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Biomedical subjects

X Ren

Publications and source records attributed to X Ren.

At least 91 records · Page 5Linked to original sources

Perspectives of pharmacotherapy in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of progressive decline of cognitive function in aged humans, and it is characterized by the presence of numerous senile plaques and neurofibrillary tangles accompanied by neuronal loss. The senile plaques are composed of amyloid beta-peptides (A beta), 40-42 amino acid peptide fragments of the beta-amyloid precursor protein. Genetic, molecular biological and neuropharmacological evidence support the 'amyloid cascade hypothesis' for the pathogenesis of the disease. We review the in vivo effects of various compounds on behavioral and neuropathological changes in the non-transgenic animal models of AD produced by continuous i.c.v. infusion of A beta. These results support therapeutic strategies such as cholinergic therapy, anti-inflammatory agents, antioxidants and estrogen replacement therapy, as well as other cognition enhancers for the treatment of AD. In addition, the amyloid cascade hypothesis offers a number of potential targets for novel therapeutic strategies in AD. We believe that our non-transgenic animal model, as well as transgenic animal models, are useful for developing novel pharmacotherapeutics in AD.

Alzheimer Disease↗

[Genetic linkage of polymorphisms of type I angiotensin II receptor gene to Chinese Han hypertension].

OBJECTIVE: To observe the CA repeat polymorphism of the type I angiotensin II receptor gene on Chinese Han people, and evaluate the genetic linking to hypertension. METHODS: The CA repeat polymorphism at 3'-flanking region of AT1R gene was studied by amplified fragment length polymorphism (Amp-FLP ) in Chinese Han people from Shandong and Xi'an. RESULTS: There were 9 alleles ranging from 130bp to 146bp in all subjects. The allele frequencies were 0.01 to 0.38, and allele A4 was more frequent in the control. The heterozygosity of CA repeat locus was 0.789, the polymorphic information content, 0.746. There was no significant difference in distribution of CA repeat polymorphism genotype between different regions in same ethnic (P>0. 05), but the allele frequency of CA repeat polymorphism in hypertensive group was significantly different from that of control (P<0.05). There was no detectable distortion from Hardy-Weinberg equilibrium in both groups. CONCLUSION: The results suggest that CA repeat polymorphism of AT1R gene be associated with Chinese Han hypertensive people.

Adult↗

Pharmacokinetic advantage of intra-arterial cyclosporin A delivery to vascularly isolated rabbit forelimb. I. Model development.

Effective antirejection therapy with minimal systemic morbidity is required if limb transplantation is to become a clinical reality. We investigated whether i.a. infusion of cyclosporin A (CSA) into the vascularly isolated rabbit forelimb will distribute drug homogeneously to the tissues and produce higher local drug levels than same-dose i.v. treatment, thereby improving the therapeutic index. CSA 4.0 mg/kg/day was infused continuously via osmotic minipump into either the right brachial artery (i.a. group) or jugular vein (i.v. group) of New Zealand rabbits. Ligation of all muscles at the right mid-arm level was performed in the i.a. group to eliminate collateral circulation and simulate allografting, while leaving bone and neurovasculature intact. On day 6, CSA concentrations were measured in skin, muscle, bone, and bone marrow samples taken from different compartments of the right and left forearms in the i.a. group and right forearm only in the i.v. group. There were no significant differences between compartmental CSA levels in all tissues examined on the locally treated, right side during i.a. infusion, indicating that drug streaming from the catheter tip is not occurring in our model. During i.a. infusion, mean CSA concentrations were 4- to 7-fold higher in the right limb than in the left limb in all four tissues examined. Tissue CSA levels in the left limb were equivalent to those achieved during i.v. infusion, but CSA concentrations in blood, kidney, and liver were higher during i.a. infusion. These favorable, preliminary, single-dose pharmacokinetic results warrant further investigation in our novel rabbit model.

Animals↗

Long-term survival of an extremity composite tissue allograft with FK506-mycophenolate mofetil therapy.

BACKGROUND: High-dose tacrolimus (FK506) monotherapy has significantly prolonged rat hindlimb allograft survival. With an eye toward direct clinical application, we used a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination FK506-mycophenolate mofetil (MMF) treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression and 9 animals received a once-daily oral FK506-MMF-prednisone regimen. Rejection was assessed by visual inspection of flap skin and was correlated with serial histopathologic examination of skin biopsy specimens. RESULTS: In all control pigs the flap was completely rejected on day 7. Of the 9 pigs receiving treatment, 3 died from pneumonia on days 29, 30, and 83 without signs of rejection and another died from gastric rupture on day 42 with persistent mild rejection. The remaining 5 animals were free of rejection at the end of the 90-day follow-up period (P < 0.005 vs controls). Overall, 5 pigs had pneumonia, 4 septic arthritis, 3 toe abscesses, and 5 diarrhea and decreased weight gain. CONCLUSIONS: Combination oral FK506-MMF treatment provided a superior antirejection effect but more produced more toxicity than that previously demonstrated with cyclosporin A-MMF therapy in our model. Our results suggest that reduction of FK506 or MMF doses might decrease both infectious and drug-specific side effects while still providing adequate prophylaxis against rejection.

Animals↗

[Study on electrochemical behavior of HL-60 cells during the etoposide-inducing apoptosis].

OBJECTIVE: To study the electrochemical behavior of apoptotic HL-60 cells induced with etoposide. METHODS: Electrochemical cytosensor was used to monitor HL-60 cells treated with etoposide. RESULTS: The peak current and electron transfer rate decreased as etoposide dosage increased. The decrease appeared at 2 micrograms/ml etoposide treatment and was remarkable at 20 micrograms/ml, which occurred before the typical changes of cell morphology and DNA contents for apoptosis. FCM-DNA analysis showed that the apoptotic cells were of 10.5%-20% while the peak current decreased from 1.8 microA to 0.4 microA after 2.3 and 4 hours treatment with 200 micrograms/ml etoposide, and the peak current after 4 hours treatment was 5 times lower than that before induction. CONCLUSION: The changes of electrochemical behavior during the early stage of apoptosis occurred earlier and could be accumulated.

Antineoplastic Agents, Phytogenic↗

[Detection of three common G6PD gene point mutations in Guangdong province by using ARMS].

OBJECTIVE: To detect three common G6PD gene point mutations, G1388A, G1376T and A95G, in Guangdong province and to estimate the approximate frequencies. METHODS: Using the amplification refractory mutation system(ARMS) method to detect G1388A and G1376T and the newly developed ARMS to identify A95G mutation. RESULTS: Ninety cases of G6PD deficient male were examined, and 42 of them were identified to be G1388A(46.7%), 14 G1376T(15.6%), and 12 A95G(13.3%). Totally 68 out of the 90 cases(75.6%) were of the three common mutations. The rest belong to rare or undefined mutations. CONCLUSION: ARMS method can be used in detecting common mutations of G6PD gene with the benefits of simple, fast, economic, and accurate.

Alleles↗

[Studies on a G6PD polymorphic site, cDNA C1311T].

OBJECTIVE: To use amplification refractory mutation system(ARMS) method to detect the G6PD cDNA C1311T mutation, estimate its frequency in a normal south Chinese population, and investigate whether IVS-11 C93T mutation is the cause of certain G6PD deficient cases. METHODS: DNA sequencing was used to confirm the C1311T and the IVS-11 C93T mutations. ARMS was set up to detect the C1311T and to estimate its frequency. RESULTS: Three cases of C1311T mutation were found in 40 G6PD deficient samples. The optimal condition for ARMS was established. Using this method, 19 cases of C1311T were detected in 103 normal men, and the frequency of this polymorphic mutation was estimated to be 18.4% in southern Chinese population. Four cases with G6PD deficiency were demonstrated to be C at the IVS-11 93 position. At the same time, a case of IVS-11 93 C-->T was found in a normal man. CONCLUSIONS: ARMS is a simple, time-saving, and reliable method for detecting known G6PD gene point mutation. The frequency of C1311T in a normal south Chinese population is 18.4%. IVS-11 C93T might be another polymorphic site of the G6PD gene, and it is not the cause of enzyme deficiency in certain G6PD deficient cases.

Asian People↗

[Epstein-Barr virus infection and expression of T-cell intracellular antigen-1 (TIA-1) in intestinal T-cell lymphoma].

OBJECTIVE: To study the status of Epstein-Barr virus (EBV) infection and the expression of TIA-1 antigen in 24 cases of intestinal T-cell lymphomas. METHODS: In situ hybridization for EBER1/2; immunohistochemical staining by three step ABC technique for TIA-1, LMP-1, CD30, CD45RO, CD3 AND CD20. 19 cases of intestinal B-cell lymphomas were used for comparison. RESULTS: (1) Of the 24 intestinal T-cell lymphoma cases, 23 were pleomorphic, medium to large cell type, and one cases was small cell type; in 20 of the 24 cases EBER1/2 signals were detected in the tumor cells; in 4 of the 20 EBER1/2 positive cases, tumor cells expressed LMP-1; EBER1/2 was not detected in 19 cases of intestinal B-cell lymphomas. (2) in 23 of the 24 cases, TIA-1 was expressed in most tumor cells, but not in the only case of small cell type; TIA-1 was negative in tumor cells of all 19 cases of intestinal B-cell lymphomas. CONCLUSIONS: A high level of EBV infection was present in this group of intestinal T-cell lymphomas, the expression of TIA-1 may be related to its cell origin. Intestinal T-cell lymphoma may be an EBV-associated extranodal NK/T cell lymphoma.

Adolescent↗

Long-term composite tissue allograft survival in a porcine model with cyclosporine/mycophenolate mofetil therapy.

BACKGROUND: Low-dose cyclosporine (CsA)/mycophenolate mofetil (MMF) therapy has significantly reduced the frequency of rejection and drug-induced side effects in rat hindlimb allograft recipients. With an eye toward direct clinical application, we developed a large-animal extremity composite tissue allograft model to assess the antirejection efficacy and systemic toxicity of combination CsA/MMF treatment. METHODS: Radial forelimb osteomyocutaneous flap transplants were performed between size-matched, outbred pigs assigned to one of two groups: 5 control pigs received no immunosuppression, and 10 pigs received a once-daily oral CsA/MMF/prednisone regimen. Rejection was assessed by visual inspection of flap skin and correlated with serial histopathologic examination of skin biopsies. RESULTS: In all control pigs, the flap was completely rejected on day 7. Of the 10 pigs receiving treatment, one died from pneumonia and an another from an anesthetic complication on days 19 and 30, respectively, without signs of rejection. Two flaps were lost on days 25 and 29 from severe rejection. Three pigs were free of rejection at the end of the 90-day follow-up period, and three had stable mild-to-moderate rejection at 90 days (P= 0.0007 vs. controls). White blood cell and platelet counts, serum creatinine values, and liver function tests remained normal in all animals receiving immunosuppressive therapy. CONCLUSIONS: Our results, to our knowledge, demonstrate for the first time that rejection can be significantly delayed in a large-animal composite tissue allograft model including skin using only orally administered agents dosed according to clinically relevant strategies without significant drug-specific systemic side effects.

Animals↗

Muscular urinary sphincter: electrically stimulated myoplasty for functional sphincter reconstruction.

PURPOSE: To reconstruct an electrically stimulated muscular urinary sphincter (MUS) using a tailored gracilis muscle free flap with intact nerve. MATERIALS AND METHODS: Unilateral surgically tailored gracilis muscle free flaps were transferred into the pelvis in eight dogs, leaving the obturator nerve intact. The muscle's pedicle vessels were anastomosed to the inferior epigastric artery and vein in the pelvis and the muscle was wrapped around the bladder neck. Electrodes were inserted into the MUS and connected to a programmable pulse generator. After 8 weeks of training the MUS, the pulse generator was programmed to be "on" for 4 hours and "off' for 15 minutes in a continuous cycle. Urodynamic studies were performed periodically, and at the end of the experiment the MUS and proximal urethra were harvested for histology. Three control dogs had sham operations. RESULTS: All MUS's functioned well following the procedure. Histology of the MUS/urethra complex showed no evidence of stricture. Except for one dog, all urethras were easily catheterized. CONCLUSIONS: This electrically stimulated innervated free-flap MUS technique effectively increases bladder outlet resistance without producing urethral obstruction.

Animals↗

Male sterility and meiotic drive associated with sex chromosome rearrangements in Drosophila. Role of X-Y pairing.

In Drosophila melanogaster, deletions of the pericentromeric X heterochromatin cause X-Y nondisjunction, reduced male fertility and distorted sperm recovery ratios (meiotic drive) in combination with a normal Y chromosome and interact with Y-autosome translocations (T(Y;A)) to cause complete male sterility. The pericentromeric heterochromatin has been shown to contain the male-specific X-Y meiotic pairing sites, which consist mostly of a 240-bp repeated sequence in the intergenic spacers (IGS) of the rDNA repeats. The experiments in this paper address the relationship between X-Y pairing failure and the meiotic drive and sterility effects of Xh deletions. X-linked insertions either of complete rDNA repeats or of rDNA fragments that contain the IGS were found to suppress X-Y nondisjunction and meiotic drive in Xh-/Y males, and to restore fertility to Xh-/T(Y;A) males for eight of nine tested Y-autosome translocations. rDNA fragments devoid of IGS repeats proved incapable of suppressing either meiotic drive or chromosomal sterility. These results indicate that the various spermatogenic disruptions associated with X heterochromatic deletions are all consequences of X-Y pairing failure. We interpret these findings in terms of a novel model in which misalignment of chromosomes triggers a checkpoint that acts by disabling the spermatids that derive from affected spermatocytes.

Animals↗

[Effects of exposure to noise in oil-drilling well sites on cochlea in guinea pigs].

OBJECTIVE: To prevent from hearing damage caused by noise in the sites with drilling wells. METHODS: Intensity and spectrum of the noise produced in the sites with drilling wells were measured and analyzed. Measures, such as sound insulation, vibration damping and changing layouts of the drilling platform, were adopted, and electrocochleography (ECochG) and scanning electron microscopy were used to observe the effects of noise in the sites where drilling wells located on the hearing organs in guinea pigs after exposure. RESULTS: There was no significant difference in APN1 latency of ECochG before and after exposure to noise. There were significant difference in hearing threshold values between the groups in a room with sound isolation, in moving status and beside the diesel engine, and no significant difference in those between the groups placed one meter horizontally and vertically away from the diesel engine on the drilling platform. Damage to hairy cell under scanning electron microscope was more severe in the guinea pigs placed beside the diesel engine and at the drilling well platform, with inclination and exfoliation of static pili of outer hairy cells, especially in the second and third lines, and part exfoliation of inner hairy cell. Hairy cells of the guinea pigs in a room with sound insulation and in moving status were basically normal. Inclination of hairy cells only could be seen in the third line. CONCLUSION: Animal experiments indicated that the measures mentioned above are effective and should be applied widely for preventing from hearing damage.

Animals↗

[Study on nuclear matrix protein in leukemia cells].

OBJECTIVE: To compare the composition of nuclear matrix proteins (NMP) between leukemia cells and normal bone marrow cells. METHODS: NMP was isolated by high-salt extration and identified by SDS-PAGE and western blotting. RESULTS: Increase in NMP was demonstrated in acute and chronic myelogenous leukemic cells as well as in the blast phase of chronic leukemia. On SDS-PAGE, NMPs with molecular weight different from what were seen in normal bone marrow cells were present in both acute and chronic myelogenous leukemias. CONCLUSION: Marked changes of NMP, not only in contents but also in compositions, exist in leukemic cells compared with normal bone marrow cells. NMP may serve as a target of chemotherapeutic drugs against leukemia.

Antigens, Nuclear↗

[A study on apoptotic cell death during chemotherapy of patients with acute leukemia].

OBJECTIVE: To investigate whether apoptosis occurs in vivo in patients with acute leukemia during induction chemotherapy and its significance. METHODS: Apoptotic effect on peripheral blood of 20 patients with different types of acute leukemia prior to and during routine chemotherapy was studied by cell morphology, DNA electrophoresis and FCM-DNA analysis. RESULTS: After chemotherapy, with falls in WBC and blast count, no apoptotic cell appeared on smears of peripheral blood, nor did ladder pattern of DNA on electrophoresis and subdiploid peak on FCM. CONCLUSION: Although anticancer drugs have been shown to induce apoptosis in vitro, circulating apoptotic cells are hardly detected probably due to their rapid clearance from the circulation. It is more difficult to study apoptosis in vivo than in vitro.

Antineoplastic Combined Chemotherapy Protocols↗

Glycophorin variants and contents of sialic acid and total sulfhydryl groups on erythrocyte membranes of residents in a malaria hyperendemic area.

OBJECTIVE: To conduct a screening survey of glycophorin (GP) variants and observe the content changes of sialic acid (SA) and total sulfhydryl (SH) groups on the erythrocyte membranes among residents in a tertian malaria hyperendemic area of Guizhou Province. METHODS: GP variants were detected in the erythrocyte hemolysates of 173 local residents at two villages of Libo County by SDS-PAGE on 10% to 15% gradients gel and Western immunoblotting. Their SA and total SH group contents were estimated in erythrocyte membranes by spectrophotometric methods. 114 healthy subjects in Changsha and 49 individuals at a neighbouring village of the above area showing low morbidity of malaria served as normal and endemic controls respectively. RESULTS: Three distinct types of GP variants were found among 19 propositi in this hyperendemic area. The incidence of GP variants was 7.9% (8/101) at Yaolu Village whose population was mainly composed of Yao ethnic group; while that of Buyi ethnic group at Maolan Village was higher (15.3%; 11/72). The erythrocyte membrane contents of SA in residents at both villages exhibited a very significant tendency of decline (P < 0.01), whereas those of total SH groups increased prominently in residents of Yaolu Village only (P < 0.05). CONCLUSIONS: The frequency of GP variants in this hyperendemic area does not depend upon the severity of malarial prevalence. The evident reduction of SA contents in the residents may be related to the breaking down of the SA residues on membrane GPs by the invasion of Plasmodium vivax.

Adolescent↗