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Biomedical subjects

M Song

Publications and source records attributed to M Song.

At least 19 recordsLinked to original sources

Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse.

Voltage-dependent calcium channels (VDCC) have a key role in neuronal function transforming the voltage signals into intracellular calcium signals. They are composed of the pore-forming alpha(1) and the regulatory alpha(2)delta, gamma and beta subunits. Molecular and functional studies have revealed which alpha(1) subunit gene product is the molecular constituent of each class of native calcium channel (L, N, P/Q, R and T type). Electrophysiological and immunocytochemical studies have suggested that at adult mouse motor nerve terminal (MNT) only P/Q type channels, formed by alpha(1A) subunit, mediate evoked transmitter release. The generation of alpha(1A)-null mutant mice offers an opportunity to study the expression and localization of calcium channels at a synapse with complete loss of P/Q calcium channel. We have investigated the expression and localization of VDCCs alpha(1) and beta subunits at the wild type (WT) and knockout (KO) mouse neuromuscular junction (NMJ) using fluorescence immunocytochemistry. The alpha(1A) subunit was observed only at WT NMJ and was absent at denervated muscles and at KO NMJ. The subunits alpha(1B), alpha(1D) and alpha(1E) were also present at WT NMJ and they were over- expressed at KO NMJ suggesting a compensatory expression due to the lack of the alpha(1A). On the other hand, the beta(1b), beta(2a) and beta(4) were present at the same levels in both genotypes. The presence of other types of VDCC at WT NMJ indicate that they may play other roles in the signaling process which have not been elucidated and also shows that other types of VDCC are able to substitute the alpha(1A) subunit, P/Q channel under certain pathological conditions.

Animals↗

Direct measurement of poloidal long-wavelength E x B flows in the HT-7 tokamak.

The poloidal long-wavelength E x B time-varying flows were directly measured using a forked Langmuir probe in the HT-7 tokamak. Low-frequency (<10 kHz) E x B flows were observed at the plasma edge, which possess many of the characteristics of zonal flows, including a poloidal long-wavelength (k(theta)rho(i) approximately 0) and narrow radial extent (k(r)rho(i) approximately 0.1). The cross bicoherence of turbulent Reynolds stress indicates the existence of nonlinear three-wave coupling processes and the generation of low-frequency E x B flows. The estimated flow-shearing rate is of the same order of magnitude as the turbulence decorrelation rate and may thus regulate the fluctuation level and thereby the turbulence-driven transport.

Journal Article↗

In situ observation of the formation of Fe3O4 in Fe4N (001) due to electron irradiation.

gamma(')-Fe4N was subjected to electron irradiation with the dose rate of 6.8 x 10(23)e m(-2) s(-1) in a 400 kV transmission electron microscope. The first in situ observation of the formation of Fe3O4 (O) on Fe4N (gamma(')) with the orientation relationship of [100](O) parallel [100](gamma(')) and <001>(O) parallel <001>(gamma(')) has been made inside the microscope with the basic column vacuum of (5-6) x 10(-5) Pa. A mechanism is proposed involving the electron-stimulated dissociation of Fe-N chemical bonds, desorption of nitrogen from the surface, adsorption of oxygen to the surface, and the oxidization of excessive metallic iron on the surface.

Journal Article↗

Altered functional coupling of coronary K+ channels in diabetic dyslipidemic pigs is prevented by exercise.

Chronic hyperglycemia and hypercholesterolemia have been shown to alter ionic currents in vascular smooth muscle. We tested the hypothesis that the combined effect of hyperglycemia and hyperlipidemia (diabetic dyslipidemia) would increase the Ca2+-sensitive K+ (KCa) current as a compensatory response to an increase in intracellular Ca2+ concentration. We also hypothesized that exercise training would prevent this elevation in KCa current. Miniature Yucatan swine were randomly assigned to five groups: control, standard pig chow (C, n = 6); hyperlipidemic, high-fat pig chow (H, n = 5); diabetic, standard pig chow (D, n = 7); diabetic, high-fat pig chow ("diabetic dyslipidemic," DD, n = 12); and exercise-trained DD (DDX, n = 9). High-fat chow consisted of standard minipig chow supplemented with cholesterol (2%) and coconut oil. Increased coronary vasoconstriction assessed in vivo and in vitro in DD was prevented by exercise. Patch-clamp experiments performed on right coronary artery smooth muscle cells resulted in greater K+ current densities in the H, D, and DD groups vs. the DDX group between -10 and 40 mV. In fura 2-loaded cells, current activated by caffeine-induced Ca2+ release was greater in H, D, and DD compared with C and DDX (P < 0.05), whereas intracellular Ca2+ concentration was not different across groups. Finally, there were no differences in the KCa or Kv channel protein content between groups. These data indicate that hyperglycemia, hyperlipidemia, and diabetic dyslipidemia lead to elevated whole cell K+ current and increased functional coupling of KCa and Ca2+ release. Endurance exercise prevented increased coupling of Ca2+ release to KCa channel activation in diabetic dyslipidemia.

Animals↗

Two cases of cross-sensitivity in subjects allergic to paraphenylenediamine following ingestion of Polaronil.

We report the cases of 2 women presenting allergy to paraphenylenediamine (PPD). Both patients had a history of eczema that worsened following the ingestion of the antihistamine Polaronil (dexamethasone/dexchlorpheniramine). This clinical presentation could be explained by cross-sensitivity to sulfanilic acid (4-aminobenzene sulfonic acid), a metabolite of sunset yellow (FD&C No. 6). Sunset yellow is an azo dye present in this tablet. Indeed, PPD-allergic subjects may suffer from cross-sensitivity to related compounds, especially to those that can be ingested such as azo dyes. Such compounds are used in some instances by the food and pharmaceutical industries, but their presence is often undisclosed.

Adult↗

Kinetics of KB and HEp-2 cell responses to an invasive, cytolethal distending toxin-producing strain of Actinobacillus actinomycetemcomitans.

The periodontal pathogen Actinobacillus actinomycetemcomitans produces cytolethal distending toxin (CDT), a complex multicomponent toxin that arrests the growth of many types of eukaryotic cell. The kinetics of the effects of CDT-containing extracts, from an invasive strain of this bacterium, were examined on epithelial-like cells routinely used in invasion studies. Both KB and HEp-2 cells were exquisitely sensitive to the effects of the CDT with TD50 of 30 and 300 pg of total bacterial protein, respectively. Initial cell morphology changes were relatively rapid, occurring within the first 13 h of exposure. CDT-treated KB cells increased in size to 4-5 times the size of untreated controls. Cytotoxicity was irreversible when attached cells were incubated, for a minimum of 120 min, with nanogram quantities of CDT-containing extract. As cultures aged, the cells became more resistant to the effects of the CDT-containing extracts. These findings have important implications for understanding the ability of A. actinomycetemcomitans to invade and multiply in epithelial cells.

Adolescent↗

Allergic contact dermatitis from cosmetics. Retrospective analysis of 819 patch-tested patients.

BACKGROUND: Cosmetics have been used since the oldest known civilisations, and nowadays almost everybody resorts to beauty products. OBJECTIVE: Considering the increasing incidence of contact dermatitis, the aim of the study is to determine the impact of allergy to cosmetics. METHODS: From January 1998 to December 1999, 819 patients were subjected to epicutaneous tests for suspicion of allergic contact dermatitis (ACD). The results were analysed retrospectively in the total population and in that of children under 16: the interest has been focused on cosmetics. RESULTS: 297 patients (36.3%) with ACD to 1 or more cosmetic ingredients have been detected. 34 (48.6%) out of 70 children patch tested showed an ACD: cosmetics represented the first cause. CONCLUSION: For two decades, the incidence of ACD has been rising; two main reasons can be put forward: a rising product consumption and a more exhaustive allergen research in patch testing.

Adolescent↗

A case of early congenital syphilis.

A case of early congenital syphilis is reported in order to emphasize that syphilis is still present nowadays and that detection of syphilis in pregnant women is primordial for the prevention of this disease.

Female↗

Multiple HPV-positive basal cell carcinomas on the abdomen in a young pregnant woman.

Basal cell carcinoma (BCC) is the most common malignant skin tumour. In the last few years, the incidence of multiple BCC has also increased in young patients. We describe the clinical case of a young 29-year-old woman who developed 7 BCC on her abdomen during her first pregnancy and 4 other similar tumours 2 years later during her second pregnancy, all located on the abdomen. Polymerase chain reaction revealed the presence of numerous human papillomavirus DNA sequences. To our knowledge, such a clinical presentation has not been previously reported. Different physiopathological considerations are discussed.

Basal Cell Carcinoma↗

Design and synthesis of new inhibitors of HIV-1 protease dimerization with conformationally constrained templates.

To inhibit the HIV-1 protease dimerization necessary to exhibit enzymatic activity, we synthesized and evaluated a new beta-sheet peptide (compound 1), containing 4-(2-aminoethyl)-6-dibenzofuranpropionic acid as a conformationally restricted linker and a non-peptidic beta-strand mimetic, 2-[3-([2-[(9-fluorenylmethoxy)carbonyl]hydrazino]carbonyl)-4-methoxyanilino]-2-oxoacetic acid (Fmoc-Hao-OH, compound 2). Kinetic analysis showed that compound 1 inhibited the dimerization of HIV-1 protease by a dissociative mechanism with a K(id) value of 5.4 microM at 37 degrees C (pH 5.0). However, compound 2 showed a small shift in the slope of the lines in the Zhang-Poorman plot (K(id)=9.1 microM), suggesting that compound 2 inhibits the dimerization of HIV-1 PR not only through a dissociative mechanism but also through an active-site directed mechanism partly. This is the first study of a non-peptidic inhibitor of HIV-1 protease dimerization.

Dimerization↗

Angiogenic role for glycodelin in tumorigenesis.

Angiogenesis plays an important role in neovascularization in tumors. Glycodelin, a hormone-responsive protein, has been detected in tumors of reproductive organs and is found in high levels in the plasma of subjects with gynecological malignancies. Glycodelin is also found in the endothelial cells of the umbilical cord and in the blood vessels of tumors. In this study, we tested whether glycodelin-rich amniotic fluid and a synthetic peptide derived from the sequence of glycodelin peptide (Gp) might promote angiogenic response by examining the migration and tube formation in human umbilical cord vein endothelial cells (HUVECs). Increased migration and tube formation of HUVECs were found in the presence of amniotic fluid and Gp, and this increase was blocked by antibody to Gp and by an anti-vascular endothelial growth factor (VEGF) antibody, suggesting that the angiogenic effects of glycodelin might be mediated by VEGF. The results also showed that Gp significantly increased the release of VEGF protein and mRNA expression in HUVECs, RL-95 (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma cells), EM42 (human endometrial epithelial cells), THP-1 (human monocyte), and MCF-7 and MDA-MB-231 (human breast adenocarcinoma cells) cell lines. VEGF receptor Fit-1 mRNA expression in HUVECs was also increased in the presence of Gp. These findings, together with the suggestion from the literature that glycodelin may have immunosuppressive properties, suggest that glycodelin might play an important role in neovascularization during embryogenesis and tumor development.

Amino Acid Sequence↗

Remodeling of Kv4.3 potassium channel gene expression under the control of sex hormones.

Kv4.3 channels are important molecular components of transient K(+) currents (Ito currents) in brain and heart. They are involved in setting the frequency of neuronal firing and heart pacing. Altered Kv4.3 channel expression has been demonstrated under pathological conditions like heart failure indicating their critical role in heart function. Thyroid hormone studies suggest that their expression in the heart may be hormonally regulated. To explore the possibility that sex hormones control Kv4.3 expression, we investigated whether its expression changes in the pregnant uterus. This organ represents a unique model to study Ito currents, because it possesses this type of K(+) current and undergoes dramatic changes in function and excitability during pregnancy. We cloned Kv4.3 channel from myometrium and found that its protein and transcript expression is greatly diminished during pregnancy. Experiments in ovariectomized rats demonstrate that estrogen is one mechanism responsible for the dramatic reduction in Kv4.3 expression and function prior to parturition. Furthermore, the reduction of plasma membrane Kv4.3 protein is accompanied by a perinuclear localization suggesting that cell trafficking is also controlled by sex hormones. Thus, estrogen remodels the expression of Kv4.3 in myometrium by directly diminishing its transcription and, indirectly, by altering Kv4.3 delivery to the plasma membrane.

Animals↗

Molten-globule structure and membrane binding of the N-terminal protease-resistant domain (63-193) of the steroidogenic acute regulatory protein (StAR).

The first step in steroidogenesis is the movement of cholesterol from the outer to inner mitochondrial membrane; this movement is facilitated by the steroidogenic acute regulatory protein (StAR). StAR has molten-globule properties at low pH and a protease-resistant N-terminal domain at pH 4 and pH 8 comprising residues 63-193. To explore the mechanism of action of StAR we investigated the structural properties of the bacterially expressed N-terminal domain (63-193 StAR) using CD, limited proteolysis and NMR. Far- and near-UV CD showed that the amount of secondary structure was greater at acidic than at neutral pH, but there was little tertiary structure at any pH. Unlike 63-193 StAR liberated from N-62 StAR by proteolysis, biosynthetic 63-193 StAR was no longer resistant to trypsin or proteinase K at pH 7, or to pepsin at pH 4. Addition of trifluoroethanol and SDS increased secondary structure at pH 7, and dodecylphosphocholine and CHAPS increased secondary structure at pH 2, pH 4 and pH 7. However, none of these conditions induced tertiary structure, as monitored by near-UV CD or NMR. Liposomes of phosphatidylcholine, phosphatidylserine and their mixture increased secondary structure of 63-193 StAR at pH 7, as monitored by far-UV CD, and stable protein-liposome complexes were identified by gel-permeation chromatography. These results provide further evidence that the N-terminal domain of StAR is a molten globule, and provide evidence that this conformation facilitates the interaction of the N-terminal domain of StAR with membranes. We suggest that this interaction is the key to understanding the mechanism of StAR's action.

Gene Products, env↗

Decreased expression of voltage- and Ca(2+)-activated K(+) channels in coronary smooth muscle during aging.

Aging is the main risk factor for coronary artery disease. One characteristic of aging coronary arteries is their enhanced contractile responses to endothelial vasoconstricting factors, which increase the risk of coronary vasospasm in older people. Because large-conductance voltage- and Ca(2+)-activated K(+) channels (MaxiK) are key regulators of vascular tone, we explored the possibility that this class of channels is diminished with increasing age. Using site-directed antibodies recognizing the pore-forming alpha subunit and electrophysiological methods, we demonstrate that the number of MaxiK channels is dramatically diminished in aged coronary arteries from old F344 rats. Channel density was reduced from 52+/-9 channels/pF (3 months old) to 18+/-5 channels/pF (25 to 30 months old), which represents a 65% reduction in the older population. Pixel intensity of Western blots was also diminished by approximately 50%. Moreover, the age-related decrease in the channel protein expression was also evident in humans, which showed approximately 80% reduction in 61- to 70-year-old subjects compared with 3- to 18-year-old youngsters and approximately 45% reduction compared with 19- to 56-year-old adults. In agreement with a reduction of MaxiK channel numbers in aging coronary arteries, old coronary arteries from F344 rats contract less effectively ( approximately 70% reduction) than young coronary arteries when exposed to the MaxiK channel blocker iberiotoxin. The contraction studies indicate that under physiological conditions, MaxiK channels are tonically active, serving as a hyperpolarizing force that opposes contraction. Thus, reduced expression of MaxiK channels in aged coronary arteries would lead to a decreased vasodilating capacity and increased risk of coronary spasm and myocardial ischemia in older people.

Adolescent↗

Accuracy of intravascular ultrasound for diameter measurement of phantom arteries.

BACKGROUND: Uniplanar quantitative angiography (QA) is the standard method for measuring vessel diameter during surgical and endovascular procedures. Intravascular ultrasound (IVUS), a relatively new technology, is another means of obtaining this measurement. This study was designed to validate the accuracy of these two modalities by comparing each to direct caliper measurement, the gold standard, using phantom femoral artery segments (PAS). MATERIALS AND METHODS: PAS diameter was measured with a 12.5-MHz mechanically rotating IVUS catheter (Boston Scientific Corp.) and QA (OEC Corp.) was compared to the direct caliper measurement (Mitutoyo Corp.) at 60 different locations within PAS. At each location minimal lumen diameter and perpendicular lumen diameter were measured and their mean was calculated. The intraclass correlation coefficients (ICCC) between direct caliper measurement and IVUS and uniplanar and biplanar angiography were calculated. Fisher's Z transformation was used to compare the correlation coefficients. RESULTS: The ICCC for IVUS was 0.89. The ICCCs for uniplanar and biplanar angiography were 0.73 and 0.82, respectively. IVUS correlated more closely with direct caliper measurement than uniplanar and biplanar angiography (P = 0.00008, 0.02) Biplanar angiography correlated more closely with direct caliper measurement than uniplanar angiography (P = 0.04). CONCLUSIONS: IVUS more accurately measures lumen diameter than uniplanar or biplanar angiography. Diameter measurement with biplanar angiography is more accurate than uniplanar angiography.

Angiography↗