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Biomedical subjects

C Santos

Publications and source records attributed to C Santos.

At least 91 records · Page 5Linked to original sources
PubMed1995

Detachment of transformed cells. Role of CD44 variants.

A parallel-plate flow chamber was used to quantify the detachment of normal cloned rat embryo fibroblasts (CREF) fibroblasts, ras-transformed CREF fibroblasts (CREF T24), and CREF T24 fibroblasts transfected with a Krev/RAP1A suppressor gene (HK B1) from a confluent monolayer of normal CREF fibroblasts to determine if the expression patterns of CD44 variants (mol wt 110 and 140 kDa) corresponded with detachment properties and metastatic potential. In the detachment assay, known shear stresses ranging from 20-24 dyn/cm2 were applied to the adherent cells and the number of cells detached from the monolayer after 180 s was determined. Results showed that cellular expression of CD44 variants correlated with the metastatic potential of the cells and with the cells' ability to detach from a monolayer of normal cells. Western blot analysis showed a low level of expression of the CD44 variants in the normal cell line, CREF, and the lowly metastatic cell line, HK B1. Detachment studies showed a low percentage of detachment of both of these cell lines from a normal cell monolayer. Tumor-derived (HK B1-T) and lung nodule-derived (HK B1-M) cell lines were established and both formed tumors and metastasis with reduced latency periods as compared to HK B1, but still showed a markedly delayed latency period compared to the highly metastatic cell line, CREF T24. Both of these cell lines showed a higher expression of the CD44 variants as compared to CREF and HK B1, and detached easier than CREF and HK B1. CREF T24 showed a much higher level of expression of the variants and had a higher percentage detachment than all other cell lines. To further test the role of the CD44 variants in the ability of the cells to detach from the normal monolayer, CREF cells were transfected with a DNA construct that constitutively expresses the CD44 variants and the detachment properties of three randomly selected clones were studied. Clones 2 and 3 showed a low level of expression of the CD44 variants after transfection and detached from the normal monolayer similar to CREF. Clone 1 showed a high level of expression of the CD44 variants and the detachment of these cells was significantly higher than CREF. From these results, it is concluded that in the five cell lines studied, expression of the CD44 variants play a significant role in the ability of the cells to detach from a monolayer of normal cells. It is hypothesized that this detachment may be an important component of a cell's ability to metastasize.

Animals↗
PubMed1995

Salbutamol inhibits pulmonary effects of platelet activating factor in man.

Inhaled platelet-activating factor (PAF) provokes considerable pulmonary gas exchange disturbances in normal man and in patients with mild asthma, similar to those observed in acute severe asthma. To further examine the mechanisms involved in PAF-induced ventilation-perfusion (VA/Q) mismatch, eight healthy, non-atopic, nonsmoking subjects were studied after administration of PAF aerosol (24 micrograms). They had been previously treated with inhaled salbutamol (300 micrograms) in a randomized, double-blind, cross-over, placebo-controlled design. After placebo, PAF provoked a fall in total arterial white cell count with a rebound leukocytosis. As shown in a previous study, an overall index of VA/Q inequality (DISP R-E*, 1.64 +/- 0.10) showed a threefold increase (P < 0.006) that accounted for the increase (79%) in AaPO2 (p < 0.04) after PAF, while the respiratory system resistance (Rrs) rose by 16% (p < 0.02). In contrast, after pretreatment with salbutamol inhaled PAF had no effects on pulmonary gas exchange, Rrs, or white cell count; facial flushing and cough were also hindered. The results are consistent with the hypothesis that salbutamol inhibits PAF-induced venoconstriction in both the airway and pulmonary microcirculation.

Administration, Inhalation↗
PubMed1995

Balanced incomplete block design: description, case study, and implications for practice.

This article discusses the use of balanced incomplete block design for process evaluation and presents a case study of its use. This technique produces a weighted ranking of program elements, showing the relative importance of each element and allowing comparison of process and content elements. The article presents a case study in which the technique was used to evaluate the Chronic Disease Self-Management Program. Participants and lay course leaders were asked to rank 13 course elements for their helpfulness. The most valued element, sharing or unstructured interactions among participants, was not an explicitly planned part of the intervention. Some of the elements least valued (nutrition, use of community resources, and medication use) are elements most emphasized by the health care system and by patient education. We found that balanced incomplete block design was easy to administer and tally. The results could be readily applied to program redesign and to needs assessment.

Activities of Daily Living↗
PubMed1994

Ribosomal protein P0, contrary to phosphoproteins P1 and P2, is required for ribosome activity and Saccharomyces cerevisiae viability.

Protein P0 in Saccharomyces cerevisiae is found only in the ribosomes and not free in a cytoplasmic pool like the structurally related acidic P1 and P2 proteins. Analogously, P0 stays bound to the particles in conditions that release the other P proteins. Attempts to obtain yeast strains carrying an interrupted P0 gene by direct gene disruption techniques of different yeast strains always resulted in haploid cells carrying one disrupted and one intact copy of the gene. Disruption of the unique P0 genomic copy seems to induce a duplication and occasionally a chromosomal transposition of the gene. Conditional null mutants of P0 were then constructed carrying the P0 gene under the control of the inducible GAL1 promoter. A 2-3-fold excess of P0 mRNA is found in the conditional mutant when grown in galactose; however, only a small increase of the P0 protein is detected in total cell extracts. No P0 protein is detected in the cell supernatant, indicating that, like the standard ribosomal proteins and opposite to the other P proteins, the protein not bound to the ribosomes is degraded. Transfer of the mutants to the restrictive conditions causes, after some generations, a growth stop that finally leads to cell death. The growth decline is paralleled by a reduction in the polysome number and the appearance of half-mer particles as well as by an accumulation of 60 S particles deficient in P0 and in the acidic proteins P1 and P2. These results indicate that P0 is required for the interaction of the acidic P1 and P2 proteins with the ribosomes, and in its absence, deficient 60 S ribosomes are assembled which are inactive in protein synthesis resulting in cell lethality.

Blotting, Southern↗
PubMed1994

Effect of acidic ribosomal phosphoprotein mRNA 5'-untranslated region on gene expression and protein accumulation.

Constructions were made from genes encoding ribosomal acidic phosphoproteins YP1 beta (L44') and YP2 beta (L45) from Saccharomyces cerevisiae in which different parts of the 5'-untranslated regions were included. The constructs were inserted into centromeric plasmids under the control of the GAL1 promoter and expressed in yeast strains in which the genes coding for each acidic protein family, P1 and P2, had been disrupted. Deletions in the 5' region of the two genes have been found to oppositely affect their expression. Deletion of most of this region strongly stimulates the expression of YP2 beta (L45), increasing the translation efficiency of the mRNA, and generating a 6-fold excess of protein in the cell. A similar deletion in the rpYP1 beta gene represses the expression of the protein, reducing drastically the amount of the mRNA in the cell. The overexpression of rpYP2 beta affects the cell growth by inhibiting protein synthesis at the level of initiation. Reduction of the YP2 beta(L45) overproduction by growing in controlled concentrations of glucose abolishes the inhibitory effect. The excess protein, probably as a high molecular weight complex, apparently interferes with the joining of the 60 S subunit to the initiation complex generating the accumulation of polysome half-mers. In addition, the results indicate the existence of a regulatory mechanism by which each one of the two acidic proteins controls the expression of the other polypeptide. YP1 beta(L44') represses the expression of YP2 beta(L45), while this protein stimulates the expression of YP1 beta(L44').

Gene Expression Regulation, Fungal↗
PubMed1994

Sharing of injection equipment among 3755 intravenous drug users in Valencia, Spain, 1987-1992.

BACKGROUND: In order to identify, in a sample of heroin intravenous drug users (IVDU), those factors associated with the predominant risk behaviour related to the transmission of HIV-1 infection--sharing of injection equipment--a cross-sectional survey was carried out in Valencia, Spain from 1987 to 1992. METHODS: Informed consent and pertinent data were obtained from 3755 heroin IVDU recruited at two public AIDS Information Centres in two cities in the region of Valencia. Data were gathered on sociodemographic variables, and sexual and drug use behaviour by interview. The subjects were subsequently tested for HIV-1 antibody. A univariate analysis was carried out to identify variables that were significantly associated with sharing injection equipment. A logistic regression model was used to control for possible confounders. RESULTS: The IVDU who were teenagers, prostitutes (OR = 1.95), who had antibodies to HIV-1 (OR = 1.30) or who had an IVDU steady partner were at significantly higher risk for sharing of injection equipment. Higher levels of education, condom use (OR = 0.65) and living in the smaller city (OR = 0.75) were inversely related to sharing injection equipment. CONCLUSIONS: Our results suggest that different subgroups of IVDU have different characteristics that place them at different risk for HIV-1 infection. These characteristics should guide the design and intensity of specific preventive interventions. Teenagers and IVDU with low educational levels should be targetted for special attention by health authorities.

Adolescent↗
PubMed1994

Effects of PEEP on VA/Q mismatching in ventilated patients with chronic airflow obstruction.

Recent work in patients with acute respiratory failure (ARF) due to exacerbation of chronic airflow obstruction (CAO) suggests that application of low degrees of positive end-expiratory pressure (PEEP) can improve rather than impair respiratory mechanics, because PEEP replaces intrinsic PEEP (PEEPi). However, the impact of PEEP on pulmonary gas exchange has not been fully investigated. We designed this study to examine the effects of PEEP and those of PEEPi on ventilation/perfusion (VA/Q) mismatching in mechanically ventilated patients with CAO. Eight patients were studied under four conditions: (1) during controlled mechanical ventilation with the ventilatory setting established by the attending physicians (PEEPi-100%), according to standard criteria; (2) after application of PEEP amounting to 50% (PEEP-50%), and then (3) to 100% (PEEP-100%) of the original PEEPi; and finally, (4) after reduction of PEEPi to 50% of the initial value (PEEPi-50%), obtained by increasing expiratory time and decreasing respiratory rate and tidal volume. Respiratory mechanics, hemodynamics, respiratory blood gases, and VA/Q distributions were measured during each ventilatory mode. At low values of PEEP (PEEP-50%) no changes in respiratory mechanics nor in hemodynamics were observed, but PaO2 moderately increased (from 103 +/- 25.2 to 112 +/- 29.6 mm Hg) and PaCO2 slightly decreased (from 42 +/- 3.7 to 40 +/- 3.3 mm Hg) essentially because of an increase in the mean VA/Q ratio (first moment) of both flood flow (Q, from 0.65 +/- 0.28 to 0.78 +/- 0.29) and ventilation (V, from 4.02 +/- 1.55 to 4.93 +/- 2.00) distributions (p < 0.05, each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Inhaled platelet-activating factor worsens gas exchange in mild asthma.

To investigate the potential effects of inhaled platelet-activating-factor (PAF) (12 micrograms) to perturb pulmonary gas exchange in bronchial asthma, six patients (mean +/- SE, 23 +/- 2 yr) with intermittent asthma (FEV1, 90% predicted) were studied before and 5, 15, and 45 min after challenge. Circulating white blood cells, respiratory system resistance (Rrs), systemic and pulmonary hemodynamics, and respiratory and inert pulmonary gas exchange were measured. Five minutes after PAF leukocytes fell, Rrs increased (by 27%). PaO2 decreased (by 15 mm Hg), and AaPO2 increased (twofold) (p < 0.05 each). Ventilation-perfusion (Va/Q) distributions worsened in a pattern similar to that commonly observed in patients with moderate to severe asthma. Dispersions of pulmonary blood flow (log SD Q) and of alveolar ventilation (log SD V), and an overall index of Va/Q heterogeneity (DISP R-E*) increased significantly (123% for DISP R-E*; p < 0.05, each). Gas exchange indices and Rrs were still minimally abnormal at 15 min but returned towards baseline at 45 min. Ventilatory and hemodynamic variables remained unaltered throughout the study. These results suggest that endogenous PAF may be implicated in the arterial blood gas abnormalities shown during exacerbations of bronchial asthma.

Administration, Inhalation↗
PubMed1994

Laminin and tenascin assembly and expression regulate HC11 mouse mammary cell differentiation.

HC11 is a normal mouse mammary epithelial cell line that requires certain growth factors, such as EGF or bFGF, to respond optimally to lactogenic hormones and produce the differentiation marker beta-casein. Growth in insulin (Ins) or PDGF does not produce cells competent to respond to lactogenic hormones. Here we show that competency for differentiation is due at least in part to the modulation of extracellular matrix components. In particular we have studied laminin and tenascin. EGF alters endogenous laminin assembly. In addition, promotion of competency can be partially mimicked by plating HC11 cells on the E8 laminin fragment, which is able to induce lactogenic responsiveness in cells grown in the absence of EGF or bFGF. The production and assembly of tenascin is also dependent upon the growth conditions of the HC11 cells. EGF- or bFGF-grown competent cells produce tenascin but do not assemble it at the extracellular matrix as efficiently as Ins- or PDGF-grown, non-competent cells. This alteration apparently leads to a change in the cellular microenvironment that supports beta-casein production. In addition, when competent cells are plated on dishes coated with tenascin, lactogenic hormone induction of beta-casein is inhibited. The data suggest that tenascin assembly and beta-casein production are opposing features of a coordinated differentiation program of HC11 cells.

Animals↗
PubMed1994

[Cholera epidemiology in Mozambique: 1973-1992].

The results of an epidemiological analysis of cholera in Mozambique from 1973 to 1992 are described. The project sought to assess the influence of socio-economic and ecological factors the spread of cholera in a country at war. Information about the incidence of cholera and the fatality rate were related to the rainfall and the annual average growth rate of the population in the main cities. Water supply, sanitation and food hygiene were also studied. The high annual average growth rate of the population was found to have a direct linear correlation to the incidence of cholera. The drought of 1991-1992 also played an important role in the increased number of cases of the disease. Cholera has presented an endemic-epidemic pattern determined by: a) the uncontrolled growth of urban population, b) the deterioration of sanitation in urban centers, c) the unhygienic commercialization of food and d) the drought.

Cholera↗
PubMed1994

[Enalapril prevents myocardial remodeling in rats with arteriovenous fistula].

AIM OF THE STUDY: To evaluate the efficacy of enalapril in preventing cardiac myocyte remodelling in rats with arteriovenous fistulas. EXPERIMENTAL DESIGN: We distributed thirty males Wistar rats in 3 groups: group A (control), group B (fistula) and group C (fistula + enalapril). An end to side fistula between the femoral artery and vein was produced in the right thighs of rats from groups B and C. Oral enalapril (0.07 mg/kg/day) was given to rats from group C. After 8 weeks the rats were sacrificed and their heart removed for pathologic study. RESULTS: Body weight evolution was similar in all groups. Heart weight increased in group B (1.78 +/- 0.2 g) when compared to group A (1.55 +/- 0.11 g), (p < 0.02), and was similar (p = n.s.) in groups A and C (1.58 +/- 0.13 g). Heart weight/Body weight ratio was also increased in group B (4.4 +/- 0.55 mg/g) when compared to group A (3.6 +/- 0.5 mg/g), (p < 0.01), but was similar in groups A and C (3.66 +/- 0.4 mg/g) (p = n.s.). An increase in wall thickness was detected in group B in the right ventricle (p < 0.03), septum (p < 0.01) and left ventricle (p < 0.01) when compared to groups A and C. Myocytes cytoplasm volume fraction was increased in group B, when compared with group A, in all segments studied (right ventricle p = 0.011, septum p = 0.025, and left ventricle p = 0.031). Groups A and C were similar. CONCLUSION: Enalapril prevents the structural remodelling of cardiac myocytes in this model of volume overload induced by an arteriovenous fistula.

Animals↗
PubMed1993

Formation of hydroxyl radicals and Co3+ in the reaction of Co(2+)-EDTA with hydrogen peroxide. Catalytic effect of Fe3+.

Co2+ ions (Co(NO3)2.6H2O) react with H2O2 only in presence of EDTA to yield OH radicals and Co3+. This reaction was carried out in unbuffered aqueous solutions (pH = 2.6). The formation of Co3+ was confirmed by spectroscopy. The Co(3+)-EDTA complex shows two typical absorptions at 382 nm and 532 nm. The Co(3+)-EDTA complex can be prepared by a number of oxidizing agents, like Fe3+, Fe(3+)-EDTA, Ag+, Ag2+, Ce4+, and hydroxyl radicals. Since Fe3+ oxidizes Co(2+)-EDTA to Co(3+)-EDTA and Fe2+ we initiate a chain reaction for .OH formation. Our results show that there are two modes for H2O2 decomposition: (1) One electron transfer to give OH radicals and (2) Decomposition of H2O2 to H2O and O2 without intermediate .OH formation. This reaction depends strongly on the pH of the buffer. The H2O2 decomposition increases with increasing pH and increasing Co2+ concentration.

Catalysis↗
PubMed1993

The acidic phosphoproteins from Saccharomyces cerevisiae ribosomes. NH2-terminal acetylation is a conserved difference between P1 and P2 proteins.

Isoelectrofocusing gels of acidic ribosomal proteins from most yeast strains reveal the presence of up to 10 bands which are the product of only 4 genes. The proteins have been characterized by NH2-terminal amino acid sequencing, specific antibodies, HPLC, and by taking advantage of acidic protein-defective yeast strains obtained by gene disruption methods. The four most basic proteins coincide with the phosphorylated and dephosphorylated forms of the YP2 proteins, YP2 alpha and YP2 beta, formerly named L44 and L45. Amino-terminal sequencing has shown that these two polypeptides have free amino-terminal ends starting at the first methionine residue. The bands defined earlier as L44' correspond to the phosphorylated and dephosphorylated processed forms of protein YB1 beta lacking the first eight amino acids. The formation of this truncated YP1 beta form seems to be stimulated by salt during protein extraction and is also favored by some modifications at the amino termini of the protein. On the other hand, the previously uncharacterized band, called Ax, corresponds to an NH2-terminal acetylated form of YP1 beta which starts at the serine in the second position of the nucleotide-derived sequence. Finally, the most acidic band is the phosphorylated product of the fourth acidic protein gene. This protein, called YP1 alpha, which is very poorly stained by silver and Coomassie blue, has not been characterized in detail previously. It is also monophosphorylated in the ribosome and, like YP1 beta, is present as an NH2-terminal acetylated form starting at the second serine residue.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1992

Stable binding of the eukaryotic acidic phosphoproteins to the ribosome is not an absolute requirement for in vivo protein synthesis.

The genes encoding the four acidic ribosomal phosphoproteins have been inactivated in Saccharomyces cerevisae by recombination with truncated genes carrying different genetic markers. By crossing single haploid disruptants, strains harboring two simultaneously inactivated acidic protein genes were constructed. None of the six possible double disruptions was lethal, but the simultaneous inactivation of either YP1 alpha and YP1 beta(L44') or YP2 alpha(L44) and YP2 beta(L45) caused an important decrease in the cell growth rate. Ribosomes isolated from these slow-growing strains did not contain acidic proteins, not even the two polypeptides whose genes were still intact, although these proteins were present in the cell extracts and they seem to be able to form high-molecular weight protein complexes. Transformation of a slow-growing double transformant with a plasmid containing one of the disrupted genes restored the presence of the acidic proteins in the ribosomes and normal growth rates. The particles of the slow-growing strains were active in an in vitro amino acid polymerizing system, although their activity could be stimulated by the exogenous addition of the missing proteins. These results indicate that in the absence of either YP1 alpha and YP1 beta(L44') or YP2 alpha (L44) and YP2 beta(L45), the remaining acidic proteins are unable to interact with the ribosome in a stable manner, but that a strong interaction of these ribosomal components with the particle is not an absolute requirement for in vivo and in vitro protein synthesis.

Blotting, Southern↗
PubMed1992

Leukonychia due to cytostatic agents.

Chromonychia induced by antineoplastic agents has been known for several years. The most frequent of these is melanonychia, either diffuse or in tranverse or longitudinal bands, that may co-exist with diffuse pigmentation of the skin. Although any cytostatic agent may be involved in melanonychia, this condition appears most commonly after treatment with adriamycin and cyclophosphamide or in polychemotherapy. Leukonychia, either true or apparent, seems to be less frequent and is the reason for our reporting two patients with this colour change.

Adult↗
PubMed1991

Identification of human papillomavirus type 16 in primary and recurrent cervical cancer following radiation therapy.

Formalin-fixed, paraffin-embedded tissue blocks from 13 women with cervical carcinoma that recurred following radiation therapy were evaluated for the presence of human papillomavirus (HPV) by in situ hybridization using ribonucleic acid 35S-labeled probes for HPV types 6, 11, 16, and 18. Ten of thirteen patients also had pretreatment biopsies from their primary tumors available for analysis. HPV 16 was detected in both primary and recurrent lesions in 4 women. In 1 case, HPV was detected in the primary tumor and not in the recurrence. HPV 16 was also present in three recurrent cancers from which primary lesions were not available for probing. Radiation therapy did not alter the hybridization signal strength or pattern, suggesting that the HPV genome copy number was not significantly affected. The persistence of HPV 16 in recurrent cervical carcinoma is consistent with the theory that HPV plays a role in maintaining the malignant state.

Adult↗