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Biomedical subjects

J C King

Publications and source records attributed to J C King.

At least 37 records · Page 2Linked to original sources

Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults.

Fifty-seven human immunodeficiency virus (HIV)-infected (CDC class A1-2) and 54 non-HIV-infected adults, not prescreened for influenza susceptibility, were randomized to receive trivalent live attenuated influenza vaccine (LAIV) or placebo intranasally. LAIV was safe and well tolerated with no serious adverse events attributable to vaccine. Reactogenicity rates were similar in LAIV and placebo recipients except that runny nose/nasal congestion was significantly more common in LAIV recipients regardless of HIV status. No prolonged shedding of LAIV was observed in HIV-infected participants. HIV RNA levels were not increased and CD4 counts were not decreased in HIV-infected LAIV recipients compared with placebo recipients after immunization. Shedding of LAIV and increases in antibody titers were infrequent, consistent with prior experience in unscreened adults. The data suggest that inadvertent vaccination with LAIV in relatively asymptomatic HIV-infected adults would not be associated with frequent significant adverse events.

Adult↗

Comparison of estimates of zinc absorption in humans by using 4 stable isotopic tracer methods and compartmental analysis.

BACKGROUND: Adjustment of gastrointestinal absorption is the primary means of maintaining zinc homeostasis; however, a precise, accurate method for measuring zinc absorption in humans has not been identified. OBJECTIVE: The purpose of this study was to compare the estimates of the fraction of dietary zinc absorbed (FZA) by using 4 stable isotopic tracer methods: mass balance (MB) corrected for endogenous secretion, fecal monitoring (FM), deconvolution analysis (DA), and the double isotopic tracer ratio (DITR) method. DESIGN: All 4 methods were applied to a single data set for each of 6 women. FZA was also determined for each subject by using a detailed compartmental model of zinc metabolism, and that value was used as the reference with which the simpler methods were compared. RESULTS: The estimates of FZA (&xmacr; +/- SD) determined by DA (0.27 +/- 0. 08) and the DITR technique in plasma (0.30 +/- 0.10), 24-h urine samples (0.29 +/- 0.09), and spot urine samples (0.291 +/- 0.089) all compared well with the FZA reference value from the compartmental model (0.30 +/- 0.10). The MB and FM methods tended to overestimate FZA compared with the reference value. CONCLUSIONS: The determination of FZA by MB or FM is laborious, is sensitive to subject compliance, and may result in an overestimate. DA, although relatively accurate, has the disadvantage of requiring multiple blood drawings over several days. In contrast, the DITR technique applied to a spot urine specimen obtained >/=3 d after tracer administration provides an accurate measure of FZA and is easy to implement; therefore, it is the recommended method for determination of FZA.

Adult↗

Physiology of pregnancy and nutrient metabolism.

Pregnancy consists of a series of small, continuous physiologic adjustments that affect the metabolism of all nutrients. The adjustments undoubtedly vary widely from woman to woman depending on her prepregnancy nutrition, genetic determinants of fetal size, and maternal lifestyle behavior. Studies of protein and energy metabolism illustrate the potential of adjusting the use of those nutrients to conserve a fetal supply. Adjustments in the metabolism of nitrogenous compounds are in place by the second quarter of pregnancy. During the last quarter of pregnancy, when fetal demands are greatest, those adjustments allow a positive nitrogen retention. The energy requirement of basal metabolism is influenced by maternal prepregnant nutrition and by fetal size. If maternal energy reserves are low at conception, the basal metabolic rate is down-regulated to conserve energy. Also, women having larger babies tend to have greater increases in their basal metabolic rate and lower rates of maternal energy storage. Changes in maternal food and physical activity behaviors during gestation may augment the physiologic adjustments. However, the substantial variability in food intakes and physical activity makes it difficult to show those changes. Thresholds in the capacity to adjust nutrient use to the amount supplied exist for all nutrients. When intakes fall below the threshold, fetal growth and development is affected more than is maternal health. Efforts to achieve good maternal nutritional status preconception as well as throughout gestation best assure a good milieu for fetal growth and development.

Dietary Proteins↗

Determinants of maternal zinc status during pregnancy.

Zinc deficiency in pregnant experimental animals limits fetal growth and, if severe, causes teratogenic anomalies. Although the data from human studies are not consistent, similar outcomes have been observed and were associated with poor maternal zinc status. This paper reviews humans studies of zinc status and pregnancy outcome, describes the physiologic adjustments in zinc utilization during pregnancy to meet fetal needs while maintaining maternal status, and identifies dietary and environmental conditions that may override those physiologic adjustments and put the health of the mother and fetus at risk. Adjustments in intestinal zinc absorption appear to be the primary means by which zinc retention is increased to meet fetal demands. However, transfer of sufficient zinc to the fetus is dependent on maintenance of normal maternal serum zinc concentrations. Conditions that could interfere with zinc absorption include intake of cereal-based diets that are high in phytate, high intakes of supplemental iron, or any gastrointestinal disease. Conditions that may alter maternal plasma zinc concentrations and the transport of zinc to the fetus include smoking, alcohol abuse, and an acute stress response to infection or trauma. Supplemental zinc may be prudent for women with poor gastrointestinal function or with any of these conditions during pregnancy.

Animals↗

Dietary calcium and pregnancy-induced hypertension: is there a relation?

The evidence that calcium plays a role in the etiology, prevention, and treatment of pregnancy-induced hypertension (PIH) is reviewed. The precise factors involved in the pathogenesis of PIH are unclear, but several alterations in calcium metabolism have been identified. Epidemiologic data suggest an inverse correlation between dietary calcium intake and incidence of PIH. Although evidence suggests a possible beneficial effect of supplemental calcium, contradictions persist in clinical trials of pregnant women. Presently, there is insufficient evidence to support routine calcium supplementation of all pregnant women. However, high-risk groups, such as pregnant teens, populations with inadequate calcium intake, and women at risk of developing PIH, may benefit from consuming additional dietary calcium.

Calcium, Dietary↗

Body weight-specific zinc compartmental masses in girls significantly exceed those reported in adults: a stable isotope study using a kinetic model.

Maintaining optimal zinc status is important for normal growth and development in children, but minimal data are available regarding zinc metabolism in this age group. Our objectives were to utilize stable isotope-based compartmental modeling techniques to investigate zinc metabolism in healthy children; to expand a current stable isotope-based model to include red blood cell data; and to compare kinetic parameters in children with those previously reported in adults. Seven healthy girls, age 9.94 +/- 0.79 y, received 1.1 mg of a (67)zinc-enriched tracer orally and 0.5 mg of a (70)zinc-enriched tracer intravenously. Blood, urine and fecal samples were collected for 6 d. Stable isotope enrichments were measured by thermal ionization magnetic sector mass spectrometry. A six-compartment model based on a model previously reported in adults was used; the model excluded red blood cell data. Body weight-corrected masses of the body zinc compartments derived using this model were significantly greater in children than those reported in adults. Modification of the model to include a red blood cell compartment increased the total identifiable zinc mass of the nongastrointestinal compartments by approximately 2.5%. We conclude that compartmental modeling can be used to describe zinc kinetics in children, and that the body weight-corrected zinc pool masses are significantly greater in children than in adults.

Adult↗

Zinc homeostasis in humans.

Maintaining a constant state of cellular zinc nutrition, or homeostasis, is essential for normal function. In animals and humans, adjustments in zinc absorption and endogenous intestinal excretion are the primary means of maintaining zinc homeostasis. The adjustments in gastrointestinal zinc absorption and endogenous excretion are synergistic. Shifts in endogenous excretion appear to occur quickly with changes in intake just above or below optimal intake. The absorption of zinc responds more slowly, but it has the capacity to cope with large fluctuations in intake. With extremely low zinc intakes or with prolonged marginal intakes, secondary homeostatic adjustments may augment the gastrointestinal changes. These secondary adjustments include changes in urinary zinc excretion, a shift in plasma zinc turnover rates and, possibly, an avid retention of zinc released from selected tissues, such as bone, in other tissues to maintain function.

Animals↗

Influenza vaccines.

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Administration, Intranasal↗

Lymphocyte metallothionein mRNA responds to marginal zinc intake in human volunteers.

Marginal Zn deficiency is thought to be prevalent in both developed and developing countries. However, the extent of Zn deficiency is not known, due to the lack of a reliable diagnostic indicator. Blood plasma and erythrocyte concentrations of metallothionein (MT) reflect Zn status, but measurement of MT is dependent on the availability of sensitive immunoassays. Our aim was to show whether measurement of T lymphocyte MT-2A mRNA, using a competitive reverse transcriptase (RT)--polymerase chain reaction (PCR) assay, could indicate Zn status in human subjects in a residential Zn-depletion study. In the study, the Zn intake of seven volunteers was maintained at 13.7 mg/d for 5 weeks (baseline) followed by 4.6 mg/d for 10 weeks (marginal intake) and then 13.7 mg/d (repletion) for 5 weeks. The quantitative assay was developed using standard techniques and concentrations of MT-2A mRNA were normalized by reference to beta-actin mRNA which was also measured by competitive RT--PCR assay. An alternative method of measuring the PCR product using capillary electrophoresis with laser-induced fluorescence detection was also evaluated. There was considerable inter-individual variation in MT-2A mRNA concentration and the mean level at the end of the baseline period was 10.3 (SE 3.7) fg MT-2A mRNA/pg beta-actin mRNA, which then decreased by 64 % during the low Zn intake period. After repletion, MT-2A mRNA returned to baseline concentrations. In contrast, plasma Zn was unchanged by marginal Zn intake or repletion. The effect of low Zn in all individuals was consistent. We conclude that this assay is a sensitive method of evaluating marginal changes in dietary Zn intake.

Electrophoresis, Capillary↗

Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode.

Adult↗

Positive sharp wave and fibrillation potential modeling.

A finite muscle fiber simulation program which calculates the extracellular potential for any given intracellular action potential (IAP) was used to model a fibrillation potential and a positive sharp wave. This computer model employs the core conductor model assumptions for an active muscle fiber and allows two distinct types of end effects: a cut or a crush. A "cut end" is defined as a membrane segment with the termination of both active and passive ion channels. The "crush end" is simulated as a focal membrane segment which blocks action potential propagation, and is connected to a region of normal membrane on either side of it so that a normal transmembrane potential is maintained beyond the crush zone. A prototypical positive sharp wave of appropriate amplitude and duration could only be detected extracellularly by using an IAP of the configuration found in denervated rat muscle recorded from a muscle fiber terminating in a crush segment of membrane.

Action Potentials↗

Motor unit action potential components and physiologic duration.

Motor unit action potentials (MUAPs) recorded from the same motor unit at two distances along the biceps brachii muscle with monopolar needle electrodes at high amplifier gains (20 microV/division) and averaged 2000-3000 times reveal total potential durations of 39.6 +/- 4.6 ms. In addition, the terminal segment for each of these two MUAPs contained a late far-field potential with a mean duration of 23.8 +/- 4.1 ms. Computer simulations of MUAPs suggest that this long-duration positive far-field mirrors the true morphology of the intracellular action potential (IAP), which is monophasic positive, possessing a terminal repolarization phase approaching 30 ms. This investigation suggests that the MUAP's physiologic duration is directly proportional to the muscle fiber length and the IAP's duration, which becomes manifest as a positive far-field potential when the IAP encounters the musculotendinous junction and slowly dissipates. The leading/trailing dipole model is used to explain qualitatively this study's quantitative clinical and computer simulation findings.

Action Potentials↗

Motor unit action potential duration and muscle length.

Motor unit action potential (MUAP) components are investigated by means of single fiber computer simulations and clinical measurements. The single fiber simulations have essentially full bandwidth without noise, whereas the clinical measurements were made with a 3-10,000-Hz bandwidth utilizing approximately 1000 averages to reduce noise optimally. These parameters allow the recording of a MUAP's complete "physiologic" duration including its very slow onset and termination. The simulation results demonstrate a constant waveform onset regardless of the electrode's recording location along the fiber. A far-field potential is initiated when the action potential encounters the muscle fiber's termination. The simulated waveform's and clinically recorded MUAP's near-field component extends between the potential's onset and its corresponding far-field potential's onset. This near-field component's duration should vary with fiber length, and this prediction is clinically confirmed by measuring three different muscle lengths. The far-field potential reveals a constant duration, independent of fiber length, and appears to be associated with the muscle fiber's intracellular action potential duration. A more complete understanding of the components contributing to MUAP duration should provide a more fundamental basis for quantitative clinical MUAP duration measurements.

Action Potentials↗

Serum extracellular superoxide dismutase activity as an indicator of zinc status in humans.

The present study focused on whether serum extracellular superoxide dimutase (EC-SOD) activity can be used as a functional indicator of marginal zinc deficiency in humans. Subjects in this study were 444 healthy adults over 30 yr of age living a normal rural life in Kyunggi province, Korea. The mean dietary zinc intake of subjects obtained from one 24-h recall was 6.41 +/- 4.35 mg and the average serum zinc concentration of the subjects was 11.06 +/- 2.44 micromol/L. Subjects were divided into three groups by serum zinc concentrations: adequate (serum zinc >10.7 micromol/L), low (serum zinc 9.0-10.7 micromol/L), and very low (serum zinc <9.0 micromol/L) groups. A total of 50 subjects were selected from the three groups for analysis of EC-SOD activities. The EC-SOD activity of subjects increased with increasing serum zinc concentrations, and the activities of the three groups were significantly different as indicated by the Kruskal-Wallis test (p = 0.0239). Also, serum EC-SOD activities were significantly correlated with serum zinc concentrations (r = 0.289, p = 0.04). Serum EC-SOD activities, however, were not significantly correlated to the dietary zinc intakes. In conclusion, these results show that EC-SOD activities are decreased in subjects with low serum zinc concentrations and suggest that EC-SOD activity may be a functional indicator of zinc nutritional status in humans.

Adult↗

Intracellular contribution to extracellularly recorded waveforms: the 'membrane rent' hypothesis.

OBJECTIVE: This investigation uses simulation studies to account for single muscle fiber waveforms with complex configurations as arising from the simultaneous recording of a partial intracellular discharge and its associated extracellular manifestation by way of an electrode-induced 'rent' or tear in the sarcolemma. METHODS: Published material on intracellular action potentials from healthy and 7 day denervated rat skeletal muscle was used as the basis for calculations. A single muscle fiber computer simulation capable of formulating a cut or crush termination effect used the modeled action potentials to generate extracellular waveforms at different locations along the muscle fiber. These extracellular waveforms were then summated with a varied fraction of the intracellular action potential to yield a combined potential. These simulated waveforms were then compared to previously recorded single muscle fiber discharges in order to establish if a combined waveform could reproduce the clinically recorded potentials' configuration. RESULTS: It was not possible to simulate any of the previously detected innervated single muscle fiber discharges by combining the action potential's intracellular and extracellular configurations. However, 12 of the 14 clinically observed complex waveforms documented in denervated tissue could be simulated with morphologies similar to the clinical potentials. CONCLUSIONS: Presumed single muscle fiber discharges with complex configurations may result from the needle electrode simultaneously recording the action potential's intracellular and extracellular waveforms secondary to a 'rent' in the sarcolemma. This explanation may in part account for some of the complex appearing potentials detected in denervated tissue, but this 'rent' hypothesis is likely not the explanation for potentials observed in innervated muscle tissue. The apparent success of the 'rent' hypothesis in denervated tissue may be a result of the denervated action potential's unique morphology rather than an actual tear in the sarcolemma. Further investigations are necessary to determine if it is possible for a needle electromyographic electrode to actually record in part the intracellular action potential without disrupting the fiber.

Action Potentials↗

Determinants of motor unit action potential duration.

OBJECTIVE: Motor unit action potential (MUAP) recordings are modeled by means of a single muscle fiber simulation program, to define two key subcomponents comprising the complete physiologic MUAP duration. A number of defining properties of these subcomponents are further developed. METHODS: A single muscle fiber simulation program is utilized with various muscle fiber lengths and conduction velocities to generate near-field and far-field waveforms. RESULTS: Two key subcomponents to the total physiologic single muscle fiber and hence MUAP duration are identified. One, defined as the near-field component, is directly dependent upon muscle fiber hemi-length. The other, defined as the far-field component, is independent of fiber length, but matches the internal action potential in duration. Both the near-field and far-field components are inversely dependent upon intracellular action potential conduction velocity. Additionally, temporal dispersion among the individual fibers contributing to a MUAP must be included in the overall MUAP duration calculation. CONCLUSIONS: It is hoped that this approach to MUAP duration may allow a more complete appreciation of the components contributing to the MUAP, than permitted by the empirically derived values for MUAP duration presently under clinical use.

Action Potentials↗