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M Novelli

Publications and source records attributed to M Novelli.

At least 55 records · Page 3Linked to original sources

CD56-positive cutaneous lymphoma: a poorly recognized entity in the spectrum of primary cutaneous disease.

CD56-positive (CD56+) lymphomas, characterized by the expression of the neural cell adhesion molecule on pathological lymphocytes, share a frequent extranodal involvement and a generally aggressive course. Five CD3- CD56+ lymphoma patients presenting with nodular lesions were identified among 180 immunophenotyped cutaneous lymphomas. All the patients were men, with ages ranging from 55 to 78 years. After staging, two patients were diagnosed as having primary cutaneous lymphomas; the remaining three had the secondary cutaneous type. The clinical course was aggressive and four patients died within 8 months from diagnosis. The remaining patient is still alive after a 17-month follow-up. The histological diagnosis was immunoblastic lymphoma in two patients, and medium and large cell pleomorphic lymphoma in three. The angiocentric infiltrate was located mainly in the dermis; azurophilic granules were present in three of the five patients. Immunogenotypic analyses suggested the natural killer cell origin of these neoplasias: all cases exhibited a CD56+ CD3- CD5- T-cell receptor (TCR) silent phenotype, and Southern blot analysis showed a germline configuration of the TCR beta-chain gene.

Aged↗

Determination of glycated hemoglobins in the rat: comparison between two different chromatographic methods and application in experimental diabetology.

Due to the unusual presence of several different hemoglobin components in the rat, determination of glycated hemoglobin (Hb) has been considered difficult and often unreliable in this animal species. In the present study, we compare a fully automated high-performance liquid chromatographic (HPLC) method of analysis of glycated hemoglobin that has been assessed for clinical use with an affinity chromatography technique using boronate micro-columns; we used blood samples taken from Sprague-Dawley rats of various ages and streptozotocin-diabetic rats. In nondiabetic rats, the sum of HbA1c and other minor glycated hemoglobins separated by the HPLC method is close to the total glycated hemoglobin obtained by affinity chromatography for each age group of animals. In diabetic rats, the glycated hemoglobins measured by whatever method show a linear increase during the first 3 weeks following streptozotocin administration, with the difference that glycated hemoglobin values obtained by affinity chromatography are markedly higher than those obtained by HPLC technique. Interestingly, a comparative determination of glycated hemoglobin in diabetic patients gives the same results with both methods. Therefore, it appears that in the rat, unlike man, at high glucose concentrations glycation occurs preferentially at the amino groups of hemoglobin components, which are not separated by the HPLC method. Our results indicate that while affinity chromatography should be used to detect the total extent of hemoglobin glycosylation in diabetic rats, the utilization of rapid and automatized HPLC procedures can be a very convenient alternative for the determination of glycated hemoglobin in both euglycemic and hyperglycemic rats.

Animals↗

Effects of tryptophan load on amino acid metabolism in type 1 diabetic patients.

Tolerance to an oral tryptophan load (50 mg/kg body weight) was evaluated in a group of 15 insulin-dependent diabetic patients of both sexes in poor metabolic control. Tryptophan was measured fluorometrically, and the plasma levels of the other physiological amino acids were determined by HPLC. The ratio of the plasma concentration of each large neutral amino acid (LNAA) to the sum of the others was calculated to serve as an index for the competitive transport of these amino acids into the brain. The results show that post-loading plasma tryptophan levels in diabetic patients increased less than in healthy controls, suggesting enhanced liver catabolism of this amino acid (as reported for diabetic animals). Small changes were observed in the post-loading plasma concentrations of other amino acids. Therefore, the increment in the tryptophan/LNAA ratio in controls (basal, 0.12 +/- 0.01; 120 min after the load, 0.89 +/- 0.04; 240 min, 0.51 +/- 0.03) was greatly attenuated in diabetic patients (basal, 0.11 +/- 0.01, NS; 120 min, 0.46 +/- 0.04, p < 0.01; 240 min, 0.31 +/- 0.04, p < 0.01). Post-loading excursions in some other ratios were slightly larger in control than diabetic subjects. These differences, which may occur to a lesser extent after a protein-rich meal, could modify the availability of precursor amino acids to the brain for synthesis of neurotransmitters. Thus, as happens in certain animal species, an impairment of the post-absorptive accumulation of tryptophan and serotonin in the brain may occur in diabetic patients as a result of altered metabolic disposal of tryptophan.

Adult↗

Keratinocytes express dipeptidyl-peptidase IV (CD26) in benign and malignant skin diseases.

CD26 expression on keratinocytes, in both normal and pathological skin, was investigated using immunohistochemical techniques. A sporadic focal CD26 positivity was found in normal skin, whereas increased expression of CD26 was observed both in cutaneous T-cell lymphomas and in inflammatory skin diseases, e.g. psoriasis, lichen planus and spongiotic dermatitis, in the basal and spinous layers. CD26 keratinocyte staining was not specific for a single disease, but seems to be associated with the presence of a reactive or neoplastic infiltrate in the epidermis. We propose that the CD26 molecule may function as a keratinocyte activation antigen.

Adult↗

Impairment of the priming effect of glucose on insulin secretion from isolated islets of aging rats.

The time-dependent potentiation (TDP) of insulin release or priming effect exerted by glucose was evaluated in the islets of Langerhans of mature and old rats. Islets isolated from 12- and 26-month-old male Sprague-Dawley rats and incubated for two consecutive 60-min periods in the presence of various stimulating agents were unable to enhance their insulin responsiveness significantly during the second incubation period and showed other abnormalities in their sensitivity to secretagogues compared with islets from 3-month-old animals. The priming action of glucose plus arginine or isobutylmethylxanthine (IBMX) was not observed in islets from 12-month-old rats, but surprisingly, islets from senescent rats showed a restoration of the beta-cell memory in the presence of IBMX. Interestingly, the islets isolated from 2-month-old animals previously exposed to an intravenous glucose load in vivo released approximately twice as much insulin as the islets taken from fed rats not subjected to the load. This potentiation exerted by the intravenous glucose administration was reduced but not abolished in the islets of glucose-intolerant, 12-month-old rats. In conclusion, the glucose TDP of insulin secretion is impaired in islets of mature and old rats, confirming an early loss of sensitivity of beta-cells to secretagogues during aging.

1-Methyl-3-isobutylxanthine↗

Adjuvant therapy of stage IIIb melanoma with interferon alfa-2b: clinical and immunological relevance.

BACKGROUND: The poor prognosis of stage IIIb melanoma (5-year survival: 36%) shows the need for effective adjuvant therapy to prolong disease-free survival. OBJECTIVE: The feasibility and efficacy of interferon alfa-2b (IFN-alpha) therapy in stage IIIb melanoma patients was investigated. METHODS: alpha-IFN was given at a dose of 3 MU i.m. three times a week to 50 patients. Clinical and immunological controls were carried out. RESULTS: The median follow-up was 43 months (range 5-84). Median survival was 43 months and median disease-free survival 39 months. Overall 5-year survival (62%) was higher than that reported in the literature to date. A significant increase of circulating CD56+ and DR+ lymphocytes after therapy was more evident in disease-free patients than in those with progressing disease. CONCLUSIONS: Adjuvant IFN-alpha therapy in stage IIIb melanoma patients is well tolerated and seems to increase survival. However, multicenter randomized trials are needed to confirm these preliminary findings.

Adult↗

Mantle zone lymphoma: an immunohistologic study of skin lesions.

BACKGROUND: Mantle zone lymphoma (MZL) is a B-cell proliferation regarded as the follicular variant of intermediate lymphocytic lymphoma (ILL). Neoplastic small lymphoid cells proliferate as wide mantles around atrophic centers of benign appearance. OBJECTIVE: The clinical, histologic, and immunohistochemical features of four cases of MZL, heralded by cutaneous lesions, are described and correlated with the lymph node pattern. RESULTS: All specimens showed extensive nodules in the reticular dermis invading the subcutaneous tissue. They were mainly composed of a proliferation of small lymphocytes with slightly irregular nuclear contours and clumped chromatin, forming wide mantles around small atrophic germinal centers. Serial biopsy specimens in case 1 revealed evolution of the skin lesions from pseudolymphoma into MZL. Their immunohistochemistry was similar to that of lymph nodes and showed that the neoplastic cells were CD5+, CD20+, CD22+, CD25+, CD74+, Leu-8+, HLA-DR+, IgM+, IgD+ with restriction for the lambda light chain, CD10-, and CD71-, whereas the germinal center cells were polyclonal. In three cases many CD38+, PCA-1+ plasma cells were present both in the grenz zone and in bordering neoplastic nodules. The clinical course was chronic. The only death occurred from unrelated causes; one patient is still alive 17 years after onset. CONCLUSION: Skin lesions may be the only manifestation of MZL for an extended period. The differentiation between pseudolymphoma and other lymphoma subtypes is based not only on the histologic and cytologic features but also on the architecture, followed by immunohistochemical confirmation.

Adult↗

Adhesion molecules in lymphomatoid granulomatosis.

The expression of some adhesion molecules of the integrin family and their ligands was investigated in skin biopsies from a patient with lymphomatoid granulomatosis (LG), who at onset presented cutaneous lesions followed by lung and brain involvement. The angiocentric and angiodestructive skin infiltrate consisted mainly of T helper 'memory' cells (CD2+, CD3+, CD4+, CD5+, CD7+, CD45RO+) with a variable expression of activation antigens (CD25-, CD38+, CD71+, HLA-DR+) and 20% Ki67+ (nearly all atypical cells). T cells highly expressed alpha 3 beta 1 and alpha 5 beta 1 integrins, along with integrins of the beta 2 family. A modification of the expression pattern in laminin and collagen IV and an increased expression of tenascin and fibronectin were also observed.

Cell Adhesion Molecules↗

Our experience in pancreatic trauma.

The authors, with this works, call fellow members attention, how is complicate the diagnosis and the following surgical treatment of the associated lesions caused by pancreatic trauma. The pancreatic traumas are today object of discussion for the surgical treatment, and for the lesions associated. In this work is described the experience of some years accumulated in the Emergency Department of the Liguria Region.

Adolescent↗

Beneficial effects of the oral administration of vanadyl sulphate on glucose metabolism in senescent rats.

We investigated the effects of the oral administration of vanadyl sulphate (0.5 mg/ml in the drinking water) on glucose homeostasis of 3-month- and 24-month-old rats. Results show that aging is associated with alteration of the oral glucose tolerance test and impairment of the postprandial accumulation of glycogen in skeletal muscles and that the oral administration of vanadyl sulphate rapidly normalizes the inbalance of glucose metabolism in senescent rats. It is suggested that vanadate administration may restore the ability of skeletal muscles of senescent rats to respond to circulating insulin efficiently.

Administration, Oral↗

Soluble interleukin-2 receptor in Sézary syndrome: its origin and clinical application.

Soluble interleukin-2 receptor (sIL-2R) serum levels were evaluated in Sézary syndrome (SS), mycosis fungoides, non-epidermotropic T-cell lymphomas, inflammatory skin diseases (eczema, psoriasis and lichen planus) and benign erythroderma. All groups displayed mean values significantly higher than controls, and values in SS were also significantly higher than those in the other diseases investigated. Follow-up of 17 SS patients showed that serum sIL-2R correlated with the clinical course of the disease and with other haematological parameters (absolute number of circulating Sézary cells, lactic dehydrogenase). Culture experiments demonstrated that, in contrast with other haematological disorders, highly enriched resting Sézary cells were unable to release sIL-2R, and failed to release normal amounts even after mitogen stimulation. Nevertheless, the leukaemic burden, together with the activation and consequent CD25 expression of leukaemic lymphocytes infiltrating the skin, may justify the hypothesis of a neoplastic sIL-2R source. To further support this hypothesis, the highest sIL-2R values were found in patients with advanced disease, in which normal reactive lymphocytes were dramatically reduced.

Adult↗

Necrobiosis lipoidica--involvement of atypical sites.

Necrobiosis lipoidica (NL) has distinctive clinical and histological appearances. The legs are the commonest site of involvement, and 85% of cases involve the legs exclusively. We describe a patient in whom NL did not involve the legs, but was found to occur on unusual areas: the back and nipple. This is possibly the first report of NL affecting the nipple.

Adult↗

Therapy for metastatic melanoma: effective combination of dacarbazine, carmustine, cisplatin and tamoxifen.

Thirty-two patients with metastatic melanoma received combination chemotherapy and hormonal therapy. Treatment included Carmustine, Cisplatin, Dacarbazine and Tamoxifen (BCDT). The overall response rate was 47%: five patients had a complete response (16%), 10 patients had a partial response (31%) and two had no response (6%). The median survival for responders was 10 months (range 2-20). The BCDT regimen was equally effective against soft tissue and visceral metastases. Neither survival or response rate was modified by pretreatment with alpha-interferon (alpha-IFN). In agreement with the results of a recent randomized trial comparing the efficacy of Dacarbazine with that of Dacarbazine plus Tamoxifen, a better survival was found in women than in men: although the response rate was identical (47%), the median duration of response was higher for women. A fall in serum soluble IL-2 receptor (sIL-2R) levels after therapy was seen in responding patients, confirming the usefulness of this parameter in monitoring disease evolution.

Adult↗

Thymopentin in Sézary syndrome.

BACKGROUND: Response to the treatment of Sézary syndrome (a cutaneous T-cell lymphoma) is poor. Since patients with this syndrome are elderly, aggressive chemotherapy is poorly tolerated and deep immunodepression may result in fatal opportunistic infections. Immunomodulating therapy seems important in the management of Sézary syndrome. PURPOSE: In a pilot study, we assessed the efficacy of thymopentin (TP-5), a synthetic pentapeptide, correlating clinical responses to the histologic and immunologic effects of the drug. METHODS: Twenty Sézary syndrome patients received 50 mg TP-5 intravenously three times a week for a mean time of 16.3 months. Skin and lymph node histology and immunohistochemistry, circulating lymphoid cell subpopulations, and soluble interleukin-2 receptors were evaluated before treatment and during follow-up. RESULTS: Eight complete remissions and seven partial remissions were obtained (75%). No change was observed in three patients, and disease progression was observed in two patients. The median duration of response was 22 months (complete remission, 25.5 months; partial remission, 14 months). Four-year survival probability was 53.9%. The responses were obtained when circulating Sézary cells were less than 2600/mm3. A significant reduction of CD4+ cells paralleled a CD8+ cell increase. An increase in NK cells (CD16+ and CD56+) was accompanied by significantly longer survival. Serum soluble interleukin-2 receptor values were a useful monitor of the clinical course and treatment. Loss of epidermotropism, reduction of Langherhans' cells, and HLA-DR+ keratinocytes were found. CONCLUSIONS: TP-5 is a potentially useful agent in the treatment of a subgroup of patients with Sézary syndrome; its activity seems to be mediated by an effect on a normal NK cell-like subpopulation. IMPLICATIONS: The biological and clinical role of this therapy in combination with conventional treatments will be the subject of future investigations.

Aged↗