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Biomedical subjects

L L Smith

Publications and source records attributed to L L Smith.

At least 127 records · Page 7Linked to original sources
PubMed1991

The effect of warm-up on responses to intense exercise.

The purpose of this study was to determine if prior physical activity (warm-up) affected physiological responses to intense exercise. Eight highly trained collegiate swimmers performed a paced 365.8-m (440 yds) intense swim (mean +/- SE, 94.4 +/- 3.3% VO2max) 5 min after the following warm-up conditions: trial N, no warm-up; trial S, an intensity-specific interval set (4 x 45.7 m with one-min rest intervals at the intense swim pace); trial M, a mild-intensity, long-duration swim (1371.6 m at 64.7 +/- 3.3% VO2max); and trial MS, a mild-intensity, long-duration swim (1188.7 m at the same pace as trial M) followed by the intensity-specific interval set (trial S). When comparing trial N with trials M and MS, stroke distance (m/stroke) was significantly (p less than 0.05) lower during the last 91.4 m of the intense, paced swim and 3-, 5-, 8- and 10-min recovery blood lactate levels and one-minute recovery heart rates were significantly elevated (p less than 0.05). There was no significant difference (p greater than 0.05) in stroke distance during the final 91.4 m of the intense swim between trials S and N. There were no significant differences for any variables between trials M and MS. These results suggest that a warm-up consisting of mild-intensity, long-duration exercise was beneficial compared to no warm-up and that intensity-specific exercise was not a vital component of warm-up. Although performance was not directly measured, these data demonstrate the benefit of warm-up.

Adult↗
PubMed1991

Obsessive-compulsive disorders in the pediatric dermatology practice.

Childhood and adolescent obsessive-compulsive disorders are sometimes seen in dermatology practice. When present, OCD is most frequently manifested in younger patients as trichotillomania, onychotillomania, onychophagia, and acne excoriée. In addition to these disorders, obsessive hand washing, AIDS phobia, and other psychosomatic dermatoses characterized by obsessive-compulsive tendencies are seen in all age groups. It is important to define the nature of any underlying psychiatric disorder before beginning drug treatment of these patients. With the availability of new medications, most notably, clomipramine and fluoxetine, there is reason for optimism regarding the treatment of OCD. Whenever feasible, the dermatologist should not hesitate to involve a psychiatrist to help with diagnosis and treatment when the diagnosis of OCD is being considered.

Child↗
PubMed1991

Psychologic aspects of acne.

Psychologic factors may play a significant role in acne in at least three ways. First, as many patients readily report, emotional stress can exacerbate acne. Second, it is common for patients to develop psychiatric problems as a consequence of the conditions, such as those related to low self-esteem, social phobias, or depression. Finally, primary psychiatric illnesses such as obsessive-compulsive disorder and psychosis may be based on a complaint that is focused on acne. In this review we hope to facilitate an understanding of how emotional factors and acne connect, and aid the dermatologist in identifying the possible presence of psychiatric problems stemming from or contributing to the disorder.

Acne Vulgaris↗
PubMed1991

Peak running velocity, submaximal energy expenditure, VO2max, and 8 km distance running performance.

The purposes of this study were to examine (1) if the peak running velocity achieved during maximal treadmill testing is related to 8 km distance running performance (DRP) and (2) if the relationship between selected physiological determinants are consistant for two 8 km races within a competitive season. Seven members of a University cross-country team (mean +/- SE) (age, 19.4 +/- 0.5 years, VO2max 67.0 +/- 1.0 ml/kg/min were tested 2-3 days following a mid-season race (Race M) and the season-ending conference championship (Race C). Despite similar weather and terrain, Race C (29:22 +/- 1:22 min:sec) was significantly (p less than 0.05) slower than Race M (28:31 +/- 0:58 min:sec). However, no significant differences (p greater than 0.05) were observed between testing sessions for calculated energy expenditure heart rate oxygen consumption and RER during submaximal running (248 and 268 m/min), postsubmaximal run lactate, peak running velocity, and VO2max. A significant correlation (p less than 0.05) was observed for Race M with with calculated energy expenditure during submaximal running at both speeds (r = 0.85) and with peak running velocity (r = -0.76). Regression analysis revealed that 92% of the total variance for Race M was accounted for by calculated energy expenditure during submaximal running and VO2max. No significant correlation or regression relationship was observed for any variables with Race C. These results suggest that peak running velocity, calculated energy expenditure during submaximal running, and VO2max can be associated with 8 km running performance. However, the relationship between 8 km DRP and the variables measured can differ for two races over a competitive season.

Adult↗
PubMed1991

Acute inflammation: the underlying mechanism in delayed onset muscle soreness?

It is well documented in animal and human research that unaccustomed eccentric muscle action of sufficient intensity and/or duration causes disruption of connective and/or contractile tissue. In humans, this appears to be associated with the sensation of delayed onset muscle soreness (DOMS). During the late 1970's, it was proposed that this sensation of soreness might be associated with the acute inflammatory response. However, subsequent research failed to substantiate this theory. The present article suggests that the results of much of the research concerning DOMS reflect events typically seen in acute inflammation. Similarities between the two events include: the cardinal symptoms of pain, swelling, and loss of function; evidence of cellular infiltrates, especially the macrophage; biochemical markers such as increased lysosomal activity and increased circulating levels of some of the acute phase proteins; and histological changes during the initial 72 h. In the final section of this paper, a theoretical sequence of events is proposed, based on research involving acute inflammation and DOMS.

Acute Disease↗
PubMed1990

An evaluation of the redox cycling potencies of paraquat and nitrofurantoin in microsomal and lung slice systems.

The redox cycling abilities of the pulmonary toxins paraquat and nitrofurantoin have been compared with those of the potent redox cyclers, diquat and menadione in lung and liver microsomes by using the oxidation of NADPH and consumption of oxygen. The relative potencies of these compounds to undergo redox cycling were in the order: diquat approximately menadione much greater than paraquat congruent to nitrofurantoin. This was partly attributed to the much lower affinity (Km) of lung and liver microsomes for paraquat and nitrofurantoin than for diquat and menadione. The potential to redox cycle was assessed in an intact cellular system by determining the oxygen consumption of rat lung slices in the presence (10(-6), 10(-5) and 10(-4) M) or absence of each of the four substrates. At concentrations of paraquat (10(-5) M) known to be accumulated by lung slices, a small but significant stimulation of lung slice oxygen uptake was observed. Nitrofurantoin (10(-4)-10(-6) M) did not affect lung slice oxygen uptake in lung slices, an observation consistent with its being a poor redox cycling compound, which is not actively accumulated into lung cells. This data has important implications in assessing the risk of exposure to paraquat. Low levels of paraquat would not be expected to cause lung damage because insufficient compound is present in the lung to exert its toxicity by redox cycling (due to the high Km observed).

Animals↗
PubMed1990

Weak bases increase surface IgM expression in 70Z/3 B lymphoid cell line without increasing kappa gene expression.

A murine B lymphoid cell line, 70Z/3, has proven to be a useful model to study the developmental transition from membrane immunoglobulin (mIgM)-negative to mIgM-positive B cells. 70Z/3 cells have normal intracellular levels of mu heavy chain but kappa mRNA is transcribed at a very low rate. Because both kappa and mu chains are required for IgM to localize on the external membrane the cells remain essentially mIgM negative. A number of biologic agents can stimulate kappa mRNA transcription leading to increased surface IgM expression. Pharmacologic agents which cause cytoplasmic alkalinization have also been shown to increase the level of surface IgM expression when assessed by FITC-labeled anti-IgM antibodies. This increase has been used to argue that cytoplasmic alkalinization is sufficient to stimulate 70Z/3 differentiation but previous studies did not measure kappa mRNA levels or rate of synthesis. In this study we set out to determine whether the increased FITC staining that follows cytoplasmic alkalinization results from increased surface IgM expression and whether that increase results from activation of kappa mRNA transcription. When cells were treated with methylamine, NH4Cl, or monensin there was transient cytoplasmic alkalinization. The levels of surface IgM expression were measured by flow cytometry of cells stained with FITC-labeled anti-mouse kappa and mu. Using this criterion, a 24-hr treatment with either weak bases or monensin increased the level of surface IgM. The increase in fluorescence was not the result of nonspecific binding or uptake by the cell because there was no increase in fluorescence when methylamine-treated cells were stained with FITC-labeled antibody directed against an antigen not found on these cells. Iodination of surface proteins confirmed that the increase in fluorescence was the result of increased levels of IgM protein on the cell surface. However, exposure of the cells to weak bases or monensin caused no increase in either the steady-state level of kappa light chain mRNA, or in the level of kappa protein. We conclude that the transient alkalinization is not sufficient to induce differentiation of the 70Z/3 cells.

Ammonium Chloride↗
PubMed1990

The identification and characterization of an uptake system for taurine into rat lung slices.

The objective of this study was to determine whether taurine was accumulated by rat lung slices and if so, to establish the role of this uptake as a source of pulmonary taurine. We have shown that taurine is accumulated into rat lung by an active uptake process that was both ATP and Na(+)-dependent and obeyed saturation kinetics, exhibiting an apparent Km of 186 microM and Vmax of 970 nmol/g wet wt/hr. Substrate specificity of the system was high and only compounds possessing anionic and cationic groups separated by two methylene groups were able to competitively inhibit taurine uptake. Subsequent to its uptake, taurine was not significantly metabolized, and since the apparent Km for the uptake process is similar to the known plasma concentration of taurine, it can be inferred that this system will contribute to pulmonary taurine uptake in vivo. Taurine has been suggested to possess antioxidant and antiinflammatory properties, and we suggest that this uptake system may contribute to the defence of pulmonary tissue against oxidative stress.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Potentiation of the cell specific toxicity of paraquat by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Implications for the heterogeneous distribution of glutathione (GSH) in rat lung.

In order to study oxidative stress in the lung, we have developed a rat lung slice model with compromised oxidative defences. Lung slices with markedly inhibited glutathione reductase activity (approximately 80% inhibition) were prepared by incubating slices, with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 microM) in an amino acid-rich medium for 45 min at 37 degrees. These lung slices had similar levels of GSH and ATP and polyamine uptake (a marker of alveolar epithelial type I and II cell function) to control rat lung slices. We have utilized these BCNU pretreated slices to study the effects of the herbicide, paraquat, in comparison to those of 2,3-dimethoxy-1,4-naphthoquinone, a potent redox cycler. Paraquat (10-100 microM) caused only minimal changes in the levels of GSH or ATP in control or compromised slices. In contrast, 2,3-dimethoxy-1,4-naphthoquinone caused a decrease in GSH in control slices but a markedly enhanced decrease in both GSH and ATP in compromised slices. Both compounds had only limited effects on putrescine and spermidine uptake in control slices. However, they caused a marked inhibition in compromised slices. Paraquat had little effect on 5-hydroxytryptamine uptake (a marker of endothelial cell function) in either control or compromised slices whereas the quinone inhibited uptake in the compromised slices. Thus, the lack of effect of paraquat on GSH and ATP does not support the involvement of oxidative stress in its toxicity. In contrast, using polyamine uptake, as a functional marker of alveolar epithelial cell damage, suggests a role for redox cycling. As paraquat is known to be accumulated primarily in alveolar type I and II cells (a small fraction of the lung cell population), our data suggest that only a small proportion of pulmonary GSH and ATP is present in alveolar epithelial type I and II cells but that much larger amounts may be present in endothelial cells. These studies highlight the problem of gross tissue measurements in heterogeneous tissues such as the lung.

Adenosine Triphosphate↗
PubMed1990

Immunoblot analysis of sera from patients with allergic bronchopulmonary aspergillosis: correlation with disease activity.

Immunoblot analysis was used to evaluate the IgG, IgE, and IgA responses to Aspergillus fumigatus antigen with the sera of five patients with allergic bronchopulmonary aspergillosis (ABPA) before, during, and after suspected exacerbation of their disease. The results revealed a heterogenous antibody response, unique for each patient, to specific Aspergillus fumigatus antigens that correlated with the molecular weights of previously well-characterized antigens of importance in the immunopathogenesis of ABPA. A rating scale was devised for measuring band intensity that allowed the patient's antibody responses to be reproducibly semiquantitated. Immunoblot analysis demonstrated qualitative and semiquantitative information that is not available with other in vitro assays used in the study of patients with ABPA, such as ELISA. These initial results emphasize the need for additional evaluation of this technique to assess its potential clinical application in this disease.

Antigens, Fungal↗
PubMed1990

A novel lung slice system with compromised antioxidant defenses.

In order to facilitate the study of oxidative stress in lung tissue, rat lung slices with impaired antioxidant defenses were prepared and used. Incubation of lung slices with the antineoplastic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) (100 microM) in an amino acid-rich medium for 45 min produced a near-maximal (approximately 85%), irreversible inhibition of glutathione reductase, accompanied by only a modest (approximately 15%) decrease in pulmonary nonprotein sulfhydryls (NPSH) and no alteration in intracellular ATP, NADP+, and NADPH levels. The amounts of NADP(H), ATP, and NPSH were stable over a 4-hr incubation period following the removal from BCNU. The viability of the system was further evaluated by measuring the rate of evolution of 14CO2 from D-[14C(U)]-glucose. The rates of evolution were almost identical in the compromised system when compared with control slices over a 4-hr time period. By using slices with compromised oxidative defenses, preliminary results have been obtained with paraquat, nitrofurantoin, and 2,3-dimethoxy-1,4-naphthoquinone.

Adenosine Triphosphate↗
PubMed1990

An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin.

The abilities of paraquat, diquat, and nitrofurantoin to undergo cyclic oxidation and reduction with rat microsomal systems have been assessed and compared to that of the potent redox cycler, menadione. Diquat and menadione were found to be potent redox cyclers with comparable abilities to elicit a nonstoichiometric increase in both the consumption of O2 and the oxidation of NADPH, compared to the amounts of substrate added. In contrast, paraquat and nitrofurantoin redox cycled poorly, being an order of magnitude less potent than either diquat or menadione. This was reflected in kinetic studies using lung and liver microsomes, which showed that NADPH-cytochrome P-450 reductase had a lower affinity (Km) for paraquat and nitrofurantoin than for menadione and diquat, although values of Vmax were comparable for all the substrates except nitrofurantoin, which was lower. In order to assess redox cycling of the substrates in an intact lung system, the O2 consumption of rat lung slices was measured in the presence of all four compounds. A small increase in lung slice O2 uptake was observed with paraquat (10(-5) M) in the first 2.5 hr of incubation, possibly because of redox cycling of a high intracellular concentration of paraquat resulting from active accumulation into target cells. This stimulation in O2 uptake was no longer observed when slices were incubated for a longer period or with higher paraquat concentrations (10(-4) M), possibly because of toxic effects in target cells. High concentrations of diquat (10(-5) M) had no effect on O2 consumption of lung slices.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The importance of epithelial uptake systems in lung toxicity.

The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization of the process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell. With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells. In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system.

Animals↗
PubMed1990

Target cell toxicity of inhaled spermidine in rat lungs.

Rats were exposed for a single 6-h period to varying concentrations of aerosols of the polyamine, spermidine trihydrochloride. They were subsequently killed at 6 h, 1, 2, 5, 9 and 14 days after the start of exposure. The lungs were examined for histopathological alterations at both light and electron microscopic level and assays of lung spermidine burdens performed. In rats killed at the 6-h termination period, lung spermidine levels had increased approximately 1.5-fold although concentrations in animals killed on days 1 and 2 showed only marginal increases. Concentrations peaked again on day 5 and henceforth decreased until control spermidine levels were again achieved on day 14. Exposure of rat lungs to spermidine resulted in a specific dose-dependent necrosis of Clara cells of the bronchiolar epithelium and alveolar Type II cells. At the lowest dose used (6 mg/m3) specific necrosis of the Clara cells was seen at the earliest time interval studied, i.e. 6 h, but these cells were rapidly lost and subsequently replaced without evidence of significant cell proliferation by the 2-day sacrifice period. At all higher dose levels additional necrosis of the alveolar Type II cells occurred which was not reversible but which progressed through alveolitis to a fully developed subchronic pneumonitis by 14 days.

Administration, Inhalation↗
PubMed1989

Properties of interleukin-1 and interferon-gamma receptors in B lymphoid cell line.

We have previously shown that interleukin-1 alpha (IL-1 alpha) and interferon-gamma (IFN-gamma) induce surface IgM expression, stimulate Na+/H+ exchange, and activate protein kinase C in the murine pre-B lymphocyte cell line, 70Z/3. Because the two structurally different lymphokines induce similar effects, in this study we set out to compare the properties of the IL-1 and IFN-gamma surface receptors. In contrast to their similar cellular effects, we found that IL-1 alpha and IFN-gamma receptors have different properties. 70Z/3 have high (100 sites/cell) and low (900 sites/cell) affinity IL-1 receptors with dissociation constants (KD) 6 x 10(-11) and 10(-9) M, respectively. In contrast, IFN-gamma receptors are of one class with a KD of 3 x 10(-10) M and are at a higher number, 8000 sites/cell. After binding to their receptors both IL-1 alpha and IFN-gamma are internalized and intracellularly degraded, but the rate of internalization of IFN-gamma is greater than IL-1 alpha. The effective median concentrations (EC50) of IL-1 alpha- or IFN-gamma-induced surface IgM expression are similar (4-5 x 10(-12) M). However, at this concentration 10-fold more of IFN-gamma than IL-1 alpha molecules are bound per cell. Our studies indicate that structurally different lymphokines can induce similar biological events even though their signaling is mediated by surface receptors whose properties are different.

Animals↗