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Biomedical subjects

P Buckley

Publications and source records attributed to P Buckley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression.

Neutrophil gelatinase-associated lipocalin (NGAL) has recently been identified in myeloperoxidase-negative neutrophil granules. Members of the lipocalin family are thought to bind and transport small lipophilic molecules such as retinoids and roles in cell regulation have been proposed. Recently, NGAL has also been demonstrated in the colonic mucosa in certain pathologic conditions. The aim of this study was to examine the distribution of NGAL in normal and neoplastic tissues by immunohistochemistry. Interestingly, NGAL was found in a variety of normal and pathological human tissues. A cell type-specific pattern of expression was seen in bronchus, stomach, small intestine, pancreas, kidney, prostate gland, and thymus. The comparative analysis of the putative rat homologue neu-related lipocalin showed a very similar pattern of expression with the exception of pancreas and kidney. Neoplastic human tissues showed a very heterogeneous expression of NGAL protein. High NGAL levels were found in adenocarcinomas of lung, colon and pancreas. In contrast, renal cell carcinomas of various subtypes and prostate cancers contained low NGAL levels. Lymphomas and thymic tumours were negative for NGAL immuno-labeling. Knowledge about the location of NGAL in normal cells and in disease states provides the first clues towards understanding its biological function.

Acute-Phase Proteins↗
PubMed1998

Analysis of primate renal allografts after T-cell depletion with anti-CD3-CRM9.

BACKGROUND: FN18-CRM9 is a CD3-specific immunotoxin that is capable of depleting CD3+ T cells. Pretreatment of rhesus monkeys with this agent before transplantation can induce donor-specific tolerance and "split tolerance" to renal allografts. METHODS: Heterotopic renal transplants were performed on monkeys that received posttransplant FN18-CRM9. Histological and immunohistological staining, as well as analysis of the intragraft cytokine profile by reverse transcriptase polymerase chain reaction, was performed on percutaneous allograft biopsies. RESULTS: Experimental monkeys had significant prolongation of allograft survival. Although an interstitial, mononuclear cell infiltrate was seen in all of the renal transplants, there was minimal evidence of acute cellular rejection. Histological evidence of alloantibody-mediated damage was detected 3 to 5 months after transplantation in the monkeys treated with FN18-CRM9. Immunohistology demonstrated the reappearance of CD3+ and CD4+ T cells, as well as CD20+ B cells, in the grafts. Cytokine analysis demonstrated expression of interferon-gamma. An intact anti-donor IgG response was seen. CONCLUSION: Treatment of monkeys with FN18-CRM9 immediately after transplantation significantly prolongs renal allograft survival. Allograft biopsies demonstrate a lack of acute cellular rejection; however, alloantibody-mediated graft damage and rejection occur, with an intact anti-donor IgG response. The intragraft expression of the interferon-gamma may reflect this ongoing humoral rejection. These data suggest that even a brief period of T-cell allosensitization may lead to humorally mediated allograft damage. Efforts to achieve tolerance with posttransplant FN18-CRM9 will require modification of the protocol to deplete T cells before allosensitization exposure or to supplement the posttransplant immunomodification strategy.

Animals↗
PubMed1998

Novel antipsychotics and the neuroleptic malignant syndrome: a review and critique.

OBJECTIVE: The authors' goal was to analyze reported cases of neuroleptic malignant syndrome in patients given clozapine and risperidone. METHOD: They assessed 19 cases of clozapine-induced neuroleptic malignant syndrome and 13 cases of risperidone-induced neuroleptic malignant syndrome against three criteria sets and against extent of exclusionary workup and then designated them as high or low probability of being neuroleptic malignant syndrome. RESULTS: Nine of the 19 cases of clozapine-related neuroleptic malignant syndrome and eight of the 13 cases of risperidone-related neuroleptic malignant syndrome were designated as having high probability of being neuroleptic malignant syndrome. The remainder were designated as having low probability because presentations were not linked to treatment or failed to meet criteria for the syndrome. CONCLUSIONS: Neuroleptic malignant syndrome can occur in patients given atypical antipsychotics and resembles "classical" neuroleptic malignant syndrome. However, side effect profiles overlap considerably with neuroleptic malignant syndrome criteria, and atypical antipsychotics may cause neurotoxicities unrelated to (but misattributed as) neuroleptic malignant syndrome. Insufficient evidence exists for "atypical" neuroleptic malignant syndrome with novel antipsychotics.

Adolescent↗
PubMed1998

Primate renal transplants using immunotoxin.

BACKGROUND: T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery. METHODS: Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner. RESULTS: Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months. CONCLUSIONS: Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.

Animals↗
PubMed1997

Main chain and side chain dynamics of peptides in liquid solution from 13C NMR: melittin as a model peptide.

Peptide backbone and lysine and tryptophan side chain mobilities in the synthetic, 26-residue peptide melittin (MLT) enriched with 13C were investigated in liquid solution by 13C T1 and steady state nuclear Overhauser effect measurements at two magnetic fields and by Trp fluorescence anisotropy measurements and were analyzed using the Lipari and Szabo model-free approach. The overall rotational correlation times at 20 degrees C were 1.28, 1.4, 2.8, and 4.2 ns for monomeric random coil MLT, for monomeric helical MLT (in CD3OD), for tetrameric MLT in neat D2O, and for the tetramer in 50 mM phosphate buffer, respectively. Motion of the backbone in the interior of the sequence was most restricted in the monomeric helix and least restricted in the tetramer. In the monomeric disordered peptide, relatively less restricted backbone motion extending from the N terminus to the fourth residue was observed. Such "end effects" continued only to the third residue in the monomeric helix and were observed just in the amino terminus glycine in the tetramer. The three Lys side chains showed the least restricted motion in the monomers and a differential restriction in the tetramers consistent with the tetramer structure. The motion of the Trp side chain was more restricted than that of Lys side chains and generally as restricted as that of the interior backbone atoms. The effective correlation times for the local motion of the backbone atoms were in the motional narrowing limit and showed distinct patterns. Agreement between NMR relaxation and Trp fluorescence anisotropy data was good for the monomer but not for the tetramer. Implications of these results for peptide dynamics in general are examined.

Amino Acid Sequence↗
PubMed1997

Alteration of the CD34+ Tf-1 beta cell line profile in response to long-term exposure to IL-15.

Interleukin 15 (IL-15) is a cytokine with many functional characteristics that are similar to IL-2. Most of the functional activities that IL-2 and IL-15 support have been evaluated in short-term assays. It was our intention, then, to determine the long-term effects of IL-15 in comparison to IL-2. These studies were performed using the growth factor-dependent myelomonocytic cell line, Tf-1, which has been well characterized with regard to morphology, CD marker expression, responses to certain growth factors and cytokines (GM-CSF, IL-4, erythropoietin), and can differentiate through the myeloid and erythroid lineages. In order to study IL-2 and IL-15 responses, Tf-1 cells were retrovirally infected with the IL-2R beta chain gene as a means to confer IL-2 responsiveness to this cell type. The results of this study demonstrate that retroviral infection of Tf-1 successfully generated a stable IL-2 responsive cell line, Tf-1 beta, without interfering with the original characteristics of the Tf-1 cell. Tf-1 beta cells respond functionally to both IL-2 and IL-15. When Tf-1 beta cells are grown for 8 weeks in IL-2 (Tf-1 beta 2), rather than GM-CSF, the original morphology, CD marker expression, esterase activity and proliferative response is unaltered in comparison to that of the original Tf-1 beta line maintained in GM-CSF. However, long-term growth of Tf-1 beta in IL-15 (Tf-1 beta 15) results in morphological alterations, downregulation of CD33, CD38, and HLA-DR, and a decreased response to IL-15 in comparison to Tf-1 beta 2. These studies support the concept that retroviral infection, even when it confers new functions upon a cell, does not necessarily alter all other functions, as assessed by evaluation of its phenotypic profile. Furthermore, the production of the Tf-1 beta 2 and Tf-1 beta 15 sublines demonstrates that IL-2 and IL-15 can support long-term cell growth. However, this long-term growth in IL-15 leads to subtle alterations in the cell profile that are not seen with IL-2, suggesting that distinctions in IL-2 and IL-15 function do exist. Further study of the Tf-1 beta 15 cell line will be useful to clarify these functional distinctions between IL-2 and IL-15.

ADP-ribosyl Cyclase↗
PubMed1997

Objective measurement of psychiatric symptoms: a quality improvement process for inpatient care.

BACKGROUND: The objective measurement of patient improvement and outcome in mental health is a welcome, if challenging, goal. A continuous quality improvement (CQI) project was undertaken at an extended care facility in northeastern Ohio. The objectives of the CQI project, as delineated in May 1994, were to improve the administration of the Brief Psychiatric Rating Scale (BPRS) and the presentation and use of findings. EVALUATION STANDARDIZATION: A cross-functional team, meeting between April and September 1994, made a series of recommendations. After a training program was initiated in fall 1994, interrater reliability of the BPRS increased. A schedule for BPRS evaluations resulted in more even distribution of evaluations within a quarter. DATABASE DEVELOPMENT: A new work group, formed in late 1994, reviewed previous system improvements and identified future directions. For example, it decided to refine the BPRS evaluation form itself to facilitate data entry of the evaluation information and to consider possible formats for clinically useful presentation of the serial evaluation data. CLINICAL OUTCOME MEASUREMENT: Actual clinical performance improvement indicators (as opposed to the administrative compliance indicators) were instituted to notify staff of significant patient improvement or deterioration, which in turn would prompt refinement of treatment. CURRENT WORK: The interrelationships and implications of BPRS-driven clinical outcome(s), length of hospital stay, and cost of services are being considered to determine the effects of new medications and other treatments. CONCLUDING REMARKS: As the complexity and demands of mental health care continue to rapidly evolve, symptom measurement and patient outcome are set to become critical determinants in the ultimate allocation of increasingly limited resources.

Adult↗
PubMed1997

Immunotoxicological assessment of cyclosporin A by conventional pathological techniques and immune function testing in the rat.

1. Groups of male rats were given different doses of cyclosporin A, ranging from the maximum tolerated dose (20 mg/kg/day) downwards, 7 days a week for 28 days using a protocol derived from OECD test guideline 407. 2. At the end of the test, one set of animals underwent a detailed necropsy and histopathological examination of lymphoid tissues. Immune function was assessed using the lymphoproliferative response and natural killer cell activity of their spleen cells. Another set of animals was immunised with sheep erythrocytes on day 25 and used to evaluate the ability to produce specific anti-sheep red blood cell antibody. 3. Cyclosporin A produced detectable effects on the immune system at all doses and at doses lower than other toxic effects. Both histopathological techniques and one of the immune function tests were able to identify changes at the lowest dose, 1.25 mg/kg/day. 4. The results of this investigation suggest that conventional histopathological techniques, if applied to a range of lymphoid organs, are sufficient to identify potential immunotoxicants without recourse to immune function tests.

Animals↗
PubMed1996

An object relations perspective on the nature of resistance and therapeutic change.

An object relations model of resistance and therapeutic change based on Fairbairn's conception of psychopathology is presented in this paper. His recasting of the nature of the repressed in terms of malevolent inner objects is described. A clinical vignette is provided to illustrate the manner in which resistance to the therapeutic alteration of the patient's pathological internal object world can be surmounted by both interpretive work and the provision of a replacement good object (the therapist) in the treatment situation.

Adult↗
PubMed1996

Rural health and IT&T in Australia--the results of qualitative and quantitative surveys of the needs, perceptions and expectations of rural and remote health professionals.

This paper reports an initial overview of the findings of qualitative and quantitative surveys of rural and remote health professionals in Australia to determine their present use of information technology and telecommunications (IT&T), barriers to the use of IT&T, and expected future uses. The survey research commissioned for this project supports the degree of importance rural and remote health professionals attach to the introduction and use of IT&T to reduce their sense of professional isolation and to support their service provision.

Attitude of Health Personnel↗
PubMed1995

The relationship of minor physical anomalies and other putative indices of developmental disturbance in schizophrenia to abnormalities of cerebral structure on magnetic resonance imaging.

Minor physical anomalies, together with obstetric complications, family history, and handedness status, were assessed to explore putative neurodevelopmental disturbance(s) in patients with schizophrenia whose cerebral structure had been examined previously by magnetic resonance imaging. Minor physical anomalies were related to negative symptoms in males and to premorbid intellectual function in females, but not to ventricular volume; however, three patients with evident neurodevelopmental anomalies of the ventricular system showed prominent minor physical anomalies. In exploratory analyses, obstetric complications were associated with left ventricular asymmetry, and a positive family history with inverse profiles of asymmetry in males vs. females; non-right-handedness was associated with increased ventricular volume in males but with poorer premorbid intellectual function in females. This nexus of relationships and their gender specificities suggest early dysmorphogenesis in schizophrenia that is related to sexual dimorphism.

Abnormalities, Multiple↗
PubMed1995

Basal ganglia T2 relaxation times in schizophrenia: a quantitative magnetic resonance imaging study in relation to tardive dyskinesia.

Transverse, or spin-spin, relaxation times (T2) from magnetic resonance images of basal ganglia structures were compared between control subjects and patients with schizophrenia, who were subdivided on the basis of the presence or absence of tardive dyskinesia. As a group, schizophrenic patients showed evidence of somewhat more prolonged T2 relaxation times in the right putamen and globus pallidus than did control subjects; there were no significant correlations between hemispheric T2 values and corresponding volumes of the lateral ventricles. Overall, there was little difference in T2 values between patients with and without tardive dyskinesia. These data extend the range of evidence for basal ganglia dysfunction in schizophrenia, but they do not support earlier reports of prominent T2 changes associated with tardive dyskinesia.

Adult↗