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Biomedical subjects

M Massa

Publications and source records attributed to M Massa.

At least 19 recordsLinked to original sources

p53 exon 7 mutations as a predictor of poor prognosis in patients with colorectal cancer.

We have studied 61 resected colorectal adenocarcinomas in order to investigate p53 mutations as a prognostic factor for this pathology. Mutations in exons 5-9 of the p53 gene were analyzed by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique followed by sequencing. Our data indicate that p53 exon 7 mutations were prevalent in the latest stages of colorectal carcinogenesis and patients bearing this alteration had the worst prognosis. Therefore, according to our results, mutations affecting exon 7 of the p53 gene could be considered as a useful marker of biological aggressiveness for colorectal cancer.

Aged

Soluble tumour necrosis factor receptor levels reflect coagulation abnormalities in systemic juvenile chronic arthritis.

The objective was to evaluate tumour necrosis factor (TNF) status in patients with systemic juvenile chronic arthritis (s-JCA). Plasma levels of TNF-alpha, and serum levels of soluble TNF receptor 1 and 2 (sTNFR1 and sTNFR2) were measured using specific immunoassays in 20 patients with s-JCA, 10 with polyarticular JCA and 15 with pauciarticular JCA, and in 20 controls comparable for age. In patients with active s-JCA, circulating levels of TNF-alpha, sTNFR1 and sTNFR2 were significantly (P < 0.001) higher than those of controls. The levels of sTNFR1 and sTNFR2, but not those of TNF-alpha, were associated with the persistence and severity of systemic symptoms and were significantly correlated with prolongation of partial thromboplastin time and decrease in prothrombin activity. In two patients evaluated during a s-JCA-associated macrophage activation syndrome, a marked increase in sTNFR1 and sTNFR2 was found. Our results suggest that in s-JCA, TNF is involved in systemic manifestations, in the subclinical coagulation abnormalities, and in the development of the macrophage activation syndrome.

Adolescent

Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis.

OBJECTIVE: To evaluate quantitative or qualitative differences in synovial fluid (SF) cytokine levels among patients with systemic juvenile rheumatoid arthritis (JRA), antinuclear antibody positive pauciarticular JRA, or adult RA. METHODS: SF levels of interleukin 1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra) IL-11, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), leukemia inhibitory factor (LIF), all measured by immunoassays, and of IL-6, measured with a bioassay using B9 cells, were evaluated in 11 patients with systemic JRA, 24 with pauciarticular JRA, and 22 adult patients with RA. RESULTS: SF IL-6 levels were significantly higher in patients with systemic JRA than patients with pauciarticular JRA (p = 0.003) or RA (p = 0.002). IL-1alpha was detectable in 12/24 SF samples from pauciarticular JRA, in 2/22 SF from RA, and in no sample from systemic JRA (p = 0.004 vs RA; p = 0.005 vs systemic JRA). SF IL-11 levels were significantly higher in patients with RA than patients with systemic JRA (p = 0.012) or pauciarticular JRA (p = 0.005). We found no significant differences in SF levels of IL-1beta, IL-1Ra, TNF-alpha, sTNFR1, or LIF. CONCLUSION: In systemic JRA, SF levels of IL-6 are significantly higher than in pauciarticular JRA or in RA; IL-1alpha is present in a significant proportion of patients with pauciarticular JRA, but not in those with RA or systemic JRA.

Adolescent

Membrane CD22 defines circulating myeloma-related cells as mature or later B cells.

Circulating clonally related earlier cells are present in multiple myeloma (MM) and may be involved in the dissemination of this disease, its recurrence, and chemoresistance. The nature, stage of differentiation, and size of this cell population remain uncertain. Unlike other B-cell markers, CD22 membrane expression is limited to the late differentiation stages comprised between mature B cells (CD22+) and plasma cells (PC; CD22-) and may thus be useful in delimiting the maturational state of circulating early myeloma cells. Peripheral blood clone-related cells were detected by anti-idiotypic (Id) monoclonal antibodies and found to express CD22 (92% to 95%), monotypic light and heavy chain (100%), and CD38 (45%), whereas bone marrow PC were CD22-negative. CD22 expression was also documented on functional myeloma PC precursors, defined as peripheral blood cells capable of in vitro cytokine-driven monotypic PC differentiation, because up to approximately 70% inhibition of this process was obtained in 10 myeloma patients through the use of biospecific antibodies (BsAb) that deliver the plant toxin saporin to CD22+ cells. As further evidence of CD22 on circulating abnormal cells, it was found that in the only patient analyzed for DNA content, a portion of the peripheral blood CD22+ cells killed were hyperdiploid. Collectively, these findings indicate that most peripheral blood myeloma PC precursors are mature or later B cells presenting membrane CD22. The pattern of CD22 expression suggests the existence in MM of a differentiation process analogous to the normal antigenic response, in which CD22+ B cells migrate to the bone marrow and lose CD22 with PC differentiation. In addition, the sensitivity of myeloma PC precursors to the cytotoxic effects of the anti-CD22 BsAb and the possibility of interfering with their differentiation have potential therapeutic relevance.

Amyloidosis

Clinical strain of Staphylococcus aureus inactivates and causes efflux of macrolides.

Searching through a collection of 124 Staphylococcus aureus clinical strains, we found one isolate, strain 01A1032, that inactivates 14- and 16-membered macrolides. The products of inactivation were purified from supernatant fluids of cultures exposed to erythromycin for 3 h and were found to be identical to products of inactivation from Escherichia coli strains that encode either an EreA or EreB esterase. Further, strain 01A1032 was shown to be resistant to azithromycin, a 15-membered macrolide, by an alternate mechanism, efflux. Thus, strain 01A1032 harbors determinants encoding an esterase activity that hydrolyzes 14- and 16-membered macrolides and a macrolide efflux system.

Anti-Bacterial Agents

Lack of temporal association of iridocyclitis with IgG reactivities to core histones and nucleosome subparticles in pauciarticular juvenile chronic arthritis.

This study aimed to measure IgG reactivities to DNA-free nucleosome subparticles (H2AH2B, H3H4) and nucleosome subparticles (H2AH2B-DNA, H3H4-DNA) and to evaluate the temporal relation of these reactivities, as well as those to single core histones, with iridocyclitis (IC) in patients with antinuclear antibody positive (ANA+) pauciarticular juvenile chronic arthritis (JCA). Reactivities to nuclear substrates were determined by enzymatic immunoassays in 120 sera from 45 children with ANA+ pauciarticular JCA. Significantly elevated IgG levels to H3 and H4, to DNA-free nucleosome subparticles, and to the nucleosome subparticle H3H4-DNA were present in patients with ANA+ pauciarticular JCA; no evidence of recognition of conformational epitopes was found. In both horizontal and follow-up studies, no relation between the reactivities studied and the development, presence, or history of IC was found. Our results show the absence of a relation of antibodies to histone molecules or to nucleosome subparticles with IC in patients with ANA+ pauciarticular JCA.

Adolescent

Circulating levels of interleukin-6, interleukin-8, and tumor necrosis factor-alpha in children with autoimmune hepatitis.

Circulating levels of the proinflammatory cytokines interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) were measured in 13 children with autoimmune hepatitis (AIH) (seven with type 1 and six with type 2). In untreated children with type 1 AIH, TNF-alpha, IL-6, and IL-8 levels were elevated when compared to those of healthy controls (p < 0.005, p < 0.02, p = 0.06, respectively), whereas in children with type 2 AIH, cytokine levels were normal in all except one sample. A significant decrease in circulating IL-6, IL-8, and TNF-alpha was observed when patients were evaluated during a subsequent remission. We found no significant correlation of cytokine levels with alanine aminotransferase (ALT) activity, total serum gamma-globulins, or prothrombin activity. In patients with cirrhosis, serum IL-8 and IL-6 levels were higher (significantly in the case of IL-8) than those of patients without cirrhosis. In conclusion, activation of the in vivo production of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha appears to be associated with type 1 but not with type 2 AIH.

Adolescent

Elevated circulating interleukin-7 levels in patients with systemic juvenile rheumatoid arthritis.

OBJECTIVE: Since interleukin-7 (IL-7) has been shown to induce monocyte production of IL-1, IL-6, IL-8, and tumor necrosis factor-alpha, we investigated plasma and synovial fluid levels of IL-7 in patients with juvenile rheumatoid arthritis (JRA). METHODS: IL-7 levels were measured using an ELISA in 60 patients with JRA and in 25 patients with other rheumatic disorders (ORD). RESULTS: In patients with systemic JRA, but not in patients with polyarticular or pauciarticular JRA or with ORD, plasma IL-7 levels were significantly higher (p < 0.0001) than those of healthy controls. IL-7 was undetected in all synovial fluid tested. Among patients with systemic JRA, those with persistent systemic symptoms had IL-7 levels significantly higher (p < 0.01) than those of patients in which systemic symptoms subsided. CONCLUSION: Plasma IL-7 levels are elevated in patients with systemic JRA and are associated with the presence and severity of systemic symptoms.

Adolescent

[Complications of elective hepatic resections. Analysis of risk factors].

In the last decades the hepatic surgery has been more and more employed thanks to improvement of the surgical technique and of the post-operative assistance which have brought the peroperative mortality of principal specialistic centres to less of 5%. The main post-operative complications which trouble the hepatic surgery, forming in same cases the cause of the death, are: hepatic insufficiency, haemorrhage, subphrenic abscess and the appearance of biliary fistulas. These complications are often connected and linked to the devitalization of a part of the residual parenchyma. We have made a retrospective study on a series of 214 hepatic resections, executed in election, to estimate the main pre and intra-operative risk factors. The operative mortality has been zero whereas the post-operative one is occurred in 4.2% of the cases with a morbidity of 27.5%. In our experience the meaning full factors to prefigure an operative risk are resulted: the associated pathologies like diabetes, cardiopathies, ipertension and bronchopathies; the length of the operation; the entity of the peroperative haematic loss and of the consequent transfusional therapy and eventually quality the residual parenchyma.

Adolescent

Hypocomplementemic urticarial vasculitis syndrome with severe systemic manifestations.

We describe two children with clinical and laboratory features of hypocomplementemic urticarial vasculitis syndrome. Both patients had severe, life-threatening manifestations: rapidly progressive glomerulonephritis (patient 1) and pulmonary hemorrhage (patient 2). We conclude that this syndrome may be a potentially severe multisystem disease.

Adolescent

Immune responses to the Escherichia coli dnaJ heat shock protein in juvenile rheumatoid arthritis and their correlation with disease activity.

Patients with juvenile rheumatoid arthritis frequently have abnormal immune responses to the hsp65 class of bacterial heat shock proteins. However, lymphocytes from children with other inflammatory diseases may also recognize hsp65, and the role of these antigens in juvenile rheumatoid arthritis remains controversial. We have studied humoral and cellular immune responses to a distinct, recently described bacterial heat shock protein, designated dnaJ. The Escherichia coli dnaJ gene was cloned and expressed, and the purified recombinant protein was used as an antigen. Neither normal children nor children with various chronic inflammatory diseases had lymphocyte proliferative responses to recombinant dnaJ. However, lymphocytes from patients with polyarticular, pauciarticular, and systemic manifestations of juvenile rheumatoid arthritis responded strongly to the antigen. Cellular immune responses to dnaJ were higher in synovial fluid than in blood and higher in children with active disease than in children in remission. These data show that increased immune reactivity to dnaJ is characteristic of juvenile rheumatoid arthritis and that the magnitude of the immune response is linked to disease activity. The results suggest that an abnormal immune response to antigens on commensal gut bacteria may contribute to the generation of chronic inflammation in juvenile rheumatoid arthritis.

Adolescent

Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis.

By using a sandwich ELISA, soluble human IL-6 receptor (sIL-6 R) levels were measured in the sera of 20 healthy children and of 25 patients with systemic juvenile rheumatoid arthritis (JRA). In patients with systemic JRA, serum sIL-6 R levels (114.6 +/- 37.7 ng/ml) were significantly lower (P < 0.01) than those of healthy children (161.2 +/- 45.5 ng/ml). Serum sIL-6 R levels were negatively correlated (r = -0.610, P < 0.001) with serum IL-6 levels measured with the B9 cells. The serum IL-6/sIL-6 R complex was detected using an ELISA based on a monoclonal antibody to IL-6 for capture and on a monoclonal antibody to human sIL-6 R for detection. Healthy controls had little, if any, detectable serum IL-6/sIL-6 R complex (OD 0.024 +/- 0.027), while the majority of patients with systemic JRA presented measurable serum IL-6/sIL-6 R complex (OD 0.492 +/- 0.546). IL-6 levels estimated in the circulating IL-6/sIL-6 R complexes were in the range of nanograms per milliliter and approximately 20-fold higher than those measured by the B9 cells. Since serum C-reactive protein concentrations were much more correlated with serum levels of IL-6/sIL-6 R complexes (r = 0.713, r2 = 0.51, P < 0.0001) than with the serum IL-6 levels measured with the B9 cells (r = 0.435, r2 = 0.19, P = 0.05), the large quantities of serum IL-6 present in IL-6/sIL-6 R complexes appear to be biologically relevant in vivo, at least as far as the induction by IL-6 of acute phase protein production.

Adolescent

Nucleosome-specific antibody from an autoimmune MRL/Mp-lpr/lpr mouse.

OBJECTIVE: To characterize the binding properties and variable-region sequences of LG4-1, a monoclonal antibody from an autoimmune MRL/Mp-lpr/lpr mouse that reacts specifically with nucleosome core particles and represents a new antinuclear antibody specificity. METHODS: The reactivity of the antibody against various nuclear substrates was determined using an enzymatic immunoassay, and the variable-region genes were sequenced from messenger RNA, using the dideoxy chain termination method. RESULTS: LG4-1 was found to react with nucleosome core particles but not with individual histones and DNA, or with various histone-histone and histone-DNA complexes. It was demonstrated that this antibody is encoded by a combination of variable-region genes and gene segments that have undergone few somatic mutations. CONCLUSION: The nucleosome core particle expresses a unique conformational autoepitope(s) resulting from the ordered association of histones and DNA.

Amino Acid Sequence

CD5-positive B cells in type 1 (insulin-dependent) diabetic children.

We have measured CD5+ B cell levels in the peripheral blood of 35 type 1 (insulin-dependent) diabetic children, aged 1.1-21.2 years (10.7 +/- 4.6 years). Patients were divided into two groups according to disease duration (group I < 6 months and group II > 1.5 years). Group I included 18 patients and group II 17 patients. Thirty-nine healthy subjects, comparable for age and sex, served as controls. CD5+ B cells were identified by double immunofluorescence staining with rhodamine-conjugated rabbit anti-human immunoglobulin and with a mouse anti-CD5 monoclonal antibody revealed by a fluorescein-conjugated goat anti-mouse immunoglobulin. We found that CD5+ B cell levels (expressed as percentages of peripheral blood B lymphocytes) were significantly higher in group I (median 24; range 4-48) than in controls (median 14; range 0-36, P < 0.001) and in group II (median 4; range 0-20, P < 0.001). A follow-up study of 12 group I patients showed a significant decline in CD5+ B cell levels. The data obtained in our diabetic patients suggest that CD5+ B cells are expanded in the early phase of type 1 diabetes mellitus and may play a role in the autoimmune process of the disease.

Adolescent

Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies.

OBJECTIVE: Using data from 3 independent studies, to quantify the interobserver reliability of semi-quantitative skin scoring methods (the original and the modified Rodnan skin thickness scores) used to assess the degree and extent of cutaneous thickening in systemic sclerosis (SSc). METHOD: Interobserver variability of the original Rodnan skin thickness score method (cutaneous thickness assessed in 26 body surface areas using a 0-4 scale) was evaluated in one study. The modified Rodnan method (cutaneous thickness assessed in 17 body surface areas using a 0-3 scale) was evaluated in 2 studies. In all 3 studies, each patient's skin thickness was assessed by 6 or 7 observers in a blinded fashion. RESULTS: The overall within patient standard deviations were not statistically different in all 3 studies (5.4, 4.6 and 4.6) irrespective of the overall mean skin thickness scores (26.6, 18.3 and 17.7). With the original Rodnan technique, the within patient standard deviation tended to be higher in patients with higher skin thickness scores. In the 2 studies which used the modified technique, no significant differences in within patient standard deviation were noted between high and low skin thickness scores. CONCLUSIONS: Three independent studies demonstrate that the Rodnan skin thickness scoring techniques are reproducible among different observers (the within patient standard deviation being consistently about 5 units). Our data provide valuable information needed for sample size calculations for SSc trials in which skin thickness score is an outcome variable.

Humans