Impaired phagocytosis among patients infected by the human immunodeficiency virus: implication for a role of highly active anti-retroviral therapy.

In patients with human immunodeficiency virus (HIV) infection, neutrophil and monocyte functions, including phagocytosis, are impaired. The purpose of this study was to investigate changes of phagocytic function and respiratory burst occurring over the course of patients infected by the HIV-1 virus. Treatment-naive patients (group B), patients receiving highly active anti-retroviral treatment (HAART) (group C) and patients in which HAART has failed (group D) were studied and compared with healthy volunteers (group A). Phagocytosis and oxidative burst were evaluated using commercially available kits. Results clearly denote a significant decrease of the phagocytic function of both cell types of groups B and C compared with group A. Among group C patients, those in the upper quartile of CD4 increase had higher oxidative burst compared with patients of the other quartiles. In addition, comparisons clearly showed a lower degree of phagocytic function and of oxidative burst of both monocytes and neutrophils of group D compared with group B. Finally, it was found that monocyte and neutrophil function was correlated inversely to the change in viral load, i.e. the greater the decrease of viral load, the better the phagocytic and oxidative activity. Innate immunity defects appear to be present in HIV-positive patients, regarding phagocytic activity and oxidative burst of monocytes and neutrophils. These defects are greatly influenced by the level of treatment efficacy, with emphasis on CD4 cell counts and viral load.

Impact of cancer patients' disease awareness on their family members' health-related quality of life: a cross-sectional survey.

BACKGROUND: Conflicting results exist concerning disease knowledge and patients' quality of life (QOL) while there is very limited information concerning the impact of awareness on caregivers' health-related quality of life. The aim of this study was to explore the influence of disease awareness on both cancer patients and their caregivers during the period of chemotherapy. MATERIALS AND METHODS: Two hundred and twelve cancer patient-caregiver dyads completed the QOL SF-36 instrument on the day of chemotherapy. Hierarchical multiple linear regression analysis was performed. RESULTS: Physical component parameters were significantly higher in the family members (p<0.001), while their mental component was lower than cancer patients. Younger patients, females, and of higher educational status were more frequently aware of their disease status while patients with gastrointestinal cancer were more likely to be unaware. Disease knowledge seems to exert a negative influence on patients' physical and mental parameters while lack of awareness affects adversely caregivers' vitality, social function, emotional role, and mental health. Multiple regression analysis confirmed disease awareness affected reversely patients' and caregivers' mental QOL while the counter-influence of the dyad was revealed. CONCLUSIONS: A holistic approach to cancer management should be followed. Patient's treatment is the major medical concern, but health system and professionals should be involved in the mental and physical support of caregivers as well. Tailored interventions that focus on the support of the dyad patient-caregiver should be developed.

DIANA-microT web server: elucidating microRNA functions through target prediction.

Computational microRNA (miRNA) target prediction is one of the key means for deciphering the role of miRNAs in development and disease. Here, we present the DIANA-microT web server as the user interface to the DIANA-microT 3.0 miRNA target prediction algorithm. The web server provides extensive information for predicted miRNA:target gene interactions with a user-friendly interface, providing extensive connectivity to online biological resources. Target gene and miRNA functions may be elucidated through automated bibliographic searches and functional information is accessible through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The web server offers links to nomenclature, sequence and protein databases, and users are facilitated by being able to search for targeted genes using different nomenclatures or functional features, such as the genes possible involvement in biological pathways. The target prediction algorithm supports parameters calculated individually for each miRNA:target gene interaction and provides a signal-to-noise ratio and a precision score that helps in the evaluation of the significance of the predicted results. Using a set of miRNA targets recently identified through the pSILAC method, the performance of several computational target prediction programs was assessed. DIANA-microT 3.0 achieved there with 66% the highest ratio of correctly predicted targets over all predicted targets. The DIANA-microT web server is freely available at www.microrna.gr/microT.

Duodeno-pancreatic neuroendocrine tumours.

Duodeno-pancreatic neuroendocrine tumours (DP-ETs) are increasingly diagnosed today due to the widespread use of modern imaging methods. Duodeno-pancreatic endocrine tumours should be treated by radical surgical resection, which offers a high chance for cure when the disease is localized. A high index of suspicion is required in these patients for the presence of a multiple endocrine neoplasia type syndrome. We present four patients with DP-ET surgically treated at our department between 2000 and 2004. Histological/immunohistochemical diagnosis was somatostatin-producing tumour in the first patient, oncocytic endocrine tumour positive for neurone-specific enolase and focally for chromogranin in the second patient, glucagonoma and pancreatic polypeptide-producing endocrine pancreatic tumour in the third patient, and gastrin, somatostatin, calcitonin, insulin and adrenocorticotropic hormone (ACTH)-producing tumour in the fourth. The second patient died 6.5 years following surgery due to disseminated disease.

Surgical pancreatic sphincteroplasty. Historic or history ? A review.

BACKGROUND: Minimal invasive techniques represent a constantly expanding field of medicine and numerous well-established operative procedures have gradually been replaced. Likewise, surgical pancreatic sphincteroplasty, which has been the cornerstone in the management of pancreatic flow disorders for decades, has been largely replaced by endoscopy. Endoscopic pancreatic sphincterotomy however, is still not widespread and carries a significant risk of complications. In this study we attempt to review the role of the surgical approach in the modern era. METHODS: Pubmed database was searched for reports concerning surgical pancreatic sphincteroplasty alone or in comparison with endoscopy, without other limitations. RESULTS: Initially, 44 studies were obtained. Finally, 22 full papers were selected, pertaining review articles, case series or clinical studies. Only four of them were recent (after 2002) series of surgical sphincteroplasty, pertaining 561 patients. No randomized-controlled trials or meta-analyses were revealed. CONCLUSIONS: Pancreatic sphincterotomy, either surgical or endoscopic offers good to excellent long-term results in several disorders, like Sphincter Oddi dysfunction, especially when underlying parenchymal disease is limited. Surgical sphincteroplasty is nowadays indicated in most cases of endoscopic failure and in cases that the papilla cannot be approached. Bariatric patients with gastric by-pass and sphincter Oddi dysfunction in particular, have reported to show excellent outcome after surgery. Regardless the method, patient selection is still a very important determinant of success.

Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients.

AIM: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. MATERIALS AND METHODS: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival. CONCLUSIONS: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.

L10-FeNi films on Au-Cu-Ni buffer-layer: a high-throughput combinatorial study.

The fct L10-FeNi alloy is a promising candidate for the development of high performance critical-elements-free magnetic materials. Among the different materials, the Au-Cu-Ni alloy has resulted very promising; however, a detailed investigation of the effect of the buffer-layer composition on the formation of the hard FeNi phase is still missing. To accelerate the search of the best Au-Cu-Ni composition, a combinatorial approach based on High-Throughput (HT) experimental methods has been exploited in this paper. HT magnetic characterization methods revealed the presence of a hard magnetic phase with an out-of-plane easy-axis, whose coercivity increases from 0.49 kOe up to 1.30 kOe as the Au content of the Cu-Au-Ni buffer-layer decreases. Similarly, the out-of-plane magneto-crystalline anisotropy energy density increases from 0.12 to 0.35 MJ/m3. This anisotropy is attributed to the partial formation of the L10 FeNi phase induced by the buffer-layer. In the range of compositions we investigated, the buffer-layer structure does not change significantly and the modulation of the magnetic properties with the Au content in the combinatorial layer is mainly related to the different nature and extent of interlayer diffusion processes, which have a great impact on the formation and order degree of the L10 FeNi phase.

The metabolic impact of extracellular nitrite on aerobic metabolism of Paracoccus denitrificans.

Nitrite, in equilibrium with free nitrous acid (FNA), can inhibit both aerobic and anaerobic growth of microbial communities through bactericidal activities that have considerable potential for control of microbial growth in a range of water systems. There has been much focus on the effect of nitrite/FNA on anaerobic metabolism and so, to enhance understanding of the metabolic impact of nitrite/FNA on aerobic metabolism, a study was undertaken with a model denitrifying bacterium Paracoccus denitrificans PD1222. Extracellular nitrite inhibits aerobic growth of P. denitrificans in a pH-dependent manner that is likely to be a result of both nitrite and free nitrous acid (pKa = 3.25) and subsequent reactive nitrogen oxides generated from the intracellular passage of FNA into P. denitrificans. Increased expression of a gene encoding a flavohemoglobin protein (Fhp) (Pden_1689) was observed in response to extracellular nitrite. Construction and analysis of a deletion mutant established Fhp to be involved in endowing nitrite/FNA resistance at high extracellular nitrite concentrations. Global transcriptional analysis confirmed nitrite-dependent expression of fhp and indicated that P. denitrificans expressed a number of stress response systems associated with protein, DNA and lipid repair. It is therefore suggested that nitrite causes a pH-dependent stress response that is due to the production of associated reactive nitrogen species, such as nitric oxide from the internalisation of FNA.

Species-related differences in steroid-binding specificity of glucocorticoid receptors in lung.

The steroid-binding affinities and specificities of pulmonary glucocorticoid receptors have been examined in different mammalian species. The receptors of all species examined are highly specific for binding glucocorticoids, the order of binding affinity being similar to the order of their biological potency. Progesterone also binds significantly to the receptors with an affinity varying between 16% and 41% of the corresponding affinity of corticosterone in different species. The affinity of triamcinolone acetonide for the receptor is highest in the rabbit, lowest in the guinea pig, and intermediate in the rat, mouse, and man, suggesting an inverse relationship between the affinity of glucocorticoids for the receptors and the level of glucocorticoids in blood. Glucocorticoid receptors of cortisol-secreting species (man, guinea pig, rabbit) bind cortisol with a much higher affinity than corticosterone, whereas glucocorticoid receptors of corticosterone-secreting species (rat, mouse) bind corticosterone with a much higher affinity than cortisol. In addition to cortisol, other 17 alpha-hydroxylated steroids also bind receptors of cortisol-secreting species with a relatively higher affinity than receptors of corticosterone-secreting species. Thus, in a given species glucocorticoid receptors seem to bind steroids better that are normally secreted by that species than steroids that are not secreted. A change in the pattern of glucocorticoids secreted during development (e.g. the rabbit fetus secretes primarily cortisol whereas the adult rabbit secretes predominantly corticosterone) is not accompanied by a corresponding change in the binding specificity of glucocorticoid receptors.

Cytoplasmic and nuclear progestin receptors in human myometrium during the menstrual cycle and in pregnancy at term.

Exchange assays have been developed for the determination of the total progestin in receptor sites (unoccupied and occupied with endogenous hormone) in the cytosol and nuclei of human myometrium using radiolabeled R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) as ligand. These assays have been applied to the measurement of cytosol and nuclear progestin receptor sites in the myometrium during the menstrual cycle and in pregnancy at term. Both the cytosol receptor levels as well as the sum of cytosol and nuclear receptor levels were highest during the proliferative phase of the cycle, dropped moderately but significantly in the secretory phase, and decreased markedly in pregnancy at term. Despite the marked drop in cytosol receptor levels, nuclear receptor levels in pregnancy at term were similar to those observed in the proliferative or secretory phase. In addition, the fraction of the total cellular receptor that was associated with the nucleus increased from 5.5% in the proliferative phase to 60% in pregnancy at term. The decrease in cytosol progestin receptor concentration as well as the relative increase in nuclear localization of the receptor in human myometrium in pregnancy at term may be related to the high circulating progesterone levels.

Unoccupied and occupied estrogen receptors in myometrial cytosol and nuclei from nonpregnant and pregnant women.

Exchange assays have been developed and used to measure the total concentration of estrogen receptor sites (unoccupied and occupied with endogenous hormone) in the cytosol and nuclei of human myometrium during the menstrual cycle and in pregnancy at term, before and during labor. A major fraction of the nuclear receptors appear to be unoccupied (not complexed with estrogen). These sites were detected in both crude and highly purified myometrial nuclei, indicating that they are located in the nucleus and do not represent a cytoplasmic or other cellular contaminant. The distribution of estrogen receptors between the cytosol and the nucleus varied in pregnant and nonpregnant patients. In pregnant patients, the receptor was detected only in the nucleus, while in nonpregnant patients most of the receptor was found in the cytosol. The levels of total receptor were considerably lower (5 times) in pregnancy at term than during the menstrual cycle. No significant differences in cytosol receptor levels or in unoccupied nuclear receptor levels were observed between the proliferative and secretory phases of the cycle. However, the levels of occupied nuclear receptors were significantly higher in the proliferative than in the secretory phase. The levels of total and occupied nuclear receptors in pregnancy at term were similar to those found during the proliferative phase and appeared to decrease somewhat during labor, although the differences were not statistically significant.

Immune abnormalities in myelodysplastic syndromes.

The immune states of 52 patients with myelodysplastic syndromes classified according to the FAB criteria were studied. Serum electrophoresis and immunoelectrophoresis, direct Coombs test, and tests for organ and non-organ specific antibodies were performed. Twenty six patients had immunoglobulin abnormalities: six (11.5%) had monoclonal gammopathy; 17 (32.6%) had polyclonal increases in serum immunoglobulin; while in three (5.8%) immunoglobulin concentrations were decreased. The distribution of immunoglobulin abnormalities among the five myelodysplastic syndrome subtypes was fairly uniform. Results of direct Coombs test were negative in all cases. Organ specific antibodies were not detected in any of the patients tested, although two patients were found positive for antinuclear antibodies. The presence of immunoglobulin abnormalities indicates an involvement of the lymphoplasmatic system in myelodysplastic syndromes.

Identification of beta-adrenergic receptors in pulmonary alveolar type II cells.

Specific beta-adrenergic receptors have been identified in dissociated preparations of rabbit lung cells greatly enriched for alveolar type II cells and compared with receptors in preparations of mixed lung cells and erythrocytes. Freshly isolated type II cells as well as mixed dissociated lung cells and erythrocytes from fetal (28 days gestation) and adult rabbits contained high-affinity, low-capacity binding sites for [3H]dihydroalprenolol (DHA). Binding to all preparations was stereospecific and characteristic of the beta 1-subtype of beta-adrenergic receptors. The concentrations of the receptors were similar in mixed lung cells and alveolar type II cells, indicating that beta-adrenergic receptors are present not only in type II cells but also in other lung cell types. When the contribution of erythrocytes to receptor concentration observed in type II cells was determined, it was found to be insignificant. In mixed lung cells, both the affinity and concentration of the receptors were higher in adult than fetal preparations. The affinity of the receptors was also higher in adult than fetal type II cells, although we did not find a significant age-related difference in receptor concentrations in this cell type. These results suggest that stimulation of surfactant secretion observed after exposure of lung tissue to beta-adrenergic agonists is mediated by specific beta-adrenergic receptors on alveolar type II cells.

Hormonal regulation of beta-adrenergic receptors in fetal rabbit lung in organ culture.

Explants of fetal rabbit lung were established on the 25th day of gestation. These were maintained in serum-free medium for periods up to 10 days. During this time, the cultures exhibited morphological changes typical of terminal lung differentiation. Morphological evidence was also obtained for synthesis and secretion of pulmonary surfactant in these explants. beta-Adrenergic receptors were identified in these lung explants. Exposure of the explants to 10(-7)M dexamethasone on the third day of culture resulted in a significant increase in the number of beta-adrenergic receptors in the tissue without a change in receptor affinity. The effect of dexamethasone in organ culture was dose-dependent, a maximum increase in receptor number being observed within 48 hours of incubation with a hormone concentration of 1 x 10(-7)M. Exposure of the explant tissue to 1 x 10(-7)M triiodothyronine resulted in no significant increase in the concentration of beta-adrenergic receptors and no change in receptor affinity. These results suggest that glucocorticoids may potentiate the effects of beta-adrenergic agents in the fetal lung by increasing the numbers of their receptors. The effects of triiodothyronine upon the fetal lung do not appear to be mediated by this mechanism.

Influence of pulmonary endothelial cells on fetal lung development.

Culture medium conditioned by pulmonary endothelial cells stimulated proliferation of cultured fetal lung cells, as measured by increases in cell numbers, incorporation of tritiated thymidine into DNA, and incorporation of labeled choline into membrane phospholipids. Medium conditioned by several other cell culture preparations of fetal lung did not elicit these effects. The growth-promoting activity was found to be concentrated in fractions of 42,000 and 89,000 molecular weight (mol wt). In addition to promoting cell growth, medium conditioned by pulmonary endothelial cells also appeared to stimulate the incorporation of labeled choline into surfactant-associated phosphatidylcholine. These results suggest that pulmonary endothelial cells may produce factors that stimulate the growth and perhaps also the differentiation of fetal lung cells in culture.

Effect of endogenous corticosterone on the determination of dexamethasone receptor levels in rat liver cytosol.

The effect of endogenous corticosterone on the quantitative measurement of dexamethasone receptors in liver cytosols from developing rats has been studied. Liver cytosols from adrenalectomized rats were preincubated with increasing concentrations of nonlabeled corticosterone and the levels of detectable dexamethasone receptors were subsequently determined either directly or after removal of unbound corticosterone. Corticosterone concentrations of 50 nM or lower had no significant effect on the specific binding of labeled dexamethasone. Higher concentrations of corticosterone resulted in under-estimation of dexamethasone receptor levels. The mean levels of endogenous corticosterone in liver cytosols from 19.5- to 21.5- day fetuses, 22-day fetuses, 6-day-old immature rats and adult rats were 27.40, 11.91, 0.81 and 4.05 nM, respectively. It is concluded that variations in the levels of circulating corticosterone in the rat under normal physiological conditions have no significant effect on the quantitative measurement of total (occupied and unoccupied) receptor sites for dexamethasone in liver cytosol. This is supported by the finding that prior treatment of liver cytosols, from rats at different stages of development, with charcoal to remove unbound steroids has no effect on the amount of detectable dexamethasone receptors.

Binding of glucocorticoids to liver nuclei and chromatin of fetal, immature and adult rats.

The interaction of dexamethasone with nuclei and chromatin was investigated following incubation of liver slices from fetal, immature (6-day-old) and adult rats with the labeled steroid at 37 degrees. The number of specific binding sites for dexamethasone in purified liver nuclei increases with the age of the animal in a manner similar to that previously reported for the cytoplasmic receptor. The high affinity nuclear binding approaches saturation at 40 and 500 nM dexamethasone in fetal and adult liver, respectively. In comparison with dexamethasone, the relative efficiency of corticosterone to accumulate in the nucleus is 9 percent in fetal liver and only 1 percent in adult liver. Specifically bound dexamethasone in adult nuclei exists in at least three forms; a Tris-soluble, a KC1-soluble, and a residual (non-extractable with KC1 or DNase) form. Part of the Tris-soluble steroid is associated with macromolecules sedimenting at about 4 S both in the presence and absence of 0.4 M KC1. This form of the receptor was not detected in fetal liver nuclei. In liver chromatin, bound dexamethasone exists in a KC1-soluble and a residual form, the latter comprising the major fraction of steroid associated with chromatin from both fetal and adult tissue (60 and 75 percent, respectively). Treatment with Triton X-100 releases about 20 percent of the radioactivity in adult liver nuclei, but has no effect on fetal liver nuclei. In contrast with the above observations in the intact tissue, the major fraction of steroid bound to chromatin in cell-free systems is KC1- and DNase-soluble, only 30 percent remaining in the residual pellet.

Tuberculous esophagitis. Report of a case and review of modern approaches to diagnosis and treatment.

We describe a patient with tuberculous esophagitis who was referred to us with low-grade fever, but no esophageal symptoms. The diagnosis was established in biopsies obtained from a deep midesophageal ulcer seen on endoscopy. Investigation of the patient failed to identify any extra-esophageal tuberculous foci, but a computed tomography scan revealed mediastinal lymphadenopathy without lung involvement. Primary infection of the esophagus by tuberculosis is questioned, and widespread use of computed tomography may show it to be a fiction.

The influence of interview on decision making and selection of prospective veterinary undergraduate students.

Interviews form part of the selection process in many veterinary programmes worldwide. This study aimed to evaluate the influence of the interview on veterinary selection decisions. An admissions cycle of interviews of 181 shortlisted school-leaving applicants to veterinary medicine was investigated. Selection panel pairs (from cohorts of 5 chairs and 11 cointerviewers) independently evaluated applicants before interview on the basis of their written application. Applicants were then interviewed and selectors repeated their evaluations, both independently and after joint discussion. Results of the preinterview and postinterview evaluations of the applicants were analysed statistically. There was slight to moderate agreement between the chair and cointerviewer on selection decisions/rankings taken before interview, but substantial agreement after interview. Agreement between postinterview decisions/rankings and consensus decisions/rankings postinterview was extremely high. Applicant attributes that had the most influence on selection decisions were: 'communication skills', 'overall knowledge gained from work experience' and 'ability to think on their feet'. There was significantly more agreement possible between interviewers with regard to selection decisions based on interview assessment compared with preinterview assessment of written applications. This study suggests that interviews may be a useful and important aid in decision making for selecting the candidates perceived as most suitable for this veterinary programme.