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Biomedical subjects

X Q Li

Publications and source records attributed to X Q Li.

At least 73 records · Page 4Linked to original sources

Cyclosporin A and tissue antigen matching in bone transplantation. Fibular allografts studied in the dog.

We studied the mechanical, metabolic, and histologic properties of short-term nonvascularized cortical bone grafts in a canine fibular graft model. Sham operated nonvascularized autotransplanted and allotransplanted bones were compared. The allografts were performed between dog leukocyte antigen (DLA) class I and II matched; DLA class I and II mismatched; and cyclosporin A (CsA) treated, DLA class I and II mismatched animals. Cyclosporin was given for 1 month, and all the animals were followed for 3 months after surgery. Mechanical properties were investigated using standard torsional tests, metabolic kinetics were assessed using isotopic prelabeling techniques, and histomorphometric analysis of cross-sectional area properties and sequential fluorochrome labels were performed. Autografts were mechanically stronger and stiffer than all the types of allograft. CsA-treated, DLA-mismatched allografts performed better than matched allografts. These in turn were stronger than non-CsA-treated, mismatched allografts, which underwent nearly complete resorption. These relationships were preserved in the metabolic and histologic analyses. In this short-term animal study, although DLA matching resulted in a slight improvement in graft outcome, mismatched grafts in dogs receiving a short course of cyclosporin A fared even better.

Animals↗

Age-related inequality between rates of formation and resorption in various whole bones of rats.

Variations in rates of bone turnover, consisting of bone formation and bone resorption, were characterized as a function of age and types of bone. Bone formation and bone resorption were quantified and compared in four ages of growing male rats (newborn, 0-2 weeks; weaning, 4-7 weeks; adolescence, 10-14 weeks; and mature, 15-23 weeks) for cephalic bone (calvaria), appendicular bone (femur), axial bones (sixth lumbar vertebrae and sternum), and the pelvis. In all four ages studied, inequality between the rates of bone formation and resorption existed in all bones, and the magnitude of the differences in metabolic imbalance turnover was age and bone type dependent. Formation was consistently higher than resorption in all five bones throughout the entire experimental periods. The ratio of resorption to formation was the lowest at birth (under 0.10:1) for all five bones and then increased. The most rapid bone growth in terms of bone calcium mass occurred at the weaning age (the net gain of calcium per bone per day was the highest) for all bones except the lumbar vertebrae, which occurred at adolescence. The magnitude of the inequality in the rates of bone formation and resorption was greatest in the newborn and diminished with age towards equality. At maturity, the ratio of resorption to formation was under 0.50:1 in the most dense or calcified bones such as the calvarium (0.40:1) and femur (0.49:1), and over 0.50:1 in the relatively thin cortex and well-trabeculated axial bones (0.60:1 in lumbar vertebrae and 0.75:1 in the sternum) and the pelvis (0.91:1). Additionally, large bones (calvaria, long bones, and pelvis) seemed to play an important role in regulating calcium homeostasis starting form the weanling age, since the amount of calcium released from each whole bone per day was high in these bones due to their large mass.

Aging↗

[Relation of left ventricular compliance and heart size].

53 patients with myocardiopathy were studied to determine the left ventricular compliance (LVC) with apexcardiography and the heart size with radiography. Relation between LVC and heart size was analysed by using linear correlation. In cardiomyopathy LVC decreased and correlated with the size of heart. It was concluded that the size of heart was one of factors which influenced LVC. The decrease of LVC may be related with the length of myocyte, the geometric shape of heart and histopathologic alteration.

Adolescent↗

Reconstitution of the mitochondrial non-selective Na+/H+ (K+/H+) antiporter into proteoliposomes.

Mitochondria contain two Na+/H+ antiporters, one of which transports K+ as well as Na+. The physiological role of this non-selective Na+/H+ (K+/H+) antiporter is to provide mitochondrial volume homeostasis. The properties of this carrier have been well documented in intact mitochondria, and it has been identified as an 82,000-dalton inner membrane protein. The present studies were designed to solubilize and reconstitute this antiporter in order to permit its isolation and molecular characterization. Proteins from mitoplasts made from rat liver mitochondria were extracted with Triton X-100 in the presence of cardiolipin and reconstituted into phospholipid vesicles. The reconstituted proteoliposomes exhibited electroneutral 86Rb+ transport which was reversibly inhibited by Mg2+ and quinine with K0.5 values of approximately 150 and 300 microM, respectively. Incubation of reconstituted vesicles with dicyclohexylcarbodiimide resulted in irreversible inhibition of 86Rb+ uptake into proteoliposomes. Incubation of vesicles with [14C]dicyclohexylcarbodiimide resulted in labeling of an 82,000-dalton protein. These properties, which are also characteristic of the native Na+/H+ (K+/H+) antiporter, lead us to conclude that this mitochondrial carrier has been reconstituted into proteoliposomes with its known native properties intact.

Animals↗

The role and regulation of tumour-associated hyaluronan.

Significantly increased levels of the glycosaminoglycan hyaluronan are often associated with human and animal tumours. In the rabbit V2 carcinoma elevated levels of tumour-associated hyaluronan are also closely correlated with invasiveness. We have therefore initiated studies to better define the role and regulation of hyaluronan synthesis in tumour tissues. In cell culture many tumour cell types have reduced capacities to synthesize hyaluronan even when derived from tumours enriched in hyaluronan. We showed that several of these same cells can nevertheless stimulate hyaluronan synthesis by normal fibroblasts. In the LX-1 human lung carcinoma cell line this stimulatory potential resides in a membrane-bound, heat-sensitive, lipophilic, cell surface glycoprotein. These data suggest that production of tumour-associated hyaluronan occurs via tumour-stromal cell interactions. We recently demonstrated that some human tumour cells also possess unoccupied, high affinity, cell surface binding sites for hyaluronan which may allow tumour cells to interact directly with hyaluronan-enriched extracellular matrices. This interaction may in turn allow tumour cells to use hyaluronan as a support for adhesion and locomotion. The spatial organization of hyaluronan could then function to guide tumour cells into surrounding stroma. We attempted to visualize this spatial deposition of hyaluronan in situ within frozen sections of human tumour tissue using a morphological probe that specifically recognizes hyaluronan. Hyaluronan appears most prominently in the partially degraded connective tissue.

Animals↗

A pharmacokinetic model in the rat and rabbit of the direct measurement of mature bone resorption in vivo with [3H]tetracycline.

This report presents a pharmacokinetic model in the rat and rabbit of the direct quantification of mature bone resorption in vivo. This is based on a first-order reaction rate describing the release of [3H]tetracycline from bone. Compared with the previous method, the model has two new means of expressing bone resorption. First, resorption rate of bone is precisely represented by explicit parameters derived from the model. Second, resorption rate of the whole skeletal system is measured and demonstrated by means of plasma, renal, and bone kinetics of elimination of the isotope. These are represented by the model parameters, the elimination constant, and the half-life of [3H]tetracycline for plasma, urine, and bone. Four ages of normal Sprague Dawley rats and one age of New Zealand white rabbits of both sexes were prelabeled extensively with [3H]tetracycline in utero or during 10 to 84 d of age. Following 1-21 d after the end of prelabeling, the loss of the isotope from femur into plasma and urine was measured at weekly intervals to determine bone resorption of mineral in vivo. The elimination constants of the isotope per day in plasma were -0.148 in weaning rats (4-7 weeks), -0.071 in adolescent rats (10-14 weeks), and -0.025 in mature rats (15-23 weeks). The urinary elimination constants of the isotope per day were 74, 76, and 76% of those in plasma in weaning, adolescent, and mature rats, respectively. The half-lives of the isotope in the femur were 10 d in neonatal rats (0-2 weeks), 32 d in weaning rats, 63 d in adolescent rats, and 198 d in mature rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Accumulation of hyaluronate in human lung carcinoma as measured by a new hyaluronate ELISA.

We have developed a new ELISA to quantify hyaluronate. This ELISA takes advantage of an anti-keratan sulfate antibody to differentiate between the coated aggregating rat chondrosarcoma proteoglycan which captures the hyaluronate and the keratan sulfate-bearing aggregating proteoglycan added subsequently. Absorbance in this assay was shown to be linear to the logarithmic concentration of hyaluronate in the range of 15 to 1000 ng/ml. Pre-treatment of hyaluronate with papain or protease did not interfere with its quantification; in contrast, pre-treatment with 0.1N NaOH significantly interferes with the subsequent measurement of the hyaluronate molecules. The size of the hyaluronate molecule was found to be an important factor in quantification: only large size hyaluronate molecules could be quantified accurately. The ELISA was used to show that human lung carcinomas contain 2 to 500 times as much hyaluronate as normal lung tissue from the same patient.

Antibodies, Monoclonal↗

A new in vivo anti-viral assay using microencapsulated infected cell cultures.

Microencapsulation technology makes it possible to encapsulate virus infected human or animal cells in microcapsules with semipermeable membranes. These may be implanted intraperitoneally into mice which may then be treated with antiviral drugs. The implanted microcapsules may be recovered at various intervals following in vivo treatment and the effect of the drug is evaluated by assaying the virus titers inside the microcapsules. In this paper, the feasibility of this model was tested using microencapsulated human or non-human cells infected with herpes simplex virus type 1. The microcapsules were implanted in the peritoneal cavity of mice, and the effect of systematically administered acyclovir on HSV-1 replication was ascertained. We found that (a) HSV-1 can replicate in both human (A549 and FEMx) and non-human (Vero) cells after they are infected and encapsulated. (b) HSV-1 replication was inhibited by 0.005 microgram/ml to 0.08 mg/ml of acyclovir in the medium when virus producing A549 cells were encapsulated or when they were in monolayers. (c) Acyclovir (20-80 mg/kg), injected twice daily by intraperitoneal, subcutaneous or intravenous routes in mice, significantly inhibited HSV-1 production in encapsulated Vero cells implanted in the peritoneal cavity. The major advantage of this in vivo model is that it can be used to study antivirals in experimental animals in which viruses do not replicate in non-permissive animals. Toxicity, pharmacokinetic and efficacy data may be obtained. It can also be used to test drugs which require activation in vivo to be effective.

Acyclovir↗

Acute effects of noradrenalin related vasoactive agents on the ototoxicity of aspirin: an experimental study in the guinea pig.

Aspirin is known to be ototoxic when administered at high doses. Its mode of action is unknown but an alteration of the vascular function has been suspected. To further document this hypothesis, acute effects of some vasoactive agents on the ototoxicity of aspirin were tested in experiments on the guinea pig using sensori-neural electrophysiological responses and morphometry of the vessels of the stria and the spiral lamina. Electrophysiological measures showed no modification of sensory responses but neural responses revealed clear changes after administration of noradrenalin related agents, limited modifications after a drug acting partly as a serotonin antagonist, and no change after a dopaminergic agent. Morphometric studies showed no modification of the strial but some effect on the spiral vessels. The results are compatible with the hypothesis of a vascular involvement in the ototoxicity of aspirin and they point toward an interaction with the noradrenergic sympathetic cochlear system in the spiral lamina.

Animals↗

Inhibition of murine thymidylate synthase and human dihydrofolate reductase by 5,8-dideaza analogues of folic acid and aminopterin.

A series of 5,8-dideaza analogues of folic acid, isofolic acid, aminopterin, and isoaminopterin were evaluated for inhibition of thymidylate synthase, TS, from mouse L1210 leukemia cells with 10-propargyl-5,8-dideazafolic acid, CB3717, 4a, as the reference inhibitor. These compounds were also tested as inhibitors of human dihydrofolate reductase, DHFR, obtained from WIL2 cells. None of the analogues studied were as potent as 4a toward TS; however, 9-methyl-5,8-dideazaisoaminopterin, 6d, was only 2.5-fold less effective. Compound 4a was prepared by direct alkylation of the di-tert-butyl ester of 5,8-dideazafolic acid followed by hydrolysis of the resulting diethyl ester, which resulted from concomitant transesterification. It was found to be identical with a sample of 4a prepared by earlier methodology by using a variety of spectroscopic techniques. Its isomer, 9-propargyl-5,8-dideazaisofolic acid, 4b, which was synthesized by an analogous approach, was found to be dramatically less inhibitory toward TS than 4a. Each of the 2,4-diamino derivatives, including those possessing an allyl or propargyl group at N9, was an excellent inhibitor of DHFR, having a level of potency similar to that of methotrexate, MTX. However, many of these 5,8-dideazaaminopterin analogues were far more inhibitory toward TS than MTX.

Aminopterin↗

[Preliminary study on the antimutagenesis of vegetables and fruits].

Possible antimutation of 108 preparations of 91 kinds of vegetables and fruits on Salmonella typhimurium TA98 and TA100 mutants was tested. 4-nitroquinoline-N-oxide (4 NQO), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), aflatoxin B1 (AFB1) and benzo (a) pyrene (BaP) were used as mutagens. The results showed that 67 (62%) preparations had antimutagenic action in vitro to different degrees. 9.6% of all preparations showed inhibition action on 4 NQO in TA100 mutant and 12.3%, in TA98, 5% on MNNG in TA100, 38% on AFB1 in TA100 and 45.1% in TA98, 28.9% on BaP in TA100. This experiment provides a scientific basis to the study of food resources as prevention of carcinogenesis.

Animals↗