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Biomedical subjects

Jun Yang

Publications and source records attributed to Jun Yang.

At least 73 records · Page 4Linked to original sources

[Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction].

OBJECTIVE: To investigate the effects of emergent intracoronary autologous bone marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and myocardium lesion area in patients with first acute inferior-wall myocardial infarction. METHODS: Forty patients with first onset of acute inferior-wall myocardial infarction, 28 males and 12 females, aged < or = 75, treated with emergent percutaneous coronary intervention (PCI) were randomly divided into 2 equal groups: group undergoing intracoronary transplantation of autologous BM-MNC via a micro-catheter right after PCI (BM-MNC group), and control group receiving normal saline and heparin. Blood routine examination, myocardium zymogram, and serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance imaging (CMR), and angiography of the coronary artery and left ventricle were conducted before the transplantation and immediately, 1 week, and 6 months after transplantation. RESULTS: CMR showed that 6 months later the left ventricular ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM-MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1 week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the myocardial lesion area of the BM-MNC group decreased more significantly in comparison with the control group. Nevertheless, there was no difference in change of left ventricular end diastolic volume (LVEDV) between these two groups. The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/- 0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6 g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac infarction, malignant arrhythmia, occur in these 2 groups. CONCLUSION: Emergent intracoronary transplantation of autologous BM-MNC in patients with acute inferior-wall myocardial infarction improves the left ventricular function and myocardial infusion, minimizes the myocardial lesion area significantly.

Aged↗

Synthesis of nano titania particles embedded in mesoporous SBA-15: characterization and photocatalytic activity.

Supported nanocrystalline titanium dioxide (TiO2) has been prepared by a post-synthesis step via Ti-alkoxide hydrolysis through the use of mesoporous SBA-15 silica. TiO2/SBA-15 composites with various TiO2 loading have been prepared and characterized by X-ray diffraction, nitrogen adsorption, Fourier transform infrared spectroscopy and diffusive reflective UV-vis spectroscopy. The addition of mesoporous SBA-15 prevents the anatase to rutile phase transformation and the growth of crystal grain. TiO2 did not block the SBA-15 pores, and their surface was fully accessible for nitrogen adsorption. Calcination in air of the composites up to 800 degrees C did not change the nanocrystal phase and slightly increased the domain size from 5.0 to 7.5 nm, indicating that the anatase TiO2 grains in the mesostructures have a relatively high thermal stability and proper pore diameter allows controlling the size of obtained titania particles. The TiO2/SBA-15 composites prepared by this study showed much higher photodegradation ability for methylene blue (MB) than commercial pure TiO2 nanoparticles P-25. Experimental results indicate that the photocatalytic activity of titania/silica mixed materials depends on the adsorption ability of composite and the photocatalytic activity of the titania, and there is an optimal ratio of Ti:Si, too high or low Ti:Si ratio will lower the photodegradation ability of the composites.

Catalysis↗

Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat.

Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

Analgesics↗

Insulin-like peptide 5: expression in the mouse brain and mobilization of calcium.

Insulin-like peptide 5 (INSL5) mRNA was detected in the mouse hypothalamus by RT-PCR. Immunohistochemical studies using an antiserum against the mouse INSL5 peptide revealed INSL5-immunoreactive (irINSL5) neurons in the paraventricular, supraoptic, accessory secretory, and supraoptic retrochiasmatic nuclei and immunoreactive cell processes in the internal layer of the median eminence. In the pituitary, irINSL5 was detected in terminal-like elements of the posterior lobe and in cells of the anterior lobe. Double-labeling experiments showed that irINSL5 is expressed in vasopressin-, but not oxytocin-containing neurons. INSL5 (100 nm) administered to dissociated and cultured mouse hypothalamic neurons elevated cytosolic calcium concentrations [Ca(2+)](i), as assessed by the microfluorimetric fura-2 method. In a Ca(2+)-free medium, INSL5 induced in dissociated neurons an increase of [Ca(2+)](i), which was sensitive to the endoplasmic reticulum calcium pump inhibitor thapsigargin (1 microm) and the IP(3) receptor blocker 2-aminoethoxydiphenyl borate (100 microm) or xestospongin C (5 microm). Our result provides the first evidence that INSL5 is expressed in a population of cells in the mouse hypothalamus and pituitary and that it elevates [Ca(2+)](i) by a mechanism involving both Ca(2+) influx and Ca(2+) release from intracellular stores. The concentration of irINSL5 in the hypothalamic-pituitary axis suggests a neuroendocrine function of this insulin superfamily member.

Animals↗

Salusin beta is a surrogate ligand of the mas-like G protein-coupled receptor MrgA1.

The mas-like G protein-coupled receptors form a subfamily of G protein-coupled receptors that includes variable member numbers across different species and that have been shown to bind a wide variety of ligands from peptides to amino acid derivatives. While screening a library of peptides against different orphan G protein-coupled receptors, we found that human salusin beta activates the mouse mas-like G protein-coupled receptor, mMrgA1 with an EC(50) of about 300 nM. Salusin beta is a bioactive peptide recently discovered through bioinformatics analysis which stimulates arginine-vasopressin release from rat pituitary and causes rapid and profound hypotension and bradycardia. However, when we further analyzed the generality of the mMrgA1 activation, we found that human salusin beta does not activate corresponding human mas-like G protein-coupled receptors. Our results show that human salusin beta is a surrogate ligand of the mouse MrgA1 and raises a cautionary flag for experiments that analyze the pharmacological profiles of mas-like G protein-coupled receptors from different species.

Adenosine Triphosphatases↗

Control of petal shape and floral zygomorphy in Lotus japonicus.

Zygomorphic flowers, with bilateral (dorsoventral) symmetry, are considered to have evolved several times independently in flowering plants. In Antirrhinum majus, floral dorsoventral symmetry depends on the activity of two TCP-box genes, CYCLOIDEA (CYC) and DICHOTOMA (DICH). To examine whether the same molecular mechanism of floral asymmetry operates in the distantly related Rosid clade of eudicots, in which asymmetric flowers are thought to have evolved independently, we investigated the function of a CYC homologue LjCYC2 in a papilionoid legume, Lotus japonicus. We showed a role for LjCYC2 in establishing dorsal identity by altering its expression in transgenic plants and analyzing its mutant allele squared standard 1 (squ1). Furthermore, we identified a lateralizing factor, Keeled wings in Lotus 1 (Kew1), which plays a key role in the control of lateral petal identity, and found LjCYC2 interacted with Kew1, resulting in a double mutant that bore all petals with ventralized identity to some extents. Thus, we demonstrate that CYC homologues have been independently recruited as determinants of petal identities along the dorsoventral axis in two distant lineages of flowering plants, suggesting a common molecular origin for the mechanisms controlling floral zygomorphy.

Alleles↗

R5 and X4 HIV envelopes induce distinct gene expression profiles in primary peripheral blood mononuclear cells.

HIV envelope binds to and signals through its primary cellular receptor, CD4, and through a coreceptor, either CC chemokine receptor 5 (CCR5) or CXC chemokine receptor 4 (CXCR4). Here, we evaluate the response of peripheral blood mononuclear cells to a panel of genetically diverse R5 and X4 envelope proteins. Modulation of gene expression was evaluated by using oligonucleotide microarrays. Activation of transcription factors was evaluated by using an array of oligonucleotides encoding transcription factor binding sites. Responses were strongly influenced by coreceptor specificity. Treatment of cells from CCR5delta32 homozygous donors with glycoprotein (gp)120 derived from an R5 virus demonstrated that the majority of responses elicited by R5 envelopes required engagement of CCR5. R5 envelopes, to a greater extent than X4 envelopes, induced the expression of genes belonging to mitogen-activated protein kinase signal transduction pathways and genes regulating the cell cycle. A number of genes induced by R5, but not X4, envelopes were also up-regulated in the resting CD4+ T cell population of HIV-infected individuals. These results suggest that R5 envelope facilitates replication of HIV in the pool of resting CD4+ T cells. Additionally, signaling by R5 gp120 may facilitate the transmission of R5 viruses by inducing a permissive environment for HIV replication.

CD4-Positive T-Lymphocytes↗

Identification and characterization of the genes encoding a unique surface (S-) layer of Tannerella forsythia.

A newly emerged periodontopathic pathogen Tannerella forsythia (formerly Bacteroides forsythus), a Gram-negative, filament-shaped, strict anaerobic, non-pigmented oral bacterium, possesses a surface (S-) layer. In our previous studies, the S-layer has been isolated, and shown to mediate hemagglutination, adhesion/invasion of epithelial cell, and murine subcutaneous abscess formation. In the present study, biochemical and molecular genetic characterization of the S-layer are reported. Amino acid sequencing and mass spectrometry indicated that the S-layer is composed of two different proteins, termed 200 and 210 kDa proteins. It was also shown that these proteins are glycosylated. The genes encoding the core proteins of these glycoproteins, designated as tfsA and tfsB, have been identified in silico, cloned, and their sequences have been determined. The tfsA (3.5 kb) and tfsB (4.1 kb) genes are located in tandem, and encode for 135 and 152 kDa proteins, respectively. An apparent discrepancy in molecular weights, 135 vs. 200 kDa and 152 vs. 210 kDa, is accounted for carbohydrate residues attached to the core proteins. Amino acid sequence comparison exhibited a 24% similarity between the 200 and 210 kDa proteins. Further sequence analyses showed that TfsA and TfsB possess putative signal peptide sequences with cleavage sites at alanine residues, and transmembrane domains on the C-terminal region. Northern blot and RT-PCR analyses confirmed an operon structure of tfsAB, suggesting co-regulation of these genes in producing the S-layer. Putative promoter sequences and transcription termination sequences for this operon have also been identified. Comparison with database indicates that the S-layer of T. forsythia has a unique structure exhibiting no homology to other known S-layers of prokaryotic organisms. The present study shows that the T. forsythia S-layer is very unique, since it appears to be composed of two large glycoproteins, and it does not reveal any homology to other known S-layer proteins or glycoproteins of prokaryotic organisms.

Bacterial Proteins↗

A comparative study of using comet assay and gammaH2AX foci formation in the detection of N-methyl-N'-nitro-N-nitrosoguanidine-induced DNA damage.

Comet assay is a useful technique in the detection of DNA damages, particularly DNA strand breaks; and it has been utilized to show that a potent carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), can induce such damages. Recently, gammaH2AX foci formation has been suggested as another sensitive way to detect DNA double strand breaks (DSBs). However, there is no systematic comparison being conducted to evaluate the consistency of these two methods. Using MNNG as a model chemical, the sensitivity of neutral comet assay and gammaH2AX foci formation in detecting MNNG-induced damage was studied. It was found that at concentrations of 0.1 and 1 microg/ml, both methods can detect MNNG-induced damage in human amnion FL cells. However, at 0.1 microg/ml, comet assay revealed more percentage of cells with DNA damage than gammaH2AX fluorescence revealed. On the other hand, while gammaH2AX foci were readily formed at very early times by 10 microg/ml MNNG treatment, neutral comet assay did not detect any significant DNA damage at the same time points. In addition, 10 microg/ml MNNG induced a distinct whole nuclei staining pattern of gammaH2AX, a type of DNA damage which was not detected by neutral comet assay but could be detected by alkaline comet assay. Therefore, gammaH2AX may be used as a sensitive indicator for DNA damage.

Cells, Cultured↗

A novel spermatogenesis-specific uPAR gene expressed in human and mouse testis.

The urokinase receptor, uPAR, which binds to the urinary-type plasminogen activator, controls matrix degradation in the processes of tissue remodeling, cell migration, and invasion. In the present study, we found a new urokinase receptor gene that encodes a 249-amino acid putative protein. Northern blot analysis showed specific expression in the testis of this gene, which we named the spermatogenesis-related gene (SGRG). In situ hybridization revealed a strong expression signal for SGRG in spermatogonia, but not in spermatocytes. Therefore, we conjecture that SGRG may regulate spermatocyte migration through breakdown of extracellular matrix protein barriers in spermatogenesis. Since SGRG is specifically expressed in spermatogonia, it provides an attractive candidate for development of a contraceptive vaccine.

Amino Acid Sequence↗

The effect of different doses of fluvastatin on inflammatory markers in the early phase of acute coronary syndrome.

BACKGROUND: Inflammation promotes acute coronary syndromes (ACS) and ensuing clinical complications. It is well known that statins decrease the risk of coronary events and may benefit the stabilization of atherosclerotic plaque with their anti-inflammatory effects. We investigated the effects of different doses of fluvastatin on serum concentrations of high-sensitive C-reaction protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) in the early phase of ACS. METHODS: We prospectively randomized 60 patients with ACS to 3 groups: (1) group A (n=20): were given routine therapy; (2) group B (n=20): were administrated routine therapy with 40 mg/d oral fluvastatin; (3) group C (n=20): received routine therapy with 80 mg/d oral fluvastatin. Twenty patients with stable coronary heart disease served as controls. The following-up period was 7 days. By immunoturbidimetric assay and ELISA methods the serum concentrations of hs-CRP and TNF-alpha were measured before and after therapy. RESULTS: (1) The serum concentrations of hs-CRP and TNF-alpha in patients with ACS was significantly higher than those in the control group (P<0.05). (2) After 1 week of therapy, the serum concentrations of hs-CRP and TNF-alpha were significantly lower in group B and group C (all P<0.01), especially in group C. (3) The serum concentrations of hs-CRP and TNF-alpha did not correlate to the concentrations of TC, TG, LDL-C, or HDL-C. CONCLUSION: Early fluvastatin intervention decreases dose-dependently the serum concentrations of hs-CRP and TNF-alpha of patients with ACS. The high-dose fluvastatin invention may play a stronger anti-inflammatory effect in ACS patients. The anti-inflammatory effect of fluvastatin may be beyond the lipid lowering.

Acute Disease↗

Preclinical pharmacology of a nonsteroidal ligand for androgen receptor-mediated imaging of prostate cancer.

Proper management of prostate cancer patients is highly dependent on the spread of the disease. High expression levels of the androgen receptor (AR) in prostate tumor offer a target for identifying cancer metastasis. We investigated the use of nonsteroidal AR ligands for receptor-mediated imaging as a diagnostic tool for prostate cancer staging. Compound S-26 [S-3-(4-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-cyano-3-iodophenyl)-propionamide]was identified from a series of iodinated ether-linked derivatives of bicalutamide due to its high-AR binding affinity of 3.3 nM (which is similar to testosterone and approximately 25% of the binding affinity of dihydrotestosterone) in an in vitro competitive binding assay using rat prostate cytosol. Furthermore, S-26 exhibited a greater binding affinity (K(i) = 4.4 nM) in a whole-cell binding assay using COS-7 cells transfected with human AR than testosterone (K(i) = 32.9 nM) and dihydrotestosterone (K(i) = 45.4 nM). We also confirmed that sex hormone-binding globulin (SHBG), a plasma protein that binds steroids with high affinity, does not bind with S-26. Cotransfection studies with the estrogen, progesterone, and glucocorticoid receptor indicated that S-26 does not cross-react with other members of the steroid hormone receptor family. The nonsteroidal structure, high-AR binding affinity, specificity, and lack of binding to SHBG indicate that S-26 exhibits favorable properties for further development as an imaging agent for prostate cancer.

Amides↗

[Inhibition of nuclear factor kappa B attenuates multiple organ injury following ruptured abdominal aortic aneurysm: an experiment with rats].

OBJECTIVE: To investigate the effect of inhibition of nuclear factor kappa B on multiple organ injury following ruptured abdominal aortic aneurysm. METHODS: Forty-five Wistar rats underwent catheterization to observe the intestinal microcirculation blood flow, and were randomly divided into 3 equal groups. Rats of the ruptured abdominal aortic aneurysm (RAAA) group underwent laparotomy and extraction of blood to cause hemorrhage shock for 1 h (hemorrhagic shock phase), by the end of this phase normal saline at the dose of 50 ml/kg was injected intravenously, after that the abdominal aorta and bilateral common iliac arteries were blocked with artery clamps for 45 min so as to cause lower torso ischemia, and then the extracted blood was reperfused. The lungs, small intestine were taken out to undergo histological examination, and examination of lung polymorphonuclear neutrophilic leukocyte (PMN) sequestration, lung wet tissues/dry (W/D) tissues ratio, and myeloperoxidase (MPO) activity. The rats of pyrrolidine dithiocarbamate (PDTC) group were perfused with PDTC, a specific inhibitor of nuclear factor kappa B (NF-kappaB), by the end of the hemorrhagic shock phase. And the rats of the sham operation group were perfused of normal saline. RT-PCR was used to detect the mRNA expression of NF-kappaB p65 and intercellular adhesion molecule (ICAM). Western blotting was used to detect the protein expression of NF-kappaB p65 and ICAM-1. Immunohistochemistry was used to detect the expression of NF-kappaB p65 and ICAM-1 in the lung and small intestine tissues. RESULTS: Histological examination showed that severe damage could be found in the lung and small intestine of the RAAA group, and damages were significantly mild in the PDTC group. Lung PMN sequestration, W/D ratio, MPO activity were significantly increased in the RAAA group and these changes were relatively mild in the PDTC group (all P < 0.01). The intestinal microcirculation blood flow was 0.25 +/- 0.04 mlxmin(-1)xg(-1) in the RAAA group, significantly less than that of the sham operation group (0.71 +/- 0.11 mlxmin(-1)xg(-1), P < 0.01), and was 0.64 +/- 0.06 mlxmin(-1)xg(-1) in the PDTC group, significantly higher than that of the RAAA group (P < 0.01). The mRNA expression of NF-kappaB p65 in the lung of the RAAA group was 0.68 +/- 0.22, significantly higher than that of the sham operation group (0.11 +/- 0.02, P < 0.01) and that of the PDTC group (0.23 +/- 0.07, P < 0.01). The mRNA expression of NF-kappaB p65 in the intestine of the RAAA group was 0.48 +/- 0.10, significantly higher than that of the sham operation group (< 0.20 +/- 0.05, P < 0.01) and that of the PDTC group (0.27 +/- 0.06, P < 0.01). The mRNA expression of ICAM-1 in the lung of the RAAA group was 0.92 +/- 0.31, significantly higher than that of the sham operation group (0.07 +/- 0.02, P < 0.01) and that of the PDTC group (0.21 +/- 0.04, P < 0.01). The mRNA expression of ICAM-1 in the intestine of the RAAA group was 0.74 +/- 0.15, significantly higher than that of the sham operation group (0.14 +/- 0.05, P < 0.01) and that of the PDTC group (0.25 +/- 0.08, P < 0.01). The protein expression of NF-kappaB p65 in the lung of the RAAA group was 1.04 +/- 0.26, significantly higher than that of the PDTC group (0.52 +/- 0.13, P < 0.01). The protein expression of NF-kappaB p65 in the intestine of the RAAA group was 1.20 +/- 0.30, significantly higher than that of the PDTC group (0.64 +/- 0.21, P < 0.01). The protein expression of ICAM-1 in the lung of the RAAA group was 0.40 +/- 0.12, significantly higher than that of the PDTC group (0.18 +/- 0.06, P < 0.01). The protein expression of ICAM-1 in the intestine of the RAAA group was 0.46 +/- 0.15, significantly higher than that of the PDTC group (0.22 +/- 0.05, P < 0.01). Immunohistochemistry showed that NF-kappaB p65 and ICAM-1 positive cells were widely distributed in the lungs and intestine of the RAAA group and were rarely distributed in the sham operation group. CONCLUSION: PDTC attenuates the multi-organ injury by inhibiting the expression of NF-kappaB p65, thus reducing the mRNA and protein expression of its downstream gene ICAM-1 gene.

Animals↗

DNA damage evaluated by gammaH2AX foci formation by a selective group of chemical/physical stressors.

It has been reported that the phosphorylated form of histone variant H2AX (gammaH2AX) plays an important role in the recruitment of DNA repair and checkpoint proteins to sites of DNA damage, particularly at double strand breaks (DSBs). Using gammaH2AX foci formation as an indicator for DNA damage, several chemicals/stress factors were chosen to assess their ability to induce gammaH2AX foci in a 24h time frame in a human amnion FL cell line. Two direct-acting genotoxins, methyl methanesulfonate (MMS) and N-ethyl-N-nitrosourea (ENU), can induce gammaH2AX foci formation in a time- and dose-dependent manner. Similarly, an indirect-acting genotoxin, benzo[a]pyrene (BP), also induced the formation of gammaH2AX foci in a time- and dose-dependent manner. Another indirect genotoxin, 2-acetyl-aminofluorene (AAF), did not induce gammaH2AX foci formation in FL cells; however, AAF can induce gammaH2AX foci formation in Chinese hamster CHL cells. Neutral comet assays also revealed the induction of DNA strand breaks by these agents. In contrast, epigenetic carcinogens azathioprine and cyclosporine A, as well as non-carcinogen dimethyl sulfoxide, did not induce gammaH2AX foci formation in FL cells. In addition, heat shock and hypertonic saline did not induce gammaH2AX foci. Cell survival analyses indicated that the induction of gammaH2AX is not correlated with the cytotoxic effects of these agents/factors. Taken together, these results suggest that gammaH2AX foci formation could be used for evaluating DNA damage; however, the different cell types used may play an important role in determining gammaH2AX foci formation induced by a specific agent.

2-Acetylaminofluorene↗

Innate immune dysfunction in HIV infection: effect of HIV envelope-NK cell interactions.

We have previously described a number of NK cell dysfunctions in HIV-viremic individuals. In the present study, we performed DNA microarray analysis followed by phenotypic and functional characterization in an effort to investigate which HIV envelope glycoproteins (gp120) affect the physiologic functions of NK cells. Upon treatment of NK cells with HIV gp120, DNA microarray analyses indicated up-regulation of several categories of genes that are associated with apoptosis, suppression of both cellular proliferation and survival, as well as down-regulation of genes that play a vital role in cell proliferation, innate immune defense mechanism, and cell survival. Both subtypes of gp120 suppressed NK cell cytotoxicity, proliferation, and the ability to secrete IFN-gamma. NK cells exposed to X4-subtype HIV gp120 showed a significant decrease in the levels of CC chemokines, while exposure to R5-subtype HIV gp120 had minimal effect. Extended exposure to HIV gp120 resulted in apoptosis of NK cells, further validating the microarray data. Our data demonstrate that exposure of NK cells to HIV envelope proteins results in profound cellular abnormalities at the level of gene expression as well as generic cell functions. These findings are likely to be a consequence of a direct HIV gp120-mediated effect on NK cells. Identification of specific surface receptors on NK cells that interact with HIV envelope proteins might explain how HIV is capable of circumventing innate immune defense mechanisms and establishing infection in susceptible individuals.

Apoptosis↗

Intermedin1-53 activates L-arginine/nitric oxide synthase/nitric oxide pathway in rat aortas.

Intermedin (IMD), a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) family, has similar or more potent vasodilatory and hypotensive actions than adrenomedullin (ADM) and CGRP. The present study was designed to observe the effects of synthetic rat IMD1-53 on L-arginine (L-Arg) cellular transport, nitric oxide synthase (NOS) activity, and nitric oxide (NO) production in the isolated rat aortic ring to illustrate its direct effect on the L-Arg/NOS/NO pathway in vasculature. IMD1-53 significantly increased NO production and cNOS activity in rat aortas and was more potent than equivalent ADM. But the peptides of both IMD and ADM had no effect on inducible NOS expression and activity. Otherwise, IMD1-53 induced a concentration-dependent increase in [3H]L-Arg transport and its effect was more potent than that of an equivalent concentration of ADM. Semiquantitative RT-PCR revealed that IMD1-53 significantly increased cationic amino acid transport (CAT)-1 and CAT-2B mRNA expression, and its effect was similar to that of ADM. All these results suggest that IMD1-53 might regulate vessel function homeostasis via upregulating the L-Arg/NOS/NO pathway.

Adrenomedullin↗

Inclusion of MUC1 (Ma695) in a panel of immunohistochemical markers is useful for distinguishing between endocervical and endometrial mucinous adenocarcinoma.

BACKGROUND: Distinguishing endocervical adenocarcinoma (ECA) from endometrial mucinous adenocarcinoma (EMMA) is clinically significant in view of the differences in their management and prognosis. In this study, we used a panel of tumor markers to determine their ability to distinguish between primary endocervical adenocarcinoma and primary endometrial mucinous adenocarcinoma. METHODS: Immunohistochemistry using monoclonal antibodies to MUC1 (Ma695), p16, estrogen receptor (ER), progesterone receptor (PR), and vimentin, was performed to examine 32 cases, including 18 EMMAs and 14 ECAs. For MUC1, cases were scored based on the percentage of staining pattern, apical, apical and cytoplasmic (A/C), or negative. For p16, cases were scored based on the percentage of cells stained. For the rest of the antibodies, semiquantitative scoring system was carried out. RESULTS: For MUC1, majority of EMMA (14 of 18 cases, 78%) showed A/C staining, whereas only few ECA (2 of 14, 14%) were positive. The difference of MUC1 expression in the two groups of malignancy was statistically significant (p < 0.001). Staining for p16 was positive in 10 of 14 (71%) ECA and 4 of 18 (22%) EMMA. Estrogen receptor was positive in 3 of 14 (21%) ECA and 17 of 18 (94%) EMMA. Progesterone receptor was positive in 3 of 14 (21%) ECA and 16 of 18 (89%) EMMA. Vimentin was positive in 1 of 14 (7%) ECA, and 9 of 18 (50%) EMA, with median and range of 0 (0-6), and 1.5 (0-9) respectively. CONCLUSION: A panel of immunohistochemical markers including MUC1, p16, ER, PR, and vimentin is recommended, when there is morphological and clinical doubt as to the primary site of endocervical or endometrial origin.

Journal Article↗