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Biomedical subjects

T Davis

Publications and source records attributed to T Davis.

At least 145 records · Page 8Linked to original sources
PubMed1986

Methylation of chromatin in vitro.

The endogenous DNA methylase in nuclei isolated from growing mouse cells preferentially methylates DNA in micrococcal nuclease-resistant regions probably as a result of the location in these regions of the preponderance of hemimethylated sites. Added mouse ascites cell DNA methylase catalyses the methylation of exposed, nuclease-sensitive DNA in chromatin from growing or non-growing mouse or insect cells. The poor acceptor ability of nuclease-resistant regions in this situation is due to the presence of histone proteins which block de novo methylation. Transcriptionally active regions of chromatin are selectively methylated in vitro by either endogenous or added DNA methylase.

Animals↗
PubMed1986

Acute complications of endotracheal intubation. Relationship to reintubation, route, urgency, and duration.

Sixty-one consecutive medical intensive care unit patients who were intubated for more than three days were prospectively studied for complications. Patients who were reintubated had a higher incidence of all complications (chi square = 5.4; p less than .025), as did those with prolonged intubation (chi square = 16.1; p less than .005). Neither route nor urgency had an adverse clinical effect. In contrast there was a 13 percent incidence of acute tracheolaryngeal complications, but no association was found with reintubation, route, urgency, or total duration of endotracheal intubation.

Adult↗
PubMed1985

Delayed methylation and the matrix bound DNA methylase.

It is shown that the methylation of DNA that occurs in isolated nuclei is "delayed methylation". This methylation is not reduced in nuclei which have been pretreated with 0.2M NaCl to extract the soluble methylase suggesting that this methylation is the product of a firmly bound matrix associated DNA methylase. Evidence is provided that, like the methylase, the DNA substrate is associated with the nuclear matrix.

Animals↗
PubMed1985

Phase I evaluation of a synthetic mutant of beta-interferon.

A synthetic mutant of beta-interferon, produced by recombinant DNA technology, was prepared with serine substituted for the naturally occurring cysteine at amino acid 17. This molecule, after purification to homogeneity, was evaluated in 23 patients with cancer for tolerated doses, safety, and pharmacokinetics. Each patient was begun on twice weekly administration, one dose i.m., then an identical dose i.v. Doses, escalated weekly, were tolerated by 9 of 12 patients at 100 X 10(6) units i.m., 11 of 14 patients at 100 X 10(6) units i.v., and 8 of 10 patients receiving i.v. doses of 200 X 10(6) units. Fever (greater than or equal to 38.9 degrees C), the commonest cause for ceasing dose escalation, occurred in 11 of 13 patients who developed limiting i.v. toxicity and 6 of 11 who developed limiting i.m. toxicity. Patients who did not have progressive cancer after completion of dose escalation received five consecutive daily doses at their maximum tolerated single dose by each route, i.m. and i.v. These two 5-day treatments were given without difficulty. All patients treated with 300 X 10(6) units or less, i.m. (n = 13) or i.v. (n = 10), were able to receive five daily doses without limiting toxicity. Peak serum titers occurred immediately after i.v. administration and declined in an exponential manner thereafter. Despite absence of measurable titers in serum after i.m. injection, fever and significant (P less than 0.05) depression of WBC and platelet counts, serum calcium, and serum cholesterol occurred (prestudy to maximum tolerated dose). An immunoglobulin antibody to beta-interferon, detected by enzyme-linked immunoabsorbent assay, developed in 17 of 23 patients. Neutralizing activity (titer 10(2] was found in only 1 of 23 patients. No immune-mediated sequelae (symptomatic or renal) were identified. Further Phase I and II trials with this molecule will determine whether it will prove to have a better therapeutic index or different spectrum of therapeutic activity from alpha-interferon or gamma-interferon.

Adult↗
PubMed1983

Do benzodiazepine receptors mediate the anticonflict action of pentobarbital?

The effects of the benzodiazepine antagonist CGS 8216 (2-phenylpyrazolo[4,3-c]quinoline-3(5H)-one) were examined in a thirsty rat conflict test in the presence and absence of pentobarbital. CGS 8216 (2.5-10 mg/kg i.p.) did not affect nonpunished responding, but doses of 5 and 10 mg/kg significantly reduced the rate of punished responding (i.e., the number of 3 second drinking episodes in a "shock" contingency). However, a dose of CGS 8216 which did not significantly alter punished responding (2.5 mg/kg) antagonized the anticonflict actions of pentobarbital. These observations suggest that while high doses of CGS 8216 may elicit an "anxiogenic" response in rodents, lower doses of CGS 8216 antagonize the anticonflict actions of a compound which has been shown to enhance benzodiazepine affinity in vitro. These data imply that the anticonflict actions of pentobarbital may be mediated through benzodiazepine receptors.

Animals↗
PubMed1981

The kinetics of peritoneal insulin absorption.

This study examined the relationship between the delivery of insulin into the peritoneal space and its absorption into the peripheral circulation. Studies were performed in conscious dogs receiving somatostatin (5.0 microgram/min) to suppress endogenous insulin secretion, and intravenous glucose (50 mg/min) to prevent hypoglycemia. The biologic effectiveness of the absorbed insulin was determined by its hypoglycemic effect. The possibility of direct absorption of insulin into the portal circulation from the peritoneal space in anesthetized, portal vein-catheterized dogs was examined with radiolabeled I125 insulin. Our results suggest that absorption of insulin from the peritoneal space is volume, concentration, and time-dependent. Maximal absorption of insulin was observed at 50 min when 1.92 U of insulin in a volume of 3 ml was infused intraperitoneally over 30 min. More rapid absorption was observed at 30 min when this quantity of insulin was given in a 1-min intraperitoneal bolus, compared to 30 min of intraperitoneal infusion. Least rapid absorption of insulin followed the delivery of 1.92 U of insulin in a volume of 15 ml. Intermediate absorption of insulin was observed at 40 min when the 1.92 U was delivered in a volume of 0.6 ml. Peripheral intravenous insulin delivery of 1.92 U reached a maximal plasma concentration at 20 min, which was more than three times the concentration observed with intraperitoneal insulin. Isotopic tracer studies, in which radioiodinated insulin was placed into the peritoneal space in anesthetized dogs, demonstrated greater radioactivity in the portal vein than in the aorta throughout a 30-min observation period. These studies demonstrate that intraperitoneal administration of insulin results in absorption of insulin which is volume, concentration, and time-dependent. Thus, the peritoneal space may be an appropriate site for insulin delivery through a transcutaneous catheter.

Absorption↗
PubMed1980

Scanning electron microscopy of an elastic fiber network which forms the internal elastic lamina in canine saphenous vein.

Scanning electron microscopy (SEM) was used to study the arrangement of elastic fibers in the canine saphenous vein as the basis for further studies of veins used in by-pass grafting operations. The elastic fiber arrangement in distended and non-distended veins was examined in both immersion-fixed and perfusion-fixed vessels. Transmission electron microscope (TEM) observation of the SEM samples confirmed the identity of these fibrillar structures as elastic fibers. In addition, specific stains for elastic fibers (Verhoeff's iron hematoxylin and orcein) were used. The elastic fibers forming the internal elastic lamina were arranged in a fishnet-like pattern. Large-diameter fibers, running longitudinally along the vascular wall, were interconnected by smaller oblique fibers. Together the fibers formed an elastic cylindrical network between the endothelium and the smooth muscle cells. The thicker longitudinal fibers were the same diameter in distended and non-distended veins. By contrast, the oblique fibers were thinner and more complexly branched in distended veins. The architecture of the elastic fiber network contributes to vascular flexibility and allows circumferential distension. The interconnecting oblique fibers presumably serve to distribute internal pressure equally around the venous wall.

Animals↗
PubMed1979

The effect of "warm-up" on exercise-induced asthma.

To determine the effect of "warm-up" on exercise-induced asthma (EIA) 18 subjects ( mean age 19.7 years) performed five minutes of submaximal treadmill running to achieve a heart rate (HR) of 85% of predicted maximum for age. One such exercise test was preceded by "warm-up" and one was not. "Warm-up" consisted of three minutes of treadmill walking or jogging to attain 60% of predicted maximun HR for age. An identical incidence (77.8%) and severity (38.1% mean decrease in FEV1) of EIA was recorded after treadmill running whether preceded by "warm-up" or not. While this study does not support the concept that "warm-up" could reduce the likelihood of EIA, it is recommended that a longer, more intense "warm-up" involving interval exercise should be evaluated before rejecting the view that "warm-up" ameliorates EIA.

Adolescent↗
PubMed1978

Prevalence of growth hormone deficiency in children with cleft lip or palate.

Two hundred children 7 to 14 years of age with isolated cleft defects of the lip, palate, or both were surveyed for stature. Twelve percent were less than the third percentile in height and were designated "short." All of the short children received an endocrine evaluation. Endogenous growth hormone was examined after two days' pretreatment with stilbesteral. Four of the 25 short children with CLP had total, and four had partial, GH deficiency. Three of the GH-deficient patients were also deficient in ACTH or TSH. In contrast, in a series of 75 short (less than third percentile) children 7 to 14 years of age without cleft defect or other apparent congenital abnormality, only two had total and two had partial GH deficiency. The data suggest that children with isolated CLP have short stature about four times more often, and GH-deficiency about 40 times more often, than children without CLP. The increased prevalence of GH-deficiency may stem from the embryologic relation of adenohypophysis and oral ectoderm.

Adolescent↗