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Biomedical subjects

J G Hay

Publications and source records attributed to J G Hay.

At least 37 records · Page 2Linked to original sources

Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis.

We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in the CF respiratory epithelium in vivo. With doses up to 2 x 10(9) pfu, there was no recombination/complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at 6-12 months demonstrated no long term adverse effects. Thus, it is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF. Correction of the CF phenotype of the airway epithelium might be achieved with this strategy.

Adenoviridae↗

Vulnerability of the human airway epithelium to hyperoxia. Constitutive expression of the catalase gene in human bronchial epithelial cells despite oxidant stress.

Although catalase is a major intracellular antioxidant, the expression of the human catalase gene appears to be limited in the airway epithelium, making these cells vulnerable to oxidant stress. The basis for this limited gene expression was examined by evaluation of the expression of the endogenous gene in human bronchial epithelial cells in response to hyperoxia. Hyperoxia failed to upregulate endogenous catalase gene expression, in contrast to a marked increase in expression of the heat shock protein gene. Sequence analysis of 1.7 kb of the 5'-flanking region of the human catalase gene showed features of a "house-keeping" gene (no TATA box, high GC content, multiple CCAAT boxes, and transcription start sites). Transfection of human bronchial epithelial cells with fusion genes composed of various lengths of the catalase 5'-flanking region and luciferase as a reporter gene showed low level constitutive promoter activity that did not change after exposure to hyperoxia. Importantly, using a replication-deficient recombinant adenoviral vector containing the human catalase cDNA, levels of catalase were significantly increased in human airway epithelial cells and this was associated with increased survival of the cells when exposed to hyperoxia. These observations provide a basis for understanding the sensitivity of the human airway epithelium to oxidant stress and a strategy for protecting the epithelium from such injury.

Base Sequence↗

Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester.

Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease, helps to protect the epithelial surface of the airways from the destructive capacity of neutrophil elastase. Based on the recognition that SLPI levels can increase in the presence of airway inflammation, we hypothesized that inflammatory stimuli should modulate the expression of the SLPI gene in airway epithelial cells. To evaluate this, the modulation of SLPI gene expression with various inflammatory stimuli was evaluated in the HS-24 human bronchial epithelial cell line. After preliminary studies showed that several inflammatory mediators enhanced SLPI messenger RNA (mRNA) levels, PMA was used as a model inflammatory stimulus. PMA significantly increased the level of 0.7-kb SLPI mRNA transcripts in HS-24 cells in a dose- and time-dependent fashion and increased the amount of SLPI protein in the culture supernatant. Nuclear run-on analyses showed that the SLPI gene transcription rate increased approximately twofold after PMA stimulation. Transfection studies using fusion genes composed of fragments of up to 1.2 kb of the 5' flanking sequence of the SLPI gene and a luciferase reporter gene demonstrated potent promoter activity in the 131-bp segment (-115 to +16 relative to the transcription start site), and all longer segments up to 1.2 kb, whereas smaller segments showed low promoter activity. An 18-bp element (-98 to -115), in a region with homology to PMA-responsive regions in the Moloney murine leukemia virus enhancer and the IL-8 gene, was shown to be of importance in the level of transcription of the SLPI gene. However, this element was not responsible for the upregulation of SLPI gene expression by PMA. Evaluation of HS-24 cells in the presence of actinomycin D demonstrated that SLPI mRNA transcripts were very stable and became more so in the presence of PMA. Thus, SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels. These mechanisms of SLPI upregulation likely play a role in defending the epithelial surface in the local milieu of inflammatory lung diseases.

Base Sequence↗

A panning DLT procedure for three-dimensional videography.

The direct linear transformation (DLT) method [Abdel-Aziz and Karara, APS Symposium on Photogrammetry. American Society of Photogrammetry, Falls Church, VA (1971)] is widely used in biomechanics to obtain three-dimensional space coordinates from film and video records. This method has some major shortcomings when used to analyze events which take place over large areas. To overcome these shortcomings, a three-dimensional data collection method based on the DLT method, and making use of panning cameras, was developed. Several small single control volumes were combined to construct a large total control volume. For each single control volume, a regression equation (calibration equation) is developed to express each of the 11 DLT parameters as a function of camera orientation, so that the DLT parameters can then be estimated from arbitrary camera orientations. Once the DLT parameters are known for at least two cameras, and the associated two-dimensional film or video coordinates of the event are obtained, the desired three-dimensional space coordinates can be computed. In a laboratory test, five single control volumes (in a total control volume of 24.40 x 2.44 x 2.44 m3) were used to test the effect of the position of the single control volume on the accuracy of the computed three dimensional space coordinates. Linear and quadratic calibration equations were used to test the effect of the order of the equation on the accuracy of the computed three dimensional space coordinates. For four of the five single control volumes tested, the mean resultant errors associated with the use of the linear calibration equation were significantly larger than those associated with the use of the quadratic calibration equation. The position of the single control volume had no significant effect on the mean resultant errors in computed three dimensional coordinates when the quadratic calibration equation was used. Under the same data collection conditions, the mean resultant errors in the computed three dimensional coordinates associated with the panning and stationary DLT methods were 17 and 22 mm, respectively. The major advantages of the panning DLT method lie in the large image sizes obtained and in the ease with which the data can be collected. The method also has potential for use in a wide variety of contexts. The major shortcoming of the method is the large amount of digitizing necessary to calibrate the total control volume. Adaptations of the method to reduce the amount of digitizing required are being explored.

Biomechanical Phenomena↗

Citius, altius, longius (faster, higher, longer): the biomechanics of jumping for distance.

The purpose of this paper is to review current knowledge concerning the long and triple jumps. Much has been learned over the past two decades about techniques in the long jump. Many myths have been dispelled and many training practices have been altered as a result. In all of this, the techniques employed during the takeoff have received little attention. It is in this area that the most important developments are likely to take place in the next decade. In contrast with the long jump, satisfactory answers have yet to be obtained to even the most fundamental of questions about techniques in the triple jump. The triple jump is an experimental task with potential for use in studies of human locomotion, of visual perception and control, of the strength of biological materials and of the mechanisms of soft tissue injury.

Biomechanical Phenomena↗

Oxygen desaturation and breathlessness during corridor walking in chronic obstructive pulmonary disease: effect of oxitropium bromide.

BACKGROUND: Although exercise induced desaturation can occur in patients with chronic obstructive pulmonary disease (COPD), little is known about its frequency during everyday exercise, or how it relates to dyspnoea or prior drug treatment. METHODS: The effects of 200 micrograms inhaled oxitropium bromide, an anticholinergic bronchodilator drug, on spirometric values, dyspnoea score, and oxygen saturation during corridor walking and cycle ergometry were studied in a double blind, randomised, placebo controlled study. RESULTS: Oxitropium produced a small increase in forced expired volume in one second (FEV1) from 0.76 (0.28) 1 to 0.93 (0.69) 1 and in six minute walking distance from 311 (93) m to 332 (86) m, but did not change progressive cycle exercise duration. Resting and end exercise breathlessness levels were reduced in both forms of exercise after oxitropium. Resting oxygen saturation fell significantly after active bronchodilator from 92.9% (3.7%) to 92.0% (4.1%) but the nadir saturation during exercise was unchanged. The patients desaturated more during corridor walking than cycle ergometry [walking 7.8% (4.4%), cycle ergometry 2.1% (2.1%)]. Baseline walking distance was related to FVC, resting breathlessness and resting oxygen saturation (multiple r2 = 0.46) but only resting saturation correlated with end exercise breathlessness (r2 = -0.25). Improvements in symptoms or exercise performance after oxitropium could not be predicted by changes in spirometric indices or oxygen saturation. CONCLUSIONS: In patients with COPD arterial oxygen desaturation during self-paced walking is common, of greater severity than that during cycle ergometry, but is unaffected by inhaled oxitropium bromide. The factors that predict initial performance are not appropriate markers of functional improvement after an active bronchodilator drug.

Double-Blind Method↗

The biomechanics of the triple jump: a review.

The purpose of this paper is to review the published opinions of coaches and the findings of scientists concerning the techniques used in the triple jump, and to identify promising avenues for future research on the subject. A model is developed to identify those factors that have a causal role in determining the official distance of a triple jump. This model is then used as a basis for the subsequent review. The review itself considers each of the biomechanical factors identified in the model, some additional factors reported in the literature, and selected characteristics of triple jumping techniques. It is concluded that research on triple jump techniques has been sparse and has had little impact on practice. Identification of the individual attributes that determine the optimum ratio of the phase distances for a given athlete, the loads to which the supporting legs are subjected and the control of balance during a triple jump are seen as challenging and potentially useful topics of future research.

Biomechanical Phenomena↗

Comparison of three different methods used to achieve local anesthesia for fiberoptic bronchoscopy.

A patient's tolerance of fiberoptic bronchoscopy depends on the effectiveness of local anesthesia. This study compares the three different methods of local anesthesia in common use After sedation, patients (n = 53) received either 4 ml of 2.5 percent cocaine by intratracheal injection (TI) (n = 18), by bronchoscopic injection (BI) (n = 19), or had 4 ml of 4 percent lidocaine delivered by nebulizer 20 min before the procedure (NEB) (n = 16). Patients and bronchoscopists scored the procedure using visual analog (VAS) and severity scales. Objective measurements of cough counts and episodes of stridor were recorded by phonopneumography. Patients' VAS scores showed a clear preference for the transtracheal method compared with either bronchoscopically injected cocaine (p less than 0.001) or nebulized lidocaine (p less than 0.001). Patients also reported that the TI method produced less cough during intubation of the larynx and inspection of the airways (BI and NEB, p less than 0.01). The TI method was also preferred by the bronchoscopists (BI and NEB, p less than 0.001); they reported less cough and easier tracheal intubation. The mean cough count was significantly lower for the TI group, 49 (43) compared with 95 (52) for BI (p less than 0.01), and 81 (43) for the NEB group (p less than 0.05). Patients' and bronchoscopists' VAS showed significant correlation with cough (r = 0.63-69, p less than 0.01). Stridor occurred in only two patients after TI, compared with 15 in the other two groups. Extra local anesthesia was required by 16 patients after BI, by all the NEB group, but by only one patient after TI. Subjective and objective measurement shows that 4 ml of 2.5 percent cocaine injected into the trachea produced excellent local anesthesia for fiberoptic bronchoscopy, there were no extra complications, and it was the method preferred by both patients and bronchoscopists.

Aerosols↗

Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease.

Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double-blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients.

Aged↗

Techniques used by elite long jumpers in preparation for takeoff.

It was hypothesized that some characteristics of the positions adopted by long jumpers during the final strides of the approach are significantly related to the distance of the jump, and that they are so related only by virtue of their relationships with the horizontal velocity at touchdown and/or the vertical velocity at takeoff. Trials by 20 male and 26 female long jumpers were recorded cinematographically and subsequently analyzed. The takeoff distance for the fourth-last stride, the landing distance for the last stride, and the height of the center of gravity (CG) at takeoff into the jump were significantly correlated with the distance of the jump. These three position variables were significantly related to the distance of the jump, through their relationships with the velocity of the approach and the vertical velocity of the CG at takeoff into the jump. Considered alone, they were not influential in determining the distance of the jump.

Biomechanical Phenomena↗

Flow visualization of competitive swimming techniques: the tufts method.

The purpose of this study was to evaluate the use of tufts to visualize the flow of water around the trunk and limbs of a swimmer. Numerous pilot studies were conducted to evaluate the effectiveness of different tuft materials, dimensions and methods of attachment for recording the characteristics of the flow around a swimmer performing various strokes and drills. Differences in the patterns of flow made visible by the tufts suggested that this method of flow visualization may well be useful in resolving both basic and applied questions concerning swimming techniques.

Biomechanical Phenomena↗

Measurement of nasal potential difference in adult cystic fibrosis, Young's syndrome, and bronchiectasis.

Previous work confirmed the abnormal potential difference between the undersurface of the inferior nasal turbinate and a reference electrode in cystic fibrosis, but the technique is difficult and the results show overlap between the cystic fibrosis and the control populations. In the present study the potential difference from the floor of the nose has therefore been assessed in normal subjects, as well as in adult patients with cystic fibrosis, bronchiectasis and Young's syndrome. Voltages existing along the floor of the nasal cavity were recorded. The mean potential difference was similar in controls (-18 (SD 5) mv) and in patients with bronchiectasis (-17 (6) mv) and Young's syndrome (-20 (6) mv). The potential difference in cystic fibrosis (-45 (8) mv) was significantly different from controls (p less than 0.002) and there was no overlap between the cystic fibrosis values and values obtained in normal and diseased controls. This simple technique therefore discriminates well between patients with cystic fibrosis and other populations, raising the possibility of its use to assist in diagnosis.

Adolescent↗

Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats.

Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum.

Animals↗

The effects of iron and desferrioxamine on the lung injury induced by intravenous bleomycin and hyperoxia.

The development of acute lung injury in rats following the intravenous injection of bleomycin was assessed by measuring the total pulmonary extravascular albumin space. Intravenous bleomycin alone produced no evidence of lung injury, yet when combined with a simultaneous exposure to hyperoxia or simultaneous tracheal instillation of ferric iron or ascorbate a severe lung injury evolved. Neither ferric iron or ascorbate alone produced lung injury when assessed in this manner, and ferrous iron, ferritin and haemoglobin did not potentiate bleomycin induced lung injury. A continuous subcutaneous infusion of desferrioxamine enhanced hyperoxia induced lung injury, and had no modulating effect on the lung injury produced by combined intravenous bleomycin and hyperoxia. These results indicate that ferric iron can potentiate bleomycin induced lung injury, and that the metal chelator desferrioxamine can have adverse effects on the development of acute lung injury.

Animals↗

The techniques of elite male long jumpers.

A model was developed to identify the characteristics of long jumping technique that determine the distance of the jump. The performances of the finalists in the TAC (U.S. national) Championships were recorded cinematographically and the best trials analyzed. The results indicated that the relative lengths of the last two strides of the approach are poor indicators of success in the event. Maximum horizontal velocities were usually attained at takeoff into the third- or second-last stride and not exclusively during the second-last stride, as previously reported. None of the subjects had either a zero or upward vertical velocity of the center of gravity at touchdown of the foot for takeoff into the jump, contrary to an argument occasionally advanced. The greatest percentages of the variance in the distance of the jump were accounted for by the horizontal velocity at takeoff into the fourth-last stride, the change in horizontal velocity during the next support phase, the horizontal and resultant velocities at takeoff and the flight distance.

Male↗

The biomechanics of the long jump.

The preceding review has been based on over 200 publications in Czech, English, French, German, Japanese, Polish, and Russian. Even a cursory perusal of these materials is sufficient to show that much has been done to try and obtain a scientific understanding of long jump techniques. It is clear, too, that still more remains to be done. Much of the work to date has been focused on just a few aspects of long jump technique. Other important aspects have received relatively little attention. The latter include the accuracy of the approach, the techniques used during the final strides of the approach, the role of elastic energy in the takeoff, the initiation and control of the jumper's angular momentum, and the techniques used in the landing. Future research efforts might well be directed towards resolving major issues concerning these aspects of long jump technique. The methods used to gather data in the studies reviewed have been rather unimaginative. Two-dimensional cinematography has been used in the vast majority of the studies and force platforms in a few. Other data-gathering procedures like three-dimensional cinematography, electromyography and accelerometry have rarely, if ever, been used. In only one or two studies was anything remotely approaching experimental or technological innovation in evidence. The methods used to analyze data have also been very limited. With the notable exception of a study by Ballreich, few papers have involved anything more sophisticated than means, standard deviations, correlation coefficients and an occasional multiple regression equation. Given these facts, it is hard to avoid the conclusion that our knowledge of long jump techniques might be greatly improved if the full range of available and appropriate procedures were turned to the purpose. Finally, no review of the literature on long jump techniques would be complete without reference to the level of scholarship displayed in the works under consideration. With only a few exceptions, the level shown in the scientific papers reviewed here left much to be desired. Time and again, variables were not defined, crucial measurement techniques were not described and major results were not presented or discussed. In addition, much of the data presented in tables and graphs were patently in error. In light of all this, it is clear that unless the level of scholarship improves, future progress in this area of sports biomechanics is likely to be very slow.

Biomechanical Phenomena↗

Relationships among anthropometric and stroking characteristics of college swimmers.

A theoretical model was developed to identify anthropometric variables relevant to success in swimming. Frontal areas, cross-sectional areas (XSA), and lengths of body segments were measured on twelve members of a men's college team using a photographic procedure. Motion-picture films were taken of the subjects competing in freestyle events and were analyzed to determine the average stroke length (SL), average stroke frequency (SF), and average stroking speed (S). Correlation and multiple regression procedures were used to determine the relationships among the anthropometric variables and SL, SF, and S, respectively. Of the 21 anthropometric variables selected with the aid of the theoretical model, 6 were found to be significantly related to one or more of the measures of swimming performance when the influence of event distance was partialled out (P less than or equal to 0.05). The anthropometric variables characterizing the subjects accounted for 89% (SL), 41% (SF), and 17% (S) of the variances in the measured characteristics of their strokes. The axilla XSA was shown to have the largest influence on both SL and SF, accounting for 57% of the variance in the SL and 24% in the SF. These results suggest that although S is little influenced by the physique of a swimmer, the combination of SL and SF used to attain a given S is very much a function of his physique.

Anthropometry↗

Transepithelial potential difference in cystic fibrosis.

In cystic fibrosis the potential difference between interstitial fluid and the surface of respiratory and sweat duct epithelia is abnormally large. This study attempted to confirm this finding and investigate its value for a diagnostic test. With a subcutaneous reference electrode the mean potential difference of the inferior turbinate was -25 mv in 19 patients with cystic fibrosis, which was significantly greater than the difference of -13 mv in 22 normal subjects (p less than 0.02). Of the observations in the patients with cystic fibrosis, 67% were greater than the largest potential difference observed in normal individuals. Potential differences from the lip and forearm were also significantly greater in cystic fibrosis than in normal subjects, but there was considerable overlap. Changes in the electrical properties of nasal epithelium and skin have been confirmed in cystic fibrosis, but these have limited use for diagnosis.

Adult↗