Biomedical subjects
P E Johnson
Publications and source records attributed to P E Johnson.
Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men.
Identification of the andrological variables most sensitive to zinc depletion would expedite the diagnosis of male reproductive pathology induced by zinc deficiency. Eleven volunteers living on a metabolic ward were fed a diet composed of a mixture of a semisynthetic formula and conventional foods supplemented with ZnSO4 to supply a total of 1.4, 2.5, 3.4, 4.4, or 10.4 mg Zn/d. After an equilibration period of 28 d (10.4 mg Zn/d), all treatments were presented for 35 d each, the first four in random order and the fifth last. Compared with when they were consuming 10.4 mg Zn/d, volunteers consuming 1.4 mg Zn/d exhibited decreased semen volumes (3.30 vs 2.24 mL) and serum testosterone concentrations (26.9 vs 21.9 nmol/L), and no change in seminal zinc concentrations. Compared with 10.4 mg Zn/d, treatments of 1.4, 2.5, and 3.4 mg Zn/d decreased the total semen zinc loss per ejaculate (6.29 vs 3.81, 4.68, and 5.03 mumols/ejaculate). Seminal loss accounted for 9% of total body zinc loss when 1.4 mg Zn/d was consumed. Seminal phosphorus concentrations were elevated during all four phases of zinc depletion (28.4 vs 32.9, 31.0, 34.2, and 33.6 mmol/L). The findings suggest that serum testosterone concentrations, seminal volume, and total seminal zinc loss per ejaculate are sensitive to short-term zinc depletion in young men.
Effects of age and sex on copper absorption, biological half-life, and status in humans.
Healthy, free-living men and women aged 20-83 y (n = 127) were studied to determine the effects of age and sex on copper absorption, biological half-life (BH), and status. Copper absorption was greater in women (71%) than in men (64%) aged 20-59 y (P = 0.02), but did not differ in men and women aged 60-83 y. BH of 67Cu ranged from 13 to 33 d and differed between men and women aged 20-59 y (P = 0.006), but not between men and women aged 60-83 y. Plasma copper, enzymatic ceruloplasmin (Cp), and immunoreactive (RID) Cp were significantly higher in women than in men (P < 0.005), but superoxide dismutase (SOD) and in vitro 67Cu uptake by red blood cells did not differ. Plasma copper, RID Cp, and cytochrome oxidase in platelets and mononuclear cells were significantly affected by age (P < 0.005). Oral contraceptives elevated plasma copper, enzymatic Cp, and SOD activity but not copper absorption and BH in women aged 20-39 y. Copper intake from self-selected diets was 0.9-1.2 mg/d for women and 1.2-1.3 mg/d for men, but net copper absorption (micrograms Cu.kg body wt-1.d-1) did not differ. Thus, dietary copper intake requirements may differ between men and women.
Effects of copper, iron, and ascorbic acid on manganese availability to rats.
Four experiments were done to characterize the interactions of copper, iron, and ascorbic acid with manganese in rats. All experiments were factorially arranged Dietary Mn concentrations were less than 1 micrograms/g (Mn0) and 50 micrograms/g (Mn+). Dietary Cu was less than 1 mg/g (Cu0) and 5 micrograms/g (Cu+); dietary Fe was 10 micrograms/g (Fe10) and 140 micrograms/g (Fe140). Ascorbic acid (Asc) was not added to the diet or added at a concentration of 10 g/kg diet. Experiment 1 had two variables, Mn and Cu; in Experiment 2, the variables were Mn and Asc. In Experiment 3, the variables were Mn, Cu, and Asc; in Experiment 4, they were Mn, Cu, and Fe. Definite interactions between Mn and Cu were observed, but they tended to be less pronounced than interactions between Mn and Fe. Cu depressed absorption of 54Mn and accelerated its turnover. In addition, adequate Cu (Cu+), compared with Cu0, depressed liver, plasma, and whole blood Mn of rats. Absorption of 67Cu was higher in animals fed Mn0 diets than in those fed Mn+. Ascorbic acid depressed Mn superoxide dismutase activity and increased Cu superoxide dismutase activity in the heart. The addition of ascorbic acid to the diet did not affect Mn concentration in the liver or blood. Absorption of 54Mn was depressed in rats fed Fe140 compared with those fed Fe10. Interactions among Fe, Cu, and Mn resulted in a tendency for Mn superoxide dismutase activity to be lower in rats fed Fe140 than in rats fed Fe10. Within the physiologic range of dietary concentrations, Mn and Cu have opposite effects on many factors that tend to balance one another. The effects of ascorbic acid on Mn metabolism are much less pronounced than effects of dietary Cu, which in turn affects Mn metabolism less than does Fe.
Effects of stearic acid and beef tallow on iron utilization by the rat.
Two experiments were done in which anemic rats were fed diets containing safflower oil or stearic acid and low (10 ppm) or adequate (39-42 ppm) iron. Diets were 24% fat by weight. In the stearic acid diets, 2% (Experiment 1) or 4% (Experiment 2) of the fat was supplied by safflower oil to satisfy essential fatty acid requirements. Repletion of hemoglobin, hematocrit, and liver iron was assessed. Compared with safflower oil in both experiments, stearic acid had a significant positive effect (P less than 0.0001) on repletion of hemoglobin (Hb), hematocrit (Hct), and liver iron concentration; the effect on Hb and Hct was most pronounced when dietary iron was low. When expressed as g Hb/mg Fe intake, Hb repletion was affected by a significant interaction between fat and Fe (P less than 0.002) and was greatest in rats fed low iron stearic acid diets. In a third experiment, rats were fed low dietary iron and 24% safflower oil, 20% stearic acid + 4% safflower oil, 3.2% stearic acid + 20.8% safflower oil, or 20% beef tallow + 4% safflower oil. The 20% beef tallow provided 3.2% stearic acid in the total diet. The response of Hb and Hct were similar to those in the first two experiments for rats fed safflower oil or stearic acid. Rats fed beef tallow had significantly greater (P less than 0.05) Hb and Hct repletion than did rats fed safflower oil, although the degree of repletion was less than that observed in rats fed 20% stearic acid. There was no difference in iron repletion of rats fed 3.2% stearic acid and rats fed beef tallow. We conclude that stearic acid enhances iron utilization by rats.
Effect of food processing and preparation on mineral utilization.
While effects of various nutrients and certain non-nutrient components of food on mineral utilization have been intensively studied, less is known about the effects of food processing and preparation procedures. Fermentation during the production of beer, wine, yogurt, and African tribal foods affects bioavailability of Zn and Fe. Baking affects the chemical form of Fe in fortified bread products and these changes can affect its bioavailability. Availability of Fe in milk-based infant formula depends on whether Fe is added before or after heat processing. Food packaging (e.g., tin cans) can alter food composition and thus potentially affects mineral bioavailability. Maillard browning has been reported to cause slight decreases in Zn availability both in vitro and in humans. However, we found that feeding of highly browned casein-glucose products to rats as 5% of diet produced no effect on Zn absorption (59.5 +/- 8.2% vs 54.1 +/- 7.3%) or Fe absorption (45.6 +/- 7.7% vs 46.9 +/- 12.6%) for browned vs control, respectively; nor did we find any of the adverse health effects reported by others. We found no effect on stable Zn or Cu absorption in seven men when browned foods were fed, compared to the same diets without browning. Zinc absorption was 34 +/- 13% (browned) vs 24 +/- 15% (unbrowned), and Cu absorption was 55 +/- 5% vs 55 +/- 8% (p greater than 0.05).
Absorption and biological half-life in humans of intrinsic and extrinsic 54Mn tracers from foods of plant origin.
Absorption and biological half-life of 54Mn were measured in adult men and women fed foods labeled intrinsically or extrinsically with 54Mn. Each subject consumed a series of three test meals consisting of a food labeled intrinsically, a food labeled extrinsically or MnCl2 (control) served in random order. The foods tested were lettuce, spinach, wheat and sunflower seeds. Lettuce meals and their controls contained 9.65 mumol Mn; other meals contained 22.50 mumol Mn. In addition to the test food or MnCl2, each meal consisted of vegetable oil (5 g), salt (NaCl, 0.15 g) and crackers (10 g), which provided 0.55 mumol Mn. There were no differences in percentage of Mn absorption or biological half-life of 54Mn for any of the intrinsically/extrinsically labeled food pairs. Absorption of 54Mn from MnCl2 (8.90%) was greater than from lettuce (5.20%), spinach (3.81%), wheat (2.16%) or sunflower seeds (1.71%), but the biological half-life did not vary with the source of Mn. Absorption of 54Mn from lettuce was significantly (P less than 0.05) greater than from wheat or sunflower seeds. Although the Mn dose in the test meal was less for lettuce than for the other foods, there was no difference in Mn absorption from MnCl2 between the subjects fed lettuce and subjects fed other foods. There was no correlation of either 54Mn absorption or biological half-life with whole blood or plasma Mn.
Screening newborns for multiple organic acidurias in dried filter paper urine samples: method development.
Screening urine for inherited and acquired organic acidurias in newborns has the potential of preventing severe disease, mental retardation, and death. A method for screening dried urine filter paper samples for acidic markers of at least 20 different metabolic conditions has been developed. These conditions include, among others, maple syrup urine disease; methylmalonic, propionic, isovaleric, glutaric, and hydroxymethylglutaric acidurias; methylcrotonylglycinuria; medium-chain acyl-CoA dehydrogenase deficiency; inherited vitamin responsive disorders B12, biotin, B2), and acquired deficiencies of these vitamins. The preparation of the urine extract is identical to the method we use to screen infants for neuroblastoma. Screening is based on a highly sensitive and specific determination of eight organic acid markers by an automated computerized gas chromatography mass spectrometry system using selected ion monitoring. The markers used for screening are methylmalonic acid, 2-hydroxyisocaproic acid, glutaric acid, propionylglycine, isovalerylglycine, 3-methylcrotonylglycine, hexanoylglycine, and 3-phenylpropionylglycine. The extraction efficiencies of these acids from dried filter paper were similar to extraction from water, ranging from about 40% to 80%, except for propionylglycine which showed a low extraction efficiency of 11-13%. The stability of these acids on filter paper exposed to room air and temperature over a period of 15 d was adequate for the use of this collection method for organic aciduria screening. Normal levels, adjusted to urinary creatinine, were established for these acids in 519 urine filter paper samples obtained from 3-wk-old newborns. This screening method was tested on samples obtained from 12 patients with known organic acidurias including stored urine filter paper collected at 3-wk of age from two infants later found to have organic acidurias.
Gestational alcoholism and fetal zinc accretion in Long-Evans rats.
An animal study was conducted to examine the effects of alcohol consumption on placental transfer of zinc during late gestation. Throughout pregnancy, rat dams were fed a nutritionally adequate diet with 30% of total kcal as alcohol. On days 18 and 21 of pregnancy, zinc-65 was injected subcutaneously into the dams and the dams were killed 24 hours later; tissues were removed for analyses. Maternal serum, liver, kidney, and heart zinc decreased with gestational age while total fetal zinc increased. Neither the decrease in maternal organ zinc nor fetal accretion were affected by alcohol consumption. Placental zinc concentration also declined with developmental age and was not influenced by alcohol consumption. The decrease in placental zinc was accompanied by a decrease in zinc associated with 4-10-kD proteins of placental cytosol. Our results suggest that zinc flux during late rat gestation is a well-regulated process that is not influenced by alcohol consumption. Coordination of the transfer apparently is influenced by maternal blood concentration of zinc, placental zinc-binding proteins, and fetal demand for zinc.
The effect of dietary protein source on manganese bioavailability to the rat.
Rats were fed diets containing 20% protein from casein, beef, chicken, tuna, or soybean. All diets contained 15% fat and were supplemented with limiting amino acids as necessary to meet National Research Council requirements. In Experiment 1, the manganese content of all diets was the same; manganese content was 5 mg/kg. In Experiment 2, a basal (adequate) level of minerals was provided in each diet but total mineral content varied depending on the contribution of the protein source; manganese was added to achieve a concentration of 5 mg/kg. In both experiments, 54Mn absorption was greatest from tuna (8.54% and 7.71%) and least from beef (4.57% and 4.14%) (P less than 0.0001). In both experiments, biologic half-life of 54Mn was longest in rats fed beef (18.5 and 26.9 days) and shortest in rats fed soy (14.5 and 16.2 days) (P less than 0.0002). Except for beef, biologic half-life was similar for dietary groups between the two experiments. In Experiment 1, only kidney manganese concentration was significantly affected by diet and was highest in soy-fed animals. In Experiment 2, plasma, kidney, and liver manganese were all significantly affected by diet and were highest in soy-fed animals and lowest in beef-fed animals.
Bilateral sudden hearing loss and metastatic pancreatic adenocarcinoma.
We report a rare case of bilateral sudden and profound hearing loss caused by bilateral temporal bone metastasis from a primary adenocarcinoma of the tail of the pancreas. The hearing loss was the patient's only reason to seek medical care. Seventh nerve involvement was very minimal, when compared with that of the eighth nerve.
Detection of labile zinc-binding ligands in biological fluids by modified gel filtration chromatography.
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Disrupting the conditioned stimulus preexposure effect in flavor-aversion learning: effects of interoceptive distractor manipulations.
Rats exposed to a flavor prior to a conditioning trial involving that stimulus learn a significantly diminished flavor aversion relative to nonpreexposed control animals. A series of four experiments investigated the ability of the conditioned stimulus (CS) preexposure effect to be disrupted by the introduction of a distractor flavor stimulus between the preexposure and conditioning episodes. Experiment 1 demonstrated that the preexposure effect could be reduced by a distractor presented immediately following the preexposure. In Experiment 2, it was discovered that a novel distractor was more effective than a familiar distractor, even though both stimuli were sensorily equivalent. Experiment 3 further analyzed the distractor effect and demonstrated that the magnitude of disruption was more pronounced with immediate than with delayed (3 hr) distractor manipulations. Finally, Experiment 4 assessed the effects of the distractor in the absence of CS preexposure. The relation of the results from these experiments to general information theory is discussed.
Zinc absorption in the rat determined by radioisotope dilution.
Zinc absorption in rats was examined by use of an isotope dilution technique. Young rats and mature rats fed varying levels of dietary zinc were injected intramuscularly with 65Zn. Nine days later, a zinc balance study was begun and continued for 5 days. The rats were then decapitated and the intestines and kidneys were removed and analyzed for zinc and 65Zn content. The feces were analyzed for zinc and 65Zn content and the specific activities of the intestines and kidneys were used to compute the contribution of endogenous zinc to total daily zinc excretion and thus calculate the true daily absorption of zinc. The zinc concentration of the intestines and kidneys did not differ significantly among groups but the specific radioactivity in these organs decreased as dietary zinc intake increased. Endogenous zinc excretion was greatest in mature rats and young rats fed the highest level of dietary zinc. Mature rats actually absorbed as much or more zinc than young rats fed the same dietary level of zinc. The results demonstrate that zinc homeostasis in rats is maintained by zinc secretion from the intestine rather than by regulation of zinc absorption.
Identification of the functional ionic groups of papain by pH/rate profile analysis.
The pH dependence of papain catalysis was analyzed by a scheme which evaluates the kinetic contribution of both protonated and unprotonated species of functional groups involved in catalysis. Kinetic measurements were made at constant pH, without buffers, by automatic titration. The rate-determining step for papain-catalyzed hydrolysis of alpha-N-benzoyl-L-arginine ethyl ester, determined by nucleophile competition, changed from acylation below pH 6.5 to mixed acylation-deacylation above pH 6.5. Kinetic analysis indicated that three prototropic groups governed the pH-specificity of alpha-N-benzoyl-L-arginine ethyl ester hydrolysis. These prototropic groups had pKa values of 4.8, 6.5 to 6.7, and 8.7. Theoretical treatment of the kinetics provided an excellent fit with the experimentally found profile when the contribution of all three prototropic groups was considered. Analysis showed that, in acid, the pathways of papain catalysis were functional with either two or three active-site protons. In base, a single functional ionic pathway is associated with an active site with only one proton. Pathways involving an unprotonated active site are catalytically inoperative in both acid and base. These results indicate that papain exhibits several catalytically functional ionic pathways. The results are discussed in terms of pKa assignments, and the mechanism of papain catalysis.
Basal cell tumors of the parotid gland.
We present two patients with parotid tumors; one had a basal cell adenoma, and the other had a malignant tumor of uncommon morphologic features that was diagnosed as basal cell carcinoma. Both tumors showed morphologic similarities: peripheral, palisading, nests-like arrangements and organelle-poor cytoplasm. This suggests the same cell of origin.
Relative zinc availability in human breast milk, infant formulas, and cow's milk.
The concentration and bioavailability of zinc was analyzed in 10 varieties of milk. The concentration of zinc averaged 4.1 microgram/ml in unprocessed (raw) cow's milk; fortified infant formulas contained about 3 to 5 microgram Zn/ml; human breast milk and processed cow's milk contained approximately 2 microgram Zn/ml; sweetened condensed milk contained 1.3 microgram Zn/ml, and reconstituted nonfat dry milk contained 0.4 microgram Zn/ml. The mean values for zinc bioavailability to rats were as follows: sweetened condensed milk = 66%; human breast milk 59.2%, processed cow's milk = 43.7 to 50.9%; unprocessed (raw) cow's milk = 42%; nonfat dry milk = 41.2%, and infant formulas = 26.8 to 39.5%. Assuming similar absorption of zinc in rats and humans, our experimental results provide some guidelines for estimating the quantity of zinc that would actually be absorbed from various types of milk.
Antiviral activity of intranasally applied human leukocyte interferon.
Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm(2)) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (P < 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application.