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Biomedical subjects

A Garrido

Publications and source records attributed to A Garrido.

At least 73 records · Page 4Linked to original sources
PubMed1992

Deficient interleukin-2 responsiveness of T lymphocytes from patients with primary biliary cirrhosis.

There is increasing evidence that primary biliary cirrhosis is associated with an alteration of the immune system. Although the cause remains unknown, it has been suggested that the immune system of patients with primary biliary cirrhosis is involved in the pathogenesis of their disease. We have investigated the T-cell function in patients with primary biliary cirrhosis and have found defective phytohemagglutinin-induced T-cell mitogenesis. Likewise, their blastogenic response to CD3 monoclonal antibody was also depressed, although the DNA synthesis induced by stimulation with phorbol esters (12-O-tetradecanoil-phorbol-13-acetate) plus ionophore (ionomycin) was normal. These alterations could not be ascribed either to a decreased synthesis of interleukin-2 or to a defective expression of interleukin-2 receptor after cellular activation. Moreover, this defective proliferative response of T lymphocytes was observed even in the presence of saturating concentrations of exogenous interleukin-2. These results represent evidence of the deficiency in the interleukin-2-dependent pathway found in T lymphocytes from patients with primary biliary cirrhosis.

Cell Division↗
PubMed1992

The effect of calcium on disodium monofluorophosphate absorption from the gastrointestinal tract of rats.

The absorption of fluoride from disodium monofluorophosphate with or without added calcium has been studied in ligated stomachs and duodena of rats, in vivo. Measurements of fluoride absorption from sodium fluoride were also carried out for comparative purposes. The formation constant of the soluble, neutral calcium monofluorophosphate complex has been determined at 20 degrees, 25 degrees and 37 degrees C. Its value at 37 degrees C being 315 +/- 10 (molar units). The influence of increasing concentrations of calcium on alkaline phosphatase (E.C.3.1.3.1) activity with disodium monofluorophosphate as substrate has been also studied. Gastric absorption of 2 mM disodium monofluorophosphate in the presence of 50 mM calcium was much slower than that of 2 mM disodium monofluorophosphate alone. The latter was slower than that of 2 mM sodium fluoride. The opposite situation has been found for the duodenal fluoride absorption. Results obtained are interpreted in terms of the occurrence of an intestinal monofluorophosphate hydrolysis prior to its absorption as fluoride. In addition, data presented suggest an independent and parallel pathway of fluoride absorption in the form of the liposoluble calcium monofluorophosphate complex.

Absorption↗
PubMed1992

Changes in the xanthine dehydrogenase/xanthine oxidase ratio in the rat kidney subjected to ischemia-reperfusion stress: preventive effect of some flavonoids.

The enzyme xanthine oxidase has been implicated in the tissue oxidative injury after ischemia-reperfusion. This enzyme, which is a source of oxygen free radicals, is formed from a dehydrogenase form during ischemia. The ratio dehydrogenase/oxidase of rat kidney homogenates decreases during the ischemia and the reperfusion. Two flavonoids, quercetin and silybin, characterized as free radical scavengers, exert a protective effect preventing the decrease in the dehydrogenase/oxidase ratio observed during ischemia-reperfusion. The mechanism of this effect and the role of flavonoids in the ischemia-reperfusion tissue damage is discussed.

Animals↗
PubMed1991

Heterogeneity of MHC-class-I antigens in clones of methylcholanthrene-induced tumors. Implications for local growth and metastasis.

We analyzed the H-2 class-I expression of different clones obtained from 4 different methylcholanthrene-induced tumors in BALB/c (H-2d) mice. The results clearly indicated high intra-tumor heterogeneity in all 4 fibrosarcomas with regard to H-2 K, D and L expression. Clones were found to be H-2-negative, H-2-positive, or to present intermediate expression. Southern blot analysis of class-I genes showed RFLPs equal to those obtained from normal BALB/c DNA, ruling out rearrangements or gross deletions in the class-I genes of different tumors. However, Northern blot studies showed a straightforward relationship between class-I mRNA levels and H-2 expression. In vivo experiments demonstrated an inverse relationship between local growth and spontaneous metastasis, e.g., H-2-positive class-I clones produced high numbers of lung colonies but very poor local growth, and vice-versa. These results paralleled the NK sensitivity or resistance of the different clones. Cross-protection experiments showed that only clones coming from the same tumor were able to protect against challenge with clones of the same neoplasia but not with clones from different chemically induced fibrosarcomas, indicating that a clone of a given tumor probably contained the same TATA. Finally, we compared the H-2, K, D and L expression and class-I mRNA levels of various metastatic colonies. Interestingly, another degree of heterogeneity was found: an H-2-negative clone (GR9.B9) gave rise to H-2-negative (B9MP6) and H-2-positive (B9MP2) metastatic colonies.

Animals↗
PubMed1991

Bone mineral density in patients with cervical and trochanteric fractures of the proximal femur.

The bone mineral density (BMD) of the proximal femur, spine and radius shaft was determined in 75 women with atraumatic fractures of the proximal femur (FXf) (average age: 70.1 +/- 9.6 years) and 51 controls of similar age. Fractures were classified as either cervical (n = 36) or trochanteric (n = 39) on the basis of radiographic and surgical finding. The BMD of spine and proximal femur was determined by dual-photon absorptiometry (Lunar DP3) and the BMD of the radius shaft by single photon absorptiometry. The BMD of patients with FXf was significantly decreased over all skeletal sites compared to controls of similar age. No significant correlation was found between age and the BMD of the femoral neck in patients with FXf. Patients with trochanteric FXf were older and thinner (average: age, 72.9 +/- 9.4 years; weight, 53.1 +/- 7.8 kg) compared with patients with cervical fractures (age, 67.2 +/- 8.9 years; weight, 59.3 +/- 8.3 kg). Likewise the BMD of trochanteric FXf was lower at all measured sites: femoral neck, 0.548 +/- 0.066 g/cm2 vs 0.624 +/- 0.055 g/cm2 (P less than 0.001); L2-L4, 0.799 +/- 0.115 g/cm2 vs 0.925 +/- 0.106 g/cm2 (P less than 0.001); radius shaft, 0.454 +/- 0.057 g/cm2 vs 0.502 +/- 0.083 g/cm2 (P less than 0.05). Of the patients with trochanteric fractures 66% had concomitant vertebral fractures, while this occurred in only 28% of the patients with cervical fractures (P (Fisher) = 0.0007). In summary, females with trochanteric FXf are older, thinner, have less bone mass in all measured sites and suffer with a significantly greater frequency of vertebral fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1991

Experimental study of the effect of 6-methyl-prednisolone on ingestion-microbicidal function activity in dog neutrophils.

The effect of increasing doses of 6-methyl-prednisolone on the ingestion-microbicidal function activity of dog neutrophils was studied. Histochemical and spectrophotometrical NAT reduction techniques, together with a direct overall method using C. albicans as a test micro-organism were carried out. Samples were analysed 2 and 48 h after inoculation of different doses. The histochemical NAT technique was not very precise, but quantification of responses using the spectrophotometric method revealed that at 48 h.p.i. neutrophil reducing activity declines continuously. At 2 h.p.i. in the first few days of the experiment (i.e. at lower doses), NAT reduction increased, but subsequently fell back to O.D. levels below those recorded at 48 h.p.i. Ingestion and destruction of C. albicans followed the same pattern as that recorded for NAT activity. Simple and differential leukocyte counts performed in all samples revealed leukocytosis (with neutrophilia and lymphopaenia) at 2 h.p.i. This returned to normal levels in the intervals between inoculations.

Animals↗
PubMed1991

Acetaminophen does not induce oxidative stress in isolated rat hepatocytes: its probable antioxidant effect is potentiated by the flavonoid silybin.

Acetaminophen hepatotoxicity is characterized by glutathione depletion and the formation of the reactive electrophilic metabolite N-acetyl-p-benzoquinone imine. The induction of oxidative stress, expressed as lipid peroxidation, is controversial in acute acetaminophen intoxication. Isolated rat hepatocytes develop spontaneously or when incubated with buthionine sulfoximide, a progressive lipid peroxidation which may be inhibited by the antioxidant flavonoid silybin. When cells are incubated with acetaminophen, lipid peroxidation is not observed, this antilipoperoxidative effect being potentiated by silybin. It is proposed that when hepatocytes are incubated with a high concentration of acetaminophen, the drug may accumulate in the cells due to saturation and/or inhibition of detoxification pathways (as in the case of silybin). Under these conditions the development of hepatocyte oxidative stress may be inhibited due to the antioxidant behaviour of acetaminophen.

Acetaminophen↗
PubMed1990

Ascitic fluid polymorphonuclear cell count and serum to ascites albumin gradient in the diagnosis of bacterial peritonitis.

The analysis of ascitic fluid has been complicated by several recently reported new tests. To simplify this assessment, we evaluated nine parameters prospectively and simultaneously in blood and ascitic fluid from 285 patients with ascites to determine which were the most reliable for immediate diagnosis of the etiology of the ascites and of its complications. Subjects were first divided into four groups: sterile cirrhotic ascites (n = 201), spontaneous bacterial peritonitis (n = 41), malignant ascites (n = 34), and miscellaneous ascites (n = 9). An ascitic fluid polymorphonuclear count greater than 500/microliters was the test with the greatest accuracy (96%) for the diagnosis of spontaneous bacterial peritonitis. Neither the most precise cutoff values for ascitic fluid pH (less than 7.32) and ascitic fluid lactate (greater than 32 mg/dl), nor their respective blood-ascitic fluid gradients (greater than 0.11 and less than -20 mg/dl) were more reliable indexes of spontaneous bacterial peritonitis, mainly due to the decreased ascitic fluid pH and increased ascitic fluid lactate observed in malignant ascites, tuberculous peritonitis, and pancreatic ascites. A blood-ascitic fluid albumin gradient less than 1.1 g/dl was the most accurate parameter for the diagnosis of malignant ascites (diagnostic efficacy, 93%). Therefore, the etiologic analysis of ascitic fluid might be simplified and the single practice of two tests, ascitic fluid polymorphonuclear cell count and blood-ascitic fluid albumin gradient, provides immediately useful information.

Adult↗
PubMed1990

Increased resistance against oxidative stress is observed during a short period of renal reperfusion after a temporal ischaemia.

Reperfusion of rat kidney submitted to temporal ischaemia induces a decrease in glutathione content. Lipid peroxidation is not detected in kidney homogenates but microsomes obtained after periods of reperfusion longer than 60 minutes show increased malondialdehyde values correlated with high oxygen consumption and superoxide free radical generation. Microsomes obtained from kidneys submitted to 15 or 60 minutes of reperfusion are resistant to NADPH-induced lipid peroxidation but after 120 minutes of reperfusion an increased lipid peroxidative response is observed. Although the mechanism of the protection found in microsomes against the induction of oxidative stress in the first 60 minutes of reperfusion is unknown, it is postulated that this subcellular fraction plays an important role in the oxidative stress observed after longer periods of reperfusion.

Animals↗
PubMed1989

Ingestion of high doses of fish oil increases the susceptibility of cellular membranes to the induction of oxidative stress.

Feeding rats with 4 g/kg body weight of sardine oil during 7 or 14 days increases the content of eicosapentaenoic acid and docosahexaenoic acid in the erythrocyte and hepatic microsomal membranes by 2 to 6%. These membranes show increased susceptibility to the induction of oxidative stress, expressed as lipid peroxidation, when they are exposed to Fe2+-ascorbate and to NADPH-FE3+-ADP, respectively. The results indicate that in order to prevent the increased susceptibility to lipid peroxidation, supplementation with larger amounts of antioxidants may be needed than those required to stabilize the oil.

Animals↗
PubMed1989

In vitro determination of phagocytosis and intracellular killing of Brucella melitensis by goat's polymorphonuclear phagocytes.

One hundred and forty samples of goats serum taken from animals suspected of having brucellosis, have been studied by trying to assess the phagocytosis in vitro of Brucella melitensis Rev-1 by polymorphonuclear neutrophil phagocytes opsonized with antibrucella serum. The serum agglutination test and the Coombs antiglobulin test were carried out with the serum samples. The opsonization ingestion, intracellular killing and germ killing power of the serum were also assessed. The results demonstrate that the phagocytic activity of the polymorphonuclear neutrophils opsonized by a particular serum can be of use to determine its titre; its opsonic activity varies according to whether the serums are inactivated or not. Likewise it shows the resistance of Brucella meilitensis Rev-1 to digestion by caprine polymorphonuclear neutrophils, this resistance being independent of the animal's degree of infection.

Agglutination Tests↗
PubMed1989

Silybin dihemisuccinate protects against glutathione depletion and lipid peroxidation induced by acetaminophen on rat liver.

Acetaminophen hepatotoxicity is characterized by glutathione depletion, cellular necrosis, and, in some instances, by the induction of lipid peroxidation. Silybin dihemisuccinate, a soluble form of the flavonoid silymarin, protects rats against liver glutathione depletion and lipid peroxidation induced by acute acetaminophen intoxication. Other biochemical parameters such as serum transaminases did not show the drastic increase observed under acetaminophen intoxication when animals were treated with the flavonoid. Preliminary results suggest that silybin dihemisuccinate may be another antidote against acetaminophen hepatotoxicity.

Acetaminophen↗
PubMed1989

H-2 antigens and tumour-associated transplantation antigens in clones derived from a methylcholanthrene-induced BALB/c tumour: their influence on the generation in vitro and in vivo of the specific anti-tumour immune response.

The methylcholanthrene GR9 tumour is a fibrosarcoma, originated in a BALB/c (H-2d) mouse, composed of different clones (A7, G2, D8, D6, B11, B3, B7, C11, B10, B9) with different class I (Kd Dd Ld) expression. We present data indicating that MHC class I differences observed between the different clones correlated with RNA levels and can be modified with recombinant interferon-gamma. We also studied the presence of tumour-associated antigens in GR9 and their different clones using the monoclonal antibody (MoAb) technology. We produced two syngeneic MoAbs, A7.2 and A7.6, which reacted to GR9 clones. These MoAbs precipitated a 70-kilodalton molecule and did not react with cells positive for the classical Gp70 antigen such as YC-8, LSTRA (H-2d) and RBL-5 (H-2b) lymphomas. A7.2 and A7.6 MoAbs were also negative with normal cells. In this well-characterized tumour model, we analysed the influence of the expression of class I molecules and tumour-associated antigens upon the generation, in vitro and in vivo, of the specific anti-tumour immune response. We produced syngeneic anti-GR9 A7 cytotoxic T lymphocytes (CTLs) which showed significant cytotoxicity against most of the GR9 clones including clones with low or no H-2 class I expression. These CTLs showed no cytotoxic activity against other tumour cells and concanavalin A blasts, neither could the CTL-specific response be inhibited with A7.2 and A7.6 syngeneic MoAbs nor with a panel of anti-class I MoAbs. In vivo experiments have shown that pre-immunization with the immunogenic clone GR9 A7 protects against a challenge of the different GR9 clones, independently of their class I expression and their in vitro susceptibility to lysis by anti-GR9 A7 CTLs. These results demonstrate the existence of cross-reactive tumor-associated transplantation antigens between different clones of the same tumour and the absence of correlation between in vitro susceptibility to lysis and in vivo tumour rejection. Finally, we discuss these results in the context of anti-tumour effector mechanisms generated in chemically induced tumours.

Animals↗