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Biomedical subjects

M J Murray

Publications and source records attributed to M J Murray.

At least 55 records · Page 3Linked to original sources

In vivo dynamics of axon pathfinding in the Drosophilia CNS: a time-lapse study of an identified motorneuron.

We developed a system for time-lapse observation of identified neurons in the central nervous system (CNS) of the Drosophila embryo. Using this system, we characterize the dynamics of filopodia and axon growth of the motorneuron RP2 as it navigates anteriorly through the CNS and then laterally along the intersegmental nerve (ISN) into the periphery. We find that both axonal extension and turning occur primarily through the process of filopodial dilation. In addition, we used the GAL4-UAS system to express the fusion protein Tau-GFP in a subset of neurons, allowing us to correlate RP2's patterns of growth with a subset of axons in its environment. In particular, we show that RP2's sharp lateral turn is coincident with the nascent ISN.

Animals↗

The incorporation of dietary n-3 polyunsaturated fatty acids into porcine platelet phospholipids and their effects on platelet thromboxane A2 release.

We investigated the dynamic changes in fatty acid (FA) composition in platelet phospholipid (PL) and in the release of thromboxane from stimulated platelets in pigs prefed a diet enriched with polyunsaturated fatty acids (PUFA) of the n-3 and n-6 families of FAs. For 20 days, we fed pigs diets supplemented with either corn oil, fish oil, or fish and borage oil. Platelets were separated from blood drawn at baseline and then on day 4, 8, 12, 16 and 20 of the dietary regimen. Analysis of the FA contained in platelet PL demonstrated that significant changes in PUFA composition occurred during dietary supplementation with fish oil and fish and borage oil. Eicosapentaenoic acid (EPA) from fish oil was rapidly incorporated into PL of platelets and reached a steady-state plateau by day 12. An increase in the content of docosahexaenoic acid (DHA) in the platelets' PL was observed in both groups receiving fish oil. This increase in n-3 PUFA in platelet PL occurred with a concomitant decrease in the content of n-6 FA, primarily of arachidonic acid (AA) in the PL of platelets in both fish oil groups. Dietary supplementation with borage oil, which contains gammalinolenic acid (GLA), increased dihomogammalinolenic acid (DGLA) content in platelet PL. Following A23187 stimulation of platelets, levels of thromboxane B2 (TxB2), the stable metabolite of thromboxane A2 (TxA2), were significantly suppressed in both fish oil groups compared to the corn oil-supplemented group. Dietary supplementation of EPA and EPA plus GLA increased platelet PL content of EPA, and EPA and DGLA, respectively. Following platelet stimulation, TxA2 production was significantly increased, an increase that was attenuated in the platelets from pigs prefed fish oil, and even more so in the fish and borage-oil-prefed pigs.

8,11,14-Eicosatrienoic Acid↗

Effects of omeprazole on healing of naturally-occurring gastric ulcers in thoroughbred racehorses.

Seventeen Thoroughbred horses with moderate to severe gastric ulceration were purchased from a race track within 10 days of racing and were treated once daily with either omeprazole (9 horses) or vehicle (8 horses) and evaluated gastroscopically for ulcer healing. Horses were administered omeprazole (1.5 mg/kg bwt/day) or vehicle by nasogastric tube once daily. Gastroscopic examination was performed on Days 0, 4, 7, 11, 14, 17, 21, 24 and 28, until lesions healed completely. Selected images of gastric lesions were captured by computer at each endoscopic examination, with a measuring caliper included in captured images. The area and perimeter of lesions were measured by computer and healing rates of specific lesions were determined by calculating the rate of linear advance of the margins toward the centre of the lesion. Additionally, the number of days to complete healing of the entire gastric squamous mucosa was compared between treatment groups. Gastric lesions healed at a significantly faster rate in horses receiving omeprazole than in vehicle-treated horses (P < 0.001). Complete healing of the entire stomach occurred in 10-21 days in omeprazole-treated horses, and 14-28 days in 3 of 8 vehicle-treated horses, with the remaining vehicle-treated horses having unhealed lesions on Day 28. In addition, 5 vehicle-treated horses developed new lesions in the squamous epithelial mucosa during the trial; no new lesions were observed in the omeprazole-treated group.

Animals↗

In vitro cytotoxic activity of equine lymphocytes on equine herpesvirus-1 infected allogenic fibroblasts.

The objectives of this study were to: (1) develop a technique to analyze the in vitro cytotoxic activity of lymphocytes from adult horses against equine herpesvirus-1 (EHV-1) infected allogenic equine dermal fibroblasts (EDF); (2) evaluate the ability of a 72-h in vitro incubation with interleukin-2 (IL-2) to enhance the lymphocytic cytolytic activity against EHV-1 infected EDF; (3) compare the cytotoxic activity of lymphocytes isolated from pregnant mares and non-pregnant mares against EHV-1 infected EDF; (4) ascertain if any correlations existed between the percent cytotoxicity and percentage of lymphocytes phenotypically identified by five different mouse-anti-equine monoclonal antibodies; and (5) determine if any correlation existed between virus-neutralizing antibody titers and the percent cytotoxicity. Results of the study indicate that in vitro cytotoxic activity of equine lymphocytes against EHV-1 infected allogenic fibroblasts can be measured with a standard 4-h 51Cr release assay. This activity was enhanced by an in vitro incubation with IL-2. The cytolytic activity of freshly isolated lymphocytes was greater for non-pregnant than pregnant mares. However, after IL-2 stimulation the cytolytic activity was greater for lymphocytes from pregnant mares. A positive correlation was not detected between the percentage of phenotypically identified cells and the percent cytotoxicity, although several negative correlations were present. This suggests that the cytotoxic activity was either not mediated by any of the phenotypically identified cell populations or that the activity was

Animals↗

Clinic follow-up from the emergency department: do patients show up?

STUDY OBJECTIVE: We examined the percentage of outpatient clinic appointments kept after referral from the emergency department. Several factors (age, sex, and specialty) were examined, to determine their effect on patient compliance. METHODS: This study was a retrospective review of the 503 appointments made in the orthopedic surgery, plastic surgery, gynecology, and urology clinics at Victoria General Hospital (VGH), Halifax, Nova Scotia, Canada, between January 1 and March 31, 1995, that were referred from the VGH ED. VGH is a 600-bed adult teaching hospital with 46,000 emergency visits each year. The patients ranged in age from 15 to 92 years. All of the patients were seen in the VGH ED and referred to an outpatient clinic in the VGH. RESULTS: Overall, 81.7% of appointments were kept. Orthopedic surgery had the best compliance rate (86.7%), gynecology the poorest (60.6%). Compliance rates increased with age, and male patients had a higher compliance rate than female patients. The average time between ED visit and outpatient appointment was 7.9 days, and 59.4% of the patients referred were male. CONCLUSION: The compliance rate at VGH is higher than any found in studies of similar American hospitals. We determined two main explanations for this phenomenon: (1) the ED clerk makes the outpatient clinic appointment before the patient leaves the ED and gives the patient a computer printout of the date and time of the appointment and a map with the location of the appointment circled, and (2) patients do not have to pay for outpatient clinic visits.

Adolescent↗

Rapid loss of oestrogen and progesterone receptors in human leiomyoma and myometrial explant cultures.

Oestrogen and progesterone are promoters of uterine leiomyoma growth: oestrogen receptors (ER) and progesterone receptors (PR) are over-expressed in these tumours. Paradoxically, there is a heterogeneity in responsiveness of leiomyoma growth to oestrogen and progesterone in culture. In this study, leiomyoma and adjacent myometrium were obtained at hysterectomy. The effect of oestrogen and progesterone on steroid receptor maintenance was examined using minced explants. Quantitative enzyme-linked immunoassay and Northern analysis were performed to assess ER and PR protein and mRNA content respectively. There was an approximately 75% decrease in ER and PR protein content within 8 h of incubation in both leiomyoma and myometrium. The presence or absence of oestrogen and/or progesterone had no effect on receptor protein loss. Northern analysis indicated a parallel loss of ER and PR mRNA transcripts. These findings suggest that the ER and PR expression in leiomyoma may require other extracellular factors. In-vitro studies designed to test the effects of sex steroids and their respective inhibitors on growth and function of leiomyoma and myometrial cells should consider this phenomenon.

Estradiol↗

Halothane resistance in Drosophila melanogaster: development of a model and gene localization techniques.

Studying genetically altered animals that are resistant to inhaled anesthetics may ultimately lead to an understanding of anesthetics' mechanism(s) of action. We studied the genetics of halothane resistance in a strain of Drosophila melanogaster that showed substantially increased resistance to halothane anesthesia. We developed a test method that allowed us to repeatedly observe several samples of flies exposed to the same concentration of halothane, and we measured halothane resistance. The 50% effective dose (ED50) of 91R flies (our resistant population) was greater than the ED50 of Canton-S (our control strain) by 69% in females and by 48% in males. By assessing the contributions of the three major chromosomes of Drosophila to resistance, this study found that the X and third chromosomes of 91R have no effect on resistance, while the second chromosome has a major impact. Resistance within the second chromosome was further localized by testing marked recombinant chromosomes. The central region of 91R's second chromosome, bounded by the genes for black thoracic color and cinnabar eye color, determined most if not all of the increase in resistance. We were not able to further localize resistance within this segment of the second chromosome (containing about 8% of the total genetic map distance). An autosomal dominant gene for halothane resistance in 91R was localized to a small region of the second chromosome.

Anesthetics, Inhalation↗

Equine herpesvirus type 2: prevalence and seroepidemiology in foals.

Whole blood and serum were collected from foals to determine the prevalence of Equine herpesvirus type 2 (EHV 2) infection in foals, age at which infection can first be identified and serological responses to infection. Equine herpesvirus type 2 was isolated from peripheral blood mononuclear cells (PBMC) from 68 of 69 foals, 1-8-months-old, sampled once. Virus isolation was performed twice at intervals of 2-7 months on PBMCs from 33 foals and EHV2 was isolated on both occasions in all but one foal (negative, then positive). Regression analysis of log2-transformed reciprocal serum EHV2 virus neutralising (VN) titres revealed that in foals age 1-7 months, EHV2 VN antibody titre was positively correlated with age (r = 0.94). Paired serum samples were obtained from 58 foals, with the first samples collected age 1-6 months and the second samples collected 2-4 months later. There were significant (P < 0.05) increases in mean VN titres to EHV2 in foals sampled initially at age 1-4. Eight foals had blood sampled prior to sucking and at age 7, 20, 30 and 45 days. Each foal was negative for EHV2 in PBMC and each foal had a negative serum EHV2 VN titre immediately after birth. Each foal was positive for EHV2 in PBMC by age 45 days, with the earliest isolation at 25 days. Tracheal aspirate fluid and peripheral blood were collected from 20 foals without clinical signs of respiratory disease and from 30 foals with clinical signs of lower respiratory disease. In 20 foals without clinical signs of respiratory disease, EHV2 was isolated from tracheal aspirates (1/20 foals) and PBMC (20/20 foals) and in 30 foals with such clinical signs, from trachea aspirates (20/30 foals: P < 0.01) and from PBMC (30/30 foals). In one 6-month-old foal, EHV1, but not EHV2, was isolated from the tracheal aspirate, 3 months after EHV2 had been isolated from a tracheal aspirate. These results demonstrate a greater prevalence of EHV2 in lower respiratory secretions in foals with clinically apparent lower respiratory disease, but a cause and effect relationship between the virus and lower respiratory disease remains to be elucidated. It is noteworthy, however, that of virus isolations performed on 50 tracheal aspirates, a virus (EHV1) other than EHV2 was isolated only once.

Actinomycetales Infections↗

Factors associated with gastric lesions in thoroughbred racehorses.

Gastroscopic examinations were performed on 67 Thoroughbred horses in training at a race track and repeat examinations performed in 35 horses, 2 to 3 months later. Horses were age 2-9 years and included 16 two-year-olds, 32 three-year-olds and 19 horses > or = 4-years-old. Forty-two of the 67 horses had raced within the 2 months before the initial examination and the remaining 25 horses were in training. Sixty-two of the 67 horses (93%) had one or more lesions present in the gastric mucosa and lesions were present in all of the 42 horses that had raced. Thirty-two of the 35 horses, examined twice (91%), had gastric lesions on the first examination and all had lesions on the second examination. Four sites of the gastric squamous epithelium were graded for lesion severity on a scale of 0 to 10 and the mean maximum squamous mucosal lesion score was significantly (P < 0.01) greater for the second examination (4.89) than for the first examination (3.63). Maximum lesion scores were greater in 24 horses, no different in 5 horses and less in 6 horses on the second examination. The difference in mean maximum lesion scores between examinations was greatest in horses age 2 years, increasing from 1.75 to 4.00 (P = 0.014). Lesions in the gastric glandular mucosa also were scored on a scale of 0 to 10 and there was no difference in mean lesion scores in the glandular mucosa between the first and second examinations (1.89 vs. 1.90). Lesion scores were compared for gender, racing history and medication with nonsteroidal anti-inflammatory drugs, systemic corticosteroid or ACTH, or frusemide within the previous 2 months. Except for racing history, there were no significant differences in mean lesion scores for squamous or glandular mucosa based on these comparisons, indicating that there was no effect of gender or medication history on ulcer severity in the horses of our study. Mean maximum gastric squamous mucosal lesion score was significantly (P < 0.01) greater in horses that had raced (4.51) than for horses that had not raced (2.36) in the 2 months before the endoscopic examination. There was no difference in mean glandular mucosal lesion scores between horses that had raced (1.93) compared to horses that had not raced (1.13).

Adrenal Cortex Hormones↗

Effects of epinephrine on regional free fatty acid and energy metabolism in men and women.

Upper-body and lower-body adipocytes respond differently to physiological catecholamines in vitro. It is not known whether this is true in vivo or whether gender differences exist in the regional adipose tissue responses to epinephrine. These studies were therefore conducted to examine free fatty acid (FFA) release ([3H]palmitate) from lower-body (leg), splanchnic, and upper-body adipose tissue in normal-weight adult men (n = 8) and women (n = 7). In response to intravenous epinephrine (10 ng.kg-1.min-1), palmitate release increased (P < 0.01) in both men (168 +/- 10 to 221 +/- 15 mumol/min) and women (177 +/- 12 to 234 +/- 18 mumol/min). Basal leg palmitate release was similar in women and men (16.8 +/- 2.9 and 12.4 +/- 1.3 mumol/min, P = not significant) but doubled (P < 0.01) in response to epinephrine in men and was virtually unchanged in women. Splanchnic palmitate release increased (P < 0.05) in men (n = 6) but not in women (n = 6), whereas nonsplanchnic upper-body palmitate release increased more in women than in men. Upper-body (splanchnic and nonsplanchnic) palmitate release increased (P < 0.05) in both men and women in response to epinephrine. In summary, lower-body adipose tissue FFA release increased in response to epinephrine in men but not women, whereas upper-body palmitate release increased in both groups. These findings are consistent with some in vitro findings and suggest that catecholamine action may play a role in determining gender-based differences in body fat distribution.

Adult↗