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Biomedical subjects

A W Davis

Publications and source records attributed to A W Davis.

At least 19 recordsLinked to original sources
PubMed2000

Characterization of defects in adult germline development and oogenesis of sterile and rescued female hybrids in crosses between Drosophila simulans and Drosophila melanogaster.

Crosses between Drosophila melanogaster and D. simulans normally result in progeny that are either inviable or sterile. Recent discovery of strains that rescue these inviability and sterility phenotypes has made it possible to study the developmental basis of reproductive isolation between these two species in greater detail. By producing both rescued and unrescued hybrids and examining the protein product staining patterns of genes known to be involved in early germline development and gametogenesis, we have found that in crosses between D. simulans and D. melanogaster, hybrid female sterility results from the improper control of primordial germline proliferation, germline stem cell maintenance, and cystoblast formation and differentiation during early oogenesis. Rescued hybrid females are fertile, yet they generally have lower amounts of adult germline from the outset and show a premature degeneration of adult germline cells with age. In addition, older rescued hybrid females also exhibit mutant egg phenotypes associated with defects in dorso-ventral patterning which may result from the improper partitioning of cytoplasmic factors during early oogenesis that could stem from the early defect. Although a variety of germline and oogenic defects are described for the hybrid females, all of them can potentially result from the same underlying primary defect. Hybrid males from these same crosses, on the other hand, have no detectable germline in adult reproductive tissues, even when hybrid sterility rescue strains are used, indicating that male sterility and female sterility stem from distinctly different developmental defects.

Animals↗
PubMed2000

Genetic analysis of speciation by means of introgression into Drosophila melanogaster.

In the last decade, the genetic basis of reproductive isolation has been shown to be surprisingly polygenic, and yet even the most efficient system currently in use could lend itself to molecular analysis only in highly selected cases. By extending the recent discovery of fertility rescue between Drosophila melanogaster and Drosophila simulans, we show that this hybridization can permit systematic and precise delineation of the genetic and molecular basis of speciation. In a region of 5% of the D. simulans genome introgressed into D. melanogaster, we discover at least six genes of hybrid male sterility and none for female sterility by deficiency mapping. A single case of hybrid inviability has been tracked down to a 3-Kb element that was inserted into the Cyclin E locus during species hybridization. The extent of interspecific genetic divergence underlying hybrid male sterility, especially in contrast with the low degree of inviability and female sterility, is far greater than expected from previous studies.

Animals↗
PubMed1999

stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster.

Adenine nucleotide translocases (ANT) are required for the exchange of ADP and ATP across the inner mitochondrial membrane. They are essential for life, and most eukaryotes have at least two different Ant genes. Only one gene had been described from Drosophila, and this had not been characterized genetically. We show that mutations in this gene correspond to the previously described loci, sesB and l(1)9Ed. Immediately adjacent to this gene is another encoding a second ANT protein, which has 78% identity to that encoded by sesB/l(1)9Ed. These two genes are transcribed from a common promoter, and their mRNAs are produced by differential splicing. Hutter and Karch suggested that the sesB ANT gene corresponded to Hmr, a gene identified by an allele that rescues otherwise inviable interspecific hybrids between Drosophila melanogaster and its sibling species. This hypothesis is not supported by our study of the ANT genes of D. melanogaster.

Amino Acid Sequence↗
PubMed1996

Camptothecin post-treatments inhibit the biochemical events linked to the tumor-promoting component of carcinogenesis in mouse epidermis in vivo.

20(S)-Camptothecin (CPT), a topoisomerase I inhibitor specifically toxic toward S-phase cells, was tested topically for its ability to inhibit the biochemical markers of skin tumor promotion. CPT has no or very little inhibitory effect on the covalent binding of an initiating dose of 7,12-dimethylbenz-[a]anthracene (DMBA) to DNA at 24 hr, but CPT post-treatments remarkably inhibit stimulations of DNA synthesis caused by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) at 16 hr and a carcinogenic dose of DMBA at 7 days. CPT is a much more potent inhibitor if it is applied 10-14 hr after TPA or 4-6 days after DMBA, when DNA synthesis starts being stimulated after the periods of early inhibition caused by TPA and DMBA. When applied 12 hr after the tumor promoter, the ability of 3-3,000 nmol of CPT to inhibit TPA-stimulated DNA synthesis at 16 hr is dose-dependent. A single dose of 500 nmol of CPT inhibits the entire time course for the stimulation of DNA synthesis observed 16-64 hr after TPA. CPT also reduces the various DNA responses to chronic TPA treatments and structurally different non-TPA-type tumor promoters. CPT may indirectly decrease the ornithine decarboxylase-inducing activity of multiple TPA treatments because it can inhibit the stimulation of RNA synthesis by this compound. However, CPT fails to alter TPA-stimulated hydroperoxide production in relation to its inability to inhibit TPA-stimulated protein synthesis. On an equal dose basis, topotecan and 10-hydroxycamptothecin are more and less effective than CPT, respectively, whereas 10,11-methylenedioxycamptothecin is much more potent than its parent compound at inhibiting the DNA response to TPA. A single dose of 400 nmol of CPT has no effect on tumor initiation when applied 4 hr before or 1 hr after a single subcarcinogenic dose of DMBA. In contrast, 400 nmol of CPT chronically applied 1 hr before or 24 hr after each treatment with TPA remarkably inhibits the complete tumor-promoting activity of this agent. CPT post-treatments also inhibit the respective activities of TPA and mezerein in the 1st and 2nd stages of skin tumor promotion.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Rescue of hybrid sterility in crosses between D. melanogaster and D. simulans.

The genetic analysis of reproductive isolation between species of Drosophila has now reached the resolution necessary to start answering one of the fundamental questions of evolution: what is the genetic basis of species differences? A.H. Sturtevant, one of the founders of Drosophila genetics, was fascinated by this question and thought he had found a way to analyse it when he realized that 'Drosophila melanogaster' was actually two species: D. melanogaster and D. simulans. By passing genes between these two species he hoped to investigate their genetic differences directly. No doubt he was disappointed to find that the D. melanogaster/D. simulans hybridization resulted only in unisexual sterile hybrids, a disappointment appreciated all the more by modern evolutionary biologists. Seventy-five years after Sturtevant's description of D. melanogaster/D. simulans hybrid sterility, we have discovered a strain of D. simulans that produces fertile female hybrids in crosses with D. melanogaster. Our discovery promises to bring the enormous resolution of D. melanogaster genetics to the study of reproductive isolation and species differences.

Animals↗
PubMed1996

Characterization of the antitumor-promoting activity of camptothecin in SENCAR mouse skin.

(+)-Camptothecin (CPT), a topoisomerase I inhibitor specifically toxic toward S phase cells, was tested topically for its ability to inhibit skin tumor initiation by 7,12-dimethylbenz[a]anthracene (DMBA) and complete tumor promotion by 12-0-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Even though CPT does not prevent the covalent binding of a subcarcinogenic dose of DMBA to DNA, it enhances early inhibition of DNA synthesis caused by this initiator and may decrease the essential role of DNA replication in tumor initiation. Indeed, CPT (400 nmol) applied 4 h before or 1 h after DMBA inhibits the yield, but not the incidence, of skin tumors initiated by this compound. Moreover, because it inhibits TPA-stimulated DNA synthesis at 16 h when applied 12 h after the tumor promoter, CPT partially decreases tumor initiation when DMBA is applied 16 h after a TPA pretreatment. CPT (400 nmol) applied 1 h before or 4, 12, 24 or 48 h after each promotion treatment with TPA remarkably inhibits the incidence and yield of skin tumors promoted by this agent. CPT delays and inhibits promotion of skin tumors the most when applied 12-24 h after each TPA treatment, at times when it can block the stimulation of DNA synthesis that follows the period of early inhibition caused by TPA. The ability of post-treatments with 25, 100 and 400 nmol CPT to inhibit skin tumor promotion is dose dependent. In the TPA (stage I)-mezerein (stage 2) protocol CPT (400 nmol) post-treatment inhibits both the first and second stages of tumor promotion, related to its ability to decrease the DNA and ornithine decarboxylase responses required for stages 1 and 2 respectively. The classic model of multistage skin carcinogenesis, therefore, may be valuable to determine if novel CPT analogs are more effective than their parent compound at inhibiting tumor initiation, promotion and progression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

The broom of the sorcerer's apprentice: the fine structure of a chromosomal region causing reproductive isolation between two sibling species of Drosophila.

How many genes contribute to reproductive isolation between closely related species? We determined the number of genes located in the 9D-12B region of the Drosophila mauritiana X chromosome that cause hybrid male sterility in a D. simulans background. Previous low resolution studies suggested that a single hybrid sterility factor was associated with this region. In this study, by taking advantage of a cluster of visible and DNA markers, we identified three D. mauritiana factors in this region and then subjected one of them to detailed analysis. This factor again turned out to be comprised of three factors; one of which, mapped to within 200 kb, may in fact be two factors. The title refers to this exercise of splitting sterile introgressions into ever smaller ones, each of which retains partial or full sterility effects. In a region representing a mere 3% of the Drosophila genome, no fewer than six loci of hybrid sterility were identified between two sibling species that have not shown clear divergence at the molecular level. These results suggest that levels of genetic divergence between closely related species may be quite high for functionally important traits even when the opposite is true for randomly chosen loci.

Animals↗
PubMed1996

Discord between the phylogenies inferred from molecular versus functional data: uneven rates of functional evolution or low levels of gene flow?

According to measures of molecular divergence, the three species of the Drosophila simulans clade are closely related to and essentially equidistant from each other. We introgressed 10% of the D. sechellia X chromosome into a pure D. simulans genetic background and found that males carrying this introgressed region were consistently fertile; in contrast, males carrying the same segment from D. mauritiana are sterile and suffer from incompatibilities at a minimum of four loci. Together with other recent results, these data suggest that D. simulans and D. sechellia are much more closely related to each other than either is to D. mauritiana. How can we reconcile the phylogeny inferred from the density of hybrid sterility genes with that inferred from molecular divergence? If the molecular phylogeny is correct, the discrepancy might be explained by uneven rates of functional evolution, resulting in the uneven accumulation of substitutions with corresponding negative effects in hybrids. If the functional phylogeny is correct, then low levels of gene flow across nascent species boundaries, particularly for loci not tightly linked to a hybrid sterility gene, may have erased the original pattern of lineage splitting. We propose tests that will allow us to discriminate between these hypotheses.

Animals↗
PubMed1994

Genetics of reproductive isolation in the Drosophila simulans clade: complex epistasis underlying hybrid male sterility.

We have analyzed the sterility associated with introgressions of the distal one-fourth of the X chromosome from either Drosophila mauritiana or Drosophila sechellia into the genome of Drosophila simulans using a series of visible and DNA markers. Because in Drosophila hybrids, male sterility is usually complete and is often tightly linked with each of several markers used in crosses, a simple genetic basis has generally been assumed. In our low resolution mapping experiment, we were not able to reject the null hypothesis that a single gene, introgressed from either D. mauritiana or D. sechellia, is the cause of male sterility. High resolution mapping, however, reveals a much more complex picture. At least three distinct factors from D. mauritiana, or two from D. sechellia, were identified that need to be jointly present to confer full sterility. Each individual factor by itself is relatively ineffective in causing sterility, or even a partial spermatogenic defect. Moreover, there appear to be more sterility factors on comparable introgressions from D. mauritiana than from D. sechellia. On the basis of these observations, we propose a model which suggests that multilocus weak allele interactions are a very common cause of reproductive incompatibility between closely related species. We also present theoretical argument and empirical evidence against extrapolating the results of within-species analysis to interpret the genetic basis of species differences. The implications of this model on the theories of evolution of species differences and the attempt to understand the mechanisms of hybrid sterility/inviability at the molecular level are discussed.

Animals↗
PubMed1994

Evidence for complex genic interactions between conspecific chromosomes underlying hybrid female sterility in the Drosophila simulans clade.

F1 hybrid females between the sibling species Drosophila simulans, Drosophila mauritiana and Drosophila sechellia are completely fertile. However, we have found that female sterility can be observed in F2 backcross females who are homozygous for D. simulans X chromosomes and homozygous for autosomal regions from either D. mauritiana or D. sechellia. Our results indicate that neither D. mauritiana autosome (2 or 3) can cause complete female sterility in a D. simulans background. The simultaneous presence of homozygous regions from both the second and third chromosomes of D. mauritiana, however, causes nearly complete female sterility which cannot be accounted for by their individual effects. The two autosomes of D. sechellia may show a similar pattern. From the same crosses, we also obtained evidence against a role for cytoplasmic or maternal effects in causing hybrid male sterility between these species. Taken with the results presented elsewhere, these observations suggest that epistatic interactions between conspecific genes in a hybrid background may be the prevalent mode of hybrid sterility between recently diverged species.

Animals↗
PubMed1991

Osteonecrosis of the femoral head. A prospective randomized treatment protocol.

Conservative treatment versus core decompression for cases of osteonecrosis (ON) of the femoral head was prospectively reviewed in 36 patients. A preoperative evaluation of the patients' history, physical examination, Harris Hip Score, roentgenograms, computed tomography, bone scan, magnetic resonance imaging, and measurement of the intraosseous pressure was used to grade the level of ON according to a rating system developed by Ficat. Hips were randomized to core decompression or conservative treatment groups. Fifty-five hips in 36 patients were randomized (29 surgical and 26 conservative). When success was gauged by Harris Hip Scores for Stage I hips, treatment was successful for seven of ten (70%) operatively treated hips and one of five (20%) non-operatively treated hips. Among Stage II hips, treatment was successful for five of seven (71%) decompressed hips and none of seven conservatively treated hips. Successful treatment was accomplished in eight of 11 hips (73%) and one of ten hips (10%) in decompression and conservative groups, respectively, for Stage III hips. Stages 0 and IV had groups too small for comparison. Less successful results were seen if roentgenographic criteria of success were used. Survival analysis showed more favorable results with surgical treatment. Core decompression produced better results than conservative treatment in the early stages of ON.

Adolescent↗
PubMed1990

Integrating the halfway house with day-hospital treatment: three perspectives.

In this paper, three treaters from three different psychiatric hospitals delineate specific criteria for developing a mutually beneficial, interactive relationship between day hospitals and halfway houses. Ideas for setting up such a cooperative venture are based on the strengths of these three existing programs at the Menninger Clinic, Timberlawn Psychiatric Hospital, and Harding Hospital. Potential problem areas are discussed such as admission and discharge criteria, communication between separate program components, treatment responsibility, staff roles, and program goals and boundaries.

Communication↗
PubMed1990

Problematic fractures and dislocations in the foot and ankle of athletes.

Foot fractures can significantly compromise an athlete's career. Early recognition and treatment of occult fractures will reduce lay-off time and decrease the likelihood of prolonged impairment of performance. The appropriate treatment of radiographically obvious fractures will have a similar effect. The key to making an early diagnosis is the recognition of characteristic patterns on physical examination and the aggressive investigation of persistent foot pain in the athlete, whether it follows an injury or not. When a fracture is not apparent on routine radiographs, special diagnostic techniques, particularly technetium bone scanning, can effectively screen for bony injury. In the competitive athlete there is no reason to adopt a "wait-and-see" attitude. The approach in treating these injuries in athletes should be similarly definitive. If continued participation will delay healing or resolution of the symptoms, it should not be tolerated.

Ankle Injuries↗
PubMed1984

Prognostic factors related to survival and complication-free times in airmen medically certified after coronary surgery.

This study was designed to identify prognostic factors for survival and complication-free times among airmen who had regained their medical certificate after coronary bypass surgery. Airmen who had petitioned the Federal Aviation Administration for a special issuance of medical certification to fly because they have had coronary bypass surgery were identified and followed retrospectively from 1970 to the end of 1980. There were 261 airmen in the study population. Demographic, medical, and prognostic information were collected on each airmen before and after surgery. Univariate and multivariate statistical methods were used in analysing the data. From the univariate analysis, presurgery diastolic blood pressure and coffee history, and postsurgery coffee history were identified as being related to complication-free time. Diagnosis for surgery, smoking history, and development of complications were identified as being related to survival after coronary bypass surgery. From the multivariate analysis, four prognostic factors: postsurgery serum cholesterol, number of grafts, postsurgery serum triglyceride, and postsurgery alcohol history were identified for complication-free time. It was concluded that using pre- and post-surgery information can help determine the long term survivors and those who will stay complication-free 11 years after coronary bypass surgery.

Aerospace Medicine↗
PubMed1982

Acupuncture therapy for the treatment of tobacco smoking addiction.

Acupuncture has been reported as an effective treatment for some addictions. The purpose of this study was to evaluate acupuncture treatment effect on the cigarette smoking habit with a motivated population in a controlled clinical setting. From a volunteer research population, sixteen matched pairs were assembled according to age, sex, and severity of smoking habit. Research subjects were randomly assigned to real or sham acupuncture treatment groups. Self-reported cigarette logs were measured pre-treatment and post-treatment. Analysis of variants confirmed homogeneity of group pre-treatment cigarette consumption. Cigarette consumption significantly decreased in both th e real and sham treatment groups. Treatment group, age, sex, or severity of smoking habit were not significant factors in treatment effects for cessation of smoking. Legitimate crossover treatment for sham research group showed a significant decrease (p less than or equal to 0.05) in cigarette consumption; this change was not statistically different from change in cigarette consumption during placebo treatment. A discussion of acupuncture point selection rationale is made as is an analysis of Tehchi sensations and subjective reports of appetite for cigarettes. Acupuncture did not enhance the cessation of cigarette smoking in this study.

Acupuncture Therapy↗
PubMed1981

Postmortem coronary atherosclerosis findings in general aviation accident pilot fatalities: 1975-77.

The autopsies of 764 pilots involved in fatal general aviation accidents during the years 1975-77 were reviewed to appraise the age specific prevalence of coronary atherosclerosis among the autopsied group. Of the pilots killed in aircraft accidents and autopsied during 1975-77, 51% were found to have some degree of coronary atherosclerosis ranging from minimal to severe. However, only about 5% of the autopsied group were categorized as having severe coronary atherosclerosis. The rate per 1,000 of severe coronary atherosclerosis increased with age from 14.5 for ages less than 30, to 89.9 for ages 50 years and above; the rate nearly tripled from ages 30-39 to 40-49 (22.1 to 63.6). The prevalence of coronary atherosclerosis among this group of autopsied airmen is less than would have been expected based on the results of other recent studies.

Accidents, Aviation↗