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Biomedical subjects

W Yu

Publications and source records attributed to W Yu.

At least 109 records · Page 6Linked to original sources

[Differentiation of achondroplasia and other similar genetic dwarfism by FGFR3 gene analysis].

OBJECTIVE: To study the gene mutation of Chinese patients with achondroplasia(ACH) and to set up a simple and rapid molecular diagnostic method to differentiate ACH from other similar genetic dwarfism. METHODS: The specific fragment of fibroblast growth factor receptor 3(FGFR3) transmembrane domain was amplified from dried blood spots of 21 patients with ACH and 6 suspicious patients with ACH by polymerase chain reaction, then mutation was screened and detected by restrictive enzyme analysis, single strand conformation polymorphism(SSCP) and denaturing gradient gel electrophoresis(DGGE). RESULTS: One out of 6 suspicious cases was ACH and 5 were pseudoachondroplasia(PSACH). Twenty-one out of 22 patients with ACH bore a G to A transition at nucleotide 1138 and 1 bore a G to C transversion at this same position. CONCLUSION: The nucleotide 1138 of FGFR3 gene is also the hotspot of mutation in Chinese patients with ACH. A simple and rapid molecular diagnostic method has been set up to differentiate ACH from other similar genetic dwarfism.

Achondroplasia↗

Postnatal handling does not attenuate hypothalamic-pituitary-adrenal hyperresponsiveness after prenatal ethanol exposure.

BACKGROUND: Prenatal ethanol exposure results in hypothalamic-pituitary-adrenal (HPA) hyperresponsiveness to stress in the adult animal. In contrast, an early environmental manipulation, termed "postnatal handling," has been shown to result in decreased and/or less prolonged HPA activity in response to moderate stressors throughout the lifespan of the animal. The effects of both prenatal ethanol exposure and postnatal handling on HPA activity may be mediated by altered feedback regulation of the HPA axis. The present study tested the hypothesis that postnatal handling could attenuate the impact of prenatal ethanol exposure on hormonal responses to stressors. METHODS: Male and female Sprague Dawley rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) groups were either handled (H) or nonhandled (NH) during the preweaning period and were tested at 4 to 5 months of age. Animals were subjected to a 60 min restraint stress, 3 hr after intraperitoneal injection with either saline (SAL) or a synthetic glucocorticoid, dexamethasone-21-phosphate (DEX), in order to examine HPA responsiveness after DEX blockade of endogenous HPA activity. Blood samples were collected via jugular cannulae immediately before restraint (0 min), during restraint (10, 30, and 60 min), and 30 min after the termination of restraint (90 min). RESULTS: For both males and females, DEX administration significantly reduced plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations compared with SAL administration. H animals showed greater suppression of HPA activity (i.e., lower ACTH and/or CORT levels) than NH animals regardless of prenatal group. In addition, E females from both the H and NH treatments showed elevated ACTH and CORT after both SAL and DEX administration, whereas H and NH E males showed elevations in ACTH and CORT only after SAL, compared with their PF and C counterparts. CONCLUSIONS: These data extend results from previous studies that demonstrated HPA hyperresponsiveness in E animals. The finding that E females but not males exhibit elevated ACTH and CORT after DEX administration suggests that prenatal ethanol exposure results in sex-specific alterations of HPA feedback. Consistent with previous data, handling in itself reduced the HPA response to restraint stress. However, handling did not attenuate either HPA hyperresponsiveness or feedback deficits in E animals.

Adrenal Glands↗

[Targeting studies of humanized scFv25 fusing to TNFalpha against hepatocellular carcinoma].

OBJECTIVE: To obtain humanized engineering bifunctional antibody, which has potentialities for clinical application. METHODS: Humanized anti-human hepatocellular carcinoma (HCC) single chain fragment (hscFv25) was linked with human TNF-alpha gene to form anti-HCC bifunctional antibody, then it was subcloned into prokaryotic GST fusion expression vector pGEX 4T-1 and expressed in the host E.coli. Indirect immunofluorescent staining was performed on HCC cell smearing slides in order to evaluate the activity of the purified aim protein, then MTT trial to evaluate the cytotoxicity of hscFv25-TNFalpha to SMMC-7721, finally primary tumor regression trial in nude mice bearing HCC to evaluate the targeting therapeutic value of hscFv25-TNFalpha. RESULTS: The hscFv25-TNFalpha had the similar specificity to parental antibody HAb25 for SMMC-7721 antigen. One hour predisposed MTT trial in control with parental antibody HAb25 affirmed that hscFv25-TNFalpha was cytotoxic to targeted cell SMMC-7721 with the IC(50) to be 7.1 microg/ml. The cytotoxicity can be inhibited by parental antibody HAb25. This indicated that the cytotoxicity of hscFv25-TNFalpha to targeted cell is antibody-mediated selective cytotoxicity. The tumor regression trial to the 3mm HCC xenografts in nude mice showed that hscFv25-TNFalpha had assured targeting cytotoxicity and the efficiency was nearly up to 3/3 (1/3 complete remission, 2/3 partial remission). The cytotoxicity of the hscFv25-TNFalpha was better than that of TNFalpha, whose efficiency was only 2/3 and without complete remission. CONCLUSION: hscFv25-TNFalpha is an anti-HCC bi-functional antibody which has potentialities for clinical application.

Animals↗

Using diagnoses to describe populations and predict costs.

The Diagnostic Cost Group Hierarchical Condition Category (DCG/HCC) payment models summarize the health care problems and predict the future health care costs of populations. These models use the diagnoses generated during patient encounters with the medical delivery system to infer which medical problems are present. Patient demographics and diagnostic profiles are, in turn, used to predict costs. We describe the logic, structure, coefficients and performance of DCG/HCC models, as developed and validated on three important data bases (privately insured, Medicaid, and Medicare) with more than 1 million people each.

Adolescent↗

[Effect of temperature and food on Spodoptera litura population].

The relationship between temperature and development of Spodoptera litura was simulated by the sine model V(T) = A + B sin(C0 + C1eC3T + C2e-C3T), and the threshold temperature and thermal requirement for its development at different stages were estimated by the direct optimum method. The model for the relationship between temperature and survival rate was fitted by the experimental data. The theoretical optimum temperature for the development of eggs, young instar larvae, old instar larvae and pupae was 26.7, 24.7, 24.9 and 25.8 degrees C, respectively. The life table parameters under different feed conditions (cabbage, lotus, sweet potato, soybean leaves) were estimated by the method of bisexual life table with age-structure. At temperature 25 degrees C, the intrinsic rates of increase under the four different feed conidtions were 0.1836, 0.1719, 0.1778 and 0.1206, respectively.

Animals↗

[The effects of the enameloplasty on the penetration and adaptation of sealant].

OBJECTIVE: To study the mechanism of enameloplasty technique by observing penetration and adaptation of sealant. METHODS: 60 extracted molars were selected and divided into three groups: pits and fissures of the samples in group A were prepared with bur(EST); those in group B were cleaned with cup-shaped brush(CST); group C, as control. RESULTS: The penetration of EST was (83.75 +/- 13.11)%, CST was (55.30 +/- 11.98)%. The presence of defects between sealants and inclines of cusp of EST and CST were 7.32% and 19.05% respectively, and between sealants and lateral walls of fissures were 16.07% and 38.93%. CONCLUSION: The penetration and adaptation of EST was superior to CST.

Dental Cavity Preparation↗

[Observation of therapeutic effect of Salviae miltiorrhiza and cytosine diphosphate-choline injection on patients with hypertensive cerebral hemorrhage].

OBJECTIVE: To assess the effect of Salviae miltiorrhiza (SM) injection in the treatment of hypertensive cerebral hemorrhage (HCH). METHODS: Fifty-one cases (age 50-78 years, 61.2 years on average) of HCH were randomly divided into three groups (SM + cytosine diphosphate-choline (CDP-C) group and para-aminomethyl benzoic acid (PAMBA) + CDP-C group as treated group, CDP-C group as control group) to observe the outcome of the clinical treatment, hematoma absorbability and changes of ADP-platelet agglutination rate (Pag), prothrombin time(PT) and function of the liver and kidney. RESULTS: The rate of good result (GR) and moderate disability (MD) in SM group was 85.71% with the method of Glasgow outcome score (GOS), others were 47.06% and 61.54% separately, they have significant difference, P < 0.05. Among them, SM group had best result. Compared the rate of hematoma absorbability of SM group with that of PAMBA, CDP-C groups, the difference was significant, P < 0.05. It did not affect the platelet coagulative function in SM group. CONCLUSION: SM injection could effectively improve the condition of patients with HCH, and without any side effect. It is worthwhile to be used in the clinical practice.

Aged↗

[Preliminary study on the effects of coagulation factor XII on fibrinolysis].

OBJECTIVE: To study the effects of FXII on fibrinolysis in patients with cerebral thrombosis. METHODS: Plasma level of FXII:C, FXII:Ag, FXIIa and beta FXIIa and fibrinolysis activities were examined by ELISA. Screening of FXII gene mutation by MOEA. RESULTS: FXII:C in 22 of 107 patients with cerebral thrombosis decreased, which was similar to the feature of FXII cross-reacting material positive (FXII CRM(+)). There were significant increase in plasma levels of PLG:A and alpha(2)AP:A and decrease in D-dimer, moreover, plasma levels of FXIIa and betaFXIIa were lower in patients than in controls. FXII gene mutation was not found in 22 of 107 patients. CONCLUSION: Decrease of FXII:C may play an important role in cerebral thrombosis by reducing activation of plasminogen. The gene mutation of FXII CRM(+)-like abnormal FXII was different from the known FXII gene mutation. Mutations in the regions of FXII Arg (334) and Arg (353) may be more important for the reducing of FXIIa, beta FXIIa levels and fibrinolysis activities. FXII assay should be included in thrombotic disorder screening.

Adult↗

[Effects of microinjection of amino acids into pre-Bötzinger complex on respiration in adult rats].

Experiments were performed on sodium pentobarbital anesthetized and bilaterally vagotomized adult SD rats. Microinjection of an excitatory neurotoxin, kainic acid, into pre-Bötzinger complex initially lengthened the duration of inspiration, shortened the duration of expiration and increased the respiratory frequency, and subsequently abolished rhythmic respiration. Injection of an excitatory amino acid, L-glutamate, shortened the duration of expiration. Injection of the inhibitory amino acids (either glycine or gamma-aminobutyric acid) shortened the duration of inspiration. These results suggest that the pre-Bötzinger complex in adult rats plays an important role in neurogenesis and maintenance of rhythmic respiration.

Animals↗

[The study on superoxide dismutase and trace element in patients with senile cataract].

PURPOSE: To investigate the relation of senile cataract with superoxide dismutase(SOD) and trace elements. METHODS: Superoxide dismutase of red blood cells and trace elements(Cu, Zn, Ca, Fe) of serum in 61 patients with senile cataract and 121 normal persons were investigated. RESULTS: The activity of superoxide dismutase in patients with senile cataract decrease dramatically in comparison with normal control, and there was no statistical difference about trace elements of Cu, Zn, Ca between senile cataract and control group. But Fe element in patients is higher than that of the normal group. CONCLUSION: The results support the hypothesis that the formation of senile cataract is capable of antioxidative scavenger system of lens decreases with age.

Aged↗

[Bone mineral density and exercises: a cross-sectional study on Chinese athletes].

OBJECTIVES: To evaluate the effect of exercise to osteoporosis by bone mineral density (BMD) measurement of athelets comparing normal individuals in general population. METHODS: BMD of radium, lumber spine, and femoral neck were measured by single photon absorptiometry (SPA), quantitative CT (QCT), and dual X-ray absorptiometry (DXA) respectively in athletes (n = 162, male 79, female 83) and age matched non-athletes normal population (n = 204, male 91, female 113) in Beijing. RESULTS: BMD of all sites in all age groups of both male and female athletes are significantly higher comparing with that in non-athletic population. This predominance in athletes is even more distinctive in peak bone mass. Peak bone mass of male athletes is significantly higher than that of female athletes. Bone loss with age is less apparent in athletes than in control. However, there is an accelerated decline of BMD in lumber spine and femoral neck in 30-39 year age group in both male and female athletes, which may be due to the wanting of physical exercise. CONCLUSIONS: Long term regular proper exercise started in adolescence may play a very important role in the prevention of osteoporosis by improving peak bone mass and decreasing bone loss.

Absorptiometry, Photon↗

Optimizing computerized treatment planning for the Gamma Knife by source culling.

PURPOSE: A good plan is crucial to the success of gamma knife treatment, which depends not only on parameters such as the number of shots, shot position, collimator sizes, and shot weight, but also on the number of blocked cobalt sources. However, during treatment, a plug is generally used to block those cobalt sources, so the beam cannot reach critical tissues. We present here an automated method to optimize all of those parameters, and to choose a source set, although the beams of some blocked sources do not hit any critical tissue. This strategy is used to achieve a high dose that better conforms to the tumor shape, and at the same time, avoids healthy tissue. METHODS AND MATERIALS: Using a workstation that integrates the gamma knife treatment planning system, we developed a two-step optimization algorithm. First, we used a modified Powell's method to optimize the location of the shot, collimator size, and shot weight; we used simulated annealing to determine if the number of shots was adequate using this parameter. Then, simulated annealing was used to determine which cobalt sources we needed to block. RESULTS: Application of this optimization method in two cases showed that the treatment plan can be much improved when the set of blocked cobalt sources has been taken into consideration. CONCLUSION: Determining the set of blocked sources is necessary in certain cases. This technique better conforms the desired isodose curves to the outline of the target volume and minimizes damage to the surrounding normal tissues.

Algorithms↗

Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme.

We have determined the nucleotide sequence of the clone pAL2 obtained from Porphyromonas gingivalis 381 in the previous study [Ansai et al. (1995) Microbiology 141, 2047-20521. The DNA sequence analysis of this fragment revealed one complete ORF and one incomplete ORF. The ORF encoded a protein (PgPepO) of 690 amino acids with a calculated molecular weight of 78796. The deduced amino acid sequence exhibited a significant homology with human endothelin-converting enzyme (ECE)-1. Recombinant PgPepO was purified to homogeneity and characterized. The purified enzyme was strongly inhibited by phosphoramidon, and converted big endothelin-1 to endothelin-1. Furthermore, the purified PgPepO strongly cross-reacted with a monoclonal antibody against rat ECE-1. These results indicate that PgPepO has striking similarity to mammalian ECE in structure and function.

Amino Acid Sequence↗

Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2.

RAG1 and RAG2 are essential for V(D)J recombination and lymphocyte development. These genes are thought to encode a transposase derived from a mobile genetic element that was inserted into the vertebrate genome 450 million years ago. The regulation of RAG1 and RAG2 was investigated in vivo with bacterial artificial chromosome (BAC) transgenes containing a fluorescent indicator. Coordinate expression of RAG1 and RAG2 in B and T cells was found to be regulated by distinct genetic elements found on the 5' side of the RAG2 gene. This observation suggests a mechanism by which asymmetrically disposed cis DNA elements could influence the expression of the primordial transposon and thereby capture RAGs for vertebrate evolution.

Animals↗

Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization.

Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.

Alleles↗

Preconception urethane or chromium(III) treatment of male mice: multiple neoplastic and non-neoplastic changes in offspring.

Increase in neoplasia in offspring after preconception exposure of parents presents puzzling features such as high frequency of effects and lack of Mendelian inheritance. The present study examined the hypothesis that preconception carcinogenesis involves an increase in the rate of occurrence of neoplasms with a spontaneous incidence. Male NIH Swiss mice (12 per group) were exposed 2 weeks before mating (once, ip) to urethane (1.5 g/kg) or chromium(III) chloride (1 mmol/kg). Offspring (48-78/sex/group) were examined for all grossly apparent changes when moribund or at natural death, followed by histopathological diagnosis and statistical analysis. Significant exposure-related changes occurred in multiple organs. Ten to 20 percent of offspring showed changes related to paternal exposure, including at least one sired by most treated males. Pheochromocytomas occurred in both male and female offspring after both treatments, with none in controls. These neoplasms are rare in mice and suggest endocrine dysfunction as a component of preconception carcinogenesis. This was supported by increases in thyroid follicular cell and Harderian gland tumors, ovarian cysts, and uterine abnormalities. Lung tumors were increased in female offspring only. Effects seen in offspring only after paternal urethane exposure were an increase in preneoplasia/neoplasia in the glandular stomach (males) and in females, increased lymphoma but decreased incidence of histiocytic sarcoma. Increases in incidence of male reproductive gland tumors and of renal non-neoplastic lesions occurred only after chromium exposure. Thus, preconception exposure of fathers to toxicants had a significant impact on both neoplastic and non-neoplastic changes in almost all tissues in which these lesions often occur naturally during the aging process.

Adenoma↗

Characterization of three splice variants and genomic organization of the mouse BMAL1 gene.

The BMAL1 gene encodes a member of the basic helix-loop-helix/PER-ARNT-SIM (bHLH/PAS) family of transcription factors. It is a key regulator of circadian rhythms. Using sequence information from human BMAL1 (hBMAL1) cDNAs previously reported by our laboratory, we have isolated and characterized cDNAs encoding three splice variants of the mouse BMAL1 (mBMAL1) gene. Of the three splice variants, mBMAL1b extends for 1878 bp in the coding sequence, which is 91% identical to that of hBMAL1b; its deduced amino acid sequence is 626 residues long and is 98% identical to that of hBMAL1b, and sequence identities in the bHLH, PAS-A, and PAS-B regions are 98, 100, and 100%, respectively. mBMAL1b' arises from alternative usage of exon 2, which results in a 7-amino-acid insertion and alternative splice acceptor usage at the intron 9/exon 10 splice junction, which causes an alanine residue deletion. mBMAL1b' encodes 632 amino acids and contains the bHLH/PAS domains. mBMAL1g' is generated by alternative splice acceptor usage at the intron 6/exon 7 splice junction, which results in a 28-bp deletion adjacent to the 5' end of the PAS domain. Since the 28-bp deletion shifts the reading frame, mBMAL1g' is predicted to encode a product of only 222 amino acids that lacks the PAS domain. The tissue distributions of the three splice variants showed some variation. The variations in the tissue distributions and predicted amino acid sequences suggest that the three splice variants may have different functions. Direct sequencing of the genomic mBMAL1 clones indicated that the coding sequence of mBMAL1 spans 32 kb and includes 17 exons. An unusual exon/intron donor sequence was found in intron 14, which begins with GC at the 5' end. Comparison with the bHLH/PAS family genes revealed that the intron/exon splice pattern of mBMAL1 most closely matches that of the mAhr, which suggests that BMAL1 and Ahr belong to the same subclass and may be derived from a common primordial gene.

ARNTL Transcription Factors↗

Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21.

The beclin 1 (BECN1) gene encodes a 60-kDa coiled-coil protein that interacts with the prototypic apoptosis inhibitor Bcl-2. Previous studies indicate that beclin 1 maps to a region approximately 150 kb centromeric to BRCA1 on chromosome 17q21 that is commonly deleted in breast, ovarian, and prostate cancer. The complete cDNA sequence of beclin 1 encodes a 2098-bp transcript, with a 120-bp 5' UTR, 1353-bp coding region, and 625-bp 3' UTR. Hybridization screening of a human genomic PAC library identified PAC 452O8, which contains the complete beclin 1 gene. Determination of the exon-intron structure of beclin 1 reveals 12 exons, ranging from 61 to 794 bp, which extend over 12 kb of the human genome. FISH analysis of human breast carcinoma cell lines using PAC 452O8 as probe identified allelic beclin 1 deletions in 9 of 22 cell lines. Sequencing of genomic DNA from 10 of these cell lines revealed no mutations in coding regions or splice junctions. Additionally, Northern blot analysis of 11 cell lines did not identify any abnormalities in beclin 1 transcripts. These results indicate that human breast carcinoma cell lines frequently contain allelic deletions of beclin 1, but not beclin 1 coding mutations.

Alleles↗