Color vision and neuroretinal function in diabetes.

PURPOSE: We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT abnormality classifications agree. METHODS: Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≤4.5°) and outside this area (peripheral IT; ≥4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined. RESULTS: CCS was greater in the NoRet (P = 0.002) and Ret (P < 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively; P < 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (P ≤ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %; P < 0.05). CONCLUSION: CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present.

Towards optimal filtering of "standard" multifocal electroretinogram (mfERG) recordings: findings in normal and diabetic subjects.

AIMS: To study the effects of two commonly used pre-amplifier filtering bandwidths on normal multifocal electroretinogram (mfERG) responses and their comparative abilities to detect retinal disease. METHODS: 103 standard mfERGs were recorded simultaneously in two channels with different pre-amplifier settings (10-100 Hz and 10-300 Hz) from one eye of each of 20 normal subjects, 17 diabetics with non-proliferative diabetic retinopathy (NPDR), and 12 diabetics without retinopathy. Signal to noise ratios (SNR) of the normal subjects' first order mfERGs were compared between channels. All subjects' amplitudes and implicit times were derived using a "template stretching" method. For comparison, implicit time was also measured using a "template sliding" method. mfERG amplitudes and implicit times were compared between the channels and among subject groups. RESULTS: Normal mean amplitudes and implicit times were similar for the two channels. However, normal 10-100 Hz recordings had significantly higher SNR and lower intersubject variability than 10-300 Hz recordings. In NPDR, the 10-100 Hz channel identified significantly more implicit time and amplitude abnormalities. In the diabetics without retinopathy, 10-100 Hz filtering identified significantly more implicit time abnormalities than 10-300 Hz filtering. For both filter settings, diabetic implicit times were more often abnormal than amplitudes. The 10-100 Hz channel was superior for both implicit time measurements. CONCLUSION: Standard mfERGs recorded from normal eyes and filtered 10-100 Hz contain less noise, higher SNR, and less intersubject variability than those filtered at 10-300 Hz. This underlies the finding that the 10-100 Hz filter setting identifies more retinal dysfunction than the 10-300 Hz setting.

Modulation of major histocompatibility complex class 1 genes in human retinoblastoma cells by interferons.

PURPOSE: To examine the mechanism(s) of interferon (IFN) induced expression of major histocompatibility complex (MHC) class 1 molecules on the human retinoblastoma cell line, Y-79. METHODS: Y-79 cells were incubated in the presence of IFN-alpha, -beta, and -gamma. Y-79 cell expression of MHC class 1 molecules was measured by flow cytometric analysis. HLA-B7 and oncogene transcription were evaluated by Northern blot analysis and nuclear runoff transcription assays. RESULTS: IFN-gamma increased MHC-class 1 antigen expression and induced a fivefold increase in its transcription rate. Posttranscriptionally, IFN-beta and -gamma increased steady state messenger RNA for the HLA-B7 gene. These effects were not associated with down regulation of N-myc oncogene nuclear transcription. Moreover, dexamethasone did not affect the IFN-gamma induced expression of MHC-class 1 molecules. CONCLUSIONS: Both transcriptional and posttranscriptional mechanisms are implicated in the modulation of class 1 molecule expression by IFN. In addition, this modulation is not associated with down regulation of N-myc oncogene expression. Spontaneous or IFN-gamma induced MHC class 1 antigen expression in retinoblastoma Y-79 cells is resistant to glucocorticoid hormones.

Intermittent cyclophosphamide for the treatment of autoimmune thrombocytopenia in systemic lupus erythematosus.

STUDY OBJECTIVE: To determine the effect of monthly intravenous cyclophosphamide therapy in patients with systemic lupus erythematosus and autoimmune thrombocytopenia. DESIGN: Uncontrolled, retrospective clinical study. SETTING: Government referral-based research hospital. PATIENTS: Seven patients with systemic lupus erythematosus and 2 or more months of thrombocytopenia refractory to or requiring excessive doses of corticosteroids. Two patients had also failed to respond to splenectomy and repeated intravenous methylprednisolone infusions. Six patients had severe active renal disease at the time of treatment. INTERVENTIONS: Cyclophosphamide, 0.75 to 1.0 g/m2 body surface area, was given intravenously every month for at least 4 months. Prednisone dose ranged between 0.5 to 1.0 mg/kg.d. MEASUREMENTS AND MAIN RESULTS: All seven patients had normal platelet counts within 2 to 18 weeks after cyclophosphamide treatment (one to four doses). Prednisone was tapered to 0.25 mg/kg on alternate days in all patients. All six patients had significant improvement in their renal disease and lupus serologies. Cyclophosphamide was discontinued after four to six doses in five patients. Four patients maintained normal platelet counts on low dose, alternate-day prednisone for a mean of 5.6 years of follow-up. Two patients had recurrence of thrombocytopenia 1 to 3 years after discontinuing cyclophosphamide. CONCLUSIONS: Monthly intravenous cyclophosphamide is potentially useful for the management of autoimmune thrombocytopenia in patients with systemic lupus erythematosus who are refractory to or dependent on unacceptably high doses of corticosteroids, or are experiencing side effects of conventional medical or surgical treatment.

Light and target distance interact to control pupil size.

Light and target distance stimuli were presented to normal human subjects, and their pupillary responses were measured. A homeomorphic computer model of the pupillary control system is presented in which the form of interaction of controller signals due to light and target distance was investigated. The error remaining when model parameters were optimized to fit experimental pupil size (area or diameter) was smaller for the linear interaction hypothesis than for either power law or logical law interaction. A generalized second-order nonlinear model with six parameters (vs. 3 for each of the other models) yielded somewhat lower residual error. With the use of a modified Akaike information criterion, the value (in an information theoretic sense) of the improved fit afforded by the three additional parameters in the generalized nonlinear model was shown to be small, and thus the generalized second-order nonlinear model was rejected in favor of the simpler and more parsimonious linear model.

c-myc proto-oncogene expression in peripheral blood mononuclear cells from patients with primary Sjögren's syndrome.

We examined peripheral blood mononuclear cells (PBMC) from 16 patients with Sjögren's syndrome (SS) and 7 normal control subjects for the expression of the c-myc proto-oncogene. Patients with SS were found to have a significantly increased expression of c-myc messenger RNA compared with normal individuals. No abnormal forms of c-myc RNA were detected in the SS patients. DNA analysis did not show deletion, rearrangement, or amplification in the c-myc proto-oncogene. The methylation status of the c-myc gene in patients with SS was found to be comparable with that of the control subjects. Nuclear run-off assays showed increased transcription of the c-myc gene in some patients but normal transcription in others, suggesting that posttranscriptional mechanisms are also involved in the increased c-myc messenger RNA observed in these patients. Two patients with primary SS and B cell lymphomas were found to have normal c-myc expression in their PBMC. These results demonstrate the presence of activated PBMC in patients with primary SS and delineate some of the mechanisms that are involved at the molecular level. We speculate that increased c-myc expression may represent an early permissive event in the progression toward neoplasia in these patients.

Oncogene expression and regulation in normal lymphocytes and lymphocytes from patients with autoimmune diseases.

The discovery of oncogenes has offered new insights into the physiology of lymphocytes. Proto-oncogenes encode proteins that are associated with the control of lymphocyte activation, proliferation and differentiation. Mononuclear cells from patients and animals with autoimmune disorders express increased quantities of oncogenes such as c-myc, c-myb and c-raf. In this review we discuss some of the cellular and molecular events associated with lymphocyte activation and the role that the oncogenes play in each of these events. The regulation of the expression of oncogenes in these cells is also reviewed. Finally, the role of the increased oncogene expression in the pathogenesis of autoimmune diseases is discussed.