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Biomedical subjects

R Bravo

Publications and source records attributed to R Bravo.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Long term survival in an HIV-immunosuppressed patient treated with foscarnet].

An HIV-infected woman with a CD4+ T-cell count below 100 x 10(6)/l survived for longer than 4 years of being diagnosed of AIDS, with acceptable health status (Karnofsky > 80%). Administration of foscarnet during two years, recommended as suppressive therapy for a previous cytomegalovirus retinitis, might have caused a sustained reduction in plasma HIV-RNA, contributing to her long-term survival.

AIDS-Related Opportunistic Infections↗
PubMed1996

[Prevalence of the genotypes of the hepatitis C virus in Spanish drug addicts with chronic hepatitis C. Spanish Group for the Study of Viral Hepatitis in HIV Positive Patients].

The hepatitis C virus (HCV) shows a wide genetic variability. The different variants of HCV have been classified into 9 types and different subtypes. Some genotypes have a characteristic geographic distribution and seem to be associated with precise ways of contagion. Serum samples from 107 spanish patients with chronic hepatitis C were studied, which were distributed as follows: 88 parenteral drug addicts (PDA) and a control group of 19 subjects made up by 4 transfused, 5 probably sexually infected and 10 with unknown contagion source (sporadic cases). HCV typing was made by means of the PCR method and later hybridization analysis with complementary probes of different types and subtypes of HCV exposed on a smooth surface (Inno-LiPA). A total to 105 (98.4%) patients had their viruses genotypes. There was more than one genotype in the same subject (co-infection) in 43.8% of cases and co-infection 1a + 1b was the most common (82.7%). While not reaching a statistic significance, co-infections were more frequent in PDA (47.1%) than in the remaining patients (27.8%). In the infected patients with only one genotype, the most common genotype was 1a, both in PDA (22.9%) and in subjects with transfusional HCV, sexual or sporadic (38.9%). In decreasing frequency came genotypes 1b (13.3%) and 3a (11.4%). Other genotypes were very uncommon (2a and 4) or were absent (2b and 5) as unique infections. In conclusion, genotypes non-1b of HCV, mainly 1a and to a lesser extent 3a, are the most common in a spanish population made up mainly by young persons with risk antecedents for HIV infection, particularly PDA. Furthermore, co-infection with HCV genotypes is frequent in this population.

Adult↗
PubMed1996

[Frequency and histopathologic features of chronic gastritis in 300 patients without endoscopic lesions].

Three gastric mucosal biopsies were obtained from 300 patients showing a normal upper digestive tract endoscopy. Histologically, in 9% of the patients the biopsies were normal: in 87%, showed a common-type chronic gastritis, and in 4% showed a reactive (chemical or reflux-type) gastritis. Helicobacter pylori was present in 25.9% of the patients without gastritis, in 33.3% of the patients with reactive gastritis, and in 87.7% of those with common-type gastritis. In 19.9% of the patients with common-type chronic gastritis there was intestinal metaplasia, consisting of type I metaplasia in 14.1%, type II in 3.1% and type III metaplasia in 2.3%. The association of type III intestinal metaplasia with the other forms of metaplasia, its lower frequency and its tendency to be present in older patients supports the hypothesis that type III incomplete colonic metaplasia represents a more advanced stage than complete and incomplete small bowed metaplasia of the gastric mucosa.

Adolescent↗
PubMed1996

RelB, a member of the Rel/NF-kappa B family of transcription factors.

RelB, originally identified as an immediate early gene product, is a member of the Rel/NF-kappa B family of transcription factors important for the regulation of genes involved in immune and inflammatory processes. RelB by itself is inactive due to its inability to homodimerize and to bind to kappa B sequences. However, in the presence of the Rel/NF-kappa B proteins p50 or p52, RelB is a potent transactivator. Transcriptional activation domains were identified in the NH2 and COOH termini of RelB separated by the approximately 300 amino acids spanning the Rel homogy domain (RHD). The last 120 amino acids of this domain are necessary for the dimerization of RelB and were analyzed in detail by in vitro mutagenesis. RelB forms complexes with p50 and p52 but not with RelA and c-Rel. In contrast to RelA-containing complexes, RelB-containing complexes are only weakly inhibited in their activity by I kappa B alpha. Furthermore, in lymphoid tissues RelB is not associated with I kappa B alpha. In contrast to other members of the Rel/NF-kappa B family, high expression of RelB is limited to interdigitating dendritic cells. Mice with a targeted disrupted relB locus show phenotypic abnormalities including multifocal, mixed inflammatory cell infiltration in several organs, myeloid hyperplasia, splenomegaly due to extramedullary hematopoiesis, and a reduced population of thymic dendritic cells.

Animals↗
PubMed1996

[Semiquantitative histopathologic analysis of chronic gastritis: extension and grading score].

Three endoscopic systematic biopsies were obtained from 261 patients showing chronic gastritis. Histopathologic features of chronic gastritis were graded from 0 to 3 points according to the Sydney System. In addition, an extension and grading histopathologic score was applied. This score was obtained from the sum of qualified grades for each feature in all three samples. Inflammation, activity, atrophy, and intestinal metaplasia were predominantly grade 1 and H pylori density was predominantly grade 2. Only 2.6% of the sections without atrophy showed intestinal metaplasia, while 79.3% of the sections depicting grade 2-3 intestinal metaplasia showed moderate to severe atrophy. Inflammation was more severe in the antral lesser curvature and the more severe atrophy was present in the antrum than in the corpus mucosa. Sydney System and extension and grading histopathologic score showed more extensive activity in patients older than 45 years. A lower histopathologic score of H pylori was seen in these patients. The presence of H pylori was directly correlated with inflammation severity and inversely with atrophy. These results, in accordance with data shown in the literature, suggest that the Sydney System and the extension and grading histopathologic score can be applied to compare chronic gastritis features in different groups of patients.

Chronic Disease↗
PubMed1995

Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1.

Transgenic mice overexpressing the chemokine monocyte chemoattractant protein-1 (MCP-1) in the thymus and central nervous system have a higher number of mononuclear cells in those tissues than do control littermates. In the thymus, there is a modest increase in the number of Mac-1 and F4/80 positive cells, but no apparent change in the number of lymphoid cells. A more pronounced mononuclear infiltrate is detected in transgenic mice expressing MCP-1 in the brain. The vast majority of the recruited cells in the brain are monocytes and macrophages, as defined by light microscopy, and ultrastructural and immunohistochemical criteria. Such cells are found in a perivascular orientation with minimal parenchymal infiltration, possibly as a consequence of the accumulation of MCP-1 in the vessels, as shown by immunohistochemistry. The mononuclear cell infiltrate in the brain can be significantly amplified by LPS treatment, suggesting that the recruitment properties of MCP-1 can be potentiated by additional factors.

Animals↗
PubMed1995

N51 competes 125I-interleukin (IL)-8 binding to IL-8R beta but not IL-8R alpha. Structure-function analysis using N51/IL-8 chimeric molecules.

We have demonstrated that the mouse chemokine N51, also known as KC, can compete for 125I-human interleukin-8 (IL-8) binding to NIH 3T3 cells expressing the human IL-8 receptor beta (NIH-IL-8R beta) but not the IL-8 receptor alpha (NIH-IL-8R alpha). In addition, we used the chimeras between N51 and IL-8 described previously (Heinrich, J. N., O'Rourke, E. C., Chen, L., Gray, H., Dorfman, K. S., and Bravo, R. (1994) Mol. Cell. Biol. 14, 2849-2861; Heinrich, J. N., and Bravo, R. (1995) J. Biol. Chem. 270, 4987-4989) to evaluate possible contributions of equivalent domains from each chemokine to binding and specificity. Specifically, the amino acid sequences between cysteines 2 and 3 or between cysteines 3 and 4 or the alpha-helical C-terminal end (domains I, II, and III, respectively) of one of the chemokines was exchanged with the corresponding sequence of the other and vice versa. Chimeras of IL-8 containing either domain II or III of N51 behaved similarly, but not identically, to IL-8 in competing 125I-IL-8 binding with both NIH-IL-8R alpha cells and NIH-IL-8R beta cells. The IL-8 chimera containing domain I of N51 did not compete. On the other hand, N51 competes 125I-IL-8 binding with NIH-IL-8R beta but not NIH-IL-8R alpha cells. The N51 chimera containing domain I of IL-8 was an agonist with NIH-IL-8R alpha cells and was an even more potent agonist with NIH-IL-8R beta cells. On the latter cells it was more potent than either IL-8 or N51. The N51 chimera containing domain II of IL-8, compared with N51, was a partial agonist with NIH-IL-8R alpha cells but was equivalent to N51 with NIH-IL-8R beta cells. However, N51 chimera containing domain III of IL-8 was a partial agonist with both cells. The results are consistent with the observations we originally made with human neutrophils and the NIH mouse IL-8R beta cells, i.e. domain I confers binding specificity for IL-8 and domains II and III of IL-8 and N51 may be interchangeable but they are not equivalent. Although we originally hypothesize that domains II and III confer binding specificity to N51, these results emphasize the role of domain III.

Amino Acid Sequence↗
PubMed1995

[Rapid progression to AIDS in a patient with infection from a strain of syncytium forming HIV-1].

A woman who had recently become infected with HIV-1 after sexual relations with a seropositive subject presented a rapid fall in CD4+ T lymphocytes and evolved to AIDS 13 months after primoinfection. The most plausible cause for the rapid disease progression in this patient was the observation of a viral syncytium forming phenotype. The plasmatic viremia was high throughout the follow up despite the administration of antiretroviral drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Morbidity and mortality associated with chronic viral hepatopathy in patients infected with the human immunodeficiency virus].

BACKGROUND: Hepatitis B, C and D virus infection is frequent in HIV-infected individuals, particularly in drug addicts. However, chronic liver disease of viral etiology has been little studied in AIDS. METHODS: The impact of infection by hepatotropic viruses on hospital morbidity/mortality was analyzed in a group of HIV positive (HIV+) patients over the period from October 1991 to April 1994. RESULTS: Viral liver disease was the cause of hospitalization in 94 (8.6%) out of 1,082 HIV+ patient admissions. Only 4 admissions were for severe or fulminant cases of acute viral hepatitis. Complicated (gastrointestinal bleeding, and spontaneous bacterial infection) or decompensated (ascites, jaundice and encephalopathy) viral liver disease was the diagnosis in the 90 remaining cases. Death directly associated to liver diseases was observed in 9 (9.5%) of these patients, globally representing 4.3% (9 out of 207) of the causes of hospital mortality during the study period, and the fifth in order of frequency. Hospital stay was significantly longer in patients admitted for decompensated or complicated chronic viral liver disease in comparison with the remaining patients (27.9 +/- 9 versus 18.4 +/- 8 days) (p < 0.05). Infection by the hepatitis C virus was observed in 88% (80 out of 90) of the hospital admissions for chronic liver disease although half presented coinfection by B or delta viruses. CONCLUSIONS: Chronic liver disease of viral etiology, mainly by the hepatitis C virus, represents an important cause of hospital morbidity and mortality in Spanish HIV+ patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

[The quantification of human immunodeficiency virus viremia in patients with rapid and slow progression of the disease].

BACKGROUND: The natural course of the human immunodeficiency virus type 1 (HIV-1) infection is very variable. The factors which appear to determine the speed of immunodeficiency progression are multiple, although the virulence of the predominant viral strain seems to be one the main factors. The plasmatic viremia in individuals with rapid and slow HIV-1 progression was analyzed in an attempt to establish the degree of correlation between HIV-1 replication and the natural course of the disease. METHODS: Forty-two samples from 34 seropositive patients, 11 with rapid progression criteria (< 5 years from acute infection and CD4+ lymphocytes < 0.2 x 10(9)/l) and 23 with slow progression (> 7 years from demonstrated infection and > 0.5 x 10(9) CD4+ lymphocytes/l) were studied. The plasmatic viremia was quantified by a new method of plasma DNA genetic amplification, denominated the branched DNA (bDNA) technique. As a reference circulating p24 was determined and the presence of several proviral regions were studied in peripheral blood lymphocytes by polymerase chain reaction (PCR). RESULTS: The presence of RNA molecules was detected in plasma of 7 (58.3%) out of 12 samples of rapid progression (RP) patients by bDNA. To the contrary, this was negative in 30 samples from slow progression (SP) patients. Four of the 5 negative RP samples corresponded to patients who had taken antiretroviral drugs at the time of the study. The p24 antigenemia was positive in 5 (41.6%) from the RP patients and in none of the SP patients. The presence of gag, pol and env sequences was positive by PCR in all RP patients and in most of the SP patients. However, repeatedly negative results by PCR were observed in 5 SP samples for all or some of the genomic regions studied. CONCLUSIONS: Patients with rapid progression of HIV-1 have higher plasmatic viremia than subjects with slow disease progression.

Adult↗
PubMed1995

Basal expression of the inducible transcription factors c-Jun, JunB, JunD, c-Fos, FosB, and Krox-24 in the adult rat brain.

Jun, Fos, and Krox proteins are inducible transcription factors contributing to the control of gene expression. The elucidation of their individual expression patterns in the nervous system provides new insights into the ability of neurons to react with changes of gene expression to external stimulation under physiological or pathological conditions. The expression of c-Jun, JunB, JunD, c-Fos, FosB, and Krox-24 was investigated in the brain of untreated male Sprague-Dawley and female BDIX rats by immunocytochemistry using specific antibodies. JunD immunoreactivity (IR) labeled the highest number of neurons, being present in almost all neurons of the brain. JunD was expressed at high levels in those areas that also exhibit c-Jun, JunB, c-Fos, and FosB-IR, such as locus coeruleus, periolivary nuclei (ncl.), pontine and central gray, lateral lemniscal ncl., inferior and superior colliculi, leaflet of geniculate ncl., midline nuclei of thalamus, dorsomedial and paraventricular ncl. of hypothalamus, ncl. supraopticus, dorsolateral part of caudate putamen and lateral septal ncl. In contrast to the high number of JunD-positive neurons, c-Jun, JunB, c-Fos, and FosB proteins were detected in rather low numbers of neurons in these brain areas; the rank of the number of immunopositive neurons was c-Fos > JunB > c-Jun > FosB. Particularly high levels of expression were observed for c-Jun in medullary motoneurons, medial geniculate ncl., arcuate ncl., and dentate gyrus, and for JunB in the CA-1 area of the hippocampus and islands of Calleja. The zinc finger protein Krox-24 was expressed in many neurons of these brain areas, with only discrete Jun- and Fos-IR; additionally, many intensely labeled nuclei were present in spinal ncl. of the trigeminal ventromedial ncl. of the hypothalamus and the CA-1 area of the hippocampus. In the cerebellum, nuclear labeling was detected only for c-Jun, JunD, and Krox-24 in granule cells. JunD-IR was also found in glial cells of gray matter and fiber tracts, whereas glial c-Jun-IR was observed only in fiber tracts. Apart from a weak JunD-IR, some areas did not express Jun, Fos, and Krox proteins such as cuneate and gracile ncl., venterobasal complex of thalamus, globus pallidum, and Purkinje cells of the cerebellum. Our data indicate that inducible transcription factors of the fos, jun, and krox gene families show patterns of individual expression in untreated animals, thereby reflecting different mechanisms and/or thresholds for induction under physiological conditions.

Animals↗
PubMed1995

Tissue-specific expression of the fos-related transcription factor fra-2 during mouse development.

The fra-2 gene is related to the proto-oncogene c-fos and encodes a member of the AP-1 transcription factor gene family. We have studied the expression of fra-2 during mouse embryonic development and compared it to the pattern of expression of other fos and jun family members. By in situ hybridization and immunohistochemical analysis we have shown fra-2 expression during late organogenesis. fra-2 transcripts are detected in several differentiating epithelia, developing cartilage and central nervous system. The pattern of fra-2 expression is distinct from that observed for other fos related genes, suggesting that fra-2 has a unique role in cellular differentiation during fetal development.

Adrenal Glands↗
PubMed1995

The orphan mouse receptor interleukin (IL)-8R beta binds N51. Structure-function analysis using N51/IL-8 chimeric molecules.

We have demonstrated that the orphan receptor representing the putative mouse (mu) homolog of the human (hu) interleukin-8 receptor beta (IL-8R beta) binds the mouse N51 cytokine, also known as KC. The muIL-8R beta gene was constitutively expressed in NIH 3T3 cells (NIH-muIL-8R beta). Cells and plasma membranes from the NIH-muIL-8R beta clone showed binding of 125I-N51 that was displaced by unlabeled N51. Other related cytokines were assayed for their ability to displace 125I-N51. MIP-2 and GRO alpha/MGSA competed as well as N51 for the receptor, but huIL-8 and NAP-2 did not compete at all. Chimeric molecules between IL-8 and N51 were used to extend the binding analysis. The segment between the conserved cysteines 2 and 3, named domain I; cysteines 3 and 4, domain II; and cysteine 4 and the C terminus, domain III of IL-8 were replaced by the corresponding domains of N51 and vice versa. When studying the binding of 125I-N51 and the hybrid molecules to the receptor, we observed that chimeras of N51 containing either domain I, II, or III of IL-8 were agonists of N51, and chimeras of IL-8 containing domain II or III of N51 were partial agonists of N51. These results demonstrate that domain I of N51 does not confer binding specificity and suggest that the region from the third cysteine to the C terminus of the N51 molecule is more important for binding to muIL-8R beta.

3T3 Cells↗
PubMed1995

Specific inhibition of RelB/p52 transcriptional activity by the C-terminal domain of p100.

The Rel/NF-kappa B family transcriptional factors plays an important role in the regulation of immune and acute phase responses. The activity of Rel/NF-kappa B complexes is regulated by their interactions with members of the I kappa B family of inhibitors. We have previously shown that the RelB/p52 heterodimer is not effectively inhibited by any of the known I kappa B molecules: I kappa B alpha, I kappa B gamma and Bcl3. Here we report that the C-terminal domain of p100 (the putative I kappa B delta) functions as a strong inhibitor of RelB/p52 transcriptional activity. In vivo interaction with I kappa B delta leads to the cytoplasmic retention and decreased DNA binding activity of RelB/p52 complexes. Thus, I kappa B delta is the only I kappa B molecule able to efficiently modulate the activity of RelB/p52 heterodimer. In Daudi cells, a 46 kD protein, probably representing the C-terminal product of the proteolytic processing of p100, remains associated with Rel/NF-kappa B complexes and might have a transient regulatory function. Our results indicate a specific role for the putative I kappa B delta and suggest a possible mechanism of how the truncation of the ankyrin domain of p100, found in a number of lymphoid neoplasias, might contribute to tumorigenesis.

Cell Line↗