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J J O'Brien

Publications and source records attributed to J J O'Brien.

At least 19 recordsLinked to original sources
PubMed2001

Rod pathways in the mammalian retina use connexin 36.

Many neurons in the mammalian retina are coupled by means of gap junctions. Here, we show that, in rabbit retina, an antibody to connexin 36 heavily labels processes of AII amacrine cells, a critical interneuron in the rod pathway. Image analysis indicates that Cx36 is primarily located at dendritic crossings between overlapping AII amacrine cells. This finding suggests that Cx36 participates in homotypic gap junctions between pairs of AII amacrine cells. Cx36 was also found at AII/cone bipolar contacts, previously shown to be gap junction sites. This finding suggests that Cx36 participates at gap junctions that may be heterotypic. These results place an identified neuronal connexin in the context of a well-defined retinal circuit. The absence of Cx36 in many other neurons known to be coupled suggests the presence of additional unidentified connexins in mammalian neurons. Conversely, Cx36 labeling in other regions of the retina is not associated with AII amacrine cells, indicating some other cell types use Cx36.

Animals↗
PubMed2001

Excitation--contraction uncoupling by a human central core disease mutation in the ryanodine receptor.

Central core disease (CCD) is a human congenital myopathy characterized by fetal hypotonia and proximal muscle weakness that is linked to mutations in the gene encoding the type-1 ryanodine receptor (RyR1). CCD is thought to arise from Ca(2+)-induced damage stemming from mutant RyR1 proteins forming "leaky" sarcoplasmic reticulum (SR) Ca(2+) release channels. A novel mutation in the C-terminal region of RyR1 (I4898T) accounts for an unusually severe and highly penetrant form of CCD in humans [Lynch, P. J., Tong, J., Lehane, M., Mallet, A., Giblin, L., Heffron, J. J., Vaughan, P., Zafra, G., MacLennan, D. H. & McCarthy, T. V. (1999) Proc. Natl. Acad. Sci. USA 96, 4164--4169]. We expressed in skeletal myotubes derived from RyR1-knockout (dyspedic) mice the analogous mutation engineered into a rabbit RyR1 cDNA (I4897T). Here we show that homozygous expression of I4897T in dyspedic myotubes results in a complete uncoupling of sarcolemmal excitation from voltage-gated SR Ca(2+) release without significantly altering resting cytosolic Ca(2+) levels, SR Ca(2+) content, or RyR1-mediated enhancement of dihydropyridine receptor (DHPR) channel activity. Coexpression of both I4897T and wild-type RyR1 resulted in a 60% reduction in voltage-gated SR Ca(2+) release, again without altering resting cytosolic Ca(2+) levels, SR Ca(2+) content, or DHPR channel activity. These findings indicate that muscle weakness suffered by individuals possessing the I4898T mutation involves a functional uncoupling of sarcolemmal excitation from SR Ca(2+) release, rather than the expression of overactive or leaky SR Ca(2+) release channels.

Animals↗
PubMed2001

Prevalence of infection in ticks submitted to the human tick test kit program of the U.S. Army Center for Health Promotion and Preventive Medicine.

In 1997, ticks removed from humans and received alive by the Tick-Borne Disease Laboratory of the U.S. Army Center for Health Promotion and Preventive Medicine (USACHPPM) were tested for pathogens by polymerase chain reaction (PCR). Thirty-three of 222 (15%) Amblyomma americanum (L.) DNAs produced amplicons of the expected size of Ehrlichia chaffeensis Anderson, Dawson & Wilson and 26/222 (12%) produced amplicons indicating Borrelia burgdorferi Johnson, Schmid, Hyde, Steigalt & Brenner. Five (2%) appeared to be co-infected with both organisms. Thirteen of 308 (4%) Dermacentor variabilis (Say) were PCR-positive for spotted fever group rickettsiae. Restriction fragment-length polymorphism analysis indicated all were Rickettsia montana. One hundred twenty-seven D. variabilis from Monroe County, WI, were tested for B. burgdorferi and 14 (11%) were positive. Five of 24 (21%) Ixodes scapularis Say were positive for B. burgdorferi and one (2%) was positive for the agent of human granulocytic ehrlichiosis. Different species of ticks transmit different pathogens, and most tick-borne diseases have similar early symptoms, therefore knowing the species and infection status of the tick enhances the physician's ability to consider tick-borne agents as a potential cause of disease and recommend appropriate therapy. Ongoing surveillance of the vector species of human diseases provides an additional estimate of human encounters with infected ticks, and testing ticks removed from humans may increase our knowledge of the vector status of tick species for transmitting tick-borne pathogens.

Animals↗
PubMed1999

Histamine immunoreactive axons in the macaque retina.

PURPOSE: The goal of these experiments was to identify the neurotransmitter in centrifugal axons of the macaque retina. METHODS: Macaca mulatta retinas and optic nerves were fixed overnight in carbodiimide and labeled with an antiserum to histamine with the use of an immunofluorescence technique. RESULTS: Several large histamine-immunoreactive axons ran from the optic nerve head to the peripheral retina, where they branched extensively and terminated in the inner plexiform layer, occasionally alongside retinal blood vessels. Other axons that emerged from the optic nerve head ran in the optic fiber layer to the central retina, circled the fovea, and then returned to the optic disc. These may be the source of histamine-immunoreactive axons that have been observed in central visual areas. No labeled cell bodies were present in the retina. Because perikarya in the posterior hypothalamus are the only known source of histamine in the primate central nervous system and because neurons there can be retrogradely labeled from the cut optic nerve, the histamine-immunoreactive axons must have originated there. CONCLUSIONS: Centrifugal axons in the macaque retina are part of the system of axons containing histamine that originate in the hypothalamus and project throughout the brain. Because the activity of these neurons is highest during the morning, histamine might play a role in preparing the retina to operate in daylight. The contacts of histamine-immunoreactive axons with blood vessels suggest that histamine may also play a role in regulating the retinal microvasculature.

Animals↗
PubMed1998

Overproduction of SM28GST in a baculovirus expression vector and its use to evaluate the in vivo immune responses of mice vaccinated against Schistosoma mansoni with naked DNA encoding the SM28GST gene.

To evaluate the immune responses of mice vaccinated intramuscularly with naked DNA encoding a single parasite-derived gene, sufficient quantities of protein are necessary for use in the immunological assays. A plasmid carrying the cDNA encoding the entire sequence for the 28-kDa Schistosoma mansoni glutathione S-transferase (Sm28GST) was used as a source of naked DNA to vaccinate mice. Using polymerase chain reaction employing custom primers to add Eco RI and Hind III restriction sites at the 5' and 3' ends, respectively, a 651-bp fragment was amplified from the vaccine plasmid. This product was isolated, ligated into the pFastBac HTb donor plasmid containing a 6X histidine (6X-his) tag, and transposed into the baculovirus expression vector system. Following blue white selection screening, high molecular weight DNA was isolated and transfected in Sf21 insect ovary cells using a liposomal preparation. Culture medium containing infective virus particles was used to infect a series of Sf21 cultures and the cells were lysed after 3-5 days. The lysates were subjected to immobilized metal (Ni-NTA) affinity chromatography from which the 6X-his-tagged recombinant Sm28GST was eluted in 250 mM imidazole. The eluted protein was probed with a polyclonal rabbit antibody specific for the Sm28GST and subsequently recognized using a monoclonal antibody specific for the 6X-his tag following concentration of the pooled fractions. Mice were vaccinated intramuscularly with purified plasmid DNA encoding either the Sm28GST or firefly luciferase. Skin tests performed using recombinant Sm28GST were positive in only those mice vaccinated with naked DNA encoding the Sm28GST gene. In a different group of experimental mice, only sera from mice vaccinated with naked DNA encoding Sm28GST contained IgG-specific anti-Sm28GST antibodies at 14 days postvaccination, and at 42 days the levels were suggestive of an anamnestic response. These results suggest that naked DNA vaccination of mice is capable of inducing both antigen-specific cell-mediated and humoral immune responses against Sm28GST and further strengthen the case for this antigen being a vaccine candidate.

Animals↗
PubMed1997

Cerebral emboli during cardiac surgery in children.

BACKGROUND: Microemboli occur commonly during cardiac surgery in adults, and, when present, increase the risk of neuropsychological deficits. Their incidence and significance during correction of congenital heart disease is unknown. The authors hypothesized that microemboli would occur before bypass with right-to-left cardiac shunts and would also occur in large numbers when the aortic crossclamp was released in children during repair of congenital heart defects. METHODS: In 25 children studied with carotid artery Doppler, embolic signals were counted and timed in relation to 13 intraoperative events. Patients were classified as either at high risk (obligate right-to-left shunt or uncorrected transposition of the great arteries) or at low risk (net left-to-right shunt or simple obstructive lesions) for paradoxical (venous to arterial) emboli. RESULTS: The median number of emboli detected was 122 (range, 2-2,664). Forty-two percent of all emboli were detected within 3 min of release of the aortic crossclamp. The high-risk group had significantly more emboli (median, 66; range, 0-116) during the time interval before cardiopulmonary bypass than did the low-risk group (median, 8; range, 0-73), with P < 0.01. There was no significant difference between the high- and low-risk groups in the total number of emboli detected. There was no apparent association between number of emboli and gross neurologic deficits. CONCLUSIONS: Microemboli can be detected in the carotid arteries of children undergoing repair of congenital heart disease and are especially prevalent immediately after release of the aortic crossclamp. The role of emboli in causing neurologic injury in children undergoing repair of congenital heart disease remains to be determined.

Cardiopulmonary Bypass↗
PubMed1995

An effective computer-based tardive dyskinesia monitoring system.

To promote early recognition and treatment of neuroleptic-induced tardive dyskinesia we used our facility's pharmacy and appointment data bases to develop an automated reminder system that significantly improved physician monitoring of patients receiving antipsychotic drug therapy. The system prompts staff to perform regular examinations for abnormal involuntary movements and to review patients' consent to therapy with antipsychotic medication. The average prevalences in the 15 months after automated reminders began, in a population of over 800 patients, increased from 53% to 85% for an annually completed abnormal involuntary movement scale in medical records and from 38 to 74% for a statement of informed consent. Now, 45 months later, prevalences of both measures approaches 100%. The integrated design of the Department of Veterans Affairs computer system allowed linking pharmacy and appointment scheduling data and facilitated the project. The reminder system effectively promoted rapid, marked, and sustained change in physicians' documentation of antipsychotic drug therapy.

Antipsychotic Agents↗
PubMed1993

Mental health services for medical students: perceptions of students, student affairs deans, and mental health providers.

PURPOSE: To examine (1) whether there is any consistency among medical schools in mental health services provided and (2) how these services are perceived by student affairs deans, mental health service providers, and the students themselves. METHOD: Questionnaires were sent in October 1991 to the student affairs dean (or director), the individual responsible for student mental health services, and a student representative in each of the 126 U.S. and Canadian medical schools. Data were sought regarding personnel, individuals served, location, hours, administration, funding, confidentiality, administrative referrals, and respondents' suggestions for improvement. Possible differences among the three groups of respondents were tested by chi-square. RESULTS: Responses were received from 75 student affairs deans, 53 mental health providers, and 30 students. There was much diversity among schools in services provided, especially in the areas of administration and funding. Although perceptions of the three respondent groups were often the same, they differed significantly in a number of areas. Suggestions for improvement of services involved funding, personnel, hours, confidentiality and privacy, specialty services, preventive and support programs, and visibility. The suggestion most frequently made by the students was for increased information and visibility. CONCLUSION: The differences among schools coupled with the differing perceptions within schools indicate a need for a comprehensive consideration of what kinds of mental health services are needed and how they can best be made accessible to a diverse body of students experiencing a variety of academic and personal challenges.

Canada↗
PubMed1992

ELISA tests for antibodies in experimental bovine tuberculosis.

It was shown that 10(4) cfu of a field isolate of Mycobacterium bovis caused illness in five experimentally infected calves; one of these died. One of three contact calves also became clinically infected. Considerable variation in the humoral response of the affected animals was demonstrated by ELISAs using purified protein derivative (PPD) and phosphatide antigens. The inoculation of antigens used in the comparative tuberculin skin test significantly enhanced the level of PPD antibodies in the affected animals whereas that of the apparently non-infected contact animals remained unchanged.

Animals↗
PubMed1991

Use of azathioprine or 6-mercaptopurine in the treatment of Crohn's disease.

The efficacy and safety of therapy with azathioprine/6-mercaptopurine was studied in 78 patients with Crohn's disease. Mean duration of therapy was 1.6 years; 52 patients were treated greater than or equal to 6 months. All patients were also on other antiinflammatory medications. Evaluations included self-assessment and physician's assessment of well-being, functional capacity, general clinical response, clinical activities indices (National Foundation for Ileitis and Colitis/International Organization for the Study of Inflammatory Bowel Disease and Harvey-Bradshaw), and achievement of specific therapeutic goals. General clinical condition improved in 70% of the patients. Median response time was 3 months. The average Harvey-Bradshaw score decreased 37% with therapy, and a decrease of greater than or equal to 30% occurred in 66% of the subjects. An overall 72% achievement rate for specified therapeutic goals included controlling refractory disease, 73%; corticosteroid "sparing," 76%; and lessening fistulization, 63%. Nine patients got worse despite therapy. Adverse effects requiring discontinuation of therapy occurred in 10%, whereas dosages were briefly lowered for mild side effects in another 10%. This study demonstrates the effectiveness and safety of azathioprine/6-mercaptopurine in the majority of selected patients with chronic, unremitting, or steroid-requiring Crohn's disease.

Adolescent↗
PubMed1991

A mathematical model for Mycobacterium bovis excretion from tuberculous cattle.

An analysis was carried out of available information from a series of experiments on the excretion of M. bovis from infected cattle. The analysis indicated that an inverse exponential relationship exists between 'dose' of organisms given and the delay before excretion commences. This relationship was represented mathematically. Available field data supported the relationship and indicated that in natural bovine tuberculosis excretion of M. bovis begins around 87 days after infection occurs. It is also suggested that the data supports the concept of single nuclei infections in cattle.

Animals↗
PubMed1990

Computed tomography evaluation of the sacroiliac joints in Crohn disease. Radiologic/clinical correlation.

Computed tomography (CT) was used in a prospective study of the sacroiliac joints in 86 patients with Crohn disease to determine the type and frequency of sacroiliac joint abnormalities present in this population. The CT findings were correlated with review of the clinical history in 64 patients. Computed tomography demonstrated changes of sacroiliitis in 29% of the study group. This high prevalence of sacroiliac joint abnormality was found even in those under 30 years of age. It exceeds the 11-19% previously reported from plain film examination, reflecting the greater sensitivity of CT. In the subgroup of 64 patients studied clinically, 19 (30%) had abnormal sacroiliac joints on CT, but only 2 (3%) reported symptoms related to the sacroiliac joints.

Adult↗
PubMed1990

Effect of creep feeding on the incidence, duration and severity of post-weaning diarrhoea in pigs.

The effect of creep feeding on the response of pigs weaned at two or three weeks old to infection with an enteropathogenic strain of Escherichia coli (O149; K91[B], K88 a, c [L]) was studied in two separate experiments. Gastric intubation was adopted to regulate the intake of creep feed during the sucking period. Animals were given the enteropathogenic strain either before weaning or at weaning and the course and outcome of the infection followed bacteriologically and clinically. The response of the animals to the infection varied considerably in accord with recent reports of multiple phenotypes (to K88 +ve organisms) among pigs but consumption of creep feed before weaning did not significantly affect the prevalence, duration or severity of the diarrhoea induced experimentally by the organism. Hence reputed immunological responses mounted against dietary antigens did not predispose to or protect against this infection.

Animal Feed↗
PubMed1989

Control, prevention and eradication of Salmonella enteritidis infection in broiler and broiler breeder flocks.

Salmonella enteritidis was identified by serological and bacteriological techniques in two clinically normal breeder flocks in an integrated broiler organisation in Northern Ireland. The organism was transmitted vertically to clinically affected progeny flocks. The infected breeder flocks were slaughtered and the infection throughout the organisation controlled and subsequently eradicated. A working group, consisting of the senior management of the broiler organisation and veterinary staff from the Veterinary Research Laboratories at Stormont, was formed to establish procedures to minimise the risk of the reintroduction of salmonella infection, by preventing vertical transmission from grandparent flocks, or lateral transmission from personnel, other animal species and fomites, or transmission through the feed. All feed was heated to a minimum of 70 degrees C for 12 minutes immediately before it was pelleted and subsequently transported to the flocks through a dedicated system of conveyor belts, bins and lorries. A comprehensive system for monitoring the efficacy of the preventive procedures was established and is now used throughout the poultry industry of Northern Ireland.

Animals↗