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Biomedical subjects

R S Green

Publications and source records attributed to R S Green.

At least 37 records · Page 2Linked to original sources

Immunization of sheep against parasitic nematodes leads to elevated levels of globule leukocytes in the small intestine lumen.

In sheep that had been given three immunizing infections with Trichostrongylus colubriformis and Ostertagia circumcincta infective (L3) larvae, drenched after the last infection and challenged with larvae of the same species, there was a significant increase in numbers of small intestine mucosal tissue globule leukocytes (TGLs) and lumenal globule leukocytes (LuGLs) compared with sheep that had only been drenched and challenged. There was a positive correlation between the numbers of LuGLs and TGLs in the small intestine but the ratio of these two cell types was lower in non-immunized than immunized sheep. In immunized sheep positive correlations were observed between LuGLs and levels of arylsulphatase and peroxidase in the intestinal mucus and between arylsulphatase and larval migration inhibition (LMI) activity in mucus. Lumen eosinophils correlated with blood eosinophils, serum antibody against T. colubriformis correlated with peroxidase in the mucus and blood eosinophils correlated with nematode specific IgM levels in the intestinal mucus. In the abomasum, TGLs were present but not LuGLs. Sheep repeatedly infected with T. axei also had significantly more LuGLs in the small intestine than control animals. Two sheep that had a surgically prepared isolated small intestinal loop, after oral infection with T. colubriformis had TGLs and LuGLs in the intact intestine, but not in the isolated loop. Significantly more LuGLs were produced in sheep by allowing repeated T. colubriformis L3 infections to develop to adult stages compared to sheep treated with the same number of larvae, but where the infections were terminated by drenching at various intervals.

Animals↗

Variation in immune responsiveness of sheep to the antigens of intestinal nematodes and blowfly larvae.

The total and IgG1 antibody responses to the intestinal nematode parasites Haemonchus contortus and Trichostrongylus colubriformis were measured in the serum of 160 lambs, 4 months of age. These antibodies had developed as the result of natural exposure to the parasites on pasture. Three sires were examined and strong sire effects on half-sib progeny were found. Plotting of ELISA antibody results in two dimensions revealed clustering of responses within sire groups. Bimodal antibody distributions were also observed within sire groups and the whole population for T. colubriformis. A bimodal distribution of antibodies to H. contortus was found for one sire group but not for the whole population. The injection of blowfly larvae (Lucilia cuprina) extract into 42/160 lambs at a later age (12 months) was followed by increased antibodies to L. cuprina and an apparent increase in antibodies to T. colubriformis. A bimodal distribution for antibodies to L. cuprina was found in one sire group and in the whole population. These bimodal distributions of antibodies to L. cuprina did not coincide with the distribution of antibodies to T. colubriformis or H. contortus, measured on the same serum samples. It was concluded that high and low responder sire groups could be differentiated in lamb populations for all three parasites. These effects persisted during lamb maturation and appeared to be genetic effects. Finally, cross-reacting antibodies between L. cuprina and T. colubriformis appear to be stimulated by injection of L. cuprina antigens.

Animals↗

Genetic factors affecting antibody responses to four species of nematode parasite in Romney ewe lambs.

Serum levels of antibodies (Ab) and immunoglobulin G1 (IgG1) to the larval (L3) stage of the internal parasites Cooperia curticei and Trichostrongylus colubriformis and levels of Ab to the L3 stages of Haemonchus contortus and Ostertagia circumcincta were determined in 1432 Romney ewe lambs which were born on one farm in 1990 and 1991 and were the progeny of 63 rams. The objectives were to estimate heritabilities of, and genetic correlations among, the serum concentrations in newly weaned lambs under commercial conditions and to estimate genetic correlations of Ab and IgG1 with production traits. Lambs were exposed to a natural parasite challenge on pasture, following an anthelmintic drench at weaning. Blood and faecal samples from 4- to 6-month-old lambs were then taken when the mean faecal nematode egg count of a monitor group reached 800-1500 eggs g-1. Heritabilities for the serum levels of the four Abs ranged from 0.25 +/- 0.05 to 0.37 +/- 0.06. Heritabilities for the level of IgG1 developed against C. curticei was 0.19 +/- 0.04 and against T. colubriformis, 0.18 +/- 0.05. Genetic correlations between Abs for the 4 species were high, averaging 0.84, and between the two IgG1s it was 0.82. The genetic correlations between Ab or IgG1 levels and weight or gain traits were negative (for the 6 significant values out of 18), with yearling fleece weight positive (for the 2 significant values out of 6), whilst those with loge faecal egg count were all negative (average -0.15).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Identification of lysyl oxidase and other platelet-derived growth factor-inducible genes in vascular smooth muscle cells by differential screening.

BACKGROUND: Atherosclerosis and arterial injury are characterized by vascular smooth muscle cell (VSMC) migration and growth and an increase in synthesis of extracellular matrix. Platelet-derived growth factor (PDGF) has been implicated in these processes. This study was designed to identify additional PDGF-regulated genes in VSMC. EXPERIMENTAL DESIGN: A cDNA library prepared from PDGF-stimulated rat aortic VSMC was screened by differential hybridization to identify clones representing PDGF-inducible genes. The time course of growth factor-induced changes in gene expression was examined by RNA blot hybridization. Assays of protein activity were also performed for selected gene products. RESULTS: Four PDGF-regulated cDNA clones were identified by DNA sequencing. These encoded the extracellular matrix proteins lysyl oxidase (LO), thrombospondin, and osteopontin and the intracellular enzyme lactate dehydrogenase (LDH). Levels of mRNA corresponding to all four genes were low in quiescent VSMC and were markedly induced by PDGF, angiotensin II, and 10% calf serum. The regulation of LO and LDH mRNA by these agonists in VSMC has not been previously reported. LO enzymatic activity in the culture media was increased by approximately equals to 700% after exposure to PDGF. In contrast, LDH activity was not increased by PDGF treatment. CONCLUSIONS: The induction of LO mRNA and its secretion by VSMC is an early event accompanying growth factor stimulation and may contribute to organization of the extracellular matrix.

Angiotensin II↗

Cloning and expression of a novel acidic calponin isoform from rat aortic vascular smooth muscle.

The actin-binding protein calponin has been implicated in the regulation of smooth muscle contraction. We have isolated cDNA clones encoding a novel acidic calponin isoform from rat aortic vascular smooth muscle cells. The initial 273 residues of the deduced 330 amino acid polypeptide (M(r) 36,377) are highly homologous to basic smooth muscle calponin isoforms, but the remaining 57 residues at the carboxyl terminus comprise a unique and strongly acidic domain. The sequence of the acidic domain shows high homology (93.3% identity) to the partial sequence of HUMXT01244, an unidentified human hippocampal gene product (Adams, M., Dubnick, M., Kerlavgne, A. R., Moreno, R., Kelly, J. M., Utterback, T. R., Nagle, J. W., Fields, C., and Venter, J. C. (1992) Nature 355, 632-634). Transcripts encoding acidic calponin are expressed in cultured rat aortic vascular smooth muscle cells and in non-muscle and smooth muscle tissues of adult rat. Based on its calculated M(r) and the tissue distribution of its expression, acidic calponin is an excellent candidate for a previously detected non-muscle calponin homolog (Takeuchi, K., Takahashi, K., Abe, M., Nishida, W., Hiwada, K., Nabeya, T., and Maruyama, K. (1991) J. Biochem. (Tokyo) 109, 311-316). Like basic calponin isoforms, acidic calponin synthesized in a bacterial expression system bound F-actin. However, unlike basic calponin, the acidic isoform did not interact with Ca2+/calmodulin, indicating a functional distinction between the muscle and non-muscle forms.

Amino Acid Sequence↗

Antibody responses of sheep to challenge with Trichostrongylus colubriformis and the effect of dexamethasone treatment.

Eight-month-old random bred Romney wether lambs were reared nematode-free in pens and assigned to 4 groups each of 5 lambs. Lambs in 3 groups were infected orally, twice a week, with 5000 Trichostrongylus colubriformis infective larvae (L3), a control group remained unifected throughout. Two infected groups were treated with dexamethasone (0.5 mg kg-1 bodyweight), one between days -7 and 77, the other between days 77-154. Nematode challenge infection was withheld from the third group from day 133 after anthelmintic treatment. Nematode eggs in sheep faeces (FEC) were monitored at weekly intervals. T. colubriformis-specific antibody levels were determined twice a week and specific immunoglobulin isotypes (IgA, IgG1, IgG2 and IgM) determined weekly in serum samples using ELISA. Resistance, as measured by FEC, was expressed by 35 days after L3 infection began but sheep dosed with dexamethasone did not develop resistance. Extant resistance was abrogated in sheep dosed with dexamethasone. Nematode challenge resulted in elevated serum levels of antibodies to T. colubriformis L3 excretory/secretory antigens, these consisted predominantly of IgG1 and IgM. The IgG1 response was more persistent than the IgM response. Specific serum IgA and IgG2 responses were low, but significant, in nematode-challenge sheep. Dexamethasone treatment prevented the antibody responses and resulted in a rapid reduction of extant antibody levels in resistant sheep. Weight gain was reduced by nematode challenge with or without dexamethasone treatment compared with control sheep.

Animals↗

Association of blood eosinophilia with the expression of resistance in Romney lambs to nematodes.

The dynamics of blood eosinophilia was studied in Romney lambs dosed twice weekly with 5000 infective larvae of Trichostrongylus colubriformis. A marked rise in blood eosinophil counts of the dosed lambs coincided with the start of the decline of faecal egg counts (FEC). Eosinophilia was also studied in grazing Romney lambs from a breeding programme, based on selection for high or low FEC. Comparison of the sire groups suggested that the magnitude of the eosinophil response was under genetic control. The significant negative correlations between blood eosinophil counts and FECs confirmed the association between eosinophilia and the expression of resistance in Romney lambs to nematodes. However, comparison of the mean blood eosinophil counts and FECs for both the ram and ewe lambs of the resistance sire groups suggested that the association of eosinophilia and resistance may be greater for some sire groups than others.

Animals↗

JE mRNA accumulates rapidly in aortic injury and in platelet-derived growth factor-stimulated vascular smooth muscle cells.

The early response to vascular injury is characterized by migration of inflammatory cells, including monocytes, and platelets to the damaged vessel wall. These inflammatory cells may serve as a source of growth factors and cytokines that stimulate vascular smooth muscle cell (VSMC) migration and proliferation associated with intimal hyperplasia. JE is a platelet-derived growth factor (PDGF)-inducible "early" gene that encodes a monocyte chemoattractant and, as such, could play an important role in inflammation. We now report that JE mRNA levels are increased in intact aorta after balloon injury. The time course of this increase, with maximal levels at 4 hours, is similar to that seen in PDGF-treated cultured rat aortic VSMCs. The accumulation of JE mRNA in cultured VSMCs is accompanied by a marked increase in the secretion of JE protein. The elevation of JE mRNA levels in VSMCs shows specificity for PDGF, because angiotensin II, alpha-thrombin, and epidermal growth factor fail to increase JE mRNA levels. In contrast to 3T3 fibroblasts, the accumulation of JE mRNA in VSMCs in response to PDGF is predominantly due to an increase in JE mRNA stability. The accumulation of JE mRNA in VSMCs stimulated by PDGF appears to occur via a novel pathway(s) independent of Ca2+ mobilization, Na(+)-H+ exchange, protein kinase C activation, or elevation in cAMP levels. These findings suggest that VSMCs may take part in the early inflammatory response after injury through the production of JE, a potent monocyte chemoattractant. Finally, our data suggest that JE may be a marker for PDGF-specific effects on VSMCs, both in vitro and in vivo. Thus, in addition to direct effects on VSMC growth and migration, PDGF may play a role in the early inflammatory response after vascular injury by inducing chemoattractants, such as that encoded by JE.

Angiotensin II↗

Effect of prazosin on hypoxemia-induced blood flow redistribution in the newborn piglet.

We examined the effect of the alpha 1-adrenergic antagonist prazosin on blood pressure, left ventricular output and blood flow redistribution during normoxemia and mild hypoxemia in the chronically instrumented, unanesthetized newborn piglet employing the radiolabeled microsphere technique. Prior to prazosin, hypoxemia caused increases in aortic pressure and blood flows to the brain, myocardium and diaphragm, accomplished by small, statistically insignificant decreases in flows to the carcass and viscera without an increase in cardiac index. Prazosin treatment during normoxemia caused a fall in blood pressure and resulted in greater blood flows of left ventricular origin to the carcass, myocardium and lung. Hypoxemia after prazosin administration increased not only aortic pressure and blood flows to the brain, myocardium and diaphragm, but also, unlike the situation before drug treatment, cardiac index. Thus, in the newborn piglet, the maintenance of critical organ oxygen delivery during hypoxemia is not blocked by prazosin, but is accomplished by an increase in cardiac index rather than simply by redistribution of blood flow.

Animals↗

In vivo and in vitro inhibition of JE gene expression by glucocorticoids.

Glucocorticoids are potent anti-inflammatory agents which affect cell growth and migration in a wide variety of systems and have profound effects on monocytes, decreasing their circulating number as well as inhibiting their accumulation at sites of inflammation and injury. Although the mechanisms by which glucocorticoids regulate gene induction have been established, the mechanisms by which they inhibit inflammation or cell growth and migration have yet to been determined. JE is one of the most abundant genes induced by platelet-derived growth factor (PDGF) in vitro and is also induced in vivo in response to ischemia or injury. JE encodes a low molecular weight glycoprotein that functions in part as a monocyte chemotactic factor and thus may be important in recruiting monocytes to sites of tissue injury and/or inflammation. We report that glucocorticoids block the induction of JE mRNA by serum or PDGF in cultured vascular smooth muscle cells. The effect of glucocorticoids appears largely due to destabilization of JE mRNA and has specificity for JE, in that other "early" PDGF-inducible genes are not inhibited by glucocorticoids. The effect of glucocorticoids also occurs in vivo: methyl prednisolone blocks the constitutive expression and inhibits the ischemia-induced elevation of JE mRNA levels in rat kidneys. The inhibition of JE mRNA accumulation by glucocorticoids may be related to the anti-inflammatory effects of these agents and defines JE as a member of what may be a group of PDGF-inducible genes that are responsive to corticosteroids.

Animals↗

Adverse reproductive outcomes among female veterinarians.

Because female veterinarians are exposed to several known reproductive hazards, the authors conducted a reproductive survey of all female graduates of a US veterinary school (n = 537) and law school (comparison group, n = 794). Analysis was confined to pregnancies completed after the second year of professional school and from 1966 to 1986. Based on one randomly chosen eligible pregnancy per woman (veterinarians, n = 176; lawyers, n = 229), spontaneous abortion rates, adjusted for elective abortions, were 13.3% for the veterinarians and 15.1% for the lawyers; these did not differ significantly. A Cox life table regression model controlling for age, smoking, alcohol use, and prior spontaneous abortion also showed no significant difference in spontaneous abortion rates between the two populations. Using all pregnancies, veterinarians who reported performing five or more radiographic examinations per week had a marginally elevated risk of spontaneous abortion, but the statistical significance disappeared when analysis was limited to one random pregnancy per woman. For one random eligible birth per woman, the mean birth weight did not differ significantly between the veterinarians and lawyers, even after controlling for possible confounders in regression analyses. A higher rate of reportable birth defects was observed among the veterinarians than among the lawyers (relative risk = 4.2, 95% confidence interval 1.2-15.1), but this unexpected result must be considered hypothesis-generating. The authors did not find an overall increased risk for spontaneous abortion or low birth weight infants among veterinarians compared with lawyers, but veterinarians who reported performing five or more radiographic examinations per week may have been at increased risk for spontaneous abortion.

Abortion, Incomplete↗

Indomethacin reduces the risks of severe intraventricular hemorrhage.

A prospective, random selection, double-blind clinical trial was carried out to determine the efficacy of indomethacin in preventing periventricular-intraventricular hemorrhage (PV-IVH). Babies who were born in our institution, had birth weights less than or equal to 1500 gm, and had no PV-IVH or grade 1 PV-IVH were given either placebo (n = 70) or indomethacin (n = 71), 0.2 mg/kg intravenously at 6 hours of age and 0.1 mg/kg at 18 and 30 hours. Two major outcomes were determined: the development of grades 2 to 4 PV-IVH and the development of severe PV-IVH (i.e., hemorrhages with blood filling greater than 50% of the ventricles and in some cases with associated parenchymal echodensities). Grades 2 to 4 PV-IVH occurred in 16 (23%) of the indomethacin group and 27 (39%) of the placebo group (p less than 0.03). The incidence of severe PV-IVH was 3% in the indomethacin-treated babies and 14% in the control group (p less than 0.02). The influence of other perinatal factors on the incidence of grades 2 to 4 or severe PV-IVH was determined by stepwise logistic regression. Placebo use, early grade 1 PV-IVH, lower birth weight, and higher fraction of inspired oxygen at 6 hours of life were associated with higher estimated odds of the development of grades 2 to 4 PV-IVH. Placebo use, male gender, lower 5-minute Apgar score, and a large base deficit were predictive of severe PV-IVH. Estimated odds ratios of severe PV-IVH with placebo use and male gender were 11.25:1 and 9:1, respectively. Thus indomethacin prophylaxis reduced the relative risk of grades 2 to 4 PV-IVH and severe PV-IVH, but other perinatal variables contributed significantly to the overall risk of PV-IVH.

Apgar Score↗

Cell wall composition and surface properties in Bacillus subtilis: anomalous effect of incubation temperature on the phage-binding properties of bacteria containing varied amounts of teichoic acid.

Adsorption of bacteriophage SP50 to walls and heat-killed cells of Bacillus subtilis 168 appeared to be irreversible at both 37 and 0 degree C. Few, if any, active phage were desorbed when phage-wall complexes, formed at either temperature, were suspended in fresh medium. Bacteria rich in wall teichoic acid (TA) bound phage rapidly at both 0 and 37 degrees C, binding at the higher temperature being approximately twice as fast. Bacteria containing diminished proportions of TA showed less rapid phage adsorption but the reduction in rate was greater at 37 than at 0 degree C and bacteria containing only small proportions of TA bound phage more rapidly at 0 degree C than they did at 37 degrees C. These findings show that at low phage receptor density the temperature affects some component(s) involved in the phage-bacterium interaction such that the collision efficiency is increased at the lower temperature. The possible effect of temperature on the organization of bacterial surface components is discussed.

Bacillus subtilis↗

Selecting a rating scale for evaluating services to the chronically mentally ill.

A multi-attribute utility analysis employing ideal outcome measure criteria was applied to seven brief rating scales in order to identify the best performing instrument. A variety of judgmental data were collected from therapists working in mental health service agencies and from evaluation research experts to contrast the performance of the seven rating scales on criteria for selecting outcome measures developed by an NIMH task force. Transformations of the performance data were weighted in accordance with priorities assigned to the criteria by the task force. Comparing the sums of the weighted scores across scales, two rating scales emerged as preferred selections for monitoring the effectiveness of programs that serve the chronically mentally ill.

Chronic Disease↗

Acute renal failure in neonates: incidence, etiology and outcome.

Acute renal failure (ARF) occurs in as many as 8% of neonates admitted to neonatal intensive care units. Most often, ARF is recognized because of oliguria (urinary flow rate less than 1 ml/kg per hour) although nonoliguric neonatal ARF is being detected with increasing frequency. Among urinary indices utilized to differentiate oliguric neonatal ARF from prerenal oliguria, a fractional excretion of sodium greater than 3% or a renal failure index (RFI) greater than 3 are helpful in confirming ARF. Such indices must be viewed with caution in very premature infants who may have a physiologically high sodium excretion rate and in neonates with the nonoliguric form of ARF. The mortality of oliguric neonatal renal failure may be as high as 60% in medical ARF and even higher in neonates with congenital heart disease, or with anomalies of the genitourinary system. In contrast, nonoliguric renal failure in neonates has an excellent prognosis. Long-term abnormalities in glomerular filtration rate and in renal tubular function are common in survivors of neonatal ARF.

Acute Kidney Injury↗

Adrenergic mediation of vasopressin secretion in newborn pigs.

Effects of inhibition of alpha 1-(prazosin) and alpha 2-(yohimbine) adrenoreceptors on plasma lysine vasopressin concentration during normotension and hemorrhagic hypotension were studied in unanesthetized newborn pigs. During the normotensive period, treatment with prazosin and yohimbine both increased plasma lysine vasopressin concentration (vehicle = 3.4 +/- 1.21 microU/ml; prazosin = 35.8 +/- 10.8 microU/ml; and yohimbine = 20.1 +/- 9.5 microU/ml). Prazosin caused a decline in arterial pressure (vehicle = 60 +/- 6 mmHg; prazosin = 49 +/- 5 mmHg), which may account for the increase in plasma lysine vasopressin concentration, whereas yohimbine increased arterial pressure (73 +/- 3 mmHg). On hemorrhage to equivalent arterial pressure, plasma lysine vasopressin concentration increased to similar levels in vehicle- (110.3 +/- 28.7 microU/ml) and prazosin-treated (92.6 +/- 14.2 microU/ml) piglets. In contrast, on hemorrhage of yohimbine-treated piglets, the increase in plasma lysine vasopressin concentration was augmented remarkably (527.0 +/- 103.2 microU/ml) in comparison to the other groups. We conclude that, in unanesthetized newborn pigs, treatment with the alpha 2-adrenoreceptor antagonist yohimbine increased plasma lysine vasopressin concentration and markedly accentuated the vasopressin response to hemorrhage. An alpha 2-adrenergic receptor-mediated mechanism appears to be an important inhibitory component in the vasopressin secretory system of the newborn pig.

Animals↗