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Biomedical subjects

J E White

Publications and source records attributed to J E White.

At least 37 records · Page 2Linked to original sources

Susceptibility of heterozygous MnSOD gene-knockout mice to oxygen toxicity.

Recent studies have shown that homozygous Mn superoxide dismutase (Sod2) gene-knockout mice (Sod2(-/-)) die shortly after birth with extensive myocardial injury, whereas heterozygous mutants (Sod2(+/-)) are phenotypically normal in room air. In the current study, we showed that Sod2(+/-) mice with approximately 50% of normal pulmonary MnSOD activity and normal levels of lung CuZnSOD, catalase, and glutathione peroxidase activities were not substantially more susceptible to 100% O2 toxicity than their normal Sod2(+/+) littermates. The mean (+/- SD) survival of Sod2(+/-) mice in 100% O2 was 101.4 +/- 14.8 h (n = 20) versus 103.2 +/- 11.3 h (n = 20) for Sod2(+/+) littermates (P > 0.60). In addition, Sod2(+/-) mice with approximately 50% of normal heart MnSOD activity and Sod2(+/+) mice did not develop any ultrastructural abnormalities in the myocardium at 75 h or 90 h after 100% O2 exposure. These results suggest that in mice, only 50% of MnSOD activity may be sufficient for normal resistance to 100% O2 toxicity.

Animals↗

Surfactant inhibits cationic liposome-mediated gene transfer.

We have demonstrated that tracheal insufflation of recombinant plasmid DNA results in transfection of rat lungs to the same extent as insufflation of plasmid-cationic liposome complex. To understand this observation better, we investigated the in vitro gene transfer of plasmid DNA in the presence and absence of cationic liposome and the effect of surfactant on gene transfer. The chloramphenicol acetyltransferase (CAT) expression plasmids pBL-CAT and pSV-CAT were studied in three cell types: rat fetal lung fibroblast (RFL-6), calf pulmonary artery endothelial cell (CPAE), and rat type II alveolar epithelial cell (type II AE). Three cationic liposomes were tested: DDAB (dimethyl-dioctadecyl ammonium bromide)-liposome, DOTAP (dioleoyltrimethyl ammonium propane)-liposome, and lipofectin. The results revealed that (i) plasmid DNA alone caused a dose-dependent, low-level transfection, most efficiently in RFL-6 followed by CPAE and type II AE, (ii) DDAB-liposome markedly enhanced gene transfer, most efficiently in RFL-6 followed by CPAE and type II AE, (iii) Survanta, a naturally derived surfactant preparation, and Exosurf, a synthetic surfactant, while having no effect on in vitro gene transfer by plasmid DNA alone, markedly inhibited cationic liposome-mediated gene transfer, (iv) dipalmitoyl phosphatidylcholine was responsible for the inhibitory effect of Exosurf, and (v) inhibition of cationic liposome-mediated gene transfer by Exosurf was not due to inhibition of plasmid DNA-cationic liposome complex uptake or interference with the promoter and enhancer. The observed inhibition of cationic liposome-mediated gene transfer by surfactant may in part explain our previous observation that tracheal insufflation of plasmid DNA and plasmid-cationic liposome complex results in equal lung gene transfer.

Animals↗

Inflammatory pseudotumor of the liver associated with extrahepatic infection.

We present two cases that support an infectious cause of inflammatory pseudotumor of the liver. Each patient had sepsis due to chronic abdominal abscesses, along with a liver mass. Both patients had exploratory celiotomy, and histologic examination of the liver mass revealed inflammatory pseudotumor of the liver. Evidence of a mixed bacterial/Actinomyces infection was noted in hepatic tissue sections in one patient, and Bacteroides caccae was cultured directly from the liver biopsy in the other patient. This is the first known report of bacteria being cultured from biopsy specimens of a hepatic pseudotumor and the only reported case of Actinomyces within a hepatic pseudotumor. Clinical and pathologic findings in these two cases indicate that an extrahepatic infectious source should be explored as a potential cause of inflammatory pseudotumor of the liver.

Abdominal Abscess↗

Sleep patterns in children with atopic eczema.

Following routine appointments in a paediatric dermatology clinic, the parents of 44 young children with atopic eczema and 18 with other skin conditions were interviewed regarding sleep patterns. Sleep disorders were more prevalent in the eczema children than in the control group and normal populations. "Night waking" problems were particularly common in the eczema children, whereas settling problems were not. An association was found between scratching habits and "night waking"--the more the children scratched, the greater the likelihood of their waking at night. Consideration is given to the management of the sleep problems of eczematous children.

Adolescent↗

Protection of rats against oxygen toxicity by tracheal administration of plasmid DNA: role of endogenous tumor necrosis factor.

Recombinant plasmid DNA alone or in conjunction with a gene delivery system has been used increasingly for in vivo gene transfer. However, little is known about the direct biological effects of plasmid DNA. In this study, we demonstrated that tracheal administration of a number of plasmid DNA protected rats against oxygen toxicity. This protection required the presence of intact plasmid DNA, was not due to endotoxin contamination, and was not shared by salmon testis DNA. The plasmid DNA-induced protection against oxygen toxicity was associated with the production of tumor necrosis factor (TNF) and the enhancement of pulmonary Mn-superoxide dismutase (MnSOD), CuZnSOD, and glutathione peroxidase activities. Coadministration of plasmid DNA and anti-TNF antibody (but not nonspecific IgG) partially abolished the protective effect and reduced the pulmonary MnSOD activity, suggesting that the plasmid DNA-induced oxygen tolerance was in part mediated by the endogenous TNF and MnSOD. In view of these observations and the known immunostimulatory effects of bacterial DNA, caution should be exercised in interpreting the results of in vivo gene transfer using recombinant plasmid DNA.

Analysis of Variance↗

Evaluation of activity-based techniques to identify transient arousal in respiratory sleep disorders.

Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep. Arousal is often associated with abrupt changes in the electroencephalogram (EEG), and such changes can be used as an index of sleep disturbance, but EEG analysis is laborious and requires trained observers. Possible alternative indices of arousal not reliant on EEG analysis were investigated. Recordings were made from 36 sleeping subjects who were being investigated for sleep-related breathing disorders. In each study awakenings and transient arousals according to EEG criteria were compared with activity in five potential indirect indicators of arousal: wrist movement, ankle movement, left and right tibial electromyogram, and phase change in ribcage-abdominal movement. The mean values of sensitivity to arousal ranged from only 25 to 45%. However, their high positive predictive accuracies (PPAs, 68 to 92%) indicated that activity, when present, was usually associated with arousal. Sensitivity to awakenings was higher (71-87%), though PPAs were lower (42 to 63%). For the indicator based on ribcage-abdominal phase, the number of periods of activity showed a significant relation to the number of arousals (r = 0.70, P < 0.001). It can be concluded that phase changes in chest/abdomen movement are a useful indicator of arousal associated with obstructive apnoea and related conditions. Limb activity has much lower sensitivity for transient arousal, but may be of value in indicating periods of wakefulness.

Adult↗

Automated recognition of EEG changes accompanying arousal in respiratory sleep disorders.

Daytime sleepiness and impaired cognitive function can be a consequence of recurrent transient arousal from sleep, associated with abrupt changes in the electroencephalogram (EEG). EEG is normally assessed by trained observers from paper records, but automation offers the advantages of speed and objectivity. We assessed 10 automated indices of EEG activity as potential indicators of arousal. Arousals from light, slow wave and rapid eye movement sleep were studied in 30 subjects. Segments of EEG recorded immediately before and after each arousal were analyzed by automated measurement of 10 EEG indices using a personal computer. We investigated the ability of each index to recognize arousal while rejecting change due to variability during sleep. Nine of the 10 indices showed significant changes with arousal (p < 0.001); the better indices were related to EEG frequency, and 3 were chosen for further study. In these indices, the mean changes with arousal were 3.8 Hz (ZeroCross), 1.7 Hz (Hjorth's Mobility) and 1.2 Hz (FrqMean, an index of central EEG frequency). With none of these three indices were significant differences in performance due to base sleep stage or subject group found. We conclude that detection of arousal is feasible using automated methods that measure simple indices related to the frequency of the EEG waveform.

Adult↗

Ocular alkali burn associated with automobile air-bag activation.

Alkali burns of the eye can result in permanent visual impairment and are therefore potentially devastating. Immedicate diagnosis and treatment are essential to a good prognosis. The authors report the case of a 52-year-old woman who suffered alkali keratitis as the result of the activation of an automobile air bag. This type of injury will be seen more frequently as more cars are equipped with air bags and should be suspected in drivers and passengers involved in accidents in which air bags have been activated.

Air Bags↗

Comparison of methods for assessing snoring.

Objective measurements of several sound level indices were made on 32 subjects referred because of snoring and who subsequently underwent uvulopalatopharyngoplasty (UPPP). The measurements were repeated approximately 6 months post-UPPP. The indices were compared with the subjective assessment of snoring by both the subject and his/her bed partner. Correlations between objective and subjective assessments were generally weak and were strongest when the supine posture only was considered. The index which correlated best with subjective assessment was the level which 1% of the sound level samples exceeded.

Abdomen↗

Objective measurement of the results of uvulopalatopharyngoplasty.

Thirty-two patients undergoing uvulopalatopharyngoplasty (UPPP) for snoring have been studied prospectively using objective measurement of snoring levels. A significant reduction was found, especially in the supine posture. The quantitative reduction was small and correlations between subjective and objective changes in snoring volume were weak.

Adult↗

Respiratory muscle activity during rapid eye movement (REM) sleep in patients with chronic obstructive pulmonary disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD) periods of hypopnoea occur during rapid eye movement (REM) sleep, but the mechanisms involved are not clear. METHODS: Ten patients with stable COPD were studied during nocturnal sleep. Detailed measurements were made of surface electromyographic (EMG) activity of several respiratory muscle groups and the accompanying chest wall motion using magnetometers. RESULTS: Hypopnoea occurred in association with eye movements during phasic rapid eye movement (pREM) sleep. During pREM sleep there were reductions in EMG activity of the intercostal, diaphragm, and upper airway muscles compared with non-REM sleep. Episodic hypopnoea due to partial upper airway occlusion ("obstructive" hypopnoea) was seen consistently in four subjects while the others showed the pattern of "central" hypopnoea accompanied by an overall reduction in inspiratory muscle activity. Although activity of the intercostal muscles was reduced relatively more than that of the diaphragm, lateral rib cage paradox (Hoover's sign) was less obvious during pREM-related hypopnoea than during wakefulness or non-REM sleep. CONCLUSIONS: Hypopnoea during REM sleep in patients with COPD is associated with reduced inspiratory muscle activity. The pattern of hypopnoea may be either "obstructive" or "central" and is generally consistent within an individual. Relatively unopposed action of the diaphragm on the rib cage during REM sleep is not accompanied by greater lateral inspiratory paradox.

Aged↗

Lung-specific direct in vivo gene transfer with recombinant plasmid DNA.

A number of gene delivery methods have been developed to facilitate gene transfer into mammalian somatic cells in vivo. In this study, we demonstrated that tracheal insufflation of two recombinant plasmids containing a bacterial gene, chloramphenicol acetyltransferase (CAT), driven by the cytomegalovirus (CMV) immediate early promoter/enhancer, either alone or complexed to cationic liposomes, resulted in efficient and selective transfection of the lungs in rats. When the simian virus 40 (SV40) promoter/enhancer was used, there was no detectable transfection. Insufflation of plasmid DNA was as efficient as plasmid-liposome complexes in transfecting the lungs. Expression of the CAT gene in the lungs was noted as early as 1 day after insufflation of plasmid DNA alone or plasmid-liposome complexes, and lasted for > 21 days. In contrast, intravenous injection of plasmid alone or plasmid-liposome complexes did not result in transfection of the lungs. Because of its simplicity, without the potential adverse effect of any gene delivery systems, intratracheal delivery of recombinant plasmid DNA may have potential implication for lung-specific gene therapy.

Animals↗