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Biomedical subjects

J Prieto

Publications and source records attributed to J Prieto.

At least 289 records · Page 16Linked to original sources

Loss of pseudorabies virus thymidine kinase activity due to a single base mutation and amino acid substitution.

The nucleotide sequences of the coding region of the thymidine kinase (TK) gene of pseudorabies virus strain NIA3 and a TK- mutant (ATK5) were determined. The coding region of the TK gene consists of 320 codons capable of producing a polypeptide with an Mr of 34979. The mutant expressed an inactive TK polypeptide when translated in vitro; a unique base substitution was detected in the mutant TK modifying amino acid position 13, at which aspartic acid replaces glycine. This modification affects the nucleotide-binding site, thus explaining the expression of an inactive TK polypeptide.

Amino Acid Sequence↗

Liver changes in patients with hyperthyroidism.

We studied liver changes in the hepatic biopsies of five patients with hyperthyroidism. A characteristic histopathologic picture consisting of mild to moderate intrahepatocytic cholestasis, lobular inflammatory infiltrate with some eosinophils, and Kupffer cell hyperplasia was found in all cases. We discuss the specificity, clinicopathological correlations and the possible pathophysiology of these lesions.

Biopsy↗

Enhanced responsiveness to CNS-induced natriuresis in anesthetized nonascitic cirrhotic rats.

Central nervous system (CNS)-induced natriuresis was investigated in nonascitic rats with CCl4-induced cirrhosis (CTC rats) under pentobarbital anesthesia. At baseline, urine sodium output (UNa+V, in mumol.min-1.100 g body wt-1) (-30%, P less than 0.01) and mean arterial pressure (MAP, in mmHg) (-12%, P less than 0.001) were significantly reduced in CTC rats (n = 32) compared with matched controls (n = 34). In response to intracerebroventricular infusion of sodium-rich (349 mM) artificial cerebrospinal fluid (Na(+)-CSF infusion), UNa+V was significantly higher in CTC rats (2.8 +/- 0.3; n = 15) than in controls (1.7 +/- 0.2; n = 17; P less than 0.01); no differences were found in pressor changes (24 +/- 3 vs. 19 +/- 2). A similar but normal sodium CSF (150 mM) infusion did not influence UNa+V or MAP in any group (n = 12, both). In contrast, CTC rats (n = 5) showed, compared with controls (n = 5), significantly reduced natriuretic (UNa+V, 6.9 +/- 0.5 vs. 12.4 +/- 0.9; P less than 0.001) and pressor (+16 +/- 3 vs. +31 +/- 2; P less than 0.01) responses to an intravenous hypertonic sodium overload. Natriuresis induced by Na(+)-CSF infusion was related to increases in creatinine clearance (similar in both groups) and in fractional sodium excretion, which was significantly higher in CTC rats (5.90 +/- 0.15%) than in controls (3.65 +/- 0.14%; P less than 0.01). In summary, CNS-dependent efferent natriuretic mechanisms were preserved in CTC rats and were able to reverse renal tubular sodium retention in these animals. It is proposed that Na(+)-CSF infusion may be a useful tool for the study of renal sodium retention in experimental liver cirrhosis.

Animals↗

Postantibiotic effect of ciprofloxacin compared with that of five other quinolones.

The antimicrobial activity (minimal inhibitory concentration, MIC, and killing kinetics) and postantibiotic effect (PAE) of different concentrations (MIC and 6 mg/1) of ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, fleroxacin and lomefloxacin on pure cultures of Staphylococcus aureus and Escherichia coli were compared in vitro. The MIC, killing kinetics and PAE were determined by standard methods. Ciprofloxacin displayed the lowest MICs, while the highest were those of norfloxacin against S. aureus and lomefloxacin against E. coli. The killing curves showed ciprofloxacin to be the most and norfloxacin the least active. The bactericidal power was dependent on the concentration. At MIC, the fluoroquinolones, with the exception of norfloxacin, induced PAEs of 1-2 h. The effect was, in all cases, greater against E. coli. When assayed at 6 mg/l the PAEs were increased to 2-5 h, the best results being obtained by ciprofloxacin followed by ofloxacin. Norfloxacin produced no PAE on S. aureus and scarcely reached 1.3 h against E. coli. There was a close relationship between bactericidal power and PAE.

Anti-Infective Agents↗

[The treatment of primary biliary cirrhosis with ursodeoxycholic acid. The short- and median-term results and their relation to the study of the disease].

We present the results of the treatment with ursodeoxycholic acid (UDCA, 7-9 mg/kg body weight daily) of 17 patients with primary biliary cirrhosis (8 in stages I-II; 9 in stages III-IV). At two months the mean values of alkaline phosphatase, gammaglutamiltranspeptidase, alanine and aspartate aminotransferase were reduced (p less than 0.001, p less than 0.001, p less than 0.01 and p less than 0.01 respectively). This improvement persisted without increase during the first year. At two months the total bilirubin value was reduced (p less than 0.01) associated with a reduction in the conjugated fraction (p less than 0.05). Cholesterol and gammaglobulin mean values also decreased at two months (p less than 0.05). We found no changes in IgM levels and antimitochondrial antibody titers. The improvement was similar in both groups (early I-II and advanced III-IV stages) and the treatment showed no undesirable effects either in early or advanced stages. Almost all the patients with pruritus (6 out of 7) improved with the treatment and the use of cholestyramine was reduced in all.

Administration, Oral↗

[Type 6 human herpes virus and chronic asthenic syndrome].

Chronic asthenia syndrome has been associated with Epstein-Barr virus (EBV). To investigate the possible role in this syndrome of human herpesvirus type 6 (HHV-6), a new herpesvirus discovered in 1986, we performed a serological study of 44 patients diagnosed of chronic asthenia syndrome and 50 controls. Fifty healthy controls (34%) and 44 patients (54.5%) had positive serological tests for HHV-6. This difference was significant (p less than 0.05). The rate of positive serological studies for CMV and EBV was higher in healthy controls (n = 50) than in patients (n = 37) (96% vs 67.7% for CMV [p less than 0.001] and 92% vs 78.4% for EBV [non significant difference]). We conclude that HHV-6 may play a role in the pathogenesis of chronic asthenia syndrome. In our group of patients there were no significant differences in the presence of anti EBV capsid antibodies.

Antibodies, Viral↗

Polarity of immunogens: implications for vaccine design.

Peptide constructs have been engineered consisting of amino acid sequence determinant recognized by T cells (TD) co-linearly linked to haptenic peptides. It was found that high anti-hapten antibody titers were induced after immunization with those constructs which had the TD sequence in the N-terminal position with respect to the hapten. Low or zero titers were elicited when the TD was in C-terminal position. Also, a high anti-hapten antibody titer corresponded to a low or zero anti-TD antibody titer and vice versa. These results suggest that immunogens are polar and stress the relevance of searching the more adequate position of the TD within a peptide construct when designing immunogens or synthetic peptide vaccines.

Amino Acid Sequence↗

Rabbit leukocyte adhesion molecules CD11/CD18 and their participation in acute and delayed inflammatory responses and leukocyte distribution in vivo.

In humans the glycoprotein complexes CD11/CD18 mediate leukocyte adhesion to cells. Mouse monoclonal antibodies (mAb) 60.3, 7E4, and IB4 to human CD18, found to cross-react with rabbit white blood cells, were used to identify the antigen in rabbit cells and to study adherence of rabbit leukocytes in vitro and in vivo. These antibodies labeled almost all unfractionated rabbit blood leukocytes and immunoprecipitated surface glycopolypeptides with apparent molecular weights of 85,000 and 150,000 from these cells. Adhesion of purified rabbit polymorphonuclear cells (PMNs) to cultured vascular endothelial cells in the presence of phorbol ester was blocked by the antibodies in a dose-dependent manner. The acute inflammatory response characterized by local accumulation of PMNs and concomitant plasma extravasation following intradermal injections of zymosan-activated serum (ZAS) in rabbits was inhibited in animals pretreated intravenously with anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 mAb. Intravital microscopy of the rabbit tenuissimus muscle demonstrated that anti-CD18 treatment specifically blocked the adhesion of activated leukocytes to the venular endothelium and thereby the subsequent diapedesis of these cells into the extravascular space. The lymphocyte-dependent tissue swelling resulting from a delayed-type hypersensitivity reaction in the rabbit ear was partially inhibited by anti-CD18 mAb. Systemic anti-CD18 treatment induced a pronounced increase in the number of circulating mononuclear and polymorphonuclear cells with a maximum at 24 hr after injection of the antibody. It is concluded that GP150/GP85 is the rabbit homologue of human CD11/CD18, and that leukocyte-cell adhesion mediated by these glycoprotein complexes participates in acute and delayed inflammatory responses and leukocyte distribution in vivo.

Animals↗

An experimental model of chronic osteomyelitis caused by Escherichia coli treated with cefotaxime.

An experimental model in Wistar rats, of osteomyelitis caused by Escherichia coli, was used to evaluate the efficacy of cefotaxime in two treatment regimens of different durations. Four groups of rats were set up: a group of rats receiving short-term treatment (14 days) with subcutaneous cefotaxime (100 mg bd), killed after 56 days; a control group receiving no treatment, killed after 56 days; a group of rats undergoing long-term treatment (28 days) with subcutaneous cefotaxime as above, killed after 70 days and a control group of rats receiving no treatment, killed after 70 days. Analysis of histopathological and microbiological findings revealed significantly better results in the long-term treatment group. No side-effects were observed during treatment or afterwards.

Animals↗

Monocyte disorder causing cellular immunodeficiency: a family study.

We report a familial type of monocyte dysfunction not recognized previously. This disorder was observed in a young adult man with a long clinical history of recurrent, self-limited episodes of cryptogenic fever accompanied by digestive and respiratory symptoms and repeated oral and skin infections. Lectin-induced lymphocyte transformation was reduced and skin tests revealed anergy to tuberculin and candidin. Monocytes from this patient exhibited markedly diminished expression of cytoskeletal vimentin intermediate filaments, HLA-DR antigens and immunological receptors for IgG Fc and C3b. These abnormal monocytes demonstrated impaired phagocytosis and reduced accessory cell function on PHA-mediated lymphocyte activation. Release of soluble lymphocyte-activating factors by these cells was found to be defective. Lymphocytes from the patient responded appropriately to lectin in the presence of normal monocytes. Two family members of the proband presented similar monocyte defects although they only manifested minor clinical symptoms. This syndrome underlines the interest of testing monocyte markers and function in subjects with clinical manifestations of immunodeficiency.

Adult↗

Tubular sodium handling in cirrhotic patients with ascites as analysed by the renal lithium clearance method.

The proximal and distal sodium reabsorption were calculated from lithium clearance in 21 healthy controls and 24 cirrhotic patients with ascites after 4 days under a sodium-restricted diet. The values of fractional lithium clearance were lower in patients than in controls (7.37 +/- 0.87 vs. 18.13 +/- 1.76%, P less than 0.001). Fractional proximal sodium reabsorption was increased in patients compared with controls (92.8 +/- 1.1 vs. 81.8 +/- 1.7%, P less than 0.001). No differences were found in fractional distal sodium reabsorption between controls and patients (96.9 +/- 0.8 vs. 98.6 +/- 0.1%). When patients were separated into two subgroups according to their sodium balance, it was found that fractional distal sodium reabsorption was increased in patients whose balance remained positive, compared with patients on a negative sodium balance (98.99 +/- 0.26 vs. 94.11 +/- 1.50%, P less than 0.05). In addition, the natriuretic response to a specific dose of spironolactone was higher in patients on positive sodium balance compared with patients on negative sodium balance (per cent increase in natriuresis after spironolactone 300 mg day-1: 355.24 +/- 73.98 vs. 84.21 +/- 15.8%, P less than 0.01). We conclude that proximal sodium reabsorption is increased in cirrhotics with ascites. In addition, distal sodium reabsorption is enhanced only in those patients which exhibit avid sodium retention.

Adult↗

Leukocyte-cell adhesion: a molecular process fundamental in leukocyte physiology.

Leukocyte-cell adhesion is a form of physical contact characterized by fast (firm) stickiness between the cells. To analyze the biology and molecular basis of this process, an adhesion-specific assay was developed: the phorbol ester-induced aggregation of human lymphocytes. This rapid and antigen-independent intercellular adhesion requires cellular metabolism, an intact cytoskeleton and extracellular divalent cations, and is mediated by preformed cell-surface proteins referred to as CAMs. Phorbol ester also induces aggregation of monocytes and granulocytes, as well as adhesion of T lymphocytes to either B cells or monocytes and of the leukocytes to vascular endothelial cells. By using the adhesion-specific assay and blocking monoclonal antibodies, several CAMs have been identified, namely the Leu-CAM family (CD11a-c/CD18) and ICAM-1 (CD54). The Leu-CAM family is composed of Leu-CAMa (CD11a/CD18), Leu-CAMb (CD11b/CD18) and Leu-CAMc (CD11c/CD18), three glycoprotein heterodimers made of a common beta-chain and distinct alpha-chains. ICAM-1 is an adhesive ligand for Leu-CAMa. Expression and use of the various CAMs is selective in different types of leukocytes. The Leu-CAMs have been purified and partially characterized. CD18, whose gene is on human chromosome 21, contains 5-6 N-linked complex-type oligosaccharides, and CD11 binds Ca++. Another adhesion pathway is mediated by CD2 and CD58. CD2, a glycoprotein selectively expressed by T cells, is a receptor for CD58, a cell-surface adhesive ligand with broad tissue distribution. Antibodies to the latter CAMs do not block the phorbol ester-induced lymphocyte aggregation. Adhesion is involved in a large variety of leukocyte functions. Anti-Leu-CAM antibodies block induction of IL-2 production and lymphocyte proliferation. Lymphocyte-mediated cytotoxicity is also inhibited. Endogenous NK and LAK cells use Leu-CAMs, ICAM-1 and CD2, and sometimes RGD receptors, to bind and kill tumor cells. Endogenous compounds such as H2O2 and LTB4 also induce Leu-CAM-dependent adhesion in monocytoid cells and granulocytes, respectively, and degranulation of the latter cells is enhanced by the adhesion process. Homologous CAMs have been identified in rabbit and mouse. In in vivo studies in the former species, anti-Leu-CAM antibodies block adhesion of leukocytes to vascular endothelium and thereby their migration into extravascular tissues. The antibodies thus inhibit granulocyte accumulation and plasma leakage in inflammatory lesions, and induce lympho- and granulocytosis, indicating that cell-adhesion contributes to the distribution of leukocytes in the body.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Post-antibiotic effect of isepamicin compared to that of other aminoglycosides.

Isepamicin is a new aminoglycoside drug derived from gentamicin, which is more stable than other aminoglycosides to inactivating enzymes and experimentally is less nephrotoxic than gentamicin or amikacin. In this work a comparative study was carried out on the antibacterial activity (MIC and lethality curves) and the post-antibiotic effect (PAE) of different concentrations of isepamicin, netilmicin and gentamicin on pure cultures of S. aureus and E. coli. The MIC and curves of lethality were determined by conventional methods. The PAE was determined after exposure of the bacterial culture to the antimicrobial one for 1 h at 37 degrees C in a bath with stirring. Elimination of the drug was made by the dilution method. Isepamicin was found to have a MIC four times greater than netilmicin and gentamicin. Its activity over time was similar to that exhibited by other aminoglycosides. At concentrations higher than the MIC, a bactericidal effect was found with the three antibiotics, although isepamicin produced it at lower concentrations. The post-antibiotic effect induced by isepamicin, the same as that of netilmicin and gentamicin, was extensive and depended on the concentration and the strain used. Isepamicin shows antibiotic activity over time and a PAE similar to the other aminoglycosides tested but, unlike them, it has a faster activity, less toxicity and better resistance to inactivating enzymes. For this reason it makes a considerable contribution to antibacterial therapies in severe conditions, including immunodepressed patients who require long-term treatment.

Anti-Bacterial Agents↗

[Influence of bacterial combinations on the post-antibiotic effect].

A study of the post-antibiotic effect (PAE) and letality curves of different concentrations of clavulanic acid, amoxycillin, amoxycillin + clavulanic acid, netilmycin and ofloxacin on mixed cultures of S. aureus and E. coli. The post-antibiotic effect was measured after one hour of exposure of bacteria to antimicrobial and the elimination of the latter by the dilution method. Amoxycillin did not induce PAE on the association. PAE only appeared at high concentrations on S. aureus when evaluated alone. Clavulanic acid induced a greater PAE than amoxycillin. The association clavulanic acid + amoxycillin was synergistic and induced a greater PAE than its components. Netilmycin and ofloxacin were the drugs that induced the greatest PAE on the bacterial association and on its strains independently evaluated.

Amoxicillin↗

[The development of a linear function for stratifying the risk of hospital mortality in acute myocardial infarct].

In spite of conventional treatment in a Coronary Unit, there is a group of patients with acute myocardial infarction who present a high mortality index. A more aggressive attitude (coronariography, angioplasty, and/or emergency coronary bypass) could improve the prognosis in some of these patients but can only be performed in a limited number of centers. In the present work, we have reviewed data obtained from the Emergency Room on 167 patients diagnosed of myocardial infarction. The variables that were correlated to mortality were: age, heart rate, blood pressure, presence of rales, radiologic heart failure cardiomegaly, ventricular extrasystoles in ECG and delay in arrival to hospital. We obtain a lineal function (z = 24.6 X1 - 0.4 X2 + 0.2 X3 + 11) which combining ventricular extrasystoles, diastolic arterial pressure, and heart rate permits to differentiate three risk groups: low, medium and high, associated to hospital mortality rates of 5.7, 36.4 and 83.3%. We suggest the use of a function of this type to select those patients who should be sent to a hospital with facilities for emergency coronary surgery.

Discriminant Analysis↗

[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon].

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.

Adult↗