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Biomedical subjects

B L Gruber

Publications and source records attributed to B L Gruber.

At least 37 records · Page 2Linked to original sources
PubMed1994

Anti-laminin autoantibodies in collagen vascular diseases: the use of adequate controls in studies of autoimmune responses to laminin.

OBJECTIVES: To determine the significance of anti-laminin antibodies in patients with collagen vascular diseases using a large control population of normal individuals. METHODS: Anti-laminin antibodies of IgG isotypes were determined using an ELISA assay in a population consisting of 73 patients with systemic sclerosis, 10 with urticarial vasculitis, five with leukocytoclastic vasculitis, 13 with giant cell arteritis, and eight with dermatomyositis. Sera from 134 healthy individuals served as controls. RESULTS: Only eight sera in the systemic sclerosis group, one in the leukocytoclastic group and one in the giant cell arteritis group were abnormal. No other sera were abnormal. CONCLUSION: These data contradict previous studies using smaller numbers of controls. The necessity for an adequate control population to define abnormal when comparing immune responses among groups is frequently under-emphasised in rheumatological studies.

Autoantibodies↗
PubMed1994

Fibrogenic growth factors in the eosinophilia-myalgia syndrome and the toxic oil syndrome.

BACKGROUND AND DESIGN: We sought to determine if growth factors of potential pathogenetic significance are deposited in the skin, muscle, and peripheral nerve lesions of eosinophilia-myalgia (EMS) and toxic oil syndrome. Immunohistochemical studies using affinity-purified peroxidase-conjugated antibodies to detect transforming growth factor-beta, platelet-derived growth factorAA and growth factorBB, fibroblast growth factor, epidermal growth factor, and interleukin 4 were performed on formalin-fixed, paraffin-embedded specimens. Seven skin biopsy specimens from EMS, six skin biopsy specimens from toxic oil syndrome, nine muscle biopsy specimens from EMS, and one sural nerve biopsy specimen from EMS were studied. RESULTS: Growth factor staining was noted primarily in the epidermis and periappendageal locations of the dermis. The presence of TGF-beta and platelet-derived growth factorAA in the periappendageal dermis was significantly more prevalent in EMS than toxic oil syndrome (57% vs 0%). Prominent staining of transforming growth factor-beta was also present in the perimysial connective tissue of five (63%) of eight EMS muscle biopsy specimens and one sural nerve biopsy specimen. CONCLUSIONS: These studies implicate transforming growth factor-beta and platelet-derived growth factorAA as potentially important cytokines in EMS and suggest that the pathogenesis of tissue fibrosis in EMS and toxic oil syndrome may be dependent on different growth factors.

Biopsy↗
PubMed1993

Immunological responses of breast cancer patients to behavioral interventions.

This article reports the results of an 18-month study of immune system and psychological changes in stage 1 breast cancer patients provided with relaxation, guided imagery, and biofeedback training. Thirteen lymph node negative patients who had recovered from a modified radical mastectomy were randomly assigned to either an immediate treatment or a delayed treatment control group. Multiple pre-post psychological measures were performed. Significant effects were found in natural killer cell (NK) activity (p < .017), mixed lymphocyte responsiveness (MLR) (p < .001), concanavalin A (Con-A) responsiveness (p < .001), and the number of peripheral blood lymphocytes (PBL) (p < .01). No significant psychological changes were detected; however, reductions were seen in psychological inventory scales measuring anxiety. The results show that behavioral interventions can be correlated with immune system measures, thereby replicating the results of an earlier pilot study from our Center. Discussion is provided on differential T-cell and B-cell responsiveness to behavioral interventions.

Adult↗
PubMed1992

Mast cell changes in scleroderma. Presence of MCT cells in the skin and evidence of mast cell activation.

OBJECTIVE: To analyze the concentration and distribution of the MCT (tryptase-positive, chymase-negative) and MCTC (tryptase-positive, chymase-positive) types of mast cell in cutaneous lesions of scleroderma. METHODS: Biopsy specimens were obtained from skin lesions in 24 patients with scleroderma, and subjected to double immunohistochemical analysis using mouse monoclonal anti-tryptase and anti-chymase antibodies. RESULTS: Dermal mast cell concentrations were below the normal range in 12 of the specimens, most of which were obtained between 1 and 4 years after disease onset. All other specimens contained normal concentrations of mast cells. MCT cells were present in 12 specimens and comprised between 8% and 100% of the total mast cells. Extracellular tissue deposits of tryptase-positive and/or chymase-positive granular material were observed in 8 specimens, suggesting possible mast cell degranulation. CONCLUSION: These findings are in contrast to those in normal skin, where MCTC cells are essentially the only type of mast cell present in the dermis. The results suggest that mast cells are involved in the pathogenesis of cutaneous lesions in scleroderma.

Adult↗
PubMed1991

Clinical follow-up and immunogenetic studies of 32 patients with eosinophilia-myalgia syndrome.

31 patients with L-tryptophan-associated eosinophilia-myalgia syndrome (EMS) that developed during the United States outbreak in 1989 were followed up prospectively at a university hospital outpatient rheumatology clinic for 16 to 24 months from the onset of their illness. Another patient with EMS associated with L-tryptophan in 1988 was followed up for 30 months. 93% of the 28 survivors from the 1989 cohort continue to have symptoms affecting 1-4 organ systems (median 3) and 3 have died, so the disorder produces considerable morbidity and mortality. The chronic sequelae most often associated with long-term disability are sclerodermatous skin thickening (54%), sensorimotor polyneuropathy (61%), proximal myopathy (36%), and severe episodic myalgias (64%). Thrombocytopenia developed in 1 patient. HLA-class II typing revealed a non-significant trend towards an association with HLA-DR4. Early therapy with corticosteroids did not seem to prevent the development of chronic manifestations.

Adult↗
PubMed1991

A double-blind randomized controlled trial of ketotifen versus placebo in early diffuse scleroderma.

To determine the efficacy of the mast cell-stabilizing drug ketotifen in scleroderma, we conducted a 6-month, randomized, prospective, double-blind, placebo-controlled trial in 24 patients. No significant improvement in the clinical parameters, pulmonary function, global assessments, and mast cell releasability was noted. Pruritus tended to improve in the group taking the active drug. Six months of treatment with ketotifen (6 mg/day), therefore, produced no apparent benefit in patients with early scleroderma. We were unable to address the role of mast cells in scleroderma since mast cell suppression was not achieved.

Adult↗
PubMed1991

Immunoglobulin E, mast cells, endogenous antigens, and arthritis.

New aspects of the biology of the mast cell and its associated products may be important to the pathogenesis of arthritis. Mast cells may be activated in human arthritides as a result of a rapidly expanding list of peptides, including cytokines and neurotransmitters. The classic immunoglobulin E-coupled mast cell activation pathways may be used in the autoimmune diseases by way of autoantibody production involving the immunoglobulin E molecule itself. This can be shown to induce mediator release in vitro. The mast cell-derived products may play a role in both the early phases of synovitis as well as the chronic destructive phase.

Antigens↗
PubMed1990

The mast cell as an effector of connective tissue degradation: a study of matrix susceptibility to human mast cells.

The susceptibility of connective tissue elements to degradation by human mast cells was explored using purified mast cell tryptase and sonicated mast cell preparations. The R-22 strain of smooth muscle cells from rat heart was used for preparation in vitro of a labelled anchored matrix. Digestion of 11.9 +/- 1.2% (n = 5) of this matrix was observed after overnight incubation with the mast cell sonicates. Pretreatment of the sonicate with a tryptase inhibitor TLCK reduced the digestion by 42%. Digestion of 12 +/- 1% (n = 4) of the matrix was observed with purified tryptase. The susceptible substrate within this anchored insoluble matrix resided in the glycoprotein compartment as defined by enzymatic characterization of the residual matrix. Mast cells may play a role in mediating connective tissue degradation through the release of proteases specifically synthesized by this cell.

Animals↗
PubMed1990

Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease.

The natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the L-tryptophan-associated eosinophilia-myalgia syndrome. Overall, cutaneous manifestations developed in 26 patients (87%). Early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities. The most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients (50%) often after a subacute stage of peripheral or truncal edema. Clinical and/or biopsy evidence of eosinophilic fasciitis was seen in nine patients (30%). Findings consistent with diffuse, limited, or localized scleroderma were subsequently observed in nine patients (33%). Small mucinous papules, similar to those seen in scleromyxedema, were found in five patients (17%). Alopecia, frequently a late sequela, developed in 11 (37%). Common histologic features included papillary dermal fibrosis, dermal and fascial infiltrates consisting of mononuclear cells and eosinophils, deposition of glycosaminoglycans in the dermis, and, in some patients, numerous mast cells.

Adult↗
PubMed1990

L-tryptophan-associated eosinophilic perimyositis, neuritis, and fasciitis. A clinicopathologic and laboratory study of 25 patients.

We have described the spectrum and prevalence of the clinical and laboratory manifestations of a multisystem disorder associated with the ingestion of L-tryptophan. At least 3 subsets of clinical disease have been identified: 1) a neuromuscular disorder which may present with myalgias and mild weakness and then progress to quadriparesis related to an axonal neuropathy and interstitial myositis (perimyositis), 2) a syndrome of eosinophilic fasciitis with characteristic cutaneous induration, and 3) the Löffler syndrome consisting of pulmonary infiltrates with eosinophilia. Corticosteroids may be useful for patients with the Löffler syndrome and offer only a modest benefit in the majority of patients with neuromuscular disease. The clinical course appears to be chronic, and the long-term sequelae of this disorder are unknown. The etiologic agent remains undetermined; however, studies are in progress to examine the mechanism of eosinophilia, appropriate therapeutic intervention, and the long-term outcome of the affected individuals.

Adult↗
PubMed1990

Eosinophilic neuritis, perimyositis, and vasculitis associated with ingestion of L-tryptophan.

Four cases are described of a clinical syndrome which developed in the setting of L-tryptophan ingestion. The major manifestations consisted of myalgias, neuropathy, weakness, and profound eosinophilia. Pathologically a vasculitis involving predominantly small veins was observed along with a mixed cellular infiltrate in the perimysium and epineurium. Clusters of eosinophils were characteristically noted in the tissue specimens. The clinical course appears to be chronic although further longterm followup will be required. One patient pursued a relentless downhill course with progressive neurologic impairment and death. Although the mechanism of tissue injury in these individuals is speculative, the possible association of this widely used nonprescription medication with this syndrome should be recognized.

Administration, Oral↗
PubMed1989

Anti-IgE autoantibodies in systemic sclerosis (scleroderma).

An enzyme immunoassay was used to determine the prevalence of anti-IgE auto-antibodies in 66 patients with systemic sclerosis (scleroderma) stratified according to extent and duration of disease. Serum IgG anti-IgE antibodies were detected in 14 (21%) patients and IgM anti-IgE antibodies in nine (14%) patients. The overall prevalence of IgG or IgM isotypes was 21/66, (32%). Anti-IgE autoantibodies were not found in six patients with undifferentiated connective tissue disease or two patients with eosinophilic fasciitis. Attempts to demonstrate histamine release from basophils in vitro by using serum samples containing high titre anti-IgE antibody were unsuccessful. By multivariate analysis the presence of anti-IgE antibody was not associated with duration of systemic sclerosis; extent of scleroderma; specific visceral features, including heart, lung, renal, and gastrointestinal involvement; or mortality.

Autoantibodies↗
PubMed1989

Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation.

Mast cells have been implicated in the pathogenesis of the matrix degradation observed in the cartilaginous and osseous structures of the rheumatoid joint. We previously reported that human mast cell tryptase, a 134-kD granule-associated neutral protease, is present in rheumatoid synovium and can activate collagenase in crude culture medium in vitro. the present study attempts to depict the precise mechanism of this activation. To express full activation of latent collagenase, matrix metalloproteinase 3 (MMP-3) or stromelysin, can be activated by tryptase in a time and dose-dependent manner. Tryptase was not capable of generating active collagenase in the crude media from cultured rheumatoid synoviocytes depleted of proMMP-3 by immunoadsorption. In addition, the function of the tissue inhibitor of metalloproteinases (TIMP) was not altered by tryptase, and SDS-PAGE analysis revealed no degradation of TIMP by tryptase. The tryptase dependent activation of synoviocyte procollagenase thereby appears to be entirely dependent upon its ability to activate proMMP-3.

Blotting, Western↗