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Biomedical subjects
D Gerrard
Publications and source records attributed to D Gerrard.
Temporal change in skeletal muscle IGF-I mRNA abundance and nitrogen metabolism responses to abomasal casein infusion in steers.
Skeletal muscle IGF-I and alpha-actin mRNA responses to increased amino acid availability were investigated in young, rapidly growing steers. Four Holstein steers (208 kg BW) were surgically implanted with an abomasal cannula and jugular catheters and allowed 2 wk to recover. Steers were offered hourly a 43:57 forage:concentrate diet at 95% of ad libitum intake supplemented with continuous abomasal infusion of glucose (to replace 12.5% of metabolizable ad libitum energy intake) for 13 d before the start of abomasal infusion of 67 g of casein N/d. Biopsies of the liver and both semimembranosus muscles were removed and frozen in liquid N, and casein infusion was begun. Muscle biopsies were collected at 8, 16, 24, and 48 h, and on d 7 and 14. Nitrogen balance increased from 23.6 to 71.5 g/d (P < .001) within 24 h and remained elevated (mean = 58.4 g/d) during the 14 d of casein infusion. Plasma urea N increased from 4 to 9.5 mg/dL at 24 h and remained unchanged to d 14. Muscle IGF-I mRNA abundance increased to 215% of basal values at 16 h (P < .01), 244% of basal values at 24 h, and 222% of basal values at 48 h after initiation of casein infusion. Values reached a maximum of 274% of basal values on d 7 and then declined to near preinfusion levels on d 14. The IGF-I mRNA abundance was approximately 100 times higher in liver than in skeletal muscle and was not different on d 0 and 14. Although plasma IGF-I concentrations were numerically higher during the first 24 h of abomasal casein infusion, they were not significantly higher during the chronic phase of treatment. Plasma IGF binding protein (BP)-2 concentrations were higher at 16, 24, and 48 h after casein infusion was begun, but IGFBP-3 concentrations were not altered at these sampling times. Neither acute (first 24 h) nor chronic (daily) plasma insulin concentrations were altered by abomasal casein infusion. Plasma somatotropin concentrations were lower (P = .008) at 24 h of casein infusion and beyond. Results suggest that enhanced amino acid availability may modulate skeletal muscle protein synthesis and accretion through an autocrine or paracrine IGF-I influence.
Abomasum↗
Transitory expression of alpha cardiac myosin heavy chain in a subpopulation of secondary generation muscle fibers in the pig.
Unlike the random distribution of fiber types seen in skeletal muscles of most mammals, pig muscle exhibits a rosette pattern consisting of islets of slow fibers surrounded by concentric circles of type IIA and IIB fibers. Within each islet of slow fibers, one of the central fibers is a primary myofiber, whereas all others are secondary fibers. The present study demonstrates that a subpopulation of the slow secondary fibers transiently expresses alpha-myosin heavy chain (MHC). Two cDNA libraries were made from longissimus dorsi skeletal muscle of 14-day-old piglet and adult pig atrium; the latter muscle is mainly composed of alpha-MHC. Screening of the libraries with a human anti-alpha-MHC mAb (F8812F8) demonstrated the presence of positive MHC clones in both libraries; the nucleotide sequence of the 3'-untranslated region (3'-UTR) was identical in both libraries. As this MHC 3'-UTR had 75% homology with the human alpha-MHC, it was identified as pig alpha-MHC. Using specific cRNA probes and mAbs against pig alpha-cardiac and beta/slow/type I MHC, we studied the expression of these MHCs in developing pig semitendinosus muscle by combining in situ hybridization and immunocytochemistry on serial sections at 90 days of gestation, and at 1, 6, 35 days and 6 months of age. The results showed that a subpopulation of secondary fibers that directly abut primary fibers, transiently produced alpha-MHC, both at the levels of the protein and its transcript. Subsequently, these fibres expressed beta-MHC. At 1 day, immunocytochemistry showed that 16% of the secondary fibers expressed alpha-MHC, among which 20% did not yet express beta-MHC. At 6 days, alpha- and beta-MHCs were mostly present in the same fibers, i.e., 23% of the secondary fibers. Thereafter, the proportion of secondary fibers reacting with alpha-MHC mAb decreased to 10% at 5 weeks and 0% at 6 months, whereas beta-MHC was still accumulating in about 38% of the secondary fibers. During the period studied, the distribution of alpha- and beta-MHC transcripts closely matched that of the corresponding proteins. Expression of alpha-MHC was not detected in primary type I muscle fibers and slow type I secondary fibers at the periphery of the rosettes of slow fibers. This study is the first unequivocal demonstration of a transitory expression of alpha-MHC in a subpopulation of secondary fibers in a limb skeletal muscle during mammalian development.
Amino Acid Sequence↗
Action of cyclosporin A on the tapeworm Hymenolepis diminuta in mice.
Cyclosporin A (CsA), administered in 5 daily subcutaneous doses of 50 mg/kg to MF1 mice immediately following infection with Hymenolepis diminuta enhanced parasite growth relative to controls. Drug administered at 24 h intervals for 10 days, and thereafter every 48 h to MF1 and CBA/Ca mice infected with H. diminuta, increased worm survival and growth, delayed host-mediated expulsion of the parasite and enabled some worms to develop to patency. Worm survival and weight both increased in a dose-dependent manner following daily CsA treatment of infected CBA/Ca and BALB/c mice (0-150 mg/kg CsA/day). Delay in parasite elimination was accompanied by increased frequency of worm-attachment in the anterior small intestine (MF1 mice given 5 daily doses of CsA [0-150 mg/kg] following infection); posteriad migration of worms was restricted in a dose-dependent manner. The data presented contrast markedly with the action of the same drug on H. microstoma in mice. Thus CsA treatment acts in opposing ways on two closely related parasites in the same host; this possibly reflects the mechanistic antagonism between immunosuppression and anthelmintic activity. This paper reports the first use of a specific T cell-suppressive drug on H. diminuta in the mouse, implicating the role of T cells in protective immunity to this parasite.
Animals↗