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Biomedical subjects

X Lu

Publications and source records attributed to X Lu.

At least 271 records · Page 15Linked to original sources
PubMed1999

[The meaning of the expression of PCNA and c-erbB-2 in the hyperplasia of laryngeal epithelium].

OBJECTIVE: This study was performed to examine the relationship between PCNA and c-erbB-2 expression and histological diagnosis. METHOD: The percentages of PCNA-positive nuclei (PCNA index) were evaluated in biopsies of 10 with epithelial simple hyperplasia, 26 with dysplasia and 30 with squamous carcinoma by immunohistochemical staining. RESULT: The PCNA indices were 6.64%, 29.36% and 62.67% respectively. There were significant statistic correlation between these indices and their histological gradies of lesions (P < 0.01). C-erbB-2 was not positive in all of dysplastic lesion and weak in carcinoma (20%). CONCLUSION: The PCNA activity in dysplastic lesions of laryngeal premalignancis is higher than that in simple hyperplastic lesions but lower than that in carcinoma. The severe dysplasia with high PCNA indices should be treated clinically as the early invasive carcinom. The method should be regarded as a useful adjunct to traditional histological techniques with allowing more objective grading of epithelial hyperplastic lesions of larynx. There was no relationship between c-erbB-2 expression and histolotical diagnosis of hyperplastic lesions.

Adult↗
PubMed1999

[Diagnosis and restitution of nasal bone fracture].

OBJECTIVE: To discuss accurate methods of diagnosis and restitution for nasal bone fracture. METHOD: 280 cases of nasal trauma were examined by lateral x-ray test (horizontal CT-scan was also used in 76 cases of these patients). RESULT: 220 cases were found with bilateral fracture of nasal bone. Unilateral fracture, simple fracture of frontal process of maxilla, compound fracture of nasal bone and frontal process of maxilla, compound fracture of nasal bone, maxilla and perpendicular plate of ethmoid bone were seen in 12, 15, 30 and 3 cases respectively. CONCLUSION: X-ray examination can only find bilateral fracture of nasal bone, but CT-scan can demonstrate unilateral fracture, fracture of frontal process of maxilla and fracture of perpendicular plate of ethmoid bone. Restitution with pincers is still a routine therapeutic method for nasal bone fracture at present, and nasal septal reconstruction is necessary when both nasal bone and perpendicular plate of ethmoid bone were involved. But for those patients with high-position compound fracture, restitution by directly visual operation through lip-dental-gum approach is the best choice.

Adolescent↗
PubMed1999

[Time-resolved fluorescence investigations of aggregation in Langmuir-Blodgett multilayers of hemicyanine dye].

UV-visible absorption and steady-state and time-resolved fluorescence techniques were used to investigate the aggregation behavior in Y-type hemicyanine Langmuir-Blodgett (LB) multilayers. Hemicyanine molecules formed H aggregates in LB films leading to blue-shifts of the absorption and fluorescence bands with respect to those of monomeric hemicyanine in chloroform solutions. The aggregates in LB films were dissociated by mixing with arachidic acid. The measurement of fluorescence decay profiles could be used to quantitatively characterize the lifetime, weights and size of aggregates.

English Abstract↗
PubMed1998

lin-35 and lin-53, two genes that antagonize a C. elegans Ras pathway, encode proteins similar to Rb and its binding protein RbAp48.

The Ras signaling pathway for vulval induction in Caenorhabditis elegans is antagonized by the activity of the synthetic multivulva (synMuv) genes, which define two functionally redundant pathways. We have characterized two genes in one of these pathways. lin-35 encodes a protein similar to the tumor suppressor Rb and the closely related proteins p107 and p130. lin-53 encodes a protein similar to RbAp48, a mammalian protein that binds Rb. In mammals, Rb and related proteins act as regulators of E2F transcription factors, and RbAp48 may act with such proteins as a transcriptional corepressor. We propose that LIN-35 and LIN-53 antagonize the Ras signaling pathway in C. elegans by repressing transcription in the vulval precursor cells of genes required for the expression of vulval cell fates.

Amino Acid Sequence↗
PubMed1998

A novel human gene, WSTF, is deleted in Williams syndrome.

Williams syndrome (WS) is a developmental disorder caused by deletion of multiple genes at chromosome 7q11.23. Here, we report the identification and characterization of a novel gene, WSTF, that maps to the common WS deletion region. WSTF encodes a novel protein of 1425 amino acids with unknown function. It contains one PHD-type zinc finger motif followed by a bromodomain. Both motifs are found in many transcription regulators, suggesting that WSTF may function as a transcription factor. WSTF is ubiquitously expressed in both adult and fetal tissues. The WSTF gene consists of 20 exons spanning about 80 kb. Fluorescence in situ hybridization analysis shows that WSTF is deleted in 50/50 WS individuals. Hemizygous deletion of WSTF may contribute to WS.

Amino Acid Sequence↗
PubMed1998

A novel human gene FKBP6 is deleted in Williams syndrome.

Williams syndrome (WS) is a developmental disorder caused by haploinsufficiency of genes at 7q11.23. We have shown that hemizygosity of elastin is responsible for one feature of WS, supravalvular aortic stenosis. We have also implicated LIM-kinase 1 hemizygosity as a contributing factor to impaired visual-spatial constructive cognition in WS. Here we identify and characterize a novel gene, FKBP6, within the common WS deletion region. FKBP6 shows homology to the FK-506 binding protein (FKBP) class of immunophilins. FKBP6 has a putative N-terminal FK-506 binding and peptidylproyl isomerase (rotamase) domain and, like known high-molecular-weight FKBPs, an imperfect C-terminal tetratricopeptide repeat domain. FKBP6 is expressed in testis, heart, skeletal muscle, liver, and kidney. FKBP6 consists of nine exons and is completely contained within a 35-kb cosmid clone. Fluorescence in situ hybridization experiments show that FKBP6 gene is deleted in 40/40 WS individuals. Hemizygous deletion of FKBP6 may contribute to certain defects such as hypercalcemia and growth delay in WS.

Amino Acid Sequence↗
PubMed1998

Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity.

FKBP ligand homodimers can be used to activate signaling events inside cells and animals that have been engineered to express fusions between appropriate signaling domains and FKBP. However, use of these dimerizers in vivo is potentially limited by ligand binding to endogenous FKBP. We have designed ligands that bind specifically to a mutated FKBP over the wild-type protein by remodeling an FKBP-ligand interface to introduce a specificity binding pocket. A compound bearing an ethyl substituent in place of a carbonyl group exhibited sub-nanomolar affinity and 1,000-fold selectivity for a mutant FKBP with a compensating truncation of a phenylalanine residue. Structural and functional analysis of the new pocket showed that recognition is surprisingly relaxed, with the modified ligand only partially filling the engineered cavity. We incorporated the specificity pocket into a fusion protein containing FKBP and the intracellular domain of the Fas receptor. Cells expressing this modified chimeric protein potently underwent apoptosis in response to AP1903, a homodimer of the modified ligand, both in culture and when implanted into mice. Remodeled dimerizers such as AP1903 are ideal reagents for controlling the activities of cells that have been modified by gene therapy procedures, without interference from endogenous FKBP.

Amino Acid Sequence↗
PubMed1998

Rhesus macaques that become systemically infected with pathogenic SHIV 89.6-PD after intravenous, rectal, or vaginal inoculation and fail to make an antiviral antibody response rapidly develop AIDS.

A new simian-human immunodeficiency virus (SHIV) stock (SHIV 89.6-PD), derived from plasma of a rhesus macaque used for in vivo serial passage of virulence-attenuated SHIV 89.6, produces systemic infection after intravenous, intravaginal, or intrarectal inoculation of rhesus macaques. Infection with this virus results in high levels of viral antigen in plasma, a precipitous decline in CD4+ T-cell counts, and a disease syndrome that is characteristic of AIDS. Rapid progression to disease was associated with failure to seroconvert to viral antigens, whereas longer survival was associated with production of antiviral antibodies. In intravenously inoculated animals, peak antigenemia occurred at 7 days postinjection (PI) and severe CD4+ depletion occurred at 14 days PI. In mucosally infected animals, peak antigenemia occurred at 14 days PI and severe CD4+ depletion was not evident until 21 days PI. The 1-week delay in both viral antigenemia and CD4+ T-cell decline in mucosally infected animals is consistent with the hypothesis that, following vaginal inoculation, virus dissemination proceeds in a stepwise manner from the mucosal surface to the draining lymph nodes and subsequently to the bloodstream. This animal model can be used to test the ability of HIV-1 envelope-based vaccines to prevent infection or disease after challenge by the three major routes of HIV transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Protein-tyrosine phosphatase Shp-2 regulates cell spreading, migration, and focal adhesion.

Shp-2, a widely expressed cytoplasmic tyrosine phosphatase with two SH2 domains, is believed to participate in signal relay downstream of growth factor receptors. We show here that this phosphatase also plays an important role in the control of cell spreading, migration, and cytoskeletal architecture. Fibroblast cells lacking a functional Shp-2 were impaired in their ability to spread and migrate on fibronectin compared with wild-type cells. Furthermore, Shp-2 mutant cells displayed an increased number of focal adhesions and condensed F-actin aggregation at the cell periphery, properties reminiscent of focal adhesion kinase (FAK)-deficient cells. This is consistent with our previous observations in vivo that mice homozygous for the Shp-2 mutation died at midgestation with similar phenotype to FAK and fibronectin-deficient embryos, having severe defects in mesodermal patterning, particularly the truncation of posterior structures. Biochemical analysis demonstrated that FAK dephosphorylation was significantly reduced in Shp-2 mutant cells in suspension. Furthermore, regulated association of Src SH2 domain with FAK and paxillin during cell attachment and detachment on fibronectin was disrupted in Shp-2 mutant cells. This report defines a unique role of the Shp-2 tyrosine phosphatase in cell motility, which might guide the design of a new strategy for pharmaceutical interference of tumor metastasis.

Animals↗
PubMed1998

Downregulation of platelet-derived growth factor receptor-beta in Shp-2 mutant fibroblast cell lines.

The SH2-containing tyrosine phosphatase Shp-2 appears to function downstream of a variety of growth factor receptors and might play a positive role in cell proliferation. Here we report that expression of the beta subunit of platelet-derived growth factor receptor (PDGFR-beta) was specifically downregulated in mutant fibroblasts lacking a functional Shp-2, while the levels of PDGFR-alpha EGFR and IGFIR were not changed. PDGF-stimulated DNA synthesis and extracellular signal regulated kinase (Erk) activation was severely suppressed in mutant cells. RasGAP, that responds to activation of PDGFR-beta but not PDGFR-alpha, was not phosphorylated on tyrosine in mutant cells upon PDGF-treatment. Northern blot analysis failed to detect PDGFR-beta mRNA in mutant cells. The transcription initiation from the PDGFR-beta gene promoter was not significantly changed, but the half-life of its mRNA was shortened in Shp-2 mutant cells. These observations indicate that Shp-2 not only participates in transmission of signals from growth factor receptors but also plays a specific role in the control of the PDGFR-beta expression. We propose that this is an important mechanism for the positive control of cell proliferation by Shp-2.

Animals↗
PubMed1998

Resistance of biofilms to the catalase inhibitor 3-amino-1,2, 4-triazole.

Consortia of catalase positive bacteria consisting of Pseudomonas aeruginosa, Pseudomonas fluorescens, and Klebsiella pneumoniae, in both the planktonic form and as biofilms, disproportionate hydrogen peroxide into oxygen and water. The biofilm, however, continued to disproportionate the hydrogen peroxide in the presence of the catalase inhibitor, 3-amino-1,2,4-triazole, while the planktonic organisms did not. While the bacterial catalase-peroxidase-dismutase system was probably responsible for the disproportionation of hydrogen peroxide in both cases, biofilms resisted inhibition of this enzyme system.

Amitrole↗
PubMed1998

Expression of p21WAF1/CIP1 in adenocarcinoma of the uterine cervix: a possible immunohistochemical marker of a favorable prognosis.

BACKGROUND: The purpose of this study was to assess the prognostic significance of the expression of estrogen receptor and cell cycle regulatory gene products in cervical adenocarcinoma. METHODS: In 40 cases of adenocarcinoma of the uterine cervix and 10 normal cervices, expression of estrogen receptor and cell cycle regulatory gene products (cyclin E, p16, p21WAF1/CIP1, p27, p53, and Ki-67) was studied using immunohistochemical techniques. The survival of the patients was analyzed in terms of such variables as the expression of these molecules in the tumor and conventional clinicopathologic features, and the Cox proportional hazards model was used to predict the survival of patients with cervical adenocarcinoma. RESULTS: Expression of estrogen receptor was consistently observed in normal cervical glands, but in cervical adenocarcinoma it was lost (in 28 cases) or significantly diminished (in 12 cases). Normal cervical glandular cells were usually negative for the cell cycle regulatory gene products, whereas 47.5-85% of cervical adenocarcinomas were positive for these molecules. When the expression of these molecules was analyzed, significant positive correlations were found between p16 and p27, cyclin E and p27, and cyclin E and p21WAF1/CIP1. Univariate survival analysis revealed that the presence of parametrial invasion, the presence of lymph node metastasis, negative staining for p21WAF1/CIP1, and a moderately or poorly differentiated tumor all correlated significantly with a poor prognosis. In a stepwise regression analysis, the expression of p21WAF1/CIP1 and negative pelvic lymph nodes were the best predictors of a favorable prognosis. CONCLUSIONS: Expression of p21WAF1/CIP1 correlated with a favorable prognosis for patients with cervical adenocarcinoma and may serve as a useful marker of survival in cases of this disease.

Adenocarcinoma↗
PubMed1998

[Association between angiotensin II type I receptor gene and human essential hypertension].

OBJECTIVE: To determine whether the angiotensin II type I receptor gene might be implicated in human essential hypertension. METHODS: This was a case-control study on hypertension and normal blood pressure in Chinese DNA abstracted samples from 51 cases of essential hypertension and 74 normal controls were analysed by polymerase chain reaction,digestion of restriction enzyme and electrophesis. RESULTS: The genotype frequency of 1166A/1166C was 0. 196 (10/51) in the essential hypertension group, 0.081 (6/74) in the control group. The genotype frequency of 1166C/1166C was 0 in both groups. The gene frequency of 1166C was 0.098 in the essential hypertension group, 0.041 in the controls. There was a significant increase in allelic frequency of 1166C in hypertension. CONCLUSION: The results indicate that the increase in allelic frequency of 1166C is a risk factor and hence suggest that the change in the angiotensin II type I receptor gene is associated with essential hypertension.

Adolescent↗
PubMed1998

Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours.

The molecular mechanisms leading to Cushing's disease are unclear. Inhibitors of cyclin-cyclin dependent kinase (CDK) complexes are regulators of the cell cycle and may function as tumour suppressor genes, many of which have been involved in the pathogenesis of several human malignancies. A member of this family, the p27/kip1 gene, maps to chromosome 12p13 and encodes an inhibitor of several cyclin-CDK complexes; these control the progression of the cell cycle from G1 to S-phase. Complete lack of p27/kip1 function, as occurs in the p27/kip1 'knockout' mouse, produces a complex phenotype associated with the development of pituitary tumours, specifically those of the intermediate lobe corticotrophs. We therefore investigated whether structural and functional abnormalities of the p27/kip1 gene and loss at the chromosome 12p13 region were present in human corticotrophin (ACTH)-secreting pituitary tumours. We studied 21 pituitary tumours, of which 20 were ACTH-secreting (two of these had biochemical and histological features of 'intermediate-lobe' tumours and one was malignant) while the remaining tumour was a prolactinoma; three ectopic secretors of ACTH (two bronchial and one thymic carcinoid); and a non-secretory thymic carcinoid. The whole coding region of the p27/ kip1 gene was screened for mutations by PCR-SSCP analysis and/or direct sequencing, while tumour mRNA expression was analysed by means of a semi-quantitative duplex PCR. Three polymorphic microsatellite markers of the 12p13 region were used to assess loss of heterozygosity (LOH) in 12 samples. Finally, tumour p27/kip1 protein expression was assessed by immunohistochemistry using a monoclonal antibody in 12 samples suitable for analysis. No sequence abnormalities were found in any of the samples other than a previously-described polymorphism. No LOH was observed in the tumours analysed. p27/kip1 mRNA expression was similar in tumour samples in comparison with normal pituitaries. Seven of the eight corticotroph tumours analysed by immunohistochemistry stained positive for p27/kip1, including the intermediate lobe. The only malignant pituitary tumour in the original series showed an absence of staining for p27/kip1. In addition, the three carcinoid tumours studied were negative on immunohistochemistry. Of a further three malignant pituitary tumours assessed, two (including a prolactinoma) were essentially negative, while the third was moderately positive. We conclude that mutations of the p27/kip1 gene, deletions of the 12p13 area or changes in expression, are not a general feature of corticotroph tumours, even those with intermediate lobe characteristics. However, other mechanisms of p27/kip1 inactivation, such as an abnormality at the post-translational level, may be related to more aggressive histological subtypes of ACTH-secreting and possibly other pituitary tumours.

Adrenocorticotropic Hormone↗