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Biomedical subjects

M Feeney

Publications and source records attributed to M Feeney.

16 recordsLinked to original sources
PubMed2004

HIV evolution: CTL escape mutation and reversion after transmission.

Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Adult↗
PubMed2001

Probiotic impact on microbial flora, inflammation and tumour development in IL-10 knockout mice.

BACKGROUND: The enteric bacterial flora has been implicated in the pathogenesis of enterocolitis and colon cancer in C57BL/6 IL-10 knockout mice. Probiotic Lactobacilli modify the enteric flora and are thought to have a beneficial effect on enterocolitis. We conducted a controlled feeding trial in IL-10 knockout mice using the probiotic Lactobacillus salivarius ssp. salivarius UCC118. AIM: To determine the effect of probiotic consumption on the gastrointestinal microflora, tumour development and colitis in IL-10 knockout mice. METHODS: Twenty IL-10 knockout mice were studied (10 consumed probiotic organisms in milk and 10 consumed unmodified milk) for 16 weeks. Faecal microbial analysis was performed weekly to enumerate excretion of the probiotic UCC118, total lactobacilli, Clostridium perfringens, bacteroides, coliforms, bifidobacteria and enterococci. At sacrifice, the small and large bowel were microbiologically and histologically assessed. RESULTS: L. salivarius UCC118 was detected in faeces from all mice in the probiotic fed group, but not the control group. Faecal coliform and enterococci levels were significantly reduced in probiotic fed animals compared to the controls (P < 0.05). At sacrifice, a significant reduction in C. perfringens numbers was observed in the test mice (P < 0.05). There were no fatalities in the test group compared to two deaths from fulminant colitis in the control group. Only one test mouse developed colonic adenocarcinoma compared to five in the control group. Test animal mucosal inflammation consistently scored lower than that of the control mice. CONCLUSION: In this placebo controlled trial, modification of enteric flora in IL-10 knockout mice by probiotic lactobacilli was associated with reduced prevalence of colon cancer and mucosal inflammatory activity.

Animals↗
PubMed2001

In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings.

The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.

Animals↗
PubMed1999

A Brunner's gland adenoma as a cause of anemia.

Benign tumors of the small bowel are rare. They present with many different manifestations depending on the size and location, and also cause a variety of symptoms that are often nonspecific. These include abdominal pain, dyspepsia, nausea, vomiting, and gastrointestinal bleeding that may be melena or hematemesis. Most of the time patients are asymptomatic and the lesions are discovered as an incidental finding. When bleeding occurs, and it may be severe in certain situations, the patient may develop signs of anemia, such as dyspnea, fatigue, and even high-output cardiac failure. The authors present a patient who was evaluated for melena and who was found to have a duodenal polyp that proved to be a Brunner's gland adenoma on pathology.

Adenoma↗
PubMed1997

A case-control study of measles vaccination and inflammatory bowel disease. The East Dorset Gastroenterology Group.

BACKGROUND: The cause of inflammatory bowel disease (IBD) remains to be established. Evidence has linked measles infection in early childhood with the subsequent risk of developing IBD, particularly Crohn's disease. A cohort study raised the possibility that immunisation with live attenuated measles vaccine, which induces active immunity to measles infection, might also predispose to the later development of IBD, provoking concerns about the safety of the vaccine. METHOD: We report a case-control study of 140 patients with IBD (including 83 with Crohn's disease) born in or after 1968, and 280 controls matched for age, sex and general practitioner (GP) area, designed to assess the influence of measles vaccination on later development of IBD. Documentary evidence of childhood vaccination history was sought from GP and community health records. FINDINGS: Crude measles vaccination rates were 56.4% in patients with IBD and 57.1% among controls. Matched odds ratios for measles vaccination were 1.08 (95% CI 0.62-1.88) in patients with Crohn's disease, 0.84 (0.44-1.58) in patients with ulcerative colitis, and 0.97 (0.64-1.47) in all patients with IBD. INTERPRETATION: These findings provide no support for the hypothesis that measles vaccination in childhood predisposes to the later development of either IBD overall or Crohn's disease in particular.

Adult↗
PubMed1997

Risk of pelvic injury from femoral neck guidewires.

Many of the devices used in the internal fixation of femoral neck fractures are cannulated and require the initial placement of one or more guidewires for accurate positioning. These wires are occasionally advanced inadvertently through the hip joint and the acetabulum. Pelvic visceral damage may follow. To assess this risk, we inserted three guidewires to a depth of 16 cm into each femoral neck of ten cadavers and explored the pelvis during autopsy. Thirty-two of the 60 guidewires had penetrated a pelvic organ. The literature on intrapelvic injuries associated with hip surgery is reviewed, and suggestions are offered on the avoidance of pelvic penetration during hip fracture fixation.

Cadaver↗
PubMed1989

Alertness of night nurses: two shift systems compared.

The alertness of hospital trainee nurses during their night shift work was assessed by recording performance at night on an arousal-sensitive unprepared simple reaction time task. One group carried out a number of separate weeks on night shift throughout their three-year course. Here performance fell from first to seventh day of the week on night shift, implying progressive sleep deprivation. Another group covered their night work by a single three-month 'permanent' night shift of four (or three) nights on and three (or four) days off each week. Here initial performance level fell by the 45th night but had returned to normal by the last (90th) night. In both systems individuals varied considerably in their ability to maintain performance during sustained night work. These results strengthen the case for permanent night shifts, with careful selection of personnel, as a means of organizing night nursing in hospitals.

Arousal↗
PubMed1983

Elimination of leukemic cells from human bone marrow using monoclonal antibody and complement.

Human leukemic cells which bear the common acute lymphoblastic leukemia antigen can be lysed with a murine monoclonal antibody (J-5) in the presence of rabbit complement. Conditions have been defined for eliminating 51Cr-labeled common acute lymphoblastic leukemia antigen-positive NALM-1 cells or cryopreserved leukemic lymphoblasts from a 100-fold excess of human bone marrow. Optimal lysis is obtained with treatment for a total of 90 min. Three treatments for 30 min are more effective than two treatments for 45 min or one treatment for 90 min. Separation of marrow on a Ficoll:diatrizoate gradient does not permit more effective elimination of leukemic cells. Tumor cell lysis is inhibited by high concentrations of common acute lymphoblastic leukemia antigen-positive cells (2 X 10(7)/ml) and by high concentrations of bone marrow (10(8)/ml). Under optimal conditions, greater than 99% of 51Cr-labeled leukemic lymphoblasts can be eliminated from a 100-fold excess of human marrow. Selective removal of leukemic cells from human bone marrow in vitro should facilitate trials of autologous marrow transplantation.

Antibodies, Monoclonal↗
PubMed1982

Autologous bone-marrow transplantation in CALLA-positive acute lymphoblastic leukemia after in-vitro treatment with J5 monoclonal antibody and complement.

A monoclonal antibody (J5) specific for the common acute-lymphoblastic-leukaemia antigen (CALLA) was used for in-vitro pre-treatment of bone-marrow before autologous transplantation in four patients with CALLA-positive acute lymphoblastic leukaemia (ALL) in relapse, who did not have HLA-compatible donors. After remission induction and intensification, bone-marrow cells were harvested, treated with J5 antibody and rabbit complement, and cryopreserved in liquid nitrogen. Patients received ablative chemotherapy and total-body irradiation before reinfusion of autologous J5-treated bone marrow. The transplantation protocol was well tolerated, and engraftment of normal myeloid cells occurred in all for patients. Two patients have continued in unmaintained remission with complete haematopoietic reconstitution for more than 1 year after autologous transplantation.

Antibodies, Monoclonal↗
PubMed1981

Reactivity of a monoclonal antibody with human ovarian carcinoma.

A murine monoclonal antibody (OC125) has been developed that reacts with each of six epithelial ovarian carcinoma cell lines and with cryopreserved tumor tissue from 12 of 20 ovarian cancer patients. By contrast, the antibody does not bind to a variety of nonmalignant tissues, including adult and fetal ovary. OC125 reacts with only 1 of 14 cell lines derived from nonovarian neoplasms and has failed to react with cryostat sections from 12 nonovarian carcinomas.

Animals↗
PubMed1981

Elimination of leukemic cells from rat bone marrow using antibody and complement.

An animal model has been developed that utilizes antibody and complement to eliminate a transplantable cloned line of Wistar/Furth acute nonlymphocytic leukemia (CI-3) from syngeneic Wistar/Furth bone marrow. The CI-3 leukemia grows progressively from an i.v. inoculum of 10(1) to 10(2) cells. Antiserum has been raised in rabbits following multiple injections of CI-3. Using optimal concentrations of absorbed antibody and complement, approximately 3 logs of tumor could be destroyed in vitro, judged by the number of cells required to produce progressive growth in vivo. Similar incubation with antibody and complement did not affect the ability of Wistar-Furth marrow to reconstitute rats that had received lethal total-body irradiation (950 R). Each of the 33 irradiated rats that received mixtures of 10(4) CI-3 and 1.6 X 10(8) nucleated bone marrow cells succumbed to leukemia within 65 days, whereas 16 of 33 rats (48%) receiving similar inocula that had been treated with antibody and complement survived greater than 180 days without evidence of tumor growth. Repeated treatment of contaminated marrow with antibody and complement following removal of mature granulocytes and erythrocytes on density gradients permitted elimination of 10(5) CI-3.

Animals↗
PubMed1980

Specificity of heteroantisera developed against purified populations of intact murine ovarian carcinoma cells.

Antisera were raised in New Zealand White rabbits against purified populations of murine ovarian carcinoma (MOT) cells that were freed from contaminating host leukocytes and erythrocytes. In contrast to other antisera raised against this tumor, heteroantisera from rabbits immunized with purified tumor cell suspensions consistently retained antitumor activity after exhaustive absorption with syngeneic (C3HeB/FeJ) adult and fetal tissues. Absorbed antisera inhibited tumor growth in vivo and reacted with MOT cells in vitro as judged by indirect immunofluorescence, binding of staphylococcal protein A, and complement-mediated cytotoxicity. Appropriately absorbed antisera failed to bind to fetal tissues or to adult spleen, ovary, and kidney cells. Antisera with similar specificity could be obtained with the use of populations purified on a fluorescence-activated cell sorter or on discontinuous rabbit serum albumin gradients. Optimal titers against tumor were raised with multiple injections of 5 x 10(5) gradient-purified MOT cells.

Animals↗
PubMedDate not supplied

Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials.

The enteric flora comprise approximately 95% of the total number of cells in the human body and are capable of eliciting immune responses while also protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract (GIT) may also be implicated in the pathogenesis of several chronic conditions such as inflammatory bowel disease (IBD). The University College Cork-based Probiotic Research Group has successfully isolated and identified lactic acid bacteria (LAB) which exhibit beneficial probiotic traits. These characteristics include the demonstration of bile tolerance; acid resistance; adherence to host epithelial tissue; and in vitro antagonism of potentially-pathogenic micro-organisms or those which have been implicated in promoting inflammation. The primary objective of this report is to describe the strategy adopted for the selection of potentially effective probiotic bacteria. The study further describes the evaluation of two members of the resulting panel of micro-organisms (Lactobacillus salivarius subsp. salivarius UCC118 and Bifidobacterium longum infantis 35624) under in vitro conditions and throughout in vivo murine and human feeding trials. Specifically, an initial feeding study completed in Balb/c mice focused upon (i) effective delivery of the probiotic micro-organisms to the GIT and evaluation of the ability of the introduced strains to survive transit through, and possibly colonise, the murine GIT; (ii) accepting the complexity of the hostile GIT and faecal environments, development of a method of enumerating the introduced bacterial strains using conventional microbiological techniques; and (iii) assessment of the effects of administered bacterial strains on the numbers of specific recoverable indigenous bacteria in the murine GIT and faeces. Additional research, exploiting the availability of murine models of inflammatory bowel disease, demonstrated the beneficial effects of administering probiotic combinations of Lactobacillus salivarius UCC118 and Bifidobacterium longum infantis 35624 in prevention of illness-related weight loss. A further ethically-approved feeding trial, successfully conducted in 80 healthy volunteers, demonstrated that yoghurt can be used as a vehicle for delivery of Lactobacillus salivarius strain UCC118 to the human GIT with considerable efficacy in influencing gut flora and colonisation.

Animals↗