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Biomedical subjects

D L Davis

Publications and source records attributed to D L Davis.

At least 73 records · Page 4Linked to original sources
PubMed1995

Estimating avoidable causes of cancer.

Evidence that much cancer is preventable derives from observations of time trends and geographic patterns of cancer, birth cohort changes, high risks in groups with well-defined exposures, and experimental studies. In an effort to identify additional opportunities for reducing the impact of cancer on society, this conference assessed avoidable causes of cancer. The magnitude and extent of preventable causes of cancer are subjects of intense debate, with discrepancies often related to the use of different time frames and different weights for epidemiologic and toxicologic evidence. There is much agreement, however, about the exposures that increase risk, notably tobacco, alcohol, diet, radiation, medications, occupational exposures, general environmental exposures, and infectious agents. Interactions between carcinogenic exposures and genetic susceptibility are also important. Concerted efforts are needed to identify avoidable causes of cancer and to apply knowledge already obtained to reduce the cancer burden.

Alcohol Drinking↗
PubMed1995

Spinal cord astrocytoma: pathological and treatment considerations.

Seventy-nine patients underwent surgery, with or without radiation therapy, for astrocytoma of the spinal cord. There were 43 tumors (54%) classified as pilocytic astrocytoma and 25 (32%) as diffuse fibrillary astrocytoma. Eleven tumors (14%) could not be classified other than as astrocytoma, "type not otherwise specified." The 10-year overall survival rate for all 79 patients was 50% but significantly differed by histological type: 81% for patients with pilocytic astrocytoma compared to 15% for those with diffuse fibrillary astrocytoma. Tumor grade by the Kernohan, et al., or St. Anne-Mayo methods was also a significant predictor of survival in patients with diffuse fibrillary astrocytoma. The extent of surgical resection (biopsy vs. subtotal resection vs. gross total resection) did not significantly impact survival among patients with pilocytic or nonpilocytic astrocytomas of the spinal cord, although there was a trend toward poorer survival in patients undergoing some degree of resection as opposed to biopsy. Postoperative radiation therapy improved survival but did so more for diffuse fibrillary astrocytoma than pilocytic astrocytoma. In this series, histological type was the most significant predictor of survival in patients with astrocytoma of the spinal cord. The survival rate was highest in patients who underwent biopsy followed by postoperative radiation therapy.

Adult↗
PubMed1994

Alternative promoter usage and splicing options result in the differential expression of mRNAs encoding four isoforms of chicken VBP, a member of the PAR subfamily of bZIP transcription factors.

We previously isolated a set of overlapping cDNA clones that encoded a unique open reading frame for the chicken VBP transcription factor. We now report the isolation of a cDNA clone that encodes a complete open reading frame for a VBP isoform that differs from the previously reported sequence at both the amino-terminal and carboxyl-terminal ends. An analysis of the VBP gene revealed that the two different amino-terminal sequences map to alternative first exons and that the two different carboxyl-terminal sequences reflect an optional splicing event which can occur only on transcripts that are polyadenylated at the more distal of two polyadenylation sites. An RT-PCR analysis further revealed that a total of four VBP isoforms are encoded by the combinatorial use of these two splicing options. The mRNAs for these four isoforms are differentially expressed in different tissues and cell types. We provide evidence that one function of the amino-terminal domains is to impose cell type specificity on a core transactivation domain that is present in all four isoforms. Since it is known that VBP can heterodimerize with other members of the PAR subfamily of bZIP factors, our evidence for four VBP isoforms greatly expands the number of complexes that may be used to effect transcriptional regulation through PAR-factor binding sites.

Alternative Splicing↗
PubMed1994

Regulation of the phosphorylation of calpain II and its inhibitor.

Phosphorylation of calpain II (or its inhibitor) by the catalytic subunit of cyclic AMP-dependent protein kinase (A-PK), cyclic GMP-dependent protein kinase (G-PK), and protein kinase C (PK-C) was analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. Among these protein kinases, the catalytic subunit of A-PK exhibited the strongest phosphorylations of both calpain II and its inhibitor. Arachidonic acid and staurosporine effectively inhibited phosphorylation regardless the type of kinase tested. Despite its lack of effect on the phosphorylation of calpain II by the catalytic subunit of A-PK, sphingosine moderately enhanced the phosphorylation of calpain II by G-PK. Other agents, including phosphatidylethanolamine, phosphatidylinositol and 1, 2-dioleoyl-sn-glycerol, had no significant effect.

Binding Sites↗
PubMed1994

Decreasing cardiovascular disease and increasing cancer among whites in the United States from 1973 through 1987. Good news and bad news.

OBJECTIVE: Trends in cancer mortality, cardiovascular mortality, and cancer incidence are assessed among US whites to determine whether aging of the population and smoking patterns completely account for increased cancer rates from 1973 through 1987. DESIGN: For mortality, percentage changes in age-specific rates were calculated. For cancer incidence, trends in age-specific rates across time periods and birth cohorts were assessed for several sites. MAIN OUTCOME MEASURES: National US cardiovascular and cancer mortality rates and incidence rates for smoking-related cancer, breast cancer, and all other types of cancer in 10% of the US population covered by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program were analyzed. RESULTS: From 1973 through 1987, cardiovascular mortality decreased 42% in the age group 0 to 54 years and decreased 33% in the age group 55 to 84 years; concurrently, cancer mortality decreased 17% in the younger group but increased 12% in the older group. By 1987, even though proportionally fewer people in the older age groups died, relatively more of them died of cancer. Men born in the 1940s had twice as much cancer as those born in 1888 through 1897 and more than twice as much cancer not linked to smoking; women born during this period had 50% and 30% more of these same cancers, respectively. Rates of smoking-related cancers in recent cohorts of women were five to six times greater than in those born in 1888 through 1897, while rates in men declined. Recent cohorts of women also had more than twice as much breast cancer as those born in 1888 through 1897. CONCLUSIONS: In recent US birth cohorts, our model found that increases in cancer have occurred that are not solely linked to aging of the population and smoking patterns. In light of these results and similar findings in Sweden, changes in carcinogenic hazards in addition to smoking are likely to have occurred and need to be studied further.

Adolescent↗
PubMed1994

Organochlorine exposure estimation in the study of cancer etiology.

This paper discusses sampling and design considerations relevant to the estimation of exposure to organochlorine compounds in epidemiological studies. We consider exposures measured directly via biomarkers of exposure in the body. It is critical for the design, implementation, and evaluation of studies that epidemiologists and biostatisticians be familiar with methodological issues relevant to the direct measure of exposure. Etiologic, toxicokinetic, quality control and quality assurance, and statistical sampling are discussed. Finally, the limitations of these studies and the need for complete reporting of methods are discussed.

Calibration↗
PubMed1994

Expression and regulation of steroid 5 alpha-reductase 2 in prostate disease.

The androgen dihydrotestosterone is synthesized by the enzyme steroid 5 alpha-reductase, and it is required for growth and development of the prostate. We used immunohistochemistry to examine the expression of the type 2 isozyme of 5 alpha-reductase in benign prostatic hyperplasia and prostate cancer. The type 2 isozyme is highly expressed within stromal cells in both disease states. No type 2 isozyme is detectable in a lymph node metastasis. Immunoblotting studies show that androgen ablation therapies substantially decrease isozyme expression in the epididymis but have a lesser effect on expression in the prostate. Finasteride therapy (2 weeks to 3 years) did not abolish expression of the prostatic type 2 isozyme nor did this drug treatment induce expression of the type 1 isozyme.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

Peri-oestrous hormone profiles, embryonic survival and variation in embryonic development in gilts and primiparous sows.

The primary objective of this study was to determine whether embryo survival in gilts and primiparous sows is related to variations in the peri-oestrous profiles of oestradiol, progesterone and LH. A secondary objective of the present work was to compare embryo development and certain endocrine characteristics in gilts and primiparous sows. Sows (n = 6) and gilts (n = 6) were catheterized in the jugular vein on the day after weaning or on day 14 of the oestrous cycle, respectively. Additional females (one gilt and seven sows) were examined only for characteristics of embryonic development. Embryos were recovered on day 11.5-11.75 of gestation, and size and volume of individual embryos were recorded. Minimal differences were observed between sows and gilts for endocrine and embryo data. Embryo recovery was 71.38 +/- 4.77% based on the number of corpora lutea. However, endocrine differences were noted for pigs with high embryo survival (> 71% recovery) compared with those with low survival. Peak oestradiol concentration occurred closer (P < 0.05) to the onset of oestrus in pigs with high embryo survival than in pigs with low embryo survival (3.3 +/- 4.6 h after oestrus versus 13.0 +/- 5.5 h before oestrus) and peak LH concentration occurred later (P < 0.05) after the onset of oestrus for pigs with high embryo survival. Peak oestradiol concentration tended (P = 0.07) to be higher in pigs with low embryo survival (35.21 +/- 2.56 pg ml-1) compared with pigs with high embryo survival (28.17 +/- 2.14 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Electronic animal identification for controlling feed delivery and detecting estrus in gilts and sows in outside pens.

The objective of the present study was to evaluate the feasibility of delivering feed and detecting estrous behavior by computer-controlled equipment in a nonconfinement environment. In Exp. 1, gilts were assigned to treatment when detected pregnant by ultrasound at 30 to 35 d after artificial insemination. They were assigned to be fed individually in stalls once/day (0830) with a scoop (controls, n = 20) or with an electronic sow feeding station (ESF, n = 20). The ESF gilts received their feed in 98.6-g aliquots at 80-s intervals as they visited the feeding station. Control vs ESF gilts did not differ (P > .8) for backfat (2.2 vs 2.1 cm) or weight (170 vs 172 kg) before farrowing, total and live pigs/litter (9.3 and 8.7 vs 9.1 and 8.8), or litter birth weight (12.7 vs 12.1). In Exp. 2, proceptive behavior, as measured by visits to a boar's pen, were recorded electronically, and observed estrus was evaluated in two groups of sows during their first (n = 11) and second and third (n = 19) estrous cycles and in one group of gilts (n = 14). A partition prevented visual and physical contact between the boar and the visiting females except where the electronic estrus detection (EED) station was installed. Feed delivery software was used to monitor boar visitation even though no feed delivery equipment was present at the boar pen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1994

Phosphorylation of endogenous substrates of yeast protein kinase C regulated by lipid-triton micelles.

In the DE-52 fraction 19 of the crude cytosolic extract of Saccharomyces cerevisiae, the 31-kDa endogenous substrate(s) of protein kinase C were detected by SDS-polyacrylamide gel electrophoresis and autoradiography. Phosphorylation of the substrate(s) depended on Ca2+, phosphatidylserine and diacylglycerol. It was also enhanced by phosphatidylinositol, phosphatidylethanolamine and phosphatidylglycerol (dioleoyl), but inhibited by arachidonic acid and sphingosine.

Arachidonic Acid↗
PubMed1994

Dual modulation of the phosphorylation of endogenous yeast proteins by arachidonic acid and phosphatidylinositol.

Phosphorylation of endogenous yeast substrates in DE-52 fractions were analysed by SDS-polyacrylamide gel electrophoresis and autoradiography. In fractions 29 and 45, phosphatidylinositol inhibited the phosphorylation of multiple peptides with a wide range of molecular mass whereas it enhanced the phosphorylation of peptides smaller than 14 kD. Similar dual modulation of the phosphorylation by arachidonic acid was observed in fraction 37 which also contained potent phosphatidylserine-activating protein kinase C.

Arachidonic Acid↗
PubMed1994

Role of biomarkers in identifying and understanding environmentally induced disease.

Establishing associations between environmental agents and disease presents challenges to both epidemiologists and toxicologists, particularly in cases of complex gene-environment interactions and when there is a long latency between exposure and disease. Biologic markers, physiological signals that reflect exposure, early cellular response, or inherent or acquired susceptibilities, provide a new strategy for resolving some of these problems. Biomarker research assumes that toxicant-induced diseases are progressive and that injury proceeds from entry of the toxicant into target cells, which induces subcellular biochemical events, to cell- and organ-level events that eventually induce irreversible or persistent organism dysfunction. The epidemiologic value of a biomarker lies in its ability to predict backward toward exposure and forward toward risk of clinical outcome, which is largely unknown. Research in mechanistic toxicology will advance the range of useful biomarkers in epidemiology and clinical medicine.

Adult↗
PubMed1994

Enhanced phosphorylation of yeast endogenous substrates by phosphatidylglycerol (dioleoyl) and phosphatidylinositol.

Protein kinases and their endogenous substrates from the crude cytosolic extract of Saccharomyces cerevisiae were coeluted in the fraction 13 on DE-52 column chromatography. Analyses of SDS-polyacrylamide gel electrophoresis and autoradiography revealed that the peptides between 14 and 34 kDa were the major phosphorylated substrates. In the presence of Ca2+ and Mg2+, the phosphorylation was suppressed strongly by the regulatory subunit of cAMP-dependent protein kinase and slightly by oleic acid, whereas it was augmented appreciably by phosphatidylglycerol (dioleoyl) and phosphatidylinositol.

Adenosine Triphosphate↗