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J S Wolinsky

Publications and source records attributed to J S Wolinsky.

At least 55 records · Page 3Linked to original sources
PubMed1998

Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis.

Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.

Atrophy↗
PubMed1998

Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Copolymer 1 Multiple Sclerosis Study Group.

When 251 relapsing-remitting patients with multiple sclerosis were randomized to receive daily subcutaneous injections of glatiramer acetate, previously called copolymer 1 (Copaxone; n = 125) or placebo (n = 126) for 24 months, there were no laboratory abnormalities associated with glatiramer acetate treatment and it was well tolerated with few side effects. Patients receiving glatiramer acetate had significantly fewer relapses and were more likely to be neurologically improved, whereas those receiving placebo were more likely to worsen. This study was extended for 1 to 11 months (mean of 5.2 months for the glatiramer acetate group and 5.9 months for the placebo group). The blinding and study conditions used during the core 24-month study were unchanged throughout the extension. The results of this extension study confirm the excellent tolerance and safety profile of glatiramer acetate for injection. The clinical benefit of glatiramer acetate for both the relapse rate and for neurologic disability was sustained at the end of the extension trial.

Adult↗
PubMed1998

The use of magnetic resonance spectroscopy in the evaluation of the natural history of multiple sclerosis.

Magnetic resonance spectroscopic imaging (MRSI) can be used to define specific chemical-pathological changes in the brain of patients with multiple sclerosis. Magnetic resonance spectroscopy offers promise for improved definition of the nature of individual lesions, the dynamics of their evolution, their effects on normal appearing white matter, and their relation to clinical disability. Combined multimodal MRSI studies of the brains of patients with multiple sclerosis therefore soon may provide efficient, specific, and quantitative new approaches to assessment of drug effects in therapeutic trials.

Axons↗
PubMed1997

The role of rubella-immunoblot and rubella-peptide-EIA for the diagnosis of the congenital rubella syndrome during the prenatal and newborn periods.

Rubella infection during the first trimester of pregnancy can cause the congenital rubella syndrome (CRS). Patients with CRS were shown to have a decreased humoral and cellular immunity. It is not known whether asymptomatic newborns who had experienced intrauterine infection with rubella virus (RV) differ in their antibody response from newborns with CRS. In this study we compared both groups for a difference which might be a useful diagnostic criterion for CRS during the prenatal and newborn periods. We used the nonreducing Rubella-Immunoblot and the Rubella-IgG-Peptide-Enzyme Immunoassay (EIA) to determine the antibodies directed to rubella proteins E1, E2 and C. The results showed that only newborns with CRS who had experienced RV infection during the first 12 weeks of gestation showed significantly reduced levels of antibodies directed to both the linear RV E1 epitope (SP 15) and the topographic RV E2 epitope. Asymptomatic newborns infected mostly later than week 10 of gestation showed normal levels of antibodies. These data suggest that the lack of antibody response in CRS is linked to the immaturity of the fetal immune system during the first trimester of gestation. Rubella-IgG-Peptide-EIA and Rubella-Immunoblot should be used additionally for CRS diagnosis in the prenatal/newborn periods. These results may have an impact on the early treatment of late-onset symptoms of CRS patients.

Antibodies, Viral↗
PubMed1997

A dual approach for minimizing false lesion classifications on magnetic resonance images.

Segmentation methods based on dual-echo MR images are generally prone to significant false lesion classifications. We have minimized these false classifications by (1) improving the lesion-to-tissue contrast on MR images by developing a fast spin-echo sequence that incorporates both cerebrospinal fluid signal attenuation and magnetization transfer contrast and (2) including information from MR flow images. Studies on patients with multiple sclerosis indicate that this dual approach to tissue segmentation reduces the volume of false lesion classifications by an average of 87%.

Algorithms↗
PubMed1997

Clinical and magnetic resonance imaging changes correlate in a clinical trial monitoring cyclosporine therapy for multiple sclerosis. The MS Study Group.

Magnetic resonance imaging (MRI) was used to monitor cyclosporine therapy for chronic progressive multiple sclerosis in a multicenter clinical trial and an analysis was performed to determine whether there was a correlation between clinical changes and MRI changes. MRI was performed on 163 patients at the onset and completion of the 2-year study. Burden of disease (BOD, lesion load) was quantitated by a single observer using a computer program. Active lesions were also identified. The Expanded Disability Status Scale (EDSS) score was determined every 3 months MRI data did not show any effect of cyclosporine treatment on BOD progression (mean 24.5% increase/yr) or lesion activity. However, there was a statistically significant positive correlation between the baseline total BOD value and the baseline EDSS score (r = 0.221, p = 0.005) and a positive correlation between the percent changes in BOD from baseline to exit and EDSS score (r = 0.186, p = 0.018). The study supports the concepts that MRI is a useful technique in monitoring therapeutic trials and that MRI is a direct measure of pathology.

Brain↗
PubMed1997

Ingested IFN-alpha has biological effects in humans with relapsing-remitting multiple sclerosis.

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses and spontaneous in vitro IFN-gamma production, reduce clinical progression, and decrease magnetic resonance imaging (MRI)-defined disease activity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies that abrogate their activity in vivo correlated with the loss of clinical benefit. Therefore, we determined whether ingested IFN-alpha was non-toxic and had biological effects in humans. Ingested hrIFN-alpha showed no toxicity in normal volunteers or patients with RRMS at doses ranging from 300 to 100,000 units. In subjects with RRMS, a significant decrease in Con A-mediated proliferation and serum soluble intercellular adhesion molecule-1 (sICAM-1), a surrogate measure for disease activity in MS, was found after ingesting 10,000 and 30,000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion after ingesting 10,000 units IFN-alpha and decreased IFN-gamma, TGF-beta and IL-10 production after ingesting 30,000 units IFN-alpha. The decreased secretion of IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IFN-alpha may cause a functional inhibition of Th J-like T helper cells in RRMS, a potential site of intervention at the level of effector T cells in MS. Our studies support the oral use of human IFN-alpha as a biological response modifier in humans.

Administration, Oral↗
PubMed1997

T cell-T cell activation in multiple sclerosis.

Activated T cells are able to stimulate proliferation in resting T cells through an antigen non-specific mechanism. The in vivo usefulness of this T cell-T cell activation is unclear, but it may serve to amplify immune responses. T cell-T cell activation could be involved in the well-documented occurrence of multiple sclerosis (MS) exacerbations following viral infections. Excessive activation via this pathway could also be a factor in the etiology of MS. We tested the hypothesis that excessive T cell-T cell activation occurs in MS patients using in vitro proliferation assays comparing T cells from MS patients to T cells from controls. When tested as responder cells, T cells from MS patients proliferated slightly less after stimulation with previously activated cells than T cells from controls. When tested as stimulator cells, activated cells from MS patients stimulated slightly more non-specific proliferation than activated cells from controls. Neither of these differences were statistically significant. We conclude that T cell proliferation in response to activated T cells is similar in MS and controls.

Antigens, CD↗
PubMed1997

IFN-beta 1b treatment of relapsing multiple sclerosis has no effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion ex vivo after nine months.

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. We have previously reported that IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6 after three months of treatment. We have now examined cytokine secretion of peripheral blood mononuclear (PMNC) cells after stimulation with OKT3 (anti-CD3) monoclonal antibody (mAb) or Con A in subjects with clinically stable relapsing MS before and three, six and nine months after initiating IFN-beta 1b treatment. At nine months Con A-induced TNF-alpha secretion decreased significantly below baseline but IFN-gamma secretion increased above baseline. There were no significant changes in Con A-induced IL-4 over the six month period and no changes in IL-10 and IL-2 over the nine month period. After nine months on treatment the CD3-induced TNF-alpha and IFN-gamma secretion was not significantly different from the original baseline values. Increased CD3-mediated IL-6 secretion in on-treatment compared to pre-treatment samples at three months gradually declined to baseline values by nine months on-treatment. There was no significant changes from baseline compared to nine months on-treatment in CD3-mediated IL-2, IL-4, IL-10. IFN-beta 1b (Betaseron) treatment has no clear persistent effect on CD3-induced inflammatory or counterregulatory anti-inflammatory cytokine secretion.

Adult↗
PubMed1997

Increased in vitro induced CD4+ and CD8+ T cell IFN-gamma and CD4+ T cell IL-10 production in stable relapsing multiple sclerosis.

Multiple sclerosis (MS) is presumed to be a T-cell mediated chronic inflammatory disease of the central nervous system. Investigators previously demonstrated increased IFN-gamma (pro-inflammatory) and IL-10 (counterregulatory anti-inflammatory) in MS. The balance of pro-inflammatory and counterregulatory anti-inflammatory cytokines may be important in the stabilization of disease activity. Purified CD4+ and CD8+ T cells from patients with clinically definite, stable relapsing MS (RRMS) were stimulated by anti-CD3 mAb or Con A for 48 hours and cytokine supernatants analysed for production of IL-2, IL-6, IFN-gamma, TNF-alpha (potential pro-inflammatory) and IL-4, IL-10, and TGF-beta (potential counterregulatory anti-inflammatory). Con A activated CD4+ and CD8+ T cell proinflammatory cytokine IL-2 secretion, CD4+ T cell IL-6 secretion, CD4+ and CD8+ T cell TNF-alpha secretion and CD8+ T cell IFN-gamma secretion was decreased significantly in RRMS subjects compared to controls. CD3 activated CD4+ and CD8+ T cell IL-6 secretion and CD4+ T cell TNF-alpha secretion was significantly decreased in MS subjects compared to controls. In contrast, there was increased CD3-induced IFN-gamma in both CD4+ and CD8+ T cells and counterregulatory anti-inflammatory CD3-induced IL-10 secretion in CD4+ T cells in RRMS compared to controls. These data suggest that an equilibrium of a pro-inflammatory (IFN-gamma) and a counterregulatory anti-inflammatory (IL-10) cytokine may define stable clinically definite early RRMS.

CD3 Complex↗
PubMed1996

Multiple sclerosis: clinical presentation, diagnosis and treatment.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system and is associated with periods of disability (relapse) alternating with periods of recovery (remission) and often results in progressive neurologic disability. Scientists believe that multiple sclerosis may be a T cell-mediated autoimmune disease. Treatment with high-dose pulses of intravenous methyl-prednisolone is usually associated with a good outcome in the short term. A recent study suggests that interferon beta-1b may decrease the number of relapses in relapsing-remitting multiple sclerosis by 30 percent and also may decrease the development of new central nervous system lesions. Recently, another clinical trial of interferon beta-1a showed a 31 percent reduction in relapse rate and a significant reduction in the average number of active lesions. A third trial showed that 20 mg of copolymer-1, a random polymer of glutamic acid, lysine, alanine and tyrosine, reduced relapses by 21 percent without significant side effects. Further investigation is needed, but these new treatments show great promise in alleviating this difficult clinical problem.

Adrenal Cortex Hormones↗
PubMed1996

A search for persistent rubella virus infection in persons with chronic symptoms after rubella and rubella immunization and in patients with juvenile rheumatoid arthritis.

Peripheral blood polymorphonuclear leukocytes, mononuclear cells, and plasma and nasopharyngeal specimens were obtained from 6 subjects with persistent symptoms following rubella immunization, 1 subject with persistent symptoms following rubella, 11 children with juvenile rheumatoid arthritis, 17 recently immunized control subjects, and 1 control subject with acute clinical rubella. Rubella virus was isolated from the blood or nasopharynx of four of the 18 control subjects. In contrast, rubella virus was not recovered from any specimens from the seven subjects with persistent symptoms following immunization or natural infection or from the 11 children with juvenile rheumatoid arthritis. A polymerase chain reaction assay detected rubella virus in the blood from three of 14 control subjects but not in the blood from two subjects with persistent symptoms following rubella immunization or in that from three children with juvenile rheumatoid arthritis. We have not been able to confirm the findings of others who have reportedly recovered rubella virus from lymphocytes of persons with persistent symptoms following rubella or rubella immunization.

Adolescent↗
PubMed1996

Interferon-beta 1b treatment decreases tumor necrosis factor-alpha and increases interleukin-6 production in multiple sclerosis.

MS is presumed to be a T-cell-mediated chronic inflammatory disease of the CNS. We examined proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 [anti-CD3] monoclonal antibody (MAb) or concanavalin A (Con A) in subjects with stable relapsing-remitting MS (RR MS) before and after initiating interferon (IFN)-beta 1b treatment. There was no significant difference in pretreatment to on-treatment anti-CD3 mAb or Con A-induced proliferation in RR MS patients. There was significantly increased Con A-induced secretion of tumor necrosis factor (TNF)-alpha, IFN-gamma, interleukin (IL)-2, IL-6, and IL-10 and decreased IL-4 secretion in on-treatment compared with pretreatment peripheral blood mononuclear cell samples. However, on-treatment CD3-mediated secretion of TNF-alpha was significantly decreased, and IL-6 secretion was significantly increased compared with pretreatment values. IFN-gamma was also decreased in on-treatment cultures stimulated with anti-CD3 MAb, but these values did not reach statistical significance. Systemic side effects from IFN-beta 1b were associated with increased IL-6 secretion. There were no significant changes in CD3-mediated IL-4, IL-10, transforming growth factor (TGF)-beta, or IL-2 secretion or Con A-induced TGF-beta secretion. IFN-beta 1b (Betaseron) decreases CD3-mediated TNF-alpha secretion but increases another inflammatory cytokine, IL-6, that could potentially counteract its beneficial immunomodulatory effects.

Autoimmune Diseases↗
PubMed1995

Decreased CD3-mediated interferon-gamma production in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that has been postulated to be T-cell mediated. We examined the proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 (anti-CD3) monoclonal antibody concanavalin A, or ionomycin plus myristic acid palmityl ester in subjects with stable relapsing-remitting MS. Control subjects demonstrated good proliferation to anti-CD3 monoclonal antibody whereas subjects with relapsing-remitting MS showed a significantly decreased anti-CD3 monoclonal antibody-mediated response. There was no difference in concanavalin or ionomycin plus myristic acid palmityl ester stimulation between control subjects and MS subjects. Secretion of interferon-gamma was significantly decreased and transforming growth factor-beta was significantly increased from cultures stimulated with anti-CD3 monoclonal antibody, but not ionomycin plus myristic acid palmityl ester or concanavalin A, in MS patients compared to control subjects. Secretion of interleukin-10 and tumor necrosis factor-alpha was not different between control subjects and MS patients following stimulation with anti-CD3 monoclonal antibody, concanavalin A, or ionomycin plus myristic acid palmityl ester, or of interleukin-2 and interleukin-4 following stimulation with anti-CD3 monoclonal antibody or concanavalin A. An abnormality of signal transduction and secretion of the immunomodulatory molecule interferon-gamma may exist in MS via the CD3 T-cell receptor complex.

CD3 Complex↗
PubMed1995

Automated proton spectroscopic image processing.

An automatic data processing and display protocol for proton magnetic resonance spectroscopic imaging is described. The spectroscopic images are generated using the fitted peak areas of phased metabolite resonances using the Levenberg-Marquardt algorithm. This automated spectroscopic image processing is tested and evaluated using phantom and human brain data. This algorithm is robust, simple to use, and minimizes user bias in processing and quantifying serial changes of metabolite levels in brain tissue.

Algorithms↗
PubMed1994

H reflex studies in cerebral palsy patients undergoing partial dorsal rhizotomy.

H reflex studies were performed in ten spastic children with cerebral palsy who underwent partial dorsal rhizotomy (PDR). Under anesthesia prior to PDR, H reflex amplitude evoked by percutaneous peripheral nerve stimulation gradually declined in all patients and became unobtainable in five. Motor responses could still be evoked by apparent dorsal root stimulation in these five, but since it was shown that they were M responses and not reflexes, PDR was performed randomly. In the other five patients, in whom H reflexes were still evokable, dorsal root stimulation evoked motor responses which were true reflex responses, and PDR was performed "selectively." Compared to preoperative values, postoperative Hmax/Mmax ratios declined, but no more so in selective than in random PDR. We conclude that current intraoperative methods for selection of "abnormal" dorsal rootlets for section may be invalid and may have no bearing on successful outcome, since spasticity improves even with random PDR.

Analysis of Variance↗
PubMed1994

Altered membrane fatty acids of cultured human retinal pigment epithelium persistently infected with rubella virus may affect secondary cellular function.

Persistent infection with rubella virus (RV) can alter secondary functions of host cells. Previously we had documented defective phagocytosis of latex beads by cultured human retinal pigment epithelial cells (RPE), persistently infected with M-33 RV (RPE/RV). Here, examining possible mechanisms for altered function, we reported significant differences between the total esterified fatty acids (FA) of RPE and RPE/RV membranes, measured by gas liquid chromatography. RPE/RV contained an increased proportion of saturated FA, particularly palmitic acid, with a presence of unusual chromatographic FA peaks co-eluting with odd-numbered long-chain carbon atom FA not normally found in human cells. Apical membrane microvilli, structures essential to phagocytic activity of RPE and RPE/RV, observed by scanning and transmission electron microscopy, were similar in number and appearance between uninfected RPE and RPE/RV cells before and after latex bead addition. However, RPE/RV microvilli, possibly reflecting altered membrane FA composition, engaged latex beads less effectively than uninfected RPE microvilli. In addition, microvilli remained abnormally distributed on RPE/RV cell surfaces at 48 h after latex addition. Thus, RV persistent infection may affect the cellular membrane fluidity and functional activity of human cells with increased saturated FA proportions and altered FA components of membrane phospholipids. These changes may participate in the defective phagocytosis of RPE/RV.

Cells, Cultured↗