Lack of association between HLA-E polymorphism and primary cutaneous melanoma in Spanish patients.
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Gene Frequency↗
Biomedical subjects
J A Lozano
Publications and source records attributed to J A Lozano.
Globally multimodal problem optimization via an estimation of distribution algorithm based on unsupervised learning of Bayesian networks.
Many optimization problems are what can be called globally multimodal, i.e., they present several global optima. Unfortunately, this is a major source of difficulties for most estimation of distribution algorithms, making their effectiveness and efficiency degrade, due to genetic drift. With the aim of overcoming these drawbacks for discrete globally multimodal problem optimization, this paper introduces and evaluates a new estimation of distribution algorithm based on unsupervised learning of Bayesian networks. We report the satisfactory results of our experiments with symmetrical binary optimization problems.
Algorithms↗
Editorial introduction: special issue on estimation of distribution algorithms.
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Algorithms↗
[Tissue reaction to breast prostheses. Periprosthetic capsular contracture].
Silicone breast prostheses prompt the development of a fibrous casing or periprosthetic capsule. Capsular contracture, due to retraction of the fibrous tissue, is the most frequent and important complication of these implants. It produces varying degrees of hardening and, in advanced cases, deformity of the breast. It has been closely related to the type of surface of the implant (smooth or textured) and with the alignment of the collagen fibers, and it has been suggested that the formation of a continuous capsule, with collagen fibers aligned in parallel and circularly around the smooth prostheses, promotes the development of concentric contractile forces that pulling in unison give rise to contracture. With microporous textured prostheses a significantly lower incidence of capsular contracture has been shown in comparison with smooth prostheses. It is believed that tissue growth within the microporous structure gives rise to multidirectional contractile forces, with a tendency to neutralize one another when their effect is added over the implant. The capsule of these implants presents a base zone composed of multiple layers of collagen fibers aligned in parallel, which might contract. However, the adherence of the microporous textured prostheses might counteract the contractile forces.
Breast Implants↗
[Breast reconstruction with latissimus dorsi musculocutaneous flap].
In breast reconstruction we try to achieve the greatest possible symmetry with the contralateral breast, with the smallest number of interventions, the least possible sequel and the greatest safety. When we find poor cutaneous quality in the thorax we must use techniques that provide a well vascularised tissue of good quality, which we obtain at a certain distance instead of using the thorax tissues themselves. This article reviews the latissimus dorsi musculocutaneous flap, the technique of elevation, variations of the flap, and the advantages and drawbacks involved. This is a very safe and versatile technique, with few sequels in the donor area, with a relatively short surgery time and with good aesthetic results.
Female↗
[Breast reconstruction with the transverse rectus abdominis musculocutaneous (TRAM) flap].
The transverse rectus abdominis musculocutaneous (TRAM) flap has been the most employed technique in autogenous breast reconstruction. It provides a new breast of adequate volume, ptosis and natural appearance, and does not require the implantation of prosthesis; a good symmetry with the contralateral breast is obtained, which lasts over time. The drawback of this technique is the morbidity of the abdominal wall. This flap sacrifices the muscle and the anterior rectus sheath which can result in consequences such as hernias and eventrations. To minimise this problem the microsurgical TRAM flap was developed, which only sacrifices a portion of muscle, significantly reducing the number of sequels. A drawback is the difficulty of the surgical technique, which requires mastery of vascular-nervous microsurgery. In conclusion, a new breast can be returned to the mastectomised woman in a completely autogenous way, with a volume, form and texture similar to the healthy side, which helps in short to recover lost self-esteem.
Female↗
[Breast reconstruction with microsurgical perforator flaps].
Autogenous breast reconstruction is frequently carried out with abdominal tissue, since a better and lasting aesthetic result is obtained, providing a new breast that is very similar in texture, consistency and ptosis to the contralateral breast. The main problem presented by this type of reconstruction is the sequel at the level of the donor abdominal area. Perforator flaps are being developed as the main resource for solving this problem, as they hardly damage the muscle and its fascia. The DIEP flap (deep inferior epigastric perforator) has proved itself to be an alternative for reconstruction for many women, with low rates of local complications, due to the absence of any sacrifice of the abdominis rectus muscle, and a significant level of satisfaction with the result obtained. One drawback is its greater technical difficulty and the need for a surgical team that is expert in vascular microsurgery. However, the DIEP flap is a surgical technique for which there is growing demand.
Female↗
[Treatment of the contralateral breast in breast reconstruction. Nipple-areola reconstruction].
The final objective of breast reconstruction is to equalize as far as possible the appearance between the reconstructed breast and the contralateral breast. To this end, once the new breast monticle has been obtained through different techniques of breast reconstruction, we employ a different series of surgical techniques that allow us to obtain symmetry. In this way, we act on the one hand on the contralateral breast (either increasing it, reducing it or raising it), and on the other we act on the reconstructed breast, recreating a new nipple-areola complex, which will complete the reconstruction by giving this breast a more real and suitable appearance.
Female↗
Training with computer-supported motor imagery in post-stroke rehabilitation.
Converging lines of evidence suggest that motor imagery (the mental simulation of a motor act within working memory) is associated with subliminal activation of the motor system. This observation has led to the hypothesis that cortical activation during motor imagery may affect the acquisition of specific motor skills and help the recovery of motor function. In this paper, we describe a clinical protocol in which we use interactive tools to stimulate motor imagery in hemiplegic stroke patients, thereby helping them to recover lost motor function. The protocol consists of an inpatient and an outpatient phase, combining physical and mental practice. In the inpatient phase, patients are trained in a laboratory setting, using a custom-made interactive workbench (VR Mirror). After discharge, patients use a portable device to guide mental and physical practice in a home setting. The proposed strategy is based on the hypotheses that: (a) combined physical and mental practice can make a cost-effective contribution to the rehabilitation of stroke patients, (b) effective mental practice is not possible without some form of support, from a therapist (as in our inpatient phase) or from technology (as in the outpatient phase), (c) the inclusion of an outpatient phase will allow the patient to practice more often than would otherwise be possible, therefore increasing the speed and/or effectiveness of learning, and (d) the use of interactive technology will reduce the patient's need for skilled support, therefore improving the cost-effectiveness of training.
Cerebral Infarction↗
Effects of several polyhydroxylated flavonoids on the growth of B16F10 melanoma and Melan-a melanocyte cell lines: influence of the sequential oxidation state of the flavonoid skeleton.
The response of B16F10 melanoma and Melan-a melanocyte cell lines to treatment with five polyhydroxylated flavonoids and gallic acid, after 24 and 72 h of exposure, was determined, and the relationship between any antiproliferative effects observed and the chemical structure is discussed. After 24 h, none of the studied compounds showed significant cytotoxic activity in the B16F10 cell line, whereas compounds with an adjacent trihydroxylated substitution pattern did affect the viability of the Melan-a cell line. After 72 h of exposure, myricetin, baicalein and gallic acid significantly inhibited both B16F10 and Melan-a cell cultures, whereas luteolin and quercetin had only a moderate effect. Eriodictyol only had an effect on Melan-a cell viability, which was reduced slightly. These results suggest that the presence of a C2-C3 double bond and three adjacent hydroxyl groups in the flavonoid A- or B-rings confers greater antiproliferative activity to the flavonoid.
Animals↗
Effects of several flavonoids on the growth of B16F10 and SK-MEL-1 melanoma cell lines: relationship between structure and activity.
Although flavonoids seem to be capable of acting at all stages of the carcinogenic process, little information is available on their action in melanoma cell lines. The aim of this study was to assess the response of B16F10 and SK-MEL-1 melanoma cell lines to treatment with six different flavonoids after 24 and 72 h of exposure and to relate the response to their structure. We then compared the findings with those for melphalan treatment. When cultures were treated for 24 h, only slight inhibition at the highest concentrations (25 and 50 microM) of tangeretin and luteolin were observed, whereas melphalan caused a dose-related inhibition of growth at all concentrations. Quercetin, hesperetin, 7,3'-dimethylhesperetin and eriodictyol did not produce any effect at 24 h on B16F10 or SK-MEL-1 cells, results which point to the low toxicity of flavonoids. After 72 h of exposure culture growth was inhibited by 7,3'-dimethylhesperetin at 50 microM, but lower concentrations had no effect. Tangeretin was the most effective of the flavonoids in inhibiting B16F10 and SK-MEL-1 cell growth, showing a clear dose-response curve after 72 h. These results suggest that the absence of the C2-C3 double bond on hydroxylated flavonoids results in a loss of effect on both the cell lines, while the higher activity of tangeretin compared with 7,3'-dimethylhesperetin suggests that the presence of at least three adjacent methoxyl groups confers a more potent antiproliferative effect.
Animals↗
The 5,6-dihydroxyindole-2-carboxylic acid (DHICA) oxidase activity of human tyrosinase.
Melanin synthesis in mammals is catalysed by at least three enzymic proteins, tyrosinase (monophenol dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) and tyrosinase-related proteins (tyrps) 1 and 2, whose genes map to the albino, brown and slaty loci in mice, respectively. Tyrosinase catalyses the rate-limiting generation of L-dopaquinone from L-tyrosine and is also able to oxidize L-dopa to L-dopaquinone. Conversely, mouse tyrp1, but not tyrosinase, catalyses the oxidation of the indolic intermediate 5,6-dihydroxyindole-2-carboxylic acid (DHICA) into the corresponding 5,6-indolequinone-2-carboxylic acid, thus promoting the incorporation of DHICA units into eumelanin. The catalytic activities of the human melanogenic enzymes are still debated. TYRP1 has been reported to lack DHICA oxidase activity, whereas tyrosinase appears to accelerate DHICA consumption, thus raising the question of DHICA metabolism in human melanocytes. Here we have used two different approaches, comparison of the catalytic activities of human melanocytic cell lines expressing the full set of melanogenic enzymes or deficient in TYRP1, and transient expression of TYR and tyr genes in COS7 cells, to demonstrate that human tyrosinase actually functions as a DHICA oxidase, as opposed to the mouse enzyme. Therefore, human tyrosinase displays a broader substrate specificity than its mouse counterpart, and might be at least partially responsible for the incorporation of DHICA units into human eumelanins.
Amino Acid Sequence↗
Partial liquid ventilation with perfluorocarbons for treatment of ARDS in burns.
Pulmonary failure remains the major determinant of mortality and morbidity following burn injury. We hypothesized that intratracheal instillation of perfluorocarbon liquids could be a therapeutic measure in combination with conventional mechanical ventilation to improve pulmonary gas exchange in acute respiratory distress syndrome with thermal injury. Forty-five New Zealand rabbits were used for this prospective and randomized experimental study. The animals were burned by scald to reach full-thickness 40% burn surface area. After inducing respiratory distress by repeated lung lavage with saline, animals were divided randomly into three groups of 15 rabbits each. First group (control group) received conventional treatment (continuous positive-pressure ventilation) using a FiO(2) of 1.0, tidal volume of 12 ml/kg, respiratory frequency of 30 cycles/min and PEEP of 6 cm H(2)O. Second group was treated with 9 ml/kg of intratracheal perfluorocarbon. Third group was treated with 15 ml/kg of intratracheal perfluorocarbon. All groups were ventilated for 6 h. In the perfluorocarbon groups, PaO(2) increased significantly (P<0.05) from 46+/-4 to 439+/-10 mmHg compared to the control group in a dose-related manner. In pulmonary parameters we observed significant (P<0.05) decrease in mean airway pressures from the pre-treatment value of 11.44+/-0.15 cm H(2)O to the post treatment 10.22+/-0.12 cm H(2)O and increase (P<0.05) in respiratory system compliance from 1.8+/-0.02 to 2.46+/-0.07 ml/cm H(2)O with the perfluorocarbon. Perfluorocarbon instillation did not result in statistically significant changes in arterial pressure, heart rate and central venous pressure. In conclusion, partial liquid ventilation with perfluorocarbon is a new technique leading to a marked and sustained improvement in oxygenation and pulmonary function in an experimental model of ARDS in burns.
Animals↗
Regulation of the murine silver locus product (gp87) by the hypopigmenting cytokines TGF-beta1 and TNF-alpha.
The melanosomal proteins encoded by the silver (si, SILV, or PMEL17) locus play important roles in melanogenesis and are actively investigated as targets for melanoma immunotherapy. The human silver locus yields two proteins, gp100 and PMEL17, by alternative splicing of a common mRNA precursor. Mouse melanocytes exclusively express the gp100 orthologue, here termed gp87, thus providing a simpler model with which to study the silver locus products. We have analyzed the effects of [Nle4, D-Phe7]-alpha melanocyte-stimulating hormone (alphaMSH) and two hypopigmenting cytokines, tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1, on the expression of gp87 in B16 mouse melanoma cells. TNF-alpha and TGF-beta1 (at saturating doses for 48 hr) decreased gp87 mRNA by 50%. The gp87 protein was almost undetectable by Western immunoblotting after TNF-alpha treatment, but was not affected by TGF-beta1. alphaMSH increased the mRNA and the gp87 protein approximately 2-fold. Moreover, the amount of gp87 was not reduced by TNF-alpha in the presence of the hormone, in spite of a 50%, decrease in its mRNA. Therefore, the levels of mRNA and gp87 protein did not correlate after treatment with the cytokines. Overall, our data suggest that the silver locus product is not regulated exclusively at the transcriptional level, and highlight the importance of still-uncharacterized regulatory translational and/or post-translational events.
Animals↗
New insights on the structure of the mouse silver locus and on the function of the silver protein.
The melanosomal proteins encoded by the silver locus play important roles in melanogenesis. The human locus yields two proteins, PMEL17 and GP100, by alternative mRNA splicing. The mouse si locus was reported to encode a Pmel17 protein, and later gp87, a GP100 homologue. When we re-examined the products of wild-type and silver-mutant mouse si loci, RT-PCR of wild-type RNA and genomic DNA sequence accounted for gp87 but excluded the occurrence of Pmel17. Analysis of cDNA from the silver (si/si) melanocyte line, melan-si, showed that the pathogenic mutation is a G to A substitution at nt 1808, which yields a premature stop codon and a predicted protein truncated in the C-terminus. This was confirmed by reaction of a specific anti-gp87 antiserum with si/si melanocyte extracts. To further explore gp87 function, we compared the DHICA oxidase activity of extracts from B16, melan-si (heterozygous for the brown mutation and homozygous for the silver mutation) and Cloudman S91 cells (homozygous for the brown mutation), since both TRP1 and gp87 are thought to be involved in DHICA oxidation/polymerization. Cloudman extracts do not oxidize significantly DHICA and its methyl ester, supporting the involvement of native mouse TRP1 in DHICA oxidation. Extracts from B16 and melan-si do not show significant differences for the oxidation of free acid and methylated dihydroxyindoles, indicating that the mechanism is not decarboxylative. Melan-si extracts are very efficient in catalyzing dihydroxyindole oxidation, in spite of being heterozygous for the TRP1 mutation, consistent with a stablin effect for the wild-type gp87 protein. On the other hand, aggregated and degraded forms of that mutant gp87 protein are found in the cytosolic fraction of melan-si, suggesting that misrouting and aberrant processing of the gp87 and tyrosinase may also be related to the high DHICA oxidase activity of these melanocytes.
Alternative Splicing↗
The mouse silver locus encodes a single transcript truncated by the silver mutation.
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Amino Acid Sequence↗
Avascular necrosis of the femoral head after intertrochanteric fractures.
OBJECTIVE: To determine factors that may influence the appearance of avascular necrosis after intertrochanteric fractures. DESIGN: Retrospective. SETTING: University hospital. PATIENTS: Twelve patients between the ages of fifty-nine and eighty-eight who had developed avascular necrosis of the femoral head after treatment of an intertrochanteric femur fracture at our institution between 1976 and 1995. Fractures were classified according to Kyle and Gustilo. There were three Type I, two Type II, six Type III, and one Type IV fractures. MAIN OUTCOME MEASURES: Risk factors for osteonecrosis, fracture pattern, surgical influence, location of the nail within the femoral head, and valgus malalignment. RESULTS: All fractures healed. Five patients had risk factors for osteonecrosis. Intertrochanteric fractures with a proximal fracture line appeared in five patients. The nail tip was situated in every quadrant of the femoral head. Valgus malalignment occurred in three cases. CONCLUSIONS: Avascular necrosis of the femoral head is an uncommon complication after intertrochanteric fractures. The pathogenesis is unknown, but in patients developing pain who have had intertrochanteric fractures, osteonecrosis should be included in the differential diagnosis, especially in cases with risk factors for osteonecrosis or a proximal intertrochanteric fracture line that perhaps disrupts the vascular anastomotic ring at the base of the femoral neck.
Aged↗
Avascular necrosis of the femoral head after intertrochanteric fractures.
OBJECTIVE: To determine factors that may influence the appearance of avascular necrosis after intertrochanteric fractures. DESIGN: Retrospective. SETTING: University hospital. PATIENTS: Twelve patients between the ages of fifty-nine and eighty-eight who had developed avascular necrosis of the femoral head after treatment of an intertrochanteric femur fracture at our institution between 1976 and 1995. Fractures were classified according to Kyle and Gustilo. There were three Type I, two Type II, six Type III, and one Type IV fractures. MAIN OUTCOME MEASURES: Risk factors for osteonecrosis, fracture pattern, surgical influence, location of the nail within the femoral head, and valgus malalignment. RESULTS: All fractures healed. Five patients had risk factors for osteonecrosis. Intertrochanteric fractures with a proximal fracture line appeared in five patients. The nail tip was situated in every quadrant of the femoral head. Valgus malalignment occurred in three cases. CONCLUSIONS: Avascular necrosis of the femoral head is an uncommon complication after intertrochanteric fractures. The pathogenesis is unknown, but in patients developing pain who have had intertrochanteric fractures, osteonecrosis should be included in the differential diagnosis, especially in cases with risk factors for osteonecrosis or a proximal intertrochanteric fracture line that perhaps disrupts the vascular anastomotic ring at the base of the femoral neck.
Aged↗