PubMed Health⌕ Search

Biomedical subjects

James T Rosenbaum

Publications and source records attributed to James T Rosenbaum.

At least 19 recordsLinked to original sources
PubMed2006

Management of orbital xanthogranuloma with methotrexate.

BACKGROUND/AIMS: To evaluate the efficacy of methotrexate (MTX) treatment for the periorbital findings in adult-onset xanthogranuloma (AOX). METHODS: The medical records of three patients with AOX, with and without asthma, who were treated with MTX at Oregon Health & Science University, Portland, Oregon, USA were examined. Diagnosis of AOX was made by biopsy in all patients. The patients were evaluated between February 1998 and July 2006. All patients had failed prior medical and/or surgical treatment. MTX was administered at 10-20 mg/week with folate supplementation and a course of corticosteroids. Efficacy was assessed on the basis of improvement in skin discoloration, involvement of the visual axis and patients' report of inflammation. RESULTS: All three patients were started on MTX, but one patient discontinued treatment after 3 weeks due to nausea. With follow-up as long as 3 years, the two patients who continued treatment lost the yellow discoloration of their skin, and they reported significantly less inflammation and ptosis after treatment. Oral corticosteroids could be reduced or discontinued. CONCLUSIONS: AOX is a rare, persistent disease that commonly involves the preseptal fat. MTX is a therapeutic option for this illness.

Adult↗
PubMed2006

Human leukocytes express ephrinB2 which activates microvascular endothelial cells.

EphrinB2-EphB4 interaction modulates the migration/adhesion of various cell types, including endothelial cells (EC) and peripheral blood leukocytes (PBLs). We hypothesize that the Ephrin/Eph signaling mechanism plays a role in mediating EC/leukocyte interactions during inflammation. PBLs were isolated from human blood, stimulated with inflammatory mediators, and total RNA or protein assayed for EphrinB2 expression. PBLs demonstrated differential expression profiles of EphrinB2 mRNA or protein, depending on cell subtype and stimulus. Human iris tissue and iris EC (HIEC) were examined for the expression of EphB4 mRNA and protein. Some blood vessels were EphB4(+), while stimulation of purified HIEC did not alter their expression of EphB4. HIEC treated with sEphrinB2/Fc from 0 to 60min did exhibit changes in their phospho-Erk1/2 levels. These observations indicate that stimulated lymphocytes express EphrinB2, which has the potential to activate EC. This suggests a novel mechanism by which EC and lymphocytes communicate to regulate cell activation/migration during inflammation.

Antigens, CD19↗
PubMed2006

Altered host:pathogen interactions conferred by the Blau syndrome mutation of NOD2.

Blau syndrome (BS) is a rare familial granulomatous disease manifested by uveitis, arthritis and skin rash. BS has recently been found to be associated with a distinctive mutation in NOD2, which encodes an intracellular toll-like receptor. We have compared host cell interaction with bacterial challenge in U937 cells expressing wild type human NOD2 (NOD2(wt)), mutant NOD2 (NOD2(Blau)), or a vector control (VC). The cells were incubated with Salmonella typhimurium. Intracellular uptake was assessed by harvesting the cells at different time points following invasion and quantitating the CFU, recovered after gentamicin treatment to kill extracellular organisms. Expression of TNF-alpha, TLR2 and TLR4 was determined by semi-quantitative RT-PCR under resting conditions and after stimulation by bacteria. Invasion of target cells with S. typhimurium was diminished in the presence of NOD2(Blau). Expression of TNF-alpha mRNA was enhanced following bacterial invasion in all cell lines but NOD2(Blau) was associated with a more rapid decline in TNF-alpha expression. Kinetics of intracellular clearance of bacteria indicated a relative defect in NOD2(Blau) compared to controls. This clearance defect may be related to the lack of sustained TNF-alpha seen in the early stages. These events were not related to differential TLR2 or TLR4 expression since there were no significant differences seen between the cell lines after bacterial stimulation. Our findings indicate that the NOD2 mutation associated with this syndrome alters host:microbial interaction, and this may have relevance to triggering factors in the ocular and joint inflammation seen in BS.

Arthritis↗
PubMed2006

Intravital microscopy of leukocyte-endothelial dynamics using the Heidelberg confocal laser microscope in scleritis and allergic conjunctivitis.

PURPOSE: To examine leukocyte-endothelial cell rolling and arrest in human ocular vessels overlying sites of inflammation in various ocular inflammatory diseases in comparison to normal controls using the Heidelberg confocal laser microscope, which provides images with greater clarity and resolution than the tandem scanning microscope that uses white light. METHODS: Healthy controls (n=8) and patients with active anterior scleritis (n=7) or allergic eye disease (n=4) were scanned using the Heidelberg confocal laser microscope (HRT II) with the Rostock cornea module attachment for a minimum of 5 min at a depth of 45-120 microm from the conjunctival epithelial surface. RESULTS: There was a marked increase in the number of rolling leukocytes in scleritis patients (534+/-119 cells per mm2/min) versus controls (6+/-6 cells per mm2/min; p=0.0002) or allergic patients (59+/-44 cells per mm2/min; p=0.009). No statistically significant increase was seen in allergic patients compared to controls (p=0.059). A similar pattern was seen in the number of arrested leukocytes in patients with scleritis (56+/-23 cells per mm2) in comparison to either those with allergic eye disease or controls (each=0 cells per mm2; p=0.02). CONCLUSIONS: Patients with scleritis have a significantly increased number of rolling and arrested leukocytes in superficial ocular vessels in comparison to patients with mild allergic conjunctivitis and controls. The image quality with this microscope is superior to prior studies with a scanning microscope.

Adult↗
PubMed2006

Primary treatment of acute retinal necrosis with oral antiviral therapy.

PURPOSE: To explore the possibility of oral antiviral therapy in lieu of intravenous acyclovir for treating acute retinal necrosis (ARN), a necrotizing retinopathy caused by herpes simplex virus type 1 or 2 or by varicella zoster virus. DESIGN: Retrospective, interventional, small case series. PARTICIPANTS: Four patients (6 eyes). METHODS: Patients were treated with oral antiviral therapy. Medications included valacyclovir (1 g 3 times daily), oral famciclovir (500 mg 3 times daily), and topical and oral corticosteroids. MAIN OUTCOME MEASURES: Improvement of symptoms, including photophobia, blurred vision, ocular discomfort, and floaters; increase in visual acuity; and resolution of vitreitis, retinitis, and retinal vasculitis, where present. RESULTS: Symptoms and visual acuity improved within 2 weeks to 1 month in 3 of 4 patients (75%) treated with oral antiviral medication. One patient required surgical treatment for asymptomatic retinal detachment after 3 weeks of treatment; retinal detachment in the fellow eye was repaired 2 months later. Duration of antiviral therapy ranged from 5 weeks to 3 months. CONCLUSIONS: For 4 patients with relatively indolent cases of ARN, oral antiviral therapy alone was effective in eliminating signs and symptoms of the disease. In particular, oral valacyclovir and famciclovir appeared to be effective, although further study is necessary to determine whether these drugs are as effective as intravenous acyclovir for initial treatment of ARN.

2-Aminopurine↗
PubMed2006

Antigen-specific accumulation of naïve, memory and effector CD4 T cells during anterior uveitis monitored by intravital microscopy.

Uveitis is an immune-mediated ocular disease and a leading cause of blindness. We characterized a novel model of uveitis with intravital microscopy. Transfer of ovalbumin-specific T cells from DO11.10 spleen to BALB/c recipients and subsequent challenge with ovalbumin in the anterior chamber of the eye resulted in anterior uveitis. Antigen-specificity was verified by injection of irrelevant antigen and transfer of T cells with a different specificity. Subsets of CD4 T cells, including naive (DO11.10 RAG(-/-)) and in vitro-activated Th2 effector CD4 T cells, infiltrated anterior segment tissues early in the inflammation. Memory-like CD44(high) CD4 T cells from unprimed transgenic mice and in vitro-activated Th1 effector CD4 T cells accumulated to larger numbers than naive or Th2 effector cells at 48 and 72 h. Of these, the alpha(2)-integrin+CD4 unprimed T cells entered the eye more efficiently, and antibody to alpha(2)-integrin markedly inhibited the inflammatory response. Intravital microscopy revealed the early arrival and antigen-specific accumulation of CD4 T cells in inflamed tissue and should be helpful in understanding T cell migration to other organs.

Animals↗
PubMed2006

Human endothelial cells express NOD2/CARD15 and increase IL-6 secretion in response to muramyl dipeptide.

Mutations in the human NOD2/CARD15 gene cause Blau syndrome, an autoinflammatory disorder involving the joints, skin and eyes. Insights into the mechanism of this association may be gained by a further understanding of where NOD2 is expressed. The objective of this study was to analyze ocular endothelial cells for NOD2 expression. Human ocular tissue was analyzed by immunohistology using anti-NOD2 antisera. RNA isolated from iris, choroid and endothelial cell lines was analyzed by reverse transcription-PCR and real-time quantitative PCR. Gene regulation was studied by treating endothelial cells with TNF-alpha and IFN-gamma. Functional responses were assessed by measuring IL-6 release from endothelial cells treated with muramyl dipeptide (MDP), synthetic lipopeptide (Pam3CSK4) and lipopolysaccharide (LPS). Immunohistological analysis revealed staining of endothelial cells in the uveal tract. NOD2 expression was detected in primary ocular endothelial cell cultures, and levels increased in response to inflammatory cytokines. Endothelial cells from choroid demonstrated enhanced release of IL-6 in response to MDP, and synergy was observed following treatment with MDP and either Pam3CSK4 or LPS. The observations that endothelial cells express NOD2, upregulate NOD2 in response to stimuli known to promote NOD2 expression and show synergistic cytokine responses to MDP and TLR ligands previously shown to be mediated by NOD2 are informative since they may be relevant to pathogenic mechanisms leading to the spectrum of inflammation seen in Blau syndrome.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2006

Pediatric granulomatous arthritis: an international registry.

OBJECTIVE: Blau syndrome and its sporadic counterpart, early-onset sarcoidosis, share an identical phenotype featuring the classic triad of arthritis, dermatitis, and uveitis and are associated with mutations of CARD15 in 50-90% of cases. We chose the term "pediatric granulomatous arthritis" to refer to both. An international registry was established in the spring of 2005 to define the phenotype spectrum and establish the mutation frequency and variants. METHODS: Histologically confirmed granuloma and arthritis were required for inclusion. Probands and relatives were genotyped for CARD15. Deidentified clinical information was collected. RESULTS: One year after the inception of the registry, 61 individuals from 22 pedigrees had been entered. Seven pedigrees with 19 individuals (8 affected, 11 unaffected) had clinical disease that was atypical, and none of the individuals in those pedigrees showed mutations. There were 9 classic simplex pediatric granulomatous arthritis pedigrees including 19 individuals (9 affected, 10 unaffected) and 6 classic multiplex pedigrees with 22 individuals (17 affected, 5 unaffected). Cutaneous presentation was the most common. Arthritis was polyarticular in 96% of patients. Isolated eye disease was never the presenting symptom, but significant/severe visual impairment was observed in 41% of patients. Eye disease was bilateral in 21 of 22 patients and was complicated by glaucoma in 6 of 22 patients and by cataracts in 50% of patients. Skin biopsy was the best diagnostic approach (because of accuracy and low invasiveness). CONCLUSION: In this series, the first combining familial and sporadic pedigrees and, to our knowledge, the largest, we further defined the phenotype and showed that all affected classic (and no nonclassic) pedigrees carry a mutation and that there is no asymptomatic carriage. If these data are confirmed, mutation analysis rather than tissue sampling may prove to be the most efficient diagnostic procedure.

Adolescent↗
PubMed2006

Borrelia hermsii causing relapsing Fever and uveitis.

PURPOSE: To describe a case of uveitis that is associated with Borrelia hermsii relapsing fever. DESIGN: Interventional case report. METHODS: A 12-year-old boy with two weeks of relapsing fevers 10 days after camping in remote eastern Oregon was examined. Borrelia hermsii immunoglobulin M and G levels were markedly elevated. Intravenous ceftriaxone, followed by four weeks of oral cephuroxime was administered, but the patient developed unilateral floaters and blurred vision in association with anterior and intermediate uveitis. RESULTS: Doxycycline was administered for presumed residual infection. Four weeks later, the visual acuity had improved. The anterior chamber was quiet, and topical corticosteroid was tapered successfully. CONCLUSION: Although rare, Borrelia hermsii should be included in the list of spirochetal diseases that are associated with uveitis.

Anti-Bacterial Agents↗
PubMed2006

Non-invasive detection of multinucleated giant cells in the conjunctiva of patients with sarcoidosis by in-vivo confocal microscopy.

AIM: To explore the use of in-vivo confocal microscopy (IVCM) as a potential non-invasive adjunctive tool for diagnosing sarcoidosis. METHODS: Conjunctivae were imaged using confocal microscopy in 10 patients with sarcoidosis and 27 control subjects. We utilized the ASL-1000 Scanning Confocal Microscope (Advanced Scanning Ltd., New Orleans, LA) and the Confoscan 3 (Nidek Co. Ltd., Gamagori, Japan). Two masked observers reviewed the in-vivo confocal images of the conjunctivae in these subjects. One masked observer was experienced in reviewing confocal images. The most striking and obvious feature seen in granulomatous inflammation on confocal microscopy is the presence of multinucleated giant cells (MGCs). RESULTS: Unmasked observation of the scans revealed MGCs in six of the 10 sarcoid patients and no MGCs in the controls. One experienced masked observer found MGCs in five of the 10 patients with sarcoidosis and had no false-positive results (Fisher's exact test, p = 0.001; specificity = 1; sensitivity = 50% for the diagnosis of sarcoidosis and 83% compared to the unmasked observer). The second less-experienced masked observer detected MGCs in three of the 10 patients and three of the 27 controls (11.1% of the controls) (p = 0.186; specificity = 0.89; sensitivity = 30% of all patients with sarcoidosis and 50% compared to the unmasked observer). CONCLUSIONS: The utilization of IVCM to visualize the basic histology and pathology in sarcoidosis of the conjunctiva is novel. Initial results indicate that trained observers can detect MGCs in granulomatous inflammation. The ASL-1000 microscope tends to have better resolution and deeper penetration of the conjunctiva compared with the Confoscan 3.

Adult↗
PubMed2005

Differential E-selectin expression by iris versus retina microvascular endothelial cells cultured from the same individuals.

The microvasculature of the eye plays a critical role in many ophthalmic diseases, including diabetic retinopathy and macular degeneration. Transcriptional profiling by gene array allows characterization of endothelial cells (EC) and can test for inherent EC diversity relative to the tissue source of the EC. Here, we established highly purified microvascular EC cultures from donor-matched human irises and retinae (4 donor pairs). We used nylon-based gene array kits to compare gene expression in paired confluent EC monolayers, under both quiescent and inflammatory agent (bacterial lipopolysaccharide, LPS; or tumor necrosis-factor alpha, TNFalpha)-activated conditions. In the absence of an inflammatory agent, iris and retinal ECs from the same donor were remarkably similar in overall gene expression profiles, except for possible differences in the expression of platelet-derived growth factor-A and a DNA mismatch repair protein (mutL homologue). Several detectable transcripts had never previously been reported in the eye. After inflammatory stimulation, significantly greater expression of the adhesion molecule E-selectin mRNA was consistently detected in retinal versus iris EC, and this difference was maintained at the protein level both in cell-surface-expressed and secreted soluble E-selectin protein in paired cultures. Thus, cultured EC derived from adjacent microvascular beds are biologically distinct. Such endothelial diversity could play a role in the pathogenesis of tissue-specific inflammation, infection, neovascularization, and malignancy.

Adolescent↗
PubMed2005

A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes.

OBJECTIVE: Infliximab, a monoclonal antibody against tumor necrosis factor alpha, is approved by the US Food and Drug Administration for treatment of numerous autoimmune disorders. We conducted a prospective, open-label phase 2 clinical trial to assess the effectiveness of infliximab in treating refractory autoimmune uveitis. METHODS: We prospectively enrolled 23 patients from the uveitis clinic of the Casey Eye Institute, Portland, Ore, into this trial. All patients meeting eligibility criteria received 3 infliximab infusions at weeks 0, 2, and 6. Clinical success was ascertained at week 10. Patients meeting initial criteria for success received an infusion at week 14 and every 8 weeks thereafter, with dose escalation permitted for breakthrough inflammation, and underwent outcome measurements at week 50. RESULTS: All patients underwent outcome assessment at week 10. Eighteen (78%) of these subjects met criteria for clinical success at this time. Success was judged by the composite clinical end point of visual acuity, control of intraocular inflammation, ability to taper concomitant medication therapy, and improvement in inflammatory signs on fluorescein angiography and/or ocular coherence tomography. Successful grading required improvement in at least 1 of 4 subcomponents and worsening in none. Seven of 14 patients enrolled for 1 year continued infliximab therapy and maintained their successful grading. Five did not complete 1 year of treatment because of significant adverse events, and 2 terminated treatment early for reasons unrelated to the study. Serious adverse events that were potentially related to infliximab included pulmonary embolus, congestive heart failure, lupus-like reaction in 2, and vitreous hemorrhage in 2 patients. Antinuclear antibodies developed in 15 of 20 enrolled patients receiving 3 or more infusions. CONCLUSIONS: Infliximab was an effective short-term immunosuppressive agent in most of the patients, with 18 of 23 meeting criteria for clinical success at week 10. Infliximab was effective in the long term in all patients able to complete 50 weeks of therapy. Although some patients achieved clear benefit, the rate of serious toxic effects was unexpectedly high. Further long-term studies are warranted to determine the safety and efficacy of infliximab in treating intraocular inflammation.

Adolescent↗
PubMed2005

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease.

OBJECTIVE: Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects approximately 40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation-AAU-of a multisystem, inflammatory, genetically complex disease, AS. METHODS: Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. RESULTS: As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. CONCLUSION: This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

Acute Disease↗
PubMed2005

Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop.

PURPOSE: To begin a process of standardizing the methods for reporting clinical data in the field of uveitis. DESIGN: Consensus workshop. METHODS: Members of an international working group were surveyed about diagnostic terminology, inflammation grading schema, and outcome measures, and the results used to develop a series of proposals to better standardize the use of these entities. Small groups employed nominal group techniques to achieve consensus on several of these issues. RESULTS: The group affirmed that an anatomic classification of uveitis should be used as a framework for subsequent work on diagnostic criteria for specific uveitic syndromes, and that the classification of uveitis entities should be on the basis of the location of the inflammation and not on the presence of structural complications. Issues regarding the use of the terms "intermediate uveitis," "pars planitis," "panuveitis," and descriptors of the onset and course of the uveitis were addressed. The following were adopted: standardized grading schema for anterior chamber cells, anterior chamber flare, and for vitreous haze; standardized methods of recording structural complications of uveitis; standardized definitions of outcomes, including "inactive" inflammation, "improvement'; and "worsening" of the inflammation, and "corticosteroid sparing," and standardized guidelines for reporting visual acuity outcomes. CONCLUSIONS: A process of standardizing the approach to reporting clinical data in uveitis research has begun, and several terms have been standardized.

Humans↗
PubMed2005

Treatment of corticosteroid dependent optic neuropathy with intravenous immunoglobulin.

PURPOSE: To report a patient with corticosteroid dependent optic neuropathy treated with intravenous immunoglobulin (IVIg). DESIGN: Interventional case report. METHODS: Records review. RESULTS: A 25-year-old woman developed bilateral vision loss with pain on eye movement in association with disk edema, dilated retinal veins, and hemorrhage. The vision improved markedly with prednisone, but she required a minimum of 20 mg/d despite concomitant therapy with methotrexate, cyclosporine, and/or mycophenolate mofetil. IVIg, 0.5 g/kg/d for 3 days each month with subsequent reduction in frequency, allowed discontinuation of all immunosuppression. CONCLUSIONS: Corticosteroid dependent optic neuropathy was successfully treated with IVIg.

Adult↗
PubMed2005

Beta 3-adrenergic receptors mediate choroidal endothelial cell invasion, proliferation, and cell elongation.

Beta(3)-adrenergic receptors have been reported to function primarily in adipose tissues to regulate thermogenesis. In this study, we determined if beta-adrenergic receptors are present on human choroidal endothelial cells and examined their ability to promote invasion, proliferation, and/or cell elongation. Using western blotting techniques and assays of cell invasion, cell proliferation, and endothelial cell elongation, we were able to determine that human choroidal endothelial cells do possess all three subtypes of beta-adrenergic receptors. Stimulation of the beta(3)-adrenergic receptor with BRL37344, a specific beta(3)-adrenergic receptor agonist, resulted in phosphorylation of Src, Akt, and ERK1/2. BRL37344 treatment also increased choroidal endothelial cell invasion by 103% above control values; the invasion response was inhibited by PP2 (Src inhibitor), LY294002 (PI3K inhibitor), Akt inhibitor (Akt-I), and matrix metalloproteinase 2/9 inhibitor (MMP-I). Invasion was not affected by PD98059 (mek inhibitor) or KT5823 (protein kinase G inhibitor). BRL37344 produced a significant increase in the total elongation of choroidal endothelial cells formed on Matrigel over a 24hr period. BRL37344 did significantly increase proliferation, although not to the same level as invasion. Stimulation of choroidal endothelial cells with dobutamine to activate beta(1)/beta(2)-adrenergic receptors did not affect invasion, proliferation, or endothelial cell elongation. In conclusion, beta(3)-adrenergic receptors may play a role in choroidal endothelial cell invasion and elongation, while playing a more limited function in regulation of cell proliferation.

Adrenergic beta-Agonists↗