In open-chest dogs (n = 5) the effects of nifedipine (25 micrograms/kg infused over a period of 15 min) on the collateral blood flow after left anterior descending coronary artery (LAD) ligation were separated from those on heterogeneous blood supply, i.e. flow of collateral origin plus flow in non-ischemic myocardium projecting into the ischemic area. This separation was possible using a technique based on microspheres, allowing analysis of perfusion via the left anterior descending coronary artery (LAD). Secondary effects on the ischemic heart induced by the hypotensive effect of nifedipine per se were minimized by counterbalancing the blood pressure change with an intra-aortic balloon. Nifedipine increased non-ischemic myocardial blood flow in the subendocardium from 1.11 +/- 0.10 to 2.71 +/- 0.17 (p less than 0.001) and in the subepicardium from 1.12 +/- 0.08 to 3.95 +/- 0.49 (p less than 0.001) (ml/min/g, mean +/- SE). Collateral blood flow in the centre of the ischemic area was not affected by nifedipine. In the subendocardium, it was 0.12 +/- 0.05 before and 0.09 +/- 0.09 after nifedipine, and in the subepicardium, the corresponding values were 0.31 +/- 0.10 and 0.29 +/- 0.04, respectively. At the lateral ischemic border, the nifedipine-induced increase in myocardial blood flow was only directed to the admixed normal tissue. When the blood flow was corrected for this overlapping non-ischemic tissue, no significant effect of nifedipine was measurable in the subendocardial blood flow, which was 0.12 +/- 0.03 before and 0.18 +/- 0.04 ml/min/g after drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMedDate not supplied

Characterization of HIV1-PAR, a macrophage-tropic strain: cell tropism, virus/cell entry and nucleotide sequence of the envelope glycoprotein.

The HIV1-PAR strain, isolated from the cerebrospinal fluid of an HIV1-seropositive man suffering from encephalopathy, replicated well in cord blood lymphocytes, poorly in peripheral blood mononuclear cells, and to different levels in blood-derived macrophage (BDM) cultures prepared from different blood donors. In marked contrast to its replication in primocultures, it did not grow in CEM and U937 cell lines. HIV1-PAR production in BDM was inhibited by more than 90% after treatment with OKT4A or 13B8.2 monoclonal antibodies (mAb) binding to adjacent epitopes of the D1 domain of the CD4 molecules. A lower but significant inhibitory effect was observed after BDM treatment with BL4 and OKT4 mAb, directed to the D2 and D3 domain of the CD4 molecule, respectively. The entire HIV1-PAR envelope glycoprotein gene was amplified by polymerase chain reaction and sequenced. The deduced amino acid sequence of HIV1-PAR gp160 revealed the presence of 847 amino acids and 86% homology with the HIV1 LAV virus prototype. An alignment of the amino acid sequence of the envelope glycoprotein of HIV1-PAR and HIV1-LAV showed that the differences were mostly clustered within the five variable regions. Five CD4-binding domains, the gp120/gp41 cleavage site, the putative gp41 fusion domain and 21 out of the 22 cysteine residues were conserved in both isolates. The results further confirm the macrophage-tropic character of the HIV1-PAR virus.

Amino Acid Sequence↗

PubMedDate not supplied

Inhibition of HIV by an anti-HIV protease synthetic peptide blocks an early step of viral replication.

The processing of the human immunodeficiency virus (HIV) gag and gag-pol precursor proteins by the virus-encoded protease is an essential step in maturation of infectious virus particles. Like most retroviral proteases, the HIV protease belongs to the aspartyl-protease family and can be inhibited by specific inhibitors. Twenty-four synthetic peptides known to be inhibitors of human renin were tested for inhibition of HIV replication in tissue cultures. One of them, a synthetic peptide analogue, SR41476, which has been shown to be a specific inhibitor of purified recombinant HIV1 protease in vitro, totally blocked infection with different isolates including the HIV1 LAV prototype, the highly cytopathic Zairian isolate HIV1 NDK, and HIV2 ROD, both in primary blood lymphocytes (PBL) and in the lymphoid cell lines MT4 and CEM, for at least 3 weeks. It also significantly reduced virus replication in chronically infected CEM cells, without any effect on cell proliferation. Radioimmunoprecipitation assay revealed that the inhibitor blocked processing of polyprotein precursors p55 gag and p40 gag into a mature form of gag proteins, p25 and p18. Synthetic peptide analogue SR 41476, when added before infection, efficiently inhibited formation of HIV DNA provirus and successfully suppressed synthesis of HIV-specific proteins. These results imply that the HIV protease inhibitor not only inhibited virus maturation in the late phase of the HIV replication cycle, but also interfered in the early phase, before the provirus was formed. This mechanism of antiviral activity provides new possibilities and strategies for AIDS chemotherapy.

Amino Acid Sequence↗

PubMedDate not supplied

Neutralizing antibodies in Brazilian sera against three strains of human immunodeficiency virus type 1 (HIV-1).

The MN strain of HIV-1 is known to be more prevalent in Brazil, the BRU strain is more prevalent in Europe, and the NDK strain in Africa. It has been suggested in the literature to include different strains in the same vaccine against HIV-1. To contribute to the studies for the development of a universal vaccine, the occurrence of antibodies (Ab) against three HIV-1 strains (MN, BRU and NDK) was determined in serum samples from 85 HIV-1-positive patients, adult volunteers seen at the University Hospital of the Faculty of Medicine of Ribeirão Preto-USP. One-hundred tissue culture infective unit (TCIU) of the viruses reacted with serial dilutions of the sera (2x) and with MT4 cells added at a final concentration of 0.3 x 10(6) cells/ml, and a cytopathic effect was observed on the 7th and 11th days of incubation. Titres of less than 1/50 were considered to be negative. In 129 tests, the sera were negative for one of the three strains: 40 for MN, 29 for BRU and 60 for NDK. There was a predominance of strains MN and BRU, most of them presenting titres from 1/50 to 1/200. Titres for NDK were detected in 25 sera. We conclude that there seems to be a predominance of strains MN and BRU among the individuals from the region tested; however, the detection of sera with positive NKD titres indicates the need for further studies of this strain in other populations and regions of Brazil.

AIDS Vaccines↗

PubMedDate not supplied

[Occurrence of false positives in tests with synthetic peptides for the analysis of antibodies against the human immunodeficiency virus type 2 (HIV-2) in Brazilian patients infected with the human immunodeficiency virus type 1 (HIV-1)].

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Adult↗

PubMedDate not supplied

Central nervous system involvement in Leber congenital amaurosis.

Sixteen patients with ocular criteria of Leber congenital amaurosis (LCA) were studied. Neurological examination was normal in 11 of 16 patients. The electroencephalogram was normal in six of eight patients, while two had nonspecific theta slowing. Computerized tomography of the brain was normal in two of five; hypoplasia of the cerebellar vermis was seen in one, and mild to moderate ventriculomegaly was seen in two of five. Six patients underwent the verbal subtests of the Wechsler Intelligence Scale and a detailed battery of neuropsychological tests. Subtests dependent on early environmental influences were most severely affected, while culture-free subtests showed average or well above average performance. These results strongly support the hypothesis that children with LCA may be capable of normal cognitive functioning, although they perform poorly on standard IQ tests. This is related to their early environmental and sensory deprivation, rather than to a primary central nervous system dysfunction.

Adolescent↗