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Biomedical subjects

L J Brown

Publications and source records attributed to L J Brown.

At least 19 recordsLinked to original sources

Gingival inflammation and subgingival calculus as determinants of disease progression in early-onset periodontitis.

This study was undertaken to test the hypothesis that gingival inflammation and dental calculus are important determinants of the development and progression of early-onset periodontitis. The study sample included 156 individuals who were 13-20 years old at baseline and who were examined 2x during 6 years to assess the attachment loss, gingival state and the presence of dental calculus. 33 (21%), 62 (40%), and 61 (39%) individuals were classified as having localized, generalized, or incidental EOP, respectively. The results showed an increase in the % of teeth with overt gingivitis and subgingival calculus, and also an increase in the % of teeth showing attachment loss during the 6-year period in all classification groups. Of teeth with 0-2 mm attachment loss at the beginning of the study and which developed > or = 3 mm attachment loss during the following 6 years, there were 2x as many teeth with overt gingival inflammation, and 4x more teeth with subgingival calculus at baseline than teeth without. Gingivitis and subgingival calculus when present at both examinations resulted in a stronger association with the development of new lesions than presence of these variables at baseline. Teeth with gingivitis at baseline had a significantly higher mean attachment loss during 6 years than teeth without gingivitis (p<0.0001), and teeth with subgingival calculus at baseline had a significantly higher mean attachment loss than teeth without subgingival calculus (p<0.0001). The presence of gingivitis and subgingival calculus at baseline and 6 years later was associated with the occurrence of even higher disease progression during this period. The association between gingival inflammation and subgingival calculus and the development and progression of attachment loss during the study period in the generalized and the localized EOP groups was significantly higher than the association in the incidental EOP group. In an appreciable % of the sites in all 3 groups, however, the presence of the 2 factors was not associated with attachment loss during 6 years. The results suggest a significant association between gingival inflammation and subgingival calculus and the development and progression of early-onset periodontitis.

Adolescent

Effects of estrogen status and aging on salivary flow rates in healthy Caucasian women.

A comparison of salivary flow rates was made between three groups of female individuals according to their menopausal status. The three groups consisted of healthy, dentate, nonmedicated women (with the exception of the use of estrogen) from the Baltimore Longitudinal Study of Aging. One group consisted of premenopausal women (n = 51), their mean age was 39 years. Another group (n = 26) was perimenopausal with a mean age of 48 years. A third group (n = 76) was postmenopausal with a mean age of 69 years. The groups were evaluated for unstimulated (UPAR) and stimulated parotid gland flow rates (SPAR), unstimulated (USUB) and stimulated submandibular/sublingual gland flow rates (SSUB), and stimulated whole-saliva flow rates (SWHOLE). The parotid flow rates were determined using a Carlson-Crittenden cup, while the submandibular/sublingual flow rates were determined using the National Institute of Dental Research collector. A 2% citrate solution was used for stimulation in glandular collections. Chewing a 1-cm3 cube of paraffin was used to stimulate whole saliva. The results showed no significant differences in UPAR, SPAR, and SWHOLE between the three groups. However, the premenopausal women had higher USUB than the postmenopausal group. The premenopausal women also had higher SSUB than perimenopausal and postmenopausal groups. There were no differences in salivary flow rates between those taking estrogen and those that were not medicated.

Adult

Mercury concentrations in urine and whole blood associated with amalgam exposure in a US military population.

Minute amounts of mercury vapor are released from dental amalgams. Since mercury vapor is known to be associated with adverse health effects from occupationally exposed persons, questions regarding the margin of safety for exposure to mercury vapor in the general population continue to be raised. To address this issue, one needs information regarding exposure to mercury vapor from dental amalgam fillings and its possible consequences for health in the general population. The NIDR Amalgam Study is designed to obtain precise information on amalgam exposure and health outcomes for a non-occupationally-exposed population of US adults. One hypothesis was that in a generally healthy population a significant association between amalgam exposure and Hg levels in urine and/or whole blood could be detected. The cohort investigated was an adult military population of 1127 healthy males. Their average age was 52.8 years, and their ages varied from 40 to 78 years. Ninety-five percent of the study participants were white males, and slightly over 50% had some college education. Five percent were edentulous. The dentate participants, on average, had 25 natural teeth, 36.9 decayed or filled surfaces (DFS), and 19.9 surfaces exposed to amalgam, with amalgam exposure varying from 0 to 66 surfaces. Their average total and inorganic urinary mercury concentrations were 3.09 microg/L and 2.88 microg/L. The average whole-blood total and inorganic mercury concentrations were 2.55 microg/L and 0.54 microg/L. Significant correlations were detected between amalgam exposure and the total (r = 0.34, p < 0.001) and inorganic 0.34 (r = 0.34, p < 0.001) urinary mercury concentrations on the original scale. Stronger correlations were found for total (r = 0.44, p < 0.001) and inorganic (r = 0.41, p < 0.001) urinary Hg on the log scale, as well as for creatinine-corrected total (r = 0.43, p < 0.001) and inorganic (r = 0.43, p < 0.001) urine concentrations. In whole blood, statistically significant, but biologically weak, correlations were detected for total (r = 0.09, p = 0.005) and inorganic (r = 0.15, p < 0.001) Hg concentrations, respectively. Based on these cross-sectional data, it is estimated that, on average, each ten-surface increase in amalgam exposure is associated with an increase of 1 microg/L mercury in urine concentration.

Adult

Differences in net incomes of male and female owner general practitioners.

The authors analyzed the mean net income of a cohort of male and female dentists with similar demographics and practice characteristics. The authors found that the average net income of these male dentists is higher than it is for their female counterparts. This difference is statistically significant and monetarily tangible, amounting to an annual net income balance of about $26,000 (22 percent) in favor of male dentists. If such a difference in net income persists, it could affect the profession as well as the distribution of dental school enrollments.

Adult

Periodontal diseases in the United States population.

Recent epidemiologic surveys and studies have provided important information on the prevalence, extent, and severity of periodontal diseases in the United States. Over 50% of adults had gingivitis on an average of 3 to 4 teeth. Subgingival calculus was present in 67% of the population. Adult periodontitis, measured by the presence of periodontal pockets > or = 4 mm, was found in about 30% of the population on an average of 3 to 4 teeth. Severe pockets > or = 6 mm were found in less than 5% of the population. Attachment loss > or = 3 mm was found in 40% of the population. Gingival recession accounted for a significant amount of attachment loss. The prevalence of early-onset periodontitis ranged from less than 1% in 14- to 17-year-olds to 3.6% in young adults aged 18 to 34. Extensive and severe periodontitis was much more prevalent in minorities, people with less than a high school education, and those who had seen a dentist infrequently and had subgingival calculus. Smoking and diabetes have been identified as risk factors, especially diabetics with poor metabolic control, a long duration of the disease, and extensive subgingival calculus. Under managed care, there has been an expansion of soft tissue management programs in the offices of general dentists and referral guidelines which limit referral of patients with moderate periodontitis. Quality-assurance mechanisms will be essential for the diagnosis and treatment of persons with periodontitis.

Adolescent

The differential regulation and secretion of proteinases from fetal and neonatal fibroblasts by growth factors.

One of the major differences between fetal and adult wound repair is the unique ability of fetal wounds to heal without scarring. Since scar formation is a function of extracellular matrix deposition, the regulation of this component is fundamental in tissue remodeling. In this study, we have characterized the differences in the secretion of matrix-degrading proteases, namely urokinase plasminogen activator and gelatinase A and B, from fetal and neonatal fibroblasts. In addition, we examined the modulation of these protease levels by growth factors known to be important in wound repair. The results indicate that the secretion of these proteases differ significantly between the two cell types. The levels of urokinase plasminogen activator and its inhibitor were notably higher in media conditioned by neonatal fibroblasts in comparison to fetal samples. In contrast, the basal level of gelatinase A was comparable in both cell types, whilst the level of gelatinase B was elevated in the fetal fibroblasts. Transforming growth factor-beta 1 reduced the level of urokinase plasminogen activator and stimulated the secretion of plasminogen activator inhibitor-1 and progelatinase B in both neonatal and fetal fibroblasts. However, only progelatinase A and an activated form of gelatinase B were significantly elevated in fetal fibroblasts. In contrast, platelet-derived growth factor stimulated urokinase plasminogen activator, its inhibitor and both gelatinase A and B, an effect which was more apparent in fetal fibroblasts. This difference in protease regulation may be reflected in the differing rate and quality of tissue remodeling observed during adult vs fetal wound repair.

Adult

Prevalence and distribution of dental restorative materials in US Air Force veterans.

OBJECTIVES: Millions of restorative procedures are performed annually in the United States, yet very little is known about their distribution in the general population. With increasing concern about potential adverse health effects of some restorative materials, a better understanding of the extent of exposure to these materials in the population is important. The purpose of this study is to report the prevalence, patterns, and distribution of dental restorative materials in a population of male veterans. METHODS: This collaborative study with the US Air Force examined 1,166 male veterans to assess exposure to dental amalgam and other restorative materials. An inventory of dental materials in the study population was obtained through oral examinations. Dental materials were classified into five categories: (1) amalgam; (2) resin; (3) porcelain, cement, or temporary, including ionomer (PCT); (4) cast gold alloys/direct filling gold; and (5) other metals (OM). The mean age of the study participants was 52.9 years. Over 94 percent of the study participants were dentate. RESULTS: The study participants averaged 45.8 restored/replaced surfaces. Restored/replaced surfaces increased with age while the number of teeth decreased with age. The most frequently used restorative material was amalgam, averaging 19.89 surfaces per subject, followed by PCT (9.38), resins (8.99), OM (5.52), and gold (4.91). The distributions of restorative materials varied by age, arch type, and location in the mouth. CONCLUSION: The study population experienced substantial exposure to dental materials.

Adult

Clinical features of early-onset periodontitis.

The authors estimate the prevalence of early-onset periodontitis, or EOP, in U.S. adolescents and describe the clinical features that occur at an early stage in those who have EOP. In 1986 and 1987, about 10.0 percent of African-American, 5.0 percent of Hispanic and 1.3 percent of white U.S. adolescents had EOP. Clinical features that may be useful in the early detection of EOP include overt gingival inflammation, dental calculus and a high rate of caries, restorations and tooth loss.

Adolescent

Putative periodontal pathogens in subgingival plaque of young adults with and without early-onset periodontitis.

This study assessed the associations between putative periodontal pathogens and early-onset periodontitis (EOP) in a population of 248 subjects, 13 to 19 years of age at baseline, derived from a representative sample of U.S. young adults. The subjects were selected based on the presence or absence of attachment loss at baseline. The attachment level was assessed clinically at baseline and at a 6-year follow-up examination, and the presence of 7 bacterial species was assessed at follow-up using DNA probes. The individuals were classified into generalized, localized, incidental EOP, and no-periodontitis groups based on the extent and severity of attachment loss; and classified as having rapid, moderate, slow, and no progression based on the rate of periodontal progression during the 6 preceding years. In the EOP groups there were significantly higher percentages of individuals with detectable levels of Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Campylobacter rectus, and Treponema denticola. In addition, the EOP group had significantly higher levels of these 5 microorganisms compared to the no-periodontitis group. There were also higher percentages of individuals with these species and higher levels of bacteria in the group showing disease progression than the group without progression. In a descending order of importance, P. gingivalis, T. denticola, and P. intermedia were the microorganisms significantly associated with the generalized and/or rapidly progressing disease. F. nucleatum and C. rectus were also associated with EOP, but to a lesser degree. In the present population Actinobacillus actinomycetemcomitans was not significantly associated with EOP, though it was recovered more often from subjects with localized EOP. Eikenella corrodens was present equally in subjects with and without disease. The results show that several bacterial species are associated with EOP, and that P. gingivalis and T. denticola are of particular importance and may play a significant role in the more severe and progressive forms of EOP.

Adolescent

Clinical classification of periodontitis in adolescents and young adults.

THE AIM OF THIS STUDY was to determine the degree to which clinical classifications based on cross-sectional assessments endure in the course of development of early-onset periodontitis (EOP), and to introduce new criteria which might improve the clinical classification of these diseases. Subjects with EOP and a matched group without EOP were identified within a national probability sample examined during the 1986/87 survey of US schoolchildren. Of these, 265 subjects (mean age 16 years) were re-examined during the 1992/93 school year. The clinical attachment level of teeth was assessed, and the individuals were classified into localized juvenile periodontitis (LJP), generalized juvenile periodontitis (GJP), incidental attachment loss (IAL), and no-periodontitis groups using three classification methods previously described. A fourth method that considered the extent and severity of attachment loss and the number of missing teeth was introduced to classify the individuals at baseline and at follow-up as having localized, generalized, or incidental EOP, and no-periodontitis groups. Furthermore, the individuals were classified using criteria based on the rate and pattern of change in attachment loss during 6 years. The results showed low correlations between the baseline classifications and the classifications at the 6-year follow-up examination, irrespective of the method used. In addition, the cross-sectional classifications were not predictive of the rate of progression of periodontal disease in these subjects. In the generalized disease group, two-thirds of the individuals exhibited moderate/rapid disease progression, while one-third had slow or no progression. In the localized disease group, one-half of the individuals had moderate/rapid disease progression and one-half had slow or no progression. In the incidental disease group one-fourth of the individuals had moderate/rapid disease progression and three-fourths had slow or no progression. We propose that the term early-onset periodontitis be used as a generic term to describe periodontal disease before its normal onset. In addition, we suggest that incidental, localized, and generalized EOP are heterogenous groups comprising rapidly and slowly progressing forms within each classification. The findings suggest that a classification system in which subsets of the disease that are defined according to a combination of cross-sectional criteria and the disease progression may be useful in studies of EOP. Furthermore, the findings suggest that clinical classifications of EOP be used as generic descriptors until a full understanding of the pathogenesis of this disease is accomplished.

Adolescent

Fine mapping of the nail-patella syndrome locus at 9q34.

Nail-patella syndrome (NPS), or onychoosteodysplasia, is an autosomal dominant, pleiotropic disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns, and nephropathy. Previous studies have demonstrated linkage of the nail-patella locus to the ABO and adenylate kinase loci on human chromosome 9q34. As a first step toward isolating the NPS gene, we present linkage analysis with 13 polymorphic markers in five families with a total of 69 affected persons. Two-point linkage analysis with the program MLINK showed tight linkage of NPS and the anonymous markers D9S112 (LOD = 27.0; theta = .00) and D9S315 (LOD = 22.0; theta = .00). Informative recombination events place the NPS locus within a 1-2-cM interval between D9S60 and the adenylate kinase gene (AK1).

Chromosome Mapping

Sequence and tissue-dependent RNA expression of mouse FAD-linked glycerol-3-phosphate dehydrogenase.

A 2432-bp cDNA for mouse FAD-linked glycerol-3-phosphate dehydrogenase, a nuclear-encoded enzyme associated with the inner mitochondrial membrane, was isolated from a Lambda ZAP phage library generated from brown adipocyte mRNA. The amino acid sequence was 95 and 93% homologous to the rat and human enzymes. PvuII and SacI polymorphisms between Mus spretus and C57BL/6J were used to map the mouse FAD-linked glycerol-3-phosphate dehydrogenase gene (Gdm1) to chromosome 2, 33 cM from the centromere. Northern blot analysis showed that brown adipose tissue predominantly expressed a 6.5-kb mRNA with lower expression of 4.5- and 2.4-kb forms, whereas brain and pancreatic islets almost exclusively expressed a 6.5-kb transcript, muscle expressed a 4.5-kb transcript, and testis expressed a 2.4-kb RNA form. Analysis of poly(A)+ RNA from brown adipose tissue suggested that all RNA forms are polyadenylated. Among the tissues examined, FAD-linked glycerol-3-phosphate dehydrogenase protein levels and enzyme activity were highest in brown adipose tissue, and a consistent correlation between protein levels and enzyme activity in all tissues was observed. RNA levels corresponded to protein levels in all tissues except testis, where high levels of 2.4-kb mRNA and relatively low protein were expressed. Exposing mice to cold temperatures induced the 6.5-kb mRNA and enzyme activity only in brown adipose tissue, suggesting a role for thermogenesis in this tissue. Although the molecular basis for the formation of the 6.5- and 4.5-kb mRNA's is not known, data suggest that the regulation of FAD-linked glycerol-3-phosphate dehydrogenase is complex and tissue-specific.

Adipose Tissue, Brown

Genetic mapping and chromosome localization of the rat mitochondrial glycerol-3-phosphate dehydrogenase gene, a candidate for non-insulin-dependent diabetes mellitus.

The mitochondrial FAD-dependent glycerol-3-phosphate dehydrogenase (mtGPD) plays an important role in the regulation of insulin secretion and has been postulated as a candidate responsible for the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) in humans as well as in rodent models of NIDDM. Recent molecular genetic studies of the Goto-Kakizaki (GK) rat model of NIDDM have identified loci linked to NIDDM. To elucidate whether rat mtGPD might play a role in the pathogenesis of NIDDM, the rat mtGPD gene (Gpd2) was cloned, and a genetic marker for Gpd2 was developed. The gene mapped to the region of rat chromosome 3 that contains a region linked to NIDDM in the GK rat. Fluorescence in situ hybridization was also carried out to verify the map position.

Animals

Structural organization and mapping of the human mitochondrial glycerol phosphate dehydrogenase-encoding gene and pseudogene.

Mitochondrial glycerol phosphate dehydrogenase (mtGPD) is the rate-limiting enzyme in the glycerol phosphate shuttle, which is thought to play an important role in cells that require an active glycolytic pathway. Abnormalities in mtGPD have been proposed as a potential cause for non-insulin-dependent diabetes mellitus. To facilitate genetic studies, we have isolated genomic clones containing the coding regions of the human mtGPD-encoding gene (GPDM). The gene contains 17 exons and is estimated to span more than 80 kb. All splice junctions contain GT/AG consensus sequences. Introns interrupt the sequences encoding the leader peptide, the FAD-binding site, the calcium-binding regions, and a conserved central element postulated to play a role in glycerol phosphate binding. Fluorescence in situ hybridization was used to map this gene to chromosome 2, band q24.1. A retropseudogene was identified and mapped to chromosome 17.

Base Sequence

Calcium activation of mitochondrial glycerol phosphate dehydrogenase restudied.

cDNAs which encode the rat testis and pancreatic islet mitochondrial glycerol phosphate dehydrogenase (mGPD) (EC 1.1.99.5), the key enzyme of the glycerol phosphate shuttle, were recently cloned and sequenced and found to contain calmodulin-like calcium-binding sequences, thus explaining the widely observed calcium activation of the enzyme from many tissues of higher eukaryotes. mGPD activity and protein, as judged from Western analysis, appear to be most abundant in testis and pancreatic islets in the rat. mGPD is known to be located within the inner mitochondrial membrane. At a physiologic concentration of glycerol phosphate (75 microM), half maximal activity of Triton X-100-solubilized testis mGPD was seen in the presence of 0.1-0.25 microM free calcium. Calcium (10(-6)-10(-5) M) lowered the Km of mGPD from 2.5 mM glycerol phosphate (islet mGPD) and 3.2 mM glycerol phosphate (testis mGPD) to 0.4 mM glycerol phosphate. Calcium activation of mGPD from both testis and islets was not prevented by calmodulin inhibitors, which is consistent with mGPD possessing regions that can mediate its own activation by calcium. 45Calcium overlay experiments, in which proteins were separated by SDS-polyacrylamide gel electrophoresis, blotted onto nitrocellulose membranes, and probed with 45Ca, showed that mGPD is a major calcium-binding protein in testis mitochondrial membranes. A hydropathy plot suggested that the mature mGPD protein has three transmembrane helices. The first membrane-spanning region coincides with the FAD site and thus this site is placed within the membrane. The hydropathy analysis indicated that the calcium-binding region and the putative glycerol phosphate-binding site lie outside the membrane exposed to the cytosolic environment. This is consistent with earlier biochemical evidence which indicated that these sites are situated outside the membrane (M. Klingenberg, Eur. J. Biochem. 13, 247-252, 1970). This suggests that cytosolic calcium can regulate mGPD activity. Since simultaneous oscillations in electrical activity, cytosolic calcium, glycolysis, and insulin release occur in the pancreatic beta cell, mGPD activity might also fluctuate and allow the glycerol phosphate shuttle to participate in glycolytic oscillations.

Amino Acid Sequence