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1.
Ann Biomed Eng ; 49(11): 3080-3090, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34654980

ABSTRACT

For the current study, an existing theater injury data set was compared to component and whole body experiments meant to replicate the theater high rate vertical loading environment. The theater injury data set was derived from real world events that were within the design range of the Warrior Injury Assessment Manikin. A qualitative and quantitative assessment of the whole body fracture patterns was developed to determine whether the laboratory loading was correctly representing the resulting injuries seen in theater Underbody Blast (UBB) events. Results indicated that most of the experimental test fracture patterns were similar to the theater injuries for Abbreviated Injury Scale body regions of interest (lower extremities, pelvis, and spine); however, some of the body regions had higher similarity scores compared to others. Whole body fracture distribution was less similar than the component tests because of differences in injury distributions. The lower extremity whole body similarity was lower than spine and pelvis similarity. This analysis was able to identify some experimental tests that might not represent theater loading. In conclusion, this analysis confirmed that some laboratory testing produced skeletal injury patterns that are seen in comparable theater UBB events.


Subject(s)
Blast Injuries , Fractures, Bone , Lower Extremity/injuries , Pelvis/injuries , Spinal Injuries , Explosions , Humans , Laboratories , Manikins , Operating Rooms , Reproducibility of Results
2.
BMC Psychiatry ; 20(1): 390, 2020 07 29.
Article in English | MEDLINE | ID: mdl-32727428

ABSTRACT

BACKGROUND: With 10 to 20% of Canadian children suffering with mental illness, the importance of early identification and accurate assessment systems is clear. Unfortunately, many do not receive the mental health treatment necessary and wait-times for assessment can span up to a year. In response, the interRAI suite of assessments were designed to comprehensively assess early signs of mental health impairments in children from birth to 18 years. METHODS: This study assesses the psychometric properties of the Anxiety Scale and addresses the identification of anxiety within children diagnosed with intellectual and developmental disabilities (IDD); a commonly underrepresented sample in mental health psychometric studies. Data was collected from children aged 4-18 years in three different samples. RESULTS: Results indicated reliable internal consistency and factor structure, as well as moderate-to-strong convergent validity. CONCLUSIONS: We conclude that the Anxiety Scale exhibits psychometric qualities which demonstrate its clinical utility for use within a child sample, as well as in children with IDD. The findings provide support to a larger body of research which show consistent psychometric rigour of the interRAI measures.


Subject(s)
Developmental Disabilities , Mental Health , Adolescent , Anxiety/diagnosis , Canada , Child , Child, Preschool , Developmental Disabilities/diagnosis , Humans , Psychometrics , Reproducibility of Results
3.
Nanotechnology ; 28(21): 215704, 2017 May 26.
Article in English | MEDLINE | ID: mdl-28471752

ABSTRACT

The effects of a 45 min anneal at 800 °C on the physical properties and microstructure of a five-period GaAs1-x Bi x /GaAs1-y Bi y superlattice with y ≠ x were studied using room-temperature photoluminesence spectroscopy, high-resolution x-ray diffraction, high-angle annular-dark-field scanning transmission electron microscopy (HAADF-STEM), and atom probe tomography (APT). The anneal resulted in a substantial increase of the photoluminesence intensity over that observed in the as-deposited sample, indicating annihilation of non-radiative recombination centers and stability of the superlattice structure during the anneal. However, some precipitation of Bi from the GaAs1-x Bi x also occurred. The characteristics of phase separation that occurred within these precipitates were investigated in detail by APT and HAADF-STEM. They indicate that the precipitation reaction involves formation of embedded nano-scale liquid droplets that can accelerate local Bi dissolution from the GaAs1-x Bi x matrix by moving through it. Preservation of nanometer scale sharp Bi concentration gradients in the growth direction suggested that very little solid state diffusion of Bi occurred during the anneal. The observed gradient in precipitate number density with distance from the sample surface further supports hypotheses of an enabling role of Ga vacancies in the precipitation process.

4.
Mech Dev ; 136: 99-110, 2015 May.
Article in English | MEDLINE | ID: mdl-25617760

ABSTRACT

We present a complete staging table of normal development for the lungless salamander, Hemidactylium scutatum (Caudata: Plethodontidae). Terrestrial egg clutches from naturally ovipositing females were collected and maintained at 15 °C in the laboratory. Observations, photographs, and time-lapse movies of embryos were taken throughout the 45-day embryonic period. The complete normal table of development for H. scutatum is divided into 28 stages and extends previous analyses of H. scutatum embryonic development (Bishop, 1920; Humphrey, 1928). Early embryonic stage classifications through neurulation reflect criteria described for Xenopus laevis, Ambystoma maculatum and other salamanders. Later embryonic stage assignments are based on unique features of H. scutatum embryos. Additionally, we provide morphological analysis of gastrulation and neurulation, as well as details on external aspects of eye, gill, limb, pigmentation, and tail development to support future research related to phylogeny, comparative embryology, and molecular mechanisms of development.


Subject(s)
Embryonic Development/physiology , Organogenesis/physiology , Urodela/embryology , Animals , Female , Gastrulation/physiology , Neurulation/physiology
5.
Rev Sci Tech ; 32(1): 189-98, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23837376

ABSTRACT

International standards are a crucial element in brucellosis prevention and management. They allow policy-makers, scientists, epidemiologists, laboratories and trade entities to have a common vocabulary for communication and understanding of the disease. These standards cover the entire spectrum of activities from surveillance, testing, prophylaxis, transport and trade to policy development, research and reporting. Developing, adhering to and monitoring standards increases both the effectiveness and efficiency of prevention and management programmes. Creating standards with the input of all stakeholders ensures that the standards do not adversely affect the requirements of any of the multiple parties involved. The World Organisation for Animal Health (OIE), in conjunction with its Member Countries, and through its standing and ad hoc committees plus expert input, has taken a key leadership role in developing and reviewing brucellosis standards. These standards are used to harmonise testing, prevention processes, vaccines and reporting, to support trade and to protect human and animal health.


Subject(s)
Brucellosis/veterinary , Health Policy/legislation & jurisprudence , Internationality/legislation & jurisprudence , Animals , Brucella Vaccine/immunology , Brucellosis/prevention & control , Disease Notification , Humans , Veterinary Medicine
6.
Child Care Health Dev ; 39(2): 296-300, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22823542

ABSTRACT

BACKGROUND: Obtaining a diagnosis of developmental co-ordination disorder (DCD) is a long, inconsistent and frustrating journey for families, with apparently little awareness of DCD in schools or the medical community. METHODS: An online survey was completed by 1297 participants: parents (n = 501), teachers (n = 202), family/general physicians (n = 339) and paediatricians (n = 255). RESULTS: Only 20% of the sample had knowledge of DCD, with 41% of the paediatricians and 23% of family/general physicians familiar. Of participants who have awareness, only 11-59% have knowledge of the impact of DCD on social, emotional and physical health. Less than 30% of physicians have awareness of the secondary consequences. Few physicians diagnose DCD and less than one-third believe it is easy to make a diagnosis; this is in contrast to the fact that most parents report confidence in their physician's ability to make a timely diagnosis. CONCLUSIONS: If less than one-half of physicians have knowledge of DCD and even fewer are knowledgeable of the secondary consequences of the condition, it is not surprising that DCD is infrequently diagnosed and that families need to search for support. This survey confirms observations that the condition is not well known and there is a need for greater awareness of DCD.


Subject(s)
Clinical Competence , Developmental Disabilities/diagnosis , Health Knowledge, Attitudes, Practice , Motor Skills Disorders/diagnosis , Canada/epidemiology , Child , Child, Preschool , Developmental Disabilities/epidemiology , Developmental Disabilities/psychology , Faculty , Female , Humans , Male , Medical Staff, Hospital/standards , Motor Skills Disorders/epidemiology , Motor Skills Disorders/psychology , Parents/psychology , Physicians, Family/standards , United Kingdom/epidemiology , United States/epidemiology
7.
J Vet Med Educ ; 33(1): 125-31, 2006.
Article in English | MEDLINE | ID: mdl-16767652

ABSTRACT

I have a little dog, a little Maltese dog, Billy Byrd. He is approaching his 14th birthday. If I ever saw in this world anything that was made by the Creator's hand that is more dedicated, more true, more undeviant, more faithful than this little dog, I am at a loss to state what it is . . .We love that little dog. (Robert S. Byrd, U.S. Senator).


Subject(s)
Curriculum , Education, Veterinary , Jurisprudence , Legislation, Veterinary , Problem-Based Learning , Teaching/methods , Educational Measurement , Human-Animal Bond , Humans , Students , United States
8.
Rev Sci Tech ; 24(2): 747-55, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16358524

ABSTRACT

Globalisation is becoming a force that is revolutionising international trade, particularly that of animals and animal products. There is increasing interest in animal welfare worldwide, and as part of its 2001-2005 Strategic Plan the World Organisation for Animal Health (OIE) identified the development of international standards on animal welfare as a priority. The OIE's scientific approach to standard-setting provides the foundation for the development, and acceptance by all OIE Member Countries, of these animal welfare guidelines. The paper discusses how these guidelines on animal welfare can be implemented, both within the provisions of World Trade Organization (WTO) agreements and within the framework of voluntary codes of conduct. Even if animal welfare guidelines are not covered by any WTO agreements in the future, bi- and multilateral agreements, voluntary corporate codes, and transparent labelling of products should result in a progressive acceptance of OIE guidelines. Ultimately, consumer demands and demonstrable gains in animal production will result in an incremental evolution in animal welfare consciousness and adherence to international standards.


Subject(s)
Animal Welfare/standards , Commerce , International Cooperation , Quality Control , Veterinary Medicine/standards , Animals , Animals, Domestic , Commerce/standards , Commerce/trends , Guideline Adherence , Guidelines as Topic , Humans
9.
Nature ; 411(6837): 558-60, 2001 May 31.
Article in English | MEDLINE | ID: mdl-11385563

ABSTRACT

The discovery of superconductivity at 39 K in magnesium diboride offers the possibility of a new class of low-cost, high-performance superconducting materials for magnets and electronic applications. This compound has twice the transition temperature of Nb3Sn and four times that of Nb-Ti alloy, and the vital prerequisite of strongly linked current flow has already been demonstrated. One possible drawback, however, is that the magnetic field at which superconductivity is destroyed is modest. Furthermore, the field which limits the range of practical applications-the irreversibility field H*(T)-is approximately 7 T at liquid helium temperature (4.2 K), significantly lower than about 10 T for Nb-Ti (ref. 6) and approximately 20 T for Nb3Sn (ref. 7). Here we show that MgB2 thin films that are alloyed with oxygen can exhibit a much steeper temperature dependence of H*(T) than is observed in bulk materials, yielding an H* value at 4.2 K greater than 14 T. In addition, very high critical current densities at 4.2 K are achieved: 1 MA cm-2 at 1 T and 105 A cm-2 at 10 T. These results demonstrate that MgB2 has potential for high-field superconducting applications.

10.
BJOG ; 108(5): 462-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11368130

ABSTRACT

OBJECTIVE: To determine the effectiveness of fluoxetine in alleviating physical symptoms of premenstrual dysphoric disorder. DESIGN: Randomised, double-blind, placebo controlled, parallel study. SETTING: Canadian University based outpatient clinics. Participants Four hundred and five subjects, of whom 320 with prospectively determined premenstrual dysphoric disorder were randomised. METHODS: Randomised women were assigned to fluoxetine 20 or 60 mg/day or placebo. Common physical symptoms associated with premenstrual dysphoric disorder including breast tenderness, bloating, and headache were evaluated by visual analog scales and the self-rated and observer premenstrual tension syndrome scales. OUTCOME MEASURES: Luteal phase change from mean baseline scores to mean treatment scores for all scales. RESULTS: Fluoxetine treatment was statistically superior to placebo, with no significant differences between the two fluoxetine dosages in their effects on physical symptoms. CONCLUSION: Daily fluoxetine treatment is superior to placebo in improving the most common physical symptoms associated with premenstrual dysphoric disorder.


Subject(s)
Fluoxetine/administration & dosage , Premenstrual Syndrome/drug therapy , Selective Serotonin Reuptake Inhibitors/administration & dosage , Adult , Analysis of Variance , Double-Blind Method , Female , Humans , Treatment Outcome
11.
J Morphol ; 247(2): 142-59, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11223925

ABSTRACT

We describe caudosacral and caudal vertebral morphology across life history stages in three caudate amphibians: Ambystoma jeffersonianum (Ambystomatidae), Desmognathus ocoee (Plethodontidae: Desmognathinae), and Hemidactylium scutatum (Plethodontidae: Plethodontinae). All three species have aquatic larvae, but adults differ in habitat and predator defense strategy. Predator defense includes tail autotomy in D. ocoee and H. scutatum but not A. jeffersonianum. Of the species that autotomize, H. scutatum has a specialized constriction site at the tail base. We investigated whether aquatic larvae exhibit vertebral features similar to those previously described for aquatic adults and examined the effect of metamorphosis, if any, on vertebral morphology and the ontogeny of specialized vertebral features associated with tail autotomy. Interspecific comparisons of cleared-and-stained specimens indicate that vertebral morphology differs dramatically at hatching and that caudosacral and caudal vertebrae undergo continuous ontogenetic change throughout larval, metamorphic, and juvenile periods. Larvae and juveniles of H. scutatum do not exhibit adult vertebral features associated with constricted-base tail autotomy. The pond-type larvae of A. jeffersonianum and H. scutatum have tapering centrum lengths posterior to the sacrum. This pattern is functionally associated with aquatic locomotion. The stream-type larvae of D. ocoee undergo enhanced regional growth in the anterior tail such that the anterior caudal centra become longer than the preceding caudosacral centra. With the exception of the first two caudal vertebrae, a similar growth pattern occurs in H. scutatum adults. We hypothesize that enhanced growth of the anterior caudal segments is associated with tail elongation and autotomy.


Subject(s)
Ambystoma/anatomy & histology , Ambystoma/physiology , Life Cycle Stages , Salamandridae/anatomy & histology , Salamandridae/physiology , Animals
12.
J Thorac Cardiovasc Surg ; 117(2): 261-6, 1999 Feb.
Article in English | MEDLINE | ID: mdl-9918966

ABSTRACT

OBJECTIVE: Radial artery harvesting for coronary artery bypass may lead to digit ischemia if collateral hand circulation is inadequate. The modified Allen's test is the most common preoperative screening test used. Unfortunately, this test has high false-positive and false-negative rates. The purpose of this study was to compare the results of a modified Allen's test with digit pressure change during radial artery compression for assessing collateral circulation before radial artery harvest. METHODS: One hundred twenty-nine consecutive patients were studied before coronary artery bypass operations. A modified Allen's test was performed with Doppler ultrasound to assess blood flow in the superficial palmar arch before and during radial artery compression. A decreased audible Doppler signal after radial artery compression was considered a positive modified Allen's test. First and second digit pressures were measured before and during radial artery compression. A decrease in digit pressure of 40 mm Hg or more (digit DeltaP) with radial artery compression was considered positive. RESULTS: Seven of 14 dominant extremities (50%) and 8 of the 16 nondominant extremities (50%) with a positive modified Allen's test had a digit DeltaP of less than 40 mm Hg (false positive). Sixteen of 115 dominant extremities (14%) and 5 of 112 nondominant extremities (4%) with a negative Allen's test had a digit DeltaP of 40 mm Hg or more with radial artery compression (false negative). CONCLUSION: Use of the modified Allen's test for screening before radial artery harvest may unnecessarily exclude some patients from use of this conduit and may also place a number of patients at risk for digit ischemia from such harvest. Direct digit pressure measurement is a simple, objective method that may more precisely select patients for radial artery harvest. Additional studies are needed to define objective digital pressure criteria that will accurately predict patients at risk for hand ischemia after radial harvest.


Subject(s)
Coronary Artery Bypass/methods , Hand/blood supply , Radial Artery/physiology , Radial Artery/transplantation , Adult , Aged , Aged, 80 and over , Blood Pressure Determination/instrumentation , Blood Pressure Determination/methods , Blood Pressure Determination/statistics & numerical data , Chi-Square Distribution , Coronary Disease/physiopathology , Coronary Disease/surgery , Female , Humans , Laser-Doppler Flowmetry/instrumentation , Laser-Doppler Flowmetry/methods , Laser-Doppler Flowmetry/statistics & numerical data , Male , Middle Aged , ROC Curve , Regional Blood Flow , Reproducibility of Results , Skin Temperature
13.
Am J Kidney Dis ; 25(1): 26-9, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7810527

ABSTRACT

Urea rebound has been documented to occur after hemodialysis, but the magnitude and causes are not clearly defined. In this study we evaluated the effect of high-flux hemodialysis on urea rebound and Kt/V. Blood urea nitrogen samples were obtained before, immediately after, and 30 minutes after hemodialysis in 49 patients. Rebound was evaluated with respect to dialysis efficiency, dialysis treatment time, the occurrence of hypotension, and hematocrit. Urea rebound was significant and resulted in an overall decrease in Kt/V from 1.2 +/- 0.3 to 1.0 +/- 0.2 (P < 0.001). Of the 45 patients with a measured Kt/V of greater than 1.0, 40% had an actual delivered Kt/V of less than 1.0 once rebound was taken into account. Urea rebound correlated strongly with dialysis efficiency but not with hypotension, suggesting that rebound resulted primarily from delayed urea mass transfer across cell membranes. We conclude that increasing dialysis efficiency increases urea rebound and increases the error in Kt/V determinations from single pool urea kinetics.


Subject(s)
Kidney Failure, Chronic/metabolism , Renal Dialysis , Urea/metabolism , Analysis of Variance , Creatinine/metabolism , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Kinetics , Time Factors , Urea/blood
14.
Proc Natl Acad Sci U S A ; 91(9): 4062-6, 1994 Apr 26.
Article in English | MEDLINE | ID: mdl-8171035

ABSTRACT

Lupus-like autoimmunity in (NZB x NZW)F1 mice is frequently marked by the development of a severe and fatal renal disease. Genes from both NZB and NZW parents are required for the full expression of disease. We applied a mapping technique based on polymorphism in simple sequence repeats to the analysis of (NZB x NZW)F1 x NZW backcross mice to determine the NZB genetic contribution to disease. The results show that a single NZB locus or tightly linked group of loci on the distal part of chromosome 4 provides the strongest association with renal disease and death. This locus, designated here as nba-1 (New Zealand Black autoimmunity), lies distal to the locus elp-1, 60-70 centimorgans from the centromere. It is of interest that a gene encoding a receptor for tumor necrosis factor maps to the vicinity of this disease-associated gene.


Subject(s)
Autoimmune Diseases/genetics , Lupus Erythematosus, Systemic/genetics , Mice, Inbred NZB/genetics , Animals , Chromosome Mapping , Female , Genetic Linkage , Heterozygote , Male , Mice , Proteinuria/genetics
15.
Microb Pathog ; 14(2): 133-47, 1993 Feb.
Article in English | MEDLINE | ID: mdl-8502162

ABSTRACT

The adherence of Candida albicans to the extracellular matrix proteins type I collagen and fibronectin (Fn) is dependent upon the presence of extracellular calcium. In the absence of calcium, 14 +/- 3% of yeast cells added to type I collagen adhered, whereas 62 +/- 3% of yeast cells adhered in the presence of 2 mM calcium. EDTA and EGTA reduced C. albicans adherence in a dose-dependent manner. Calcium, and to a lesser extent, cesium and magnesium, enhanced yeast cell adherence. The fluorescent probe, terbium (Tb+3), bound to the surface of yeast cells in a dose-dependent manner demonstrating the presence of cationic metal-binding sites on the yeast cell surface. When extracts of C. albicans yeast cells were applied to columns of Fn or gelatin coupled to agarose, two surface proteins of C. albicans were specifically eluted with 10 mM EDTA, 2% alpha-methylmannopyranoside or an Arg-Gly-Asp-containing peptide. The fungal proteins had relative molecular masses of 60,000 and 105,000 in the unreduced state. The proteins were present in the cell membrane as well as the cell wall and were demonstrated to be glycoproteins by their ability to bind concanavalin A. Immunoblot analysis of yeast extracts demonstrated that anti-integrin antibodies to the human fibronectin, vitronectin and complement receptor cross-reacted with the Candida 60 kDa glycoprotein. Thus, calcium-dependent fungal cell wall glycoproteins likely related to integrins may be receptors responsible for yeast cell adherence to host tissue such as the extracellular matrix.


Subject(s)
Calcium/metabolism , Candida albicans/metabolism , Collagen/metabolism , Fibronectins/metabolism , Membrane Glycoproteins/metabolism , Amino Acid Sequence , Candida albicans/pathogenicity , Cell Adhesion , Humans , Molecular Sequence Data , Oligopeptides/metabolism
16.
Science ; 251(4996): 934-6, 1991 Feb 22.
Article in English | MEDLINE | ID: mdl-2000493

ABSTRACT

The traditional view that Old World fruit bats (Megachiroptera) and insect bats (Microchiroptera) are closely related has been challenged by claims that Megachiroptera are the sister group to flying lemurs (Dermoptera) or Primates. We found that the specialized muscles of the rostral part of the wing in Microchiroptera and Megachiroptera receive double innervation by both the facial nerve and cervical spinal nerves, suggesting that bats are monophyletic. Innervation by the facial nerve also occurs in Dermoptera and suggests that bats and Dermoptera share a common ancestor that had wings.


Subject(s)
Chiroptera/physiology , Cranial Nerves/physiology , Muscles/innervation , Spinal Nerves/physiology , Animals , Cranial Nerves/anatomy & histology , Flight, Animal , Phylogeny , Species Specificity , Spinal Nerves/anatomy & histology , Wings, Animal/innervation
18.
Transplantation ; 50(2): 278-81, 1990 Aug.
Article in English | MEDLINE | ID: mdl-2382294

ABSTRACT

An autoimmune syndrome occurs in cyclosporine-treated, lethally irradiated, and marrow-reconstituted rats after cyclosporine is discontinued. This syndrome, referred to as cyclosporine-induced autoimmunity, requires the presence of a thymus. In this report, we demonstrate that the disease will occur in animals transplanted with thymus tissue from an allogeneic donor, incompatible with the recipient at the major histocompatibility complex. T cells generated from these allogeneic thymic chimeras respond in vitro to thymic donor antigens, suggesting that cyclosporine inhibits self-tolerance induction in the thymus. Because disease is more frequent when the tolerizing antigens expressed in the thymus differ from those expressed in the periphery, the possibility that cyclosporine may mediate its effect via the downregulation of self-antigen presented in the thymus is discussed.


Subject(s)
Autoimmune Diseases/chemically induced , Cyclosporins , Thymus Gland/transplantation , Animals , Antigens, Differentiation, B-Lymphocyte/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , Histocompatibility Antigens Class II/analysis , Lymphocyte Activation , Lymphocytes/immunology , Rats , Rats, Inbred Strains , Thymus Gland/immunology
19.
Ren Fail ; 12(2): 89-92, 1990.
Article in English | MEDLINE | ID: mdl-2236731

ABSTRACT

Thirteen patients found to be hypertensive following renal transplantation were treated with either a calcium channel blocker or other antihypertensive therapy for control of blood pressure. Immunosuppression was either with cyclosporine and prednisone alone or with cyclosporine, azathioprine, and prednisone. Patients had weekly or biweekly cyclosporine whole-blood levels measured by radioimmunoassay drawn approximately 12 h after their last dose. Patients treated with cyclosporine and prednisone alone had their cyclosporine dosage adjusted to maintain their cyclosporine level between 400 and 900 ng/mL between 1 and 6 months following transplantation. Patients treated with cyclosporine, azathioprine, and prednisone had their cyclosporine level adjusted to be between 100 and 400 ng/mL during this same time period. Cyclosporine levels were significantly higher in verapamil-treated patients and significantly lower in nifedipine-treated patients as compared to controls. The dose of cyclosporine administered was significantly lower in the verapamil-treated patients and higher in the nifedipine-treated patients than controls. Normalizing the whole-blood cyclosporine level for the dose of cyclosporine, and verapamil-treated patients had a significantly greater, and the nifedipine-treated patients a significantly lower value than control patients. These data suggest the verapamil treatment results in significantly higher levels of cyclosporine whereas nifedipine therapy may actually result in lower cyclosporine levels for a given dose of cyclosporine than seen in patients not exposed to these drugs.


Subject(s)
Calcium Channel Blockers/therapeutic use , Cyclosporins/administration & dosage , Hypertension/drug therapy , Kidney Transplantation , Adult , Cyclosporins/blood , Cyclosporins/therapeutic use , Drug Interactions , Drug Therapy, Combination , Female , Humans , Immunosuppression Therapy , Male , Middle Aged , Nifedipine/therapeutic use , Verapamil/therapeutic use
20.
Clin Immunol Immunopathol ; 53(2 Pt 2): S35-46, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2571438

ABSTRACT

Our understanding of the immune mechanisms that lead to systemic lupus erythematosus has been greatly advanced by the availability of murine models which display both serological and clinical features of the human disease. Studies have demonstrated that CD4+ T cells are required for the full expression of disease in these mice. (NZB X NZW)F1 mice exhibit a lupus-like disease (elevated levels of IgG antinuclear antibodies and a fatal glomerulonephritis) that is not characteristic of either parent. At least three gene loci have been identified in NZW mice that could potentially contribute to a T cell-dependent autoimmune disease, including the T cell receptor alpha- and beta-chain gene complexes and the major histocompatibility complex (MHC). The NZW T cell receptor beta-chain complex appeared to be particularly unusual in that the C beta 1, D beta 2, and J beta 2 gene segments have been deleted. However, an analysis of (NZB X NZW)F1 X NZB back-cross mice revealed no association of disease expression with the presence of this allele. There was also no correlation of disease incidence with the presence of the NZW T cell receptor alpha-chain allele. In contrast, nearly 90% of the backcross mice with the NZW MHC expressed severe autoimmune disease compared with 12% of the mice that did not carry this haplotype. Additional studies strongly suggested that the gene(s) within the NZW MHC is the only dominant NZW genetic contribution to F1 disease. We also determined if self-reactive T cells are able to escape thymic tolerance in autoimmune New Zealand and MRLlpr/lpr mice. In nonautoimmune mice expressing I-E, T cells utilizing V beta 17a and V beta 11 encoded domains have been shown to be clonally eliminated in the thymus. Similarly, V beta 8.1+ and V beta 6+ T cells are tolerized in nonautoimmune mice expressing Mls-1a. These T cell subsets were quantified in the lymph nodes and spleens of (NZB X NZW)F1, (NZB X SWR)F1, and MRL-lpr/lpr mice before and after the development of lupus-like disease. The results indicate that peripheral T cells in these mice, including the massive CD4-, CD8- T cell population in lpr mice, have been modified by normal mechanisms of tolerance such that potential self-reactive V beta specificities have been eliminated in the thymus.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Immune Tolerance , Lupus Erythematosus, Systemic/immunology , T-Lymphocytes/immunology , Animals , Autoantigens/immunology , Genotype , Lupus Erythematosus, Systemic/genetics , Mice , Mice, Inbred Strains/genetics , Thymus Gland/immunology
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