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J J Murphy

Publications and source records attributed to J J Murphy.

At least 19 recordsLinked to original sources
PubMed2007

Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.

OBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C). CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.

Adult↗
PubMed2006

Embryo survival in dairy cows managed under pastoral conditions.

Efficient pasture-based milk production systems require a compact calving pattern aligned to the onset of the grazing season, a 365-day calving interval and low culling rates for infertility. Achievement of these targets requires high herd reproductive performance. While high genetic merit Holstein cows produce more milk in grass-based systems their fertility is compromised. Management of the modern high genetic merit Holstein dairy cow presents a major challenge in pasture-based systems of production. It appears that the extent of early embryo loss is greater (up to 20% points greater) in the modern high-producing dairy cow and that a much higher proportion of the embryos die before day 7 following insemination in contrast to heifers and lower yielding cows. About 7-8% of pregnancies are lost between days 30 and 90 of gestation with no evidence that loss rate is related to cow genetic merit, parity or level of production. Systemic concentrations of progesterone during both the cycle preceding and following insemination affect embryo survival rate with evidence that too low or indeed too high a concentration of progesterone been negatively associated with embryo survival rate. Peripheral concentrations of both progesterone and oestradiol are lowered by increased plane of feed intake due to increased metabolic clearance rate of the steroids, which is related to liver blood flow. It appears that high producing dairy cows have an increased risk of embryo death as a result of lowered peripheral concentrations of progesterone as a consequence of increased hepatic metabolism of progesterone. Uterine expression of mRNA for progesterone receptor, oestradiol receptor and retinol binding protein mRNA appears to be sensitive to changes in peripheral concentrations of progesterone during the first week after AI. It would appear that energy balance and dry matter intake during the 4 weeks, immediately after calving are critically important in determining conception rate when cows are inseminated at 70-100 days post-calving. Concentrate supplementation of cows at pasture during the breeding period has minimal affects on conception rates though sudden reduction in dietary intake should be avoided. For pasture-based systems of milk production more balanced breeding strategies, with greater emphasis on fertility and feed intake must be developed.

Animal Husbandry↗
PubMed2006

Effect of milking frequency and diet on milk production, energy balance, and reproduction in dairy cows.

The objective of this study was to determine the effects of reduced milking frequency and increased dietary energy density in early lactation on milk production, energy balance, and subsequent fertility. Sixty-six spring-calving, multiparous Holstein-Friesian cows were assigned to 1 of 3 treatment groups: once-daily milking on a standard diet (1xST); 3-times daily milking on a standard diet (3xST); and 3-times daily milking on a high-energy diet. Treatments were imposed for the first 28 d of lactation, after which all groups were milked twice daily and fed the standard diet. During the treatment period, the 1xST cows had 19.6% lower milk yield and higher milk fat and milk protein concentrations (15.7 and 10.2%, respectively) compared with 3xST. Dry matter (DM) intake was similar between 1xST and 3xST during the treatment period (12.64 vs. 13.25 kg/ d; SED = 0.82). Daily energy balance was less negative for 1xST compared with 3xST during wk 1 to 3 of lactation [-3.92 vs. -5.30 unité fourragère lait (UFL)/d; SED = 0.65; 1 UFL is equal to the net energy for lactation of 1 kg of standard air-dry barley]. During the treatment period, the cows on the high-energy diet had 17% higher milk yield, higher DM intake (15.5 vs. 13.9 kg/d; SED = 0.71), and similar energy balance (-4.45 vs. -4.35 UFL/d; SED = 0.65) compared to 3xST. Diet had no significant effect on any of the fertility variables measured. The interval to first ovulation was shorter for 1xST than 3xST (18.3d vs. 28.6d; SED = 1.76). In conclusion, once-daily milking in early lactation may promote earlier resumption of ovarian cyclicity, mediated through improved nutritional status.

3-Hydroxybutyric Acid↗
PubMed2005

Effects of diets fed to dairy cows before and after calving on their plasma progesterone profiles after calving.

Four weeks before their predicted mean second lactation calving date, 60 spring-calving Holstein-Friesian cows were blocked into groups of six on the basis of their predicted calving date and body condition score, and allocated at random to one of six dietary treatments in a factorial design: ad libitum grass silage, ad libitum grass silage plus barley straw or ad libitum grass silage plus 3 kg of concentrates, was offered for four weeks before the expected calving date, and after calving they were offered either 4 kg or 8 kg of concentrates plus ad libitum grass silage for eight weeks. On average, the first luteal activity occurred in all the groups at 29 days after calving. Seventeen of the cows had an atypical first plasma progesterone profile; 12 were anovulatory, three had prolonged luteal phases and two became anovulatory after having been cyclic. The cows offered grass silage only before calving had a significantly shorter mean (se) interval between calving and second luteal activity (44.9 [2.1] days), than the cows offered grass silage and straw (53.5 [1.9] days) or grass silage and concentrates (51.5 [3.2] days) (P<0.05). After calving none of the 28 cows offered grass silage and 4 kg of concentrates started cycling before day 21, whereas five of the 30 cows offered grass silage and 8 kg of concentrates cycled before day 21 (P<0.05).

Animal Feed↗
PubMed2005

One year results of the Middlesbrough early revascularisation to limit infarction (MERLIN) trial.

OBJECTIVE: To report one year results of the MERLIN (Middlesbrough early revascularisation to limit infarction) trial, a prospective randomised trial comparing the strategy of coronary angiography and urgent revascularisation with conservative treatment in patients with failed fibrinolysis complicating ST segment elevation myocardial infarction (STEMI). The 30 day results have recently been published. At the planning stage of the trial, it was determined that follow up of trial patients would continue annually to three years to determine whether late benefit occurred. SUBJECTS: 307 patients who received a fibrinolytic for STEMI but failed to reperfuse early according to previously described ECG criteria and did not develop cardiogenic shock. METHODS: Patients were randomly assigned to receive either emergency coronary angiography with a view to proceeding to urgent revascularisation (rescue percutaneous coronary intervention (rPCI) arm) or continued medical treatment (conservative arm). The primary end point was all cause mortality at 30 days. The secondary end points included the composite end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure at 30 days. The same end points were evaluated at one year and these results are presented. RESULTS: All cause mortality at one year was similar in the conservative arm and the rPCI arm (13.0% v 14.4%, p = 0.7, risk difference (RD) -1.4%, 95% confidence interval (CI) -9.3 to 6.4). The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure was significantly higher in the conservative arm (57.8% v 43.1%, p = 0.01, RD 14.7%, 95% CI 3.5% to 25.5%). This was driven almost exclusively by a significantly higher incidence of subsequent unplanned revascularisation in the conservative arm (29.9% v 12.4%, p < 0.001, RD 17.5%, 95% CI 8.5% to 26.4%). Reinfarction and clinical heart failure were numerically, but not statistically, more common in the conservative arm (14.3% v 10.5%, p = 0.3, RD 3.8%, 95% CI -3.7 to 11.4, and 31.2% v 26.1%, p = 0.3, RD 5.0%, 95% CI -5.1 to 15.1). There was a strong trend towards fewer strokes in the conservative arm (1.3% v 5.2%, p = 0.06, RD -3.9%, 95% CI -8.9 to 0.06). CONCLUSION: At one year of follow up, there was no survival advantage in the rPCI arm compared with the conservative arm. The incidence of the composite secondary end point was significantly lower in the rPCI arm, but this was driven almost entirely by a highly significant reduction in the incidence of further revascularisation.

Adult↗
PubMed2003

Effect of offering rumen-protected fat supplements on fertility and performance in spring-calving Holstein-Friesian cows.

The objective of this study was to evaluate the effect of two different rumen-protected fat supplements, on reproductive performance and milk production, in grass-based spring calving cows. Two hundred and one Holstein-Friesian cows with an average lactation number of 3.6 (20% first lactation, 16% second lactation and 64% third lactation or greater) were grouped into blocks of three on the basis of calving date, lactation number and previous lactation milk yield for cows of second lactation or greater and on the basis of calving date for first lactation animals. From within-blocks individual animals were assigned at random, within 10 days post-calving, to one of the following three treatments: (1) Megalac Plus 3% (MP; 0.4kg/day, containing Ca salt of palm fatty acids and Ca salt of methionine hydroxy analogue), (2) Megapro Gold (MPG; 1.5kg/day, containing Ca salt of palm fatty acids, extracted rapeseed meal and whey permeate), and (3) Control (C; unsupplemented). Cows were supplemented for on average 103 days (range 54-134 days). The average milk yield over the first 12 weeks of lactation was higher (P<0.05) for both fat supplements compared to C and was higher for MP compared to C over the full lactation. Both supplements reduced (P<0.05) milk protein concentration over the first 6 weeks of lactation. MPG increased (P<0.05) conception rate to first service compared to C. Conception rate to first service was similar (P=0.14) on MP compared to C. For pregnancy to second service, C had a higher (P<0.05) conception rate than MP. There were no significant differences between treatments in overall pregnancy rate, services per conception, number of cows served in the first 3 weeks of the breeding season or the 6-weeks in-calf rate. Comparing the combined fat treatments to C resulted in a higher (P<0.05) conception rate to first service for the fat treatments but no significant difference in overall pregnancy rate. In conclusion, fat supplements increased conception rate to first service but did not significantly affect the proportion of cows pregnant at the end of the breeding season.

Animals↗
PubMed2003

The prevalence and clinical significance of autoantibodies to plasminogen activator inhibitor 1 in systemic lupus erythematosus.

We have recently described the novel autoantigen plasminogen activator inhibitor (PAI-1) in systemic lupus erythematosus (SLE). The aim of this study was to determine the prevalence and clinical significance of anti-PAI-1 autoantibodies in patients with SLE. Autoantibodies to recombinant PAI-1 were measured in retrospective sera of 48 lupus patients by immunoassay in order to assess their clinical significance. This showed that 71% of sera from 48 lupus patients had significantly elevated anti-PAI-1 autoantibodies as compared with normal control subjects (P < 0.0001). There was a weak but significant (P < 0.043) correlation with anti-dsDNA autoantibodies. In longitudinal studies, autoantibodies against PAI-1 correlated with clinical parameters measured by the BILAG disease activity index including global clinical score. Our study demonstrates the high frequency of novel autoantibodies to PAI-1 in patients with lupus. The serial clinical correlations with anti-PAI-1 autoantibodies also support the hypothesis that these autoantibodies may play a pathogenic role in lupus.

Adult↗
PubMed2003

Peritoneal involvement in stage II colon cancer.

A pathologist (K.S.) reviewed histologic slides for peritoneal involvement by tumor cells for 118 patients with stage II colon cancer. Patients were followed up for a median of 6 years. Tumor cells were found free in the peritoneal space in 16 cases (13.6%). The presence of cancer cells free in the peritoneal space was associated with lymphovascular invasion (P = .001) and neural invasion (P < .001). The overall 5-year survival was 80% in the patient population, but was 39% and 86% for those with and without tumor cells free in the peritoneal space, respectively (P < .0001). Multivariate analysis confirmed that free tumor cells within the peritoneal space (P < .0001) and lymphovascular invasion (P = .007) were related independently to outcome. Peritoneal involvement with tumor cells free in the peritoneal space in stage II colon cancer is a powerful indicator of outcome; patients have a survival similar to that for patients with stage III disease.

Adult↗
PubMed2003

Evaluation of different energy feeding systems with production data from lactating dairy cows offered grass silage-based diets.

A set of data from 838 lactating dairy cows, drawn from 12 long-term feeding studies (at least 8 wk/period), was used to evaluate the energy feeding systems for dairy cows currently adopted in Australia, France, The Netherlands, the United Kingdom, and the United States. The animals were offered mixed diets of concentrates, forage [grass silages (n = 33) and corn silages (n = 5)] ad libitum. Data used in the present evaluation were either measured [dry matter (DM) intake, milk production and live weight], measured/estimated [dietary metabolizable energy (ME) concentration] or estimated [milk energy output and live weight change (LWC)]. The mean-square prediction error (MSPE) was used for the evaluation. Total ME intake, milk yields, and LWC varied from 91 to 338 MJ/d, 7.7 to 48.9, and -1.23 to 1.73 kg/d, respectively. Australian and French systems predicted total energy requirement and milk yield relatively well, while British, Dutch and American systems underpredicted total energy requirement by proportionately 0.06, 0.04, and 0.03, respectively; and overpredicted milk yield by 0.09, 0.06, and 0.04. The Agricultural and Food Research Council (AFRC) each produced a relatively larger error of the bias (predicted - actual data) over the total MSPE for ME requirement and milk yield and a relatively smaller error of random than other systems. However, an addition of proportionately 0.05 to the total predicted ME requirement of AFRC, as suggested in this system and currently used in the UK, indicated the prediction accuracy of ME requirement and milk yield is similar to Australian and French systems. Nevertheless, all the systems had a poor prediction of LWC. For each system, the total prediction error (total MSPE) was mainly derived from the line (slope; 0.49 to 0.64 of total MSPE), while less derived from the random (0.20 to 0.48 of total MSPE), indicating a large variation between the predicted and actual LWC existed among individual cows. The residual plots of the residual differences in LWC against predicted LWC revealed that the prediction error was greater with increasing LWC. It is concluded that Australian and French systems have a better prediction of total energy requirement and milk yield than other systems, and LWC is an inappropriate indicator of energy balance in lactating dairy cows.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Effects of different transition diets on dry matter intake, milk production, and milk composition in dairy cows.

The primary objective of this study was to evaluate the effect on dry matter intake (DMI), milk yield, milk composition, body weight (BW), and body condition score (BCS) change of cows offered diets differing in energy density in the last 4 wk of gestation and in the first 8 wk of lactation. Three diets (grass silage:straw, 75:25 on a dry matter basis (SS), grass silage (S), and grass silage + 3 kg concentrate daily (C)) precalving, and two diets (4 kg [LC] or 8 kg [HC] concentrate daily + grass silage ad libitum) postcalving were combined in a 3 x 2 factorial design. Sixty Holstein-Friesian cows entering their second lactation were blocked according to expected calving date and BCS into groups of six and were then allocated at random to the treatments. Individual feeding started 4 wk prior to the expected calving date and measurements were made until the end of the 8th wk of lactation. Mean DMI differed between each of the precalving treatments (7.4, 8.1, and 9.9 kg/d for SS, S, and C, respectively) in the precalving period. The DMI also differed between SS and C for wk 1 to 8 (13.5 and 14.2 kg/d) postcalving. Postcalving, milk (24.2, 26.2, and 28.2 kg/d), fat (933, 1063, and 1171 g/d), and protein (736, 797, and 874 g/d) yields differed between SS, S, and C, respectively. The BCS changes differed between SS and C (-0.09 and 0.12 of a BCS) in the precalving period and between SS and S compared with C (0.02, 0.06, and -0.26 of a BCS) for wk 1 to 8 postcalving. The BW change differed between SS and S compared with C in both wk 1 to 4 (-0.23, -0.37, and -1.25 kg/d) and wk 1 to 8 (0.18, 0.10, and -0.58 kg/ d) postcalving. The BW and BCS were lower at calving for cows on SS compared with C. The greater amount of concentrate supplement postcalving increased DMI, yields of milk, fat, and protein and decreased BW loss in the first 8 wk of lactation. In conclusion, these results indicate that a greater energy density diet in the final 4 wk of the dry period improves cow production in early lactation.

Animal Nutritional Physiological Phenomena↗
PubMed2002

Effects of calcium salts of fatty acids and calcium salt of methionine hydroxy analogue on plasma prostaglandin F2alpha metabolite and milk fatty acid profiles in late lactation Holstein-Friesian cows.

Effects of a dietary lipid supplement containing calcium salts of fatty acids and methionine hydroxy analogue on plasma prostaglandin F2alpha (PGF2alpha) metabolite (PGFM) and milk fatty acid profiles were examined in 40 late lactation, nonpregnant, Holstein-Friesian cows for a period of 70 days. Effects on milk production, milk composition, and blood metabolites were also examined. Cows were paired on the basis of lactation number (first lactation, n = 8; second lactation, n = 32) and randomly assigned from within pairs to one of two dietary treatments: unsupplemented control (C) or 400 g per cow per day of the lipid supplement (S). Cows receiving the supplement had higher (P < 0.05) total milk production, total fat production (kg), and total lactose production (kg). Plasma cholesterol was significantly higher (P < 0.01) after 30 days of treatment in cows receiving the supplement. Cows receiving the supplement had lower (P < 0.01) concentrations of short chain milk fatty acids (C4:0 to C14:1) and higher concentrations of long chain fatty acids (C18:1 and C18:2; P < 0.01) than control animals. Oxytocin-induced prostaglandin release on Day 16 postovulation was increased (P < 0.01) in cows receiving the supplement. In conclusion, supplementation with calcium salts of fatty acids and methionine hydroxy analogue significantly increased milk yield and plasma PGFM.

Animals↗
PubMed2001

Importance of dose of type II collagen in suppression of collagen-induced arthritis by nasal tolerance.

OBJECTIVE: To determine the influence of the dose of collagen given nasally on the induction of specific mucosal tolerance in collagen-induced arthritis. METHODS: The severity of clinical arthritis induced in DBA/1 mice was studied after the nasal administration (before disease induction) of 1 of 4 doses (across a 2-log range) of bovine type II collagen (CII). Parameters of immunity included lymphocyte proliferation and cytokine production in vitro in response to antigen stimulation, and the production of anticollagen IgG antibody subclasses. RESULTS: The 3 highest doses (20, 80, and 320 microg) ameliorated disease severity, whereas the lowest dose (5 microg) aggravated disease. These findings correlated well with antigen-specific T cell proliferation and cytokine and antibody production. T cell proliferation was suppressed by the higher doses of CII, whereas the low dose enhanced T cell proliferation, indicating it primed the T cells. Suppression of T cell proliferation could be overcome by the addition of exogenous interleukin-2 (IL-2) to these cultures. Decreased T cell proliferation was associated with suppression of both Th1 (interferon-gamma [IFNgamma]) and Th2 (IL-4) cytokines and all the subclasses of anticollagen IgG in mice receiving 20, 80, or 320 microg of collagen. Overall, the highest dose of collagen (320 microg) was less effective at suppressing the immune response and disease than the 20-microg or 80-microg doses. There was an increased production of antibodies of all IgG isotypes, and of the Th1-associated cytokines IFNgamma and IL-2, in animals that had received the lowest dose of 5 microg collagen nasally. CONCLUSION: Nasal administration of antigens is effective in inducing tolerance and reducing disease severity, but the effects are dose dependent. Low doses can prime the immune system and aggravate disease; high doses may not suppress disease. Suppression of the immune response, which correlates with suppression of disease, is not obviously associated with a type I to type II T cell switch, but rather with an overall suppression of both forms of T cell response, with a potential role for anergy of T cells in this process.

Administration, Intranasal↗
PubMed2001

Post-partum ovarian vein thrombosis.

Post-partum ovarian vein thrombosis (POVT) is uncommon, but the true incidence is not known. Ninety per cent of cases present as right iliac fossa pain within 10 days of delivery. Anti-coagulation and intravenous antibiotics are the mainstay of treatment. We report three cases that were referred to our unit. These cases illustrate the difficulty in the clinical diagnosis of POVT and highlight the importance of its inclusion in the differential diagnoses of an acute abdomen in post-partum patients. POVT can be accurately diagnosed by appropriate noninvasive investigations and a laparotomy avoided.

Adult↗
PubMed2000

Local staging of Wilms' tumor--computerized tomography correlation with histological findings.

PURPOSE: The aim of this study was to assess the accuracy of computed tomography (CT) in the local staging of Wilms' tumor. METHODS: Twenty-six patients with unilateral, nonmetastatic Wilms' tumors were accrued over the period of 1990 through 1997. Preoperative CT staging was performed before surgical biopsy or excision. The abdominal CT images were reviewed and staged for local disease according to National Wilms' Tumour Study (NWTS) Group Staging V as either intrarenal disease (Stage I), local extrarenal extension amenable to complete local excision (Stage II), or advanced local disease (Stage III). Patients with metastatic (Stage IV) and bilateral disease (Stage V) were excluded from our study. Results were compared to histological findings. RESULTS: CT scan correctly staged 10 of 26 cases (38%) of Wilms' tumor. CT scan overstaged 12 of 16 (75%) localized renal disease (Stage I) and local extension (Stage II) tumors, and understaged 4 of 10 (40%) localized spread (Stage III) tumors. CONCLUSIONS: CT scan appears to have poor correlation to histological staging. Therefore, basing therapy solely on radiological imaging may lead to some patients receiving more intense therapy than necessary, whereas others do not receive sufficient therapeutic regimens. Histological assessment of the excised mass should remain the standard for staging Wilms' tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Breast cancer in a 6-year-old child.

A 6-year-old girl presented for a second opinion with a 1-year history of an enlarging soft tissue mass just lateral to the right areola. She had been seen by a pediatric surgeon elsewhere who reassured the parents that the lesion was benign. Ultrasound scan showed a 1.5- x 1.5-cm cystic structure adjacent to the right breast bud. Excisional biopsy results showed secretory ductal adenocarcinoma. Modified radical mastectomy with axillary node dissection was performed. All 11 nodes were negative for metastatic disease. She is now disease free 3 years after diagnosis. Estrogen-progesterone receptors were negative, as was screening for BCR 1 and 2. This is the first report of cytogenetics showing an abnormal cell line with a reciprocal translocation between 12p and 15q. Although breast cancer is extremely rare in children, a history of a painless, enlarging, firm breast mass should raise concern about possible neoplastic disease. Cystic appearance on ultrasound scan caused by the pseudocapsule around the tumor may be a marker for secretory carcinoma. Histological evaluation of all suspicious masses should be obtained. Because of the risk of local recurrence and axillary metastases, the authors recommend modified radical mastectomy with axillary node dissection for children with secretory carcinoma of the breast.

Biopsy, Needle↗