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Biomedical subjects

A Reynolds

Publications and source records attributed to A Reynolds.

At least 19 recordsLinked to original sources
PubMed2000

Oxidant stress in sled dogs subjected to repetitive endurance exercise.

OBJECTIVE: To determine whether repetitive endurance exercise in sled dogs was associated with substantial lipid peroxidation, decreases in antioxidant capacity of the serum, and skeletal muscle damage. ANIMALS: 24 lightly trained sled dogs. PROCEDURE: 16 dogs completed a 58-km run on each of 3 consecutive days; the other 8 dogs (control) did not exercise during the study. Blood samples were collected before the first exercise run and after the first and third exercise runs. Plasma isoprostane and serum vitamin E concentrations, total antioxidant status of plasma, and serum creatine kinase activity were measured. RESULTS: Plasma isoprostane concentrations in dogs in the exercise group were significantly increased after the first exercise run and further significantly increased after the third exercise run. Serum vitamin E concentration was significantly decreased after the first exercise run in dogs in the exercise group, and this change persisted after the third exercise run. There was a significant linear relationship between plasma isoprostane concentration and the logarithm of serum creatine kinase activity (adjusted ? = 0.84). CONCLUSIONS AND CLINICAL RELEVANCE: Results demonstrate that repetitive endurance exercise in dogs is associated with lipid peroxidation and a reduction in plasma antioxidant concentrations. We interpret these results as indicating that the antioxidant mechanisms of minimally trained dogs may, in some instances, be inadequate to meet the antioxidant requirements of repetitive endurance exercise.

Animal Feed↗
PubMed1999

Iris crystals in chronic uveitis.

AIMS: To analyse the unusual physical sign of iris crystals occurring in patients with uveitis. METHODS: Demographic details and clinical features were documented in 24 patients with chronic uveitis and iris crystals. Plasma immunoglobulin subclasses were measured, and a histopathological review of iridectomy specimens from 33 patients with chronic uveitis was also undertaken. RESULTS: The mean age of patients was 38 years, with a slight preponderance of females. 17 patients had Fuchs' heterochromic cyclitis although a number of other uveitis entities were represented. There was no correlation between severity of clinical signs and presence of iris crystals. Over a mean follow up period of 15 months no significant change in the number, size, or position of the crystals was seen except in four patients who underwent intraocular surgery. Only three patients had raised plasma IgG1. The review of the histology of iridectomy specimens failed to show evidence of Russell body formation in any patient. CONCLUSIONS: Iris crystals appear to be rare but may be underreported as they are small and can easily be missed. They are likely to be associated with disease processes in which there is active immunoglobulin production within the anterior chamber, such as Fuchs' heterochromic cyclitis.

Adolescent↗
PubMed1998

Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms.

Catenins were discovered as proteins that are linked to the cytoplasmic domain of transmembrane cadherins. Among these junctional plaque proteins are several members of the Armadillo gene family: beta-catenin, plakoglobin, and p120ctn. Recently it became clear that some catenins also mediate nuclear signaling. We performed a detailed analysis of the human p120ctn gene (HGMW-approved symbol CTNND1) and its transcripts. The human p120ctn gene comprises 21 exons, potentially encoding up to 32 protein isoforms as products of alternative splicing. Human isoforms, designated 1 to 4, differ from each other by the start codon used. Additional isoforms are derived from combinations with alternatively used exons A (exon 18) and B (20), near the end of the open reading frame, and also with exon C (11) in the middle of the open reading frame. Hence, the longest isoform is of type 1ABC and comprises 968 amino acid residues. The functional consequence of the observed multitude of p120ctn splice variants awaits further study, but tissue-specific expression was obvious. Further, we demonstrate that the exon organization, which is not simply related to the Armadillo repeat structure, is very well conserved between the p120ctn gene and the related ARVCF gene, but not at all between these two genes and the beta-catenin or plakoglobin genes. The present data favor the concept that p120ctn is the prototype of a subfamily of Armadillo proteins, comprising ARVCF, p0071, delta-catenin/NPRAP, and plakophilins 1 and 2, that are more related to each other than to other Armadillo proteins.

Alternative Splicing↗
PubMed1998

Harpin and hydrogen peroxide both initiate programmed cell death but have differential effects on defence gene expression in Arabidopsis suspension cultures.

Programmed cell death is increasingly viewed as a key component of the hypersensitive disease resistance response of plants. The generation of reactive oxygen species (ROS) such as H2O2 triggers a cell death programme in Arabidopsis suspension cultures following challenge with the bacterial elicitor harpin. Both harpin and exogenous H2O2 initiate a cell death pathway that requires gene expression, and also act as signalling molecules to induce the expression of plant defence genes encoding enzymes such as phenylalanine ammonia-lyase (PAL), glutathione S-transferase (GST) and anthranilate synthase (ASA1), an enzyme of phytoalexin biosynthesis in Arabidopsis. H2O2 induces the expression of PAL1 and GST but not that of ASA1. Harpin initiates two signalling pathways, one leading to increased ROS generation and expression of PAL1 and GST mRNA, and another leading to increased GST and ASA1 expression, independent of H2O2.

Anthranilate Synthase↗
PubMed1998

Congenital myotonic dystrophy requiring prolonged endotracheal and noninvasive assisted ventilation: not a uniformly fatal condition.

In this report we present two infants with congenital myotonic dystrophy (CMD) who were successfully weaned from prolonged ventilatory support using nasal continuous positive airway pressure (N-CPAP). The first infant received 127 days of endotracheal mechanical ventilation as part of 141 days of total ventilatory support, including N-CPAP; the second infant received 27 days of endotracheal mechanical ventilation as part of 84 days of total ventilatory support. Noninvasive N-CPAP facilitated weaning these two infants from ventilatory support, thereby minimizing the morbidity associated with prolonged intubation. The developmental outcomes of our two infants were comparable to infants not requiring prolonged endotracheal mechanical ventilation. We suggest that this noninvasive modality of ventilatory support may be advantageous in the management and beneficial to the outcome of infants with CMD who are respirator-dependent >30 days.

Adult↗
PubMed1998

TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues.

TRAF-4 was discovered because of its expression in breast cancers and is a member of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of putative signal-transducing proteins. In vitro binding assays demonstrated that TRAF-4 interacts with the cytosolic domain of the lymphotoxin-beta receptor (LT beta R) and weakly with the p75 nerve growth factor receptor (NGFR) but not with TNFR1, TNFR2, Fas, or CD40. Immunofluorescence analysis of TRAF-4 in transfected cells demonstrated localization to cytosol but not nucleus. Immunohistochemical assays of normal human adult tissues revealed prominent cytosolic immunostaining in thymic epithelial cells and lymph node dendritic cells but not in lymphocytes or thymocytes, paralleling the reported patterns of LT beta R expression. The basal cell layer of most epithelia in the body was very strongly TRAF-4 immunopositive, including epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus. Similar findings were obtained in 12- to 18-week human fetal tissue, indicating a highly restricted pattern of expression even during development in the mammary gland, epithelial cells of the terminal ducts were strongly TRAF-4 immunopositive whereas myoepithelial cells and most of the mammary epithelial cells lining the extralobular ducts were TRAF-4 immunonegative. Of 84 primary breast cancers evaluated, only 7 expressed TRAF-4. Ductal carcinoma in situ (DCIS) lesions were uniformly TRAF-4 immunonegative (n = 21). In the prostate, the basal cells were strongly immunostained for TRAF-4, whereas the secretory epithelial cells were TRAF-4 negative. Basal cells in prostate hypertrophy (n = 6) and prostatic intraepithelial neoplasia (PIN; n = 6) were strongly TRAF-4 positive, but none of the 32 primary and 16 metastatic prostate cancer specimens examined contained TRAF-4-positive malignant cells. Although also expressed in some types of mesenchymal cells, these findings suggest that TRAF-4 is a marker of normal epithelial stem cells, the expression of which often ceases on differentiation and malignant transformation.

Adult↗
PubMed1997

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

Amino Acid Sequence↗
PubMed1997

Capsulorhexis phymosis following uncomplicated phacoemulsification surgery.

PURPOSE: The aim of the study was to assess and compare the degree of capsulorhexis phymosis following uncomplicated phacoemulsification cataract surgery in polymethylmethacrylate (PMMA) and silicone lens implants. METHOD: Sixty-four patients were evaluated 1 day, 6 weeks and 6 months following phacoemulsification cataract extraction. The anterior capsular diameters were measured with the illuminated beam of the slit lamp at 45 degrees and 135 degrees and the surface area of the opening calculated. We have measured and compared the change in the capsulorhexis size for both lens types and assessed its statistical significance with a paired Student's t-test. RESULTS: A statistically significant contraction of the capsulorhexis was noted in all patients within the first 6 weeks (p < 0.001). Capsular contraction continued between 6 weeks and 6 months post-operatively but to a lesser extent (p < 0.05). The difference in the degree of phymosis between the first period (1 day to 6 weeks) and the second (6 weeks to 6 months) was statistically highly significant for all patients (p < 0.001). The capsular areas for the silicone lens implants were significantly smaller than for the PMMA implants at 6 weeks and 6 months. None of our patients had a clinically significant capsular contracture requiring Nd:YAG laser capsulotomy. CONCLUSION: Anterior capsular contraction is commonly observed following capsulorhexis in phacoemulsification surgery. This study demonstrates that the maximum rate of contraction occurs in the first 6 weeks following surgery and is more pronounced with silicone lens implants.

Aged↗
PubMed1997

Variation in astigmatism following the single-step, self-sealing clear corneal section for phacoemulsification.

PURPOSE: A single-step, self-sealing, 3.2 mm clear corneal section is described and the incidence and variation of surgically induced astigmatism following phacoemulsification over a period of 3 months is determined. METHODS: Twenty-two patients who underwent uncomplicated 3.2 mm clear corneal phacoemulsification with foldable Allergan silicone intraocular lens implantation were autorefracted pre-operatively and on day 1, week 1, week 6 and at 3 months. The variation in induced astigmatism was analysed using the subtraction method and vector analysis. The change in direction of the cylindrical axis was examined. RESULTS: The induced astigmatism represented by the total vector on day 1 was 1.17 D and vector decomposition ratio, ATR:WTR (against-the-rule:with-the-rule), was 21.05:78.95. The total vector increased by 0.5 D in the first week and then stabilised. Vector decomposition showed an against-the-rule astigmatic drift so that by 3 months the ATR:WTR was 40.49:59.91. There was a tendency of the axis of the negative cylinder to swing towards the corneal section meridian on day 1 and to oscillate around that meridian at week 1 and week 6. By 3 months the direction reverted to that pre-operatively, in most cases. CONCLUSIONS: The single-step, self-sealing clear corneal section is mechanically stable and, though there is some variability in the measured astigmatism, there is an acceptable functional result throughout the post-operative period.

Aged↗
PubMed1997

Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo.

We describe the use of 11CRTI-55 and the Multiple Objects Coincidences Counter (MOCC) to detect in-vivo binding to peripheral serotonin reuptake sites (left chest comprising platelet and lung serotonin reuptake sites) in man. Displacement and preloading experiments with clomipramine and venlafaxine in two healthy volunteers demonstrated that 11CRTI-55 binding is decreased in a dose-dependent fashion by both these drugs which bind to the serotonin transporter. In addition parallel data from the total head curve (representing 11CRTI-55 binding to central serotonin and dopamine (DA) reuptake sites) suggest that prior blockade of the serotonin transporter may be a useful strategy to maximize radioactive counts in the head when measuring the DA transporter. The MOCC is likely to be useful to determine sequential indices of relative serotonin reuptake blockade in patients on treatment.

Adult↗
PubMed1996

IL-12 enhances vaccine-induced immunity to schistosomes by augmenting both humoral and cell-mediated immune responses against the parasite.

The production of Th1-type cytokines is associated with strong cell-mediated immunity, while Th2-type cytokines typically dominate humoral immune responses. In mice vaccinated a single time with attenuated cercariae of Schistosoma mansoni, the protection induced is associated with Th1 cytokine-dependent, cell-mediated immunity. In contrast, mice vaccinated multiple times display a more Th2-type dominant cytokine response and develop Ab-dependent resistance. We have previously shown that IL-12 enhances cell-mediated immunity in singly vaccinated mice. In the present study, we asked what effects administering IL-12 as an adjuvant would have on the development of a protective humoral response in multiply immunized animals. We found that multiply immunized/IL-12-treated mice displayed a marked increase in resistance to challenge infection, with some animals demonstrating complete protection. The IL-12-vaccinated mice developed strongly polarized Th1 responses but, importantly, also showed significant increases in parasite-specific Ab and, in particular, IgG2a, IgG2b, and IgG1 isotypes. Passive transfer demonstrated an enhanced ability of serum from these animals to protect naive recipients. In addition, animals vaccinated in the presence of IL-12 also developed macrophages with increased nitric oxide-dependent killing activity against the parasites. Together, these data demonstrate that IL-12, initially described as an adjuvant for cell-mediated immunity, may be used to simultaneously to promote both humoral and cell-mediated protective responses against infection.

Animals↗
PubMed1996

Long-term survival of Molteno glaucoma drainage devices.

PURPOSE: To evaluate the long-term outcome of the Molteno implant drainage device using survival analysis. METHODS: A retrospective chart review was performed on 77 eyes of 71 patients that underwent Molteno implantation for intractable glaucoma unresponsive to conventional management from October 1984 to April 1990 at the University of Washington Eye Center and had at least 6 months of follow-up data. Success was defined as a postoperative intraocular pressure of 22 mmHg or lower with (qualified success) or without (complete success) glaucoma medications and no additional glaucoma surgery, phthisis, or loss of light perception. RESULTS: The median follow-up was 44 months (range, 6-107 months). Indications for Molteno implantation were aphakia/pseudophakia (n=24), neovascular glaucoma (n=20), uveitic glaucoma (n=12), failed trabeculectomy (n=9), traumatic glaucoma (n=8), and congenital glaucoma (n=4). The total success was 57% (23% complete; 34% qualified) at the last follow-up. Kaplan-Meier survival curves demonstrated a continuous and relatively linear attrition of success over at least 5 1/2 postoperative years. The uveitic glaucoma group had the highest success rate of 75%. Eyes with neovascular glaucoma failed significantly more frequently than those with uveitic glaucoma (P<0.01). There was no significant difference in outcome based on sex, race, single versus double plate, anterior chamber versus posterior chamber tube placement, or two-stage versus single-stage surgery. Younger age was associated with a significantly higher failure rate after controlling for glaucoma category (P<0.01). CONCLUSION: The Molteno implant drainage device offers a reasonable long- term outcome in eyes with intractable glaucomas. However, an ongoing rate of failure, not unlike that seen after other filtration surgery, is to be expected.

Adolescent↗