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J D Armstrong

Publications and source records attributed to J D Armstrong.

At least 19 recordsLinked to original sources
PubMed1992

Photoreactivation implicates cyclobutane dimers as the major promutagenic UVB lesions in yeast.

Previously we compared the mutational specificities of polychromatic UVB (285-320 nm) and UVC (254 nm) light in the SUP4-o gene of the yeast Saccharomyces cerevisiae. Striking similarities in the types and distributions of induced SUP4-o mutations were consistent with roles for cyclobutane dimers and pyrimidine(6-4)pyrimidone photoproducts in mutation induction by UVB. To assess the relative importance of cyclobutane dimers, we have now examined the effect of photoreactivation (PR), which specifically reverses these lesions, on UVB and UVC induction of SUP4-o mutations. PR reduced the frequencies of both UVB and UVC mutagenesis by approximately 75%. Collections of 138 and 158 SUP4-o mutants induced by treatment with UVB plus PR or UVC plus PR, respectively, were characterized by DNA sequencing and the results were compared to those for 208 UVB and 211 UVC-induced mutants analyzed earlier. PR decreased the frequency of UVB-induced G.C----A.T transitions by 85%, diminished the substitution frequencies at individual sites by 64% on average, and reduced the mutation frequencies at the five UVB hotspots by 87%. A more detailed examination revealed that the transition frequencies at the 3' base of 5'-TC-3' and 5'-CC-3' sequences were decreased by 90% and 72%, respectively. Finally, PR appeared to occur to the same extent on both the transcribed and non-transcribed strands of SUP4-o. Similar results were obtained for PR following UVC irradiation. Our findings indicate that cyclobutane dimers are responsible for the majority of UVB mutagenesis in yeast.

Base Sequence↗
PubMed1992

Effect of active immunization against growth hormone releasing factor on concentrations of somatotropin and insulin-like growth factor I in lactating beef cows.

Two experiments were conducted to determine the effects of immunoneutralization of growth hormone-releasing factor [GRF(1-29)-NH2] on concentrations of somatotropin (ST) and insulin-like growth factor I (IGF-I) in lactating beef cows. In Experiment 1, multiparous Hereford cows were immunized against 2 mg GRF(1-29)-(Gly)4-Cys-NH2 conjugated to human serum albumin (GRFi, n = 3) or 2 mg human serum albumin (HSAi, n = 3) at 52 +/- 1 d prior to parturition. Boosters (1 mg) were administered on days 12, 40 and 114 postpartum (pp). Serum samples were collected at 15-min intervals for 5 hr on days 18, 46 and 120 pp, followed by administration (IV) of an opioid agonist (FK33-824; 10 micrograms/kg) and an antagonist (naloxone; .5 mg/kg) at hours 5 and 7, respectively. A GRF-analog ([desamino-Tyr1, D-Ala2, Ala15] GRF (1-29)-NH2; 3.5 micrograms/kg) and arginine (.5 g/kg) were administered at hour 10 on days 47 and 121, respectively. Percentage binding of [125I]GRF (1:100 dilution of serum) 28 d after primary immunization was greater in GRFi (14.3 +/- 4.9) than in HSAi (.7 +/- .3) cows. Binding increased to 29.3 +/- 6.5% after first booster in GRFi cows. Episodic release of ST was abolished by immunization against GRF; concentration and frequency of release of ST were lower (P less than .05) in GRFi than in HSAi cows on all days pp. Concentrations of IGF-I were lower in GRFi than in HSAi cows throughout lactation. Serum ST failed to increase following FK33-824 or arginine in GRFi; however, ST increased after both compounds in HSAi cows. Concentrations of ST following GRF-analog were greater (P less than .05) in HSAi than in GRFi cows. Experiment 2 was conducted to determine if a lower dose of antigen and a single booster would be sufficient to lower ST and IGF-I in lactating cows. Multiparous Hereford and Angus cows were assigned to GRFi (n = 6) or HSAi (n = 6). Primary (1.2 mg) and booster (.5 mg) immunizations were administered -14 and 8 d from calving, respectively. Cows were restricted to 60% of recommended intake of energy during lactation in order to elevate concentrations of ST. Serum samples were collected at 15-min intervals for 6 hr on days 26, 50, 73, 90 and 109 pp. Two of six GRFi cows had binding less than 10% (1:1,000 dilution of serum) and were omitted from further analyses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Excision repair influences the site and strand specificity of sunlight mutagenesis in yeast.

A collection of 384 mutations recovered in a tRNA gene (SUP4-o) following exposure of isogenic excision-repair-proficient (RAD1) or deficient (rad1) strains of the yeast Saccharomyces cerevisiae to sunlight was characterized by DNA sequencing. In each case, greater than 90% of the mutations were single base-pair substitutions with events at G.C pairs constituting most of the changes. However, more than half of these substitutions were transversions in the RAD1 strain whereas transitions predominated in the rad1 strain. Tandem double substitutions were recovered in both strains and the individual changes were exclusively G.C----A.T transitions. The majority of single substitutions, and all tandem double changes, were at base-pairs where the pyrimidine(s) was part of a dipyrimidine sequence and the site specificities were consistent with cyclobutane dimers and/or pyrimidine (6-4) pyrimidone photoproducts contributing to sunlight mutagenesis. Yet, the data also pointed to an important role for lesions that form at G.C pairs and give rise to transversions. Analysis of the strand specificity of sunlight mutagenesis indicated that transitions or transversions at G.C pairs occurred preferentially in SUP4-o at sites where a dipyrimidine or a guanine, respectively, was on the transcribed strand. These biases required a functional excision-repair system.

Base Sequence↗
PubMed1992

Radiology ethics.

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Ethics, Medical↗
PubMed1992

Effect of prepartum administration of growth hormone-releasing factor on somatotropin, insulin-like growth factor I, milk production, and postpartum return to ovarian activity in primiparous beef heifers.

Forty-one primiparous beef heifers were used over 2 yr to evaluate the effect of prepartum administration of a growth hormone-releasing factor analog (GRF-A) or growth hormone-releasing factor (GRF(1-29)-NH2) on somatotropin (ST), insulin-like growth factor I (IGF-I), milk production, heifer BW, and postpartum (PP) return to ovarian activity. Beginning on d -11 +/- 1 from parturition, heifers were administered (s.c.) GRF-A ([desNH2-Tyr1,D-Ala2,Ala15]GRF(1-29)-NH2, 2.5 micrograms/kg; Yr 1) or GRF(1-29)-NH2 (12.5 micrograms/kg; Yr 2) (GRF; n = 17) or vehicle (CON; n = 24) for seven consecutive days. Blood samples were collected at 20-min intervals from -60 to 300 min from the first and fourth injections. Samples were also collected at 20-min intervals for 6 h on d 25 and 69 +/- 1 PP. Area under the curve of ST (nanograms.minute-1.milliliter-1) was greater (P less than .01) in GRF than in CON heifers (9,671 +/- 677 vs 2,611 +/- 237). Increases in ST after GRF-A or GRF(1-29)-NH2 were similar. On d 25 +/- 1 PP, frequency of ST release (pulses per 6 h) was greater (P less than .01) in CON (3.3 +/- .2) than in GRF (2.1 +/- .2) heifers. Milk production was similar (P greater than .1) for the two treatments. Heifer BW loss from d -16 to 81 after parturition was greater (P less than .01) in GRF (88 +/- 5) than in CON (68 +/- 5) heifers. Postpartum return to ovarian activity (progesterone greater than 1 ng/mL for two consecutive weeks) was delayed (P less than .05) in GRF (97 +/- 14) vs CON (71 +/- 8) heifers. After accounting for variation due to treatment and year, a negative (P less than .02) correlation (r = -.39) was detected between concentrations of IGF-I during the first 30 d PP and PP interval to ovarian activity. These results indicate that prepartum administration of GRF altered the release pattern of ST after parturition and was associated with greater PP BW loss and delayed PP return to ovarian activity in heifers.

Animals↗
PubMed1992

Endocrine events prior to puberty in heifers: role of somatotropin, insulin-like growth factor-I and insulin-like growth factor binding proteins.

We have utilized active immunization against growth hormone releasing factor (GRF) to investigate relationships among somatotropin (ST), insulin-like growth factor-I (IGF-I), IGF binding proteins (IGFBP) and ovarian function in heifers. Active immunization against GRF (GRFi) has been demonstrated to abolish episodic release of ST and decrease serum concentrations of IGF-I. In initial experiments investigating onset of puberty, breeds of heifers differing in growth rate and reproductive traits (Angus, Charolais and Simmental) were immunized against GRF or served as controls (immunized against carrier protein, human serum albumin, HSAi). GRFi decreased rate of muscle and skeletal growth, but increased deposition of adipose tissue. In Angus and Charolais, but not Simmental heifers, GRFi at 6 mo of age significantly delayed onset of puberty beyond 18 mo of age. Retrospective analyses of serum IGF-I revealed that GRFi heifers reaching puberty at a normal age had greater pre-treatment (6 mo of age) IGF-I than GRFi heifers in which puberty was delayed. Collectively, these results strongly indicate that the bovine hypothalamic-hypophyseal-ovarian axis is particularly sensitive to changes in metabolism at or near 6 mo of age. Another series of experiments tested the hypothesis that lowering serum IGF-I via GRFi initially at 3 mo of age would increase the percentage of Angus and Simmental heifers not reaching puberty. Three mo old Angus and Simmental heifers were assigned to GRFi (n = 18), HSAi (n = 14) or received no treatment (controls, n = 16). HSAi and GRFi heifers were unilaterally ovariectomized (ULO) at 6 mo of age. As anticipated, GRFi at a younger age increased percentage of heifers not reaching puberty; over 75% of control and HSAi heifers reached puberty by 14 mo of age compared to 22% of GRFi heifers. Serum and follicular fluid (FFL; follicles < or = 4 mm) concentrations of IGF-I were suppressed by GRFi. Serum, but not FFL concentrations of IGF binding protein-2 (IGFBP-2) were greater in GRFi than in HSAi heifers. GRFi delayed puberty apparently by suppressing follicular growth because number of follicles < or = 7 mm was significantly lower in GRFi than in HSAi heifers. In conclusion, active immunization against GRF at 3 or 6 months of age delays puberty in beef heifers. Delayed puberty was preceded by suppression of follicular growth, and decreased concentrations of IGF-I in serum and follicular fluid.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1991

Effect of active immunization against growth hormone-releasing factor on growth and onset of puberty in beef heifers.

Angus and Charolais heifers (195 +/- 7 kg) were actively immunized against growth hormone-releasing factor (GRF) to evaluate the effect on concentrations of somatotropin (ST), insulin-like growth factor I (IGF-I), insulin (INS), growth, and onset of puberty. Primary immunizations were given at 184 +/- 7 d of age (d 0 of experiment) by injecting (s.c.) 1.5 mg of GRF-(1-29)-Gly-Gly-Cys-NH2 conjugated to 1.5 mg of human serum albumin (GRFi, n = 22) or 1.5 mg of human serum albumin (HSAi, n = 21). Booster immunizations of .5 mg of antigen were given on d 62, 92, 153, and 251. Antibody binding (percentage at 1:2,000 dilution) to [125I]GRF on d 69 was greater (P less than .01) in GRFi (53.7 +/- 4.5) than in HSAi (10.1 +/- .6) heifers. Serum concentration (ng/ml) and frequency (peaks/5 h) of ST release, respectively, on d 78 were lower (P less than .01) in GRFi than in HSAi heifers (3.3 +/- .1 vs 5.6 +/- .2 and .9 +/- .3 vs 2.3 +/- .2). Serum IGF-I (ng/ml) was lower (P less than .01) in GRFi than in HSAi heifers on d 69 (41 +/- 5 vs 112 +/- 4). Serum INS (microU/ml) on d 78 was lower (P less than .05) in GRFi (2.2 +/- .1) than in HSAi (3.8 +/- .2) heifers. Feed intake, ADG, and feed efficiency were lower (P less than .05) in GRFi than in HSAi heifers. Hip height was lower (P less than .01) and fat thickness was greater (P less than .05) in GRFi than in HSAi heifers by d 132 and 167, respectively. Percentage of heifers attaining puberty (progesterone greater than 1 ng/ml for two consecutive weeks) by d 209 and 379 (12.9 and 18.5 mo of age), respectively, was lower (P less than .05) in GRFi (40.9 and 45.5) than in HSAi (81.0 and 100). In conclusion, growing heifers were successively immunized against GRF. Active immunization against GRF resulted in decreased serum concentration of ST, IGF-I, and INS. In addition, GRF immunization led to lowered feed intake, ADG, and feed efficiency, increased fat depth, and delayed onset of puberty in heifers. We propose that ST and IGF-I are important metabolic mediators involved in the initiation of puberty in heifers.

Animals↗
PubMed1991

Changes in growth hormone and luteinizing hormone following acute or chronic administration of an opioid agonist, FK33-824, in wethers.

Two experiments were conducted to determine the effect of acute or chronic administration of an opioid agonist, (D-Ala2,MePhe4,Met(O)5-ol)-enkephalin (FK33-824), on concentrations of growth hormone (GH) and LH in castrate sheep (wethers). In Exp. 1, we evaluated the effect of acute administration (two injections or infusion for 2 h) of FK33-824 on GH and LH. Wethers (31 +/- 1 kg; n = 12) received FK33-824 or saline via one of the three following routes of deliver: 1) i.v. (8 micrograms/kg) at 0 and 60 min (i.v., n = 4), 2) s.c. (16 micrograms/kg) at 0 and 60 min (s.c., n = 4), or 3) i.v. infusion (8 micrograms.kg-1.h-1) for 120 min (inf., n = 4) preceded by a single injection (8 micrograms/kg). Wethers received FK33-824 and saline on d 1 and 2 or d 2 and 1, respectively. Concentrations of GH were consistently elevated (P less than .05) by FK33-824 regardless of route of delivery. Infusion of FK33-824 for 120 min maintained GH concentrations greater (P less than .05) than pretreatment or those during infusion of saline. Average LH was decreased consistently by FK33-824, independent of its route of administration; episodic release of LH was suppressed. In Exp. 2, crossbred wethers (36 +/- 2 kg; n = 12) were used to determine the effect of chronic administration (s.c.) of FK33-824 on the concentrations of GH and LH and retention of N and energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Changes in metabolites, metabolic hormones, and luteinizing hormone before puberty in Angus, Braford, Charolais, and Simmental heifers.

We determined changes in insulin, glucose, free fatty acids (FFA), growth hormone (GH), insulin-like growth factor I (IGF-I) and LH before puberty in Angus, Braford, Charolais, and Simmental heifers. Our primary objective was to identify metabolites and metabolic hormones that serve as metabolic cues for onset of puberty. Angus (n = 12). Braford (n = 7), Charolais (n = 9), and Simmental (n = 7) heifers were assigned at weaning (289 +/- 25 d of age; 264 +/- 23 kg) to open-sided pens with slotted floors, and they were fed a corn silage-concentrate diet formulated to provide gains of .91 kg/d. Puberty was defined as the 1st d (d 0) that serum progesterone (determined in blood samples collected at weekly intervals) exceeded 1 ng/ml. Blood samples were collected before and after feeding at 15-min intervals for 8 h at 21-d intervals before puberty in a subsample of heifers (at least five per breed). Angus and Simmental heifers weighed less and were younger (P less than .05) at puberty than Charolais and Braford heifers. Serum FFA before feeding and frequency of LH release increased (P less than .05) from d-40 +/- 3 to d-17 +/- 3 in all breeds. Conversely, concentrations of insulin were greater (P less than .05) at -40 than at -17 d from puberty in Angus, but not in Braford, Charolais, or Simmental heifers. Frequency of GH release was greater at d -40 than at d -17 in Angus heifers; however, in Braford and Charolais heifers frequency of GH release was greater at d -17 than at d -40. Concentrations of IGF-I (measured every 2 wk) increased linearly (P less than .07) from d -56 to 0 from puberty in Angus but not in other breeds. In conclusion, frequency of LH release and concentrations of FFA increased before puberty in all breeds; however, consistent changes in other metabolites and hormones were observed only in Angus heifers.

Age Factors↗
PubMed1990

Opioid control of growth hormone in the suckled sow is primarily mediated through growth hormone releasing factor.

Endogenous opioid peptides mediate the effect of suckling on LH and PRL in the domestic pig. However, the role of opioids in modulating GH during lactation in swine is not known. Primiparous sows that had been immunized against GRF(1-29) conjugated to human serum albumin (GRF-HSA, n = 5) or HSA (n = 4) were used to determine changes in GH after naloxone. Treatments were imposed in all sows on day 21 of lactation when antibody titers were 9100 +/- 1629. All sows received (i.v.) naloxone (0.25 mg/kg) or saline (0.0125 ml/kg) at 15 min intervals for 165 min. Active immunization against GRF-HSA during lactation decreased (P less than 0.05) mean concentration (4.8 +/- 0.2 vs 2.6 +/- 0.1 ng/ml) and frequency (1.5 +/- 0.3 vs 0.4 +/- 0.2 peaks/4 hr). Concentrations of LH and PRL were similar in GRF-HSA and HSA immunized sows. Naloxone suppressed (P less than 0.05) GH in all sows. In HSA sows, naloxone abolished episodic release of GH and decreased average, but not basal, concentrations of GH. In sows immunized against GRF-HSA, naloxone decreased (P less than 0.05) average and basal GH but failed to decrease frequency of GH release. Naloxone failed to alter frequency of LH release. Concentrations of PRL decreased (P less than 0.05) after naloxone in all sows. In conclusion, immunization against GRF-HSA blocked most of the effect of lactation on GH. Blocking opioid receptors with naloxone decreased GH and PRL in all sows. In contrast to previous findings naloxone had no effect on LH. Opioids alter concentrations of GH through a GRF dependent and GRF independent pathway.

Animals↗
PubMed1990

Site and strand specificity of UVB mutagenesis in the SUP4-o gene of yeast.

DNA sequencing was used to characterize 208 mutations induced in the SUP4-o tRNA gene of the yeast Saccharomyces cerevisiae by UVB (285-320 nm) radiation. The results were compared to those for an analysis of 211 SUP4-o mutations induced by 254-nm UVC light. In each case, greater than 90% of the mutations were single base-pair changes but G.C----A.T transitions predominated and accounted for more of the mutations induced by UVB than UVC. Double substitutions, single base-pair deletions, and more complex events were also recovered. However, UVB induced 3-fold more tandem substitutions than UVC and nontandem double events were detected only after irradiation with UVC. Virtually all induced substitutions occurred at sites where the pyrimidine of the base pair was part of a dipyrimidine sequence. Although the site specificities were consistent with roles for cyclobutane dimers and pyrimidine-pyrimidone(6-4) lesions in mutation induction, preliminary photoreactivation data implicated cyclobutane dimers as the major form of premutational DNA damage for both agents. Intriguingly, there was a preference for both UVB- and UVC-induced mutations to occur at sites where the dipyrimidine was on the transcribed strand.

Base Sequence↗
PubMed1990

Active immunization of pigs against growth hormone-releasing factor: effect on concentrations of growth hormone and insulin-like growth factor 1.

Cyclic gilts (96 +/- 1 kg) were used to determine the effect of active immunization against growth hormone-releasing factor GRF(1-29)-NH2 on concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Gilts were immunized against GRF conjugated to human serum albumin (GRF-HSA, n = 5) or HSA alone at 180 d of age (wk 0). Booster doses were administered at wk 9 and 13. Seven days after the second booster (wk 14), blood samples were collected at 15-min intervals for 6 h before feeding and 30, 60, 120, 180 and 240 min after feeding. Eight days after the second booster, all gilts were administered a GRF analog, [desNH2Tyr1,Ala15]-GRF(1-29)-NH2, followed by an opioid agonist, FK33-824. Blood samples were collected at 15-min intervals from -30 to 240 min after injection. Immunization against GRF-HSA resulted in antibody titers, expressed as dilution required to bind 50% of [125I]GRF, ranging from 1:11,000 to 1:60,000 (wk 11 and 14); binding was not detectable or was less than 50% at 1:100 in HSA gilts (P less than .05). Episodic release of GH was abolished by immunization against GRF-HSA (P less than .05). Mean GH was decreased (P less than .07), but basal GH concentrations were not altered (P greater than .15) by immunization against GRF-HSA. Serum concentrations of IGF-1 were similar at wk 0, but concentrations were lower in GRF-HSA than in HSA gilts (P less than .05) at wk 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of prostaglandin on the reproductive performance of dairy cows.

A single injection of a synthetic analogue of prostaglandin F2 alpha (fenprostalene; Syntex) on the day of calving or between days 14 and 21 after calving did not affect the calving to first service interval, the number of services per conception or the conception rate of dairy cows. In a second trial, cows calved more than 45 days were injected once weekly with prostaglandin F2 alpha (dinoprost; Upjohn) or fenprostalene until served at the first detected oestrus. The calving to first service interval and the conception rate were not affected. Following injection of either prostaglandin, the spread in the pattern of onset of oestrus and the range in the proportion of cows (75 to 98 per cent) seen in oestrus within seven days were similar. This variation in the time of onset of oestrus after the administration of prostaglandin precludes limiting oestrus detection to four or five days per week, and is a major limitation to the use of prostaglandins in breeding programmes in dairy cows.

Animals↗
PubMed1989

Disruption of the RAD52 gene alters the spectrum of spontaneous SUP4-o mutations in Saccharomyces cerevisiae.

Defects in the RAD52 gene of the yeast Saccharomyces cerevisiae confer a mutator phenotype. To characterize this effect in detail, a collection of 238 spontaneous SUP4-o mutations arising in a strain having a disrupted RAD52 gene was analyzed by DNA sequencing. The resulting mutational spectrum was compared to that derived from an examination of 222 spontaneous mutations selected in a nearisogenic wild-type (RAD52) strain. This comparison revealed that the mutator phenotype was associated with an increase in the frequency of base-pair substitutions. All possible types of substitution were detected but there was a reduction in the relative fraction of A.T----G.C transitions and an increase in the proportion of G.C----C.G transversions. These changes were sufficient to cause a twofold greater preference for substitutions at G.C sites in the rad52 strain despite a decrease in the fraction of G.C----T.A transversions. There were also considerable differences between the distributions of substitutions within the SUP4-o gene. Base-pair changes occurred at fewer sites in the rad52 strain but the mutated sites included several that were not detected in the RAD52 background. Only two of the four sites that were mutated most frequently in the rad52 strain were also prominent in the wild-type strain and mutation frequencies at almost all sites common to both strains were greater for the rad52 derivative. Although single base-pair deletions occurred in the two strains with similar frequencies, several classes of mutation that were recovered in the wild-type background including multiple base-pair deletions, insertions of the yeast transposable element Ty, and more complex changes, were not detected in the rad52 strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Composition↗