PubMed Health⌕ Search

Biomedical subjects

F Speranza

Publications and source records attributed to F Speranza.

At least 19 recordsLinked to original sources

Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection.

In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomyopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.

AIDS-Related Opportunistic Infections↗

Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role.

A study is presented on cyclic adenosine monophosphate- (cAMP-) dependent phosphorylation of mammalian mitochondrial proteins. Immunodetection with specific antibodies reveals the presence of the catalytic and the regulatory subunits of cAMP-dependent protein kinase (PKA) in the inner membrane and matrix of bovine heart mitochondria. The mitochondrial cAMP-dependent protein kinase phosphorylates mitochondrial proteins of 29, 18, and 6.5 kDa. With added histone as substrate, PKA exhibits affinities for ATP and cAMP and pH optimum comparable to those of the cytosolic PKA. Among the mitochondrial proteins phosphorylated by PKA, one is the nuclear-encoded (NDUFS4 gene) 18 kDa subunit of complex I, which has phosphorylation consensus sites in the C terminus and in the presequence. cAMP promotes phosphorylation of the 18 kDa subunit of complex I in myoblasts in culture and in their isolated mitoplast fraction. In both cases cAMP-dependent phosphorylation of the 18 kDa subunit of complex I is accompanied by enhancement of the activity of the complex. These results, and the finding of mutations in the NDUFS4 gene in patients with complex I deficiency, provide evidence showing that cAMP-dependent phosphorylation of the 18 kDa subunit of complex I plays a major role in the control of the mitochondrial respiratory activity.

Animals↗

Binocular detection of masked patterns in young and old observers.

A visual pattern embedded in noise is detected appreciably better when the stimulus complex contains interocular cues (dichoptic condition) than when such cues are absent (binoptic condition). In a recent study (F. Speranza, G. Moraglia, & B. A. Schneider, 1995) the authors showed that the relative difference between binoptic and dichoptic thresholds does not change with age. However, older adults showed higher binoptic and dichoptic thresholds, thus suggesting an age-related difficulty with degraded stimulation. In this article the authors first replicated these findings and proceeded next to investigating whether age-related changes in processing efficiency, additive internal noise, and the spatial frequency bandwidth of the detecting filters could account, separately or concurrently, for the elevated thresholds in noise exhibited by the older adults. Results indicate that this increase is not attributable to age-related changes in filter bandwidth or internal noise. Rather, the findings can be explained in terms of a decrease in processing efficiency with age.

Adult↗

Monocular unmasking of noise-embedded patterns.

Binocular disparity cues may help an observer "unmask" a target in a background, thereby enhancing its detectability (e.g., Moraglia & Schneider, 1992). Here, we sought to determine whether similar effects could be produced by monocular displacement cues resulting from a two-frame sequential presentation of a Gabor pattern (a sinusoidal modulation of luminance combined with a Gaussian modulation of local contrast) embedded in an unvarying field of two-dimensional Gaussian noise. The Gabor in the second frame was spatially displaced relative to its location in the first frame; the horizontal displacement corresponded to a phase shift of the peak spatial frequency of the Gabor of 0 degree, 90 degrees, 180 degrees, 360 degrees, or 540 degrees. Monocular detection thresholds for the Gabor were appreciably lower for the 90 degrees, 180 degrees, and 540 degrees shift, than for the 0 degree and 360 degrees values. We explain these findings in terms of a model that constitutes the monocular analog of our summation model of binocular unmasking.

Adult↗

Levels of the bcl-2 protein, fibronectin and alpha(5)beta(1) fibronectin receptor in HIV-1-infected patients with Kaposi's sarcoma.

Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferation of neoplastic cells (spindle cells) mixed with endothelial and inflammatory cells. In this study we evaluated the role of the adhesive glycoprotein, fibronectin (FN) and its receptor alpha(5)beta(1) (FNR), and the proto-oncogene bcl-2, an anti-apoptotic protein. Significantly decreased serum levels of FN were noted in HIV-1-infected patients with KS, whereas serum levels of FNR were significantly increased in the same patients. Furthermore, increased FNR expression was observed on CD4 cells from KS patients. Serum levels of bcl-2 protein were significantly decreased in asymptomatic seropositive patients, whereas HIV-1-infected patients with KS showed increased serum levels of bcl-2. These results provide further information about interaction between integrins and the extracellular matrix and bcl-2 protein that can support cell survival either of neoplastic cells or endothelial and inflammatory cells.

AIDS-Related Opportunistic Infections↗

How aging affects the reading of words in noisy backgrounds.

Young and old adults were shown simple sentences masked by visual noise. In half of the sentences, the final word was predictable; in the other half, it was not. The older participants were able to identify the same number of final words as the younger ones only when the intensity of the visual noise was significantly diminished. However, the difference in the number of correct identifications between predictable and unpredictable conditions was higher for the older observers than for the younger observers, indicating that older observers benefit from context more.

Adult↗

Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethyl-L-arginine in mice intranasally infected.

To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production, on regulation of inflammatory responses to Bordetella pertussis infection, mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decrease of cellular accumulation of neutrophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally. In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitoneally) for 5 consecutive days showed higher mortality rate than untreated mice infected with B. pertussis, and the number of B. pertussis in lungs of mice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B. pertussis.

Animals↗

Binocular vision enhances phase discrimination by filtering the background.

Previous studies have shown that the detectability of a noise-masked target can be enhanced under stereoscopic viewing when the target's interocular disparity differs from that of the noise. This enhanced detectability can be accounted for by a model postulating that the binocular system linearly sums the left-eye and right-eye views of a visual scene. This model also predicts enhanced phase discrimination under specifiable interocular disparities of target and noise. Two experiments were conducted in which subjects were asked to discriminate between two luminance patterns (target and foil) that differed only in phase. The target patterns were constructed by summating two vertical sinusoidal gratings in which the phase difference between the higher and the lower spatial frequency gratings was 45 degrees. The foils contained the same two component frequencies, with a phase difference of -45 degrees. Thus, targets and foils were mirror images of one another. The ability of subjects to discriminate between these stereoscopically viewed mirror-image patterns was investigated under two sets of interocular disparities: those that, according to our model, would unmask one or both spatial frequency components, and those that would leave both components masked by the noise. Phase discrimination was enhanced only when both component frequencies of the target and foil were unmasked. The implications of these findings for template-matching and phase-discrimination models of pattern discrimination are considered.

Female↗

A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.

AIMS OF THE STUDY: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). PATIENTS AND METHODS: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. RESULTS: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. CONCLUSIONS: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

AIDS-Related Opportunistic Infections↗

A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.

To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.

AIDS-Related Opportunistic Infections↗

Age-related changes in temporal resolution: envelope and intensity effects.

Gap-detection thresholds were determined for 10 younger and 10 older adults at two sensation levels (40 and 60 dB SL) for tone pips with Gaussian amplitude envelopes whose standard deviations were 0.5, 1, 1.5, and 2 ms. Gap-detection thresholds were larger for the older participants under all conditions. For all participants, gap-detection thresholds increased with the standard deviation of the Gaussian amplitude envelope, were relatively independent of sensation level, and were independent of the degree of hearing loss. Because spectral splatter decreases with increasing standard deviation of the Gaussian amplitude envelope, the age-related differences in gap-detection cannot be attributed to differences between how young and old listeners are affected by off-frequency cues. Furthermore, the consistent age difference in gap-detection at all amplitude envelope standard deviations was shown to be incompatible with the hypothesis that temporal integration time is longer for older listeners.

Adult↗

Serum levels of Fas/Apo-1 and Bcl-2 in children with HIV-1 infection.

Apoptosis of CD4-positive T cells is considered to be involved in depletion of CD4-positive T cells in adult patients with HIV-1 infection. In this report we evaluated serum levels of soluble Fas/Apo-1 and circulating bcl-2 protein (an antiapoptotic molecule) in HIV-1-infected children, and 30 HIV-1 seronegative children. Significantly higher levels of Fas/Apo-1 were observed in 13 HIV-1-infected children than in non-infected control children (p < 0.001), whereas serum levels of bcl-2 were significantly decreased (p=0.002). Seronegative children born to HIV-infected mothers displayed significantly decreased (p < 0.05) serum levels of bcl-2. By contrast, children born to HIV-seronegative mothers and suffering from acute lower respiratory infection had normal levels of bcl-2 and Fas/Apo-1. These data suggest that upregulation of Fas/Apo-1 along with downregulation of bcl-2 protein may contribute to apoptosis in children with HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group.

The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.

AIDS-Related Opportunistic Infections↗

Noise-limited detection in young and old observers.

11 young (M age = 24.3 yr.) and 11 old (M age = 67.4 yr.) observers attempted to detect signals of limited bandwidth in visual noise. The older observers did not perform as well as the young ones. We considered whether, as suggested by a current hypothesis, these differences could be attributed to higher internal additive noise in the elderly observers. The results suggested that internal noise did not differ across the two age groups and that the lower performance of the older observers stemmed instead from reduced processing efficiency.

Adult↗

Topology of the mitochondrial cAMP-dependent protein kinase and its substrates.

In intact bovine heart mitochondria, cAMP-dependent phosphorylation of 42, 29, 18 and 6.5 kDa proteins was inhibited by carboxyatractyloside. This shows that both mitochondrial cAMP-dependent protein kinase (mtPKA) and its protein substrates are localized at the matrix side of the inner mitochondrial membrane. Proteins of 42, 29, 18, and 6.5 kDa were also bound at the outer surface of mitochondria where they were phosphorylated by the added purified catalytic subunit of PKA. In the cytosol from bovine heart proteins of the above molecular weights were phosphorylated by the cytosolic PKA.

Animals↗

The nuclear-encoded 18 kDa (IP) AQDQ subunit of bovine heart complex I is phosphorylated by the mitochondrial cAMP-dependent protein kinase.

In bovine heart mitochondria a protein of M(r) 18 kDa, phosphorylated by mtPKA, is associated to the NADH-ubiquinone oxidoreductase in the inner membrane and is present in purified preparation of this complex. The 18 kDa phosphoprotein has now been isolated and sequenced. It is identified as the 18 kDa (IP) AQDQ subunit of complex I, a protein of 133 amino acids with a phosphorylation consensus site RVS at position 129-131.

Amino Acid Sequence↗

In vitro and in vivo induction of nitric oxide by murine macrophages stimulated with Bordetella pertussis.

Nitric oxide (NO) exhibits potent antimicrobial activity in vitro. The function of NO in host defenses in vivo, however, is presently unclear. Experiments were undertaken to determine the production of NO in vitro from murine peritoneal and alveolar macrophages, and murine macrophage cell line (J774A.1) stimulated with Bordetella pertussis or pertussis toxin (PT). In addition, we determined circulating levels of NO in the sera and bronchoalveolar lavage (BAL) fluids of mice infected intranasally with B. pertussis. The results of this study showed that in vitro murine peritoneal macrophages induce production of NO in response to B. pertussis and PT. In addition, murine macrophage cell line, J774A.1 also induces NO production after stimulation with B. pertussis. NO production was also detected in alveolar macrophages from mice infected intranasally with B. pertussis. Finally, a significant increment of circulating levels of NO was noted, in the sera but not in the BAL fluids, of mice infected intranasally with B. pertussis.

Administration, Intranasal↗