Search PubMed⌕ Search

Biomedical subjects

B D Johnson

Publications and source records attributed to B D Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Hypoxic effects on exercise-induced diaphragmatic fatigue in normal healthy humans.

We examined the effects of hypoxia on exercise-induced diaphragmatic fatigue. Eleven subjects with a mean maximal O2 uptake of 52.4 +/- 0.7 ml.kg-1.min-1 completed one normoxic (arterial O2 saturation 96-94%) and one hypoxic (inspiratory O2 fraction = 0.15; arterial O2 saturation 83-77%) exercise test at 85% maximal O2 uptake to exhaustion on separate days. Supramaximal bilateral phrenic nerve stimulation (BPNS) was used to determine the pressure generation of the diaphragm pre- and postexercise at 1, 10, and 20 Hz. There was increased flow limitation during hypoxic vs. normoxic exercise. There was a decrease in hypoxic exercise time (normoxic 24.9 +/- 0.7 min vs. hypoxic 15.8 +/- 0.8 min; P < 0.05). After exercise the BPNS transdiaphragmatic pressure (Pdi) was significantly reduced at 1 and 10 Hz after both exercise tests. The BPNS Pdi was recovered to control values by 60 min postnormoxic exercise but was still reduced 90 min posthypoxic exercise. The mean percent fall in the stimulated BPNS Pdi was similar (normoxic -24.8 +/- 4.7%; hypoxic -18.8 +/- 3.0%) after both exercise conditions. Experiencing the same amount of diaphragm fatigue in a shorter time period in hypoxic exercise may have been due to 1) the increased expiratory flow limitation and diaphragmatic muscle work, 2) decreased O2 transport to the diaphragm, and/or 3) increased levels of circulating metabolites.

Adult↗
PubMed1995

Regulation of ventilatory capacity during exercise in asthmatics.

In asthmatic and control subjects, we examined the changes in ventilatory capacity (VECap), end-expiratory lung volume (EELV), and degree of flow limitation during three types of exercise: 1) incremental, 2) constant load (50% of maximal exercise capacity; 36 min), and 3) interval (alternating between 60 and 40% of maximal exercise capacity; 6-min workloads for 36 min). The VECap and degree of flow limitation at rest and during the various stages of exercise were estimated by aligning the tidal breathing flow-volume (F-V) loops within the maximal expiratory F-V (MEFV) envelope using the measured EELV. In contrast to more usual estimates of VECap (i.e., maximal voluntary ventilation and forced expiratory volume in 1 s x 40), the calculated VECap depended on the existing bronchomotor tone, the lung volume at which the subjects breathed (i.e., EELV), and the tidal volume. During interval and constant-load exercise, asthmatic subjects experienced reduced ventilatory reserve, higher degrees of flow limitation, and had higher EELVs compared with nonasthmatic subjects. During interval exercise, the VECap of the asthmatic subjects increased and decreased with variations in minute ventilation, due in part to alterations in their MEFV curve as exercise intensity varied between 60 and 49% of maximal capacity. In conclusion, asthmatic subjects have a more variable VECap and reduced ventilatory reserve during exercise compared with nonasthmatic subjects. The variations in VECap are due in part to a more labile MEFV curve secondary to changes in bronchomotor tone. Asthmatics defend VECap and minimize flow limitation by increasing EELV.

Adult↗
PubMed1994

Voltage-dependent potentiation of L-type Ca2+ channels in skeletal muscle cells requires anchored cAMP-dependent protein kinase.

Skeletal muscle L-type Ca2+ channels respond to trains of brief depolarizations with a strong shift of the voltage dependence of channel activation toward more negative membrane potentials and slowing of channel deactivation. Increased Ca2+ entry resulting from this potentiation of channel activity may increase contractile force in response to tetanic stimuli. This voltage-dependent Ca2+ channel potentiation requires phosphorylation by cAMP-dependent protein kinase (PKA) at a rate that suggests that kinase and channel may be maintained in close proximity through kinase anchoring. A peptide derived from the conserved kinase-binding domain of a PKA-anchoring protein (AKAP) prevents potentiation by endogenous PKA as effectively as inhibition of PKA by a specific peptide inhibitor or by omission of ATP from the intracellular solution. In contrast, a proline-substituted mutant of AKAP peptide has no effect. Potentiation in the presence of 2 microM exogenous catalytic subunit of PKA is unaffected, indicating that kinase anchoring is specifically blocked by the AKAP peptide. No effects of these agents were observed on the level or voltage dependence of basal Ca2+ channel activity before potentiation, suggesting that close physical proximity between the skeletal muscle Ca2+ channel and PKA is critical for voltage-dependent potentiation of Ca2+ channel activity but not for basal activity.

Adenosine Triphosphate↗
PubMed1994

Ca2+ channel Ca(2+)-dependent inactivation in a mammalian central neuron involves the cytoskeleton.

Ca2+ channel inactivation was investigated in acutely isolated hippocampal pyramidal neurons from adult rats and found to have a component dependent on intracellular Ca2+. Ca(2+)-dependent inactivation was indentified as the additional inactivation of channel current observed when Ca2+ replaced Ba2+ as the current carrying ion, and was found to be an independent process from that of Ba2+ current inactivation based on three lines of evidence: (1) no correlation between Ca(2+)-dependent inactivation and Ba2+ current inactivation was found, (2) only Ca(2+)-dependent inactivation was reduced by intracellular application of Ca2+ chelators, and (3) only Ca(2+)-dependent inactivation was sensitive to compounds which alter the cytoskeleton. Drugs which stabilize (taxol and phalloidin) and destabilize (colchicine and cytochalasin B) the cytoskeleton altered the development and recovery from Ca(2+)-dependent inactivation, indicating that the neuronal cytoskeleton may mediate Ca2+ channel sensitivity to intracellular Ca2+. Ca(2+)-dependent inactivation was not associated with a particular subset of Ca2+ channels, suggesting that all Ca2+ channels in these neurons are inactivated by intracellular Ca2+.

Animals↗
PubMed1994

Contractile properties of the developing diaphragm correlate with myosin heavy chain phenotype.

The objective of this study was to determine the relationship between developmental transitions in myosin heavy chain (MHC) composition and changes in maximum unloaded shortening velocity (Vo) and maximum specific force (Po) of the rat diaphragm muscle. The diaphragm was excised at postnatal days 0, 3, 7, 14, 21, and 28 and in adults. MHC isoform expression was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and laser densitometry. In muscle fiber bundles, Vo was determined at 15 degrees C by use of the "slack" test. Isometric Po was determined at 15 and 26 degrees C. Simple and stepwise regressions were used to evaluate the correlations between Vo, Po, and MHC phenotype transitions and the various developmental ages. The progressive increases in Vo and Po with age were found to be inversely correlated to MHC-neonatal isoform expression (r2 = -0.84 and -0.63, respectively) and positively correlated to MHC-2X (r2 = 0.78 and 0.57) and MHC-2B (r2 = 0.51 and 0.40) isoform expression (P < 0.001). Changes in MHC-neonatal isoform expression contributed to most of the developmental variance in Vo and Po, with changes in MHC-2X and MHC-2B expression also contributing significant increments to total variance. The postnatal increase in Vo most likely relates to differences in the actomyosin adenosinetriphosphatase activity between neonatal and adult fast MHC phenotypes. The increase in Po may reflect inherent differences in myofibrillar density, cross-bridge cycling kinetics, and/or the force produced per cross bridge among fibers composed of the different MHC isoforms.

Aging↗
PubMed1994

Age-related differences in diaphragm muscle injury after lengthening activations.

The susceptibility of postnatal day 15 and adult rat diaphragms (DIAs) to acute injury after repetitive isovelocity lengthening activations was examined in vitro. Forces were measured during two phases of each stimulation protocol: 1) isometric phase: during the first 300 ms of each 500-ms train, DIA length was not changed; and 2) isovelocity lengthening phase: during the remaining 200 ms of each stimulus train, DIA was lengthened at a constant velocity from 90 to 110% of optimal length. At maximal activation (75 Hz and a lengthening velocity of 1.0 optimal length per second), the maximum force measured during the isometric phase and that measured during the isovelocity lengthening phase were both greater in adult DIAs than in day 15 DIAs but both declined to a greater extent in adults with repetitive activation. Ultrastructural analysis showed that after lengthening activations muscle fiber injury was very evident in adult but much less prevalent in day 15 DIAs. This difference in susceptibility between the adult and day 15 DIAs did not depend on differences in peak force or absolute velocity of lengthening. We conclude that lengthening activations result in DIA injury and that the adult is more susceptible than its younger counterpart.

Aging↗
PubMed1994

Age-related changes in diaphragm muscle contractile properties and myosin heavy chain isoforms.

The present study sought to examine the effects of aging on the isometric contractile and fatigue properties as well as the myosin heavy chain (MCH) isoform composition of the rat diaphragm muscle. Male Fischer 344 (F344) specific pathogen-free rats 6 and 24 mo old were used in the study. Peak twitch force was approximately 23% lower (p < 0.05) in the senescent diaphragm compared with the young. Time to peak twitch force and one-half relaxation time of twitch force did not differ between groups. There was a significant decrease (15 to 18%, p < 0.05) in the specific force (N/cm2) of the senescent diaphragm at all stimulation frequencies (10 to 100 Hz) examined. In addition, the fatigability of the diaphragm did not significantly differ between the two groups. No significant changes in the distribution of MHC 1 and 2A isoforms were observed with aging. However, the contribution of MHC 2X significantly decreased with senescence (young, 37.5%; senescent, 30.5%), whereas the contribution of MHC 2B in the senescent diaphragm was significantly higher (young, 6.5%; senescent, 15.0%; p < 0.05). We conclude that the age-related decline in diaphragm muscle specific force is caused by intrinsic factors other than changes in MHC composition.

Aging↗
PubMed1994

Psychophysiological responses of parents to pediatric critical care stress.

Psychological factors are associated with how parents cope during a child's intensive care hospitalization. However, little is known about the role of physiological-stress responses in parents' coping and adaptation to such situations. This study investigates the relationship between parents' psychophysiological-stress responses, as measured by urine catecholamine excretion, and their coping and activities during a child's intensive care experience. Parents who appraised the situation as one that is amenable to change and who used more problem-focused strategies, such as seeking social support, had lower anxiety and lower catecholamine levels. Further, parents who were more problem focused performed more child care activities during the experience. The results of this study provide information for planning interventions to promote parental coping and adjustment to the child's critical care situation.

Adaptation, Psychological↗
PubMed1994

The shifting importance of alcohol and marijuana as gateway substances among serious drug abusers.

Prior research based on representative samples drawn from the general population suggests persons tend to follow a common developmental pathway from use of alcohol as youths through possible use of marijuana as teens potentially leading to use of more serious substances as adults. Based on this model, alcohol and marijuana act as gateways, whereby persons who do not onset to alcohol rarely onset to marijuana; similarly, non-marijuana users rarely onset to more serious substance use and abuse. This study examines whether a sample of serious drug abusers recruited from New York City in 1988-89 followed the same developmental pathway as observed in general populations. The results suggest that alcohol is not a prerequisite for progression to marijuana, but marijuana use nearly always precedes use of more serious substances such as cocaine, crack and heroin. Furthermore, with the growing prevalence of marijuana (since 1965) the importance of alcohol as a gateway to marijuana use appears to have declined and marijuana's role as a gateway to serious drug use appears to have increased.

Adult↗
PubMed1994

Clinical evaluation of the efficacy and safety of a new sonic toothbrush.

The efficacy and safety of a new sonic toothbrush were studied in this single-blind study. The sonic toothbrush combines acoustic vibrations and dynamic fluid activity surrounding the bristles with direct mechanical scrubbing of tooth surfaces. Fifty-one subjects were randomly assigned to either the sonic or the manual toothbrush. Plaque scores were assessed before and after a 2-minute brushing at baseline and 1, 2, and 4 weeks. Gingivitis and sulcular bleeding scores were also taken at each evaluation. To assess long-term safety, 29 subjects returned after 6 months of product use. Repeated measures analysis of variance of the total mean plaque score indicated a significant difference between the devices over time (P < 0.01), with the sonic toothbrush demonstrating a greater level of plaque removal on all tooth surfaces. On average, the plaque reduction from the baseline score for the sonic toothbrush was 3 times greater than the manual brush. However, when broken down by dental region, the sonic toothbrush demonstrated an improved level of plaque removal ranging from 1.5 to 11.9 times better than the manual brush, with the greatest improvement in the interproximal and lingual areas. Both the gingivitis and sulcular bleeding scores exhibited a similar, significant reduction (P < 0.005) over time for both devices with an approximate 17% decrease in the gingivitis index and a 33% decrease in sulcular bleeding sites. Safety assessment after 6 months of use indicated no soft tissue abnormalities which could be attributed to the products.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A recent decline in cocaine use among youthful arrestees in Manhattan, 1987 through 1993.

OBJECTIVES: Cocaine use among youths as measured by several annual surveys was most popular from about 1979 to 1986, after which it declined. This study carefully examines the nature of the decline by focusing on microdata for youthful arrestees in Manhattan. METHODS: Multiple statistical analyses examine whether the decline in cocaine use detected by urinalysis is attributable to fewer arrested youths born more recently having become regular users (cohort effect), to regular users decreasing their consumption (period effect), or to changes in arrest or sampling priorities (artifact). RESULTS: All analyses suggest that the dramatic decline in detected cocaine use among arrestees--from 69% in 1987 to 17% in 1993--was a cohort effect. Detected cocaine use, which was highest (78%) among arrestees reaching 18 in 1986 at the height of the crack epidemic in New York City, subsequently declined to a low of 10% among arrestees reaching 18 in 1993. DISCUSSION: These findings suggests that the epidemic in use of cocaine and crack entered a decline in the late 1980s. However, widespread use of these drugs will probably continue to prevail as an aging population with established habits persists in its use.

Adolescent↗
PubMed1994

Impact of the aging pulmonary system on the response to exercise.

The older adult demonstrates several alterations in the ventilatory response to exercise relative to the young adult. These differences are primarily caused by the aging-induced loss of elastic recoil of the lung, which reduces expiratory airflow rates along the effort-independent portion of the maximal volitional flow-volume envelope. Despite these distinctions in the response to exercise of the aged adult, alveolar ventilation is adequate for carbon dioxide elimination (even during maximal exercise), and arterial oxygen homeostasis is generally maintained.

Adult↗
PubMed1993

Induction of porcine granulocyte-mediated tumor cytotoxicity by two distinct monoclonal antibodies against lytic trigger molecules (PNK-E/G7).

PNK-E and G7 mAb bind to distinct porcine granulocyte function-associated molecules and induce granulocyte-mediated cytotoxicity against tumor targets. PNK-E mAb binds to a 205-kDa molecule that reduces to a dispersed band of 50 kDa on SDS-PAGE analysis. Previous work demonstrates that G7 mAb immunoprecipitates a molecule that appears as a heterodispersed 40-kDa band under both reducing and nonreducing conditions on SDS-PAGE analysis. Whole but not F(ab')2 PNK-E and G7 mAb induce dose-dependent porcine granulocyte-mediated lysis of FcR+ but not FcR- targets, suggesting a redirected cytotoxicity mechanism of granulocyte-mediated killing. Fresh porcine granulocytes also mediate significant levels of antibody-dependent cellular cytotoxicity (ADCC) against nucleated (SB) target cells. Neither whole nor F(ab')2 PNK-E mAb affects granulocyte-mediated ADCC against SB target cells. However, both whole and F(ab')2 G7 mAb inhibit granulocyte-mediated ADCC against SB targets by approximately 50%. Bound F(ab')2 G7 mAb inhibits PNK-E mAb-induced granulocyte-mediated cytotoxicity against K562 targets, but bound F(ab')2 PNK-E mAb does not inhibit G7 mAb-induced granulocyte-mediated cytotoxicity, suggesting a physical association between the PNK-E and G7 molecules on the surface of porcine granulocytes. PNK-E and G7 hybridoma cells are readily lysed by granulocyte effectors, further supporting that the PNK-E and G7 molecules are cytolytic trigger molecules on granulocytes. These data demonstrate that PNK-E and G7 mAb bind to distinct granulocyte lytic trigger molecules and induce potent granulocyte-mediated cytotoxicity against nucleated tumor targets through a mechanism of redirected cytotoxicity.

Animals↗
PubMed1993

Influence of two substrate analogues on thermodynamic properties of medium-chain acyl-CoA dehydrogenase.

The objective of this work was to identify the key structural functionalities of substrate or product that modulate the thermodynamic properties of medium-chain acyl-CoA dehydrogenase (MCAD). In order to achieve this, two classes of substrate analogues, acetyl-CoA and thioether-CoAs, were complexed with MCAD and their effects on the redox properties of MCAD were measured. A pH dependence study of the redox potential of uncomplexed MCAD allowed us to compare redox properties between complexed and uncomplexed MCAD and to calculate the dissociation constants of the analogues to the three redox states of MCAD. The results from this work indicate that these analogues are not influencing the thermodynamic behavior of MCAD in the same way as natural substrate. Thus, we propose that the following two key structural features of the binding ligand are necessary for mimicking the thermodynamic effects natural substrate has on MCAD: a thioester carbonyl on carbon 1 and a fatty acyl-CoA chain length around 8 carbon units. Furthermore, with the advent of structural knowledge, insights into the interactions of these structural features with MCAD and their influence on MCAD's highly regulated dehydrogenation mechanism are discussed.

Acetyl Coenzyme A↗
PubMed1993

Preparation of substituted N-phenyl-4-aryl-2-pyrimidinamines as mediator release inhibitors.

The role of immunologically released mediators, such as histamine, leukotrienes, and platelet-activating factor, is well-established for asthma and other allergic disorders. Developing therapeutic agents which would block mediator release from mast cells and other relevant cell types would provide a rational approach to asthma therapy. Using human basophil as a screen, a series of 4-aryl-2-(phenylamino)pyrimidines was found which inhibited mediator release. These compounds were prepared by condensing acetyl heterocycles with dimethylformamide dimethyl acetal to form enaminones which are cyclized with aryl guanidines to give pyrimidines. After examining a large number of analogs, N-[3-(1H-imidazol-1-yl)phenyl]-4-(2-pyridinyl)-2- pyrimidinamine (1-27) was chosen for toxicological evaluation.

Animals↗
PubMed1993

Two distinct porcine natural killer lytic trigger molecules as PNK-E/G7 molecular complex.

PNK-E and G7 mAbs regulate porcine NK and ADCC activities by binding to distinct NK function-associated trigger molecules on porcine NK cells. Previous work demonstrates that PNK-E mAb binds to a 205-kDa tetrameric molecule composed of two 47-kDa peptides and two 50-kDa peptides and G7 mAb binds to a distinct 40-kDa heterodispersed monomeric peptide on porcine NK cells. The data presented herein demonstrate that all PNK-E+ PBLs are G7+ and all G7+ PBLs are PNK-E+ indicating that the PNK-E and G7 molecules are coexpressed by porcine NK cells. Bound G7 mAb blocks subsequent binding of PNK-E mAb but not the converse. Bound F(ab')2 G7 mAb abrogates the ability of whole PNK-E mAb to enhance NK activity but bound F(ab')2 PNK-E mAb has no affect on G7 mAb enhancement of NK activity. PNK-E mAb enhanced NK activity is inhibited by binding of F(ab')2 G7 mAb even though whole PNK-E mAb remains bound. However, bound F(ab')2 PNK-E mAb has no affect on G7 mAb-enhanced NK activity. When PNK-E and G7 mAbs were tested alone and together in NK assays, comparable levels of enhancement were observed. PNK-E and G7 hybridomas express surface mAb through which NK cells bind and specifically lyse these hybridomas. Lysis of PNK-E and G7 hybridomas is inhibited by pretreatment of PBLs with F(ab')2 G7 mAb. These data indicate a physical association between the PNK-E and G7 molecules on NK cells and suggest that the G7 molecule is external to the PNK-E molecule.

Animals↗
PubMed1993

A cytoskeletal mechanism for Ca2+ channel metabolic dependence and inactivation by intracellular Ca2+.

Many different types of voltage-dependent Ca2+ channels inactivate when intracellular ATP declines or intracellular Ca2+ rises. An inside-out, patch-clamp technique was applied to the Ca2+ channels of Lymnaea neurons to determine the mechanism(s) underlying these two phenomena. Although no evidence was found for a phosphorylation mechanism, agents that act on the cytoskeleton were found to alter Ca2+ channel activity. The cytoskeletal disrupters colchicine and cytochalasin B were found to speed Ca2+ channel decline in ATP, whereas the cytoskeletal stabilizers taxol and phalloidin were found to prolong Ca2+ channel activity without ATP. In addition, cytoskeletal stabilizers reduced Ca(2+)-dependent channel inactivation, suggesting that both channel metabolic dependence and Ca(2+)-dependent inactivation result from a cytoskeletal interaction.

Actins↗