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L Xu

Publications and source records attributed to L Xu.

At least 703 records · Page 39Linked to original sources

The cytoplasmic domain of the interleukin-1 receptor is required for nuclear factor-kappa B signal transduction.

Interleukin-1 (IL-1) plays a central role in mediating immune and inflammatory responses. Binding of IL-1 to the type I 80-kDa receptor results in generation of intracellular signals and activation of the transcription factor NF-kappa B. However, the nature of the signals required to generate NF-kappa B binding activity remains unclear. In this paper, we show that NF-kappa B1 (p50) and RelA (p65) were specifically translocated to the nucleus following activation of intact type I IL-1 receptor (IL-1R). The C-terminal region of the type I IL-1R is required for this effect, and deletion of its cytoplasmic domain abrogates the activation of NF-kappa B by IL-1. These results provide evidence that IL-1 modulates the activity of NF-kappa B through the type I IL-1 receptor and identifies a domain required for signal transduction to this specific transcription factor.

Base Sequence↗

Consistent chromosomal losses in head and neck squamous cell carcinoma cell lines.

Clonal chromosomal abnormalities were characterized in nine cell lines established from squamous cell carcinomas of the head and neck. Aneuploidy was a common feature; one cell line was near-diploid, three were near-triploid, four were near-tetraploid, and one cell line showed extensive variation in chromosome numbers. Consistent numerical abnormalities included loss of the sex chromosomes in six cell lines, losses of chromosomes 2 and 21 in six and five cell lines, respectively, and gain of chromosome 20 in five cell lines. Recurrent structural rearrangements included del(10)(q22-q26) (seven cell lines), i(5)(p10) (six cell lines), i(8)(q10) (six cell lines), add(19)(q13) (six cell lines), del(4)(q21-q31.3) (five cell lines), i(3)(q10) (four cell lines), del(12)(p11.1-p12) (four cell lines), and add (18)(q21-q23) (four cell lines). Other changes were noted in lower frequencies. Loss of specific regions on chromosomes 2, 3p, 4q, 5q, 8p, 10q, 12p, 18q, 19q, and 21 suggests that they may represent sites of putative tumor suppressor genes, loss of which may play a role in the pathogenesis of squamous cell carcinomas of the head and neck. Alternatively, gain of chromosomal region 3q, 5p, and 8q due to isochromosome formation suggests that more than one mechanism is involved in malignant transformation. Cytogenetic evidence of gene amplification was found in two cell lines; as an hsr(11)(q13) in one and as dmins in the other. The clonal karyotypes of four cell lines were compared with those of their respective primary tumors. In all cell lines, clonal evolution had occurred, with loss of some rearrangements present in the primary tumors or the gain of additional abnormalities.

Aged↗

Cloning in a plasmid of an MMTV from a wild Chinese mouse: sequencing of the viral LTR.

Plasmid subcloning by conventional techniques of full length exogenous mouse mammary viruses (MMTV) has not been realized because of the involvement of host-mediated structural changes in the viral gag gene. To circumvent this problem, an alternative subcloning method, excision of phagemid (pBluescript SK) from lambda ZAP II, was successfully used to subclone a novel exogenous MMTV (JYG-MMTV) provirus fragment containing an intact gag gene. Sequence analysis revealed that the LTR of this virus is significantly different from the LTR of C3H-MMTV in the U3 region.

Amino Acid Sequence↗

Role of specific isoforms of protein kinase C in angiotensin II and lipoxygenase action in rat adrenal glomerulosa cells.

Evidence indicates that the lipoxygenase (LO) pathway of arachidonic acid is a key mediator of angiotensin II (AII)-induced aldosterone synthesis in adrenal glomerulosa cells. Although protein kinase C (PKC) may play a role in AII action, the precise PKC isoforms involved and whether LO products can activate PKC is not clear. We therefore evaluated the effect of AII and LO products such as 12- and 15-hydroxyeicosatetraenoic acids (HETEs) on PKC activation in isolated rat adrenal glomerulosa cells. PKC activity was measured by the phosphorylation of a PKC specific peptide while the PKC isoforms were identified by Western immunoblotting using antibodies that recognize the alpha, beta, gamma or epsilon isoforms of PKC. Treatment of the cells for 15 min with AII (10[-8]M) or the LO products 12- or 15-HETE caused a marked increase in PKC activity in membrane fractions with reciprocal decreases in the cytosolic PKC activity. Rat glomerulosa cells expressed only the alpha, and epsilon isoforms of PKC. AII increased membrane bound levels of both PKC-alpha and -epsilon (1.9- and 1.5-fold, respectively), whereas the LO products predominantly activated PKC-epsilon. Reciprocal decreases in immunoreactive cytosolic PKC levels were seen. AII-induced aldosterone synthesis was blocked by H-7 and retinal as well as by a PKC-specific pseudosubstrate inhibitor, PKC(19-36). These results suggest that AII and LO pathway-induced actions in the adrenal glomerulosa may be mediated by specific PKC isoforms.

Angiotensin II↗

Peripheral analysis of frequency in human ears revealed by tone burst evoked otoacoustic emissions.

Otoacoustic emissions were evoked in the same ears with single tone bursts at 1, 2 and 3 kHz and with a complex stimulus consisting of a digital addition of the three tone bursts. Stimuli were presented at 75, 59 and 37 dB SPL to 28 ears of human subjects with normal hearing. The purpose was to determine if comparisons of responses to the complex stimulus with a posthoc addition of responses from single tone bursts could delineate features of cochlear frequency analysis of short-duration signals. For processing of the data, the results from the individual tone bursts were combined offline to form a composite response. This was then compared with the response obtained with the complex stimulus. Results revealed close correspondence between the spectra of the complex and composite responses in all ears despite interindividual differences in response morphology. Correlations between the complex and composite waveforms exceeded 80% for all stimulus levels. Subtractions of the two spectra revealed that the majority of the differences occurred at frequencies on the high-frequency slopes of the 1- and 2-kHz spectral peaks. This was due to a reduction in energy for the responses obtained with the complex stimulus. There was little variation between the two response types in the peak frequencies of their spectra, in the energy at frequencies on the lower frequency sides of the spectral peaks at 1 and 2 kHz, or in the spectral components at 3 kHz. Results reveal characteristics of the analysis of frequency in the preneural stages of cochlear processing.

Acoustic Stimulation↗

A comparative study of particle size dependency of IR and XRD methods for quartz analysis.

Quartz (SiO2) is considered a probable carcinogen. In order to enforce health and safety standards, techniques that can accurately determine the quartz content of materials are necessary. Currently, two techniques dominate quartz analysis--the infrared (IR) spectrophotometry method and the X-ray diffraction (XRD) method. Unfortunately, there are problems associated with these techniques, such as sample preparation and particle size effect. This study focuses on particle size effect on quartz determination by both IR and XRD. Seven size groups of pure quartz samples, with mean diameters from 1.5 to 20 microns, were used. A set of samples with different quartz masses was prepared for each size group and subjected to both IR and XRD analysis. Two sets of calibration curves, one each from IR and XRD, were obtained. It was found that both IR and XRD methods are size-dependent but in an opposite way. As particle size increases, IR peak height decreases and XRD peak height increases for the same quartz content (mass). Since both methods are particle size-dependent, it is important that the standard quartz sample and samples of interest have similar particle size distributions. Specifically, when coal dust samples are ashed before analysis, the after-ashing particle size distribution should be used. Particle size distribution will change after ashing and it is the after-ashed particles that directly affect the IR and XRD analysis.

Calibration↗

IFN-gamma represses epsilon germline transcription and subsequently down-regulates switch recombination to epsilon.

Cytokines have the ability to regulate the isotypes of antibodies produced during an immune response. For instance, IL-4 has been shown to induce the production of IgE by B cells, while IFN-gamma has been shown to inhibit this induction. Recent work has revealed that IL-4 appears to induce class switching to epsilon through its ability to specifically induce germline epsilon transcripts. Germline epsilon transcription appears to target class-switch recombination to the epsilon locus. However, the mechanism by which IFN-gamma inhibits the IL-4 induction of IgE is unknown. We hypothesized that IFN-gamma and IL-4 may have antagonistic effects on the same stage of B cell differentiation. Northern blotting analyses show that IFN-gamma suppresses the IL-4 induction of germline epsilon transcripts. In transient transfection assays, the IL-4 induction of transcription imparted by the minimal 179 bp germline epsilon promoter is repressed by IFN-gamma. Utilizing a digestion circularization-polymerase chain reaction assay we show that IL-4 induces switch recombination to epsilon, while IFN-gamma suppresses switch recombination to epsilon. These studies support a model that, through their differential effects on a cis-controlling element that regulates germline epsilon transcription, IL-4 and IFN-gamma are able to modulate B cell switch recombination to epsilon in a coordinated manner.

Animals↗

Overexpression of p53 protein in squamous cell carcinomas of head and neck without apparent gene mutations.

Structural alterations of p53 and overexpression of the p53 protein are found in a large proportion of human cancers. In this study, we examined the frequency of p53 mutations and p53 overexpression in squamous cell carcinomas (SQCC) of head and neck. Expression of p53 was detected by immunochemistry (IHC) with monoclonal antibodies defining three distinct epitopes: PAb421 (species cross-reactive epitope on normal and mutated p53), PAb1801 (epitope on normal and mutated human p53), and PAb240 (conformational epitope of mutated p53 and denatured normal p53). Genetic alterations of p53 were identified by single-strand conformational polymorphism (SSCP) analysis and DNA sequencing in selected cases. IHC assays revealed nuclear p53 immunostaining in 53% of cases (32 of 60) with PAb1801, 38% (23 of 60) with PAb421, and 32% (19 of 60) with PAb240. Cases positive with PAb421 or PAb240 were also positive with PAb1801, whereas PAb421 and PAb240 identified overlapping but distinct tumor subsets. Areas of carcinoma in situ present in the tumor specimens showed nuclear p53 immunostaining in 11 of 26 cases. SSCP analysis for exons 5-9, the most common sites of p53 abnormalities, revealed mutations in 26% (15 of 58) of the evaluable cases. Comparison of the SSCP results with the IHC results for PAb1801 identified 11 cases that were positive by both methods, 4 cases with p53 mutations that were negative by IHC, 20 cases positive by IHC but without detectable p53 mutations, and 23 cases negative by both methods. IHC with PAb240, which is thought to be specific for mutated p53, was positive in 9 cases with demonstrable p53 mutations and in 9 cases with no detectable mutations. DNA sequence analysis of nine tumors identified point mutations, nonsense mutations, and frame-shift mutations. In conclusion, our study shows that p53 overexpression in SQCC of head and neck as detected by IHC is a frequent finding, and that overexpression is associated with common types of p53 mutations in some cases. However, IHC identifies p53 overexpression in some tumors with apparently normal SSCP patterns and, conversely, tumors with nonsense or frameshift mutations may not express any p53 detectable by IHC.

Base Sequence↗

Molecular biology of rotaviruses. IX. Conservation and divergence in genome segment 5.

Nucleotide sequencing of RNA segment 5 from seven strains of group A rotavirus has been carried out to investigate the extent of diversity and conservation, as well as possible selective pressures involved in driving the fixation of sequence changes in this gene. Analyses of the derived sequences revealed that sequence conservation could not be correlated either with rotavirus serotype or the species of origin of the virus strain. These sequences together with other published and unpublished sequences of this gene have raised the total number available for comparison to 17. Alignment of all the available sequences revealed that only 88 amino acid positions (17.6%) in the protein encoded by gene 5 (VP5) are absolutely conserved but that the metal-binding motif reported by others is conserved in all sequences. Despite the high degree of sequence divergence, alignment of secondary structure predictions for VP5 showed a high level of conservation, suggesting that constraints on sequence divergence may operate at the level of overall higher-order structure of the encoded protein.

Amino Acid Sequence↗

A finite element analysis of the human temporomandibular joint.

A 2-D finite element model of the human temporomandibular joint (TMJ) has been developed to investigate the stresses and reaction forces within the joint during normal sagittal jaw closure. The mechanical parameters analyzed were maximum principal and von Mises stresses in the disk, the contact stresses on the condylar and temporal surfaces, and the condylar reactions. The model bypassed the complexity of estimating muscle forces by using measured joint motion as input. The model was evaluated by several tests. The results demonstrated that the resultant condylar reaction force was directed toward the posterior side of the eminence. The contact stresses along the condylar and temporal surfaces were not evenly distributed. Separations were found at both upper and lower boundaries. High tensile stresses were found at the upper boundaries. High tensile stresses were found at the upper boundary of the middle portion of the disk.

Bias↗

Nonsyndromic hearing loss: an analysis of audiograms.

We examined features of the audiograms of 136 individuals, from 28 families, affected by nonsyndromic genetic hearing loss. There were 83 (12 families) with autosomal dominant (AD) loss, 50 (15 families) with autosomal recessive (AR) loss, and 3 (1 family) with X-linked recessive loss. The main audiogram shapes found were sloping (50.3%), residual (26.5%), and flat (21.0%). Specific shapes (ascending and U-shaped) only occurred in 3.7% of AD cases. Audiogram shapes were found to be significantly different between AD and AR families, and showed intrafamilial and interfamilial variability. In the AR group, the main shapes were residual and sharply sloping, and in the AD group, sharply sloping, flat, and gently sloping. There was a significant difference in the degree of hearing loss between AD and AR types, with AD being milder than AR. It has been shown that there is more marked intrafamilial variation in the degree of hearing loss in AD families than in AR ones. The results suggest that the audiograms of nonsyndromic hearing loss are usually nonspecific and that counseling of family members would be better based on the specific family's condition rather than on group information.

Adolescent↗

Different potential of cellular and viral activators of transcription revealed in oocytes and early embryos of Xenopus laevis.

Many protein domains for transcriptional activation also function when fused to a heterologous DNA binding domain. In mammalian/HeLa cells, we have previously characterized the activation domains of several transcription factors using GAL4 fusion proteins. Here we have tested their transcriptional activity in oocytes and developing embryos of the clawed toad Xenopus laevis. We find that the "acidic" C-terminal domain of the herpesvirus VP16 (= Vmw65) activator, which is active from yeast to man, is also very active in the two Xenopus systems. The constitutive nature of this viral domain may have evolved to be refractory to cellular defense mechanisms. By contrast, activation domains from cellular eukaryotic transcription factors (TFE3, ITF2, MTF-1) are differentially active in oocytes and early embryos. This indicates that their activity can be regulated by protein modification and/or availability of specific coactivators. We have also compared VP16 induced enhancement of transcription from remote and promoter-proximal positions. In both oocytes and late blastula embryos, activation from a promoter-proximal position was more than 50 fold, while only a moderate stimulation (3-8 fold) was observed from remote positions. This may mean that frog oocyte and early embryos are not yet fully geared for gene control by remote enhancers, i.e. respond predominantly to close-by regulatory sequences. The fact that cellular enhancers are naturally located at various distances from the responsive promoters may thus be exploited by multicellular organisms for differential gene control at early and late stages of development.

Animals↗

Rak, a novel nuclear tyrosine kinase expressed in epithelial cells.

We have identified a new tyrosine kinase from human breast cancer cells called Rak (a Russian word for cancer) that shares 51% identity with c-Src. Sequencing of the full-length complementary DNA revealed that Rak is a tyrosine kinase with a molecular weight of 54,000 that contains SH2 and SH3 domains, as well as tyrosine residues analogous to the autophosphorylation and regulatory tyrosines of the Src family. Biochemical and site-directed mutagenesis analyses revealed that a carboxy-terminal peptide of p54rak was phosphorylated by a cytoplasmic tyrosine kinase (CSK) and that, as in the Src family, it is the COOH-terminal tyrosine that is phosphorylated by CSK. However, there were some properties of Rak that are distinct from Src-like kinases: (a) expression of Rak was predominantly in epithelial-derived cell lines and tissues, especially normal liver and kidney, and cell lines of breast and colon origin; (b) Rak does not harbor the NH2-terminal glycine essential for myristylation and membrane localization; and (c) Rak possesses a putative bipartite nuclear localization signal in the SH2 domain, and subcellular fractionation studies revealed that p54rak resides predominantly in the nucleus. In addition, p54rak was overexpressed in subsets of primary human epithelial tumors, suggesting that p54rak may have a role in human cancer. Thus, Rak is a novel epithelial-associated nuclear tyrosine kinase that may represent a unique subfamily of the Src-related kinases.

Amino Acid Sequence↗

A clinical analysis of 38 patients with primary tracheo bronchial tumors.

During a 17-year period, 38 patients with primary tracheobronchial tumors received surgical treatment in PUMC Hospital. Among the 38, 12 had low-malignancy tracheal tumors, 11 had benign tracheal tumors, 14 had low malignancy bronchial tumors and 1 had a benign bronchial tumor. Fifteen operations were performed on 12 patients with low-malignancy tracheal tumors, including local resection of the tumor and tracheal wall in 4 and curettage of the tumor plus electrical cauterization in 10. Postoperative radiotherapy was used as an adjuvant treatment in 8 patients with adenocystic carcinoma. Eight patients have survived for more than 5 years and 3 patients have survived for longer than 10 years postoperatively. All 11 patients with benign tumors received curettage of the tumor and were followed up for an average of 6.5 years. Among them, 9 are still alive. Of the 14 patients with low malignancy bronchial tumors, 5 underwent curettage of the tumor plus electrical cauterization through incision of the main bronchus or intermedial bronchus, and 7 underwent lobectomy or pneumonectomy. The authors conclude that the correct diagnosis rate can be increased by enhancing recognition of this disease and applying tracheal tomography and bronchoscopy.

Adolescent↗

[The clinical characters and treatment of lung cancer in youth].

From January 1970 to December 1990, 67 patients with lung cancer aged younger than 40 years, were treated in the PUMC Hospital. There were 43.3% with SCLC and 37.3% with adenocarcinoma. Twenty-eight patients underwent resection of the lung. Thirty-five cases received chemotherapy or radiotherapy only. The clinical and pathological characteristics of lung cancer in youth, and the influence of surgical and non=surgical treatments to the patients with lung cancer are discussed. The authors consider that the bronchoscopic and sputum smear examinations are very helpful for diagnosing lung cancer in the early stage. Postoperative adjuvant chemo- and radio-therapy is suggested because of the high incidence of SCLC and adenocarcinoma in the young patients with lung cancer.

Adenocarcinoma↗

[Report on the first nationwide survey of the distribution of human parasites in China. 1. Regional distribution of parasite species].

A nationwide (Taiwan Province not included) survey of the distribution of human parasites in China during 1988-1992 was conducted under the auspices of the Ministry of Public Health, with stratified masses randomly sampling. A total of 2,848 pilot sites in 726 counties with a population of 1,477,742 were surveyed, according to unified standard, unified diagnostic method and control quality. The overall infection rate of parasites was 62. 632%. Among them, the infection rate was over 50% in 17 provinces/autonomous regions/municipalities (P/A/M), over 80% in Hainan, Guangxi, Sichuan, Fujian, Zhejiang and Guizhou, being highest in Hainan (94. 735%). Altogether 56 species were detected. Centrocestus formosanus is reported for the first time at home, Echinochasmus liliputanus and Echinostoma angustitestis are reported for the first time at home and abroad. Echinochasmus fujianensis is a new species. E. histolytica, G. lamblia, A. lumbricoides, whipworm and pinworm were distributed nationwide, while Cysticercus (27 P/A/M), Taenia (27), hookworm (26), Balantidium coli (22), Clonorchis sinensis (22), Paragonimus westermani (21), H. diminuta (21), Echinococcus (18), H. nana (17), Fasciolopsis buski (16), T. spiralis (12) were distributed non-nationwide. A preliminary suggestion on intervention of the common and/or most detrimental parasitic diseases was submitted, including hydatidosis, taeniasis, cysticercosis, clonorchiasis, paragonimiasis, trichinellosis, hookworm disease, ascariasis, trichuriasis and enterobiasis.

Animals↗