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Biomedical subjects

C C Chen

Publications and source records attributed to C C Chen.

At least 487 records · Page 27Linked to original sources

Differentiation of renal Na(+)-K(+)-ATPase in control and streptozotocin-induced diabetic mice by G-protein acting toxins and phorbol esters.

The specific activity of Na(+)-K(+)-ATPase in the renal medulla and cortex of 50-day-old streptozotocin (STZ)-induced diabetic mice was increased 58% and 50%, respectively, as compared to controls. Km values of Na+ and K+ for this enzyme were unaltered, while that of ATP was decreased in diabetic mice. The Na(+)-K(+)-ATPase in control medulla and cortex was activated by both cholera and pertussis toxins, while this effect was abolished in diabetics. Since dibutyryl cAMP stimulates cortical Na(+)-K(+)-ATPase activity in control mice, the activation effect of cholera toxin on this enzyme might be due to its interaction with a Gs-protein and the persistent stimulation of adenylate cyclase activity, while the effect of pertussis toxin might be due to its masking of the inhibitory action of a Gi-protein on adenylate cyclase activity. However, the protein kinase C (PKC)-associated Na(+)-K(+)-ATPase might also be quiescent in diabetes, because the stimulating effect of phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on this enzyme was abolished in diabetic cortex. In addition, nicardipine and ouabain were found to have differential effects on this enzyme derived from control and diabetic mice.

Adenylate Cyclase Toxin↗

Dicentrine, a novel antiplatelet agent inhibiting thromboxane formation and increasing the cyclic AMP level of rabbit platelets.

Dicentrine is an antiplatelet agent isolated from the Chinese herb Lindera megaphylla. We examined the in vitro effects of dicentrine on various aspects of platelet reactivity. Dicentrine inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA), collagen, ADP, platelet-activating factor (PAF), thrombin and U46619. Dicentrine also inhibited the thromboxane B2 formation caused by AA, collagen and thrombin in washed intact platelets or that induced by AA in lysed platelet homogenate, while prostaglandin D2 formation caused by AA was not increased. The generation of inositol monophosphates (in the presence of indomethacin) caused by thrombin, collagen and PAF was not suppressed significantly, nor did dicentrine suppress fibrinogen-induced aggregation of elastase-treated platelets. Dicentrine inhibited the intracellular Ca2+ increase in quin-2/AM-loaded platelets caused by thrombin, PAF, collagen and AA. The cyclic AMP level was elevated by dicentrine in a concentration-dependent manner. These data indicate that the inhibitory effect of dicentrine on platelet aggregation and ATP release was due to the inhibition of thromboxane formation and the elevation of the level of cyclic AMP.

Adenosine Triphosphate↗

A molecular thermodynamic approach to predict the secondary structure of homopolypeptides in aqueous systems.

Under physiological conditions, many polypeptide chains spontaneously fold into discrete and tightly packed three-dimensional structures. The folded polypeptide chain conformation is believed to represent a minimum Gibbs energy of the system, governed by the weak interactions that operate between the amino acid residues and between the residues and the solvent. A semiempirical molecular thermodynamic model is proposed to represent the Gibbs energy of folding of aqueous homopolypeptide systems. The model takes into consideration both the entropy contribution and the enthalpy contribution of folding homopolypeptide chains in aqueous solutions. The entropy contribution is derived from the Flory-Huggins expression for the entropy of mixing. It accounts for the entropy loss in folding a random-coiled polypeptide chain into a specific polypeptide conformation. The enthalpy contribution is derived from a molecular segment-based Non-Random Two Liquid (NRTL) local composition model [H. Renon and J. M. Prausnitz (1968) AIChE J., Vol. 14, pp. 135-142; C.-C. Chen and L. B. Evans (1986) AIChE J., Vol. 32, pp. 444-454], which takes into consideration of the residue-residue, residue-solvent, and solvent-solvent binary physical interactions along with the local compositions of amino acid residues in aqueous homopolypeptides. The UNIFAC group contribution method [A. Fredenslund, R. L. Jones, and J. M. Prausnitz (1975) AIChE J., 21, 1086-1099; A. Fredenslund, J. Gmehling, and P. Rasmussen (1977) Vapor-Liquid Equilibrium Using UNIFAC, Elsevier Scientific Publishing Company, Amsterdam], developed originally to estimate the excess Gibbs energy of solutions of small molecules, was used to estimate the NRTL binary interaction parameters. The model yields a hydrophobicity scale for the 20 amino acid side chains, which compares favorably with established scales [Y. Nozaki and C. Tanford (1971) Journal of Biological Chemistry, Vol. 46, pp. 2211-2217; E. B. Leodidis and T. A. Hatton (1990) Journal of Physical Chemistry, Vol. 94, pp. 6411-6420]. In addition, the model generates qualitatively correct thermodynamic constants and it accurately predicts thermodynamically favorable folding of a number of aqueous homopolypeptides from random-coiled states into alpha-helices. The model further facilitates estimation of the Zimm-Bragg helix growth parameter s and the nucleation parameter sigma for amino acid residues [B. H. Zimm and J. K. Bragg (1959) Journal of Chemical Physics, Vol. 31, pp. 526-535]. The calculated values of the two parameters fall into the ranges suggested by Zimm and Bragg.

Models, Molecular↗

Sequence comparison of two highly homologous phycoerythrins differing in bilin composition.

Genes encoding the alpha and beta subunits of class II phycoerythrin from Synechococcus sp. strain WH8103 were cloned and sequenced. The deduced amino acid sequences were compared to class II phycoerythrin from Synechococcus sp. strain WH8020 and found to share 92% identity, yet the proteins differ in the bilin isomer (phycoerythrobilin versus phycourobilin) bound to two of the six chromophore attachment sites. Amino acid residues which might contact the bilin at each of the two variable sites were inferred by sequence alignment with phycocyanins. Putative bilin-contacting residues differing between the two phycoerythrins were identified which may determine bilin specificity.

Amino Acid Sequence↗

Anti-inflammatory and analgesic effects of magnolol.

Magnolol, isolated from Magnolia officinalis, inhibited mouse hind-paw edema induced by carrageenan, compound 48/80, polymyxin B and reversed passive Arthus reaction. Acetic acid-induced writhing response was depressed by magnolol, indomethacin and ibuprofen. The lethality of endotoxin challenge was reduced by pretreatment with magnolol, indomethacin and BW755C, a dual cyclo-oxygenase/lipoxygenase inhibitor. The recovered myeloperoxidase activity in edematous paw was significantly decreased in mice pretreated with magnolol and BW755C. Suppression of edema was demonstrated not only in normal mice but also in adrenalectomized animals. Magnolol was less potent on reducing PGD2 formation in rat mast cell than that of indomethacin. Unlike dexamethasone, magnolol did not increase liver glycogen level. The results suggest that the anti-inflammatory effect of magnolol was neither mediated by glucocorticoid activity nor through releasing steroid hormones from adrenal gland. The action of magnolol is proposed to be dependent on reducing the level of eicosanoid mediators.

Adrenalectomy↗

Meconium ileus-like condition in Chinese neonates.

Between January 1985 and May 1990, 16 neonates were treated for meconium ileus (MI) at this hospital. All babies were born to Chinese couples. Seven of them were premature, but none of them weighed less than 1,000 g. Eight patients underwent operations either because of mistaken diagnosis, as ileal atresia or long-segment Hirschsprung's disease, or because of complicated MI, including two meconium peritonitis and one associated with ileal atresia. Gastrograffin enema was successful in management of eight uncomplicated MI. The albumin content in the meconium of the last nine cases, including four complicated cases, ranged from 9.2 to 93.3 mg/g dry meconium. Usually, albumin is not present in normal meconium. All cases received sweat test, which were negative. Three patients died in the follow-up period. Sepsis of unknown origin, multiple congenital anomalies, and severe metabolic problems were the causes of death. The other 13 patients are doing well. They have exhibited no pulmonary or digestive problems during their follow-up period, which ranged from 11 months to 5 years. They are healthy and receive regular diets. Growth and development are appropriate for their age groups.

Albumins↗

Aerosol penetration through surgical masks.

BACKGROUND: Surgical masks are used in hospitals to reduce postoperative infection in patients. The presence of aerosols containing pathogens makes it desirable to protect the medical staff as well. METHODS: The collection efficiencies of surgical masks measured with two aerosol-size spectrometers. The flow rates through the masks were varied from 5 to 100 L/min to study the flow dependency. For comparison, several industrial-type respirators were also tested. RESULTS: A surgical mask consisting of filter material performed better than did a surgical mask consisting only of a shell with a coarse pore structure. The latter passed 80% of submicrometer-sized aerosols with little flow dependency, whereas the penetration of submicrometer-sized aerosols through the mask made of filter material ranged from 25% at a flow rate of 5 L/min to 70% at 100 L/min. CONCLUSIONS: The mask that has the highest collection efficiency is not necessarily the best mask from the perspective of the filter-quality factor, which considers not only the capture efficiency but also the air resistance. Although surgical mask media may be adequate to remove bacteria exhaled or expelled by health care workers, they may not be sufficient to remove the submicrometer-size aerosols containing pathogens to which these health care workers are potentially exposed.

Aerosols↗

Characteristics of face seal leakage in filtering facepieces.

Several studies have found that aerosol size, testing method, leak size, leak position, sampling probe location, and the mixing condition inside the respirator affect the results of fit factor measurements. This study focuses on the effect of leak shape and filter resistance because leaks have been reported to vary in shape from circular to slit-like. Four leaks of different shape but the same cross-sectional area were used to study their effect on aerosol penetration. Dust-mist and high-efficiency particulate air filtering facepieces provided different filter resistances. An aerodynamic particle sizer and a laser aerosol spectrometer were used to measure the particle size-dependent aerosol concentrations inside and outside the respirators. The filtering facepieces were sealed to a mannequin and artificial leaks were inserted near the right cheek. Aerosol penetration was measured for five flow rates ranging from 5 to 100 L/min. The pressure drop across the mask was monitored with an inclined manometer. At a given pressure differential, a slit-like leak and multiple circular leaks have been found to pass less aerosols than a single circular leak of equal cross-sectional area because the leak flow decreases with an increase in leak shape complexity. If there is substantial lack of face seal fit and the breathing rate is low, a HEPA respirator may provide less protection than a dust-mist respirator because the pressure drop is considerably higher for a HEPA respirator, resulting in more aerosol flow through the leak.

Aerosols↗

Aerosol penetration through filtering facepieces and respirator cartridges.

Air-purifying respirators must be certified following the National Institute for Occupational Safety and Health (NIOSH) filter test criteria (30 CFR 11). The criteria specify a range for the mean particle size and the measure of spread permissible for the test aerosol. The authors' experiments have shown that aerosol penetration as a function of particle size differs considerably among certified respirators of the same type. Filtering facepieces (disposable respirators) and cartridges of the dust-mist, dust-mist-fume, and high-efficiency particulate air type were tested. The respirators were sealed to mannequins in a test chamber. The aerosol concentrations inside and outside the respirator were measured by an aerodynamic particle sizer and a laser aerosol spectrometer over a particle size range of 0.1 to 15 microns. Five flow rates ranging from 5 to 100 L/min were used to study flow dependency. The aerosol penetration through the filters is presented as a function of particle size. Aerosol penetration and pressure drop are combined to express the performance of each filter in terms of "quality factor." Under the same test conditions, the quality factor of one respirator may be as much as 6.6 times more than that of another respirator of the same type. The filter quality factor has a greater aerosol size dependency as airflow and aerosol size increase. In general, cartridges have a larger surface area than filtering facepieces but not necessarily lower filter penetration or higher filter quality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Precorneal sampling techniques for ophthalmic gels.

Drug-cornea contact time is a critical issue in ocular drug delivery. Existing methods for its experimental determination are developed mainly for eye drops and ointments, and have not been reported for ophthalmic gels. The present study evaluated two tear film sampling techniques (capillary tubes and Schirmer strips) and one recovery technique (cotton swab) for their suitability for the determination of precorneal drug concentration as a function of time for ophthalmic gels. The study was conducted using the rabbit eye model, and the gel studied was a commercial polyacrylate-based gel containing pilocarpine HCl. The three techniques explored yield similar results with respect to drug-cornea contact time, about one hour for the gel studied. The strip method suffers from a gel-carry-over problem at the early time points; therefore it is not recommended for tear sampling until most of the gel is cleared from the cul-de-sac. Successful tear sampling was accomplished using capillary tubes. Drug concentration in the tear film as a function of time determined using this technique reveals not only the duration of contact between the drug and the cornea, but also demonstrates a nonuniform drug distribution in the tear film at the early time points (10 and 30 minutes). Finally the cotton swab technique is gentle, easy, and nondestructive. It recovers total drug remaining in the cul-de-sac but does not yield information for the tear film.

Animals↗

Abrogation of killing and neoplastic transformation of C3H10T1/2 cells due to 7,12-dimethylbenz[a]anthracene.

The combined action of 7,12-dimethylbenz[a]anthracene (DMBA) and alpha-naphthoflavone (alpha NF) on the survival and neoplastic transformation of C3H10T1/2 mouse embryo fibroblasts has been examined and correlated with DNA adduct formation and removal. When a 24 h DMBA treatment of asynchronously growing cells was followed for the next 24 h by a treatment with alpha NF + DMBA, both killing and transformation per viable cell were abrogated to a large extent. In some instances, transformation was completely abrogated--i.e. reduced to control frequencies--even at nontoxic concentrations of DMBA, indicating that changes in survival were not the reason for the reduction in transformation. Even at toxic concentrations of DMBA, post-treatment with alpha-NF + DMBA resulted in 10-fold reductions in transformation frequency. 3-Methylcholanthrene (3MC) also reversed DMBA cytotoxicity but with a dependence on 3MC concentration that was qualitatively different from that for alpha NF. The abrogation of cell killing occurred at lower molar ratios of alpha NF:DMBA than the abrogation of transformation; less than or equimolar concentrations resulted in maximal abrogation of killing, but about equal concentrations were required to abrogate transformation. Although the preceding findings suggest that different mechanisms may be involved in these endpoints, taken together they suggest that second treatments make apparent the repair of lesions due to a first treatment with DMBA alone. To test this hypothesis, the formation and removal of DMBA-DNA adducts were measured. Adducts were not removed when the second treatment was growth medium alone, but enhanced removal was observed when second treatments consisted of DMBA alone or DMBA plus one of several other polycyclic aromatic hydrocarbons (PAHs). Relative to killing and neoplastic transformation, these results suggest DMBA induces a repair process that limits its own effectiveness--a process that can be sustained by other PAHs.

9,10-Dimethyl-1,2-benzanthracene↗

Voluntary intake of alcohol is attenuated by ipsapirone in mice and role of 5-HT1A receptor.

Emerging evidences have suggested that the brain serotonin (5-hydroxytryptamine, 5-HT) neurotransmitter system is involved in the compulsive alcohol-seeking behaviors in humans and animal models. The aim of this study is to examine the effect of ipsapirone, which is a specific 5-HT1A agonist with a pyrimidinylpiperazine structure, on alcohol consumption in mice (C57BL/6J) by a voluntary alcohol intake paradigm. When the consumed alcohol was expressed as g/kg B.W., the total 12-day amount was significantly lower in the ipsapirone-treated mice than in the saline-treated mice. However, 5-HT1A receptor binding sites labeled with [3H]8-OH-DPAT in hippocampal membranes did not differ significantly in either the total number of binding sites (Bmax) or dissociation constant (Kd) between the two groups. The possible mechanism regarding the role of ipsapirone that attenuated the alcohol consumption, and its relationship to the subtyping 5-HT receptors are further discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Increase of xanthan production by cloning xps genes into wild-type Xanthomonas campestris.

Previously, genomic banks of Xanthomonas campestris were constructed in Escherichia coli, using mobilizable broad-host-range cosmids as the vectors. Following conjugal transfer, genes involved in the biosynthesis of xanthan polysaccharide (XPS) were cloned by the ability to restore the mucoid phenotype to the non-mucoid mutants. In this study, all clones were transferred into the wild-type strain Xc17 to evaluate the effects of the cloned genes on XPS production. Most clones showed no significant effect; however, two plasmids, pP2401 and pP2201, caused 10 and 15% yield increases, respectively, compared with that of controls. While it was not clear how pP2201 caused the yield increase, the effect of pP2401 seemed to result from elevated phosphomannose isomerase activity. Since XPS synthesis in X. campestris is a very efficient process, only relatively small increases are to be expected; an enhancement of productivity by 10-15% is important to the commercial production of xanthan.

Carbohydrate Sequence↗

Haemodynamic effects of dicentrine, a novel alpha 1-adrenoceptor antagonist: comparison with prazosin in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

1. The haemodynamic effects of dicentrine, an aporphine derivative isolated from the plant Lindera megaphylla, were investigated and compared with prazosin in rats. 2. In anaesthetized normotensive Wistar-Kyoto (WKY) rats, i.v. administration of dicentrine (0.1, 0.5, 1.0 mg kg-1) and prazosin (0.01, 0.05, 0.1 mg kg-1) induced a dose-related reduction of mean arterial pressure (MAP) which reached a maximal effect 5-10 min after injection and persisted for 2 h. 3. In anaesthetized WKY rats, a higher dose of dicentrine (1.0 mg kg-1, i.v.) did not cause any significant changes in heart rate (HR), cardiac output (CO) and stroke volume (SV) but markedly increased tail blood flow. In contrast, a higher dose of prazosin (0.1 mg kg-1, i.v.) produced a decrease in HR which paralleled the time course of the hypotensive response. 4. The hypotensive activity of dicentrine was completely abolished by alpha-adrenoceptor blockade. Both dicentrine and prazosin significantly attenuated pressor responses to noradrenaline but failed, even at maximal hypotensive doses, to impair the pressor effects of angiotensin II or vasopressin. These observations suggest that dicentrine appears to exert its hypotensive action through alpha 1-adrenoceptor blockade. 5. In conscious normotensive and spontaneously hypertensive (SH) rats, dicentrine (0.5-2.0 mg kg-1, i.v.) and prazosin (0.05-0.2 mg kg-1, i.v.) also evoked dose-related decreases in MAP which were of greater magnitude in SH rats. Oral administration of dicentrine (5 and 8 mg kg-1) to conscious SH rats caused a hypotensive effect which persisted for over 15 h.6. These results suggest that dicentrine may have therapeutic potential as an oral antihypertensive drug via alpha-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗