7H-benzo[c]fluorene: a major DNA adduct-forming component of coal tar.

Coal tar is a complex mixture that exhibits high carcinogenic potency in lungs of animals when administered in the diet. Studies have noted that lung tumor induction does not correlate with the benzo[a]pyrene content of coal tar, suggesting that other hydrocarbons may be involved in the observed tumorigenicity. Our previous studies have demonstrated that a major 'unknown' chemical-DNA adduct is formed in the lung of mice exposed to coal tar. We have used an in vitro rat microsomal activation system to generate the 'unknown' adduct with neat coal tar and fractions of coal tar obtained by chemical fractionation and HPLC. Chemical-DNA adduct formation was evaluated by (32)P-postlabeling using both multi-dimensional TLC and HPLC. GC-MS analysis of the coal tar fractions obtained from HPLC, which produced the 'unknown' adduct in vitro, demonstrated that the adducting hydrocarbon had a mass of 216. A careful evaluation of candidate hydrocarbons led to the conclusion that a benzofluorene derivative may be responsible for forming the 'unknown' chemical-DNA adduct. Comparative in vitro and in vivo studies on the adducting properties of all three isomers of benzofluorene indicated that 7H-benzo[c]fluorene is responsible for producing the 'unknown' adduct observed in the lung of mice ingesting coal tar. Animal feeding studies also demonstrated that 7H-benzo[c]fluorene formed considerably more lung DNA adducts than 11H-benzo[a]fluorene and 11H-benzo[b]fluorene. These data indicate that the four-ring polycyclic aromatic hydrocarbon 7H-benzo[c]fluorene, a hydrocarbon not previously shown to form DNA adducts in lung, is in fact a potent lung DNA adductor and is a candidate PAH for causing lung tumors in animals treated with coal tar.

Interrelationships of spontaneous growth hormone axis activity, body fat, and serum lipids in healthy elderly women and men.

Aging is associated with decreased growth hormone (GH) secretion and plasma insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GH/IGF-I axis function in the elderly is related to the lipid profile independently of body fat, we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levels, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P < .005) to DEXA total and abdominal fat and MRI visceral fat in both genders. Log IAUPGH was inversely related to visceral fat in women (P < .005) and men (P < .0001), but was not significantly related to total fat in either gender. In women, log IAUPGH was related inversely to total and LDL cholesterol and positively to HDL cholesterol (P < .008). In men, log IAUPGH was inversely related to total cholesterol and triglycerides (P < .005). In women, HDL cholesterol was inversely related to the WHR (P < .005). In men, triglycerides were positively related (P < .001) to the WHR and DEXA abdominal and MRI visceral fat. Multivariate regression revealed log IAUPGH, but not DEXA total body fat, to be an independent determinant of total (P < .001 for women and P = .01 for men) and LDL (P < .007 and P = .05) cholesterol in both sexes and of HDL cholesterol (P < .005) and triglycerides (P < .03) in women. Log IAUPGH, but not DEXA abdominal fat, was related to total (P < .005 and P < .03) and LDL (P < .03 and P = .05) cholesterol in both genders and to HDL in women (P < .05). Log IAUPGH, but not MRI visceral fat, was related to total cholesterol (P < .03 and P = .05) in women and men. Age, IGF-I, and IGFBP-3 were not significantly related to any body fat or lipid measures, except for a positive correlation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that it is an independent cardiometabolic risk factor in healthy elderly people.

Comparison of neurotoxic effects and potential risks from oral administration or ingestion of tricresyl phosphate and jet engine oil containing tricresyl phosphate.

Neurotoxicity of tricresyl phosphates (TCPs) and jet engine oil (JEO) containing TCPs were evaluated in studies conducted in both rat and hen. Results for currently produced samples ("conventional" and "low-toxicity") were compared with published findings on older samples to identify compositional changes and relate those changes to neurotoxic potential. Finally, a human risk assessment for exposure by oral ingestion of currently produced TCPs in JEO at 3% (JEO + 3%) was conducted. TCPs and certain other triaryl phosphates administered as single doses inhibited brain neuropathy target esterase (B-NTE; neurotoxic esterase) in the rat and the hen (hen 3.25 times as sensitive), and both species were deemed acceptable for initial screening purposes. Neither rat nor hen was sensitive enough to detect statistically significant inhibition of B-NTE after single doses of IEO + 3% "conventional" TCP. Subacute administration of 2 g/kg/d of JEO + 3% "conventional" TCP to the hen produced B-NTE inhibition (32%), which did not result in organophosphorus-induced delayed neurotoxicity (OPIDN). Subchronic administration of JEO + 3% TCP but not JEO + 1% TCP at 2 g/kg/d produced OPIDN. Thus, the threshold for OPIDN was between 20 and 60 mg "conventional" TCP/kg/d in JEO for 10 wk. The current "conventional" TCPs used in JEO and new "low-toxicity" TCPs now used in some JEO are synthesized from phenolic mixtures having reduced levels of ortho-cresol and ortho-xylenols resulting in TCPs of very high content of meta- and para-substituted phenyl moieties; this change in composition results in lower toxicity. The "conventional" TCPs still retain enough inhibitory activity to produce OPIDN, largely because of the presence of ortho-xylyl moieties; the "low-toxicity" TCPs are largely devoid of ortho substituents and have extremely low potential to cause OPIDN. The TCPs produced in the 1940s and 1950s were more than 400 times as toxic as the "low-toxicity" TCPs produced today. Analysis of the doses required to produce OPIDN in a subchronic hen study suggests that the minimum toxic dose of "conventional" TCP for producing OPIDN in a 70-kg person would be 280 mg/d, and for JEO containing 3% TCP, 9.4 g/d. Food products could be inadvertently contaminated with neat "conventional" TCP but it is unlikely that food such as cooking oil would be contaminated with enough JEO + 3% TCP to cause toxicity. Further, at the dosage required for neurotoxicity, it would be virtually impossible for a person to receive enough JEO + 3% TCP in the normal workplace (or in an aircraft) to cause such toxicity. There is no record of a JEO formulated with the modern "conventional" TCP causing human neurotoxicity.

Muscle quality. I. Age-associated differences between arm and leg muscle groups.

To determine the differences between arm and leg muscle quality (MQ) across the adult life span in men and women, concentric (Con) and eccentric (Ecc) peak torque (PT) were measured in 703 subjects (364 men and 339 women, age range 19-93 yr) and appendicular skeletal muscle mass (MM) was determined in the arm and leg in a subgroup of 502 of these subjects (224 men and 278 women). Regression analysis showed that MQ, defined as PT per unit of MM, was significantly higher in the arm ( approximately 30%) than in the leg across age in both genders (P < 0.01). Arm and leg MQ declined at a similar rate with age in men, whereas leg MQ declined approximately 20% more than arm MQ with increasing age in women (P

Serum levels of insulin-like growth factor-I are related to age and not to body composition in healthy women and men.

BACKGROUND: Aging is accompanied by decreased bone and lean body mass, increased fat mass, and reduced growth hormone (GH) axis function, reflected in diminished levels of insulin-like growth factor-I (IGF-I). Similar changes in body composition occur in nonelderly, GH-deficient adults and are reversible with GH administration, suggesting that diminished GH/IGF-I axis activity may contribute to such age-related changes. To determine the precise pattern of IGF-I decline with age, and to test the hypothesis that this decline is related to concomitant changes in body composition and bone metabolism independent of age, we conducted a cross-sectional survey in 351 healthy participants in the Baltimore Longitudinal Study of Aging. METHODS: We evaluated relationships among IGF-I, age, and total and regional adiposity, as assessed by body mass index (BMI) and waist-to-hip ratio (WHR); lean body mass, as estimated from urinary creatinine excretion (Crex/ht); bone mineral density (BMD), as assessed by single and dual photon absorptiometry scanning; and circulating levels of parathyroid hormone (PTH), 1,25-(OH)2 D3, 25-OHD, and osteocalcin. RESULTS: Serum IGF-I levels declined with age (p < .0001) in both men (r = -.51) and women (r = -.67). In men, the decline was linear, whereas IGF-I levels decreased faster in women < 45 years of age than in older women (p < .01) or in men (p < .001). IGF-I was inversely related to BMI (p < .005), WHR (p < .001), and PTH (p < .01) in women. IGF-I was positively related to BMD of the hip and radius in both genders (p < .0003) and to Crex/ht (p < .0005) and osteocalcin (p < .0001) in men. With increasing age, Crex/ht and BMD decreased (p < .0001) and WHR, PTH, and osteocalcin increased (p < .005) in both genders, whereas BMI increased only in women (p < .005). After adjustment for age, IGF-I was not significantly related to BMI, WHR, Crex/ht, or BMD in either gender. IGF-I was positively related to 1,25-(OH)2 D3 (p < .01) independently of age in women. CONCLUSIONS: Advancing age, rather than declining serum levels of IGF-I, appears to be a major determinant of life-time changes in body composition and BMD in women and men.

Differential development of umbilical and systemic arteries. I. ANG II receptor subtype expression.

In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1 mediates vasoconstriction in adult tissues. Thus differences in reactivity could reflect differences in subtype expression. Using competitive radioligand binding assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral arteries. Steady-state responses to intravenous ANG II (0.229-1.72 micrograms/min) were studied in 16 fetuses with umbilical and/or femoral artery flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade. ANG II dose dependently (P < 0.001) increased umbilical resistance more than arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular resistance also increased dose dependently (P = 0.02), but responses were less than umbilical (P = 0.0001) and paralleled increases in MAP; blood flow was unaffected. Cumulative local doses of L-158,809 (125 micrograms) inhibited all responses (P < 0.001); however, 1,000 micrograms of the AT2 antagonist had no effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas PRA doubled (P = 0.001) after systemic infusion of only 50 micrograms of the AT1 antagonist and remained elevated. Differences in umbilical and femoral vascular responses to ANG II are in large part due to differences in AT subtype expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is mediated by AT1 receptors, and it is substantially more sensitive to receptor blockade than the vasculature.

Use of a surrogate aerosol in a preliminary screening for the potential carcinogenicity of coal coated with No. 6 fuel oil.

Coal, which contains significant amounts of water, can be ground and dried to produce an efficient fuel for electric power plants; however, spontaneous combustion can occur in the dried coal. Liquid petroleum hydrocarbons inhibit this combustion, but not all petroleum streams are effective. No. 6 fuel oil, a readily available and inexpensive stream, provides an effective coating, but the carcinogenic potential of coal particles treated with No. 6 fuel oil, which contains polynuclear aromatic hydrocarbons (PNAs), was undefined. As part of the assessment process, a series of studies was conducted to compare this treated coal with similar particles (petroleum coke) that had been tested by chronic inhalation in monkeys and rats. The amounts of PNAs in petroleum coke and treated coal were compared in extraction studies; the treated coal had only two-thirds of the organics extractable with benzene compared with coke and only 7% as much of the 3-7 ring PNAs, the likely tumorigenic compounds. In addition, the analytical profile of 3-7 ring PNAs was of lower molecular weights in the coal treated with fuel oil. The mutagenicity of extracts from treated coal was much less than with petroleum coke and markedly less than that of No. 6 fuel oil itself. The percutaneous absorption of 3H-benzo(a)pyrene from both particles and from their benzene extracts, as measured in vitro, was approximately eight times greater with petroleum coke than with treated coal. Based on these preliminary results, there is no evidence suggesting that the treated coal would pose any greater carcinogenic risk than petroleum coke.

SAR models for estimating the percutaneous absorption of polynuclear aromatic hydrocarbons.

A structure-activity relationship (SAR) of the in vitro percutaneous absorption of polycyclic aromatic hydrocarbons (PAH) is described. The data set consisted of 60 three to seven ring PAH. Over 50 numeric descriptors were generated from the modeled molecular structures. Computer aided methods were used to evaluate descriptors and develop linear expressions relating the percent of dermally applied PAH dose absorbed through skin (PADA) to PAH structure. Three regression models with one and two variables were developed. The log octanol/water partition coefficient (log P) was the most important variable in determining percutaneous absorption. An inverse relationship between log P and the skin penetration properties of the PAH was observed. Nearly 40 of 60 PAH tested had PADA-values within a factor of two of benzo[a]pyrene (BaP); well over 50 of 60 had PADA-values within a factor of three. The results lend support to the use of isotopically labeled BaP as a surrogate for measuring the dermal flux (in vivo and in vitro) and estimating the dermal bioavailability of PAH from complex mineral oil and coal-tar derived mixtures.

Age and gender comparisons of muscle strength in 654 women and men aged 20-93 yr.

To assess age and gender differences in muscle strength, isometric, concentric (Con), and eccentric (Ecc) peak torque was measured in the knee extensors at a slow (0.52 rad/s) and fast (3.14 rad/s) velocity in 654 subjects (346 men and 308 women, aged 20-93 yr) from the Baltimore Longitudinal Study of Aging. Regression analysis revealed significant (P < 0.001) age-related reductions in Con and Ecc peak torque for men and women at both velocities, but no differences were observed between the gender groups or velocities. Age explained losses in Con better than Ecc peak torque, accounting for 30% (Con) vs. 19% (Ecc) of the variance in men and 28% (Con) vs. 11% (Ecc) in women. To assess age and gender differences in the ability to store and utilize elastic energy, the stretch-shortening cycle was determined in a subset of subjects (n = 47). The older women (mean age = 70 yr) showed a significantly greater enhancement in the stretch-shortening cycle, compared with men of similar age (P < 0.01) and compared with younger men and women (each P < 0.05). Both men and women showed significant declines in muscle quality for Con peak torque (P < 0.01), but no gender differences were observed. Only the men showed a significant decline in muscle quality (P < 0.001) for Ecc peak torque. Thus both men and women experience age-related losses in isometric, Con, and Ecc knee extensor peak torque; however, age accounted for less of the variance in Ecc peak torque in women, and women tend to better preserve muscle quality with age for Ecc peak torque. In addition, older women have an enhanced capacity to store and utilize elastic energy compared with similarly aged men as well as with younger women and men.

Axial and hip bone mineral density and radiographic changes of osteoarthritis of the knee: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To examine the relationship between axial and hip bone mineral density (BMD) and radiographic changes of knee osteoarthritis (OA). METHODS: BMD of the lumbar spine and/or right hip was measured, using dual photon absorptiometry, in 402 men and 247 women in the Baltimore Longitudinal Study of Aging who had bilateral standing knee radiographs taken between 1984 and 1991. Radiographs were read for features of OA using Kellgren-Lawrence and reliable individual feature scales. The relationship between BMD and radiographic changes of OA was examined using multiple linear regression adjusting for age, body mass index, and smoking. Additional analyses with adjustment for menopausal status and estrogen replacement therapy were performed in a subset of women. RESULTS: Adjusted mean lumbar spine BMD was higher in subjects with knee osteophytes in both sexes: 1.23 +/- 0.02 vs 1.18 +/- 0.01 g/cm2 (p = 0.02) in men, and 1.12 +/- 0.02 vs 1.08 +/- 0.01 g/cm2 (p = 0.07) in women. There were no differences in levels of adjusted hip BMD by presence of any radiographic features of OA in either men or women. CONCLUSION: These results show that both men and women with radiographic changes of knee OA, specifically osteophytosis, have higher levels of adjusted spine but not hip BMD.

Light catalytically cracked naphtha: subchronic toxicity of vapors in rats and mice and developmental toxicity screen in rats.

Both a subchronic inhalation study and a developmental toxicity screen were performed with vapors of light catalytically cracked naphtha (LCCN). In the subchronic study, four groups of mice and rats (10 animals per sex per species) were exposed for approximately 13 wk (6 h/d, 5 d/wk) to concentrations of LCCN vapors of 0, 530, 2060, or 7690 mg/m3. An untreated control group was also included. Animals were observed daily and body weights were taken weekly. No significant treatment-related changes were found in clinical signs, body weight, serum chemistry, hematology, histopathology of 24 tissues, or weights of 12 organs. A marginal decrease was noted in the number of sperm per gram of epididymis. In the developmental toxicity screen, presumed-pregnant Sprague-Dawley rats were exposed to 0, 2150, or 7660 mg/m3 of LCCN vapors, 6 h/d on d 0-19 of gestation. Females were sacrificed on d 20; dams and fetuses were examined grossly and fetuses were later evaluated for skeletal and visceral effects. The number of resorptions was increased by approximately 140% in the group receiving 7660 mg/m3; no other definite treatment-related changes were observed. Overall, the effects of exposure to partially vaporized LCCN were minimal.

Comparison of ANG II in fetal and pregnant sheep: metabolic clearance and vascular sensitivity.

Fetal sheep appear less responsive to infused angiotensin II (ANG II) than pregnant ewes. This may reflect a greater fetal metabolic clearance rate (MCRANGII) and thus lower plasma ANG II levels. We therefore determined fetal MCRANGII, half-life (T1/2), and placental removal of ANG II. Fetal sheep (n = 13; 113-139 days of gestation) received 0.573-5.73 micrograms ANG II/min iv for 30 min while arterial pressure and heart rate were monitored. Serial blood samples were obtained before and during a 30-min infusion to measure ANG II and calculate MCRANGII and after stopping the infusion to determine T1/2. MCRANGII was similar across gestation and at doses < or = 2.29 micrograms/min (683 +/- 49 vs. 74 +/- 5 ml.min-1.kg-1 for adults) but was 30-40% lower with 5.73 micrograms ANG II/min (494 +/- 57 ml.min-1.kg-1, P < 0.05). T1/2 was 15-21 s. Fetal placental ANG II removal averaged 87 +/- 3 vs. 20 +/- 6% for uteroplacental removal; this was unaffected by dose and was linear with plasma ANG II levels, and saturation was not evident. Plasma ANG II levels rose proportionally with infusion rate and did not change significantly over time; thus fetal plasma ANG II concentrations can be predicted from MCRANGII. Measured and predicted ANG II levels at each infusion rate and time point were similar: r = 0.87, slope = 0.87 (P < 0.001). At equivalent predicted plasma ANG II levels fetal and maternal pressor responses were similar (P > 0.1); however, increases in umbilical vascular resistance exceeded those in uteroplacental vascular resistance (P < 0.03). Fetal MCRANGII is approximately 10-fold greater than maternal, partially reflecting the extensive capacity of ANG II removal by the placental circulation. Contrary to previous conclusions, fetal-maternal pressor sensitivity to ANG II does not differ, whereas the placental vasculature is more sensitive to ANG II than the uteroplacental circulation.

Hand dominance and bilateral asymmetry in the structure of the second metacarpal.

Bilateral asymmetry in the structure of the second metacarpal was examined in relation to functional hand dominance in a large, clinically nonselected, healthy population sample from the Baltimore Longitudinal Study of Aging. Bilateral bone measurements were made from anteroposterior hand radiographs of a total of 992 individuals, 609 males and 383 females, with an age range of 19-94 years. Hand dominance was determined on the basis of personal impression. Total width and medullary width at the midshaft of the second metacarpal were measured to 0.05 mm using a Helios caliper. These two measurements were used to derive cortical thickness, cortical bone area, periosteal (total) area, medullary area, percent cortical area, and the second moment of area in the mediolateral plane. In both right and left-handed individuals, statistically significant side differences were found in the calculated bone areas and the second moment of area, with the dominant hand being larger. Cortical thickness did not show significant side-related differences for either handedness. These results show that functional handedness leads to periosteal and endosteal expansion of the second metacarpal cortex on the dominant side, increasing bone strength without increasing cortical thickness. This is the first time this pattern of asymmetry has been reported in left-handers as well as right-handers. Our results argue for the primacy of environmental (mechanical) effects in determining bilateral asymmetry of limb bone structural properties.

Safety evaluation of petroleum products using an in vitro eye irritation test battery.

An in vitro eye irritation test battery (IVEye) composed of the EYTEX and Modified Agarose Diffusion Method (MADM) assays was evaluated for use as a predictive, economical screen and/or adjunct for the Draize eye test. EYTEX mimics corneal opacification using a synthetic matrix of proteins that is intended to produce measurable opacity on exposure to chemical irritants in proportion to their ocular irritation potential. MADM is a cytotoxicity-based assay consisting of NCTC clone 929 mouse fibroblasts overlayed with 1% agarose in culture medium. Potential eye irritation is measured macroscopically as the area of decolorization (neutral red release) around the area of chemical application and microscopically as the percentage of cell lysis resulting from chemical application. Of the 70 materials tested in the IVEye for which Draize eye test data also exist, the battery correctly identified 38 materials as non-irritants and 30 as irritants, with two false positives and no false negatives. Non-parametric analysis of the data show the battery to have a sensitivity of 100%, a specificity of 95% and a predictive value of 94%. The irritation class correlation (equivalence; irritation ranking) between EYTEX alone and the Draize data was 85%. These data support the use of IVEye as an accurate, reproducible and cost-effective in vitro method for identifying the eye irritation potential of petroleum products.

Evaluation of the EYTEX system as a screen for eye irritancy of petroleum products.

89 petroleum products were tested in the EYTEX in vitro assay and the results were compared with data from Draize tests on the same materials. All 26 chemicals assessed as irritant in the Draize test were classified as irritant by the EYTEX assay; 61 of the 63 non-irritants were correctly classified by the in vitro assay. The correlation between the results from the EYTEX system and the Draize data was 89%, and the predictive value of the EYTEX system (percentage of EYTEX irritants that are true irritants) was 93%. When the same chemicals were tested in another laboratory, the coefficient of determination for the comparison of the EYTEX scores from the two laboratories was R(2) = 0.86. The results demonstrate the reliability and interpretability of the EYTEX assay carried out in our laboratory and therefore the viability, if not the validity, of this in vitro method as a screening test for the Draize assay.

Biochemical parameters associated with low bone density in healthy men and women.

A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women.

Vasoconstrictor-induced secretion of ANP in fetal sheep.

Fetal secretion of atrial natriuretic peptide (ANP) increases during volume expansion and hypoxia. It is unknown whether this is associated with alterations in right atrial pressure (RAP) or distension and whether increases in ANP secretion reflect effects of specific vasopressors. To address this we studied fetal sheep (n = 13) at 125-140 days gestation, infusing either angiotensin II (ANG II; 0.023-5.73 micrograms/min) or the alpha-agonist phenylephrine (Phen; 0.031-7.64 micrograms/min) while monitoring mean arterial pressure (MAP), RAP, heart rate, and amniotic sac pressure. Arterial blood was obtained before and at 5 min of infusion to measure ANP, blood gases, and pH; umbilical venous blood was collected to determine placental clearance of ANP. ANG II caused dose-dependent increases in MAP and plasma ANP (P less than 0.05), whereas Phen caused dose-dependent increases in MAP, but ANP rose only with the highest dose (40 +/- 12%). delta MAP and delta RAP were highly correlated for Phen (r = 0.74, P = 0.002) and ANG II (r = 0.90, P less than 0.001), but for both agents the increase in delta RAP was proportionately greater than delta MAP, and increases in plasma ANP were greater per millimeter mercury rise in RAP than that observed with MAP. Increases in ANP were associated with a dose-dependent rise in hematocrit, suggesting decreases in intravascular volume. There was no fetal placental clearance of ANP. As in adults, ANG II- and alpha-agonist-induced fetal ANP secretion appears to primarily reflect increases in RAP and thus right atrial distension.

Effect of the sex-linked dwarfing gene (dw) upon skeletal development of young broiler chicks.

The influence of the sex-linked dwarfing gene (dw) on growth and skeletal development in young male broiler chicks was investigated. Chickens that were homozygous (dw/dw) for the dwarfing gene had significantly lower BW and tibiotarsus lengths when compared with the heterozygous (Dw/dw) or normal (Dw/Dw) genotypes. All genotypes exhibited similar incidences of tibial dyschondroplasia. In contrast to several other types of dwarfism, there was no effect of the dw gene on the width of the epiphyseal growth plate or the proteoglycan content of this tissue.