Biomedical subjects

R M Welch

Publications and source records attributed to R M Welch.

At least 37 records · Page 2Linked to original sources

PubMed1990

Physiological Characteristics of Fe Accumulation in the ;Bronze' Mutant of Pisum sativum L., cv ;Sparkle' E107 (brz brz).

The pea (Pisum sativum L.) mutant, E107 (brz, brz) accumulated extremely high concentrations of Fe in its older leaves when grown in light rooms in either defined nutrient media or potting mix, or outdoors in soil. Leaf symptoms (bronze color and necrosis) were correlated with very high Fe concentrations. When E107 plants were grown in nutrient solutions supplied 10 mum Fe, as the Fe(III)-N,N'-ethylenebis[2-(2-hydroxyphenyl)glycine] chelate, their roots released higher concentrations of Fe(III) reducing substances to the nutrient media than did roots of the normal parent cv, ;Sparkle.' Reciprocal grafting experiments demonstrated that the high concentrations of Fe in the shoot was controlled by the genotype of the root. In short-term (59)Fe uptake studies, 15-day-old E107 seedlings exhibited higher rates of Fe absorption than did ;Sparkle' seedlings under Fe-adequate growth conditions. Iron deficiency induced accelerated short-term Fe absorption rates in both mutant and normal genotypes. Iron-treated E107 roots also released larger amounts of both protons and Fe(III) reductants into their nutrient media than did iron-treated ;Sparkle' roots. Furthermore, the mutant translocated proportionately more Fe to its shoot than did the parent regardless of Fe status.

Journal Article↗

PubMed1990

Physiological Characterization of a Single-Gene Mutant of Pisum sativum Exhibiting Excess Iron Accumulation: I. Root Iron Reduction and Iron Uptake.

Root systems of mutant (E107) and parental (cv ;Sparkle') Pisum sativum genotypes were studied to determine the basis for excess Fe accumulation in E107. Plants were grown with (+Fe-treated) or without (-Fe-treated) added Fe(III)-N,N'-ethylenebis[2-(2-hydroxyphenyl)glycine] in aerated nutrient solutions. Daily measurements of Fe(III) reduction indicated a four-to seven-fold higher reduction rate in +Fe- or -Fe-treated E107, and -Fe-treated Sparkle, when compared with +Fe-treated Sparkle. An agarose-based staining technique used to localize Fe(III) reduction, revealed Fe(III) reduction over most of the length of the roots (but not at the root apices) in both E107 treatments and -Fe-treated Sparkle. In +Fe-treated Sparkle, Fe(III) reduction was either nonexistent or localized to central regions of the roots. Measurements of short-term Fe influx (with 0.1 millimolar (59)Fe(III)-ethylenediaminetetraacetic acid) was also enhanced (threefold) in +Fe- or -Fe-treated E107 and -Fe-treated Sparkle, relative to +Fe-treated Sparkle. The physiological characteristics of E107 root systems, which are similar to those seen in Fe-deficient Sparkle, have led us to conclude that the mutation causes E107 to act functionally as an Fe-deficient plant, and appears to explain the excess Fe accumulation in E107.

Journal Article↗

PubMed1990

Does Iron Deficiency in Pisum sativum Enhance the Activity of the Root Plasmalemma Iron Transport Protein?

Roots of Fe-sufficient and Fe-Deficient pea (Pisum sativum L.) were studied to determine the effect of Fe-deficiency on the activity of the root-cell plasmalemma Fe(2+) transport protein. Rates of Fe(III) reduction and short-term Fe(2+) influx were sequentially determined in excised primary lateral roots using Fe(III)-ethylene-diaminetetraacetic acid (Fe[III]-EDTA). Since the extracellular Fe(2+) for membrane transport was generated by root Fe(III) reduction, rates of Fe(2+) influx for each root system were normalized on the basis of Fe(III) reducing activity. Ratios of Fe(2+) influx to Fe(III) reduction (micromole Fe(2+) absorbed/micromole Fe[III] reduced) revealed no enhanced Fe(2+) transport capacity in roots of Fe-deficient peas (from the parental genotype, Sparkle) or the functional Fe-deficiency pea mutant, E107 (derived from Sparkle), relative to roots of Fe-sufficient Sparkle plants. Data from studies using 30 to 100 micromolar Fe(III)-EDTA indicated a linear relationship between Fe(2+) influx and Fe(III) reduction (Fe(2+) generation), while Fe(2+) influx saturated at higher concentrations of Fe(III)-EDTA. Estimations based on current data suggest the Fe(2+) transport protein may saturate in the range of 10(-4.8) to 10(-4) molar Fe(2+). These results imply that for peas, the physiological rate limitation to Fe acquisition in most well-aerated soils would be the root system's ability to reduce soluble Fe(III)-compounds.

Journal Article↗

PubMed1989

Bioavailability of and interactions between zinc and selenium in rats fed wheat grain intrinsically labeled with 65Zn and 75Se.

A whole-body radioassay procedure was used to assess the absorption by male rats of zinc (Zn) and selenium (Se) in wholewheat grain labeled either intrinsically or extrinsically with 65Zn and 75Se. Test meals fed to zinc-depleted and to zinc-adequate rats contained grain harvested from plants grown in nutrient solutions with varying amounts of zinc and selenium. Absorption of intrinsic 65Zn by zinc-depleted rats ranged from about 46 to 57% of the dose, and 65Zn absorption decreased as the selenium content of the grain increased. Absorption of intrinsic 65Zn by zinc-adequate rats ranged from about 21 to 26% of the dose, and 65Zn absorption was not affected by the amount of either zinc or selenium in the meal. Absorption of intrinsic 75Se ranged from about 43 to 52% of the dose in zinc-depleted rats and from about 35 to 48% of the dose in zinc-adequate rats. Absorption of intrinsic 75Se by zinc-adequate rats decreased as the zinc content of the grain increased. Relative to the absorption and retention by rats of intrinsic zinc and selenium in wholewheat grain, interactions occurred between natural forms of zinc and selenium at concentrations potentially encountered in wheat. Selenium had an antagonistic effect on zinc absorption by zinc-depleted rats, and zinc had an antagonistic effect on selenium absorption by zinc-adequate rats.

Animals↗

PubMed1989

Plant contents of magnesium, calcium and potassium in relation to ruminant nutrition.

Grass tetany and wheat pasture poisoning are metabolic diseases of mature, lactating beef cattle. In some other countries, similar problems occur with dairy cattle. In grass tetany, the animals generally are grazing cool-season forages in which Mg concentration or bioavailability of plant Mg is low. Levels of Mg in the blood serum also generally are low. Grass tetany can occur in beef cattle fed hay made from grass, small grains or alfalfa Medicago sativa L.). In wheat pasture poisoning where animals are grazing small grains forages, blood levels of Ca often are low, and blood Mg also may be low. Both grass tetany and wheat pasture poisoning occur when plants are growing rapidly in the spring, at the time of heavy lactation demand by ruminants for Mg and Ca. When the temperature increases and plants start to grow rapidly in the spring, concentrations of K, N, organic acids, and the ratio of K/(Ca + Mg) all increase, and the percent dry matter decreases. Much research remains to be done to understand all the soil, plant, and animal aspects of grass tetany and wheat pasture poisoning.

Animal Nutritional Physiological Phenomena↗

PubMed1989

In vitro metabolism of mivacurium chloride (BW B1090U) and succinylcholine.

The in vitro rates of metabolism of mivacurium chloride and succinylcholine in pooled human plasma were compared. In addition, the rate of metabolism of mivacurium in buffered solutions of butyrylcholinesterase (E.C. 3.1.1.8) and acetylcholinesterase (E.C. 3.1.1.7) was determined. Succinylcholine concentrations were measured spectrophotometrically, and mivacurium concentrations were determined with a high-pressure liquid chromatographic assay. The hydrolysis of mivacurium in plasma followed first-order kinetics, and the rate of hydrolysis decreased as plasma was serially diluted. The Michaelis-Menten constant (Km) for mivacurium metabolism in plasma was 245 mumol/L, and the maximum velocity (Vmax) was 50 U/L; the Km for succinylcholine was 37 mumol/L, and Vmax was 74 U/L. At comparable multiples of the Km the hydrolysis rate of mivacurium was 70% of that of succinylcholine. Mivacurium was metabolized significantly in solutions containing butyrylcholinesterase, but only minimally in solutions containing acetylcholinesterase.

Butyrylcholinesterase↗

PubMed1987

Bioavailability to rats of iron in six varieties of wheat grain intrinsically labeled with radioiron.

Bioavailability to anemic rats of iron in six varieties of wheat grain was assessed by a whole-body radioassay procedure. Intrinsically labeled kernels were harvested from plants grown in 59Fe-labeled nutrient solutions. The varieties used were selected from 18 varieties of field-grown wheat grain that were analyzed for iron, protein and phytate content. Concentrations of iron, phytate and protein in grain of field-grown varieties ranged from 34 to 55 ppm, 0.7 to 1.2% dry wt and 11.3 to 15.4% dry wt, respectively. In grain from varieties grown in nutrient solutions, iron, phytate and protein concentrations ranged from 35 to 50 ppm, 1 to 1.2% dry wt, and 13.8 to 16.8% dry wt, respectively. Depending on the variety of intrinsically labeled grain fed in test meals to anemic rats (hemoglobin averaged 5.8 g/dL), absorption of 59Fe ranged from about 62 to 74% of the dose; differences among varieties were not significant (P greater than 0.05). Rats fed 59Fe-labeled FeCl3 absorbed about 71% of the dose, which was similar to the average amount (69% of dose) absorbed by rats fed wheat. We concluded that selection of wheat varieties for increased yield or protein content has not adversely affected the bioavailability of iron in the grain.

Anemia, Hypochromic↗

PubMed1987

Nickel: a micronutrient essential for higher plants.

Nickel was established as an essential micronutrient for the growth of temperate cereal crops. Grain from barley (Hordeum vulgare L. cv ;Onda'; containing 40 to 80 nanograms of Ni per gram dry weight) grown in solution culture with negligible Ni concentrations (< 30 nanograms of Ni per liter) exhibited greatly reduced germination rates (i.e. 50% less than grain from Ni-adequate plants) and seedling vigor of the viable grain was greatly depressed. Grain containing less than 30 nanograms per gram dry weight was inviable. Under Ni-deficient conditions, barley plants fail to produce viable grain because of a disruption of the maternal plant's normal grain-filling and maturation processes that occur following formation of the grain embryo. The observations that (a) barley plants fail to complete their life cycle in the absence of Ni and (b) addition of Ni to the growth medium completely alleviates deficiency symptoms in the maternal plants satisfies the essentiality criteria; thus, Ni should be considered a micronutrient for cereals. Because Ni is required by legumes, and is now established as essential for cereals, we conclude that Ni should be added to the list of micronutrients essential for all higher plant growth.

Journal Article↗

PubMed1987

Pharmacological significance of the species differences in bupropion metabolism.

Bupropion provided a dose-dependent prevention of tetrabenazine-induced sedation in mice but not rats. Bupropion was extensively metabolized in mice, rats, dogs and man. About 85% of the dose was excreted in urine of rats and man. The predominant metabolites in rat urine were side chain cleavage products of bupropion (m-chlorobenzoic acid) with a minor fraction consisting of basic side chain hydroxylated metabolites. Mice, dogs and man form a major side chain hydroxylated product (BW 306U) which appeared in higher concentration than bupropion in plasma of these species but not rats. The relatively high plasma levels of BW 306U in mice but not rats may account for the species difference in pharmacological response observed with bupropion.

Animals↗

PubMed1986

Comparative disposition of codeine and pholcodine in man after single oral doses.

Four healthy male subjects received single oral doses of 15, 30 and 60 mg of codeine and pholcodine according to a balanced cross-over design with an interval of 7 days between the six treatments. Blood samples were collected for 8 h after each drug administration. In phase 2 of the study six different male volunteers received single oral doses of 60 mg of codeine and pholcodine with a 14 day interval between successive drug treatments. Blood was sampled for 12 h after codeine and 121 h after pholcodine administration. Plasma concentrations of free (unconjugated) and total (unconjugated plus conjugated) codeine, pholcodine and morphine were determined by radioimmunoassay and selected pharmacokinetic parameters were derived from these data. Pharmacokinetics of both drugs were independent of dose. Codeine was absorbed and eliminated relatively rapidly [elimination t1/2 = 2.3 +/- 0.4 h (mean +/- s.d.)]. While codeine kinetics were adequately described by a one-compartment open model with first-order absorption, a two-compartment model was required to describe pholcodine elimination from plasma (t1/2,z = 37.0 +/- 4.2 h). Plasma concentrations of conjugated codeine were much greater than those of the unconjugated alkaloid. By contrast, pholcodine appeared to undergo little conjugation. Biotransformation of codeine to morphine was evident in all subjects, although the extent of this metabolic conversion varied considerably between subjects. Morphine was not detectable in the plasma of any subject after pholcodine administration.

Administration, Oral↗

PubMed1985

Effects of Ni Deficiency on Some Nitrogen Metabolites in Cowpeas (Vigna unguiculata L. Walp).

Cowpeas grown in nutrient solutions, from which Ni had been removed by a ligand exchange technique, accumulated urea in most tissues. Urea levels were highest (up to 3.1 percent dry weight) in necrotic leaf tips. Urea accumulation in Ni-deficient cowpea tissues amounted to about 1 percent of the total N. The accumulation of urea was presumably associated with the catabolism of N compounds in older tissues and the redistribution of N catabolites within the plant during the reproductive growth. The exclusion of N salts from the nutrient media at a late stage of growth, either with or without added Ni, led to a general amelioration of urea accumulation and a lower level of the related amino acid, arginine, in root and stem tissue. Plant leaves that contained toxic levels of urea and displayed necrotic symptoms had tissue Ni levels ranging from less than 0.01 to 0.15 mug Ni per gram dry weight. Nickel concentrations in tissue from plants not treated with Ni, were initially very low, but increased as the cowpeas matured. Apparently, there was a source of Ni contamination in the Ni-deficient growth media which provided a source of Ni for uptake by the plants during growth. Ureide levels were low and unaffected by Ni deprivation. No evidence for free purines or uric acid accumulation in plant tissues could be found. It is hypothesized that Ni (and urease) participates in the normal N metabolism of these plants during the reproductive phase of growth.

Journal Article↗

PubMed1985

Major differences in the specificity and regulation of mouse renal cytochrome P-450-dependent monooxygenases. A comparison of xenobiotic and endogenous substrates.

In the present study we have investigated the influence of sex on the specificity of mouse renal microsomes toward endogenous and xenobiotic substrates. Renal microsomes from C3H/HeJ mice were characterized by the following: a 4- to 5-fold male predominance in cytochrome P-450 concentration; a difference between male and female renal microsomes in the absorption maximum for the reduced P-450 . CO complex, 450 and 452 nm, respectively; a lack of a sex difference in lauric acid 12-hydroxylase activity; an 18-fold sex difference (M greater than F) in progesterone 16 alpha-hydroxylase activity; and 8- to 10-fold sex differences (M greater than F) in progesterone 15 alpha-hydroxylase, dimethylnitrosamine demethylase, and lauric acid 11-hydroxylase activities. Treatment of female mice with testosterone propionate selectively induced lauric acid 11-hydroxylase and dimethylnitrosamine demethylase activities 8- and 14-fold, respectively, but had no effect on progesterone 15 alpha- and 16 alpha-hydroxylase activities or on the high female rate of lauric acid 12-hydroxylation. Inhibition studies conducted with male mouse renal microsomes revealed that of the substrates examined, only testosterone inhibited the 15 alpha- and 16 alpha-hydroxylations of progesterone in vitro. In addition, progesterone 15 alpha-hydroxylase was distinguished from 16 alpha-hydroxylase by the greater degree of testosterone inhibition (68 and 44%, respectively) and by sensitivity to metyrapone inhibition. Mouse renal cytochrome P-450 heterogeneity is indicated by the selective effects of androgen induction and metyrapone inhibition. Moreover, distinct modes of regulation are observed between the isozymes involved in steroid hydroxylation and those which catalyze the 11- and 12-hydroxylations of lauric acid in mouse renal microsomes.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1984

Triprolidine radioimmunoassay: disposition in animals and humans.

A hapten derivative of triprolidine, bearing an acrylic acid side chain ortho to the pyridine ring nitrogen atom, was synthesized and coupled to bovine serum albumin. Immunization of New Zealand White rabbits with the resulting drug-protein conjugate resulted in the production of antisera capable of binding a radioiodinated tyramine conjugate of the triprolidine hapten derivative at high antiserum dilutions (1:70,000-1:150,000). These antisera were used to develop a radioimmunoassay (RIA) for triprolidine in human plasma with a sensitivity limit of 0.1 ng/mL (0.01 ng of actual mass). The known hydroxymethyl and carboxyl metabolites of triprolidine cross-reacted weakly (less than 2 and less than 0.05%, respectively) with this antiserum. The RIA could be used for the direct analysis of triprolidine in human and rabbit plasma, but not for rat or dog plasma, presumably due to the presence of other interfering substances (possibly metabolites). The validity of the RIA procedure in human plasma was demonstrated by comparative analysis of a number of samples by quantitative TLC (r = 0.985, slope = 1.076). The assay was employed to describe the pharmacokinetics of triprolidine in the rabbit (t 1/2, beta = 1.7 h). The assay had adequate sensitivity to detect low circulating drug concentrations in humans after therapeutic oral doses and also substantiated previous disposition experiments with triprolidine in humans (t 1/2, beta = 2.27 h). TLC analysis demonstrated that the absolute oral bioavailability of triprolidine (1-mg/kg dose) in the dog was low (4%). A comparison of triprolidine pharmacokinetic parameters in dogs, rabbits, rats, and humans revealed considerable similarity in elimination characteristics in these species.

Animals↗

PubMed1984

A simple plant nutrient solution purification method for effective removal of trace metals using controlled pore glass-8-hydroxyquinoline chelation column chromatography.

Column chelation chromatography on controlled pore glass-8-hydroxyquinoline was demonstrated to be a very efficient method for removing trace metal contaminants from concentrated macronutrient salt solutions used to prepare nutrient media. By using (63)Ni and (65)Zn radio-isotopes as tracers, controlled pore glass-8-hydroxyquinoline column packings were found to retain 99.9% of the radiotracer and quantitative recovery of the radioisotopes from these columns was obtained by eluting with 1.2 n HCl. This method has several advantages over liquid-liquid extraction methods of purification which previously have been used in plant micronutrient research.

Journal Article↗

PubMed1984

Nickel in higher plants: further evidence for an essential role.

Soybeans (Glycine max [L.] Merr.) grown in Ni-deficient nutrient solutions accumulated toxic urea concentrations which resulted in necrosis of their leaflet tips, a characteristic of Ni deficiency. Estimates of the Ni requirement of a plant were made by using seeds produced with different initial Ni contents. When compared to soybeans grown from seeds containing 2.5 nanograms Ni, plants grown from seeds containing 13 nanograms Ni had a significantly reduced incidence of leaflet tip necrosis. Plants grown from seeds containing 160 nanograms Ni produced leaves with almost no leaflet tip necrosis symptoms. Neither Al, Cd, Sn, nor V were able to substitute for Ni.In other experiments, a small excess of EDTA was included in the nutrient solution in addition to that needed to chelate micronutrient metals. Under these conditions, nodulated nitrogen-fixing soybeans had a high incidence of leaflet tip necrosis, even when 1 micromolar NiEDTA was supplied. However, in nutrient solutions containing inorganic sources of N, 1 micromolar NiEDTA almost completely prevented leaflet tip necrosis, although no significant increase in leaf urease activity was observed. Cowpeas (Vigna unguiculata [L.] Walp) grown in Ni-deficient nutrient solutions containing NO(3) and NH(4) also developed leaflet tip necrosis, which was analogous to that produced in soybeans, and 1 micromolar NiEDTA additions prevented these symptoms.These findings further support our contention that Ni is an essential element for higher plants.

Journal Article↗

PubMed1984

Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers.

Plasma and milk concentrations of pseudoephedrine and triprolidine were determined (by radioimmunoassay) in three lactating mothers over 12-48 h after ingestion of a combination medication containing 60 mg of pseudoephedrine hydrochloride and 2.5 mg of triprolidine hydrochloride monohydrate. Pseudoephedrine concentrations in milk were consistently higher than those in plasma. The total amount of drug in milk, as judged by areas under the respective curves (AUC), was two to three times greater than in plasma. Triprolidine concentrations in milk and plasma were more variable between subjects than those of pseudoephedrine. AUC values for milk and plasma were similar for one subject, while the plasma value exceeded that for milk in another woman. The fraction of the dose excreted in milk was estimated to be 0.4-0.7% for pseudoephedrine and 0.06-0.2% for triprolidine.

Adult↗

PubMed1983

Acetaminophen metabolism in subjects fed charcoal-broiled beef.

The effects of consumption of charcoal-broiled beef on the metabolism of acetaminophen by conjugation were determined in nine normal subjects. We had reported that beef prepared in this manner accelerates the oxidative metabolism of drugs, including the oxidation of phenacetin to N-acetyl-p-aminophenol (acetaminophen). In nine normal subjects, a control diet was followed by a charcoal-broiled beef diet, which was followed by the control diet. The charcoal-broiled beef had little or no effect on the plasma-level profile of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate, or on the urinary excretion of acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, 3-methoxy-acetaminophen, or the cysteine and mercapturic acid conjugates of acetaminophen. Results indicate that the enzyme systems that conjugate acetaminophen in man are subject to little or no influence by charcoal-broiled beef. Therefore dietary factors that increase drug oxidations cannot be assumed to have a similar effect on drug conjugation.

Acetaminophen↗

PubMed1983

Nickel is not required for apourease synthesis in soybean seeds.

Soybeans (Glycine max L. Merr. cv ;Maple Presto') harvested from plants cultured in nickel-free medium had <0.005% the activity of nickel-sufficient beans and only 15% the activity of a urease-null variety, Itachi. However, whereas Itachi has no detectable urease protein, nickel-free beans of the variety Maple Presto exhibit normal or near normal levels of urease apoprotein. Thus, nickel isn't necessary for urease apoprotein synthesis. The apoprotein wasn't activated by nickel in vitro but, upon seed imbibition of nickel, urease was partially activated. This in vivo activation was not inhibited by cychoheximide.

Journal Article↗