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Biomedical subjects

L Ellis

Publications and source records attributed to L Ellis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of prenatal ethanol exposure on fetal calcium metabolism.

Alcohol consumption has adverse effects on both adult and developing bone. The mechanisms by which alcohol affects bone, however, are unknown. This study examined the possibility that maternal alcohol consumption may affect fetal bone development by altering fetal levels of parathyroid hormone (PTH), 1,25(OH)2D, or calcitonin (hormones that regulate calcium (Ca) and bone metabolism in the adult animal). Female Sprague-Dawley rats were bred and divided into three groups: 1 group was fed lab chow ad libitum (Control; C) and the other 2 groups received a liquid diet with (Ethanol; E) or without (Pair-fed; PF) ethanol. Blood from dams and fetuses was collected on day 21 of gestation, and selected fetuses were stained for determination of the degree of bone ossification. Mean fetal body weight and fetal skeletal ossification were reduced in the E compared with PF and C groups. Total Ca levels in fetal serum, however, showed a trend to be increased in E compared with PF and C fetuses, and no significant group differences were found in fetal serum levels of albumin, PTH, or calcitonin. Serum levels of 25-OH-D and 1,25(OH)2D were significantly decreased in E and PF, compared with C fetuses. Total Ca levels in maternal serum did not vary with the group; however, serum albumin levels were higher in E, compared with PF and C dams, suggesting that serum ionic Ca levels may have been reduced in the E dams. Serum levels of 25-OH-D were reduced in the E, compared with PF and C dams, whereas levels of 1,25(OH)2D were elevated. PTH levels did not vary among groups. Interestingly, serum calcitonin levels were elevated in the E, compared with PF and C, dams. These results indicate that the effects of ethanol on fetal bone development do not appear to be related to alterations in fetal serum levels of PTH, 1,25(OH)2D, or calcitonin. Maternal ethanol consumption, however, results in reduced appetite and a decrease in dietary Ca intake. Despite the reduced Ca intake, the ability of the dam to maintain Ca homeostasis appeared intact, although this may be dependent on the duration of ethanol consumption.

Alcohol Drinking↗
PubMed1996

Effects of gender on listeners' judgments of speech intelligibility.

Effects of gender on listeners' judgments of intelligibility were investigated. Subjects (15 women; 15 men) provided magnitude-estimation scaling responses and over-all impression of the intelligibility of a male and female speaker's comparable versions of audiotaped speech samples varying systematically in terms of the number of phonemes produced correctly. There was no significant difference between male and female subjects' magnitude-estimation scaling responses; however, their over-all impressions of the intelligibility of the speakers tended to differ. Women indicated that the male speaker was more understandable, and men indicated that the female speaker was more understandable. Magnitude-estimation scaling may provide an objective means for evaluating a speaker's intelligibility. It appears to transcend gender-biases associated with judgments of speech intelligibility.

Adult↗
PubMed1995

Expression, characterization, and crystallization of the catalytic core of the human insulin receptor protein-tyrosine kinase domain.

The deduced primary sequence of the cytoplasmic protein-tyrosine kinase domain of the insulin receptor contains a conserved kinase homology region (receptor residues 1002-1257) flanked by a juxtamembrane region and a C-terminal tail. A soluble 48-kDa derivative (residues 959-1355) containing these regions but lacking the first six residues of the juxtamembrane region had earlier been synthesized in Sf9 cells using a baculovirus expression system. The catalytic core of the kinase domain was studied first by proteolytic analysis of the 48-kDa kinase and then by expressing a series of truncated kinase domains in transiently transfected COS cells. Based on these studies, two core kinases of 34 (residues 985-1283) and 35 (residues 978-1283) kDa, respectively, were overexpressed in Sf9 cells. Biochemical characterization of the 35-kDa kinase revealed that the core kinase conserved the major functional properties of the native receptor kinase domain. Activity of the 35-kDa kinase toward a synthetic peptide increased more than 200-fold upon autophosphorylation, which occurred exclusively at Tyr-1158, Tyr-1162, and Tyr-1163; the largest increase was observed between bis- and trisphosphorylation of the kinase. The activated 35- and 48-kDa kinases were similar with respect to specific activity and ATP and Mg2+ requirements for peptide phosphorylation. Moreover, autophosphorylation appeared to initiate predominantly at Tyr-1162, immediately followed by phosphorylation at Tyr-1158 and then at Tyr-1163. The rate of autophosphorylation was dependent on enzyme concentration, consistent with a trans-phosphorylation mechanism. Finally, the 35-kDa kinase was crystallized, making possible elucidation of its three-dimensional structure by x-ray crystallography.

Amino Acid Sequence↗
PubMed1995

Glycine conjugation of para-aminobenzoic acid (PABA): a quantitative test of liver function.

OBJECTIVE: To evaluate glycine conjugation of para-aminobenzoic acid (PABA) to the hippurated metabolites, para-aminohippuric acid (PAHA), and para-acetamidohippuric acid (PAAHA) as a quantitative liver function test in patients with liver disease. DESIGN AND METHODS: Serum concentrations of PABA and metabolites were measured by high pressure liquid chromatography in 24 controls and 50 patients with hepatobiliary disease. RESULTS: Hippurate formation was significantly decreased in all patient groups with chronic liver disease versus controls. The hippurate ratio (% hippurated metabolites formed) correlated with severity of disease, serum albumin, and factor VII concentrations. PAHA concentration was a better prognostic indicator than factor VII concentrations in patients with acute liver disease; concentrations of zero correctly predicted a poor outcome in patients with fulminant liver failure. CONCLUSIONS: Glycine conjugation of PABA may be useful as a quantitative liver function test in patients with hepatobiliary disease and as a prognostic index in patients with fulminant liver failure.

4-Aminobenzoic Acid↗
PubMed1994

Structural determinants of substrate selection by the human insulin-receptor protein-tyrosine kinase.

Using NMR spectroscopy to visualise tyrosine phosphorylation kinetics in real time, we have investigated the sequence-dependent determinants of the selectivity of the human insulin receptor protein-tyrosine kinase for different tyrosine residues. The peptides used encompass the multiple-tyrosine-containing autophosphorylation site sequences from the insulin receptor kinase core domain (Tyr1158, Tyr1162 and Tyr1163) and from its specific C-terminal tail domain (Tyr1328 and Tyr1334). Comparison of the phosphorylation kinetics with those found for the tyrosine residues on a peptide comprising the regulatory tyrosine phosphorylation site of cdc2 points to the role of the primary sequence context of the phosphate acceptor. The particularly deleterious influence of a basic residue immediately C-terminal to the tyrosine is discussed in relation to the autophosphorylation properties of the regulatory loop regions of the insulin and epidermal growth factor receptor kinases. The data further suggest that receptor tyrosine kinase active sites and their substrate targets act in concert to ensure that specific downstream effects are activated.

Amino Acid Sequence↗
PubMed1994

Phosphorylation effects on flanking charged residues. Structural implications for signal transduction in protein kinases.

1H-NMR and 31P-NMR spectroscopy were employed to assess the electrostatic consequences of phosphorylation of single and multiple tyrosine residues in peptides derived from the core and tail autophosphorylation regions of the human insulin receptor tyrosine-kinase domain. In both peptides, phosphorylation was accompanied by changes in the resonances from basic side-chains; those from acidic residues were unaffected. Tyrosine phosphorylation caused increases of up to one in the pKa values of histidine residues situated up to eight residues away in the primary sequence. Titration curve analysis by Hill plots suggested some cooperativity of histidine and phosphate ionizations. Behaviour closely analogous to that of the insulin receptor tail peptide was observed during changes in phosphorylation of the intact insulin receptor kinase domain, suggesting that the electrostatic dissemination effects seen for the isolated peptide are retained by the peptide sequence in the context of the much larger protein. Similar changes in the behaviour of basic residues were also observed upon tyrosine phosphorylation of a cdc2-derived peptide, suggesting that this potential of phosphorylation events to propagate directed structural changes may find a widespread utility in the activation of protein kinases and in the transduction of phosphorylation-based signalling.

Amino Acid Sequence↗
PubMed1994

Use of high-fat formula for premature infants with bronchopulmonary dysplasia: metabolic, pulmonary, and nutritional studies.

The use of dietary fat in preference to carbohydrate offers the theoretic advantage of diminishing carbon dioxide production and thus the respiratory quotient, which may be beneficial for babies with chronic lung disease. Ten premature infants (birth weight (mean +/- SEM), 1.13 +/- 0.12 kg; postnatal age, 9 +/- 1 weeks) with bronchopulmonary dysplasia were alternately fed a high-fat and a high-carbohydrate formula each for 1 week, in randomized order. Lower rates of carbon dioxide production (6.6 +/- 0.3 versus 7.4 +/- 0.4 ml/kg per minute; p < 0.05), and consequently lower respiratory quotients (0.80 +/- 0.02 versus 0.94 +/- 0.01 ml/kg per minute; p < 0.005), were observed during the administration of the high-fat formula. There were no significant differences in results of pulmonary function tests with the use of either formula. Both formulas were equally well tolerated and able to promote adequate growth and normal biochemical profiles. However, weight gain was significantly greater with the administration of the high-carbohydrate formula, possibly because of an increase in the accretion of body fat. We conclude that the short-term use of high-fat formula for infants with bronchopulmonary dysplasia decreases carbon dioxide production while maintaining adequate growth and nutritional status.

Bottle Feeding↗
PubMed1994

A new transgenic mouse model of chronic hyperglycemia.

Expression under the control of the mouse transferrin promoter of a transgene encoding a soluble secreted derivative of the ectodomain of the human insulin receptor in transgenic mice results in the accumulation of this high-affinity insulin-binding protein in the plasma. Alterations of glucose homeostasis are observed including postabsorptive hyperglycemia concomitant with increased hepatic glucose production and hyperinsulinemia. Thus, this is the first transgenic animal model of chronic hyperglycemia with alterations in glucose homeostasis that are produced without a targeted alteration of pancreatic function. These mice provide a new experimental model to follow the progression and long-term consequences of chronic hyperglycemia.

Animals↗
PubMed1994

Magnitude-estimation scaling: an effective method for the measurement of the quality of filtered speech.

17 subjects provided magnitude estimations in the form of quality judgments of a filtered speech stimulus which was a nonsense sentence containing all of the consonants of English from Fairbanks. It was presented to subjects at 8 high-pass and 8 low-pass filtering conditions. Consistent magnitude estimations to the filtered stimulus were similar for both conditions. Also, for both conditions, subjects' numerical responses consistently increased in value as stimulus quality was judged to be poorer.

Adult↗
PubMed1993

Home-delivered meals programs for the elderly: distribution of services in New York State.

This study examined the ability of six countywide home-delivered meals programs in upstate New York to meet the challenge of serving the elderly in geographically isolated and impoverished regions. The six counties were divided geographically into county subdivisions. For each subdivision, program client levels were analyzed in relation to two subdivision-level census statistics: poverty rates and population densities for community-residing individuals aged 65 years and older. Client levels were positively correlated with population densities but not with poverty rates. These findings suggest that service delivery was concentrated in densely populated regions. In contrast, impoverished and sparsely populated regions received minimal services.

Aged↗
PubMed1993

In the fast lane.

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History, 20th Century↗
PubMed1993

Prolactin variants in term and preterm human milk: altered structural characteristics, biological activity and immunoreactivity.

This study was undertaken to determine if PRL variants differing in structural characteristics as well as biological activity and immunoreactivity are present in human milk and to assess whether the physiological state of the mammary gland (premature initiation of lactation, progression of lactation) influences the forms or activity of human milk-borne PRL. Human milk samples were collected in early (day 1-5) or mature lactation (1-4 months) from women delivering term (T) or preterm (PT) infants. Milk was fractionated on Sephadex G-100, Concanavalin A-Sepharose, or Phosphogel to estimate molecular weight (MW), degree of glycosylated PRL(G), and degree of phosphorylated (P) PRL, respectively. Prolactin-like bioactivity (B) was measured by the PRL-dependent proliferation of the Nb-2 lymphoma cell and PRL-like immunoreactivity (I) by radioimmunoassay (RIA) using NIDDK reagents. Milk obtained from mothers of T infants contained significantly greater B than I-PRL at each stage of lactation (early: B = 132 +/- 13.9 P.E./ml, I = 83.43 +/- 12 P.E./ml, mature: B = 41.74 +/- 8.9 P.E./ml, I = 27.19 +/- 5.5 P.E./ml; P < 0.01-0.001). PRL-like bioactivity was greatest in early milk produced by mothers of T infants and declined as lactation progressed. No differences in B or I-PRL were evident for milk collected from mothers of preterm infants at any stage of lactation. In early lactation the PRL-like bioactivity of milk collected from mothers of T infants was significantly greater than in unfractionated milk collected from mothers of PT infants (P < 0.05). The number of PRL variants present in milk was characteristic of the stage of lactation and gestation (T early > PT early; T early > T mature). Early milk from mothers of T infants contained an average of 5 bioactive PRL variants, early milk from mothers of PT infants an average of 4 bioactive variants, and mature milk from mothers of T infants an average of 3 bioactive variants. The distribution of molecular weights associated with PRL variants in milk infranatant was variable among subjects within a specific stage of lactation/gestation. However, the representative range of molecular weights of PRL variants identified in milk sample was similar between groups (T early: < 8, 16, 20, 24, 25-28, 32, 42, > 66; PT early: 16, 20, 23, 25-28, 32, > 66; T mature: 20, 25-28, 32, 35, > 66).(ABSTRACT TRUNCATED AT 400 WORDS)

Breast↗
PubMed1993

The religiosity of mothers and their offspring as related to the offspring's sex and sexual orientation.

This study sought to determine the nature and extent of the relationship between the religiosity of mothers and their offspring, taking both the sex and the sexual orientation of the offspring into account. Religiosity was measured in terms of both intensity (importance of religion, frequency of church attendance) and denominational preference. Female offspring were found to be more religious than male offspring, and their religiosity tended to more closely resemble that of their mothers than did the religiosity of males. Offspring of both sexes who were not exclusively heterosexual in orientation tended to be less religious and less likely to emulate their mother's religiosity as compared to exclusively heterosexual offspring.

Adolescent↗
PubMed1992

Insulin receptor tyrosine kinase domain auto-dephosphorylation.

We have observed dephosphorylation of the soluble, 48 kDa insulin receptor tyrosine kinase domain following its tyrosine autophosphorylation. Dephosphorylation was associated with generation of inorganic phosphate, thereby making catalysis by reversal of the kinase reaction unlikely. The kinase domain preparations could not be shown to contain detectable, contaminating protein tyrosine phosphatase activity. In addition, dephosphorylation was insensitive to protein phosphatase inhibitors. However, it was blocked by the kinase inhibitor staurosporine. These results are consistent with insulin receptor kinase domain auto-dephosphorylation via catalysis involving the kinase itself. These findings raise the possibility of a novel mechanism for termination of the insulin receptor signal.

Animals↗