PubMed Health⌕ Search

Biomedical subjects

M Busso

Publications and source records attributed to M Busso.

At least 19 recordsLinked to original sources

Ultrasound diagnosis of pneumothorax.

PURPOSE: The purpose of this study was to show the effectiveness of ultrasound (US) in the evaluation of pneumothorax by comparison with X-rays and computed tomography (CT). MATERIALS AND METHODS: A series of 184 patients (130 men and 54 women), aged 26 to 82 years, underwent chest US after percutaneous needle biopsy. US findings were compared with CT postbiopsy selective slices and to X-rays. RESULTS: Pneumothorax was identified in 46 patients (25%) by CT, in 44 by US, with no false positives, and in 19 by X-rays. US sensitivity was 95.65%, specificity 100% and diagnostic effectiveness 98.91%. CONCLUSIONS: Chest US was found to be a valuable diagnostic tool in pneumothorax diagnosis, with diagnostic effectiveness well beyond X-rays and similar to CT.

Adult↗

Local-MP2 electron correlation method for nonconducting crystals.

Rigorous methods for the post-HF (HF-Hartree-Fock) determination of correlation corrections for crystalline solids are currently being developed following different strategies. The CRYSTAL program developed in Torino and Daresbury provides accurate HF solutions for periodic systems in a basis set of Gaussian type functions; for insulators, the occupied HF manifold can be represented as an antisymmetrized product of well localized Wannier functions. This makes possible the extension to nonconducting crystals of local correlation linear scaling On techniques as successfully and efficiently implemented in Stuttgart's MOLPRO program. These methods exploit the fact that dynamic electron correlation effects between remote parts of a molecule (manifesting as dispersive interactions in intermolecular perturbation theory) decay as an inverse sixth power of the distance R between these fragments, that is, much more quickly than the Coulomb interactions that are treated already at the HF level. Translational symmetry then permits the crystalline problem to be reduced to one concerning a cluster around the reference zero cell. A periodic local correlation program (CRYSCOR) has been prepared along these lines, limited for the moment to the solution of second-order Moller-Plesset equations. Exploitation of point group symmetry is shown to be more important and useful than in the molecular case. The computational strategy adopted and preliminary results concerning five semiconductors with tetrahedral structure (C, Si, SiC, BN, and BeS) are presented and discussed.

Journal Article↗

Bednar tumor (pigmented dermatofibrosarcoma protuberans) occurring in a site of prior immunization: immunochemical findings and therapy.

Bednar tumor is a rare pigmented variant of dermatofibrosarcoma protuberans (DFSP). Because of its rarity, information is lacking regarding the optimal therapy and potential utility of immunohistochemistry in diagnosis. We report a case of Bednar tumor in which the diagnosis was aided by immunohistochemistry for CD34, an antigen known to be expressed in DFSP but not previously reported in Bednar tumor. Our case was also striking because it represents the first reported appearance of a Bednar tumor at a site of prior immunization, a phenomenon previously noted in some cases of DFSP. The patient was treated effectively with Mohs surgery and is without recurrence at 9 months.

Adult↗

Discovery, synthesis, and bioactivity of bis(heteroaryl)piperazines. 1. A novel class of non-nucleoside HIV-1 reverse transcriptase inhibitors.

A variety of analogues of 1-[4-methoxy-3,5-dimethylbenzyl]-4-[3-(ethylamino)-2-pyridyl]piperazine hydrochloride (U-80493E) were synthesized and evaluated for their inhibition of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). Replacement of the substituted aryl moiety with various substituted indoles provided bis(heteroaryl)piperazines (BHAPs) that were 10-100-fold more potent than U-80493E. The pyridyl portion of the lead molecule was found to be very sensitive to modifications. Extensive preclinical evaluations of several of these compounds led to the selection of 1-[(5-methoxyindol-2-yl)carbonyl]-4-[3-(ethylamino)-2- pyridyl]piperazine methanesulfonate (U-87201E, atevirdine mesylate) for clinical evaluation.

Aminopyridines↗

Development of an assay that detects transcriptionally competent human immunodeficiency virus type one particles.

To study the functional properties of HIV-1 reverse transcriptase (RT) from intact viral particles without the requirement for tissue culture expansion, a method that couples HIV-1 reverse transcription utilizing its endogenous RT (ERT) with polymerase chain reaction amplification (PCR) was developed. Detection of endogenous reverse transcripts from HIV particles by ERT-PCR was compared to HIV RNA PCR detection using avian myeloblastosis virus (AMV) RT from plasma samples from 45 HIV-1 infected patients. The HIV ERT-PCR method was capable of detecting plasma viremia with the same efficiency (29/29 patients) as the AMV RT HIV RNA PCR in patients with CD4 cell counts of less than 500/mm3. The determination of HIV-RT drug sensitivities using four well-characterized HIV-1 lab strains was assessed. The ERT-PCR method detected reduced sensitivity to TIBO R82150 (10 microM) in a TIBO resistant strain but not in the TIBO sensitive HTLV-IIIB viral mixture or an HTLV-IIIB clone. In summary, the HIV ERT-PCR method provides a useful approach for the detection of HIV and the characterization of RT sensitivities among HIV-1 strains.

Antiviral Agents↗

U-90152, a potent inhibitor of human immunodeficiency virus type 1 replication.

Bisheteroarylpiperazines are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT). We describe a novel bisheteroarylpiperazine, U-90152 [1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4-[3-(1-methyl eth yl-amino)pyridinyl]piperazine], which inhibited recombinant HIV-1 RT at a 50% inhibitory concentration (IC50) of 0.26 microM (compared with IC50s of > 440 microM for DNA polymerases alpha and delta). U-90152 blocked the replication in peripheral blood lymphocytes of 25 primary HIV-1 isolates, including variants that were highly resistant to 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine, with a mean 50% effective dose of 0.066 +/- 0.137 microM. U-90152 had low cellular cytotoxicity, causing less than 8% reduction in peripheral blood lymphocyte viability at 100 microM. In experiments assessing inhibition of the spread of HIV-1IIIB in cell cultures, U-90152 was much more effective than AZT. When approximately 500 HIV-1IIIB-infected MT-4 cells were mixed 1:1,000 with uninfected cells, 3 microM AZT delayed the evidence of rapid viral growth for 7 days. In contrast, 3 microM U-90152 totally prevented the spread of HIV-1, and death and/or dilution of the original inoculum of infected cells prevented renewed viral growth after U-90152 was removed at day 24. The combination of U-90152 and AZT, each at 0.5 microM, also totally prevented viral spread. Finally, although the RT amino acid substitutions K103N (lysine 103 to asparagine) and Y181C (tyrosine 181 to cysteine), which confer cross-resistance to several nonnucleoside inhibitors, also decrease the potency of U-90152, this drug retains significant activity against these mutant RTs in vitro (IC50s, approximately 8 microgramM).

Antiviral Agents↗

Nonnucleoside reverse transcriptase inhibitors that potently and specifically block human immunodeficiency virus type 1 replication.

Certain bis(heteroaryl)piperazines (BHAPs) are potent inhibitors of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) at concentrations lower by 2-4 orders of magnitude than that which inhibits normal cellular DNA polymerase activity. Combination of a BHAP with nucleoside analog HIV-1 RT inhibitors suggested that together these compounds inhibited RT synergistically. In three human lymphocytic cell systems using several laboratory and clinical HIV-1 isolates, the BHAPs blocked HIV-1 replication with potencies nearly identical to those of 3'-azido-2',3'-dideoxythymidine or 2',3'-dideoxyadenosine; in primary cultures of human peripheral blood mononuclear cells, concentrations of these antiviral agents were lower by at least 3-4 orders of magnitude than cytotoxic levels. The BHAPs do not inhibit replication of HIV-2, the simian or feline immunodeficiency virus, or Rauscher murine leukemia virus in culture. Evaluation of a BHAP in HIV-1-infected SCID-hu mice (severe combined immunodeficient mice implanted with human fetal lymph node) showed that the compound could block HIV-1 replication in vivo. The BHAPs are readily obtained synthetically and have been extensively characterized in preclinical evaluations. These compounds hold promise for the treatment of HIV-1 infection.

Animals↗

HIV-induced syncytium formation requires the formation of conjugates between virus-infected and uninfected T-cells in vitro.

The transmission of HIV requires the interaction of the cell-surface CD4 receptor and the viral envelope glycoprotein. Experiments were performed to determine the role of other cell-surface molecules in the development of HIV-induced syncytia. Although CEM and MT-2 cells had similar cell-surface CD4 receptor densities, less than 1% of CEM cells and greater than 95% of MT-2 cells formed syncytia with H9 cells chronically infected with HIV-1 (H9-IIIB). When compared with CEM cells, MT-2 cells exhibited a 10-fold and threefold greater capacity to form homotypic and heterotypic conjugates with H9 cells, respectively. Increasing the conjugate formation capacity of CEM cells with the lectin wheat germ agglutinin led to a greater than 30-fold increase in the formation of syncytia with H9/IIIB cells. The formation of syncytia between MT-2 and H9/IIIB cells was magnesium-, energy-, temperature-, and actin-cytoskeleton-dependent, and could be inhibited (65%) by an anti-LFA-1 monoclonal antibody. The combination of anti-leukocyte function-associated antigen-1 (LFA-1) and anti-CD2 monoclonal antibodies resulted in a synergistic inhibition (89%) of syncytium formation. These results indicate that integrins and other cell-surface adhesion molecules regulate HIV-induced syncytium formation.

CD4 Antigens↗

Effects of long-term zidovudine treatment on cell-mediated immune response and lymphokine production.

The effects of long-term zidovudine treatment on functional parameters of cell-mediated immunity were investigated in 15 symptomatic HIV-antibody-positive patients with clinical evidence of opportunistic infections. Mononuclear leukocytes were obtained before administering the drug, and after 3 and 6 months of treatment. The cells were stimulated with lectins in order to assess variations of mitogen-induced lymphocyte proliferation and production of gamma-interferon (IFN) and interleukin-2 (IL-2), and with Newcastle disease virus (NDV) to assess variations of alpha-IFN production. Mean proliferative responses to PHA and Con-A did not show any significant change between baseline, 3 months, and 6 months values (25,158 +/- 11,763, 24,662 +/- 8,955, and 34,924 +/- 16,283 D-cpm, respectively, for PHA, p greater than 0.05; and 5,470 +/- 1,890, 4,953 +/- 2,518, and 4,539 +/- 3,286 D-cpm, respectively, for Con-A, p less than 0.05). Mean response to PWM (9,707 +/- 4,429 D-cpm at entry) increased significantly after 3 months, but returned to baseline values at 6 months (17,039 +/- 5,123 and 10,314 +/- 3,855 D-cpm, respectively, p = 0.016). IL-2 production (5.51 +/- 4.0 I.U. at entry) rose particularly at 3 months and persisted at the same levels at 6 months (9.6 +/- 4.8 and 9.5 +/- 6 I.U., respectively, p less than 0.05). By contrast, a moderate but significant decrease in gamma- and alpha-IFN production was observed (65 +/- 2.2, 35.1 +/- 1.6, and 22 +/- 2 I.U., respectively, for gamma-IFN, p less than 0.05; 60 +/- 3, 64 +/- 2.6, and 12 +/- 1.5 I.U., respectively for alpha-IFN, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Effects of ofloxacin on cell-mediated immune response and lymphokine production.

The effects of orally administered ofloxacin on functional parameters of cell-mediated immunity were investigated in 15 patients with respiratory or urinary tract infections. Mononuclear leucocytes were obtained before administering the drug, 1 h after the first dose, and five days later. The cells were stimulated with lectins, tetanus toxoid and Newcastle Disease virus in order to assess mitogen- and antigen-induced lymphocyte proliferation and production of gamma-interferon, interleukin-2 and alpha-interferon. An increase in proliferative response to pokeweed mitogen and a slight but significant decrease in alpha-interferon production were observed, while other parameters remained unaffected by treatment.

Analysis of Variance↗

Nucleotide dimers suppress HIV expression in vitro.

A series of nucleotide homo- and heterodimers [3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-di-deoxy-5' adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2', 3'-dideoxy;-5'-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxy-5'-thymid ilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.

Antiviral Agents↗

Spontaneous release of interferon as a predictor of clinical evolution in HIV-positive subjects.

In order to establish a correlation with disease progression we prospectively evaluated ten clinical and immunologic parameters in 102 consecutive HIV-positive subjects. The eight immunologic variables were: in vitro spontaneous interferon release by peripheral blood monocytic cells, alpha- and gamma-interferon production induced by Newcastle Disease Virus and PHA, Multitest Mérieux score, PHA- and CON-A-induced lymphocyte transformation, absolute number of CD4+ cells and CD4/CD8 ratio, respectively. The two baseline clinical variables were risk factor and disease presentation. Generalized Wilcoxon analysis indicated a significant correlation of one clinical (disease presentation at entry) and three immunologic variables (spontaneous interferon release, CD4+ cell number, Multitest Mérieux) with disease progression. Baseline spontaneous release of alpha, acid-labile interferon showed the best correlation with disease progression, and appeared to be significantly associated with CD4+ cell loss. Spontaneous release of acid-labile alpha interferon by mononuclear cells in vitro could be highly predictive of disease evolution in HIV-Ab positive, AIDS-free subjects.

Evaluation Studies as Topic↗