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Biomedical subjects

L Lightstone

Publications and source records attributed to L Lightstone.

17 recordsLinked to original sources
PubMed2006

Urinary proteomic profiles distinguish between active and inactive lupus nephritis.

OBJECTIVES: Key aims of the treatment of lupus nephritis (LN) are to induce and maintain remission with minimal side effects. However, assessing ongoing renal inflammatory activity is poorly served by current diagnostic tests apart from renal biopsy, but frequent biopsies cannot be justified. Our long-term aim is to identify novel biomarkers from urinary protein profiles to improve diagnosis and monitoring of activity and response to therapy in LN. METHODS: We used surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) to identify biomarkers able to discriminate between urine samples from patients with inactive (n= 49) and active (n= 26) LN. Discriminant function analysis was used to define the minimum number of proteins whose levels best distinguished between the two patient groups. Serial urines of six biopsied patients were studied prospectively, and multiple regression (MR) scores calculated. RESULTS: Proteins with masses of 3340 and 3980 distinguished active from inactive LN with 92% sensitivity and specificity of 92% each. The prospective study of the biopsied patients demonstrated that MR scores could predict both relapse and remission earlier than traditional clinical markers. CONCLUSIONS: SELDI-TOF MS identified potential biomarker profiles strongly associated with activity in LN. Identification of these proteins will allow us to devise specific assays to routinely monitor disease progression, and alter immunosuppressive drug regimens accordingly. These proteins may also play a critical role in the pathogenesis of glomerulonephritis, and could therefore provide targets for therapeutic intervention.

Adult↗
PubMed2001

Reasons for failure of the ketogenic diet.

This study examined reasons why patients discontinue the ketogenic diet. A total of 46 children placed on the ketogenic diet between November 1994 and August 1996 were followed prospectively. Reasons for discontinuing the diet prior to 6 months were analyzed. Nineteen (41%) children discontinued the diet for either medical or nonmedical reasons. Nonmedical reasons were caregiver issues and patients' unwillingness to follow the diet. Noncompliance was more common in older children. The ketogenic diet, while effective, is a very stringent diet. Nonmedical reasons for discontinuation are as common as the traditional medical reasons of lack of efficacy or complications.

Adolescent↗
PubMed1999

Quinine-induced immune thrombocytopenic purpura followed by hemolytic uremic syndrome.

Immune thrombocytopenic purpura (ITP) mediated by quinine-dependent platelet reactive antibodies is well recognized. More recently there have been a number of reports of quinine-induced hemolytic-uremic syndrome (HUS). We describe a patient with quinine-induced immune thrombocytopenia who subsequently developed HUS after re-exposure to a single dose of this drug. To our knowledge, this is the first such case reported. Multiple quinine-dependent antibodies have been characterized in the patient's serum. Initially, quinine-dependent antibodies were directed solely against the platelet glycoprotein complex GPIb/IX. After rechallenge with quinine, there was broadening of quinine-dependent antibody specificities, which were now also directed against the platelet glycoprotein complexes GPIb/IX and GPIIb/IIIa, endothelial cells, and leukocytes. We have shown quinine-dependent antibody-mediated endothelial cell activation, which supports an immunopathogenic role for quinine-dependent antibodies in the causation of this disease.

Antibodies↗
PubMed1998

Issues related to caring for infants to adults on an integrated epilepsy unit.

We integrated the care of patients of all ages (ranging thus far from 4 weeks to 73 years) in our dedicated 8-bed Epilepsy Unit. Administrative issues pertaining to admission and discharge criteria, unit policies and procedures and an interdisciplinary quality assurance plan were examined in relation to the impact of combining both pediatric and adult patients. Clinical considerations included the diversified abilities needed to care for pediatric and adult patients both in relation to the technical skills as well as psychosocial skills required. The advantages of integrating patients of all ages on one unit include having a staff highly trained in assessment and intervention skills for a particular disorder. The psychosocial issues that arise in these patients, regardless of age, tend to encompass the entire family; therefore a holistic approach is appropriate for both children and adults. An autonomous nursing practice was established with the development of critical pathways and patient care protocols. Our experience suggests that integrated specialized units can enhance the care of patients with intractable seizures.

Adolescent↗
PubMed1997

In the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM.

The independent influences of invariant chain (Ii) and HLA-DM molecules on the array of naturally processed peptides displayed by HLA-DR molecules were studied using transfected cell lines. The absence of Ii led to an altered set of HLA-DR-bound peptides as judged by the discriminating responses of alloreactive T cell clones. While most T cell clones raised against DR+Ii+DM+ peripheral blood mononuclear cells (PBMC) failed to respond to DR+Ii-DM- cells, T cell clones raised against DR+Ii-DM- transfectants were not stimulated by DR+Ii+DM+ cells. Furthermore, coexpression of HLA-DM with HLA-DR1 in the absence of Ii augmented responses of anti-PBMC T cell clones but inhibited allorecognition by T cell clones raised against DR+Ii-DM- transfectants. The conformational integrity of the class II molecules, as judged by serology, suggests that the patterns of reactivity of the T cell clones reflect specificity for different alloantigen-bound peptides. Hence, discordant regulation of expression of major histocompatibility complex class II, Ii, and HLA-DM molecules in vivo may lead to the display of novel self-peptides and possible interruption of self-tolerance.

Antigen-Presenting Cells↗
PubMed1996

Antigen presentation by T cells inhibits IL-2 production and induces IL-4 release due to altered cognate signals.

Conflicting results of the effects of Ag presentation by MHC class II-expressing T cells have been described. In some studies class II-expressing T cells have been shown to act as effective APCs, while others have reported that the recognition of Ag on the surface of another T cell inactivates IL-2 production. In this study we have investigated the mechanisms involved in Ag presentation by T cells. The results obtained suggest that 1) lack of costimulation is not responsible for the inhibitory effects of T cell Ag presentation on IL-2 production; the provision of costimulation by immobilized anti-CD28 Ab or by the addition of accessory cells failed to reverse the effects of T cell Ag presentation, but restored the response to immobilized anti-CD3; 2) T cell Ag presentation induced a minimal increase in intracellular Ca2+ compared with that induced by antigen-pulsed B cells; this difference in the calcium response is not explained by quantitative differences in ligand density between B cells and T cells; and 3) despite the weak calcium signal, T cell presentation supported IL-4 release in the absence of IL-2 production. Taken together these data suggest that T cell Ag presentation leads to altered TCR/CD3-transduced signals, which biases the T cell towards a Th2 phenotype.

Animals↗
PubMed1995

Expression in vivo of CD45RA, CD45RB and CD44 on T cell receptor-transgenic CD8+ T cells following immunization.

We used mice transgenic for a major histocompatibility complex class I-restricted T cell receptor to study the changes of phenotype in vivo which follow priming by antigen of CD8 T cells. We show that following priming with peptide, CD44 on CD8 T cells is up-regulated. The change of phenotype was relatively stable, as primed CD8 cells isolated from thymectomized mice 6 weeks after priming still expressed increased levels of CD44. CD8 T cells in these mice are still responsive to peptide and could represent long-lived primed cells. No down-regulation in vivo of the CD45RA or CD45RB isoforms was found, indicating that there is a differential regulation of the expression of CD44 and CD45RB by activated CD8 transgenic T cells. These results contradict earlier studies in vitro which showed that CD8 T cells which have been primed earlier belong to the CD45RA- or CD45RB- subset.

Animals↗
PubMed1995

Protocol for ACTH administration in refractory childhood seizures: educational strategies.

Adrenocorticotropic hormone (ACTH) in gel form is increasingly being used in the treatment of a variety of childhood seizure disorders. The therapy involves intramuscular injections and can be associated with significant morbidity. A teaching/learning plan for parents or caregivers based on Knowles' theory of adult learning was developed and incorporated into the ACTH protocol presented here. Twenty-nine families completed this protocol. Despite a wide range of educational levels and support systems, all caregivers proved capable of administering the medication. Few complications were encountered. In interviews with the caregivers regarding the teaching-learning process, caregivers believed it contributed to their ability to complete the therapeutic program.

Adrenocorticotropic Hormone↗
PubMed1995

High incidence of end-stage renal disease in Indo-Asians in the UK.

In a retrospective survey, we show that the incidence of end-stage renal disease (ESRD) is significantly raised among immigrant Indo-Asians referred to two UK renal units (p < 0.001). In addition to the expected increase in diabetic nephropathy, glomerulonephritis and chronic pyelonephritis are also seen more frequently in Indo-Asians. The most striking finding was a five-fold increase in ESRD of uncertain cause (p < 0.001) presenting with small smooth kidneys, which was strongly associated with active, mostly non-renal tuberculosis. The causes of this generalized increased susceptibility to renal disease are unknown. These findings have important implications both for primary health care screening and for planning the provision of renal replacement therapy.

Adolescent↗
PubMed1993

CD45RA+ T cells: not simple virgins.

1. The T cells which mediate immunological memory remain elusive. Identification of such cells would open the door to increasingly specific immunotherapy in areas such as transplantation and autoimmunity. 2. Over the last few years attempts have been made to identify phenotypic markers which can distinguish naive or virgin T cells from primed or memory ones. In humans, great hopes were raised when it was shown that the level of expression of the higher-molecular-mass isoforms (CD45RA) of the tyrosine phosphatase, CD45, correlated with previous exposure to antigen. 4. However, our studies in the mouse and more recent studies in rat and human suggest that expression of CD45RA more closely correlates with the state of responsiveness of the T cell. 5. Thus, with time, activated/memory T cells return to a state of quiescence or hypo-responsiveness and express high levels of CD45RA. Hence, not all CD45RA+ T cells are virgins.

Aging↗
PubMed1989

Problems in the physiology of class I and class II MHC molecules, and of CD45.

1. Co-processing of alloantigens suggests that epitope-loaded MHC class I molecules may pass from tissue cells to dendritic cells. 2. Antigen-presenting cells in the thymus need some special trick in order to load their MHC class II molecules with epitopes from "intermediate concentration" self-proteins in order to induce self-tolerance in developing cells. 3. Cell-cell interactions may transmit signals simply by rearranging surface glycoproteins and thus locally perturbing a phosphorylation equilibrium. 4. The CD45 and STB1 phenotype of most cells in the thymus may be characteristic of a doomed cell.

Animals↗
PubMedDate not supplied

Acute renal failure.

Explore the source record for details and available documents.

Acute Kidney Injury↗