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M Novelli

Publications and source records attributed to M Novelli.

70 records · Page 4Linked to original sources

Expression and role of integrin receptors in Sézary syndrome.

The potential role of integrins in the epidermotropism of the atypical lymphocytes of Sézary syndrome was studied by monitoring the expression of alpha and beta chains and their major ligands in skin biopsies and peripheral blood cells in patients at different progression stages. Most mononuclear cell integrins were also detected on infiltrating cells including the leukocyte complex CD11/CD18, alpha 4 beta 1, and their ligands, ICAM-1 and VCAM-1. Conversely, alpha 6 and beta 4 were present only in epidermal basal cells. Mononuclear infiltrates of SS were positive for both alpha 3 and alpha 5 chains, whereas in inflammatory cutaneous diseases only alpha 5 was expressed, indicating that a major feature of Sézary cells is the unique expression of alpha 3 beta 1. Significant changes of alpha 3 beta 1 were monitored in the follow-up of Sézary patients and correlated with the results of the therapy. The heterodimer alpha 1 beta 1 was absent from mononuclear cells except in one case. Among matrix molecules, laminin and type IV collagen displayed a pattern similar to that of the controls, whereas fibronectin and tenascin deposition were apparently increased. Circulating Sézary cells, both at diagnosis and during follow-up, were alpha 3 and alpha 5 negative and failed to acquire these adhesion molecules after mitogenic stimulation. We propose that the expression of alpha 3 beta 1 is a distinguishing feature of skin-infiltrating Sézary cells and may be related to their epidermotropism. It could also be adopted as an additional parameter of the progression and therapeutic stage of Sézary syndrome.

Antigens, CD↗

Soluble interleukin-2 receptor, CD4 and CD8 levels in melanoma: a longitudinal study.

Serum levels of soluble(s) interleukin-2 receptor (IL-2R), sCD4 and SCD8 were analysed in 227 melanoma patients, using a sandwich enzyme immunoassay. Different stages of the disease were considered, and a longitudinal study with a 2-year follow-up was performed. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. sCD8 increases with stage progression were less striking, while sCD4 values were always in the normal range. We conclude that sIL-2R measurement is a useful clinical parameter in monitoring disease evolution in melanoma.

Adult↗

Application of amino acid analysis by high-performance liquid chromatography with phenyl isothiocyanate derivatization to the rapid determination of free amino acids in biological samples.

An amino acid analysis by reversed-phase high-performance liquid chromatography after precolumn derivatization with phenyl isothiocyanate was adapted to the determination of free amino acids in plasma or other biological fluids and in tissue homogenates. Preparation of samples included deproteinization by 3% sulphosalicylic acid, and careful removal under high vacuum of residual phenyl isothiocyanate after derivatization. A Waters Pico-Tag column (15 cm long) was used, immersed in a water-bath at 38 degrees C. In rat or human plasma, separation of 23 individual amino acids, plus the unresolved pair tryptophan and ornithine, was obtained within 13 min. Including the time for column washing and re-equilibration, samples could be chromatographed at 23-min intervals. Variability was tested for each amino acid by calculating the coefficients of variation of retention times (less than 1% in the average) and peak areas (less than 4% for both intra-day and inter-day determinations). The linearity for each standard amino acid was remarkable over the concentration range 3-50 nmol/ml. The mean recovery of amino acid standards added to plasma prior to derivatization was 97 +/- 0.8%, except for aspartate (82%) and glutamate (81%). This method is rapid (almost three samples per hour can be analysed, more than in any other reported technique), with satisfactory precision, sensitivity and reproducibility. Therefore, it is well suited for routine analysis of free amino acids in both clinical and research work.

Amino Acids↗

Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions.

Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.

Antibodies, Monoclonal↗

Protection by 3-aminobenzamide and nicotinamide against streptozotocin-induced beta-cell toxicity in vivo and in vitro.

To increase knowledge about the defense mechanisms of pancreatic beta-cells exposed to acute injury, the patterns of protection exerted by 3-aminobenzamide and nicotinamide against the effects of streptozotocin have been studied in vivo and in vitro. It was found that 3-aminobenzamide, a strong inhibitor of the NAD-consuming nuclear enzyme poly(ADP-ribose) synthetase, is maximally effective against streptozotocin-induced diabetes in the rat when administered 45-60 min after the beta-cytotoxic agent, unlike nicotinamide, which exerts best protection when given very close to streptozotocin. A partial protection is still afforded by 3-aminobenzamide administered as long as 120 minutes after streptozotocin. In isolated islets, each protective agent, if added to the incubation medium 20 or even 40 minutes after the exposure of the islets to streptozotocin, is able to partially prevent the effects of the damaging drug on glucose-stimulated insulin release. However, best protection in vitro is obtained when either 3-aminobenzamide or nicotinamide is added simultaneously with the toxic agent. Our results support the concept that the reversibility of streptozotocin-induced acute damage in beta-cells depends on the preservation of intracellular NAD pools during critical time intervals. This can be achieved by two different partially overwhelming mechanisms: a) early stimulation of NAD biosynthesis (prevailing effect of nicotinamide) and b) strong inhibition of poly ADP-ribosylation activity (main effect of 3-aminobenzamide).

Animals↗

[Serum levels of soluble receptors of interleukin-2 in skin pathology].

The antigenic activation of T lymphocytes depends on the production of interleukin-2 (IL-2) and on the expression of a membrane-specific receptor (IL-2R). This receptor, a dimer composed of a 57 kD chain, is also present on some B lymphocytes and activated macrophages (anti-TAC) grouped together in CD25. A soluble form of IL-2R (sIL-2R) was recently identified, comprising the extracellular part of the chain (45 kD) which is released by the cell in body fluids. The presence of sIL-2R in serum can be assayed using ELISA (Cell free, T cell Sciences, Cambridge, MA). Normal values range between 100 and 500 U/ml, with a mean value of 375 U/ml. Marked increases of sIL-2R, with levels of up to 50,000 U/ml, have been observed in various diseases: hairy cell leukemia, Hodgkin's disease, non-Hodgkin lymphoma, acute leukemia, B-CLL, ATL and Sezary's syndrome. Lesser increases are also found in autoimmune diseases, viral infections, and following organ transplantation. Many Authors have described the close correlation between sIL-2R levels and the clinical evolution of the disease. Soluble IL-2 receptors were studied in 184 patients affected by skin diseases: eczematous dermatitis, lichen, psoriasis, erythroderma psoriaticum, dermatomyositis, scleroderma bullous dermatosis, melanoma, Kaposi's disease, lymphomatoid papulosis, non-Hodgkin lymphoma, mycosis fungoides (MF), Sezary's syndrome (SS). Increased serum levels of sIL-R2 were found in non-neoplastic dermatological diseases, including autoimmune related pathologies. Values were normal (396 +/- 170 U/ml) in patients affected by Stage 1 melanoma, but increased (558 +/- 291 U/ml) in cases with visceral involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Plasma protein's glycation is decreased in Sprague Dawley rats under caloric restriction.

Different dietary regimens were applied to three cohorts of rats. The first was fed ad libitum every day (AL), the second was fed ad libitum every other day (EOD) and the third was fed a diet equivalent to 60% of the caloric intake (60% CI) of the AL cohort. Levels of stable early glycation products in plasma proteins were then measured according to two different methods. Glycation of plasma proteins progressively increased in AL animals belonging to the 2-12 month age interval, while it showed a less pronounced age-dependent increase in EOD and 60% CI animals. The lowest degree of glycation was detected 2-3 months after the beginning of caloric restriction. After 12 months of age a lower level of glycation was detected in 60% CI rats than in EOD animals. Body weight was lower in restricted animals than in AL animals and was lowest in 60% CI rats. During the life span, glycemia was lower in fasting 60% CI than in EOD or AL rats.

Journal Article↗

Age-dependent changes in insulin-like immunoreactivity in rat submandibular salivary glands.

In recent years, a growing interest had arisen in hormonal factors in salivary glands. We have investigated the changes in the content of an insulin-like immunoreactive (ILI) compound in the submandibular salivary glands of Sprague Dawley rats during physiological aging, in the range 15 days-27 months. The amount of ILI in the submandibular glands of young adult rats was found to be doubled in the post-natal period until the age of puberty and was maintained in senescence. No significant correlation was found between age-dependent variations in ILI levels of submandibular salivary glands and circulating insulin concentrations, further supporting previous indications that ILI is being synthesized in situ. It is possible that ILI could exert paracrine effects within the glands, as regards the development of other glandular structures during the first months of life, as well as the preservation of glandular function in senescent animals as well.

Age Factors↗

Peripheral blood involvement in a mycosis fungoides patient with limited skin lesions: phenotypical features and homing molecule pattern.

Peripheral blood involvement in mycosis fungoides (MF) patients is more frequent in the advanced stages and is associated with a worse prognosis. We report a MF patient with limited patch lesions on her shoulders, upper chest and thighs (T2N0M0) and peripheral blood involvement. Clonality in the peripheral blood was demonstrated by the PCR assay and confirmed by the expansion of the same restricted variable region of the TCR beta-chain (vbeta17) expressed in the cutaneous infiltrate. The patient was treated with fludarabine achieving a complete hematological response followed by an early relapse, whilst the cutaneous lesions remained unchanged. The soluble interleukin-2 receptor levels showed a decrease from baseline levels down to normal values at hematological remission, followed by a further increase. The low sLex/CLA expression in the cutaneous lymphoid infiltrate could have given rise to a higher recruitment in the peripheral blood.

Aged↗

[Choledochal calculosis due to a suture thread].

The authors recently observed a patient suffering from recurrent choledochal, postcholecystectomy calculosis caused by suture thread. Given the relative rarity of this pathology, the difficulty of preoperative diagnosis and the possible confusion with other anatomoclinical syndromes, they take this opportunity to make a number of diagnostic and therapeutic comments in the light of the latest literature on this subject.

Cholecystectomy↗