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Biomedical subjects

M Salvi

Publications and source records attributed to M Salvi.

At least 73 records · Page 4Linked to original sources
PubMed1992

Nature and significance of orbital autoantigens and their corresponding autoantibodies in thyroid-associated ophthalmopathy.

There is now considerable evidence that the pathogenesis of thyroid-associated ophthalmopathy is closely linked to the presence of a shared autoantigen(s) in the thyroid and the eye muscle, against which cytotoxic mechanisms are directed. Although the orbital connective tissue is certainly involved in the orbital inflammatory process, a 64 kDa membrane protein expressed by both the eye muscle and the thyroid and recognized consistently by antibodies in the sera of TAO patients, seems to be the most likely target candidate. While its presence in non ocular skeletal muscle is not as well established, more recent data tend to suggest the existence of a 64 kDa molecule in the three tissues. The availability of a cDNA encoding a 572 amino acid protein corresponding to a MW of 63-64 kDa, which may be the same molecule, will allow us to determine more clearly the structural characteristics of the different molecules proposed as targets. The role of the corresponding autoantibodies in the pathogenesis of the eye disease is far less well defined. Whether they play a role in the induction of the ophthalmopathy or only represent helpful markers remains to be clarified.

Autoantibodies↗
PubMed1992

Cell-mediated immunity to orbital tissue antigens in thyroid-associated ophthalmopathy determined using the leukocyte procoagulant activity assay.

While it is generally accepted that thyroid-associated ophthalmopathy (TAO), a progressive inflammatory disorder of the extraocular muscle and orbital connective tissue (OCT), is immunologically mediated the nature of the underlying abnormalities is poorly understood. Although there is considerable evidence for antibody-mediated immunity against both eye muscle (EM) and OCT antigens in TAO a role of cell-mediated immunity (CMI) has not been studied in detail. We have used a new sensitive test for CMI, the leukocyte procoagulant activity (LPCA) assay and tested blood leukocytes from patients with TAO and autoimmune thyroid disease (ATD) without evident ophthalmopathy for reactivity against pig eye muscle (PEM) and human thyroid and OCT membrane and soluble fractions. In some cases human EM fractions were also tested. Preparations of PEM membrane (PEMM) and human thyroid membrane induced a significant LPCA response in both groups of patients. PEM cytosol, human OCT membrane and cytosol and human spleen membrane did not evoke a significant response in either group of patients. There were significant positive correlations in patients with TAO between (i) LPCA in response to PEMM and that to human thyroid membrane and (ii) LPCA in response to human thyroid membrane and that to human EM membrane. In patients with TAO there were no significant associations between LPCA response to PEMM and the detection of serum antibodies to a 64 kDa EM membrane protein in immunoblotting, or between LPCA response to PEMM and the duration or severity of the ophthalmopathy or clinical evidence for eye muscle involvement. These findings confirm a role of cell-mediated immunity against eye muscle antigens in thyroid-associated ophthalmopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Muscle and species reactivity of mouse monoclonal antibodies to human eye muscle membrane antigens.

We studied the tissue and species reactivity of mouse monoclonal antibodies (MCAB) produced by immunizing mice with a 100,000g ultracentrifuged preparation of human eye muscle (HEM) membranes. Twenty-three MCABs, 20 of which reacted in an enzyme-linked immunosorbent assay (ELISA) with HEM membrane, 2 with human thyroid membrane, and 1 nonreactive negative control, were selected for the study. The muscle and species specificity of 6 of the most reactive and more restrictively reactive MCAB were studied in more detail. All reacted in ELISA with human skeletal muscle membrane and, to a lesser extent, with human cardiac muscle membrane, but not with human brain membrane. The 6 MCAB cross-reacted with eye muscle membrane prepared from pig but not rat, although reactivity with human tissue was greatest for all MCAB tested. When tested in immunoblotting with HEM and thyroid membranes, 3 of 6 MCAB reacted with a 64-kDa protein in HEM, 2 of which also reacted with an antigen of the same molecular weight in thyroid membrane. In a complement-mediated antibody-dependent cytotoxicity assay, 5 of 19 MCAB lysed HEM cells, 6 of 21 lysed human skeletal muscle cells, and 10 of 22 lysed human thyroid cells. These findings support results from earlier clinical studies which showed that eye muscle membrane reactive autoantibodies in the serum of patients with thyroid-associated ophthalmopathy cross-react with membrane prepared from other striated muscle. The significance of eye muscle, skeletal muscle, and thyroid cross-reactivity of MCAB is discussed in the context of autoimmune thyroid disease and ophthalmopathy.

Abdominal Muscles↗
PubMed1991

Thyroid-associated ophthalmopathy--a model for the association of organ-specific autoimmune disorders.

The development of a characteristic ophthalmopathy is a feature of autoimmune diseases of the thyroid. The link between the conditions has not yet been discovered, but here Jack Wall and colleagues develop the theory that an autoimmune response to a 64 kDa antigen expressed on both thyroid and eye muscle membranes is responsible for this thyroid-associated ophthalmopathy.

Autoantigens↗
PubMed1991

Prevalence of antibodies reactive with a 64 kDa eye muscle membrane antigen in thyroid-associated ophthalmopathy.

We have determined the prevalences of antibodies reactive with certain pig eye muscle membrane antigens, as determined from SDS-polyacrylamide gel electrophoresis (PAGE) and western blotting, in patients with autoimmune thyroid disorders with or without associated ophthalmopathy. The most frequently detected antibody was that directed against a protein of 64 kDa. Antibodies against this antigen were detected in 33% of unselected patients with ophthalmopathy and in 75% of those with severe, active, orbital inflammation of less than 12 months duration. Such antibodies were detected also in 33% of patients with Graves' hyperthyroidism with no apparent eye disease and in 17% of patients with Hashimoto's thyroiditis with no eye disease but were not detected in patients with nonautoimmune thyroid disorders in 25 normal subjects tested. In the majority of sera showing reactivity with this protein, reactivity with membrane antigens of 55 and 95 kDa also were observed, suggesting that the three proteins were conformationally associated. Cytotoxic antibodies against human eye muscle cells, measured in antibody-dependent cell-mediated cytotoxicity (ADCC), were demonstrated in 37% of patients with ophthalmopathy. There was no significant correlation, in patients with eye disease, between positive ADCC tests and antibodies to the 64 kDa protein, the 64 kDa reactive antibody being found in 50% of patients with positive ADCC and in 35% of those with negative tests. In this study, a clear association has been shown between thyroid-associated ophthalmopathy and the detection, in immunoblotting, of antibodies reactive with a 64 kDa eye muscle membrane antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Immunologically mediated cytotoxicity against human eye muscle and thyroid cells in euthyroid and thyrotoxic Graves' ophthalmopathy.

We have studied the role of eye muscle and thyroid autoimmunity in patients with Graves' hyperthyroidism with or without ophthalmopathy in an area of relatively low iodine intake. Antibody dependent cell mediated cytotoxicity (ADCC) and complement mediated antibody dependent cytotoxicity (CMAC) against thyroid and eye muscle cells, and levels of antibodies against TSH receptor antigen and the thyroid microsomal antigen (thyroid peroxidase) were determined in three groups of patients: (1) thyrotoxic with exophthalmos (TX, n = 28), (2) thyrotoxic without ophthalmopathy (GR, n = 10), and (3) euthyroid ophthalmopathy (EU, n = 12). The thyroid glandular mass of the EU group was significantly less (P less than 0.01) compared with TX or GR. Mean (+/- SD) TSH receptor antibody (TRAb) level was 27 +/- 14% in EU which was significantly lower compared with TX (52.4 +/- 20%) and GR (59 +/- 18%). The prevalence of microsomal antibodies were similar and not significantly different in the three groups. On the other hand the prevalence of positive ADCC and CMAC tests was significantly greater, and at higher levels, in EU (ADCC THY CELLS 10.9 +/- 8.9% SL, ADCC Eye muscle = 25.9 +/- 20% SL, CMAC = 70.2 +/- 43% SL) and TX (ADCC THY CELLS = 9.3 +/- 9.2% SL, ADCC Eye muscle = 20.1 +/- 19% SL, CMAC = 62.4 +/- 30% SL) compared to GR (ADCC THY CELLS = 4.4 +/- 9.5% SL, ADCC Eye muscle = 7.7 +/- 6.7% SL, CMAC = 24.7 +/- 23% SL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Isotype and immunoglobulin subclass distribution of eye muscle membrane reactive antibodies in the serum of patients with thyroid-associated ophthalmopathy as detected in Western blotting.

We have determined the immunoglobulin (Ig) class (isotype) and IgG subclass of autoantibodies in the serum of patients with thyroid-associated ophthalmopathy (TAO) or autoimmune thyroid disorders without evident ophthalmopathy reactive in Western blotting with antigens of 55, 64, 75 and 95 kDa in pig eye muscle membrane (PEMM). The 22 sera studied were shown, previously, to contain IgG antibodies reactive with one or more of the four antigens. The majority of sera antibodies reactive with PEMM antigens were of two or more IgG subclasses. Of the IgG subclass specificities IgG3 and IgG4 subclass antibodies were, overall, the most common. We were unable to demonstrate IgG subclass restriction for antibodies reactive with the 95 or 55 kDa antigens in PEMM, antibody activity being equally distributed in all four subclasses tested. While most of the sera which recognized a 64 kDa antigen did so with an IgG4 antibody, all other subclasses were also represented. On the other hand all 13 sera reactive with a 75 kDa antigen did so using Ig of the IgG3 subclass and 12 of these used the IgG4 subclass as well, IgG1 and IgG2 subclasses being represented in only 3 and 4 sera, respectively. There were no differences, in respect to Ig class or IgG subclass distribution of eye muscle reactive antibodies between patients with Graves' hyperthyroidism with ophthalmopathy and those with Hashimoto's thyroiditis, and eye disease. Control sera from five normal subjects and three patients with nonautoimmune thyroid disorders did not contain antibodies reactive with these PEMM antigens of any Ig class or IgG subclass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Binding of peripheral blood and thyroidal T lymphocytes to thyroid cell monolayers: possible role of "homing-like" receptors in the pathogenesis of thyroid autoimmunity.

The specific binding of blood lymphocyte populations to non-antigenic receptors on high endothelial cells in peripheral lymphoid organs is well established. Such "homing" receptors in target tissues may also play a role in the early phase of organ specific autoimmunity. In this study binding of peripheral blood and thyroid-derived T cells to human thyroid (THY) cells was examined. Binding was measured as the percentage 51Cr-labelled T cells bound to THY monolayers. Interferon-gamma (IFN-gamma) enhanced the binding of peripheral blood T cells (PBL-T) from patients with Graves' disease (GD) and normals, but not from patients with Hashimoto's thyroiditis (HT), to allogeneic THY monolayers. The binding of T cells from patients with HT to untreated allogeneic THY monolayers was significantly greater than that for T cells from patients with GD or normals. TSH inhibited the IFN-gamma enhancement of binding of PBL-T from 4 normals and one HT patient to both allogeneic (n = 5) and autologous (n = 4) THY monolayers. Intra-thyroid T cells (ITL-T) bound to autologous THY monolayers significantly more than PBL-T from the same patient, while ITL from patients with HT or Graves' disease bound more than their PBL-T to both allogeneic and autologous THY monolayers. ITL-T, but not PBL-T, bound significantly more to autologous THY than to autologous thyroid-derived fibroblast monolayers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Ultrastructure of periprosthetic Dacron knee ligament tissue. Two cases of ruptured anterior cruciate ligament reconstruction.

Light- and electron-microscopic investigations were performed on two failed Dacron ligaments that had been removed from 2 patients shortly after failure of the implant 2-3 years after reconstruction of the anterior cruciate ligament. Two different cell populations and matrices were correlated with closeness to the Dacron threads. Fibroblasts surrounded by connective tissue with collagen fibrils were located far from the Dacron threads. Roundish cells, appearing to be myofibroblasts surrounded by a more lax connective tissue and elastic fibers, were found close to the Dacron threads. The presence of myofibroblasts and the matrix differentiation could be attributed to the different mechanical forces acting on the Dacron and on the connective tissue because of their different coefficients of elasticity. The sparse occurrence of inflammatory cells in the synovial membrane and in the connective tissue surrounding the Dacron supports the biologic inertness of this artificial material. However, the repair tissue was not structured to resist tension stresses.

Adult↗
PubMed1991

Adrenal cyst: a case report.

The authors describe the case of a patient with a large adrenal cyst. They review the existing literature and discuss the problem of diagnosis an treatment.

Adolescent↗
PubMed1991

Ultrastructural aspects of human nonunion.

A histological study on the tissue of nonunion of tibias of two young patients was performed to evaluate the ability of cells to start the mineralization of the matrix. The observations can be summarized as follows: 1) Tissue vessels often appear occluded by thrombotic material; 2) Fibroblasts and chondrocytes found in the nonunion tissue seemed normal, with a good secretion apparatus; 3) The cell membranes were able to produce matrix vesicles; 4) Matrix vesicles and cell membrane looked positive to ALPase reaction, 5) Hydroxyapatite crystals could be observed in the cell matrix or inside matrix vesicles. It may be concluded that cells populating nonunion tissue are well equipped to induct the mineralization of the matrix, but the absence of a blood supply, enough to bring them a normal calcium amount, is the real reason for the nonunion.

Adolescent↗
PubMed1990

Chronic treatment with a long-acting somatostatin analogue in a patient with intestinal carcinoid tumor: occurrence of cholelithiasis.

The long-acting somatostatin analogue SMS 201-995 has been used efficaciously in the therapy of metastatic carcinoid tumor, vasoactive intestinal peptide producing islet cell carcinoma, acromegaly, and TSH secreting pituitary tumors. We report the development of a gallstone in a patient treated for 23 months with a long acting somatostatin analogue for a metastatic carcinoid tumor. Symptomatic improvement and a reduction in the urinary excretion of 5-hydroxyindoleacetic acid occurred. There was no evidence of a gallstone on ultrasound and CT scan of the abdomen prior to somatostatin therapy. A progressively enlarging, asymptomatic gallstone developed during therapy.

Carcinoid Tumor↗
PubMed1990

B-mode imaging and histomorphometric evaluation of carotid atherosclerosis.

The quantitative and qualitative evaluation of atherosclerotic lesions by the ultrasonography has presented several problems, above all, the determination of accuracy and reproducibility of this methodology in humans. The present study aims to evaluated the results of B-mode imaging of extracranial carotid arteries in patients selected for surgery as compared with histologic results of the observations of the samples obtained by endarterectomy. Shrinkage effects of the histologic samples were taken into consideration. Several bidimensional images of atherosclerotic lesions, as obtained by ultrasound at different incident angles, were used to establish their maximum thickness. The maximum degree of the vessel stenosis calculated by ultrasound showed a high correlation (Y = 0.47X + 42.4, se = 0.11, r = 0.5, p less than 0.001) compared with the one obtained by histology. The imaging methodology provided however, a mean overestimation of the stenosis of about 7%. Relationships among the amount of calcium (p less than 0.03); necrotic core p less than 0.056); and echogenic types, ie, soft, mixed, and hard; have been suggested by a statistical trend. The results suggested that of the vascular lumen due to advanced atherosclerotic lesions. Qualitative interpretation of atherosclerosis by B-mode imaging, ie, morphologic characteristics, seem, at present, to be of value, but more investigations in depth are needed.

Arteriosclerosis↗
PubMed1990

Patients with endocrine ophthalmopathy not associated with overt thyroid disease have multiple thyroid immunological abnormalities.

Twenty-two apparently euthyroid patients with endocrine ophthalmopathy not associated with goiter, antithyroid microsomal or antithyroglobulin antibodies, or overt thyroid disease (so-called ophthalmic Graves' disease) were tested for subclinical hyperthyroidism or hypothyroidism. We measured 131I uptake and scan, serum T3 (by RIA), and serum TSH using a sensitive (by immunoradiometric assay) assay. Three patients were found to be hyperthyroid, and 1 was hypothyroid. The remaining 18 patients, who remained euthyroid throughout the study period, were investigated for evidence for antibody-mediated immunity against thyroid antigens. We measured antibody-dependent cell-mediated cytotoxicity against fresh thyroid cells using a 51chromium release assay, thyroid membrane-reactive antibodies in an enzyme-linked immunosorbent assay incorporating solubilized thyroid membranes, and TSH receptor-binding antibodies using a RRA and carried out sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting with patient sera for antibodies reactive with 64 and 110 kDa (thyroid peroxidase) membrane proteins. Bands were demonstrated, on SDS-PAGE, at 64 or 110 kDa in 13 patients, antibody-dependent cell-mediated cytotoxicity tests were positive in 7 patients, and enzyme-linked immunosorbent assay was positive in 4 of the 17 patients tested. In addition, TSH receptor antibody tests were positive in 5 patients, none of whom had other evidence for hyperthyroidism. Finally, significant lymphocyte infiltration was demonstrated on aspiration biopsy in 3 patients. All 18 patients had positive tests in at least 1 of the immunological assays. We believe that these data support the hypothesis that endocrine ophthalmopathy always occurs in patients with overt or subclinical Graves' hyperthyroidism, Hashimoto's thyroiditis, or thyroid immunological abnormalities. Those patients previously described as having euthyroid Graves' disease should, thus, be considered to have associated thyroid immunological abnormalities even though histological confirmation (from aspiration needle biopsy) may be obtained in only a minority of the patients. The possibility that the mechanism for this close association is cross-reactivity of cytotoxic antibodies against a thyroid/eye muscle cell surface shared antigen is discussed in the context of recent evidence from the authors' laboratory.

Adult↗
PubMed1990

Significance of cytotoxic eye muscle antibodies in patients with thyroid-associated ophthalmopathy.

We have studied the clinical significance of cytotoxic antibodies against human eye muscle cells in patients with thyroid-associated ophthalmopathy (TAO). Eye muscle reactive antibodies were measured in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. A positive test was defined as % specific lysis greater than the upper limit of normal, taken as the mean plus two standard deviations for normal subjects tested concurrently. As parameters of the severity of the ophthalmopathy we measured the degree of proptosis (mm), level of intraocular pressure (IOP) (mmHg) and American Thyroid Association classes (0-6). ADCC tests were positive in 21 out of 42 patients with TAO and in 8 out of 14 patients with Graves' disease without evident eye disease but in none of 12 normal subjects tested. In patients with TAO mean (+/- SE) IOP was significantly greater than that in patients with Graves' disease without apparent eye involvement for the primary position and for all gaze positions. There were significant positive correlations between levels of eye muscle reactive cytotoxic antibodies and the severity of the eye disease quantitated as American Thyroid Association classes 0-6, the IOP in the primary position and on downgaze, but not with the degree of proptosis. These results suggest that cytotoxic antibodies, as detected in ADCC, may play a role in the eye muscle damage of TAO and that their measurement may provide a useful clinical test.

Adult↗
PubMed1990

Eye muscle membrane reactive antibodies are not detected in the serum or immunoglobulin fraction of patients with thyroid-associated ophthalmopathy using an ELISA and crude membranes.

We tested sera and purified immunoglobulin (Ig) fractions from patients with autoimmune thyroid disorders (AITD), with and without ophthalmopathy, and normal subjects, for the presence of antibodies reactive with eye muscle membrane antigens in an optimized enzyme-linked immunosorbent assay (ELISA). We found no correlation between ELISA results and the presence or severity of ophthalmopathy in patients with AITD for either serum or Ig, and there were no significant differences between the mean values (+/- SE) for the three groups (AITD with ophthalmopathy, AITD without ophthalmopathy and normals) for either serum or Ig. In contrast Ig from 8 of 19 (45%) patients with thyroid-associated ophthalmopathy reacted with a 64 kDa eye muscle membrane antigen in SDS-polyacrylamide gel electrophoresis and Western blotting, while tests were positive in only one of the 8 patients with AITD without eye disease and in none of the 8 normal subjects. The presence of antibodies to a 64 kDa antigen in immunoblotting did not correlate with the levels of antibodies measured in ELISA. We conclude that the ELISA, incorporating a crude membrane fractions as antigen, is not useful as a clinical test for eye muscle autoantibodies.

Adult↗
PubMed1990

[Variations in the rate of erythrocyte sedimentation in the postoperative orthopedic and traumatologic course and their clinical significance].

The authors report their results on E.S.R. variations within the first month post-surgery in 38 traumatologic and orthopaedic patients, to evaluate the time of normalization and its attendibility in case of infection. Normalization was found within the first month postoperatively, without significant differences between orthopaedic and traumatologic patients. They think that the E.S.R. becomes significant on the control of postoperative subacute infection after the third postoperative day and propose E.S.R. evaluation after this period.

Adolescent↗