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T M Hassell

Publications and source records attributed to T M Hassell.

At least 19 recordsLinked to original sources
PubMed1997

Evidence for genetic control of changes in f-actin polymerization caused by pathogenic microorganisms: in vitro assessment using gingival fibroblasts from human twins.

Attachment to and migration upon a substratum, as well as other functions of connective tissue cells, are regulated mainly by cytoplasmic structural proteins, particularly filamentous actin (f-actin). Pathogenic microorganisms exert negative effects on cytoskeletal proteins. In the present study, normal gingival fibroblasts from 10 sets of human twins (6 fraternal, DZ; 4 identical, MZ) were exposed to soluble extracts from Porphyromonas gingivalis or Fusobacterium nucleatum, then f-actin was stained using FITC-labeled phalloidin. Cells were examined under fluorescence, and a computer-assisted image analyzer quantitated f-actin polymerization as fluorescence intensity on a per-cell basis. Intraclass correlation coefficients for f-actin in MZ/MZ vis-a-vis DZ/DZ paired cell cultures were determined to assess the possible heritability of responses to the microorganism preparations. F-actin labeling was significantly different between control cultures and those exposed to the extracts. Both F. nucleatum and P. gingivalis effected f-actin and fibroblast morphology. When the data were adjusted for gender and age effects, and for differences in control f-actin levels, fibroblasts from MZ twin pairs were moderately similar in both absolute and relative responses to bacterial challenges; cells from DZ twins showed little similarity when response was measured on the absolute scale, and moderate similarity using the relative scale.

Actins↗
PubMed1995

Genetic influences in caries and periodontal diseases.

Deciphering the relative roles of heredity and environmental factors ("nature vs. nurture") in the pathogenesis of dental caries and diseases of the periodontium has occupied clinical and basic researchers for decades. Success in the endeavor has come more easily in the case of caries; the complex interactions that occur between host-response mechanisms and putative microbiologic pathogens in periodontal disease have made elucidation of genetic factors in disease susceptibility more difficult. In addition, during the 30-year period between 1958 and 1987, only meager resources were targeted toward the "nature" side of the nature/nurture dipole in periodontology. In this article, we present a brief history of the development of genetic epistemology, then describe the three main research mechanisms by which questions about the hereditary component of diseases in humans can be addressed. A critical discussion of the evidence for a hereditary component in caries susceptibility is next presented, also from a historical perspective. The evolution of knowledge concerning possible genetic ("endogenous", "idiotypic") factors in the pathogenesis of inflammatory periodontal disease is initiated with an analysis of some foreign-language (primarily German) literature that is likely to be unfamiliar to the reader. We identify a turning point at about 1960, when the periodontal research community turned away from genetics in favor of microbiology research. During the past five years, investigators have re-initiated the search for the hereditary component in susceptibility to common adult periodontal disease; this small but growing body of literature is reviewed. Recent applications of in vitro methods for genetic analyses in periodontal research are presented, with an eye toward a future in which persons who are at risk--genetically predisposed--to periodontal disease may be identified and targeted for interventive strategies. Critical is the realization that genes and environment do not act independently of each other; the appearance or magnitude of heritability may differ with various environments.

Adult↗
PubMed1994

Gingival overgrowth in cyclosporine A treated multiple sclerosis patients.

Correlations have been reported between cyclosporine A (CsA)-induced gingival overgrowth (OG) and plaque-induced gingivitis, duration of CsA therapy, and blood and tissue drug levels. We evaluated the relative importance of such factors using data from a 2-year, double-blind study of CsA therapy in multiple sclerosis (MS) patients. Ninety subjects (40 taking CsA; 50 placebo) were evaluated for plaque, calculus, gingivitis, probing depths, attachment levels, and CsA levels in blood and saliva. OG was determined by a panel of 11 calibrated examiners from standardized clinical photographs taken at the end of the study. Logistic regression was used to determine which factors were associated with occurrence of OG. Four (17%) out of 23 CsA patients with CsA trough blood levels < 400 ng/ml exhibited OG. In contrast, 10 (59%) out of 17 CsA patients with CsA trough blood levels > or = 400 ng/ml were affected with OG. Logistic regression analysis resulted in odds ratios of 0.74 (P = 0.009), 17.3 (P = 0.024) and 10.1 (P = 0.030) for the associations between OG and age, CsA trough blood levels > or = 400 ng/ml, and the interaction "color x tone," respectively. In conclusion, the incidence of CsA induced OG appears to be higher with CsA trough blood levels greater than 400 ng/ml.

Adolescent↗
PubMed1991

Effect of folic acid on recurrence of phenytoin-induced gingival overgrowth following gingivectomy.

This study examined the effect of folic acid supplementation on the recurrence of phenytoin-induced gingival overgrowth following gingivectomy. 8 residents of an institution for the developmentally disabled were randomly assigned to a treatment (N = 4) or control (N = 4) group. Subjects in the treatment group received an oral supplementation of 5 mg of folic acid daily during the study; those in the control group did not. A gingivectomy with an external beveled incision made to the crest of the alveolus was completed by quadrants. The following data were obtained prior to gingivectomy, 2 weeks following the last quadrant of surgery, and at 3 and 6 months post-surgery: plaque and gingival index scores, red blood cell folic acid levels, free phenytoin blood levels, photographs, and impressions. % change in overgrowth was determined from cross-sectional area measurements made on dies obtained from bucco-lingual cuts on stone models. Differences across time between and within groups were tested by a two-factor repeated measure analysis of variance. The groups did not differ in plaque and gingival index scores or free phenytoin blood levels. The treatment group had significantly higher red blood cell folic acid levels (p less than or equal to 0.0001). Reduction in gingival overgrowth as a result of surgery was similar in both groups. Although the treatment group had significantly less recurrence of gingival overgrowth (p less than or equal to 0.05), the mean differences amounted to only 6-7% at 3 and 6 months.

Adult↗
PubMed1990

[Cyclosporine-induced gingival hyperplasia in renal transplant patients].

Cyclosporine-induced gingival hyperplasia was investigated in a clinical study of 80 renal transplant patients. 34% of the patients exhibited at least mild gingival hyperplasia in the anterior, and 9% presented this finding also in the posterior region. No direct correlation was found between the oral dose or the whole blood concentration of cyclosporine and the presence of gingival overgrowth. Young and female patients were at a significantly greater risk of developing cyclosporine-induced gingival hyperplasia than the other patients. The presence of dental plaque or gingival inflammation was not found to be related to the incidence of gingival hyperplasia.

Adolescent↗
PubMed1989

Genetic control of variation in human gingival fibroblast proliferation rate.

Logarithmic proliferation rate (Days 1 to 6) of gingival fibroblasts derived from 15 pairs of monozygotic (MZ) and 9 pairs of dizygotic (DZ) human twins was compared under optimal and suboptimal growth conditions. Cell proliferation rates exhibited considerable variability among strains. For Caucasian donors (13 MZ, 6 DZ pairs) DZ twins demonstrated significantly greater (P less than 0.01) within-pair variance in cell proliferation rate compared to MZ twins when evaluated under optimal growth conditions. Heritability analysis indicated strong genetic control of proliferation rate of human gingival fibroblasts (HGF) under optimal growth conditions (1.0 +/- 0.67), whereas proliferation rate of HGF under suboptimal growth conditions revealed less genetic control (0.42 +/- 0.61). These findings emphasize the importance of carefully matching control and test HGF in assays dependent on cellular proliferation.

Adolescent↗
PubMed1989

Cutaneous papillomatous hyperplasia in cyclosporine-A treated beagles.

All twelve Beagle dogs undergoing long-term therapy (26 weeks) with the immunosuppressive drug cyclosporine-A (30 mg/kg), developed cutaneous papillomatous hyperplasia. By week 7 all dogs developed generalized lesions distributed over the entire body. These occurred as irregular, oval, sessile, unpigmented, firm masses. The incidence and severity of the skin lesions varied among dogs and anatomic site, with no correlation to the blood level of cyclosporine. Microscopic analysis revealed that the epidermis formed short papillary folds on broad fibrovascular stalks and was hyperkeratotic and acanthotic. Mild hyperplasia of hair follicles and sebaceous glands was also evident. A mild diffuse infiltrate of lymphocytes and plasma cells was present in the papillary dermis. No histopathologic changes typical of papillomavirus infection were identified, nor were papillomavirus group-specific antigens or viral DNA detected. Other cutaneous side effects included hyperkeratosis of footpads, increased growth of hair and nails, and hyperkeratinization of the haired skin of the prepuce. All cutaneous lesions regressed spontaneously within 8 weeks following termination of cyclosporine administration. The hyperplastic lesions may have resulted from the action of cyclosporine via the T-lymphocyte system. Conversely a direct action of this drug on epithelial cells may have stimulated proliferation and keratinization.

Animals↗
PubMed1989

Cyclosporine-induced gingival overgrowth in beagle dogs.

Development of gingival overgrowth during daily long-term cyclosporine A treatment was studied in 2-yr-old beagles. Gingival enlargement developed in five of 12 dogs (42%), primarily in the mandibular anterior area. The earliest gingival changes occurred by 3 wk as an increase in the size of the interdental papillae. The lesions progressively became more severe, in some cases obscuring portions of teeth by wk 6. The redundant tissue exhibited an increase in connective tissue components and an inflammatory infiltrate primarily of plasma cells. Severity of the overgrowth varied in responding animals; both incidence and severity were related to the CSA concentration in blood. The mean CSA blood levels of responders were significantly greater than nonresponders at wk 3, 6 and 10. Since beagles develop gingival overgrowth similar to humans, they provide an excellent model to investigate the roles of local and systemic factors in the induction of gingival overgrowth.

Animals↗
PubMed1987

Enhancement by extracts of mineralized tissues of protein production by human gingival fibroblasts in vitro.

Non-confluent cell cultures were exposed to both guanidine and guanidine-EDTA extracts of cementum, dentine and alveolar bone, at concentrations from 2 to 50 micrograms/ml for 48 h. The cells were radioactively labelled during the last 24 h. Total protein production was measured via incorporation of radioactive proline; collagen production was estimated by digestion of the radioactive protein mixture with bacterial collagenase. All guanidine-EDTA extracts elicited statistically-significant increases in total protein production when compared to controls. At 50 micrograms/ml of extract, the increase in protein production was 340, 143 and 338 per cent for bone, cementum and dentine, respectively. Similar results were obtained for collagen production. Guanidine-EDTA extracts also stimulated an increase in the production of specific proteins, as ascertained by gel electrophoresis. In contrast, the guanidine extracts had no effect on either protein or collagen production. Thus the functions of gingival fibroblasts can be altered by proteins from associated mineralized tissues. Identification of such proteins and their biological functions would enhance knowledge of the mechanisms that regulate connective-tissue regeneration.

Alveolar Process↗
PubMed1986

Synthetic activities of mass cultures and clones of human gingival fibroblasts.

The percentage of synthesis dedicated to collagen is elevated in low-density cultures of human gingival fibroblasts, as is per-cell total protein synthetic activity and glycosaminoglycan accumulation. These observations can be explained, in part, by a decrease in membrane transport of precursor substance in high-density cultures. Synthetic activity by human fibroblasts can be reliably assayed in vitro using as few as 500 cells sparsely seeded. Such low-cell number assay is essential for study of single-cell clones, where replicative life span is limited.

Biological Transport↗
PubMed1985

Characterization of collagens in phenytoin-enlarged human gingiva.

The collagen content and composition of human gingivae enlarged due to phenytoin medication were compared to normal and inflamed gingival tissues. Phenytoin-enlarged gingiva contained significantly higher amounts of collagen. The ratio of type I to type III collagen was different in enlarged tissue, with less type I and an elevated amount of type III collagen present. The amount of type V collagen did not differ among normal, inflamed and phenytoin-enlarged gingivae.

Adolescent↗
PubMed1984

Phenytoin metabolism in the cat after long-term oral administration.

The metabolism of sodium phenytoin (PHT) in the cat was studied by gas-liquid chromatographic analyses of the drug and its metabolites extracted from plasma, urine, and feces during a 5-month course of daily oral administration. Plasma PHT levels of 15-18 micrograms/ml were observed. Urine contained 5-(4-hydroxyphenyl)-5-phenylhydantoin, 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin, 1-deoxy-1-(5,5-diphenylhydantoin-3-yl)-beta-D-glucopyranuronate, and unmetabolized PHT. Large quantities of PHT (32-63% of the daily dose) were observed in feces. We suggest that gastrointestinal malabsorption, extensive N-glucuronidation, and limited hydroxylation determine the fate of orally administered PHT in the cat. This is not the case in humans.

Administration, Oral↗