DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study.

OBJECTIVE: To examine any possible links between exposure to DDE (1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene), the persistent metabolite of the pesticide dicophane (DDT), and breast cancer. DESIGN: Multicentre study of exposure to DDE by measurement of adipose tissue aspirated from the buttocks. Laboratory measurements were conducted in a single laboratory. Additional data on risk factors for breast cancer were obtained by standard questionnaires. SETTING: Centres in Germany, the Netherlands, Northern Ireland, Switzerland, and Spain. SUBJECTS: 265 postmenopausal women with breast cancer and 341 controls matched for age and centre. MAIN OUTCOME MEASURE: Adipose DDE concentrations. RESULTS: Women with breast cancer had adipose DDE concentrations 9.2% lower than control women. No increased risk of breast cancer was found at higher concentrations. The odds ratio of breast cancer, adjusted for age and centre, for the highest versus the lowest fourth of DDE distribution was 0.73 (95% confidence interval 0.44 to 1.21) and decreased to 0.48 (0.25 to 0.95; P for trend = 0.02) after adjustment for body mass index, age at first birth, and current alcohol drinking. Adjustment for other risk factors did not materially affect these estimates. CONCLUSIONS: The lower DDE concentrations observed among the women with breast cancer may be secondary to disease inception. This study does not support the hypothesis that DDE increases risk of breast cancer in postmenopausal women in Europe.     

Stages of regulated exocytosis

Despite its unique features of spatial organization, Ca;2;+ regulation and speed, neurotransmitter secretion is a paradigm for studies of membrane fusion because it shares homologous proteins and common mechanisms with constitutive exocytosis in all eukaryotic cells.Recent advances have expanded knowledge of the number of gene products required for neurosecretion, and a current major challenge is to determine their mechanisms of action and the stages at which they function in the multistep exocytic pathway.This review discusses progress in this direction from in vivo and in vitro studies that have characterized roles for specific proteins in post-docking steps proximal to membrane fusion.     

Mdp1, a Saccharomyces Cerevisiae Gene Involved in Mitochondrial/Cytoplasmic Protein Distribution, Is Identical to the Ubiquitin-Protein Ligase Gene Rsp5

Alteration of the subcellular distribution of Mod5p-I, a tRNA modification enzyme, member of the sorting isozyme family, affects tRNA-mediated nonsense suppression. Altered suppression efficiency was used to identify MDP genes, which, when mutant, change the mitochondrial/cytosolic distribution of Mod5p-I,KR6. MDP2 is the previously identified VRP1, which encodes verprolin, required for proper organization of the actin cytoskeleton. MDP3 is identical to PAN1, which encodes a protein involved in initiation of translation and actin cytoskeleton organization. We report here the cloning and characterization of wild-type and mutant MDP1 alleles and the isolation and characterization of a multicopy suppressor of mdp1 mutations. MDP1 is identical to RSP5, which encodes ubiquitin-protein ligase, and mdp1 mutations are suppressed by high copy expression of ubiquitin. All four characterized mdp1 mutations cause missense changes located in the hect domain of Rsp5p that is highly conserved among ubiquitin-protein ligases. In addition to its well-known function in protein turnover, ubiquitination has been proposed to play roles in subcellular sorting of proteins via endocytosis and in delivery of proteins to peroxisomes, the endoplasmic reticulum and mitochondria. mdp1, as well as mdp2/vrp1 and mdp3/pan1 mutations, affect endocytosis. Further, mdp1 mutations show synthetic interactions with mdp2/vrp1 and mdp3/pan1. Identification of MDP1 as RSP5, along with our previous identification of MDP2/VRP1 and MDP3/PAN1, implicate interactions of the ubiquitin system, the actin cytoskeleton and protein synthesis in the subcellular distribution of proteins.     

Grenzen der Kompensation: Energiebudgets von Ringelg?nsen (Branta b. bernicla) — die Wirkung von St?rreizen

Zusammenfassung Der Einfluß von Störreizen auf das Energiebudget von Ringelgänsen wurde im Frühjahr 1991 in zwei Vorland-Salzwiesen des Nationalparks Schleswig-Holsteinisches Wattenmeer vergleichend untersucht. Die Häufigkeit störreizbedingter Reaktionen der Gänse (Störreizhäufigkeit) wurde als Index für die anthropogene Beeinflussung der Gebiete herangezogen. Die Beeinflussung war in Westerhever mit 1,5±0,7 Reaktionen/h signifikant größer als vor dem Norderheverkoog (1,0±0,6 Reaktionen/h). Mit zunehmender Aktivitätszeit wurde in beiden Gebieten im Verlauf des Frühjahres mehr umsetzbare Energie aufgenommen. In Westerhever haben die Gänse im Vergleich zu denen vor dem Norderheverkoog mit Ausnahme des Mai jeweils mehr umsetzbare Energie aufgenommen. Die energetischen Kosten (DEE) der Gänse wurden anhand der Zeit-Energie-Budget Methode und über die gemessene Körpermasseentwicklung von Fänglingen berechnet. Beide Methoden erzielten vergleichbare Ergebnisse; die Unterschiede betrugen je nach Gebiet 0,4 bis 4,5 %. In Westerhever verzeichneten die Gänse im Vergleich zu denen vor dem Norderheverkoog im Monatsmittel höhere energetische Kosten. Aus dem budgetierten Energieüberschuß (E) wurde die theoretisch mögliche Reservestoffanlagerung (Änderung der Körpermasse) der Gänse berechnet. In Westerhever konnten die Gänse im Verlauf des Frühjahres 357 g Körperreserven anlagern. Bei den Gänsen vor dem Norderheverkoog waren es 399 g. Der Unterschied betrug 11,7 %, war aber nicht signifikant. Anhand von Fangdaten ist bekannt, daß Ringelgänse im langjährigen Mittel Körperreserven von 380 bis 400 Gramm anlagern. Die Störreizhäufigkeit des Tages bewirkte eine signifikante Veränderung der Budgetparameter DME und DEE und E auf stündlicher Basis. In Westerhever stieg die Aufnahme an umsetzbarer Energie signifikant mit steigender Störreizhäufigkeit an. Vor dem Norderheverkoog verringerte sich diese jedoch signifikant. Die Energieaufwendungen stiegen in beiden Gebieten signifikant mit steigender Reizhäufigkeit an. Der Überschuß in der Energiebilanz der Gänse in Westerhever war an Tagen mit einer großen Störreizhäufigkeit um 8,7 % gegenüber den Tagen mit einer geringen Reizhäufigkeit verringert. Aufgrund fehlender kompensatorischer Nahrungsaufnahme war der Überschuß bei den Gänsen vor dem Norderheverkoog um maximal 27,5 % vermindert. Die Gänse in Westerhever haben störreizbedingte Zeitverluste bei der Nahrungsaufnahme und erhöhte energetische Kosten durch Verhaltensänderung und eine erhöhte Nahrungsaufnahme pro Zeit kompensiert. Aufgrund physiologischer Zwänge sind sie jedoch in dem stark vom Menschen beeinflußten Gebiet an die Grenzen ihrer Kompensationsmöglichkeit angelangt. Die errechnete Reservestoffanlagerung und auch der Jungvogelanteil im nachfolgenden Herbst waren geringer als bei den Gänsen vor dem Norderheverkoog.

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Compensatory limits: energy budgets of Brent Geese,Branta b. bernicla, the influence of human disturbance

The impact of human disturbances on the energy budget of Brent Geese,Branta b. bernicla, during spring migration was investigated in two different salt marsh areas within the national park Schleswig-Holsteinisches Wattenmeer, Germany. We used the frequency of disturbance-related reactions of the birds as an indicator of the anthropogenic influencing of the sites. The disturbance frequency was significantly higher in the Westerhever salt marsh (1,5±0,7 reactions/h) than in the Norderheverkoog area (1,0±0,6 reactions/h). Monthly activity and energy budgets of the birds were calculated from March to May, based on several simultaneous day-round field observations per month. The amount of daily metabolizable energy (DME) was calculated via dropping rate and digestability of the food. The daily energy expenditure (DEE) was calculated by means of the time-energy-budget methods and by calculations, using the bodymass changes of caught birds during spring. With both methods very similar results were obtained; they varied between 0,4 to 4,5 % per areas and month. The daily energy budget (Æ E) was calculated from DEE — DME. Due to an increasing daily activity time from March to Mai the DME increased in both areas. Compared to the Norderheverkoog area the DME of the birds in Westerhever was higher in March and April, and similar in Mai. DEE increased in both areas too and was in all months higher in Westerhever than in Norderheverkoog. The calculated bodymass changes of the birds during spring was 357 g for the birds in Westerhever and 399 g for the birds in Norderheverkoog. Bodymass measures from caught birds revealed a mean mass gain of 380 to 400 g during spring. The daily disturbance frequency caused a significant change in the budget parameters DME, DDE and E on a hourly base. In Westerhever DME/h increased, while in Norderheverkoog DME/h decreased significantly with increasing disturbance frequency. At the same time DEE/h increased in both areas significantly. As a consequence E/h was reduced at days with a high disturbance frequency; in Westerhever by 8,7 % and in Norderheverkoog by 27,5%. In the disturbed area the birds compensated the time-loss during feeding and the higher energetic costs during disturbance-related flights by a change in activity pattern and by an increased food consumption per time unit. Based on physiological constraints the birds reached their compensatory abilities. The calculated bodymass gain and the proportion of young birds in the flocks was reduced in autumn.

     

Glucose Transporter (GLUT-4) Is Targeted to Secretory Granules in Rat Atrial Cardiomyocytes

The insulin-responsive glucose transporter GLUT-4 is found in muscle and fat cells in the transGolgi reticulum (TGR) and in an intracellular tubulovesicular compartment, from where it undergoes insulindependent movement to the cell surface. To examine the relationship between these GLUT-4–containing compartments and the regulated secretory pathway we have localized GLUT-4 in atrial cardiomyocytes. This cell type secretes an antihypertensive hormone, referred to as the atrial natriuretic factor (ANF), in response to elevated blood pressure. We show that GLUT-4 is targeted in the atrial cell to the TGR and a tubulo-vesicular compartment, which is morphologically and functionally indistinguishable from the intracellular GLUT-4 compartment found in other types of myocytes and in fat cells, and in addition to the ANF secretory granules. Forming ANF granules are present throughout all Golgi cisternae but only become GLUT4 positive in the TGR. The inability of cyclohexamide treatment to effect the TGR localization of GLUT-4 indicates that GLUT-4 enters the ANF secretory granules at the TGR via the recycling pathway and not via the biosynthetic pathway. These data suggest that a large proportion of GLUT-4 must recycle via the TGR in insulin-sensitive cells. It will be important to determine if this is the pathway by which the insulin-regulatable tubulo-vesicular compartment is formed.     

Ventilatory response to helium-oxygen breathing during exercise: effect of airway anesthesia

Krishnan, Bharath S., Ron E. Clemens, Trevor A. Zintel,Martin J. Stockwell, and Charles G. Gallagher. Ventilatory response to helium-oxygen breathing during exercise: effect of airwayanesthesia. J. Appl. Physiol. 83(1):82-88, 1997.The substitution of a normoxic helium mixture(HeO₂) for room air (Air) during exercise results in a sustained hyperventilation, which is present evenin the first breath. We hypothesized that this response is dependent onintact airway afferents; if so, airway anesthesia (Anesthesia) shouldaffect this response. Anesthesia was administered to the upper airwaysby topical application and to lower central airways by aerosolinhalation and was confirmed to be effective for over 15 min. Subjectsperformed constant work-rate exercise (CWE) at 69 ± 2 (SE) % maximal work rate on a cycle ergometer on three separate days: twiceafter saline inhalation (days 1 and3) and once after Anesthesia(day 2). CWE commenced after a briefwarm-up, with subjects breathing Air for the first 5 min (Air-1),HeO₂ for the next 3 min, and Airagain until the end of CWE (Air-2). The resistance of the breathingcircuit was matched for Air andHeO₂. BreathingHeO₂ resulted in a small butsignificant increase in minute ventilation(I) anddecrease in alveolar PCO₂ in both theSaline (average of 2 saline tests; not significant) and Anesthesiatests. Although Anesthesia had no effect on the sustainedhyperventilatory response to HeO₂breathing, theI transientswithin the first six breaths ofHeO₂ were significantly attenuatedwith Anesthesia. We conclude that theI response to HeO₂ is not simply due to areduction in external tubing resistance and that, in humans, airwayafferents mediate the transient but not the sustained hyperventilatoryresponse to HeO₂ breathing duringexercise.

     

Phylogenetic relationships in Maloideae (Rosaceae): evidence from sequences of the internal transcribed spacers of nuclear ribosomal DNA and its congruence with morphology

We used sequences from both internal transcribed spacers (ITS) and a small portion of the 5.8S gene of nuclear ribosomal DNA (nrDNA) for phylogenetic reconstruction of 19 genera of Maloideae and four potential outgroups from the Rosaceae. Parsimony analyses indicate that Maloideae are not monophyletic; Vauquelinia, which is traditionally placed in Spiraeoideae, and two genera of the Maloideae, Eriobotrya and Rhaphiolepis, form a well-supported clade that is the sister to the remainder of the subfamily. Although our ITS phylogenetic hypothesis is highly resolved, there is considerable homoplasy, and support, as indicated by bootstrap values and decay indices, is relatively weak for all groups except four: Eriobotrya-Rhaphiolepis-Vauquelinia, Crataegus-Mespilus, Amelanchier-Peraphyllum-Malacomeles, and Cydonia-Pseudocydonia. Our DNA sequence data do not support a broad interpretation of Sorbus. Intergeneric hybridization, which is prevalent in Maloideae, occurs between genera that are far removed from one another on our most-parsimonious trees. We infer an overall phylogeny from separate analyses of ITS DNA sequences and recently published morphological and wood anatomical studies of Maloideae and from analyses after pooling these data sets. The four most strongly supported clades of the ITS phylogeny appear in the phylogeny based on pooled data.