Biomedical subjects

Q Pan

Publications and source records attributed to Q Pan.

At least 37 records · Page 2Linked to original sources

PubMed2001

Presence of antibody against the inducible Hsp71 in patients with acute heat-induced illness.

Antibodies against heat shock or stress proteins (Hsps) have been reported in a number of diseases in which they may be involved in the pathogenesis of the disease or may be of use for prognosis. Heat-induced diseases, such as heat cramps, heat exhaustion, or heat stroke, are frequent in hot working or living environments. There are still few investigations on the presence and possible significance of autoantibodies against Hsps in heat-induced illnesses. Using an immunoblotting technique with recombinant human Hsps, we analyzed the presence and titers of antibodies against Hsp60, Hsp71, and Hsp90alpha, and Hsp90beta in a group of 42 young male patients who presented with acute heat-induced illness during training. We also examined the presence of antibody against Hsp71 in a second group of 57 patients with acute heat-induced illness and measured the changes in titers of anti-Hsp71 antibodies in 9 patients hospitalized by emergency physicians. In the first group of young persons exercising in a hot environment, the occurrence of antibodies against Hsp71 and Hsp90alpha was significantly higher among individuals with symptoms of heat-induced illness (P < 0.05) than in the matched group of nonaffected exercising individuals. Moreover titers of antibody against Hsp71 were higher in individuals of the severe and mild heat-induced illness groups, the highest titer being found in the most severe cases. The results from the second group of 57 heat-affected patients exposed to extreme heat were similar. Again, patients with the more severe heat-induced symptoms showed a significantly higher incidence of antibodies to Hsp71 than controls and the titer of anti-Hsp71 was higher in the severely affected group. Finally, in a study of 9 patients, it was observed that the titer of anti-Hsp71 decreased during recovery from severe heat symptoms. These results suggest that measurement of antibodies to Hsps may be useful in assessing how individuals are responding to abnormal stress within their living and working environment and may be used as one biomarker to evaluate their susceptibility to heat-induced diseases.

Adolescent↗

PubMed2001

Antisense knockout of HOXB4 blocks 1,25-dihydroxyvitamin D3 inhibition of c-myc expression.

The expression of c-myc is decreased by 1,25-(OH)2D(3) during HL-60 cell differentiation. Concomitantly, 1,25-(OH)2D(3) increases the expression and DNA binding activity of HOXB4, a homeobox gene. HOXB4 binds to the c-my c gene at sites involved in blocking c-myc transcription elongation. In this study, a phosphorothioate antisense oligonucleotide targeted against HOXB4 was examined for its effect on 1,25-(OH)2D(3) inhibition of c-myc expression. Alone, 1,25-(OH)2D(3) (20 nM) increased HOXB4 levels by 103+/-7% (mean+/-s.e., n=3) and decreased c-myc levels by 89+/-5% (mean+/-s.e.m., n=3) at 48 h of treatment. HOXB4 antisense treatment completely blocked the induction of HOXB4 by 1,25-(OH)2D(3). In addition, HOXB4 antisense partially blocked 1,25-(OH)2D(3)-mediated decrease in c-myc levels (46+/-6% inhibition) and promotion of HL-60 cell differentiation (20+/-2% and 25+/-3% inhibition as assessed by nitroblue tetrazolium and non-specific esterase assays respectively). The data further establish that HOXB4 levels are regulated by 1,25-(OH)2D(3) and reveal that HOXB4 participates in the down-regulation of c-myc expression.

Alkaloids↗

PubMed2001

[Comparative study on liquid-based cytology for cervical carcinoma screening in a high-risk area of China].

OBJECTIVE: To evaluate the efficacy of liquid-based cytology (ThinPrep Pap Test) for cervical carcinoma screening in a high incidence area, Xiangyuan county of Shanxi province. METHODS: This study was performed on 1997 women residing in Xiangyuan county, a high incidence of cervical carcinoma. Exfoliative cervical samples and subsequent colposcopic biopsies were taken from all subjects. Cervical samples were collected into a liquid buffer for both ThinPrep Pap Test cytologic screening and human papilloma virus (HPV) DNA test. All tests were carried out independently and blindly of which the results were compared with those of HPV DNA detection and colposcopic biopsies. RESULTS: When the cytologic diagnosis of atypical squamous cells of determined significance (ASCUS) was taken as the detection threshold and compared with the "standard" biopsy, the ThinPrep slides were able to detect 100%(12/12) of squamous cell carcinoma (SCC) and 93.2% high grade squamous intraepithelial lesions (HSIL) which included 96.8% (30/31) CIN III, 90.7% (39/43) CIN II and 72.4%(92/127) low grade squamous intraepithelial lesions (LSIL). When cytologic diagnosis of HSIL was used as the detection threshold, the ThinPrep slides were able to detect 100% (12/12) SCC and 87%(27/31) CIN III. CONCLUSION: Cervical specimens collected into a liquid buffer are suitable for both cytologic screening and human papilloma virus test. The ThinPrep cytology demonstrates a high sensitivity for the detection of high grade squamous intraepithelial lesions and squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed2000

An efficient and concise regioselective synthesis of alpha-(1 --> 5)-linked L-arabinofuranosyl oligosaccharides.

A series of alpha-(1 --> 5)-linked L-arabinofuranosyl di-, tetra-, hexa- and octameric derivatives were synthesized efficiently. The process was carried out in a regio- and stereoselective manner using perbenzoylated arabinofuranosyl trichloroacetimidates as glycosyl donors and unprotected or partially protected arabinofuranosides as glycosyl acceptors in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf).

Arabinose↗

PubMed2000

Two clusters of acidic amino acids near the NH2 terminus of complement component C4 alpha'-chain are important for C2 binding.

Previous work has indicated a role for the NH2-terminal segment of the C3 alpha'-chain in the binding interactions of C3b with a number of its protein ligands. In particular, we have identified two clusters of acidic residues, namely, E736 and E737 and to a lesser extent D730 and E731, as being important in the binding of C3b to factor B and complement receptor 1 and the binding of iC3b to complement receptor 3. Whereas human C3 and C4 have an overall sequence identity of 29%, over a segment near the NH2 termini of their respective alpha'-chains the sequence identity is 56% (70% chemical similarity). Given the functional similarity between the C4b-C2 and C3b-B interactions in the respective formation of the classical and alternative pathway C3 convertases, as well as the sequence conservation of two acidic clusters, we hypothesized that residues 744EED and 749DEDD within the NH2-terminal segment of the C4 alpha'-chain would mediate in part the binding of C2 to C4b. We tested this hypothesis using three independent approaches. Site-directed mutagenesis experiments revealed that replacing subsets of the charged residues by their isosteric amides within either acidic cluster resulted in molecules having reduced C2 binding activity. Moreover, a synthetic peptide (C4 residues 740-756) encompassing the two acidic clusters was a specific inhibitor of the binding of C2 to red cell-associated C4b. Finally, Ab raised against the above peptide was able to block the interaction between red cell-associated C4b and fluid phase C2. Taken together, these results strongly suggest that the NH2-terminal acidic residue-rich segment of C4 alpha'-chain contributes importantly to the interaction of C4b with C2.

Amino Acid Sequence↗

PubMed2000

Regulation of germline promoters by the two human Ig heavy chain 3' alpha enhancers.

The human IgH 3' enhancers, located downstream of each of the two Calpha genes, modulate germline (GL) transcription of the IgH genes by influencing the activity of promoter-enhancer complexes upstream of the switch and intervening (I) regions. The regulation of GL alpha1 and alpha2 promoters by different human 3' enhancer fragments was investigated in cell lines representing various developmental stages. Both alpha1HS1,2 and alpha2HS1,2 fragments show equally strong enhancer activity on the GL alpha1 and alpha2 promoters in both orientations when transiently transfected into a number of mature B cell line (DG75, CL-01, and HS Sultan). However, there is no activity in a human pre-B cell line (NALM-6) nor a human T cell line (Jurkat). HS3 shows no enhancer activity by itself in any of the cell lines, whereas a modest effect is noted using HS4 in the three mature B cell lines. However, the combination of the alpha2HS3-HS1,2-HS4 fragments, which together form a potential locus control region, displays a markedly stronger enhancer activity than the individual fragments with a differential effect on the alpha1 and alpha2 promoters as compared with the gamma3 promoter. Our results suggest that the human GL alpha promoter may be regulated by two independent pathways. One pathway is induced by TGF-beta1 which directs IgA isotype switch through activation of the GL alpha promoter and no TGF-beta1-responsive elements are present in the different 3' enhancer fragments. The other route is through the human 3' enhancer regions that cis-up-regulate the GL alpha promoter activity in mature B cells.

3' Untranslated Regions↗

PubMed2000

Two functionally distinct forms of NKX2.1 protein are expressed in the pulmonary epithelium.

The homeodomain transcriptional factor NKX2.1 is critical for normal morphogenesis of the lung, thyroid, and the brain. In the lung, NKX2. 1 binds to and activates the expression of pulmonary differentiation-specific genes SP-A, SP-B, and SP-C. The Nkx2.1 gene is comprised of three exons separated by two introns. In both thyroid and lung, the predominant Nkx2.1 transcript includes exons II and III and is translated into a 371 amino acid protein. A minor transcript also exists which includes all three exons. This transcript encodes a 401 amino acid isoform of NKX2.1. The 30 amino acid extension is highly conserved amongst various mammalian species. In the current study, we demonstrate that the two NKX2.1 isoforms are functionally distinct and their corresponding transcripts are expressed differentially during mouse embryonic lung development. The results demonstrate that the longer isoform of NKX2.1 exhibits reduced activity in transactivating an SP-C target promoter when compared to the truncated major NKX2.1 protein. Site directed mutagenesis of the 30 amino acid peptide extension suggests that this fragment alters the activity of 5E likely by steric interference.

Amino Acid Sequence↗

PubMed2000

Synthesis of a tetrasaccharide representing a minimal epitope of an arabinogalactan.

The hydrophobic alkyl chain-containing tetrasaccharide, dodecyl beta-D-galactopyranosyl-(1-->6)-beta-D-galactopyranosyl-(1-->6)-[alpha-L - arabinofuranosyl-(1-->2)]-beta-D-galactopyranoside, was synthesized efficiently using a convergent strategy. In coupling reactions, protected trichloroacetimidates proved to be better donors than their corresponding bromides in the preparation of the dodecyl disaccharide and trisaccharide. Zemplén deacylation provided the target tetramer in good overall yield.

Carbohydrate Sequence↗

PubMed2000

Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds.

OBJECTIVE: To assess the frequency of SCA1 (spinocerebellar ataxia type 1), SCA2, SCA3/MJD (spinocerebellar ataxia type 3/Machado-Joseph disease), SCA6, SCA7, and DRPLA (dentatorubropallidoluysian atrophy) CAG trinucleotide repeat expansions [(CAG)n] among persons diagnosed with hereditary SCA from Chinese families. PATIENTS AND METHODS: Spinocerebellar ataxia type 1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA (CAG)n mutation were detected with the polymerase chain reaction, highly denaturing polyacrylamide gel electrophoresis, and silver staining technique in 167 patients with autosomal dominant SCA from 85 Chinese families and 37 patients with sporadic SCA. RESULTS: Spinocerebellar ataxia type 1 (CAG)n mutation in 7 patients from 4 kindreds (4.70%) was expanded to 53 to 62 repeats. Spinocerebellar ataxia type 2 (CAG)n mutation in 12 patients from 5 kindreds (5.88%) was expanded to 42 to 47 repeats. Spinocerebellar ataxia type 3/Machado-Joseph disease (CAG)n mutation in 83 patients from 41 kindreds (48.23%) was expanded to 68 to 83 repeats. Sixty-five patients from 35 kindreds (41.19%) and 37 patients with sporadic SCA did not test positive for SCA1, SCA2, SCA3/MJD, SCA6, SCA7, or DRPLA. There was a predictable inverse relationship between the number of CAG repeats and the age at onset for SCA3/MJD and SCA2. Clinically, dementia and hyporeflexia were more frequent in patients with SCA2, while spasticity, hyperreflexia, and Babinski signs were more frequent in patients with SCA3/ MJD, and those might be helpful in clinical work to primarily distinguish patients with SCA3/MJD and SCA2 from others with different types of SCA. CONCLUSIONS: The frequency of SCA3/MJD is substantially higher than that of SCA1 and SCA2 in patients with autosomal dominant SCA from Chinese kindreds, who are non-Portuguese. Clinical expressions of the various types of SCAs overlap one another; therefore, for clinical study it is important to make a gene diagnosis and genetic classification for patients with SCA.

Adolescent↗

PubMed2000

Regulation of the promoter for human immunoglobulin gamma3 germ-line transcription and its interaction with the 3'alpha enhancer.

The mechanism underlying the differential regulation of switching to human IgG subclasses is still largely unknown. We demonstrate that the region upstream of the initiation sites for gamma3 germ-line (GL) transcripts contains a functional promoter which is synergistically induced by IL-4, antibody to CD40 and phorbol dibutyrate in transient transfection assays in the human DG75 cell line. Linker-scanning mutations identified multiple elements in the 3' half of the evolutionarily conserved sequence that are required for inducibility. Electrophoretic mobility shift assays showed that Stat6 and NF-kappaB p50 / p65 are induced after stimulation, and bind to specific sequence motifs within the promoter. Overexpression of Stat6, NF-kappaB p50 / p65 and C / EBPgamma synergistically induced the GL gamma3 promoter. Insertion of DNA segments from the human 3' IgH regions, which may function as a locus control region for switch recombination, greatly activated the promoter in an orientation-independent manner. Duplication of the enhancer fragments resulted in a further increase of promoter activity. The greater enhancement of the HS1,2 fragment from the 3' alpha1 rather than the alpha2 locus may suggest a mechanistic explanation for the differential expression of various isotypes.

B-Lymphocytes↗

PubMed2000

An allotype-associated polymorphism in the gamma3 promoter determines the germ-line gamma3 transcriptional rate but does not influence switching and subsequent IgG3 production.

The human IgG3 (b) allotype is associated with a high and the (g) allotype with a low mean serum level of IgG3 which is due to a low frequency of B cell switching in the latter. In the present study, we found a polymorphism in position -73 (C --> A), located in the 4th NF-kappaB site of the germ-line (GL) gamma3 promoter, resulting in a significant decrease of both the basal and induced activity in the (g) allotype-associated promoter. Over-expression experiments also showed that this polymorphism reduced the synergistic activation of the promoter by Stat6 + NF-kappaB p50 / p65 or Stat6 + C / EBPgamma. A low level of GL gamma3 transcripts was also observed in individuals carrying the (g) allotype-associated promoter region. However, an individual homozygous for a crossover between the promoter and switch region, i. e. with a (g) allotype-associated promoter and a (b) allotype-associated switch region, showed a normal level of switching and IgG3 serum level. This suggests that although the (g) allotype-associated promoter is functionally inferior to that of the (b) allotype-associated promoter, these differences do not affect switching and final production of IgG3 and that polymorphisms in the switch region are more important in controlling this process.

B-Lymphocytes↗

PubMed2000

Divergent evolution of plant NBS-LRR resistance gene homologues in dicot and cereal genomes.

The majority of plant disease resistance genes are members of very large multigene families. They encode structurally related proteins containing nucleotide binding site domains (NBS) and C-terminal leucine rich repeats (LRR). The N-terminal region of some resistance genes contain a short sequence called TIR with homology to the animal innate immunity factors, Toll and interleukin receptor-like genes. Only a few plant resistance genes have been functionally analyzed and the origin and evolution of plant resistance genes remain obscure. We have reconstructed gene phylogeny by exhaustive analysis of available genome and amplified NBS domain sequences. Our study shows that NBS domains faithfully predict whole gene structure and can be divided into two major groups. Group I NBS domains contain group-specific motifs that are always linked with the TIR sequence in the N terminus. Significantly, Group I NBS domains and their associated TIR domains are widely distributed in dicot species but were not detected in cereal databases. Furthermore, Group I specific NBS sequences were readily amplified from dicot genomic DNA but could not be amplified from cereal genomic DNA. In contrast, Group II NBS domains are always associated with putative coiled-coil domains in their N terminus and appear to be present throughout the angiosperms. These results suggest that the two main groups of resistance genes underwent divergent evolution in cereal and dicot genomes and imply that their cognate signaling pathways have diverged as well.

Amino Acid Sequence↗

PubMed2000

Molecular basis of IgG subclass deficiency.

IgG subclass deficiency was recognized as a separate disease entity in the early seventies and was shown to be associated with an increased susceptibility to infections. Although deletions of the corresponding gamma genes have been demonstrated in a few cases, a majority of patients suffer from a regulatory dysfunction, and the deficiencies are most often relative rather than absolute. Some of the molecular mechanisms underlying the disorder have been unraveled recently. In this review we will touch upon the deletions described within the IGHC locus but mainly concentrate on the regulatory aberrations involved in IgG subclass deficiency.

Gene Deletion↗

PubMed2000

Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1.

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.

China↗

PubMed2000

Comparative genetics of nucleotide binding site-leucine rich repeat resistance gene homologues in the genomes of two dicotyledons: tomato and arabidopsis.

The presence of a single resistance (R) gene allele can determine plant disease resistance. The protein products of such genes may act as receptors that specifically interact with pathogen-derived factors. Most functionally defined R-genes are of the nucleotide binding site-leucine rich repeat (NBS-LRR) supergene family and are present as large multigene families. The specificity of R-gene interactions together with the robustness of plant-pathogen interactions raises the question of their gene number and diversity in the genome. Genomic sequences from tomato showing significant homology to genes conferring race-specific resistance to pathogens were identified by systematically "scanning" the genome using a variety of primer pairs based on ubiquitous NBS motifs. Over 70 sequences were isolated and 10% are putative pseudogenes. Mapping of the amplified sequences on the tomato genetic map revealed their organization as mixed clusters of R-gene homologues that showed in many cases linkage to genetically characterized tomato resistance loci. Interspecific examination within Lycopersicon showed the existence of a null allele. Consideration of the tomato and potato comparative genetic maps unveiled conserved syntenic positions of R-gene homologues. Phylogenetic clustering of R-gene homologues within tomato and other Solanaceae family members was observed but not with R-gene homologues from Arabidopsis thaliana. Our data indicate remarkably rapid evolution of R-gene homologues during diversification of plant families.

Alleles↗

PubMed2000

Antibiotics and return visits for respiratory illness: a comparison of pooled versus hierarchical statistical methods.

BACKGROUND: Antibiotic prescribing for respiratory illness has been associated with small reductions in return visits in an analysis of a large practice-based network. In this study, we apply hierarchical analytical methods that account for the clustering of patients by practices to identify whether antibiotic prescribing by primary care physicians reduces subsequent visits for 6 acute respiratory illnesses-upper respiratory infection, pharyngitis, bronchitis, otitis media, sinusitis, and cough. METHODS: The study data came from 318 family physicians and internists in 45 practices in the Practice Partner Research Network from January 1995 through December 1996, with 255,564 active patients. Patients treated with antibiotics were compared with those who were not on the frequency of revisit within the next 14 days. A simple pooling model and 3 hierarchical statistical models (fixed-effects, random-effects, and Bayesian) were used to compare the odds-ratios for return visits. RESULTS: Statistically significant results were found only for bronchitis and sinusitis by the hierarchical models, but the simple pooling model produced statistically significant results for all study conditions. CONCLUSION: We conclude that antibiotics may reduce return visits for patients with bronchitis and sinusitis, but not for patients with other respiratory illness (upper respiratory infection, pharyngitis, otitis media, or cough). Studies of large clinical databases should use methods of analysis that account for the grouping of patients by practice to avoid false positive associations (type I errors.)

Academic Medical Centers↗

PubMed2000

[Molecular cytogenetics study in a case with unbalanced chromosome translocation].

OBJECTIVE: To analyze the chromosome structural aberration in a case of unbalanced chromosome translocation by fluorescence in situ hybridization technique. METHODS: The 1,18 whole chromosome specific painting probe were used to confirm chromosome abnormality suggested by high resolution G-banding examination. RESULTS: An unbalanced translocation t(1;18)(q42;q22) was detected in the patient, which caused partial trisomy of 1q42-qter and partial monosomy of 18q22-qter. CONCLUSION: The identified translocation suggested a potential site for congenital heart disease.

Heart Defects, Congenital↗

PubMed2000

[Antitumor effect of arsenic trioxide on mice experimental liver cancer].

OBJECTIVE: To investigate the antitumor activity of arsenic trioxide on mice experimental liver cancer. METHODS: Mice bearing HepA solid and ascitic liver tumor were used in vivo experiments. RESULTS: The tumor-bearing mice were treated with arsenic trioxide 2.0mg/kg/d and 3.5mg/kg/d intravenously for 7 days. After the administration of arsenic trioxide, the growth of solid tumor were obviously inhibited, the inhibitory rate were 31.63% and 42.13% respectively. Under the inspection of transmission electron microscope, some cells of the solid tumor showed the typically morphological characteristics of apoptosis. The apoptotic cells were detected by in situ TdT-mediated dUTP nick end labeling (TUNEL). The immunohistochemical staining showed that the number of bcl-2 protein positive cells decreased, but the number of bax protein positive cells increased. It also showed that arsenic trioxide could significantly prolong the mean survival time in ascitic-tumor-bearing mice, the prolonging rate of life span was 59.29% and 76.69% respectively. The sub-G1 peaks were observed by flow cytometry on the ascitic specimen and the apoptotic rate were 25.98% and 53.17% respectively. CONCLUSION: arsenic trioxide has obvious antitumor activity on HepA liver tumor-bearing mice. The mechanism of arsenic trioxide may mainly be inducing liver cancer cells to undergo apoptosis, which may be related to downregulate the expression of bcl-2 genes and upregulate the expression of bax genes.

Animals↗