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Biomedical subjects

M García

Publications and source records attributed to M García.

At least 163 records · Page 9Linked to original sources

Microglial activation induced by factor(s) contained in sera from Alzheimer-related ApoE genotypes.

Several factors that increase the likelihood of developing Alzheimer's disease (AD) have already been identified. A correct evaluation of these may contribute to a better understanding of the etiology of the disease. The risk of developing AD definitely increases with (a) age, (b) head injuries, (c) family history of AD or Down syndrome, (d) sex (higher prevalence of AD in women), (e) vascular disease, (f) exposure to environmental toxins, (g) infectious processes, or (h) changes in immune function, and recent advances in molecular genetics have suggested that genetic predisposition (i) can be considered one of the most important risk factors in the development of AD. A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (ApoE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of ApoE. A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with amyloid plaques. It has become evident that a dysregulation of cytokine release appears within lesions of many types of brain disorders including infection, trauma, stroke, and neurodegenerative diseases. Many studies have shown that microglia secrete both cytokines and cytotoxins and since reactive microglia appears in nearly every type of brain damage, it is likely that their secreted products ultimately help to determine the rate of damaged brain tissue. In this study, in vitro cell cultures were established to investigate the effect of different concentrations of human sera (2.5% and 10%) with specific ApoE genotypes from Alzheimer's and non-Alzheimer's subjects on ameboid and flat microglial cells obtained from neonatal rat hippocampi. Results show that a modulation in the proliferation and activation of microglial cells was obtained and that AD sera, mainly in the ApoE 3/4 and 4/4 genotype contain factor(s) which are able to induce morphological changes, as measured by an increase in the ameboid cell type. In addition, major histocompatibility complex (MHC) class II antigen expression, as measured by flow cytometric analysis, and interleukin-1beta (IL-1beta) release as measured by enzyme linked immunoadsorbent assay (ELISA), in comparison with control groups and lipopolysaccharide (LPS)-treated cells, clearly demonstrate a direct effect of ApoE 3/4 and 4/4 and/or an indirect effect mediated by the release of IL-1beta on microglia activation. These results strongly suggest that primary in vitro microglial cell cultures can be used as a screening model to test human sera as well as the effect of new potential drugs aimed at down-regulating microglia activation.

Aged↗

Enhancement of the immunogenicity of a synthetic peptide bearing a VP3 epitope of hepatitis A virus.

The immune responses elicited in mice by different forms of the VP3(110-121) B-epitope of the hepatitis A virus (HAV) were studied. Different forms of incorporation in liposomes were tested, encapsulation, rather than surface exposure, being the best antigenic preparation. Three larger peptides of the VP3 epitope, two of them containing a hepatitis B virus T-epitope, and a third containing a putative T-epitope of HAV (VP3(102-121)) were assayed. While this latter T-epitope induced an enhancement of the response against the VP3 B-epitope, the artificially coupled T-epitopes failed to induce a significant increase. The administration of two multiple antigenic peptide (MAP) constructs, the first containing the VP3(110-121) and VP1(11-25) HAV sequences and the second only the VP1(11-25) sequence, also suggested the presence of a T-epitope, since the response against the VP1 peptide was increased in the first construct.

Animals↗

A Study of the Aggregation Behavior of Hexyltrimethylammonium Bromide in Aqueous Solution.

The self-association of n-hexyltrimethylammonium bromide (C6TAB) in aqueous solution has been examined as a function of temperature and electrolyte concentration. The critical micelle concentration (CMC) and the degree of counterion binding (beta) were determined by conductivity measurement at temperatures over the range 288.15-318.15 K. Ultrasound velocity measurements were used to obtain the CMC in water and in a range of concentrations of electrolyte (0.1 to 0.6 mol kg-1 NaBr) and static light scattering to obtain the aggregation number and the degree of counterion binding in water at 298.15 K. The enthalpy change on micellization in water was measured by microcalorimetry. Apparent adiabatic compressibilities were calculated from a combination of density and ultrasound velocity measurements. Changes in the thermodynamic properties on micellization were determined by applying the mass action model; good agreement was found between experimental and theoretical enthalpy changes. From comparison with the properties of other n-alkyltrimethylammonium bromides it has been shown that the CMC of C6TAB in water is lower than that predicted from the linear relationships between CMC and the number of carbon atoms in the alkyl chain. Similarly, the standard Gibbs energy of micellization is less negative than predicted, and the degree of counterion binding is much lower than for other CnTABs. It is suggested that the anomalous behavior of C6TAB is a consequence of the more highly organized core of the aggregates of very low aggregation number (3-4) and the high degree of exposure of the micellar components to the aqueous environment. Copyright 1998 Academic Press.

Journal Article↗

Posttransplant liver granulomatosis associated with hepatitis C?

BACKGROUND: Liver granulomatosis is an occasional finding in posttransplant liver biopsies. Its diagnosis is made more difficult by the variety of conditions that can lead to it. In the nontransplant setting, the association of liver granulomatosis and hepatitis C virus (HCV) infection has occasionally been described. METHODS: We describe the case of a patient with a liver transplantation for an HCV-associated cirrhosis who developed an alteration of liver tests. Granulomatosis was detected on the liver biopsy. RESULTS: Other causes of granulomatosis were satisfactorily excluded. The development of the lesions coincided with a viral flare-up. CONCLUSION: We think that HCV can be listed among the possible causes of liver granulomas in the posttransplant setting and that it must be considered in the differential diagnosis of this condition.

Adult↗

Interocular effect of actin depolymerization on spinule formation in teleost retina.

Teleost retinas adapted to light show numerous spinules invaginated in the cone pedicles whereas darkness induces a reduction in the number of spinules. Horizontal cells show nematosomes whose size decreases as the number of spinules increases. We have investigated the involvement of actin filaments in spinule formation, by using cytochalasin D through intraocular injection into an eye. The ultrastructural analysis reveals that cytochalasin D impairs spinule formation and nematosome-size reduction in both treated and contralateral untreated retinas.

Actins↗

Lack of a specific immune response against a recombinant capsid protein of Jaagsiekte sheep retrovirus in sheep and goats naturally affected by enzootic nasal tumour or sheep pulmonary adenomatosis.

Enzootic nasal tumour (ENT) and sheep pulmonary adenomatosis (SPA) are two contagious adenocarcinomas of the respiratory tract of sheep and goats. Both diseases are associated with related, but distinct, type-D-retroviruses (ENTV and JSRV respectively). No evidence of circulating antibodies has been described in animals affected by either ENT or SPA using antigens from natural sources. We evaluated the usefulness of a recombinant JSRV capsid protein (JSRV-CA) as antigen to study the antibody responses of animals naturally affected by ENT or SPA, using immunoblotting. Positive reactions were detected in the sera of both affected and unaffected sheep and goats. The reactivity was abolished completely by absorption with the GST fusion partner but not by JSRV-CA, suggesting that it was not specific. The results support prior observations indicating that sheep and goats infected by JSRV and ENTV do not develop specific humoral responses to these retroviruses.

Animals↗

Osteopenia in rats with liver cirrhosis: beneficial effects of IGF-I treatment.

BACKGROUND/AIMS: Liver cirrhosis is associated with osteopenia and also with low levels of IGF-I. This hormone has been reported to stimulate bone formation in states of undernutrition and low bone turnover. Our aims were to evaluate whether osteopenia develops in male Wistar rats with CCl4-induced cirrhosis and whether IGF-I is effective in the restoration of bone mass in these animals. METHODS: Cirrhotic rats were distributed into two groups: group CI (n = 12) which received placebo and group CI + IGF (n = 12) which was treated with human recombinant IGF-I (2 microg/100 g bw/day, s.c., 21 days). Twelve normal animals which received placebo constituted the control group. On the 22nd day, the animals were sacrificed, and bone parameters were analyzed in femur and/or tibia. RESULTS: Posterior-anterior and latero-medial diameters were similar in all groups. Also, no significant differences were observed in bone contents of calcium, total proteins, collagen and hydroxyapatite in CI rats as compared with controls. However, CI rats showed significant reductions in bone weight (-13.5%, p < 0.001), total bone density (-9.28%, p < 0.001), and increased perimedullar bone resorption and urinary levels of deoxypyridinoline (a marker of bone resorption). In CI + IGF rats these parameters improved significantly as compared with CI animals. CONCLUSIONS: Osteopenia characterized by loss of bone mass and preserved bone composition is found in rats with CCl4-induced cirrhosis. This bone disorder is partially corrected by treatment with low doses of IGF-I. Since osteoporosis seems to be the predominant form of osteopenia in patients with cirrhosis, IGF-I should be considered as a possible therapy for this disorder.

Alanine Transaminase↗

Syringe and needle exchange as HIV/AIDS prevention for injection drug users in Puerto Rico.

This study evaluated the effectiveness of the first needle exchange program (NEP) established in Puerto Rico. The data for this study were collected during the first months of the NEP from July 1995 to March 1996 in 13 communities of the San Juan metropolitan area. Subjects were the participants of two modalities of the NEP: a mobile team and a community-based drug treatment program. During the 3-week evaluation period, 2401 injection drug users (IDUs) were recruited, resulting in a total of 19,195 exchange contacts and 146,323 syringes exchanged. No significant change in drug injection was observed. However, the program was effective in reducing sharing of syringes and cookers. The study suggests that the NEP did help in reducing needle sharing in Puerto Rico. However, the HIV seropositivity in returned syringes suggests the need to continue aggressive prevention programs to arrest the epidemic among IDUs. However, factors related to the socio-cultural environment as well as cultural norms and traditions need to be considered when planning and expanding NEPs.

HIV Infections↗

Development of a biparametric bioanalyser for creatinine and urea. Validation of the determination of biochemical parameters associated with hemodialysis.

The construction and evaluation of an automated urea and creatinine biparametric biosystem using flow injection analysis (FIA) are described. The biosystem uses enzyme reactions that hydrolyse urea and creatinine producing ammonium ions. The enzymes used were creatinine deiminase and urease, which are immobilized covalently in flow reactors. The reactor with creatinine deiminase has the enzyme immobilized on controlled-pore glass beads, whereas urease is immobilized on a nylon open tubular reactor. Detection is realised with a flow-through ammonium ion-selective electrode with an inner solid-state contact (graphite-epoxy composite). Ammonium ions are separated from alkali ion interferents through a gas-diffusion cell. The bioanalyser is fully automated using software and electronics developed ex profeso in our laboratories. The analyser was validated off-line by measuring urea and creatinine from discrete effluent samples from hemodialysis equipment. Results agreed with concurrent analyses realised using hospital laboratory methods. There were no significant differences between the two sets of results at the 95% confidence level. Finally, the biparametric bioanalyser was validated on-line by measuring creatinine and urea levels in artificial kidney effluents. These measurements were useful in the determination of key biochemical parameters of clinical interest such as the mass of urea and creatinine extracted from the patient as well as the initial concentration of creatinine and urea in blood plasma. When the results of the bioanalyser were compared with those yielded by the usual methods, they showed no significant differences at the 95% confidence level when determining the mass of the analytes extracted by the hemodialyser or when determining the urea concentration in blood plasma. However, when measuring the creatinine concentration in blood plasma using the developed bioanalyser, significant differences appeared.

Biological Assay↗

Physico-chemical characterization of liposomes with covalently attached hepatitis A VP3(101-121) synthetic peptide.

The covalent conjugation of a 20-mer peptide belonging to the VP3 capsid protein of hepatitis A virus to the surface of preformed liposomes was investigated. Three different bonds (disulfide, thioether and amide) were established between the peptide sequence and liposomes bearing at their surface appropriate reactive groups. The effect of the relative concentration of the N-[4-(p-maleimidophenyl)butyryl]dipalmitoylphosphatidylethanolamine anchor in liposomes on stability during coupling of the peptide sequence was studied. The interaction of the three liposomal preparations with phospholipids in a biomembrane model system, monolayers at the air-water interface, is also reported. The results showed that although the peptides associate with liposomes in similar yields for the three strategies studied, differences can be observed when their interaction with phospholipid monolayers composed of dipalmitoylphosphatidylcholine is analysed.

Adjuvants, Immunologic↗

APOE-induced microglial activation: an in vitro assay to screen sera from Alzheimer's disease patients and novel therapeutic compounds.

Recent advances in molecular genetics have suggested that genetic predisposition can be considered one of the most important risk factors for Alzheimer's disease (AD) development. A significant increase in the number of amyloid plaques in AD patients with an apolipoprotein E4 (APOE) allele has been observed and the results of several genetic studies indicate that the etiology of this neurodegenerative disease is associated with the presence of the allele E4 of APOE gene. A potential source of damage in the AD brain is an altered response triggered by microglial activation, which is associated with senile plaque formation. In this study, in vitro cell cultures were established to investigate the effect of different concentrations of human sera (2.5% and 10%) with specific APOE genotypes from Alzheimer and non-Alzheimer subjects on ameboid and flat microglial cells obtained from adult rat hippocampus. Results show that this in vitro test can be applied as an in vitro model to test specific responses of microglia to human sera as well as a primary screening procedure to evaluate the effect of novel compounds for the treatment of AD and neuroimmune-associated disorders.

Adult↗

The synaptic process in Locusta migratoria spermatocytes by synaptonemal complex analysis.

We describe the synaptic process during meiotic prophase in spermatocytes from Locusta migratoria, using synaptonemal complex (SC) spreads analyzed by light (LM) and electron (EM) microscopy. At leptotene, a stage of short duration, unpaired axial elements begin to be assembled. Synapsis starts at zygotene, beginning usually at the terminal regions of the bivalents, either at the proximal, centromeric end or at the distal, non-centromeric end; interstitial initiation of synapsis was only occasionally observed in the longer chromosomes. Pairing is asynchronous, and shorter chromosomes are the first to complete synapsis. At pachytene all bivalents are fully synapsed. Diplotene is characterized by the progressive fragmentation of SCs; fragmentation is asynchronous, and affects mainly the longer chromosomes, while the shorter ones maintain their morphology up to late diplotene.

Animals↗

Abnormal immunological response to Mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis.

The pathogenic mechanisms of immunosuppression leading to susceptibility of Mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4+, CD8+, TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4+, V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens-stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4+ and CD8+. T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders.

Adult↗

[Tumor invasion in gallbladder cancer. Importance of blood vascular tumor infiltration diagnosis].

BACKGROUND: The infiltration of venous blood vessels in gallbladder carcinoma and its importance as a prognostic factor has not been well studied. Victoria blue stain has been used to identify vascular involvement in gastric and thyroidal carcinomas. AIM: To assess blood vessel infiltration using Victoria blue stain in gallbladder carcinomas. MATERIAL AND METHODS: One hundred forty eight samples of gallbladder carcinomas, coming from 24 men and 123 women aged 60.4 +/- 12.2 years old, were studied. They were stained with Victoria blue stain to quantify blood vessel invasion. RESULTS: Twenty nine percent of tumors had blood vessel infiltration, 61% had lymph vessel and 20% had perineural infiltration. Lymph vessel or perineural involvement was found in 81% and 31% of those tumors with blood vessel infiltration, respectively. Perineural infiltration was associated with lymph or vascular involvement in 93 and 40% of tumors, respectively. None of the early carcinomas had blood vessel infiltration, whereas 33% of advanced tumors had this type of infiltration (p < 0.001). No differences in vascular infiltration were observed according to the differentiation of the tumor. CONCLUSIONS: Blood vessel infiltration was observed only in advanced gallbladder carcinomas and was tightly related to the degree of gallbladder wall infiltration. The presence of perineural infiltration was the best marker of lymph or blood vessel infiltration.

Adenocarcinoma↗

[Diagnostic value of Gram staining of peri-catheter skin and the connection in the prediction of intravascular-catheter-related bacteremia].

BACKGROUND: To evaluate the diagnostic value of Gram stain of pericatheter skin swabs and the intravascular device hub in detecting catheter-related bacteremia (CRB) in critically-ill patients. METHODS: Over a 12-month period, 170 intravascular catheters (> 7 days in place) suspected as being the primary source of CRB were prospectively examined in adult patients admitted to 10 intensive care units of different hospitals in Spain. Blood cultures, Gram staining and culture of swabs obtained from skin entry side and catheter hub were performed before catheter removal. A semiquantitative culture of the catheter tip was carried out. Catheter-associated bacteremia was considered to be present if the same organism was isolated from the catheter tip, skin and/or hub, and blood cultures. RESULTS: The incidence rate of CRB was 15%. Staphylococcus epidermidis was the most frequently isolated microorganism. Considered together, the sensitivity, specificity, positive predictive value and negative predictive value for Gram staining of the skin and hub were 80, 81.9, 35.3 and 97.1%, respectively. CONCLUSIONS: The Gram stain of skin and hub swabs has a great utility in predicting CRB, specially in the absence of microorganisms. Gram stains of the above mentioned sites could be recommended as an easy and fast method to rule out the presence of CRB.

Adult↗

[Biochemical status and iron intake in a population of pregnant women of Buenos Aires, Argentina].

The iron (Fe) nutritional status was studied in 113 healthy pregnant women, age: 24.8 +/- 6.1 Ys. During the second trimester (gestational age: 16.9 +/- 3.8 weeks), a 24 h dietary recall was carried out and daily Fe intake was calculated, according to Latinoamerican and German Food Composition Tables. On the same day, hematocrit (Hct), hemoglobin (Hb), erythrocyte protoporphyrin (EP) and serum ferritin (SF) were determined in fasting blood samples. Mean daily Fe intake was 10.8 +/- 4.6 mg. The percentage of population with abnormal biochemical values was: Hb (g/dL) < 10.5: 2%; PE > 70 microgram/dL of red blood cells: 6.5%; SF (ng/mL) < 12-20: 16%. According to the new recommendations of the American Institute of Medicine, Fe supplementation would be necessary in women with SF < 20 ng/ml (22%). Therefore, the follow-up of iron stores would be necessary in those with SF > 20 ng/mL before Fe administration.

Adult↗

[Application of modified comparative genomic hybridization in the genetic analysis of 5 lymphoid neoplasms].

To analyze the utility of performing modified comparative genomic hybridization (mCGH) as a complementary technique to conventional cytogenetic techniques in the genetic analysis of lymphoid neoplasms. Modified comparative genomic hybridization and subsequent FISH techniques were performed in 5 lymphoid neoplasms cases diagnosed in Fundación Jiménez Díaz. The latter was done in order to confirm the results obtained with mCGH. Gains of chromosomal regions not detected with conventional cytogenetic techniques were detected by mCGH. A good correlation in the results obtained between conventional cytogenetic and mCGH techniques was observed. Nevertheless, mCGH enables the detection and subsequent identification of gains of genetic sequences undetectable with cytogenetic techniques with possible diagnostic and prognostic value.

Chromosomes, Human, Pair 10↗