Search PubMed⌕ Search

Biomedical subjects

J J Murphy

Publications and source records attributed to J J Murphy.

At least 37 records · Page 2Linked to original sources

Identification of candidate endothelial cell autoantigens in systemic lupus erythematosus using a molecular cloning strategy: a role for ribosomal P protein P0 as an endothelial cell autoantigen.

OBJECTIVE: To attempt to characterize the diversity and nature of antigens recognized by anti-endothelial cell antibodies (AECA) in patients with systemic lupus erythematosus (SLE) using a molecular cloning strategy. METHODS: AECA in sera of 15 SLE patients were measured by ELISA and Western blot analysis was used to examine the diversity of autoantigen targets in two clinically active patients. A human umbilical vein endothelial cell cDNA expression library was immunoscreened with sera from these two patients to identify their autoantigen targets. An anti-ribosomal P peptide antibody ELISA was used to assess the clinical significance of anti-ribosomal P protein antibodies in the sera of one patient. RESULTS: Significantly higher AECA levels were found in five patients with active disease and nephritis than in five patients with clinically inactive disease. Sera from two clinically active patients were found to recognize distinct spectra of autoantigens. The candidate autoantigens that were identified included (1) endothelial cell-specific plasminogen activator inhibitor; (2) the classical lupus antigen, i.e. ribosomal P protein P0; and (3) proteins never before described as putative autoantigens in SLE, including ribosomal protein L6, elongation factor 1alpha, adenyl cyclase-associated protein, DNA replication licensing factor, profilin II and the novel proteins HEAPLA 1 and HEAPLA 2 (human endothelial associated putative lupus autoantigens 1 and 2). In one patient, antibodies against ribosomal P protein P0 were predominant and levels of these antibodies correlated with total AECA levels, anti-DNA antibody titres, overall clinical score and renal disease in a longitudinal study. CONCLUSIONS: A panel of candidate endothelial autoantigens in SLE, which includes previously described autoantigens and novel targets, has been identified by a molecular cloning strategy. This novel molecular approach could also be applied to the identification of autoantigens in other autoimmune vascular diseases.

Autoantibodies↗

Life-threatening gastrointestinal hemorrhage due to juvenile polyposis.

A 14-yr-old, previously healthy boy presented with massive lower GI hemorrhage. After the routine endoscopic and radiological evaluation, laparotomy and intraoperative colonoscopy revealed multiple polyps in the colon. A hemicolectomy was performed because of the severity of hemorrhage. A diagnosis of juvenile polyposis was made based upon histological findings and the family history. This is an extremely unusual presentation of juvenile polyposis and has been reported only once before. The clinical features, diagnosis, and therapeutic options for juvenile polyposis are discussed. Juvenile polyposis, although a rare condition in the pediatric population, should be considered in the differential diagnosis of life-threatening GI hemorrhage.

Adenomatous Polyposis Coli↗

Presentation of low anorectal malformations beyond the neonatal period.

OBJECTIVE: Anorectal malformations are usually diagnosed at birth, but some patients have presented to this institution beyond the early newborn period without recognition of their anorectal malformations. To quantify the extent of this problem, we undertook a review of all patients presenting to this hospital with anorectal malformations. METHODS: We reviewed all new cases of anorectal malformations treated at British Columbia's Children's Hospital during the past 11 years. We looked specifically at the time of diagnosis, patient age, sex and mode of presentation, the type of anorectal malformations, and any associated anomalies. RESULTS: One hundred twenty new cases of anorectal malformations were seen here, of whom, 15 patients (9 girls and 6 boys) presented beyond the early newborn period. Of these, 1 male infant was diagnosed at 2 weeks of age and another girl at 14 years of age. The remaining 13 presented between 3 and 11 months of age because of increasing constipation, usually associated with the introduction of solid foods. All had low anorectal malformations. Nine patients had at least 1 other feature of the VACTERL complex. CONCLUSIONS: Most anorectal malformations are identified at birth, but a significant number of the milder lesions may not be recognized until later. Therefore, this condition must be considered in older infants and children presenting with constipation, particularly if they also have cardiac or genitourinary anomalies. constipation, imperforate anus, VACTERL.

Adolescent↗

Neutropenic enteropathy: a 10-year review.

PURPOSE: With the advent of more aggressive chemotherapy, the incidence of neutropenic enteropathy is increasing. This review was performed to (1) determine which children are affected, (2) identify predisposing factors, and (3) assess efficacy of treatment. METHODS: A 10-year (1988 to 1997) review identified 33 children who had 38 episodes of neutropenic enteropathy. Each presented with fever, abdominal pain, and chemotherapy-induced neutropenia. All were treated with fluid resuscitation, bowel rest, and broad-spectrum antibiotics. Surgical intervention was reserved for children with bowel perforation. RESULTS: Neutropenic enteropathy occurred in 24 children with hematologic malignancies and nine with solid tumors. This disease developed in three children after bone marrow transplantation for leukemia. All five patients in whom recurrent episodes developed were receiving chemotherapy for Burkitt's lymphoma. Cytosine arabinoside and VP16 were the most commonly implicated chemotherapeutic agents. Four children required laparotomy and right hemicolectomy, and all survived. Overall survival was 94%. CONCLUSIONS: Although previously described in children receiving chemotherapy for hematologic malignancies, neutropenic enteropathy also occurs in children who have solid tumors and after bone marrow transplantation. The use of cytosine arabinoside and VP16 may predispose patients to this disease. Children receiving chemotherapy for Burkitt's lymphoma are at increased risk for recurrent episodes. Excellent survival rate was attained with supportive care being used as the primary treatment modality.

Adolescent↗

Fibromatoses: clinical and pathological features suggestive of recurrence.

BACKGROUND/PURPOSE: Fibromatoses represent a spectrum of nonneoplastic spindle cell tumors frequently identified in childhood. Although they may be locally aggressive, they do not metastasize. The authors have reviewed their experience of these lesions in an attempt to identify clinical and pathological features suggestive of recurrence. METHODS: Clinical records and pathological specimens from 55 cases of fibromatosis diagnosed and treated at British Columbia's Children's Hospital from 1982 to 1995 were reviewed. RESULTS: Thirty boys and 25 girls with ages ranging from 1 month to 14 years were identified. Eighteen tumors (33%) were congenital. Diagnoses were as follows: musculoaponeurotic fibromatosis (n = 27), infantile myofibromatosis (n = 10), Dupuytren-type fibromatosis (n = 7), fibromatosis colli (n = 7), and digital fibroma (n = 4). Clinical follow-up showed a survival rate of 98%. The single mortality occurred in an infant born with an intraabdominal visceral myofibromatosis, which proved unresectable. Fifteen cases recurred (27%), and nine cases (16%) of infantile myofibromatosis spontaneously regressed. All remaining cases were controlled successfully by surgical resection. CONCLUSIONS: Clinical features suggestive of recurrence included (1) presentation at greater than 5 years of age, (2) extremity location of disease, and (3) incomplete surgical resection. Pathological features suggestive of recurrence were (1) microscopic evidence of tumor at resection margins, (2) mitotic index of 5 or more per 10 high-power fields, and (3) areas of necrosis and inflammation within the tumor.

Adolescent↗

Effects of stocking density and concentrate supplementation of grazing dairy cows on milk production, composition and processing characteristics.

The effects on milk composition and processing characteristics of varying grass supply by changing stocking density and of offering a concentrate supplement were investigated. The experiment was conducted over 28 weeks of the lactation (April-October) using 48 spring-calved Friesian-Holstein cows. Three herds each of 16 cows were offered a restricted grass supply, a standard grass supply and a standard grass supply with a supplement of 3 kg concentrate/d. Treatment groups were grazed separately with a residence time of 3 d/paddock. Milk production, composition and processing characteristics such as renneting properties, ethanol stability and plasmin activity were measured weekly. Increasing stocking density above the standard system resulted in significant reductions in milk fat and protein yields, the concentrations of total protein, casein and whey proteins, and a deterioration in most processing characteristics. Imposing concentrate supplementation on the standard system increased total protein, casein and whey protein concentrations but generally did not improve processing characteristics except for ethanol stability. These results suggest that the standard grass supply in a rotational grazing paddock system can support efficient production of quality milk, and concentrate supplementation will not improve processing characteristics when an adequate supply of good quality herbage is available.

Animal Feed↗

Cougar attacks on children: injury patterns and treatment.

PURPOSE: Cougar attacks on humans appear to be on the rise. A review of all attacks on children was performed to determine the method of attack and injury patterns so that a treatment regimen as well as possible preventative measures could be determined. METHODS: A review of all attacks, including attacks on children, was performed, including three recent attacks treated at our institution. Situation, adult supervision, patient age, injuries recorded, survival, and mode of attack, if known, were reviewed. RESULTS: There were 50 documented attacks on children with a 25% fatality rate. Most children were not alone at the time of the attack (92%), and in many instances adult supervision was present or nearby. Severe head and neck lacerations along with puncture wounds were the most common injury. Examples of typical cervical injuries include a nonfatal vertebral artery injury, phrenic nerve injury, a fatal internal carotid artery injury, and a fatal cervical spine injury. The cougar was rabid in two cases. Pasteurella resulted in late infections in two patients. CONCLUSIONS: Based on the pattern of injuries, the authors recommend aggressive evaluation for occult cervical injuries as well as surgical debridement. Antibiotics should cover oropharyngeal flora including Pasteurella multocida. Rabies prophylaxis is indicated. Adult supervision in wilderness areas is not necessarily protective.

Animals↗

Effect of altering the daily herbage allowance to cows in mid lactation on the composition, ripening and functionality of low-moisture, part-skim Mozzarella cheese.

Milk was collected from three spring-calving herds, on different daily herbage allowances (DHA) of perennial rye-grass (16, 20 or 24 kg dry matter (DM)/cow for a 17 week period. On five occasions, at weekly intervals in the middle of the period, the three different milks were converted into low-moisture part-skim Mozzarella cheese. Increasing the DHA resulted in significant increases in the concentrations of protein in the cheesemilk (P < 0.05) and cheese whey (P < 0.02). The moisture-adjusted cheese yield increased significantly (P < 0.01) on raising the DHA from 16 to 24 kg grass DM/cow. DHA had no significant effects on any of the gross compositional values of the cheese (although moisture and fat-in-DM levels tended to decrease and increase respectively with increasing DHA). The hardness of the uncooked cheese and functionality of cooked cheese (i.e. melt time, flowability, stretch and viscosity) were not significantly influenced by DHA over the 115 d ripening period at 4 degrees C.

Animals↗

Effect of amount of dietary supplement and source of protein on milk production, ruminal fermentation, and nutrient flows in dairy cows.

An experiment with a multiple Latin square design using 36 midlactation Friesian cows was carried out to determine the effect of fish meal or soybean meal in a supplement fed at two amounts (3.5 or 7 kg/d) with grass silage. The diets were also fed to four ruminally and duodenally cannulated cows to determine digestibility, ruminal fermentation, and nutrient flows. Dry matter intake, milk production, milk constituent yields, and concentrations of protein and lactose were significantly increased by the supplements when provided at 7 kg/d. The supplement containing fish meal increased milk production, protein and lactose yields, and milk protein concentration, but the increases were smaller than those obtained by increasing the amount of supplement fed. Neither the type nor the amount of supplement fed affected digestibility of dry matter or organic matter, and few significant effects on ruminal fermentation were observed. Supplements fed at the higher allowance significantly increased the flow of dry matter, organic matter, all nitrogenous components, and amino acids to the duodenum. The supplement containing fish meal significantly increased the duodenal flow of nonammonia nonmicrobial N and some amino acids. Results indicated that an increase in the concentration of supplement in the diet is more effective in increasing milk production, protein concentration and yield, and flow of amino acids to the duodenum than is increasing the concentration of ruminally undegradable protein in the supplement.

Animal Nutritional Physiological Phenomena↗

Elevation of conjugated cis-9, trans-11-octadecadienoic acid in bovine milk because of dietary supplementation.

Cows on pasture were fed full fat soybeans (toasted, flaked, and pelleted) or ground full fat rapeseeds to investigate effects on cis-9, trans-11-octadecadienoic acid in milk. Three herds of 16 cows each that were on pasture were fed 3.1 kg/d of unmolassed beet pulp (control), 3.0 kg/d of rapeseed concentrate, or 3.1 kg/d of a soybean supplement. The concentration of cis-9, trans-11-octadecadienoic acid in the milk of cows fed the rapeseed and soybean supplements was significantly higher than in the milk of cows fed the control diet during the feeding trial. Over the trial, the cis-9, trans-11-octadecadienoic acid concentration in the milk of individual cows varied from 6.8 to 25.7 mg/g of fat in the control herd, from 10.6 to 33.5 mg/g of fat in the herd fed the rapeseed concentrate, and from 8.8 to 30.5 mg/g of fat in the herd fed the soybean supplement. The concentration of cis-9, cis-12-octadecadienoic acid, the substrate for cis-9, trans-11-octadecadienoic acid synthesis in the rumen, was 4.9 g/100 g of fatty acid methyl esters in the milk fat of cows fed the soybean supplement, 2.5 g/100 g of fatty acid methyl esters in the milk fat of cows fed the rapeseed concentrate, and 2.3 g/100 g of fatty acid methyl esters in the milk fat of the control cows. Milk yield and milk constituent yields were not affected by supplementation of either full fat soybeans or rapeseeds compared with controls, but milk protein concentration was significantly reduced by both oilseed supplements.

Animals↗

Ectopic expression of Bcl-2, but not Bcl-xL rescues Ramos B cells from Fas-mediated apoptosis.

The human Burkitt lymphoma Ramos B cell line can be induced to undergo apoptosis in response to a variety of different agents, including calcium ionophores, anti-immunoglobulin (Ig) and macromolecular synthesis inhibitors. In addition, following up-regulation of the Fas (CD95) surface receptor by CD40 ligation, these cells also become susceptible to apoptosis induction by Fas ligation. We have previously shown that protection from calcium ionophore- and macromolecular synthesis inhibitor-induced apoptosis by CD40 ligation is associated with a rapid up-regulation of Bcl-xL followed by a more moderate and delayed up-regulation of Bcl-2. We show here that overexpression of Bcl-xL, like Bcl-2, protects Ramos cells from apoptosis induction in response to calcium ionophore, anti-Ig and macromolecular synthesis inhibition. However, in contrast to Bcl-2, ectopic overexpression of Bcl-xL does not rescue from Fas-mediated apoptosis. Thus, in Ramos B cells, the Fas apoptotic pathway exhibits differential sensitivity to inhibition by Bcl-2 family members. These findings also suggest that CD40 signaling provides a switch which renders the cells susceptible to Fas-ligand mediated apoptosis through up-regulation of Fas whilst affording protection from anti-Ig-induced apoptosis through up-regulation of Bcl-xL.

Apoptosis↗