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Biomedical subjects

L Nigro

Publications and source records attributed to L Nigro.

At least 19 recordsLinked to original sources

Ribavirin up-regulates IL-12 p40 gene expression and restores IL-12 levels in Leishmania-treated PBMCs.

Ribavirin, a nucleoside analogue that interferes with viral mRNA synthesis and inhibits the replication of RNA and DNA viruses, has been recently proposed as an effective immune response modulator. In the present report, we studied the effect of ribavirin on IL-12 p40 gene expression in peripheral blood mononuclear cells (PBMCs) of healthy subjects. We also studied ribavirin effects on PBMCs activated with lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) and treated with Leishmania donovani antigens. We provide evidence that ribavirin was able to up-regulate IL-12 p40 gene expression and to restore levels of IL-12 p40 gene expression and IL-12 secretion in fully activated PBMCs that were strongly inhibited by L. donovani antigens. Because effective management of leishmanial disease is usually associated with a prevalent T-helper 1 immune response with elevated production of IL-12,our preliminary results may be of particular interest, provided that they will be confirmed by further in vitro and in vivo studies, when considering a possible use of ribavirin as adjuvant in severe leishmanial disease.

Adolescent↗

Reduction of serum melatonin levels in HIV-1-infected individuals' parallel disease progression: correlation with serum interleukin-12 levels.

BACKGROUND: During the natural history of human immunodeficiency virus type I (HIV-1) infection, an impairment of interleukin-12 (IL-12) production precedes a switch from a T-helper 1 (Th1) to a T-helper 2 (Th2) stage of cellular immunity. Melatonin, the main hormone produced by the pineal gland, seems to promote a Th1 response by increasing the production of IL-12 in vitro. The aim of this study was to measure and correlate serum levels of melatonin and IL-12 in a cohort of HIV-1-infected individuals. PATIENTS AND METHODS: 77 anti-HIV-1-positive subjects were enrolled: 20 were in CDC stage A, 25 in CDC stage B and 32 in CDC stage C. 30 healthy HIV-1-seronegative subjects were recruited as controls. IL-12 and melatonin concentrations were quantitated in serum samples. RESULTS: Mean levels of serum melatonin were significantly lower in HIV-1-infected individuals in comparison with controls (p < 0.001). Within the HIV-1-seropositive group, mean melatonin and IL-12 concentrations were significantly lower in patients in CDC stage C, as compared with patients in CDC stages B and A (p < 0.01). CONCLUSION: During the natural history of HIV-1 disease, serum melatonin levels are progressively reduced. This reduction may be related to the impairment of Th1 immunoresponses.

Analysis of Variance↗

Visceral leishmaniasis in those infected with HIV: clinical aspects and other opportunistic infections.

Cases of visceral leishmaniasis (VL) in HIV-positive individuals have been reported from most areas of the world where the geographical distributions of the two infections overlap. The majority of the co-infected cases that have been recorded, however, live around the Mediterranean basin. In these subjects, the length of the incubation period of VL is presumably very short, particularly in those who have severe immunodepression. At diagnosis, almost all cases of VL/HIV co-infection have been found to have fewer than 200 CD4+ cells/microl blood, and about 50% meet the AIDS-defining criteria during their first episode of VL. The clinical manifestations of VL in HIV-infected individuals may be similar to those seen in HIV-negative cases; fever, pancytopenia and hepato-splenomegaly, for example, are found in 75% of all the HIV-positive cases. Following the dissemination of the parasites, however, the HIV-positive cases may develop unusual, multi-organ pathology. Almost all the cases of co-infection are very prone to VL relapses, even after carefully managed antileishmanial treatment. The opportunistic infections that are often seen in HIV-positives frequently develop during VL episodes, the signs and symptoms of the leishmaniasis then confusingly overlapping with those of the other infections.

AIDS-Related Opportunistic Infections↗

Clinical survey of Leishmania/HIV co-infection in Catania, Italy: the impact of highly active antiretroviral therapy (HAART).

The clinical and parasitological features of visceral leishmaniasis (VL) were investigated, retrospectively, in 27 HIV-infected patients who attended the out-patient clinic of Catania University's Department of Infectious Diseases between 1990 and 1998. The aim was to evaluate the epidemiological, clinical, therapeutic and prognostic characteristics of the co-infection, to determine if there were any interactions between the two infections, and to see if the use of highly active antiretroviral therapy (HAART) had any impact on the leishmaniasis. The most dramatic observation was a marked, HAART-attributable reduction in the annual incidence of VL relapses among the patients.

AIDS-Related Opportunistic Infections↗

Visceral leishmaniasis and HIV co-infection: a rare case of pulmonary and oral localization.

Visceral leishmaniasis (VL) has increased as a complicating infection in subjects with human immunodeficiency virus (HIV) in countries bordering the Mediterranean sea. The clinical course as well as organ involvement of VL are often atypical in HIV positive subjects. In this study a case of VL with pulmonary and oral mucose localisation in a patient with acquired immune deficiency syndrome (AIDS), is reported. These findings, together with the presence of the parasite in the peripheral blood smear, confirm that in HIV positive patients the impaired immune system allows the spreading and the atypical localisation of the Leishmania amastigotes more easily than in immuno-competent individuals. In endemic areas and in HIV positive subjects a systemic and careful parasitological follow-up is necessary to ensure that any clinical form of leishmaniasis is not overlooked.

Acquired Immunodeficiency Syndrome↗

Feasibility in needle exchange programme: an evaluation of a pilot programme in Catania, Sicily.

INTRODUCTION: Intravenous drug use (10 V) is a primary transmission route for HIV and other blood borne disease. A criminal approach to illicit drug use leads to aggressive attitudes towards drug users and forces them underground, thus hindering their access to Health Service outlets. A 6-month pilot Needle Exchange Programme was set up in Catania, with the aim of reducing the negative effects and consequences of drug use, preventing the spread of blood borne diseases by encouraging the use of clean needles and reduction of needle sharing. To establish contact with the hidden population of the city's, intravenous drug users (IDUs) and promote condom use and safer sex. METHOD: An equipped camper was parked daily in two of the city's main public squares according to a preset timetable, morning and afternoon. A flexible needle exchange policy, i.e. free clean needles given out regardless of those returned, was adopted as a strategy considered necessary in order to, ensure maximum user-friendliness. Safer shooting information leaflets were given out alongside material for the correct use of the condom and condoms. RESULT: The number of IDUs, contacted who had previously been referred to a National Health Service Drug Unit (Ser.T.) and not, and number of syringes exchanged were low but increased month by month. CONCLUSION: Future projects should be undertaken after building up, a collaborative network between Street Unit and local courts; the city police force; social service outlets; hospitals and other health outlets; Ser.T. units and local pharmacies. In the light of our current experience, the one to one strategy instead to the flexible strategy could lead to stricter adherence to harm reduction strategies amongst IDUs.

Journal Article↗

Mitochondrial DNA sequences in prehistoric human remains from the Alps.

The spread of agriculture that started in the Near East about 10 000 years ago caused a dramatic change in the European archaeological record. It is still unclear if that change was caused mostly by movement of people or by cultural transformations. In particular, there is disagreement on what proportion of the current European gene pool is derived either from the pre-agricultural, paleolithic and mesolithic people, or from neolithic farmers immigrating from the south-east. To begin to characterise the mtDNA gene pool of prehistoric Europe we examined five human remains from the Eastern Italian Alps, dated between 14 000 and 3000 years ago. Three of them yielded sufficient amount of mtDNA for analysis. DNA extracts were prepared in two independent laboratories, and PCR products from the first hypervariable segment of the mtDNA control region were cloned and sequenced. Together with the 5200 year old 'ice man', these DNA sequences show that European mtDNA diversity was already high at the beginning of the neolithic period. All the neolithic sequences have been observed in contemporary Europeans, suggesting genealogical continuity between the neolithic and present-day European mtDNA gene pool. The mtDNA sequence from a 14 000 year-old specimen was not observed in any contemporary Europeans, raising the possibility of a lack of continuity between the mesolithic and present-day European gene pools.

Agriculture↗

AIDS-associated Kaposi's sarcoma is more aggressive in women: a study of 54 patients.

OBJECTIVE: To describe the epidemiologic and clinical features of AIDS-associated Kaposi's sarcoma (KS) in women compared with men. METHODS: In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on death's risk. RESULTS: KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival. CONCLUSIONS: This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.

AIDS-Related Opportunistic Infections↗

Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism.

We present a survey of nucleotide polymorphism of three novel, rapidly evolving genes in populations of Drosophila melanogaster and D. simulans. Levels of silent polymorphism are comparable to other loci, but the number of replacement polymorphisms is higher than that in most other genes surveyed in D. melanogaster and D. simulans. Tests of neutrality fail to reject neutral evolution with one exception. This concerns a gene located in a region of high recombination rate in D. simulans and in a region of low recombination rate in D. melanogaster, due to an inversion. In the latter case it shows a very low number of polymorphisms, presumably due to selective sweeps in the region. Patterns of nucleotide polymorphism suggest that most substitutions are neutral or nearly neutral and that weak (positive and purifying) selection plays a significant role in the evolution of these genes. At all three loci, purifying selection of slightly deleterious replacement mutations appears to be more efficient in D. simulans than in D. melanogaster, presumably due to different effective population sizes. Our analysis suggests that current knowledge about genome-wide patterns of nucleotide polymorphism is far from complete with respect to the types and range of nucleotide substitutions and that further analysis of differences between local populations will be required to understand the forces more completely. We note that rapidly diverging and nearly neutrally evolving genes cannot be expected only in the genome of Drosophila, but are likely to occur in large numbers also in other organisms and that their function and evolution are little understood so far.

Animals↗

In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from subjects coinfected with human immunodeficiency virus and Leishmania infantum.

To explore the type 1 and type 2 cytokine profile in cases coinfected with human immunodeficiency virus (HIV) and Leishmania infantum, production of interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-gamma (IFN-gamma), and interleukin-2 receptor (IL-2R) was investigated in mitogen-stimulated and unstimulated peripheral blood mononuclear cell cultures from eight HIV/Leishmania coinfected subjects matched with eight anti-HIV-positive subjects with no evidence of Leishmania coinfection. Levels of IL-4 and IL-2R increased significantly from the baseline levels in the peripheral blood mononuclear cell supernatants of HIV/Leishmania coinfected subjects following stimulation with phytohemoagglutin, whereas the postchallenge concentration of IFN-gamma was significantly increased in the HIV-infected group. The levels of IL-4 and IL-10 were significantly higher in the HIV/Leishmania group throughout evaluation. Post-stimulation IFN-gamma production was significantly higher in the HIV-positive group in comparison with that of the HIV-Leishmania coinfected subjects. These observations support the notion that a Th2 cytokine response is present during a Leishmania infection, even among HIV-coinfected individuals.

Adult↗

Mitochondrial lineages in Ladin-speaking communities of the eastern Alps.

European mitochondrial alleles cluster into five haplogroups. Haplogroup 2 is rare in general, but represents more than half of the few known sequences among Ladin speakers of the Alps. Here we describe DNA diversity in control region I of the hypervariable D-loop in 43 Ladins, and in 25 Italian speakers. Analysis of these data, and of previously published sequences, confirms a high degree of differentiation among Ladins and their geographical neighbours. This cannot be regarded as a simple effect of isolating factors, geographic or linguistic, as diversity is high within Ladin communities too. Rather, allele genealogies, population trees, and principal component analysis suggest a relationship between Ladin and Near Eastern samples. Two evolutionary hypotheses seem compatible with these findings. The view whereby Ladins could be descended from Palaeolithic inhabitants of the Alps is supported by the identification, in this study, of the probable ancestral haplotype of group 2, never previously observed in central Europe. Alternatively, a comparatively recent, Neolithic immigration of the ancestors of current Ladin speakers seems consistent with recent linguistic theories. In both cases, the number of lineages present, and their extensive diversity, are not compatible with a serious bottleneck in the Ladin population's history.

Alleles↗

Microevolutionary divergence pattern of the segmentation gene hunchback in Drosophila.

To study the microevolutionary processes shaping the evolution of the segmentation gene hunchback (hb) from Drosophila melanogaster, we cloned and sequenced the gene from 12 isofemale lines representing wild-type populations of D. melanogaster, as well as from the closely related species Drosophila sechellia, Drosophila orena, and Drosophila yakuba. We find a relatively low degree of sequence variation in D. melanogaster (theta = 0.0017), which is, however, consistent with its chromosomal location in a region of low recombination. Tests of neutrality do not reject a neutral-evolution model for the whole region. However, pairwise tests with different subregions indicate that there is a relative excess of polymorphic sites in the leader and the intron. Codon usage pattern analysis shows a particularly biased codon usage in the highly conserved regions, which is in line with the hypothesis that selection on translational accuracy is the driving force behind such a bias. A comparison of the expression pattern of hb in different sibling species of D. melanogaster reveals some regulatory changes in D. yakuba, which could be interpreted as changes in the timing of secondary expression domains.

Animals↗

Serum cytokines as predictors of clinical outcome in AIDS-related intestinal cryptosporidiosis.

BACKGROUND: Clinical variability in the natural course of cryptosporidiosis in patients affected by acquired immunodeficiency syndrome has been correlated to the degree of T-cell immunosuppression; however, cryptosporidiosis can occur as a self-limiting disease even in patients with very low T-lymphocyte count. AIMS: We tested the serum values of a panel of cytokines in AIDS patients with cryptosporidial enteritis in order to evaluate their role in predicting the clinical outcome of the disease. PATIENTS AND METHODS: Thirty one HIV-positive patients with cryptosporidiosis and a CD4+ count of less than 100/mm3 were studied. Interleukin-2, Interleukin-4, Interleukin-10, Interferon-gamma, Interleukin-12, Tumor Necrosis Factor alpha values were measured in serum at diagnosis. RESULTS: Interleukin-4 and Interleukin-10 concentration was significantly lower in patients with mild disease whereas serum Interleukin-2 and -12 was higher in this same group. The serum level of Interferon-gamma did not differ in relation to the severity of the disease. Patients with self-limiting diarrhoea showed significantly lower levels of Tumor Necrosis Factor-alpha than subjects who did not show any clinical improvement. CONCLUSIONS: In our study, it has been shown that cytokine levels in serum may represent early predictive markers both for the severity of symptoms and the clinical outcome of cryptosporidial enteritis in AIDS patients with a low CD4+ count.

AIDS-Related Opportunistic Infections↗

Eosinophilic ileocolitis by Enterobius vermicularis: a description of two rare cases.

BACKGROUND: Human enterobiasis is usually mild. Occasionally, however, an "ectopic" disease may occur with a more severe course. Two rare cases of eosinophilic ileocolitis due to Enterobius vermicularis infection are reported here. CASE REPORTS: Case n degree 1 was 46 years old, presenting with fever and bloody diarrhoea. Blood eosinophilia was present. Stool microscopy demonstrated red blood cells and leukocytes. A 2 mm long worm with bilateral cervical wings was found in wet-mount preparations of faecal samples. The Scotch tape test was positive for Enterobius vermicularis eggs. Colon biopsy specimens showed massive eosinophilic infiltration and a typical pinworm section overlying the infiltrated mucosa. Case n degree 2 was a 24-year-old, anti-HIV negative homosexual, presenting with watery diarrhoea. Tests for malabsorption were negative. Three mm long adult male E. vermicularis were found on stool microscopy. Biopsy specimens from the colon showed eosinophilic infiltration. In both cases a 200 mg/day course of oral mebendazole eliminated the symptoms within 3 days. CONCLUSIONS: In these two cases the clinical presentation of enterobiasis was atypical. A common finding was the eosinophilic infiltration of bowel mucosa, although it is still uncertain whether the worm per se may induce mast cell degranulation and eosinophil activation. Nevertheless, the possibility of Enterobius vermicularis infection should be considered in the presence of eosinophilic ileocolitis.

Adult↗

Methadone maintenance and hepatitis C virus infection among injecting drug users.

Harm reduction strategies for the prevention of transmission of human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs) have been widely implemented in Australia and are seen to have been effective in preventing the spread of HIV. A major strategy has been increasing the availability of and accessibility to methadone maintenance therapy (MMT) programmes. We have reviewed the experience of a major MMT general practice with hepatitis C virus (HCV) infection from 1991 to 1995. Of 1741 individuals tested for HCV antibodies at least once 66.7% were positive. Of 73 IDUs who were initially seronegative and were retested at least once, 19 were subsequently seropositive. Seroconverters to HCV were younger than non-seroconverters, and were more likely to have evidence of previous hepatitis B infection. The overall HCV incidence rate was 22 cases per 100 person-years, and this did not differ between those on MMT programs (continuous or interrupted) between HCV tests and those not on MMT. These findings suggest that the role of MMT in the control of the spread of HCV infection among IDUs needs further assessment, and that control of the current epidemic of HCV infection among IDUs in Australia will be very difficult.

Adult↗

Comparison of the indirect immunofluorescent antibody test and the direct agglutination test for serodiagnosis of visceral leishmaniasis in HIV-infected subjects.

One hundred subjects positive for anti-human immunodeficiency virus (HIV) antibodies were tested for anti-Leishmania antibodies by the indirect immunofluorescent antibody test (IFAT) and the direct agglutination test (DAT). Subjects were subsequently followed for two years to monitor the onset of visceral leishmaniasis. Fifteen subjects were positive for anti-Leishmania antibodies in either one or both tests. Eleven were positive only by IFAT, one only by DAT, and three by both tests. During the two-year follow-up period, nine subjects developed visceral leishmaniasis; of these, six were serologically positive, four by IFAT alone and two by both tests. The results indicate that IFAT and DAT have a similar specificity but that IFAT has a higher sensitivity and a greater diagnostic significance.

Adult↗

Large differences in substitutional pattern and evolutionary rate of 12S ribosomal RNA genes.

We demonstrate using Drosophila, periodical cicadas, and hominid primates, that the molecular clock based on animal mitochondrial small-subunit (12S) rRNA genes ticks at significantly different relative rates depending on which taxa and which region of the gene are examined. Drosophila, which are commonly used as model taxa, are evolving in a highly peculiar manner with the majority of sites in the 3' half of the 12S gene apparently invariant. The analogous 3' half of the mitochondrial large-subunit rRNA gene (16S) appears to be similarly constrained. It is surprising that these regions that are already highly constrained in all animals should be even more constrained in Drosophila, especially when the Drosophila mitochondrial genome as a whole does not display a similar rate slowdown. This extreme 12S rate slowdown is not apparent in periodical cicadas or hominid primates and appears to be related to strong structural and functional constraints rather than a depressed mutation rate. Finally, the slow average rate of evolution in the third domain of Drosophila does not imply that the few variable sites lack multiple hits.

Animals↗