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Biomedical subjects

D L Davis

Publications and source records attributed to D L Davis.

At least 91 records · Page 5Linked to original sources

Chicken repeat 1 elements contain a pol-like open reading frame and belong to the non-long terminal repeat class of retrotransposons.

Chicken genomes contain approximately 30,000 chicken repeat 1 (CR1) elements scattered among single-copy sequences, but no information has yet been presented to account for how these elements could have dispersed. The fact that CR1 elements have common (although atypical) 3' ends and variable 5' truncations suggested to us that they might belong to the class of non-long terminal repeat retrotransposons that encode reverse transcriptases. From an analysis of unusually large CR1 elements, we now provide evidence for the presence of such a reverse transcriptase open reading frame. CR1 elements are distantly related to previously described non-long terminal repeat retrotransposons; however, we find that frog and torpedo ray genomes contain dispersed open reading frame segments that have > 50% identity to the CR1 open reading frame. This result suggests that CR1-like elements exist in several vertebrate classes that have evolved independently for approximately 400 million years.

Amino Acid Sequence↗

Secretion of beta-amyloid precursor protein cleaved at the amino terminus of the beta-amyloid peptide.

The accumulation in brain of senile plaques containing beta-amyloid protein (A beta) is a defining feature of Alzheimer's disease. The amyloid precursor protein (APP)4 from which A beta is derived is subject to several genetic mutations which segregate with rare familial forms of the disease, resulting in early onset of dementia and plaque formation, suggesting that APP metabolism plays a causal role in the disease. Various cell types have been shown to release a soluble form of A beta, thus allowing for the in vitro study of A beta generation. We report here evidence that a substantial portion of the APP secreted by human mixed brain cell cultures, as well as that present in cerebrospinal fluid, is of a novel form cleaved precisely at the amino terminus of A beta, suggesting that a secretory pathway is involved in A beta genesis.

Amyloid beta-Protein Precursor↗

Agricultural exposures and cancer trends in developed countries.

Recent increases have been reported in industrial countries for several sites of cancer. The causes of these increases remain unknown. Efforts should proceed to identify those occupational groups with increases in the same sites, as these may indicate relevant exposures. Two analyses were undertaken: trends in cancer mortality in industrial countries were reviewed to identify recently increasing sites and summaries were compiled of studies on farmers which have shown increased risks for these same sites of cancer. Using data provided by the World Health Organization, age-specific rates were developed for a number of sites of cancer from 1968 to 1986. Trends in the ratio of male to female cancer mortality were also assessed for several of these countries. Based on a literature review by the National Cancer Institute, patterns of cancer in farmers reported in 20 studies from 8 countries are summarized, weighting each study by its size to create combined relative risks. In industrial countries, rates of cancer mortality increased for a number of sites, including melanoma, prostate, non-Hodgkin's lymphoma, multiple myeloma, breast, brain, and kidney cancer. The ratio of male to female cancer mortality (for all sites of cancer excluding lung) has generally increased in several countries during this same time period. Many of the same sites that have increased in the general population have also been found to be increasing in farmers. Significant excesses occurred for Hodgkin's disease, multiple myeloma, leukemia, skin melanomas, and cancers of the lip, stomach, and prostate. Nonsignificant increases in risk were also noted for non-Hodgkin's lymphoma and cancers of connective tissue and brain in many surveys.(ABSTRACT TRUNCATED AT 250 WORDS)

Agricultural Workers' Diseases↗

Medical hypothesis: xenoestrogens as preventable causes of breast cancer.

Changes in documented risk factors for breast cancer and rates of screening cannot completely explain recent increases in incidence or mortality. Established risk factors for breast cancer, including genetics, account for at best 30% of cases. Most of these risk factors can be linked to total lifetime exposure to bioavailable estrogens. Experimental evidence reveals that compounds such as some chlorinated organics, polycyclic aromatic hydrocarbons (PAHs), triazine herbicides, and pharmaceuticals affect estrogen production and metabolism and thus function as xenoestrogens. Many of these xenoestrogenic compounds also experimentally induce mammary carcinogenesis. Recent epidemiologic studies have found that breast fat and serum lipids of women with breast cancer contain significantly elevated levels of some chlorinated organics compared with noncancer controls. As the proportion of inherited breast cancer in the population is small, most breast cancers are due to acquired mutations. Thus, the induction of breast cancer in the majority of cases stems from interactions between host factors, including genetics and environmental carcinogens. We hypothesize that substances such as xenoestrogens increase the risk of breast cancer by mechanisms which include interaction with breast-cancer susceptibility genes. A series of major epidemiologic studies need to be developed to evaluate this hypothesis, including studies of estrogen metabolism, the role of specific xenoestrogenic substances in breast cancer, and relevant genetic-environmental interactions. In addition, experimental studies are needed to evaluate biologic markers of suspect xenoestrogens and biologic markers of host susceptibility and identify pathways of estrogenicity that affect the development of breast cancer. If xenoestrogens do play a role in breast cancer, reductions in exposure will provide an opportunity for primary prevention of this growing disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Failure of dietary amino acid supplementation at weaning to influence reproductive traits of sows.

Primiparous and multiparous sows received a single dietary supplement of either L-tyrosine, L-phenylalanine, or L-glutamate in their feed on the day after weaning and effects on various reproductive traits were evaluated in three experiments. In Exp. 1 and 2, sows received either 0 (control; n = 22 and 64, respectively) or 100 mg of L-tyrosine/kg BW (n = 24 and 62, respectively) on the day after weaning. In Exp. 1, days from weaning to estrus (5.5 +/- .3 vs 5.3 +/- .3 d) and ovulation rate (15.6 +/- .9 vs 15.6 +/- 1) were similar in control and tyrosine-supplemented sows. In Exp. 2, interval from weaning to estrus was extended (P < .01) in tyrosine-supplemented sows (6.4 +/- .5 d) compared with controls (4.5 +/- .5 d), but this was due to long return intervals in 7 of 62 tyrosine-supplemented sows. Total number of pigs born (10.2 +/- .4 vs 10.0 +/- .4) was similar in control and tyrosine-supplemented sows. In Exp. 3, sows received either no supplemental amino acids (n = 31) or their diet was supplemented with 100 mg/kg BW of either L-tyrosine (n = 31), L-phenylalanine (n = 33), or L-glutamate (n = 32). Neither days from weaning to estrus nor subsequent farrowing traits were altered in sows that received supplemental amino acids on the day after weaning. In conclusion, a single dietary supplementation of either tyrosine, phenylalanine, or glutamate to sows on the day after weaning failed to improve interval from weaning to estrus, ovulation rate, or litter traits at subsequent farrowing.

Amino Acids↗

Studies of uterine secretions and products of primary cultures of endometrial cells in pigs.

The uterus plays a central role in the reproductive biology of mammals. Adaptation of the uterus from an oviparous to a viviparous nature required changes that involved production of a uterine environment that could support the development of the embryo and fetus. Production of a suitable environment includes the synthesis and secretion of products by the uterine endometrium. However, the uterine endometrium is not a single homogeneous unit, but rather consists of several cell populations. Recent accomplishments in cell culture techniques provide a means for examining the contributions and secretory control of different endometrial cell populations. Furthermore, it is possible to recombine specific cell types to study their interaction. It is clear that the luminal epithelium, glandular epithelium and endometrial stroma produce different secretory products. Some secretions (for example uteroferrin) are secreted by only one cell type; others (for example prostaglandins, PGs) are secreted by all types of cell. There is much to be learned about the functions and regulations of endometrial secretions and there are important aspects of the role of the endometrium in pregnancy that present concepts do not address. For example, there is no explanation for the required synchrony between the embryo and uterus before day 10 and the implications of control of the uterine environment by progesterone from day 4 to day 10 are not understood. Almost all of the uterine secretory proteins are produced after day 10. In this review, we consider the protein and prostaglandin products from the different cell populations of the pig endometrium and propose a model to explain the integration of multiple sources of PGs and multiple regulators of PG secretion. Our purpose is to facilitate a more complete understanding of the individual uterine cell populations and a better understanding of how these cell types interact to function as a complete unit.

Animals↗

Modulation of the activity of calpain II by phosphorylation--changes in the proteolysis of cyclic AMP-dependent protein kinase (peak II, DEAE).

The proteolysis of the 32P-labeled holoenzyme of cyclic AMP-dependent protein kinase (A-PKII:DEAE, peak II fraction) was analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. The contaminants of the A-PKII and calpain II apparently did not interfere with the accuracy of this highly sensitive analysis. Phosphorylation of calpain II by the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK) greatly enhanced the proteolysis of A-PKII, whereas phosphorylation by protein kinase C (PK-C) or cyclic GMP-dependent protein kinase (G-PK) slightly altered the proteolysis.

Calpain↗

Regulation of the phosphorylation of histones and glycogen synthase.

The phosphorylation of histones and glycogen synthase by protein kinases was analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. The phosphorylation of histone III-S by the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK) or cGMP-dependent protein kinase (G-PK) was inhibited by archidonic acid, sphingosine and staurosporine. Using the catalytic subunit of A-PK, the phosphorylation of histone VIII-S was inhibited by Ca2+, arachidonic acid and staurosporine; the phosphorylation of histone II-S was inhibited by phosphatidyl ethanolamine, phosphatidyl inositol, arachidonic acid and staurosporine; and the phosphorylation of glycogen synthase was inhibited by arachidonic acid and staurosporine. After being phosphorylated by the catalytic subunit of A-PK, calpain II with 4 microM Ca2+ was less effective in degrading histone III-S, which had been prephosphorylated by PK-C.

AMP-Activated Protein Kinases↗

Isolation of a chicken HMG2 cDNA clone and evidence for an HMG2-specific 3'-untranslated region.

HMG1 and HMG2 (high-mobility group proteins) are two of the most abundant nonhistone chromosomal proteins in higher eukaryotes. Mammalian HMG1 cDNA sequences have the unusual feature of being conserved not only over their coding regions, but also over large segments of their 3'-untranslated regions (3' UTRs) as well. In contrast, the only reported mammalian HMG2 cDNA clone has a distinct 3' UTR. We now report the isolation of a chicken HMG2 cDNA clone and show that it is markedly similar to the mammalian HMG2 cDNA clone over both its coding regions and 3' UTRs. We therefore infer that the 3' UTRs of the HMG1 and HMG2 genes are subject to distinct evolutionary pressures. Our data, along with published data, also serve to highlight 26 amino acid positions where HMG1 and HMG2 are distinctly conserved, and we note that trout HMG-T conforms to the HMG1 paradigm at most of these diagnostic positions.

Amino Acid Sequence↗