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Biomedical subjects

R Goswami

Publications and source records attributed to R Goswami.

At least 19 recordsLinked to original sources
PubMed2006

Extensive DNA methylation in normal colorectal mucosa in hyperplastic polyposis.

BACKGROUND: Hyperplastic polyposis of the colorectum is a precancerous condition that has been linked with DNA methylation. The polyps in this condition have been distinguished from typical small hyperplastic polyps and renamed sessile serrated adenomas. Sessile serrated adenomas also occur sporadically and appear to be indistinguishable from their counterparts in hyperplastic polyposis. AIMS AND METHODS: The existence of distinguishing molecular features was explored in a series of serrated polyps and matched normal mucosa from patients with and without hyperplastic polyposis by assessing mutation of BRAF, DNA methylation in 14 markers (MINTs 1, 2 and 31, p16, MGMT, MLH1, RASSF1, RASSF2, NORE1 (RASSF5), RKIP, MST1, DAPK, FAS, and CHFR), and immunoexpression of MLH1. RESULTS: There was more extensive methylation in sessile serrated adenomas from subjects with hyperplastic polyposis (p<0.0001). A more clearcut difference in patients with hyperplastic polyposis was the finding of extensive DNA methylation in normal mucosa from the proximal colon. CONCLUSIONS: A genetic predisposition may underlie at least some forms of hyperplastic polyposis in which the earliest manifestation may be hypermethylation of multiple gene promoters in normal colorectal mucosa. Additionally, some of the heterogeneity within hyperplastic polyposis may be explained by different propensities for MLH1 inactivation within polyps.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Familial pachydermoperiostosis in association with protein-losing enteropathy.

In this report we describe a rare association of pachydermoperiostosis with protein-losing enteropathy (PLE) in a family of three brothers. The first brother had the complete form of pachydermoperiostosis along with PLE. The second brother had the 'forme fruste' of pachydermoperiostosis, with minimal skin changes, bony abnormalities and PLE, which was due to intestinal lymphangiectasia. The third brother had an incomplete form of pachydermoperiostosis without evidence of PLE. To our knowledge, the association of pachydermoperiostosis with PLE due to intestinal lymphangiectasia has not been reported previously.

Adolescent↗
PubMed2006

Promoter region -318 C/ T and -1661 A/G CTLA-4 single nucleotide polymorphisms and type 1 diabetes in North Indians.

Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been associated with manifestation of type 1 diabetes in several populations. We assessed the association of five SNPs present in the CTLA-4 gene [-318C/T, -1661A/G and -1722C/T in the promoter region, +49A/G in exon 1 and CT60 in the 3' untranslated region (UTR) region] with type 1 diabetes in North Indian subjects. Genotyping was performed in the patients (n = 130) and the healthy control (n = 180) subjects by polymerase chain reaction-fragment length polymorphism analysis using MseI, BbvI, BstEII and NcoI restriction endonucleases for the -318, -1661, -1722, +49 and CT60 SNPs, respectively. The frequency of G alleles at -1661 locus was significantly higher in the patient group compared with the control subjects. Although the frequency of T alleles at -318 SNP was significantly higher in patients with type 1 diabetes compared with the controls, it did not remain significant after Bonferroni correction for the number of alleles tested. The frequencies of C/T alleles and genotypes at -1722C/T and G allele at +49A/G and CT60 SNPs were not significantly different between the patient and the control groups. Of the various possible haplotypes constructed using the five genetic loci tested (-318, -1661, -1722, +49, CT60), the frequency of 'TGTAG' haplotype was significantly higher in the patients when compared with the controls. The results of the present study indicate that the presence of G allele at -1661 locus at the CTLA-4 gene (IDDM12 locus) is associated with increased susceptibility to type 1 diabetes in North Indians, whereas A allele is protective.

Adult↗
PubMed2006

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene R620W variant and sporadic idiopathic hypoparathyroidism in Asian Indians.

Recently, a gain of function variant C1858T of the lymphoid-specific protein tyrosine phosphatase non-receptor (LYP, PTPN22) gene has been reported to be associated with several autoimmune disorders including Graves' disease, type 1 diabetes, rheumatoid arthritis and vitiligo. The present study was carried out in 80 patients with sporadic idiopathic hypoparathyroidism (SIH) [43 males and 37 females, mean +/- SD age and duration of symptoms 32.5 +/- 14.1 years and 6.7 +/- 7.2 years (range 1 day to 35 years), respectively] and 193 healthy controls (male : female ratio 91:102, mean +/- SD age, 43.1 +/- 11.6 years) to assess association of 1858T allele with the disease. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to genotype C1858T variant. The frequency of occurrence of 1858T allele was 4/160 (2.5%) in SIH and 5/386 (1.3%) in the control alleles (odds ratio 1.95, 95% CI 0.51-7.37). Thus, the present study reveals that 1858T allele is rare (1.3%) in Asian Indians. The trend of higher prevalence of 1858T allele in patients with SIH needs to be studied further in other population with higher rate of the allele to support the autoimmune basis of the disease.

Adult↗
PubMed2006

Infections in infancy and the presence of antinuclear antibodies in adult life.

There has been limited success defining environmental factors important to the development of connective tissue diseases such as systemic lupus erythematosus (SLE). Recent work has suggested that the perinatal environment may be important. To investigate this we measured antinuclear antibodies (ANA) in a general population with well-defined early lives to see whether fetal and infant growth and infections were associated with ANA positivity in adult life. Included in our investigation were 1334 individuals (668 men, 666 women) from the Hertfordshire cohort study. ANA was measured using an ANA ELISA and confirmed using immunofluorescence. We investigated associations between the presence of ANA and early growth and infectious exposure in infancy in men and women combined, but with adjustment for gender throughout. A positive ANA was present in 73 (10.9%) of men and 81 (12.2%) women. Of these, 26 women and 14 men were positive using IF on HEP2 cells. Sharing a bedroom during childhood was associated with a higher risk of being ANA positive (odds ratio (OR), 1.42, 95% confidence interval (CI) 1.00-2.01, P = 0.05). A record of diarrhoeal illness (OR 2.12 95% CI 1.07, 4.23, P = 0.03) and rubella or mumps during the first year of life (OR 16.12, 95% CI 2.92, 88.94, P = 0.001) was also significantly associated with ANA in adult life. Higher ANA titres by Inova ELISA were associated with infections in the first year of life from mumps (2.74-fold higher, 95% CI 0.98, 7.64, P = 0.05) and rubella (3.90-fold higher, 95% CI 1.89, 8.04, P < 0.001). In addition, higher ANA titres were also associated with mumps (1.26-fold higher, 95% CI 1.02, 1.56, P = 0.03) between one and five years of age. Our results suggest that a developing immune system exposed to increased infection is more likely to produce ANA in adult life and perhaps begin the pathological process that leads to SLE.

Antibodies, Antinuclear↗
PubMed2005

Ceramide regulation of the tumor suppressor phosphatase PTEN in rafts isolated from neurotumor cell lines.

The neutral sphingolipid ceramide has been implicated in the apoptotic death of cells by a number of different mechanisms, including activation of protein kinase B (Akt) phosphatase. Here we present evidence that ceramide recruits the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) into membrane microdomains (rafts), where it could act to reduce the levels of polyphosphoinositides necessary for the activation of Akt. A PTEN construct with a red-fluorescent protein (RFP) tag was overexpressed in both a human cell line derived from oligodendroglioma (HOG) and a rat pheochromocytoma cell line (PC12) by means of an inducible promoter system (Tet-Off). Induction of PTEN by removal of doxycycline enhanced both capsase-3 and cell death with staurosporine, wortmannin, or C2-ceramide, whereas antisense PTEN had the reverse effect. Overexpression of PTEN also increased acid sphingomyelinase (ASMase) activity. PTEN normally has a generalized (cytosolic/membrane) distribution, but treatment with C2-ceramide translocated a fraction of the PTEN to the plasma membrane, showing a plasma membrane distribution similar to that observed for a prenylated green-fluorescent (GFP) construct. PTEN was then shown to translocate to the detergent-resistant membrane microdomain fraction (raft) of the plasma membrane. The colocalization of sphingomyelinases, ceramide, polyphosphoinositides, and PTEN in the raft fraction further suggests that the association of these lipids is critical for regulating cell death.

Androstadienes↗
PubMed2005

Growth and infectious exposure during infancy and the risk of rheumatoid factor in adult life.

BACKGROUND: The contribution of the environment to rheumatoid arthritis (RA) remains uncertain. Intrauterine and early postnatal life may be important. Rheumatoid factor (RF) found in around 10% of the normal population confers a risk of developing RA and may be present years before onset of clinical disease. The immune pathology leading to RA and RF may have similar genetic and environmental influences. OBJECTIVE: To measure RF in people for whom data on birth weight, infant growth, and markers of infectious exposure during infancy and childhood, had been previously recorded. METHODS: 675 men and 668 women aged 59-67 years, born and still resident in Hertfordshire, UK, were studied. RF was measured with an ELISA. Associations between presence of RF, early growth, and markers of hygiene in infancy, were investigated. RESULTS: RF was detected in 112/675 (16.6%) men and 79/668 (11.8%) women. No significant relationships existed between early growth and presence of RF in men or women. Among women, sharing a bedroom during childhood was associated with a lower risk of RF positivity (OR = 0.48, 95% CI 0.30 to 0.78, p = 0.003). CONCLUSIONS: A developing immune system exposed to increased infectious exposure is less likely to produce RF in adult life; this may reduce the pathological process which leads to RA.

Aged↗
PubMed2005

Differential regulation of ceramide in lipid-rich microdomains (rafts): antagonistic role of palmitoyl:protein thioesterase and neutral sphingomyelinase 2.

Cell differentiation and myelination involve a fine balance between stasis and programmed cell death, yet the genes that regulate this have not been clearly defined. We therefore studied two key gene products involved in oligodendrocyte plasma membrane lipid metabolism and their antagonistic role in ceramide-mediated cell death signaling. Overexpression of palmitoyl:protein thioesterase (PPT1; verified by Western blot of the V5-tagged protein and increased enzyme activity) resulted in decreased ceramide in the detergent-resistant microdomain (DRM, or raft) relative to cholesterol and sphingomyelin (SM). This PPT1 overexpression also resulted in protection against cell death induced by either staurosporine or C(2)-ceramide. In contrast, overexpression of neutral sphingomyelinase 2 (NSMase2; verified by Western blot of the FLAG-tagged protein and increased enzyme activity) resulted in increased membrane NSMase and increased ceramide in rafts relative to cholesterol and SM. The difference in SM and ceramide turnover was quantitated by [(3)H]palmitate pulse-chase labeling. Furthermore, when NBD-SM was added to cells, it was hydrolyzed by NSMase-transfected cells at more than twofold the rate in untransfected cells. NSMase2 overexpression enhanced cell death induced by staurosporine or C(2)-ceramide, in contrast to the protective effect of PPT1 overexpression. The presence of a fraction of both PPT1 and NSMase2 in rafts together with their substrates (palmitoylated proteins and SM, respectively) suggests a mechanism for dynamic palmitoylation/depalmitoylation of certain proteins in controlling cell death via NSMase activation.

Animals↗
PubMed2005

Can propofol precipitate pancreatitis in patients with Cushing's syndrome?

We encountered two cases of acute pancreatitis in patients with Cushing's disease following transnasal transsphenoidal hypophysectomy. In both cases propofol was used in bolus doses, and is thought to be the probable factor for its development. Since elevated cortisol levels in Cushing's disease poses a threat for pancreatitis, there is a possibility that patients with Cushing's disease might be more prone to acute pancreatitis following propofol administration. Anaesthesiologists and physicians dealing with the management of Cushing's disease need to be aware of this possibility.

Acute Disease↗
PubMed2005

Polymorphisms at +49A/G and CT60 sites in the 3' UTR of the CTLA-4 gene and APECED-related AIRE gene mutations analysis in sporadic idiopathic hypoparathyroidism.

Autoimmune diseases such as Graves' disease and type 1 diabetes have been linked with +49A/G and CT60 single nucleotide polymorphisms (SNPs) in the 3' UTR of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene. Both these SNPs are functionally relevant and linked with T-lymphocyte activation. Hypoparathyroidism is seen in 70% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome (APECED). Although calcium sensing receptor autoantibodies (CaSRAb) and generalized activation of T lymphocytes are reported among patients with sporadic idiopathic hypoparathyroidism (SIH), CTLA-4 gene SNPs and APECED-related autoimmune regulator (AIRE) gene mutations have not been assessed in them. We studied lead CTLA-4 gene SNPs and APECED-related AIRE gene mutations in 73 patients with SIH and 114 healthy subjects. The CTLA-4 gene SNPs +49A/G in exon 1, CT60A/G in 3' UTR and -318C/T in the promoter region were genotyped by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) using BstEII, NcoI and MseI endonucleases, respectively. The APECED-related AIRE gene mutations, which is R257X (Finn-major) in exon 6, 4-bp insertion and 13-bp deletion in exon 8, and Iranian Jews population 'Y85C' mutation in exon 2, were studied by PCR-RFLP (Taq-I), PCR and nucleotide sequencing, respectively. CaSRAb were studied by immunoblotting. The frequencies of CTLA-4 A/A(49), A/G(49) and G/G(49) genotypes in the patients (47.9%, 38.4% and 13.7%) and controls (45.6%, 39.5% and 14.9%, respectively) and the frequencies of CT60 A/A, A/G, and G/G genotypes in the patient (42.4%, 37.0% and 20.6%) and the control (38.6%, 40.4% and 21.0%, respectively) groups were not significantly different. The frequencies of various haplotypes including genetic loci +49A/G and CT60 and frequencies of G alleles at these positions were comparable between patient and the control groups and its presence did not correlate with clinical and biochemical indices of the disease. None of the patients had APECED-related AIRE gene mutations. Lack of significant difference in the pattern of CTLA-4 A/G(49) and/or CT60A/G genotypes and absence of common APECED syndrome-related AIRE gene mutations among patients and controls suggest that these sites do not play a role in the development of the SIH.

3' Untranslated Regions↗
PubMed2004

Templateless room-temperature assembly of nanowire networks from nanoparticles.

We demonstrate a new, room-temperature approach to assemble two-dimensional and three-dimensional networks of gold nanowires by agitating nanoparticles in a toluene-aqueous mixture, without the use of templates. The nanowires have a uniform diameter of about 5 nm and consist of coalesced face-centered cubic nanocrystals. Toluene molecules passivate the gold surfaces during nanoparticle coalescence, rendering the nanowires hydrophobic and enabling their transfer into the toluene layer. Such templateless low-temperature assembly of mesostructures from nanoscale building blocks open up new possibilities for creating porous self-supporting nanocatalysts, nanowires for device interconnection, and low-density high-strength nanofillers for composites.

Journal Article↗
PubMed2004

Acid sphingomyelinase and inhibition by phosphate ion: role of inhibition by phosphatidyl-myo-inositol 3,4,5-triphosphate in oligodendrocyte cell signaling.

There is ample evidence that both acid (ASMase) and neutral (NSMase) sphingomyelinases play a role in cell death so inhibitors of either enzyme could have significant value as protectors against neurodegeneration. We used a fluorogenic sphingomyelinase substrate, 6-hexadecanoylamino-4-methylumbelliferyl-phosphorylcholine, and a [(14)C]choline-labeled sphingomyelin substrate to screen large numbers of phosphocompounds for inhibition of ASMase in extracts of human oligodendroglioma cells (HOG) and neonatal rat oligodendrocytes. Non-competitive inhibition was observed with inorganic phosphate and AMP, which was a more potent inhibitor of ASMase than cyclic AMP, ADP or ATP. However, other nucleotide phosphates, sugar phosphates, nucleotide sugars and glycerol phosphate did not inhibit ASMase. Our key finding was that phosphatidyl-myo-inositol 3,4,5-triphosphate [PtdIns (3,4,5)P(3)] was a much more potent inhibitor of ASMase than lysophosphatidic acid or phosphatidyl-myo-inositol 4,5-diphosphate [PtdIns(4,5)P(2)]. When PtdIns(3,4,5)P(3) was added to cultured cells we observed 50% inhibition of ASMase but no inhibition of other lysosomal hydrolases. After transfection of HOG cells with the tumor supressor phosphatase and tensin homolog protein (PTEN), which hydrolyses PtdIns(3,4,5)P(3) to PtdIns(4,5)P(2), we observed a two-fold increase in ASMase activity. Furthermore, the phosphatidylinositol-3-kinase inhibitor wortmannin (which reduces PtdIns(3,4,5)P(3) levels) also resulted in activation of ASMase. We propose that the small amount of ASMase activity associated with detergent-resistant cell membranes (Rafts) is regulated by PtdIns(3,4,5)P(3) and is most likely involved in receptor clustering and capping.

Adenosine Monophosphate↗
PubMed2004

Molecular basis of predisposition to develop type 1 diabetes mellitus in North Indians.

Type 1 diabetes (T1D) mellitus is a multifactorial autoimmune disease where more than 90% of insulin-producing pancreatic beta cells are destroyed before the clinical manifestations, warranting a need to identify the children predisposed to get the disease. Of the 20 genomic intervals implicated for the risk to develop T1D, the major histocompatibility complex (MHC) region on chromosome 6p21.31 (IDDM1) has been the major contributor, followed by 5' regulatory region of the insulin (INS) gene on chromosome 11p15.5 (IDDM2). MHC has a role in antigen presentation and IDDM2 has been shown to have a role in transcription of insulin in the thymus. Hence, alleles of human leukocyte antigen (HLA)-DRB1, DQB1, and insulin-linked variable number of tandem repeats (INS-VNTR) were studied in 110 T1D patients and 112 healthy controls using polymerase chain reaction and hybridization with sequence-specific oligonucleotide probes (PCR-SSOP) and PCR restriction fragment length polymorphism (PCR-RFLP), respectively. HLA-DRB1*0301 was significantly increased in the T1D patients along with associated DQB1*0201 followed by DRB1*0401 and DRB1*0405. DRB1*0701 was observed to be the most protective allele followed by DRB1*0403 and DRB1*0404. Although DQB1*0302 which is associated with both the protective and susceptible DR4 alleles was not significantly increased, heterozygous DQB1*0201, *0302 was significantly increased in the TID patients. Because INS-VNTR class I homozygosity was also significantly increased in the patients, simultaneous presence of DRB1*0301 along with homozygous INS-VNTR class I, gave a relative risk (RR) of 70.81. However, a similar analysis of DQB1*0201 and *0302 along with INS-VNTR alleles did not give such high RRs. Thus, the two independently assorting alleles at two loci i.e., DRB1*0301 and INS-VNTR class I, on two different chromosomes may have the potential to predict a prediabetic in North India.

Adolescent↗
PubMed2002

Reversible peripheral neuropathy in idiopathic hypoparathyroidism.

We describe a 40-year-old male with idiopathic hypoparathyroidism presenting with tetany, proximal weakness, signs of hypocalcaemia including Chvostek and Trousseau's and diminished tendon reflexes in the upper and lower limbs. Electrophysiological studies revealed a sensory-motor neuropathy, predominantly axonal as evidenced by decreased CMAP amplitudes, with normal distal latencies-velocites, except for median nerve where a prolonged distal latency was observed. Serial nerve conduction studies were performed at repeated intervals for 2 years, while he received treatment for hypoparathyroidism (calcium and vitamin D supplementation). A progressive improvement in neuropathy both clinical and on electrophysiological studies was observed. Occurrence of peripheral neuropathy in hypocalcaemic states such as hypoparathyroidism and its reversibility after normalization of calcium homeostasis lend proof to the role of critical Ca2+ ion concentration in the normal functioning of the peripheral axons.

Adult↗
PubMed2001

Islet cell autoimmunity in youth onset diabetes mellitus in Northern India.

We characterised a consecutive cohort of 132 youth onset diabetic individuals (age at onset<30 years, mean duration of disease 5.5+/-6.0 years) from North India, by serological determination of the determination of the islet cell autoantibodies, GAD(65) and IA2, and clinically for coexisting autoimmune thyroid disease, malnutrition and pancreatic calcification. Five types of diabetes were delineated: Type 1 (37%), ketosis resistant (32%), Type 2 (13%), fibrocalculous pancreatopathy (11%) and autoimmune polyglandular syndrome (7%). C-peptide response to glucagon was assessed in a representative subset of 50 patients with Type 1, ketosis resistant, and autoimmune polyglandular syndrome. A total of 22.4% of Type 1 and 30% of autoimmune polyglandular syndrome subjects showed both GAD(65) plus IA-2 autoantibody positivity, significantly more than the 4.7% positivity shown by the ketosis resistant type. However, GAD(65) antibody positivity alone was seen in 38% of ketosis resistant subjects which was significantly more than the 14.2 and 10% positivity seen in Type 1 and autoimmune polyglandular groups, respectively. The fibrocalculous pancreatopathy group showed GAD(65) plus IA-2 autoantibody positivity in 14.2% and GAD(65) autoantibody alone positivity in 7.1%. 26 and 60%, respectively, of the Type 1 and autoimmune polyglandular syndrome groups had thyroid microsomal autoantibody positivity. Type 1 showed significantly less C-peptide response to glucagon when compared to the ketosis resistant and autoimmune polyglandular syndrome groups. The controls and Type 2 diabetic individuals tested negative for islet cell autoimmunity markers. These findings demonstrate a role of islet cell autoimmunity in the pathogenesis of four out of the five clinical types of youth onset diabetes seen in North India.

Adolescent↗
PubMed2001

Prevalence of urinary tract infection and renal scars in patients with diabetes mellitus.

In a case control study, we assessed the prevalence of bacterial urinary tract infections (UTI) and renal scarring in 155 consecutive type 1 (n=102) and type 2 (n=53) diabetic individuals and 128 healthy controls. Subjects who received antibiotics during the past 6 months, pregnant women and those with overt renal failure were excluded. In all subjects, urine culture and 99m Technetium (Tc) dimercapto-succinic acid renal scan was performed. UTI was diagnosed if two consecutive urine cultures grew the same organism with at least 10(5) colony forming unit (cfu)/ml in asymptomatic and at least 10(4) cfu/ml in symptomatic subjects, respectively. Renal scan was considered abnormal if focal or multiple tracer uptake defects and/or break in cortical outline were observed. The prevalence of UTI in diabetes mellitus was higher, when compared to that in controls (9% vs. 0.78%, P=0.005). Escherichia coli was the most commonly grown organism (64.3%), followed by Staphyloccocus aureus (21.4%) and Klebsiella pneumoniae (14.3%). Prevalence of renal scarring was higher in patients with diabetes (28/155, 18.0%), when compared to that of controls (7/128, 5.4%, P=0.002). Fifty percent of patients with diabetes and UTI had renal scarring. The prevalence in diabetics with no UTI was also higher, when compared to controls (14.8 vs. 5.5%, P<0.01). The prevalence of UTI as well as renal scarring was significantly higher in females, when compared to male diabetics. No significant difference in vascular events, hypertension, proteinuria, renal function tests and HbA1 was observed in patients with and without renal scar. Thus, patients with diabetes mellitus have 10- and 3-folds increased risk of UTI and renal scarring, respectively. The results could help prioritize protocols for management of UTI among patients with diabetes mellitus.

Adult↗
PubMed2001

Mechanism of biochemical action of substituted benzopyran-2-ones. Part 8: Acetoxycoumarin: protein transacetylase specificity for aromatic nuclear acetoxy groups in proximity to the oxygen heteroatom.

Our earlier work established a convenient assay procedure for acetoxycoumarin (AC): protein transacetylase (TA) by indirectly quantifying the activity of glutathione (GSH)-S-transferase (GST), the extent of inhibition of GST under the conditions of the assay represented TA activity. In this communication, we have probed the specificity for TA with respect to the number and position of acetoxy groups on the benzenoid as well as the pyranone rings of the coumarin system governing the efficient transfer of acetyl groups to the protein(s). For this purpose, coumarins bearing one acetoxy group, separately at C-3 or C-4 position and 4-methylcoumarins bearing single acetoxy group, separately at C-5, C-6 or C-7 position were synthesized and specificities to rat liver microsomal TA were examined. Negligible TA activity was discernible with 3-AC as the substrate, while the substrate efficiency of other AC were in the order 7-acetoxy-4-methylcoumarin (7 AMC)>6 AMC>5 AMC=5 ADMC=4 AC. To achieve a comparable level of GST inhibition which was proportional to the enzymatic transfer of acetyl groups to the protein (GST), the concentrations of 7-AMC, 6-AMC, 5-AMC and 4-AC were in the order 1:2:4:4, respectively. One diacetoxycoumarin, i.e., 7,8-diacetoxy-4-methylcoumarin (DAMC) was also examined and it was found to elicit maximum level of GST inhibition, nearly twice that observed with 7-AMC. These observations lead to the logical conclusion that a high degree of acetyl group transfer capability is conferred when the acetoxy group on the benzenoid ring of the coumarin system is in closer proximity to the oxygen heteroatom, i.e., when the acetoxy groups are at the C-7 and C-8 positions.

Aflatoxin B1↗