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Biomedical subjects

X Ren

Publications and source records attributed to X Ren.

At least 73 records · Page 4Linked to original sources

Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to hypoxia in humans.

In cell culture, hypoxia stabilizes a transcriptional complex called hypoxia-inducible factor-1 (HIF-1) that increases erythropoietin (Epo) formation. One hallmark of HIF-1 responses is that they can be induced by iron chelation. The first aim of this study was to examine whether an infusion of desferrioxamine (DFO) increased serum Epo in humans. If so, this might provide a paradigm for identifying other HIF-1 responses in humans. Consequently a second aim was to determine whether an infusion of DFO would mimic prolonged hypoxia and increase the acute hypoxic ventilatory response (AHVR). Sixteen volunteers undertook two protocols: 1) continuous infusion of DFO over 8 h and 2) control. Epo and AHVR were measured at fixed times during and after the protocols. The results show that 1) compared with control, Epo increased in most subjects at 8 h [52.8 +/- 57.7 vs. 6.9 +/- 2.5 (SD) mIU/ml, for DFO = 4 g/70 kg body wt, P < 0.05] and 12 h (63.7 +/- 76.3 vs. 7.3 +/- 2.5 mIU/ml, P < 0.001) after the start of DFO administration and 2) DFO had no significant effect on AHVR. We conclude that, whereas infusions of DFO mimic hypoxia by increasing Epo, they do not mimic prolonged hypoxia by augmenting AHVR.

Acute Disease↗

Loss of fhit expression in invasive cervical carcinomas and intraepithelial lesions associated with invasive disease.

Allelic losses involving chromosome 3p are frequently observed in cervical cancers. Deletion mapping studies of primary cervical carcinomas have localized common regions of deletion to 3p14.2 and 3p21. The candidate tumor suppressor gene FHIT has been mapped to 3p14.2, and previous studies have demonstrated reduced or aberrant FHIT transcripts and reduced or absent Fhit protein expression in a large percentage of cervical cancer-derived cell lines and primary cervical carcinomas. To expand these observations to preinvasive cervical epithelial lesions and to determine whether loss of Fhit protein expression might be associated with tumor progression, immunohistochemical methods were used to examine Fhit expression in 95 invasive cervical carcinomas, 33 high-grade squamous intraepithelial lesions (HSILs) associated with concurrent invasive cancer, 38 HSILs unassociated with invasive cancer, 24 low-grade squamous intraepithelial lesions, and 22 normal cervix samples. All normal cervical epithelia and low-grade squamous intraepithelial lesions exhibited diffuse cytoplasmic immunostaining of moderate to strong intensity. Fhit protein expression was markedly reduced or absent in 67 of 95 (71%) invasive cancers, 17 of 33 (52%) HSILs associated with invasive cancer, and 8 of 38 (21%) HSILs without associated invasive cancer. The results confirm that Fhit protein expression is reduced or absent in the majority of cervical carcinomas and suggest that loss of Fhit expression often accompanies cervical tumor progression. Moreover, absent or reduced Fhit protein is observed at a significantly higher frequency in HSILs associated with progression to invasive cancer than in HSILs with unknown risk for progression (P = 0.012). These findings suggest that loss of Fhit expression in HSILs could serve as a useful marker of high-grade preinvasive lesions that have an increased likelihood of progression to invasive carcinoma.

Acid Anhydride Hydrolases↗

Localization of myocilin to the golgi apparatus in Schlemm's canal cells.

PURPOSE: Biochemical and genetic evidence suggests that overexpression of or mutations in myocilin within the cells of the aqueous humor outflow pathway play a significant role in the development of steroid-induced and several other open-angle glaucomas. As a baseline to understanding the normal and pathologic function of myocilin, we determined the subcellular localization of myocilin in steroid-treated human Schlemm's canal endothelial (SC) cells. METHODS: SC cells were grown to confluence, treated with dexamethasone for 10 days, and then stained using antibodies against myocilin, tubulin, or beta-COP (a specific golgi protein) or vital stains for endoplasmic reticulum (ER) and golgi. Brefeldin A (BFA) and nocodazol (NZ) were used to disrupt the golgi or microtubules. RESULTS: The authors found that myocilin staining was (a) always centered around the centrosome, (b) very similar to the pattern seen with NBD-ceramide, (c) was disrupted in characteristic ways by BFA and NZ and (d) showed extensive colocalization with beta-COP. CONCLUSIONS: Results indicate that myocilin is localized to the golgi in SC cells. Such localization is consistent with myocilin being processed for secretion but is also consistent with sequence analysis and other data that suggest that myocilin or myocilin mutations might be targeted to the cytoplasmic face of the golgi, and under some circumstances play a role in or interfere with golgi or vesicle function. How such interference could eventually lead to open angle glaucoma is discussed.

Brefeldin A↗

Measurement of mRNAs for TGFss and extracellular matrix proteins in corneas of rats after PRK.

PURPOSE: To assess the role of the transforming growth factor (TGF)ss system in formation of corneal haze after excimer laser photorefractive keratectomy (PRK), levels of mRNAs for three TGFss isoforms (TGFss1, TGFss2, and TGFss3), the TGFss type II receptor (TssRII), and extracellular matrix (ECM) genes including fibronectin (FN), collagen I, collagen III, and collagen IV were measured in rat corneas. METHODS: Corneas were graded for corneal haze at 0, 1.5, 7, 21, 42, and 91 days after PRK. Total RNA was isolated from pooled corneas, and the levels of mRNAs were measured using competition-based quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Severe corneal haze developed by day 42 and persisted to day 91. Levels of TGFss1 mRNA were high in rat corneas before PRK and remained relatively constant. In contrast, levels of TGFss2 and TGFss3 mRNAs were very low in normal corneas, increased 300-fold and 25-fold, respectively, on day 21, and remained elevated on day 91. Levels of mRNA for TssRII increased, with a peak elevation of 50-fold on day 42 after PRK. Levels of mRNAs for ECM proteins also increased. Fibronectin mRNA was nondetectable in normal corneas but rapidly increased to 675 copies/cell on day 7 and remained elevated to day 91. Collagen III mRNA levels peaked on day 21 with a 700-fold increase compared with a very low level of expression in normal cornea, and then decreased on day 91. Expression of collagen I mRNA lagged expression of collagen III mRNA and peaked at day 42 after PRK with a 1200-fold increase over normal cornea. In contrast, mRNA for collagen alpha(1)IV, a major component in basement membranes, remained relatively stable through day 21 and then increased slightly on days 42 and 91. CONCLUSIONS: The synchronized increase in mRNA synthesis for both the TGFss system and key ECM genes supports the hypothesis that TGFss is a key growth factor promoting stromal haze formation in corneas after PRK and suggests that limiting TGFss system may reduce corneal scarring after excimer laser ablation.

Animals↗

[Construction and nucleotide sequence assay of human anti-HBs variable region single-chain antibody gene].

The VH and Vk gene which were acquired using phage display technology have been combined by a linker encoding a flexible peptide (Gly4 Ser)3 to form a single-chain. Its nucleotide sequence was assayed after cloning the scFv gene into middle plasmid. The successful construction of single-chain gene lays the foundations for the subsequent expression and production of double functional antibody.

Amino Acid Sequence↗

[Comparative study of three common G6PD gene mutations in Yao and Han People in Guangxi].

OBJECTIVE: To study G6PD gene mutation diversity in Yao and Han people in Guangxi and compare the genotypic frequencies. METHODS: The three common G6PD gene mutations in Chinese were investigated in 34 G6PD deficient individuals from Yao and 37 from Han people by using an amplification refractory mutation system (ARMS). RESULTS: Among 34 cases of G6PD deficiency of Yao people, the genotypic frequencies of G1376T, G1388A and A95G were 41.2%, 26.5% and 14.7%, respectively. A case of C1311T was detected. As compared with that in Han people, the respective frequencies were 16.2%, 40.6% and 5.4%. CONCLUSION: The main G6PD mutations in Yao people were the same with Han people in Guangxi, but G1376T mutation was higher than that in Han people. The C1311T mutation in Yao people in Guangxi was reported for the first time.

Adolescent↗

[Mobilization of autologous peripheral blood stem cells by chemotherapy and recombinant granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)].

OBJECTIVE: To observe the efficacy of chemotherapy and recombinant granulocyte colony-stimulating factor (G-CSF, Glycosylated) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in autologous peripheral blood stem cells (APBSC) mobilization. METHODS: The mobilization regimen: CBP 350 mg/m(2) intravenously injected at day 1, Vp16 350 mg/m(2) intravenously injected from day 1 to day 3. G-CSF and GM-CSF 5 microg x kg(-1) x d(-1) each, subcutaneously injected and DXM 5 mg/d intramuscularly injected, from the day of white blood cell (WBC) recovery to (2.4 - 6.4) x 10(9)/L from nadir to the day before the end of APBSC harvesting. APBSC harvesting started when WBC > 20.0 x 10(9)/L and ended when accumulated mononuclear cells (MNC) > 5 x 10(8)/kg. CFU-GM assay and CD(34)(+) cells counting of the APBSC were performed. RESULTS: Twenty cases underwent APBSC mobilization. APBSC harvest began at day 22.15 +/- 3.66 for two successive days. Accumulated MNC was (5.93 +/- 1.62) x 10(8)/kg, CD(34)(+) cells (23.10 +/- 11.53) x 10(6)/kg and CFU-GM (3.44 +/- 2.85) x 10(5)/kg. No severe toxicity was observed. Hematopoiesis was well reconstituted in 8 patients received single and in 1 patient received double APBSC transplantations. CONCLUSION: Chemotherapy combined with G-CSF + GM-CSF was a safe and highly effective method for APBSC mobilization.

Adult↗

[Influence of the administrators of family planning on the spread of norplant in countryside of Sichuan].

The purpose of the study was to understand the family planning administrators' knowledge of Norplant and their fluence on the spread of Norplant in countryside of Sichuan. 156 administratoras were surveyed. It was found that most of the administrators worked hard on education, propagation, organization and management of using Norplant, and they recognized the contraceptive efficacy of Norplant. However, the educational level of the administrators was generally low. They were short of the training on Norplant related knowledge(training rate was only 36.5%). The degree of the users' satisfaction and the administrators' knowledge on Norplant varied between areas. The result indicated that the basic quality of the administrators and their knowledge of Norplant were influences on the spread of Norplant in the countryside of Sichuan. Soit is very important to improve the basic quality and knowledge of the administrators of family planning.

Adolescent↗

[Conformity of cancerous diagnosis of serum-fluorimetry under the influence of carotenoid fluorescence].

We observed that carotenoid had sensitization for fluorescence of porphyrin as cancerous diagnostic technology was applied in clinic by serum-fluorimetry. The Forster theory was used in order to analyse sensitized fluorescence between carotenoid and porphyrin in this paper. Transfer characteristic between energy donor and energy acceptor was calculated and discussed its influence on cancerous diagnosis.

Biomarkers, Tumor↗

[The preparation of electric arc method and spectral analysis on long persistence luminescent chinaware of SrAl2O4:Eu2+].

Luminescent chinaware of long persistence of SrAl2O4:Eu2+ has been prepared with using are method. Fluorescence and excitation spectra were measured in order to study its luminescence and long persistence properties. Results show that both of luminescent chinaware and polycrystalline powdered phosphor are the same in luminescence decay and consist of an initial fast process and a later extremely slow process. Long persistence properties of luminescent chinaware are better more than polycrystalline powdered phosphor, and its function of environment-resistant has been improved prominently.

English Abstract↗

Truncation of the C terminus of the rat brain Na(+)-Ca(2+) exchanger RBE-1 (NCX1.4) impairs surface expression of the protein.

The C terminus of the rat brain Na(+)-Ca(2+) exchanger (RBE-1; NCX1. 4) (amino acids 875-903) is modeled to contain the last transmembrane alpha helix (amino acids 875-894) and an intracellular extramembraneous tail of 9 amino acids (895-903). Truncation of the last 9 C-terminal amino acids, Glu-895 to stop, did not significantly impair functional expression in HeLa or HEK 293 cells. Truncation, however, of 10 amino acids (Leu-894 to stop; mutant C10) reduced Na(+) gradient-dependent Ca(2+) uptake to 35-39% relative to the wild type parent exchanger, and further truncation of 13 or more amino acids resulted in expression of trace amounts of transport activity. Western analysis indicated that Na(+)-Ca(2+) exchanger protein was produced whether transfection was carried out with functional or non-functional mutants. Immunofluorescence studies of HEK 293 cells expressing N-Flag epitope-tagged wild type and mutant Na(+)-Ca(2+) exchangers revealed that transport activity in whole cells correlated with surface expression. All cells expressing the wild type exchanger or C9 exhibited surface expression of the protein. Only 39% of the cells expressing C10 exhibited surface expression, and none was detected in cells transfected with non-functional mutants C13 and C29. Since functional and non-functional mutants were glycosylated, the C terminus is not mandatory to translocation into the endoplasmic reticulum (ER). Endoglycosidase H digestion of [(35)S]methionine-labeled protein derived from wild type Na(+)-Ca(2+) exchanger and from C10 indicated that resistance to the digestion was acquired after 1 and 5 h of chase, respectively. C29 did not acquire detectable resistance to endoglycosidase H digestion even after 10 h of chase. Taken together, these results suggest that the "cellular quality control machinery" can tolerate the structural change introduced by truncation of the C terminus up to Ser-893 albeit with reduced rate of ER-->Golgi transfer and reduced surface expression of the truncated protein. Further truncation of C-terminal amino acids leads to retention of the truncated protein in the ER, no transfer to the Golgi, and no surface expression.

Amino Acid Sequence↗

[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.

Journal Article↗

Ventilatory responses to hypercapnia and hypoxia after 6 h passive hyperventilation in humans.

1. Acute exposure to hypoxia stimulates ventilation and induces hypocapnia. Long-term exposure to hypoxia generates changes in respiratory control known as ventilatory acclimatization to hypoxia. The object of this study was to investigate the degree to which the hyperventilation and hypocapnia can induce the changes known as ventilatory acclimatization to hypoxia, in the absence of the primary hypoxic stimulus itself. 2. Three 6 h protocols were each performed on twelve healthy volunteers: (1) passive hypocapnic hyperventilation, with end-tidal CO2 pressure (PET,CO2) held 10 Torr below the eupnoeic value; (2) passive eucapnic hyperventilation, with PET,CO2 maintained eucapnic; (3) control. 3. Ventilatory responses to acute hypercapnia and hypoxia were assessed before and half an hour after each protocol. 4. The presence of prior hypocapnia, but not prior hyperventilation, caused a reduction in air-breathing PET,CO2 (P < 0.05, ANOVA), and a leftwards shift of the ventilatory response to hypercapnia (P < 0.05). The presence of prior hyperventilation, but not prior hypocapnia, caused an increase in the ventilatory sensitivity to CO2 (P < 0.05). No significant effects of any protocol were detected on the ventilatory sensitivity to hypoxia. 5. We conclude that following 6 h of passive hyperventilation: (i) the left shift of the VE-PET,CO2 relationship is due to alkalosis and not to hyperventilation; (ii) the increase in slope of the VE-PET,CO2 relationship is due to the hyperventilation and not the alkalosis; and (iii) ventilatory sensitivity to hypoxia is unaltered.

Acclimatization↗

Scoring of skin rejection in a swine composite tissue allograft model.

BACKGROUND: For the first time, we define and correlate visual and histologic grading systems of composite tissue allograft (CTA) skin rejection in a large-animal model and determine the utility of these grading systems for early diagnosis and monitoring of rejection. MATERIALS AND METHODS: Sixteen pairs of outbred swine underwent transplant of a forelimb osteomyocutaneous free flap. Group I (n = 6) did not receive immunosuppressive therapy. Group II (n = 10) received oral cyclosporin A, mycophenolate mofetil, and prednisone. The flap was visually inspected and protocol skin biopsies were taken at frequent intervals over a 90-day period. Visual Grades 0 (no rejection) to 4 (severe rejection) were assigned based on skin color, bleeding from biopsy site, and blister formation. Histologic Grades 0 to 4 were assigned based on the degree of vasculitis, folliculitis, dermal inflammation, and epidermal degeneration present. RESULTS: All Group I animals progressively rejected their graft by Day 7. Group II grafts survived from 19 and 90 days; 93% of 115 biopsy specimens were read to be within +/-1 histologic score of their assigned flap visual grade. Visual assessment carried an 8% false positive and 39% false negative rate with regard to biopsy-proven rejection. However, 81% of missed rejection specimens were histologic Grade 1. Biopsy, when visually indicated, would detect all rejection episodes when histologically Grade 1 or 2 and still potentially reversible. CONCLUSIONS: Visual scoring of CTA skin serves as a useful tool for initially detecting rejection, but repeated histologic evaluation is necessary for monitoring the subsequent course of the graft.

Animals↗

Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice.

The juvenile development and fertility-2 (jdf2) locus, also called runty-jerky-sterile (rjs), was originally identified through complementation studies of radiation-induced p-locus mutations. Studies with a series of ethylnitrosourea (ENU)-induced jdf2 alleles later indicated that the pleiotropic effects of these mutations were probably caused by disruption of a single gene. Recent work has demonstrated that the jdf2 phenotype is associated with deletions and point mutations in Herc2, a gene encoding an exceptionally large guanine nucleotide exchange factor protein thought to play a role in vesicular trafficking. Here we describe the molecular characterization of a collection of radiation- and chemically induced jdf2/Herc2 alleles. Ten of the 13 radiation-induced jdf2 alleles we studied are deletions that remove specific portions of the Herc2 coding sequence; DNA rearrangements were also detected in two additional mutations. Our studies also revealed that Herc2 transcripts are rearranged, not expressed, or are present in significantly altered quantities in animals carrying most of the jdf2 mutations we analyzed, including six independent ENU-induced alleles. These data provide new molecular clues regarding the wide range of jdf2 and p phenotypes that are expressed by this collection of recently generated and classical p-region mutations.

Alleles↗

Long-term deprivation of oestrogens by ovariectomy potentiates beta-amyloid-induced working memory deficits in rats.

1 In the present study, we examined whether deprivation of oestrogens by ovariectomy could modify learning and memory deficits caused by a continuous intracerebroventricular (i.c.v.) infusion of amyloid beta-peptide (Abeta), the major constituent of senile plaques in AD. 2 Neither long-term (3 months) nor short-term (1 month), deprivation of oestrogens by ovariectomy caused a significant impairment in spatial learning and memory in a water maze and spontaneous alternation behaviour in a Y-maze. 3 A continuous i.c.v. infusion of Abeta-(1-42) caused spatial learning and memory deficits in both ovariectomized and sham-operated rats. 4 The Abeta-induced working memory deficits were significantly potentiated in ovariectomized rats compared with sham-operated rats when mnemonic ability was examined 3 months after ovariectomy. 5 These results suggest that long-term deprivation of oestrogens induced by ovariectomy increases susceptibility to memory deficits produced by Abeta-(1-42) in rats.

Amyloid beta-Peptides↗

Somatic mutations of the PPP2R1B candidate tumor suppressor gene at chromosome 11q23 are infrequent in ovarian carcinomas.

Previous studies have demonstrated frequent allelic losses of distal chromosome 11q in ovarian carcinomas. The tumor suppressor gene(s) presumably targeted by these losses have not yet been identified. PPP2R1B is a candidate tumor suppressor gene at 11q23 that has recently been shown to be mutated in a subset of colorectal and lung cancers. We evaluated 5 ovarian carcinoma cell lines and 27 primary ovarian carcinomas for allelic losses of 11q23 and for mutations in the open reading frame of PPP2R1B. We also evaluated the primary tumors for allelic losses at 17p13, another chromosomal region frequently affected by losses of heterozygosity (LOH) in ovarian cancers. 11q23 and 17p13 allelic losses were identified in 25% and 74% of the carcinomas, respectively. No mutations within PPP2R1B coding sequences were found. These findings indicate that mutations of the PPP2R1B gene are infrequent in ovarian cancer and that deletions affecting the distal portion of chromosome 11q in ovarian cancer likely target inactivation of other genes.

Alleles↗

Detection of the most common G6PD gene mutations in Chinese using amplification refractory mutation system.

Glucose-6-phosphate dehydrogenase (G6PD) is the most common human enzymopathy. To date more than 122 mutations in the G6PD gene have been discovered, among which 12 point mutations are found in the Chinese. The 2 most common mutations, G1388A and G1376T, account for more than 50% of mutations representing various regions and ethnic groups in China. Setting up a simple and accurate method for detecting these mutations is not only useful for studying the frequency of the G6PD genotypes, but also for finding new mutations. The purpose of this study was to find a simple, inexpensive and accurate method for detecting these common mutations. The amplification refractory mutation system (ARMS) method was used in this study. Samples from 28 G6PD-deficient males were investigated. The natural and mismatched amplification and restriction enzyme digestion method was used as a standard method to evaluate the nature of the point mutations. Sixteen cases were found carrying the G1388A mutation and 12 the G1376T mutation. Fourteen cases of G1388A and 10 cases of G1376T were confirmed by ARMS. Four cases were not in concordance with the results obtained by the mismatched amplification-restriction enzyme digestion. These 4 cases were then judged by direct PCR sequencing at exon 12. The DNA sequencing data supported the results obtained by ARMS. Thus we concluded that the ARMS is a rapid, simple, inexpensive and accurate method for detecting the most common G6PD gene mutations among the Chinese.

Asian People↗