Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As more women with cystic fibrosis (CF) live to childbearing age, more become pregnant and deliver healthy infants. A 1980 review shows 129 pregnancies in 100 CF women. 80% were full term. The perinatal mortality rate was 8.5% (almost all deaths were premature infants). 18% of the mothers dies within 2 years of delivery, but none died during pregnancy. This mortality rate matched the expected rate for nonpregnant CF women at the same age. If CF women are in sound health and want to have children, physicians should encourage them to do so. Despite rumors to the contrary and theoretical problems with dehydrated cervical mucus, women with mild CF have little difficulty conceiving. Overall contraception issues are the same for both CF women and non-CF women. A few differences do exist, however. CF women should prevent unwanted pregnancy because an abortion poses special risks for them and the child adds more demands on a woman who often needs hospital care. Unpredictable absorption in the intestines makes oral contraceptives unreliable for CF women. A CF woman must consider timing, family support, and genetics of the father when planning a pregnancy. Pregnancy may not affect lung function greatly because lung volume in CF women depends on the condition of the airways rather than the size of the thoracic cage. In pregnant women with severe CF, minute ventilation cannot rise enough so hypercapnia occurs, and blood volume and cardiac output may increase 50% in the 3rd trimester. All these changes could trigger cor pulmonale in these women. Pregnancy is contraindicated for CF women with raised PaCO2, and SaO2 of 90%, and cor pulmonale. Physicians should manage pregnant CF women the same as they would other women, but increase emphasis on controlling pulmonary infection and adequate nutrition. They should also avoid teratogenic drugs and drugs with no proven record.
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PMID:Cystic fibrosis and pregnancy. 159 39

Bedside measurement of respiratory frequency is commonly performed in a cursory manner and judged to be of little clinical importance. However, in a recent study of patients being weaned from mechanical ventilation, we found that tachypnea was quite accurate in predicting an unsuccessful weaning outcome. The present study was undertaken to examine the relationship between nonobtrusive measurements of respiratory frequency, using a calibrated inductive plethysmograph, and detailed measurements of pulmonary function in 11 adult patients with cystic fibrosis of varying severity. Respiratory frequency was increased in the patients with cystic fibrosis compared with a group of healthy control subjects, as was minute ventilation and mean inspiratory flow. Respiratory frequency was a sensitive predictor of respiratory dysfunction, being significantly (p less than 0.05) correlated with airway obstruction (r = 0.76), hyperinflation (r = 0.52), arterial oxygenation (r = -0.59), rib cage-abdominal discoordination (r = 0.54), and maximum ventilation during exercise (r = 0.66). Despite the presence of tachypnea, the patients did not display shallow breathing; indeed, tidal volume was not correlated with any of the above abnormalities. In conclusion, respiratory rate was a useful indicator of respiratory dysfunction in this group of patients with cystic fibrosis.
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PMID:Importance of respiratory rate as an indicator of respiratory dysfunction in patients with cystic fibrosis. 234 15

The main cause of secondary pulmonary hypertension in the view of a pulmonologist is alveolar hypoventilation - eventually potentiated by acidosis and hypercapnia - which leads to reflectory hypoxemic vasoconstriction of the small pulmonary arteries. Anatomic changes in the pulmonary vessels may be absent or may be limited to medial hypertrophy of the arterioles. If the underlying cause of the hypoxia can be corrected, this reflectory pulmonary hypertension is reversible. In diffuse progressive lung disease, interstitial fibrosis with destruction of the alveolar wall and capillaries may occur, leading to restriction of the pulmonary vascular bed. In such cases pulmonary hypertension may not be completely reversible. The most frequent causes of pulmonary hypertension in childhood are obstructive (e.g. Cystic Fibrosis) or restrictive lung diseases (e.g. interstitial fibrosis). Rare but important in the differential diagnosis are upper airway obstruction, thoracic cage deformity, neuromuscular disorders, high altitude and respiratory center dysfunction. The therapy is elimination of the underlying disease or optimal treatment. In addition prophylactic or therapeutic longterm application of oxygen is more efficient than treatment with pulmonary vasodilators or modern substances like Almitrine. Right heart decompensation should be treated by diuretics. The longterm prognosis is dependent of the underlying disease and is poor in a chronic progressive lung disease like cystic fibrosis and certain types of lung fibrosis.
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PMID:[Pulmonary hypertension from the viewpoint of the pediatric pulmonologist]. 310 Dec 91

Chronic pulmonary infections with Pseudomonas aeruginosa remain a serious problem in patients with cystic fibrosis. Structurally altered lung mucosa and local inflammation may impair bacterial clearance from the airways. This hypothesis was investigated in (1) the reserpinized rat, (2) proteinase-pretreated rat lungs, and (3) Type III hypersensitivity rat lung models. Reserpine treatment led to surface alterations of Type I epithelial lung cells and diminished food uptake. Significantly enhanced P. aeruginosa colony-forming units (CFU) were found in all (12 of 12) rat lungs 48 h after challenge compared to partially starved rats (p less than 0.025) or untreated rats (p less than 10(-6)). Pretreatment of normal rat lungs with elastase from polymorphonuclear leukocytes (PMN-elastase) resulted in extensive tissue damage, and 48 h after bacterial challenge the mean P. aeruginosa CFU of 12 animals was significantly higher 1.1 X 10(4) +/- 1.0 X 10(4) CFU; p less than 0.01) than in the reserpinized rat lungs. P. aeruginosa organisms were also found in PMN-elastase-treated rat lungs not challenged with bacteria (five of 12 animals), suggesting cross infection from infected animals in the same cage. In immunized rats that were challenged with aerosolized antigen (bovine serum albumin) and P. aeruginosa, bacterial CFU after 10 h were significantly higher than in nonimmune animals (p less than 0.005), and highest after 48 h when P. aeruginosa alkaline proteinase was used as the antigen (1.2 X 10(5) +/- 1.4 X 10(5) CFU). These data provide new evidence that clearance of P. aeruginosa from lung tissue is impaired after malnutrition, epithelial cell alteration, or epithelial cell damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clearance of Pseudomonas aeruginosa in different rat lung models. 314 14

Although there has been extensive research into the control of breathing in adults with chronic obstructive lung diseases, there is little information in this area in children with cystic fibrosis (CF). The purpose of this study was to investigate the respiratory response of children with CF to CO2 under hyperoxic conditions. Using a standard CO2 rebreathing technique, we studied 14 children with CF. We evaluated their response to CO2 in terms of ventilation (VE), mean inspiratory flow rate (VT/TI), and the pressure generated at the mouth after 0.1 s of an inspiratory effort against an occlusion (P0.1). In order to understand the contributions of the rib cage and abdominal components to ventilation, we assessed the volume change in each compartment by attaching magnetometers to the chest and abdomen. Overall changes in lung volume were assessed in a volume displacement plethysmograph. We found that, when corrected for the height of the child, the slope of VE versus end tidal CO2 (PETCO2), as well as the slope of VT/TI versus PETCO2 correlated significantly with the degree of airway obstruction as expressed by the forced expiratory flow between 25 and 75% of vital capacity. The values for P0.1 were all within the normal range and showed no correlation with the degree of airway obstruction. The contribution of the rib cage and abdomen to ventilation during rebreathing was similar to that previously reported for adults. No changes were observed in functional residual capacity during rebreathing. We showed that tests involving a mechanical response to CO2 correlated with the degree of airway obstruction, but there was no evidence that the neuromuscular drive was abnormal.
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PMID:Ventilation, respiratory center output, and contribution of the rib cage and abdominal components to ventilation during CO2 rebreathing in children with cystic fibrosis. 679 78

To assess the mechanism of the decrease in hemoglobin O2 saturation during rapid-eye-movement sleep, we studied 5 normal subjects 22 to 30 yr of age and 20 patients with cystic fibrosis 9 to 29 yr of age. The largest decrease in arterial O2 saturation, as monitored with an ear oximeter during sleep, occurred during rapid-eye-movement sleep, with a mean +/- SEM decrease of 2 +/- 0.31% in the normal subjects and 7.4 +/- 1.3% in the patients in both groups. Rapid-eye-movement sleep was associated with a significant loss of intercostal and diaphragmatic tonic muscle activity (p < 0.01), as monitored with surface electrodes, and a decrease in the baseline position of the rib cage and abdomen, as recorded by magnetometers (p < 0.01). This suggests a decrease in functional residual capacity, which was accompanied by a consistently lower arterial O2 saturation during rapid-eye-movement sleep. Short periods (< 20 s) of inhibition of phasic respiratory muscle activity during rapid-eye-movement sleep were followed by further decreases in arterial O2 saturation. We conclude that the desaturation during rapid-eye-movement sleep in all subjects was mainly due to a decrease in functional residual capacity, leading to airway closure in the dependent lung regions. The hemoglobin desaturation was further aggravated by transient periods of hypoventilation.
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PMID:Mechanism of hemoglobin desaturation during rapid-eye-movement sleep in normal subjects and in patients with cystic fibrosis. 741 80

We have measured static lung volumes after heart-lung transplantation (HLT) in seven patients with cystic fibrosis (CF) (Group 1), three patients with chronic hyperinflation due to diseases other than CF (Group 2), and six patients with primary pulmonary hypertension (PPH) (Group 3). Total lung capacity was within normal limits at 1 yr after surgery in all patients. Similarly, FRC was within the normal range in Groups 2 and 3. On the other hand, patients with CF showed a persistent increase in FRC; at 1 yr after HLT, FRC averaged 4.13 +/- 0.52 L compared with a predicted value of 3.20 +/- 0.23 L (p < 0.01). The postoperative static pressure-volume curve of the lung in the patients with CF was superimposed on the predicted one, suggesting that the increased FRC originated in the chest wall. Additional studies with computerized tomographic scans demonstrated that the rib cage anteroposterior diameter at FRC averaged 12.1 +/- 1.6 cm in patients with CF, 9.5 +/- 1.2 cm in patients with PPH, and 9.4 +/- 0.7 cm in a group of healthy subjects matched with the patients with CF (p < 0.01). We conclude that after HLT, patients with CF show persistent hyperinflation due to rib cage expansion along the anteroposterior dimension. This shape change may represent a structural adaptation that occurs in response to chronic pulmonary hyperinflation acquired during rib cage growth.
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PMID:Persistent hyperinflation after heart-lung transplantation for cystic fibrosis. 784 17

Patients with cystic fibrosis (CF) often hypoventilate during sleep with marked falls in oxygen saturation (SaO2%). This occurs most commonly during REM sleep, when there is a reduction in rib cage excursion and a fall in end-expiratory lung volume (EELV). The aim of this study was to examine the effect of nocturnal nasal continuous positive airway pressure (nCPAP) on SaO2 and the respiratory disturbance index (RDI) during sleep in patients with CF and severe lung disease. Seven patients (FEV1% pred, 23 +/- 5; range, 14 to 28%) were evaluated during sleep on two nights, control and nCPAP (11 +/- 2 cm H2O; range, 8 to 16 cm H2O), with four patients breathing room air and three patients breathing supplemental oxygen on both nights. Mean awake SaO2 was 91 +/- 1% (range, 89 to 93%). All patients showed significant oxyhemoglobin desaturation and respiratory disturbance in the control study. The maximal falls in SaO2 (15 +/- 10%) were most often associated with phasic eye movements, and a decline in rib cage excursion and the sum signal (Respitrace) during REM sleep. Nasal CPAP resulted in a significant improvement in the mean minimum oxygen saturation (MMOS) during both NREM (nCPAP 91 +/- 3% vs control 88 +/- 2%, p < 0.05) and REM sleep (nCPAP 89 +/- 6% vs control 83 +/- 6%, p < 0.05). Transcutaneous CO2 measurements were not significantly different between the control and the nCPAP studies. The RDI was also significantly reduced with nCPAP especially during REM sleep (9 +/- 7 events per hour vs control 25 +/- 11 events per hour, p < 0.05). Nasal CPAP caused no change in total sleep time or sleep efficiency yet significantly reduced the RDI and improved baseline SaO2 during both NREM and REM sleep.
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PMID:Benefits of nocturnal nasal CPAP in patients with cystic fibrosis. 798 90

Breast cancer antigens RAK-p120, -p42, -p25 were detected in 100% of breast cancer cases tested (71 cases). Only 10% of adjacent tissue cases tested positive for all three cancer antigens, and 17.5% of the cases tested positive for two antigens only. Eighty-five percent of histologically normal breast tissue samples, isolated either from breast cancer patients or patients with advanced fibrocystic disease, tested RAK-negative, with the exception of low expression of p25, observed in some patients. Polymerase chain reaction (PCR) with HIV-1 gp 41-derived primers revealed cancer-associated DNA fragments of similar size (140 bp) as in HIV-1 genome. Fifty-four percent of cancer adjacent tissues, and 50% of malignancy-free breast tissue samples, tested PCR-negative. It is suggested that genetic predisposition to cancer may be associated with the presence of RAK genes, while expression of RAK antigens marks an already ongoing process of malignant changes.
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PMID:New protein and PCR markers RAK for diagnosis, prognosis and surgery guidance for breast cancer. 902 74

No transgenic cystic fibrosis (CF) mouse model developed to date mimics the major clinical phenotype found in humans with CF, chronic Pseudomonas aeruginosa lung infection. In a transgenic CF transmembrane conductance regulator (cftr) mouse colony, we found WT, heterozygous, and homozygous CF mice housed in the same cage became chronically colonized in the oropharynx with environmental P. aeruginosa when the bacterium was present in drinking water. Elimination of P. aeruginosa from drinking water resulted in clearance in most WT and CF heterozygous, but not homozygous mice. For experimental evaluation, a combination of specific animal husbandry techniques and an oral infection route showed cftr(-/-) mice but not WT mice can be chronically colonized by P. aeruginosa with subsequent lung translocation, yielding a pathologic picture indicative of chronic lung infection. In some instances, mucoid isolates of P. aeruginosa were recovered from lungs, indicating conditions were present for conversion to mucoidy. Overexpression of human CFTR in the lungs of WT mice markedly accelerated the clearance rate of P. aeruginosa, demonstrating that lung levels of CFTR play an important role in defense against infection. P. aeruginosa mutants unable to express the surface polysaccharide alginate or the global regulator GacA were deficient in their ability to colonize the mice. CF mice made potent immune responses to P. aeruginosa outer membrane antigens. Overall, we found that under the proper conditions, transgenic CF mice are hypersusceptible to P. aeruginosa colonization and infection and can be used for evaluations of lung pathophysiology, bacterial virulence, and development of therapies aimed at treating CF lung disease.
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PMID:Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. 1257 88


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