Effects of food nutrient content, insect age and stage in the feeding cycle on the FMRFamide immunoreactivity of diffuse endocrine cells in the locust gut

We have studied the influence of variations in dietary protein and digestible carbohydrate content, of insect age and of time during the feeding cycle on the endocrine cells of the ampullar region of the midgut in the African migratory locust Locusta migratoria L. Morphometric analysis of FMRFamide-like immunoreactivity was used as an indirect measure of the amount of FMRFamide-related peptides (FaRPs) stored in the gut endocrine cells. There was a highly significant correlation between FaRP content and the nutritional quality of the food, measured relative to the concentrations and ratio of protein to digestible carbohydrate in a nutritionally optimal diet. The direction of the relationship between FaRP content and diet quality varied with age during the fifth stadium. On day 1, FaRP levels increased with the nutritional quality of the food, while on day 4 the opposite relationship was observed. Release of peptide was triggered by the onset of a meal during ad libitum feeding, with cell FaRP levels returning to premeal values within 15 min of the meal ending. The results also suggested that cell contents were released during food deprivation beyond the normal intermeal interval. Locusts switched for a single meal during ad libitum feeding on day 4 from a low- to a high-carbohydrate food did not respond by reducing endocrine cell FaRP content. Our results show a relationship between the diffuse gut endocrine system and feeding and nutrition in locusts. The ampullar endocrine cells are in three-way contact with the midgut luminal contents, with the primary urine from the Malpighian tubules and with the haemolymph. They are thus ideally positioned to play an integrative receptor-secretory function in the regulation of a variety of post-ingestive processes, such as enzyme secretion, absorption, gut motility or nutrient metabolism

Dietary influences over proliferating cell nuclear antigen expression in the locust midgut

We have studied the influence of variations in dietary protein (P) and digestible carbohydrate (C), the quantity of food eaten, and insect age during the fifth instar on the expression of the proliferating cell nuclear antigen (PCNA) in the epithelial cells of the midgut (with special reference to the midgut caeca) in the African migratory locust, Locusta migratoria. Densitometric analysis of PCNA-immunostained cells was used as an indirect measure of the levels of expression of PCNA, and a PCNA cellular index (PCNA-I) was obtained. Measurements of the DNA content of the cells have also been carried out by means of microdensitometry of Feulgen-stained, thick sections of midgut. A comparison between the PCNA nuclear level and the DNA content was performed. The PCNA levels were significantly different among the cells of the five regions studied: caeca, anterior ventricle, medial ventricle, posterior ventricle and ampullae of the Malpighian tubules. We have studied in more detail the region with highest PCNA-I, i.e. the caeca. The quality and the quantity of food eaten under ad libitum conditions were highly correlated with both the PCNA and DNA levels in the caeca cells. Locusts fed a diet with a close to optimal P:C content (P 21%, C 21%) showed the highest PCNA and DNA content. In locusts fed a food that also contained a 1:1 ratio of P to C but was diluted three-fold by addition of indigestible cellulose (P 7%, C 7%), a compensatory increase in consumption was critical to maintaining PCNA levels. Our measurements also showed that the nuclear DNA content of the mature and differentiated epithelial cells was several-fold higher than the levels in the undifferentiated stem cells of the regenerative nests. These results, combined with the low number of mitotic figures found in the regenerative nests of the caeca and the marked variation in PCNA levels among groups, suggest that some type of DNA endoreduplication process may be taking place. Our data also indicate that the DNA synthetic activity in the midgut is related to feeding in locusts. The possible dietary and nutritional regulatory mechanisms and the significance of the differences found are discussed

Congenital infiltrating lipoma of the upper limb in a patient with von Willebrand disease

Infiltrating lipoma is a rare variety of lipoma, characterized by an infiltration of the adipose tissue of the muscles. Infiltrating lipomas are usually classified in two groups: intermuscular infiltrating lipoma and intramuscular infiltrating lipoma. Most are acquired, and they usually appear in middle-aged individuals. Exceptionally, they are congenital. In such cases they are not related to other diseases. We report an 8-year-old boy with a congenital infiltrating lipoma of the upper limb and von Willebrand disease. Both diseases are linked to an alteration in chromosome 12, but this clinical association seems to be random rather than causal

Genomic imbalances detected by comparative genomic hybridization are prognostic markers in invasive ductal breast carcinomas

AIMS: The aim of this work is the study of the prognostic significance of the chromosomal aberrations described in a series of invasive ductal breast carcinomas. METHODS AND RESULTS: We analysed by comparative genomic hybridization a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas. Aberrations showed a frequency similar to previous studies using frozen tumours. Interestingly, we identified gains involving 6q16-q24 more frequently than in other series. We analysed the association among the chromosomal imbalances, 11 histopathological factors, relapse rate and overall survival of patients. Associations showed 16q losses as a potential marker of good prognosis, as they were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063; P=0.066). Within the good prognosis group of lymph node-negative patients, 17q and 20q gains identify a subgroup with increased relapse rate (P=0.039). CONCLUSIONS: Chromosomal imbalances, together with histopathological factors, may help to predict outcome in breast cancer patients

Cáncer de próstata localizado de alto riesgo tratado mediante prostatectomía radical. Pronóstico y estudio de variables influyentes

Fundamento. Estudiar la supervivencia libre de progresión bioquímica (SLPB) que ha obtenido un grupo de pacientes de alto riesgo de acuerdo con la clasificación de D’Amico mediante prostatectomía radical. Identificar las variables clínico-patológicas influyentes en la supervivencia libre de progresión bioquímica y diseñar con ellas, si es posible, un modelo pronóstico. Material y métodos. Se estudian 232 pacientes, de una serie de 1.054, diagnosticados de cáncer de próstata clínicamente localizado y calificados de alto riesgo en la clasificación de D’Amico (PSA >20 ng/ml ó Gleason 8-10 ó T3) tratados mediante prostatectomía radical. Se estudia la SLPB y se analizan las variables clínico-patológicas recogidas (PSA, Gleason de la biopsia y de la pieza, estadio clínico y patológico, afectación unilateral o bilateral, márgenes de la pieza de prostatectomía, expresión de Ki-67) para identificar si influyen en la SLPB. Se ha utilizado para el estudio estadístico: tablas de contingencia y para el análisis de la supervivencia: Kaplan-Meyer, Log-rank y modelos de Cox. Resultados. Estudio descriptivo: PSA: 23,3 ng/ml (mediana); cGleason 2-6: 33%; 7: 13%; 8-10: 54%; T2: 58%; Afectación bilateral en la biopsia diagnóstica: 59%; RNM T2: 60%; RNM T3: 40%. pGleason 2-6: 24%; 7: 28%; 8-10: 48%; pT2: 43%; pT3a: 30%; pT3b: 27%; Margen afectado: 51%; N1:13%. Supervivencia libre de progresión: con una media y mediana de seguimiento de 64 meses; el 53% evidencia progresión bioquímica. La mediana hasta progresión: 42 meses. La supervivencia libre de progresión a 5 y 10 años es 43±3% y 26±7%. El estudio multivariado (modelos de Cox) evidencia que las variables influyentes de forma independiente en la SLPB son la afectación de márgenes (HR: 3,5; 95% IC.1,9-6,7; p<0001); y Ki67 >10% (HR: 2,3; 95% IC: 1,2-4,3; P: 0,009). Grupos de riesgo: utilizando las dos variables influyentes y utilizando modelos de Cox se diseñan tres grupos de riesgo como mejor modelo: Grupo 1 (0 variables presentes); Grupo 2 (1 variable); Grupo 3 (2 variables). La supervivencia libre de progresión es de 69±8%; 27±6% y 18±11% a los 5 años. Las diferencias son significativas entre los tres grupos. Conclusión. El grupo de alto riesgo de la clasificación de D’Amico es heterogéneo en relación con la progresión bioquímica y puede ser desglosado en tres grupos de riesgo utilizando las dos variables de influencia independiente (márgenes afectados y porcentaje de Ki67)

Desarrollo de la técnica de FICTION como nueva herramienta para el diagnóstico precoz de cáncer de pulmón

El cáncer de pulmón es una de las causas de muerte más frecuentes en el mundo occidental. La supervivencia global de los pacientes no supera el 15% a los 5 años, debido principalmente a que la mayor parte de los casos se diagnostican en estadios avanzados. Además de la prevención primaria, mediante la reducción del consumo de tabaco, son necesarias nuevas tecnologías para el diagnóstico precoz de la enfermedad. Estudios recientes han demostrado que el TAC helicoidal del tórax es efectivo en la detección de nódulos pulmonares malignos en estadios precoces. En la actualidad se está valorando su eficacia en series amplias de pacientes de alto riesgo. Recientemente se ha desarrollado una nueva técnica de citogenética molecular, el FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasms). Esta técnica permite el análisis simultáneo de marcadores inmunofenotípicos y alteraciones genéticas presentes en las células tumorales. El objetivo de nuestro proyecto es su puesta a punto para el estudio de muestras de esputo y lavado broncoalveolar de pacientes con cáncer de pulmón. El fin último es estudiar la posibilidad de que esta técnica pueda ser utilizada, junto con el TAC helicoidal, en programas de detección precoz de cáncer de pulmón, para pacientes de alto riesgo. En este trabajo presentamos una revisión de la contribución de las distintas técnicas de citogenética al estudio del cáncer de pulmón y la metodología de trabajo que vamos a llevar a cabo en nuestro proyecto

Respuesta y supervivencia libre de progresión en tumores vesicales en estadiosT2-T4 tratados con tratamiento trimodal de conservación vesical

Objective: Toevaluatetheresponseandthefree-survivalprogressioninpacientsdiagnosed of invasivebladdercancerwhohavebeentreatedwithtransurethralresection, chemotherapyandradiotherapy.Thismultimodaltreatmentiscomparedwithanot random serieofpatientstreatedbyradicalcistectomy. Material andmethods: Retrospectiveanalysisof43casesofinvasivebladdercancertreated with twoschemesofbladderpreservationbetween1994–2007.Theyarecomparedwith145 cases treatedwithradicalcistectomyinthesameperiodoftime. Pronosticvariablesincludedinthestudyareclinicalstage,gradeofdifferentiation, presence ofureteralobstruction,chemotherapymodality,radiotherapydosesandp53and ki-67 expression. Results: Meanandmediantimeare51and39monthsinpatientswithmultimodal treatment.Completeresponseisachievedin72%ofcasestreatedwithbladder preservation.Ureteralobstructionisaprognosticfactor(OR:7,3;p:0,02).72%patientswith complete responsemantainitattheendofthestudy.Noneofanalyzedvariablesare predictors ofmaintenanceoftheresponse. Survivalrateswithaintactbladderwere6977% and6177% atthreeandfiveyears. Radiotherapydosesgreaterthan60Gy(OR:6,1;po0,001) andtheabsenceofureteral obstruction (OR:7,5;po0,002) werepronosticvariables. Free-survivalinpatientswithcompleteresponsewas8077% and58710% atthreeand five years. At theendofthestudy,53,5%ofpatientshadaintactbladderandfree-disease. Inthesameperiodoftime,145radicalcistectomieswereperformedduetomuscleinvasive bladdercancer.Meanandmediantimeinthisgroupwere29and18monthsrespectively. Stadisticalanalysisrevealsaworseclinicalstageinthegroupofpatientstreatedwith multimodaltreatment(p:0.01). Free-survivalwas7275% and6377%at3and5yearsinthegroupofradical cistectomies.Therewasnotstadisticalsignificantdifferencesbetweencistectomiesand bladderpreservation. Conclusions: Patientstreatedwithbladderpreservationhaveafree-survivalsimilartothose tretedwithradicalcistectomy.Radiotherapy doses greaterthan60Gyandabsenceofureteral obstructionwerefree-survivalprognosticvariables

Valor de la PET en la recurrencia del cáncer de próstata con PSA < 5 ng/ml

We intend to evaluate the usefulness of PET scans in diagnosing recurrent prostate cancer after a curative attempt using radical treatment. MATERIAL AND METHODS: 92 consecutive prostate cancer patients in biochemical progression following radical surgery (63) or radiation treatment (29) were studied with positron emission tomography (PET). In all cases two scans were performed in the same day (11C-choline and 18F-FDG). PET efficacy was evaluated both globally (by employing the results achieved with both 11C-choline and 18F-FDG) and using both radiotracers independently to detect recurrence in patients with biochemical progression. For this purpose, we used comparison of means for k-independent samples, 2 x 2 and 2 x X contingency tables and ROC curves. RESULTS: 1. Global PET: there is evidence of PET alteration regarding the PSA level (P=.003): the clinical stage (P=.01). There are no statistically significant PET alterations regarding the affected biopsy (uni or bilateral), surgical margins, pathological stage and time to progression. ROC curve PET-PSA is statistically significant (P< .0001) permitting calculation of different cut-off points, with a specificity of 91% (highest) for a PSA of 4.3 ng/ml. 2. PET 18FDG: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 6.51 ng/ml. 3. PET 11choline: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 5.15 ng/ml. CONCLUSIONS: PET is a useful tool for diagnosing prostate cancer recurrence after a curative attempt using radical treatment

Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly

De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancementRamon y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723)Peer reviewe

FISH analysis of hematological neoplasias with 1p36 rearrangements allows the definition of a cluster of 2.5 Mb included in the minimal region deleted in 1p36 deletion syndrome

Rearrangements in the distal region of the short arm of chromosome 1 are recurrent aberrations in a broad spectrum of human neoplasias. However, neither the location of the breakpoints (BP) on 1p36 nor the candidate genes have been fully determined. We have characterized, by fluorescence in situ hybridization (FISH), the BP in 26 patients with hematological neoplasias and 1p36 rearrangements in the G-banding karyotype. FISH allowed a better characterization of all samples analyzed. Nine cases (35%) showed reciprocal translocations, 15 (58%) unbalanced rearrangements, and two (7%) deletions. We describe two new recurrent aberrations. In 18 of the 26 cases analyzed the BP were located in band 1p36, which is 25.5 Mb long. In 14 of these 18 cases (78%) and without distinction between myeloid and lymphoid neoplasias, the BP clustered in a 2.5 Mb region located between 1p36.32 and the telomere. Interestingly, this region is contained in the 10.5 Mb cluster on 1p36.22-1pter defined in cases with 1p36 deletion syndrome. The 2.5 Mb region, located on 1p36.32-1pter, has a higher frequency of occurrence of tandem repeats and segmental duplications larger than 1 kb, when compared with the 25.5 Mb of the complete 1p36 band. This could explain its proneness for involvement in chromosomal rearrangements in hematological neoplasias