Biomedical subjects

A F Ofulue

Publications and source records attributed to A F Ofulue.

6 recordsLinked to original sources

PubMed1991

Morphometric and biochemical changes in lungs of growing rats treated with a calmodulin antagonist.

To determine the role of calmodulin in postnatal lung growth and development, 4-week-old rats were injected intraperitoneally on consecutive days with trifluoperazine (TFP), a potent and specific calmodulin antagonist, for a period fo 3 weeks and studied in comparison with normal controls and undernourished weight-matched animals. TFP treatment resulted in stunting of lung growth such that observed normal increments in morphometrically determined total number of alveoli and alveolar surface area and in biochemically determined DNA, elastin, and collagen contents of the lungs were diminished in comparison with age-matched normal controls. However, the TFP treatment also resulted in reduced daily food intake and body weight gain. In the TFP group, lung weight and lung volume were also reduced compared with the weight-matched control group. This resulted in reduced alveolar surface area, total number of alveoli, DNA, collagen, and elastin in the TFP group compared with values in the weight-matched controls. Thus the TFP-induced lung changes were not due to inanition and/or reduced somatic growth. The TFP treatment resulted in reduced activities of calmodulin and cyclic adenosine monophosphate (cAMP)-phosphodiesterase in the lungs of the animals, independent of their nutritional status. Based on these findings, we suggest that calmodulin may be an important regulatory component of postnatal lung growth and development.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1988

Experimental diabetes and the lung. I. Changes in growth, morphometry, and biochemistry.

Diabetes induced by streptozotocin at 3 wk of age in rats resulted in diminished somatic growth by 7 wk of age. Specific lung volume and weight (volume or weight per 100 gram body weight) were increased. The amount of lung DNA was decreased, and collagen and elastin were increased. The volume proportion of alveolar walls was increased at the expense of alveolar air. Air spaces were diminished in size, and alveoli increased in number. Total phospholipids and disaturated phosphatidylcholine (DSPC) were decreased, but they were normal relative to alveolar surface area. These changes reverted towards normal as a result of insulin treatment. Rats matched in weight (undernourished animals) for the diabetic animals showed relative preservation of lung weight, increased DNA, and reduced nonconnective tissue protein, RNA, collagen, and elastin. Air spaces were enlarged, alveolar surface area was decreased, and alveoli were decreased in number. Total phospholipids and DSPC were decreased, but normal when expressed per alveolar surface area. We conclude that diabetes and undernourishment have different effects on connective tissue synthesis in the lung that affect lung growth and structure, providing further evidence for the "fishnet" hypothesis of alveolar growth.

Animals↗

PubMed1988

Experimental diabetes and the lung. II. In vivo connective tissue metabolism.

In vivo lung connective tissue and DNA synthesis, following intraperitoneal injection of [14C]proline and [3H]thymidine, were studied in streptozotocin-induced diabetic rats fed ad libitum. Insulin-treated diabetic and normal rats similarly fed, and undernourished rats weight-matched to the untreated diabetics, served as comparison groups. The ratio of unbound [14C]hydroxyproline to total [14C]hydroxyproline in the lung was used to assess connective tissue degradation. Compared to the normal group, the untreated diabetic animals showed similar synthesis of collagen and elastin, reduced synthesis of total protein and DNA, and decreased degradation of connective tissue. When compared with the normal group, the undernourished animals showed diminished synthesis of total protein, collagen, elastin, and DNA, and increased degradation of connective tissue. In comparison to the undernourished group, the untreated diabetic animals indicated increased synthesis of collagen and elastin, and diminished degradation of connective tissue; total protein and DNA syntheses were similar. The insulin-treated diabetic animals showed increased collagen and DNA synthesis. We conclude that experimental diabetes has a profound effect on lung connective tissue metabolism, supporting previous observations of connective tissue abnormalities and morphometric changes. The increase in lung collagen and elastin in diabetes is in part due to reduced breakdown of the connective tissue proteins.

Animals↗

PubMed1987

Does the PI polymorphism alone control alpha-1-antitrypsin expression?

Whether genetic factors other than the protease-inhibitor (PI) polymorphism itself contribute to variation in alpha-1-antitrypsin is of both theoretical and practical interest. We have measured the quantity of alpha-1-antitrypsin (by an immunoturbidometric assay) and its activity (by assaying elastase inhibitory capacity [EIC]) in 583 individuals from 114 twin kinships who were also typed for PI by isoelectric focusing. Models of variation were fitted directly to the raw observations by a maximum-likelihood method. Specification of phenotypic means led to highly significant improvements in fit over models including only individual environment variance and additive genetic variance. The 29 phenotype means could also be described as the appropriate additive combinations of the 12 allelic effects. Only small improvements in fit could then be obtained by addition of polygenic components of variance. We conclude that nearly all genetic variation in alpha-1-antitrypsin quantity and activity can be explained by detectable variation at the PI locus and that this variance is largely additive. Bivariate analysis of alpha-1-antitrypsin and EIC revealed marginal evidence for differences in specific activities of molecules coded by different PI alleles. The correlation between environmental deviations for the two measures was only .63, which may reflect, in part, the rather low reliability of the assays and account for the modest heritabilities (less than .5) of the two measures. An intriguing finding was the presence of significant differences in E1 variance for different PI types, suggesting that different phenotypes have differing capacities to react to environmental challenges.

Adolescent↗

PubMedDate not supplied

Lung growth in rats subsequent to administration of intraperitoneal elastase during the first 4 weeks of life.

Male rats received intraperitoneal injections of porcine pancreatic elastase twice weekly during the first 4 weeks of life. Saline-injected male rats served as controls. After a 4-week recovery period, the rats were sacrificed, and the excised lungs were studied using saline- and air-filled volume-pressure curves, morphology, and biochemistry. Both air- and saline-filled volume-pressure curves showed loss of elastic recoil in the elastase-treated animals. In elastase-treated animals the mean linear intercept was increased, the numbers of alveoli per unit area, per unit volume, and per lung decreased, and alveolar surface area decreased. These animals also showed a disproportionate increase of alveolar duct air at the expense of the proportion of alveolar air. Morphometric differences between the elastase-treated animals and the controls were somewhat smaller in this experiment than in a previous one in which the animals were sacrificed immediately after 4 weeks of intraperitoneal elastase. We attribute this difference to alveolar multiplication between 4 and 8 weeks of age. However, evidence is presented that these alveoli were abnormal. Loss of recoil properties was more evident after the 4-week recovery period than at the termination of elastase administration, suggesting that the newly formed alveoli were functionally abnormal. Collagen content was increased in the elastase group, but elastin was significantly decreased. This may be a good elastase model for assessing the hypothesis that lungs minimally damaged in infancy may have an increased susceptibility to environmental damage in later life.

Animals↗

PubMedDate not supplied

Changes of growth hormone, somatomedin C, and bombesin following pneumonectomy.

Left pneumonectomy (PX) was performed on 14-day-old pregnant rats. Serum growth hormone (GH), lung somatomedin-C-like immunoreactivity (SmC), and lung bombesin-like immunoreactivity (BLI), using optimized radioimmunoassays and lung protein concentration (P), were measured 3 h, and 1, 2, 3, 5, and 7 days following pneumonectomy. These levels were compared to two groups of similar animals: sham operated animals and animals not subjected to surgery. Serum GH, lung SmC, and BLI levels were similar in the last two groups of animals, suggesting that surgery had no effect on GH, SmC, and BLI levels. These two control groups were combined and compared to the post-pneumonectomy animals. The post-pneumonectomy animals had significantly higher levels of serum GH at postoperative day 3 and significantly higher levels of SmC at days 2 and 5 without any significant difference in total BLI level and body weight. These results suggest that, first, GH and SmC may play a part in post-pneumonectomy compensatory lung growth and these two may also be interrelated in this response and, second, BLI material(s) perhaps do not play a role in post-pneumonectomy lung growth.

Animals↗