PubMed Health⌕ Search

Biomedical subjects

J C Wheeler

Publications and source records attributed to J C Wheeler.

15 recordsLinked to original sources

Genetic analysis reveals the wild ancestors of the llama and the alpaca.

The origins of South America's domestic alpaca and llama remain controversial due to hybridization, near extirpation during the Spanish conquest and difficulties in archaeological interpretation. Traditionally, the ancestry of both forms is attributed to the guanaco, while the vicuña is assumed never to have been domesticated. Recent research has, however, linked the alpaca to the vicuña, dating domestication to 6000-7000 years before present in the Peruvian Andes. Here, we examine in detail the genetic relationships between the South American camelids in order to determine the origins of the domestic forms, using mitochondrial (mt) and microsatellite DNA. MtDNA analysis places 80% of llama and alpaca sequences in the guanaco lineage, with those possessing vicuña mtDNA being nearly all alpaca or alpaca-vicuña hybrids. We also examined four microsatellites in wild known-provenance vicuña and guanaco, including two loci with non-overlapping allele size ranges in the wild species. In contrast to the mtDNA, these markers show high genetic similarity between alpaca and vicuña, and between llama and guanaco, although bidirectional hybridization is also revealed. Finally, combined marker analysis on a subset of samples confirms the microsatellite interpretation and suggests that the alpaca is descended from the vicuña, and should be reclassified as Vicugna pacos. This result has major implications for the future management of wild and domestic camelids in South America.

Animals↗

Mechanisms of transcriptional regulation by Runt domain proteins.

Runt domain proteins have vital roles in regulating transcription in developmental pathways extending from sex determination and segmentation in fruit fly embryos to the development of blood and bone in mammals. Many of the insights into the mechanisms by which these proteins act to regulate transcription originate either from studies on the Drosophila runt gene, the founding member of this family, or from work on the mammalian PEBP2/CBF transcription factor. Genetic experiments in the Drosophila system reveal that runt functions both to activate and to repress transcription of different downstream target genes and indicate that different mechanisms are used in the regulation of different specific downstream target genes. These studies have also identified other nuclear factors that work with Runt in some of these pathways. Studies in mammalian systems have provided additional evidence for the complexity of transcriptional regulation by Runt domain proteins and have identified other transcription factors that cooperate with Runt domain proteins to regulate the activity of different specific cis-regulatory enhancers. The emerging view from studies in both systems is that these proteins act as context-dependent regulators of transcription, activating or repressing gene expression dependent upon the constititution of a particular promoter/enhancer in a particular cell type. These results have yielded new insights into the molecular mechanisms that control animal development and provide a framework for investigating fundamental issues in eukaryotic transcriptional regulation.

Animals↗

Doxycycline-induced transgene expression during Drosophila development and aging.

The "reverse" tetracycline repressor (rtR) binds a specific DNA element, the tetracycline operator (tetO), only in the presence of tetracycline, or derivatives such as doxycycline (dox). Fusion of rtR to the transcriptional activation domain of herpes virus protein VP16 produces a eukaryotic transactivator protein (rtTA). rtTA has previously been shown to allow dox-dependent transcription of transgenes linked to tetO sequences in mammals. To adapt this system to Drosophila, the Actin5C promoter was used to drive constitutive expression of rtTA in transgenic flies. Three reporter constructs, each encoding E. coli beta-galactosidase (beta-gal), were also introduced into transgenic flies. In one reporter seven tetO sequences were fused to the Adh core promoter. The other two reporter constructs contain seven tetO sequences fused to the hsp70 core promoter. Feeding of transgenic Drosophila containing the rtTA construct and any one of the three reporter constructs with dox caused up to 100-fold induction of beta-gal. Dox induced beta-gal expression in all tissues, in larvae and in young and senescent adults. Induction of beta-gal in adults had no detectable effect on life span. These results suggest the potential usefulness of this system for testing specific genes for effects on Drosophila development and aging.

Actins↗

Oral squamous cell carcinoma in association with dental osseointegrated implants. An unusual occurrence.

The major risk factors for developing oral cavity squamous cell carcinoma in the United States include smoking, alcohol, syphilis, and herpes simplex virus type 1. It is difficult to locate a report of squamous cell carcinoma arising in association with osseointegrated dental implants, despite their frequent use. We report an unusual series of 3 cases of squamous cell carcinoma arising around an implant.

Aged↗

Potential toxicity of retrograde uterine passage of particulate matter.

Dusting powders are commonly used on surgical gloves, examination gloves, and condoms. In addition, they are used in diaphragms, sanitary napkins, and toiletries. These dusting powders can gain access to the abdominal cavity through the vagina or through surgical intervention. The toxicity of these dusting powders in the abdominal cavity can be divided into acute and chronic complications that may be life-threatening. The use of medical and surgical products without dusting powders is strongly recommended.

Condoms↗

Evolution of hydrogel polymers as contact lenses, surface coatings, dressings, and drug delivery systems.

Hydrogel polymers are hydrophilic resins that display excellent biocompatibility, which has allowed their application in diverse fields of surgery and medicine. The original hydrogel polymer, a copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate, was developed by Wichterle and Lim in 1954. The development of the first soft hydrogel contact lenses by Wichterle in 1961 represented the first successful clinical application of hydrogel polymers and remains one of the most important uses of hydrogels today. The biocompatibility of hydrogel polymers may be adapted to diverse tissue types by small variations in the makeup of the polymer, including varying the type and amount of monomers and differing the amounts and characteristics of the cross-linking agents used to create the polymer chains. Hydrogels have been successfully developed for use as coatings, soft contact lenses, wound dressings, and drug delivery systems.

Bandages↗

Muscle-specific expression of Drosophila hsp70 in response to aging and oxidative stress.

Induction of Drosophila hsp70 protein was detected during aging in flight muscle and leg muscle in the absence of heat shock, using an hsp70-specific monoclonal antibody, and in transgenic flies containing hsp70-beta-galactosidase fusion protein reporter constructs. While hsp70 and reporter proteins were induced during aging, hsp70 message levels were not, indicating that aging-specific induction is primarily posttranscriptional. In contrast, hsp22 and hsp23 were found to be induced during aging at the RNA level and with a broader tissue distribution. The same muscle-specific hsp70 reporter expression pattern was observed in young flies mutant for catalase (H2O2:H2O2 oxidoreductase, EC 1.11.1.6). In catalase (cat) hypomorphic lines where flies survived to older ages, the time course of hsp70 reporter expression during aging was accelerated, and the initial and ultimate levels of expression were increased. The hsp70 reporter was also induced in young flies mutant for copper/zinc superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1). Taken together, the results suggest that aging-specific hsp70 expression may be a result of oxidative damage.

Aging↗

Molecular evolution of the family Camelidae: a mitochondrial DNA study.

We report the first molecular evolutionary analysis of the family Camelidae by analysing the full DNA sequence of the mitochondrial cytochrome b gene. Estimates for the time of divergence of the Old World (Camelini) and New World (Lamini) tribes obtained from sequence data are in agreement with those derived from the fossil record. The DNA sequence data were also used to test current hypotheses concerning the ancestors of the domesticated llama and alpaca. The results show that hybridization has occurred in the ancestry of both domesticated camelids, obscuring the origin of the domestic species.

Animals↗

Sequence requirements for upregulated expression of Drosophila hsp70 transgenes during aging.

hsp70 protein and hsp70:lacZ fusion reporters are upregulated during aging and in response to oxidative stress in the thorax of Drosophila. hsp70 expression was increased during aging in each of seven different Drosophila genetic backgrounds tested, 2.6-4.8-fold. DNA sequence requirements were investigated by analysis of nine distinct hsp70:lacZ fusion reporter constructs in multiple independent transgenic lines. hsp70 sequences -194 to +276 supported an average 2.7-fold increase during aging. This increase was reduced or eliminated by deletion or point mutation of the heat shock response elements, consistent with a transcriptional mechanism. Similar sequence requirements were observed for increased expression in response to catalase null mutation as a model of oxidative stress. hsp70 5'UTR sequences were required for efficient basal expression of transgenes, but were not sufficient to confer detectable upregulation during aging. Inclusion of additional hsp70 coding region sequences from +276 to + 1011 created a larger hsp70:lacZ fusion protein and had two effects: dramatic reduction of the overall expression level of the fusion protein, and an additional three to fourfold upregulation during aging. These results suggest that the coding region sequences reduce fusion protein abundance and that this negative effect decreases as a function of age. The data support a model for increased expression of hsp70 transgenes during aging involving both transcriptional and posttranscriptional components.

Aging↗

Industrial high-voltage electrical burn of the skull, a preventable injury.

Deep burns of the scalp and skull are often caused by high-voltage electrical injuries. Patients with such injuries should be referred to regional burn centers that are prepared to excise necrotic burn tissue and cover the devitalized bone with a well-vascularized flap. Strategies for prevention of these electrical burns are discussed.

Accidents, Occupational↗

The evolution of functional endoscopic sinus surgery in the Commonwealth of Virginia.

This is the largest retrospective analysis of sinus surgery ever reported involving 5,860 surgical as well as 6,769 diagnostic sinus procedures during a six year period, 1988-1993. During this time interval, the frequency of endoscopic procedures has increased dramatically. Because of the increased frequency of this procedure, we see the need for strict definition of the clinical indications for surgery for patients with chronic or acute sinusitis. In addition, the number of open procedures, namely the Caldwell-Luc procedure, as a treatment for sinusitis remained relatively constant despite the frequent use of endoscopic technique. Because of the endoscopic surgery's increased acceptance and advantages over the open surgical technique, we emphasize the need for continuing educational programs to train surgeons to perform the endoscopic procedure or referral of the patient to an otolaryngologist experienced in this technique.

Adult↗