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Biomedical subjects

S Moretti

Publications and source records attributed to S Moretti.

At least 127 records · Page 7Linked to original sources

Adhesion molecule profile and malignancy of melanocytic lesions.

The ability of melanoma cells to metastasize is largely dependent upon cell surface molecules that mediate cell-matrix and cell-cell interactions. Our aim was to investigate the expression of such molecules (adhesion molecules) on tissue sections of a series of melanocytic lesions in different stages of tumour progression. Four common naevi, four congenital naevi, four dysplastic naevi, three Spitz naevi, 20 primary melanomas and 15 metastatic melanomas were tested with an alkaline phosphatase/anti-alkaline phosphatase technique and a panel of monoclonal antibodies directed toward different alpha subunits of VLA receptors, beta 1, VNR-alpha and beta 3 subunit, and CD44 hyaluronate receptor. Only metastatic melanomas expressed the alpha 4 subunit, and only thick primary melanomas and metastases expressed the beta 3 subunit. The alpha 6/beta 1 chain was expressed at significantly higher levels on benign lesions, and a trend towards increased expression of alpha 2 and alpha 3 subunits was found in malignant versus benign lesions. Our results show that the pattern of integrin expression changes in melanocytic lesions along with malignant transformation.

Antibodies, Monoclonal↗

AIDS patients with bacterial lower respiratory tract infections: treatment with ofloxacin versus sulbactam-ampicillin.

In this open-label, randomized, parallel-groups study the Authors compare the parenteral administration of a beta-lactamase inhibitor associated with a semisynthetic penicillin (sulbactam-ampicillin) with the oral administration of a 3rd-generation quinolone (ofloxacin), in 20 HIV-infected subjects suffering from lower respiratory tract (LRT) infections. 12 patients were classified as AIDS, 6 as ARC (AIDS related complex) and 2 as asymptomatic seropositives. The risk of becoming HIV-infected and the work load for the health staff were also evaluated. The clinical and microbiological results indicate that oral ofloxacin is as effective as parenteral sulbactam-ampicillin for the treatment of LRT infections in HIV-positive individuals. In addition, the members of the health staff reported significantly less difficulty in administering ofloxacin in respect to sulbactam-ampicillin.

AIDS-Related Opportunistic Infections↗

The prognostic significance of histologic regression in cutaneous melanoma.

A retrospective evaluation of 201 stage I cutaneous melanomas was performed to investigate the prognostic significance of histological regression (present in 67 cases). Thin melanomas showed regression more frequently than thick lesions (48% less than or equal to 0.75 mm vs 12% greater than 3 mm). The mean disease-free interval was 33.53 months in regressing tumours and 19.9 in non-regressing tumours (p = 0.07): differences between the survival curves were not significant (p = 0.61). Metastases developed in 13 (19.40%) patients with regressing tumours and by 40 (29.85%) patients with non-regressing tumours. Although we observed a higher frequency of regression in thin melanomas we could not demonstrate an influence of regression on disease-free interval and survival.

Female↗

Increasing epidermal growth factor receptor expression in human melanocytic tumor progression.

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.

Blotting, Northern↗

Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes.

In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects.

Aged↗

[Fluorocytometric study of proliferation antigens, nuclear proteins and ploidy in acute leukosis].

P53 protein, Ki67 proliferative associated antigen and DNA content have been studied by flow cytometry in the blood blastic cells from 41 patients with acute leukemia. The results were compared with the F.A.B. classification. Cells were permeabilised and fixed by PLP solution before using the FITC conjugated Ki67 MoAb and the p53 MoAb (clone 1801). Propidium iodide and RNAase has been used in order to determine ploidy. Ki67 and p53 protein were found to be expressed at higher level in leukemia cells than in normal bone marrow cells; however there was no correlation between Ki67 and p53 expression and F.A.B. subtype. In acute leukemia patients the range of positivity of Ki67 was 1.1-52.1% while it ranged from 1.8% to 80.1% for the p53 protein. On the basis of these findings we conclude that the flow cytometry evaluation of Ki67 and p53 represents a useful tool for the study of the biologic characteristics of the leukemic cells in patients with acute leukemia.

Acute Disease↗

Expression of p53 gene in B-CLL peripheral lymphocytes.

The p53 tumor suppressor gene expression has been studied in 23 B-CLL cases at different clinical stages. The analysis failed to show a direct correlation with each stage, but the significantly lower frequency of a BglII RFLP in the pathologic population suggests a role of this gene in B-CLL. Northern Blot analysis showed the expression of p53 mRNA in all the B-CLL cases. A protocol for the RT-PCR methods was set up to study a very small amount of materials which should be better used for sequence analysis.

DNA, Neoplasm↗

BANS: a discussion of the problem.

The significance of the BANS location (upper Back, posterior Arm, Neck and Scalp) as a prognostic factor in patients with stage I melanoma is controversial. A meta-analysis performed by Weinstock et al. on their own and five comparable studies corroborated the hypothesis that this location is influential in the prognosis of intermediate thickness (0.76-1.69 mm) melanomas. Our study investigated the relationship between BANS subsites, thickness and prognosis in 1,082 stage I melanoma patients from two major Italian centres, Turin and Florence. A BANS primary was observed in 212 (19.5%) patients: recurrences occurred in 85 of them (40.1%) vs 309/870 non-BANS patients (35.5%). Overall survival probabilities were significantly shorter (p less than 0.01) in the BANS group (69.1% vs 76.7% at 5 years; 59% vs 68.5% at 10 years). The prognostic value of the BANS location was confirmed by a multivariate analysis using the Cox proportional hazards model. Stratification of BANS and non-BANS groups by thickness clusters showed a significant difference in both survival (p less than 0.001) and disease-free interval (p less than 0.05) in the 3.01-4.00 mm thickness subset, due to the greater incidence of distant and visceral metastases. In the 0.76-1.69 mm thickness range the significance was p = 0.06.

Adolescent↗

Cytochemically unreactive neutrophils from subjects with myeloperoxidase (MPO) deficiency show a complex pattern of immunoreactivity with anti-MPO monoclonal antibodies: a flow cytometric and immunocytochemical study.

Neutrophil granulocytes from 12 subjects with primary myeloperoxidase (MPO) deficiency (six totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO antibodies, in combination with either a flow-cytometric technique or an immunoalkaline phosphatase staining method. Results demonstrated three different cytofluorimetric patterns of immunoreactivity with the MPO protein: (a) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable to that observed in the control group); (b) a medium MPO antigenic expression, typical of subjects with primary partial MPO deficiency; and (c) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two antibodies. Furthermore, in two individuals with complete primary enzyme deficiency, the single histogram analysis of MPO fluorescence determined by flow cytometry seemed to show that only 38% (case 1) and 44% (case 2) of neutrophils were reactive with the anti-MPO antibodies: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrated that all the cells express a low density of MPO antigen. These data were more or less confirmed by the APAAP labeling method, which showed a reduced straining only in subjects with primary deficiency, while all patients with secondary deficiency had scores similar to those observed in controls (healthy subjects). Compared with the immunoenzymatic technique, the flow-cytometric procedure showed a higher sensitivity to MPO, being able to estimate even minor decreases in neutrophil MPO antigenic expression, as previously postulated by other authors. This work suggests that patients with primary MPO deficiency have different amounts of MPO antigens in the neutrophil granulocytes, and the levels of MPO fluorescence seem to decline concurrently with the enzyme activity, thereby suggesting the presence of a diminished MPO production. In contrast, the normal antigenic reactivity of neutrophils from patients with acquired MPO deficiency indicates the presence of a functionally inactive form of the enzyme.

Antibodies, Monoclonal↗

Inosine pranobex in the treatment of HIV infection: a review.

Inosine pranobex (InPx) could prove a valuable and innovative approach to the treatment of HIV-infected patients, since InPx administration has been shown in two multicenter trials to effectively delay the progression of HIV infection to overt AIDS. However, further studies are strongly required to optimize both the dosage of inosine pranobex and the administration schedules. Furthermore, clinical trials evaluating combination therapy of HIV infection with both InPx and zidovudine should ultimately provide an important advance in the management of HIV-infected patients. Our finding that concomitantly administered InPx to zidovudine-receiving patients increased the plasma levels of zidovudine as well as prolonged zidovudine mean half-life during InPx treatment suggests several potential advantages of the combination treatment with both InPx and zidovudine, such as a need for lower zidovudine dosage and a longer interval period between administering zidovudine to obtain sustained plasma levels as well as a potential to enhance residue immune function resulting from inosine pranobex treatment.

Drug Therapy, Combination↗

The effect of tarsorrhaphy on normal healing of corneal epithelial defects in a rabbit model.

The presumed benefits of occlusive patching are patient comfort and enhancement of corneal healing. However, there is little experimental evidence to document a beneficial effect of eyelid occlusion on corneal healing. We produced corneal abrasions by mechanical debridement within a 4 mm trephine-marked area on 1 eye each of 23 New Zealand albino rabbits. Homatropine 5% solution and erythromycin ointment were instilled. Then we divided the animals into three groups. The abraded eyes of the first group (7 rabbits) were sutured shut by a temporary tarsorrhaphy. The eyes of the second group (7 rabbits) were left open until 12 h postinjury, when they were sutured shut in a similar fashion. The abraded eyes of the control group (9 rabbits) were left open for the entire observation period. We monitored fluorescein staining patterns of the epithelial defects photographically at a set focal length at 12-h intervals. By 48 h, corneal staining had resolved in 87% of eyes. We performed computerized planimetry on the photographs of wound size for each time point. There was no statistically significant difference in the rate of healing of corneal abrasions in the occluded versus of the unoccluded eyes.

Animals↗

Open randomized controlled parallel study of ofloxacin versus trimethoprim-sulfamethoxazole treatment of lower respiratory tract and urinary infections.

A total of 60 patients with lower respiratory tract or urinary tract infections were enrolled in an open, randomized, controlled, parallel study comparing 300 mg ofloxacin (OFX) b.i.d. with trimethoprim + sulfamethoxazole (TMP 800 mg + SMX 160 mg), 1 tablet, b.i.d. The signs and symptoms of low respiratory tract infection were cured in 12 patients (80%) of the OFX group and improved in 2 other patients (13%); at the end of therapy, the 2 germs that persisted were Streptococcus pneumoniae and Branhamella catarrhalis. Clinical cure was achieved in 13 patients (86%) in the TMP-SMX group, while 2 patients were considered as failures (14%); after therapy, the 3 organisms that persisted were 2 S. pneumoniae and 1 Pseudomonas aeruginosa. As far as urinary tract infections are concerned clinical cure and complete eradication of bacteria were achieved in 14 patients in the OFX group (93%); the germ that persisted was Escherichia coli (100,000 CFU), but the patient was asymptomatic. In patients of the TMP-SMX group the urinary infections were cured in 11 subjects (73%); the germs that persisted were 2 E. coli and 1 Proteus mirabilis. Adverse effects were reported for 3 patients (10%) in the OFX group and 4 patients (13%) in the TMP-SMX group. The measurement of serum and intracellular (polymorphonuclear cells and lymphocytes) levels of OFX and TMP-SMX and the assessment of the host's immunocompetence ruled out the possibility of any immunotoxicological side effect.

Acute Disease↗

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↗

Langerhans cells and mycosis fungoides--a critical overview of their pathogenic role in the disease.

Skin biopsies from seven patients with mycosis fungoides in various clinical stages (patches, plaques, nodules) were studied immunohistochemically and ultrastructurally, with the aim of investigating and quantifying the distribution of Langerhans cells and their relationships to mycosis cells. Our findings have revealed that in patches and plaques both Langerhans cells and mycosis cells were numerous in the epidermis. Notwithstanding this, in all the specimens examined, only one Langerhans cell forming close contact with a mycosis cell was detected. In the nodules, Langerhans cells and mycosis cells were sparse in the epidermis and no contacts were seen between them. Moreover, in all the patients studied, only a single Langerhans cell was found in the dermal infiltrate without any closely related mycosis cells. Conversely, numerous interdigitating cells have been found in the dermis of patches and plaques, often tightly adhering to mycosis cells. In the nodule, a few scattered interdigitating cells were seen, but often these had close contacts with neoplastic lymphoid cells. These findings indicate that close apposition between Langerhans cells and mycosis cells, which led previous authors to hypothesize a persistent stimulatory action of Langerhans cells on T lymphocytes, eventually leading to the malignant transformation of the latter, is unusual in mycosis fungoides. Therefore, if such a pathogenic role may be attributed to accessory cells in mycosis fungoides it is more probably exerted by dermal interdigitating cells and not by Langerhans cells, as previously proposed.

Humans↗

HLA-DR and 96-K antigens and intratumoral lymphocytic infiltrate in primary cutaneous melanoma as markers of tumor progression.

It was recently demonstrated that HLA-DR antigens in primary melanomas are correlated with 96-K antigen expression and with the presence of an intratumoral lymphocytic infiltrate (ILI). As HLA-DR antigens are known to be associated with advanced phases of tumor progression in melanocytic lesions, we investigated whether primary melanomas in different progression phases could be distinguished on the basis of the expression of HLA-DR and 96-K antigens and of the presence of an ILI. A concordant presence of the two antigens and of an ILI was frequent both in vertical growth pattern melanomas and in melanomas thicker than 1 mm. On the contrary, both antigens and the ILI were frequently absent both in thin melanomas (less than 1 mm) and in radial growth pattern melanomas. These observations suggest that a joint study of HLA-DR and 96-K antigens and of the ILI is useful to define the phase of progression of primary melanomas.

Antibodies, Monoclonal↗

[The use of dynamic electrocardiographic monitoring in scleroderma patients].

A comparative analysis of arrhythmias by "basal" electrocardiogram (ECG) and by continuous 24-hour Holter electrocardiogram monitoring was performed in 17 patients with systemic sclerosis (16 women and one man). Our study confirms that rhythm disturbances are better detectable using Holter monitoring. In fact, no patients had ventricular arrhythmias detected by ECG; on the contrary, Holter monitoring revealed ventricular arrhythmias in nine patients (53.3%). This method also revealed a ventricular tachycardia, not detected by ECG. In two patients ventricular repolarisation abnormalities without symptoms was revealed.

Adult↗