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Biomedical subjects

T C Hart

Publications and source records attributed to T C Hart.

At least 73 records · Page 4Linked to original sources
PubMed1997

Genetic studies of syndromes with severe periodontitis and palmoplantar hyperkeratosis.

The Papillon-Lefèvre and Haim Munk syndromes are characterized by the presence of both palmoplantar hyperkeratosis (PPK) and severe early onset periodontitis. It is the early onset periodontal disease component that distinguishes these from other more common forms of PPK. It has been proposed that the periodontal disease component may be a casual association in individuals with PPK. Genetic syndromes with palmoplantar keratosis and severe ealry onset periodontitis may be due to specific bacterial infections in individuals with PPK. Recently, keratin gene mutations have been identified in several conditions typified by palmoplantar keratosis. The present study sought to test the hypothesis that a keratin gene defect similar to those previously identified in other PPK conditions is responsible for the Haim Munk and the Papillon. Lefèvre syndromes. We have performed genetic linkage studies to test for linkage between polymorphic DNA loci within 2 cytokeratin gene families and the disease phenotype in Haim Munk syndrome and Papillon-Lefèvre syndrome. Families with individuals segregating for the Haim Munk syndrome and the Papillon-Lefèvre syndrome were examined to determine disease status, and genotyped for microsatellite DNA markers closely linked to the acidic (type I) and the basic (type II) cytokeratin genes on chromosomes 12 and 17. Genotype data were evaluated for microsatellite allele homozygosity in affected individuals. Results of these preliminary genetic studies suggest that the gene defect in Haim Munk syndrome is not due to a gene defect in either the type I or the type II keratin gene clusters. These findings suggest that Haim Munk syndrome may be genetically distinct from other more common forms of PPK that have been linked to the cytokeratin gene families, and suggest that mutations in genes other than keratin genes are responsible. Additional family studies are needed to confirm these preliminary findings.

Adult↗
PubMed1997

Applications of molecular epidemiology to head and neck cancer.

Cancer may be viewed as a genetic disease characterized by the failure of cellular mechanisms to maintain genomic integrity. Molecular progression models defining genetic damage are being developed for a number of solid tumors including head and neck squamous cell carcinoma. Genetic alteration of certain classes of genes, the tumor suppressor genes and proto-oncogenes, seem to be common events in such models. Host modulation of environmental carcinogens, however, also may be an important disease determinant. Interindividual differences in susceptibility to the genotoxic effects of environmental carcinogens may be genetically determined. With technologic advances in molecular genetics, it is now possible to identify specific genetic alterations that occur in different stages of neoplasia. Correlation of these genetic alterations with susceptibility models for solid tumors has important implications for the field of molecular epidemiology.

Carcinogens↗
PubMed1996

Partial expression of the Papillon-Lefèvre syndrome in 2 unrelated families.

The Papillon-Lefèvre syndrome (PLS) is a rare, autosomal recessive trait that is characterized by palmar plantar keratosis (PPK) and severe, early onset periodontitis, affecting both deciduous and permanent dentitions. The clinical presentation of PLS is variable; the disease occurs so infrequently as to limit clinical cases for study. The exception is a few families with extensive consanguinity in which numerous cases occur. Of particular interest to mapping the genetic origin of the syndrome is the co-expression of the major traits of hyperkeratosis and periodontitis, and their severity. In this paper, we report 2 families with multiple affected individuals from geographically remote areas. A large extended family, from the Cochin region of India, currently residing in Israel, in which there is documented consanguinity and a family from the southwest region of Germany. In each family, 1 individual presents with hyperkeratotic lesions with the complete absence of periodontal lesions. Further, the difference in severity of the hyperkeratotic lesions between families is marked, and one sibling in the German family expressed rapid, early onset periodontitis in the absence of PPK. The genetic nature and penetrance of the genetic defect are discussed.

Adult↗
PubMed1996

Relationship of other joint problems and anterior disc position in symptomatic TMD patients and in asymptomatic volunteers.

Anterior disc position has been highly correlated with temporomandibular disorders (TMD). It was hypothesized that internal derangement of the temporomandibular joint may be a part of a joint phenotype that imparts an increased risk for joint disorders. If this hypothesis is true, an increased prevalence of joint disorders in individuals diagnosed with displaced discs should be expected. A total of 263 symptomatic TMD patients and 82 asymptomatic volunteers was examined. Asymptomatic volunteers with anteriorly displaced discs were twice as likely as asymptomatic volunteers without disc displacements to report pain/dysfunction in other joints. Symptomatic patients with and without displaced discs reported an increase in other joint problems three to four times greater than in asymptomatic subjects. Compared to symptomatic TMD patients without disc displacement, symptomatic TMD patients with anteriorly displaced discs were also twice as likely to report other family members as being affected by TMD. Familial aggregation of TMD and an increased prevalence of other joint problems in these individuals may represent more than a serendipitous occurrence.

Adolescent↗
PubMed1994

Selective antagonism of dopamine D1 and D2 receptors does not block the development of behavioral sensitization to cocaine.

The objective of this study was to determine whether the development of behavioral sensitization to cocaine could be prevented by either D1 or D2 selective dopamine receptor antagonists. Male Wistar rats were treated daily for 7 days with either cocaine (15 mg/kg, IP) or vehicle in combination with the D1 dopamine antagonist SCH 23390 (0.3 mg/kg, SC), the D2 dopamine antagonist sulpiride (100 mg/kg, IP), or vehicle. After the daily injections, the rats were tested for locomotor activity in photocell arenas. Twenty-four hours after the last pre-exposure test session, all rats were given a challenge injection of cocaine (15 mg/kg, IP) and tested for activity. Cocaine treatments produced a greater relative increase in locomotor activity with repeated exposure (i.e. sensitization). Moreover, this increase in cocaine-induced locomotor activity was attenuated by both SCH 23390 and sulpiride. In contrast, neither sulpiride nor SCH 23390 blocked the development of behavioral sensitization to cocaine. That is, rats pretreated with sulpiride or SCH 23390 and cocaine did not differ from rats pre-exposed only to cocaine when given a cocaine challenge injection. These results suggest that behavioral sensitization to cocaine may develop through either D1 or D2 dopamine receptor stimulation or possibly through stimulation of some non-dopaminergic receptor.

Animals↗
PubMed1994

Cephalometric analysis of Rapp-Hodgkin syndrome.

Rapp-Hodgkin syndrome (RHS) is a rare form of ectodermal dysplasia with variable involvement of the hair, eyes, sweat glands, nails, and teeth. Oral findings may include hypodontia, hypoplastic enamel, cleft lip/palate, and a pronounced midfacial hypoplasia. The objective of this study was to determine if the pronounced midfacial hypoplasia is the result of a true tissue hypoplasia or displacement of midfacial tissues. We have identified a family in which three members, a mother and two daughters, display clinical features characteristic of RHS. Clinical and intraoral examination of these affected persons showed manifestations characteristic of RHS, and several new findings were observed, including subcutaneous abscesses, palmoplantar keratosis, and keratotic lesions located on the chest and trunk. To assess the midfacial hypoplasia, lateral cephalometric analysis was performed on lateral headplates. Results of the cephalometric analysis suggest that the midfacial hypoplasia results from both a deficiency and a displacement of the maxilla. These findings are significant because successful dental treatment of RHS relies upon accurate assessment of current and projected orofacial development, particularly for the skeletal relations of the maxilla and mandible.

Adolescent↗
PubMed1994

Neutrophil defects as risk factors for periodontal diseases.

There are several hypotheses proposed for the etiologic mechanisms causing periodontal diseases. These include a paradigm in which all individuals are equally susceptible to one or several pathogenic bacteria; a second paradigm that holds that all bacteria are equally virulent and that host susceptibility determines onset of disease; or a combination of the above. In this review, we analyze the role of neutrophil dysfunction as a risk factor for the onset of periodontitis. Both intrinsic or genetically inherited abnormalities of neutrophils and acquired neutrophil abnormalities are considered. While a large body of data implicates neutrophil dysfunction, either intrinsic or acquired (bacterially or extrinsically induced), as a significant risk factor for the periodontal diseases, clear, prospective, longitudinal epidemiologic studies to evaluate this association remain to be performed.

Bacterial Physiological Phenomena↗
PubMed1994

Genetic considerations of risk in human periodontal disease.

Increasingly, evidence suggests that underlying host susceptibility factors play a significant role in periodontitis in high-risk patients and that this risk may be partly under genetic control. Support for a heritable component to periodontitis risk comes from the consistent association of periodontitis with certain monogenic traits, as well as from formal genetic studies of both twins and early onset periodontitis. It is significant that not all genetic predispositions to periodontitis involve defects of the immune system. Structural or developmental defects in collagen, cementum, and epithelium also appear to be significant risk factors for periodontitis. Dissection of a genetic model system for periodontitis may prove valuable in fully understanding disease pathogenesis in periodontitis, particularly for understanding the role of host susceptibility factors.

Aggressive Periodontitis↗
PubMed1993

Reevaluation of the chromosome 4q candidate region for early onset periodontitis.

Evidence of linkage (lod = 3.1, theta = 0.05) was reported previously in one large kindred (the Brandywine genetic isolate) for an autosomal dominant form of early onset periodontitis (EOP) with a protein polymorphism in the vitamin D binding protein (GC) located on chromosome 4q12-q13. To evaluate the generality of this finding, 19 unrelated families (228 individuals), each with two or more EOP affected individuals, were ascertained and sampled. A restriction fragment length polymorphism (RFLP) at the GC locus and eight other polymorphic DNA markers and two red blood cell antigens located on proximal chromosome 4q in the vicinity of the GC locus were typed. Twelve genetic models of EOP were evaluated, which varied in diagnostic classification, penetrance, and mode of disease transmission. Results for all models strongly exclude linkage between an EOP susceptibility gene and this chromosomal region assuming locus homogeneity. Our data statistically exclude (lod < or = -2.0) the possibility that more than 40% of our families are linked to this candidate region for one model tested. Linkage under heterogeneity was excluded less strongly for other models, but no significant evidence in support of linkage was obtained for any model. Our results indicate that either the previous report of linkage was a false positive, or that there are two or more unlinked forms of EOP, with the form located in 4q12-q13 being less common.

Adolescent↗
PubMed1992

A localized absence of interleukin-4 triggers periodontal disease activity: a novel hypothesis.

Pathogenic bacteria constitute the primary extrinsic agent in the etiology of Adult periodontitis. In addition to direct toxic effects, bacteria induce destructive immunologic and other inflammatory reactions in the host, leading to the observed pathologic alteration in the tissue. The risk to develop periodontal disease is not equal for all individuals, suggesting host factors are important in determining an individuals disease susceptibility. Regulation of immune response is important in maintaining the equilibrium between periodontal health and disease. We hypothesize that, in the case of Adult periodontitis, a localized lack of the regulatory cytokine interleukin-4 (IL-4) in the gingival tissues predisposes susceptible individuals to progress from gingivitis to periodontitis.

Adult↗
PubMed1992

Re-interpretation of the evidence for X-linked dominant inheritance of juvenile periodontitis.

Several studies have provided evidence supporting the inheritance of juvenile periodontitis (JP) in a Mendelian fashion, and both X-linked and autosomal modes of transmission have been proposed. Re-examination of the evidence for the X-linked dominant hypothesis reveals that two assumptions were crucial in favoring the X-linked rather than an autosomal hypothesis of JP transmission. The first assumption was that females are more likely than males to have JP by ratios of approximately 2.5:1. The second key observation was the reported lack of father to son transmission of the trait. However, the data that these assumptions were based on may be interpreted differently. Although the number of females reported to be affected by JP is greater than the number of affected males, this is probably a reflection of the greater number of females incorporated into these studies. When the proportions of affected males and females are examined, rather than total numbers of affected individuals, the proportion of affected males and females is similar. Additionally, the reported lack of father to son transmission for JP appears to be the result of incomplete family data. The female ascertainment bias inherent in many JP studies, compounded by the lack of male participation in such studies, appears to have resulted in the perception of a lack of male to male transmission of JP. This lack of observed father to son transmission of JP in incomplete data sets has been regarded as proof of no male to male transmission for the trait. Studies of more complete family data, however, do document father to son transmission of JP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Comparison of dentofacial morphology in monozygotic twin pairs with their siblings using LISREL.

Lateral cephalometric radiographs from 33 families of monozygotic twins and their siblings were digitized. Seven dentofacial parameters were measured: 1 to SN, 1 to NA, 1 to NA(mm), 1 to 1, 1 to Mandibular Plane Angle, 1 to NB(mm) and 1 to APg(mm). Data from monozygotic twin pairs and siblings were analyzed using LISREL to determine variance components of heredity, common environment and random environment. Five of the parameters measured showed heredity as the primary factor of variance, while two, 1 to NB(mm) and 1 to APg(mm) showed a common environment as having the greatest effect.

Adolescent↗
PubMed1991

No female preponderance in juvenile periodontitis after correction for ascertainment bias.

Juvenile periodontitis (JP) is generally recognized to exist in 2 clinical forms: localized and generalized. Historically, females have been reported to be affected by both forms of JP at rates of 2 to 10 times greater than males. However, evidence suggests that females are more likely than males to seek dental care. If this is true, females will be diagnosed with JP more often than males even if juvenile periodontitis is equally prevalent among males and females in the general population. Thus, previous reports of a female predominance for JP may simply reflect this selection bias. The purpose of this study was to test our hypothesis that juvenile periodontitis occurs with equal frequency in males and females after correcting for selection bias. Twenty-four juvenile periodontitis probands were ascertained from the VCU/MCV dental clinics. The families of these individuals were examined to determine the relative prevalence of JP among male and female relatives of these probands. Our results indicate that while females are 3 times more likely than males to be initially ascertained as juvenile periodontitis probands, among relatives of probands the proportion of affected males and females is equal.

Adolescent↗
PubMed1991

Analysis of antibody profiles in children with whooping cough.

Development of antibody titres in non-vaccinated children with whooping cough of different duration (all confirmed by positive culture) were investigated by ELISA using lymphocytosis promoting factor (LPF, pertussis toxin), filamentous haemagglutinin (FHA), 69 kDa protein and lipopolysaccharide (LPS) as antigens. The antibody responses occur in three different patterns: Firstly, the LPF antibody response develops very quickly starting with the first day of clinical cough with all three classes, IgG, IgM and IgA appearing simultaneously; LPF antibody appears to be a dominant feature. Secondly, FHA and 69 kDa antibodies appear, starting as IgM with the shift to IgG and IgA later. The third pattern is represented by LPS antibody, the IgA appearing early, but with IgM predominant. Higher titres of IgG reacting with LPS were observed in vaccinated children. Transplacental transfer of antibody was also studied. All antibody titres determined in maternal blood and cord blood were proportional except for anti-LPS antibody which was retarded. Most IgG antibody was IgG1 subclass; surprisingly the 69 kDa antibody consisted of a mixture of approx. 90% IgG1 and 10% IgG4.

Antibodies, Bacterial↗