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Biomedical subjects

A Gutierrez

Publications and source records attributed to A Gutierrez.

At least 55 records · Page 3Linked to original sources

Increased cardiac troponin T and endothelin-1 concentrations in dialysis patients may indicate heart disease.

BACKGROUND: Cardiac troponin T (cTnT) is a highly sensitive marker for the detection of myocardial damage. However, patients maintained on chronic dialysis often have increased serum cTnT concentrations without evidence of acute myocardial injury. The reason for this is unclear. In chronic haemodialysis patients, elevated plasma concentrations of big endothelin-1 (big ET-1) and endothelin-1 (ET-1) have been reported which may be associated with ischaemic heart disease. The aim of the present study was to investigate possible associations between cTnT, big ET-1, ET-1, other cardiac markers and cardiac disease in dialysis patients. METHODS: Thirty-six haemodialysis (HD) patients and 26 peritoneal dialysis (PD) patients without symptoms of acute myocardial ischaemia were investigated. In all patients, serum concentrations of cTnT (2nd generation ELISA), cardiac troponin I (TnI) (Opus, Behring), creatine kinase MB (CKMB) mass and creatine kinase (CK) were determined, in HD patients before and after dialysis. Additionally, in HD patients, plasma ET-1 and big ET-1 were measured. In 27 HD patients, left ventricular mass index (LVMI) was determined. Patients with ischaemic heart disease (IHD) were compared with non-IHD patients. RESULTS: Serum cTnT was elevated (> or =0.10 microg/l) in 20 of 36 HD patients and in eight of 26 PD patients. cTnI was elevated (> or =0.5 microg/l) in four of 62 dialysis patients. HD+PD patients with IHD showed higher cTnT than HD+PD patients without IHD, and ET-1 concentrations were higher in HD patients with than without IHD. In HD patients, there was a positive correlation between cTnT and big ET-1. In HD patients with left ventricular hypertrophy (LVH), serum cTnT, CKMB mass and post-dialysis plasma big ET-1 were higher than in patients with normal LVMI. Furthermore there was a positive correlation between cTnT levels and LVMI. CONCLUSION: These findings suggest that circulating cTnT may reflect left ventricular hypertrophy and/or myocardial ischaemia in dialysis patients, and indicate that ET-1 and big ET-1 might be associated with these conditions.

Adult↗

Activity of different bicyclam derivatives against human immunodeficiency virus depends on their interaction with the CXCR4 chemokine receptor.

Bicyclams represent a novel class of selective anti-HIV inhibitors with potent activity against T-cell tropic strains of HIV. The prototype compound, the bicyclam AMD3100, has an EC50 of 1 to 10 ng/ml against different strains of HIV-1, including clinical isolates. AMD3100 was shown to interact with the CXC-chemokine receptor CXCR4, the main coreceptor used by T-cell tropic strains of HIV. Here we describe the interaction of different bicyclam derivatives with CXCR4. A close correlation (r2 = 0.7) was found between the anti-HIV potency of the bicyclams and their ability to inhibit the binding of an anti-CXCR4 monoclonal antibody or the intracellular Ca++ signal induced by the stromal cell-derived factor-1alpha, the natural ligand of CXCR4. These results indicate that the mechanism of action of bicyclams is primarily mediated by their interaction with CXCR4. The most potent interaction with CXCR4 and thus anti-HIV activity was shown by bicyclam analogs with cyclam rings composed of fourteen members that are linked by an aromatic (phenyl) bridge. Elucidating the structural requirements for receptor interaction and the site(s) of interaction of bicyclams with CXCR4 will aid in the understanding of HIV-cell fusion.

Animals↗

Fungal degradation of lipophilic extractives in eucalyptus globulus wood

Solid-state fermentation of eucalypt wood with several fungal strains was investigated as a possible biological pretreatment for decreasing the content of compounds responsible for pitch deposition during Cl2-free manufacture of paper pulp. First, different pitch deposits were characterized by gas chromatography (GC) and GC-mass spectrometry (MS). The chemical species identified arose from lipophilic wood extractives that survived the pulping and bleaching processes. Second, a detailed GC-MS analysis of the lipophilic fraction after fungal treatment of wood was carried out, and different degradation patterns were observed. The results showed that some basidiomycetes that decreased the lipophilic fraction also released significant amounts of polar extractives, which were identified by thermochemolysis as originating from lignin depolymerization. Therefore, the abilities of fungi to control pitch should be evaluated after analysis of compounds involved in deposit formation and not simply by estimating the decrease in the total extractive content. In this way, Phlebia radiata, Funalia trogii, Bjerkandera adusta, and Poria subvermispora strains were identified as the most promising organisms for pitch biocontrol, since they degraded 75 to 100% of both free and esterified sterols, as well as other lipophilic components of the eucalypt wood extractives. Ophiostoma piliferum, a fungus used commercially for pitch control, hydrolyzed the sterol esters and triglycerides, but it did not appear to be suitable for eucalypt wood treatment because it increased the content of free sitosterol, a major compound in pitch deposits.

Journal Article↗

Is there an ecological relationship between rates of antibiotic resistance of species of the genus Streptococcus? The Spanish Surveillance Group for Respiratory Pathogens.

The relationship between resistance to antibiotics on the part of Streptococcus pneumoniae and Streptococcus pyogenes was studied by comparing different prevalences of resistance among hospitals obtained from a recent microbiological surveillance of community-acquired respiratory tract infections. A high correlation for erythromycin resistance was found between S. pneumoniae isolates from lower respiratory tract infections and S. pyogenes isolates collected from pharyngeal swabs.

Drug Resistance, Microbial↗

Shift of clinical human immunodeficiency virus type 1 isolates from X4 to R5 and prevention of emergence of the syncytium-inducing phenotype by blockade of CXCR4.

The emergence of X4 human immunodeficiency virus type 1 (HIV-1) strains in HIV-1-infected individuals has been associated with CD4(+) T-cell depletion, HIV-mediated CD8(+) cell apoptosis, and an impaired humoral response. The bicyclam AMD3100, a selective antagonist of CXCR4, selected for the outgrowth of R5 virus after cultivation of mixtures of the laboratory-adapted R5 (BaL) and X4 (NL4-3) HIV strains in the presence of the compound. The addition of AMD3100 to peripheral blood mononuclear cells infected with X4 or R5X4 clinical HIV isolates displaying the syncytium-inducing phenotype resulted in a complete suppression of X4 variants and a concomitant genotypic change in the V2 and V3 loops of the envelope gp120 glycoprotein. The recovered viruses corresponded genotypically and phenotypically to R5 variants in that they could no longer use CXCR4 as coreceptor or induce syncytium formation in MT-2 cells. Furthermore, the phenotype and genotype of a cloned R5 HIV-1 virus converted to those of the R5X4 virus after prolonged culture in lymphoid cells. However, these changes did not occur when the infected cells were cultured in the presence of AMD3100, despite low levels of virus replication. Our findings indicate that selective blockade of the CXCR4 receptor prevents the switch from the less pathogenic R5 HIV to the more pathogenic X4 HIV strains, a process that heralds the onset of AIDS. In this article, we show that it could be possible to redirect the evolution of HIV so as to impede the emergence of X4 strains or to change the phenotype of already-existing X4 isolates to R5.

Adaptation, Biological↗

Comparative effectiveness of three adult mosquito sampling methods in habitats representative of four different biomes of California.

The effectiveness of New Jersey (NJ) light, dry ice baited, and gravid female traps for collecting adult mosquitoes was compared at representative habitats in the Coachella, San Joaquin, and Sacramento valleys and the Los Angeles basin of California. The NJ light traps effectively sampled Anopheles freeborni, Culex tarsalis, Psorophora columbiae, and several Aedes when abundance was high in rural areas with minimal competitive illumination. Dry ice-baited encephalitis virus surveillance or CDC style traps collected significantly more females of most species at most localities than did NJ light traps, regardless of background illumination. The Cummings modification of the Reiter gravid female trap baited with a bulrush (Schoenoplectus) infusion was the best method for collecting Culex pipiens complex females in most habitats. In the Los Angeles basin, gravid traps baited with bulrush infusion collected, on average, 4.5 times more Culex quinquefasciatus females than did traps baited with the Reiter infusion. The bulrush infusion in combination with the Cummings trap design seemed to provide resting site cues and collected males as well as empty and bloodfed females. Mosquito surveillance programs in California should include the systematic operation of dry ice-baited and gravid female traps to improve surveillance sensitivity for selected species in appropriate habitats.

Animals↗

Prominence of the dopamine D2 short isoform in dopaminergic pathways.

As a result of alternative splicing, the D2 gene of the dopamine receptor family exists in two isoforms. The D2 long is characterized by the insertion of 29 amino acids in the third cytoplasmic loop, which is absent in the short isoform. We have produced subtype-specific antibodies against both the D2 short and D2 long isoforms and found a unique compartmentalization between these two isoforms in the primate brain. The D2 short predominates in the cell bodies and projection axons of the dopaminergic cell groups of the mesencephalon and hypothalamus, whereas the D2 long is more strongly expressed by neurons in the striatum and nucleus accumbens, structures targeted by dopaminergic fibers. These results show that the splice variants of the dopamine D2 receptor are differentially distributed and possess distinct functions. The strategic localization of the D2 short isoform in dopaminergic cell bodies and axons strongly suggests that this isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is primarily a postsynaptic receptor.

Alternative Splicing↗

The expression of genes involved in parasitism by Trichoderma harzianum is triggered by a diffusible factor.

The mycoparasite Trichoderma harzianum has been extensively used in the biocontrol of a wide range of phytopathogenic fungi. Hydrolytic enzymes secreted by the parasite have been directly implicated in the lysis of the host. Dual cultures of Trichoderma and a host, with and without contact, were used as means to study the mycoparasitic response in Trichoderma. Northern analysis showed high-level expression of genes encoding a proteinase (prb1) and an endochitinase (ech42) in dual cultures even if contact with the host was prevented by using cellophane membranes. Neither gene was induced during the interaction of Trichoderma with lectin-coated nylon fibres, which are known to induce hyphal coiling and appressorium formation. Thus, the signal involved in triggering the production of these hydrolytic enzymes by T. harzianum during the parasitic response is independent of the recognition mediated by this lectin-carbohydrate interaction. The results showed that induction of prb1 and ech42 is contact-independent, and a diffusible molecule produced by the host is the signal that triggers expression of both genes in vivo. Furthermore, a molecule that is resistant to heat and protease treatment, obtained from Rhizoctonia solani cell walls induces expression of both genes. Thus, this molecule is involved in the regulation of the expression of hydrolytic enzymes during mycoparasitism by T. harzianum.

Base Sequence↗

Factors affecting length of stay and need for rehabilitation after hip and knee arthroplasty.

The purpose of this study was to determine the factors that predict the length of stay on a surgical service after total hip or knee arthroplasty and the factors that predict whether a patient will require admission to a rehabilitation unit before he or she is ready to return home. The authors reviewed the records of all patients admitted to the Albany Medical Center for elective total hip or total knee arthroplasty in 1995. The study looked for correlations of patients' age, sex, marital status, body mass index, and comorbid illnesses with length of stay on the surgical service and need for inpatient rehabilitation. The only factor that correlated with length of stay on the surgical unit was age. The factors that correlated with the need for inpatient rehabilitation were age and diabetes mellitus.

Age Factors↗

An experimental model of diabetes and cancer in rats.

The aim of this study was to develop an experimental model for the study of cancer associated with diabetes. For diabetes induction, Sprague-Dawley rats were given streptozotocin (STZ, 90 mg/kg body weight (BW), by intraperitoneal injection on the second day of life. For mammary tumour induction, rats were injected with 50 mg/kg BW of N-nitroso-N-methylurea (NMU) at 50, 80 and 110 days old. The neoplastic process and the effect of tamoxifen treatment was examined in non-diabetic and diabetic rats. The latency period, NMU-induced tumour incidence and the number of tumours per rat in diabetic rats versus controls were 117 +/- 7 days versus 79 +/- 9 days (P < 0.001); 93% versus 95% (NS); and 5.2 +/- 1.6 versus 2.7 +/- 0.5 (P < 0.02). A more benign histological pattern for tumours in diabetic animals was observed. Mammary tumours in diabetic rats grew more slowly than in controls. Tamoxifen (1 mg/kg/day) treated diabetic rats showed tumour regression in 67% of NMU-induced mammary tumours versus 53% in controls (NS). Our results show that tumour progression seems to be affected by diabetes in this experimental model. We suggest this is the result of changes to insulin-like growth factors and their receptors, which occur in diabetics, and our future research will examine this hypothesis.

Animals↗

Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.

Adult↗

A luminometric assay for determination of ethanol in microdialysates.

In microdialysis, samples from the extracellular fluid are analysed in the outgoing dialysate. By adding ethanol to the ingoing perfusate and following its exchange in the dialysate, an outflow/inflow ratio is obtained. This ratio has been shown to correlate with the tissue blood flow. An automatic luminometric ethanol assay that quantifies the light produced from three coupled enzyme reactions is described. Alcohol dehydrogenase catalyses the oxidation of ethanol with formation of NADH, which is monitored using NADH:FMN oxidoreductase and bacterial luciferase. Each assay can be individually calibrated by measuring the increased rate of NADH formation through the addition of a known amount of ethanol. The linear range of the assay was 0.05-10 mmol l-1 in microdialysate samples. The within-run imprecision was 1.4% CV in 10 mmol l-1 samples, and ethanol recovery was almost 100%. The assay was applied to microdialysates that were generated from probes implanted in the vastus lateralis muscle in fasting subjects (n = 12) and perfused with 5 mmol l-1 ethanol at 3 microliter min-1. An outflow/inflow steady-state ratio of 27% (range 19-47%) appeared after about 1 h, followed by a within-run variability of 4.7% CV (range 2.5-7.7% CV), as calculated from samples collected every 15 min up to 4 h after stabilization. In conclusion, a sensitive ethanol assay, suitable for studies of microcirculatory exchange of solute molecules over the dialysis probe is presented.

Alcohol Dehydrogenase↗

Construction and properties of a fragmentary D-amino acid aminotransferase.

D-Amino acid aminotransferase [EC 2.6.1.21] catalyzes the inter-conversion between various D-amino acids and alpha-keto acids. The subunit of the homodimeric enzyme from Bacillus sp. YM-1 consists of two domains connected by a single loop, which has no direct contact with the active site residues or the cofactor, pyridoxal 5'-phosphate [Sugio, S., Petsko, G.A., Manning, J.M., Soda, K., and Ringe, D. (1995) Biochemistry 34, 9661-9669]. We constructed two plasmids, one encoding a polypeptide fragment corresponding to the N-terminal domain, and the other a fragment corresponding to the C-terminal domain. When both polypeptide fragments were expressed together in the same host cell, an active fragmentary enzyme consisting of two sets of the two polypeptide fragments was produced. When the two polypeptide fragments were expressed separately, each of them provided a soluble protein but with no activity. However, D-amino acid aminotransferase activity appeared upon incubation of a mixture of the two fragments. The active fragmentary enzyme was purified to homogeneity and characterized; it was found to be similar to the wild-type enzyme in various enzymological properties except substrate specificity, inhibition by alpha-ketoglutarate, and thermostability. The fragmentary enzyme showed higher catalytic activity toward several substrates, such as D-lysine and D-arginine, than the wild-type enzyme.

Alanine Transaminase↗

A mutant D-amino acid aminotransferase with broad substrate specificity: construction by replacement of the interdomain loop Pro119-Arg120-Pro121 by Gly-Gly-Gly.

D-amino acid aminotransferase (EC 2.6.1.21) catalyzes the interconversion of various D-amino acids and 2-oxo acids. Each homodimer subunit consists of two domains, which are connected by a single loop, Asn118-Pro119-Arg120-Pro121. The loop has no direct contact with the active site region or the cofactor, pyridoxal 5'-phosphate. We attempted to increase the conformational flexibility of this loop through a triple glycine substitution. The resultant mutant P119G-R120G-P121G has features clearly different from the wild-type enzyme under overall as well as half-reaction conditions. The pre-steady-state kinetic analyses of half reactions showed that the mutant enzyme has kmax values higher than the wild-type enzyme towards most D-amino acids examined. A concomitant decrease in substrate affinity (1/Kd), particularly for acidic amino acids, was also observed. A putative binding site for the distal carboxyl group of acidic amino acids in the wild-type enzyme was incidentally displaced by the loop mutation, indicating a functional linkage between the interdomain loop and the active site region. This study has exemplified the usefulness of engineering relatively distant loops as a means to modify substrate specificity of an enzyme.

Amino Acid Substitution↗

Microbiology of acute otitis media in Costa Rican children.

BACKGROUND: Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide, an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world. OBJECTIVE: To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media. METHODS: Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media. Middle ear fluid was obtained for culture and minimal inhibitory concentrations were determined by the E-test technique in those isolates obtained between October, 1995, and January, 1997. RESULTS: The most common pathogens cultured were Streptococcus pneumoniae (30%), Haemophilus influenzae (14%), Staphylococcus aureus (4%) and Streptococcus pyogenes (4%). Moraxella catarrhalis was uncommon. Beta-lactamase production was low (3.7%) among the H. influenzae isolates but frequent among the Staphylococcus aureus (57.1%) and M. catarrhalis (100%) strains. Overall 9 of 46 S. pneumoniae isolates (19.6%) exhibited decreased susceptibility to penicillin of which 8 isolates (17.4%) showed intermediate and one strain (2.2%) high level resistance. Among the penicillin-susceptible S. pneumoniae isolates, susceptibility to the following antimicrobials was: 81%, azithromycin; 89%, clarithromycin; and 100%, ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX). Among the penicillin-resistant S. pneumoniae isolates the percentage of susceptible strains was 89% for azithromycin, clarithromycin and ceftriaxone and 67% for TMP-SMX. CONCLUSIONS: Based on this microbiologic information the agents considered first line drugs in the treatment of acute otitis media in Costa Rica remain amoxicillin or TMP-SMX.

Acute Disease↗

Human immunodeficiency virus glycoprotein gp120 as the primary target for the antiviral action of AR177 (Zintevir).

The human immunodeficiency virus (HIV) inhibitor AR177 (T30177, Zintevir) has been identified as a potent inhibitor of HIV integrase in vitro. The compound is currently the subject of clinical phase I/II trials. However, the primary target for the mechanism of action in vivo has not been identified unequivocally. We have found that AR177 inhibits syncytium formation between MOLT-4 cells and HUT-78 cells persistently infected with the HIV-1IIIB or NL4-3 strain, at a 50% effective concentration of 3 microg/ml, roughly 3-fold higher than the concentration required to inhibit HIV replication. Furthermore, flow cytometric analysis has shown that AR177 at 25 microg/ml interferes with the binding of the monoclonal antibody 9284 (directed to the V3 loop of gp120) on HIVIIIB-infected HUT-78 cells, pointing to inhibition of virus binding or virus fusion as the mechanism of action of AR177. To precisely characterize the site/target of intervention by AR177, we have selected HIV-1 (NL4-3) strains resistant to AR177. The binding of the AR177-resistant strain, unlike the parental HIV-1 NL4-3 strain, could not be inhibited by AR177. The resistant phenotype was associated with the emergence of mutations in the gp120 molecule. DNA sequence analysis revealed the presence of the K148E, Q278H, K290Q, and F391I mutations and a deletion of 5 amino acids (FNSTW) at positions 364-368 in the V4 region of the resistant strain but not of the wild-type HIV strain. Selection of resistant strains, although it takes a relatively long time to develop, may also select for strains with lower replicative capacity. No mutations were found in the integrase enzyme gene. Our data argue against HIV integrase being the primary target for the mechanism of anti-HIV action of AR177.

Amino Acid Sequence↗

Cocaine-induced peripheral vascular occlusive disease--a case report.

Two patients with cocaine-induced peripheral vascular occlusive disease are presented. A 37-year-old man was admitted to the hospital for evaluation of severe pain and numbness of his feet. He had used cocaine prior to admission. Arteriography showed bilateral occlusions of superficial femoral, popliteal, and trifucation arteries. Despite repeated infusions of urokinase, he developed progressive bilateral gangrene of both legs necessitating bilateral below-knee amputations. The second patient developed similar symptoms after smoking cocaine. Arteriography showed vasospasm bilaterally from the iliac arteries distally. I.v. nitroglycerin infusion caused resolution of the vasospasm and ischemic symptoms.

Acute Disease↗

Radiologic features of Rhodococcus equi pneumonia in AIDS.

This report outlines the radiological features observed in three cases of Rhodococcus equi (R. equi) pneumonia in AIDS (acquired immunodeficiency syndrome) and reviews another 45 radiological reports published of this emerging opportunistic pneumonia in Human Immunodeficiency Virus (HIV) infected patients. The clinical signs in our three patients consisted in a subacute onset of respiratory symptoms and fever. A low lymphocyte count (< 200 cells/mm3), pulmonary infiltrates, and pleural effusion was present in all three cases. Cavitary pneumonia was observed in two patients, and pericardial effusion in another. In this series CD4 lymphocyte count < 200/mm3 was seen in 29 of the 48 patients (60.4%). All 48 patients had abnormal findings on chest radiographs. Abnormalities involved the upper lobes in 26 of the 48 patients (55%). Cavitation was reported in 37 of the 48 cases (77%). R. equi pneumonia may not be as the paucity of case reports suggest. Consequently, a cavitary pneumonia in HIV infected patients with a low CD4 lymphocyte count (< 200 mm3) with a subacute onset, an upper lobe predilection, and/or a poor response to conventional antibiotic therapy should be considered as suspect of R. equi infection.

Acquired Immunodeficiency Syndrome↗