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Biomedical subjects

J D Johnson

Publications and source records attributed to J D Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Evidence that D2 receptor-mediated activation of hypothalamic tuberoinfundibular dopaminergic neurons in the male rat occurs via inhibition of tonically active afferent dynorphinergic neurons.

The purpose of the present study was to determine if D2 receptor-mediated activation of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons occurs via afferent neuronal inhibition of tonically active inhibitory dynorphinergic neurons in the male rat. To this end, the effects of either surgical deafferentation of the mediobasal hypothalamus or administration of a kappa opioid receptor agonist (U-50,488) or antagonist (nor-binaltorphimine (NOR-BNI)) on D2 receptor-mediated activation of TIDA neurons were assessed. For comparison, the activity of mesolimbic DA neurons was also determined in these studies. TIDA and mesolimbic DA neuronal activities were estimated by measuring dopamine synthesis (accumulation of 3,4-dihydroxyphenylalanine (DOPA) following decarboxylase inhibition) and metabolism (concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC)) in terminals of these neurons in the median eminence and nucleus accumbens, respectively. Intraperitoneal administration of the D2 receptor agonist quinelorane caused a dose-dependent increase in DOPAC in the median eminence and a decrease in DOPAC in the nucleus accumbens; surgical deafferentation of the mediobasal hypothalamus prevented the effect of quinelorane in the median eminence, but not the nucleus accumbens. Activation of kappa opioid receptors with U-50,488 had no effect per se, but blocked quinelorane-induced increases in median eminence DOPA. In contrast, U-50,488 had no effect on DOPA in the nucleus accumbens of either vehicle- or quinelorane-treated rats. Blockade of kappa opioid receptors with NOR-BNI increased median eminence DOPA, and prevented the stimulatory effects of quinelorane on dopamine synthesis. Administration of prolactin also increased median eminence DOPA, but did not alter the ability of quinelorane to stimulate dopamine synthesis. Neither NOR-BNI nor prolactin had any effect on DOPA in the nucleus accumbens of vehicle- or quinelorane-treated rats. These results suggest that D2 receptor-mediated activation of TIDA neurons occurs via an afferent neuronal mechanism involving, at least in part, inhibition of tonically active inhibitory dynorphinergic neurons in the male rat.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

The fourth EF-hand of calmodulin and its helix-loop-helix components: impact on calcium binding and enzyme activation.

CaM (4 cTnC) is a calmodulin--cardiac troponin C chimeric protein containing the first, second, and third calcium-binding EF-hands of calmodulin (CaM) and the fourth EF-hand of cardiac troponin C (cTnC) [George, S.E., Su, Z., Fan, D., & Means, A.R. (1993) J. Biol. Chem. 268, 25213-25220]. CaM (4 cTnC) showed 2-fold-enhanced carboxy-terminal Ca2+ affinity relative to CaM and also exhibited impaired activation of the CaM-regulated enzymes smooth muscle myosin light chain kinase (smMLCK), neuronal nitric oxide synthase (nNOS), and phosphodiesterase (PDE). To investigate the molecular basis for these effects, we constructed (1) additional chimeras, replacing most of CaM helix 7, Ca2+-binding loop 4, and helix 8 with the corresponding helices and loops of cTnC; and (2) point mutants in the fourth EF-hand of CaM. Replacement of CaM's fourth loop with the corresponding loop of cTnC enhanced Ca2+ affinity by over 3-fold through an increase in the Ca2+ on rate and also reduced cooperativity of Ca2+ binding. In contrast, substitution of CaM helix 7 or 8 modestly decreased Ca2+ affinity by increasing the Ca2+ off rate, without impairment of cooperativity. All three of the helix and loop chimeras fully activated PDE, with minor shifts in Kact. CaM (helix 7 cTnC) showed a significantly impaired ability to activate smMLCK and nNOS, whereas the other two chimeras retained about 80% of the maximal smMLCK and nNOS activation observed with CaM.

Calcium↗
PubMed1996

Effects of myosin light chain kinase and peptides on Ca2+ exchange with the N- and C-terminal Ca2+ binding sites of calmodulin.

Myosin light chain kinase and peptides from the calmodulin (CaM) binding domains of myosin light chain kinase (RS-20, M-13), CaM kinase II, and the myristoylated alanine-rich protein kinase C substrate protein slowed Ca2+ dissociation from CaM's N-terminal sites from 405 +/- 75/s to 1.8-2.9/s and from CaM's C-terminal sites from 2.4 +/- 0.2/s to 0.1-0.4/s at 10 degrees C. Since Ca2+ dissociates 5-29 times faster from the N-terminal in these CaM.peptide complexes and both lobes are required for activation, Ca2+ dissociation from the N-terminal would control target protein inactivation. Ca2+ binds 70 times faster to the N-terminal (1.6 x 10(8) M-1 s-1) than the C-terminal sites (2.3 x 10(6) M-1 s-1). In a 0.6-ms half-width Ca2+ transient, Ca2+ occupied > 70% of the N-terminal but only 20% of the C-terminal sites. RS-20 produced a 9-fold and CaM kinase II a 6.3-fold increase in C-terminal Ca2+ affinity, suggesting that some target proteins may be bound to the C-terminal at resting [Ca2+]. When this is the case, Ca2+ exchange with the faster N-terminal sites may regulate CaM's activation and inactivation of these target proteins during a Ca2+ transient.

Amino Acid Sequence↗
PubMed1996

Breast cancer patients' personality style, age, and treatment decision making.

BACKGROUND: Previous studies have shown that whereas nearly all cancer patients want information, far fewer wish to make treatment decisions. Although breast cancer patients who were given a choice of lumpectomy versus mastectomy and were encouraged to make the decision were believed to do better psychologically, a 1994 study refuted this. Some authors suggest that patient personality style is an important consideration in decisional preference. METHODS: Newly diagnosed breast cancer patients (n = 76) were surveyed within 6 months of surgery. They answered seven questions about patient and physician roles in the decision-making process. Additionally, they completed the Miller Behavioral Style Scale (MBSS), which categorizes "monitors," or information seekers, and "blunters," or information avoiders. Chi-square analyses were used to explore the relationship of personality style and age to treatment decision-making preferences. RESULTS: Although 80% of women wanted a role in decision making, 74% wanted their surgeons to make a recommendation and when given, 94% followed the recommended treatment plan. Monitors and blunters were equally likely to want physician recommendations. Younger women, particularly those under age 40, were more likely to want a physician's recommendation. Of those women who had specific fears about their cancer (76%), only half of them revealed such fears to their doctors. CONCLUSIONS: The notion that health care consumers, particularly younger ones, desire an independent choice of treatment was contradicted in this study. Physicians are encouraged to provide information and to probe regarding the fears of breast cancer patients in order to reduce anxiety while recognizing that treatment recommendations are desired by most women.

Adult↗
PubMed1996

Comparative absorption of lead from contaminated soil and lead salts by weanling Fischer 344 rats.

A 44-day dosed feed study was performed to compare the bioavailability of lead from contaminated soil versus two lead salts and the effect of soil on gastrointestinal absorption of ingested lead. Male Fischer rats (approximately 4 weeks of age) received lead, 17, 42, or 127 ppm, in the form of lead acetate, lead sulfide, lead-contaminated soil, or combinations thereof in the diet for 7, 15, or 44 days. Control soil was added to the diets of some animals to determine how it might alter lead bioavailability. Blood Delta-aminolevulinic acid dehydratase (Delta-ALAD) and blood, bone, kidney, and liver lead were determined in groups of animals at each time-point. Blood Delta-ALAD was inhibited in a dose-dependent manner and to the greatest degree in the lead acetate and lead acetate/control soil groups, followed by the lead sulfide and lead-contaminated soil groups. Bone and tissue lead levels increased in a dose-dependent manner and were greatest in animals receiving lead acetate and significantly less in animals receiving lead sulfide and lead-contaminated soil. Blood lead levels were generally greatest by 7 days and stabilized at lower levels thereafter. Bone lead concentration-time patterns did not demonstrate the biphasic change seen with tissues and continued to increase in most treatment groups through the course of the study. The presence of soil in the diet clearly attenuated the absorption of lead acetate, but had little effect on the absorption of lead sulfide. Results of these studies confirm previous observations that lead absorption is highly dependent on the form of lead ingested and the matrix in which it is ingested. More important, these studies demonstrate that lead in soil may be significantly less available than estimated by current default assumptions and that the presence of soil may decrease the availability of lead from lead salts on which the default assumptions are based. Results presented here also demonstrate that the weanling rat may represent an appropriate model that could be used to obtain relatively rapid and economical estimates of the availability of lead in complex matrices such as soil.

Absorption↗
PubMed1996

Parvalbumin relaxes frog skeletal muscle when sarcoplasmic reticulum Ca(2+)-ATPase is inhibited.

Inhibition of sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBQ) in frog skeletal muscle fibers at 10 degrees C prolonged the half time of the fall of the Ca2+ transient by 62% and twitch force by 100% and increased peak force by 120% without increasing the amplitude of the Ca2+ signal. In the presence of TBQ the rate of relaxation and the rate of fall of Ca2+ became progressively slower in a series of twitches until relaxation failed. Relaxation rate decreased with a time course (approximately 2 s-1) similar to the Mg2+ off rate from purified parvalbumin (PA; 3.6 s-1). TBQ slowed the rate of fall of Ca2+ (5-fold) and force (8-fold) in a 0.3-s tetanus so that the rate of fall of Ca2+ (approximately 2.5 s-1) was similar to the Mg2+ off rate from PA. TBQ caused a near total failure of both Ca2+ sequestration and relaxation in a 1.1-s tetanus, during which PA would be saturated with Ca2+ and could not contribute to relaxation. Thus, when the SR Ca(2+)-ATPase is inhibited, Mg(2+)-PA can sequester Ca2+ and produce relaxation at a rate that is defined by the Mg2+ off rate from PA.

Aniline Compounds↗
PubMed1996

Demographics of brain metastasis.

Brain metastases are the most common intracranial tumor, significantly out-numbering primary brain tumors. The apparent increase in the ratio of brain metastases to primary tumors may be the result of a number of factors, including the possibility of a CNS "pharmacologic sanctuary," an aging population, and improved imaging studies. Among adults, the most common origins of brain metastasis include primary tumors of the lung, breast, skin (melanoma), and gastrointestinal tract. Among patients under 21 years of age, brain metastases most often arise from the sarcomas and germ cell tumors.

Adolescent↗
PubMed1996

Evaluating lead bioavailability data by means of a physiologically based lead kinetic model.

A method of bioavailability estimation is presented in which a physiologically based kinetic model of lead kinetics is fit simultaneously to blood and bone lead concentrations after a period of exposure to dietary lead. Optimization of the simultaneous fit, varying only fractional absorption, gives the best estimate of fractional bioavailability for each treatment group. The analysis was applied to data from three separate studies in which rats were fed for 30 consecutive days purified diets containing lead added as lead acetate, mine waste-contaminated test soils, or mine waste itself. Fractional absorption decreased as lead intake increased, regardless of the source of the lead; but the magnitude of this dose dependence was lead source-dependent. There were no differences in lead absorption by male and female rats when lead intake was expressed per unit body weight. Fractional absorption varied from 4 to 5%, at low exposure rates (1-2 mg lead/kg/day) when lead acetate was added to the diet, to 0.24% at a high exposure rate (24 mg/kg/day) when a mine waste-contaminated test soil was added to the diet. Comparison of the results of this analysis with the results of a more conventional analysis, in which the bone and blood lead concentrations were separately compared with bone and blood lead concentrations in rats given daily injections of lead acetate intravenously for 29 consecutive days, demonstrated that the standard analysis failed to reveal the dose dependence of fractional absorption.

Animal Feed↗
PubMed1995

Characterization and partial purification of two pre-tRNA 5'-processing activities from Daucus carrota (carrot) suspension cells.

Two distinct RNase P-like activities which cleave leader sequences from pre-tRNA molecules to give mature 5' ends have been identified in carrot suspension-culture cells. An Escherichia coli pre-tRNA(Phe) and a tobacco pre-tRNA(Tyr) were transcribed in vitro then used as substrates for processing reactions in a cell-free extract. The pre-tRNA(Tyr) transcript was used to establish optimal salt and divalent cation requirements for processing. Kinetic experiments were then carried out on both substrates to determine if 5' and 3' processing were ordered. Primer extension analysis of processing intermediates and stable products verified that an ammonium sulfate fraction of the extract was indeed capable of accurately processing the 5' ends of both pre-tRNAs. Subsequent fractionation of the 5' end-processing activity by chromatography on phosphocellulose revealed two distinct activities, eluting at 0.1 and 0.5 M KCI, when assayed with the tobacco pre-tRNA(Tyr) substrate. When the same fractions were assayed with the E. coli pre-tRNA(Phe), only the 0.1 M KCI fraction exhibited activity. Both of the active fraction display sensitivity to micrococcal nuclease (MN) and proteinase K indicating each is a ribonucleoprotein, a result not seen with other plant RNase Ps. Subsequent FPLC fractionation of the two activities using Mono Q and Mono S columns demonstrated that the two activities could be further distinguished on the basis of their chromatographic behavior.

Base Sequence↗
PubMed1995

Characterization of the induced response of slash pine to inoculation with bark beetle vectored fungi.

Six 25- to 30-year-old slash pine, Pinus elliottii Englm. var. elliottii, trees were inoculated with Ophiostoma minus (Hedgc.) H.P. Sydow, O. ips (Rumb.) Nannf or sterile water. Two, 4 and 6 weeks after inoculation, the lengths of developing lesions and the monoterpene concentration of the necrotic tissue within each lesion were measured. Both sterile and fungal wounding resulted in the development of lesions in the phloem-outer xylem. At both 4 and 6 weeks after inoculation, lesions induced by O. minus were significantly larger than lesions induced by O. ips or sterile water, whereas the lesions induced by O. ips and sterile water were similar in size at all sampling periods. At 2, 4 and 6 weeks after inoculation, lesions induced by O. minus had significantly greater concentrations of monoterpenes than lesions induced by O. ips or sterile water. The monoterpene concentration of lesions induced by O. ips was significantly greater than that of lesions induced by sterile water only at the 6-week sampling period. Visual examination of the lesions indicated that O. minus but not O. ips was inhibiting the development of callus tissue, suggesting that the strain of O. ips was either nonpathogenic or avirulent.

Journal Article↗
PubMed1995

Using ulcer surface area and volume to document wound size.

The evaluation of ulcer size is normally limited to measuring length, width, and depth, and comparing those figures to previously obtained values. These comparisons are grossly inaccurate, and a more representative technique can be used by treating the ulceration as a three-dimensional object. The author proposes several mathematical formulae that are easily computed on a hand-held calculator. The formulae use the measurements of length, width, and depth, and translate those dimensions into surface area and volume.

Foot Ulcer↗
PubMed1995

Bullosis diabeticorum.

The authors present a case of bullous dermatosis in a diabetic patient. The lesions were drained and deroofed, and at 1-year follow-up, the patient related no problems. Proper diagnosis and treatment of these lesions will avoid infection and ulceration.

Diabetic Foot↗
PubMed1994

Absolute bioavailability of lead acetate and mining waste lead in rats.

The primary purpose of this study was to generate data that could be used to determine the absolute bioavailability of lead using data from a previous study in which soil containing lead from mining waste was mixed with feed. Young male and female Sprague-Dawley rats (7-8 weeks of age, five/sex/group) were given either soluble lead acetate mixed in a purified diet (AIN-76) at three different dose levels (1, 25, and 250 ppm Pb for 30 consecutive days) or intravenously at doses of 0.02, 0.20, and 2.0 mg Pb/kg BW for 29 days. A control group (purified diet only) was also included. The intravenous groups were used to provide maximal absorption (lead presumed to be 100% bioavailable) and accumulation data for lead in blood, bone, and liver. The lead acetate groups were used to evaluate the comparability of the present study with a previous study that compared bioavailable lead from ingested soil and lead acetate. Group mean whole blood, bone and liver lead concentration values increased with increasing dose levels for all treatment groups. A linear relationship was observed between blood lead concentration and dose following intravenous administration of lead and this provided empirical support for using blood lead concentrations at supposed steady state (approximately 30 days) to compute the bioavailability of lead administered by different routes and from different sources. The absolute bioavailability values of mining waste lead in soil were low based on the results for all tissue types. Absolute bioavailability values for lead acetate in dosed feed for blood, bone, and liver were approximately 6-, 19-, and 20-fold greater, respectively, than mining waste lead. Based on the current design and test system used, the absolute bioavailability of mining waste lead in soil administered in feed was approximately 3% based on blood data and less than 1% based on bone and liver data. These data are consistent with the low solubility of the constituent lead mineral phases in Butte soils.

Administration, Oral↗
PubMed1994

Positively charged side chains in the insulin-like growth factor-1 C- and D-regions determine receptor binding specificity.

Human insulin-like growth factor-1 (hIGF-1) contains seven positively charged residues in the A-, C-, and D-regions that are not present in similar positions in insulin. To determine whether these residues contribute to receptor binding specificity for the insulin-like growth factor-1 receptor (IGF-1R) relative to the insulin receptor (IR) we examined the binding of hIGF-1 analogs in which these residues have been replaced with either alanine or the corresponding residue of insulin. To improve expression and facilitate purification we employed insulin-like growth factor (IGF-1) analogs modified with an N-terminal 8-amino acid epitope. This additional epitope did not alter receptor binding specificity. Alanine substitution for the positively charged residues in the C- and D-regions of IGF-1 led to 15- and 10-fold losses, respectively, in binding potency for the human IGF-1R, but they increased the potency of binding to the human IR 29- and 6-fold, respectively. In contrast, substitution of the positively charged side chains in the A-region with the corresponding uncharged residues of insulin had little effect on binding to either receptor. These data suggest that the positive charges in the C- and D-regions of IGF-1 contribute significantly to the binding preference of the IGF-1R for IGF-1. In complementary experiments using chimeric receptors we have also shown that the IGF-1 receptor elements required to discriminate in favor of the positive charges in the C- and D-regions are contained in the N-terminal 283 amino acids of the alpha-subunit. Insulin receptor elements that discriminate against these charges are within the N-terminal 225 amino acids of its alpha-subunit.

Amino Acid Sequence↗
PubMed1994

Modulation of Ca2+ exchange with the Ca(2+)-specific regulatory sites of troponin C.

Calcium (Ca2+) binding to the N-terminal Ca(2+)-specific sites on troponin C (TnC) regulate the contraction-relaxation cycle of skeletal muscle. A mutant TnC (F29W) and dansylaziridine-labeled TnC undergo large fluorescence increases when Ca2+ binds to their Ca(2+)-specific sites (half-maximal at pCa 5.8). Calmidazolium and the additional mutation of Met-82 to Gln (F29W,M82Q) increased Ca2+ affinity at these Ca2+ sites by approximately 4-fold (half-maximal at pCa approximately 6.4). Calmidazolium and the M82Q mutation decreased the rate of Ca2+ dissociation from the Ca(2+)-specific sites approximately 3.4-fold (from approximately 462 +/- 84/s to approximately 138 +/- 30/s) at 22 degrees C. Ca2+ associated with the Ca(2+)-specific sites of these proteins at 1-2 x 10(8) M-1 s-1 at 4 degrees C. These drug- and mutation-induced increases in Ca2+ affinity occur solely from large decreases in the Ca2+ off-rate without an effect on the Ca2+ on-rate. Thus, Ca2+ can bind to the Ca(2+)-specific sites of TnC as rapidly as it can diffuse to the protein, consistent with the extreme speed of skeletal muscle contraction. Drugs and/or site-directed mutagenesis can modify the Ca2+ sensitivity and the rate of Ca2+ exchange with TnC's Ca(2+)-specific sites to perhaps alter the rate of relaxation and/or the rate of rise of tension.

Animals↗