PubMed HealthSearch

Biomedical subjects

G Mancuso

Publications and source records attributed to G Mancuso.

At least 19 recordsLinked to original sources

Induction of tumor necrosis factor alpha by Leishmania infantum in murine macrophages from different inbred mice strains.

The present study was undertaken to determine whether the viscerotropic species, Leishmania infantum, endemic in Italy, could induce tumor necrosis factor alpha (TNF alpha) in murine macrophages. Genetically susceptible (Lshs) and resistant (Lshr) mice were used in the attempt to correlate TNF alpha production with the ability to control parasite growth and replication. Resident peritoneal macrophages of C3H/HeN, DBA/2, CBA (Lshr), C57BL/10 and BALB/c (Lshs) mice were infected in vitro with promastigotes at a parasite to cell ratio of 8:1. No significant differences in the percentages of infected peritoneal cells of Lshs versus Lshr mice were observed until 72 h of in vitro culture. On the contrary, Kupffer cells from Lshr mice inhibited Leishmania replication. Peritoneal macrophages of resistant mice produced significantly higher amounts of TNF alpha as compared to susceptible mice. TNF alpha production of both resistant and susceptible mice peaked at about 5 h after the challenge with the parasite. No TNF alpha was found in supernatants of infected Kupffer cells from all the strains tested. The ability of macrophages from susceptible or resistant mice strains to produce TNF alpha after challenge with Leishmania infantum does not seem related to their capacity to control parasite replication in vitro.

Animals

Specificity and protective activity of murine monoclonal antibodies directed against the capsular polysaccharide of type III group B streptococci.

We have obtained 41 monoclonal antibodies directed against type III group B streptococci by immunizing Balb/c mice with formalin-killed bacteria. All of these antibodies reacted with purified type-specific carbohydrate by enzyme-linked immunosorbent assay and immunoprecipitation tests. The epitope recognized by all of these antibodies was associated with terminal sialic acid residues, as indicated by abrogation of immune reactions by treatment of the type-specific carbohydrate with neuraminidase. Two purified monoclonal antibodies (the IgM P9D8 and the IgG3 P4F12) were further characterized for their protective activity in a neonatal rat model of infection. P9D8 and P4F12 antibodies were significantly protective when administered in a dose of 0.5 and 2.5 mg/kg, respectively, at the same time as 3 x 10(5) colony forming units of type III streptococci. Protection was still observed when the antibodies were given up to 9 h after challenge. No protection was afforded against infections with type Ia/c and II streptococci. Similarly, both antibodies effectively opsonized type III, but not Ia, Ib or II bacteria, in an in vitro assay. These and similar, previously described, monoclonal antibodies may be useful, possibly after "humanization" by genetic engineering, for the therapy of neonatal group B streptococcal infections.

Animals

GH assessment and three years' hGH therapy in girls with Turner syndrome.

Fifteen girls with Turner syndrome (TS) were submitted to GH secretion assessment before undergoing hGH therapy. In the first 9 months, hGH was given at a dose of 0.5 IU/kg/week s.c. daily; afterward, the dose was increased to 1 IU/kg/week s.c. daily. The girls were prepubertal, with a mean (SD) chronological age (CA) of 12.5 (2.6) years, and a mean (SD) bone age of 10.5 (1.8) years. A clonidine stimulation test, 1-29 GHRH test and GH spontaneous nocturnal secretion assessment were performed in all patients. Results showed a variable pattern of GH secretion in 10 patients, in only 2 did we find all values definitely normal, and in 3 we found a total GH deficiency. Height velocity, expressed as standard deviation scores (SDS) for CA according to Turner references, during the first year of treatment increased significantly: 0.36 (1.15) -3.30 (2.87) (p < 0.001), and the increment remained quite unchanged during both the second and third years: 3.16 (2.96) and 2.55 (3.87), respectively (n.s.). Height, expressed in SDS for CA for Turner references, increased significantly throughout the whole period of treatment and reached the highest value at the end of the third year of therapy. GH secretion parameters poorly correlated with pretreatment auxological data or response to treatment. Our long-term study confirms that in TS GH measurement is not useful in indicating hGH therapy or in predicting the response.

Adolescent

Production of tumor necrosis factor-alpha and interleukin-6 in mice infected with group B streptococci.

Group B streptococci (GBS) are a leading cause of sepsis and meningitis in neonates. Since cytokines are thought to play an important role in septic shock, we have studied serum levels of tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) in BALB/c mice infected with type III GBS. TNF alpha and IL-6 were detected by the L929 cytotoxicity and the B9 proliferation assays, respectively, in serial serum samples obtained after infection. After i.p. challenge with an LD50, serum TNF alpha rose above baseline values as early as 3 hr, peaked at 7 hr, and returned to baseline values at 20 hr. IL-6 serum levels rose concomitantly with TNF alpha, peaking 8 hr after challenge. No serum TNF alpha activity was detected in the course of sublethal infections. However, a transient rise in TNF alpha levels was observed after i.v. inoculation of high numbers (greater than or equal to 1 x 10(8) of heat-killed GBS. When groups of mice were injected i.v. with a single dose of anti-TNF alpha rabbit serum 2 hr before challenge with an LD90 or LD30, no effect was noted in terms of survival, although the serum TNF alpha peak was completely abrogated. Serum TNF alpha does not seem to play an obligatory role in GBS-induced lethality of adult mice. However, further studies are needed to assess better the role of this cytokine in the pathogenesis of GBS sepsis.

Animals

Modulation of the intrinsic antiviral activity by Escherichia coli endotoxin in macrophages from patients with neoplasia.

Macrophages from patients with breast cancer showed an impairment of their antiviral activity. The capability to hinder herpes simplex virus type 2 replication of macrophages from healthy donors and from patients with breast cancer was compared to the in-vitro treatment with Escherichia coli lipopolysaccharide (LPS). The LPS showed a dose-dependent effect on the different macrophage populations studied. Nevertheless, macrophages from healthy donors appeared to be more sensitive to LPS in comparison with macrophages from the patients under our observation. On these cells LPS treatment was not able to modify the antiviral property, when these macrophages were differentiated in autologous serum.

Analysis of Variance

Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent.

Hemophilia A (HA), a common inherited bleeding disorder in humans, is due to the deficiency or absence of the factor VIII (FVIII) activity. The cloning of the FVIII gene has made molecular probes available for the characterization of the basic defect in this disease. In this study we describe six different mutations in the FVIII gene detected by DNA analysis of 100 HA patients of Italian descent. In two of them, with a severe clinical picture, we identified two novel deletions, one in the middle of the FVIII gene from exons 7 to 22 and the other encompassing the entire factor VIII gene. Both of these patients produced antibodies to factor VIII. In a patient with mild HA we detected a duplication of exon 13, which is a rearrangement not yet described within the FVIII gene. A possible explanation for the mild phenotype in this patient is that the molecular defect results in the production of an unstable FVIII protein with residual 10% FVIII activity. Screening by Taq I restriction endonuclease detected three mutations that were further characterized by direct sequencing on amplified DNA: a C-T substitution at codon 1960, in exon 18, converting the codon for arginine to a non-sense codon; and a G-A substitution at codon 2228 and 2326, in exons 24 and 26 respectively, resulting in the substitution of glutamine for arginine. All three of these mutations have been previously described. The non-sense mutation and the codon 2228 G-A mutation was found in patients with severe HA, while the codon 2326 G-A mutation was associated with a quite severe condition. These results confirm that the molecular bases of HA are very heterogeneous and provide further evidence that recurrent mutations are not uncommon in this system.

Base Sequence

Occupational dermatitis in animal feed mill workers.

In an epidemiological study of occupational dermatitis in 15 different northern Italian animal feed mills, 204 workers were interviewed, examined and patch tested to 34 allergens, selected from the additives most commonly used in the animal feed mills under consideration. The prevalence of occupational contact dermatitis was 13.7% (28/204): 7.8% (16/204) irritant contact dermatitis and 5.8% (12/204) allergic contact dermatitis from animal feed additives. Among the latter, there were sensitizations, to our knowledge hitherto unreported in the literature: to indigo carmine (2 cases), monensin sodium (1 case), thiabendazole (1 case), methylchlorpindol (1 case) and amprolium hydrochloride (1 case). 3.9% (8/204) of the workers complained only of pruritus sine materia on exposed areas of the body. Contact dermatitis increased with respect to duration of employment: the difference in the rate of contact dermatitis between workers employed in animal feed mill for greater than 10 years and those employed for less than 10 years was statistically significant (p less than 0.05). 6.8% (14/204) had latent sensitivity, which was more frequent in workers with less than 1 year of employment with respect to more experienced colleagues.

Adult

Cutaneous necrosis and calcinosis following electroencephalography.

The authors report 2 children who developed circumscribed dystrophic calcifications at the site of electrode placement after electroencephalographic examination. Deep cutaneous necrosis was a prominent clinical feature. A biopsy showed focal dermal calcification confirmed by a diffractometer analysis of a calcific granule. Cutaneous calcinosis is a possible risk of the usage of an electrode paste containing calcium chloride. Prolonged exposure and damaged skin seem to be prerequisites for this uncommon but harmful condition.

Calcinosis

Role of Salmonella enteritidis lipopolysaccharide on anti-HSV activity of macrophages from different anatomical sites.

It is generally agreed that endotoxins from Gram-negative bacteria play a modulatory role on several macrophage functions. The intrinsic activity versus herpes simplex virus type 1 and type 2 of Kupffer cells, peritoneal and alveolar macrophages, harvested from normal and tumour-bearing rats, was evaluated. Moreover, the effects of different intravenous treatments with S. enteritidis endotoxin were investigated. The antiviral activity of peritoneal, alveolar macrophages and Kupffer cells from tumour-bearing rats is definitely impaired but it appears to be positively modulated by in-vivo administration of S. enteritidis lipopolysaccharide (LPS).

Animals

Treatment of acute idiopathic thrombocytopenic purpura (AITP): cooperative Italian study group results.

A cooperative Italian study group on acute idiopathic thrombocytopenic purpura (AITP) has been designed to evaluate efficacy and safety of no treatment at the onset of the disease and sequential treatment with immunoglobulin and high dose steroid. One hundred thirty-eight patients with AITP entered in the trial. Eleven patients were treated before the end of the waiting period because of bleeding. One hundred twenty-seven (92%) received no treatment for the first 10 days of the disease, 65 patients (51.18%) recovered spontaneously, 62 patients were treated with immunoglobulin, and 52 (83.8%) of them responded positively but only 36 (58.06%) permanently. There was no statistical difference between the results obtained with 400 mg/kg for 5 days versus 200 mg/kg. Twenty-four patients were treated with high doses of steroids, 20 (83.3%) with positive response, and 10 (41.66%) were permanently cured. Four (3.14%) of the patients enrolled in the protocol still had active disease at the end of treatment, and 10 relapsed within 4 months after the end of the treatment.

Adolescent

AIDS in Sicily: prevalence of antibodies to human immunodeficiency virus (HIV) in low and high risk groups.

A seroepidemiological survey, carried out to evaluate the prevalence of antibodies to HIV in patients with ARC and in healthy individuals at risk for AIDS, showed the infection to be widespread in the groups at risk, namely in drug abusers and hemophiliacs. However, remarkable difference existed between the prevalence of antibodies to HIV in drug abusers of the city of Palermo and those of other Sicilian provinces. Spread of the virus among Sicilian thalassemics, however, was very low and quite similar in all geographic areas. Antibodies were found very rarely (0.06%) in unpaid voluntary blood donors. The spread of the virus is still confined in high risk groups, and the major part of the seropositive blood donors were identified a posteriori as drug abusers.

AIDS-Related Complex

Seeking clues for a positive diagnosis of the irritable bowel syndrome.

Despite its high prevalence the irritable bowel syndrome (IBS) lacks acceptable pathophysiological markers and its diagnosis largely depends on the exclusion of underlying organic disease. Systemic acid-base balance, serum electrolytes and the composition of faecal water (electrolytes and organic anions), were studied in thirty-eight diarrhoeal patients out of a series of ninety-three consecutive IBS patients. Only patients with diarrhoea as the predominant symptom were included in the study to evaluate whether this subgroup could provide the clue for a positive diagnosis of the syndrome. Serum electrolytes and systemic acid-base balance were within the normal range. Faecal electrolytes were also normal (Na 26.6 +/- 19.3 SD; K 66.8 +/- 28.3; Cl 19.1 +/- 15.2 mEq 1(-1)), despite the finding of a moderately increased 24-h faecal output. The K:Na ratio was also within the normal range. These data are in agreement with the lack of systemic changes observed in IBS patients even with profuse or longstanding diarrhoea. Both faecal short chain fatty acids and lactic acid were increased in patients vs. controls, but a considerable overlap with normal values was observed (131.4 +/- 62.6 SD vs. 108.5 +/- 58.3 mEq 1(-1). Only lactic acid concentration was significantly higher than in controls (1.3 +/- 1.2 vs. 0.5 +/- 0.2). Despite these findings it is concluded that the subgroup of IBS patients with diarrhoea also appears to lack a pathophysiological marker and does not provide clues for a positive diagnosis of this syndrome.

Acid-Base Equilibrium