was turned off in tissues undergoing compression on the opposite side of the bend. Our results suggest a unique role for PtCesA in cellulose biosynthesis in both tension-stressed and normal tissues in aspen, and that the on/off control of PtCesA expression may be a part of a signaling mechanism triggering a stress-related compensatory deposition of cellulose and lignin that is crucial to growth and development in trees.

Arabidopsis Proteins↗
PubMed2000

Molecular identification of main cellular lineages as a tool for the classification of gastric cancer.

Gastric carcinomas (GC) are heterogeneous tumors comprising variable amounts of cells of different lineage phenotype, including gastric mucous cells (surface--SMC or gland--GMC) and intestinal cells (IC). The evaluation of tumor behavior has classically depended on strictly morphological classifications of tumors. Microsatellite instability (MSI) is frequently detected in GC, but whether MSI affects all gastric cellular lineages or exclusively occurs in unique cellular lineages in GC is not known. The aims of this study were to test a combination of anti-mucin antibodies to classify gastric cancer into predominant cell lineage phenotype and to determine whether MSI in GC is associated with particular cellular tumor phenotypes. Fifty-five GC were immunophenotyped with antibodies specific for SMC, GMC, or IC. DNA was extracted from tumor and non-neoplastic gastric tissues and amplified with 5 microsatellite markers. A mixed cellular pattern was the most frequent phenotype of GC (61%) and was seen in both glandular (63%) and diffuse (58%)-type tumors. No significant difference in the rate of MSI was found in tumors with predominant gastric, intestinal or mixed phenotype. However, tumors with null or low-level expression of cellular lineage differentiation markers displayed MSI more frequently than tumors with high-level expression (40% v 20%). In conclusion, different gastric carcinoma cell lineage patterns can be easily identified with the 3 immunohistochemical markers used in this study. The 3 main cellular lineage components of gastric cancer can be similarly affected by microsatellite instability, consistent with the notion that MSI is an early event in gastric carcinogenesis.

Adult↗
PubMed2000

Loss control of Mcm5 interaction with chromatin in cdc6-1 mutated in CDC-NTP motif.

Saccharomyces cerevisiae Cdc6 plays an essential role in establishing and maintaining the prereplicative complex (pre-RC) by interacting with the origin recognition complex (ORC) and associating with chromatin origins. These interactions are required to load minichromosome maintenance proteins (MCMs) and other initiator proteins onto replication origins. Although the temperature-sensitive cdc6 mutant, cdc6-1, has been widely used for these studies, the molecular mechanism of the cdc6-1 mutation has been unclear. In this study, we have identified a base substitution at Gly260-->Asp, near the CDC-NTP motif. Using a chromatin immunoprecipitation assay (CHIP), we found that cdc6-1 fails to load Mcm5 onto the replication origins. Chromatin fractions were used to study Mcm5 binding in both the wildtype and mutant background. These studies indicated that Cdc6 is also involved in unloading Mcm5 from chromatin. Specifically, the cdc6-1 mutation protein, cdc6(G260D), which failed to load Mcm5 onto replication origins, also failed to unload the Mcm5 protein. Furthermore, the overexpression of wildtype CDC6 accelerated the unloading of Mcm5 from chromatin fractions. In the absence of functional Cdc6, the Mcm5 protein showed nonorigin binding to chromatin with the cell cycle arrested at the G1S phase transition. Our results suggested that the cdc6(G260D) mutant protein fails to assemble an operational replicative complex and that wildtype Cdc6 plays a role in preventing re-replication by controlling the unloading the MCMs from chromatin origins.

Amino Acid Substitution↗
PubMed2000

DEC-205 as a marker of dendritic cells with regulatory effects on CD8 T cell responses.

We have previously reported that a population of lymphoid-related CD8alpha(+) DEC-205(+) dendritic cells (DC) from mouse spleen have 'regulatory' effects on the T cells they activate. CD8 T cells produce IL-2 and give a sustained proliferative response to allogeneic CD8alpha(-) DEC-205(-) splenic DC, but produce little IL-2 and give a limited response to allogeneic CD8(+) DEC-205(+) splenic DC. Although CD8alpha and DEC-205 correlate closely among splenic DC, lymph nodes (LN) include a large population of CD8alpha(low) DEC-205(high) DC. By i.v. transfer of purified thymic early lymphoid precursors into irradiated recipient mice we now demonstrate that these CD8alpha(low) but DEC-205(high) LN DC can be the progeny of a lymphoid precursor population, apparently corresponding to the CD8alpha(high) DEC-205(high) DC progeny of the same precursors in spleen and thymus. By culture of the separated, purified DC with allogeneic CD8 T cells we demonstrate that the CD8alpha(low) DEC-205(high) DC of LN are also functionally equivalent to the CD8alpha(high) DEC-205(high) DC of spleen. Therefore, DEC-205 but not CD8alpha serves to segregate functionally distinct DC types in LN. However, DC isolated from the spleens of genetically manipulated DEC-205(null) mice and separated on the basis of CD8alpha expression have a similar capacity to stimulate CD8 T cells as their heterozygous littermate controls, with the CD8alpha(+) but now DEC-205(null) DC still giving restricted responses. In conclusion, high expression of DEC-205 appears to be a good marker of the lymphoid-related regulatory type of DC, but DEC-205 itself is not responsible for transmitting negative signals to the T cells.

Animals↗
PubMed2000

A binary architectural grading system for uterine endometrial endometrioid carcinoma has superior reproducibility compared with FIGO grading and identifies subsets of advance-stage tumors with favorable and unfavorable prognosis.

The International Federation of Gynecology and Obstetrics (FIGO) grading of uterine endometrial endometrioid carcinoma requires evaluation of histologic features that can be difficult to assess, including recognition of small amounts of solid growth, distinction of squamous from nonsquamous solid growth, and assessment of degree of nuclear atypia. The authors describe a novel, binary architectural grading system that uses low-magnification assessment of amount of solid growth, pattern of invasion, and presence of necrosis to divide endometrioid carcinomas into low- and high-grade tumors. The authors analyzed its performance for predicting prognosis and with respect to intra- and interobserver reproducibility. A total of 141 endometrioid carcinomas from hysterectomy specimens were graded according to the FIGO system, nuclear grading, and the binary architectural system. A tumor was classified as high grade if at least two of the following three criteria were present: (1) more than 50% solid growth (without distinction of squamous from nonsquamous epithelium); (2) a diffusely infiltrative, rather than expansive, growth pattern; and (3) tumor cell necrosis. For tumors that were confined to the endometrium, only percent solid growth and necrosis were evaluated, and those with both solid growth of more than 50% and necrosis were considered high grade. All tumors were graded independently by three pathologists on two separate occasions. Both inter- and intraobserver agreement using the binary grading system (kappa = 0.65 and 0.79) were superior compared with FIGO (kappa = 0.55 and 0.67) and nuclear grading (kappa = 0.22 and 0.41). The binary grading system stratified patients into three distinct prognostic groups. Patients with stage I low-grade tumors with invasion confined to the inner half of the myometrium (stages IA and IB) had a 100% 5-year survival rate. Patients with low-grade tumors that invaded beyond the outer half of the myometrium (stage IC and stages II-IV) and those with high-grade tumors with invasion confined to the myometrium (stages IB and IC) had a 5-year survival rate of 67% to 76%. In striking contrast to patients with advance-stage low-grade tumors, patients with advance-stage high-grade tumors had a 26% 5-year survival rate. This binary grading system has advantages over FIGO and nuclear grading that permit greater interobserver and intraobserver reproducibility and should be tested in other studies of endometrial endometrioid carcinomas to validate its reproducibility and use for segregating patients into different prognostic groups.

Adolescent↗
PubMed2000

Involvement of the cyclic GMP pathway in the superoxide-induced IP3 formation in vascular smooth muscle cells.

OBJECTIVE: To investigate whether cGMP or cAMP signal pathway is indirectly involved in the effect of superoxide on the IP3 formation in vascular smooth muscle cells (SMC) from rat mesenteric arteries. METHODS: Cultured smooth muscle cells from rat mesenteric arteries were prelabelled with myo-(2-(3)H) inositol for evaluation of IP3 formation. Quantitative cAMP and cGMP levels were determined using cAMP [3H] or cGMP [125I] assay systems. RESULTS: In the present study, it was found that superoxide significantly inhibited the basal level of cGMP and also suppressed the sodium nitroprusside (SNP)-induced cGMP formation in SMCs from rat mesenteric arteries. The inhibitory effect of superoxide on basal level of cGMP was similar in the absence or presence of ODQ (a guanylyl cyclase inhibitor). Moreover, the superoxide-induced increase in IP3 formation was significantly inhibited by SNP or s-nitroso- n-acetylpenicillamine but was significantly potentiated by ODQ or KT5823 (a cGMP-dependent protein kinase inhibitor). Superoxide had no effect on the basal or on the forskolin-induced cAMP production and the inhibition of adenylyl cyclase or cAMP-dependent protein kinase did not affect the superoxide-enhanced IP3 formation. CONCLUSION: The decreased cross-inhibition of IP3 pathway by cGMP may contribute to the superoxide-enhanced IP3 formation in SMCs from mesenteric arteries. The cross-talk between cGMP and IP3 pathways provides a novel mechanism for the signalling role of superoxide in vascular SMCs.

Adenylyl Cyclases↗
PubMed2000

An overview on the isolation and analysis of circulating tumor DNA in plasma and serum.

Molecular biology has brought about a new dimension to our understanding and analysis of human cancer. Diagnosis and prognosis of cancer have increasingly benefited from the use of molecular markers and molecular approaches. Although the description of circulating tumor DNA in the blood has a long history, the clinical implications of its presence require a large body of well-controlled and stringently performed large research and clinical tests. This chapter has provided an overview of the essential elements for the preparation and analysis of circulating DNA in the plasma or serum. We hope that the basic approaches and tips summarized here will serve as a foundation for the rigorous and comprehensive molecular analysis of circulating nucleic acids in the years to come.

DNA, Neoplasm↗
PubMed2000

Variation of measured sound speeds in gaseous and liquid air with temperature and pressure

Based on sound speeds in gaseous and liquid air measured by Younglove and Frederick [Int. J. Thermophys. 13(6), 1033-1041 (1992)], empirical equations for the computation of sound speeds in the above media at relatively smaller temperature and pressure ranges were derived. For gaseous air, over a temperature range from 200 to 300 K and pressure from 0.614 to 10.292 MPa, the maximum deviation between the measured sound speeds and those computed with the empirical equation is 56 ppm. For liquid air, over the ranges from 90 to 110 K for temperature and from 0.763 to 13.823 MPa for pressure, the corresponding deviation is 173 ppm.

Journal Article↗
PubMed2000

Nitrite reductase genes (nirK and nirS) as functional markers to investigate diversity of denitrifying bacteria in pacific northwest marine sediment communities.

Genetic heterogeneity of denitrifying bacteria in sediment samples from Puget Sound and two sites on the Washington continental margin was studied by PCR approaches amplifying nirK and nirS genes. These structurally different but functionally equivalent single-copy genes coding for nitrite reductases, a key enzyme of the denitrification process, were used as a molecular marker for denitrifying bacteria. nirS sequences could be amplified from samples of both sampling sites, whereas nirK sequences were detected only in samples from the Washington margin. To assess the underlying nir gene structure, PCR products of both genes were cloned and screened by restriction fragment length polymorphism (RFLP). Rarefraction analysis revealed a high level of diversity especially for nirS clones from Puget Sound and a slightly lower level of diversity for nirK and nirS clones from the Washington margin. One group dominated within nirK clones, but no dominance and only a few redundant clones were seen between sediment samples for nirS clones in both habitats. Hybridization and sequencing confirmed that all but one of the 228 putative nirS clones were nirS with levels of nucleotide identities as low as 45.3%. Phylogenetic analysis grouped nirS clones into three distinct subclusters within the nirS gene tree which corresponded to the two habitats from which they were obtained. These sequences had little relationship to any strain with known nirS sequences or to isolates (mostly close relatives of Pseudomonas stutzeri) from the Washington margin sediment samples. nirK clones were more closely related to each other than were the nirS clones, with 78.6% and higher nucleotide identities; clones showing only weak hybridization signals were not related to known nirK sequences. All nirK clones were also grouped into a distinct cluster which could not be placed with any strain with known nirK sequences. These findings show a very high diversity of nir sequences within small samples and that these novel nir clusters, some very divergent from known sequences, are not known in cultivated denitrifiers.

Bacteria↗
PubMed2000

Three-dimensional structure of the human herpesvirus 8 capsid.

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus implicated in all forms of Kaposi's sarcoma and certain lymphomas. HHV-8 has been extensively characterized, both biochemically and immunologically, since its first description in 1994. However, its three-dimensional (3D) structure remained heretofore undetermined largely due to difficulties in viral purification. We have used log-phase cultures of body cavity-based lymphoma 1 cells induced with 12-O-tetradecanoylphorbol-13-acetate to obtain HHV-8 capsids for electron cryomicroscopy and computer reconstruction. The 3D structure of the HHV-8 capsids revealed a capsid shell composed of 12 pentons, 150 hexons, and 320 triplexes arranged on a T=16 icosahedral lattice. This structure is similar to those of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), which are prototypical members of alpha- and betaherpesviruses, respectively. The inner radius of the HHV-8 capsid is identical to that of the HSV-1 capsid but is smaller than that of the HCMV capsid, which is consistent with the relative sizes of the genomes they enclose. While the HHV-8 capsid exhibits many structural similarities to the HSV-1 capsid, our reconstruction shows two major differences: its hexons lack the "horn-shaped" VP26 densities bound to the HSV-1 hexon subunits, and the HHV-8 triplexes appear smaller and less elongated than those of HSV-1. These differences are in excellent agreement with our sequence comparisons of HHV-8 and HSV-1 capsid proteins. This gammaherpesvirus capsid structure complements previous structural studies on alpha- and betaherpesviruses in providing an account of structural similarities and differences among capsids representing all human herpesvirus subfamilies.

Capsid↗
PubMed2000

E2F-Rb complexes assemble and inhibit cdc25A transcription in cervical carcinoma cells following repression of human papillomavirus oncogene expression.

Expression of the bovine papillomavirus E2 protein in cervical carcinoma cells represses expression of integrated human papillomavirus (HPV) E6/E7 oncogenes, followed by repression of the cdc25A gene and other cellular genes required for cell cycle progression, resulting in dramatic growth arrest. To explore the mechanism of repression of cell cycle genes in cervical carcinoma cells following E6/E7 repression, we analyzed regulation of the cdc25A promoter, which contains two consensus E2F binding sites and a consensus E2 binding site. The wild-type E2 protein inhibited expression of a luciferase gene linked to the cdc25A promoter in HT-3 cervical carcinoma cells. Mutation of the distal E2F binding site in the cdc25A promoter abolished E2-induced repression, whereas mutation of the proximal E2F site or the E2 site had no effect. None of these mutations affected the activity of the promoter in the absence of E2 expression. Expression of the E2 protein also led to posttranscriptional increase in the level of E2F4, p105(Rb), and p130 and induced the formation of nuclear E2F4-p130 and E2F4-p105(Rb) complexes. This resulted in marked rearrangement of the protein complexes that formed at the distal E2F site in the cdc25A promoter, including the replacement of free E2F complexes with E2F4-p105(Rb) complexes. These experiments indicated that repression of E2F-responsive promoters following HPV E6/E7 repression was mediated by activation of the Rb tumor suppressor pathway and the assembly of repressing E2F4-Rb DNA binding complexes. Importantly, these experiments revealed that HPV-induced alterations in E2F transcription complexes that occur during cervical carcinogenesis are reversed by repression of HPV E6/E7 expression.

Binding Sites↗
PubMed2000

Altered L-type Ca(2+) channel currents in vascular smooth muscle cells from experimental diabetic rats.

Vascular complications of diabetes are associated with abnormal Ca(2+) handling by vascular smooth muscle cells (SMCs) in which the alteration in L-type voltage-dependent Ca(2+) channel (VDCC) currents may play an important role. In the present study, the characteristics of L-type VDCC currents in tail artery SMCs from streptozotocin-induced diabetic rats were examined. The densities, but not the voltage dependence, of L-type VDCC currents were reduced as diabetes progressed from 1 wk to 3 mo. The inhibitory effect of dibutyryl-cAMP on L-type VDCC currents was greater in diabetic SMCs than in age-matched control cells (P < 0.01). Both the stimulatory effect of BAY K 8644 and the inhibitory effect of nifedipine on L-type VDCC currents were significantly enhanced in diabetic cells. The diabetes-related abnormalities in L-type VDCC currents were mimicked by culturing SMCs with a high concentration of glucose. Our results suggest that the properties of L-type VDCC in diabetic vascular SMCs were significantly altered, partially related to the increased L-type VDCC sensitivity to cAMP and hyperglycemia.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗