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Biomedical subjects

D L Davis

Publications and source records attributed to D L Davis.

At least 127 records · Page 7Linked to original sources

Pig endometrial cells in primary culture: morphology, secretion of prostaglandins and proteins, and effects of pregnancy.

Luminal epithelial, glandular epithelial, and stromal cells were isolated from pig endometrium by enzymatic dispersion and sieve filtration. The three cell types, maintained in primary culture, showed distinctly different morphologies when viewed by light and scanning electron microscopy. Immunocytochemical staining indicated that luminal and glandular epithelial cells were positive for both cytokeratin and vimentin. However, stromal cells were positive only for vimentin. Acid phosphatase activity was detected in the culture medium of glandular cells and increased (P less than .05) when progesterone (.1 microM) was included in the culture medium. The secretion of uteroferrin by glandular cells was also indicated by one-dimensional PAGE and Western blot analysis. Stromal cells produced more (P less than .01) prostaglandin E (PGE) than prostaglandin F2 alpha (PGF2 alpha), whereas glandular cells secreted more (P less than .01) PGF2 alpha than PGE. Pregnancy status affected prostaglandin secretion in that stromal cells secreted less (P less than .01) PGE and PGF2 alpha and glandular cells secreted less (P less than .05) PGF2 alpha when they were harvested from pregnant vs cyclic pigs. Furthermore, the PGE:PGF2 alpha ratio in medium from stromal cells was greater (P less than .01) for cells collected from pregnant pigs. This culture system provides an in vitro model for studying the hormonal regulation of the endometrium and potentially may be useful for studying interactions between endometrial cells and embryos in the pig.

Acid Phosphatase↗

Sound localization and sensitivity to interaural time differences in human infants.

The role of interaural time differences in infants' sound localization was investigated. One experiment on free-field sound localization corroborated previous findings that the minimum audible angle changes substantially toward the end of the first half year after birth, and 3 experiments explored interaural time discrimination in that age range. The first of these 3 experiments used an adaptive psychophysical procedure, showing that infants responded appropriately in a sound lateralization task that provides a direct measure of interaural time discrimination. The other 2 experiments improved on the psychophysical procedure by taking into account the ceiling level on performance in the task. Infants aged 16, 20, and 28 weeks had thresholds in the range of 50 to 75 microsec, with no apparent age difference. These thresholds were much lower than would be predicted from studies of free-field sound localization, indicating that sensitivity to interaural time differences is not a limiting factor for the precision of sound localization in this age range. Instead, age-related changes in free-field sound localization may reflect the need to integrate across different localization cues and to calibrate the changing values of cues due to head growth.

Acoustic Stimulation↗

Ophthalmomyiasis during Operation Desert Shield.

A case of fly larva infestation of the eye (ophthalmomyiasis) is reported in an American soldier serving in Operation Desert Shield. Background information, prognosis, and treatment are discussed.

Adult↗

International trends in cancer mortality in France, West Germany, Italy, Japan, England and Wales, and the USA.

Age-specific worldwide trends in cancer mortality were reviewed, with emphasis on cancer sites where increases have been reported in the USA. Cancer rates vary by factors as high as 30 between all countries, and 5-fold within and between industrialised countries. In Italy, Japan, Federal Republic of Germany, England and Wales, and the USA, patterns of cancer mortality have shifted uniformly over the past two decades. Stomach cancer continues to decline, while brain and other central-nervous-system cancer, breast cancer, multiple myeloma, kidney cancer, non-Hodgkin lymphoma, and melanoma have increased in persons aged 55 and older. Cancer of the lung is starting to decline for men under age 85 and women under age 60 in England and Wales and men under age 45 in the USA, but is still rising for men and women in other countries. All forms of cancer are increasing in persons over age 54 except lung and stomach (which together comprise between 20% and 43% of all cancer in males in these countries). Studies of the quality of ascertainment and enumeration indicate that these increases are not attributable solely to diagnostic artifacts or to increased access to health care, although both these factors may be involved. These recorded increases in cancer should be assessed in greater detail to provide better projections of health care needs and to identify causal factors that may be controlled. The changes in cancer other than lung are so great and rapid that their causes demand intensive investigation.

Adult↗

Estradiol-15 alpha-hydroxylation: a new avenue of estrogen metabolism in peri-implantation pig blastocysts.

Pig blastocysts have the capacity to convert estradiol into catechol estrogens. Our present study shows that they also have the capacity to hydroxylate estradiol in cycloaliphatic C-atom 15, and this aliphatic hydroxylation reaction is more predominate than the aromatic hydroxylations. The conversion of [4-14C]estradiol to [4-14C]15 alpha-hydroxyestradiol by mitochondrial-rich/microsomal fractions was examined by isolation of this product using reversed phase high-performance liquid chromatography (HPLC) attached to a radiometric flow detector, and its identification by gas chromatography-mass spectrometry. The enzyme kinetics for estrogen 15 alpha-hydroxylase were performed in the pig blastocyst obtained on Day 13 of pregnancy (Day 0 = first acceptance of the male). The enzyme follows classical Michaelis-Menten kinetics. The apparent Kms for estradiol were 2.47 and 1.85 microM, and the apparent Vmaxs were 0.25 and 0.197 nmol/mg/min in the mitochondrial-rich and microsomal fractions, respectively. The enzyme activity was inhibited by different steroidal compounds and non-steroidal estrogens, as well as by CO, SKF-525A, piperonyl butoxide and antibody to cytochrome P450 reductase. Ontogenesis of the blastocyst's estrogen 15 alpha-hydroxylase follows a similar pattern to that of estrogen-2/4-hydroxylase. Thus, highest activity was observed on Days 12 and 13 and lowest was on Day 15 of pregnancy. Furthermore, the enzyme is abundant primarily in the extraembryonic tissues rather than in the embryo proper. The abundance of the enzyme in the extraembryonic tissues, and its surge at a critical time of pregnancy recognition and just prior to implantation suggest that 15 alpha-hydroxylated estradiol could be involved in these processes.

Animals↗

Is brain cancer mortality increasing in industrial countries?

This paper analyzes recent age-specific trends in brain and other central nervous system cancer mortality from 1968 to 1986-1987 in the United States, United Kingdom, Italy, France, and West Germany. It also examines changes in the use of diagnostic confirmation technology in the U.S. SEER program from 1973 to 1987 to estimate the influence of such factors on recent mortality trends. Other sources of error have not been evaluated in this paper. In the United States and Sweden, deaths due to brain and other central nervous system cancer, adjusted to the overall population, are unchanging. However, age-specific analyses of brain and other nervous system cancer in six major industrial countries show markedly different trends at different age groups, with drastic increases in brain tumor rates in the old: rates doubled in persons ages 75 to 84. In the United States, microscopic or radiographic confirmation occurred throughout this time period in 96% of all incident cases of brain and other central nervous system cancers diagnosed before death in the SEER program, with older persons receiving consistently more radiographic tests than younger persons. The use of diagnostic technology may change over time and across populations, but it is not known to what extent it accounts for these increasing trends, which require careful additional study.

Adolescent↗

Analyses of changes in the ratios of male-to-female cancer mortality. A hypothesis-generating exercise.

Site-specific cancer trends are particularly useful indicators to identify cancers that should be subject to further case-control research to identify causes of the rate changes. One of the most sensitive of trends is that of the ratio of male-to-female rates, especially by age groups. This ratio is likely to eliminate rate changes due to better diagnosis, treatment, and cancer ascertainment. Also some lifestyle changes may be eliminated by considering the male-female ratio as they equally affect both genders. On the other hand, some may produce substantial effects. The finding of large increases in male-female cancer mortality ratios at specific sites in the United States and in all cancers, except lung, in several countries suggests that case-control studies of some sites are worthy of consideration to identify the gender-related differences. Because most male rates are increasing relative to females, any case-control study should certainly include occupational factors among those investigated.

Adult↗

Acquired aprosodia in children.

In adults, the affective components of language, including certain aspects of prosody and gesturing, appear to be a dominant function of the right hemisphere. The various combinations of affective processing deficits associated with focal right brain damage are called aprosodias and have functional and anatomical correlates similar to the propositional language deficits associated with aphasias secondary to focal left brain damage. Developmental affective-prosodic deficits have been reported recently in children with congenital or very early right hemisphere injury. We now report two school-aged children with acquired motor-type aprosodias following acute right focal brain injury. Their affective prosody and singing were also analyzed acoustically during the acute and recovery phases of illness. Based on these cases, we propose the term children aprosodia to describe affective-prosodic deficits that result from acquired lesions of the right hemisphere in children.

Affective Symptoms↗

The O-methylation of catechol oestrogens by pig conceptuses and endometrium during the peri-implantation period.

Pig conceptuses display a surge in oestrogen and catecholoestrogen synthetic activity during the peri-implantation period. However, the pathways of catecholoestrogen metabolism in pig conceptuses and endometrium are unknown. O-Methylation is an important route of catecholoestrogen metabolism. Therefore, the O-methylations of 2- and 4-hydroxy-oestradiols (2- and 4-OH-oestradiol) by cytosol of pig conceptuses and endometrium during the peri-implantation period were studied. Kinetic studies performed in tissues obtained on day 13 of pregnancy (day 0 = first acceptance of the male) indicated that the O-methylation of 2-OH-oestradiol displayed simple Michaelis-Menten kinetics in both tissues. In blastocysts, the apparent Michaelis constant (Km) and maximum velocity (Vmax) for the O-methylation of 2-OH-estradiol were 1.4 mumol/l and 11.27 pmol/mg protein per min respectively, and when 4-OH-oestradiol was used as substrate, the values were 2.53 mumol/l and 9.86 pmol/mg protein per min respectively. The apparent Km and Vmax values for the O-methylation of 2-OH-oestradiol in endometrium were 0.77 mumol/l and 19.6 pmol/mg protein per min respectively, and for the O-methylation of 4-OH-oestradiol were 2.44 mumol/l and 10.38 pmol/mg protein per min respectively. Ontogenesis of catechol-O-methyltransferase (COMT) in conceptuses and endometrium was studied from day 10 to day 19 of pregnancy. Conceptus COMT activity was lowest on day 10 and increased gradually to day 19 of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vitro synthesis of prostaglandin E and F2 alpha by pig endometrium in the presence of estradiol, catechol estrogen and ascorbic acid.

These experiments were undertaken to determine the potential for estradiol-17 beta (E2), 2-hydroxyestradiol-17 beta (2-OH-E2) and 4-hydroxyestradiol-17 beta (4-OH-E2) to regulate prostaglandin (PG) E and F2 alpha synthesis by pig endometrium. Endometrium was collected from pigs on d 10 of pregnancy and incubated (15 to 20 mg/well) for three 2-h periods in 2 ml of medium in 24-well culture plates. At the end of each period, the medium was removed and frozen. Later media were thawed and assayed for PGE and PGF2 alpha. During Periods 2 and 3, the medium contained 0, 25, 50, 100 or 150 microM 2-OH-E2 (Exp. 1); 0, 25 or 50 microM 4-OH-E2 (Exp. 2); or 0, 25 or 50 microM E2 (Exp. 3). Each experiment was a factorial with 2-OH-E2, 4-OH-E2 or E2 as one main effect and 0 or 1 mM ascorbate as a second main effect. Ascorbate decreased (P less than .01) PGE and PGF2 alpha release in all experiments. Two-hydroxyestradiol-17 beta decreased (P less than .01) PGE and PGF2 alpha release into the medium during Periods 2 and 3 in a dose-dependent manner (Exp. 1). In Exp. 2, 4-OH-E2 decreased (P less than .07) endometrial release of PGE and PGF2 alpha in Periods 2 and 3 and increased (P less than .01) the PGE:PGF2 alpha in Period 3. In Exp. 3, E2 decreased release of PGE during Period 3 and PGF2 alpha release during Period 2. The PGE:PGF2 alpha was not altered by E2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme.

The conversion of cholesterol into bile acids in the liver represents the major catabolic pathway for the removal of cholesterol from the body. In this complex biosynthetic pathway, at least 10 enzymes modify both the ring structure and side chain of cholesterol, resulting in the formation of the primary bile acids, cholic acid, and chenodeoxycholic acid. To gain insight into the details and regulation of this pathway, we have used protein sequencing and molecular cloning techniques to isolate and characterize a cDNA encoding the rabbit mitochondrial sterol 26-hydroxylase. This enzyme catalyzes the first step in the oxidation of the side chain of sterol intermediates in the biosynthesis of bile acids. The structure of the sterol 26-hydroxylase, as deduced by both DNA sequence analysis of the cDNA and protein sequence analysis, reveals it to be a mitochondrial cytochrome P-450. A signal sequence of 36 residues precedes a coding region of 499 amino acids, predicting a molecular weight of 56,657 for the mature protein. The identity of the 26-hydroxylase cDNA was further confirmed by expression in monkey COS cells employing a versatile eukaryotic expression vector. Blotting experiments revealed that the mRNA for this enzyme is expressed in many tissues and that it is encoded by a low copy number gene in the rabbit genome.

Amino Acid Sequence↗

Development of pig blastocysts in vitro is altered by serum, bovine serum albumin and amino acids and vitamins.

We tested the effects of the amino acids and vitamins in minimum essential medium (MEM) and Eagle's medium (BME) on pig blastocyst development and nuclei number. Embryos were recovered either 5 or 6 d after first detected estrus and were cultured for 96 h in U-bottomed wells (0.2 ml). In Experiment 1, addition of MEM amino acids and vitamins to modified Krebs-Ringer bicarbonate (MKRB) medium containing either bovine serum albumin (BSA, 4 mg/ml) or lamb serum (10%, v/v) resulted in fewer (P<0.001) nuclei and smaller (P<0.05) embryo volumes at the end of culture as compared to embryos cultured in MKRB without MEM-supplements. Addition of MEM-amino acids without glutamine (Experiment II) depressed blastocyst volume and rate of hatching, but glutamine (2 mM) had no effect on embryo development. Dialysis (molecular weight > 12,000 retained) of fetal bovine serum (Experiment III) did not affect blastocyst expansion but reduced (P<0.05) the number of nuclei/blastocyst at the end of the culture. Embryos cultured in MKRB with dialyzed serum and the amino acids and vitamins in BME were smaller (P<0.05) and had fewer (P<0.05) nuclei than embryos cultured in MKRB with dialyzed serum but without the BME-supplements. We conclude that, under our culture conditions, MEM and BME amino acids and vitamins are detrimental to the development of early pig blastocysts and that this effect is not due to glutamine. Also, dialysis of fetal bovine serum removes some component(s) that are important for cell division by pig embryos, but it does not affect blastocyst expansion.

Journal Article↗