PubMed Health⌕ Search

Biomedical subjects

J Phelan

Publications and source records attributed to J Phelan.

At least 19 recordsLinked to original sources
PubMed2006

Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland.

The objectives of the study were to quantify the levels of badger exposure for cattle and to test the hypothesis that increased badger exposure does not increase the risk of bovine tuberculosis (BTB) in a herd. Information that became available from the targeted removal of badgers over the study period, and from a badger-removal project in county Kilkenny, during 1996-1999 was used. The specific location of cattle within each farm, and the length of time that cattle spent in each farm field during the grazing season, and in the barnyard during winter, was used to build an exposure coefficient to quantify the amount of badger exposure that cattle encountered either on pasture or in the barn. The study design was a matched case-control study in which the control herds were selected using incidence density sampling. During the 4-year study period, 543 badgers were removed and of these 96 badgers were classified as tuberculosis positive; 96 BTB herd breakdowns occurred. There was a significant association between case herds and having a higher badger sett exposure coefficient during 1996-1998. No significant association between case herds and having a higher exposure coefficient based on the number of badgers, or the number of tuberculous badgers, during September 1997-December 1999 was found.

Animals↗
PubMed2004

Identification of gammadeltaT lymphocytes in human periapical lesions.

Endodontic (root canal) therapy is required when the pulp of a tooth becomes necrotic due to a bacterial infection or trauma. A proportion of patients who receive endodontic therapy subsequently have periapical (around the tooth root) lesions detected by radiolucency. Currently, there are no means to identify susceptible patients. Although tissue from periapical lesions has been described as inflammatory, inflammatory cell types and their functions have been poorly characterized. For example, T lymphocytes were identified using pan specific anti-CD3 mAb, which recognizes both alphabeta and gammadeltaT cells. Using the current model of gammadeltaT cells as immunoregulatory cells; gammadeltaT cells can mediate protective or destructive milieus. We postulated that patients who have a periapical lesion, as identified by radiographic bone loss, mount a gammadeltaT cell response. We collected specimens removed by surgery from both periapical lesions and other oral tissues, generated total RNA and performed reverse-transcriptase polymerase chain reaction to identify rearranged delta genes. Results were confirmed with semi-nested polymerase chain reaction. In addition, we demonstrate that these lesions contain a population of CD3+ cells that are alphabetaT cell receptor negative, implying that these cells are gammadeltaT cells. Here we show that 36/37 of periapical lesions and only 2/11 of other lesions contain gammadeltaT cells (P<0.0001). Vdelta2+ T cells were the most common subtype identified (30/36) in these samples. This is the first report in the literature of the presence of gammadeltaT cells in human periapical lesions.

Adult↗
PubMed2003

Expression, purification and preliminary X-ray analysis of the BRCT domain from Rhp9/Crb2.

The BRCT domain from Rhp9 (a Schizosaccharomyces pombe DNA-damage checkpoint protein) has been expressed, purified and crystallized. Overexpression in bacterial cells was achieved by minimizing aeration during host cell growth. A robotic screen was used to determine the solubility parameters; concentration of the protein was achieved by exploiting this information. Single crystals suitable for X-ray analysis were obtained in two forms by vapour diffusion (trigonal, unit-cell parameters a = b = 228.04, c = 70.42 A, and tetragonal, P4/m Laue group symmetry, unit-cell parameters a = b = 72.3, c = 91.1 A).

Automation↗
PubMed2001

Crystal structure of the fission yeast mitochondrial Holliday junction resolvase Ydc2.

Resolution of Holliday junctions into separate DNA duplexes requires enzymatic cleavage of an equivalent strand from each contributing duplex at or close to the point of strand exchange. Diverse Holliday junction-resolving enzymes have been identified in bacteria, bacteriophages, archaea and pox viruses, but the only eukaryotic examples identified so far are those from fungal mitochondria. We have now determined the crystal structure of Ydc2 (also known as SpCce1), a Holliday junction resolvase from the fission yeast Schizosaccharomyces pombe that is involved in the maintenance of mitochondrial DNA. This first structure of a eukaryotic Holliday junction resolvase confirms a distant evolutionary relationship to the bacterial RuvC family, but reveals structural features which are unique to the eukaryotic enzymes. Detailed analysis of the dimeric structure suggests mechanisms for junction isomerization and communication between the two active sites, and together with site-directed mutagenesis identifies residues involved in catalysis.

Amino Acid Sequence↗
PubMed2001

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

AIDS-Related Opportunistic Infections↗
PubMed2001

Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase.

Nitric oxide synthase is inhibited by asymmetric NG-methylated derivatives of arginine whose cellular levels are controlled in part by dimethylarginine dimethylaminohydrolase (DDAH, EC 3.5.3.18). Levels of asymmetric NG,NG-dimethylarginine (ADMA) are known to correlate with certain disease states. Here, the first structure of a DDAH shows an unexpected similarity to arginine:glycine amidinotransferase (EC 2.1.4.1) and arginine deiminase (EC 3.5.3.6), thus defining a superfamily of arginine-modifying enzymes. The identification of a Cys-His-Glu catalytic triad and the structures of a Cys to Ser point mutant bound to both substrate and product suggest a reaction mechanism. Comparison of the ADMA-DDAH and arginine-amidinotransferase complexes reveals a dramatic rotation of the substrate that effectively maintains the orientation of the scissile bond of the substrate with respect to the catalytic residues. The DDAH structure will form a basis for the rational design of selective inhibitors, which are of potential use in modulating NO synthase activity in pathological settings.

Amidohydrolases↗
PubMed2000

Association of natural killer cell depletion with induction of mixed chimerism and allograft tolerance in non-human primates.

BACKGROUND: Nonmyeloablative T cell depletion followed by donor bone marrow infusion has proved to be an effective approach to induction of mixed chimerism and tolerance of organ allografts in non-human primates. To help define the mechanisms involved we have compared T cell depletion with ATG versus anti-CD2 monoclonal antibody with respect to establishment of mixed chimerism and induction of tolerance. METHOD: Both nonmyeloablative regimens included low dose total body irradiation (1.5 Gy x 2), thymic irradiation (7 Gy), splenectomy and kidney plus donor bone marrow transplantation, followed by a 4-week posttransplant course of cyclosporine. In addition, the ATG group (13 recipients) received antithymocyte globulin, although the LOCD2b group (10 recipients) were treated with an anti-CD2 monoclonal antibody (LOCD2b). RESULTS: In the ATG group, 11 of 13 monkeys developed multilineage chimerism and 9 survived for more than 100 days without kidney allograft rejection. In contrast, 0/10 monkeys in the LOCD2b group developed chimerism, 5 died of infection and 5 suffered progressive rejection; only 1 recipient survived beyond 100 days. Sequential monitoring of peripheral blood mononuclear cells revealed greater T cell (CD3+) depletion in the LOCD2b-treated animals compared to those receiving ATG. However, NK cells (CD16+CD8+) were significantly more depleted in the ATG group and NK function remained abrogated longer after ATG than LOCD2b treatment (3 weeks vs. <5 days). CONCLUSION: Despite excellent T cell depletion by LoCD2b, ATG was more effective in inducing chimerism and tolerance. This difference correlated with anti-NK activity of the two reagents. These data suggest that NK cells may also resist engraftment of allogeneic bone marrow cells in this model.

Animals↗
PubMed2000

Salivary gland disease in human immunodeficiency virus-positive women from the WIHS study. Women's Interagency HIV Study.

OBJECTIVE: To determine the prevalence of enlargement, tenderness, and absence of saliva on palpation as indicators of salivary gland disease in women who are human immunodeficiency virus (HIV)-positive. STUDY DESIGN: The study subjects are participants in the Women's Interagency HIV Study (WIHS), a multicenter study examining HIV-seropositive women and at-risk HIV-seronegative women. A total of 576 HIV-positive women and 152 HIV-negative women were examined at their baseline oral visit for clinical markers of salivary gland disease. Viral load levels, CD4 counts, and CD8 counts were obtained as part of the related core study. RESULTS: HIV-positive women had higher rates of salivary gland enlargement (4.3%), tenderness (6.9%), and absence of saliva on palpation (26.6%) compared with HIV-negative women, who had rates of 1.3%, 4.6%, and 13.2%, respectively. Absence of saliva was significantly different (P =. 001) between the 2 groups. When 2 of the 3 clinical findings were combined, comparisons between the HIV-positive women and HIV-negative women became significant at the P <.05 level for every combination, except for enlargement/tenderness for the submandibular/sublingual gland. For the HIV-positive women, the viral load was significantly related to enlargement (P =.019) and enlargement/absence of saliva on palpation (P =.037) for the parotids and enlargement (P =.046), absence of saliva (P =.043), and enlargement/absence of saliva (P =.022) for the submandibular/sublingual glands. Significant linear trends were found for increasing viral load and enlargement (P =.013) and enlargement/tenderness (P =.024) for the submandibular/sublingual glands. Significance was present for submandibular/sublingual absence of saliva and tenderness/absence of saliva for CD4 and CD8 medians. CONCLUSIONS: Serostatus is related to salivary gland disease as assessed by glandular enlargement, tenderness, and absence of saliva on palpation. Furthermore, our findings indicate that a multidimensional approach to gland assessment may provide a more complete and perhaps more adequate description of glandular involvement with HIV infection.

Adolescent↗
PubMed2000

Beliefs about and use of occupational medicine practice guidelines by case managers and insurance adjusters.

Workers' compensation case managers and adjusters have increased their use of practice guidelines recently, partly in response to state regulations. However, informally reported rates of use are not as high as desired for the best managed care practices and the greatest reductions in lost work time. Although there are several studies of physicians' use of guidelines, there are few if any studies about case managers' and adjusters' beliefs about, and utilization of, either general medical or occupational medical practice guidelines. Information about attitudes, beliefs about practice guidelines, and actual use should help developers make the guidelines more usable and bring about more effective interaction among case managers, adjusters, treating physicians, and other health professionals. This article reports on pre- and post-training surveys of a cohort of case managers and adjusters who participated in a case-based guideline training course. It then compares their responses to those of the physicians whose cases they might manage.

Case Management↗
PubMed2000

The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women.

The association of xerostomia and salivary gland hypofunction with HIV infection has been established for men but not for women. We investigated the prevalence of these conditions in a national cohort (n = 733) of HIV-positive and at-risk HIV-negative women. Participants in this prospective cross-sectional study were recruited from the Women's Interagency HIV Study (WIHS) at five outpatient USA clinics. Xerostomia was assessed based on "yes" responses to a dry-mouth questionnaire. Samples of unstimulated whole and chewing-stimulated whole saliva were collected under standardized conditions. The major salivary glands were also evaluated clinically. The prevalence of dry-mouth complaint, the absence of saliva upon palpation, and zero unstimulated whole saliva (flow rate = 0 mL/min) were significantly (p = 0.001) higher in HIV-positive women. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher in HIV-positive women vs. HIV-negative women (OR = 2.86; 95% CI, 1.23 to 6.63). Significant (p = 0.03) univariate association was found between zero unstimulated whole saliva and CD4 counts. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher for HIV-positive women with CD4 < 200 compared with those with CD4 > 500 (OR = 2.61; 95% CI, 1.17 to 5.85). Chewing-stimulated flow rates were not significantly different between seropositive and seronegative women. The prevalence of xerostomia and salivary gland hypofunction appears to be significantly higher in HIV-positive women relative to a comparable group of at-risk seronegative women. Immunosuppression levels measured by CD4 cell counts are significantly associated with xerostomia and salivary gland hypofunction in a population of HIV-positive women.

Adolescent↗
PubMed1999

The role of computed tomography with contrast and small bowel follow-through in management of small bowel obstruction.

BACKGROUND: In a significant percentage of patients, radiologic evaluation other than plain abdominal films are required to confirm or exclude the presence of small bowel obstruction. METHODS: Over a 1-year period, 55 patients had both computed tomography and small bowel follow-through studies. Patients were classified as having (1) paralytic ileus, (2) low-grade obstruction, (3) high-grade obstruction, or (4) complete mechanical obstruction. The gold standard for diagnosis was celiotomy in 42 patients and clinical follow-up in 13 patients. RESULTS: Thirty-six out of 42 patients had proven intestinal obstruction at the time of celiotomy. Computed tomography identified 32 out of the 36 high-grade and complete mechanical obstructions. Computed tomography was superior to small bowel follow-through in identifying masses, malignancies, and features of strangulation. Small bowel follow-through correctly identified "insignificant obstructions" when contrast reached the cecum within 4 hours in 18 of 19 patients. CONCLUSIONS: In patients with equivocal findings of small bowel obstruction, computed tomography should be used initially and then small bowel follow-through if computed tomography is not diagnostic. Computed tomography was superior in this study for detecting the cause of the intestinal obstruction and presence of strangulation.

Adolescent↗
PubMed1999

A nested PCR for the ssrRNA gene detects Trypanosoma binneyi in the platypus and Trypanosoma sp. in wombats and kangaroos in Australia.

Trypanosome infections in their natural hosts are frequently difficult to detect by microscopy, and culture methods are unreliable and not suitable for all species of Trypanosoma. A nested PCR strategy for detecting and identifying Trypanosoma species, suitable for detecting both known and unknown trypanosomes, is presented. Thirty-two blood samples from 23 species of Australian birds and mammals were screened by a nested PCR for the presence of Trypanosoma sp. ssrRNA. Three infections were detected, one in an eastern grey kangaroo (Macropus giganteus), one in a common wombat (Vombatus ursinus) and one in a platypus (Ornithorhynchus anatinus). The kangaroo and wombat are new host records for Trypanosoma sp.; the platypus parasite was Trypanosoma hinneyi. The three parasites could be distinguished by restriction fragment length polymorphisms of the amplified fragment of the ssrRNA gene. The kangaroo and wombat parasites were also isolated in a semi-solid blood agar medium. The culture forms of the kangaroo trypanosome had an expanded flagellar sheath in which structures similar to hemidesmosomes were detected by EM. The nested PCR was at least as sensitive as culture, and analysis of the PCR products gave parasite-specific fingerprints. Therefore this method could be suitable for rapidly screening host animals for the presence of trypanosomes and identifying the infecting strain.

Animals↗
PubMed1998

Psychotic symptoms and violent behaviors: probing the components of "threat/control-override" symptoms.

Evidence for an association between mental illness and violence has grown in recent years, leading many to ask why such an association exists. One hypothesis links elevated rates of violence among people with mental illness to a small set of psychotic symptoms--so called threat/control-override (TCO) symptoms. Several studies have supported this hypothesis, but none has examined which of the components, threat or control-override--if either--predominates in explaining violence. To explore this issue we used data from a two-stage epidemiological study (n = 2741) conducted in Israel. Data on TCO symptoms were collected using two methods--fixed-format self-report questions from the first stage and psychiatrists' ratings based on interviews using the Schedule for Affective Disorders and Schizophrenia (SADS) from the second. Results show that both a measure of threat and a measure of control-override are independently associated with violent behaviors. Results also show that neither method--neither fixed-format questions nor psychiatrist rating--predominates in explaining violence. In sum, these results indicate that both the threat and the control-override components of the TCO concept are useful in predicting violent behaviors and that a better measurement of the TCO concept is achieved using a multimethod approach.

Adult↗
PubMed1998

Clinical issues surrounding the use of terbutaline sulfate for preterm labor.

beta-mimetics have been prescribed by physicians to arrest or prevent premature labor for more than 20 years. Although not approved by the Food and Drug Administration (FDA) for tocolytic use, terbutaline sulfate has been the most widely prescribed beta-mimetic in the United States. Recently, the role of terbutaline in the treatment and prevention of preterm labor has been questioned by the FDA. Because the off-label use of drugs is a formally accepted practice in medicine when scientific studies support such use, we reviewed the currently available clinical literature on terbutaline use in various routes of delivery: intravenous, oral, and subcutaneous via infusion pump. This review describes the clinical evidence that supports the safe and effective use of terbutaline as a tocolytic agent in certain patient populations. Practicing physicians should continue to have unrestricted use of terbutaline for tocolysis as one of the few remaining therapeutic options remaining in the fight against preterm birth.

Administration, Oral↗
PubMed1998

Allergic rhinitis history as a predictor of other future disqualifying otorhinolaryngological defects.

BACKGROUND: Problems with the otorhinolaryngological system represent the largest category of pilot referrals for specialist assessment and possible waiver recommendation in the U.S. Navy. Most of these referrals deal with allergic rhinitis (AR). Approximately 3% of all Naval aircrew have a waiver for AR. This paper tests the hypothesis that the identification of a history of AR is a predictor for the development of future disqualifying otorhinolaryngological (ear, nose, and throat, or ENT) diseases such as chronic sinusitis, alternobaric disease, conductive hearing loss, or the need for various surgical procedures (i.e., Caldwell Luc antrostomy, myringotomy, polypectomy, mastoidectomy, and functional endoscopic sinus surgery. METHODS: The U.S. Navy Aviation Medical Data Retrieval System (AMDRS) was searched for aircrew who were diagnosed only with AR in 1988. These aircrew were matched with a control group from the 1988 database who had no diagnoses of AR or any of the other disqualifying ENT diseases. The AR cohort and controls had their physical examinations up to 1995 assessed to see if any of the disqualifying ENT conditions had developed. RESULTS: There was a statistically significant increase in the number of identifiable chronic sinusitis cases but there was no significant relationship between an AR history and the development of any of the other ENT disease categories. CONCLUSION: Based on the study findings, it is doubtful that uncomplicated AR as an isolated historical diagnosis should be disqualifying for either candidate or designated aircrew.

Aerospace Medicine↗
PubMed1997

Rapid determination of clonality by detection of two closely-linked X chromosome exonic polymorphisms using allele-specific PCR.

We reported two specific, reproducible, and quantitative clonality assays based on detection of exonic polymorphisms of the X chromosome genes p55 and G6PD using rtPCR-LDR. These assays are inconvenient for screening purposes. This study sought to develop a simple, reproducible assay, practical for screening genomic DNA samples for p55/G6PD genotypes, rapid clonality determination, and to determine the linkage relationship between these closely related loci. The salient feature of ASPCR is the performance of two PCR rounds. The first generates template; the second, using one aliquot of first-round products in two reaction tubes, each containing one allele-specific primer, detects each allele. ASPCR and rtPCR-LDR produced identical p55/G6PD results in 91 normal female genomic DNAs, and in 12 clonal hematopoietic disorder cDNAs, confirming assay validity. 209 female and 207 male genomic DNA samples were analyzed for p55/G6PD genotype by ASPCR; 60% of females were heterozygous at one or both loci. G6PD and p55 allelic frequencies were significantly different among African-American men and women, but were not significantly different among Caucasian men and women. These loci were in linkage equilibrium among African Americans, but not among Caucasians. ASPCR is a rapid, sensitive, and specific method for screening large numbers of genomic DNAs, and for rapid clonality determination.

Alleles↗