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Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 955 records · Page 53Linked to original sources

Development of a guinea-pig model for potency/immunogenicity evaluation of diphtheria, tetanus acellular pertussis (DTaP) and Haemophilus influenzae type b polysaccharide conjugate vaccines.

We have evaluated a guinea pig model for assessing the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines, acellular pertussis vaccine and combination vaccines-consisting of tetanus toxoid (TT), diphtheria toxoid (DT), acellular pertussis vaccine and Hib-TT (Hib-T) conjugate vaccine. The model was based on the United States (US) potency test for TT and DT which requires injection of guinea pigs with a single dose of undiluted vaccine. Guinea pigs showed dose-dependent antibody responses to pertussis toxoid (PTxd) and filamentous haemagglutinin (FHA), two important components of acellular pertussis vaccine. Antibody response of guinea pigs to commercially available Hib conjugate vaccines qualitatively resembled those of human infants. Unconjugated polyribosylribitolphosphate (PRP) was not immunogenic; PRP-D conjugate produced a low antibody response, HbOC, PRP-T (Merieux) and Hib-T (MPHBL) produced a low response to the first dose and a strong anamnestic response to the booster dose. PRP-OMP uniquely produced a strong response after the first dose which was boosted by the second dose. In preliminary experiments, injection of guinea pigs with the combined vaccine formulations consisting of TT, DT, whole cell or acellular pertussis vaccine (Ptxd and FHA) and Hib-T conjugate showed that these vaccines were immunogenic when combined, with some effects on the antibody responses of certain components. This model for testing potency/immunogenicity of combined vaccines substantially reduces the number of animals needed to test each lot of vaccine. To reduce the use of animals in testing vaccines further, we propose the use of a Vero cell assay for titrating diphtheria antitoxin and ELISA for measuring IgG antibody to tetanus toxin. The guinea pig model may also be useful for evaluating combination vaccines.

Animal Testing Alternatives↗

Allosteric uncoupling after chronic benzodiazepine exposure of recombinant gamma-aminobutyric acid(A) receptors expressed in Sf9 cells: ligand efficacy and subtype selectivity.

By using the baculovirus expression system, we report decreases in allosteric coupling at individual gamma-aminobutyric acid (GABA)(A) receptor subtypes (alpha-1, beta-2 and gamma-2, alpha-2, beta-3 and gamma-2 and alpha-5, beta-3 and gamma-2) after chronic benzodiazepine exposure that replicate coupling changes measured in rat cortical membranes after in vivo benzodiazepine exposure. The appearance of uncoupling was time-dependent and the magnitude of uncoupling at expressed GABA(A) receptor subtypes after chronic exposure was dependent upon the efficacy of the ligand in a subtype-specific manner. In addition, the expression of uncoupling was not accompanied by changes in benzodiazepine receptor number or affinity at any expressed GABA(A) subtype examined. The specificity of the coupling change was further shown by the ability of a brief exposure to the benzodiazepine receptor antagonist, Ro15-1788, to reverse the uncoupling induced by chronic benzodiazepine exposure. These findings suggest that alterations at the GABA(A) receptor complex after chronic benzodiazepine exposure are mediated directly by agonist effects at the GABA(A) receptor complex and are not the product of the changes in the surrounding neuronal environment. Furthermore, the present study shows that drug efficacy, and not simply affinity, plays a critical role in determining the degree of uncoupling, and perhaps, in the development of tolerance and dependence.

Allosteric Regulation↗

Improved and simplified methods for specifying positions of the electrode bands of a cochlear implant array.

OBJECTIVE: To develop techniques for measuring the positions of the individual electrodes of a multiple channel cochlear implant and for estimating associated characteristic frequencies. BACKGROUND: Information concerning the positions of the individual electrodes of a cochlear implant array is important for analyzing speech perception or psychophysical data and for optimizing speech-processing strategies. This study presents two techniques for obtaining such information from postoperative plain film radiographs. METHODS: A template spiral shape, derived from analysis of the radiographs of 30 cochlear implant patients, is used to obtain measurements of the angular positions of the electrode bands within scala tympani. A research technique measures angular positions and estimates characteristic frequencies for all electrode bands but requires that the positions of two cochlear landmarks and all electrode bands be digitized. A clinical technique provides similar angle and frequency estimates but requires a minimum of information to be extracted visually from the radiograph. The lateral positions of the bands are estimated, in the research technique, using mean outer and inner wall functions obtained from 11 Silastic molds of scala tympani. RESULTS: The mean position of the implanted array relative to the mean scala tympani outer wall function was consistent with published histologic observations of implanted temporal bones. Measured angles did not vary greatly with experimenter or with rotation of the cochlea relative to the radiographic beam by up to 20 degrees. CONCLUSIONS: The techniques described allow, principally, measurement of the longitudinal positions of the bands of a cochlear implant in scala tympani and estimation of corresponding characteristic frequencies.

Cochlea↗

Studies on the reaction model for the immobilized Streptomyces aureofaciens's protoplasts used to convert lincomycin.

A reaction kinetic model is proposed for immobilized S. aureofacien's protoplasts which can facilitate the conversion of lincomycin into clindamycin. The simulation result of the model has been given. Effects of various kinetic parameters of the reaction on the conversion rate are given in the formula. The formulas which can be used to calculate the maximum conversion rate and the optimal reaction time have been given. The results of model simulation are in good agreement with the experimental results.

Clindamycin↗

Effects of selective head cooling on brain cell membrane activity during postischemic reperfusion.

OBJECTIVE: To examine the effect of selective head cooling (SHC) on brain cell membrane activity involving ATPase, phospholipase A2, content of total membrane phospholipids during postischemic reperfusion, so as to elucidate the possible underlying mechanism on resuscitating effect of SHC. MATERIALS AND METHODS: Complete cerebral ischemia (CCI) was induced by the four-vessel model. 56 New Zealand rabbits were allocated randomly into two groups, non-ischemic control group had 30, 180 and 360 minutes reperfusion after CCI (n = 8); and SHC group with the same ischemic-reperfusion insult were all treated with SHC (28 degrees C, surface cooling method). Changes of Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase, phospholipase A2, total phospholipids of brain cell membrane were observed. Comparison of data between two groups was made by Students' t test. RESULTS: Compared with non-ischemic controls following 30 minutes CCI, activities of Na+, K(+)-ATPase stepwisely decreased at 30, 180 and 360 minutes, Ca2+, Mg(2+)-ATPase dropped at 180 and 360 minutes, phospholipidase A2 increased markedly at 30, 180, 360 minutes, and total phospholipids decreased at 180 and 360 minutes reperfusion (P < 0.01). Selective head cooling inhibited all the above changes significantly (P < 0.01). CONCLUSION: The results suggest that selective head cooling initiated soon after reperfusion is beneficial for brain cell membrane function recruitment, which provides favourable effects on the damaged but still remediable brain cells for their resuscitation.

Animals↗

[Cleft palate repair with a combined method of mucosal flap pushback of the hard palate].

From January of 1992, we applied a combined method to repair cleft palate in 20 patients and received satisfactory results. The method is characterized by pushing back the mucosal flap of the hard palate, a Z-plasty on the nasal mucosa, repositioning the levator muscle to lengthen the palate, circumferential pharyng oplasty using denervated extensor hallucis brevis muscle, without making relaxing incisions and elevating the mucoperiosteal flap, avoiding interference to the greater and lesser palatine vessels and nerves, without relaxing palatal aponeurosis. The advantages of this method are preserving the normal anatomy and function of the palate and nasopharyngeal cavity, improving the function of velopharyngeal closure and minimizing secondary deformities.

Adolescent↗

[A study on neural regeneration after experimental epikeratophakia].

OBJECTIVE: To assess the effect of epikeratophakia (EKP) on corneal nerve regeneration and the recovery of corneal sensitivity. METHODS: 36 adult rabbits underwent epikeratophakia with either 0.2 mm or 0.3-0.35 mm circular trephination. A histochemical technique (acetylcholine esterase staining) was used to investigate the process of corneal nerve regeneration, and the recovery of corneal sensitivity was determined in 36 rabbits at various intervals after EKP. RESULTS: The corneal sensory nerves began to regenerate just peripheral to the host-donor interface 3 weeks following EKP, the nerve fibers traveled toward the stroma of the lenticules at 2 months, and formed a sparse subepithelial plexus at 8 months after surgery. A relative hyposthesia was found in the central zone of the lenticule when compared with its peripheral zone 4 months postoperatively. The sensitivity of the central zone remained lower at 5-8 months after EKP though it had remarkably increased. The density of re-innervated fibers was higher in the shallow incision than that in deeper one. CONCLUSION: It is suggested that the factors affecting the corneal innervation and the recovery of corneal sensitivity following EKP include; (1) the scar formation as a barrier; (2) the adaptation to the micro-environment around the lenticule; and (3) the depth of trephine cut. Therefore, a 0.2-0.25 mm depth of trephine incision is advantageous to the lamellar dissection, graft suturation and corneal nerve regeneration.

Animals↗

Promotion of differentiation and proliferation of peripheral blood CD34+ cells in vitro by G-CSF.

OBJECTIVE: To observe the effect of granulocyte-colony stimulating factor (G-CSF) on differentiation and proliferation of CD34+ cells from peripheral blood in presence of recombinant hematopoietic growth factor (HGF). METHODS: Peripheral blood mononuclear cells mobilized by G-CSF were obtained from patients suffering from carcinoma, preparing for autologous bone marrow transplantation. CD34+ cells were isolated by derivatized polystyrene tissue culture flask which had covalently immobilized soybean agglutinin lectin and was coated with anti-CD34 antibody; and this kind of cells were incubated in liquid culture medium for up to 28 days under the stimulation of combination of growth factors, i.e., stem cell factor (SCF) and interleukin-3 (IL-3) with or without G-CSF. The changes of nucleated cells, colony forming unit-granulocyte and monocyte (CFU-GM), burst forming unit-erythrocyte (BFU-E), colony forming unit-megakaryocyte (CFU-MK), and myeloid-associated markers were evaluated. RESULTS: An increase of nucleated cells (mean 640-fold increase) occurred during culture CFU-GM production is parallel to the nucleated cell production until the 11th day (mean 82-fold increase) in combination of 3 HGF, i.e., G-CSF, IL-3 and SCF. A large number of cells expressing late myeloid markers appeared on the 11th day in suspension culture of CD34+ cells. CONCLUSION: G-CSF was found to synergize with IL-3 and SCF in inducing rapid proliferation of purified CD34+ cells and differentiation to multiple myeloid lineages. The stroma-free, cytokine-driven culture system could achieve a degree of amplification of colony forming cells, suggesting the feasibility of culture of hematopoietic progenitor cells in vitro as an adjunct to hematopoietic stem cell transplantation.

Antigens, CD34↗

[Granulocyte-macrophage colony-stimulating factor (GM-CSF), preclinical and phase I clinical investigations].

OBJECTIVE: To conduct preclinical studies and phase I trial of the recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). METHODS: Pharmacodynamics, pharmacokinetic and toxicology of the rhGM-CSF were studied in animal models, and the safety was also evaluated in humans. RESULTS: The human bone marrow cells could be stimulated by purified rhGM-CSF to form multilineage colonies (CFU-GM and BFU-E). The rhGM-CSF administered for 7 days to Beagle dogs and monkeys subjected to 60Co r-ray irradiation was shown to induce both rapid and sustained increase in circulating leukocyte counts. Toxicology testing showed that the LD50 (i.v) was over 5000 micrograms/kg, and LD50 (i.p) over 10000 micrograms/kg in mice. Administration of the rhGM-CSF in excess of four times as much as clinical dosages was not associated with severe chronic toxicities. Most injected rhGM-CSF was excreted from urine, and did not accumulate in the body. In the phase I clinical trial, injecting 2.5-7.5 micrograms/day of rhGM-CSF was safe. CONCLUSION: It is effective and safe to use rhGM-CSF in the treatment of leukocytopenia.

Adolescent↗

[Navelbine as a single agent to treat advanced breast cancers].

From March 1994 to March 1995, 14 cases of refractory advanced breast cancers were treated with Navelbine (NVB). NVB as a single agent was given weekly 40-60mg (24.9mg-33.3 mg/m2), every 2 weeks for one cycle. Six of fourteen cases (42.9%) achieved partial response (PR). The median remission duration of PR patients was 5 months (range 2-10 months). NVB was given 85 times, the main side effects were myalgia and arthralgia (80.0%), phlebitis (57.6%). Sixty-five of eighty five pretreatment WBC counts were below 4.0 x 10(9)/L, and the severity of leukopenia was related to pretreatment WBC level. No patient died of infection.

Adult↗

[Clinical application of repeated tissue expansion].

Since 1992, the technique of repeated tissue expansion has been used to repair defects from resection of burn scars. Ten patients were treated with this technique and obtained satisfactory results. The clinical application demonstrated that a new expander could be placed again at the time of the expanded flap advancement for repeated expansion. The operative procedure, advantages, indications and key points were discussed. We concluded that repeated tissue expansion is an effective technique for the repair of large skin defects.

Adult↗

[Experimental study on adenosine hypothesis of bradyarrhythmias occurring in myocardial hypoxia and its clinical significance].

Important role of endogenous adenosine in the pathogenesis of hypoxic bradyarrhythmias was verified experimentally both in vivo and in vitro models of myocardial hypoxia in 180 guinea pigs and 40 rabbits by using enzyme differential spectrophotometry, synchronous quantitative analysis of correlated factors and adenosine antagonist. Results disclosed that endogenous adenosine in hypoxic myocardium increased markedly from a gram myocardial tissue 5.8 +/- 1.7 nmol of the control group to 27.5 +/- 2.0 nmol of 5% O2 inhalation group (P < 0.01). Sinus bradycardia and A-V block induced by injection of exogenous adenosine were closely akin to those caused by myocardial hypoxia both in ECG characteristics and dose-response curve. Both of their His electrograms showed prolongation of A-H interval but nochange of H-V interval, indicating the same locality of conduction block. Synchronous quantitative analysis of 3 related factors revealed a correlation coefficient of 0.99 (P < 0.01) between endogenous adenosine and bradyarrhythmias, denoting a subordinate instead of coordinate relation. Moreover, cause and effect relation could be shown between them from the result that aminophylline (50 mg, i.p.) could abolish completely II degrees-III degrees A-V block which would otherwise be bound to occur after inhalation of 5% O2. The present study is the first in vivo experimental verification of adenosine hypothesis throughout the world which not only can well explain those atropine-resistant cases, but also opens up the way to an entirely new therapeutic strategy for these kinds of bradyarrhythmias, i.e. instead of M-cholinoceptor blocker, adenosine antagonist (methylxanthines, e.g. aminophylline) should be prescribed.

Adenosine↗

[Study on correlation between postures and gastroesophageal reflux].

Simultaneous esophageal and gastric manometry and intraesophageal pH monitoring were performed in 12 patients with gastroesophageal reflux diseases in order to compare the frequency and mechanism of reflux in upright and supine postures. It was found that there was no differences in the number of reflux episodes, acid clearance time and percentage time of pH below 4 (P > 0.05). Frequency of reflux associated with lower esophageal sphinter relaxation (LESR) and gastric press increase was similar in two postures (P > 0.05). The results suggest that upright reflux may be as important as supine reflux in the development of reflux esophagitis. The main machanism of reflux in the two postures is LESR. Increase of gastric press may be a factor leading to gastroesophageal reflux.

Adult↗

[Studies on the septal ultrastructure of Armilaria mellea].

The structure and development of septum in Armillaria mellea were studied under the electronmicroscope. Hyphal septum was developed by inside wall of hyphae in cross direction, leaving a small pore in the center. Then the septal plate arround the pore became swollen, and formed a septal pore apparatus called dolipore septum. With subsequent development of endoplasmic reticulum septal pore caps appeared on each side of the pore. Organelles, such as mitochondrium and Golgi body in hyphal cells were all related with the development of septa. Thin-walled narrow hyphae of the medualla in mature rhizomorph were in a state of dormancy, and their septa were similar to those of the hyphae growing from liquid fermentation. Both of them were short of septal pore caps, but the latter had larger septal pores, the protoplasm flow from cell to cell through the pore was visible, and fusion rate between the hyphae was much higher. The relationship between the structural changes and functions of septa in A. mellea was also systematically discussed in this paper.

Agaricales↗

Comparative study on the mechanism of formation of pulse manifestations in coronary heart disease and hematopathic patients.

Most patients suffering from coronary heart disease have string--like pulse due mainly to disorder of cardiac function, lowered arterial compliance and increased total peripheral resistance. The common type of pulse in hematopathy patients is rapid, thready, string--like and slippery, due mainly to increased compensatory pumping action of heart, shortening of ejection time of left ventricle, relatively better vessel compliance and blood rheology as well as low total peripheral resistance.

Adolescent↗