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Biomedical subjects

M Cutolo

Publications and source records attributed to M Cutolo.

At least 109 records · Page 6Linked to original sources
PubMed1996

Androgen and estrogen receptors are present in primary cultures of human synovial macrophages.

Macrophages, as antigen-processing and -presenting cells to T lymphocytes, play a key role in the immune system and are suspected to be target cells of the sex hormone-related dimorphism in the immune response peculiar to rheumatoid arthritis (RA) pathology. In the present study, the use of specific monoclonal antibodies revealed immunostaining for androgen and estrogen receptors in primary cultures of macrophages obtained from synovial tissues of patients affected by RA and controls without RA disease. Soluble and nuclear type I (high affinity, low capacity) and type II (lower affinity, greater capacity) sites of androgen or estrogen binding were detected in primary cultures of RA macrophages using radioligand binding assay. Higher levels of type I and type II estrogen receptor compared to those of androgen receptor were found, particularly in the soluble fraction; however, contrary to what was observed in whole synovial tissues, higher steroid receptor concentrations were found in the soluble than in the nuclear fraction of RA synovial macrophages. Binding affinities and receptor contents of cultured synovial macrophages were comparable to those previously reported in other well established sex hormone-responsive cells and tissues. Further, specific messenger ribonucleic acids for sex hormone receptors, encoding for a sequence of the DNA-binding domain of the receptor proteins were revealed by RT-PCR.

Adult↗
PubMed1995

Macroamylasemia: a possible cause of unexplained hyperamylasemia in rheumatoid arthritis.

Macroamylasemia is a benign acquired condition, characterized by a serum amylase unusually large in molecular size that has been found to occur in apparently healthy humans as well as in a variety of diseases including liver disease, diabetes, cancer malabsorption and autoimmune disorders. Most commonly macroamylasemia results from the formation of immune complexes between amylase and immunoglobulins. We describe the first case of an association between macroamylasemia/hyperamylasemia and rheumatoid arthritis characterized by the absence of immunoglobulins, as amylase binding globulins, within the macroamylase complex. Failure to identify macroamylase as the cause of unexplained but benign hyperamylasemia correctly, can lead to costly studies (e.g. ultrasonography, computerized tomography) to rule out pancreatic disease, and could induce prescription of unnecessary elemental diets and replacement therapies, as reported in our patient.

Amylases↗
PubMed1994

Sex differences in inflammation induced cartilage damage in rodents. The influence of sex steroids.

OBJECTIVE: To investigate sex differences in granulomatous inflammation and its effects upon articular cartilage and to assess the potential role of sex steroids in the process. METHODS: The cotton-pellet cartilage implant model was used with male and female mice in the presence and absence of gonadectomy and hormone replacement. The effects of granulomatous tissue upon articular cartilage was assessed and tissue content of interleukin 1 (IL-1) was determined. The expression of sex hormone receptors in inflammatory tissue was investigated by immunocytochemistry. RESULTS: Female mice showed a higher ability than males to degrade cartilage irrespective of the sex of the cartilage implanted. Gonadectomy resulted in a significant acceleration of cartilage damage in both sexes, which was reverted by estrogen replacement in females and androgen replacement in males. Female granulomata had significantly higher IL-1 content than those from males. Gonadectomy was associated with an increased IL-1 content in males but not in females, the effects being abolished by androgen replacement in males. Estrogen and androgen receptors were identified in inflammatory cells from the granulomatous tissue. CONCLUSION: Our data demonstrate that sex hormones affect inflammation induced cartilage degradation in male and female mice probably through the modulation of cytokine production and release in the granulomatous tissue. Further investigation on the effects of sex steroids in inflammation induced cartilage degradation may help elucidate their pathogenic role and therapeutic potential in human disease.

Animals↗
PubMed1993

Presence of estrogen-binding sites on macrophage-like synoviocytes and CD8+, CD29+, CD45RO+ T lymphocytes in normal and rheumatoid synovium.

OBJECTIVE: To study the presence of estrogen-binding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age- and sex-matched healthy controls. METHODS: Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran-coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti-estrogen receptor antibody (anti-ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti-ER MAb and with specific MAb to detect different macrophage antigens (Ber-MAC3, MAC387, CD68) and CD8+ T cell subsets (CD29+, CD45RO+ and CD29-, CD45RO-) was performed. RESULTS: Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor-positive cells to be the macrophage-like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells. CONCLUSION: It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage-like synoviocytes, functioning as antigen-processing and antigen-presenting cells, and on antigen-experienced (memory) CD8+ T lymphocytes (CD29+, CD45RO+).

Adult↗
PubMed1993

Evidence for soluble and nuclear site I binding of estrogens in human aorta.

The purpose of this study was to establish the estrogen receptor (ER) expression and content in human aorta fragments removed at the time of by-pass surgery. To this end, we adopted a radioligand binding assay to evaluate either soluble (S) or nuclear (N) ER using dextran-coated charcoal (DCC) and filtration methods, respectively. To better define the intratissular distribution and content of ER, we also measured the presence of a 27 kDa heat shock protein (HSP27), a well established ER-associated protein, using D5 monoclonal antibody. Finally, we analysed the different molecular isoforms of both S and N ER using size exclusion-high performance liquid chromatography (SE-HPLC). High affinity (type I) sites of estrogen binding were detected in 17 out of 19 samples in either S or N fraction, although only 9 out of 19 cases displayed site 1 ER in both cell compartments. ER levels in aortic tissues, detected by radioligand method, compare well with those we have found in other hormone-sensitive human cancer tissues and cells. SE-HPLC analysis revealed two main receptor isoforms in the soluble fraction, having 65 kDa and 18 kDa molecular mass, while a minor component of 29 kDa was also found; the nuclear fraction displayed again two major components of 38 and 23 kDa. Using the HSP27 immunohistochemistry we observed a major staining occurring in smooth muscle cells (SMC), with an increasing intensity towards the lumen. All samples, including the ER negative ones, exhibited some degree of histochemical staining. Using an arbitrary cut-off value, 7 out of 12 samples displayed a highly positive staining, 6 of which showed nuclear ER. Furthermore, SE-HPLC separation indicated the presence of a 64.9 kDa component in the soluble fraction, according to the well known relative molecular mass of ER. Following HSP27 immunohistochemistry, the overall staining intensity in aortic SMC approaches that seen in endometrial and breast epithelia, whilst the muscle ER content is generally lower. Although our data are compatible with a direct role of estrogens in arterial function, the extent of the link with arterial disease remains to be established.

Adult↗
PubMed1993

Rheumatoid arthritis with monoclonal IgE rheumatoid factor.

We studied a patient with rheumatoid arthritis (RA) and a high titer of IgE that could be attributed to a mono or oligoclonal expansion of IgE+ B lymphocytes. These IgE had no specificity for known allergens but bound to a panel of self (including Fc fragment of IgG) and exogenous antigens, displaying properties typical of polyspecific antibodies. We concluded that (1) RA can be associated with increased amounts of polyspecific IgE antibodies; (2) clonal excess populations of B cells are not a unique feature of malignant lymphoma, but may occur in autoimmune diseases in the form of a benign oligoclonal B cell proliferation.

Antibody Specificity↗
PubMed1992

Evidence for the presence of androgen receptors in the synovial tissue of rheumatoid arthritis patients and healthy controls.

OBJECTIVE: To study the presence of androgen receptors in the synovial tissue of male and female patients with rheumatoid arthritis (RA) and matched healthy controls. METHODS: Both site I (high affinity, low binding capacity) and site II (reduced affinity, higher binding capacity) androgen receptors were investigated in soluble and nuclear fractions of homogenized synovial samples, using the dextran-coated charcoal method. The finding of pure, high-affinity site I receptors in both fractions was considered indicative of androgen receptor positivity. In order to determine what type of synovial cell was positive for androgen receptors, cryosections of synovial tissues were immunostained with a specific monoclonal anti-androgen receptor antibody (MAb), using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with this MAb and specific MAb directed toward different macrophage/granulocyte antigens was also performed. RESULTS: Remarkable differences were found between male and female controls: Most males were positive for androgen receptors, and most females were negative. The fetomolar content of androgen receptor in the nuclear fraction was fairly constant, but the soluble fraction showed a higher femtomolar concentration in female RA patients than in controls of either sex, as well as in male RA patients compared with female RA patients. The androgen receptor-positive cells in both RA and control synovial cryosections were found by immunostaining to be macrophage-like synoviocytes, and were also found to be HLA-DR positive. CONCLUSIONS: The immunosuppressive action exerted by androgens might, at least in part, be mediated through their interaction with macrophage-like synoviocytes functioning as antigen-processing and antigen-presenting cells in rheumatoid synovia.

Aged↗
PubMed1992

Tenascin and fibronectin distribution in human normal and pathological synovium.

Tenascin is a glycoprotein found mainly in the extracellular matrix of developing and malignant tissues. The distribution of this molecule in normal and pathological synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was investigated by indirect immunofluorescence utilizing specific monoclonal antibodies. The same technique was used to study total fibronectin (tFn) in synovial tissues as well as ED-A and ED-B containing fibronectin (Fn) isoforms (A-Fn, B-Fn), generated by alternative splicing of pre-mRNA. Tenascin was found in normal synovium just beneath the whole lining cell layer. However, a higher density and spreading pattern of distribution was observed in OA and RA sections. A-Fn and B-Fn isoforms were prominent and widespread throughout the normal synovial lining; in hypercellular synovial lining (in RA and OA samples), A-Fn and B-Fn were also observed spreading in the sublining, as well as tFn.

Antibodies, Monoclonal↗
PubMed1991

Androgen replacement therapy in male patients with rheumatoid arthritis.

A hypogonadic condition characterized by low serum testosterone levels has been identified in male patients with rheumatoid arthritis (RA). Seven men with active RA were treated daily for 6 months with oral testosterone undecanoate plus a nonsteroidal antiinflammatory drug in an attempt to evaluate the immunologic response, the overall clinical response, and the sex hormone response to such replacement therapy. At the end of the 6 months, there was a significant increase in serum testosterone levels (P less than 0.05), an increase in the number of CD8+ T cells, and a decrease in the CD4+:CD8+ T cell ratio. The IgM rheumatoid factor concentration decreased significantly (P less than 0.05). There was a concurrent significant reduction in the number of affected joints (P less than 0.05) and in the daily intake of nonsteroidal antiinflammatory drugs (P less than 0.01). The well-known immunosuppressive action of androgens probably contributed to our findings in these RA patients.

Administration, Oral↗
PubMed1991

Adult-onset Still's disease associated to toxoplasma gondii infection.

Adult-onset Still's disease is characterized by high spiking fever, evanescent maculopapular rash and arthritis. Several recent reports have associated its development with a variety of infectious agents. We describe the case of a 25-year old woman presenting high fever, maculopapular rash and seronegative polyarthritis associated with lymphoadenopathy, splenomegaly and neutrophil leucocytosis together with acute acquired toxoplasmosis. Other causes of systemic illness were excluded by appropriate laboratory, radiological and histological investigations. Clinical, radiological and laboratory findings as well as possible etiopathogenetic correlations among both pathological conditions are discussed. Toxoplasma gondii should be considered as a further possible triggering agent associated with the development of adult-onset Still's disease.

Adult↗
PubMed1990

Nail involvement in osteoarthritis.

Two cases of nail involvement associated with primary interphalangeal osteoarthritis of the hand, including leukonychia and longitudinal nail ridge, are reported. Osteoarthritic changes of the distal interphalangeal joints may cause nail lesions by exerting direct pressure on the nail matrix or by interfering with local blood flow. Moreover, inflammation of the Heberden's nodes is often present and seems to participate in the development of nail alteration. In our patients, leukonychia disappeared after local steroidal anti-inflammatory treatment of the osteoarthritic node and longitudinal nail ridge disappeared after treatment with nonsteroidal anti-inflammatory agents.

Aged↗