Oligodontia, the congenital absence of six or more permanent teeth, is a common developmental ano... more Oligodontia, the congenital absence of six or more permanent teeth, is a common developmental anomaly of human dentition whose genetic basis is poorly understood. We recently reported a nonsyndromic form of oligodontia involving mostly all permanent molars in a large kindred, caused by a frameshift mutation in exon 2 of the human PAX9 gene [3]. To better understand the genotype/phenotype correlation in non-syndromic familial oligodontia, we identified additional families with a similar pattern of molar oligodontia. We hypothesize that molar oligodontia is due to allelic heterogeneity involving different mutations in PAX9. To test this hypothesis, we performed pedigree analysis followed by mutational analysis. Pedigree analysis revealed that the oligodontia trait is inherited in an autosomal dominant fashion. Mutational analysis of PAX9 thus far excludes the presence of the previously identified frameshift mutation.
Our objective is to identify molecular factors which contribute to the increased risk of smokers ... more Our objective is to identify molecular factors which contribute to the increased risk of smokers for oral squamous cell carcinoma (OSCC). In the present study, we investigated the effects of cigarette smoke condensate (CSC) on gene expression profiles in different human oral cell phenotypes: normal epidermal keratinocytes (NHEK), oral dysplasia cell lines (Leuk1 and Leuk2), and a primary oral carcinoma cell line (101A). We determined differential gene expression patterns in CSC-exposed versus non-exposed cells using high-density microarray RNA expression profiling and validation by quantitative real-time RT-PCR. A set of 35 genes was specifically up-or down-regulated following CSC treatment (25 g/ml for 24 h) by at least 2-fold in any one cell type. Notably, five genes of the cytochrome P450 (CYP1A1, CYP1B1) and aldo-keto reductase (AKR1C1, AKR1C3, AKR1B10) families were highly increased in expression, some of them 15-to 30-fold. The timing and extent of induction for these genes differed among the four cell phenotypes. A potential biological interaction network for the CSC response in oral cells was derived from these data, proposing novel putative response pathways. These CSC-responsive genes presumably participate in the prevention or repair of carcinogen-induced DNA damage in tobacco-related oral carcinogenesis, and may potentially be exploited for determining the severity of exposure and for correcting mutagenic damage in exposed tissues of the oral cavity.
Plants can be exposed to mercury either by direct administration as antifungal agents, mainly to ... more Plants can be exposed to mercury either by direct administration as antifungal agents, mainly to crop plants through seed treatment or foliar spray, or by accident. Mercury poisoning has become a problem of interest on a global scale. Natural emissions of mercury form two-thirds of the input; man-made releases form about one-third. Significant amounts of mercury may be added to agricultural land with sludge, fertilizers, lime and manures. Total mercury levels were determined in six breeds of quality protein maize using cold vapor atomic absorption spectrometry (CVAAS). The breeds analyzed were Aziga, Abeleehi, Akposoe, Golden Jubilee, Etubi and Obaatanpa. Proximate composition of these breeds was also determined. The objective of this study was therefore to assess the effect of mercury on the proximate composition of quality protein maize. The proximate composition of the maize varieties analyzed showed that the moisture content ranged from 11.57% ± 0.205% to 12.76% ± 0.042%, ash from 1.11% ± 0.064% to 1.58% ± 0.021%, protein, 6.51% ± 0.307% to 10.39% ± 0.306%, fiber 1.44% ± 0.071% to 1.87% ± 0.057%, fat 1.84% ± 0.078% to 2.75% ± 0.092% and carbohydrate 71.77% ± 0.035% to 76.54% ± 0.216%. The total mercury levels in the maize breeds analyzed ranged from 0.0010 ± 1.17E-05 µg/g to 0.0079 ± 1.00E-05 µg/g. The mercury levels detected were lower than the WHO limit for mercury in food of 0.5 µg/g in all the maize breeds. The low levels of mercury in the maize samples show they are safe for consumption.
Categorization is a fundamental psychological ability necessary for problem solving and many othe... more Categorization is a fundamental psychological ability necessary for problem solving and many other higher-level cognitive tasks. In organic chemistry, students must establish groupings of different chemical compounds in order not only to solve problems, but also to understand ...
Our objective is to identify molecular factors which contribute to the increased risk of smokers ... more Our objective is to identify molecular factors which contribute to the increased risk of smokers for oral squamous cell carcinoma (OSCC). In the present study, we investigated the effects of cigarette smoke condensate (CSC) on gene expression profiles in different human oral cell phenotypes: normal epidermal keratinocytes (NHEK), oral dysplasia cell lines (Leuk1 and Leuk2), and a primary oral carcinoma cell line (101A). We determined differential gene expression patterns in CSC-exposed versus non-exposed cells using high-density microarray RNA expression profiling and validation by quantitative real-time RT-PCR. A set of 35 genes was specifically up-or down-regulated following CSC treatment (25 g/ml for 24 h) by at least 2-fold in any one cell type. Notably, five genes of the cytochrome P450 (CYP1A1, CYP1B1) and aldo-keto reductase (AKR1C1, AKR1C3, AKR1B10) families were highly increased in expression, some of them 15-to 30-fold. The timing and extent of induction for these genes differed among the four cell phenotypes. A potential biological interaction network for the CSC response in oral cells was derived from these data, proposing novel putative response pathways. These CSC-responsive genes presumably participate in the prevention or repair of carcinogen-induced DNA damage in tobacco-related oral carcinogenesis, and may potentially be exploited for determining the severity of exposure and for correcting mutagenic damage in exposed tissues of the oral cavity.
Background: Historical proven wood species have no reported adverse health effect associated with... more Background: Historical proven wood species have no reported adverse health effect associated with its past use. Different historical proven species have traditionally been used to manufacture different wooden food contact items. This study uses survey questionnaires to assess suppliers', manufacturers', retailers' and consumers' (end-users') preferences for specific wood species, to examine the considerations that inform these preferences and to investigate the extent of awareness of the chemical benefits and chemical hazards associated with wooden food contact material use.
A method for the determination of residues of the insecticide diflubenzuron, 1-(4-chlorophenyl)-3... more A method for the determination of residues of the insecticide diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, in apples using gas chromatography with electron-capture detection has been developed and validated. The three solvents ethyl acetate, acetone and dichloromethane were tested for extraction of diflubenzuron residues from apples. Dichloromethane gave the highest recovery and the lowest background and was chosen as the extraction solvent. After extraction the residue of diflubenzuron was derivatized with heptafluorobutyric anhydride. The derivative was purified by silica solid-phase extraction using toluene as the eluent. The external standard calibration was linear over the range 0.05-1.0 Ixg/ml and the limit of quantification was 0.03 mg/kg apple using 25 g samples. Recovery of diflubenzuron from spiked apples (0.1-0.8 mg/kg) was 80-88% with a relative standard deviation of less than 10% (n=5). The method was applied to the determination of diflubenzuron residues in apples from a treated field.
Pax9 is a paired domain-containing transcription factor that plays an essential role in the patte... more Pax9 is a paired domain-containing transcription factor that plays an essential role in the patterning of murine dentition. In humans, mutations in PAX9 are associated with unique phenotypes of familial tooth agenesis that mainly involve posterior teeth. Among these, a frameshift mutation (219InsG) within the paired domain of PAX9 produces a protein product associated with a severe form of molar agenesis in a single family. The objectives of this study were to gain new insights into the molecular pathogenesis of the 219InsG mutation and its role in tooth agenesis. Here we describe functional defects in DNA binding and transactivation of mutant 219InsGPax9. Although wild type Pax9 binds to the high affinity paired domain recognition sequences, e5 and CD19 -2(A-ins), the 219InsGPax9 mutant protein was unable to bind to these cognate DNA-binding sites. In co-transfection assays, wild type Pax9 activated reporter gene transcription although the mutant was transcriptionally inactive. Immunolocalization data show that Pax9 and 219InsGPax9 proteins are synthesized in mammalian cells but that the nuclear localization of the mutant Pax9 protein is altered. Furthermore, transactivation by the full-length Pax9 protein from paired domain binding sites was not impaired by the 219InsGPax9 mutant. The latter did not alter the DNA binding activities of wild type Pax9 in gel mobility shift assays. The combined defects in DNA binding activities and transactivation function of mutant 219InsG-PAX9 likely alter the selective activation and/or repression of PAX9 effector genes during odontogenesis. This loss-of-function of PAX9 most likely results in its haploinsufficiency during the patterning of dentition and the subsequent loss of posterior teeth.
Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cell... more Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cellular and physiological functions including cell-autonomous defense against intracellular pathogens. Here, we screened the Rab family of membrane trafficking regulators for effects on autophagic elimination of Mycobacterium tuberculosis var. bovis BCG and found that Rab8b and its downstream interacting partner, innate immunity regulator TBK-1, are required for autophagic elimination of mycobacteria in macrophages. TBK-1 was necessary for autophagic maturation. TBK-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on Ser-403, a residue essential for its role in autophagic clearance. A key proinflammatory cytokine, IL-1b, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1b activity was dependent on TBK-1. Thus, TBK-1 is a key regulator of immunological autophagy and is responsible for the maturation of autophagosomes into lytic bactericidal organelles.
Gene expression profiling of oral premalignant (OPM) cells and normal oral epithelial (NOR) cells... more Gene expression profiling of oral premalignant (OPM) cells and normal oral epithelial (NOR) cells showed that EMMPRIN expression was markedly upregulated in OPM cells compared to NOR cells. We used an oral squamous cell carcinoma (OSCC) progression model composed of cell lines, organotypic cultures and tissue specimens to characterize EMMPRIN expression patterns by microarray analysis, qRT-PCR, Western blotting and immunohistochemistry. EMMPRIN levels are elevated in OPM and primary and metastatic OSCC cells as compared to NOR. EMMPRIN was detected as high and low glycosylated forms in the OPM and OSCC cellular extracts and was released in the media by OSCC cells but not by OPM cells. EMMPRIN expression in an organotypic culture model of normal and OPM mucosae mirrored the expression patterns in the respective tissues in vivo. EMMPRIN expression was limited to basal cells of normal, benign hyperkeratotic and inflammatory (lichen planus) oral mucosa. EMMPRIN expression is increased in dysplastic leukoplakias spreading to more superficial layers, and its expression levels correlated significantly with the degree of dysplasia. Primary and metastatic OSCC showed strong cell surface expression of EMMPRIN. These results suggest that EMMPRIN overexpression occurs at a very early stage of oral carcinogenesis and plays a contributing role in OSCC tumorigenesis.
The leaves of Persea americana are widely used for ethno-medicinal purposes worldwide. This study... more The leaves of Persea americana are widely used for ethno-medicinal purposes worldwide. This study assessed the antimicrobial and antioxidant activities of the methanol, ethyl acetate, chloroform and petroleum ether leaves extracts of P. americana. Extracts displayed variable antimicrobial activities that were microorganism-specific. The methanolic extract displayed the most potent antimicrobial activities with the largest zones of inhibition (0-1.8 mm) in the agar diffusion assay and with the lowest minimum inhibitory concentration (MIC) in the broth dilution assay against a panel of microorganisms that included Bacillus subtilis, Escherichia coli, Salmonella typhi, Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. The ethyl acetate extract exhibited the most potent antioxidant potential with the lowest EC 50 of 4.15x10-30 g/ml for the peroxide radical scavenging activities. The data supports the ethnomedicinal use of the leaves of P. americana for the management of infections and for other symptoms whose etiology may be linked to oxidative stress.
Oligodontia, the congenital absence of six or more permanent teeth, is a common developmental ano... more Oligodontia, the congenital absence of six or more permanent teeth, is a common developmental anomaly of human dentition whose genetic basis is poorly understood. We recently reported a nonsyndromic form of oligodontia involving mostly all permanent molars in a large kindred, caused by a frameshift mutation in exon 2 of the human PAX9 gene [3]. To better understand the genotype/phenotype correlation in non-syndromic familial oligodontia, we identified additional families with a similar pattern of molar oligodontia. We hypothesize that molar oligodontia is due to allelic heterogeneity involving different mutations in PAX9. To test this hypothesis, we performed pedigree analysis followed by mutational analysis. Pedigree analysis revealed that the oligodontia trait is inherited in an autosomal dominant fashion. Mutational analysis of PAX9 thus far excludes the presence of the previously identified frameshift mutation.
Our objective is to identify molecular factors which contribute to the increased risk of smokers ... more Our objective is to identify molecular factors which contribute to the increased risk of smokers for oral squamous cell carcinoma (OSCC). In the present study, we investigated the effects of cigarette smoke condensate (CSC) on gene expression profiles in different human oral cell phenotypes: normal epidermal keratinocytes (NHEK), oral dysplasia cell lines (Leuk1 and Leuk2), and a primary oral carcinoma cell line (101A). We determined differential gene expression patterns in CSC-exposed versus non-exposed cells using high-density microarray RNA expression profiling and validation by quantitative real-time RT-PCR. A set of 35 genes was specifically up-or down-regulated following CSC treatment (25 g/ml for 24 h) by at least 2-fold in any one cell type. Notably, five genes of the cytochrome P450 (CYP1A1, CYP1B1) and aldo-keto reductase (AKR1C1, AKR1C3, AKR1B10) families were highly increased in expression, some of them 15-to 30-fold. The timing and extent of induction for these genes differed among the four cell phenotypes. A potential biological interaction network for the CSC response in oral cells was derived from these data, proposing novel putative response pathways. These CSC-responsive genes presumably participate in the prevention or repair of carcinogen-induced DNA damage in tobacco-related oral carcinogenesis, and may potentially be exploited for determining the severity of exposure and for correcting mutagenic damage in exposed tissues of the oral cavity.
Plants can be exposed to mercury either by direct administration as antifungal agents, mainly to ... more Plants can be exposed to mercury either by direct administration as antifungal agents, mainly to crop plants through seed treatment or foliar spray, or by accident. Mercury poisoning has become a problem of interest on a global scale. Natural emissions of mercury form two-thirds of the input; man-made releases form about one-third. Significant amounts of mercury may be added to agricultural land with sludge, fertilizers, lime and manures. Total mercury levels were determined in six breeds of quality protein maize using cold vapor atomic absorption spectrometry (CVAAS). The breeds analyzed were Aziga, Abeleehi, Akposoe, Golden Jubilee, Etubi and Obaatanpa. Proximate composition of these breeds was also determined. The objective of this study was therefore to assess the effect of mercury on the proximate composition of quality protein maize. The proximate composition of the maize varieties analyzed showed that the moisture content ranged from 11.57% ± 0.205% to 12.76% ± 0.042%, ash from 1.11% ± 0.064% to 1.58% ± 0.021%, protein, 6.51% ± 0.307% to 10.39% ± 0.306%, fiber 1.44% ± 0.071% to 1.87% ± 0.057%, fat 1.84% ± 0.078% to 2.75% ± 0.092% and carbohydrate 71.77% ± 0.035% to 76.54% ± 0.216%. The total mercury levels in the maize breeds analyzed ranged from 0.0010 ± 1.17E-05 µg/g to 0.0079 ± 1.00E-05 µg/g. The mercury levels detected were lower than the WHO limit for mercury in food of 0.5 µg/g in all the maize breeds. The low levels of mercury in the maize samples show they are safe for consumption.
Categorization is a fundamental psychological ability necessary for problem solving and many othe... more Categorization is a fundamental psychological ability necessary for problem solving and many other higher-level cognitive tasks. In organic chemistry, students must establish groupings of different chemical compounds in order not only to solve problems, but also to understand ...
Our objective is to identify molecular factors which contribute to the increased risk of smokers ... more Our objective is to identify molecular factors which contribute to the increased risk of smokers for oral squamous cell carcinoma (OSCC). In the present study, we investigated the effects of cigarette smoke condensate (CSC) on gene expression profiles in different human oral cell phenotypes: normal epidermal keratinocytes (NHEK), oral dysplasia cell lines (Leuk1 and Leuk2), and a primary oral carcinoma cell line (101A). We determined differential gene expression patterns in CSC-exposed versus non-exposed cells using high-density microarray RNA expression profiling and validation by quantitative real-time RT-PCR. A set of 35 genes was specifically up-or down-regulated following CSC treatment (25 g/ml for 24 h) by at least 2-fold in any one cell type. Notably, five genes of the cytochrome P450 (CYP1A1, CYP1B1) and aldo-keto reductase (AKR1C1, AKR1C3, AKR1B10) families were highly increased in expression, some of them 15-to 30-fold. The timing and extent of induction for these genes differed among the four cell phenotypes. A potential biological interaction network for the CSC response in oral cells was derived from these data, proposing novel putative response pathways. These CSC-responsive genes presumably participate in the prevention or repair of carcinogen-induced DNA damage in tobacco-related oral carcinogenesis, and may potentially be exploited for determining the severity of exposure and for correcting mutagenic damage in exposed tissues of the oral cavity.
Background: Historical proven wood species have no reported adverse health effect associated with... more Background: Historical proven wood species have no reported adverse health effect associated with its past use. Different historical proven species have traditionally been used to manufacture different wooden food contact items. This study uses survey questionnaires to assess suppliers', manufacturers', retailers' and consumers' (end-users') preferences for specific wood species, to examine the considerations that inform these preferences and to investigate the extent of awareness of the chemical benefits and chemical hazards associated with wooden food contact material use.
A method for the determination of residues of the insecticide diflubenzuron, 1-(4-chlorophenyl)-3... more A method for the determination of residues of the insecticide diflubenzuron, 1-(4-chlorophenyl)-3-(2,6-difluorobenzoyl)urea, in apples using gas chromatography with electron-capture detection has been developed and validated. The three solvents ethyl acetate, acetone and dichloromethane were tested for extraction of diflubenzuron residues from apples. Dichloromethane gave the highest recovery and the lowest background and was chosen as the extraction solvent. After extraction the residue of diflubenzuron was derivatized with heptafluorobutyric anhydride. The derivative was purified by silica solid-phase extraction using toluene as the eluent. The external standard calibration was linear over the range 0.05-1.0 Ixg/ml and the limit of quantification was 0.03 mg/kg apple using 25 g samples. Recovery of diflubenzuron from spiked apples (0.1-0.8 mg/kg) was 80-88% with a relative standard deviation of less than 10% (n=5). The method was applied to the determination of diflubenzuron residues in apples from a treated field.
Pax9 is a paired domain-containing transcription factor that plays an essential role in the patte... more Pax9 is a paired domain-containing transcription factor that plays an essential role in the patterning of murine dentition. In humans, mutations in PAX9 are associated with unique phenotypes of familial tooth agenesis that mainly involve posterior teeth. Among these, a frameshift mutation (219InsG) within the paired domain of PAX9 produces a protein product associated with a severe form of molar agenesis in a single family. The objectives of this study were to gain new insights into the molecular pathogenesis of the 219InsG mutation and its role in tooth agenesis. Here we describe functional defects in DNA binding and transactivation of mutant 219InsGPax9. Although wild type Pax9 binds to the high affinity paired domain recognition sequences, e5 and CD19 -2(A-ins), the 219InsGPax9 mutant protein was unable to bind to these cognate DNA-binding sites. In co-transfection assays, wild type Pax9 activated reporter gene transcription although the mutant was transcriptionally inactive. Immunolocalization data show that Pax9 and 219InsGPax9 proteins are synthesized in mammalian cells but that the nuclear localization of the mutant Pax9 protein is altered. Furthermore, transactivation by the full-length Pax9 protein from paired domain binding sites was not impaired by the 219InsGPax9 mutant. The latter did not alter the DNA binding activities of wild type Pax9 in gel mobility shift assays. The combined defects in DNA binding activities and transactivation function of mutant 219InsG-PAX9 likely alter the selective activation and/or repression of PAX9 effector genes during odontogenesis. This loss-of-function of PAX9 most likely results in its haploinsufficiency during the patterning of dentition and the subsequent loss of posterior teeth.
Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cell... more Autophagy is a fundamental biological process of the eukaryotic cell contributing to diverse cellular and physiological functions including cell-autonomous defense against intracellular pathogens. Here, we screened the Rab family of membrane trafficking regulators for effects on autophagic elimination of Mycobacterium tuberculosis var. bovis BCG and found that Rab8b and its downstream interacting partner, innate immunity regulator TBK-1, are required for autophagic elimination of mycobacteria in macrophages. TBK-1 was necessary for autophagic maturation. TBK-1 coordinated assembly and function of the autophagic machinery and phosphorylated the autophagic adaptor p62 (sequestosome 1) on Ser-403, a residue essential for its role in autophagic clearance. A key proinflammatory cytokine, IL-1b, induced autophagy leading to autophagic killing of mycobacteria in macrophages, and this IL-1b activity was dependent on TBK-1. Thus, TBK-1 is a key regulator of immunological autophagy and is responsible for the maturation of autophagosomes into lytic bactericidal organelles.
Gene expression profiling of oral premalignant (OPM) cells and normal oral epithelial (NOR) cells... more Gene expression profiling of oral premalignant (OPM) cells and normal oral epithelial (NOR) cells showed that EMMPRIN expression was markedly upregulated in OPM cells compared to NOR cells. We used an oral squamous cell carcinoma (OSCC) progression model composed of cell lines, organotypic cultures and tissue specimens to characterize EMMPRIN expression patterns by microarray analysis, qRT-PCR, Western blotting and immunohistochemistry. EMMPRIN levels are elevated in OPM and primary and metastatic OSCC cells as compared to NOR. EMMPRIN was detected as high and low glycosylated forms in the OPM and OSCC cellular extracts and was released in the media by OSCC cells but not by OPM cells. EMMPRIN expression in an organotypic culture model of normal and OPM mucosae mirrored the expression patterns in the respective tissues in vivo. EMMPRIN expression was limited to basal cells of normal, benign hyperkeratotic and inflammatory (lichen planus) oral mucosa. EMMPRIN expression is increased in dysplastic leukoplakias spreading to more superficial layers, and its expression levels correlated significantly with the degree of dysplasia. Primary and metastatic OSCC showed strong cell surface expression of EMMPRIN. These results suggest that EMMPRIN overexpression occurs at a very early stage of oral carcinogenesis and plays a contributing role in OSCC tumorigenesis.
The leaves of Persea americana are widely used for ethno-medicinal purposes worldwide. This study... more The leaves of Persea americana are widely used for ethno-medicinal purposes worldwide. This study assessed the antimicrobial and antioxidant activities of the methanol, ethyl acetate, chloroform and petroleum ether leaves extracts of P. americana. Extracts displayed variable antimicrobial activities that were microorganism-specific. The methanolic extract displayed the most potent antimicrobial activities with the largest zones of inhibition (0-1.8 mm) in the agar diffusion assay and with the lowest minimum inhibitory concentration (MIC) in the broth dilution assay against a panel of microorganisms that included Bacillus subtilis, Escherichia coli, Salmonella typhi, Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. The ethyl acetate extract exhibited the most potent antioxidant potential with the lowest EC 50 of 4.15x10-30 g/ml for the peroxide radical scavenging activities. The data supports the ethnomedicinal use of the leaves of P. americana for the management of infections and for other symptoms whose etiology may be linked to oxidative stress.
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Papers by John Mensah