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Biomedical subjects

D Ryan

Publications and source records attributed to D Ryan.

At least 19 recordsLinked to original sources

Nest- and colony-mate recognition in polydomous colonies of meat ants (Iridomyrmex purpureus).

Workers of polydomous colonies of social insects must recognize not only colony-mates residing in the same nest but also those living in other nests. We investigated the impact of a decentralized colony structure on colony- and nestmate recognition in the polydomous Australian meat ant (Iridomyrmex purpureus). Field experiments showed that ants of colonies with many nests were less aggressive toward alien conspecifics than those of colonies with few nests. In addition, while meat ants were almost never aggressive toward nestmates, they were frequently aggressive when confronted with an individual from a different nest within the same colony. Our chemical analysis of the cuticular hydrocarbons of workers using a novel comprehensive two-dimensional gas chromatography technique that increases the number of quantifiable compounds revealed both colony- and nest-specific patterns. Combined, these data indicate an incomplete transfer of colony odor between the nests of polydomous meat ant colonies.

Aggression↗

The impact of ice-skating injuries on orthopaedic admissions in a regional hospital.

Since the opening of a temporary ice-rink in our hospital's catchment area, we have observed an increase in patients requiring in-patient treatment for orthopaedic intervention. The authors performed a prospective analysis of all patients admitted to our unit over a one-month period. Epidemiological data, wearing of protective gear and skater experience were collected. Fracture type, treatment required, average length of hospital stay and number of days missed from work was also recorded. Ice-skating injuries accounted for 7.7% of our total admissions over the study period. There was a significant variation noted in the types of fracture sustained ranging from comminuted fractures of the radial head to spiral fractures of the tibia. The average length of hospital stay was 2.6 days and average time missed from work was 6.1 weeks. This paper highlights the potential serious injuries that can occur in ice-skating and their impact on admissions to our orthopaedic unit.

Adolescent↗

Efficacy of an internet-based behavioral weight loss program for overweight adolescent African-American girls.

OBJECTIVE: This randomized controlled trial tested the efficacy of an internet-based lifestyle behavior modification program for weight management in African-American girls. DESIGN: African-American girls were randomly assigned to an interactive behavioral internet program or an internet health education program, the control condition. The behavioral intervention included internet counseling and was highly interactive. The control intervention was a passive (non-interactive) educational program. Parents were also participants in the study. Participants in both treatment groups met in face-to-face sessions on four occasions over the first 12 weeks of a 6-month intervention. SUBJECTS: The study enrolled 57 African-American adolescent girls (ages 11 to 15 years) who were overweight or obese and had at least one biological parent who was obese [body mass index (BMI) >30 kg/m2]. Of the 57 participants, 50 (88%) completed the 6-month trial. MEASUREMENTS: Outcome data, including BMI, body weight, body composition, dietary intake, and weight loss behaviors were collected at baseline and 6-months later. A computer server tracked utilization of the websites. Participation in the program was measured by number of "hits" on the website. RESULTS: Compared to the control condition, adolescents in the behavioral treatment lost more body fat (group difference =1.6% body fat) and parents lost significantly more body weight (group difference =2.1 kg). Utilization of the behavioral website by adolescents and parents was associated with positive outcome. Dietary fat intake was lowered for adolescents and parents in the behavioral treatment group. CONCLUSION: An internet-based behavioral intervention was superior to internet-based health education and yielded decreased body fat for adolescent girls and decreased body weight for parents.

Absorptiometry, Photon↗

Percent body fat measured by BIA and DEXA in obese, African-American adolescent girls.

OBJECTIVE: To compare the estimation of body fat between bioelectrical impedance analysis (BIA) and dual energy X-ray absorptiometry (DEXA) in overweight, African-American female adolescents. SUBJECTS: In total, 54 African-American adolescent female subjects were recruited for Study 1. Each adolescent's body mass index was greater than the 85th percentile and their average body fat was 45% according to DEXA. A total of 26 African-American adolescent female subjects were available for Study 2, and had an average body fat of 26% according to DEXA. MEASUREMENTS: Percent body fat was measured by DEXA and BIA. Seven different BIA equations were tested. Both sets of data were analyzed using Bland-Altman regression analyses, utilizing percent body fat measured by DEXA as the criterion. RESULTS: The Kushner equation provided estimates that were unaffected by body fat in both studies. Estimates were unbiased when applied to the exclusively overweight sample and biased when utilized with the separate sample of normal weight and obese girls. The remaining equations were biased, provided inconsistent estimates across body weight, or were biased and provided inconsistent estimates. Ethnicity-specific and ethnicity-combined equations performed similarly in the obese sample, but became more disparate when applied to a sample encompassing a wider body weight range. The limits of agreement between all BIA equations and the DEXA estimates ranged from 6 to 9%. CONCLUSION: The study suggests that the Kushner BIA equation is appropriate for use with African-American female adolescents across the weight spectrum, while the majority of BIA equations underestimated percent body fat as body fat increased.

Absorptiometry, Photon↗

Recombinant NY-ESO-1 cancer antigen: production and purification under cGMP conditions.

The cancer-testis antigen, NY-ESO-1, has been engineered into a bacterial expression plasmid which incorporates a His6-tag. The plasmid was transfected into E. coli strain BL21 and Master and Working cell banks generated from this expression system. Three 15-litre fermentations were performed under cGMP (code of Good Manufacturing Practice) conditions and the crude NY-ESO-1 tagged protein isolated as solubilised inclusion bodies. A three-step cGMP chromatography process (immobilised metal affinity, anion exchange, and hydrophobic interaction) was utilised to purify the protein. The purified NY-ESO-1 is being used in early stage human cancer vaccine trials in Australia and the U.S.A.

Antigens, Neoplasm↗

A survey of trainees' opinions and current clinical practice after behaviour therapy training.

The widespread use of cognitive behaviour therapy principles in psychiatric/mental settings has been an ongoing feature of health and social care since at least the 1960s. The current study evaluated the training process as well as the use of the skills by course participants on a dedicated behaviour therapy course in Ireland. A cross sectional study was undertaken, using postal distribution of a questionnaire based on a similar study undertaken in the UK. The sample comprised all graduates of the course from 1986 to 1999 (N = 257). Thirty-three per cent of respondents report using their behaviour therapy skills to a high level since completion of the course. Approximately 53% of respondents reported having changed job since completion of the course. Significant differences emerged within this group in relation to their ratings of the importance of various elements of the course and also in relation to the perceived enhancement of both general clinical skills (P = 0.000) and specific behaviour therapy skills (P = 0.000) as well as the rating of current skills (P = 0.015) and the respondents' use of behaviour therapy since completing the course (P = 0.015). While a high proportion of participants had some prior theoretical or experiential exposure to behaviour therapy, the findings report high satisfaction levels with the training they received. However, the survey signals deficits in terms of the usage of the skills. While on the one hand, the general and specific skills acquired while on the course seem to transfer quite easily across functions and levels of responsibility, it is of concern that over a 13-year period, only 17% of respondents indicated that behaviour therapy was the main focus of their work. The implications of these findings are discussed in relation to policy and practice issues.

Adult↗

Mobile phone technology in the management of asthma.

Peak flow monitoring is widely recommended as part of a self-management plan for asthma. We conducted an observational study using electronic peak flow monitoring and mobile phone technology in a UK general practice population over a nine-month period. Patients between 12 and 55 years of age who required treatment with regular inhaled steroids and (as needed) bronchodilators were recruited from nine general practices. Patients were included if their asthma was considered stable (i.e. no exacerbation in the previous three months). No therapeutic intervention was proposed. The primary outcome measure was compliance. In all, 69% of the 46 participants who filled in the post-study questionnaire were 'satisfied' or 'very satisfied' by the study, citing the ease of use and the increased autonomy and understanding of asthma as the main advantages. In total, 74% indicated that the system had helped to improve their ability to manage their symptoms. The most positive features of the telemedicine system were described as follows: increased awareness and information about asthma, improved ability to monitor/manage the condition with the feedback screens on the mobile phone and ease of use.

Adolescent↗

Limestone-particle-stabilized macroemulsion of liquid and supercritical carbon dioxide in water for ocean sequestration.

When liquid or supercritical CO2 is mixed with an aqueous slurry of finely pulverized (1-20 microm) limestone (CaCO3) in a high-pressure reactor, a macroemulsion is formed consisting of droplets of CO2 coated with a sheath of CaCO3 particles dispersed in water. The coated droplets are called globules. Depending on the globule diameter and the CaCO3 sheath thickness, the globules sink to the bottom of the water column, are neutrally buoyant, or float on top of the water. The CaCO3 particles are lodged at the CO2/ H2O interface, preventing the coalescence of the CO2 droplets, and thus stabilizing the CO2-in-water emulsion. We describe the expected behavior of a CO2/H2O/CaCO3 emulsion plume released in the deep ocean for sequestration of CO2 in the ocean to ameliorate global warming. Depending on the amount of CO2 injected, the dense plume will descend a few hundred meters while entraining ambient seawater until it acquires neutral buoyancy in the stratified ocean. After equilibration, the globules will rain out from the plume toward the ocean bottom. This mode of CO2 release will prevent acidification of the seawater around the release point, which is a major environmental drawback of ocean sequestration of liquid, unemulsified CO2.

Calcium Carbonate↗

In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb).

Natural antibodies (Abs), predominantly anti-Gal alpha 1-3Gal (Gal) Abs, in non-human primates and human beings present a major hurdle to successful pig-to-primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naïve baboons using non-specific immunosuppressive or B cell-specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and total immunoglobulin (Ig)-secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme-linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments.

Animals↗

Bone marrow transplantation from alpha1,3-galactosyltransferase gene-knockout pigs in baboons.

BACKGROUND: Successful hematopoietic cell allotransplantation results in donor-specific tolerance, but this approach has been unsuccessful in the wild-type pig-to-baboon xenotransplantation model, as pig cells were lost from the circulation within 5 days. However, after cessation of immunosuppressive therapy on day 28, all baboons demonstrated non-specific unresponsiveness on mixed leukocyte reaction (MLR) for at least 30 days. We have now investigated the transplantation of bone marrow (BM) cells from miniature swine homozygous for alpha1,3-galactosyltransferase gene-knockout (GalT-KO). METHODS: Baboons (n = 3) were pre-treated with whole body and thymic irradiation, anti-thymocyte globulin, and splenectomy, and received immunosuppressive and supportive therapy for 28 days. BM was harvested from GalT-KO swine (n = 3). The baboons were monitored for the presence of pig cells by flow cytometry and colony-forming units (CFUs), and for cellular reactivity by MLR. RESULTS: A mean of 11 x 10(8) BM cells/kg was infused into each baboon. The mean absolute numbers and percentages of pig cells detected in the blood at 2 h and on days 1, 2 and 4, respectively, were 641/microl (9.5%), 132/microl (3.4%), 242/microl (3.9%), and 156/microl (2.9%). One baboon died (from accidental hemorrhage) on day 6, at which time chimerism was present in the blood (2.0%) and BM (6.4%); pig cell engraftment in the BM was confirmed by polymerase chain reaction (PCR) of CFUs. In the two other baboons, blood chimerism was lost after day 5 but returned at low levels (<1%) between days 9 to 16 and 7 to 17, respectively, indicating transient BM engraftment. Both surviving baboons showed non-specific unresponsiveness on MLR until they were euthanized on days 85 and 110, respectively. CONCLUSIONS: By using BM cells from GalT-KO pigs, chimerism was detected at levels comparable with previous studies when 30-fold more growth factor-mobilized peripheral blood progenitor cells had been transplanted. In addition, cellular hyporesponsiveness was prolonged. However, long-term engraftment and chimerism were not achieved.

Animals↗

Assessment of risk for type 2 diabetes mellitus in a Caribbean population with high diabetes-related morbidity.

Diabetes mellitus is a major cause of morbidity in Trinidad and Tobago. Screening programmes are not incorporated in the health sector and the population at risk remains unaware of the benefits of screening. We investigated the risk of developing Type 2 diabetes mellitus in office workers with one risk factor. Participants were randomly selected from the urban corporate sector in Port of Spain. Fasting capillary blood glucose and the American Diabetes Association (ADA) questionnaire for major diabetes risk factors were used to assess risk. Student pharmacists approached 482 persons, of whom 317 consented to participate (66% response rate). There were 101 (32%) men and 216 (68%) women, 37 (39%) were of African ancestry and 28% each were of East Indian and mixed ancestry. Family history was positive in 54%. Thirty per cent (95) of the volunteers were at risk of developing Type 2 diabetes mellitus (41 men; 54 women). Based on the ADA questionnaire, 82% (78) of volunteers were at high risk for developing Type 2 diabetes mellitus. The ADA risk test and Impaired Fasting Glucose were both positive in 13 (14%) volunteers. In subjects at risk, Body Mass Index (BMI) was > 25 kg/m2 in 74% (78) and the waist/hip ratio was 0.85. Approximately 30% of office staff was at risk of developing diabetes mellitus. The ADA questionnaire is a useful non-invasive measure which pharmacists can use to assess risk for Type 2 diabetes mellitus. The glucometer can be used for risk assessment providing that it is associated with a quality assurance programme and that diagnosis is confirmed with laboratory testing.

Adult↗

Metastases to the breast revisited: radiological-histopathological correlation.

Metastases to the breast from extramammary tumours are infrequent. The main challenge in diagnosis is differentiating them from primary breast cancer. Radiologically this can be difficult as there are no specific imaging characteristics for metastases to the breast. Cytopathological evaluation, as well as full radiological assessment, is vital to avoid unnecessary surgery. Sources of primary tumours include a wide variety of cancers. In this pictorial review we illustrate a number of the commonest sources of primary tumours including lymphoma, lung, ovarian and cervical carcinoma, intestinal carcinoid and rare cases of Ewing's sarcoma and malignant pigmented melanocytic schwannoma (low-grade malignant melanoma).

Adult↗

An exploratory investigation of the effect of arsenic trioxide on anti-Gal antibody production in baboons.

BACKGROUND: Arsenic trioxide (As2O3) is an anticancer drug that has been reported to induce apoptosis and inhibit differentiation in human plasmacytoma and normal plasma/B cells without significant myelosuppression. We assessed the ability of As2O3 as single therapy or in combination with an anti-CD20 monoclonal antibody (mAb) and whole body irradiation (WBI) to deplete B and plasma cells, both in vitro and in vivo, and to reduce the level of anti-alphaGal1-3Gal antibody (anti-Gal Ab) in baboons. METHODS: In vitro the effect of As2O3 on antibody secretion (anti-Gal IgM, total IgG and IgM) was measured by enzyme-linked immunospot assay (ELISPOT). Its inhibition of proliferation of baboon splenocytes and the NCI-H929 human plasmacytoma cell line was measured by tritiated thymidine uptake. In vivo: all baboons (n=7) had undergone splenectomy. The effects of As2O3 (0.18 to 0.36 mg/kg) on B/plasma cell depletion and anti-Gal Ab production were assessed in three baboons. For comparison, three baboons received either WBI (2 x 150 cGy) or anti-CD20 mAb (20 mg/kg x 4 doses), or both WBI and anti-CD20 mAb. A final baboon received As2O3 + WBI (150 cGy) + anti-CD20 mAb. Anti-Gal Ab levels were measured daily by ELISA. Depletion of B cells from blood and bone marrow (BM) was monitored by flow cytometry and by histology of lymph nodes (LN). Autopsy was performed in three baboons. RESULTS: In vitro: As2O3 (at 5 x 10-6 mol/l) reduced anti-Gal IgM and total IgM secretors by 76% (P=0.53) and 95% (P < 0.001), respectively, but did not reduce total IgG secretors. As2O3 inhibited in a dose-dependent manner the proliferation of activated splenocytes and of the NCI-H929 plasmacytoma cell line; complete inhibition was achieved at a dose of 1 x 10-5 mol/l. In vivo: As2O3 was found to be toxic at the doses given and was associated with the deaths of two of the four baboons that received it. Daily intravenous therapy with As2O3 alone reduced B cells (CD20+) in the blood (by 50 to 90%), BM (40%) and LN (20 to 30%), but anti-Gal Ab levels were not significantly decreased. Anti-CD20 mAb therapy alone or WBI alone depleted B cells by 100% in the blood and BM, and 80 to 100% in the LN. The combination of anti-CD20 mAb + WBI led to depletion of B cells in blood, BM and LN for 3 months, but reduction of anti-Gal Ab remained marginal. The combination of As2O3 + anti-CD20 mAb + WBI did not reduce anti-Gal Ab levels further. At autopsy in the latter baboon, B cells remained present in Peyer's patches and tonsils. CONCLUSIONS: In vitro: As2O3 reduced B/plasma cell numbers and suppressed IgM secretors, but not IgG secretors. In vivo: As2O3 was not as effective as either anti-CD20 mAb or WBI in depleting B/plasma cells, and was largely ineffective in reducing anti-Gal Ab levels. Its administration was associated with considerable toxicity. Autopsy in one baboon suggested that B cells in Peyer's patches and tonsils may be resistant to therapy and remain a source of continuing production of anti-Gal Ab.

Animals↗

Inadequate rates are lower when FNAC samples are taken by cytopathologists.

Inadequate rates (IR) in FNAC from different sources were compared. The rates were lowest when FNAC was performed by a cytopathologist (12%) and highest when done by a non-cytopathologist (32%). These differences were mirrored in high IRs in breast cancer cases. IR was not significantly improved when non-cytopathologist FNAC was attended by a cytotechnician.

Biopsy, Fine-Needle↗

Benign cementoblastoma: a case report.

Benign cementoblastoma is an odontogenic tumour of mesenchymal origin. It usually presents as a distinct lesion with characteristic radiographic and histopathologic features. The tumour is attached to the roots of the teeth and commonly occurs in the posterior mandible. The case of a 19-year old female with a benign cementoblastoma is presented. The clinical histopathologic and therapeutic aspects of the tumour are described.

Adult↗

Phosphotyrosyl peptides block Stat3-mediated DNA binding activity, gene regulation, and cell transformation.

Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic signaling proteins that participates in normal cellular responses to cytokines and growth factors. Frequently, however, constitutive activation of certain STAT family members, particularly Stat3, has accompanied a wide variety of human malignancies. To identify small molecule inhibitors of Stat3, we investigated the ability of the Stat3 SH2 domain-binding peptide, PY*LKTK (where Y* represents phosphotyrosine), to disrupt Stat3 activity in vitro. The presence of PY*LKTK, but not PYLKTK or PFLKTK, in nuclear extracts results in significant reduction in the levels of DNA binding activities of Stat3, to a lesser extent of Stat1, and with no effect on that of Stat5. Analyses of alanine scanning mutagenesis and deletion derivatives of PY*LKTK reveal that the Leu residue at the Y+1 position and a substituent at the Y-1 position (but not necessarily Pro) are essential for the disruption of active Stat3, thereby mapping the minimum active sequence to the tripeptide, XY*L. Studies involving bead-coupled PY*LKTK peptide demonstrate that this phosphopeptide directly complexes with Stat3 monomers in vitro, suggesting that PY*LKTK disrupts Stat3:Stat3 dimers. As evidence for the functional importance of peptide-directed inhibition of Stat3, PY*LKTK-mts (mts, membrane translocating sequence) selectively inhibits constitutive and ligand-induced Stat3 activation in vivo. Furthermore, PY*LKTK-mts suppresses transformation by the Src oncoprotein, which has been shown previously to require constitutive Stat3 activation. Altogether, we have identified a minimal peptide that inhibits Stat3 signaling and provides the conceptual basis for use of this peptide as a lead for novel peptidomimetic drug design.

3T3 Cells↗

S100A7, S100A10, and S100A11 are transglutaminase substrates.

S100 proteins are a family of 10-14 kDa EF-hand-containing calcium binding proteins that function to transmit calcium-dependent cell regulatory signals. S100 proteins have no intrinsic enzyme activity but bind in a calcium-dependent manner to target proteins to modulate target protein function. Transglutaminases are enzymes that catalyze the formation of covalent epsilon-(gamma-glutamyl)lysine bonds between protein-bound glutamine and lysine residues. In the present study we show that transglutaminase-dependent covalent modification is a property shared by several S100 proteins and that both type I and type II transglutaminases can modify S100 proteins. We further show that the reactive regions are at the solvent-exposed amino- and carboxyl-terminal ends of the protein, regions that specify S100 protein function. We suggest that transglutaminase-dependent modification is a general mechanism designed to regulate S100 protein function.

3T3 Cells↗

Green/red dual fluorescence detection of total protein and alkaline phosphate-conjugated probes on blotting membranes.

A two-color fluorescence detection method is described based upon covalently coupling the succinimidyl ester of BODIPY FL-X to proteins immobilized on poly(vinylidene difluoride) (PVDF) membranes, followed by detection of target proteins using the fluorogenic substrate 9H-(1,3-dichloro-9,9-dimethylacridin-2-one-7-yl(DDAO)-phosphate in combination with alkaline-phosphatase-conjugated reporter molecules. This results in all proteins in the profile being visualized as green signal while those detected specifically with the alkaline-phosphatase conjugate appear as red signal. The dichromatic detection system is broadly compatible with a wide range of analytical imaging devices including UV epi- or transilluminators combined with photographic or charge-coupled device (CCD) cameras, xenon-arc sources equipped with appropriate excitation/emission filters, and dual laser gel scanners outfitted with a 473 nm second-harmonic generation or 488 nm argon-ion laser as well as a 633 nm helium-neon or 635 nm diode laser. The dichromatic detection method permits detection of low nanogram amounts of protein and allows for unambiguous identification of target proteins relative to the entire protein profile on a single electroblot, obviating the need to run replicate gels that would otherwise require visualization of total proteins by silver staining and subsequent alignment with chemiluminescent or colorimetric signals generated on electroblots.

Acridines↗