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Biomedical subjects

W H Johnson

Publications and source records attributed to W H Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1993

The effect of a depot injection of recombinant bovine somatotropin on follicular development and embryo yield in superovulated Holstein heifers.

Superovulated Holstein heifers (n = 32) were given a depot injection of 500 mg recombinant bovine somatotropin (rBST) or vehicle at Day 4 of the estrous cycle (7 days before the first FSH injection); at Day 11, coincidentally with the first FSH injection; or at Day 15, the time of artificial insemination. Embryos were collected nonsurgically, and the number of corpora lutea was counted by ultrasonography at Day 7 after insemination. Blood samples were taken every second day, from Day 2 of the superovulatory cycle until the day of embryo collection, and were analyzed for progesterone, somatotropin and insulin-like growth factor-1 (IGF-1). Somatotropin-treated heifers at Day 11 had a significantly higher mean number of corpora lutea than the controls (18.1 vs 13.4; P </= 0.05). Day 4 treatment tended to increase the mean number of corpora lutea (15.4; P <- 0.10), and significantly increased the overall percentage of transferable embryos (74.6 vs 58.6%; P </= 0.01). In the control animals, plasma IGF-1 was uncorrelated to somatotropin (P > 0.63), but it was negatively correlated with progesterone (P </= 0.01), suggesting that IGF-1 production in the superovulated heifer may be related to ovarian development.

Journal Article↗
PubMed1993

Motion sickness, vascular changes accompanying pseudo-coriolis-induced nausea.

We have previously shown that objective measurements of blood flow changes constitute a useful index in assessing susceptibility to nausea produced by cross-coupled angular accelerations (Coriolis stimulation). The findings of this study confirm the value of using the same technique for assessing the degree of nausea produced by pseudo-Coriolis effects.

Adult↗
PubMed1992

Scrotal circumference does not accurately predict degree of germinal epithelial loss or semen quality in yearling Hereford and Simmental bulls.

The accuracy of scrotal circumference as a predictor of specific pathologic changes within testicular parenchyma was assessed by scoring 121 Hereford and Simmental bulls for scrotal circumference, degree of germinal epithelial loss and semen quality. Scrotal circumference was not linearly related to the degree of germinal epithelial loss or to the percentage of tubules (Grade 4+ or higher, no germinal epithelium) for either breed (P>0.1). Thirty-two centimeters was the minimal acceptable scrotal circumference to ensure both a low prevalence of tubules with irreversible loss of germinal epithelium and acceptable semen quality. Scrotal circumference had a positive predictive value (the proportion of test-positive animals truly diseased) of 0.07 (95% confidence interval [CI] of 0 to 0.29) and a specificity (the proportion of test positive individuals that are diseased) of 0.89 (95% CI of 0.83 to 0.95) for 25% Grade 4+tubules. For acceptable semen morphology (>or=75% morphologically normal spermatozoa), scrotal circumference had a positive predictive value of 0.08 (95% CI of 0 to 0.34), a sensitivity (the proportion of diseased individuals testing positively) of 0.06 (95% CI of 0 to 0.24), and a specificity of 0.88 (95% CI of 0.80 to 0.95). For acceptable sperm motility (>or=30% progressively motile spermatozoa) scrotal circumference had a positive predictive value of 0.0 (95% CI of 0 to 0.22), a sensitivity of 0.0 (95% CI of 0 to 0.15), and a specificity of 0.87 (95% CI of 0.80 to 0.94). Although scrotal circumference is widely accepted as a useful test, its accuracy should be recognized as low when 32 cm is used as the minimal acceptable scrotal circumference in predicting unacceptable testicular histology or unacceptable semen quality in a healthy population of yearling bulls.

Journal Article↗
PubMed1992

Serum testosterone concentration in response to exogenous GnRH does not predict service rates or pregnancy rates by yearling, performance tested, crossbred bulls.

Ten bulls with a scrotal circumference of less than 30 cm at the end of growth performance testing, and 10 cohorts of the same age, size and breed type with a scrotal circumference greater than 30 cm were used to evaluate if testosterone response following GnRH administration could be used to test for fertility, for semen quality, and for specific pathologic testicular parenchymal changes. Serum testosterone concentrations were determined immediately before and 2 to 3 hours following intramuscular injection of 250 ug GnRH. Bulls were examined for breeding soundness, then fertility was tested in a breeding trial; testicular histology was assessed by determining the percentage of cross-sections of seminiferous tubules with no spermatocytes. The mean (+/-SEM) post-GnRH serum testosterone concentration for all bulls was 11.71 (+/-0.64) ng/ml. In order to examine for an association, the GnRH response was classified as above or below the mean for resultant serum testosterone concentration. The GnRH response classification was not related to the scrotal circumference, percentage of tubules devoid of spermatocytes, or percentage of progressively motile spermatozoa (P>0.10). The percentage of morphologically normal spermatozoa was significantly higher (P<0.05) in the bulls with a higher than mean testosterone secretion in response to GnRH injection. In the breeding trial, the percentage of heifers bred and the percentage of heifers pregnant (60 days post breeding) were not significantly different (P>0.10) between the 2 classifications of GnRH response. The GnRH response test was related to the percentage of morphologically normal spermatozoa but did not predict fertility of yearling bulls in this study.

Journal Article↗
PubMed1992

Measurement of the cytotoxic effects of different strains of Mycoplasma equigenitalium on the equine uterine tube using a calmodulin assay.

The cytopathic effects induced by five strains of Mycoplasma equigenitalium for cells of equine uterine tube explants were tested by measuring changes in cellular and extracellular concentrations of calmodulin (CaM). Calmodulin concentrations in samples of total homogenate (TH) and total homogenate supernates (THS) of the infected equine uterine tube explants were significantly lower than respective measurements on noninfected controls. In tissue culture medium fractions (TCM) of some infected explants, CaM concentrations were significantly higher than noninfected controls (p > 0.95). The results suggest that M. equigenitalium colonization on ciliated cells of the equine uterine tube can affect the permeability of the cell membrane leading to leakage or release of CaM during cell breakdown. Measurement of CaM concentrations in samples of TH revealed significant differences in the cytotoxic effects induced by different strains of M. equigenitalium on the equine uterine tube (EUT). The data suggests that some strains of M. equigenitalium may have a role in reproductive failure in the mare. In addition comparisons of the means of the concentrations of CaM in samples of TH or THS in EUT explants from four mares in the follicular and four in the luteal phase of the estrous cycle were found to be not significantly different.

Animals↗
PubMed1991

The effect of co-treatment with recombinant bovine somatotrophin on plasma progesterone concentration and number of embryos collected from superovulated Holstein heifers.

Mature Holstein heifers were induced to superovulate with twice-daily injections of porcine follicle-stimulating hormone (FSH), and were given either 20 mg i.m. of recombinant bovine somatotrophin (rBST) or saline with each FSH injection. The animals were artificially inseminated and the embryos were collected nonsurgically at Day 7. There was no significant difference in the mean (+/-S.D) total number of embryos collected from rBST-treated animals (8.3+/-5.3) when compared with that of the controls (7.2+/-6.6), or in the mean number of transferable embryos (5.3+/-4.0 vs 5.2+/-4.5). However, co-treatment with rBST tended to increase the ovulatory response, and it significantly increased plasma progesterone concentrations at Day 6 (P = 0.04). Based on these latter observations, we conclude that treatment with rBST enhanced the superovulatory response in heifers.

Journal Article↗
PubMed1991

Progesterone profiles in postpartum Holstein dairy cows as an aid in the study of retained fetal membranes, pyometra and anestrus.

This study was carried out to investigate the utility of enzymeimmunoassay (EIA) - derived progesterone profiles in the investigation of postpartum reproductive abnormalities and the effect of their use on reproductive performance in Holstein cows. Whole milk samples, collected twice weekly from parturition until confirmation of pregnancy or removal from the herd, were assayed for progesterone (P4) concentration using a commercially available microtitre plate EIA. The sensitivity, specificity, precision and accuracy were satisfactory to distinguish cyclic changes of P4 reflecting ovarian activity. The P4 profiles indicated that retained fetal membranes and anestrus were associated with increased mean intervals to first ovulation and first estrus (P < 0.05). The first luteal phase of cows with pyometra was prolonged compared with that of normal herdmates (P < 0.05). Anestrus cows had an increased number of ovulations before first service and before pregnancy (3.9 and 5.9) in comparison with normal herdmates (2.1 and 3.5; P < 0.05). Calving to pregnancy interval was increased above normal (74.8) for pyometra (125.0) and anestrus (152.7) (P < 0.05). Pregnancy rate for anestrus cows (82%) was lower than for normal cows (100%) and more anestrous cows were culled (27%) than normal cows (5%) (P < 0.5). The P4 profiles indicated that the major problem in the herd studied, anestrus (32% incidence rate), was most likely due to the failure to observe estrus rather than acyclicity.

Journal Article↗
PubMed1991

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 4. Addition of chromone moiety enhances leukotriene D4 receptor binding affinity.

The combination of the benzopyran-4-one ring, a moiety found in the prototype leukotriene antagonist, FPL 55,712, with the (2-quinolinylmethoxy)phenyl group led to a significant increase in leukotriene receptor binding affinity. This modification resulted in a 10,000-fold improvement in binding affinity compared to FPL 55,712. Compound 7 (RG 12553), with a Ki value of 0.1 nM, has higher affinity than the natural agonist LTD4 and is one of the most potent LTD4 antagonists reported. The structure-activity relationships of this series of potent leukotriene antagonists are discussed.

Animals↗
PubMed1991

Potent collagenase inhibitors prevent interleukin-1-induced cartilage degradation in vitro.

The matrix metalloproteinases (MMPs) collagenase, gelatinase and stromelysin, contribute to the destruction of articular cartilage which occurs during rheumatoid and osteoarthritis. Ro 31-4724, a substrate analogue containing a hydroxamic acid function, is a potent but non-selective inhibitor of all three MMPs (I50, collagenase = 10 nM), whereas Ro 31-7467, a phosphinic acid transition-state analogue, shows 14-fold and 12-fold selectivity for collagenase (I50 = 17 nM) over gelatinase and caseinase (stromelysin) respectively. The effects of these inhibitors on interleukin-1-induced bovine nasal cartilage degradation were examined. The hydroxamate Ro 31-4724 inhibits proteoglycan and collagen loss, whereas the phosphinic acid Ro 31-7467 selectively inhibits collagen breakdown in this model. This represents the first demonstration of potent and selective inhibition of IL1-induced cartilage degradation in vitro by MMP inhibitors. These results suggest that collagenase is responsible for collagen loss and that a different enzyme, possibly stromelysin, is responsible for proteoglycan degradation in this model.

Animals↗
PubMed1991

Developmental changes in ECG associated with heart rate are similar in squirrel monkey and human infants.

Interest in refining noninvasive methods of diagnosis and further characterization of squirrel monkeys (Saimiri sp.) as a model for pediatric cardiology studies led to this investigation of electrocardiogram (ECG) changes associated with changes in age and position. During a single delivery season, ECGs were performed at 1 day, 1 month, and 1 year of age. For each age group, ECGs were recorded with animals in dorsal, ventral, and right lateral recumbency. The 1-day-old group had the lowest heart rates (271 +/- 10, right lateral recumbency, mean +/- SEM) relative to the other age groups. One-year-old monkeys had heart rates of 333 +/- 18. One-month-old infants had rates significantly higher than the other two age groups (366 +/- 4). The QRS frontal-plane axis showed an age-related leftward change from 1 day (151 +/- 28 degrees) to 1 year of age (121 +/- 44 degrees) while the P-wave frontal plane axis remained nearly constant over a narrow range at all ages. The pattern of heart rate changes with age were similar to those in humans, although the ranges of absolute heart rates were markedly different. These data suggest that factors that influence maturational changes in heart rate, conduction time (as reflected by ECG intervals) and cardiac chamber size and position (inferred from axis and voltage) are similar among primates of widely variant body sizes.

Animals↗
PubMed1991

Endometrial biopsy in Holstein-Friesian dairy cows. I. Technique, histological criteria and results.

Endometrial biopsies were taken for histological assessment from 97 cows which calved in a commercial dairy herd between April and August 1984. Sixty-two cows were biopsied at both day 26 and 40 postpartum, 23 cows at only day 26, and 12 at day 40 only. Subjective and quantitative histological criteria were assessed. Ninety-five percent of biopsies were adequate for at least subjective assessment. The distribution of criteria within each horn-day category, as well as combined readings by day and by gravid or nongravid horn were computed and significant differences noted. There was more severe inflammation and more segmented cells at day 26 than 40 postpartum, and in the gravid compared to the nongravid horn. The distribution patterns for the criteria examined provide an overview of histological characteristics in this group of postpartum cows.

Animals↗
PubMed1990

Systemic heparinization does not prevent clot formation in coil embolization.

Therapeutic transcatheter closure with Gianturco-type steel coils has been applied to a variety of vascular communications in children with congenital heart disease. Vessel closure depends upon successful thrombus formation around the coil. Since systemic anticoagulation with heparin is commonly used during catheterization and cardiac surgery, we studied the effect of systemic heparinization on the efficiency of vessel occlusion by coil embolization in lambs. Catheters inserted in femoral arteries were used to arteriographically locate and size 36 systemic arteries in 9 lambs weighing 4.2 to 7.4 kg. Twenty-four vessels were embolized prior to heparinization with 400 u/kg heparin, IV. Effective anticoagulation was demonstrated by post-heparin activated clotting time (ACT) values greater than 300 sec. Seven vessels (29%) were not successfully coil-embolized because of inadequate coil position or distant embolization of the coil; 17 (71%) of these vessels were shown to be successfully occluded by arteriography 6 to 77 min later. After a period of systemic heparinization ranging from 71 to 159 min, 9/17 arteries remained occluded, 7/17 could not be examined arteriographically due to early demise of the animal, and only 1/17 showed recanalization. A second group of 12 vessels were embolized after heparinization. Eight (75%) were successfully occluded, and 4 (25%) were not successfully coil-embolized because of inadequate coil position or coil embolization to distant arteries. We conclude that systemic heparinization had no measurable effect on occlusion rates in coil-embolized systemic arteries in the lamb. These data support the use of systemic heparinization, when indicated, during or following therapeutic coil embolization in children.

Animals↗
PubMed1990

The effect of prostaglandin administration to Holstein-Friesian cows at Day 26 postpartum on clinical findings, and histological and bacteriological results of endometrial biopsies at Day 40.

Ninety-two cows that calved between April and August 1984 in a commercial dairy herd were studied. The cows were randomly assigned to receive either cloprostenol (500 mug) or saline placebo on Day 26 postpartum. In addition, each cow was examined per rectum, had three endometrial biopsies taken and milk progesterone level determined. Double-blind techniques were used in administering treatments and in assessing response to treatment. The results of histological and bacteriological assessment of endometrial biopsies and clinical findings at Day 40 were compared between the cows that received prostaglandin at Day 26 and those that did not. Each Day 40 variable which was significantly associated with prostaglandin treatment at Day 26 was regressed against the treatment variable and progesterone level at Day 26 as well as a prostaglandin progesterone interaction term. Prostaglandin-treated cows had less vaginal discharge, smaller diameter uterine horns, less inflammation and fibrosis in the endometrium, and were less likely to have Actinomyces pyogenes isolated from a biopsy at Day 40 than untreated cows. These effects were independent of progesterone level at the time of treatment.

Journal Article↗
PubMed1990

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships.

This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.

Animals↗
PubMed1990

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene D4 receptor antagonists. 2. Effects of an additional phenyl ring on receptor affinity.

This series of reports describe the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. The compounds reported in this paper contain an additional phenyl ring, which has significantly improved the receptor affinity. The effect of changes in the linkage between the two phenyl rings as well as the orientation of the acidic functional group on biological activity are discussed. Many of these compounds have high affinity to the sulfidopeptide leukotriene D4 receptors with Ki values ranging between 2 and 20 nM and are orally active. Compound 27 [RG 12525, 5-[[2-[[4-(2-quinolinylmethoxy)phenoxy]- methyl]phenyl]methyl]-1H-tetrazole] represents the best combination of in vitro and in vivo biological activity in this series and has been selected for further evaluation in clinical studies of asthma.

Animals↗
PubMed1990

The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency.

This paper is the third in a series outlining the development of orally active sulfido peptide leukotriene antagonists containing a (quinolin-2-ylmethoxy)phenyl moiety. In this work the systematic variation of the acid side chain substituents led to dramatic and reproducible changes in the oral activity of these compounds, presumably due to alterations in their pharmacokinetic properties. The most potent compound identified, 5-[4-[4-(quinolin-2-yl-methoxy)phenyl]-3-methylbutyl]tetrazole (32), represents a convergence of good in vitro antagonist activity and a 3-10-fold improvement in oral potency over the current clinical candidate 2. The new findings from these optimization studies are as follows: oxygen substitution in the acid side chain was not necessary for antagonist activity, in vitro and in vivo activity was enhanced by alkyl or phenyl substitution on the gamma-carbon of the acid side chain of para-substituted (quinolin-2-ylmethoxy)phenyl derivatives, and free rotation about the side chain carbon atom adjacent to the (quinolin-2-ylmethoxy)phenyl ring was required for activity. The lead compound of this report (32) is a competitive inhibitor of [3H]LTD4 binding to receptor membrane purified from guinea pig lung (Ki = 12 +/- 3 nM) and of the spasmogenic activity of LTC4, LTD4, and LTE4 in guinea pig lung strip. Dosed orally in guinea pigs, this compound blocks LTD4-induced bronchoconstriction (ED50 0.8 mg/kg) and antigen-induced systemic anaphylaxis (ED50 = 1.2 mg/kg).

Animals↗
PubMed1990

Failure to maintain interspecific pregnancy after transfer of Dall's sheep embryos to domestic ewes.

Over a 3-year period, 32 Dall's sheep (Ovis dalli dalli) embryos were transferred into 24 domestic sheep (O. aries) recipients and 4 were transferred into 2 Dall's sheep recipients. In the first year, none of the 10 O. aries recipients was diagnosed pregnant. In the following 2 years, 9 (37%) of the domestic sheep recipients were pregnant on Day 18, 8 (33%) on Day 40, 6 (25%) on Day 90 and 4 (16%) on Day 120; 1 aborted at Day 125 and another at Day 145. Pregnancies were established only in ewes that had previously been recipients of Dall's sheep embryos. The 2 remaining pregnant sheep were treated with progesterone from Day 125 until the fetuses were determined to be dead at Day 145. Both of the Dall's sheep recipients (Year 2) established pregnancies; 1 live Dall's sheep lamb was born 174 days after mating. No differences in serum progesterone, oestrone, prostaglandin F-2 alpha metabolites or cortisol concentrations could be detected during pregnancy between recipients carrying Dall's sheep embryos, recipients receiving progesterone treatment or domestic ewes carrying domestic sheep pregnancies. Six fetuses were necropsied (1 at Day 125 and 5 at Day 145-146): all fetuses were premature and had various degrees of hydranencephaly. No significant differences were found when cotyledon numbers were compared among domestic ewes carrying Dall's sheep lambs. Dall's sheep ewes lambing naturally and domestic ewes lambing naturally. These results demonstrate that the transfer of Dall's sheep embryos to domestic ewes results in the establishment but subsequent loss of pregnancy and that these losses occur throughout gestation.

Animals↗