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Biomedical subjects

X Cai

Publications and source records attributed to X Cai.

At least 73 records · Page 4Linked to original sources

Hydrocephalus in the H-Tx rat: a monogenic disease?

The H-Tx rat is a genetic model of hydrocephalus for which thereis a poor understanding of the mode of inheritance. Previous studies suggested a polygenicmode of inheritance but the breeding data to supportthis hypothesis have not been reported. In an attempt to clarify the hereditary mode we have analyzed the data from eight generations of H-Tx rats and four generations of cross-matings between H-Tx rats and Sprague-Dawley (SD) rats. In the H-Tx rat colony 113 of 129 random brother-sister matings (87.60%) produced hydrocephalic offspring, with males and females being equally affected. The overall incidence varied greatly with an average of 30. 35%. In matings with more than three litters, all mating pairs yielded hydrocephalic pups. In cross-matings both hydrocephalic and normal H-Tx rats were mated with normal SD rats. No hydrocephalus was observed in the first generation of 124 pups (F1). Subsequent brother-sister matings of F1 animals generated hydrocephalic pups in the F2 generation with a lower incidence (4.67% in hydrocephalic HTx/SD matings and 5.11% in normal HTx/SD matings, respectively) than in the H-Tx rat colony (30.35%). Back-cross-matings between F2 rats and normal H-Tx rats yielded an incidence of hydrocephalus higher than that of the cross-matings but lower than that of the H-Tx colony. These data strongly suggest that the H-Tx rat is a homozygous carrier of an autosomal recessive hydrocephalus gene with incomplete penetrance. Furthermore, the data clearly rule out sex-linked and polygenic modes of inheritance and provide further insight with respect to genetic inheritance of hydrocephalus.

Animals↗

Association of the R485K polymorphism of the factor V gene with poor response to activated protein C and increased risk of coronary artery disease in the Chinese population.

Inherited predisposition to thrombosis contributes to the initiation and progression of coronary artery disease (CAD). The present study was designed to explore the relationship between genetic variation of coagulation factor V and occurrence of CAD. A total of 141 unrelated patients with CAD and 175 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) for variation detection in all 25 exons of the factor V gene. Among the study subjects, 55 CAD patients and 73 controls were evaluated at random for response to activated protein C (APC) by Coatest APC resistance test. Polymorphisms in exon 4, 10, 13 and 16 of factor V gene were documented [642G-->T(S156), 1628--> A(R485K), 4070A-->G(H1299R) and 5380G A(V1736M), respectively]. The study also identified a novel polymorphism 327A G in exon 2 which did not alter the amino acid residue. Leiden mutation (R506Q) was not detected in any of our 316 subjects. Among the five polymorphisms, the allele frequency of 1628G--> A was significantly different between the CAD patients and the controls (0.36 vs. 0.21, p < 0.05). Subjects homozygous or heterozygous for the A allele of 1628G-->A polymorphism had lower normalized APC ratios than those with the GG genotype in the CAD group (1.16+/-0.13 and 1.18+/-0.23 vs. 1.36+/-0.33, p <0.05) and in the controls, indicating that A(1628) allele was associated with a poor response to APC. We conclude that the 1628G-->A (R485K) polymorphism of factor V is associated with a poor response to APC and increased risk for CAD.

Activated Protein C Resistance↗

Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia.

Recent studies showed that arsenic trioxide (As2O3) could induce apoptosis and partial differentiation of leukemic promyelocytes. Here, we addressed the possible mechanisms underlying these two different effects. 1.0 microM As2O3-induced apoptosis was associated with condensation of the mitochondrial matrix, disruption of mitochondrial transmembrane potentials (DeltaPsim) and activation of caspase-3 in acute promyelocytic leukemia (APL) cells regardless of their sensitivity to all-trans retinoic acid (ATRA). All these effects were inhibited by dithiothreitol (DTT) and enhanced by buthionine sulfoximine (BSO). Furthermore, BSO could also render HL60 and U937 cells, which had the higher cellular catalase activity, sensitive to As2O3-induced apoptosis. Surprisingly, 1.0 microM As2O3 did not induce the DeltaPsim collapse and apoptosis, while 0.1 microM As2O3 induced partial differentiation of fresh BM cells from a de novo APL patient. In this study, we also showed that 0.2 mM DTT did not block low-dose As2O3-induced NB4 cell differentiation, and 0. 10.5 microM As2O3 did not induce differentiation of ATRA-resistant NB4-derived sublines, which were confirmed by cytomorphology, expression of CD11b, CD33 and CD14 as well as NBT reduction. Another interesting finding was that 0.10.5 microM As2O3 could also induce differentiation-related changes in ATRA-sensitive HL60 cells. However, the differentiation-inducing effect could not be seen in ATRA-resistant HL60 sublines with RARalpha mutation. Moreover, low-dose As2O3 and ATRA yielded similar gene expression profiles in APL cells. These results encouraged us to hypothesize that As2O3 induces APL cell differentiation through direct or indirect activation of retinoic acid receptor-related signaling pathway(s), while DeltaPsim collapse is the common mechanism of As2O3-induced apoptosis.

Antineoplastic Agents↗

Study on the growth inhibition of human multiple myeloma cells by an IL-6Ralpha mutant.

DM650, a soluble human IL-6Ralpha mutant with mutation of C277D/H280I, was previously shown to exhibit an antagonism to IL-6, which resulted in growth-inhibition of human multiple myeloma cell line AF-10 autocrining as the growth-stimulating factor. We investigated here the nature of the growth inhibition by examining cell apoptosis. Flow-cytometric analysis of the DNA fragmentation demonstrated that 7.2% of the AF-10 cells were apoptotic after 24 h of treatment with DM650. The constitutive gene expression of bcl-2 in AF-10 cells indicated that apoptosis suppressed by IL-6 was independent of bcl-2 regulation. The altered gene expression of c-myc and p53 suggested that a novel apoptosis pathway, other than that suppressed by IL-6, might be triggered by a complex of DM650 and IL-6.

Apoptosis↗

Thioguanine substitution alters DNA cleavage mediated by topoisomerase II.

Thiopurines and topoisomerase II-targeted drugs (e.g., etoposide) are widely used anticancer drugs. However, topoisomerase II-targeted drugs can cause acute myeloid leukemia, with the risk of this secondary leukemia linked to a genetic defect in thiopurine catabolism. Chronic thiopurines result in thioguanine substitution in DNA. The effect of these substitutions on DNA topoisomerase II activity is not known. Our goal was to determine whether deoxythioguanosine substitution alters DNA cleavage stabilized by human topoisomerase II. We studied four variations of a 40 mer oligonucleotide with a topoisomerase II cleavage site, each with a single deoxythioguanosine in a different position relative to the cleavage site (-1 or +2 in the top and +2 or +4 in the bottom strand). Deoxythioguanosine substitution caused position-dependent quantitative effects on cleavage. With the -1 or +2 top and +2 or +4 bottom substitutions, mean topoisomerase II-induced cleavage was 0.6-, 2.0-, 1.1-, and 3.3-fold that with the wild-type substrate (P=0. 011, < 0.008, 0.51, and < 0.001, respectively). In the presence of 100 microM etoposide, cleavage was enhanced for wild-type and all thioguanosine-modified substrates relative to no etoposide, with the +4 bottom substitution showing greater etoposide-induced cleavage than the wild-type substrate (P=0.015). We conclude that thioguanine incorporation alters the DNA cleavage induced by topoisomerase II in the presence and absence of etoposide, providing new insights to the mechanism of thiopurine effect and on the leukemogenesis of thiopurines, with or without topoisomerase inhibitors.

Base Sequence↗

Exact equations and scaling relations for f0 avalanche in the Bak-Sneppen evolution model.

An infinite hierarchy of exact equations is derived for the newly observed f0 avalanche in the Bak-Sneppen model. By solving the first-order exact equation, we find that the critical exponent gamma, governing the divergence of the average avalanche size, is exactly 1 (for all dimensions), which has been confirmed by extensive simulations. Solution of the gap equation yields another universal result rho = 1 (rho is the exponent of relaxation to attractor). Scaling relations are established among the critical exponents (gamma, tau, D, sigma, and nu) for the f0 avalanche.

Biological Evolution↗

Spatial-temporal correlations in the process to self-organized criticality.

A different type of spatial-temporal correlation in the process approaching the self-organized criticality is investigated for the two simple models for biological evolution. The changed behaviors of the position with minimum barrier are shown to be quantitatively different in the two models. Different results of the correlation are given for the two models. We argue that the correlation can be used, together with the power-law distributions, as criteria for self-organized criticality.

Biological Evolution↗

Different hierarchy of avalanches observed in the bak-sneppen evolution model

A quantity &fmacr; denoting the average fitness of an ecosystem is introduced in the Bak-Sneppen model. Through this quantity, a different hierarchy of avalanches, &fmacr;(0) avalanche, is observed in the evolution of Bak-Sneppen model. An exact gap equation, governing the self-organization of the model, is presented in terms of &fmacr;. It is found that self-organized threshold &fmacr;(c) can be exactly obtained. Two basic exponents of the new avalanche tau, avalanche distribution, and D, avalanche dimension are given through simulations of one- and two-dimensional Bak-Sneppen models. It is suggested that &fmacr; may be a good quantity in determining the emergence of criticality.

Journal Article↗

Analytic results for scaling function and moments for a different type of avalanche in the bak-sneppen evolution model

Starting from the master equation for the hierarchical structure of avalanches of a different kind within the frame of the Bak-Sneppen evolution model, we derive the exact formula of the scaling function describing the probability distribution of avalanches. The scaling function displays features required by the scaling ansatz and verified by simulations. Using the scaling function we investigate the avalanche moment, denoted by (Delta&fmacr;). It is found that for any non-negative integer k, (Delta&fmacr;) diverges as Delta&fmacr;(-k), which gives an infinite group of exact critical exponents. Simulation outcomes of avalanche moments with k=1,2,3, are found to be consistent with the corresponding analytical results.

Journal Article↗

Change in dimerization mode by removal of a single unsatisfied polar residue located at the interface.

The importance of unsatisfied hydrogen bonding potential on protein-protein interaction was studied. Two alternate modes of dimerization (conventional and flipped form) of an immunoglobulin light chain variable domain (V(L)) were previously identified. In the flipped form, interface residue Gln89 would have an unsatisfied hydrogen bonding potential. Removal of this Gln should render the flipped dimer as the more favorable quaternary form. High resolution crystallographic studies of the Q89A and Q89L mutants show, as we predicted, that these proteins indeed form flipped dimers with very similar interfaces. A small cavity is present in the Q89A mutant that is reflected in the approximately 100 times lower association constant than found for the Q89L mutant. The association constant of Q89A and Q89L proteins (4 x 10(6) M(-1) and >10(8) M(-1)) are 10- and 1,000-fold higher than that of the wild-type protein that forms conventional dimers clearly showing the energetic reasons for the flipped dimer formation.

Crystallography, X-Ray↗

[Histological and ultrastructural characteristics of interface membrane around aseptically loosened prostheses].

OBJECTIVE: To investigate the effect of wear particles on prosthetic loosening by analyzing the histological and ultrastructural characteristics of interface membrane around aseptically loosened prostheses. METHODS: Slices of interface membranes around aseptically loosened hip prostheses of 51 cases were stained with HE, Safranin O-Briliant green and CD68 Mab immunohistochemical technique respectively. The histological structure of the membranes and the kinds of wear particles and their distribution characters were observed. The size of particles and the number of CD68 positive cells were measured. Ultrastructure of cells in the membrane and the characters and size of the particles phagocytozed by M phi were also observed and measured. RESULTS: Interface membrane consisted of fibromatrix, fibroblasts, M phi[CD68 positive, occupying (23 +/- 5)% (x +/- s)], and foreign body giant cells. In the membranes at the site of osteolysis, great amount of UHMWPE particles, PMMA particles and Ti alloy or CoCr alloy particles collected at the side attaching to the implant and caused chronic foreign body inflammatory reaction. Most of the particles outside M phi were less than 15 microns while that inside M phi were less than 1 micron. Different kinds of wear particles could exist in the lysosomes of one M phi. No particles but cartilage-like tisses appeared in the membranes at the site without osteolysis. CONCLUSION: Wear particles in the interface membrane have relations with osteolysis and fibrous tissue proliferation at bone-implant interface, which plays an important role in aseptic loosening.

Granuloma, Foreign-Body↗

Arg485Lys polymorphism of factor V increases the risk of coronary artery disease in a Chinese population.

OBJECTIVE: To explore the relationship between genetic variation in coagulation factor V and the occurrence of coronary arterial disease (CAD). METHODS: Unrelated 86 patients with CAD and 102 healthy controls were analyzed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) to detect variations in the entire twenty-five exons of the factor V gene. RESULTS: Polymorphisms in exon 4 [642 G-->T (Ser156)], exon 10 [1628 G-->A (Arg485Lys)], exon 13 [4070 A-->G (His1299Arg)] and exon 16 [5380 G-->A (Val1736Met)] were documented. The study also identified a novel polymorphism in exon 2 (327 A-->G) which did not result in amino acid residue substitution. The Leiden mutation (Arg506Gln) was not detected in any of our 188 subjects. Among the 5 polymorphisms, the allele frequency of 1628 G-->A was significantly different between CAD patients and controls (0.69 vs 0.81, chi 2 = 6.908, P < 0.01). This is the first report of this finding in a Chinese population. CONCLUSION: 1628 G-->A polymorphism is associated with CAD and it may be a risk factor for CAD morbidity in the Chinese population.

Aged↗

[Intraoperative endoscopic sphincterotomy for common bile duct stones during laparoscopic cholecystectomy].

OBJECTIVE: To assess the effects of approach-intraoperative endoscopic sphincterotomy (IOES) for common bile duct (CBD) stones during laparoscopic cholecystectomy (LC). METHODS: Twenty-seven patients with secondary CBD stones were treated by IOES during LC. Therapeutic effects were evaluated on the basis of the cure rate, early complications, and days of hospitalization. RESULTS: IOES was successfully performed in 26 (96.30%) of 27 cases, and their CBD stones were cleared completely. Two cases (7.69%) were complicated by mild acute pancreatitis. CONCLUSION: IOES as an alternative to the treatment of CBD stones during LC is safe and avoids reoperation.

Adult↗

[Computer-aided compose panoramic arthroscopic images of the temporomandibular joint].

OBJECTIVE: The computer-aided image processing method is established to compose arthroscopic images of temporomandibular joints(TMJs). METHODS: Arthroscopic images were input directly into a personal computer and recorded at a compact disk. By using the software- Photoshop 5.0 for Window 95, the images were edited and adjusted to form sagittal and/or coronal panoramic images of articular surfaces. RESULTS: The normal sagittal and coronal two-dimensional integrated panoramic arthroscopic images of TMJ were obtained, and qualities of these images were satisfied. CONCLUSION: The arthroscopic panoramic images established by using this method can demonstrate integrated structures of articular surfaces directly.

Arthroscopy↗

[Clinical application of computed arthroscope of the temporomandibular joint].

OBJECTIVE: The effect of clinical application on the computed arthroscope of the temporomandibular joint (TMJ) is evaluated. METHODS: The single arthroscopic images were input into computer and memorized into magneto optical disk. With the help of Photoshop 5.0 in WINDOWS 95, the images were combined by technique of virtual process, adjusted by rotation of images, marginal blur, and chromatism correction to compound sagittal and/or coronal panoramic images of articular surfaces. According to different needs, the composite images can be printed with different printers. During the period from May 1998 to May 1999, the TMJ preoperative panoramic images were composed with computed arthroscope (CA) in the 32 joints. Of them, there were 12 joints with internal derangement (ID), 8 osteoarthrosis (OA), 8 adhesion, 2 disk perforation, and 2 synovial chondromatosis. The post-operative panoramic images were also made up to evaluate the surgical effects in 10 joints. RESULTS: In all of 32 joints, the 32 panoramic arthroscopic images of upper cavities were composed. In addition, the images of lower cavities were composed in 2 OA and 1 perforation. The postoperative panoramic images were also made up in 4 OA, 4 adhesion, and 2 synovial chondromatosis. All of the above-mentioned images showed integrally the entire structure of articular cavity, intracapsular pathologic/surgical appearances, and the relationships among the different tissues or articular surfaces. CONCLUSION: The CA can enhance the comprehensive ability of diagnostic arthroscope, and help to exchange and spread the experiences of the TMJ arthroscopic surgery.

Arthroscopy↗

[Isolation and identification of a killing maggots bacterium].

A notably killing maggots bacterium was isolated from natural dead maggots in the manure pits in the countryside of Yancheng. Its pathogenicity was confirmed by the law of KOCK. The results of preliminary bioassay show that the pathogen can infect the larvas of greenbottle flies and other larvas of flies in a certain extent, but can't infect animals and fowls. The G + C content of its DNA is 62.46%. The hybridization ratio of its DNA and the Pseudomonas pseudoalcaligenes' (AS1.1806) is 81.2%. According to Bergey's Manual of Systematic Bacteriology Ninth edition, the strain of the bacterium was primarily identified as Pseudomonas pseudoalcaligenes.

Animals↗

[Cloning and expression of metallothionein gene of Bombyx mori].

Yeast MTI gene from vector pCMI-1 was used as a probe. It appeared strong hybridization signals when the total DNA of Bombyx mori Huishu eggs hybridizes with the probe. The 1-6 kb DNA fragments were isolated from the EcoR I digested total DNA of Bombyx mori Huishu eggs and ligated with M13- vector digested by restriction EcoR I. The ligation mixtures were used to transform E. coli DH5 alpha. blue/White colonies selection was used to identify colonies with insert. Approximately 4000 white colonies were selected, so the part genomic library of Bombyx mori was constructed. Three positive colonies were gained from the genomic library by southern blotting analysis, designated T1 (pZHC-1), T5 (pZHC-5), T7 (pZHC-7). Digesting the recombinant plasmid pZHC-5 with 12 restriction enzymes, the results suggested that the inserted fragment was about 1.2 kb and there was only a Hind III site. The experiment of resistant to CuSO4 proved that the DH5 alpha cells contain recombinant plasmids were more resistance than the recepient DH5 alpha cells. According to these results, the inserted fragment possibly contains the gene encoding Metallothionein of Bombyx mori. The sequence analysis of the inserted fragment and its high-expressions in E. coli are in progress.

Animals↗