Showing papers by "University of Extremadura published in 1995"

Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow‐derived macrophages by TH 1 and TH 2 cytokines

Abstract: Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase. Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline. NO is important in the bactericidal and cytotoxic activities of macrophages. An equivalent functional role of arginase and its products is not known. We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-γ (IFN-γ), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E2 (PGE2). We find that PGE2 and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase. In contrast, the TH 1 cytokine IFN-γ does not induce arginase. Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase. Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase. Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase. The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena. The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH 1 and TH 2 cytokines, respectively.

Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population

Abstract: The occurrence of multiple copies of the CYP2D6 gene was investigated 217 white healthy Spaniards by the combined use of Xba I and Eco RI restriction fragment length polymorphism (RFLP) analyses. About 3.5% of the alleles yielded an 12.1 kb Eco RI-RFLP product in combination with the 42 kb Xba I-RFLP product, which is indicative of multiple CYP2D6. The prevalence of subjects carrying multiple CYP2D6 was 7%. The 12.1 kb Eco RI-RFLP product was highly associated (60%) with the presence of the genotype 29wt/42wt, as characterized by mutation-specific polymerase chain reaction and Xba I-RFLP analyses. Six subjects who had multiple CYP2D6 had other genotypes, namely, 44wt/42wt (four subjects), 29C/42wt (one subject), and one subject had a 12.1 kb product plus the CYP2D6C mutation associated with the 44 kb/42 kb genotype. All subjects identified as carrying multiple CYP2D6 had only two CYP2D6 copies in the same chromosome and were classified as carriers of the (CYP2D6L)2 allelic variant. Phenotyping with debrisoquin indicated an increase in the oxidative capacity as a function of the number of functional CYP2D6 genes. The metabolic ratio and the 95% confidence limits were as follows: subjects lacking functional genes, 48.8 (95% confidence limits, 14.4 to 79.3); subjects with one functional gene, 2.14 (95% confidence limits, 0.61 to 3.67); subjects with two functional genes, 1.5 (95% confidence limits, 0.88 to 2.14); and subjects with three functional genes, 0.33 (95% confidence limits, 0.22 to 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)

Dual-Level Reaction-Path Dynamics (the /// Approach to VTST with Semiclassical Tunneling). Application to OH + NH3 .fwdarw. H2O + NH2

Abstract: We consider a new approach to reaction-path dynamics calculations in which the reaction path is calculated at a low level (LL) of theory and stationary point information from a high level (HL) of theory is used to interpolate corrections to energetic quantities, vibrational frequencies, and moments of inertia. Such a calculation is labeled XII/Y, where X denotes the high level and Y the low level. The theory is applied to the reaction OH + NH[sub 3] and three isotopomeric analogs. The highest-level optimization reported for the saddle point is QCISD(T)//MP2/aug-cc-pVTZ, which yields a classical barrier height of 3.65 kcal/mol. The rate constant is calculated at two levels, QCISD(T)//MP2/aug-cc-p VTZ[MP2/aug-cc-p VDZ] ///MP2/6-31G** and QCISD(T)//MP2/aug-cc-pVTZ[MP2/aug-cc-pVDZ] ///PM3-SRP; the calculated rare constant for the unsubstituted reaction is approximately invariant to the low level used in the dual-level scheme and agrees with experiment within a factor of 1.13 at 250 K and within a factor of 1.14 at 1500 K. 79 refs., 4 figs., 13 tabs.

Sexual selection in the barn swallow Hirundo rustica. VI. Aerodynamic adaptations

Abstract: Secondary sexual characters are assumed to be costly to produce and maintain, and this will select for morphological modifications that reduce the magnitude of such costs. Here we test whether a feather ornament, the sexually exaggerated outermost tail feathers of male barn swallows Hirundo rustica, a trait currently subject to a directional female mate preference, and other aspects of the morphology used for flight have been modified to increase aerodynamic performance. This was done by making comparisons among sexes within populations, among individuals varying in tail length within populations, and among populations from different parts of Europe. Male barn swallows experienced reduced drag from their elongated tail feathers by morphological modifications of the ornamental feathers as compared to females. Morphological features of the outermost tail feathers were unrelated to tail length in both males and females within populations. Wing and tail morphology (length of central tail feathers and wings, wing span, wing area, wing loading, and aspect ratio) was modified in males compared to females. Barn swallows with long tails had morphological tail and wing modifications that reduced the cost of a large ornament, and similar modifications were seen among populations. The costs of the exaggerated secondary sexual character were therefore reduced by the presence of cost-reducing morphological modifications. The assumptions of reliable signalling theory, that signals should be costly, but more so to low than to high quality individuals, were not violated because long-tailed male barn swallows had the largest cost-reducing morphological characters.

Morphological changes in the normal pattern of ventricular myoarchitecture in the developing human heart

Abstract: Background: The aim of the present study was to describe the morphological changes in the normal pattern of ventricular myoarchitecture in the prenatal and adult human heart, to understand the three-dimensional organization of the muscle fibers and their active functional role in valvular dynamics. Methods: We used dissection and histological techniques in 56 human hearts from fetuses and adults of both sexes. Results: In all hearts, the ventricular wall was arranged in three different layers: superficial (subepicardial), middle, and deep (subendocardial) myocardium. The superficial and deep layer are present in both ventricles, whereas the middle layer is found only in the left ventricle. Age-related differences were noted in the pattern of myoarchitecture of the superficial layer, mainly in the fetal period, and especially in the right ventricle; however, the middle layer always shows a circumferential pattern, which is specially evident in elderly hearts. The ventricular fibers in the superficial and deep layers are anchored in the ventricular orifices. Conclusions: Our findings reveal that muscle fiber architecture showed age-but not sex-related differences. These variations may reflect a mechanism of adaptation of the heart to functional demands throughout life. © 1995 Wiley-Liss, Inc.

Evaluating and refining computational models of spatial relations through cross-linguistic human-subjects testing

Abstract: Human-subjects testing based on a sound formal model is outlined as an effective way to evaluate and refine computational models of spatial relations. The cognitive response of a subject (person) to a real-world situation depends on the characteristic of the situation and the characteristics of the subject. Spatial entities can be characterized by topological relations, metric, scale (scope), kinds of phenomena (semantics), motion (time), and (for maps and displays) graphic presentation. Subjects' responses may vary according to their natural languages, their cultures, and individual characteristics such as gender, age, and handedness. Given this conceptual background, seven human-subjects testing protocols are introduced. Each test is described, and results of applications of these tests are summarized where possible. The tests are compared with their requirements, and the different aspects of human spatial cognition that they might test. Lastly, a program for applying these tests and refining the formal models based on test results is presented.

Lateral root initiation by asymmetrical transverse divisions of pericycle cells in four plant species:Raphanus sativus, Helianthus annuus, Zea mays, andDaucus carota

Abstract: In roots ofRaphanus sativus, Helianthus annuus, Zea mays, andDaucus carota, lateral root initiation occurs when a pair of neighbouring elongated and highly vacuolated pericycle cells in the same column almost simultaneously undergo asymmetrical transversal division. This produces a pair of very short pericycle cells lying end-to-end, flanked above and below by two longer cells. This occurs because both mitoses occur close to the ends of the neighbouring pericycle cells. The two longer daughter pericycle cells divide again later. In roots of radish, sunflower, and carrot these cells divide transversely and asymmetrically, producing more short cells adjacent to the previous ones. In corn roots, they undergo oblique divisions. Much later, the first pair of short pericycle cells undergoes periclinal divisions. Although such periclinal divisions of pericycle cells are generally thought to mark lateral root initiation, our results show that the first pair of short neighbouring pericycle cells in the same column offers another morphological criterion which permits identification of the site of lateral root initiation, both earlier and nearer to the apex than previously documented.

Lung cancer and mutations at the polymorphic NAT2 gene locus

Abstract: The prevalence of seven point mutations on the polymorphic NAT2 gene was studied in DNA from 108 patients with histologically proved bronchogenic carcinoma and 243 healthy controls. By means of a mutation-specific polymerase chain reaction analysis, the wild-type and fourteen mutant allelic variants of the NAT2 gene were identified. The prevalence for the poor acetylator genotypes in patients and control subjects were similar, however the frequency of mutant alleles was higher in patients with lung cancer. This was attributable to an increase in the prevalence of the allelic variants 590A and 341C + 481T + 803G among patients (p < 0.05 and 0.06, respectively). These allelic variants were at increased frequency in patients with adenocarcinoma, squamous cell or small cell lung cancer. Subjects poor acetylators that are homozygous for the allelic variant 341C + 481T + 803G seem to be at increased risk to develop lung cancer (odds ratio; 95% CI = 1.75; 0.99-3.12). We conclude that the acetylator status is not a major factor in lung cancer risk, however the presence of the 341C + 481T + 803G and the 590A alleles of the polymorphic NAT2 gene may be a secondary risk factor for the development of lung cancer.

Association between the oxidative polymorphism and early onset of Parkinson's disease

Abstract: The frequency of five cytochrome P450IID6 allelic variants was studied in deoxyribonucleic acid from 123 patients with Parkinson's disease and 150 healthy volunteers. This was achieved by the use of mutation-specific polymerase chain reaction and restriction fragment length polymorphism. The analyses of the CYP2D6 genotype revealed no evidence for a higher prevalence of poor metabolizers among patients with Parkinson's disease. However, increased frequency of patients with Parkinson's disease with the genotype CYP2D6wt/CYP2D6B was observed. This is attributable exclusively to subjects with early onset of the disease (28 to 49 years), with a relative risk ratio of 4.16 (95% confidence limits, 2.0 to 8.3; p or = 50 years) had genotypes and CYP2D6 allele frequencies similar to the healthy subjects. This indicates that the oxidative polymorphism is related to early-onset but not to late-onset Parkinson's disease. A different influence of CYP2D6 genotype on the risk of development of Parkinson's disease is observed in Spaniards, compared with previous findings in British subjects. These results suggest the combined effect of environmental toxins and CYP2D6 in the cause of Parkinson's disease.

A study of the role of corticosterone as a mediator in exercise‐induced stimulation of murine macrophage phagocytosis.

Abstract: 1. It is generally accepted that physical activity provokes changes in the immune system. Previous studies have demonstrated that the stress of physical activity (swimming until exhaustion) increases the phagocytic activity of peritoneal macrophages. However, the precise mechanisms remain unknown. 2. Two experiments were performed in the present study. (A) Peritoneal macrophages from control mice were incubated with plasma from three different groups of mice: (1) mice subjected to swimming until exhaustion with no previous training, (2) mice subjected to the same activity but with 1 month of training (30 min day-1), and (3) a control (non-exercised) group. The differences in the resulting phagocytic (attachment and ingestion) capacity were measured. (B) Changes in the concentration of plasma corticosterone after exercise were also measured, and the effect of incubation with the postexercise plasma corticosterone level on the phagocytic activity of peritoneal macrophages was then studied in vitro. 3. The results were: (A) incubation with plasma from both groups of exercised mice (with and without previous training) led to increased levels of phagocytic capacity (number of C. albicans cells ingested per 100 macrophages). (B) Incubation with a corticosterone concentration of 0.72 mumol l-1 (similar to that observed in plasma immediately after exercise) raised the phagocytic capacity (144 +/- 12 after incubation with 0.72 mumol l-1 vs. 93 +/- 19 after incubation with 0.24 mumol l-1). This increase was also significantly greater than that observed with 7.2 mumol l-1 corticosterone. 4. It is concluded that corticosterone may mediate the increased phagocytic function of peritoneal macrophages induced by exercise.

Molecular biology of yeast exoglucanases

Abstract: Three exoglucanase (Exg) genes have been reported in Saccharomyces cerevisiae. Gene EXG1 encodes the major isoenzyme (Exgl). Differential glycosylation of the primary translation product throughout the secretory pathway results in the secretion of several glycoforms. The major glycoform (Exglb) contains two short carboxypeptidase Y-like oligosaccharides attached to both potential glycosylation sites present in the molecule. A minor glycoform (Exgla) arises from the former by elongation of the second oligosaccharide. The protein portion is processed in the secretory pathway by the Kex2 protease. Gene EXG2 encodes a 63 kDa polypeptide with 12 potential glycosylation sites. The predicted protein, Exgll, carries a signal peptide at the amino terminus and a glycosyl-phosphatidyl inositol anchoring motif at the carboxyl end. The latter appears responsible for the particulate nature of this isoenzyme, since its elimination results in the secretion of this activity into the culture medium. Gene SSG1 encodes a 52 kDa polypeptide which is specifically synthesized during sporulation of diploids. SSC1 expression is under control of both sexual (a1-α2 element) and nutritional control. Although homozygous ssg1 / ssg1 diploid strains are still able to complete sporulation, they exhibited a delay in the appearance of mature asci. Single or double disruption of EXG1 and EXG2 did not result in any relevant phenotype and the triple mutant behaved as ssg1 /ssg1. A Exgl-related enzyme is secreted by Candida albicans. All these four enzymes share 8 highly conserved regions in the same relative positions, indicating that they derive from a common ancestor. However, no clear function has so far been demonstrated for them.

Kabuki make-up (Niikawa-Kuroki) syndrome in five Spanish children.

Abstract: We describe 5 Spanish children with Kabuki make-up syndrome (KMS)—3 females and 2 males—identified in Badajoz, Spain, between 1988 and 1990. All had the characteristic clinical and radiological manifestations of the syndrome. Psychomotor/mental retardation, postnatal growth deficiency, distinctive facial appearance, sagittal vertebral clefts, and dermatoglyphic abnormalities were present in all 5. Congenital heart defects were present in 4 patients. In addition, one had myopia, astigmatism, and bilateral paralysis of the VI cranial nerve. Another had apparent fusion of the hamate and capitate. An additional patient, as well as his mother, had an apparently balanced 15/17 translocation [46,XY,t(15;17) (15q;21q)]. The fact that these patients were ascertained in a catchment area of approximately 250,000 inhabitants and in a relatively limited period of time suggests that the prevalence of the KMS may be higher than previously recognized. © 1995 Wiley-Liss, Inc.

Influence of geology and soil particle size on the surface-area/volume activity ratio for natural radionuclides

Abstract: The radioactive concentrations of226Ra,232Th,235U and40K in surface soil of the province of Caceres (Spain) were studied as a function of the geology and grain size. The activities of the four radionuclides in granitic and metamorphic soils have normal frequency distributions, with the mean value being significantly higher for the granitic soils than for the metamorphic soils. Sedimentary soils present asymmetric distributions, and their activities lie between the previous two types. The specific activities of the four radionuclides rises as the particle radius decreases. The equationAe=(P1/R)+P2 describes the dependence of the specific activityAe on radiusR, P1 andP2 being parameters that are related to the surface area and volume activities of the grains. The isotopes226Ra,232Th and235U accumulate with greater intensity on the surface of the grains than40K. This effect is more pronounced in granitic and sedimentary soils than in metamorphic soils.

Foraging costs of a tail ornament: Experimental evidence from two populations of barn swallows Hirundo rustica with different degrees of sexual size dimorphism

Abstract: Secondary sexual characters are assumed to be costly to produce or maintain. A test of this assumption was performed using the sexually exaggerated outermost tail feathers of male barn swallows Hirundo rustica, a trait currently subject of a directional female mate preference. A possible cost of sexual signalling in male barn swallows arises from increased flight cost during foraging in this aerially insectivorous species. A longer tail may impose a greater drag during flight and thereby affect foraging ability. This was tested by determining the relationship between experimentally modified male tail lengths and number and size of prey delivered to offspring in Spain, where sexual size dimorphism in tail length is small, compared to Denmark, where dimorphism is large. Food boluses contained significantly fewer small insects in Spain than in Denmark. Males with elongated tails captured more and smaller insects while males with shortened tails captured fewer and larger prey items at both sites. Males with naturally long tails were less affected by experimental treatment in terms of effects on the number and the size of prey delivered to their offspring, a finding consistent with a long tail being a condition-dependent viability indicator. The effect of a given degree of tail manipulation on prey size and number of prey per bolus was larger in Spain than in Denmark. These results demonstrate that (1) tail length in male barn swallows affects foraging, and (2) larger sexual size dimorphism occurs where the foraging cost of an increment in ornament size is smallest.

The monoclonal antibody JIM5 indicates patterns of pectin deposition in relation to pit fields at the plasma-membrane-face of tomato pericarp cell walls

Abstract: The use of the anti-pectin monoclonal antibody JIM5 in conjunction with immunofluorescence microscopy and also confocal microscopy has indicated that the JIM5 epitope is associated with structural features of the plasma-membrane-face of the cell wall of tomato pericarp cells. JIM5 recognized the primary pit fields of the cell walls, as identified by co-staining with callose-reactive aniline blue. In addition, abundant linear arrays of the pectin epitope were observed to radiate out from the primary pit fields in parallel, as well as random, arrangements. These observations have implications for our understanding of the organization of the polymer networks that comprise the primary cell wall.

On the origin and evolution of the genetic code

Abstract: Two ideas have essentially been used to explain the origin of the genetic code: Crick's frozen accident and Woese's amino acid-codon specific chemical interaction. Whatever the origin and codon-amino acid correlation, it is difficult to imagine the sudden appearance of the genetic code in its present form of 64 codons coding for 20 amino acids without appealing to some evolutionary process. On the contrary, it is more reasonable to assume that it evolved from a much simpler initial state in which a few triplets were coding for each of a small number of amino acids. Analysis of genetic code through information theory and the metabolism of pyrimidine biosynthesis provide evidence that suggests that the genetic code could have begun in an RNA world with the two letters A and U grouped in eight triplets coding for seven amino acids and one stop signal. This code could have progressively evolved by making gradual use of letters G and C to end with 64 triplets coding for 20 amino acids and three stop signals. According to proposed evidence, DNA could have appeared after the four-letter structure was already achieved. In the newborn DNA world, T substituted U to get higher physicochemical and genetic stability.

Fully differential basic building blocks based on fully differential difference amplifiers with unity-gain difference feedback

Abstract: A set of truly fully differential (FD) basic building blocks is presented. They are based on differential difference amplifiers with differential output (FDDA, fully differential difference amplifier) in unity gain difference feedback configuration. Simulation results at the transistor level demonstrate their suitability for FD signal processing. >

Clitoromegaly in neurofibromatosis.

Abstract: Genitourinary neurofibromas are rare and clitoral involvement in neurofibromatosis (NF) has been reported infrequently. However, when it occurs, clitoromegaly is often the presenting sign. In many cases, it is congenital. In 236 families with type 1 neurofibromatosis (NF-1) evaluated through the USF Regional Genetics Program between January 1982 and September 1993, four patients had clitoral involvement. In three, involvement was limited to the clitoris. Biopsy/surgical excision in two of them showed a neurofibroma in one and non-specific hamartomatous soft tissue overgrowth in the other. In the fourth patient, the involvement was asymmetric and extended to the labia majora and mons pubis. Endocrine studies and chromosomes in all patients were normal; there was no exposure to androgens, progestins, or coumadin. There was no gestational history of maternal luteomas. Review of the literature documented 26 patients with NF and clitoral involvement. Clitoral involvement in NF-1 appears to be more common than previously reported and the differential diagnosis of ambiguous genitalia should include clitoromegaly due to NF. Pathogenesis of clitoral lesions appears similar to other lesions of NF. Biopsy of such lesions appears to be justified only when malignancy is suspected.