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Biomedical subjects

R Guerra

Publications and source records attributed to R Guerra.

At least 19 recordsLinked to original sources

Impact of dredging in a shallow coastal lagoon: Microtox Basic Solid-Phase Test, trace metals and Corophium bioassay.

The aim of this work was to measure survival of the amphipod Corophium insidiosum and luminescence inhibition in the marine bacterium Vibrio fisheri on surface sediment samples collected from a shallow coastal lagoon (Pialassa Baiona, northern Adriatic Italian coast) before execution of dredging operations to deepen the main inner channel of the lagoon and restore the water circulation. Trace metal (Cd, Cu, Cr, Hg, Ni, Pb) concentrations, grain size and organic carbon matter content as loss of ignition were also measured. Toxicity testing with V. fisheri was carried out according to the Microtox Basic Solid-Phase Test (BSPT) protocol. The preliminary outcomes of this work show that: (a) the investigated area can be categorised as moderately degraded; (b) there is no evident spatial pattern in sediment toxicity and trace metal concentrations; (c) Microtox responses are not biased by sediment characteristics such as silt, clay and organic matter content.

Amphipoda↗

Evidence of reduced frequency of spinal muscular atrophy type I in the Cuban population.

The authors reviewed all cases of type I spinal muscular atrophy (SMA) in Cuba over a 6-year period. The incidence of SMA type I was 3.53 per 100,000 livebirths. When the population was classified according to self-reported ethnicity, the incidence was eight per 100,000 for whites; 0.89 per 100,000 for blacks, and 0.96 per 100,000 for those of mixed ethnicity. Type 1 SMA may occur less frequently in individuals of African ancestry.

Black People↗

Effect of sediment turbidity and color on light output measurement for Microtox Basic Solid-Phase Test.

In this work, sediment samples collected from several Spanish harbours were tested with two toxicity procedures, designed for solid samples: the Microtox Basic Solid-Phase Test (BSPT) and a modified procedure of the previous test protocol (mBSPT). According to the BSPT procedure, after initial light readings, pure bacteria were exposed to sediment suspension dilutions and light production was directly measured on suspended sediments without any further manipulation. As measurements are likely to be affected by sediment turbidity and color, a variation in initial light measurement has been here suggested, in order to consider the sample effect at all time readings during the test. Firstly, when sediment suspensions at different concentrations were added to bacteria suspension, immediately the initial light output drastically decayed by more than 50% in signal difference, resulting in a false inhibition, as effect of sample turbidity/color. This effect was more evident at high EC50 values, when slightly or not toxic samples were assessed. Secondly, the comparison of the EC50 obtained with both procedures, demonstrated that the mBSPT produced higher EC50 values (less toxic) than those obtained with the standard procedure. The mBSPT procedure resulted rapid and effective and it could be applied simultaneously with BSPT, in order to better evaluate the toxicity.

Algorithms↗

Effect of apolipoprotein B polymorphism in kidney transplantation.

INTRODUCTION: In kidney transplant recipients, dyslipidemia is a cardiovascular risk factor that also contributes to the development and progression of chronic allograft nephropathy. Apolipoprotein B (ApoB), present in low-density lipoproteins (LDL), is an important protein component of chylomicrons and very-low-density lipoproteins (VLDL). The del allele of the ApoB signal peptide polymorphism has been associated with elevated levels of total and LDL cholesterol and greater risk of coronary disease. OBJECTIVE: The objective of this study was to assess the influence of ApoB polymorphism on allograft and patient survival among kidney transplant recipients. METHODS: In this study, we analyzed 516 renal transplant recipients (38% were women, 62% were men), aged 46 +/- 15 years, with a minimum follow-up of 12 months (mean, 1854 +/- 806 days). The ApoB signal peptide was analyzed (insertion/deletion) using polymerase chain reaction (PCR) using genomic DNA. Clinical donor-recipient variables were assessed using a Cox multivariate model. RESULTS: Polymorphism distribution was as follows: insertion/insertion (ins/ins) 51%, insertion/deletion (ins/del) 39%, and deletion/deletion (del/del) 9%, with no differences between the genders. Cholesterol levels at 12 months showed no differences between the ins/ins (217 +/- 46), ins/del (228 +/- 50), and del/del (227 +/- 54) groups. Presence of the ApoB signal peptide del/del or ins/del genotype was independently associated with lower patient survival in the group of men younger than 60 years (P < .05). Among the total deaths, cardiovascular causes predominated in the ins/del and del/del groups (50%) as compared with the ins/ins group (33%) (P < .01). CONCLUSIONS: ApoB genetic polymorphism (del allele) seems to have an adverse effect on the long-term survival of kidney transplant recipients.

Adult↗

Effect of calcineurin inhibitors on low-density lipoprotein oxidation.

INTRODUCTION: Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients. OBJECTIVE: The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients. METHODS: We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels. RESULTS: The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s]). CONCLUSIONS: In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment.

Adult↗

Ecotoxicological and chemical evaluation of phenolic compounds in industrial effluents.

The aim of this paper was to evaluate the ecotoxicological response of industrial effluents containing phenolic compounds. All complex effluents collected from a chemical plant and then after both a chemical-physical and biological treatment were characterised with chemical analysis, biodegradability tests and four ecotoxicological tests (Daphnia magna, Artemia salina, Brachionus plicatilis and Vibriofisheri with Microtox). The evaluation of the chemical and ecotoxicological data was useful for predicting the effect of the raw effluent on the treatment plant and the impact of the final treated effluent on the receiving water. Besides the toxicity of the effluent from the chemical plants, the acute toxicity of its main components was also determined. The results of the tests and toxicity data from literature were transformed in Toxic Units (TUs). Effluent toxicity was under- or over-estimated by calculating the sum of the TUs of the individual components, depending on which toxicity data and test organisms were used.

Animals↗

Increased stability and catalytic efficiency of yeast hexokinase upon interaction with zwitterionic micelles. Kinetics and conformational studies.

The effect of ligands (glucose, ATP and Mg2+) and zwitterionic micelles of lysophosphatidylcholine (LPC) or N-hexadecyl-N,N-dimethyl-3-ammonium propanesulfonate (HPS) in the yeast hexokinase (HK) stability was studied at 35 degrees C. The thermal inactivation kinetics followed one-exponential decay. The effect of ligands on protecting the enzyme against inactivation followed the order: glucose > glucose/Mg2+ >ATP/Mg2+ approximately or approximately equal to Mg2+l approximately or approximately equal to buffer only. Both LPC and HPS micelles increased the enzyme stability only when the incubation medium contained glucose or glucose/Mg2+, suggesting that the protein conformation is a key prerequisite for the enzyme-micelle interaction to take place. This enzyme-micelle interaction resulted in an increased catalytic efficiency (with a decrease in Km for ATP and increase in Vmax as well as in changes on the tertiary (intrinsic fluorescence) structure of the yeast hexokinase.

Adenosine Triphosphate↗

Chromatin condensation during Scrobicularia plana spermiogenesis: a controlled and comparative enzymatic ultracytochemical study.

In Scrobicularia plana testis, a nuclear acid phosphatase (ACPase) activity was detected in mid and late spermatids with the improved Gomori-chloride procedure. Lead deposits were first observed in mid spermatids at focal points over condensed chromatin strands, increasing in density as chromatin further condensated. In late spermiogenesis, lead deposits became concentrated between chromatin aggregates, and after total DNA compaction were transfered to the nuclear periphery and then shed into the cytoplasm. The specificity of the nuclear ACPase was tested against different pH values (3.9, 7.2, 7.8, 9.0), substrates (TPP, IDP, TMP, p-NCS, ATP, GTP, AMP, ADP, AMP-PNP) and inhibitors (NaF, levamisole, Zn, vanadate, theophylline). To further specify the nature of this nuclear ACPase, other enzymes were comparatively studied at their optimal pH values and at pH 5.0: nucleoside-diphosphatase, thiamin-pyrophosphatase, inorganic trimetaphosphatase, lysosomal arylsulfatases A and B, ATPase, GTPase, 5'-nucleotidase, adenylate kinase, and adenylate cyclase. Several other controls were introduced to exclude artefactual deposits induced by lead ions and tissue molecules. The results showed that the enzyme has an optimal pH at 5.0, a high specific affinity for beta-GP, and is inhibited by NaF, which suggests that it behaves as a type B-ACPase, and all controls demonstrated the specificity of the enzymic activity. Because lead deposits were specifically and temporally associated with spermatid chromatin condensation, when DNA and RNA synthesis, histones, phosphoproteins and RNA molecules strongly decrease, it is possible to suggest that the nuclear ACPase could be associated with DNA processing during chromatin compaction or involved in the hydrolysis of 2' and 3' nucleotides resulting from nuclear RNase action during RNA degradation.

Acid Phosphatase↗

Mie and debye scattering in dusty plasmas

We calculate the total field scattered by a charged sphere immersed in a plasma using a unified treatment that includes the usual Mie scattering and the scattering by the Debye cloud around the particle. This is accomplished by use of the Dyadic Green function to determine the field radiated by the electrons of the Debye cloud, which is then obtained as a series of spherical vector wave functions similar to that of the Mie field. Thus we treat the Debye-Mie field as a whole and study its properties. The main results of this study are (1) the Mie (Debye) field dominates at small (large) wavelengths and in the Rayleigh limit the Debye field is constant; (2) the total cross section has an interference term between the Debye and Mie fields, important in some regimes; (3) this term is negative for negative charge of the grain, implying a total cross section smaller than previously thought; (4) a method is proposed to determine the charge of the grain (divided by a certain suppression factor) and the Debye length of the plasma; (5) a correction to the dispersion relation of an electromagnetic wave propagating in a plasma is derived.

Journal Article↗

High prevalence of celiac sprue-like HLA-DQ genes and enteropathy in patients with the microscopic colitis syndrome.

OBJECTIVE: Celiac sprue is associated with specific HLA-DQ genes (mainly DQ2). Because there are epidemiological and histopathological similarities between celiac sprue and microscopic colitis, we hypothesized that these syndrome may share an HLA genetic predisposition and pathogenesis. METHODS: The HLA-DQ genes of 25 patients with celiac sprue, 53 patients with the microscopic colitis syndrome, and 429 normal controls were typed and compared. Serum was analyzed for antigliadin and antiendomysial antibodies. Small intestinal biopsies were analyzed for signs of histopathology. RESULTS: HLA-DQ2 or DQ1,3 (the latter as DQ1,7,DQ1,8, or DQ1,9) were seen more frequently in both patient groups relative to controls. In patients with the microscopic colitis syndrome, serological tests for celiac sprue were weakly positive in 17%; mild inflammation of the small intestine without villous atrophy was present in 43%, and inflammation plus partial or subtotal villous atrophy was present in 27%. CONCLUSIONS: A shared set of predisposing HLA-DQ genes account for the epidemiological overlap of celiac sprue and microscopic colitis. Mild to moderate mononuclear cell inflammation of the small intestine, often accompanied by partial or subtotal villous atrophy, is frequent in patients with the microscopic colitis syndrome. Although further studies will be necessary to determine if this enteropathy is induced by dietary gluten, we speculate that the small intestinal but not colonic histopathology in patients with microscopic colitis is caused by immunological gluten sensitivity.

Adult↗

[The long-term effects of dual-chamber stimulation in 8 patients with hypertrophic obstructive cardiomyopathy and symptoms refractory to medical therapy].

BACKGROUND: The issue of DDD pacing as a therapeutic option for patients with obstructive hypertrophic cardiomyopathy is still under debate. Moreover, some authors stress the concept of the placebo effect of electrical therapy in this particular setting. METHODS: We retrospectively evaluated 8 symptomatic patients with obstructive hypertrophic cardiomyopathy despite medical therapy, who underwent DDD pacemaker implantation as an adjunctive therapeutic strategy. All patients were evaluated with a two-dimensional/Doppler echocardiogram at baseline, shortly after the beginning of DDD pacing and at follow-up. In 3 patients dobutamine stimulation was necessary to elicit the intraventricular gradient. RESULTS: At follow-up (21 +/- 19 months, range 1-54 months) the peak gradient declined from 86 +/- 27 to 34 +/- 27 mmHg (55.2%). In 4 patients the peak gradient sharply declined after pacemaker implantation with active pacing and remained stable throughout the follow-up. In 2 patients we noted a continuous reduction in the peak gradient during the follow-up, while in 2 patients it returned to baseline values after 1 year and 1 month, respectively, despite an early reduction with DDD pacing. All patients experienced symptomatic amelioration throughout the follow-up. Two patients developed angina at the end of our observation together with an increase in the peak gradient. CONCLUSIONS: We believe that DDD pacing may be considered as a practical therapeutic option for patients with obstructive hypertrophic cardiomyopathy who would otherwise be regarded as candidates for surgery.

Adult↗

[Long-term clinical assessment of single-lead VDD electric stimulation].

BACKGROUND: During the last decade single lead VDD pacing has been progressively affirmed as an electrotherapy of choice in patients with advanced atrioventricular block without alterations of the sinus function. It combines the benefits of P-synchronous ventricular pacing with an easy implant procedure when compared to the conventional DDD approach. The aim of this study was to evaluate the validity of such an approach in a large population of patients, all implanted in a single center. METHODS: From 1987 up to now, 317 patients, all affected by advanced atrioventricular block and without sinus node dysfunction, were implanted in our center with a single lead VDD pacemaker. During follow-up the persistence of a proper atrioventricular synchronization was assessed and evaluated. RESULTS: The mean follow-up was 3.9 +/- 2.7 years/patient (range 6-138 months). The 94.6% of implanted systems maintained the normal VDD pacing function. Permanent reprogramming in VVI mode was necessary in 17 patients (5.36%); in 12 (3.78%) because of chronic atrial fibrillation and in 5 (1.63%) for loss of atrial sensing. The percentage of atrial synchronization was optimal (> 98%) and acceptable (> 95%) in 81% and 19% of patients, respectively. Episodes of paroxysmal atrial fibrillation occurred in 3 patients. Neither inhibition by myopotentials nor occurrence of sinus node disease was observed during follow-up. These results are in accordance with those reported by previous studies, performed on a smaller population or on a multicenter basis, and are comparable with the results reported for conventional DDD pacemaker. CONCLUSIONS: Our results confirm the high reliability of the single lead VDD pacing system concerning the long-term persistence of a proper atrioventricular synchronization. Data showed above enforce our opinion that this pacing approach should be considered the treatment of choice in patients with advanced atrioventricular block and preserved sinus node function.

Aged↗

Structure, cytoskeleton, and development of the acrosome of Platycleis albopunctata (Orthoptera: Tettigoniidae).

The acrosome of Platycleis albopunctata (Orthoptera: Tettigoniidae) is relatively large and complex, consisting of an apical vesicle and two large wing-like extensions that give the spermatozoon the shape of an arrow. The wings have actin microfilaments and microtubules and are covered with a noticeable extracellular material. Actin filaments are present in the acrosome when it first appears in spermatid stages. The acrosome and the acrosomal attachment to the nucleus are more resistant than other structures to the reducing agents DTT and SDS. At the end of spermiogenesis, groups of spermatozoa juxtapose their sperm heads and become joined to form a spermatodesm encircled by an amorphous material. Treatment with the ionophore A23187 rapidly disrupted acrosomes of the free gametes, but acrosomes from spermatozoa contained in the spermatodesm were not disassembled. Packaging of sperm in a spermatodesm appears to protect the acrosome.

Acrosome↗

Meta-analysis by combining parameter estimates: simulated linkage studies.

Several meta-analytic techniques have been developed for combining information from multiple studies in contexts other than linkage detection. We apply the technique of combining parameter estimates to the problem of finding disease loci in the simulated data and compare results with those obtained by reanalyzing pooled raw data. To facilitate the combination of study results, we highly recommend that parameter estimates and their standard errors be reported in published studies. If different research groups were to make original data available, progress toward disease gene location and characterization may be more quickly made.

Genetic Linkage↗

Meta-analysis by combining p-values: simulated linkage studies.

Meta-analysis has been little explored to make an overall assessment of linkage from different studies. In practice, it is likely that published linkage studies will only report p-values. We compared the performance of the widely used Fisher method for combining p-values with that of pooling raw data. More loci were consistently found by pooling raw data. In the absence of further information, combining p-values can provide an overall, but limited, assessment of different linkage studies. However, meta-analysis would be better viewed as a preliminary step toward the goal of analyzing the pooled raw data.

Genetic Linkage↗

A statistically robust variance-components approach for quantitative trait linkage analysis.

Previously we showed (Wang, Guerra & Cohen 1998) that a statistically robust version of the Haseman & Elston (1972) sib-pair method greatly increased power to detect linkage in the presence of outliers. In this paper we report on M-estimation to accommodate outliers in the variance-components approach to linkage analysis developed by Amos (1994). Simulations show that in the presence of outliers the robust variance-components approach provides substantially greater power, more precise estimation of heritabilities, and better false-positive rates than the original Gaussian based approach. In the absence of outliers the performance of the robust variance-components approach is similar to that of the Gaussian based approach. For illustration we apply the method to two well characterized lipoprotein systems.

Alleles↗

Testing for linkage under robust genetic models.

Robust genetic models are used to assess linkage between a quantitative trait and genetic variation at a specific locus using allele-sharing data. Little is known about the relative performance of different possible significance tests under these models. Under the robust variance components model approach there are several alternatives: standard Wald and likelihood ratio tests, a quasilikelihood Wald test, and a Monte Carlo test. This paper reports on the relative performance (significance level and power) of the robust sibling pair test and the different alternatives under the robust variance components model. Simulations show that (1) for a fixed sample size of nuclear families, the variance components model approach is more powerful than the robust sibling pair approach; (2) when the number of nuclear families is at least approximately 100 and heritability at the trait locus is moderate to high (>0.20) all tests based on the variance components model are equally effective; (3) when the number of nuclear families is less than approximately 100 or heritability at the trait locus is low (<0. 20), on balance, the Monte Carlo test provides the best power and is the most valid. The different testing procedures are applied to determine which are able to detect the known association between low density lipoprotein cholesterol and the common genotypes at the locus encoding apolipoprotein E. Results from this application show that the robust sibling pair method may be more effective in practice than that indicated by simulations.

Alleles↗

Linkage between cholesterol 7alpha-hydroxylase and high plasma low-density lipoprotein cholesterol concentrations.

Interindividual differences in plasma low-density lipoprotein cholesterol (LDL-C) levels reflect both environmental variation and genetic polymorphism, but the specific genes involved and their relative contributions to the variance in LDL-C are not known. In this study we investigated the relationship between plasma LDL-C concentrations and three genes with pivotal roles in LDL metabolism: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and cholesterol 7alpha-hydroxylase (CYP7). Analysis of 150 nuclear families indicated statistically significant linkage between plasma LDL-C concentrations and CYP7, but not LDLR or APOB. Further sibling pair analyses using individuals with high plasma LDL-C concentrations as probands indicated that the CYP7 locus was linked to high plasma LDL-C, but not to low plasma LDL-C concentrations. This finding was replicated in an independent sample. DNA sequencing revealed two linked polymorphisms in the 5' flanking region of CYP7. The allele defined by these polymorphisms was associated with increased plasma LDL-C concentrations, both in sibling pairs and in unrelated individuals. Taken together, these findings indicate that polymorphism in CYP7 contributes to heritable variation in plasma LDL-C concentrations. Common polymorphisms in LDLR and APOB account for little of the heritable variation in plasma LDL-C concentrations in the general population.

Adult↗