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Biomedical subjects

P M Farrell

Publications and source records attributed to P M Farrell.

At least 145 records · Page 8Linked to original sources
PubMed1976

Isolation of cells that retain differentiated functions in vitro: properties of clonally isolated type II alveolar pneymonocytes.

We have isolated byclonal culture techniques a diploid cell strain (L-2) from adult rat lung. These cells appear to retain differentiated functions that are present in type II alveolar epithelial cells of intact lung. The L-2 cells are diploid, epithelial cells, they contain osmiophilic lamellar bodies in their cytoplasm and they synthesize lecithin by the same de novo pathways as whole lung.

Animals↗
PubMed1976

Fluctuations of unbound whole blood polyamine levels during the menstrual cycle.

Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.

Adult↗
PubMed1976

Fetal lung lecithin metabolism in the glucose-intolerant Rhesus monkey pregnancy.

Fetal lung lecithin metabolism was examined in rhesus monkey gestations complicated by glucose intolerance secondary to maternal streptozotocin (STZ) administration. Fetuses of STZ-treated mothers were delivered at 85% to 89% of term and were compared to two control groups of fetuses from normal pregnancies--one group age-matched to the STZ pregnancies, and the other composed of fetuses delivered in the final 10% of gestation. In the glucose-intolerant pregnancies, two measures of fetal lung lecithin biosynthesis--the amniotic fluid lecithin-to-sphingomyelin (L/S) ratio and the rate of 14C-choline incorporation into lecithin in fetal lung slices--were significantly greater than in age-matched normal gestations and were similar to results in late-gestation controls. However, lung lecithin concentrations in the glucose-intolerant group were comparable to the age-matched controls, and both were significantly less than in the late-gestation controls. Since the gestational age, mode of delivery, and fetal acid-base status were the same in the age-matched groups, we conclude that these changes in fetal lung lecithin metabolism are due to the effects of maternal glucose intolerance.

Amniotic Fluid↗
PubMed1976

Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome.

Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis.

Acidosis↗
PubMed1976

The prevention of hyaline membrane disease: new concepts and approaches to therapy.

New approaches to hyaline membrane disease have emerged in recent years. These developments are principally attributable to advances in our understanding of the following: (1) the pathophysiology and pathogenesis of HMD in relationship to pulmonary surfactant, (2) fundamental aspects of fetal lung development, including the movement of surfactant phospholipids from fetal pulmonary fluid to the amniotic space, (3) mechanisms for accelerating lung maturation, particularly with maternally administered prenatal glucocorticoids, and (4) ventilatory techniques effective in protecting and conserving alveolar surfactant by the continuous application of end expiratory pressure. Prenatal assessment of the risk for developing hyaline membrane disease is now routinely possible by amniocentesis and analysis of the ratio of lecithin to sphingomyelin in amniotic fluid. Such predictability, coupled with the ability to postpone delviery, allows the perinatologist in some instances to provide the fetus with ample opportunity for lung development in utero. Recent clinical trials around the world with pregnant women in premature labor document a significantly lower incidence of hyaline membrane disease after antenatal glucocorticoid treatment. In neonates with the disease weighing more than 1500 gm, it is now established that reduced mortality rates accrue from the use of end expiratory positive pressure. These clinical advances offer great promise in changing the nature of HMD management from procedures that are largely supportive to approaches that are truly preventative.

Amniotic Fluid↗
PubMed1976

Epidemiology of hyaline membrane disease in the United States: analysis of national mortality statistics.

National mortality statistics for hyaline membrane disease (HMD) and respiratory distress syndrome (RDS) were examined in this study for the years 1968 to 1973. Detailed data were obtained by computer analysis of magnetic tapes from the National Center for Health Statistics. During the six-year interval, HMD/RDS was determined to be the underlying cause of death in 54,064 infants or 9,010 +/- 560 (mean +/- SD) infants per year. Analysis of individual death certificates for 1968 revealed the disease to a major contributing factor in another 24%. Thus, it may be estimated that HMD was involved in the demise of nearly 12,000 neonates per year over this period. This amounts to approximately 20% of all neonatal deaths. On the basis of mortality rates, a trend toward an increased incidence of fatal HMD/RDS was established from 1968 to 1973. Deaths tend to cluster in the summer months and January-February represent the lowest months of recorded fatalities. Analysis of the age at death, reflecting time course of the disease, revealed idential patterns for 1968 to 1970. The number of deaths was found to decline exponentially between the first and fourth 24-hour periods so that 92% of all deaths occurred by 4 days of age. Boys contributed more prominently to the death totals than girls with ratios from 1.62 to 1.76. Examination of mortality rates by race suggested that black permatures have a lower incidence of fatal HMD/RDS. In addition to nationwide figures, those of individual states were compared for three years. Generally, HMD/RDS mortality rates correlated with overall neonatal mortality statistics. Exceptions were observed, however, such as Illinois where low rates for the former coexist with relatively high neonatal death rates. These data respresent the first national mortality statistics for HMD and may prove useful in planning and providing intensive neonatal care.

Black People↗
PubMed1976

Distribution of spermidine and spermine in blood from cystic fibrosis patients and control subjects.

Previous studies have shown an abnormality of the spermidine-to-spermine (Spd/Spm) ratio in whole blood of cystic fibrosis homo-and heterozygotes. To investigate Spd and Spm distribution amoung blood components as a possible cause of the abnormality, blood was fractionated using Rabinowitz's glass bead technique and Boyum's Ficoll-Hypaque method. Free (unconjugated) polyamines were extracted with perchloric acid and quantitated on an amino acid analyzer. In controls, mean +/- SEM concentrations in nmoles/10(9) cells of Spd and Spm, respectively, were 1.02 +/- 0.08 and 0.894 +/- 0.28 for erythrocytes; 126 +/- 31 and 357 +/- 105 for lymphocytes; 36 +/- 16 and 240 +/- 33 for granulocytes; and less than 0.5 and less than 0.5 nmoles/ml for plasma. When converted to the concentration in whole blood, it was found that greater than 90% of Spd and over 70% of Spm was associated with erythrocytes. While the higher cellular concentration in leukocytes was not unexpected, the fact that Spd and Spm in whole blood were primarily associated with erythrocytes was a new finding. Comparison with controls revealed that the Spd/Spm ratio in both whole blood and erythrocytes was significantly higher in the group of cystic fibrosis patients.

Cell Fractionation↗
PubMed1975

Polyamine alterations in blood of male homozygotes and heterozygotes for cystic fibrosis.

The polyamines, spermidine and spermine, have been measured in whole blood extracts from control volunteers, patients with cystic fibrosis, and obligate cystic fibrosis heterozygotes. Male homo- and heterozygotes for cystic fibrosis exhibit a consistent and significant decrease in blood spermine resulting in an elevated spermidine/spermine ratio when compared to control males. In contrast, control females exhibited reduced spermidine and spermine levels as compared to control males. Blood from female cystic fibrosis homo- and heterozygotes showed similar results. The sex difference is probably due to fluctiations of blood polyamines during the menstrual cycle. Abnormal polyamine levels are the first observation of an alteration of a low molecular weight metabolite characteristic of both male homo- and heterozygotes for cystic fibrosis.

Cystic Fibrosis↗
PubMed1975

Megavitamin E supplementation in man.

To assess possible toxic and/or beneficial effects of vitamin E supplementation, a group of 28 adults voluntarily ingesting 100 to 800 IU/day of tocopherol for an average of 3 years were evaluated in this study. Half of the subjects claimed a feeling of improved health or well being, but no specific beneficial effects were noted consistently; the other half indicated no change in health status after beginning vitamin E supplements. No gross evidence of toxicity was apparent on reviewing past medical histories with the subjects. Plasma alpha-tocopherol was found to be elevated significantly in the group from 650 micrograms/100 ml (control mean) to 1,340 micrograms/100 ml; however, 25% of the values were within 2 SD of the control mean. Plasma alpha-tocopherol levels did not correlate with total daily dose but did relate to plasma triglyceride and cholesterol concentrations. Total plasma carotenoids were also significantly increased along with vitamin A levels; the former did not correlate with plasma vitamin E, whereas the latter showed a significant correlation. Laboratory screening for toxic side effects of vitamin E supplementation by performance of 20 standard clinical blood tests failed to reveal any disturbance in liver, kidney, muscle, thyroid gland, erythrocytes, leukocytes, coagulation parameters, or blood glucose. It is concluded that megavitamin E supplements in this group produced no apparent toxic side effects and that subjective claims for beneficial effects were highly variable.

Adult↗
PubMed1975

Hyaline membrane disease.

In addition to confirmation of earlier epidemiologic observations, major advances have occurred in the past few years with respect to the diagnosis and treatment of hyaline membrane disease. Prenatal assessment of the risk for developing the disorder is now routinely possible by amniocentesis and analysis of the ratio of lecithin to sphingomyelin in amniotic fluid, or by surfactant titer ("shake test"). Such predictability and numerous other lines of evidence provide strong support for the hypothesis that hyaline membrane disease fundamentally reflects a deficiency of pulmonary surfactant. In accordance with the apparent primacy of surfactant deficiency, recent improvements in management are directed toward either increasing lung volume at end expiration by application of continuous distending airway pressure, or accelerating fetal lung maturation, with respect to the synthesis and secretion of surfactant, by prenatal administration of glucocorticoids.

Amniocentesis↗
PubMed1975

Tracheal mucociliary transport in patients with cystic fibrosis and its stimulation by terbutaline.

Tracheal mucous velocity was measured by observing the motion of teflon discs across the tracheal mucosa through a fiberoptic bronchoscope. The average rate of movement in 14 adult patients with cystic fibrosis was 2.6 mm per min plus or minus 3.3 SD, compared with 20.1 mm per min plus or minus 6.3 in 20 normal subjects of the same age (P less than 0.001). This failure of mucociliary transport may play a role in the pathogenesis of the pulmonary disease in cystic fibrosis. Administration of a beta-adrenergic agent, terbutaline, increased the average mucous velocity in the patients with cystic fibrosis (to 5.5 mm per min plus or minus 3.6 SD, P less than 0.001) but not in control subjects. This observation has potential therapeutic significance.

Adolescent↗
PubMed1975

The choline incorporation pathway: primary mechanism for de novo lecithin synthesis in fetal primate lung.

The two pathways of de novo lecithin synthesis, choline incorporation (I) and phosphatidylethanolamine methylation (II), were examined in lung slices from rhesus monkey fetuses throughout the last half of gestation. Incorporation rates of pathway-specific radioactive precursors were used as a measure of lecithin production. At all stages of development studied, pathway I incorporated 10-50 times more precursor ([14C]choline) into lecithin than did pathway II ([14C]methionine or [14C]ethanolamine). In addition, although methylation activity did not change significantly during gestation, choline incorporation showed three distinct phases: (1) a stable, relatively low rate in early gestation, (2) an abrupt, twofold increase at approximately 90 percent of term, and (3) a return to lower activity levels in late gestation. This correlates with reports that lung lecithin concentration in fetal primates increases significantly in the last 10 percent of gestation. The lecithin to spingomyelin (L/S) ratios measured in amniotic fluid samples obtained at abdominal delivery were compared with pathway activities in lung slices from the same fetuses. Significant correlation was found between the amniotic fluid L/S ratio and pathway I activity (r = 0.77, P less than 0.001); in contrast, pathway II activity showed no relationship to the amniotic fluid L/S ratio. Thus, the L/S ratio appears to be a reflection of lung lecithin synthesis through the choline pathway. The conclusion that the choline pathway is the primary route of de novo lecithin synthesis in the nonhuman fetal primate lung is supported by three lines of evidence, (1) the predominance of choline incorporation into lecithin, (2) the late gestational rise in conversion of choline to lecithin, and (3) the correlation between pathway I activity and both lung lecithin concentration and amniotic fluid L/S ratio.

Adenosine Triphosphate↗
PubMed1975

Growth characteristics and protein content of tissue-cultured fibroblasts from cystic fibrosis patients.

Proliferation rates and cellular protein content have been measured in cultured fibroblasts derived from the skin of normal volunteers and cystic fibrosis patients. Three methods of measuring growth indicated that under our conditions, CF fibroblasts divide normally with a mean doubling time of 29 hr. During the logarithmic growth phase, however, lower cell protein/DNA ratios were observed consistently in CF cultures. This difference was not present in contact-inhibited, confluent fibroblasts. The finding of an apparent reduction in protein synthesis during rapid division, coupled with an observation by others that CF fibroblasts fail to normally induce collagen formation, suggests the possibility of a disturbance in the biochemical regulation of protein synthesis.

Biopsy↗
PubMed1973

Induction of choline phosphotransferase and lecithin synthesis in the fetal lung by corticosteroids.

Rabbit fetuses 23 to 24 days of gestation were injected with either 9-fluoroprednisolone acetate or saline. Three days later the lungs of steroid-treated animals showed a significant increase in lecithin concentration and cholinephosphotransferase activity. In addition, lung slices from these animals incorporated more [(14)C]choline into lecithin. The rise in enzyme activity and [(14)C]choline incorporation was blocked by prior treatment of fetuses with cycloheximide but not by treatment with actinomycin D. It is proposed that the corticosteroids induce de novo synthesis of the lung enzyme, which in turn leads to increased synthesis of lecithin through the choline incorporation pathway. Furthermore, it appears that the site of regulation involves translation of messenger RNA.

Animals↗