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Biomedical subjects

E D Shields

Publications and source records attributed to E D Shields.

At least 19 recordsLinked to original sources

Technical note: Stafne static mandibular bone defect-further expression on the buccal aspect of the ramus.

The anatomic distribution of the Stafne static mandibular bone defect (SSBD) is extended with a description of a cavitation defect on the buccal ramus of the mandible. The anatomical placement of SSBD thus correlates precisely with the submandibular and parotid salivary glands, and gives further evidence that an increase in major salivary gland size is associated with the defect. The global latitudinal variation in the population prevalence of SSBD ranges from 10% in the tropics to virtually 0% in most of the arctic. Globally the defect directly correlates with parasite load and diversity, and may be a marker for of a history of an environment with high levels of enteric macroparasite infestation.

Anthropology, Physical↗

Her name is "Lucy", our three-million-year-old ancestor.

Dental anthropology is a key discipline in studies to determine the evolutionary history of our hominid ancestors, to identify the origin and dispersal of modern humans, and to reconstruct the source of observed dental variation. A survey of hominid and modern human evolutionary history, emphasizing results from powerful multivariate dental morphometric methodologies, suggests a single African origin of modern humans > 150,000 years before present from a Homo heidelbergensis ancestor. A continuum among modern humanity is described, with, first, sub-Saharan Africans, then southeast Asian Negrito, and Australian aborigines at its extant root. Other interpretations of the available data are possible. Examinations of the progress of the evolution of teeth through time give significant insight into dental morphogenetics and variation, and the biology of dental evolution. The mechanisms of evolution which fashion a phenotype and the methods of molecular and dental phylogenetics are reviewed and evaluated. This is an exciting time for dental anthropology, with fascinating and challenging questions to address, but anthropologists, not dentists, dominate the field. The perspective of a dentist can meaningfully add to the dynamics of dental anthropology.

Animals↗

Dorset and Thule divergence from East Central Asian roots.

The history of the immigration of East Asians to America during the last glacial period remains controversial. In an attempt to add critical data to this problem, a large sample of whole teeth derived from Southeast Asian, Mongolian, Thule, Western Inuit, and pre-Inca (Huari) people was quantified (N = 4,507 teeth from 495 individuals; approximately 30 variables per tooth). Multivariate analysis helped establish that all Native Americans were likely derived from one ancient, extinct population that resided in the region of Mongolia (east Central Asia), and that Mongolians and Southeast Asians are two independent groups. A controversial and enigmatic Central Canadian Arctic "Thule culture Inuit" group on Southampton Island that survived until 1902 was identified as a relic, mainly Paleoeskimo Dorset community. Surprisingly, there was little, or no, indication of Dorset-to-Thule gene flow. Cumulatively, the data suggest that a small population of Paleoindian founders remained resident in Beringia, may have blocked further immigration, and were the antecedents to the Thule/Inuit. With the confluence of the Arctic and Pacific oceans at the breakup of Beringia, the resulting increased availability of marine animal food sources allowed this population to increase in size and expand throughout the eastern Arctic.

Arctic Regions↗

Heterochronic quantitative microevolution: dental divergence in aboriginal Americans.

Studies of tooth crown morphology alone have proven valuable in defining human population differentiation. We test the hypothesis that quantitative comparisons of more complex whole tooth structure may prove informative in understanding human diversity. Three disparate populations in Native American genetic history were compared: Kodiak Island Western Eskimos, Peruvian Inca Amerindians, and Southeast Asians. Enamel depth (an increasing gradient extended from Southeast Asians to the Inca) and root parameters were the most discriminating variables. The observed microevolution appears to result from variation in timing of known X-linked, Y-linked, and autosomal genes that affect either ameloblast or odontoblast differentiation. The dental traits were sexually dimorphic, the effect being more pronounced in aboriginal Americans, with male teeth having robust roots and thin enamel compared to female. Southeast Asians were isometrically related. The prominence of sexual dimorphism and the importance of sex-linked genes in the determination of the dental phenotypes suggest that sexual selection was one evolutionary force acting on early Asian populations. Subsequently, the selection appears to have been relaxed in Southeast Asians. Observed divergence of tooth shape among the populations, i.e., differences in the appropriation process of tooth primordia, was mainly the consequence of genetic drift modulating heterochronic regulators of homeotic genes.

Analysis of Variance↗

Locomotor phenotypes of unstimulated CD45RAhigh and CD45ROhigh CD4+ and CD8+ lymphocytes in three-dimensional collagen lattices.

The spontaneous locomotion of immunomagnetically isolated resting CD4+ and CD8+ lymphocytes in three-dimensional collagen gels was recorded by time-lapse videomicroscopy. Two-dimensional projections of the paths of randomly selected individual cells were digitized, plotted and quantitatively analysed. Among five different donors 46 +/- 10% of CD4+ and CD8+ lymphocytes (n = 180) showed initial spontaneous locomotion (individual speed 5-25 microns/min; mean speed CD4+ 5.2 +/- 3.6 microns, CD8+ 3.23 +/- 2.72 microns). Active CD4+ cells were constantly migrating for more than 4 hr, whereas CD8+ lymphocytes significantly slowed down after 60-90 min in the collagen gel (P < 0.003). Quantitative analysis of the paths indicated at least three migratory phenotypes: (1) spontaneously locomoting cells exhibiting high speed and low frequency of stopping; (2) a major non-motile fraction without significant displacement; and (3) a subpopulation within CD4+ and CD8+ cells with intermediate activity of speed and stopping. Further subtype analysis of immunomagnetically isolated CD45RAhigh/ROlow or CD45RAlow/ROhigh lymphocytes showed that more than 90% of CD4+ CD45RAhigh/ROlow cells were actively locomoting. In contrast, only 20% of the CD4+ CD45ROhigh/RAlow phenotype showed spontaneous motility to a limited degree. The data indicate that resting CD4+ and CD8+ lymphocytes comprise further locomotory subpopulation related to the expression of different CD45 isoforms.

CD4-Positive T-Lymphocytes↗

Does a genetically determined aggressive locomotion favour the establishment of intracellular macrophage parasites?

A novel computerized methodology was used to quantify, for the first time, the 3-dimensional locomotory phenotypes of individual macrophages moving within an extracellular matrix-like hydrated collagen lattice/gel. Comparisons between two macrophage lines genetically susceptible to intracellular parasites (B10S4 and ANA-1) and two genetically resistant (B10R4 and CD2) demonstrated that Bcgs alleles consistently endowed macrophages with an outward searching and active locomotion, whereas Bcgr imparted a retrocessive phenotype. Several different macrophage pathogens may have exploited this genetically determined aggressive locomotory behavior of susceptible macrophages to allow them to rapidly enter a sanctuary.

Alleles↗

Changes in cell three-dimensional locomotory characteristics upon expression of the EJ-ras oncogene.

Activation of the ras oncogene induces ruffling of membranes, enhances cell locomotion and has been implicated in the invasive process. We have investigated the locomotory changes of a 212 cell line due to ras activation using a novel system for determining the three-dimensional trajectories of cells migrating within collagen lattices. It was found that a small, yet statistically significant increase in cell speed resulted and that the duration of locomotory periods was prolonged in ras activated cells. These locomotory periods was prolonged in ras activated cells. These locomotory periods were cyclic in nature with a periodicity of approximately 30 min. These results are discussed in the relation to the current hypotheses concerning the molecular mechanisms involved in pseudopod kinetics.

Blotting, Western↗

Locomotory characteristics of fibroblasts within a three-dimensional collagen lattice: modulation by a helium/neon soft laser.

It has been postulated that low energy (soft) lasers can enhance wound healing. Considering the importance of cell locomotion in the wound healing process, we have studied the effects of a helium/neon laser upon the locomotory behaviour of a population of fibroblasts migrating within a three-dimensional hydrated collagen lattice. Statistical methods were used to quantify cell three-dimensional trajectories obtained using a computer-assisted tracking system. A two-minute exposure of embryonic fibroblasts to soft laser light decreased the speed and increased the frequency and duration of stops compared to controls. The locomotory phenotype induced in embryonic fibroblasts by the laser light resembled that of the developmentally older c20 fibroblasts, which are known to express a more mature locomotory phenotype. The relevance of these results to wound healing is discussed.

Animals↗

X-linked hypophosphatemia: the mutant gene is expressed in teeth as well as in kidney.

Mutation at a locus (HPDR) on the X chromosome (McKusick 30780 [HPDR1]; 30781 [HPDR2]) causes impaired renal phosphate transport, hypophosphatemia, and an associated impairment in the process of mineralization in bone and teeth (X-linked hypophosphatemia [XLH]). We measured the dental pulp profile area (PRATIO [= pulp area/tooth area]) and serum phosphorus (Pi) values in uniformly treated XLH patients (six males, 81 teeth, 1,457 Pi values; 11 females, 129 teeth, 1,439 Pi values). Serum Pi values, reflecting the metabolic environment of tooth development, were obtained by repeated measurement between 1 mo and 26 years of age during treatment. PRATIO values calculated from standardized Rinn radiographs were used as outcome measurements of tooth development in XLH patients and in age-matched controls (12 males, 100 teeth; 27 females, 275 teeth). Age-dependent serum Pi values were not different in the treated XLH males and females. In teeth forming primary dentin there was no gene dosage effect on PRATIO values apparent in subjects below 15 years of age. However, in teeth forming secondary dentin a gene dosage was found in the subjects aged 15 to 25 years: XLH male teeth (n = 65) mean +/- SD = 0.163 +/- 0.046; XLH female teeth (n = 75) mean +/- SD = 0.137 +/- 0.039; control teeth (n = 209) mean +/- SD = 0.116 +/- 0.023; (higher PRATIO values mean less development or mineralization of secondary dentin); differences in these PRATIO values (males vs. female and XLH vs. control) were significant by mixed-model analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Odontometric variation among American black, European, and Mongoloid populations.

Quantified dental parameters (including root and pulp areas and shape variables) derived from periapical radiographs were used to make comparisons among a sample of American Black (8 males--124 teeth, 9 females--138 teeth), European derivative (31 males--304 teeth, 43 females--497 teeth) and Mongoloid populations (12 males--166 teeth, 19 females--252 teeth). The magnitude of sexual dimorphism within each ethnic stock was also examined. Teeth from American Black males were robust. Sexual dimorphism was unambiguous in all groups although a hierarchical order existed from the highly dichotomous American Black sample to the more homogeneous European sample. The female dental phenotype was down-scaled from their male counterparts, but not gracile in form. Easily obtained area and shape parameters derived from dental radiographs proved useful as discriminators among racial groups and the sexes. The relationships among these data lend further support to the hypothesis of an African origin of modern humans.

Adolescent↗

Time-based changes in fibroblast three-dimensional locomotory characteristics and phenotypes.

Three-dimensional locomotory trajectories have been determined for an embryonic fibroblast population and also for these cells after a 20-day period in tissue culture (C-20 cells). Differences in locomotory characteristics between these two cell populations are reported. Applying factor analysis to the distribution of angle changes between vectors in a cell's trajectory reveals the possibility that different locomotory phenotypes exist. Of the three phenotypes detected in the embryonic population only one continues in the C-20 population while a new phenotype appears in the latter. These results document changes in locomotory characteristics and phenotypes in an embryonic population with time.

Animals↗

Oral findings in patients with autosomal dominant hypophosphatemic bone disease and X-linked hypophosphatemia: further evidence that they are different diseases.

Oral examinations were performed on 5 patients with hypophosphatemic bone disease (HBD) (2 males and 3 females), 14 patients with X-linked hypophosphatemia (XLH), and 4 affected XLH relatives (6 males and 12 females). The control subjects were the unaffected siblings and parents of the patients and unrelated healthy, gender- and age-matched subjects. Serum phosphorus values were the same by disease type and gender in patients with HBD and XLH. They shared certain dental abnormalities, in particular pulpal necrosis and large pulp spaces. However, only patients with XLH had Class III malocclusions and mild enamel defects, and males with XLH had more severe occlusal and enamel defects than females with XLH. Different dental phenotypes are further evidence that XLH and HBD are different diseases. The dental abnormalities were not prevented by treatment, instituted early in life, which raised serum phosphorus to the near normal range.

Adolescent↗

Methodology for detection of heterogeneity of cell locomotory phenotypes in three-dimensional gels.

A computer-driven, three-dimensional, optical, cell-tracking system was used to quantify the locomotory phenotypes of Mos-11 cells in a collagen gel. Factor analysis was used as a statistical means to make the complex variables generated by the system more tractable to analysis. Heterogeneity in locomotory behavior (two independent locomotory phenotypes) was detected among a sample of 54 cells.

Cell Line↗

Genetic epidemiology of the susceptibility to leprosy.

To test the hypothesis that genetic factors are operative in the predisposition to leprosy (Hansen's disease) in humans, a genetic epidemiologic investigation was performed on 269 leprosy kindreds containing 552 affected individuals from an isolated population in Papua New Guinea. The community, and not the family, was the basic social unit. Leprosy, an infectious disease, was not communal but strongly familial within the Karimui. Segregation analysis, to determine whether a major gene for the susceptibility to leprosy was segregating within a single multi-generational kindred, could not differentiate between a Mendelian genetic and a purely environmental hypothesis. The composite kindred data, however, suggest a genetic hypothesis for the non-immunologically induced susceptibility to leprosy per se. Within familial kindreds leprosy invariably emanated from a common ancestral sibship, and risk was associated with the closeness of kin but not with infectivity or severity.

Adult↗

Cleft palate: a genetic and epidemiologic investigation.

An examination of kindred histories of 561 Danish probands who have non-syndromic CP has indicated that neither a multifactorial-threshold model nor a single major locus model is completely compatible with the data. This suggests etiologic heterogeneity for CP, which was tested with kindred data. As recommended by Smith (1976), at attempt to define partially this heterogeneity within the CP phenotype was undertaken by grouping and comparing the kindred data. It is both reasonable and heuristic to propose that CP,, as defined in this investigation, is composed of three groups: (1) Syndromic CP; (2) Familial CP, which appears to have an autosomal dominant component to its etiology, and (3) Non-familial CP which, by demonstrating an increasing frequency of CP and a maternal age effect, appears to be related to environmental factors which may cause CP or other malformations.

Abnormalities, Multiple↗

Facial clefts in Danish twins.

A total of 74 Danish twin pairs with cleft lip +/- palate (CL(P)) and isolated cleft palate (CP) born in Denmark from 1941 to 1969 were studied. Eight pairs were of indeterminate zygosity status' and 26 pairs of unlike sex were dizygous (DZ). Of the remaining 42 like-sexed pairs, zygosity assignments were made from genotyping and physical resemblance data. Twelve pairs were given MZ status and thirty pairs DZ status. The following data was calculated: 1) in contrast to other reports, the incidence of either CL(P) or CP was not increased for either MZ or DZ twins; 2) using the pairwise method for concordance rate calculation, concordance rates for CL(P) twins were: MZ = 36 per cent; DZ = 1.5 per cent. For CP, MZ = 33 per cent; DZ = 0 per cent. The results support the concept that heredity is a prime factor in the etiology of clefting, but the low MZ concordance rates also suggest genetic heterogeneity in this cleft population.

Cleft Lip↗