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Biomedical subjects

A D Stiles

Publications and source records attributed to A D Stiles.

51 records · Page 3Linked to original sources
PubMed1989

Production and action of insulin-like growth factor I/somatomedin C in primary cultures of fetal lung fibroblasts.

Production of insulin-like growth factor I/somatomedin C (IGF-I) by 19-day-gestation fetal rat lung fibroblasts was studied, and a paracrine (local production and action) mitogenic activity of this growth factor was explored. Specific IGF-I mRNAs were demonstrated in these cells, consistent with production of IGF-I. Using an IGF-I monoclonal antibody, IGF-I-like material was isolated from fetal lung fibroblast conditioned medium (FCM) and separated by molecular weight. Several molecular weight species were identified, including an 8,000 to 10,000 molecular weight species, a weight similar to purified IGF-I. IGF-I binding proteins elaborated by these cells were also demonstrated. The possibility of a paracrine mitogenic activity of the fetal lung fibroblast-produced IGF-I in cultures was suggested by demonstrating a reduction in DNA synthesis in cultures incubated with either the IGF-I monoclonal antibody or an IGF-I receptor antibody. These findings indicate that 19-day-gestation fetal rat lung fibroblasts produce IGF-I that acts in a paracrine fashion and suggest that this growth factor is biologically active during fetal lung development.

Animals↗
PubMed1987

Characterization of proteoglycans synthesized by fetal rat lung type II pneumonocytes in vitro and the effects of cortisol.

The synthesis of proteoglycans by primary cultures of 19-day gestation fetal rat lung Type II pneumonocytes was studied. The cells were grown in the presence of [3H]-glucosamine and/or [35S]-Na2SO4 and the radioactive label incorporated into proteoglycans was analyzed. Proteoglycans of high molecular weight (approximately 200 Kd) were isolated by gel permeation chromatography and contained both [3H] and [35S]. The glycosaminoglycan composition of the proteoglycans was determined by electrophoresis and autoradiography. The medium contained 65-80% of the labeled proteoglycans and was enriched for hyaluronate, with lesser amounts of the sulfated glycosaminoglycans (dermatan sulfate greater than heparan sulfate greater than chondroitin sulfate). The cell layers retained 20-35% of the labeled proteoglycans and was enriched for heparan sulfate, with lesser amounts of chondroitan sulfate greater than dermatan sulfate greater than hyaluronate. The synthesis of proteoglycans was time-dependent and was stimulated by increasing concentrations of fetal bovine serum. Cortisol inhibited proteoglycan synthesis, apparently by decreasing the availability of proteoglycan core-protein.

Animals↗
PubMed1986

Reciprocal autocrine and paracrine regulation of growth of mesenchymal and alveolar epithelial cells from fetal lung.

The regulation of DNA synthesis in 19 day rat fetal lung epithelial (alveolar type II) and mesenchymal (fibroblast) cells by protein growth factors has been studied. In each case a single growth factor is capable of stimulating 3H-thymidine incorporation into DNA: platelet-derived growth factor in the case of the alveolar type II cell and epidermal growth factor in the case of the fetal lung fibroblast. We hypothesize that these results indicate that the type II cell endogenously produces progression activities (i.e., epidermal growth factor-like and somatomedin-like activity) while the fibroblast produces competence (i.e., platelet-derived growth factor-like) and progression (i.e., somatomedin-like activity). The latter is in keeping with previous observations with skin fibroblasts. To test the above hypothesis, the effect of fetal lung fibroblast-derived conditioned media upon the growth of fetal alveolar type II cells has been determined. The results indicate that, indeed, such media contain competence activity for this cell type. The mitogenic activity was further characterized as heat-sensitive, trypsin-sensitive, and has an apparent molecular weight of 30,000 Daltons. It is not synthesized by 19 day fetal liver, kidney or skin fibroblasts and its synthesis is higher in lung fibroblasts isolated from 19 day fetuses as compared to those isolated on day 16 or day 22.

Animals↗
PubMed1985

Relation of kidney tissue somatomedin-C/insulin-like growth factor I to postnephrectomy renal growth in the rat.

In kidney tissue extracts, we observed elevated somatomedin-C (SmC) tissue concentrations in the kidney remaining after nephrectomy compared to those in the kidney removed at surgery or kidneys from sham-operated animals. In hypophysectomized animals, we observed a response of the same magnitude, but from significantly lowered basal SmC concentrations. In neither case did nephrectomy affect SmC levels in serum or other tissues studied (liver and lung). The increased tissue levels of SmC in the regenerating kidney, with a return to baseline levels within 30 days, along with the absence of elevated serum levels suggest a local role for this mitogen in organ growth.

Animals↗
PubMed1984

Tissue concentrations of somatomedin C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action.

We have validated a method for extracting and measuring the tissue content of somatomedin C (Sm-C)/insulin-like growth factor I (IGF-I), a growth-hormone-dependent, growth-promoting peptide. The Sm-C content of tissue extracts was strongly growth-hormone dependent because most of the tissues studied from hypophysectomized rats contained significantly less Sm-C than normal tissues. The intraperitoneal administration of ovine growth hormone (oGH) to hypophysectomized rats caused tissue extractable Sm-C to increase in kidney, liver, lung, heart, and testes. Tissue Sm-C responses to oGH were maximal after 12 hr, 6 hr before the maximal increment in serum. In liver and lung, the tissue Sm-C response to various doses of oGH fit linear regression models, and the doses of oGH needed to increase the Sm-C are in the range of those required to increase protein synthesis. Although these results do not exclude the possibility that the somatomedins act by hormone-like endocrine mechanisms, they add support to the concept that these peptides act through autocrine or paracrine mechanisms, being produced at multiple sites and acting at or near their sites of production.

Animals↗
PubMedDate not supplied

Early postnatal dexamethasone diminishes transforming growth factor alpha localization within the ileal muscularis propria of newborn mice and extremely low-birth-weight infants.

Focal small bowel perforation (FSBP) occurs most commonly in the ileum of extremely low-birth-weight (ELBW) infants. Early postnatal dexamethasone (EPD) administration results in an increased risk for FSBP in this patient population, but the mechanism by which this occurs is unknown. Infants with FSBP have healthy mucosa but thinned smooth muscle, suggesting a mechanism involving the muscularis propria for these perforations. One explanation for these findings would be that dexamethasone alters the tissue availability of pertinent growth factors to the smooth muscle. To explore this possibility, we administered dexamethasone or saline by intraperitoneal injection to newborn mice for 3 days (dosed at 1 microg/g of body weight/day) to simulate EPD protocols. The animals were sacrificed after 72 h of treatment and their ileums harvested and prepared for microscopy. Immunolocalization was performed for three related growth factors (epidermal growth factor [EGF], heparin-binding EGF [h-EGF], and transforming growth factor alpha [TGF-alpha]) and their common receptor. We found TGF-alpha to be abundant and discretely localized in the muscularis propria in control animals but to be diminished in dexamethasone-treated animals. EGF-receptor immunostaining was also decreased with dexamethasone but there was minimal to no detection of EGF or h-EGF in either treatment condition. Surgical and autopsy specimens of the ileum were obtained from seven ELBW infants who either received EPD or not. These tissues were used for immunolocalization of the same growth factors and similar distributions for TGF-alpha were observed in several of these cases. These findings are consistent with an autocrine role for TGF-alpha in ileal smooth muscle proliferation and suggest a mechanism by which EPD might mediate smooth muscle thinning.

Animals↗
PubMedDate not supplied

The incidence and effects of motion sickness among medical attendants during transport.

Motion sickness is a common and often debilitating problem. The purpose of this study was to determine the incidence and effects of the motion sickness syndromes, the Nausea and Sopite Syndromes, among medical transport personnel. Members of the Transport Teams of the University of North Carolina Hospitals completed a questionnaire to identify a history of susceptibility to motion sickness. An additional questionnaire evaluated each individual for symptoms of motion sickness during transport. The Digit Span Test portion of the Mini-Mental Status Examination (DST-MMSE) was used to evaluate cognitive function after transport. Control data on each subject were obtained by testing during nontransport shifts. The Nausea Syndrome was observed during transport in 46% of subjects; 65% experienced symptoms consistent with the Sopite Syndrome. Pretransport surveys were predictive of the Nausea Syndrome, but not of the Sopite Syndrome. The Nausea Syndrome was related to subjective assessments of the severity of motion experienced; the Sopite Syndrome did not correlate with the severity of motion. The DST-MMSE scores after transport were significantly lower than scores during nontransport periods in 85% of personnel. We conclude that transport personnel are susceptible to motion sickness manifested by both the Nausea Syndrome and the Sopite Syndrome. The presence of motion sickness is associated with a significant decline in performance on tests of attention and concentration.

Air Ambulances↗
PubMedDate not supplied

Programmed cell death in normal fetal rat lung development.

Lung development is a coordinated process regulated by the interactions of extracellular and intracellular factors, yet little is known about the process of programmed cell death during lung development. To study this question, we examined fetal rat lung from the pseudoglandular period (gestational day 15) to the day of birth (gestational day 21) using BrdU incorporation into DNA as a proliferative marker, while in parallel examining several markers of programmed cell death including terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), DNA "laddering, " and expression of programmed cell death pathway proteins. Cell proliferation was ongoing throughout fetal days 15 to 21 with a decrease in proliferation over days 20 and 21. Programmed cell death in fetal lung also appeared to be present at all ages examined, but demonstrated 2 peaks of activity at fetal days 15 and 18 to 20. Bcl-XL expression was detected on fetal days 15 to 21, with diminished expression on days E15 to E18. Cleaved poly(ADP-ribose)polymerase (PARP), activated caspase-3, Bax, and Bad were increased on days 18 to 20. We conclude that proliferation is the primary process driving fetal lung development with programmed cell death occurring throughout the lung developmental process to refine structural remodeling.

Animals↗
PubMedDate not supplied

Expression of the insulin-like growth factor system in postpneumonectomy lung growth.

The insulin-like growth factors (IGF-I and IGF-II) may play an important role in postpneumonectomy compensatory lung growth by translating hormonal inputs and mechanical forces into cellular proliferation signals. We examined the mRNA abundance of IGF-I, IGF-II, and IGF binding proteins (IGFBPs) in lungs of rats on postoperative days 1, 2, 3, 5, and 7 following left pneumonectomy (PNX) or shamoperation (SC) and in normal animals (CON). There was no difference in the abundance of lung IGF-I mRNA (measured by Northern analysis) or serum IGF-I (measured by radioimmunoassay (RIA)) between SC and PNX animals. IGF-II mRNA abundance was initially decreased following PNX (73% decrease compared to SC animals on day 1, p < .05) and then rose to approach SC group values on subsequent days. Transcripts for IGFBP-2, -3, -4, -5, and -6 were decreased in both the SC and PNX groups compared to CON animals on the day following pneumonectomy, then rose back to baseline by postoperative day 2-3. Tissue IGFBPs, measured by ligand blot analyses, were not different in either the SC or PNX groups. In contrast, all serum IGFBP bands were increased on postoperative day 1 following either sham or PNX surgery. In addition, serum IGFBP-4 was increased in PNX animals compared to the SC group on days 1 and 2 (increase of 38% and 78%, respectively, p < .05). We conclude that the changes observed in lung IGF and IGFBP expression following pneumonectomy do not represent major.

Animals↗
PubMedDate not supplied

Comparison of 6-hour infusion versus bolus furosemide in premature infants.

STUDY OBJECTIVE: To compare the renal, hemodynamic, and pulmonary effects of a 6-hour infusion of furosemide versus conventional bolus administration in premature infants. DESIGN: Prospective, blinded, placebo-controlled, randomized study. SETTING: Two level III, university-based neonatal intensive care units. PATIENTS: Thirty premature infants with significant lung disease, requiring furosemide after a red cell infusion. INTERVENTIONS: Infants received furosemide 1 mg/kg over 2 minutes, followed by a 6-hour placebo infusion, or a small loading dose of 0.1 mg/kg, followed by a slow infusion of 0.9 mg/kg over 6 hours. Serum and urine were collected to determine percentage fractional excretion of sodium (FENa). MEASUREMENTS AND MAIN RESULTS: Urine output and blood pressure were measured every 2 hours after furosemide administration. Percentage FENa was measured immediately before furosemide and compared with pooled urine from an 8-hour collection after furosemide administration. Serum sodium, creatinine, and calcium were measured before and 24 hours after drug administration. Mean airway pressure and percentage inspired oxygen were compared before, 1-4 hours after, and 4-12 hours after drug administration. No significant differences were detected between the two methods of drug administration. CONCLUSION: Our data suggest that a 6-hour infusion of furosemide does not offer substantial clinical advantage over conventional bolus administration in premature infants when focusing on urine output, blood pressure, FENa, or pulmonary effect.

Blood Pressure↗