Adrenomedullin (AM)1 is a recently identified hypotensive peptide initially isolated from human pheochromocytoma (1). AM and its gene-related peptide, proadrenomedullin N-terminal 20 peptide (PAMP), are the two known bioactive products generated from post-translational enzymatic processing of the 185-amino acid prepro-AM molecule (1-3). Both AM and PAMP are amidated peptides. However, they have been shown to mediate their vasodilatory effects through distinctly different receptor systems (4). AM stimulates adenyl cyclase activity which elevates cAMP levels in smooth muscle cells. It is structurally related to calcitonin gene-related peptide (CGRP), and its vasodilatory effect is inhibited by the CGRP antagonist, CGRP 8 -37 (5-10). Conversely, PAMP has no amino acid sequence homology to AM or CGRP and its biological effects are not blocked by CGRP 8 -37 suggesting the involvement of a separate receptor system (4). Human AM cDNA has been cloned and mRNA expression identified in the adrenal glands, lung, kidney, and heart (2). A high degree of base sequence homology has been found between AM mRNAs isolated from other mammalian species, including rat and pig (11,12). AM has been also implicated as an important regulator of renal function having natriuretic and diuretic action (13, 14), a potent bronchodilator (15), a regulator of certain central brain actions (16,17), and a suppressor of aldosterone, adrenocorticotropin and insulin release (18 -20). The receptor for AM (AM-R) was recently cloned and sequenced (21); it contains seven transmembrane domains and belongs to the G protein-linked receptor superfamily. Finally, we and others have shown that AM is expressed in a variety of human tumors of both pulmonary and neural lineage including small cell lung cancer, adenocarcinoma, bronchoalveolar carcinoma, squamous cell carcinoma, and lung carcinoids; and ganglioblastoma and neuroblastoma (22,23). In an attempt to further study the distribution of AM and its receptor in human tumors and determine their role in these malignant disorders, we have used molecular, biochemical, and in vitro techniques to analyze a variety of human cancer cell lines of lung, breast, brain, ovary, colon, prostate, and hemopoietic lineages. MATERIALS AND METHODS Cell Lines and NormalTissue-Tumor cell lines evaluated in this study were as follows: small cell lung carcinomas (SCLC, H60, H69c, H82, H146, H187, H209, H345, H446, N417, H510, N592, H735, H774, H889, H1092), non-small cell lung carcinomas (NSCLC, H23, H157, H460, H676, H720, H727, H820, H1264, H1385, H1404, H2087, H2228, A549, UMC11), breast (SK-BR-3, ZR75-1, MCF-7, BT-20, MDA-MD231, BT-474, H2380), colon (H630, SNUC-1), nervous system (T98G (glioblastoma), TC106, CHP100, TC17, PNET, Peii, SY5Y, AS, LAN-1, KCNR-C, KCNR-DRA (neuroblastomas of the peripheral nervous system)), ovarian (NIH:OVCAR-3, SKOV3, OVT2, A2780, CP70), prostate (DU-145), adrenal (H295), chondrosarcoma (SW578), and chronic monocytic leukemia (U937). Additional NSCLC cell lines used to evaluate AM-R that are not ...

The objective of the experiment was to evaluate effects of increased milk replacer feeding on growth, intake, feed efficiency, and health parameters in stressed calves. Holstein bull calves (n = 120; approximately 3 to 8 d of age) were purchased from sale barns and dairy farms and housed in fiberglass hutches. In addition, wood shavings contaminated with coronavirus were mixed with clean shavings and added to each hutch before the start of the experiment. Calves were fed either a fixed amount (454 g/d) of a 20% crude protein (CP), 20% fat milk replacer to weaning at 28 d or a variable amount (454, 681, 908, and 454 g/d on d 0 to 7, 8 to 14, 15 to 31, and 32 to 41, respectively) of a milk replacer containing 28% CP and 17% fat without or with added dietary supplement containing bovine serum. Calves were also fed commercial calf starter and water ad libitum. Plasma IgG concentration in most calves on arrival at the facility was < 10 g/L. Intake, change in body weight, feed efficiency, morbidity and mortality, and selected plasma metabolites were determined. Body weight at 28 d, 56 d, daily body weight gain, intake of milk replacer, fecal scores, days with diarrhea, and days treated with antibiotics were increased with feeding variable amount of milk replacer over the 56-d study. Starter intake from d 1 to 56 was reduced from 919 to 717 g/d in calves fed fixed and variable amounts of milk replacer, respectively. Morbidity, measured as the number of days that calves had diarrhea, was increased by 53% when a variable amount of milk replacer was fed. Calves fed variable milk replacer were treated with antibiotics for 3.1 d compared with 1.9 d for calves fed 454 g of milk replacer/d. Concentrations of plasma glucose, urea N, and insulin-like growth factor-I were increased when calves were fed variable amount of milk replacer. Dietary supplement containing bovine serum had no effect on any parameter measured. There was no effect of milk replacer feeding on concentrations of nonesterified fatty acids, total protein, or growth hormone concentrations. Plasma tumor necrosis factor-alpha was highest in calves with the highest plasma IgG concentrations on the day of arrival and might be related to the calf's ability to identify pathogens in the environment. Under conditions of this study, calves fed variable amount of milk replacer and exposed to immunological challenge before weaning had greater BW gain, but also increased incidence of diarrhea that required added veterinary treatments.

Heat stress (HS) jeopardizes human and animal health and reduces animal agriculture productivity; however, its pathophysiology is not well understood. Study objectives were to evaluate the direct effects of HS on carbohydrate and lipid metabolism. Female pigs (57 ± 5 kg body weight) were subjected to two experimental periods. During period 1, all pigs remained in thermoneutral conditions (TN; 20°C) and were ad libitum fed. During period 2, pigs were exposed to: (1) constant HS conditions (32°C) and fed ad libitum (n = 7), or (2) TN conditions and pair-fed (PFTN; n = 10) to minimize the confounding effects of dissimilar feed intake. All pigs received an intravenous glucose tolerance test (GTT) and an epinephrine challenge (EC) in period 1, and during the early and late phases of period 2. After 8 days of environmental exposure, all pigs were killed and tissue samples were collected. Despite a similar reduction in feed intake (39%), HS pigs tended to have decreased circulating nonesterified fatty acids (NEFA; 20%) and a blunted NEFA response (71%) to the EC compared to PFTN pigs. During early exposure, HS increased basal circulating C-peptide (55%) and decreased the insulinogenic index (45%) in response to the GTT. Heat-stressed pigs had a reduced T3 to T4 ratio (56%) and hepatic 5′-deiodinase activity (58%). After 8 days, HS decreased or tended to decrease the expression of genes involved in oxidative phosphorylation in liver and skeletal muscle, and ATGL in adipose tissue. In summary, HS markedly alters both lipid and carbohydrate metabolism independently of nutrient intake.