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Biomedical subjects

F Lai

Publications and source records attributed to F Lai.

At least 19 recordsLinked to original sources

Adaptive filtering of evoked potentials using higher-order adaptive signal enhancer with genetic-type variable step-size prefilter.

An adaptive signal enhancer based on third-order statistics with a genetic-type, variable step-size prefilter is introduced to recover evoked potentials (EPs). EPs are usually embedded in the ongoing electroencephalogram with a very low signal-to-noise ratio (SNR). As a higher-order statistics technique has a natural tolerance to Gaussian noise, it is applicable for filtering EPs. An adaptive signal enhancer based on third-order statistics was used as the major filter in this study. However, the efficiency of the adaptive signal enhancer was reduced when the total power of uncorrelated noises was large. To improve the performance for EPs under poor SNR, a low-noise signal is required. Therefore a prefilter with a genetic-type, variable step-size algorithm was employed to enhance the SNR of the signal in this study. The fundamental idea of a genetic-type, variable step-size algorithm is that its step-sizes are regularly readjusted to optimum. Therefore this algorithm can be used as a prefilter with different noise levels. Experimental results showed that, for filtering EPs, the proposed scheme is superior to the adaptive signal enhancer with a normalised least mean square algorithm.

Algorithms↗

[Immunohistochemical localization of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in tuberculous pleuritis].

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found by ELISA and gelatine zymography in different concentrations in pleural fluid in tuberculous (TB) pleuritis. For further differentiation MMP and TIMP were localized in pleural biopsies by immunhistochemical staining with antibodies directed against MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 using the Labelled-Avidin-Biotin (LAB). Immunohistological reactivity of MMP-1 was found in epitheloidcellular histiocytes, Langhans' giant cells, lymphocytes, macrophages, as well as in fibroblasts of granulomatous reactions. MMP-2 was found in a few epitheloid cellular histiocytes, fibroblasts, and inflammatory cells. MMP-3 was weakly positive in a few lymphocytes only. MMP-9 was found in a few fibroblasts, epitheloid cells, and inflammatory cells, foremost, however, in pleural mesothial cells. A few fibroblasts only showed immunoreactivity of TIMP-1 and TIMP-2. The observed inhomogenous staining pattern could be explained by the different state of activation of individual cellular units. In conclusion, the immunohistochemical demonstration of MMP and TIMP in pleural cells and tissue structures indicates their local involvement in fibrosing reactions in TB-pleuritis.

Female↗

Discriminating two classes of toxicants through expression analysis of HepG2 cells with DNA arrays.

Microarray technology provides a rapid and cost-effective method to associate specific cellular responses with unique gene expression patterns. If characteristic expression patterns of a small number of genes could be associated with drug toxicity, this association may be used for toxicity prediction, and thereby to reduce the need for traditional toxicity testing. To test this hypothesis, we have designed an array composed of 92 known human genes of toxicological interest (including seven housekeeping genes) and eight bacterial controls. HepG2 cells were treated with either ethanol or one of two quinone containing anticancer drugs, mitomycin C or doxorubicin. RNA was isolated from treated and untreated cells, differentially labeled with fluorescent dyes, and then hybridized to the array. Our results show that the expression patterns induced by ethanol and the anticancer drugs are different. Both of the anticancer drugs, but not ethanol had a differential effect on the regulation of several genes, including CYP4F2/3, CYP3A3, TNFRSF6 and CHES1, demonstrating that the two drugs might function through a similar mechanism, which differs from that of ethanol. These results suggest that microarray-based expression analysis may offer a rapid and efficient means for assessing drug toxicity.

Antineoplastic Agents↗

Comparison of L-bupivacaine 0.75% and lidocaine 2% with bupivacaine 0.75% and lidocaine 2% for peribulbar anaesthesia.

BACKGROUND: L-Bupivacaine has a safer side-effect profile than bupivacaine. We compared the efficacy of a mixture of L-bupivacaine 0.75% and lidocaine 2% with bupivacaine 0.75% and lidocaine 2% for peribulbar anaesthesia in cataract surgery. METHODS: Ninety patients were allocated randomly to receive 8 ml of a mixture of equal parts of bupivacaine 0.75% and lidocaine 2% or an equal volume of L-bupivacaine and lidocaine 2%. Hyaluronidase 15 IU ml(-1) was added to both solutions. RESULTS: There were significant differences between the groups in clinical end-points. The median time at which the block was adequate to start surgery was 4 min (interquartile range 4-8 min) in the bupivacaine group and 8 min (5-12 min) in the L-bupivacaine group (P=0.002). Median ocular and eyelid movement scores were similarly significantly decreased in the bupivacaine group compared with the L-bupivacaine group at all times (P</=0.03). There was no difference between groups in the incidence of minor complications. CONCLUSIONS: A mixture of bupivacaine 0.75% and lidocaine 2% provides faster onset time than a mixture of L-bupivacaine 0.75% and lidocaine 2%.

Adult↗

Transcript map and comparative analysis of the 1.5-Mb commonly deleted segment of human 5q31 in malignant myeloid diseases with a del(5q).

Loss of a whole chromosome 5, or a del(5q), are recurring abnormalities in malignant myeloid diseases. In previous studies, we defined a commonly deleted segment (CDS) of 1.5 Mb between D5S479 and D5S500 in patients with a del(5q), and we established a P1 artificial chromosome-based contig encompassing this interval. To identify candidate tumor suppressor genes (TSGs), we developed a transcript map of the CDS. The map contains 18 genes and 12 expressed sequence tags/UniGenes. Among the 18 genes are 10 genes that were previously cloned and 8 novel genes. The newly identified genes include CDC23, which encodes a component of the anaphase-promoting complex; RAB6KIFL, which encodes a kinesin-like protein involved in organelle transport; and KLHL3, which encodes a human homologue of the Drosophila ring canal protein, kelch. We determined the intron/exon organization of 14 genes and eliminated each gene as a classical TSG by mutation analysis. In addition, we established a single-nucleotide polymorphism map as well as a map of the mouse genome that is syntenic to the CDS of human 5q31. The development of a transcription map will facilitate the molecular cloning of a myeloid leukemia suppressor gene on 5q.

Acute Disease↗

[Effect of xanthnotoxol on contractility of isolated rabbit ileum].

OBJECTIVE: To study the effect of Xanthnotoxol on contractility of isolated rabbit ileum and its relationship with Ca2+. METHOD: Routine experimental methods for isolated ileum were adopted. RESULT: Xanthnotoxol (XT) and Verapamil (Ver) inhibited the contraction of isolated rabbit ileum smooth muscle induced by submaximal concentrations of acetylcholine (ACh) and serotonim (5-TH), with a IC50 value (mumol.L-1) of 10.495 +/- 1.521, 0.428 +/- 0.001 and 18.132 +/- 1.627, 0.249 +/- 0.003, respectively. XT and Ver inhibited the contraction induced by Ca2+ after high K+ depolarization and for noncompetitively antagonist CaCl2 cumulative dose-response curve, the pD'2 value was 4.69 +/- 0.03 and 6.35 +/- 0.10, respectively. XT (10 mumol.L-1) and Ver(0.06 mumol.L-1) inhibited the contraction induced by ACh in Ca(2+)-free medium, while XT (100 mumol.L-1) but not Ver(0.6 mumol.L-1) inhibited the extracellar CA(2+)-dependent contraction induced by ACh. CONCLUSION: XT has a calcium-antagonistic effect which was not similar to that of Ver.

Animals↗

cDNA cloning and genomic structure of three genes localized to human chromosome band 5q31 encoding potential nuclear proteins.

Loss of a whole chromosome 5, or a del(5q), is a recurring abnormality in malignant myeloid diseases. By cytogenetic and molecular analyses, we delineated previously a 1- to 1.5-Mb region that is deleted in all patients with a del(5q). In our efforts to identify a myeloid tumor suppressor gene within the commonly deleted segment (CDS), we have cloned and characterized the genes encoding three putative nuclear proteins, each of which contains a bipartite nuclear localization signal (NLS). In addition, C5ORF5 contains a putative rhoGAP domain at the N-terminus, C5ORF6 has a proline-rich sequence near the N-terminus, and C5ORF7 has a zinc-finger domain that partially overlaps the NLS. All three genes are ubiquitously expressed and encode novel proteins. The C5ORF5 cDNA is 5.47 kb encoding a protein of 915 amino acids (aa) with a predicted molecular mass of approximately 105 kDa. C5ORF5 has 23 exons spanning over 27 kb. The C5ORF6 transcript is 4.1 kb encoding a protein of 392 aa with a predicted molecular mass of approximately 43 kDa. C5ORF6 has 5 exons and spans approximately 11 kb. The C5ORF7 cDNA is 6.3 kb and encodes a protein of 1417 aa with a predicted molecular mass of approximately 155 kDa. C5ORF7 has 24 exons spanning approximately 64 kb. All three genes were localized to the distal half of the CDS between D5S1983 and D5S500. We evaluated each as a candidate tumor suppressor gene by the analysis of myeloid leukemia cells from patients with -5/del(5q), but no inactivating mutations were identified.

Amino Acid Sequence↗

Molecular characterization of KLHL3, a human homologue of the Drosophila kelch gene.

The Drosophila kelch protein is a structural component of ring canals and is required for oocyte maturation. Here, we report the cloning and genomic structure of a new human homologue of kelch, KLHL3. At the amino acid level, KLHL3 shares 77% similarity with Drosophila kelch and 89% similarity with Mayven (KLHL2), another human kelch homolog. The approximately 6.5-kb mRNA has a single open reading frame encoding a protein of 587 amino acids with a predicted molecular mass of 650 kDa. Like kelch and KLHL2, the KLHL3 protein contains a poxvirus and zinc finger domain at the N-terminus and six tandem repeats (kelch repeats) at the C-terminus. At least three isoforms, which differ in the length of the N-terminus, are produced and may be the result of alternative promoter usage. We also identified alternative polyadenylation sites and alternative splicing; thus, as many as 12 mRNA variants and six putative protein isoforms could be produced. The KLHL3 gene is mapped to human chromosome 5, band q31, contains 17 exons, and spans approximately 120 kb of genomic DNA. KLHL3 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no inactivating mutations of KLHL3 in malignant myeloid disorders with loss of 5q.

Acute Disease↗

cDNA cloning, expression pattern, genomic structure and chromosomal location of RAB6KIFL, a human kinesin-like gene.

Kinesin-like proteins are microtubule-associated motors that play important roles in intracellular transport and cell division. We report here the characterization of a new human kinesin-like protein, Rabkinesin6 (RAB6KIFL). The composite cDNA sequence is 2957bp, and encodes a protein of 890 amino acids with a predicted molecular weight of 100kDa. It has high homology (93% similarity) with the mouse kinesin-like protein, Rab6kifl, indicating that it is the human homologue of the mouse gene. RAB6KIFL has all of the structural characteristics required to function as a microtubule-associated motor. Unlike the mouse gene which is ubiquitously expressed, RAB6KIFL expression appears to be tissue specific. It is widely expressed in fetal tissues, abundantly expressed in adult thymus, bone marrow and testis, and is expressed at low levels in heart, placenta and spleen. The RAB6KIFL gene is mapped to human chromosome 5, band q31, spans approximately 8.5kb of genomic DNA, and contains 19 exons. RAB6KIFL maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no mutations of RAB6KIFL in malignant myeloid disorders with loss of 5q. The description of this human kinesin-like protein may provide a better understanding of the diversity of this large family of proteins.

Acute Disease↗

Genomic structure of murine Rab11 family members.

Rab11a, Rab11b, and Rab25 in mammals are thought to comprise a subfamily of Rab proteins, although Rab25 has two amino acid differences in its effector domain. We have isolated and characterized the genomic sequences of murine Rab11a and Rab25 and compared them with those of previously characterized mammalian Rab genes. The Rab11a gene spans 29 kb and Rab25 spans 9 kb. The genes have TATA-less promoters, but contain GC-rich areas in their upstream 5' regions. Both genes have 5 exons, with the introns containing characteristic repeats. Rab11a has an unusually long 8. 5-kb fourth intron. The Rab11a and Rab25 genes are localized to chromosomes 9C and 3E3/F1, respectively. The overall organization of the Rab11a, Rab11b, and Rab25 genes is similar, with homologous exon-intron boundaries, and differs markedly from those of Rab3A and Rab1A. These results confirm that Rab11A, Rab11b, and Rab25 represent a closely related gene family.

Amino Acid Sequence↗

A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains.

Members of the double-stranded RNA- (dsRNA) specific adenosine deaminase gene family convert adenosine residues into inosines in dsRNA and are involved in A-to-I RNA editing of transcripts of glutamate receptor (GluR) subunits and serotonin receptor subtype 2C (5-HT(2C)R). We have isolated hADAR3, the third member of this class of human enzyme and investigated its editing site selectivity using in vitro RNA editing assay systems. As originally reported for rat ADAR3 or RED2, purified ADAR3 proteins could not edit GluR-B RNA at the "Q/R" site, the "R/G" site, and the intronic "hot spot" site. In addition, ADAR3 did not edit any of five sites discovered recently within the intracellular loop II region of 5-HT(2C)R RNAs, confirming its total lack of editing activity for currently known substrate RNAs. Filter-binding analyses revealed that ADAR3 is capable of binding not only to dsRNA but also to single-stranded RNA (ssRNA). Deletion mutagenesis identified a region rich in arginine residues located in the N-terminus that is responsible for binding of ADAR3 to ssRNA. The presence of this ssRNA-binding domain as well as its expression in restricted brain regions and postmitotic neurons make ADAR3 distinct from the other two ADAR gene family members, editing competent ADAR1 and ADAR2. ADAR3 inhibited in vitro the activities of RNA editing enzymes of the ADAR gene family, raising the possibility of a regulatory role in RNA editing.

Adenosine Deaminase↗

[Separation of thoracopagus conjoined twins].

OBJECTIVE: To sam up the experience in diagnosis and separation of a thoracopagus conjoined twins. METHODS: Thoracopagus twin boys were admitted for evaluating possible separation and repair at age of 21 days. X-rays, CT, MRI, and ultrasound scan of torso showed separate and normal gastrointestinal and biliary tracts, little shared vasculature, but shared pericardium, diaphragm and liver parenchyma. The chest junctions were at the sternums and the most inferior two pairs of the ribs. One twin (twin A) had a protruding heart with VSD and ASD. RESULTS: The infants were separated successfully at age of 45 days. The chest defect of twin A was closed with aid of a polyester pericardial patch graft and a silicon supporter. Managing anesthesia met some difficulty in understanding of the anatomical and physiological consequences of the complex anomaly. They are had brain edema and multiple system organ failures after separation, and were cured under intensive care. They are alive and well 6 months after surgery. CONCLUSIONS: Careful preoperative evaluation proper anesthesia and surgical technique, and postoperative care are essential to the successful separation of the conjoined twins.

Anesthesia↗

TTID: A novel gene at 5q31 encoding a protein with titin-like features.

A deletion of the long arm of chromosome 5 is a recurring abnormality in malignant myeloid disorders. In previous studies, we identified an approximately 1-Mb segment in 5q31 that was deleted in all patients examined. As part of a positional cloning project to identify transcribed sequences in this region, we identified and characterized the TTID gene. This gene contains 10 exons that extend over 19 kb. The composite cDNA is approximately 2.3 kb and encodes a protein of 498 amino acids, with a predicted molecular mass of 55 kDa. The C-terminal half of this putative protein contains an internally repeated domain of 43 amino acids, which resembles the N-terminal half of an immunoglobulin domain from the immense skeletal muscle protein titin. The TTID gene is expressed in multiple muscle tissue types as well as in thyroid gland and bone marrow. We evaluated the gene as a candidate tumor suppressor gene by searching for mutations in malignant myeloid disorders with abnormalities of chromosome 5. However, we detected no inactivating mutations. A single nucleotide change (G to A) was identified at nucleotide position 1889 in the untranslated region of the mRNA, which may represent a polymorphism. Therefore, TTID is unlikely to be the candidate tumor suppressor gene involved in malignant myeloid disorders.

Amino Acid Sequence↗

APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome.

BACKGROUND: Alzheimer disease (AD) neuropathology is present in Down syndrome (DS) after age 35, but dementia onset varies from ages 40 to 70 years. Because of small sample sizes and nonuniform determination of dementia, previous studies produced differing results on the influence of APOE subtypes on AD in DS. OBJECTIVE: To determine the influence of the APOE genotype and gender on development of AD in adults with DS to ascertain similarities with AD in the general population. METHODS: A total of 100 adults with DS (ages 35 to 79 years), almost all of whom were longitudinally assessed by neurologists, underwent APOE genotyping. Dementia onset was determined using criteria applied from the Tenth International Classification of Mental and Behavioral Disorders. This cohort contains the largest number of DS subjects with dementia (n = 57) in a single study, thus increasing reliability of the results. RESULTS: The epsilon2 allele frequency was 4% in those with dementia versus 13% in those without dementia (p = 0.03); epsilon4 allele frequency was 18% in those with dementia versus 13% in those without dementia (p = 0.45). Using APOE-epsilon3/3 as the reference group, the risk ratio for the development of AD at any given time was 0.34 for the APOE-epsilon2/3 group (p = 0.04) and 1.44 for the APOE-epsilon(3/4,4/4) group (p = 0.25). Women were 1.77 times as likely to dement as men at any given point in time (p = 0.04). CONCLUSIONS: The epsilon2 allele confers a protective effect, and women with DS have an increased risk for AD, as in the general population. In this sample, epsilon4 does not confer a significantly increased risk for AD in DS.

Adult↗

Human CDC23: cDNA cloning, mapping to 5q31, genomic structure, and evaluation as a candidate tumor suppressor gene in myeloid leukemias.

The transition from metaphase to anaphase and exit from mitosis involve the degradation of active cyclin B-CDC2 complexes by ubiquitin-mediated proteolysis. The anaphase-promoting complex (APC) catalyzes the formation of cyclin B-ubiquitin conjugates, thereby targeting cyclin B for degradation. The APC is composed of eight proteins, including four members of a family characterized by multiple tetratricopeptide repeats (TPR). We mapped two overlapping expressed sequence tag clones within a genomic contig on human chromosome 5, band q31. A search revealed high homology to Saccharomyces cerevisiae CDC23, a TPR protein component of the APC. We have isolated the human CDC23 cDNA containing the full-length predicted open reading frame. The approximately 3.3-kb message is ubiquitously expressed and encodes a protein with 591 amino acids (MW = 68,293 Da) and 9 TPR units. The protein has 30% identity and 51% similarity to the S. cerevisiae protein. The human CDC23 gene contains 16 exons and spans approximately 31 kb. CDC23 maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no mutations of CDC23 in leukemia cells with loss of 5q. Thus, CDC23 is unlikely to be involved in the pathogenesis of myeloid leukemias characterized by abnormalities of chromosome 5.

Amino Acid Sequence↗