Solitary fibrous tumour of pleura: CT differentiation of benign and malignant types.

AIM: To analyse and compare the computed tomography (CT) features of benign and malignant types of histopathologically proven cases of solitary fibrous tumours of pleura (SFTP). MATERIALS AND METHODS: Retrospective analysis of preoperative CT images of 28 cases of histopathologically proven and classified SFTP from three participating institutions was performed. Patient demographics and lesion characteristics including size, borders, presence of a pedicle, extension into the fissure, attenuation, enhancement, pleural effusion, and calcifications were recorded and correlated with the final histopathological diagnosis. Type and results of preoperative biopsy were also recorded. Follow-up imaging and the clinical charts were reviewed to identify recurrence. RESULTS: Out of 28 cases (15 women and 13 men), 18 were proven to be benign and 10 were malignant. The mean age of patients was 58.1±15.9 and 66.5±11.8 years (p=0.1564) for benign and malignant tumours, respectively. The median (interquartile range) diameter was 6.05 (3.2-10.9) cm for benign and 15.7 (7.1-17.5) cm for malignant type tumours (p=0.0291). Tumours had lobulate borders in 28% (5/18) of benign cases and in 80% (8/10) of malignant cases (p=0.0163). Extension into adjacent fissure was seen in 22% (4/18) of benign lesions and 40% (4/10) of malignant lesions (p=0.40). A pedicle was present in 17% (3/18) of benign and 10% (1/10) of malignant lesions (p=1). Heterogeneous attenuation was present in 61% (11/18) of benign and 90% (9/10) of malignant lesions (p=0.19). Calcification was present in 17% (3/18) of benign tumours and in 70% (7/10) of malignant tumours (p=0.0113). Pleural effusion was present in 6% (1/18) of benign and 40% (4/10) of malignant lesions (p=0.04). Only 1/13 preoperative fine-needle aspirates yielded diagnosis of SFTP. Preoperative diagnosis of SFTP was made in all cases (11/11) with core biopsies. At follow-up (1-10 years, mean 3 years), local recurrence occurred in 3/6 (50%) patients with malignant SFTP and in none of the 10 patients with benign SFTP. CONCLUSION: No definite imaging feature to differentiate benign from malignant SFTP was found. Large size, lobulate borders, presence of calcification, and ipsilateral pleural effusion were the only CT features predictive of malignancy. In suspected cases, core biopsies should be performed rather than fine-needle aspiration.

Improving molecular testing and personalized medicine in non-small-cell lung cancer in Ontario.

BACKGROUND: Although molecular testing has become standard in managing advanced nonsquamous non-small-cell lung cancer (nsclc), most patients undergo minimally invasive procedures, and the diagnostic tumour specimens available for testing are usually limited. A knowledge translation initiative to educate diagnostic specialists about sampling techniques and laboratory processes was undertaken to improve the uptake and application of molecular testing in advanced lung cancer. METHODS: A multidisciplinary panel of physician experts including pathologists, respirologists, interventional thoracic radiologists, thoracic surgeons, medical oncologists, and radiation oncologists developed a specialty-specific education program, adapting international clinical guidelines to the local Ontario context. Expert recommendations from the program are reported here. RESULTS: Panel experts agreed that specialists procuring samples for lung cancer diagnosis should choose biopsy techniques that maximize tumour cellularity, and that conservation strategies to maximize tissue for molecular testing should be used in tissue processing. The timeliness of molecular reporting can be improved by pathologist-initiated reflex testing upon confirmation of nonsquamous nsclc and by prompt transportation of specimens to designated molecular diagnostic centres. To coordinate timely molecular testing and optimal treatment, collaboration and communication between all clinicians involved in diagnosing patients with advanced lung cancer are mandatory. CONCLUSIONS: Knowledge transfer to diagnostic lung cancer specialists could potentially improve molecular testing and treatment for advanced lung cancer patients.

In utero gene transfer into the pulmonary epithelium.

In early gestation the internal surface of the lung is structurally simple and an ideal target for somatic gene transfer. The transfer of genes into the growing lung would be particularly useful in the prenatal correction of cystic fibrosis, which has devastating pulmonary complications. In addition, in utero gene therapy has the potential to immunotolerize the individual, and thereby to avoid the immune reactions now seen with the current generation of adenoviral vectors. We injected a replication-defective adenoviral vector containing the lacZ reporter gene (Ad5.CMVlacZ) into the amniotic fluid of rat pups on the 16th day of gestation. At 16 days of gestation, rat lungs are equivalent in maturity to those of a 22-week human fetus as their airways are lined with undifferentiated multipotential stem cells. The pups showed high-level reporter gene expression in their airways a week following birth (13 days following infection). The expression was maintained during a time when the lung volume increased approximately 20-fold, alveolarization occurred, and the epithelial cells differentiated. These data establish gene targeting of undifferentiated fetal cells as an effective means of gene therapy.

Crizotinib inhibition of ROS1-positive tumours in advanced non-small-cell lung cancer: a Canadian perspective.

The ros1 kinase is an oncogenic driver in non-small-cell lung cancer (nsclc). Fusion events involving the ROS1 gene are found in 1%-2% of nsclc patients and lead to deregulation of a tyrosine kinase-mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. ROS1 fusion is a distinct molecular subtype of nsclc, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology. Targeted inhibition of the aberrant ros1 kinase with crizotinib is associated with increased progression-free survival (pfs) and improved quality-of-life measures. As the sole approved treatment for ROS1-rearranged nsclc, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the ROS1 rearrangement. Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced nsclc, regardless of clinical characteristics, be tested for ROS1 rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced nsclc. If a ROS1 rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop.

Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys.

It is well established that maternal smoking during pregnancy is a leading preventable cause of low birth weight and prematurity. Less appreciated is that maternal smoking during pregnancy is also associated with alterations in pulmonary function at birth and greater incidence of respiratory illnesses after birth. To determine if this is the direct result of nicotine interacting with nicotinic cholinergic receptors (nAChRs) during lung development, rhesus monkeys were treated with 1 mg/kg/day of nicotine from days 26 to 134 of pregnancy. Nicotine administration caused lung hypoplasia and reduced surface complexity of developing alveoli. Immunohistochemistry and in situ alpha-bungarotoxin (alphaBGT) binding showed that alpha7 nAChRs are present in the developing lung in airway epithelial cells, cells surrounding large airways and blood vessels, alveolar type II cells, free alveolar macrophages, and pulmonary neuroendocrine cells (PNEC). As detected both by immunohistochemistry and by alphaBGT binding, nicotine administration markedly increased alpha7 receptor subunit expression and binding in the fetal lung. Correlating with areas of increased alpha7 expression, collagen expression surrounding large airways and vessels was significantly increased. Nicotine also significantly increased numbers of type II cells and neuroendocrine cells in neuroepithelial bodies. These findings demonstrate that nicotine can alter fetal monkey lung development by crossing the placenta to interact directly with nicotinic receptors on non-neuronal cells in the developing lung, and that similar effects likely occur in human infants whose mothers smoke during pregnancy.

Chronic maternal nicotine exposure alters neuronal systems in the arcuate nucleus that regulate feeding behavior in the newborn rhesus macaque.

It is well known that maternal smoking during pregnancy can lead to low birth weight and low body fat in human newborns. The purpose of this study was to determine whether chronic maternal nicotine treatment alters levels of known regulators of energy balance in the newborn offspring. Pregnant rhesus monkeys were treated with nicotine tartrate (1.5 mg/kg x d) starting on d 26 of pregnancy and maintained through d 160 of gestation. Nicotine exposure had no significant effect on absolute birth weights of the neonatal monkeys, although there was a 10% reduction in birth weights with nicotine exposure when they were normalized to maternal weight. Postnatal d 1 plasma leptin levels were significantly reduced by about 50% in the nicotine treatment group compared with saline controls, suggesting that the infant monkeys exposed to nicotine may also have lower body fat levels. In situ hybridization studies demonstrated that chronic nicotine exposure resulted in a significant decrease in arcuate NPY mRNA expression in the neonatal monkeys. In addition, there was a 2-fold increase in POMC mRNA in the arcuate nucleus in the nicotine-exposed group. These data suggest that nicotine exposure during pregnancy may increase energy expenditure in the developing fetus through actions on hypothalamic systems, resulting in lower birth weights and body fat levels.

Rat pleural mesothelial cells show damage after exposure to external but not internal cigarette smoke.

The combination of cigarette smoke and high-level occupational asbestos exposure produces a synergistic increase in the incidence of lung cancer; however, smoking does not affect the incidence of mesothelioma. Here we present the results of tests of two theories that have been proposed to explain this phenomenon; namely, that pleural mesothelial cells are resistant to cigarette smoke-induced damage and that the pleural connective tissue acts as a barrier that prevents smoke from reaching the mesothelial cells. To test these hypotheses, excised whole rat lung preparations were exposed to either internal (intratracheal) or external (pleural surface) smoke. For comparison, additional excised lung preparations were exposed to solutions of hydrogen peroxide either externally or intratracheally. Mesothelial cells exposed to external smoke showed widespread, dose-dependent uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke did show uptake, but to a lesser degree than externally exposed mesothelial cells. Examination by scanning and transmission electron microscopy showed that internal smoke did not affect mesothelial cell ultrastructure, whereas external smoke produced obvious mesothelial cell damage and mesothelial cell detachment. Catalase and deferoxamine, scavengers of active oxygen species, provided protection against smoke-induced mesothelial cell injury, but inactivated catalase did not. External hydrogen peroxide produced a very similar, dose-dependent pattern of Trypan blue uptake and ultrastructural changes. Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of damage was always less than with comparable concentrations of external hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Late relapse of myelodysplasia after allogeneic transplantation concomitant with new presentation of invasive liposarcoma as a secondary neoplasm.

Second malignancies are uncommon events in the survivors of allogeneic transplant procedures, although they are increased compared to normal control populations. Among these malignancies, sarcomas are exceedingly rare. In addition, relapse of primary myelodysplasia rarely occurs after 5 years from the time of allogeneic transplantation. This report describes an unusual presentation of liposarcoma with concomitant relapse of underlying myelodysplasia developing in a patient 9 years after the first of two allogeneic transplantations.

Pulmonary blood volume and edema in postpneumonectomy lung growth in rats.

After pneumonectomy in young animals, the contralateral lung undergoes compensatory growth and generally attains the same weight and air space volume as both lungs in age-matched controls. In this study, we determined the contribution of lung edema and increased blood volume to the weight gain in rats. Three weeks after pneumonectomy (n = 18) or sham pneumonectomy (n = 17), the pulmonary blood volume and the extravascular water and albumin were evaluated by use of 51Cr-labeled erythrocytes and 125I-labeled albumin. The air space volume, blood-free lung weights, and DNA and protein content were also compared. The data show that the total pulmonary blood volumes and the blood volume per gram of blood-free dry lung were similar in pneumonectomized and age-matched sham controls. The total extravascular albumin and the extravascular albumin per gram of blood-free dry lung were also similar as well as the extravascular lung water, wet-to-dry weight ratios, DNA and protein content, and air space volumes. These data indicate that the increased weight of the postpneumonectomy lung was due to cellular and stromal proliferation. The blood volume and interstitial fluid increased in proportion to the increase in lung parenchyma. Neither vascular congestion nor increased extravascular protein and water contributed to the observed weight gain.

A comparative study of postpneumonectomy compensatory lung response in growing male and female rats.

Postpneumonectomy compensatory lung response and normal lung growth in the early postnatal period were studied in male and female rats. Four-week-old litter-matched male and female Sprague-Dawley rats were subjected to left pneumonectomy or sham operation and followed for 3 wk. In both sexes after pneumonectomy, lung weight (WL), lung volume (VL), alveolar surface area (Sw), total alveolar number (N(at)), and the amount of DNA and protein increased significantly. In both males and females, WL, VL, and Sw matched those of both lungs of the sham-operated group, but N(at) and the amount of DNA and protein did not. Female pneumonectomy and sham-operated rats were smaller in body weight than males. Absolute WL, VL, Sw, N(at), and the amount of DNA and protein were significantly lower, but specific parameters (per unit body weight) were significantly greater in females than in males. After pneumonectomy, the postcaval lobe increased most in volume (70 and 73% in males and females, respectively). Mean linear intercept and mean chord length of alveoli increased, and the number of alveoli per unit volume decreased more in the postcaval and middle lobes than in upper and lower lobes in both sexes. Postpneumonectomy, loss of elastic lung recoil was observed in females. We conclude that, in certain aspects (WL, VL), compensatory growth matched both lungs of controls, but in others (biochemical, morphometric) it did not. There was evidence of alveolar multiplication, but the dominant effect was enlargement of air spaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung growth in hypobaric normoxia, normobaric hypoxia, and hypobaric hypoxia in growing rats. I. Biochemistry.

Adaptive changes in cellular and connective tissue components of the lung after chronic exposure to reduced ambient oxygen and/or pressure were studied. Four-week-old male Sprague-Dawley rats were randomly divided into five groups (n = 12 each): 1) general control, room air (GC); 2) hypobaric normoxic; 3) normobaric hypoxic; 4) hypobaric hypoxic; and 5) weight-matched control, restricted food intake (WMC; weight matched to hypobaric hypoxic animals). Lung growth (lung weight and DNA, RNA, protein, hydroxyproline, and desmosine contents) diminished in WMC compared with GC. Somatic growth decreased in hypobaric and normobaric hypoxic rats compared with GC. Lung weight; DNA, RNA, protein, hydroxyproline, and desmosine contents; and RNA/DNA, protein/DNA, and desmosine/DNA ratios increased in both hypobaric and normobaric hypoxic rats compared with WMC. Hydroxyproline and desmosine contents and the hydroxyproline/DNA ratio were significantly higher in hypobaric than normobaric hypoxic rats. Hypobaric normoxia caused a slight somatic growth reduction, but biochemical parameters of lung growth remained unaffected. In conclusion, in growing animals, despite inhibition of lung growth due to reduced food consumption, accelerated lung growth in hypobaric or normobaric hypoxia occurs by hyperplastic and hypertrophic changes. Hypobaric normoxia does not affect lung growth, but connective tissue proteins accumulate slightly more in hypobaric hypoxia than in hypoxia alone.

Lung cytokinetics after exposure to hypobaria and/or hypoxia and undernutrition in growing rats.

Lung cellular dynamics were examined in growing rats from 4 to 7 wk of age after exposure to 1) room air (general controls), 2) hypobaric normoxia, 3) normobaric hypoxia, 4) hypobaric hypoxia, and 5) room air and restricted food intake (weight-matched controls). Tritiated thymidine ([3H]TdR) incorporation diminished in weight-matched controls. In both hypoxic groups, maximum [3H]TdR incorporation occurred on day 3 in all cells of peripheral alveoli, capillary endothelium of central alveoli, airway walls and epithelium, and arterial wall and endothelium, but maximum [3H]TdR labeling of interstitial and unidentifiable cells of central alveoli occurred on day 5. The percent labeling with [3H]TdR was higher in cells of peripheral alveolar walls than in cells of central alveolar walls. Labeling of the interstitium was higher in hypobaric hypoxic than normobaric hypoxic rats. In hypobaric normoxia, DNA synthetic activity increased in alveolar wall cells, except for capillary endothelium. In hypobaric hypoxia, DNA synthesis occurred primarily because of low O2, but low pressure may also affect cytokinetics. [3H]TdR incorporation is greater and earlier in the alveoli of the peripheral part of the lung than central alveoli, and the cellular response of the various cells types is not synchronous.

Pulmonary function alterations after 3 wk of exposure to hypobaria and/or hypoxia in growing rats.

We studied lung growth in rats between 4 and 7 wk of age under different conditions. There were five groups, seven animals in each: 1) general controls (ambient pressure and room air, food ad libitum); 2) hypobaric normoxic [barometric pressure (PB) 410 mmHg, PO2 153 Torr]; 3) normobaric hypoxic (ambient pressure, PO2 80 Torr); 4) hypobaric hypoxic (PB 410 mmHg, PO2 80 Torr); and 5) weight-matched controls to hypobaric hypoxic. Residual volume, functional residual capacity, vital capacity, and total lung capacity grew 10-20% more in both hypoxic groups than in weight-matched and general controls. Expiratory flow rates corrected for forced vital capacity decreased, and specific airway resistance increased significantly. In addition, the ratio of forced expiratory volume in 0.1 s to %forced vital capacity, peak expiratory flow rate, and forced maximal midexpiratory flow were also lower in normobaric hypoxic animals compared with weight-matched controls. Above a transpulmonary pressure of 6 cmH2O, flows were reduced in both hypoxic groups. No differences were observed between hypobaric normoxic and general control groups for lung volume and lung function. In weight-matched animals, total lung capacity decreased but lung function remained unchanged. We conclude that accelerated lung growth in hypobaric hypoxia and normobaric hypoxia is dysanaptic. Lung growth in hypobaric hypoxia is primarily induced by low oxygen, but differences between hypobaric hypoxia and normobaric hypoxia suggest a beneficial effect of low pressure.

Synthesis of acetylcholine by lung cancer.

The role of autocrine growth factors in the stimulation of lung cancer growth is well established. Nicotine is an agonist for acetylcholine receptors and stimulates lung cancer growth. This suggests that if lung cancers synthesize acetylcholine (ACh), then ACh may be an autocrine growth factor for lung cancer. Analysis of normal lung demonstrated that the cells of origin of lung cancers express the proteins necessary for non-neuronal ACh storage and synthesis. Analysis of mRNA from squamous cell lung carcinoma, small cell lung carcinoma (SCLC) and adenocarcinoma showed synthesis of choline acetyltransferase (ChAT) and nicotinic receptors. Immunohistochemical analysis of a retrospective series of SCLC and adenocarcinomas showed that more than 50% of the lung cancers screened expressed ChAT and nicotinic receptors. To study the effect of endogenous ACh synthesis on growth, SCLC cell lines were studied. SCLC cell lines were found to express ChAT mRNA and to secrete ACh into the medium as measured by HPLC separation and enzymatically-coupled electrochemical detection. The SCLC cell line NCI-H82 synthesized highest levels of ACh. Showing that the endogenously synthesized ACh interacted with its receptors to stimulate cell growth, addition of muscarinic and nicotinic antagonists slowed H82 cell proliferation. These findings demonstrate that lung cancer cell lines synthesize and secrete ACh to act as an autocrine growth factor. The existence of a cholinergic autocrine loop in lung cancer provides a basis for understanding the effects of nicotine in cigarette smoke on lung cancer growth and provides a new pathway to investigate for potential therapeutic approaches to lung cancer.

The in vitro effect of triamcinolone acetonide on branching morphogenesis in the fetal rat lung.

We have studied the effect of triamcinolone acetonide (TAC) on airway morphogenesis of the Sprague-Dawley fetal rat in whole organ lung cultures from day 15 to day 21 of equivalent gestational age (6 days in culture). TAC produced an increased number of peripheral buds from day 18 onward and the airway and airspaces had larger lumens. Airway branching was increased compared to controls, and there was a higher proportion of airway epithelium and a lower proportion of mesenchyme. Cell height was significantly lower in TAC treated lungs except on day 17. This was due to accumulation of glycogen prior to the increased branching activity. In both controls and TAC-treated lungs, peripheral bud number and volume proportion of epithelium increased with time in culture, whereas volume proportion of mesenchyme, mean chord length of airways and airspaces, and epithelial cell height decreased. These changes were more pronounced in the TAC-treated group and were significant. However, TAC-treated lungs were morphologically irregular. We conclude that TAC has a direct effect on airway morphogenesis and it promotes growth of morphologically abnormal lungs. TAC also appears to enhance airway branching and morphologic changes interpreted as increased epithelial maturation.

In vitro branching morphogenesis of the fetal rat lung.

We studied the pattern of airways branching in the fetal rat lung in vitro. Lung primordia of gestational ages 13, 14, and 15 days were allowed to grow in culture to a gestational age equivalent to 21 days. The first generation airways appear by a single new bud (monopodial budding) from the left main airway (lateral appearing before the medial). They elongate to form branches and then bud dichotomously (2 buds occurring simultaneously and adjacent to each other) at their tips. Then monopodial branching takes place along their sides. The same cycle of budding and branching seems to be repeated for the following generation of the airways. The total number of the peripheral (subpleural) buds was greatest in the day 15 explants and least in day 13 explants throughout the whole culture period, but the statistical model used indicated faster budding in the 13 day explants. Morphometric assessment showed no difference in the ratios between the lung components in the 3 age groups and that the peripheral epithelial measurements were the same in the 3 groups at an equivalent gestational age of 21 days. We have also shown that lobes do not form in the right lung, although appropriate airways do. This may indicate the importance of mesothelial covering of the lung in the process of lobe formation. The method is useful for studying the control of lung morphogenesis.

Comparative biochemistry of gestational and postnatal lung growth and development in the rat and human.

We compared the ontogeny of collagen (hydroxyproline), elastin (desmosine), soluble protein, and DNA in the lungs of rate and humans during gestation and postnatal life. In humans, lung weight/body weight ratios declined faster during gestation than postnatally, whereas in rats lung weight/body weight ratio declined little during gestation and then suddenly on the first day of life. Lung weight/body weight ratios may be lower than expected around term in humans, and prediction data are given to assess human pulmonary hypoplasia. Rats and humans differed in water content of their lungs, with rats showing a sharper decline during gestation. In the human lung, collagen and elastin made their appearance at an early stage of gestation; elastin. In particular, increased rapidly during gestation, suggesting a role in intrauterine alveolar formation. In the rat, elastin accumulation is primarily a postnatal event, as is alveolar formation. Hydroxyproline concentrations increased with conceptual age and continued to increase rapidly postnatally between 4 and 7 weeks in the rat, but slowed in the human after 60 weeks of conceptual age. Desmosine concentrations level off at the end of the study period in rats, while these are still increasing, although slowly, in humans. Overall lung growth, as assessed by weight, was linear in humans, but phases of lung growth were apparent in the rat, including one of minimal growth in the immediate postnatal period.

Effect of triamcinolone acetonide on the development of the pulmonary airways in the fetal rat.

Triamcinolone acetonide (TAC) has a potent teratogenic effect on various mammalian fetal tissues as well as a steroid effect on the lung. Less well documented is the fact that it produces profound oligohydramnios. We wished to determine what effect TAC would have on branching morphogenesis and other aspects of lung development, using an in vivo model described previously. Thirty rats were randomized to receive 0.6 mg/kg of TAC or saline on days 12, 13, and 14 of gestation. At gestational days 15, 17, 18, and 21, the left lungs of 365 fetuses were studied by dissecting microscopy, histology, and morphometry. TAC produced profound pulmonary hypoplasia (dry Jung weight/body weight 0.025, compared with 0.06 in controls) on day 21. TAC decreased maternal weight gain, fetal weight, placental weight, aminiotic fluid, and pole to pole length (PTP), while it increased the peripheral airway count (PAC). The number of central and intermediate airway branches was reduced, and they were dilated. Growth of peripheral airways was enhanced. In treated fetuses epithelial cells lining these airspaces were histologically more mature and the mesenchyme thinner than in controls. These findings were confirmed by the morphometric measurements. We conclude that when TAC is administered in the early phase of fetal rat lung development, the lungs become hypoplastic, with hypoplasia of the intermediate airways, an increase in the number of peripheral airways, and increased differentiation. We speculate that these effects are primarily due to the steroid action of TAC and that the mechanisms of monopodial branching are different from those of dichotomous branching.

Development of the pulmonary airways in the fetal rat and its relation to the prenatal environment.

We studied the left lung using multi-focus microphotography in 378 rat fetuses, assessing airway branching from day 13 to day 19 of gestation, and lung growth variables from day 13 to day 21. Longitudinal growth, and monopodial and dichotomous branching brought about a consistent airway pattern with variations within each day of gestation and a small overlap between adjacent days. Amniotic fluid weight and pole to pole (PTP) distance of the lung increased quadratically with age, while fetal weight and the peripheral airway count (PAC) increased exponentially. The location of the fetus within the uterus had no effect on fetal variables, but correlations were found between maternal weight gain and both fetal weight and PTP. Fetal weight was the best predictor of PAC from gestational ages 15 to 19 days (P < 0.008). The method described allows for observations that are reproducible within the environmental variations present in normal gestation and can be used to study the effect of external factors on lung development.

Insulin receptor characteristics of erythrocytes from human newborns.

Erythrocytes from human newborns were observed to have specific insulin receptors. The characteristics of these receptors were similar to those of the normal adult subjects. An observed slight increase in R(o) and a decrease in K̄(e) of insulin receptors in erythrocytes may be speculated to facilitate the transfer of insulin from the fetal erythrocytes to other rapidly growing fetal tissues at a rate faster than that present in the circulation of the adult subjects.