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Biomedical subjects

T M Hassell

Publications and source records attributed to T M Hassell.

At least 37 records · Page 2Linked to original sources
PubMed1983

Evidence that healthy human gingiva contains functionally heterogeneous fibroblast subpopulations.

Six mass cultures of human fibroblasts derived from a single biopsy of a normal gingival papilla tip were studied with regard to their protein, collagen and glycosaminoglycan synthesis in vitro, using incorporation of radiolabelled substances. The proliferation rates, replicative life-spans and cell-size distributions of these mass cultures were determined. There were significant differences among the 6 cultures and these differences persisted throughout numerous cell replications in vitro. It is suggested that functional heterogeneity exists among phenotypically stable fibroblast subpopulations or subpopulation mixtures from normal tissue. The concept of participation of fibroblast subpopulations in disease pathogenesis is supported by these preliminary findings.

Adult↗
PubMed1983

Phenytoin sensitivity of fibroblasts as the basis for susceptibility to gingival enlargement.

A side effect of long-term administration of the anti-epileptic drug phenytoin is overgrowth of the connective tissues surrounding the teeth. In this in vitro study of protein and collagen synthesis by diploid fibroblasts from 17 nonepileptic young persons with healthy gingivae, only seven strains of cells responded to phenytoin in culture medium. Because not all phenytoin-treated individuals develop gingival overgrowth, we suggest that susceptibility is predicated upon the presence of a (genetically determined) phenytoin-sensitive subpopulation of gingival fibroblasts. The concept of the participation of sensitive cell subpopulations in other connective tissue disorders is supported by these findings.

Cells, Cultured↗
PubMed1982

Preliminary study of the effects of carbamazepine on congenital orofacial defects in offspring of A/J mice.

Carbamazepine (CBZ; Tegretol) is an effective anticonvulsant drug. We assessed putative CBZ teratogenicity in a sensitive animal model, the A/J mouse. Plasma CBZ levels were determined by gas-liquid chromatography. To achieve the accepted human plasma therapeutic range (TR) of CBZ (8-12 micrograms/ml), up to a 6X human oral dose was given. Test Group A received 300 mg pure crystalline CBZ/kg, suspended in 1.25% carboxymethylcellulose (CMC), at 6 a.m., noon, 6 p.m., and midnight on gestational day 10 (previously determined to be the peak sensitive time for cleft lip and palate induction in the A/J) and at 6 a.m. on day 11. Test Group B received 150 mg/kg of an experimental CBZ elixir (Tegretal Sirup) on the same regimen. Plasma levels rose to above TR within 15 min, then fell steadily, exiting the TR by 5 hr postgavage. Test Group C was given the experimental CBZ elixir at 4-h intervals for 36 hr. The rapid rise and fall of CBZ plasma levels again occurred, but the time within the therapeutic range was greatly increased (through 6 p.m. day 11). Control groups received the appropriate quantity of the CMC vehicle. Fetuses were harvested on day 17. Compared to control animals, none of the CBZ regimens was associated with a major increase in incidence of cleft lip or palate.

Abnormalities, Drug-Induced↗
PubMed1982

Quantitative histopathologic assessment of developing phenytoin-induced gingival overgrowth in the cat.

Phenytoin (Dilantin) induces gingival overgrowth characterized by an accumulation of connective tissue The cell-to-matrix ratio in the mature lesion is normal, yet there must be more fibroblasts per oral cavity if there is excessive tissue mass. Using a mongrel cat model system, we studied the early, developing phenytoin-induced lesion by quantitating fibroblasts per unit of tissue in papilla biopsies collected over a 3-month period of daily drug administration. At 6 and 8 weeks, the number of fibroblasts per unit of tissue increased dramatically. By 3 months, as the lesions matured, the fibroblast-to-matrix ratio returned to normal. We suggest that the drug interacts with resident gingival fibroblasts, causes them to proliferate and thus induces a true, but transient, hypercellularity. Cell division then appears to slow or cease, and rapid production of connective tissue matrix ensues, returning the cell-to-matrix ratio to normal.

Animals↗
PubMed1982

Evidence for production of an inactive collagenase by fibroblasts from phenytoin-enlarged human gingivae.

When measured by radioimmunoassay, fibroblasts derived from the overgrown gingivae of phenytoin-treated epileptic individuals synthesize and release elevated amounts of collagenase in vitro, as compared to similar-appearing fibroblasts from normal, non-phenytoin-treated persons. However, it appears that much of the immunoreactive enzyme is unable to degrade reconstituted collagen in culture. This preliminary finding in 9 different strains of cells indicates that reduced collagenase activity by a subpopulation of cells may contribute to the development of phenytoin-induced gingival overgrowth.

Adolescent↗
PubMed1981

Hemophilic dog model for evaluating therapeutic effectiveness of plasma protein fractions.

Therapeutic effectiveness of factor VIII inhibitor bypassing materials has been evaluated in dogs with hemophilia A. A standardized template gingival biopsy was performed using local anesthesia. Hemophilic dogs bled extensively from the biopsy site, whereas in normal dogs the wound was sealed within 5 + /- 2 min. If untreated, the hemophilic dogs frequently bled for several days. Factor VIII infusion stopped the bleeding promptly. Some experimental preparations of factor VIII inhibitor bypassing materials were shown to be therapeutically effective, whereas others were not. Intravascular thrombi could not be demonstrated histologically. The model should prove useful for evaluating factor VIII inhibitor bypassing materials and also for evaluating their mechanism of action.

Animals↗
PubMed1976

Diphenylhydantoin (dilantin) gingival hyperplasia: drug-induced abnormality of connective tissue.

Various degrees of gingival overgrowth may occur in individuals taking diphenylhydantoin, a drug used widely in the treatment of epilepsy. The tissue overgrowth is made up predominantly of collagen, and may therefore be a useful model for analysis of fibrosis and some other connective tissue abnormalities. Fibroblasts derived from the overgrown tissue exhibit a level of protein synthetic activity approximately twice that of comparable cells obtained from nonepileptic control individuals and from the gingiva of age-matched epileptics taking the drug but not exhibiting gingival enlargement. In addition, 20% of the protein synthesized by cells from the affected tissue is collagen, whereas collagen accounts for only about 11% of the total protein produced by control cells of both types. The drug appears to induce or select for fibroblasts characterized by enhanced levels of protein synthesis and collagen production. This alteration persists through several cell replications in vitro in the absence of drug.

Collagen↗