Search PubMed⌕ Search

Biomedical subjects

T T Wheeler

Publications and source records attributed to T T Wheeler.

At least 37 records · Page 2Linked to original sources

Large-format, two-dimensional polyacrylamide gel electrophoresis of ovine periimplantation uterine luminal fluid proteins: identification of aldose reductase, cytoplasmic actin, and transferrin as conceptus-synthesized proteins.

Early pregnancy in ruminants, such as the sheep, is characterized by relatively extensive development of the conceptus before attachment to the endometrium. Between the period of blastocyst hatching and initial attachment, the uterus responds to signals from the conceptus and adapts to provide an environment that permits the establishment of pregnancy. We used large-format two-dimensional (2D) PAGE to analyze the dynamic changes in protein composition of uterine luminal fluid (ULF) during this stage of pregnancy, and we determined the contribution of each of the extraembryonic membranes and the endometrium to these changes. The majority of the more than 40 pregnancy-associated proteins in ULF at Day 17 were secreted by the conceptus. By 2D gel map comparison and Western blotting, we identified transferrin, secreted by the yolk sac from Day 15, and cytoplasmic actin, one of the most abundant proteins produced by the trophoblast at Day 17. Apolipoprotein A1 and aldose reductase, whose abundance were markedly increased in pregnancy, were identified by peptide microsequencing. Aldose reductase, an enzyme required for the conversion of glucose to fructose, was shown to be synthesized by the trophoblast, and its detection even before the formation of the placenta suggests that the synthesis of fructose may occur much earlier than previously reported.

Actins↗

Mammary Stat5 abundance and activity are not altered with lactation state in cows.

Stat5 is a key intracellular mediator of prolactin signalling and can activate transcription of milk proteins in response to prolactin. Therefore, in animals such as mice where lactation is dependent on prolactin, Stat5 is likely to play an important role in establishing or maintaining lactation in the mammary gland. However, little is known about its role in lactation in the dairy cow. In order to address this, the levels of Stat5a and Stat5b protein, mRNA and Stat5 DNA-binding activity were measured in mammary tissue from mice and cows at different lactational states. In the cow, Stat5a and Stat5b protein and mRNA levels, as well as Stat5 DNA-binding activity were unaltered between pregnancy and established lactation. In contrast, in the mouse Stat5a and Stat5b protein, as well as Stat5 DNA-binding activity were clearly increased during lactation whereas Stat5a and Stat5b mRNA levels were highest during pregnancy as has been previously described. In both species only a minority of the epithelial cell nuclei were Stat5 positive during established lactation. These results suggest that there are significant differences in the biological role of Stat5 in controlling lactation between ruminants and rodents.

Animals↗

Inducibility of E4BP4 suggests a novel mechanism of negative gene regulation by glucocorticoids.

The major biological effects of glucocorticoids are thought to be initiated through changes in the expression of cellular genes. However, the mechanisms involved in the suppression of some gene products by glucocorticoids are not well defined. ID13 mouse fibroblast cells were treated with the synthetic glucocorticoid dexamethasone (Dex) or with vehicle. Plus/ minus (+Dex/-Dex) cDNAs were used to screen an ID13 cDNA library. Using this method, we found that the recently identified human protein adenovirus E4 promoter binding protein (E4BP4) mRNA was induced by Dex in the ID13 cell line. E4BP4 is a transcriptional repressor and binds to a specific DNA element. Further investigation indentified E4BP4-like DNA elements located in the promoters of glucocorticoid repressed genes Cox-2, iNOS, and cPLA2. These findings suggest that E4BP4 may play a role in the glucocorticoid repression of these and other genes.

Adenoviridae↗

Bovine papillomavirus E5 oncogene stimulates DNA synthesis in C127 fibroblasts without general effects on growth factor responsive protein phosphorylations.

The bovine papillomavirus (BPV) transforming gene E5 is thought to modulate growth factor receptor function leading to a stimulation of growth factor signal transduction pathways. However, the influence of E5 on the range of receptor mediated changes in protein phosphorylation has not been addressed. We looked for the influence of E5 on DNA synthesis as well as the phosphorylation of over 1000 cellular phosphoproteins in mouse C127 fibroblasts and subclones harboring wild type (ID13)-, E5- mutant (XL3-2), and E6- (E6oCl) mutant BPVs. The cells containing E5 had an altered growth response to fresh serum or PDGF but we observed no general influences of E5 transformation on sets of serum-, phorbol ester-, and PDGF-responsive phosphoproteins, comprising 25, 18, and 16 overlapping members, respectively. Indeed, most of the phosphoproteins comprising these sets remain equally responsive to these growth factors in all four cell lines. The only evidence of an E5-specific influence on protein phosphorylation was with 4 phosphoproteins, two whose PDGF-responsiveness was abolished and two with abolished serum-, phorbol ester- and PDGF-responsiveness. Thus E5 modulates only a subset of the cascade of receptor-mediated downstream protein phosphorylations.

Animals↗

Lactation-associated and prolactin-responsive changes in protein synthesis in mouse mammary cells.

Lactational function in the mammary epithelial cell is subject to complex regulation, most probably involving multiple extracellular and intracellular proteins that act at any of a number of levels. Although some of these proteins have been identified it is likely that additional controllers of lactation exist, but have yet to be discovered. In an effort to identify such proteins, a search was made for non-milk lactation-associated or prolactin-responsive proteins in primary mouse mammary epithelial cells and the mouse mammary epithelial cell line, COMMA-D using two-dimensional electrophoresis on large-format gels. These analyses revealed 12 proteins whose rate of synthesis was dependent on lactation state or on response to prolactin. Two of these (p77 and p63) were lactation-associated in primary cells and prolactin-responsive in COMMA-D cells. These two proteins were identified by amino acid sequencing as glucose-regulated protein 78 (GRP78) and protein disulphide isomerase (PDI). The localization of these proteins in the endoplasmic reticulum and their presence in other secretory cell types and tissues suggests that they have a function in the processing or secretion of milk proteins.

Animals↗

Differences in the abundance of nuclear proteins in the bovine mammary gland throughout the lactation and gestation cycles.

The mechanisms that control the synthesis of milk protein are not fully understood and could well involve undiscovered proteins within the mammary gland. A search for such proteins in high salt extracts of nuclei that had been isolated from bovine mammary tissues was undertaken using two-dimensional electrophoresis on large format gels. The sensitivity of the procedure was sufficient to detect the transcription factors Sp1 and NF-1 by Coomassie blue stain; over 300 proteins were routinely detected. Analysis of mammary tissue taken from 5 nonlactating cows in midpregnancy, 5 cows in late lactation, and 4 cows in early involution revealed five proteins where relative abundance was altered with stage of lactation or reproductive cycle. Four of these proteins were identified by Western blotting or amino acid sequencing as lactoferrin, annexin II, vimentin, and heavy-chain immunoglobulin. Analysis of proteins after further enrichment of the extracts by heparin-Sepharose affinity chromatography revealed an additional protein that was substantially more abundant in samples from lactating cows. This 90-kDa protein did not react with anti-Stat5 antibodies. Conceivably, one or more of these six proteins could play a role in the lactational function of the bovine mammary gland.

Animals↗

Imprecision in orthodontic diagnosis: reliability of clinical measures of malocclusion.

The study examined the reliability among seven orthodontists in judging dental and facial aspects of malocclusion in a screening of elementary schoolchildren. Data included measures typically recorded during a clinical orthodontic examination: facial assessment of skeletal/incisor relationships and individual measures of morphologic malocclusion. Interexaminer reliability data were collected on 52 children. Pairwise comparisons between orthodontists were made using exact percent agreement and agreement within one category. Kappa statistics and one-sided Z-tests were used to evaluate observed agreement compared with agreement that would be expected by chance. Median Kappa statistics indicated that the reliability of maxillary and mandibular anteroposterior positions, incisor exposure, interlabial gap, and maxillary crowding was poor (K < 0.40). Acceptable reliability existed for mandibular anterior crowding, facial convexity, overbite, overjet, and molar classification (median Kappas ranged from 0.48 to 0.72). Excellent reliability existed only for evaluating the presence of a posterior crossbite (K = 0.79). The results caution that the language of clinical orthodontic diagnosis is imprecise.

Cephalometry↗

Risk factors associated with incisor injury in elementary school children.

This study examined risk factors associated with incisor injury in 3396 third and fourth grade school children in Alachua County, Florida. One of six orthodontists completed a standardized examination form for each child to assess severity of incisor injury, gender, age, race, skeletal relationships, morphologic malocclusion, incisor exposure, interlabial gap, TMJ sounds, chin trauma, and history of lower facial trauma. One in five (19.2%) exhibited some degree of incisor injury. This was limited to a single tooth in 73.1% of those with injury, while enamel injury predominated (89.4%). The majority of the injuries (75.4%) were localized in the maxillary arch, with central incisors the most frequently traumatized. Chi-square tests of association indicated that gender, race, school, orthodontist, history of lower facial trauma, chin trauma, profile, and maxillary and mandibular horizontal positions were associated with incisor injury (P < 0.05). Wilcoxon rank sum tests identified differences in age, overjet, time of screening, and interlabial gap between those with and without injury (P < 0.05). Results of logistic regression analyses indicated risk of incisor injury was greater for children who had a prognathic maxilla, a history of trauma, were older, were male, and had greater overjet and mandibular anterior spacing.

Age Factors↗

The relative abundance of a salivary protein, bSP30, is correlated with susceptibility to bloat in cattle herds selected for high or low bloat susceptibility.

Pasture bloat is a serious economic and animal welfare problem in cattle grazed on legumes in New Zealand. Analysis of salivary proteins from dairy cattle in herds bred for either low or high susceptibility to bloat has resulted in the identification of a 30 kilodalton protein, which we term bSP30, whose relative abundance is negatively correlated with bloat score (r = -0.40 +/- 0.12). From 74 animals sampled, relative abundance of bSP30 was 66 +/- 15% higher in the low-susceptibility herd than in the high-susceptibility herd. Relative abundance of bSP30 also varied significantly within individuals, according to feeding or time of day, and from day to day. A sequence homology search of 38 amino acids derived from three tryptic fragments of the protein suggests that the amino acid sequence of bSP30 has not been described previously. Amino acid analysis indicates that bSP30 is not a member of the proline-rich family of salivary proteins. The function of bSP30 is unknown but it is conceivable that it plays a role in the aetiology of bloat.

Amino Acid Sequence↗

Milk protein synthesis, gene expression, and hormonal responsiveness in primary cultures of mammary cells from lactating sheep.

A ruminant mammary cell culture that accurately reproduces mammary function in vitro would be a valuable tool in studies of ruminant lactation. With this in mind, we have examined milk protein synthesis and secretion, milk protein mRNA abundance, and hormonal responsiveness in primary cultures of mammary acini from lactating sheep. alpha- and beta-casein protein synthesis, beta-lactoglobulin synthesis, and alpha-casein, beta-casein, and beta-lactoglobulin secretion are maintained at high levels for 8 h in culture, but then decline to approximately 25% of maximal rates between 8 and 24 h in culture, whereas synthesis of other proteins remains unaltered. The relative abundance of alpha-S1-casein, beta-lactoglobulin, and alpha-lactalbumin mRNAs similarly decline between 8 and 24 h in culture. Extracellular labeled alpha-casein is increased fourfold in the presence of fetal calf serum (FCS). In total, FCS alters the abundance of 47 of 68 secreted proteins detected by two-dimensional electrophoresis. However, FCS and lactogenic/galactopoietic hormones had no effect on the rate of decline of mammary function and did not promote any regaining of function when present for up to 9 days in culture. These results suggest that providing its limitations are recognized, this primary cell culture system may be useful in studying some aspects of ruminant mammary function in vitro.

Animals↗

Temporomandibular disorders after early Class II treatment with bionators and headgears: results from a randomized controlled trial.

Symptoms and signs of temporomandibular disorders were assessed in children enrolled in a randomized controlled trial of early treatment for Class II malocclusion. Children (mean age of 9.8 years) were assigned to a treatment protocol (bionator, n = 60; observation, n = 60; headgear/bite plane, n = 71) using randomized block stratification. Temporomandibular joint (TMJ) sounds, joint capsule pain to palpation, and muscle pain to palpation were scored as binary responses (present/absent in a subject). Determinations were made by blinded, calibrated examiners initially (DC1) and after a Class I molar correction was achieved or 2 years had elapsed (DC3). Univariate relationships among explanatory factors (group assignment, gender, age, time interval between DC1 and DC3, Class II severity, mandibular plane angle, preparatory treatment, whether Class I molar relation was achieved) and binary responses were explored using Chi square tables and ANOVA methods. Logistic regression modeled the relationship between binary responses and the explanatory variables. At DC1, the 3 groups were equivalent in the explanatory variables (P > .05). Subjects with a TMJ sound, joint pain, and/or muscle pain at follow-up were more likely those who had the sign at baseline (P < .01). Early treatment with bionators and headgear/bite planes did not place healthy children without these signs at risk for developing these signs. Only increasing age (for the development of sounds, P < .04) and failure to achieve a Class I molar relation (for development of muscle pain, P < .04) placed sign-free children at greater risk. Subjects with TMJ pain at baseline were 7 times more likely to have pain at follow-up if they had been treated with a headgear/bite plane or observed than if they had been treated with a bionator (P = .007). We conclude that an immediate benefit or risk for children receiving early Class II treatment with bionators and headgear/bite planes with respect to temporomandibular joint function does not exist with the prospect that Class II children with TMJ capsule pain may benefit from bionator therapy.

Activator Appliances↗

Dental, visual, auditory and olfactory complications in Paget's disease of bone.

OBJECTIVE: To determine the prevalence of dental problems in Paget's patients and in a control population without Paget's disease. The relationship of localization of bony involvement of Paget's disease with the prevalence of dental, auditory, visual, and smell changes is examined. DESIGN: Cross-sectional national survey. PARTICIPANTS: Four hundred ninety-eight subjects with Paget's disease were generated randomly from the mailing list of the Paget Foundation. INTERVENTION: Each subject was sent a cover letter, two questionnaires, and a stamped, addressed return envelope. One questionnaire contained questions specific for the individual with Paget's disease. Subjects were asked to give the other questionnaire, which contained the same questions except for those asking about the specifics of Paget's disease, to an unaffected spouse or a similar aged friend. MEASUREMENTS: All subjects were asked about their age, gender, race, educational level, income, living situation, chronic medical conditions, self-rating of their general physical and dental health, the number of teeth present, and the presence of dental, auditory, visual, and olfactory problems. Paget's subjects were also asked to indicate which bones were affected. RESULTS: Paget's disease subjects assessed their oral health to be poorer than the controls. Paget's subjects were more likely to report pain when opening the mouth and were more likely to have had dental extractions. A significantly higher percentage of Paget's individuals with facial or maxillomandibular involvement reported having heart trouble. Paget's individuals with skull, facial or maxillo-mandibular involvement were more likely to report a change in their hearing, sight, and smell than Paget's subjects without involvement of the craniofacial complex. Dental problems were reported by 93% of those Paget's subjects with maxillomandibular involvement, compared with only 10% for those with skull involvement only or involvement at sites distant to the craniofacial complex. CONCLUSIONS: Patients with Paget's disease of bone involving facial or maxillo-mandibular parts of the skeleton have a higher prevalence of change in hearing, sight, smell, and dental problems. We also have found an association of heart disease in patients who have involvement of facial or maxillo-mandibular bones.

Adult↗

Pilot study comparing parents' and third-grade schoolchildren's attitudes toward braces and perceived need for braces.

An instrument developed for third-grade schoolchildren and their parents was pilot-tested for its ability to measure orthodontic attitudes and perception of the child's need for braces. Seventy-eight children and 54 parents were surveyed. Forty-six percent of the children wanted braces while 61% believed that they needed braces. Correlation between desire for braces and perceived need was 0.47, suggesting that desire and perceived need were only moderately correlated in children. Sixty-three percent of the parents believed that their child needed braces. Despite such proportions of children and parents perceiving a need for treatment, three-fourths of the children and two-thirds of the parents were satisfied with the appearance of the child's teeth. Attitude subscales, derived from the attitude survey, and clinical orthodontic parameters were used to model children's and parents' perceived need for braces in the child. No clinical parameter was a significant correlate in either children's or parents' model of perceived need. Neither race nor gender contributed significantly to either model. The subscales Concern for Appearance and Social Aspects of Braces were the strongest covariates of children's perceived need for braces. Concern for Appearance was the most important correlate in the parents' model. These data suggest that parents' perceived need for orthodontic treatment for their third-grade children is determined primarily by a concern for appearance rather than clinical status. In third-graders, perceived aesthetics and social aspects apparently have more influence than clinical status in creating a perception of need for braces.

Attitude to Health↗

Glucocorticoid and phorbol ester effects in 3T3-L1 fibroblasts suggest multiple and previously undescribed mechanisms of glucocorticoid receptor-AP-1 interaction.

A number of mechanisms have been proposed to account for glucocorticoid hormone and mitogen effects observed on the transcription of engineered exogenous target genes. However, the effect of the co-addition of these agents on the full range of endogenous responsive genes in a given cell type has not been addressed. We detected 19 metabolically labeled proteins or in vitro translation products whose synthesis was altered in 3T3-L1 fibroblasts in response to glucocorticoid hormone using two-dimensional electrophoresis on large-format gels. Co-addition of the mitogenic phorbol ester, tetradecanoylphorbolacetate (TPA), with glucocorticoid hormone resulted in independent (one species), synergistic (six species), and antagonistic (five species) effects on the glucocorticoid regulation of individual gene products, while seven other glucocorticoid regulated species were not affected. These and additional observations suggest direct and gene-specific effects of glucocorticoid receptor and AP-1 on the transcription of responsive genes, and for some of these genes the pattern of regulation is not accounted for by mechanisms described to date. In addition, the pattern of regulation of five species is consistent with a role in mediating the opposing physiological effects of glucocorticoid hormone and growth factors in these cells.

3T3 Cells↗

Orthodontic treatment demand and need in third and fourth grade schoolchildren.

There have been few reports worldwide addressing orthodontic need and demand in children and no recent reports in the United States. The purpose of this study was to examine the orthodontic need and demand in third and fourth grade children (n = 3696). Data including age, sex, race, orthodontic status, socioeconomic status, availability of specialist treatment services, as well as thorough occlusal data, were collected. Orthodontic demand was significantly higher in girls (9.5%) than boys (6.8%), whereas need had the inverse relationship (41.8%, 44.2%, respectively). There were no meaningful differences in age among the demand, need, and no need groups. Demand was greater in white than in black children (11.8% versus 1.2%); however, need was observed to be less in black (35.3%) than in white children (47.2%). Demand was greater in the urban schools (8.9%) than in the rural schools (6.3%), whereas need was found to be similar. There was more demand in the higher socioeconomic groups (11.7%) than in the lower groups (1.8%), whereas need was similar in all the groups. The demand group had a significantly greater number of orthodontists within a radius of up to 5 miles of the school than the need and no need groups. Logistic regression models to examine factors that distinguish the groups show that when demand versus need/no need groups are compared, those students with an increased "risk" of previous treatment are more likely to have more orthodontists nearby, to be in higher socioeconomic groups, and to be female students.

Black or African American↗

Risk factors associated with temporomandibular joint sounds in children 6 to 12 years of age.

The relationship between temporomandibular joint (TMJ) sounds and a person's dental and skeletal characteristics is poorly understood. In this study, data were obtained from 3428 grade schoolchildren (mean age = 9.0 years, SD = 0.8, range 6 to 12 years), without a history of orthodontic treatment. Each child had been examined independently by one of six orthodontists to assess: TMJ sounds (none, click, crepitus), gender, age, race (white/black), skeletal relationships (convexity, maxillary, and mandibular positions), malocclusion (molar class, overjet, overbite, anterior crowding, posterior crossbite), maximum opening, chin trauma (none, cut, scar), and history of lower facial trauma. Temporomandibular joint sounds were present in 344 children (10.0% of the sample); 276 (8.1%) had an isolated unilateral sound, 254 (7.4%) had unilateral clicking, 50 (1.5%) had bilateral clicking, 22 (0.6%) had unilateral crepitus, and 11 (0.3%) had bilateral crepitus. Univariate analyses compared children with and without sounds for each variable; logistic regression analyses examined the relationship between groups of variables and TMJ sounds. The prevalence of TMJ sounds was associated with examiner (chi 2 = 23.4, df = 5, p < 0.001); increased prevalence of TMJ sounds occurred in children with maxillary anterior crowding (t = 2.8, p < 0.006), mandibular anterior crowding (t = 3.0, p < 0.002), and increased maximum opening (t = 4.7, p < 0.001). In contrast to other reports on children, the prevalence of joint sounds was not associated with age, race, gender, or molar class.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Characterization of the synthesis and secretion of transforming growth factor-alpha from salivary glands and saliva.

Whole saliva collected from rat, mouse, and human sources was found to contain high concentrations of transforming growth factor-alpha (TGF alpha) when analyzed by RIA. The concentrations of TGF alpha in unstimulated human saliva (age, 30-45 yr; n = 10; 1.5 +/- 3.1 nM) was reduced with age (age, 55-70 yr; n = 10; 0.4 +/- 0.1 nM), but increased in oral pathologies manifested in xerostomia (age, 57-70; n = 6; 0.8 +/- 0.2 nM) and Paget's disease (age, 58-76; n = 8; 2.0 +/- 0.6 nM). Immunohistochemical localization of TGF alpha in the salivary glands of rats and mice revealed specific immunostaining of the granular ductal cells of the parotid and submandibular glands. Reverse transcription followed by polymerase chain reaction amplification of total RNA from the parotid and submandibular glands of rats and mice demonstrated the presence of TGF alpha mRNA, suggesting endogenous synthesis by the salivary glands. Thus, salivary glands appear to be an exocrine source for a second member of the epidermal growth factor-like growth factor family in the oral cavity.

Adult↗