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1.
Health Policy ; 128: 18-27, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36543694

ABSTRACT

Family caregivers in Canadian long-term care homes are estimated to provide 10 h per week of direct care to approximately 30% of residents through roles including mobility support, mealtime assistance, personal care, social interaction, psychological care, care coordination, and advocacy. Despite these contributions, they continue to be viewed as visitors rather than as key participants in the interdependent relationships that support the long-term care sector. Their marginalization was evident during the COVID-19 pandemic, as Canadian public health policy focused on preventing them from entering long-term care, rather than supporting personal risk management, symptom screening, personal protective equipment, and other mechanisms for safe involvement in care. Several iatrogenic resident outcomes have been attributed to this, including decreased cognitive function, decreased mobility, increased incontinence, weight loss, increased depression and anxiety, increased responsive behaviours amongst those living with dementia, and increased delirium. In this commentary article, we argue that family caregiver presence was conflated as a risk when instead, it contributed to unintended harm. We identify nine well-known human social cognitive predispositions that may have contributed to this. We then examine their implications for trust in long-term care, and consider how quality and safety can be further fostered in long-term care by working in partnership with family caregivers to rebuild trust through enquiry and collaboration. We advocate incorporating trust as an essential measure of quality health service.


Subject(s)
COVID-19 , Humans , Long-Term Care , Trust , Pandemics , Canada
2.
J Prev Alzheimers Dis ; 6(4): 256-266, 2019.
Article in English | MEDLINE | ID: mdl-31686098

ABSTRACT

BACKGROUND: The CHARIOT PRO Main study is a prospective, non-interventional study evaluating cognitive trajectories in participants at the preclinical stage of Alzheimer's disease (AD) classified by risk levels for developing mild cognitive impairment due to AD (MCI-AD). OBJECTIVES: The study aimed to characterize factors and markers influencing cognitive and functional progression among individuals at-risk for developing MCI-AD, and examine data for more precise predictors of cognitive change, particularly in relation to APOE ε4 subgroup. DESIGN: This single-site study was conducted at the Imperial College London (ICL) in the United Kingdom. Participants 60 to 85 years of age were classified as high, medium (amnestic or non-amnestic) or low risk for developing MCI-AD based on RBANS z-scores. A series of clinical outcome assessments (COAs) on factors influencing baseline cognitive changes were collected in each of the instrument categories of cognition, lifestyle exposure, mood, and sleep. Data collection was planned to occur every 6 months for 48 months, however the median follow-up time was 18.1 months due to early termination of study by the sponsor. RESULTS: 987 participants were screened, among them 690 participants were actively followed-up post baseline, of whom 165 (23.9%) were APOE ε4 carriers; with at least one copy of the allele. The mean age was 68.73 years, 94.6% were white, 57.4% were female, and 34.8% had a Family History of Dementia with a somewhat larger percentage in the APOE ε4 carrier group (42.4%) compared to the non-carrier group (32.4%). Over half of the participants were married and 53% had a Bachelor's or higher degree. Most frequently, safety events typical for this population consisted of upper respiratory tract infection (10.4%), falls (5.2%), hypertension (3.5%) and back pain (3.0%). Conclusion (clinical relevance): AD-related measures collected during the CHARIOT PRO Main study will allow identification and evaluation of AD risk factors and markers associated with cognitive performance from the pre-clinical stage. Evaluating the psycho-biological characteristics of these pre-symptomatic individuals in relation to their natural neurocognitive trajectories will enhance current understanding on determinants of the initial signs of cognitive changes linked to AD.


Subject(s)
Alzheimer Disease/epidemiology , Cognition , Cognitive Dysfunction/epidemiology , Aged , Aged, 80 and over , Alzheimer Disease/genetics , Alzheimer Disease/psychology , Anxiety/psychology , Apolipoprotein E4/genetics , Cognitive Dysfunction/genetics , Cognitive Dysfunction/psychology , Cohort Studies , Depression/psychology , Efficiency , Female , Healthy Volunteers , Humans , Longitudinal Studies , Male , Mental Status and Dementia Tests , Middle Aged , Neuropsychological Tests , Prospective Studies , Risk Factors , Sleep , United Kingdom/epidemiology , Work
3.
Nutr Diabetes ; 7(4): e263, 2017 04 10.
Article in English | MEDLINE | ID: mdl-28394362

ABSTRACT

OBJECTIVES: Despite long hours of sunlight in Qatar and other regions of the Middle East, vitamin D deficiency has been rising. In parallel, the prevalence of metabolic syndrome has also been increasing in Qatar. Vitamin D levels have been associated with metabolic syndrome but the data are inconsistent and no studies have addressed these inter-relationships in a Middle Eastern population where the prevalence of these conditions is high. The objective is to investigate the prevalence of vitamin D deficiency and its association with metabolic syndrome and its components in the Qatar Biobank population. METHODS: A cross-sectional study of 1205 participants (702 women and 503 men) from the Qatar Biobank, comprising Qataris and non-Qataris between the ages of 18 and 80 years, was used to perform multivariate linear regression analyses to examine the association between metabolic syndrome and prevalence of vitamin D deficiency (defined as <20 ng ml-1 serum vitamin D levels) adjusting for age, sex, ethnicity, season of blood collection, physical activity and education. Odds ratios and 95% confidence intervals were calculated for all analyses. RESULTS: Approximately 64% of participants were vitamin D deficient (<20 ng ml-1) with more men being deficient (68.6%) than women (61.3%). Serum vitamin D was 8% lower in individuals with metabolic syndrome (RR: 0.92, 95%CI: 0.87-0.98, P-value: 0.01) compared to individuals without metabolic syndrome. Waist circumference and HDL as well as high triglyceride levels were also significantly positively associated with vitamin D deficiency. No association was found between the other components of metabolic syndrome or diabetes and the presence of vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent in this Qatari population. Presence of metabolic syndrome was associated with presence of vitamin D deficiency. Future prospective studies need to be conducted to investigate the potential for causality.


Subject(s)
Cholesterol, HDL/blood , Metabolic Syndrome/etiology , Triglycerides/blood , Vitamin D Deficiency/complications , Vitamin D/blood , Waist Circumference , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Metabolic Syndrome/blood , Middle Aged , Prevalence , Qatar , Sex Factors , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology , Young Adult
4.
Eur J Clin Nutr ; 66(3): 296-304, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22045223

ABSTRACT

BACKGROUND/OBJECTIVES: Prospective diet diaries may be more accurate than retrospective food frequency questionnaires (FFQ). The objective of this study was to compare FFQ and 7-day diet diary (7DD) measurements of fibre intake with the incidence of coronary heart disease (CHD). SUBJECTS/METHODS: We compared 7DD and FFQ fibre intake in a nested case-control study in a population of 25639 men and women aged 40-79 years, surveyed in 1993-97 and followed up until 2007. Among 2151 CHD cases and 5354 controls, FFQ and 7DD fibre intake (6 g/day) was examined in relation to serum total cholesterol and CHD using linear and logistic regression adjusted for age and additionally for body mass index, physical activity, smoking status, family history of CHD, social class, diabetes, alcohol, energy, saturated fat and use of lipid lowering medication, antihypertensive medication or aspirin. RESULTS: Age-adjusted serum total cholesterol was inversely associated with 7DD fibre among men and women, but with FFQ fibre among men only. In the multivariate analysis, associations with 7DD fibre were attenuated among men (regression coefficient -0.036 mmol/l, s.e. 0.021, P-value 0.087) and women (regression coefficient -0.069 mmol/l, s.e. 0.036, P-value 0.053), and were non-significant for FFQ fibre. Among men, age-adjusted CHD risk was inversely associated with 7DD fibre (odds ratio (OR) 0.84, 95% confidence interval (CI) 0.79-0.90), but not with FFQ fibre (OR 0.96, 95% CI 0.90-1.12). Among women, age-adjusted CHD risk was inversely associated with 7DD fibre (OR 0.83, 95% CI 0.75-0.93), and had a weaker inverse borderline-significant association with FFQ fibre (OR 0.93, 95% CI 0.87-1.01). Multivariate models yielded similar results. CONCLUSIONS: Inconsistencies in diet-CHD relationships in population studies may be associated with the use of different dietary assessment methods.


Subject(s)
Cholesterol/blood , Coronary Disease/prevention & control , Diet Records , Diet , Dietary Fiber/therapeutic use , Nutrition Assessment , Surveys and Questionnaires , Adult , Aged , Case-Control Studies , Coronary Disease/etiology , Dietary Fiber/administration & dosage , Female , Humans , Linear Models , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Prospective Studies , Retrospective Studies , Risk Factors , Sex Factors
5.
Int J Tuberc Lung Dis ; 9(2): 164-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15732735

ABSTRACT

OBJECTIVE: To review the outcome for MDR-TB treatment among potential migrants from Vietnam. SETTING: All cases of documented MDR-TB treated by the International Organization of Migration (IOM) in Vietnam from 1989 to 2000 were reviewed. METHODS: MDR-TB was defined as isoniazid- and rifampicin-resistant Mycobacterium tuberculosis. All cases of TB treated by the IOM and recorded in the computerised database were reviewed to identify MDR-TB cases. Demographics, chest radiograph results, drug resistance, drug use and dosage, duration of treatment, and outcome were analysed. RESULTS: Forty-four cases of MDR-TB were identified. Treatment consisted of ambulatory directly observed treatment with an 8-drug protocol: isoniazid, rifampicin, pyrazinamide, ethambutol, capreomycin, ethionamide, ofloxacin and cycloserine. This initial protocol was modified due to drug availability or drug intolerance. Patients were treated with a median of 8 drugs (range 6-12). Mean duration of treatment for MDR-TB was 23.0 (SD+/-11.4) months. Thirty-eight (86%) patients were cured and emigrated, one failed treatment (2%), three were lost to follow-up (7%) and two died (4%). CONCLUSION: Treatment for MDR-TB provided by the IOM was effective in preparing a low-income population for migration.


Subject(s)
Emigration and Immigration , Tuberculosis, Multidrug-Resistant/drug therapy , Capreomycin/administration & dosage , Cycloserine/administration & dosage , Drug Therapy, Combination , Ethambutol/administration & dosage , Ethionamide/administration & dosage , Female , Humans , Isoniazid/administration & dosage , Male , Middle Aged , Ofloxacin/administration & dosage , Pyrazinamide/administration & dosage , Rifampin/administration & dosage , Treatment Outcome , Vietnam/ethnology
6.
Int J Tuberc Lung Dis ; 8(5): 593-7, 2004 May.
Article in English | MEDLINE | ID: mdl-15137536

ABSTRACT

OBJECTIVE: To compare the extent of pulmonary tuberculosis amongst patients detected by screening (active case finding) with that in patients detected by symptoms (passive case finding), and to identify early symptoms of pulmonary tuberculosis. SUBJECTS AND METHOD: In this cross-sectional study, Tuberculosis Control Program records were reviewed for method of detection and extent of disease in Canadian Plains Aborigines between 1 January 1991 and 30 June 1999. RESULTS: Among 903 cases, method of detection was active in 450 (49.8%) and passive in 453 (50.2%). Cough and fever were the most common symptoms in both methods of detection, and were significantly more frequent in passive detection (P < 0.05). Cough was present in 59% and fever in 19% of actively detected cases compared to 84% and 47%, respectively, of passively detected cases. Age was significantly different between the two methods of detection. Hemoptysis, weight loss and method of detection were associated with increased risk of infectiousness among those < or = 19 years, while cough, hemoptysis and weight loss were associated among those >19 years. CONCLUSION: Method of detection rather than age contributed to infectiousness in children and adolescents. Daily cough for more than 1 month and unexplained fever for more than 1 week should raise the suspicion for TB.


Subject(s)
Contact Tracing , Mass Screening , Patient Acceptance of Health Care , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Early Diagnosis , Female , Humans , Infant , Male , Middle Aged , Saskatchewan/epidemiology , Tuberculosis, Pulmonary/complications
7.
Neurology ; 61(4): 500-6, 2003 Aug 26.
Article in English | MEDLINE | ID: mdl-12939424

ABSTRACT

OBJECTIVE: To determine whether an fMRI memory encoding task distinguishes among cognitively normal elderly individuals, patients with mild cognitive impairment (MCI), and patients with early Alzheimer's disease (AD). METHODS: Twenty-nine subjects (11 normal, 9 MCI, 9 AD) were studied with an fMRI memory encoding task. A passive sensory task was also performed to assess potential intergroup differences in fMRI responsiveness. Activation in the medial temporal lobe for the memory task and in the anatomic rolandic area for the sensory task was studied. Intergroup comparisons were performed using receiver operating characteristic (ROC) analyses. The ROC method provides rigorous control of artifactual false-positive "activation." Subjects were tested for recall and recognition of the encoding task stimuli following the fMRI study. RESULTS: Medial temporal lobe activation was greater in normal subjects than MCI and AD patients (p = 0.03 and p = 0.04). There was no difference between AD and MCI patients in fMRI memory performance [corrected]. There was an association between fMRI memory activation (area under the ROC curve) and post-fMRI performance on recognition and free recall. There was no difference among the three groups on the sensory task. CONCLUSIONS: MCI and AD patients had less medial temporal lobe activation on the memory task than the normal subjects but similar activation as normal subjects on the sensory task. These findings suggest decreased medial temporal activation may be a specific marker of limbic dysfunction due to the neurodegenerative changes of AD. In addition, fMRI is sufficiently sensitive to detect changes in the prodromal, MCI, phase of the disease.


Subject(s)
Alzheimer Disease/psychology , Brain Mapping , Cognition Disorders/psychology , Magnetic Resonance Imaging , Memory Disorders/psychology , Somatosensory Cortex/physiopathology , Aged , Alzheimer Disease/complications , Alzheimer Disease/physiopathology , Cognition Disorders/complications , Cognition Disorders/physiopathology , Female , Humans , Male , Memory/physiology , Memory Disorders/etiology , Memory Disorders/physiopathology , Mental Recall , Neuropsychological Tests , Photic Stimulation , ROC Curve , Somatosensory Cortex/pathology
8.
Neuroimage ; 14(5): 1122-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11697943

ABSTRACT

Neuroanatomic substrates of specific cognitive functions have been inferred from anatomic distributions of activated pixels during fMRI studies. With declarative memory tasks, interest has focused on the extent to which various medial temporal lobe anatomic structures are activated while subjects encode new information. The aim of this project was to examine how commonly used variations in fMRI data processing methods affect the distribution of activation in anatomically defined medial temporal lobe regions of interest (ROIs) during a complex scene-encoding task. ROIs were drawn on an MRI anatomic template formed from 3D SPGR scans of eight subjects combined in Talairach space. Separate ROIs were drawn for the posterior and anterior hippocampal formation, parahippocampal gyrus, and entorhinal cortex. Twelve different activation maps were created for each subject by using four correlation coefficients and three cluster volumes. Friedman's two-way ANOVA by ranks was used to test the hypothesis that the distribution of activated pixels among defined anatomic ROIs varied as a function of the data processing method. By simply varying the combination of correlation coefficient and cluster volume, significantly different distributions of activation within named medial temporal lobe structures were obtained from the same fMRI datasets (P < 0.015; P < 0.001). The number of subjects studied (n = 8) is in a range commonly found in the literature yet this clearly resulted in spurious associations between processing parameter variations and activation distribution. Using data processing methods that are independent of the arbitrary selection of cutoff values for thresholding activation maps may reduce the likelihood of obtaining spurious results.


Subject(s)
Hippocampus/physiology , Magnetic Resonance Imaging/methods , Mental Recall/physiology , Nerve Net/physiology , Pattern Recognition, Visual/physiology , Temporal Lobe/physiology , Adult , Brain Mapping , Echo-Planar Imaging , Female , Hippocampus/anatomy & histology , Humans , Male , Nerve Net/anatomy & histology , Sensitivity and Specificity , Temporal Lobe/anatomy & histology
9.
J Am Acad Dermatol ; 44(4): 675-80, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11260547

ABSTRACT

A patient with posttransplant cutaneous lymphoma is described. Although most posttransplant lymphomas are of B-cell origin, this patient's lymphoma is a primary cutaneous lymphoma of T-cell origin. Another report exists of the first case of posttransplant primary cutaneous T-cell lymphoma localized to the lower extremities. Our patient's involvement was generalized with tumor nodules on the face and anterior chest. Reduced immune surveillance, chronic antigenic stimulation caused by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have all been suggested as mechanisms. Prompt recognition of this condition and initiation of appropriate therapy with reduction of high-dose immunosuppression can lead to better patient outcomes.


Subject(s)
Immunosuppression Therapy/adverse effects , Kidney Transplantation , Lymphoma, T-Cell, Cutaneous/etiology , Postoperative Complications/etiology , Skin Neoplasms/etiology , Female , Humans , Middle Aged
10.
Magn Reson Med ; 43(3): 459-69, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10725890

ABSTRACT

Corruption of the image time series due to interimage head motion limits the clinical utility of functional MRI. This paper presents a method for real-time prospective correction of rotation and translation in all six degrees of rigid body motion. By incorporating an orbital navigator (ONAV) echo for each of the sagittal, axial, and coronal planes into the fMRI pulse sequence, rotation and translation can be measured and the spatial orientation of the image acquisition sequence that follows can be corrected prospectively in as little as 160 msec. Testing of the method using a computerized motion phantom capable of performing complex multiaxial motion showed subdegree rotational and submillimeter translational accuracy over a range of +/-8 degrees and +/-8 mm of motion. In vivo images demonstrate correction of simultaneous through-plane and in-plane motion and improved detection of fMRI activation in the presence of head motion.


Subject(s)
Head Movements , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Artifacts , Brain/anatomy & histology , Brain/physiology , Humans , Phantoms, Imaging , Rotation , Signal Processing, Computer-Assisted
11.
AJNR Am J Neuroradiol ; 20(8): 1511-9, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10512239

ABSTRACT

BACKGROUND AND PURPOSE: Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. METHODS: We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. RESULTS: Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. CONCLUSION: Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.


Subject(s)
Brain Mapping , Brain Neoplasms/surgery , Epilepsy/surgery , Evoked Potentials, Motor/physiology , Evoked Potentials, Somatosensory/physiology , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Adolescent , Adult , Brain Neoplasms/diagnosis , Brain Neoplasms/physiopathology , Cerebral Cortex/physiopathology , Cerebral Cortex/surgery , Child , Epilepsy/etiology , Epilepsy/physiopathology , Feasibility Studies , Female , Humans , Male , Middle Aged , Patient Care Planning , Preoperative Care , Retrospective Studies , Treatment Outcome
12.
J Laser Appl ; 10(5): 224-8, 1998 Oct.
Article in English | MEDLINE | ID: mdl-10186963

ABSTRACT

The five years survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100% mortality. Special problems include: (1) lesions often present late; (2) position: lesions overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions; and (3) difficulty in differentiating normal brain from malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of (nontoxic) dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. A fine laser endoscopic technique was devised for removal of brain lesions, which minimized thermal damage and shock waves. A compatible endoscopic fluoroscopic laser technique was developed to differentiate brain tumor from normal brain.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/surgery , Endoscopy/methods , Laser Therapy/methods , Brain/surgery , Brain Diseases/diagnosis , Brain Diseases/surgery , Endoscopes , Fiber Optic Technology/methods , Humans , In Vitro Techniques , Laser Therapy/adverse effects , Laser Therapy/instrumentation , Reference Values , Robotics , Sensitivity and Specificity , Staining and Labeling , Stereotaxic Techniques , Therapy, Computer-Assisted
13.
Dev Immunol ; 2(1): 51-66, 1992.
Article in English | MEDLINE | ID: mdl-1387829

ABSTRACT

Phenotypic profiles of the thymic stromal components provide an excellent approach to elucidating the nature of the microenvironment of this organ. To address this issue in chickens, we have produced an extensive panel of 18 mAb to the thymic stroma. These mAb have been extensively characterized with respect to their phenotypic specificities and reveal that the stromal cells are equally as complex as the T cells whose maturation they direct. They further demonstrate that, in comparison to the mammalian thymus, there is a remarkable degree of conservation in thymic architecture between phylogenetically diverse species. Eleven mAb reacted with thymic epithelial cells: MUI-73 was panepithelium, MUI-54 stained all cortical and medullary epithelium but only a minority of the subcapsule, MUI-52 was specific for isolated stellate cortical epithelial cells, MUI-62, -69, and -71 were specific for the medulla (including Hassall's corpuscle-like structures), MUI-51, -53, -70, and -75 reacted only with the type-1 epithelium, or discrete regions therein, lining the subcapsular and perivascular regions and MUI-58 demonstrated the antigenic similarity between the subcapsule and the medulla. Seven other mAb identified distinct isolated stromal cells throughout the cortex and medulla. Large thymocyte-rich regions, which often spanned from the outer cortex to medulla, lacked epithelial cells. These mAb should prove invaluable for determining the functional significance of thymic stromal-cell subsets to thymopoiesis.


Subject(s)
Thymus Gland/immunology , Animals , Antibodies, Monoclonal , Antibody Specificity , CD8 Antigens/biosynthesis , Chickens , Fluorescent Antibody Technique , Immunoglobulin G/biosynthesis , Immunoglobulin M/biosynthesis , Immunophenotyping , Receptors, Antigen, T-Cell, alpha-beta/biosynthesis , Receptors, Antigen, T-Cell, gamma-delta/biosynthesis , T-Lymphocytes/immunology
14.
Dev Comp Immunol ; 15(4): 369-81, 1991.
Article in English | MEDLINE | ID: mdl-1663462

ABSTRACT

The effect of infectious bursal disease virus (IBDV) was studied on adult specific pathogen-free (SPF) white Leghorn chickens through analysis of peripheral blood cell suspensions and histological staining patterns on various tissue types, with specific mAbs. A rapid, progressive loss of B lymphocytes was observed in the bursal cortex and medulla, peripheral blood and thymic medulla. There was, however, a resistant population of MUI-36+ cells at the bursal cortico-medullary junction and scattered around splenic periellipsoidal sheaths. These resistant cells were suggested to be a subpopulation of macrophages which expressed the MUI-36 marker; alternatively these may have phagocytosed virally infected B cells or their remnants. Throughout the period of infection, T lymphocytes appeared nonsusceptible. Further, while the distribution of stromal cell antigens within the bursal cortex remained unaltered, particular epitopes on the surface epithelium and in the medulla were lost as a consequence of viral infection. The data presented therefore suggests that immunodepression of chickens post-IBDV infection, may arise as a direct consequence of infection of B lymphocytes; additionally, it is possible that the elimination of certain crucial elements within the bursal microenvironment may contribute to this state.


Subject(s)
B-Lymphocytes/pathology , Bursa of Fabricius/pathology , Chickens/immunology , Infectious bursal disease virus/physiology , Lymphopenia/veterinary , Poultry Diseases/immunology , Reoviridae Infections/veterinary , Animals , Antibodies, Monoclonal/immunology , Lymphopenia/immunology , Lymphopenia/microbiology , Lymphopenia/pathology , Macrophages/pathology , Necrosis , Poultry Diseases/microbiology , Poultry Diseases/pathology , Reoviridae Infections/immunology , Reoviridae Infections/microbiology , Reoviridae Infections/pathology , Specific Pathogen-Free Organisms , Spleen/pathology , Thymus Gland/pathology
15.
J Biol Chem ; 265(18): 10410-8, 1990 Jun 25.
Article in English | MEDLINE | ID: mdl-2113054

ABSTRACT

The CD4 cell surface antigen is of interest as a marker of T lymphocytes that recognize foreign antigens in the context of MHC Class II antigen, as a receptor for the human immunodeficiency virus (HIV) and as a member of the immunoglobulin superfamily (IgSF) with four Ig-like domains present in the extracellular domain. In order to produce large amounts of soluble CD4 for x-ray crystallography and other molecular studies, a recently developed expression system based on selection via glutamine synthetase was used. Expression was attempted for rat CD4 corresponding to the full extracellular sequence (sCD4; domains 1-4), the NH2-terminal half (domains 1 and 2) and the first domain alone. Stable transfected Chinese hamster ovary cell lines were obtained that expressed sCD4 and sCD4 (half) at typical maximal levels in spent tissue culture supernatant of greater than 80 and 25 mg/liter, respectively. Domain 1 alone was not expressed and introduction of a N-linked glycosylation site did not facilitate expression. The role of glycosylation in the expression of sCD4 was investigated by mutagenesis of the constructs to remove each of the two N-linked glycosylation sites in turn and both together. All three forms were expressed at 60-120 mg/liter. The sCD4 (half) was not expressed after deletion of its N-linked site. The disulfide bonds of sCD4 were determined to be within domains 1, 2, and 4 and isolation of glycopeptides showed that both N-linked sites were glycosylated. Analysis of the hydrodynamic properties of sCD4 suggested that the molecule adopted an extended conformation in solution rather than folding to form a compact structure like an Fab. The possibility of dimerisation of CD4 was investigated but sCD4 dimers were not seen at an affinity cut-off of about 4 x 10(5) M-1.


Subject(s)
CD4 Antigens/genetics , Gene Expression , Genetic Variation , T-Lymphocytes/immunology , Amino Acid Sequence , Animals , CD4 Antigens/immunology , CD4 Antigens/isolation & purification , Cell Line , Cricetinae , Cricetulus , Female , Genes, MHC Class II , Glycopeptides/isolation & purification , Glycosylation , Molecular Sequence Data , Ovary , Peptide Fragments/isolation & purification , Rats , Transfection
16.
Dev Immunol ; 1(1): 41-51, 1990.
Article in English | MEDLINE | ID: mdl-2136204

ABSTRACT

Many, if not all, of the different phases of intrabursal B-cell maturation are controlled by the stromal components. We have used an extensive panel of mAb to provide a detailed phenotypic profile of these cells. Antigenic specificities were defined for the entire surface epithelium, interfollicular surface epithelium, follicle-associated epithelium, basement membrane, basement membrane-associated epithelium. Several mAb were specific for the medulla, including those reactive with the stellate network of epithelial cells, isolated macrophages, and granular, apparently secreted antigens. One of these, MUI-92, appears to be bursa-specific. Two mAb reacted strongly with stellate cortical macrophages, one of which weakly stained similar cells in the medulla. MHC-class II antigens were expressed on endothelium of the corticomedullary junction, macrophagelike cells in the cortex, and medulla and B lymphocytes predominantly in the cortex. Collectively, these mAb have demonstrated the antigenically distinct nature of discrete regions in the bursa, but also the continuity of the surface epithelium with the corticomedullary junction and medulla. They represent excellent reagents for defining the stromal cell contribution of B-cell development.


Subject(s)
Bursa of Fabricius/cytology , Bursa of Fabricius/immunology , Animals , Antibodies, Monoclonal , Antigens, Differentiation , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Cell Differentiation , Chickens , Fluorescent Antibody Technique , Phenotype
17.
Cell Tissue Res ; 252(1): 199-206, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3288348

ABSTRACT

The function of the metrial gland of the rat, and particularly of its characteristic population of granulated cells, remains unknown. However, several lines of evidence suggest that the granulated cells may derive from lymphocytes, and play a role in the immunology of pregnancy. In this study, antigen expression by granulated and other cell populations from the metrial glands of rats at Days 13 and 14 of pregnancy was studied by an indirect immunoperoxidase method. Acetone-fixed frozen sections, and cytocentrifuge preparations of collagenase-dispersed metrial gland tissue in which numbers of granulated cells had been increased by density-gradient centrifugation, were used. The primary antibodies used recognised, inter alia, B lymphocytes (MRC OX-3, MRC OX-6, MRC OX-12), T lymphocytes (MRC OX-8, W3/25, MRC OX-19), neutrophils (MRC OX-42) and cells of the monocyte/macrophage series (MRC OX-3, MRC OX-6, MRC OX-42, MRC OX-43). The majority of the granulated cells, including smaller, "immature" forms, were unlabelled by any of these antibodies. Some lymphocytes, and varying numbers of larger, non-granulated cells, were labelled by OX-6, OX-12, W3/25, OX-42 and OX-43. In addition to lymphocytes, labelled cells included neutrophils (OX-42), endothelial cells (OX-43), and probably some macrophages (OX-6, OX-43). OX-12, which recognises the kappa chain of rat IgG, labelled some large cells which may have been stromal cells. These findings do not support the concept that the granulated cells are derived from lymphocytes.


Subject(s)
Histocompatibility Antigens/analysis , Pregnancy, Animal/immunology , Animals , Female , Immunoenzyme Techniques , Leukocytes/cytology , Leukocytes/immunology , Lymphocytes/cytology , Lymphocytes/immunology , Pregnancy , Rats
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