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Biomedical subjects

E Torres

Publications and source records attributed to E Torres.

At least 19 recordsLinked to original sources

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗

Gold and silver uptake and nanoprecipitation on calcium alginate beads.

Calcium alginate beads were investigated for their biosorption performance in the removal of gold and silver from aqueous solutions. It was found that uptake capacities were significantly affected by the solution pH, with optimum pH values of 2 and 4 for gold and silver, respectively. Kinetic and isotherm experiments were carried out at the optimum pH. The maximum uptake capacities were 290 mg/g for Au and 52 mg/g for Ag. FTIR analysis indicated that both carboxylic and hydroxylic functional groups in alginate beads are involved in the metal binding and later reduction of gold (+3) and silver (+1) to gold (0) and silver (0). SEM and X-ray diffraction confirmed the formation of gold and silver nanoparticles.

Adsorption↗

A marked increase in organ donation in Puerto Rico.

During its first years of existence, the Puerto Rico Transplant Program barely reached 18 to 20 renal transplants per year. A brain death amendment to the law improved the numbers but only to a stable thirty/year. Polls and studies showed that, although people knew about transplantation and expressed willingness to donate, the powerful emotional grief reaction, as well as a peculiar decision-making process, all militated against effective donation. In 1995, LifeLink of Puerto Rico was created as part of the very successful LifeLink Foundation of Tampa, staffed by local professionals. Cadaveric donation increased exponentially by 1227% and in 2004, 22.4 donors per million population were recovered, up from 1.5, one of the steepest growth curves in the United States. As a result, kidney transplantation increased, a cardiac transplant program was inaugurated, a pancreas transplant program has started, and liver will follow. The success is the result of well-trained, culturally sensitive coordinators and requestors; continuous education to the public, hospitals, administrators, neurospecialists, and critical care units; hospital development; implementation of federal law; and a sensitive approach the deceased donor family, and not only to the waiting list patients. The results demonstrate that organizational and educational factors can override cultural obstacles.

Brain Death↗

Muscular strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides.

AIMS: To evaluate the association of acute organophosphate (OP) poisoning with chronic sensory and motor neurological impairment. METHODS: This study concerns the third of a series of three examinations of hand strength and vibration thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men. The first two examinations were performed at hospital discharge and seven weeks after poisoning, and the present examination two years later. Twenty eight cattle ranchers and fishermen who had never experienced pesticide poisoning were examined as controls, also three times over the two year period. The poisonings were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each subdivided in moderate and severe poisonings. RESULTS: Men poisoned with OP insecticides had persistent reduced hand strength. We previously reported weakness at hospital discharge for OP poisoned in all categories that worsened seven weeks later for those severely poisoned with neuropathic OPs. Strength improved over time, but the poisoned were still weaker than controls two years after the poisoning, most noticeably among the subjects most severely poisoned with neuropathic OPs. Also, index finger and toe vibration thresholds were slightly increased at the end of the two year period, among men with OP poisonings in all categories, but patterns of onset and evolvement of impairment of vibration sensitivity were less clear than with grip and pinch strength. CONCLUSIONS: Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.

Acute Disease↗

In vivo induction of insulin secretion by ornithine alpha-ketoglutarate: involvement of nitric oxide and glutamine.

We previously demonstrated that ornithine alpha-ketoglutarate (OKG), known for its anabolic properties, induces insulin secretion in vitro. The present study was undertaken to further characterize this effect in vivo and investigate a possible interaction with glucose both in vivo and in vitro. Male Wistar rats received an intravenous bolus of OKG (25 mg/kg) and/or glucose (0.8 g/kg) or saline, and their plasma insulin and glucose levels were monitored for 30 minutes. OKG alone increased plasma insulin to a similar extent to glucose. In combination with glucose, OKG significantly increased glucose-induced insulin secretion in vivo and in vitro, and led to a significant increase in glucose utilization in vivo. The absence of significant variations in plasma arginine and glutamine suggests a direct effect of OKG on the pancreas. To assess the involvement of the synthesis of nitric oxide and glutamine in OKG-induced insulin secretion, the experiments were repeated in the presence of inhibitors of these 2 pathways, respectively L-nitroarginine-methylester (L-NAME) and methionine sulfoximine (MSO). Both inhibitors were able significantly to reduce OKG-induced insulin secretion without affecting either basal or glucose-induced insulin release. Thus OKG acts directly with glucose on islets to induce insulin secretion via mechanisms involving NO and glutamine synthesis. In addition, our results suggest that OKG and glucose act via separate pathways.

Animals↗

A single growth hormone (GH) determination is sufficient for the diagnosis of GH-deficiency in adult patients using the growth hormone releasing hormone plus growth hormone releasing peptide-6 test.

BACKGROUND: The diagnosis of GH deficiency in adults is based on the provocative testing of GH secretion. When testing a patient with suspected GH deficiency, clinicians assess the whole secretory curve and select the GH peak as an index of secretory capability. This procedure is time consuming and the determination of GH in several samples is necessary. The combined administration of growth hormone releasing hormone (GHRH) plus growth hormone releasing peptide-6 (GHRP-6) is an effective test of GH secretion, and it has been unambiguously demonstrated that the elicited GH peak is capable of segregating normal GH secretion subjects from GH deficient patients on an individual basis. The GHRH + GHRP-6 test biochemically classifies patients into three groups; those with a stimulated GH peak >/= 20 micro g/l are considered normal and those with peaks at </= 10 micro g/l as GH deficient. The group comprising individuals between these parameters is considered uncertain, and the results are further interpreted according to clinical information, or by other tests. OBJECTIVE: As the GHRH + GHRP-6 test induces GH peaks consistently in the first 30 minutes, the working hypothesis assessed in this study was whether a single determination of GH 30 minutes after stimulus could provide the same clinical classification as the whole secretory curve. PATIENTS AND METHODS: Three hundred and forty-nine adult subjects (146 patients with organic pituitary disease and 203 healthy subjects) were studied. All were administered GHRH 1 micro g/kg i.v. plus GHRP-6 1 micro g/kg i.v. at 0 minutes, and blood samples were obtained at regular intervals. GH was determined in all samples. RESULTS: GHRH + GHRP-6-evoked GH peaks in controls and patients were not correlated with GH basal values, making this determination useless for test validation. In contrast, an excellent correlation was observed between GH values at 30 minutes and the GH peaks (r = 0.994, P < 0.0001). When comparing the 30-minute GH values against the peaks, the biochemical classification changed from normal toward uncertain in only five out of 203 control subjects, which is without clinical relevance according to Bayes theorem. Similarly, when the 30-minute value was used instead of the peak in GH deficient patients, only two out of 146 patients moved from the uncertain area toward the GH deficient one. Thus, better diagnostic classification was provided for patients. CONCLUSIONS: The GHRH + GHRP-6 test is a convenient, safe and reliable, provocative test of GH reserve in adults, which can be reduced to a single fixed GH determination 30 minutes after stimulus.

Adolescent↗

Role of adipocyte differentiation-related protein in surfactant phospholipid synthesis by type II cells.

Adipocyte differentiation-related protein (ADrP) is an intrinsic lipid storage droplet protein that is highly expressed in lung. ADrP localizes to lipid storage droplets within lipofibroblasts, pulmonary cells characterized by high triacylglycerol, which is a precursor for surfactant phospholipid synthesis by alveolar type II epithelial (EPII) cells. The developmental pattern of ADrP mRNA and protein expression in lung tissue parallels triacylglycerol accumulation in rat lung. ADrP mRNA levels are relatively high in isolated lipofibroblasts, accounting for the high ADrP expression in lung. Isolated EPII cells, which do not store neutral lipids but derive them from lipofibroblasts, have low levels of ADrP mRNA expression. ADrP is found around lipid droplets in cultured lipofibroblasts, but not in EPII cells isolated from developing rat lung. After coculture with lipofibroblasts, EPII cells acquired ADrP, which associates with lipid droplets. Furthermore, (3)H-labeled triolein in isolated ADrP-coated lipid droplets is a tenfold better substrate for surfactant phospholipid synthesis by cultured EPII cells than (3)H-labeled synthetic triolein alone. Antibodies to ADrP block transfer of neutral lipid. These data suggest a role for ADrP in this novel mechanism for the transfer of lipid between lipofibroblasts and EPII cells.

Animals↗

Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation.

Developing rat lung lipofibroblasts express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a paracrine signaling "loop." This hypothesized mechanism is supported by the following experimental data: 1) leptin stimulates the de novo synthesis of surfactant phospholipid by both fetal rat type II cells (400% x 100 ng(-1) x ml(-1) x 24 h(-1)) and adult human airway epithelial cells (85% x 100 ng(-1) x 24 h(-1)); 2) leptin is secreted by lipofibroblasts in amounts that stimulate type II cell surfactant phospholipid synthesis in vitro; 3) epithelial cell secretions such as parathyroid hormone-related protein (PTHrP), PGE(2), and dexamethasone stimulate leptin expression by fetal rat lung fibroblasts; 4) PTHrP or leptin stimulate the de novo synthesis of surfactant phospholipid (2- to 2.5-fold/24 h) and the expression of surfactant protein B (SP-B; >25-fold/24 h) by fetal rat lung explants, an effect that is blocked by a leptin antibody; and 5) a PTHrP receptor antagonist inhibits the expression of leptin mRNA by explants but does not inhibit leptin stimulation of surfactant phospholipid or SP-B expression, indicating that PTHrP paracrine stimulation of type II cell maturation requires leptin expression by lipofibroblasts. This is the first demonstration of a paracrine loop that functionally cooperates to induce alveolar acinar lung development.

Animals↗

Examining monophyly in a large radiation of Madagascan butterflies (Lepidoptera: Satyrinae: Mycalesina) based on mitochondrial DNA data.

The satyrine butterfly subtribe Mycalesina has undergone one of the more spectacular evolutionary radiations of butterflies in the Old World tropics. Perhaps the most phenotypically pronounced diversification of the group has occurred in the Malagasy region, where 68 currently recognized species are divided among five genera. Here, we report the results of phylogenetic analyses of sequence data from the cytochrome c oxidase II and cytochrome b mitochondrial genes, for a total of 54 mycalesine taxa, mostly from Madagascar. These molecular data complement an existing data set based on male morphological characters. The molecular results support the suggestion from morphology that three of the five Malagasy genera are paraphyletic and support the monophyly of at least three major morphological clades. Novel hypotheses of terminal taxon pairs are generated by the molecular data. Dense taxon sampling appears to be crucial for elucidating phylogenetic relationships within this large radiation. A potentially complex scenario for the origin of Malagasy mycalesines is proposed.

Animals↗

Dentoalveolar response after protraction mask and expansion in males and females in the mixed dentition.

The purpose of this study was to determine the dentoalveolar response of class III patients in the mixed and late mixed dentition phases fitted with a protraction mask and expansion. The before and after cephalometric records of 74 patients divided by sex were analyzed at ages 6 to 9 and 9 to 12 years to assess the dentoalveolar changes. Data was correlated by means of paired t tests and Scheffe's multiple contrasts. No significant changes were seen in all dentoalveolar relationships between the ages of 6 to 9 years and 9 to 12 years and between males and females. Maxillary teeth tended to be proclined, while mandibular teeth to become retroclined.

Age Factors↗

Native and artificial reticuloplasmins co-accumulate in distinct domains of the endoplasmic reticulum and in post-endoplasmic reticulum compartments.

We compared the subcellular distribution of native and artificial reticuloplasmins in endosperm, callus, and leaf tissues of transgenic rice (Oryza sativa) to determine the distribution of these proteins among endoplasmic reticulum (ER) and post-ER compartments. The native reticuloplasmin was calreticulin. The artificial reticuloplasmin was a recombinant single-chain antibody (scFv), expressed with an N-terminal signal peptide and the C-terminal KDEL sequence for retrieval to the ER (scFvT84.66-KDEL). We found that both molecules were distributed in the same manner. In endosperm, each accumulated in ER-derived prolamine protein bodies, but also in glutelin protein storage vacuoles, even though glutelins are known to pass through the Golgi apparatus en route to these organelles. This finding may suggest that similar mechanisms are involved in the sorting of reticuloplasmins and rice seed storage proteins. However, the presence of reticuloplasmins in protein storage vacuoles could also be due to simple dispersal into these compartments during protein storage vacuole biogenesis, before glutelin deposition. In callus and leaf mesophyll cells, both reticuloplasmins accumulated in ribosome-coated vesicles probably derived directly from the rough ER.

Calcium-Binding Proteins↗

Alcoholic liver cirrhosis is associated with a decreased expression of the CD28 costimulatory molecule, a lower ability of T cells to bind exogenous IL-2, and increased soluble CD8 levels.

Despite the existence of high interleukin (IL)-12 serum levels in patients with chronic active alcoholism, previous studies from our group have shown that, during active ethanol intake, alcoholic patients with alcoholic liver cirrhosis (ALC) display an impaired T-helper-1 response together with abnormalities in the peripheral blood (PB) cytotoxic compartment. The aim of the present study was to gain further insights into the mechanisms underlying these abnormalities. For that purpose, we analyzed the expression on PB B- and T-cell subsets of both the CD28 and CD80 costimulatory molecules, the ability of T lymphocytes to bind to exogenous recombinant IL-2, and the serum levels of soluble CD8 (sCD8) that might interfere with CD8+ T-cell activation in a group of 10 ALC patients with active ethanol intake (ALCET group). As reference groups, we analyzed 10 healthy individuals, 10 chronic alcoholic patients without liver disease (AWLD group) but with active ethanol intake, and 10 ALC patients who had quit drinking for at least 1 year. Our results showed that ALCET patients display a significant decrease in the number of PB CD28+/CD8(hi) T cells (P < 0.05) and CD80+ B cells (P < 0.01) compared with both healthy controls and AWLD patients. In addition, in ALCET patients, PB T cells also showed a decreased ability to bind to exogenous IL-2 (P < 0.01). This was associated with the existence of increased serum levels of sCD8 in ALC patients, the highest levels being detected in the ALCET group (P < 0.01). Altogether, our results point to the existence of several abnormalities that would affect the cytotoxic response in ALCET patients.

Adult↗

GH-releasing hormone and GH-releasing peptide-6 for diagnostic testing in GH-deficient adults.

BACKGROUND: The diagnosis of growth hormone (GH) deficiency in adults is based on provocative testing of GH secretion. The insulin tolerance test (ITT), currently the favoured test for this diagnosis, has been criticised for poor reproducibility and inconvenience. Since the combined administration of GH-releasing hormone (GHRH) plus GH-releasing peptide-6 (GHRP-6) is the most potent stimulus of GH secretion, we did a multicentre study comparing GH peaks elicited by ITT with those elicited by the GHRH/GHRP-6 test in healthy controls and GH-deficient individuals (cases). METHODS: 125 adult patients with organic pituitary disease and 125 healthy individuals were studied. All cases and controls were given GHRH 1 microg per kg bodyweight intravenously plus GHRP-6 1 microg per kg intravenously at 0 min and blood samples were obtained during a subsequent 120 min period. 27 controls and all cases had an ITT. Inclusion criteria were severe GH deficiency--ie, a GH peak after ITT of < or = 3 microg/L. Results of the GHRH/GHRP-6 test were analysed by receiver-operating characteristic curve methodology. FINDINGS: GH peaks seen after the GHRH/GHRP-6 test did not result in any side-effects and were not affected by age, sex, amount of adipose tissue, or by the GH assay system used. The GH mean peak after the GHRH/GHRP-6 test was 59.2 microg/L (SD 2.2) for controls and 4.1 microg/L (0.3) for cases, whereas after ITT the mean peak was 14.3 microg/L (1.7) and 0.5 microg/L (0.06), respectively. The differential peak responses of controls and cases was greater (p<0.001), for GHRH/GHRP-6 test than for ITT. When individually analysed GH peaks were a continuum, from 139.0 microg/L to 0.01 microg/L, with a cut-off point of 15.0 microg/L. The GHRH/GHRP-6 test performed well under the ROC curve analysis. For clinical utility, it is then proposed that values > or = 20.00 microg/L be considered normal and < or = 10.00 microg/L as GH deficient. INTERPRETATION: The GHRH/GHRP-6 test is a convenient, safe and reliable test for adult GH deficiency and is not confounded by clinical factors known to alter GH secretory patterns. An evoked GH concentration of > or = 15.0 microg/L accurately distinguishes between healthy and GH-deficient adults.

Adolescent↗

Chemical modification of hemoglobin improves biocatalytic oxidation of PAHs.

Chemical modifications on human hemoglobin were performed with the aim to change both surface and active-site hydrophobicities. The modifications included covalent coupling of poly(ethylene)glycol (5000 MW) on free amino groups and the methyl esterification of free carboxylic groups. The modified hemoglobin was assayed for the oxidation of 11 polycyclic aromatic hydrocarbons (PAHs) and 2 organosulfur aromatic compounds. Acenaphthene, anthracene, azulene, benzo(a)pyrene, fluoranthene, fluorene, phenanthrene, and pyrene were transformed to their respective quinones, while for chrysene and biphenyl no biocatalytic reaction could be detected. Dibenzothiophene and thianthrene were oxidized to form sulfoxides. The doubly modified hemoglobin, PEG-Met-hemoglobin, showed up to 10 times higher activity than the unmodified protein. The kinetic constants show that the PEG-Met-hemoglobin has a significantly higher catalytic efficiency. The equilibrium substrate binding constants for unmodified and PEG-Met-modified hemoglobis and hemoglobin show that this catalytic enhancement could be attributed to the affinity increase for hydrophobic substrates in the modified protein.

Catalysis↗

Potential use of flow cytometry in toxicity studies with microalgae.

Cytotoxic effects of aquatic pollutants on microalgae are very heterogeneous, and they are influenced by environmental conditions and the test species. Stress produced by copper or paraquat addition to the culture medium of two microalgae was analysed by flow cytometry. Parameters assayed were: cell volume, chlorophyll a fluorescence and cell viability. The variety of results obtained in the present study reveals that flow cytometry is a useful tool in the toxicity tests with microalgae, both marine and freshwater species, and for different kind of pollutants.

Cell Division↗

Amino terminal peptides of the ring infected erythrocyte surface antigen of Plasmodium falciparum bind specifically to erythrocytes.

The Ring-Infected Erythrocyte Surface Antigen (Pf155/RESA) sequence was chemically synthesized in fifty four 20-mer sequential peptides, covering the entire protein, each of which was tested in erythrocyte binding assays. Peptides 6671 and 6673, corresponding to residues 141-160 and 181-200, respectively, presented a high specific binding activity to erythrocytes with affinity constants of 190 nM and 105 nM respectively. Their binding was sensitive to previous enzymatic treatment of erythrocytes. A region of peptide 6673 has been identified, very recently, as a B-cell epitope, target of neutralizing antibodies (Siddique AB, Iqbal J, Ahlborg N, Wâhlin FB, Perlmann P, Berzins K. Antibodies to nonrepeat sequences of antigen Pf155/RESA of Plasmodium falciparum inhibit parasite growth in vitro. Parasitol Res 1998;84:485-91). The critical residues for erythrocyte binding for peptide 6671 (MTDVNRYRYSNNYEAIPHIS) and for peptide 6673 (LGRSGGDIIKKMQTLWDEIM) were recognized. Based on these data, the presence of five functional regions of RESA is postulated.

Amino Acid Sequence↗

Lymphatic filariasis in the Philippines.

Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout most of the southern half of the Philippine archipelago. Economic and manpower shortages prior to 1996 made it difficult to acquire new prevalence data and vector control data concurrently from all provinces. Nevertheless, analysis of cumulative prevalence data on filariasis indicates the persistence of filariasis in each of the three major island groups - Luzon, Visayas and Mindanao - including 45 out of 77 provinces. Here, Michael Kron and colleagues summarize the prevalence data, and review host, parasite and vector characteristics relevant to the design and implementation of disease control initiatives in the Philippines planned for the year 2000.

Animals↗

Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies.

This report describes the stable expression of a medically important antibody in the staple cereal crops rice and wheat. We successfully expressed a single-chain Fv antibody (ScFvT84.66) against carcinoembryonic antigen (CEA), a well characterized tumor-associated marker antigen. scFv constructs were engineered for recombinant antibody targeting to the plant cell apoplast and ER. Up to 30 microg/g of functional recombinant antibody was detected in the leaves and seeds of wheat and rice. We confirmed that transgenic dry seeds could be stored for at least five months at room temperature, without significant loss of the amount or activity of scFvT84.66. Our results represent the first transition from model plant expression systems, such as tobacco and Arabidopsis, to widely cultivated cereal crops, such as rice and wheat, for expression of an antibody molecule that has already shown efficacy in clinical applications. Thus, we have established that molecular pharming in cereals can be a viable production system for such high-value pharmaceutical macromolecules. Our findings provide a strong foundation for exploiting alternative uses of cereal crops both in industrialized and developing countries.

Animals↗