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Biomedical subjects

R A Schneider

Publications and source records attributed to R A Schneider.

At least 19 recordsLinked to original sources

Amelogenins in human developing and mature dental pulp.

Amelogenins are a group of heterogenous proteins first identified in developing tooth enamel and reported to be present in odontoblasts. The objective of this study was to elucidate the expression and function of amelogenins in the human dentin-pulp complex. Developing human tooth buds were immunostained for amelogenin, and mRNA was detected by in situ hybridization. The effects of recombinant amelogenins on pulp and papilla cell proliferation were measured by Brd U immunoassay, and differentiation was monitored by alkaline phosphatase expression. Amelogenin protein was found in the forming dentin matrix, and amelogenin mRNA was localized in the dentin, presumably in the odontoblast processes. Proliferation of papilla cells was enhanced by recombinant human amelogenin rH72 (LRAP+ exon 4), while pulp cells responded to both rH72 and rH58 (LRAP), with no effect by rH174. These studies suggest that odontoblasts actively synthesize and secrete amelogenin protein during human tooth development, and that low-molecular-weight amelogenins can enhance pulp cell proliferation.

Alternative Splicing↗

Cranial skeletal biology.

To artists, the face is a mirror of the soul. To biologists, the face reflects remarkable structural diversity--think of bulldogs and wolfhounds or galapagos finches. How do such variations in skeletal form arise? Do the same mechanisms control skeletogenesis elsewhere in the body? The answers lie in the molecular machinery that generates neural crest cells, controls their migration, and guides their differentiation to cartilage and bone.

Animals↗

The cellular and molecular origins of beak morphology.

Cellular and molecular mechanisms underlying differences in beak morphology likely involve interactions among multiple embryonic populations. We exchanged neural crest cells destined to participate in beak morphogenesis between two anatomically distinct species. Quail neural crest cells produced quail beaks in duck hosts and duck neural crest produced duck bills in quail hosts. These transformations involved morphological changes to non-neural crest host beak tissues. To achieve these changes, donor neural crest cells executed autonomous molecular programs and regulated gene expression in adjacent host tissues. Thus, neural crest cells are a source of molecular information that generates interspecific variation in beak morphology.

Animals↗

Local retinoid signaling coordinates forebrain and facial morphogenesis by maintaining FGF8 and SHH.

Correlations between facial anomalies and brain defects are well characterized throughout the clinical literature, yet a developmental basis for this association has not been identified. We demonstrate that the frontonasal process, which gives rise to the mid- and upper face, and the forebrain are linked early in their morphogenesis by a local retinoid signaling event that maintains the expression of key regulatory molecules. First, we show that aldehyde dehydrogenase 6, which synthesizes the ligand, retinoic acid, is localized to the ventral epithelium of the presumptive frontonasal process of chick embryos. At least two retinoid receptors are expressed in adjacent populations of mesenchyme. Second, using synthetic pan-specific retinoid antagonists, we transiently inhibit the ability of retinoid receptors to bind retinoic acid in the rostral head and we generate embryos with a hypoplastic forebrain, fused eyes, and no frontonasal process-derived structures such as the upper beak. These defects are not due to eliminating mesenchymal progenitors, as neural crest cells still migrate into the frontonasal process, despite disruptions to retinoid signaling. Rather, these malformations result from loss of fibroblast growth factor 8 and sonic hedgehog expression, which leads to increased programmed cell death and decreased proliferation in the forebrain and frontonasal process. Most significantly, we can rescue the morphological defects by re-introducing retinoic acid, or fibroblast growth factor and sonic hedgehog proteins into antagonist-treated embryos. We propose that the local source of retinoic acid in the rostral head initiates a regulatory cascade that coordinates forebrain and frontonasal process morphogenesis.

Animals↗

Preliminary data on the Multidimensional Fatigue Inventory-20 from female caregivers of male hemodialysis patients.

To test the reliability and concurrent validity of the Multidimensional Fatigue Inventory-20, 45 spouses or first-degree female caregivers of male hemodialysis patients in northern and eastern Iowa were administered the Multidimensional Fatigue Inventory-20 and the Rhoten Fatigue Scale. Four of the five subscales had a high Cronbach alpha (.76 to .82). There were low to moderate statistically significant Pearson correlations between scores on the Rhoten Fatigue Inventory and the MFI-20 subscales (.40 to .72). Limitations of generalizations are addressed.

Aged↗

Genetic and teratogenic approaches to craniofacial development.

Craniofacial malformations are the most common birth defects that occur in humans, with facial clefting representing the majority of these defects. Facial clefts can arise at any stage of development due to perturbations that alter the extracellular matrix as well as affect the patterning, migration, proliferation, and differentiation of cells. In this review, we focus on recent advances in the understanding of the developmental basis for facial clefting through the analysis of the effects of gene disruption experiments and treatments with teratogens in both chickens and mice. Specifically, we analyze the results of disruptions to genes such as Sonic hedgehog (Shh), epidermal growth factor receptor (EGFR), Distal-less (Dlx), and transforming growth factor beta 3 (TGFbeta3). We also describe the effects that teratogens such as retinoic acid, jervine, and cyclopamine have on facial clefting and discuss mechanisms for their action. In addition to providing insight into the bases for abnormal craniofacial growth, genetic and teratogenic techniques are powerful tools for understanding the normal developmental processes that generate and pattern the face.

Animals↗

Neural crest can form cartilages normally derived from mesoderm during development of the avian head skeleton.

The lateral wall of the avian braincase, which is indicative of the primitive amniote condition, is formed from mesoderm. In contrast, mammals have replaced this portion of their head skeleton with a nonhomologous bone of neural crest origin. Features that characterize the local developmental environment may have enabled a neural crest-derived skeletal element to be integrated into a mesodermal region of the braincase during the course of evolution. The lateral wall of the braincase lies along a boundary in the head that separates neural crest from mesoderm, and also, neural crest cells migrate through this region on their way to the first visceral arch. Differences in the availability of one skeletogenic population versus the other may determine the final composition of the lateral wall of the braincase. Using the quail-chick chimeric system, this investigation tests if populations of neural crest, when augmented and expanded within populations of mesoderm, will give rise to the lateral wall of the braincase. Results demonstrate that neural crest can produce cartilages that are morphologically indistinguishable from elements normally generated by mesoderm. These findings (1) indicate that neural crest can respond to the same cues that both promote skeletogenesis and enable proper patterning in mesoderm, (2) challenge hypotheses on the nature of the boundary between neural crest and mesoderm in the head, and (3) suggest that changes in the allocation of migrating cells could have enabled a neural crest-derived skeletal element to replace a mesodermal portion of the braincase during evolution.

Animals↗

From head to toe: conservation of molecular signals regulating limb and craniofacial morphogenesis.

Recent evidence indicates that many molecules involved in generating and patterning the limbs also play a role during craniofacial morphogenesis. On the surface, this is an unexpected finding given that these regions of the body have separate evolutionary origins, are composed of different embryonic tissues, and are quite dissimilar in their anatomy. Results from several experiments involving Sonic hedgehog and retinoic acid point to a remarkable conservation of the signaling pathways mediated by these morphogens across multiple organ systems. Moreover, mutants such as the extra-toes and doublefoot mouse, and the talpid chicken also provide insights on common developmental processes that underlie the formation of the limbs and face. The identification of highly conserved aspects of morphogenesis is important for understanding fundamental mechanisms of development, as well as for revealing the common denominator of countless birth defects and providing new strategies for their prevention and cure.

Animals↗

Proprioception and neuromuscular control of the shoulder after muscle fatigue.

OBJECTIVE: To examine the effects of fatigue on proprioception and neuromuscular control of the shoulder. DESIGN AND SETTING: Subjects were randomly assigned to either an experimental group or control group. Subjects were tested using either the active angle-reproduction or the single- arm dynamic stability test. The subjects were then fatigued using a dynamometer performing continuous, concentric rotation exercises of the shoulder. Once fatigued, the subjects were posttested using the same test. One week later, the subjects returned and were pretested, fatigued, and posttested using the other test. SUBJECTS: Thirty-two college-age (18 to 25 years) subjects (16 males, 16 females) with no history of glenohumeral instability or upper extremity injury volunteered for this study. MEASUREMENTS: Absolute angular error was measured using an electrogoniometer present within the isokinetic dynamometer, while sway velocity was measured using a force-plate system. RESULTS: Repeated-measures analysis of variance revealed a significant difference between the pretest and posttest values for absolute angular error in the experimental group, whereas no significant difference was revealed between pretest and posttest sway velocity for either the control or experimental group. CONCLUSIONS: Fatigue of the internal and external rotators of the shoulder decreased proprioception of the shoulder, while having no significant effect on neuromuscular control.

Journal Article↗

Have gene knockouts caused evolutionary reversals in the mammalian first arch?

Many recent gene knockout experiments cause anatomical changes to the jaw region of mice that several investigators claim are evolutionary reversals. Here we evaluate these mutant phenotypes and the assertions of atavism. We argue that following the knockout of Hoxa-2, Dlx-2, MHox, Otx2, and RAR genes, ectopic cartilages arise as secondary consequences of disruptions in normal processes of cell specification, migration, or differentiation. These disruptions cause an excess of mesenchyme to accumulate in a region through which skeletal progenitor cells usually migrate, and at a site of condensation that is normally present in mammals but that is too small to chondrify. We find little evidence that these genes, when disrupted, cause a reversion to any primitive condition and although changes in their expression may have played a role in the evolution of the mammalian jaw, their function during morphogenesis is not sufficiently understood to confirm such hypotheses.

Animals↗

Reliability and validity of the Multidimensional Fatigue Inventory (MFI-20) and the Rhoten Fatigue Scale among rural cancer outpatients.

Cancer patients typically experience fatigue while undergoing treatment for their disease. This study was an effort to identify a reliable and economical measure of fatigue. In particular, scores on the five subscales of the Multidimensional Fatigue Inventory (MFI-20) were analyzed for internal consistency and then correlated with scores on the Rhoten Fatigue Inventory to establish a measure of validity. Moderate-to-high Cronbach alphas coefficients were established for the General Fatigue subscale of the MFI-20 using a sample of 97 rural oncology outpatients (1). Partial associations with the Rhoten Fatigue Scale lend evidence to the validity of the MFI-20 measures.

Adult↗

Expression of heat-stable enterotoxin STb by adherent Escherichia coli is not sufficient to cause severe diarrhea in neonatal pigs.

The role of Escherichia coli heat-stable enterotoxin B (STb) in neonatal porcine diarrhea caused by enterotoxigenic E. coli was examined by comparing adherent isogenic strains with or without STb. The cloned STb gene (in the plasmid pRAS1) was electroporated into a nonenterotoxigenic strain (226M) which expresses the F41 adhesin. Strain 226M pRAS1 adhered and expressed STb in vivo, causing fluid secretion in ligated ileal loops in neonatal pigs. Although strain 226M pRAS1 caused very mild diarrhea in some orally inoculated neonatal pigs, the weight loss in these pigs was similar to that caused by the parental strain without STb. We conclude that STb does not significantly contribute to diarrhea caused by enterotoxigenic E. coli in neonatal pigs.

Animals↗

Concurrent validity of the Beck Depression Inventory and the multidimensional fatigue inventory-20 in assessing fatigue among cancer patients.

Cancer patients experience both fatigue and depression while undergoing treatment for their disease. A number of authors have conceptualized such depression among this populations as secondary to fatigue. This study of 54 patients was done to test the concurrent validity of two inventories. Scores on the five subscales of the 20-item Multidimensional Fatigue Inventory were correlated with those on the 21-item Beck Depression Inventory. Moderate correlations are reported and the potential usefulness of the Multidimensional Fatigue Inventory is discussed.

Adaptation, Psychological↗

Virulence attributes of Escherichia coli isolated from dairy heifer feces.

Escherichia coli isolates from 1,305 (of 6,894) fecal samples collected during the 1991-1992 USDA, Animal and Plant Health Inspection Service, National Health Monitoring System, Diary Heifer Evaluation Project were tested for virulence attributes associated with human enterohaemorrhagic E. coli (EHEC) and the enterotoxin commonly associated with diarrhoea in newborn calves. Single, random isolates from each heifer were hybridized to probes derived from the 60 mDa EHEC plasmid (CVD 419), E. coli attaching and effacing gene (eae), Shiga-like toxin (slt) genes I and II, and E. coli heat-stable enterotoxin a (STaP). Seventy-seven of the 1305 isolates (5.9%) were slt-positive. Most (81.8%) slt-positive E. coli were also CVD 419 and eae-positive. Only 2 of the slt-positive E. coli isolates were STaP-positive.

Animals↗

Characterization of Escherichia coli isolated from the tonsils of cattle.

During our studies on tonsillar colonization by Pasteurella haemolytica, we consistently found Escherichia coli to be one of the most prominent and prevalent bacterial species in the tonsils of healthy cattle. Since tonsillar isolates have not been characterized, we grouped 124 isolates from 87 healthy cattle from eight sources by hemolytic zone size and by carbon source utilization and probed them for selected virulence genes. They formed 3 groups by hemolytic zone size and 18 groups (of 2 to 31 isolates) by their metabolic patterns. Most groups included isolates from more than one source. Two isolates contained the Shiga-like toxin gene, and nine others contained the F41 accessory gene.

Animals↗

A monoclonal antibody identifies 2134P fimbriae as adhesins on enterotoxigenic Escherichia coli isolated from postweaning pigs.

Fimbriae (pili) of enterotoxigenic Escherichia coli (ETEC), including K88, K99, 987P, and F41, are adhesins that facilitate intestinal colonization in neonatal pigs. K88 is also associated with some ETEC isolated from weaned pigs. Many ETEC isolates from weaned pigs do not express known adhesins and are termed 4P-. A novel bacterial adhesin, 2134P, was recently identified on two 4P- ETEC isolates from weaned pigs. In this study, we identified a 2134P-specific monoclonal antibody, mAb 6C7/C1, that blocked the binding of 2134P+ bacteria to intestinal epithelial cells. Indirect immunofluorescent antibody and immunoperoxidase assays using mAb 6C7/C1 confirmed that the 2134P adhesin is expressed in vivo by adherent bacteria in pigs challenge-exposed with 2134P+ ETEC. 2134P was detected on 31% of 189 postweaning diarrhea 4P- ETEC isolates from the National Animal Disease Center's culture collection by dot blot immunoperoxidase assays using mAb 6C7/C1. We conclude that 2134P is a bacterial adhesin and is an important virulence attribute of some ETEC that cause diarrhea in weaned pigs.

Adhesins, Escherichia coli↗

Identification of plasmid and chromosomal copies of 987P pilus genes in enterotoxigenic Escherichia coli 987.

A DNA probe derived from the subunit gene of a cloned 987P determinant was used to characterize the locations of the 987P genes in several Escherichia coli strains. We examined E. coli 987, a nonpiliated mutant of strain 987 (I36) that does not express 987P in vitro, and a variant of I36 that expressed 987P following growth in vivo. We found that plasmid and chromosomal copies of the 987P subunit gene could be differentiated in strain 987 by restriction endonuclease analysis and Southern blot hybridization. The nonpiliated mutant I36 had lost the plasmid copy but retained the chromosomal copy of the 987P gene. A 987P-piliated variant of I36, which did not contain the 987P plasmid, colonized and caused diarrhea in neonatal pigs similarly to wild-type 987. The plasmid that hybridized with the 987P probe was transferred from strain 987 to an E. coli K-12 strain by conjugation. We were unable to demonstrate expression of 987P by these transconjugants. The data suggest that the chromosomal and plasmid copies of the 987P genes may interact to influence 987P expression.

Adhesins, Escherichia coli↗

An F41-K88-related genetic determinant of bovine septicemic Escherichia coli mediates expression of CS31A fimbriae and adherence to epithelial cells.

A genetic determinant related to that encoding the F41 fimbrial adhesin was cloned from a bovine septicemic isolate of Escherichia coli. This determinant was found to mediate expression of morphologically distinct fimbriae in E. coli HB101. The gene encoding the fimbrial subunit protein was identified, and the nucleotide sequence was determined. Homology with the amino-terminal amino acid sequence of CS31A (J. Girardeau, M. Der Vartanian, J. Ollier, and M. Contrepois, Infect. Immun. 56:2180-2188, 1988) was observed, suggesting that this determinant encodes expression of the CS31A fimbrial antigen. The CS31A subunit gene was found to share extensive homology in its signal sequence to the subunit genes encoding the F41 and K88 adhesins. No apparent homology between the mature F41 and CS31A subunits was identified. However, substantial relatedness to the K88 fimbrial subunit was observed. Analysis of the protein products encoded by the CS31A, F41, and K88 determinants in maxicells established that despite extensive genetic similarities between the determinants, each encodes a distinct profile of proteins. E. coli HB101 harboring the cloned CS31A determinant was found to adhere to epithelial cells in a tissue culture assay, suggesting a role for CS31A in adherence. A CS31A-specific DNA hybridization probe detected homologous sequences among enterotoxigenic as well as septicemic E. coli isolates from calves.

Amino Acid Sequence↗