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S Cousins

Publications and source records attributed to S Cousins.

At least 19 recordsLinked to original sources
PubMed2004

The Mouse Genome Database (MGD): integrating biology with the genome.

The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a community database resource for the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about the mouse with experiments and data annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genetic, genotype (sequence) and phenotype information including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent developments in MGD discussed here include an extensive integration of the mouse sequence data and substantial revisions in the presentation, query and visualization of sequence data.

Animals↗
PubMed2002

Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs.

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

Alternative Splicing↗
PubMed2001

Surgical management of secondary glaucoma after pars plana vitrectomy and silicone oil injection for complex retinal detachment.

OBJECTIVE: To evaluate the outcomes of surgical intervention for secondary glaucoma after pars plana vitrectomy and silicone oil injection for repair of complex retinal detachment. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Forty-three eyes of 43 patients who underwent incisional surgery for secondary glaucoma after pars plana vitrectomy and silicone oil injection for repair of complex retinal detachment over a 9-year period. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), intraoperative and postoperative complications, visual acuity, and the need for further surgical intervention for glaucoma. Success was defined as IOP < or =21 mmHg and > or =5 mmHg with or without medication but without surgical reoperation for glaucoma. RESULTS: Findings associated with elevated IOP included emulsified oil in the anterior chamber (n = 14), pupillary block from silicone oil (n = 13), open-angle glaucoma without silicone oil in the anterior chamber (n = 9), and angle-closure glaucoma without pupillary block (n = 7). The mean (+/- standard deviation) IOP was 41.4 +/- 15.1 mmHg before surgery for glaucoma and 17.2 +/- 10.2 mmHg after an average follow-up of 19.6 months (P < 0.001). Cumulative success was 69%, 60%, 56%, and 48% at 6, 12, 24, and 36-months respectively. In patients who underwent silicone oil removal alone for surgical management of glaucoma (n = 32), 11 of 12 IOP failures (92%) were due to uncontrolled IOP, whereas most IOP failures in the group who underwent silicone oil removal plus glaucoma surgery (n = 8) failed because of hypotony (3 of 4, 75%, P = 0.027). Of three patients who underwent glaucoma surgery alone to control IOP, one failed because of hypotony. There was no significant change in visual function at last follow-up (logarithm of the minimum angle of resolution [logMAR] 2.01) compared with preoperative visual function (logMAR 2.07, P = 0.74). CONCLUSION: Surgical management of secondary glaucoma after silicone oil injection for complex retinal detachment may achieve good IOP control and stabilization of visual function in most patients. Patients who undergo silicone oil removal alone to control IOP are more likely to have persistent elevation of IOP and possibly undergo reoperation for glaucoma, whereas patients who undergo concurrent silicone oil removal and glaucoma surgery are more likely to have hypotony.

Female↗
PubMed1997

Radioimmunoassay of zidovudine: extended use and potential application.

When first approved, the dosing regimens for zidovudine were 1,200-1,500 mg/day; however, because toxicity developed, the daily dose had to be reduced to 500-600 mg/day. At these lower doses, plasma concentrations for a considerable segment of the dosing interval are often below the assay sensitivity for the high-performance liquid chromatography (HPLC) method. Although commonly used, the zidovudine radioimmunoassay has had minimal documentation for the quantitative analysis of clinical samples, especially at current doses. The authors' findings indicate that plasma, urine treated with phosphate buffer, and cerebrospinal fluid samples may be assayed using a commercially available radioimmunoassay. A good correlation was found for clinical samples measured by radioimmunoassay and HPLC (R2 = 0.85). The greater assay sensitivity, ability to process multiple specimens, and the relatively rapid turnaround time suggest that the zidovudine radioimmunoassay may have an important role in clinical trials evaluating zidovudine pharmacokinetics. This report summarizes the authors' experience with the zidovudine radioimmunoassay and focuses on its potential use in studying the role of therapeutic drug monitoring for zidovudine.

Chromatography, High Pressure Liquid↗
PubMed1994

Portable software tools for 3D radiation therapy planning.

PURPOSE: Produce a collection of software tools (computer programs) that support three-dimensional (3D) radiation therapy planning. The tools are not a complete 3D planning system. Instead, they work with any 3D planning system that meets certain minimal specifications. The tools assist in deriving anatomic data from images, generating target volume contours, evaluating treatment plans, and verifying accurate treatment delivery. The tools are portable: they can run without source code changes in any computing environment that provides a library of functions and data definitions called the Foundation. The Foundation couples the portable tools to the (usually nonportable) file system and dose calculation associated with a particular 3D planning system. METHODS AND MATERIALS: Tools were written at three different (geographically separated) institutions. Software developers from all three sites specified the Foundation. The programmers' interface to the Foundation is portable, but a Foundation implementation need not be portable. Each group implemented a Foundation adapted to the (different) 3D planning system used at their site. RESULTS: All tools run at all three sites without source code changes. Each Foundation was implemented in a few person-months of programming effort. The program text and documentation for the tools have been placed in the public domain. CONCLUSIONS: It is practical and economical to produce portable radiotherapy treatment planning tools. Providers of 3D planning programs should offer Foundations for their systems, so they can be used with tools. Researchers considering new computer programs should write them as tools, so they can work with any 3D planning system.

Costs and Cost Analysis↗
PubMed1992

Are sense-antisense peptide interactions between HIV-1 (gp120), CD4, and the proto oncogene product p56lck important?

The finding that codons for hydrophobic and hydrophilic amino acids are generally complemented by codons for hydrophilic and hydrophobic amino acids respectively has led to a novel observation. The antisense peptides coded for by the complementary DNA strand of biologically active peptides are able to bind their active sense counterparts with high specificity. Sense-antisense relationships have been observed in several peptide species as well as in receptor-ligand interactions. The idea that sense-antisense interactions are biologically relevant and indeed feasible among complex molecules prompts the examination of virus-host cell interactions. We propose such a sense-antisense interaction exists between the HIV glycoprotein gp120 and the intracellular domain of the HIV receptor CD4. This interaction is at a site which may be occupied by the proto oncogene product p56lck.

Amino Acid Sequence↗
PubMed1992

Eye-derived cytokines and the immunosuppressive intraocular microenvironment: a review.

The normal aqueous humor contains a variety of soluble immunosuppressive factors, including transforming growth factor-beta, alpha-melanocyte stimulating hormone, and vasoactive intestinal peptide. These factors are largely the secretory products of parenchymal cells of the iris and ciliary body. TGF beta has recently been shown to alter the functional capacity of intraocular antigen presenting cells, such that they are capable of inducing Anterior Chamber Associated Immune Deviation (ACAID). This deviant systemic immune response is characterized by an impaired capacity to mount an effective cell-mediated immune attack directed at antigens that are placed in, or arise within, the eye. A second property of immunosuppressive factors in aqueous humor is to suppress directly the expression of delayed hypersensitivity in the anterior chamber. In fact, even when the intraocular microenvironment is disturbed by local instillation of gamma-interferon, making it possible for limited expression of cell-mediated immunity in the eye, the microenvironment of the anterior chamber remains profoundly immunosuppressive. In this latter instance, prostaglandins replace TGF beta as the major molecular mediators of suppression in the aqueous humor. In the aggregate, factors present in the normal (or perturbed) intraocular microenvironment have the capacity to modify both the afferent and efferent limbs of the systemic immune response, and this accounts for the longstanding observation that the anterior chamber is an immunologically privileged site. Since evidence suggests that the eye can mobilize more than one molecular mechanism in its effort to limit the sight-destroying potential of immunogenic inflammation, we believe that elucidation of intraocular cytokines and factors that create and maintain an immunosuppressive microenvironment will contribute to a better understanding of the pathogenesis of the acute and chronic uveitides, especially those of autoimmune and infectious etiology.

Animals↗
PubMed1992

Effect of intraocular gamma-interferon on immunoregulatory properties of iris and ciliary body cells.

Resistance of the anterior chamber (AC) of mouse eyes to expression of cell-mediated immunity can be overcome by pre-treating the eye with a dose of recombinant rat gamma-interferon (gamma IFN) that is of itself noninflammatory. To study the mechanism of this form of intraocular inflammation, cells of the tissues surrounding the AC (iris, ciliary body, cornea) were studied in vivo for alterations in phenotype and in vitro regarding their effects on antigen-driven T cell activation. The results indicate that gamma IFN: (1) induced class II major histocompatibility complex (MHC) expression on resident bone marrow-derived cells of iris and ciliary body (I/CB), but not the cornea; (2) led to recruitment of bone marrow-derived cells into the I/CB stroma; and (3) failed to induce class II MHC expression on ocular epithelial cells. Cell suspensions prepared from gamma IFN-treated I/CB superficially resembled normal I/CB cells in that neither were able to activate allogeneic T cells and both were able to suppress antigen-driven T cell activation in vitro. However, unlike cells from normal eyes, I/CB cells from gamma IFN-treated eyes suppressed T cell activation primarily through the secretion of prostaglandins. These results indicate that the ability of gamma IFN-treated eyes to display immunogenic inflammation probably does not result merely from the restoration of conventional antigen presenting cells to this environment, but appears to correlate with a critical change in the molecular mediators of immunosuppression. The findings are discussed in terms of the possibility that the eye may be able to respond to abrogation of its primary immunosuppressive microenvironment by erecting a secondary microenvironment that also is capable of suppressing immunogenic inflammation with a different set of antiinflammatory mediators.

Animals↗
PubMed1990

Ocular molecules and cells that regulate immune responses in situ.

Regulation of T cell-dependent immune responses is mediated in part by bone marrow-derived antigen presenting cells (APC) that (a) process and present antigens which engage the T cell receptor and (b) secrete cytokines that influence the threshold of T cell activation. The anterior chamber of the eye is lined by the corneal endothelium (which rests on a stroma and epithelium that is devoid of class II MHC + APC) and iris/ciliary body (which contain significant numbers of bone marrow-derived cells, one third of which are class II MHC +). When tested in vitro, these potential APCs fail to present antigens in a form that activates T cells. Moreover, iris/ciliary body cells actually suppress activation of T cells exposed to antigens on conventional APC. In addition, aqueous humor under normal circumstances contains factors (one of which is TGFB) that are potent inhibitors of antigen-driven T cell activation, but spare other aspects of T cell function. Evidence suggests that the bone marrow-derived cells in iris/ciliary body are the source of this factor. Thus, the anterior chamber contains powerful forces that can prevent induction and can suppress expression of T cell mediated immunity. It is proposed that these forces are responsible for immunologic privilege and anterior chamber associated immune deviation, and for suppressing pathologic proliferation and inflammation in the anterior segment of the eye.

Animals↗
PubMed1990

Myocutaneous flaps. Surgical treatment of severe pressure ulcers.

Surgical treatment of pressure ulcers using the myocutaneous flap procedure is a relatively new approach for patients with spinal injuries. First, the pressure ulcers are treated conservatively; however, if they become large or infected, surgery is considered. We have performed approximately 1,500 of these surgeries in the past five years. Only 5% of the cases have developed complications. The primary complication experienced was small wound dehiscence, which we attributed to mechanical interference with wound healing. We attribute the overall success of these surgeries to the rigid protocol and interdisciplinary approach to management.

Humans↗
PubMed1987

Histopathologic characteristics of two forms of experimental herpes simplex virus retinitis.

Herpes simplex virus type 1 (HSV-1) inoculated intracamerally into one anterior chamber of a BALB/c mouse produces retinitis in the uninoculated contralateral eye within 7 to 10 days while the retina of the inoculated eye is spared. In sharp contrast, animals receiving HSV type 2 (HSV-2) by the anterior chamber route develop a dramatic retinitis in the inoculated eye by day 7 postinoculation while the retina of the contralateral eye remains uninvolved. Histopathologic examination of retinal destruction in the HSV-2-infected ipsilateral eye revealed features which were distinct from those observed in the contralateral eye of HSV-1-infected animals. Whereas HSV-1 produced a rapid, explosive, retinitis which led to destruction of all cell layers of the contralateral retina, HSV-2 induced a retinitis in the ipsilateral eye that was more gradual in onset. Ipsilateral HSV-2 retinitis was characterized initially by disruption of the ganglion and inner nuclear layers which progressed by day 10 to 14 to complete replacement of the retina by a fibrocellular scar. These changes were dominated by a vigorous mononuclear cell infiltrate, a feature not observed in the HSV-1-infected contralateral retinitis. These results suggest that experimental retinitides produced by HSV-1 and HSV-2 are of diverse pathogenesis.

Animals↗
PubMed1986

Pseudophakic retinal detachments in the presence of various IOL types.

A series of 600 pseudophakic retinal detachments in 578 patients undergoing surgical repair between 1974 and 1984 was reviewed. Patients with previous retinal surgery of less than six months follow-up were excluded. The series included 395 iris-fixated (IF) lenses, 130 anterior chamber (AC) lenses, and 75 posterior chamber (PC) lenses. The overall success rate for retinal detachment was 88% but was significantly better in the PC lens group and significantly worse in the AC lens group. Forty-one percent of all cases achieved 20/40 visual acuity or better, although the AC lens group did worse (28%), while the PC lens group did significantly better (48%). Risk factors that were predictive of failure also were identified. Many of these factors occurred more frequently in the AC lens group and probably are related to the overall worse outcome in eyes with AC lens implants. The implications of these results for retinal and cataract surgeons are discussed.

Humans↗
PubMed1986

Infective complications of aplastic anaemia.

Patients with aplastic anaemia have a relatively specific immune defect--leucopenia with neutropenia. We have carried out a retrospective analysis of infective episodes in 11 patients with aplastic anaemia. 5723 follow-up days accrued and 29 infective episodes were documented. Overall the number of infective episodes was significantly associated with the mean white cell and monocyte counts (r = 0.59, 0.02 less than P less than 0.05) but not with length of follow-up, presentation values of white cell, neutrophil and monocyte counts, or mean neutrophil count. The patients appeared to divide clinically into two groups, those at low risk (seven patients) and those high risk (four patients) of infection. Patients in the high risk group had significantly more infections (P = 0.01) and significantly lower monocyte counts (0.02 less than P less than 0.05) than patients in the low risk group. These results are in contrast to similar studies in patients with chemotherapy-induced neutropenia; in our patients the overall rate and severity of infection was low, Gram negative infections were uncommon and monocytopenia appeared to be of greater importance than neutropenia in determining susceptibility to infection.

Adolescent↗
PubMed1984

A simple quantitative estimate of the function of radiolabelled platelets.

The function ex vivo of autologous platelets, labelled with 111In, was evaluated at various times following injection by comparing the retention on foreign surfaces of radioactivity with the retention of total platelets (represented almost entirely by unlabelled and therefore unmanipulated platelets) after the application of fresh un-anticoagulated whole blood to (a) filter paper and (b) glass bead columns. Relative retentions were similar for the two materials, with labelled platelet retention being about 80% that of native platelet retention. Prior to injection, when labelled platelets were returned to an excess of freshly drawn whole blood, retention of radioactivity was greater than that of native platelets with a ratio significantly greater than that seen with labelled platelets tested ex vivo. Filter paper retention provides a simple technique which may be useful for the evaluation of labelled platelet function as a function of platelet age and also, with further standardisation, as an inexpensive rapid test of unlabelled platelet function.

Blood Platelets↗
PubMed1984

Abnormal corneal and eyelid development in the repeated epilation mouse.

Development of the eyelids and cornea in repeated epilation (Er/Er) mice is characterized by fusion of the tarsal conjunctiva to the epithelia of the bulbar conjunctiva and cornea. We investigated the ultrastructural features of this malformation and tested for abnormal expression of filaggrin by immunofluorescence. Heterozygous (Er/+) breeding stock were mated and 13,14,15, and 19-day-old embryos were studied by light and electron microscopy. Fusion occurred in all Er/Er specimens and was associated with abnormal migration of surface ectodermal cells onto the cornea. Immunofluorescence studies with antimouse filaggrin antibody on day 13 and day 15 revealed the presence of filaggrin precursors in the fused epithelia of mutants, but not in normal corneal or conjunctival epithelia. The results suggest defective regulation of the synthesis of cellular proteins and altered cell surface properties in the Er/Er ocular epithelia.

Abnormalities, Multiple↗