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Biomedical subjects

T Taylor

Publications and source records attributed to T Taylor.

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

The effects of anterior hypothalamic deafferentation on thyrotropin (TSH) biosynthesis and response to TSH-releasing hormone.

The effects of hypothalamic deafferentation on TSH synthesis were studied by making cuts of 180 degrees arc in the anterior hypothalamus (n = 18) or sham cuts (n = 12) in rats. After 21 days, pituitaries were incubated with [35S]methionine (MET), [3H]glucosamine (GLCN), with or without 10(-8)M TRH for 24 h. TSH and free alpha-subunits were immunoprecipitated and analyzed by gel electrophoresis. In the deafferented group as compared to sham, MET incorporation into both subunits of secreted TSH was decreased (alpha, 96 +/- (SE) 9 X 10(3) vs. 180 +/- 20 X 10(3) dpm/mg protein; beta, 35 +/- 9 X 10(3) vs. 84 +/- 15 X 10(3) dpm/mg protein; P less than 0.05). Basal GLCN incorporation into both subunits of secreted TSH was also decreased in the deafferented group (alpha, 6.5 +/- 11 X 10(3) vs. 132 +/- 17 X 10(3) dpm/mg protein; beta, 36 +/- 8 X 10(3) vs. 101 +/- 29 X 10(3), P less than 0.05). In vitro TRH did not stimulate MET incorporation into secreted TSH in the sham controls but did in the deafferented group (alpha, 270% of basal; beta, 374% of basal; P less than 0.01). In vitro TRH increased GLCN incorporation in secreted TSH in both the sham (alpha, 253% of basal; beta, 245% of basal; P less than 0.02) and the deafferented group (alpha, 692% of basal; beta, 630% of basal; P less than 0.01). GLCN/MET ratio, reflecting relative glycosylation, did not differ for sham or deafferented groups but increased 2-fold with in vitro TRH in each group for both secreted subunits (P less than 0.01). Free alpha-synthesis and intrapituitary TSH were not altered by deafferentation or TRH. In summary, 1) anterior hypothalamic deafferentation decreases basal TSH protein and carbohydrate synthesis; 2) such deafferentation increases sensitivity to TRH stimulation of TSH synthesis, most notably apoprotein synthesis; 3) TRH increases relative glycosylation of secreted TSH in both deafferented and sham groups. These data suggest that TRH plays a significant role in regulating basal TSH protein and carbohydrate synthesis, glycosylation of TSH subunits, and subsequent bioactivity.

Animals↗
PubMed1986

In vitro bioassay of erythropoietic activity in serum using mouse spleen cells. The effect of heat inactivation on serum erythropoietin.

Untreated human serum is known to be toxic to in vitro assays for erythropoietin, including the mouse spleen cell assay system (MSCA). This phenomenon had previously been shown to be mediated by complement-dependent IgM heteroantibodies and can be overcome by heating the serum at 56 degrees C for 30 minutes. Using the MSCA, we have found that the toxic effect of serum could also be removed by treatment with a precipitating antibody against the C3c component of complement. The effects of the two methods of complement inactivation on the measurement of stimulatory activity in serum have been compared. For normal serum, the results after heat inactivation and antibody treatment were similar. In contrast, serum from a patient with aplastic anemia gave a result equivalent to 327 mU erythropoietin/ml after heat treatment, but after antibody treatment equivalent to 1,520 mU erythropoietin/ml. Gel permeation chromatography of unheated, heated, and antibody-treated sera showed that heating markedly reduced the activity of the erythropoietin peak. Seventy percent of the activity of partially purified urinary erythropoietin was lost during heating in the presence of normal serum. In addition, heating caused the appearance of high molecular weight compounds that are stimulatory in the MSCA. The level of this activity appeared to be directly related to the stimulatory activity of the unheated serum.

Anemia, Aplastic↗
PubMed1986

Radiation-induced hemopoietic death in mice as a function of photon energy and dose rate.

Radiation-induced hemopoietic death was measured in mice exposed to photons of four different energies: 250-kVp X rays, 60Co gamma rays (1.25 MeV), and 6- and 25-MV photons from a linear accelerator. For each radiation source, the lethal dose which killed 50% of the population in 30 days (LD50/30) associated with the hemopoietic syndrome was determined in groups of mice exposed to graded doses from 600 to 1150 cGy at dose rates of 20, 40, and 80 cGy/min. The calculated LD50/30 values for 25 and 6 MV were significantly different from each other at all exposure rates while no difference was observed between 6 MV and 60Co. Using 60Co gamma rays as the standard, the relative biologic effectiveness was as follows: 250 kVp greater than 25 MV greater than 6 MV = 60Co. The data suggest that there may be a greater damage to tissue within the marrow cavities following exposure to very high megavoltage radiation, a factor which must be considered with the increasing utilization of linear accelerators in the clinic and laboratory.

Animals↗
PubMed1985

Effects of spinal fusion on the proteoglycans of the canine intervertebral disc.

Posterior lumbar two-level spinal fusion was undertaken in 10 mature beagles. The animals were sacrificed 6 and 12 months later. Two months before sacrifice control and experimental animals received intravenously Na2(35)SO4 (1 mCi/kg). Discs encompassed by the fusion and those adjacent to it were dissected into the nucleus pulposus and annulus fibrosus (AF), which were analysed separately. Proteoglycans (PGs) were extracted with 4.0 M guanidine HCl and purified by CsCl density gradient ultracentrifugation. The hydrodynamic size and ability of the PG subunits to aggregate in the presence of hyaluronic acid were investigated by Sepharose CL-2B chromatography. The PG subunits were analysed for their galactosamine (galN), glucosamine (glcN), hexuronic acid, and protein content or were subjected to digestion with papain or chondroitin-ABC-lyase to establish the size of the chondroitin (CS) and keratan (KS) sulphate chains and the KS-PG core protein complex. Decreased ability to aggregate of PGs isolated from discs 6 and 12 months after surgery was demonstrated. While their hydrodynamic size after 6 months was generally the same or smaller than those in control tissues, the PG population present after 12 months was larger, particularly in the AF. Analysis of PG subunits from fusion discs afforded galN/glcN, galN/protein, and hexuronic acid/protein ratios that were compatible with the presence in these tissues of PGs in which the proportion of CS attached to core protein was greater than in control tissues. These studies provide the first experimental evidence that a metabolic response of discs in a fused segment may be accompanied by the biosynthesis of a new PG population whose structure is similar to that present in immature tissues.

Animals↗
PubMed1985

An analysis of the magnitude of clinical-reasoning deficiencies in one class.

Clinical-reasoning ability is indispensable to a good doctor, but students are generally expected to "pick it up" in the course of their clinical clerkships. Concern by the University of Washington School of Medicine that some students did not master the concepts of clinical reasoning led to the formation of an ad hoc committee whose retrospective study on the class of 1981 is reported here by the authors. Nineteen students (11 percent of the graduating class) who were repeatedly noted by faculty members to have problems with clinical reasoning throughout their clinical clerkships were identified as a result of this study.

Achievement↗
PubMed1985

Differential regulation of thyrotropin subunit apoprotein and carbohydrate biosynthesis by thyroid hormone.

The regulation of TSH apoprotein and carbohydrate biosynthesis by thyroid hormone was studied by incubating pituitaries from normal and hypothyroid (3 weeks post-thyroidectomy) rats in medium containing [14C]alanine and [3H] glucosamine. After 6 h, samples were sequentially treated with anti-TSH beta to precipitate TSH and free TSH beta, anti-LH beta to clear the sample of LH and free LH beta, then anti-LH alpha to precipitate free alpha-subunit. Total proteins were acid precipitated. All precipitates were subjected to electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, which were then sliced and assayed by scintillation spectrometry. In hypothyroid pituitaries plus medium, [14C]alanine incorporation in combined and free beta-subunits was 26 times normal (P less than 0.001) and considerably greater than the 3.4-fold increase seen in total protein (P less than 0.05); combined and free alpha-subunits showed no specific increase in apoprotein synthesis. [3H]Glucosamine incorporation in combined alpha- and beta-subunits in hypothyroid samples was 13 and 21 times normal, respectively, and was greater than the 1.9-fold increase in total protein (P less than 0.05); free alpha-subunit showed no specific increase in carbohydrate synthesis. The glucosamine to alanine ratio, reflecting relative glycosylation of newly synthesized molecules, was increased in hypothyroidism for combined alpha-subunits (P less than 0.001), but not for combined beta-subunits, free alpha-subunits, or total proteins. In summary, short term hypothyroidism selectively stimulated TSH beta apoprotein synthesis and carbohydrate synthesis of combined alpha- and beta-subunits. Hypothyroidism also increased the relative glycosylation of combined alpha-subunit. Thus, thyroid hormone deficiency appears to alter the rate-limiting step in TSH assembly (i.e. beta-subunit synthesis) as well as the carbohydrate structure of TSH, which may play important roles in its biological function.

Animals↗
PubMed1985

Thyrotropin (TSH)-releasing hormone regulation of TSH subunit biosynthesis and glycosylation in normal and hypothyroid rat pituitaries.

The regulation of TSH apoprotein and carbohydrate biosynthesis by TRH was studied by incubating pituitaries from normal and hypothyroid (3 weeks postthyroidectomy) rats in medium containing varying doses of TRH, [14C] alanine or [35S]methionine, and [3H]glucosamine. Samples were sequentially treated with anti-TSH beta to precipitate TSH and free TSH beta, anti-LH beta to remove LH and free LH beta, and anti-LH alpha to precipitate free alpha-subunits. Total proteins were acid precipitated. All precipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In hypothyroid samples, acute TRH (6 h) stimulated [3H] glucosamine incorporation into secreted combined alpha-subunit to 204% and secreted combined beta-subunit to 227% of control values (P less than 0.01), and stimulated [14C]alanine incorporation into secreted combined alpha-subunit to 201% and secreted combined beta-subunit to 258% of control values (P less than 0.01); pituitary content was not altered by TRH. In hypothyroid incubates, the half-maximal response was 8 X 10(-10) M TRH for both labeled precursors. In contrast, in normal samples, acute TRH (6 H) did not stimulate TSH subunit carbohydrate and apoprotein synthesis, but after 24 h, TRH stimulated [3H]glucosamine incorporation into both subunits of TSH to 270% of control values (P less than 0.02), with no change in [14C]alanine incorporation. Free alpha-subunit synthesis was not altered by TRH in normal or hypothyroid incubates. The glucosamine to alanine ratio of total newly synthesized TSH, reflecting its relative glycosylation, was increased by TRH in both combined subunits in hypothyroid samples as early as 6 h (P less than 0.05) and in normal samples only at 24 h (P less than 0.01). In summary, 1) TRH in hypothyroid incubates stimulated apoprotein and carbohydrate synthesis in combined alpha- and beta-subunits, but not free alpha-subunits, at 6 and 24 h. 2) In normal pituitary incubates, TRH stimulated TSH subunit carbohydrate, but not apoprotein, synthesis only at 24 h. 3) TRH increased the relative glycosylation of TSH in hypothyroid and normal rat pituitary incubates. Such alterations in TSH glycosylation may be due to structural changes in the carbohydrate moiety and may be important for hormone release, biological activity, or clearance.

Animals↗
PubMed1985

beta-Endorphin stimulates plasma renin and aldosterone release in normal human subjects.

To determine the effect of beta-endorphin on the renin-angiotensin-aldosterone system, human synthetic beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min) was infused iv in normal subjects. Each dose was administered for 30 min, and a control infusion of 5% dextrose and water was given on another day. Ten subjects were studied recumbent and in balance while ingesting a 10-meq Na+ diet. Plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (F) were measured basally and every 30 min for 210 min. The increments in PRA and PA above basal significantly (P less than 0.05) increased (3.1 +/- 1.2 ng/ml X h and 12.2 +/- 5.3 ng/dl, respectively; P less than 0.05) at the end of the beta-endorphin infusion. beta-Endorphin also significantly (P less than 0.01) suppressed F levels. Since in the low salt study, beta-endorphin suppressed F release while stimulating renin secretion, an additional five subjects were pretreated with dexamethasone (0.5 mg every 6 h) and were studied in balance while ingesting a 200-meq Na+ diet to suppress the renin-angiotensin system. Significant (P less than 0.025) increments in PRA (2.1 +/- 0.7 ng/ml X h) and PA (4.1 +/- 1.7 ng/dl) levels above basal were again found during the sequential dose infusion of beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min). However, PA elevations were sustained for at least 120 min after the beta-endorphin infusion was stopped despite a drop in PRA 90 min earlier. In additional studies, an attempt was made to define the minimal effective dose of beta-endorphin by 60-min infusions (0.03, 0.1, and 0.3 micrograms/kg X min) in subjects on a 200-meq Na+ diet who were dexamethasone pretreated. The PRA and PA levels rose significantly (P less than 0.05) above basal at the 0.3 micrograms/kg X min dose, but not at the 0.03 or 0.1 micrograms/kg X min dosage levels. There were no changes in blood pressure or potassium during either the 10 or 200-meq Na+ studies. Thus, beta-endorphin stimulates aldosterone release in vivo. However, the underlying mechanisms are complex, since renin levels also increased. The data suggest that the early aldosterone rise may be secondary to an increase in renin release, but renin cannot account for the sustained postinfusion elevations of aldosterone.

Adult↗
PubMed1985

Medical ethics.

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Aged↗
PubMed1985

Bioavailability studies of etofibrate in rhesus monkeys.

Etofibrate (Lipo-Merz) is a newer antilipaemic agent that contains the nicotinic and clofibric acid moieties joined together through a diester link with ethylene glycol. The bioavailability of these moieties in etofibrate was compared to that from equimolar amounts of these drugs administered alone to rhesus monkeys (clofibric acid 354 mg, nicotinic acid 203 mg). For this comparative purpose, analytical methods were chosen which converted etofibrate and its initial metabolites into clofibric and nicotinic acid. Following this treatment, the rate and extent of bioavailability of unchanged nicotinic acid from etofibrate was significantly lower (P less than 0.01) than that from nicotinic acid alone. Mean peak whole blood levels of 11.9 micrograms/ml at 2.8 h and 35.3 micrograms/ml at 1.3 h, respectively, occurred after administration of etofibrate and nicotinic acid alone. The extent of bioavailability of clofibric acid hydrolysed from etofibrate was not significantly different (P greater than 0.05) from that from clofibric acid alone. However, mean peak plasma levels of 127.3 micrograms/ml at 3.6 h and 170.8 micrograms/ml at 2.4 h, respectively, occurred after administration of etofibrate and clofibric acid alone and were significantly different (P less than 0.01). The rates and extent of bioavailability of nicotinic acid or clofibric acid administered as a mixture were similar to that from these drugs administered alone. Thus either drug did not affect the absorption of the other in rhesus monkeys. The half-lives of nicotinic acid (in whole blood) and clofibric acid (in plasma) in rhesus monkeys when these drugs were administered alone were 9.9 h and 1.8 h, respectively.

Animals↗
PubMed1984

Fetal weight/placental weight ratio and perinatal outcome.

The relationship of placental size to perinatal outcome was investigated in a population of low-risk infants. A trimmed and drained placenta was weighed for each of 417 low-risk infants, and for 108 infants whose intrapartum course was complicated only by compression of the umbilical cord. Tracings from intrapartum electronic fetal heart rate monitoring were analyzed by an investigator who was unaware of the fetal weight/placental weight ratio. The incidence of perinatal problems was increased in those infants whose fetal weight/placental weight ratio was greater than 11: intrapartum fetal distress, 20% (p = 0.0046); meconium-stained amniotic fluid, 28.9% (p = 0.0017); Apgar score less than 7, 11.1% (p = 0.04); and hyperbilirubinemia, 24.4% (p = 0.0008). On the basis of these data, the conclusion drawn was that there is a population of presumably low-risk infants who are at increased risk because they have outgrown their placentas.

Amniotic Fluid↗
PubMed1984

Isosorbide dinitrate plasma concentrations and bioavailability in human subjects after administration of standard oral and sublingual formulations.

The bioavailability of isosorbide dinitrate from formulations containing 5, 10, and 20 mg in tablets and 10 mg in solution for oral use and 5 mg in tablets for sublingual use, has been compared. When adjusted for dose, the peak mean plasma drug concentrations after oral administration were similar (e.g., 9.2 ng/mL after a 10-mg tablet) and about one-half that obtained after sublingual administration. Drug concentrations declined monoexponentially with mean half-lives ranging from 25-36 min. The relative bioavailability of isosorbide dinitrate from the oral formulations was not significantly different (p greater than 0.05) over the dose range studied, whereas the relative bioavailability after sublingual administration was about twice as great (p less than 0.01) as that after oral administration. The plasma drug concentration-time profile after administering the 5-mg sublingual tablet was similar to that obtained after administering orally a solution containing 10 mg, indicating that the latter should be as clinically effective as the former.

Administration, Oral↗
PubMed1984

Isosorbide 5-mononitrate kinetics.

The kinetics of isosorbide 5-mononitrate (5-ISMN) were studied in 12 healthy subjects after intravenous infusion and oral doses of 20 mg. Kinetic parameters calculated by model-independent methods or by assumption of a one-compartment open model were in good agreement. Mean (+/- SD) systemic clearance of 5-ISMN was 127 +/- 21 ml/min, volume of distribution was 48.5 +/- 6.1 l, t 1/2 was 4.4 +/- 0.5 hr, and mean residence time was 6.2 +/- 0.7 hr. At the end of intravenous infusion of 5-ISMN at a rate of 8 mg/hr for 2.5 hr, mean plasma drug concentrations reached 356 +/- 39 ng/ml. Oral doses of 5-ISMN were essentially completely absorbed (93% +/- 13% systemic availability), and mean peak plasma drug concentrations of 388 +/- 70 ng/ml occurred at 0.83 +/- 0.46 hr. Mean absorption t 1/2 was 19 +/- 12 min. Unlike other vasodilator organic nitrates in clinical use, 5-ISMN is notable for its relatively long t 1/2, essentially complete oral absorption, lack of active metabolites, and low intersubject variability in kinetics.

Absorption↗
PubMed1984

Saliva concentrations of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate.

Correlations between saliva and plasma concentrations of isosorbide dinitrate (ISDN), and its active metabolites, isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) were examined. In the case of 5-ISMN (r = 0.98, P less than 0.01), saliva concentrations are probably reliable indices of the plasma concentrations of this drug and their measurement should provide a useful non-invasive procedure to assess compliance during the clinical use of products containing either ISDN or 5-ISMN: it may also be helpful in assessing the clinical pharmacokinetics of 5-ISMN. Less satisfactory correlations were obtained for ISDN (r = 0.84) and 2-ISMN (r = 0.83).

Adult↗
PubMed1984

Human platelet angiotensin II receptors: regulation by the circulating angiotensin level.

Human platelets possess angiotensin II (AII) receptors which increase in number in response to sodium loading, a response similar to that reported for animal smooth muscle and renal AII receptors. In these studies, we studied platelet AII binding (by Scatchard analysis of competitive binding curves) in normal subjects as they changed their dietary sodium intake from 200 to 10 to 200 meq/day. Binding capacity fell significantly after 24 h of sodium restriction and furosemide diuresis, declining to a nadir of 40% of the binding capacity found during sodium loading (from 23 to 10 fmol AII/10(9) platelets). Binding increased again after 24 h of sodium loading. There were no significant changes in receptor affinity during either low or high salt intake. The binding changes were significantly inversely correlated with the changes in plasma AII levels (r = -0.87), suggesting that AII itself is the regulator of the platelet AII receptor. Short term increases in AII level (by furosemide administration or AII infusion) did not alter platelet AII binding, indicating that the changes in platelet binding were not due simply to receptor occupancy changes. These results show that platelets have the capacity for dynamic rapid up- and down-regulated of their AII receptors and that these receptor changes are regulated by the plasma AII level.

Adult↗