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Biomedical subjects

C M Tang

Publications and source records attributed to C M Tang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Reduced expression of APC and DCC gene protein in breast cancer.

AIMS: To investigate if the adenomatous polyposis coli (APC) protein and the deleted in colorectal cancer (DCC) protein expression can be demonstrated by an immuno-histochemical method and to study the role of APC and DCC gene inactivation in the development and progression of breast cancer using colorectal cancer as a control model. METHODS AND RESULTS: The reduced or loss of protein expression of the APC and DCC genes was studied in 27 surgical specimens of primary breast cancer using an immunohistochemical method. Reduced or lost expression was identified in 11 out of 27 samples (40.7%) for the APC gene and 15 out of 27 samples (55.6%) for the DCC gene. No statistically significant difference was observed between the reduced or lost protein expression and the histological grading of breast tumour for both the APC and the DCC gene. CONCLUSIONS: Both gene proteins can be demonstrated by the immunohistochemical method. Reduced or loss of APC and DCC gene product were observed in 40.7% and 55.6% cases of primary breast cancer respectively. Further work is required to investigate the significance of the finding.

Adenomatous Polyposis Coli Protein↗
PubMed1999

Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis.

We investigated the conservation and antibody accessibility of inner core epitopes of Neisseria meningitidis lipopolysaccharide (LPS) because of their potential as vaccine candidates. An immunoglobulin G3 murine monoclonal antibody (MAb), designated MAb B5, was obtained by immunizing mice with a galE mutant of N. meningitidis H44/76 (B. 15.P1.7,16 immunotype L3). We have shown that MAb B5 can bind to the core LPS of wild-type encapsulated MC58 (B.15.P1.7,16 immunotype L3) organisms in vitro and ex vivo. An inner core structure recognized by MAb B5 is conserved and accessible in 26 of 34 (76%) of group B and 78 of 112 (70%) of groups A, C, W, X, Y, and Z strains. N. meningitidis strains which possess this epitope are immunotypes in which phosphoethanolamine (PEtn) is linked to the 3-position of the beta-chain heptose (HepII) of the inner core. In contrast, N. meningitidis strains lacking reactivity with MAb B5 have an alternative core structure in which PEtn is linked to an exocyclic position (i.e., position 6 or 7) of HepII (immunotypes L2, L4, and L6) or is absent (immunotype L5). We conclude that MAb B5 defines one or more of the major inner core glycoforms of N. meningitidis LPS. These findings support the possibility that immunogens capable of eliciting functional antibodies specific to inner core structures could be the basis of a vaccine against invasive infections caused by N. meningitidis.

Animals↗
PubMed1999

trans repression of the human metallothionein IIA gene promoter by PZ120, a novel 120-kilodalton zinc finger protein.

Metallothioneins are small, highly conserved, cysteine-rich proteins that bind a variety of metal ions. They are found in virtually all eukaryotic organisms and are regulated primarily at the transcriptional level. In humans, the predominant metallothionein gene is hMTIIA, which accounts for 50% of all metallothioneins expressed in cultured human cells. The hMTIIA promoter is quite complex. In addition to cis-acting DNA sequences that serve as binding sites for trans-acting factors such as Sp1, AP1, AP2, AP4, and the glucocorticoid receptor, the hMTIIA promoter contains eight consensus metal response element sequences. We report here the cloning of a novel zinc finger protein with a molecular mass of 120 kDa (PZ120) that interacts specifically with the hMTIIA transcription initiation site. The PZ120 protein is ubiquitously expressed in most tissues and possesses a conserved poxvirus and zinc finger (POZ) motif previously found in several zinc finger transcription factors. Intriguingly, we found that a region of PZ120 outside of the zinc finger domain can bind specifically to the hMTIIA DNA. Using transient-transfection analysis, we found that PZ120 repressed transcription of the hMTIIA promoter. These results suggest that the hMTIIA gene is regulated by an additional negative regulator that has not been previously described.

Amino Acid Sequence↗
PubMed1998

Ki-ras codon 12 point mutational activation in Hong Kong colorectal carcinoma patients.

This study investigated the frequency and importance of Ki-ras codon 12 mutations in 99 Hong Kong Chinese colorectal carcinoma specimens by allele-specific oligonucleotide hybridization. The frequency of mutations detected was 30% and the most common mutation observed resulted in aspartic acid substitutions. Previous studies showed that specific Ki-ras mutations have been significantly associated with prognosis. Ki-ras codon 12 point mutational activation in CRC was significantly associated with the differentiation status of tumors in this study. Ethnic differences in the patterns of Ki-ras codon 12 point mutations were observed.

Adult↗
PubMed1998

p53 inactivating mutations in Chinese nasopharyngeal carcinomas.

Previously a low frequency of p53 mutations was detected in nasopharyngeal carcinoma (NPC) using molecular techniques to screen for mutations, yet immunohistochemical staining revealed a high frequency of p53 aberrant proteins. These findings might be attributed to the occurrence of p53 mutations outside the common hot spots and/or the inactivation of the protein through interactions with cellular or viral proteins. Using a previously established simple and sensitive p53 yeast functional assay, we blindly screened 25 nasopharyngeal biopsies for p53 mutations from exons 4 to 11. p53 was mutated in 27.3% of NPC specimens and in 0% of the nasopharyngeal biopsies from patients with non-malignant diseases. Two p53 mutations were detected in exon 7 and two were detected in exon 8. Interestingly, the exon 8 mutations observed in NPC lie in codons which appear to be hot spots for mutations in other head and neck cancers.

Adolescent↗
PubMed1998

Cloning and characterization of the mouse histone deacetylase-2 gene.

Histone deacetylase-2 (HDAC2) is a component of a complex that mediates transcriptional repression in mammalian cells. A mouse HDAC2 cDNA was used to identify several recombinant clones containing the entire mouse HDAC2 gene. The mouse HDAC2 gene spans over 36 kilobase pairs and is composed of 14 exons (ranging from 58 to 362 nucleotides in length) and 13 introns (ranging from 75 base pairs to 19 kilobase pairs in length). Primer extension analysis with total RNA from NIH3T3 cells revealed a major transcriptional start site at 221 base pairs 5' of the ATG translational start codon. Upstream of the transcriptional start site, no canonical TATA box was found, but binding sites for several known transcription factors were identified. Transient transfection studies with 5' deletion mutants localized the promoter to no more than 76 base pairs upstream from the major transcriptional start site. Fluorescence in situ hybridization mapped mouse HDAC2 to chromosomal location 10B1, which is in close proximity to the growth factor-inducible gene fisp-12. Information concerning the genomic organization and promoter of HDAC2 will be useful in studies of the regulation of histone deacetylase activities, which in turn are important in studies of the regulation of transcriptional repression in mammalian cells.

Animals↗
PubMed1998

Novel natural product 5,5-trans-lactone inhibitors of human alpha-thrombin: mechanism of action and structural studies.

High-throughput screening of methanolic extracts from the leaves of the plant Lantana camara identified potent inhibitors of human alpha-thrombin, which were shown to be 5,5-trans-fused cyclic lactone euphane triterpenes [O'Neill et al. (1998) J. Nat. Prod. (submitted for publication)]. Proflavin displacement studies showed the inhibitors to bind at the active site of alpha-thrombin and alpha-chymotrypsin. Kinetic analysis of alpha-thrombin showed tight-binding reversible competitive inhibition by both compounds, named GR133487 and GR133686, with respective kon values at pH 8.4 of 1.7 x 10(6) s-1 M-1 and 4.6 x 10(6) s-1 M-1. Electrospray ionization mass spectrometry of thrombin/inhibitor complexes showed the tight-bound species to be covalently attached, suggesting acyl-enzyme formation by reaction of the active-site Ser195 with the trans-lactone carbonyl. X-ray crystal structures of alpha-thrombin/GR133686 (3.0 A resolution) and alpha-thrombin/GR133487 (2.2 A resolution) complexes showed continuous electron density between Ser195 and the ring-opened lactone carbonyl, demonstrating acyl-enzyme formation. Turnover of inhibitor by alpha-thrombin was negligible and mass spectrometry of isolated complexes showed that reversal of inhibition occurs by reformation of the trans-lactone from the acyl-enzyme. The catalytic triad appears undisrupted and the inhibitor carbonyl occupies the oxyanion hole, suggesting the observed lack of turnover is due to exclusion of water for deacylation. The acyl-enzyme inhibitor hydroxyl is properly positioned for nucleophilic attack on the ester carbonyl and therefore relactonization; furthermore, the higher resolution structure of alpha-thrombin/GR133487 shows this hydroxyl to be effectively superimposable with the recently proposed deacylating water for peptide substrate hydrolysis [Wilmouth, R. C., et al. (1997) Nat. Struct.Biol. 4, 456-462], suggesting the alpha-thrombin/GR133487 complex may be a good model for this reaction.

Acylation↗
PubMed1998

Microbial genome sequencing and pathogenesis.

The year 1997 saw the publication of the complete nucleotide sequence of Helicobacter pylori and Escherichia coli. It is conceivable that the complete nucleotide sequence for all the major human bacterial pathogens will be available by the end of the century. Database alignments have been used to ascribe the putative functions of open reading frames in the sequenced isolates and to define the differences between bacterial species at the nucleotide level. The most striking finding from all genome projects has been the high proportion of open reading frames that have no known function. Experimental data demonstrating the utility of the genome sequencing projects are only just beginning to emerge.

Antigenic Variation↗
PubMed1998

Prevalence and manifestations of hepatitis C seropositivity in children in an endemic area.

BACKGROUND: According to our previous studies, Paisha Township in Penghu Islets is an endemic area for hepatitis B virus and hepatitis C virus (HCV) infection and for hepatocellular carcinoma. We conducted this study to understand the prevalence of anti-HCV seropositivity among children in this area and to observe clinical manifestations of anti-HCV-positive children. METHODS: In March, 1994, 1164 (93.6%) of 1243 students from all 6 kindergartens, 9 primary schools and 3 middle schools in Paisha Township participated in the screening for anti-HCV by enzyme immunoassay with second generation commercial kits (Abbott EIA 2.0). Anti-HCV tests were duplicated for the positive sera in 2 laboratories. All anti-HCV-positive children were followed annually for 2 years. RESULTS: The prevalences of children from kindergartens (ages 3 to 6 years), primary schools (ages 7 to 12 years) and middle schools (ages 13 to 15 years) were 0% (0 of 229), 0.8% (5 of 617) and 1.9% (6 of 318), respectively. Initially the optic density (OD) values of anti-HCV were > 2.0 in 4 cases (36%), between 1.0 and 2.0 in 2 cases, and < 1.0 in the other 5 cases. None had sonographic parenchymal changes in the liver. In the 2-year follow-up of the anti-HCV-positive subjects, type 2a HCV-RNA persisted in 3 of 4 children with an OD of anti-HCV more than 2.0; 2 of them had 2 elevations of alanine transaminase values. Four of 7 children with an OD of 2.0 or less had a decrease in OD values in the follow-up examinations, and 2 of them became anti-HCV-negative. CONCLUSION: Only 36% (4 of 11) of anti-HCV-positive children had an OD of > 2.0. Subjects with sequentially low OD might recover from chronic HCV infection without detectable HCV RNA and with normal alanine aminotransferase values.

Adolescent↗
PubMed1998

Disseminated Penicillium marneffei infection presenting as a right upper lobe mass in an HIV positive patient.

A 35 year old HIV positive patient from Hong Kong presented with a fever, cough and a skin rash in association with a lung mass, all of which were due to disseminated Penicillium marneffei infection. He made a good response to antifungal therapy. The lung mass is a previously undescribed pulmonary manifestation of disseminated Penicillium marneffei infection. Infections with this fungus should be suspected in any patient with HIV and respiratory symptoms who has visited southeast Asia.

AIDS-Related Opportunistic Infections↗
PubMed1998

Temporal integration can readily switch between sublinear and supralinear summation.

Temporal summation at dendrites of cultured rat hippocampal neurons was examined as a function of the interval separating two dendritic inputs. A novel method that relies on single-mode optical fibers to achieve rapid photorelease of glutamate was developed. Dendritic excitation achieved with this approach resembles that associated with miniature excitatory postsynaptic currents (mEPSCs), but the strengths, sites, and timing of the inputs can be precisely controlled. Dendritic summation deviated markedly from behavior predicted by passive cable theory. Subthreshold temporal summation varied as a triphasic function of the interpulse interval. As the interpulse interval decreased, local dendritic Na+ conductances were recruited to generate a marked transition from sublinear to supralinear summation. These results suggest that active dendritic conductances acting in concert with passive cable properties may serve to boost coincident synaptic inputs and attenuate noncoincident inputs.

Animals↗
PubMed1997

N-Nmoc-L-glutamate, a new caged glutamate with high chemical stability and low pre-photolysis activity.

We report the synthesis, the physicochemical characterization, and biological evaluation of a new caged glutamate, N-(o-nitromandelyl)oxycarbonyl-L-glutamic acid (Nmoc-Glu), that liberates free glutamate on photolysis. The low affinity of certain glutamate receptors and their rapid entry into desensitization have effectively prevented the creation of an ideal caged glutamate. In the absence of an ideal compound, Nmoc-Glu was designed to resist spontaneous hydrolysis while maintaining reasonable photorelease yield and kinetics. Chemical and physiological analyses reveal that Nmoc-Glu, indeed, has exceptionally low residual activity and high chemical stability. The quantum yield of Nmoc-Glu is 0.11. Photolytic uncaging and release of free glutamate occur in two steps, consisting of an initial light-induced cleavage that proceeds on the sub-millisecond time scale, and a subsequent light-independent, pH-dependent decarboxylation step that proceeds on the millisecond time scale. The low residual activity and high chemical stability of Nmoc-Glu are important advantages in applications where pre-photolysis Glu receptor activation and desensitization must be minimized.

Animals↗
PubMed1997

p16 tumor suppressor gene mutations in Chinese esophageal carcinomas in Hong Kong.

The frequency and nature of genetic alterations in the p16 tumor suppressor gene in 25 esophageal squamous cell carcinoma specimens from Chinese patients were investigated by PCR-SSCP and DNA sequencing techniques. No gross deletions occurred in either exon 1 and 2 of the gene by PCR amplification. However, genetic changes were observed in three cases. These included a point mutation in codon 12 of exon 1 with a resulting Ala --> Thr amino acid substitution, a point mutation at base 91 in the non-coding region of exon 1, and a 1 base pair insertion in codon 116 of exon 2. The low mutation frequency of 12% is consistent with that of three previous studies involving Japanese and Caucasian patients (8, 16 and 21% frequency: Esteve et al., 1996, Igaki et al., 1995 and Zhou et al., 1994). p16 gene mutations do not appear to play a major role in esophageal carcinogenesis.

Aged↗
PubMed1997

Haemophilus influence: the impact of whole genome sequencing on microbiology.

The publication of the Haemophilus influenzae genome sequence in 1995 was a landmark in microbiological research. It has changed our understanding of the prokaryotic world, and will influence the approach and focus of research on microorganisms over the next few years. In this article we outline what has been learned from this and other genome sequencing projects, and discuss some of the potential avenues of investigation that will follow in the 'post-genome era'.

Biological Evolution↗
PubMed1997

p53 mutations detected in colorectal carcinoma patients in Hong Kong.

A mutational spectrum for exons 5-8 of the p53 tumor suppressor gene in colorectal carcinomas in Hong Kong Chinese was established. Ninety-nine colorectal carcinomas from Hong Kong patients were analyzed for mutations in p53 gene by PCR-single-strand conformation polymorphism analysis and direct DNA sequencing. Thirty-five of the 99 tumors (35.4%) contained mutations. Point mutations accounted for 80% of all genetic changes and were predominantly base transitions at CpG dinucleotide sites, mutations that were also predominant in Caucasian carcinomas. The major hot spots at codons 175 and 248 of p53 in Caucasians are also hot spots in the Chinese gene. Identical mutations in codons 152 and 306 were detected in two independent tumors in the Chinese, which were reported only rarely in Caucasians. Moreover, a significantly higher frequency (20%) of deletion and insertion mutations was observed in Hong Kong colorectal cancer patients. Distinct genetic and/or environmental factors may contribute to these findings.

Adult↗
PubMed1996

Replication protein A is a component of a complex that binds the human metallothionein IIA gene transcription start site.

Previous studies revealed that sequences surrounding the initiation sites in many mammalian and viral gene promoters, called initiator (Inr) elements, may be essential for promoter strength and for determining the actual transcription start sites. DNA sequences in the vicinity of the human metallothionein IIA (hMTIIA) gene transcription start site share homology with some of the previously identified Inr elements. However, in the present study we have found by in vitro transcription assays that the hMTIIA promoter does not contain a typical Inr. Electrophoretic mobility shift assays identified several DNA-protein complexes at the hMTIIA gene transcription start site. A partially purified protein fraction containing replication protein A (RPA) binds to the hMTIIA gene transcription start site and represses transcription from the hMTIIA promoter in vitro. In addition, overexpression of the human 70-kDa RPA-1 protein represses transcription of a reporter gene controlled by the hMTIIA promoter in vivo. These findings suggest that hMTIIA transcription initiation is controlled by a mechanism different from most mammalian and viral promoters and that the previously identified RPA may also be involved in transcription regulation.

Amino Acid Sequence↗