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Biomedical subjects

Y Yin

Publications and source records attributed to Y Yin.

At least 91 records · Page 5Linked to original sources

Involvement of p85 in p53-dependent apoptotic response to oxidative stress.

Reactive oxygen species have damaging effects on cellular components and so trigger defensive responses by the cell and even programmed cell death, although the mechanisms by which mammalian cells transmit signals in response to oxidative damage are unknown. We report here that the protein p85, a regulator of the signalling protein phosphatidyl-3-OH kinase (PI(3)K), participates in the cell death process that is induced in response to oxidative stress and that this role of p85 in apoptosis does not involve PI(3)K. We show that disruption of p85 by homologous recombination impairs the cellular apoptotic response to oxidative stress. Because the protein p53 is required for cell death induced by oxidative damage, we examined the relation between p85 and p53. Using a chimaeric p53 fusion protein with the oestrogen receptor (p53ER) to supply p53 (p53 is induced upon binding of p53ER to oestradiol) in a p53-deficient cell line, we found that p85 is upregulated by p53 and that its involvement in p53-mediated apoptosis is independent of PI(3)K. We propose that p85 acts as a signal transducer in the cellular response to oxidative stress, mediating cell death regulated by p53.

Androstadienes↗

Stereoselective pharmacokinetics of chlorpheniramine and the effect of ranitidine.

This single-dose, randomized, crossover study was carried out to investigate the potential effect of ranitidine on the pharmacokinetics of chlorpheniramine. The study also afforded an opportunity to add to the limited data currently available on the stereoselective pharmacokinetics of chlorpheniramine. Healthy subjects received a single oral 4 mg dose of racemic chlorpheniramine on two separate occasions: alone, and on day 6 of dosing with ranitidine 75 mg b.i.d. for 8 days. Serum concentrations and urinary recovery of (S)-(+)- and (R)-(-)-chlorpheniramine were unaffected by administration of ranitidine, indicating no pharmacokinetic drug-drug interaction. The observed chlorpheniramine pharmacokinetic data were consistent with previous data and indicated approximately 2.5-fold higher serum concentrations of the (S)-(+) enantiomer. Previously reported high variability in chlorpheniramine pharmacokinetics was greatly reduced by well-controlled food and fluid intake.

Adolescent↗

Heat-induced testicular apoptosis occurs independently of hormonal depletion.

Previous studies have demonstrated that testicular germ cell apoptosis can be induced both by heat stress and by withdrawal of androgens and gonadotrophins. To investigate whether heat-induced germ cell apoptosis occurs independently of the altered levels of hormones that occur with heat exposure, mouse testicular apoptosis was studied using an in vitro system with controlled levels of testosterone, FSH and LH. It was observed that cells underwent apoptosis sooner in the absence of hormones at the same temperature. Apoptosis also occurred earlier at abdominal temperature compared to scrotal temperature with the same hormonal levels. No somatic tissues studied underwent apoptosis at 37 degrees C under the same culture conditions. These results suggest that heat stress may independently activate an apoptotic pathway in the testis, and that hormone deprivation may induce apoptosis via a separate mechanism.

Journal Article↗

Experimental cryptorchidism induces testicular germ cell apoptosis by p53-dependent and -independent pathways in mice.

Cryptorchidism is associated with male infertility: germ cell loss occurs by apoptosis in response to elevated temperature. Since the tumor suppressor p53 is highly expressed in the testis and is known to induce apoptosis, an investigation was undertaken to establish whether heat stress causes p53-mediated germ cell apoptosis. Using a mouse model of experimental unilateral cryptorchidism, it was observed that testicular weight reduction, germ cell loss, and DNA fragmentation all began in the cryptorchid testes on Day 6-7 in wild-type mice. In contrast, these changes were delayed by 3 days in p53-/- mice. These results suggest that abdominal heat stress induces germ cell loss through two apoptotic pathways: a p53-dependent pathway responsible for the initial phase of germ cell apoptosis, and a p53-independent pathway that accounts for subsequent apoptosis.

Animals↗

Childhood incidence of acute lymphoblastic leukaemia and exposure to broadcast radiation in Sydney--a second look.

INTRODUCTION: Recent findings of an apparent association between incidence of childhood leukaemia and radio frequency radiation (RFR) from television transmission antennas in Sydney, NSW, are examined. METHODS: Incidence of childhood (0-14 years) acute lymphoblastic leukaemia (ALL) at the local government area (LGA) level is related to estimated exposure levels of RFR from television transmission antennas, using Poisson regression techniques. RESULTS: Most of the association between ALL incidence and television transmission RFR is shown to be the result of an influential observation: one of the highly exposed LGAs contributes all the excess, while in a similarly exposed LGA childhood ALL incidence was found to be no higher than the rate expected for NSW. With the influential observation excluded from the analysis, no positive correlation between exposure to RFR and leukaemia is evident. Conversely, under the assumption of an association with RFR, the low probability of the observed incident cases in LGAs under conditions of relatively high exposure to RFR conflicts with the assumption of an effect. CONCLUSION: The apparent association between childhood ALL incidence and RFR radiation from television towers is weaker when an LGA-level analysis is conducted.

Adolescent↗

[Study of HDV infection in Shandong province].

To understand the situation of HDV infection in Shandong province and to explore the relationship between HDV and HBV infections, 2681 samples infected with HBV were tested for serum anti-HDV with enzyme linked immunosorbent assay, in Shandong. Among them, 207 (7.72%) were found to be anti-HDV positive. Anti-HDV positive rates in HBsAg carriers and in hepatitis B patients were 3.16% and 13.15%, respectively. A significant difference (P < 0.001) was noticed between the two groups. In the second group, anti-HDV positive rates in patients with chronic active hepatitis and severe hepatitis were both higher than those in patients with acute hepatitis and chronic persistent hepatitis and the difference was significant (P < 0.001). The longer the history and the more severe the condition the higher of the anti-HDV positive rate was seen. The results indicated that the combined and over-lapping HDV infections were both responsible for the chronic status of hepatitis B and its deterioration.

Adolescent↗

[Correlation between accumulation of (99m)Tc-MIBI in breast cancer or benign lesion, cell proliferation and angiogenesis].

OBJECTIVE: To study the accumulation of (99m)Tc-MIBI in breast cancer or benign lesions and the correlation between cell proliferation and angiogenesis. METHOD: (99m)Tc-MIBI positive imaging was performed on 38 patients with palpable breast mass. A ratio of radioactivity value of mass to normal tissue was assessed 10 minutes after injection of (99m)Tc-MIBI in posterior oblique view. Cell proliferation and angiogenesis were assessed by immunostaining of proliferating cell nuclear antigen (PCNA) and ulex europaeus I lectin (UEA- I). Data were analyzed by T-test, correlation and regression analysis. RESULT: We studied 17 true-positive, 5 false-negative, 15 true-negative, and 1 false positive patients (chi(2) = 18.74, P < 0.001). In patients with positive (99m)Tc-MIBI scans, the diameter of mass (4.00 +/- 1.95 cm) was larger and the percentage of PCNA positive cell (74.13% +/- 13.84%) was significantly higher than that in patients with negative scans (2.14 +/- 1.00 cm, 43.76% +/- 20.78%, P < 0.01). No significant evidence of difference between the number of angiogenic vessels of the two groups (181.3 +/- 71.7, 138.3 +/- 103.0, P = 0.141). The accumulation of (99m)Tc-MIBI was most strongly correlated with the percentage of PCNA positive cell (r = 0.56, P = 0.000), but was not related to the number of vessels (r = 0.31, P = 0.056). In stepwise regression analysis, the variance number of vessels was not included in the model. CONCLUSION: The accumulation of (99m)Tc-MIBI in breast cancer is an indicator of cell proliferation, and no evident relationship with angiogenesis has been found.

Adult↗

[Low temperature FTIR study of the structure of ruthenium polyhydrides].

A novel compound of Ru2H4 (CO) (PPh3)4 (A) is synthesized under hydrogen atmosphere. An in situ infrared apparatus which can be operated at liquid nitrogen temperarure is established. The structural conversion of RuH4 (PPh3)3 between dihydrogen and dihydride is observed firstly at room temperature. It is suggested that a fluxional molecule between terminal and bridged hydrogen appears in (A) with temperature changes. H2 molecule coordinated in ruthenium complex is rather easy to be substituted by CO, N2 and small organic molecule, this property is very important for activing molecular hydrogen and using in hydrogenation of unsaturated compounds.

English Abstract↗

Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9.

Previously we identified a partial human cDNA for a novel cochlear transcript, hCoch-5B2 (HGMW-approved symbol D14S564E), using subtractive hybridization techniques. Herein we report isolation and characterization of both human and mouse (D12H14S564E) cDNAs for Coch-5B2. Full-length Coch5B2 deduced amino acid sequences reveal a very high degree of conservation in the coding region (89% nucleotide and 94% amino acid identity and a potential signal peptide and two regions of extensive homology to the collagen-binding type A domains of von Willebrand factor, also present in other secreted proteins, including extracellular matrix components. High levels of hCoch-5B2 expression are seen only in human fetal inner ear structures, cochlea, and vestibule, among a large panel of human fetal and adult tissues. Coch-5B2 expression in the mouse is more widespread than in the human, with message detected in mouse adult spleen, cerebrum, cerebellum/medulla, and thymus. In both species very low level expression is detected in total eye. More specifically, mouse retina shows a higher level of mCoch-5B2 message than sclera and choroid. We have mapped hCoch-5B2 to human 14q11.2-q13 by somatic cell hybrid analysis and FISH and, more precisely, using radiation hybrids to a region of markers linked to DFNA9, a nonsyndromic autosomal dominant sensorineural hearing loss with vestibular defects. Furthermore, we detect hCoch-5B2 on three overlapping YACs, two of which also contain one of the markers linked to DFNA9. mCoch-5B2 was genetically mapped in the mouse to chromosome 12, in a region of homologous synteny with human 14q11.2-q13, which contains the asp1 (audiogenic seizure prone) locus in the mouse.

Amino Acid Sequence↗

An ancient conserved gene expressed in the human inner ear: identification, expression analysis, and chromosomal mapping of human and mouse antiquitin (ATQ1).

We constructed and screened a human fetal cochlear cDNA library to identify genes involved in hearing and deafness. From this library we isolated a cDNA corresponding to the highly conserved ancient gene antiquitin (ATQ1). The plant homolog of ATQ1 is thought to be involved in regulating turgor pressure, a function that also would be essential for cells of the mammalian cochlea. Northern blots of 13 human fetal tissues show antiquitin to be highly expressed in cochlea, ovary, eye, heart, and kidney. Using RT-PCR of rat cochlear hair cell-specific cDNA libraries, we detect antiquitin expression in outer hair cells, but not in inner or vestibular type 1 hair cells, suggesting that antiquitin is not expressed ubiquitously in the cochlea. Human ATQ1 was mapped to human chromosome region 5q31 using fluorescence in situ hybridization, and mouse ATQ1 was mapped to mouse chromosome 18 by single-strand conformation polymorphism mapping of interspecific backcross progeny DNAs. Four human antiquitin-like sequences, possibly pseudogenes, were also identified and mapped.

Adaptor Proteins, Signal Transducing↗

RF2a, a bZIP transcriptional activator of the phloem-specific rice tungro bacilliform virus promoter, functions in vascular development.

Rice tungro bacilliform virus (RTBV) replicates only in phloem cells in infected rice plants and its promoter drives strong phloem-specific reporter gene expression in transgenic rice plants. We isolated a cDNA encoding a basic leucine zipper (bZIP) protein, RF2a, which binds to the Box II cis element that is important for expression from the promoter. RF2a, which stimulates Box II-dependent transcription in a homologous in vitro transcription system, accumulates in nuclei of phloem and certain other cell types in shoots, but is found at only very low levels in roots. Transgenic antisense plants in which RF2a accumulation was suppressed had normal roots but stunted, twisted leaves with small, disorganized vascular bundles, an enlarged sclerenchyma and large air spaces. We propose that the RTBV promoter exploits a host transcription factor that is critical for leaf tissue differentiation and vascular development for its expression.

Amino Acid Sequence↗

p53 is associated with the nuclear envelope in mouse testis.

p53 has been postulated to play a role in meiosis as well as in the regulation of germ cell numbers by apoptosis. This study investigated the subcellular localization of p53 in the testis, including conditions known to induce germ cell apoptosis. Western blot analysis showed that p53 was enriched in the nuclear envelope fraction, and confocal microscopy confirmed that p53 was associated with the nuclear envelope of germ cells. Exposure of the testis to heat stress induced translocation of p53 into the nucleus. Nuclear envelope binding provides an optimal site for rapid entry of p53 into the nucleus, where it may act as a DNA-binding protein to induce apoptosis or cell cycle arrest in response to appropriate stimuli. The nuclear envelope sequestration of p53 also provides a framework to understand how mitosis and meiosis in the testis may proceed despite high intracellular concentration of p53.

Animals↗

A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibited.

TLS (FUS) and the related gene EWS encode the N-terminal portion of many fusion oncoproteins involved in human sarcomas and leukemia. TLS is an RNA-binding nuclear protein that is identical to hnRNP P2 and may be implicated in mRNA metabolism. When RNA polymerase II is inhibited, TLS immunostaining in the nucleus is dramatically altered, from its normal diffuse nucleoplasmic pattern to accumulation in dense nuclease-resistant aggregates. Co-immunostaining with antibodies to fibrillarin or p80 coilin and immunoelectron microscopy revealed that the TLS aggregates are associated with the nucleolus and are distinct from other known structures such as the coiled body or the interchromatin granule. Injection of cells with an oligodeoxynucleotide that disrupts splicing does not result in redistribution of TLS, indicating that the event is specific to inhibition of transcription. Oncoproteins that contain the N-terminal domain from either TLS, EWS or their Drosophila homologue, SARFH (CAZ), are also targeted to the same structure. These findings suggest a correlation between the topogenic and transforming activities of TLS and EWS N-termini and imply the existence of cellular targets that are shared by the germ-line encoded proteins and their oncogenic derivatives.

3T3 Cells↗

Pharmacokinetics and pharmacodynamics of ranitidine in renal impairment.

OBJECTIVE: The pharmacodynamics and pharmacokinetics of ranitidine were examined in subjects with varying degrees of renal function to determine the effect of this condition on acid-antisecretory activity. METHODS: Subjects with creatinine clearances (Ccr) ranging from 0 to 213 m1.min-1 received single 50-mg and 25-mg i.v. doses of ranitidine. This was followed by determination of serum and urine ranitidine concentrations, and continuous gastric pH monitoring for 24 h. RESULTS: Serum ranitidine concentrations were described by a two-compartment model linked to a sigmoidal Emax model describing gastric pH. Ranitidine renal clearance, ranging from 0 to 1003 m1.min-1, correlated with CPAH (r2 = 0.707), while non-renal clearance was unaltered. Steady-state volume of distribution decreased by half in severe renal impairment. No changes in the effective concentration at half-maximal response (EC50), maximal response (Emax), or basal response (E0) were observed. Thus, renal elimination of ranitidine declined in parallel with renal function, while sensitivity to the pharmacologic effect (gastric pH elevation) was unaltered. Ranitidine was cell tolerated in these renally impaired subjects. CONCLUSION: These data indicate that the current recommendation for renal impairment dose reduction (by two-thirds when Ccr < 50 m1-min-1) might result in under-treating moderately impaired patients, and suggests a less conservative dose reduction (by half when Ccr < 10 m1.min-1) to avoid therapeutic failure while remaining within the wide margin of safety for this drug.

Adult↗

Imaging of the hand and wrist.

This article reviews many of the most commonly used modalities for imaging the hand and wrist. Particular attention is paid to proper radiographic positioning, with emphasis on the four-view wrist series. Standard wrist measurements are detailed, and wrist arthrography is also discussed. Techniques for cross-sectional imaging, computed tomography, and MR imaging are reviewed, and several examples are presented as to where MR imaging is diagnostically valuable.

Anthropometry↗

Ligamentous instabilities of the wrist.

Carpal ligament instabilities are conditions in which the individual carpal bones have become unstable due to abnormal ligament support. Early diagnosis of ligamentous wrist instabilities is important because late diagnosis or failed diagnosis may lead to severe complications such as osteoarthritis. This article reviews the most common ligamentous instability patterns of the wrist and focuses on how to perform and obtain radiograms which will allow reliable diagnosis of wrist instabilities.

Algorithms↗

Promoter elements required for phloem-specific gene expression from the RTBV promoter in rice.

Previous studies indicated that a DNA fragment comprising nucleotides (nt) -164 to +45 of the RTBV promoter is sufficient to drive phloem-specific expression of a reporter gene in transgenic rice plants. In addition, two potential cis elements, Box I (nt -3 to +5) and Box II (nt -53 to -39) were identified by DNA-protein interaction assays. In this study, the results of further in vivo studies involving mutagenesis of selected DNA sequences and analysis of expression of a reporter gene in transgenic rice plants revealed that, in addition to Box I and Box II, other elements are required for phloem-specific gene expression, among which are a direct repeat (ASL Box, nt -98 to -79) and a GATA motif (nt -143 to -135). All the these elements bind rice nuclear factors specifically, and mutations of the elements were identified that resulted in loss-of-competition in electrophoretic mobility shift assays. A DNA fragment comprising nt -164 to -32, which contains Box II, the ASL Box and the GATA motif, conferred phloem-specific reporter gene expression independent of Box I when fused to a heterologous CaMV 35S minimal promoter and introduced to transgenic rice plants. Studies that introduced point mutations suggested that in the context of the -103 to +45 promoter fragment, Box II and the ASL Box act synergistically to confer tissue-specific gene expression. Similar studies in the -164 to +45 promoter fragment indicated that the -164 to -103 region, which includes the GATA motif, contains sequences that are functionally redundant with those in the -103 to -32 region, including the ASL Box and Box II. It is concluded that these regions act additively to direct phloem-specific gene expression.

Badnavirus↗