Insetos indutores de galhas da porção sul da Cadeia do Espinhaço, Minas Gerais, Brasil

A riqueza de insetos galhadores é maior nas latitudes intermediárias em hábitats quentes e com vegetação esclerófila sob estresse hídrico e de nutrientes. Em regiões tropicais, os campos rupestres são indicados como hábitats ricos em espécies de insetos galhadores. Neste trabalho, foram descritas as galhas induzidas por insetos e suas plantas hospedeiras na porção sul da Cadeia do Espinhaço, sudeste do Brasil. Foram selecionados 60 sítios em seis regiões ao longo na porção sul da Cadeia do Espinhaço no estado de Minas Gerais. Em cada sítio 100 plantas foram amostradas totalizando 6.000 plantas censuradas ao longo de um gradiente altitudinal de 668 a 1860m. Foram encontrados 241 morfotipos de galhas em 142 espécies de plantas distribuídas em 29 famílias e de um total de 384 espécies de plantas amostradas. As famílias mais ricas em espécies de insetos galhadores foram Asteraceae (42%), principalmente espécies do gênero Baccharis. A maior parte das galhas (85%) foi induzida por insetos da família Cecidomyiidae seguidos por Lepidoptera (4%) e Homoptera (3%). Os ramos foram os órgãos mais freqüentemente atacados (72%) enquanto que os morfotipos mais comuns foram o elíptico (37%) e o globóide (36%). A espécie de planta hospedeira que apresentou mais morfotipos de galhas foi Baccharis pseudomyriocephala com 10 galhas distintas. Este estudo sustenta a afirmativa que campos rupestres apresentam uma elevada riqueza em espécies de insetos galhadores.

Estado reproductivo, fecundidad parcial y frecuencia de desove de la anchoveta peruana a inicios de otoño 1998. Crucero BIC Humboldt 9803-05 de Tumbes a Tacna

Durante la ejecución de este crucero, efectuado entre el 20 de marzo y el 7 de mayo de 1998, se estudió el estado reproductivo de la anchoveta, a través del análisis histológico, por grados latitudinales, registrándose anchoveta desovante en el área comprendida entre 8°S y 13°S. Desde el 14°S al 18°S la especie se encontró en un periodo de reposo reproductivo con valores de ovarios desovantes (con folículos post-ovulatorios y ovocitos hidratados) comparativamente menores a los registrados en la zona norte-centro. Los resultados de la muestra fueron ponderados a las capturas efectuadas por grados latitudinales. Los individuos jóvenes (11,5 a 14,0 cm) resultan ser la fracción de adultos más importante de la población, sobre todo en la zona sur. La fecundidad parcial estimada fue de 6.668 ovocitos por bache de desove, con una desviación estándar de 212, y el peso promedio de los ovarios en estado de hidratación fue de 1,25 g, lo cual resulta ser extremadamente bajo en comparación a lo observado a lo observado en años anteriores.

The trail making test as a screening instrument for driving performance in older drivers; a translational research.

BACKGROUND: In many countries, primary care physicians determine whether or not older drivers are fit to drive. Little, however, is known regarding the effects of cognitive decline on driving performance and the means to detect it. This study explores to what extent the trail making test (TMT) can provide indications to clinicians about their older patients' on-road driving performance in the context of cognitive decline. METHODS: This translational study was nested within a cohort study and an exploratory psychophysics study. The target population of interest was constituted of older drivers in the absence of important cognitive or physical disorders. We therefore recruited and tested 404 home-dwelling drivers, aged 70 years or more and in possession of valid drivers' licenses, who volunteered to participate in a driving refresher course. Forty-five drivers also agreed to undergo further testing at our lab. On-road driving performance was evaluated by instructors during a 45 minute validated open-road circuit. Drivers were classified as either being excellent, good, moderate, or poor depending on their score on a standardized evaluation of on-road driving performance. RESULTS: The area under the receiver operator curve for detecting poorly performing drivers was 0.668 (CI95% 0.558 to 0.778) for the TMT-A, and 0.662 (CI95% 0.542 to 0.783) for the TMT-B. TMT was related to contrast sensitivity, motion direction, orientation discrimination, working memory, verbal fluency, and literacy. Older patients with a TMT-A ≥ 54 seconds or a TMT-B ≥ 150 seconds have a threefold (CI95% 1.3 to 7.0) increased risk of performing poorly during the on-road evaluation. TMT had a sensitivity of 63.6%, a specificity of 64.9%, a positive predictive value of 9.5%, and a negative predictive value of 96.9%. CONCLUSION: In screening settings, the TMT would have clinicians uselessly consider driving cessation in nine drivers out of ten. Given the important negative impact this could have on older drivers, this study confirms the TMT not to be specific enough for clinicians to justify driving cessation without complementary investigations on driving behaviors.

Bulles de papes. Titres des maisons de LA JUGIE (1313-1623). — MELANGES (1222-1623).

Contient : Titres de la Jugie ; N° 623 (1) Contrat de mariage de Jacques de la Jugie et de Guillemette de la Borgayrie (23 juillet 1313) ; copie du 18 mars 1314 a. st ; N° 624 (2) Contrat de mariage de Pierre de la Jugie et de Jeanne Pebeyre (août1316) ; restes de sceau sur simple queue ; N° 625 (3) Testament de Geraud de Rajaut, de Tulle, damoiseau (9 août 1329) ; N° 626 (4) Contrat de mariage de Gui Aimoin de Puydeval et d'Hélie de la Jugie (14 décembre 1339) ; N° 627 (5) Donation de biens faite par Guillemette de la Limosnie à Gui de Puydeval, son oncle (30 janvier 1351) ; copie du XVIIe siècle ; N° 628 (6) Accord entre Archambaud, vicomte de Comborn, et Gui de Puydeval (24 mai 1351) ; copie contemporaine ; N° 629 (7) Contrat de mariage de Raimond de Bossac et de Marie de Puydeval (2 août 1352) ; N° 630 (8) Testament de Gui de Puydeval (26 janvier 1371 a. st.) ; copie du XVIIe siècle ; N° 631 (9) Testament de Nicolas de la Jugie, seigneur de Levinerie (26 mars 1374 a. st.) ; vidimus du 18 mai 1402 ; N° 632 (10) Testament de Guillaume de la Jugie, alias de Puydeval (20 août 1397) ; N° 633 (11) Testament d'Aelis de la Jugie (19 juillet 1409) ; N° 634 (12) Décisions prises par divers seigneurs du Limousin, relativement à l'expédition contre les Anglais, pour la levée du siège d'Auberoche (4 septembre 1419) ; N° 635 (13) Contrat de mariage d'Aimar de Puydeval et de Marguerite de Gimel (12 juillet 1426) ; N° 636 (14) Testament d'Hélène de Puydeval, veuve de Jean « de Sadone » (2 juin 1436) ; N° 637 (15) Testament de Jean de la Jugie, alias de Puydeval (7 décembre 1461) ; N° 638 (16) Contrat de mariage de Jean de Sourries, seigneur de Vaur, et d'Anne de Puydeval (29 janvier 1492 a. st.) ; copie, papier ; N° 639 (17) Testament d'Antoine de Puydeval (9 octobre 1495) ; copie du 28 mars 1502, a. st ; N° 640 (18) Contrat de mariage de Pons de Gourdon, seigneur de La Roque, et de Françoise de Puydeval (20 janvier 1497 a. st.) ; copie du 23 août 1579 ; N° 641 (19) Quittance générale donnée par Blanche de Malesec, veuve d'Antoine de Puydeval, à Gilles de Malesec, son frère (23 juin 1512) ; N° 642 (20) Testament de Gabrielle de Puydeval, dame de Miremont (20 mars 1516-1517) ; copie du XVIe siècle ; N° 643 (21) Testament de Denis de Puydeval (18 août 1523) ; copie du XVIe siècle ; N° 644 (22) Quittance générale donnée à Géraud de Puydeval par Pierre de Rajaut et Anne de Puydeval sa femme, 2 août 1534 ; N° 645 (23) Contrat de mariage de Rigaut de Saint-Martial, baron de Conros, et de Françoise de Puydeval (18 juin 1559) ; copie du 22 juillet 1583 ; N° 646 (24) Testament de Géraud de Puydeval (20 mai 1563) ; N° 647 (25) Procès-verbal de visite de bois faite par les arbitres choisis par les seigneurs de Puydeval et de Vaur (5 janvier 1564) ; N° 648 (26) Accord entre Géraud de Puydeval et Bonaventure de Sourries, seigneur de Vaur, au sujet du lieu de La Reynie (21 novembre 1560) ; N° 649 (27) Accord entre Anne de Puydeval, veuve de Jean de Sourries, seigneur de Vaur, et Bonaventure de Sourries (27 septembre 1559) ; N° 650 (28) Testament d'Anne de Puydeval, veuve de Jean [de Sourries, seigneur de] Vaur (8 septembre 1555) ; N° 651 (29) Testament de Jean de Puydeval, doyen de l'église de Tulle ; N° 652 (30) Testament de Françoise de Puydeval, veuve de Rigaut de Saint-Marsal, baron de Conros (16 juin 1601) ; N° 653 (31) Autre testament de ladite dame (22 août 1604) ; N° 654 Copie du précédent testament ; N° 655 (32) Accord entre Josias de Cosnac, seigneur d'Assy, et sa soeur, Marie de Cosnac, femme de Henry de Puydeval, baron de Conros (31 mars 1623 ; N° 656 (33) Contrat de mariage de Pierre de Soudeilles et d'Anne de Puydeval (s. d.) ; N° 657 (33 bis) Copie de la pièce précédente ; Mélanges ; N° 658 (1) Accord entre Guillaume, évêque de Paris, et son chapitre, d'une part, et Philippe-Auguste, de l'autre, au sujet des droits de l'église de Paris (décembre 1222) ; N° 659 (2) Accord entre Philippe le Bel et l'église de Paris pour l'affectation de certaines redevances à la réparation des ponts de la Seine (mars 1296-1297) ; N° 660 (3) Décret de l'Université de Paris établissant des règlements pour le collège de Narbonne, à Paris (4 octobre 1377) ; N° 661 (4) Sentence rendue par Jean, abbé de Saint-Taurin d'Evreux, sur le procès entre Jacques Sacquespée, docteur en médecine, et Jean Daigny, chanoine de la Sainte-Chapelle de Paris (15 mai 1428) ; N° 662 (15) Articles de la Ligue (s. d. [1586 (?)]) ; N° 663 (6) Privilèges accordés par Louis, comte de Flandre, aux marchands castillans trafiquant en Flandre (15 avril 1366) ; copie du XVe siècle ; N° 664 (7) Serment prêté au duc d'Alençon par le chapitre de Cambrai (20 août 1580) ; N° 665 (8) Serment prêté au même personnage par les échevins de la ville de Cambrai (même date) ; N° 666 (9) Aveu rendu à Henri, comte de Rodez, par Pierre de Panat, pour divers fiefs, (juillet 1280) ; N° 667 (10) Aveu rendu par Bernard, comte d'Armagnac et de Rodez, à Guillaume, évêque de Mende, pour les fiefs tenus par ledit comte dans ce diocèse (2 mai 1309) ; N° 668 (11) Autorisation donnée par l'archevêque Michel et le chapitre d'Arles à Jean [de Matha], fondateur de l'Ordre de la Trinité, d'établir une église et un cimetière dans la ville d'Arles (novembre 1203) ; N° 669 (12) Charte de G[uillaume], comte de Forcalquier, abandonnant divers droits à l'église de Ganagobie (10 juin 1206) ; à la suite est transcrite une lettre de A., prieur du dit lieu, à G[uillaume], abbé de Cluny, relative à la donation précédente ; N° 670 (13) Lettres de Charles II, roi de Sicile, comte de Provence, chargeant Hugues de Voisines, senéchal de Provence, de faire sortir du royaume de France la somme de 50.000 livres autorisée par le Roi (24 mars 1297) ; N° 671 (14) Lettres de l'empereur Henri VII, autorisant Gaillard, archevêque d'Arles, à poursuivre la révocation des aliénations de biens ecclésiastiques consenties par ses prédécesseurs (9 juillet 1312) ; N° 672 (15) Lettres de Jean de Clermont, cardinal-évêque de Tusculum, légat du pape dans les provinces de Vienne, Aix, etc., chargeant Jean Ferrier, archevêque d'Arles, de l'assister dans ses fonctions (9 juillet 1533) ; N° 673 (16) Lettres de Raoul de Sendelay, trésorier d'Angleterre, portant donation de terres près de Rouen à Michel de Paris, son ancien serviteur (3 janvier 1445-1446) ; N° 674 (17) Lettre de l'empereur Ferdinand au pape Urbain VIII (28 avril 1635) ; N° 675 (18) Aveu rendu à Bernard, abbé de Charroux, par Jean de Rochefort, pour le château de Saint-Angel (18 mai 1393) ; copie du 17 juillet 1407 ; N° 676 (19) Lettres de l'Université d'Avignon conférant à Pierre Charpin le titre de docteur en droit canon (16 septembre 1405) ; N° 677 (20) Contrat de mariage de Charles d'Apchon, vicomte de Mirmont, et de Lucrèce de Gadaigne (3 août 1579) ; N° 678 (21) Procuration donnée par Philippe de Commynes à Baude Talboein, son secrétaire (9 mars 1474) ; signature autographe ; N° 679 (22) Ratification par Galéas-Marie Sforza du traité conclu en son nom à Amboise entre Tristan Sforza et Louis XI (21 avril 1468) ; N° 680 (23) Lettres d'Etat accordées par le roi Charles VI à Lermite, seigneur de La Faye, son chambellan, envoyé en Angleterre (28 octobre 1407) ; copie du 4 novembre 1407 ; papier ; N° 681 (24) « Plaintes sur le trépas du sage et vertueux chevalier... Jean de La Roche-Aymon ; » pièce de vers (s. d. [1522]) ; miniature en tête ; N° 682 (25) Lettres de Raimond « de Poioliis », archidiacre de Périgueux, recteur du duché de Spolète, pour le paiement de la compagnie de Guillaume de Primat ; N° 683 (26) Lettres de l'Université d'Orléans accordant à Hugues Berthelot le titre de bachelier en droit canon (28 juillet 1409) ; N° 684 (27) Lettres de l'Université d'Orléans au prieur de Marcigny, pour faire pourvoir d'un bénéfice Raoul « Druci », prêtre, licencié en décret (2 septembre 1460 ; N° 685 (28) Lettres de l'Université de Paris à l'abbé de Cluny, pour faire pourvoir d'un bénéfice Jean de Mont, maître ès arts et bachelier en théologie (3 mars 1478-1479) ; N° 686 (29) Lettres de l'Université de Paris à l'abbé de Cluny pour faire pourvoir d'un bénéfice Jean Paulain, maître ès arts (21 février 1538-1539) ; N° 687 (30) Testament de Jacques de Plaigne, seigneur dudit lieu (5 mars 1551-1552) ; copie contemporaine ; N° 688 (31) Contrat de mariage de Pierre de Guasquet et de Marguerite d'Henry (31 mars 1581) ; copie contemporaine ; N° 689 (32) Testament d'Antoine de Guasquet, seigneur de Paramelle (30 août 1585) ; copie contemporaine ; N° 690 (33) Testament de Jean Chantois, sieur de Laumosnerie (30 septembre 1617) ; copie contemporaine ; N° 691 (34) Testament de Claude des Rozières, seigneur de Cherouac (octobre 1623) ; copie contemporaine ; N° 692 (35) Délibération de l'assemblée du clergé de la ville de Reims au sujet de la répartition des deniers à lever sur ledit clergé (30 mars 1585) ; N° 693 (36) Lettre de J[ean de] C[andida] à [Denis Briçonnet], évêque de Saint-Malo (16 novembre, s. d.)

p27 and Skp2 immunoreactivity and its clinical significance with endocrine and chemo-endocrine treatments in node-negative early breast cancer.

BACKGROUND: Low p27 and high Skp2 immunoreactivity are associated with a poor prognosis and other poor prognostic features including resistant phenotypes and antiestrogen drug resistance. We investigated these proteins in two International Breast Cancer Study Group trials studying node-negative early breast cancer. PATIENTS AND METHODS: Trial VIII compared chemotherapy followed by goserelin with either modality alone in premenopausal patients. Trial IX compared chemotherapy followed by tamoxifen with tamoxifen alone in postmenopausal patients. Central Pathology Office assessed p27 and Skp2 expression in the primary tumor by immunohistochemistry among 1631 (60%) trial patients. RESULTS: p27 and Skp2 were inversely related; 13% of tumors expressed low p27 and high Skp2. Low p27 and high Skp2 were associated with unfavorable prognostic factors including larger size and higher grade tumors, absence of estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 overexpression and high Ki-67 (each P < 0.05). Low p27 and high Skp2 were not associated with disease-free survival (P = 0.42 and P = 0.48, respectively). The relative effects of chemo-endocrine versus endocrine therapy were similar regardless of p27 or Skp2. CONCLUSIONS: We confirm the association of low p27 and high Skp2 with other poor prognostic features, but found no predictive or prognostic value, and therefore do not recommend routine determination of p27 and Skp2 for node-negative breast cancer.

Efectos de la presencia social de las lenguas escolares en el desarrollo lingüístico del alumnado extranjero. Un estudio empírico en Cataluña = The Social Presence of School Languages and Their Effects on the Development of Immigrant Students’ Linguistic Proficiency. An Empirical Study in Catalonia

El estudio de las variables relacionadas con la adquisición de las lenguas escolares en contextos bilingües y multilingües ha resurgido a raíz de la incorporación de alumnado extranjero al sistema educativo español. En este sentido, y gracias a su peculiar situación sociolingüística, Cataluña se ha convertido en un observatorio perfecto para estudiar el proceso de adquisición de lenguas del alumnado extranjero. En este artículo presentamos una parte de los datos obtenidos en la evaluación del conocimiento de catalán y del castellano de 668 alumnos extranjeros de sexto de Primaria escolarizados en 57 centros de Cataluña. Con ello pretendemos estudiar los efectos de la presencia y del uso social de las lenguas escolares en el conocimiento lingüístico de este alumnado. La hipótesis principal es que el desarrollo de buenos niveles de conocimiento escrito de las lenguas escolares por parte de los alumnos extranjeros depende, en buena medida, de las oportunidades que haya en el entorno social para que ellos puedan utilizar estas lenguas en los intercambios comunicativos informales con sus compañeros o con otros adultos. Las conclusiones del trabajo señalan las relaciones existentes entre el desarrollo de habilidades lingüísticas conversacionales y el de habilidades lingüísticas cognitivo-académicas (Cummins, 1979b), en el sentido de que tanto el conocimiento escrito de catalán como el de castellano que tiene el alumnado extranjero están condicionados por el nivel de desarrollo conversacional previo en ambas lenguas. Además, apuntan a que la transferencia de habilidades lingüísticas cognitivo-académicas no se produce directamente entre el catalán y el castellano, sino que depende fundamentalmente de la presencia social que tengan estas lenguas y de sus usos informales. Así, en la medida en que un buen número de estudiantes extranjeros no desarrolla suficiente competencia lingüística conversacional ni en catalán ni en castellano, el proceso de adquisición de las lenguas escolares se alarga más allá de los seis años

[Sienne. Duomo]

Référence bibliographique : Weigert, 668

Proximate basis of the covariation between a melanin-based female ornament and offspring quality.

In contradiction to sexual selection theory, several studies showed that although the expression of melanin-based ornaments is usually under strong genetic control and weakly sensitive to the environment and body condition, they can signal individual quality. Covariation between a melanin-based ornament and phenotypic quality may result from pleiotropic effects of genes involved in the production of melanin pigments. Two categories of genes responsible for variation in melanin production may be relevant, namely those that trigger melanin production (yes or no response) and those that determine the amount of pigments produced. To investigate which of these two hypotheses is the most likely, I reanalysed data collected from barn owls ( Tyto alba). The underparts of this bird vary from immaculate to heavily marked with black spots of varying size. Published cross-fostering experiments have shown that the proportion of the plumage surface covered with black spots, a eumelanin composite trait so-called "plumage spottiness", in females positively covaries with offspring humoral immunocompetence, and negatively with offspring parasite resistance (i.show $132#e. the ability to reduce fecundity of ectoparasites) and fluctuating asymmetry of wing feathers. However, it is unclear which component of plumage spottiness causes these relationships, namely genes responsible for variation in number of spots or in spot diameter. Number of spots reflects variation in the expression of genes triggering the switch from no eumelanin production to production, whereas spot diameter reflects variation in the expression of genes determining the amount of eumelanin produced per spot. In the present study, multiple regression analyses, performed on the same data sets, showed that humoral immunocompetence, parasite resistance and wing fluctuating asymmetry of cross-fostered offspring covary with spot diameter measured in their genetic mother, but not with number of spots. This suggests that genes responsible for variation in the quantity of eumelanin produced per spot are responsible for covariation between a melanin ornament and individual attributes. In contrast, genes responsible for variation in number of black spots may not play a significant role. Covariation between a eumelanin female trait and offspring quality may therefore be due to an indirect effect of melanin production.

gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.

Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.05-8.9%). Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy. Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide. However, correlated functional and phenotype analysis of IVS-expanded postvaccine CD8(+) T cells demonstrated the proliferation of functionally anergic gp100(209-2M)- tetramer(+) CD8(+) T cells in several patients and also indicated interpatient variability of gp100(209-2M) stimulated T-cell proliferation. Flow cytometry analysis of cryopreserved postvaccine PBMCs from representative patients showed that the majority of tetramer(+) CD8+ T cells (78.1 +/- 4.2%) had either an "effector" (CD45 RA(+)/CCR7(-)) or an "effector-memory" phenotype (CD45RA(-)/CCR7(-)). Notably, analysis of PBMCs collected 12-24 months after vaccine therapy demonstrated the durable presence of gp100(209-2M)-specific memory CD8(+) T cells with high proliferation potential. Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component. The data further support the combined use of tetramer binding and functional assays in correlated ex vivo and IVS settings as a standard for immunomonitoring of cancer vaccine patients.

Mico-cocktail validation for CYP3A and CYP2D6 assessment using a low dose of midazolam (0.075 mg) and dextromethorphan (2.5 mg)

Background/Aim: Cocktail approach is generally preferred to individual administration of probes in order to characterize the activity of multiple enzymes. However, cocktail strategy has several drawbacks such as drug-drug interactions, tolerability and toxicity. Hence, there is a need to develop cocktails using low doses of probes. Our aim was to investigate whether the simultaneous oral administration of microdoses of midazolam (MDZ) and dextromethorphan (DEM) can be used to assess the simultaneous activities of CYP3A and CYP2D6. Methods: As part of a 5 arm randomized cross-over control trial on the analgesic efficacy of oxycodone, ten healthy young non-smoking males received the following combinations of drugs: Quinidine (Q)+ ketoconazole (K) or Q+placebo (P) or K+P or P+P. In all cases MDZ (0.075 mg) and DEM (2.5 mg) were administrated 1 hour after Q, K or P. CYP2D6 and CYP3A activities were determined after urine collection during 8 hours (ratio DEM/DOR), and a blood sample (EDTA) after 30 min (ratio 1-OH-MDZ/MDZ). DEM and DOR analysis was performed using LC-fluorescence. MDZ and 1-OH-MDZ determination was performed using GC-MS. Allele's variants of CYP2D6 were detected using the AmpliChipTMCYP450 (Roche). Results: CYP2D6 genotype predicted 1 poor (PM), 1 intermediate (IM), 7 extensive (EM) and 2 ultra rapid (UM) metabolizers. A good correlation was obtained between the predicted and the measured phenotypes except for 1 EM phenotyped as UM. Two duplications for alleles *41/*41xN and *1/*2xN were detected and the two volunteers were phenotyped as UM. A potent inhibition of CYP2D6 or CYP3A4 was obtained when Q or K were used. Mean metabolic ratio DEM/DOR in P and K groups were 0.015 (±0.028) and 0.015 (±0.019). It significantly increased in Q and QK groups (0.668 (±0.676) and 0.743 (±1.038)). Mean 1-OH-MDZ/MDZ in P, Q were 2.73 (±1.05) and 2.55 (±1.40) while it significantly decreased in K and QK groups (0.11 (±0.05), 0.10 (±0.05)). Moreover, there were no statistically significant differences between QK and K sessions for CYP3A and between QK and Q for CYP2D6 which indicate that there is no interaction between the two metabolic pathways. Conclusion: Simultaneous assessment of CYP3A and CYP2D6 activities can be obtained by low oral doses (micro-cocktail) of MDZ and DEM. Specific inhibitors such as Q or K modulates selectively CYP2D6 or CYP3A activities.

Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments.

Pooled F(ab')2 fragments of three MAbs against distinct epitopes of carcinoembryonic antigen (CEA) were used for radioimmunotherapy of nude mice bearing a subcutaneous human colon carcinoma xenograft. 9-10 d after transplantation when tumor nodules were in exponential growth, 36 mice were treated by intravenous injection of different amounts of 131I-labeled MAb F(ab')2. All 14 mice injected with a single dose of 2,200 (n = 10) or 2,800 microCi (n = 4) showed complete tumor remission. 8 of the 10 mice treated with 2,200 microCi survived in good health for 1 yr when they were killed and shown to be tumor free. Four of nine other mice treated with four fractionated doses of 400 microCi showed no tumor relapse for more than 9 mo. In contrast, all 15 mice injected with 1,600-3,000 microCi 131I-control IgG F(ab')2 showed tumor growth retardation of only 1-4 wk, and 15 of 16 mice injected with unlabeled anti-CEA MAb F(ab')2 showed unmodified tumor progression as compared with untreated mice. From tissue radioactivity distributions it was calculated that by an injection of 2,200 microCi 131I-MAb F(ab')2 a mean dose of 8,335 rad was selectively delivered to the tumor, while the tissue-absorbed radiation doses for the normal organs were: peripheral blood, 2,093; stomach, 1,668; kidney, 1,289; lung, 1,185; liver, 617; spleen, 501; small intestine, 427; large intestine, 367; bone, 337; and muscle, 198. These treatments were well tolerated since out of 19 mice with complete tumor remission only 4 required bone marrow transplantation and 17 were in good health for 6-12 mo of observation. The results demonstrate the selective destruction of established human colon carcinoma transplants by intravenous injection of either single or fractionated doses of 131I-MAb F(ab')2.

A Y-like social chromosome causes alternative colony organization in fire ants.

Intraspecific variability in social organization is common, yet the underlying causes are rarely known. In the fire ant Solenopsis invicta, the existence of two divergent forms of social organization is under the control of a single Mendelian genomic element marked by two variants of an odorant-binding protein gene. Here we characterize the genomic region responsible for this important social polymorphism, and show that it is part of a pair of heteromorphic chromosomes that have many of the key properties of sex chromosomes. The two variants, hereafter referred to as the social B and social b (SB and Sb) chromosomes, are characterized by a large region of approximately 13 megabases (55% of the chromosome) in which recombination is completely suppressed between SB and Sb. Recombination seems to occur normally between the SB chromosomes but not between Sb chromosomes because Sb/Sb individuals are non-viable. Genomic comparisons revealed limited differentiation between SB and Sb, and the vast majority of the 616 genes identified in the non-recombining region are present in the two variants. The lack of recombination over more than half of the two heteromorphic social chromosomes can be explained by at least one large inversion of around 9 megabases, and this absence of recombination has led to the accumulation of deleterious mutations, including repetitive elements in the non-recombining region of Sb compared with the homologous region of SB. Importantly, most of the genes with demonstrated expression differences between individuals of the two social forms reside in the non-recombining region. These findings highlight how genomic rearrangements can maintain divergent adaptive social phenotypes involving many genes acting together by locally limiting recombination.

Cytolytic T lymphocyte recognition of the murine cytomegalovirus nonstructural immediate-early protein pp89 expressed by recombinant vaccinia virus.

The murine immediate-early (IE) protein pp89 is a nonstructural virus-encoded phosphoprotein residing in the nucleus of infected cells, where it acts as transcriptional activator. Frequency analysis has shown that in BALB/c mice the majority of virus-specific CTL recognize IE antigens. The present study was performed to assess whether pp89 causes membrane antigen expression detected by IE-specific CTL. Site-directed mutagenesis has been used to delete the introns from gene ieI, encoding pp89, for subsequent integration of the continuous coding sequence into the vaccinia virus genome. After infection with the vaccinia recombinant, the authentic pp89 was expressed in cells that became susceptible to lysis by an IE-specific CTL clone. Priming of mice with the vaccinia recombinant sensitized polyclonal CTL that recognized MCMV-infected cells and transfected cells expressing pp89. Thus, a herpesviral IE polypeptide with essential function in viral transcriptional regulation can also serve as a dominant antigen for the specific CTL response of the host.