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Biomedical subjects

S McDougall

Publications and source records attributed to S McDougall.

At least 55 records · Page 3Linked to original sources
PubMed1998

Efficacy of two antibiotic treatments in curing clinical and subclinical mastitis in lactating dairy cows.

AIM: To compare the bacteriological and clinical cure rates for clinical and subclinical mastitis in New Zealand dairy cows following treatment with either an intramammary penicillin-dihydrosptreptomycin preparation or a subcutaneous injection of penethamate hydriodide. METHODS: Milk samples were collected from clinical and subclinical cases of mastitis before and 14 and 21 days after initiation of treatment for bacteriological culture, somatic cell count determination and conductivity testing. RESULTS: No significant differences in the bacteriological cure rate of major Gram-positive pathogens, clinical cure rate, somatic cell count or conductivity were found between treatments. However, the bacteriological cure rate of coagulase-negative staphylococcus infections and the overall bacteriological cure rate was lower for quarters treated with penethamate than with penicillin-dihydrosptreptomycin. CONCLUSIONS: The bacteriological cure rate of mastitis caused by major Gram-positive pathogens, the clinical cure rate, somatic cell count and conductivity did not differ between the two antibiotic treatments. .

Journal Article↗
PubMed1997

Multiplex sequencing of 1.5 Mb of the Mycobacterium leprae genome.

The nucleotide sequence of 1.5 Mb of genomic DNA from Mycobacterium leprae was determined using computer-assisted multiplex sequencing technology. This brings the 2.8-Mb M. leprae genome sequence to approximately 66% completion. The sequences, derived from 43 recombinant cosmids, contain 1046 putative protein-coding genes, 44 repetitive regions, 3 tRNAs, and 15 tRNAs. The gene density of one per 1.4 kb is slightly lower than that of Mycoplasma (1.2 kb). Of the protein coding genes, 44% have significant matches to genes with well-defined functions. Comparison of 1157 M. leprae and 1564 Mycobacterium tuberculosis proteins shows a complex mosaic of homologous genomic blocks with up to 22 adjacent proteins in conserved map order. Matches to known enzymatic, antigenic, membrane, cell wall, cell division, multidrug resistance, and virulence proteins suggest therapeutic and vaccine targets. Unusual features of the M. leprae genome include large polyketide synthase (pks) operons, inteins, and highly fragmented pseudogenes.

Amino Acid Sequence↗
PubMed1996

Age-related changes in osteogenic stem cells in mice.

Osteoblasts arise from partially differentiated osteogenic progenitor cells (OPCs) which in turn arise from undifferentiated marrow stromal mesenchymal stem cells (MSCs). It has been postulated that age-related defects in osteoblast number and function may be due to quantitative and qualitative stem cell defects. To examine this possibility, we compared osteogenic stem cell number and in vitro function in marrow cells from 4-month-old and 24-month-old male BALB/c mice. Histologic studies demonstrated that these mice undergo age-related bone loss resembling that seen in humans. In primary MSC cultures grown in media supplemented with 10 nM dexamethasone, cultures from older animals yielded an average of 41% fewer OPC colonies per given number of marrow cells plated (p < 0.001). This implies that for a given number of marrow cells there are fewer stem cells with osteogenic potential in older animals than there are in younger animals. The basal proliferative rate in cultures from older animals, as measured by 3H-thymidine uptake, was more than three times that observed in cultures from young animals (p < 0.005). However, the increase in proliferative response to serum stimulation was 10-fold in the younger cultures (p <0.001) and insignificant (p <0.4) in the older cultures. Colonies in both age groups became alkaline phosphatase positive at the same rate, and virtually all colonies were positive after 12 days of culture. Cultures from both age groups produced abundant type I collagen. These studies suggest that defects in the number and proliferative potential of MSCs may underlie age-related defects in osteoblast number and function.

Aging↗
PubMed1996

Surface adhesion-mediated regulation of chondrocyte-specific gene expression in the nontransformed RCJ 3.1C5.18 rat chondrocyte cell line.

Recent evidence suggests that decreased chondrocyte function in osteoarthritis and other articular disorders may be due to chondrocyte dedifferentiation produced by altered regulatory signals from the cartilage extracellular matrix (ECM). However, there are currently no mammalian chondrocytic cell line systems adapted to the study of this process. We therefore examined the effects of ECM growth conditions on markers of differentiated chondrocytic phenotype expression in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line, including type II collagen expression, aggrecan production, link protein gene expression, and parathyroid hormone (PTH) receptor number. RCJ cells grown in monolayer on plastic exhibited a dedifferentiated phenotype characterized by flattened cell morphology, with > 80% type I collagen and < 5% type II collagen production, as determined by two-dimensional gel mapping electrophoresis of collagen cyanogen bromide peptides. In addition, aggrecan production was low, and link protein mRNA was not expressed at detectable levels. After transfer to growth under minimal attachment conditions on the surface of a composite type I collagen/agarose (0.15%-0.8%) gel (CAG) for 7 days, RCJ cells developed a rounded, chondrocytic morphology and a pattern of differentiated, chondrocytic gene expression, with 79% type II and 8% type I collagen production. Steady-state type I and type II procollagen mRNA levels were altered in parallel with collagen protein expression. In cells grown on CAG, aggrecan production increased 6-fold, and there was a marked increase in both aggrecan core protein and link protein mRNA levels. In addition, maximal PTH-stimulated cAMP generation increased 15-fold in association with an increased PTH receptor number. Therefore, the RCJ chondrocyte cell line is highly sensitive to ECM regulation of chondrocyte-specific gene expression.

Animals↗
PubMed1996

Prostaglandin E2 induces Egr-1 mRNA in MC3T3-E1 osteoblastic cells by a protein kinase C-dependent pathway.

Prostaglandin E2 (PGE2) plays an important role in the regulation of osteoblast metabolism. However, the nuclear signal transduction mechanisms involved in the actions of PGE2 have not been clearly defined. One mechanism may involve induction of immediate early genes such as the transcription factor Egr-1. In the present study, we examined the effects of PGE2 on induction of Egr-1 mRNA in MC3T3-E1 osteoblasts. Time course studies with 2 microM PGE2 showed maximal induction of Egr-1 mRNA at 30 min. In cells pretreated with cycloheximide (CHX), induction of Egr-1 mRNA reached a maximum at 60 min and remained elevated for at least 240 min. Preincubation with CHX was associated with superinduction of Egr-1. Inhibition of protein kinase C activity by pretreatment with 1 microM chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) attenuated the induction of Egr-1 mRNA by 2 microM PGE2. These data indicate that in MC3T3-E1 cells, PGE2 increase Egr-1 mRNA levels via a protein kinase C-dependent pathway.

Alkaloids↗
PubMed1996

Effects of prostaglandins on deoxyribonucleic acid and aggrecan synthesis in the RCJ 3.1C5.18 chondrocyte cell line: role of second messengers.

PGs play an important role in regulating articular chondrocyte function in both normal and pathological states. However, the mechanisms of the effects of PG on chondrocyte function remain undefined. We, therefore, examined the effects of PGE1, PGE2, and PGE2 alpha on second messenger generation in relation to DNA and aggrecan synthesis in the nontransformed rat RCJ 3.1C5.18 (RCJ) chondrocyte cell line. RCJ cells were grown under minimal attachment conditions on a composite collagen-agarose (0.15%/0.8%) gel to maintain a differentiated phenotype. PGE1 and PGE2 (0.001-100 microM) produced a similar dose-related increase in cAMP accumulation, with a maximal 8-fold increase over basal values, whereas PGF2 alpha produced a minimal 1.3-fold increase in cAMP levels only at 100 microM. On the other hand, both PGE2 and PGE2 alpha raised the intracellular free calcium ([Ca2+]i) concentration, derived primarily from extracellular sources, whereas PGE1 was without effect on [Ca2+]i. These three PGs also had divergent effects on DNA synthesis, as measured by [3H]thymidine ([3H]TdR) incorporation. PGF2 alpha (0.001-5 microM) produced a dose-related increase in [3H]TdR incorporation, with a maximal 1.6-fold increase over baseline values at 5 microM and a slight decline to below maximal levels at 10 microM. PGE2 exhibited a contrasting inverse biphasic response, with an initial small suppressive effect that was maximal at 0.1 microM and a secondary stimulatory phase producing a small increase over control values at 5 microM. PGE1 had a uniformly suppressive effect, producing a 30% decrease at 10 microM. Despite the divergent effects of PGE1, PGE2, and PGE2 alpha on second messenger generation and DNA synthesis, all three PGs produced a dose-related stimulation of aggrecan synthesis. PGF2 alpha was the most potent, producing significant stimulation at 0.001 microM and a maximal 104% increase at 5 microM. PGE1 and PGE2 were approximately equipotent and approximately 60% as effective as PGF2 alpha in stimulating aggrecan synthesis. Northern analysis demonstrated that the effects of PG on aggrecan synthesis were not accompanied by changes in aggrecan core protein steady state messenger RNA levels. Thus, the effects of PG on aggrecan production in RCJ cells appear to be regulated at the posttranscriptional level. Forskolin and (Bu)2cAMP mimicked the suppressive effects of PGE1 on [3H]TdR incorporation, as well as the stimulatory effect of PGE1 on aggrecan synthesis. In addition, the phorbol ester 12-O-tetradecanoyl phorbol acetate mimicked PGF2 alpha stimulation of [3H]TdR incorporation and aggrecan synthesis, and the effects of PGE2 alpha on these processes were blocked by protein kinase C inhibitors. Therefore, it appears that in mammalian chondrocytes, PGE1 primarily activates the cAMP-protein kinase A second messenger system, PGE2 alpha affects primarily the Ca2(+)-protein kinase C system, and PGE2 activates both pathways. Moreover, PG posttranscriptional regulation of aggrecan synthesis in chondrocytes involves both the cAMP-protein kinase A and Ca2(+)-protein kinase C second messenger systems.

Aggrecans↗
PubMed1995

Epidermal growth factor induces Egr-1 messenger RNA and protein in mouse osteoblastic cells.

The nuclear signaling events activated when epidermal growth factor (EGF) interacts with osteoblasts to produce effects on growth and differentiation are not clearly understood, and may include induction of immediate early genes such as Egr-1, a zinc finger transcription factor. In the present study, Northern analyses were performed to define the effects of EGF on the expression of Egr-1 mRNA in MC3T3-E1 mouse osteoblastic cells. Following treatment of quiescent, subconfluent MC3T3-E1 cells with 0.1-100 ng/ml EGF for various periods, maximal induction of Egr-1 mRNA occurred when cells were treated for 30-60 minutes with 1-10 ng/ml EGF. Inhibition of protein kinase C activity by pretreatment with 1 microM chelerythrine chloride or by prolonged stimulation with 50 ng/ml tetradecanoyl phorbol acetate (TPA) partially diminished the induction of Egr-1 by EGF. Using an immunohistochemical approach, 10 ng/ml EGF was observed to induce Egr-1 protein within 30-60 minutes and this induction was localized to the nucleus. These observations indicate that EGF induces Egr-1 mRNA and protein via protein kinase C and other signaling pathways, and that Egr-1 may be part of the regulatory network mediating the actions of EGF on growth and differentiation of osteoblasts.

Animals↗
PubMed1995

Patterns of follicular development during periods of anovulation in pasture-fed dairy cows after calving.

The ovaries of 17 Friesian cows aged two to seven years were examined daily by transrectal ultrasound from one week after calving. The position and size of all follicles more than 2 mm in diameter were recorded. A large (more than 9 mm in diameter) follicle was present on at least one ovary by six to 17 days after calving, and in two of the cows it ovulated; the remaining cows had from two to nine large follicles before they ovulated. The mean (SEM) interval from calving to the first ovulation was 43.4 (5.3) (range 13 to 93) days, after 4.2 (0.6) waves of follicles.

Animal Feed↗
PubMed1995

Some effects of feeding pasture silage as a supplement to pasture on reproductive performance in lactating dairy cows.

Supplementation of a ryegrass/white clover pasture diet with pasture silage is a common management practice in New Zealand dairy herds. The effect of this supplementation on reproductive performance has not been investigated. Five herds of 20 cows were formed before calving commenced on 1 June 1992. From 5 August to 4 September, two of these herds were fed 5 kg/cow/day of pasture silage in addition to the ryegrass/white clover pasture offered to all herds. Pasture silage supplementation did not alter the intervals from calving to first ovulation, first oestrus, or to conception. However, it reduced the first service conception rate (37.5% v. 53.3%; difference +/- sed = 15.8 +/- 10.0%, for pasture and silage and pasture only cows, respectively). A positive effect on reproductive performance of pasture silage supplementation was not demonstrated in this trial.

Journal Article↗
PubMed1995

Physiological effects of undernutrition on postpartum anoestrus in cows.

The focus of this review is the physiological effects of undernutrition on ovarian follicle growth and the occurrence of ovulation in postpartum cows. Evidence suggests that moderate levels of underfeeding, before or after calving, may interfere with the mechanism(s) of final follicle maturation and ovulation, whereas more pronounced nutritional deficiencies may affect the mechanism(s) regulating dominant follicle size and the dynamics of dominant follicle growth and regression. Severe undernutrition may result in the absence of follicles > 5 mm in diameter. These changes are consistent with likely effects of reduced LH or FSH secretion that have been associated with inhibition of both tonic and surge release of GnRH from the hypothalamus. As yet, there is no direct evidence for local effects of undernutrition on ovarian function in cows, and studies examining this tissue often ignore dynamic interdependencies between the hypothalamus, anterior pituitary gland, and the ovaries, and possible nutritional modulation of ovarian feedback mechanisms that affect gonadotrophin secretion. Further research is required to elucidate nutritional effects on the positive feedback regulation of gonadotrophin secretion and on the expression of behavioural oestrus. Further studies are also needed to determine whether nutritional or metabolic state may influence ovarian function directly in a manner that affects the duration of postpartum anoestrus and fertility in postpartum cows.

Anestrus↗
PubMed1994

Learning to read: the role of short-term memory and phonological skills.

This study investigates the relationships between reading, short-term memory and phonological skills, and the mechanisms responsible for the short-term memory differences found between groups of children differing in reading ability. Differences were found between groups of good, average, and poor readers in verbal, but not visual, short-term memory and these differences were well explained in terms of differences in speech rate (an index of rehearsal rate) between the groups. Measures of phonological ability, rhyme awareness and phoneme deletion, also showed strong differences between the different reading ability groups. Regression analyses showed that rhyme awareness, phoneme deletion, and speech rate (but not verbal short-term memory) had independent predictive relationships to reading skill. These findings show that phonological skills do not represent a unitary trait, and that different facets of phonological ability are important in predicting the development of reading skills.

Child↗
PubMed1994

GATA elements are necessary for the activity and tissue specificity of the T-cell receptor beta-chain transcriptional enhancer.

Three high-affinity binding sites for the GATA family of transcriptional regulators have been identified within the T-cell receptor beta-chain (TCR beta) transcriptional enhancer, and their functional significance has been determined in an effort to understand the T-cell specificity of the enhancer more fully. One site, TE4, is important for activity of the enhancer in T cells. Neither site TE1 nor site TE2 can functionally replace a mutated TE4 site in T cells; however, the same protein, probably GATA-3, binds all three sites, as judged by electrophoretic mobility shift, oligonucleotide competition, and proteolytic clipping assays. These data suggest that additional proteins are critical for the ability of GATA-3 to activate the TCR beta enhancer. In fibroblasts, the GATA sequence at site TE1 appears to bind a negative regulator. Since this is not true in B cells, B cells and fibroblasts appear to have different mechanisms for negative regulation of the TCR beta enhancer.

Animals↗
PubMed1991

Cellular immunosenescence: an overview.

Recent studies on space flights suggest that certain T cell immunologic activities are vulnerable to microgravitation. It would be desirable to know the extent to which these changes can be prevented or reversed. Since the changes observed are analogous to the effects of aging on immunity, a brief overview is presented of our current knowledge of age-related changes in immune cells and of the various interventional methods which have been used successfully in preventing the decline with age and in elevating the levels of immune functions of old individuals.

Aging↗
PubMed1990

Mechanisms of thymic lymphomagenesis by the retrovirus SL3-3.

These studies report changes occurring in the thymus of AKR and NFS/N mice after infection with the lymphomagenic retrovirus SL3-3. In virus-infected AKR fetal thymus, the programmed cell death caused by treatment with antibody to CD3 was remarkably diminished. A method of establishing thymic stromal cultures from mice of 1 to 3 wk of age is described. Using this method, it was found that SL3-3 virus infection by neonatal inoculation allowed establishment of thymic stromal cultures from organs removed from AKR mice of 30 to 50 days of age and from lymphomas, whereas thymic stromal cultures could not be established from control mice after 30 days of age. Using NFS/N mice which have no endogenous virus, it was shown that infection of thymic stroma precedes infection of thymocytes and that thymocytes are permissive for infection with SL3-3 virus but not for the nononcogenic retrovirus, Akv, yet Akv virus replicates efficiently in thymic stroma. SL3-3 virus integrates randomly in each lymphoma induced by this virus. The lymphomas are clonal or oligoclonal. Pim-1 and c-myc genes commonly rearranged in other virus-induced thymic lymphoma showed rearrangement in only a few lymphomas. A theory is proposed, based on the work presented here and in recent studies, which states that SL3-3 virus infection of thymic stroma allows infection of thymocyte progenitors entering from the bone marrow. These cells are then altered so that their maturation is delayed and their intrathymic survival is prolonged. This permits virus integration and reintegration that results in the genetic changes which transform the cell.

Animals↗