Interesting case: an unusual case of oral ulceration.
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Biomedical subjects
Publications and source records attributed to C Liew.
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To study the dispersal of dengue vector mosquitoes in Singapore, females of Aedes aegypti (L.) and Aedes albopictus (Skuse) (Diptera: Culicidae) were fed blood containing rubidium (Rb), which was detectable in their eggs by means of Graphite Furnace Atomic Absorption Spectrophotometry (GFAAS). Laboratory calibration of the Rb reading, for a range of egg numbers from Rb-fed females, indicated a reasonably linear relationship and an unequivocal distinction between results with zero and one marked egg. Rb-marked female Aedes mosquitoes aged 3-5 days were released in semi-rural and urbanized parts of Singapore, with an array of ovitraps extending to a radius of 320 m from the release point. Subsequently, Rb-marked Aedes eggs were detected throughout the array, with similar distributions on each of the 4 days after release. More Rb was detected nearer the release point. However, when correction was made for the greater areas of zones further from the release point (and therefore presumably existence of more alternative oviposition sites), there were no significant differences in the numbers of marked eggs per ovitrap in the zones nearer or further from the release points. It is concluded that females of both these Aedes (Stegomyia) species could disperse easily and quickly throughout areas of radius 320 m in search of oviposition sites. This contrasts with the general belief that Ae. aegypti seldom flies more than 50 m and that control operations can safely be based on such an assumption. Releases on level 12 of a 21-storey apartment block, with ovitraps on each storey, showed similar easy and rapid dispersal to the top and bottom of the block.
The rotary processor can be used for single step spheroid production directly from powder with multiple formulation and process variables involved. In this study, a frictional base plate with teardrop studs was used. Four selected independent variables, base plate rotational speed during liquid addition (A), spray rate of water (B), total amount of water added (C) and base plate rotational speed during the tumbling stage (D), were put into an orthogonal design with three levels for each variable. Mean spheroid size and size distribution were used as the response variables to evaluate the effect of these independent variables. The variables C and D were identified as more important among the four variables and should be at optimal levels for producing good quality spheroids.
Identifying key genes that regulate the complex diseases of the cardiovascular system can be greatly facilitated with the use of microarrays. In an effort to obtain a global portrait of gene expression in the failing heart, we have constructed in-house a glass microscope slide cDNA microarray (termed "CardioChip") containing 10,368 redundant and randomly-selected sequenced expressed sequence tags (representing known genes, other matched ESTs, and novel, unmatched ESTs) derived from several human heart and artery cDNA libraries. From our preliminary data with Cy3- and Cy5-labeled probes, we have identified 38 transcripts showing a minimum twofold differential expression, among which are several novel or previously-uncharacterized genes. This array-representing what we believe to be the largest cardiovascular-based cDNA array to date-establishes a practical and invaluable platform for obtaining a global genetic portrait of complex cardiovascular diseases, particularly in the failing heart.
OBJECTIVE: Fifteen loci on chromosome 9p and 17 were analyzed to clarify the involvement of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC) in Chinese patients positive for hepatitis B (HBV) and/or hepatitis C (HCV) infection. Expression of tumor suppressor genes (TSG) of p53, p16, and p15 gene was found to correlate with a deletion of these genes. METHODS: Immunohistochemistry and PCR-based microsatellite polymorphism analysis techniques were used. RESULTS: A high frequency of LOH was detected on chromosome 9p24 at locus D9S54 (61.8%) and 9p21, concentrated at loci D9S1747 (52.4%) and D9S1752 (51.8%). On chromosome 17, high frequent LOH was concentrated on 17p at the p53 gene locus (53.8%) and locus D17S520 (52.8%). p53 protein expression was increased in HCC, which correlated with p53 gene loss. Expression of p16 and p15 protein decreased in HCC when LOH occurred at locus D9S1752 (p15 gene locus) or at locus D9S1747 and D9S1748 (p16 gene is located between these 2 loci). LOH at the p53 gene and p15 gene loci was closely associated with HBV and HCV co-infection in HCC. No significant relationship between LOH and HCC clinico-pathological outcomes was observed. CONCLUSION: High frequency LOH occurs on chromosomes 9p and 17 in HCC in Chinese patients. Such sites may contain several putative tumor suppressor genes critically involved in the development and/or progression of HCC. Deletion of p53, p16, or p15 tumor suppressor genes may cause abnormal expression of the protein product of these genes. HBV and/or HCV infection may be closely associated with LOH p53 and/or p15 gene expression.
Friend of GATA-1 (FOG-1) is a zinc finger protein that has been shown to interact physically with the erythroid DNA-binding protein GATA-1 and modulate its transcriptional activity. Recently, two new members of the FOG family have been identified: a mammalian protein, FOG-2, that also associates with GATA-1 and other mammalian GATA factors; and U-shaped, a Drosophila protein that interacts with the Drosophila GATA protein Pannier. FOG proteins contain multiple zinc fingers and it has been shown previously that the sixth finger of FOG-1 interacts specifically with the N-finger but not the C-finger of GATA-1. Here we show that fingers 1, 5 and 9 of FOG-1 also interact with the N-finger of GATA-1 and that FOG-2 and U-shaped also contain multiple GATA-interacting fingers. We define the key contact residues and show that these residues are highly conserved in GATA-interacting fingers. We examine the effect of selectively mutating the four interacting fingers of FOG-1 and show that each contributes to FOG-1's ability to modulate GATA-1 activity. Finally, we show that FOG-1 can repress GATA-1-mediated activation and present evidence that this ability involves the recently described CtBP co-repressor proteins that recognize all known FOG proteins.
OBJECTIVE: Both cytogenetic and molecular genetic analyses have unveiled non-random genomic alterations in the distal short arm of human chromosome 1 associated with a number of human malignancies including heptatocellular carcinoma (HCC). The aim of this investigation is to determine the precise region of deletion that may harbor the putative tumor suppressor genes in HCC. METHODS: For the study of the loss of heterozygosity (LOH), 38 cases of hepatitis B virus (HBV) associated HCC and their corresponding non-tumor liver tissues were detected with 43 microsatellite polymorphic markers particularly focusing on 1p. RESULTS: Twenty-eight of the 38 (74%) tumors showed LOH on at least one locus on 1p36.2-p36.3. Two distinct smallest common deleted regions (SCDRs) with different patterns of deletion were identified. The first SCDR is located on locus D1S2795 at 1p36.3, between loci D1S2145 and D1S2893. The second SCDR is located at 1p36.2, between loci D1S244 and D1S489. Both of the SCDRs have not been previously described in HCC. In addition, a region of possible homozygous deletion (HD) was also detected within the second SCDR between loci D1S1597 and D1S489 by comparative multiplex PCR. This is the first observation of a possible homozygous deletion on the distal short arm of chromosome 1 in HCC as well as in human tumors. CONCLUSIONS: The high-resolution deletion mapping of 1p36.2-p36.3 in HCC in this study confirmed the presence of two distinct regions of deletion. Our data strongly suggest the presence of at least two tumor suppressor regions on 1p36.2-p36.3 and play an important role in the pathogenesis of HBV associated HCC. These results also provide a basis for further studies directed at cloning potential tumor suppressor genes in these regions.
We have isolated the full-length human 56 kDa selenium binding protein (hSP56) cDNA clone, which is the human homolog of mouse 56 kDa selenium binding protein. The cDNA is 1,668 bp long and has an open reading frame encoding 472 amino acids. The calculated molecular weight is 52.25 kDa and the estimated isoelectric point is 6.13. Using Northern blot hybridization, we found that this 56 kDa selenium binding protein is expressed in mouse heart with an intermediate level between those found in liver/lung/kidney and intestine. We have also successfully expressed hSP56 in Escherichia coli using the expression vector-pAED4. The hSP56 gene is located at human chromosome 1q21-22).
The prevalence of human immunodeficiency virus (HIV) in male prisoners in South Australia from July 1989 to June 1994 was ascertained from a repeated cross-sectional study. We also compared the criminological and demographic characteristics and histories of drug use of 39 HIV-infected prisoners and a randomly selected sample of 86 uninfected prisoners admitted at the same time. The numbers of HIV-infected prisoners in prison in any month ranged from 4 to 12. Prevalence among the total prison population ranged from 0.4 per cent to 1.4 per cent, and among the subpopulation of injecting drug users from 1.25 per cent to 4.36 per cent. Many HIV-infected prisoners continued after their diagnosis to have lifestyles that resulted in imprisonment. Infected prisoners were significantly older, had spent longer in prison and were more likely to be users of heroin (OR = 13.1) and methadone (OR = 25.4) than controls. Infection with HIV among South Australian prisoners has been continuous since at least the mid-1980s. The recidivism among many of the infected prisoners contributes to the variation in prevalence but also raises concerns about their management. Greater effort to minimise the recidivism of the HIV-infected prisoners could reduce the prevalence of HIV in the prison population.
Aberrant crypt foci (ACF) are putative preneoplastic lesions that develop after treatment of animals with colon carcinogens, including cooked-meat heterocyclic amines such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 rats given IQ by gavage on alternating days for 2 wk (130 mg/kg body weight) and killed 12 wk after the final carcinogen dose had an average of 4.4 ACF/colon and an average of 3.2 crypts/focus. The DNA from these ACF was amplified by the polymerase chain reaction and analyzed by 3'-primer mismatch and direct sequencing methods for mutations in the Ki-ras proto-oncogene. Of the 37 IQ-induced ACF screened, three contained a GGT-->GAT mutation in codon 12 and one contained a GGC-->GCC mutation in codon 13. The approximately 11% frequency of mutation in IQ-induced ACF is within the range of previous ACF studies of azoxymethane, which reported a 7-37% incidence of Ki-ras mutation. These findings suggest that for both compounds, ras mutations occur during early stages of colorectal tumorigenesis. However, while ras mutations can be detected with increasing frequency in azoxymethane-induced adenomas and carcinomas, they are reportedly absent in IQ-induced colon tumors. Thus, for IQ and related compounds additional factors (possibly increased cell proliferation) may be important in the later stages of colorectal tumorigenesis.
Grilled ground beef contains a number of heterocyclic amine carcinogens, such as 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), as well as anticarcinogenic conjugated linoleic acids (CLA). In the present study, CLA was administered to male F344 rats by gavage on alternating days in weeks 1-4, while IQ was given by gavage every other day in weeks 3 and 4 (100 mg/kg body wt). Rats were killed 6 h after the final carcinogen dose 16 in order to score colonic aberrant crypt foci (ACF). In the ACF study, CLA had no effect on the size of the foci, but inhibited significantly (P < 0.05) the number of ACF/colon, from 4.3 +/- 2.4 in controls to 1.1 +/- 1.3 in CLA-treated rats (mean +/- SD, n = 10). Rats given CLA also had significantly lower IQ-DNA adducts in the colon as determined by 32P-postlabeling analysis; relative adduct labeling levels (RAL x 10(7) for the major adduct were 9.13 +/- 2.6 in controls versus 5.42 +/- 1.8 in CLA-treated animals (P < 0.05). Mechanism studies indicated that CLA and other fatty acids interact with certain heterocyclic amines in a manner consistent with substrate-ligand binding. However, no such interaction occurred with IQ, and CLA failed to inhibit significantly the mutagenicity of N-hydroxy-IQ in the Salmonella assay. Liver microsomes from CLA-treated rats exhibited lower activities for dealkylation of 7-ethoxyresorufin and methoxyresorufin and activated IQ to DNA binding species less effectively than microsomes from control animals. Direct addition of CLA to the in vitro incubation inhibited IQ-DNA binding and was associated with increased recovery of unmetabolized parent compound. In the Salmonella assay, CLA inhibited the mutagenic activity of IQ in the presence of S9 or ram seminal vesicle microsomes. Collectively, these results support a mechanism involving inhibition of carcinogen activation by CLA, as opposed to direct interaction with the procarcinogen, scavenging of electrophiles or selective induction of phase I detoxification pathways.
Proplast is an ultra-porous composite material that has been used widely to augment the facial skeleton. In recent years, however, the popularity of this material has declined because of complications associated with its use. This paper presents a retrospective study of 36 cases treated with 88 Proplast implants at one unit over a nine-year period. The results suggest that infection of the implant is the most common post-operative complication. Infection may occur at any time following implantation and appears to be more likely when implantation is associated with an osteotomy procedure. In addition, the overall rate of infection in this study (16%) was higher than reported previously and the male-female ratio was 2:1. The possible factors involved in infection are discussed.
Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits antimutagenic activity in several short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo. The effect of CHL pretreatment on the excretion of mutagens in the urine and feces of male Sprague-Dawley rats has been studied using the Salmonella mutagenicity assay. Animals were given 1 percent CHL in the drinking water for 2 days before administering a single dose of 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) by oral gavage. Rats pretreated with CHL had higher levels of mutagens in the urine and feces compared with animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose excreted was < 4% in controls vs. 18% in rats given CHL. Mutagenicity required the presence of an activation system, was unaffected by treatment with beta-glucuronidase or arylsulfatase, and in both the urine and feces was accounted for by increased elimination of unmetabolized parent compound. The results support the view that CHL may operate in vivo as a "desmutagen" or interceptor molecule, interacting with IQ in the gut and tissues, and reducing carcinogen bioavailability.
During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures.
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