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Biomedical subjects

M Parkar

Publications and source records attributed to M Parkar.

At least 19 recordsLinked to original sources
PubMed2007

Acute effects of periodontal therapy on bio-markers of vascular health.

AIM: We aimed to study the impact of periodontal therapy on several bio-markers related to vascular health. MATERIAL AND METHODS: Fifty-five consecutive subjects (age range 30-64 years) having severe periodontitis received an intensive session of periodontal therapy under local anaesthesia and provided blood samples before and 1 and 7 and 30 days following therapy. High-sensitivity assays were utilized to quantify serum concentrations of inflammatory markers [interleukin (IL)-1beta, tumour necrosis factor-alpha], plasma haemostatic (D-dimer) and endothelial soluble markers [soluble E-selectin (s-Es) and von Willebrand factor antigen (r-WF:Ag)]. RESULTS: Periodontal therapy elicited a significant activation of the haemostatic system (38% and 68% mean increases of plasma D-dimer 1 and 7 days after therapy, respectively, p<0.001), together with moderate endothelial dysfunction (10% and 30% mean increases at 24 h in plasma soluble E-selectin, p<0.05 and von-Willebrand factor, p<0.01, respectively). D-Dimer and s-Es acute changes were significantly correlated with periodontal treatment time (p<0.05). Cigarette smoking status and body mass index strongly influenced the acute release of IL-1beta (p<0.05), D-dimer (p<0.01) and s-Es (p<0.01). CONCLUSIONS: Periodontal therapy represents a novel and reliable non-drug-induced model to investigate in vivo the interplay between inflammation, coagulation and endothelial cell activation.

Acute-Phase Reaction↗
PubMed2006

NADPH oxidase (CYBA) and FcgammaR polymorphisms as risk factors for aggressive periodontitis: a case-control association study.

INTRODUCTION: Neutrophils (PMN) in aggressive periodontitis (AgP) patients have been reported to be hyperactive especially with regards to superoxide production. Polymorphisms in genes influencing PMN function have been proposed as candidate risk factors for AgP. The aim of this study was to test the association of specific gene polymorphisms affecting PMN functions with AgP. MATERIALS AND METHODS: Two hundred and twenty-four patients with confirmed diagnosis of AgP and 231 subjects with healthy periodontium took part in the study. A blood sample was collected from subjects and genotypes for p22phox (CYBA) NADPH oxidase, FP, Fcalpha and Fcgamma receptors were analysed in a blind fashion. RESULTS: The C242T p22phox NADPH oxidase T allele was significantly associated with AgP in a multiple logistic regression model adjusting for confounders, and this was observed for all subjects [p = 0.002, odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.27-2.83] and Caucasians (p = 0.009, OR=2.07, 95% CI = 1.20-3.59). Concomitant presence of C242T p22phox NADPH oxidase T allele and FcgammaRIIIb NA1 homozygosity was associated with the generalized AgP phenotype in Caucasians (p = 0.001, OR = 30.35, 95% CI = 3.81-241.97). CONCLUSIONS: C242T p22phox NADPH oxidase and FcgammaR polymorphisms may predispose to AgP through a modulation of neutrophil superoxide production.

Adult↗
PubMed2005

Periodontal therapy: a novel acute inflammatory model.

OBJECTIVE AND DESIGN: We designed a clinical trial at the Eastman Dental Hospital with the objective of developing a novel in vivo inflammatory model. SUBJECTS: We recruited 55 subjects suffering from severe periodontitis. TREATMENT: Participants received intensive periodontal therapy. METHODS: Blood samples were collected at baseline and 1 and 7 and 30 days after treatment and processed for a series of biomarkers (TNF-alpha, IL-6, CRP and Fibrinogen) by high-sensitivity assays and differential blood counts (standard laboratory procedures). RESULTS: TNF-alpha levels were significantly raised only after 1 day of therapy (P<0.01) whereas IL-6 (P<0.01), CRP (P<0.001) and Fibrinogen (P<0.001) concentrations peaked 24 hrs after and returned to baseline values within one month following therapy. Mild neutrophilia, monocytosis and lymphopenia were also observed. CONCLUSIONS: Intensive periodontal therapy induces a one week moderate inflammatory response and therefore it is proposed as a novel therapeutic and reliable non drug-induced in vivo model of acute inflammation.

Acute Disease↗
PubMed2005

Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol.

Severe periodontitis has been associated with increased systemic inflammation. In a three-arm preliminary randomized trial, we investigated the impact of standard (SPT) and intensive periodontal therapy (IPT) on serum inflammatory markers and cholesterol levels. Medical and periodontal parameters, C-reactive protein (CRP), interleukin-6 (IL-6), total cholesterol, and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis. Two months after treatment, both SPT and IPT resulted in significant reductions in serum CRP compared with the untreated control (0.5 +/- 0.2 mg/L for SPT, P = 0.030 and 0.8 +/- 0.2 mg/L for IPT, P = 0.001). Similar results were observed for IL-6. Changes in inflammation were independent of age, gender, body mass index, and ethnicity, but a significant interaction between cigarette smoking and treatment regimen was found. The IPT group also showed a decrease in total and LDL cholesterol after 2 months. Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects.

Adult↗
PubMed2005

Functional gene polymorphisms in aggressive and chronic periodontitis.

There is strong evidence that genetic as well as environmental factors affect the development of periodontitis, and some suggestion that aggressive and chronic forms of the disease share the same genetic predisposition. This study addresses the hypothesis that there are both shared and unique genetic associations in these forms of periodontitis. A sample of 51 patients with aggressive disease, 57 patients with chronic disease, and 100 healthy controls was recruited for this study. Ten functional polymorphisms in 7 candidate genes were genotyped. The results show statistically significant (p <or= 0.05) differences between genotype frequencies in aggressive and controls (IL-1B +3954 & IL-6 -174); chronic and controls (IL-6 -174 & VDR -1056); chronic and aggressive periodontitis (IL-1A -889); and periodontitis as a whole and controls (VDR -1056, TLR-4 399 & IL-6 -174). These results suggest that there are in fact both shared and unique genetic associations in aggressive and chronic periodontitis.

Alleles↗
PubMed2004

Gene polymorphisms in pro-inflammatory cytokines are associated with systemic inflammation in patients with severe periodontal infections.

The inflammatory response to chronic infections such as periodontitis may be central to the systemic implications of these diseases. This study examined the possible association between specific gene polymorphisms and the systemic inflammatory response in individuals suffering from severe generalized periodontitis. Ninety-four subjects with periodontitis were genotyped for polymorphisms in IL-1A (-889), IL-1B (-511, +3954), TNF-A (-308), IL-6 (-174) and TLR4 (-299, -399) genes. We found that the genotypes for IL-1A or IL-6 are associated with higher levels of serum IL-6 (P < 0.03) and serum CRP (P < 0.05), similarly the TNF-A genotype is associated with higher levels of serum IL-6 (P < 0.05) after correction for age, body mass index, gender, ethnicity and cigarette smoking. Systemic inflammatory responses are higher in severe periodontitis patients carrying rare alleles for functional inflammatory gene polymorphisms. These results suggest that cytokine genotypes are important determinants of the systemic inflammatory response in subjects with periodontitis. Genetic polymorphism therefore, may in part explain the reported association between periodontitis and systemic disease.

Base Sequence↗
PubMed2004

Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers.

Severe periodontitis is associated with elevated inflammatory markers in otherwise healthy populations. However, the nature of this association has not been determined. Our aim was to assess whether the degree of response to periodontal therapy was associated with changes in serological markers of systemic inflammation. Ninety-four systemically healthy subjects with severe generalized periodontitis participated in a prospective six-month blind intervention trial. Periodontal parameters and inflammatory markers [C-reactive Protein (CRP) and Interleukin-6 (IL-6)] were evaluated prior to and 2 and 6 mos after delivery of standard non-surgical periodontal therapy. Six months after treatment, significant reductions in serum IL-6 (p < 0.001, median decrease 0.2 ng/L, 95% CI 0.1-0.4 ng/L) and CRP (p < 0.0001, median decrease 0.5 mg/L, 95% CI 0.4-0.7) were observed. Decreases in inflammatory markers were significant in subjects with above average clinical response to periodontal therapy after correction for possible confounders. Periodontitis may add to the systemic inflammatory burden of affected individuals.

Aggregatibacter actinomycetemcomitans↗
PubMed2002

Expression profiling of periodontal ligament cells stimulated with enamel matrix proteins in vitro: a model for tissue regeneration.

Several studies have examined the role of enamel matrix proteins in root formation and periodontal regeneration, although most of these have focused on a few specific genes which had previously been implicated. However, recent advances in expressional profiling have made it possible to examine the range of genetic responses involved in these processes. In the present experiments, we have therefore utilized this technique to determine the effects of enamel matrix proteins on the gene activities of periodontal ligament cells in vitro. Such cells were found to have an elevated level of RNA synthesis compared with control cells. Moreover, hybridization of the cDNA prepared from this RNA to gene array filters showed that there was differential expression of 121 genes, most of which had not previously been associated with periodontal regeneration. Some of these selective changes in gene activity might thus reflect the fundamental events that underlie periodontal development.

Adult↗
PubMed1998

IL-6 expression by oral fibroblasts is regulated by androgen.

Interleukin 6 (IL-6) is a multi-functional cytokine which has a major role in tissue damage. It is secreted by many types of cell, including oral fibroblasts, and has been implicated in the pathogenesis of periodontal diseases, particularly those associated with sex hormones. In the present study we investigated whether the androgen dihydrotestosterone (DHT) affects the expression and regulation of IL-6 in gingival fibroblasts. Using a 'capture' ELISA assay, it was found that increasing DHT concentrations progressively reduced IL-6 production by gingival cells from normal individuals and from patients with gingival inflammation and gingival hyperplasia. In contrast, cells from periodontal ligament tissue produced only barely detectable levels of IL-6. The anti-androgen cyproterone acetate acted as an androgen analogue in the gingival fibroblasts, potently inhibiting IL-6 production, and did not reverse the DHT-mediated downregulation of the cytokine. Flutamide also failed to abrogate DHT inhibition of IL-6 production, and it had no effect on IL-6 production in the absence of DHT. Moreover, semi-quantitative RT-PCR showed that DHT acted at the level of transcription of the IL-6 gene, causing a marked reduction in the relative level of IL-6 mRNA in the gingival cells.

Androgen Antagonists↗
PubMed1994

Genetic mapping of two loci, DXS454 and DXS458, with respect to the X-linked agammaglobulinemia gene locus.

The dinucleotide repeat sequences at the DXS454 and DXS458 loci have been mapped genetically to Xq22, to the interval between DXS3 and DXS17. We have now mapped them with respect to XLA and five other loci, to within the DXS3 to XLA interval. The more precise localisation of these polymorphic loci will be useful for the fine-mapping of disease loci on the long arm of the X chromosome and enable these probes to be used for prenatal diagnosis and carrier status determination in families with XLA.

Agammaglobulinemia↗
PubMed1993

Genetic linkage analysis identifies new proximal and distal flanking markers for the X-linked agammaglobulinemia gene locus, refining its localization in Xq22.

Genetic linkage analysis has been instrumental in mapping the gene for X-linked agammaglobulinemia (XLA) to the proximal long arm of the human X chromosome, to Xq22. Due to the relative rarity of this disease the localization of the gene within Xq22 has remained imprecise. We have investigated twenty-nine families affected by XLA and have found no recombinants with the DXS178 locus in over 30 informative meioses. DXS178 is now the most reliable and informative locus for use in pre-natal diagnosis and carrier detection of XLA. In addition, we have identified new closely linked proximal and distal flanking markers for XLA, DXS442 and DXS101, respectively. These loci are separated by 2cM, considerably reducing the extent of DNA within which the XLA locus can be contained. This will open up the way for more directed positional cloning efforts for the isolation of the XLA gene.

Agammaglobulinemia↗
PubMed1988

The human alpha-1-antitrypsin-related sequence gene: isolation and investigation of its expression.

A genomic sequence approximately 5 kb in length designated the alpha-1-antitrypsin-related gene (ATR), showing considerable homology to the human alpha-1-antitrypsin (AAT) gene, was identified 10 kb downstream of the authentic AAT gene. The AAT and ATR genes were introduced separately into L-cells by transfection in order to establish a method for distinguishing between expression of the two genes. RNA probes from the cloned ATR region were then used in a ribonuclease protection assay against RNA from a range of human adult and fetal tissues. No evidence of expression of ATR was found, indicating that this region is probably a pseudogene.

Animals↗
PubMed1986

Characterization and chromosomal assignment of a human cell surface antigen defined by the monoclonal antibody AUAI.

We describe the chromosomal assignment and biochemical characterization of the genetic locus controlled by a human cell surface antigen which is defined by the monoclonal antibody (MAb) AUAI. This gene product is only expressed on epithelial cells. Therefore, human-mouse somatic cell hybrids of epithelial origin were used to assign this gene to chromosome 2. Cell surface iodination of the hybrids and parental cells followed by immunoprecipitation and polyacrylamide gel electrophoresis showed that AUAI detected a single 35-kDa protein. The MAb AUAI reacted on tissue sections with a subset of normal epithelial cells, but in tumours it showed a much wider distribution, though still only on epithelium-derived tumours.

Antibodies, Monoclonal↗
PubMed1986

The gene for human muscle specific carbonic anhydrase (CAIII) is assigned to chromosome 8.

A cDNA clone complementary to the mRNA encoding the human muscle specific carbonic anhydrase CAIII has been used as probe in the analysis of DNA from panels of rodent/human somatic cell hybrids. The presence of the CA III gene in all hybrids correlates with the presence of chromosome 8. This is the first assignment of the CAIII gene in any species and, together with published mapping data, indicates that all of the human CA loci are situated on chromosome 8.

Animals↗
PubMed1986

Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.

Carcinoma, Transitional Cell↗