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Biomedical subjects

A T Davis

Publications and source records attributed to A T Davis.

At least 91 records · Page 5Linked to original sources

Effect of fibronectin supplementation in endotoxic shock in the dog.

An earlier study by our group demonstrated significant amelioration of hypotension, hypoglycemia, and acidosis in dogs treated with purified human plasma fibronectin prior to induction of endotoxic shock. The present study was completed to determine whether treatment with purified human plasma fibronectin 1 hr after induction of endotoxic shock would provide similar benefits. To this end, selected hemodynamic, pulmonary, acid-base, metabolic, hematological, and serum chemistry parameters were monitored for 6 hours in two groups of anesthetized dogs in Escherichia coli endotoxic shock. One group was given an intravenous injection of purified human plasma fibronectin, and the other received an equal volume of saline 1 hr after shock induction. Between-group analysis of the data revealed no significant differences between any parameter excepting modest differences in plasma glucose, albumin, alkaline phosphatase, and BUN concentrations. However, even these differences, although statistically significant, were sporadic and unimpressive. This study suggested that treatment of dogs with fibronectin during gram-negative endotoxic shock was not efficacious.

Animals↗

Outpatient oral rehydration in the United States.

Twenty-nine dehydrated, well-nourished infants, who were 3 to 24 months of age and had acute gastroenteritis, were enrolled in a prospective randomized study that compared the safety, efficacy, and costs of oral vs intravenous rehydration. The study was designed to assess the use of a holding room in the emergency room for the outpatient rehydration of dehydrated infants. The oral solution that was used contained 60 mEq/L of sodium, 20 mEq/L of potassium, 50 mEq/L of chloride, 30 mEq/L of citrate, 20 g/L of glucose, and 5 g/L of fructose. Thirteen of 15 patients were successfully rehydrated orally as outpatients; two patients, who were subsequently discovered to have urinary tract infections, required hospitalization due to persistent vomiting. Orally rehydrated outpatients spent a mean of 10.7 hours in the holding room, as compared with intravenously rehydrated inpatients, who were hospitalized for a mean of 103.2 hours. Outpatient oral rehydration therapy was significantly less costly than inpatient intravenous therapy (+272.78 vs +2,299.50). Our results indicate that oral rehydration is a safe and cost-effective means of treating dehydrated children in an outpatient setting in the United States. The use of a holding room for observation in the emergency room can markedly decrease health care costs and unnecessary hospitalizations.

Acute Disease↗

Purification of nuclear cAMP-independent protein kinases from rat ventral prostate.

Two nuclear cAMP-independent protein kinases (designated PK-N1 and PK-N2) were purified from rat ventral-prostate and liver. The yield of enzyme units was 4-5% and 7-9% for each enzyme from the prostatic nuclei and liver nuclei, respectively. The average fold purification for prostatic nuclear protein kinase N1 and N2 was 1360 and 1833, respectively. The respective average specific activity of the two enzymes towards casein was 81,585 and 110,000 nmol 32P incorporated/hr/mg of enzyme. Protein kinase N1 comprised one polypeptide of Mr 35,000 which underwent phosphorylation in the presence of Mg2+ + ATP. Protein kinase N2 comprised two polypeptides Mr 40,000 and 30,000 of which only the Mr 30,000 polypeptide was autophosphorylated. Both enzymes were active towards casein, phosvitin, dephosphophosvitin, spermine-binding protein, and non-histone proteins in vitro. Little activity was detected towards histones. Both enzymes were stimulated by 150-200 mM NaCl. MgCl2 requirement varied with the protein substrate but was between 2-4 mM for both enzymes. With dephosphophosvitin as substrate, the apparent Km for ATP for N1 protein kinase was 0.01 mM. GTP did not replace ATP in this reaction. Protein kinase N2 was active in the presence of ATP or GTP. The apparent Km was 0.01 mM for ATP, but 0.1 mM for GTP.

Animals↗

Carnitine metabolism in lean and obese Zucker rats during starvation.

Carnitine metabolism during starvation was studied in adult lean and obese female Zucker rats. Comparisons were made between rats starved for 0, 3, 6 or 9 d. Total plasma carnitine was not affected by obesity or starvation, but free plasma carnitine decreased with starvation. Plasma acid-soluble acylcarnitine was lower in obese than in lean rats, and increased with starvation in both lean and obese rats. Plasma acid-insoluble acylcarnitine was not affected by obesity but increased with starvation. Liver free and acid-soluble acylcarnitine were lower in obese rats than lean rats, and starvation increased liver free carnitine and acid-insoluble acylcarnitine. Free carnitine was lower in muscle from obese rats than from lean rats. In kidney, free carnitine decreased during starvation. Heart carnitine was not affected by obesity or starvation. Urinary free carnitine and acid-soluble acylcarnitine clearance decreased during starvation. These studies indicate that: 1) lean and obese Zucker rats conserve carnitine during starvation; and 2) the decreases in liver carnitine concentration reflect the loss of cellular constituents rather than increases in total hepatic carnitine.

Animals↗

Effect of starvation on the disposition of free and peptide-linked trimethyllysine in the rat.

Free and peptide-linked trimethyllysine were measured in fed and 5-d starved rats. The trimethyllysine content of liver and kidney was significantly increased on d 5 of starvation to two to three times the levels found in fed animals. Skeletal muscle of fed rats contained over six times as much trimethyllysine (19.3 nmol/g) as that found in liver (3.2 nmol/g) or kidney (2.7 nmol/g). Plasma free trimethyllysine significantly increased from 1 nmol/ml in fed rats to 2.2 nmol/ml in 5-d starved rats. During this same period, daily total trimethyllysine excretions averaged approximately 400 nmol/d. Urinary free trimethyllysine was significantly depressed during starvation. Assuming that trimethyllysine in plasma does not exist in a protein-bound form, clearance calculations based on concentrations of plasma and urinary trimethyllysine indicated that this compound is readily reabsorbed by the kidney. As previous studies have indicated that trimethyllysine is not readily absorbed by other tissues, this indicates that the kidney may be the primary regulatory site for the disposition free of free trimethyllysine in plasma and urine. Estimates of the efficiency of entry of trimethyllysine into the carnitine biosynthetic pathway were calculated and ranged from 41% in 3-d starved rats to 80% in fed rats. We conclude that carnitine biosynthesis is limited by the availability of trimethyllysine, which, in the starved rat, is limited by the rate of protein turnover.

Animals↗

Addition of branched-chain amino acids to parenteral nutrition of stressed critically ill patients.

We compared the efficacy of a total parenteral nutrition solution supplemented with 44.6% branched-chain amino acids (BCAA) to standard total parenteral nutrition (19.0% BCAA) in the support of critically ill patients. After a 4-day administration of a randomly assigned solution, amino acids were assayed from femoral venous and arterial samples. The BCAA-supplemented solution caused increases in arterial concentrations of valine, isoleucine, and leucine compared to the control solution. The femoral arteriovenous differences for these BCAA were more positive in patients given the control solution. There were no significant differences in nitrogen balance. Since previous studies showing promotion of nitrogen balance with BCAA did not use a balanced substrate for nonprotein caloric support, the lack of a significant difference in the present study may be due to effective utilization of lipid as a fuel source by both groups.

Adult↗

Polyamine-stimulated phosphorylation of prostatic spermine-binding protein is mediated only by cyclic AMP-independent protein kinases.

Spermine-binding protein (a rat ventral prostatic protein with high affinity for spermine) was phosphorylated in situ through the action of intrinsic cellular protein kinase(s), suggesting it to be a phosphoprotein in vivo. The purified protein served as a substrate in a number of cyclic AMP-independent protein kinase reactions in vitro, but not for cyclic AMP-dependent, Ca2+ + calmodulin-dependent or Ca2+ + phospholipid-dependent protein kinases. Available data indicate that at least one of the cyclic AMP-independent protein kinases (cytosolic protein kinase C2) may be physiologically relevant in mediating the phosphorylation of this protein. The phosphorylation reaction was stimulated several-fold in the presence of spermine. Spermidine was somewhat less effective, whereas putrescine, cadaverine and 1,6-hexanediamine were minimally active. Phospho amino acid analysis of 32P-labelled spermine-binding protein indicated that phosphoserine was the only labelled phospho amino acid. Spermine-binding protein did not undergo autophosphorylation, or modify the stimulative effect of spermine on the phosphorylation of other substrates such as non-histone proteins. In situ the phosphorylation of spermine-binding protein in tissue from castrated rats was markedly diminished as compared with the normal. Since the phosphorylation of spermine-binding protein appears to be mediated by cyclic AMP-independent protein kinase(s) whose activity in the prostate is under androgenic control, it is suggested that androgen-dependent modulation of the protein kinase(s) exerts a regulatory control (via phosphorylation-dephosphorylation) on the spermine-binding activity and stability of this protein in vivo. Further, since this protein is a substrate for only the cyclic AMP-independent protein kinases, it could serve as a tool for the investigation of such kinases.

Amino Acids↗

Oral glucose-electrolyte solutions as maintenance therapy of acute diarrhea.

Sixty well-nourished, well-hydrated infants, 3 to 24 months of age with uncomplicated acute gastroenteritis, were enrolled in a prospective, randomized, double-blind study that compared the safety and efficacy of two oral solutions. The solutions differed primarily in the sodium concentration (60 v 30 mEq/L) and glucose concentration (2% v 5%). The mean serum sodium concentrations of the two groups did not differ significantly from each other at entry or at the end of the study period. In addition, there were no significant changes in the mean serum sodium concentration within each group at the end of the study period. No child in either group became hypernatremic. Our results indicate that a solution with a high concentration of sodium initially designed for the rehydration of dehydrated children also can be safely and effectively used as a maintenance solution for the treatment of well-hydrated children older than 3 months of age with acute gastroenteritis.

Blood Glucose↗

Short-term holding room treatment of asthmatic children.

We undertook a randomized trial to compare holding room treatment vs hospitalization of patients with childhood status asthmaticus. Two thirds of 51 patients were discharged from a holding room within 24 hours (mean 11.8 +/- 4.61 hours); the others required hospitalization. One third of 52 hospitalized patients received less than or equal to 1 day of intravenously administered therapy, and two thirds received less than 2 days of therapy (mean 45.6 +/- 12 hours). There were no statistically significant differences in recurrence rates between the two groups in the 28 days following status asthmaticus. For patients receiving less than or equal to 1 day of therapy, the holding room cost was $526 +/- $226 vs $1439 +/- $339 for hospitalized patients (P less than 0.001). Thus, holding room therapy for childhood status asthmaticus is both medically and economically effective.

Aminophylline↗

Fibronectin. A new nutritional parameter.

Acute and chronic malnutrition is associated with increased morbidity and mortality in surgical patients. Plasma fibronectin levels have been shown to correlate with reticuloendothelial function and are reduced in burns, shock, trauma, and sepsis. Patients failing to show an increase in fibronectin levels after stress have been shown to do poorly. Starvation studies in human volunteers have demonstrated decreasing plasma fibronectin levels until feeding was resumed. The purpose of this study is to examine the usefulness of fibronectin as an assessment parameter in nutritionally depleted hospitalized patients. Eight patients initiated on parenteral nutrition were studied. Plasma fibronectin, albumin, and transferrin levels were drawn before TPN and repeated at various intervals after total parenteral nutrition (TPN) was begun. Mean pre-TPN transferrin was 198.1 +/- 16.1 gm/dl (nl 220-400). Transferrin levels remained statistically unchanged after 8 to 11 days of TPN. Mean pre-TPN albumin was 3.0 +/- 0.2 gm/dl (nl 3.6-4.8) and also remained statistically unchanged after 8 to 11 days of TPN. The mean fibronectin level pre-TPN was 236.4 +/- 24.4 microgram/ml (nl 370-410). Fibronectin rose statistically (P less than 0.005) after 1 to 4 days of TPN to a mean of 341.9 +/- 30.1 microgram/ml and remained elevated and statistically unchanged after 8 to 11 days of TPN. Six of the eight patients studied survived and had demonstrated at least a 30 per cent increase in fibronectin after 1 to 4 days of TPN. Both patients who died demonstrated minimal increase in fibronectin levels after 1 to 4 days of TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Determination of free trimethyllysine in plasma and tissue specimens by high-performance liquid chromatography.

A method for the determination of 6-N-trimethyllysine in tissues and plasma is described. Trimethyllysine and the chemically analogous 6-N-triethyllysine (internal standard) were isolated from acid-soluble fractions of tissue homogenates or plasma by combined ion-exchange--ion-exclusion chromatography. Trimethyllysine and triethyllysine were separated from other sample constituents by reversed-phase ion-pair high-performance liquid chromatography, derivatized post-column by reaction with o-phthalicdicarboxaldehyde and 2-mercaptoethanol, and detected fluorometrically. Standard curves were linear over a sample concentration range of 0.5--4 nmol/ml. The detection limit corresponded with 25 pmol trimethyllysine injected into the chromatograph. The procedure was used for the determination of trimethyllysine in plasma, liver, kidney, and mixed skeletal muscle of rat.

Animals↗

Treatment of infantile colic with dicyclomine hydrochloride.

We performed a prospective, randomized, double-blind, placebo-controlled clinical trial of dicyclomine hydrochloride using specific diagnostic criteria for infantile colic: spells of unexplained irritability, agitation, fussiness or crying lasting greater than or equal to 3 hours/day, occurring greater than or equal to 3 days/week, and continuing for greater than or equal to 3 weeks. Dicyclomine eliminated colic in 15 of 24 (63%) infants, whereas placebo was effective in six of 24 (25%) (corrected X2 = 5.42, P = 0.02). The study also addressed the hypothesis that parental distress caused by infantile colic affects subsequent temperament and sleep patterns. The data fail to document easier temperaments or longer sleep durations at 4 months in infants whose colic ceased during treatment.

Clinical Trials as Topic↗

Night waking in 4- to 8-month-old infants.

Parental reports of night waking and sleep patterns were obtained for 141 normal 4- to 8-month-old infants from middle-class families. A group of infants was identified who had a past history of colic and who were perceived to have a current night waking "problem." These infants awoke more often than other infants and also had significantly briefer total sleep duration. Night waking was described as a problem in infant boys more often than in infant girls. A second group of infants who awoke frequently was reported to snore or mouth breathe when asleep. This group of infants did not have a past history of colic, was not perceived to have a night waking problem, and was not overly represented by boys. Ordinal position, father's education level, gender, and method of feeding did not affect reported sleep patterns.

Child Behavior↗

Differential effects of polyamines on the phosphorylation of chromatin-associated proteins.

Studies are presented on the nature of chromatin-associated phosphoproteins whose phosphorylation is influenced by polyamines. After labelling with 32P, chromatin-associated proteins were separated into four fractions. Fraction I comprised neutral and basic non-histone phosphoproteins, including high-mobility-group non-histones; fraction II consisted mostly of histones; fraction III consisted of a class of (salt-soluble) acidic non-histone phosphoproteins; and fraction IV consisted of residual (salt-insoluble) acidic non-histone phosphoproteins. The average relative distribution of protein in the four fractions (I-IV) was about 1:4:2:1 for both liver and prostate. However, tissue-dependent differences were observed in the incorporation of 32P in various protein fractions. In the presence of polyamines (e.g. 1 mM-spermine or 2 mM-spermidine) maximal stimulation of phosphorylation was observed in non-histone proteins of fraction I (160-180%), followed by that in non-histone proteins of fraction III (80-110%). The phosphorylation of residual non-histone proteins in fraction IV, and the small extent of phosphorylation of histones in fraction II, remained unaltered in the presence of polyamines. Thus polyamines do not stimulate the phosphorylation of all non-histone proteins; their stimulative effect is most prominent in the phosphorylation of neutral and basic non-histone proteins and a class of salt-soluble acidic non-histone proteins. In accord with our hypothesis, these differential effects of polyamines on phosphorylation of endogenous non-histone proteins may relate to the conformation of these substrates rather than to endogenous kinases.

Animals↗

Effect of starvation in the rat on trimethyllysine in peptide linkage.

Trimethyllysine residues in peptide linkage, precursors of carnitine biosynthesis, were measured in fed and 3-day fasted rats. Whole-body peptide-linked trimethyllysine in fasted rats was significantly less than in fed rats when expressed per initial body weight (17.8 vs 24.8 mumol/100 g initial body weight). Skeletal muscle had the highest peptide-linked trimethyllysine content (2.5 nmol/mg protein), followed by heart (1.9 nmol/mg protein). The content in kidney, liver and small intestine were similar, but less than in heart. Of the eight tissues tested, the brain had the only significant increase with fasting. The hepatic peptide-linked trimethyllysine in fasted rats was significantly decreased when expressed per milligram DNA. The study shows a commensurate loss of peptide-linked trimethyllysine accompanying protein loss during fasting. The study also shows that muscle contains over 65% of the whole-body peptide-linked trimethyllysine, and as such is a major reservoir of precursor for carnitine biosynthesis.

Animals↗

Signs of airway obstruction during sleep and behavioral, developmental, and academic problems.

This case control study of healthy children utilized parents' reports to determine whether behavioral, developmental, or academic problems were associated with signs of partial airway obstruction (snoring, difficult or labored breathing, and mouth breathing) during sleep. Results suggest an association between the signs of airway obstruction during sleep and problems when awake. Children with behavioral, developmental, or academic problems had a significantly later bedtime hour, briefer duration of total sleep, longer night awakenings, and an increased latency to sleep, as compared to children without those problems.

Airway Obstruction↗

Threonine imbalance and the threonine requirement of the chicken.

Experiments were conducted to determine the influence of dietary amino acids on the threonine requirement of chicks. A diet limiting in threonine and containing the equivalent of 20.6% crude protein was imbalanced by supplements of 0.9 to 1.5% L-tryptophan, 3.0% L-serine, a mixture of 2% each, leucine, isoleucine and valine or a 6.0% mixture of all essential amino acids but threonine. All amino acid supplements decreased the growth of chicks, and decreased food intake and/or efficiency of food utilization (P less than 0.05). Supplemental threonine prevented these effects in all cases except for 1.5% tryptophan in which the adverse effect of tryptophan was not prevented completely. The threonine requirement of Leghorn chicks was 0.69 to 0.72 percent of the diet when the diet did not contain the imbalancing amino acid supplements. We concluded that the threonine requirement of the chick is higher than previously reported, and is influenced by the amino acid content of the diet.

Amino Acids↗