Search PubMed⌕ Search

Biomedical subjects

C Ma

Publications and source records attributed to C Ma.

At least 109 records · Page 6Linked to original sources

A unique pattern of photoreceptor degeneration in cyclin D1 mutant mice.

Cyclin D1-deficient mice have small eyes with thin retinas. We observed that there was a lower level of retinal cell proliferation and a unique pattern of photoreceptor cell death. Death was first observed in scattered clusters of cells in the retina. It then appeared to spread from these few cells to nearby photoreceptors, eventually producing extensive holes in the photoreceptor layer. These holes appeared to be filled with interneurons from the inner nuclear layer. The death mainly occurred during the second to fourth postnatal weeks. Other models of photoreceptor degeneration in rodents differ in that they occur more uniformly across the retina, with death proceeding over a longer period of time until all, or nearly all, of the photoreceptors degenerate. We also tested whether expression of a bcl-2 transgene could prevent the death and found that it could not.

Animals↗

Synthesis and evaluation of analogues of the partial agonist 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC) and the full agonist 6-(benzyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (Zk 93423) at wild type and recombinant GABAA receptors.

A pharmacophore and an alignment rule have previously been reported for BzR agonist ligands. The design and synthesis of 6-(propyloxy)-4-(methoxymethyl)-beta-carboline-3-carboxylic acid ethyl ester (6-PBC, 24, IC50 = 8.1 nM) was based on this pharmacophore. When evaluated in vivo this ligand exhibited anticonvulsant/anxiolytic activity but was devoid of the muscle relaxant/ataxic effects of "classical" 1,4-benzodiazepines (i.e., diazepam). Significantly, 6-PBC 24 also reversed diazepam-induced muscle relaxation in mice. The 3-substituted analogues 40-46 and 48 of 6-PBC 24 and Zk 93423 27(IC50 = 1 nM) were synthesized and evaluated in vitro to determine what affect these modifications would have on the binding affinity at recombinant BzR subtypes. With the exception of the 3-amino ligands 40 and 41, all the beta-carbolines were found to exhibit high binding affinity at BzR sites. The 3-propyl ether derivative 45 was also evaluated in vivo and found to be devoid of any proconvulsant or anticonvulsant activity at doses up to 40 mg/kg. The 6-(1-naphthylmethyloxy) and 6-octyloxy analogues 25, 26, 28, and 29 of 6-PBC 24 were synthesized to further evaluate the proposed alignment of agonists vs inverse agonists in the pharmacophore of the BzR. In addition, ligands 26 and 29 were designed to probe the dimensions of lipophilic pocket L3 at the agonist site. The activity of 29 was evaluated in vivo; however, this analogue elicited no pharmacological effects at doses up to 80 mg/kg. These and other related beta-carbolines were also examined in five recombinant GABAA receptor subtypes. Ligands 52-61 all exhibited moderate to high affinity at GABAA receptors containing alpha1 subunits. These ligands will be useful in further defining the pharmacophore at alpha1 beta3 gamma2 receptors.

Animals↗

Correlation of plasma clearance of 54 extensively metabolized drugs between humans and rats: mean allometric coefficient of 0.66.

PURPOSE: To evaluate the distribution of allometric exponents for relationship of total plasma clearance of 54 extensively metabolized drugs, with wide-ranging linear clearance values, between humans and rats, to provide a rationale for the observed data, and to discuss potential significance of the findings. METHODS: Human and rat plasma clearance values of 54 drugs with markedly different physicochemical properties were obtained from the literature. Standard allometric analysis was performed for each drug using both rat and human data. Unbound vs. total plasma clearances were obtained for 15 out of 54 drugs and their correlations between humans and rats were compared. RESULTS: The mean+/-SD of the allometric exponent for the 54 drugs studied is 0.660+/-0.190. The median clearance ratio based on unit body weight is 7.41 and the median exponent is 0.645. Excluding two outliers the correlation coefficient of plasma clearance between humans and rats was 0.745 (p < 0.0001). For the 15 drugs, use of unbound plasma clearance approach seems to significantly improve the correlation coefficient compared to total plasma clearance (0.940 vs. 0.841). CONCLUSIONS: The present study indicates that on average, humans and rats may eliminate extensively metabolized drugs at a rate similar to that expected from the allometric or body surface area relationship of basal metabolic rate between the two species. A simple statistical distribution hypothesis is used to rationalize the species difference in plasma drug clearance. Rat may serve as an useful animal model to predict (unbound) plasma clearance of drugs in humans.

Animals↗

A 3',5' cyclic AMP (cAMP) phosphodiesterase modulates cAMP levels and optimizes competence in Haemophilus influenzae Rd.

Changes in intracellular 3',5' cyclic AMP (cAMP) concentration regulate the development of natural competence in Haemophilus influenzae. In Escherichia coli, cAMP levels are modulated by a cAMP phosphodiesterase encoded by the cpdA gene. We have used several approaches to demonstrate that the homologous icc gene of H. influenzae encodes a functional cAMP phosphodiesterase and that this gene limits intracellular cAMP and thereby influences competence and other cAMP-dependent processes. In E. coli, expression of cloned icc reduced both cAMP-dependent sugar fermentation and beta-galactosidase expression, as has been shown for cpdA. In H. influenzae, an icc null mutation increased cAMP-dependent sugar fermentation and competence development in strains where these processes are limited by mutations reducing cAMP synthesis. When endogenous production of cAMP was eliminated by a cya mutation, an icc strain was 10,000-fold more sensitive to exogenous cAMP than an icc+ strain. The icc strain showed moderately elevated competence under noninducing conditions, as expected, but had subnormal competence increases at onset of stationary phase in rich medium, and on transfer to a nutrient-limited medium, suggesting that excessive cAMP may interfere with induction. Consistent with this finding, a cya strain cultured in 1 mM cAMP failed to develop maximal competence on transfer to inducing conditions. Thus, by limiting cAMP levels, the H. influenzae cAMP phosphodiesterase may coordinate its responses to nutritional stress, ensuring optimal competence development.

3',5'-Cyclic-AMP Phosphodiesterases↗

Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes.

The nematode Caenorhabditis elegans possesses six morphologically similar neurons that are responsible for sensing gentle touch to the body. Previous genetic studies identified genes that are necessary for the production and differentiation of these touch cells. In particular, unc-86 encodes a POU-type homeodomain protein needed for the production of the touch cells, while mec-3 encodes a LIM-type homeodomain protein needed for the differentiation of the touch cells. Molecular studies showed that MEC-3 and UNC-86 bind cooperatively to sites in the mec-3 promoter and can synergistically activate transcription from it in vitro. Here we show that UNC-86::MEC-3 hetero-oligomer-binding sites are also found in the promoters of two presumed targets of mec-3, the mec-4 and mec-7 genes, that are necessary for the function of the touch cells. These sites, which are well-conserved in the related nematode C. briggsae, are required for promoter activity. When one of the binding sites is cloned into a heterologous promoter, expression is found in the touch cells and two to four other cells that express mec-3 and unc-86. These data support a model in which touch-cell differentiation is specified, in part, by the UNC-86::MEC-3 hetero-oligomer and not by MEC-3 alone. Ectopic expression of mec-3, driven by a heat-shock promoter, also supports this hypothesis: the acquisition of touch-cell characteristics by several additional cells under these conditions required unc-86. Since the touch-cell lineages express UNC-86 before MEC-3, MEC-3 appears to modify the activity of UNC-86, leading to touch-cell-specific gene expression. Because both UNC-86 and MEC-3 have activation domains, the formation of the hetero-oligomer may create a strong activator. In the modification of UNC-86 function by MEC-3 in the touch cells, these studies provide an example of how the sequential activation of transcription factors can determine cell fate within particular cell lineages.

Animals↗

[High tibial osteotomy combined with autogenous periosteal graft for osteoarthritis of knee].

The osteoarthritis of knee is a common disorder but no always to be treated satisfactorily. Between 1988 and 1992, the method, a high tibial osteotomy to correct the genu varum combined with autogenous periosteal or perichondrial graft to deal with the chondromalacia patella was used. Thirty-two patients (51 knees) were treated by this method and the patients were followed up for an average of 5.1 years. The excellent and good results were obtained in 90.2%. This method was obviously better than any other simple high tibial osteotomy. Therefore, this method was considered to be effective for treatment of osteoarthritis of knee with varum deformity and chondromalcia patella.

Female↗

[Protective effect of hyperin on cerebral infarction in rats].

OBJECTIVE: To study the protective effect of hyperin (Hyp) on cerebral infarction. METHOD: The cerebral infarction in rats was made by ligating the right common carotid artery and the right middle cerebral artery. The infarction weight was determined by NBT stain. The cerebral cortex was taken to measure nitric oxide (NO) and malondialdehyde (MDA). The cerebral blood flow(CBF) was measured with H2 clearance method. RESULT: Hyp 6.25, 12.5, 25 mg.kg-1 markedly improved the abnormal nervous symptoms, and 12.5, 25 mg.kg-1 Hyp significantly reduced the infarction weight and inhibited the increase of MDA and NO in the cerebral cortex. Hyp(25, 12.5 mg.kg-1) could increase the CBF of the cerebral cortex. CONCLUSION: Hyp has a protective effect on cerebral infarction via attenuating lipid peroxidation and NO.

Animals↗

[Acetabular dysplasia:an experimental study].

OBJECTIVE: To demonstrate whether acetabular dysplasia represents a primary feature of congenital dislocation of the hip or secondary defect. METHOD: The capsule of twelve puppies aged five to nine weeks was incised and the ligamentum teres was completely severed under anaesthesia. A part of gluteal medium muscle was implanted in the acetabulum and the head of the femur was dislocated from acetabulum. Roentagenogram was made three weeks after dislocation in all animals. RESULT: As early as three weeks after dislocation, acetabular dysplasia was clearly noted in all animals. There was more acetabular obliquity and increase of acetabular index. CONCLUSION: The acetabular dysplasia is the result but not the cause of congenital dislocation of the hip. This result provides probably support for the concept of developmental dislocation of the hip.

Acetabulum↗

[Protective effect of hyperin against cerebral ischemia-reperfusion injury].

The protective effect of hyperin (Hyp) against cerebral ischemia-reperfusion injury was studied. On the cerebral ischemia-reperfusion model in mice, Hyp (50, 100 mg.kg-1, i.p.) was shown to markedly and dose-dependently inhibit the decrease of lactate dehydrogenase (LDH) in cerebrum and improve the learning and memory impairment on the step down test. On the four-vessel occlusion model in rats, Hyp(50 and 100 mg.kg-1, i.p.) significantly reduced the decreases of glutathione peroxidase(GSH-Px), superoxide dismutase(SOD) and LDH activities in the cerebrum. Hyp was also shown to inhibit the increase of nitric oxide (NO) and malondialdehyde (MDA) contents in the cerebrum and promote the recovery of EEG activities. These results suggest that Hyp has protective effect against cerebral ischemia-reperfusion injury via attenuating free radical and NO.

Animals↗

[Studies on analytical method for 10 drugs of abuse in urine using HPLC].

A systematic determination method for 10 drugs of abuse, morphine, codeine, 6-monoacetylmorphine, heroin, levorphanol, pethidine, ethylmorphine, anadol, pentazocine and ethamivan, using high performance liquid chromatography is described. Separation of the 10 drugs was achieved on a 25 cm x 4.6 mm ID, 10 microns Zorbax C8 column, using methanol--0.05 mol.L-1 KH2PO4--diethyl amine (27:73:0.5, pH 4) as mobile phase. Codeine was used as the interal standard. Calibration graphs were linear over the concentration range of 10-200 micrograms.ml-1 and regression equations showed correlation coefficients of greater than 0.999. Precision (RSD) were found to be better than 3% for each compound. Precision and linearity of the method are satisfactory for clinical toxicological applications. The extraction procedure yielded cleaner extracts. The recovery rates from urine were all above 87% without interference. This method is rapid, sensitive and specific.

Chromatography, High Pressure Liquid↗

[An epidemiological survey of schistosome cercarial dermatitis among the residents living along the banks of the Huaihe River system].

AIM: To make an epidemiological survey of schistosome cercarial dermatitis among the residents living along the banks of the Huaihe River. METHODS: Making inquiries about signs and symptoms of schistosome cercarial dermatitis, and physical examinations of manifestation in the residents (fishermen and peasants). Cercariae shed from the Radix auricularia collected in the field were used to infect ducklings. The eggs and miracidia separated from the feces of the full grown ducks bred by fishermen were used to infect Radix auricularia. RESULTS: Schistosome dermatitis locally known as "duck itch" (meaning duck-fecesdermatitis) was discovered among the residents living along the Huaihe River bank. The main signs and symptoms of the dermatitis included diffuse erythema or red papular eruption with areorae, urticae, urticant itch or titillation around the affected areas (including thoracic part, abdomen and lower limbs etc). The cercariae with eye spot were found from Radix auricularia collected from Huaihe riverside and were identified to be the species of Trichobilharzia can both hatch miracidium, which laboratory-reared Radix auricularia were infected with miracidia hatched from the two types of eggs, rhomboid eggs and crescent eggs, found in the feces of full grown ducks bred by fishermen and shed the same cereariae with eye spot. Besides, adult worms of Trichobiharzia were obtained by dissecting both experimentally infected ducklings bred in the laboratory and naturally infected ducks bred in the Huaihe river-side area. The above-mentioned eggs, miracidia, cercariae and adult worms were all identified to belong to the life-phase of Trichobilharzia. CONCLUSION: The epidemic disease known as schistosoma cercarial dermatitis harmful to the health of the residents living along the banks of Huaihe River is caused by the cercariae of Trichobilharzia.

Adult↗

Receptor-mediated endocytosis of antigens overcomes the requirement for HLA-DM in class II-restricted antigen presentation.

HLA-DM- APC are unable to present soluble Ags to T cells in the context of class II DR molecules. This defect in DM- APC can be overcome by receptor-mediated delivery of Ag into cells. Ag conjugated to ligands for cell surface receptors, such as transferrin or goat anti-human Ig, was processed and presented by DM- T2.DR4 cells. Intracellular processing of Ag conjugates was required, as receptor cross-linking alone did not restore presentation by DM- APC. Ag conjugates targeted by transferrin receptors to endosomes or via surface Ig to endosomal and lysosomal compartments, were each efficiently presented by DM- cells. These Ag conjugates were predominantly localized in light density endosomes in T2.DR4 cells. This study demonstrates that the facilitated uptake and sorting of exogenous Ag by cell surface receptors allow efficient class II-restricted presentation even in the absence of HLA-DM.

Antigen Presentation↗

A polarity field is established early in the development of the Drosophila compound eye.

The photoreceptors within the ommatidia of the Drosophila compound eye form a trapezoid. This occurs in two chiral forms in the dorsal and ventral half of the eye. We have used two manipulations to induce ectopic ommatidia, in combination with molecular markers for specific positions in the retinal field. We find that ectopic morphogenetic furrows induced on the eye field margin (or midline) and those induced in the body of the field have different consequences for the establishment of retinal polarity. Furthermore, the dorsal/ventral vector field is established early in development, prior to and independent of the initiation of the morphogenetic furrow. An 'early equator' model is presented to account for these and previously published data.

Animals↗

Subunit composition of pro-phenol oxidase from Manduca sexta: molecular cloning of subunit ProPO-P1.

Phenol oxidase (PO) is known to play an important role in defense mechanisms in insect immunity. It is present as a zymogen in insect hemolymph, and can be activated by a specific proteolytic reaction that is stimulated by microbial cell wall components. The pro-phenol oxidase (pro-PO) purified from the larval hemolymph of Manduca sexta contains two polypeptides in equal amounts as revealed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A cDNA for one of the polypeptides, now designated proPO-p2, has been isolated (Hall et al. (1995) Proc. Natl. Acad. Sci. USA, 92, 7764-7768). We purified pro-PO from plasma of M. sexta and characterized its subunit composition. A cDNA for M. sexta proPO-p1 was isolated from a larval hemocyte cDNA library. M. sexta proPO-p1 is 78% identical in amino acid sequence to Bombyx mori proPO-p1, but only 50% to M. sexta or B. mori proPO-p2. Immunofluorescence labelling and in situ hybridization showed that the pro-PO is synthesized in a single hemocyte type, the oenocytoids. Analysis of pro-PO by size exclusion high-pressure liquid chromatography (HPLC) revealed that pro-PO exists as monomeric, dimeric, trimeric or multimeric structures depending on the ionic strength. All of these isoforms of the protein have phenol oxidase activity upon activation with a detergent, cetylpyridinium chloride. In analysis by non-denaturing PAGE, the majority of the purified pro-PO was present as two dimers of distinct mobility (fast and slow forms). Both forms contain proPO-p1 and proPO-p2, suggesting that they are heterodimers. Individual larvae can contain the slow form, the fast form, or both, which suggests that the slow and fast forms of proPO are allelic variants. These results indicate that there are two pro-PO genes in M. sexta, which are coordinately expressed in oenocytoids, and whose products form predominantly heterodimers in plasma.

Amino Acid Sequence↗

[Cultivation of intra-pulmonary arteriolar smooth muscle cell from rabbit].

By perfusion with trypsin at low concentration, the intra -pulmonary arterioles were separated carefully and cut into fine tissue pieces. These pieces were then washed with culture medium and used for culture of smooth muscle cells by method of adhesion to wall. Cells cultured were typical smooth muscle cells under light microscope, electron microscope and immunohistochemical test. The method is simple and convenient. It is also applicable to culture of vascular smooth muscle cells from other organs and provides ideal materials for vascular physiopathologic studies.

Animals↗

[Revascularization of isolated bone in dogs].

To elucidate whether the revascularization of isolated bone could be built and what is the influence on osteogenesis. We studied eighteen adult mongrel dogs and divided them into three groups in random. Osteotomy was performed on the two condyles of the tibia and the periosteum was removed. Two pieces of silica gel sheet were inserted into the gaps of osteotomy to block blood supply, then immobolization was made. The vascular bundle of anterior tibia artery and vein was separated and ligated. Subsequently, it was directly implanted into the isolated bar of tibia (Group A, n = 7). It implanted after holes were made (Group B, n = 7). Controls (Group C, n = 4) were observed without transplantation. The animals were investigated by angiography, casting mode of vascular net, mass and histologic and electromircroscopeic examination at different intervals. Osteonecrosis was occurred in the tested bone because of ischemia. The proliferation of vascular net was occurred and prosperous osteogenesis was found in the medullary cavity after transplanting a vascular bundle. Revascularization of necrotic bone was able to be established by transplanting a vascular bundle. Both membranous and lndochondral ossification play an important role in osteogenesis.

Animals↗

[Chemical constituents of the leaves of Ginkgo biloba].

Four compounds were isolated from ethyl acetate extract of the leaves of Ginkgo biloba. Compounds II, III, IV were identified as ginkgolides A, B and C respectively, Compound I, which was obtained from the leaves of G. biloba for the first time, was identified as 3,3'-dimethoxy-4,4'-dihydroxy-stilbene by spectroscopic methods.

Diterpenes↗