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Biomedical subjects

B D Johnson

Publications and source records attributed to B D Johnson.

At least 127 records · Page 7Linked to original sources

Further characterization of PNK-E: a monoclonal antibody enhancing porcine natural killer cell activity.

Monoclonal antibody PNK-E binds to approximately 15% of porcine peripheral blood lymphocytes (PBL) which are PT4 negative and PT8 positive. When cells from tissues of adult pigs are treated with PNK-E, enhancement of natural killer (NK) cell activity is observed from PBL and spleen cells, and a dramatic induction of NK activity is observed from bone marrow cells. With cells derived from tissues of neonatal piglets, PNK-E induces NK activity from PBL and bone marrow cells. To investigate the mechanism of PNK-E-mediated enhancement of NK, proliferation assays, calcium-pulse assays, single-cell assays, and kinetic analyses were performed. PNK-E did not induce proliferation of PBL. PNK-E could be added as late as 30 min prior to termination of Ca(2+)-pulse assays and still enhance NK activity. Using kinetic analysis PNK-E was found to increase the rate of NK lysis (Vmax) and rate of lytic programming per NK cell (k2). In addition, results from single-cell assays indicate that PNK-E activates a population of normally inactive effector cells. These results indicate that PNK-E enhances the lytic capacity of mature NK cells and induces a population of nonlytic cells to become highly cytolytic cells. Furthermore, the enhancing effects are immediate and do not require an induction period. Thus, PNK-E recognizes and activates a unique triggering molecule that is present on NK cells.

Age Factors↗

Flow limitation and regulation of functional residual capacity during exercise in a physically active aging population.

In 29 older (69 +/- 1 yr), physically active subjects (VO2max = 44 +/- 2 ml.kg-1.min-1), we determined the effect of an age-related decline in elastic lung recoil (i.e., Vmax50 = 65% of 30-yr-old adults) on the ventilatory response to progressive exercise. More specifically, we assessed if expiratory airflow limits were achieved and how this may modulate the regulation of end-expiratory lung volume (EELV). We found that with only mild to moderate (50 to 75% VO2max) exercise, the mean EELV was reduced 0.38 +/- 0.07 L, and that expiratory flow limitation was present over 25 +/- 4% of the VT. In 11 subjects during this intensity of exercise, EELV was within their closing capacity. As exercise intensity progressed, VT plateaued at 58 +/- 2% of the vital capacity, and increased expiratory air flow rates were achieved by significantly increasing the EELV back to near resting levels, thereby moving a portion of the expiratory tidal flow-volume envelope away from the constraints of the effort independent portion of the maximal flow-volume curve. During heavy exercise, end-inspiratory lung volume (EILV) approached 90% of TLC. To achieve greater expiratory flow with maximal exercise, EELV remained similar to the previous intensity, and a significantly greater portion of the tidal expiratory flow-volume envelope (greater than 40% of the VT) became flow-limited. Despite this significant expiratory limitation, a rise in EELV, and an EILV approaching TLC, TI/Ttot remained constant throughout exercise, and the ventilatory response for the metabolic demand (VA/VCO2) was appropriate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Mechanical constraints on exercise hyperpnea in a fit aging population.

We studied 12 physically fit (VO2 max = 44 ml.kg-1.min-1) older subjects (age = 63 to 77 yr) who showed the usual age-related declines in lung function (i.e., reduced maximal expiratory flow rates, vital capacity and increased functional residual capacity, closing capacity, and residual volume). We measured the optimal transpulmonary pressures for maximal expiratory airflow and the capacity of the muscles of inspiration for developing pleural pressure (taking into account the effects of lung volume and flow rate). Within these mechanical constraints to ventilation we plotted tidal pleural pressure-volume loops for mild through maximal exercise according to a measured end-expiratory lung volume (EELV). We found EELV to decrease a mean of 0.26 +/- 0.09 L and maximal effective pleural pressures to be reached in nine subjects near EELV with only light to moderate exercise intensities, whereas peak inspiratory pressure was only 45% of the capacity for pressure generation. With progressive increases in exercise intensity, EELV increased, and pleural pressures encroached to a greater extent on the maximal effective pressures; however, they remained effective in the majority of subjects. During maximal exercise EELV was 0.13 +/- 0.10 L greater than resting values, 20% of the Vt reached maximal effective pressures, and 83% of the capacity for inspiratory pressure was achieved. Three subjects significantly surpassed their maximal effective expiratory pressures, and four subjects achieved 95 to 100% of the capacity for inspiratory pressure generation. These subjects also showed no further increase in ventilation while breathing 0.02 to 0.05 FICO2 at maximal exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Humoral immune responses to Porphyromonas gingivalis before and following therapy in rapidly progressive periodontitis patients.

We have performed studies aimed at elucidating the nature of the humoral immune response in rapidly progressive periodontitis (RPP). We analyzed the sera of 36 periodontally normal subjects and 36 RPP patients for titers and avidities of IgG antibodies reactive with the antigens of Porphyromonas gingivalis using ELISA, prior to and following treatment. We used whole-cell sonicate, purified lipopolysaccharide (LPS), and total extractable protein as plate antigens. Twelve of the patients had antibody titers at least 2-fold greater than the median of the controls and were designated as seropositive. The remaining 24 patients had titers that did not exceed twice the median titer of the controls and were designated as seronegative. For both patient groups, antibody titers were highest when whole-cell antigen was used, intermediate for LPS, and lowest for the protein fraction. Following treatment, median titer for seropositive patients decreased from pretreatment values of 241.7 to 76.5, while median titer for seronegative patients increased from 39.5 to 80.1. Avidities of pretreatment sera from both patient groups for all 3 antigen preparations were lower than the median avidities of the control sera. Avidity significantly increased following treatment to levels greater than those for control sera in both patient groups. Thus, some young adults with severe periodontitis mount a humoral immune response and produce high levels of serum IgG antibodies reactive with antigens of P. gingivalis, while others do not. The antibodies produced are of relatively low avidity, and may therefore be relatively ineffective biologically. Therapy, which greatly reduces antigen load, appears to stimulate production of higher avidity IgG antibodies in both patient groups; in the seropositive group, low avidity antibodies appear to be replaced by antibodies of higher avidity. Both the purified LPS and protein fractions contain reactive antigen(s), although LPS binds more antibody. Our data are consistent with the idea that many RPP patients do not produce protective levels of biologically functional antibody during the course of their natural infection, but they may be stimulated to do so by treatment.

Adult↗

Characterization of a monoclonal antibody enhancing porcine natural killer cell activity (PNK-E).

A monoclonal antibody, termed PNK-E, that functionally enhances porcine natural killer (NK) cell activity but not antibody-dependent cellular cytotoxicity (ADCC) is investigated in this report. When PNK-E and K562 target cells were simultaneously added to effector cells, killing of target cells could be detected as early as 30 min, and a dramatic enhancement of killing activity was observed in short term 51Cr-release assays. When a panel of five NK-sensitive targets were tested, PNK-E enhanced the killing of K562, MOLT-4, and U937 cells, but not the killing of CEM and YAC-1. F(ab)'2 fragments of PNK-E did not enhance NK activity, indicating a requirement for the Fc portion of PNK-E to elicit enhancement of NK. Immunofluorescence analysis shows that PNK-E antigen is expressed on approximately 15% of peripheral blood lymphocytes with a relatively dull fluorescence staining pattern. PNK-E-positive sorted cells were enriched for large granular lymphocytes (LGL) and contained all detectable NK activity as compared to the PNK-E-negative sorted cells. When analyzed by polyacrylamide gel electrophoresis, PNK-E antibody immunoprecipitated a protein from 125I-labeled peripheral blood lymphocyte (PBL) cell lysates that resolved as a single band of approximately 205 kDa under nonreducing conditions and as two bands of approximately 50 kDa and 47 kDa under reducing conditions. The present data demonstrate a functional association between PNK-E antigen and NK cell activation.

Animals↗

Cranial electrostimulation (CES) use in the detoxification of opiate-dependent patients.

This paper reviews the scientific literature on cranial electrostimulation (CES) as a non-chemical means to alleviate opiate withdrawal symptoms. CES involves applying small amounts of electrical stimulation through electrodes applied to the skin surface over the cranium. The paper summarizes major theories (gate, endorphin, and Chinese acupuncture) which attempt to explain how CES may help alleviate drug withdrawal and craving. Two of the studies reviewed show that CES patients experienced more severe withdrawal during the early part of treatment than comparison groups of methadone patients. Other studies show that CES patients did better than methadone patients. The findings from all studies reviewed, however, were limited because of low participation rates, high dropout rates, difficulties in blinding subjects and evaluators, and the absence of standardized procedures and equipment. The evidence reviewed suggests that CES is a promising line of inquiry for continued efforts to develop nonchemical ways to detoxify opiate-dependent individuals. Improved research designs, larger sample sizes, more integrity in data collection, and improved data analysis are needed in the future.

Acupuncture Therapy↗

Effect of cell donor age on the synthetic properties of fibroblasts obtained from phenytoin-induced gingival hyperplasia.

Diploid fibroblasts obtained from explants of human gingiva and maintained in vitro undergo a several-fold decrease in protein and collagen synthesis as a function of increasing donor age. Using drug-induced gingival hyperplasia as a model, we performed experiments to learn whether fibroblasts derived from hyperplastic tissue behave in a similar manner. Fibroblast strains were established from explants of hyperplastic gingiva obtained from 10 patients chronically ingesting phenytoin and ranging in age from 9 to 45 years. Protein production and degradation were compared to previously reported data similarly obtained from periodontally normal donors ranging in age from 12 to 68 yr. The total quantity of protein and collagen produced by the phenytoin cells was significantly greater than previously reported for cells from normal gingiva. No donor age-related decrease in protein and collagen production nor in the proportion of cell synthetic activity committed to collagen production was observed for cultures of phenytoin cells. The gross pattern of proteins produced, as assessed by 2-dimensional gel electrophoresis, was unrelated to donor age in both normal and phenytoin cells, but three polypeptides ranging in size from about 20 kD to 40 kD that were not found in the cultures of normal cells were produced by five of seven phenytoin cells strains. The observations demonstrate that the phenytoin cells do not undergo the donor age-dependent decrease in synthesis observed for normal cells. This abnormality may account in part for the phenytoin-induced hyperplasia. The phenytoin cells appear to be a unique phenotype.

Adolescent↗

Adaptation of the inert gas FRC technique for use in heavy exercise.

We automated the inert gas rebreathe technique for measurement of end-expiratory lung volume (EELV) during heavy exercise. We also assessed the use of two gas tracers (He and N2) vs. a single gas tracer (He) for measurement of this lung volume and compared the two-tracer EELV to changes in the inspiratory capacity (defined with transpulmonary pressure) and shifts in the end-expiratory pressure from rest through heavy exercise. A computer program switched a pneumatic valve when flow crossed zero at end expiration and defined points in the He and N2 traces for calculation of EELV. An inherent delay of the rebreathing valve (50 ms) caused virtually no error at rest and during light exercise and an error of 74 +/- 9 ml in the EELV at peak inspiratory flow rates of 4 l/s. The measurement of EELV by the two gas tracers was closely correlated to the single-gas tracer measurement (r = 0.97) but was consistently higher (120 +/- 10 ml) than when He was used alone. This difference was accentuated with increased work rates (2-5% error in the EELV, rest to heavy exercise) and as rebreathe time increased (2-7% error in the EELV with rebreathe times of 5-20 s for all work loads combined). The double-gas tracer measurement of EELV agreed quite well with the thoracic gas volume at rest (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Adaptations and limitations in the pulmonary system during exercise.

In most circumstances in health, efficient alveolar ventilation and alveolar-to-arterial exchange of O2 and CO2 are among the strongest of links in the gas-transport chain during maximal exercise. Indeed, in most instances, the metabolic cost of ventilation represents the only significant contribution of the pulmonary system to the limitation of O2 transport of locomotor muscles and thus to the limitation of maximum performance. Of the "weaknesses" inherent in the healthy pulmonary system response to exercise, the most serious one may well be its absence of structural adaptability to physical training or to the trained state. Thus, the lung's diffusion capacity and pulmonary capillary blood volume remain unaltered in the highly trained human or horse, while maximum pulmonary blood flow rises linearly with the enhanced max VO2. Similarly, ventilatory requirement rises markedly, with no alteration in the capability of the airways to produce higher flow rates or of the lung parenchyma to stretch to higher tidal volumes, and little or no change in the pressure-generating capability of inspiratory muscles. The case of the elderly athlete who remains capable of achieving high maximum pulmonary blood flows and ventilatory requirements and whose lung undergoes a normal aging process underscores the importance of deficits (from "normal") on the capacity end of this continuum of cost versus capacity in the pulmonary system. The asthmatic athlete may represent another such example of limited flow-generating capacity; and the healthy, young, highly fit athlete who shows marked reductions in SaO2 and in max VO2 at even moderately high altitudes demonstrates that, in many situations, precious little room can be added to the demand side or removed from the capacity side before signs of failure can be seen.

Adaptation, Physiological↗

Pharmacological management of recurrent oral mucosal ulceration.

A number of diseases can cause recurrent intraoral ulceration. This review focuses principally on drug management of intraoral ulceration associated with local and systemic conditions most likely to be observed on an outpatient basis by the general practitioner. These consist of recurrent aphthous stomatitis, erosive lichen planus, benign mucous membrane pemphigoid (BMMP), erythema multiforme. Behçet's disease, allergic stomatitis and infection. Information is provided on a spectrum of medication found useful in ulcer management, including topical antimicrobial and antifungal agents, topical and systemic corticosteroids, topical and systemic analgesics, and systemic immunosuppressive and anxiolytic drugs, plus details of dosage, important adverse reactions and interactions. A treatment guide for management of recurrent aphthae is presented. The reader is presumed to be familiar with differential diagnosis and the importance of establishing an accurate impression before starting drug therapy.

Humans↗

Aging or disease? Periodontal changes and treatment considerations in the older dental patient.

The segment of our society over age 65 is growing, and many more of these people are keeping their teeth for a longer period of time. This suggests that there will be additional need for periodontal therapy in the future, but it also implies that disease-related events must be distinguished from age-related changes. Changes in the periodontium with aging are reviewed, and periodontal disease management strategies in the older patient are discussed.

Aged↗

Patient expectations of radiology in noninteractive encounters.

Open-ended interviews with 107 patients documented specific patient expectations of radiologic procedures during which there was no direct radiologist-patient interaction. Patient expectations could be classified into those related to the facility and those related to interactions with radiology staff. Among facility-related expectations, waiting time far outweighed all other concerns. Interpersonal skills were the predominant expectation of radiology staff. The role of the radiologist in fulfilling patient expectations was less clear. Only 10% of unprompted patients cited the radiologist as a factor in their expectations. When patients were specifically prompted to discuss the radiologist's role, communication skills, accuracy of interpretation, and interpersonal skills were the predominant concerns.

Attitude↗

Cardiopulmonary and gas exchange responses to acute strenuous exercise at 1,270 meters in sickle cell trait.

The impact of strenuous exercise and environmental hypoxia on sickle cell trait (SCT) remains controversial. To determine if these factors induce cardiopulmonary and gas exchange abnormalities in SCT, healthy, young black male volunteers, 25 with SCT (HbAS) and 16 control subjects (HbAA), were evaluated during incremental and steady-state exercise tests using a cycle ergometer at 1,270 meters and 24 degrees C. Peak incremental exercise values for power (242 +/- 7 versus 253 +/- 10 watts), oxygen consumption (3.08 +/- 0.1 versus 3.26 +/- 0.14 liters/minute), heart rate (188 +/- 2 versus 189 +/- 3 beats/minute), minute ventilation (129 +/- 4.6 versus 144 +/- 7.7 liters/minute), oxygen pulse (16.4 +/- 0.5 versus 17.3 +/- 0.8 ml/beat), and respiratory exchange ratio (1.31 +/- 0.01 versus 1.33 +/- 0.02) revealed no significant differences (p less than 0.05) between the SCT and control groups, respectively. Peak incremental exercise values for arterial oxygen tension (82 +/- 1.7 versus 82 +/- 2.2 mm Hg), arterial carbon dioxide tension (32 +/- 0.7 versus 31 +/- 0.9 mm Hg), and alveolar-arterial oxygen pressure differences (19 +/- 1.4 versus 21 +/- 1.9 mm Hg) were similar for the SCT and control groups, respectively. Steady-state exercise results corroborate incremental exercise findings. It is concluded that cardiopulmonary and gas exchange responses to a brief period of strenuous exercise performed at low altitude at 24 degrees C in a well-characterized SCT sample of recruits were within normal limits and comparable to those of a carefully selected control sample.

Adult↗

Effect of moderate inspiratory hypoxia on exercise performance in sickle cell trait.

In previous work (Weisman IM, Zeballos RJ, Johnson BD: Cardiopulmonary and gas exchange responses to acute strenuous exercise at 1,270 meters in sickle cell trait. Am J Med 1988; 84: 377-383), no significant differences in cardiopulmonary and gas exchange responses to acute, strenuous exercise were observed between volunteers with sickle cell trait (SCT) and control subjects at an altitude of 1,270 meters. The current study was designed to evaluate the effect of a greater hypoxic stimulus on the response of healthy, black male basic recruits, 11 with SCT (HbAS) and 11 control subjects, to acute strenuous exercise. Simulated 2,300-meter and simulated sea-level conditions were achieved by adjustment of the fraction of inspired oxygen (simulated condition of 2,300 meters equal to 18 percent; simulated sea-level condition equal to 24 percent) at the same barometric pressure (656 mm Hg). For each simulated condition, the subjects performed an incremental exercise test to exhaustion on a cycle ergometer. One steady-state exercise test with radial arterial access for arterial blood gases was performed under each condition on Day 2. Peak incremental exercise values for oxygen consumption (2.9 versus 2.81 liters/minute), heart rate (189 versus 187 beats/minute), oxygen pulse (15.4 versus 15.1 ml/beat), and anaerobic threshold (1.59 versus 1.62 liters/minute), at the simulated 2,300-meter height revealed no significant differences between men with SCT and control subjects, respectively. A 5 to 9 percent decrement in exercise performance at the simulated 2,300-meter level compared with exercise performance at the simulated sea-level condition was noted for both groups. Steady-state exercise values for arterial oxygen tension (64 versus 65 mm Hg), arterial oxygen saturation (90 versus 90 percent), alveolar-arterial oxygen pressure difference (22 versus 21 mm Hg), and physiologic dead space to tidal volume ratio (12 versus 11) at the simulated condition of 2,300 meters were similar for the SCT and control groups, respectively. It is concluded that in a moderate hypoxic environment, the cardiopulmonary and gas exchange responses of persons with SCT during brief episodes of exhaustive exercise were comparable to those of control subjects.

Adult↗