969 resultados para Xeroderma pigmentosum group D


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Stress-aktivierte-Protein-Kinasen (c-Jun-N-terminal kinases) SAPK/JNK werden sehr schnell nach Exposition von Zellen mit verschiedensten Noxen, wie beispielsweise Genotoxinen, aktiviert. Sie sind allerdings noch nicht als Teil der DNA-Schadensantwort etabliert. In dieser Arbeit sollte gezeigt werden, das SAPK/JNK einen wichtigen Teil innerhalb der DNA-Schadensantwort spielen. Aus diesem Grund wurde zu frühen (z.B.: 4 h) als auch zu späten Zeiten (z.B.: 24 h) die Bildung von DNA-Addukten nach Cisplatin Exposition untersucht und überprüft, ob diese mit dem Aktivierungsstatus der SAPK/JNK nach Cisplatinbehandlung korreliert. Menschliche Fibroblasten, die einen Defekt in der Transkription gekoppelten Nukleotid-Exzisionsreparatur (TC-NER) aufwiesen, wie beispielsweise CSB-Zellen (Cockayne Syndrom B) oder XPA-Zellen (Xeroderma Pigmentosum A), sind charakterisiert durch einen erhöhten Phosphorylierungsstatus der SAPK/JNK, 16 h nach Cisplatingabe, im Vergleich zu normalen Wildtyp-Fibroblasten. Die nach Cisplatin Exposition beobachtete Aktivierung der SAPK/JNK ist quantitativ jedoch nicht vergleichbar mit dem Level an gebildeten Cisplatin-DNA-Addukten, wie in den Southwestern- und Massenspektrometrischen Untersuchungen gezeigt werden konnte. Es konnten jedoch Parallelen zwischen der Aktivierung der SAPK/JNK, sowie den gezeigten γ-H2AX-Foci als auch der Aktivierung von Check-Point Kinasen gefunden werden. Dies lässt darauf schließen, dass DNA-Doppelstrangbrüche (DSB) an der späten Aktivierung des SAPK/JNK Signalweges beteiligt sind. Dementsprechend lässt sich ebenfalls in Zellen, die einen Defekt in der Reparatur von Doppelstrangsbrüchen aufweisen, wie beispielsweise DNA-PKcs Zellen, eine erhöhte, durch Cisplatin hervorgerufene späte Phosphorylierung der SAPK/JNK als auch eine vermehrte γ-H2AX-Foci Bildung und Check-Point Kinasen Aktivierung nachweisen. Vergleichend dazu zeigten Zellen mit einem Defekt in ATM (Ataxia telegiectasia mutated protein) oder XPC keine erhöhte Phosphorylierung zu späten Zeiten nach Cisplatin Behandlung. Weiterhin bleibt festzuhalten, dass die späte, durch Cisplatin hervorgerufene Schadensantwort unabhängig von p53, ER-Stress oder MKP-1 ist. Die SAPK/JNK Aktivierung nach Cisplatin Exposition erfordert funktionsfähige Rho-GTPasen und kann durch pharmakologische Hemmung der Tyrosin-Kinasen und durch N-Acetylcystein gehemmt werden. Es lässt sich zusammenfassend sagen, dass die durch Cisplatin induzierte späte SAPK/JNK Aktivierung durch die Formation von DSB initiiert wird und XPC, Rho-Proteine sowie Tyrosin Kinasen an der Signalweiterleitung beteiligt sind.

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The factors mediating the accumulation of thyroglobulin are of great importance to the understanding of the pathogenesis of human and experimentally induced colloid goiters. To elucidate further the underlying cellular mechanism, thyroid fragments from newborn rats were incorporated into semisolid alginate beads and were cultured as three-dimensional organoids for up to 21 d. In five parallel cultures, the medium contained either no supplements (group A), Nal (group B), thyroid-stimulating hormone (TSH) (group C), Nal plus TSH in the same concentrations as B and C (group D), or Nal and TSH (as in group D) plus methimazole (MMI, group E). The thyroid organoids maintained morphological integrity, functional activity, and ability to proliferate in vitro. Addition of iodine to the cultures significantly increased mean (+/-SEM) follicular diameters from 19.5 +/- 0.7 microm in controls to 33.9 +/- 2.2 microm (p < 0.0001) when NaI was added alone (group B), and 30.4 +/- 1.7 microm (p < 0.0001) when combined with TSH (group D). The effect of NaI on follicular size was abolished by MMI (group E, follicular diameter 23.5 +/- 1.3 microm). The results presented support the recent finding, using a rat colloid goiter model, that not only TSH but also iodine organification or its inhibition are important factors in modulating follicular morphology.

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OBJECTIVE: To evaluate the effects of a single preoperative dose of steroid on thyroidectomy outcomes. BACKGROUND: Nausea, pain, and voice alteration frequently occur after thyroidectomy. Because steroids effectively reduce nausea and inflammation, a preoperative administration of steroids could improve these thyroidectomy outcomes. METHODS: Seventy-two patients (men = 20, women = 52) undergoing thyroidectomy for benign disease were included in this randomized, controlled, 2 armed (group D: 8 mg dexamethasone, n = 37; group C: 0.9% NaCl, n = 35), double-blinded study (clinical trial number NCT00619086). Anesthesia, surgical procedures, antiemetics, and analgesic treatments were standardized. Nausea (0-3), pain (visual analog scale), antiemetic and analgesic requirements, and digital voice recording were documented before and 4, 8, 16, 24, 36, and 48 hours after surgery. Patients were followed-up 30 days after hospital discharge. RESULTS: Baseline characteristics were similar among the 2 treatment groups. Nausea was pronounced in the first 16 hours postoperatively (scores were <0.3 and 0.8-1.0 for group D and C, respectively (P = 0.005)), and was significantly lower in group D compared with group C during the observation period (P = 0.001). Pain diminished within 48 hours after surgery (visual analog scale 20 and 35 in group D and C, respectively (P = 0.009)). Antiemetic and analgesic requirements were also significantly diminished. Changes in voice mean frequency were less prominent in the dexamethasone group compared with the placebo group (P = 0.015). No steroid-related complications occurred. CONCLUSION: A preoperative single dose of steroid significantly reduced nausea, vomiting, and pain, and improved postoperative voice function within the first 48 hours (most pronounced within 16 hours) after thyroid resection; this strategy should be routinely applied in thyroidectomies.

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BACKGROUND: In tuberculosis (TB), the risk of exposure is determined mainly by the proximity to and the hours of direct contact with an infectious patient. We describe the contact investigation after detection of an infectious form of TB in a military camp using an Interferon-g-Release-Assay (IGRA, QuantiFERON-TB Gold In Tube [QTF-GIT]) eight weeks after detection of the index case. INDEX PATIENT: The index patient presented with fever, cough and weight loss in the military hospital six weeks after entering the camp. TB was suspected and anti-tuberculous therapy given immediately. Subsequently, TB was microbiologically confirmed. METHODS: Four exposure groups were formed a priori based on the proximity and the hours of direct contact to the index case. 168 (95.5%) agreed to be investigated: - Group A: sharing the same dormitory (15 persons) - Group B: same platoon, but not sharing the dormitory (20 persons) - Group C: staff and patients of the military hospital (22 persons) - Group D: other three platoons and senior military staff (111 persons). RESULTS: 34 (20.2%) out of 168 contacts tested positive in the QFT-GIT assay. For the exposure groups, the respective QFT-GIT testing results were: group A, 14/15 (93%); group B, 4/20 (20%); group C, 5/22 (22.7%); and group D, 11/111 (9.9%). No secondary TB cases were identified. CONCLUSIONS: In our study, test results show a correlation with the risk of exposure, suggesting that IGRA may be useful for the assessment of TB infection in TB contacts. The high mobility of recruits reduced traceability of contacts. In this context, QFT-GIT allowed for an efficient screening of contacts at a single time point.

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PURPOSE: The aim of the present study was to test the effects of interdental cleansing with dental floss on supragingival biofilm removal in natural dentition during a 3-week period of experimental biofilm accumulation. MATERIALS AND METHODS: The present study was performed as a single-blind, parallel, randomised, controlled clinical trial using the experimental gingivitis model (Löe et al, 1965). Thirty-two students were recruited and assigned to one of the following experimental or control groups: Group A used a fluoride-containing dentifrice (NaF dentifrice) on a toothbrush for 60 s twice a day, Group B used an unwaxed dental floss twice a day, Group C used a waxed dental floss twice a day in every interproximal space and Group D rinsed twice a day for 60 s with drinking water (control). RESULTS: During 21 days of abolished oral hygiene, the groups developed various amounts of plaque and gingivitis. Neither of the cleansing protocols alone allowed the prevention of gingivitis development. Toothbrushing alone yielded better outcomes than did any of the flossing protocols. Interdental cleansing with a waxed floss had better biofilm removal effects than with unwaxed floss. CONCLUSIONS: Toothbrushing without interdental cleansing using dental floss and interdental cleansing alone cannot prevent the development of gingivitis.

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BACKGROUND Perioperative chemotherapy improves survival in patients with advanced esophagogastric cancer, but the optimal treatment regimen remains unclear. More intensive chemotherapy may improve outcome, but also increase toxicity and complications. METHODS A total of 843 patients were included in this retrospective study and stratified in 4 groups: doublet therapy with cisplatin or oxaliplatin and 5-fluorouracil (groups A/B) or triplet therapy with additional epirubicin or taxane (groups C/D). The influence of the different neoadjuvant chemotherapy regimens on response, prognosis, and complications was assessed. RESULTS Clinical and pathological response were associated with longer overall survival (OS; p < 0.001). No significant differences regarding response or OS were found, but there was a trend toward better outcome in group D (taxane-containing triplet). In the subgroup of 669 patients with adenocarcinomas of the esophagogastric junction (AEG), patients who had received taxane-containing regimens had a significantly longer OS (p = 0.037), but taxane use was not an independent factor in multivariate analysis. Triple therapy with taxanes did not result in a higher complication rate or postoperative mortality. CONCLUSIONS Although no superior neoadjuvant chemotherapy regimen was identified for patients with esophagogastric adenocarcinoma, taxane-containing regimens should be further investigated in randomized trials, especially in patients with AEG tumors.

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PURPOSE The objective of this study was to evaluate stiffness, strength, and failure modes of monolithic crowns produced using computer-aided design/computer-assisted manufacture, which are connected to diverse titanium and zirconia abutments on an implant system with tapered, internal connections. MATERIALS AND METHODS Twenty monolithic lithium disilicate (LS2) crowns were constructed and loaded on bone level-type implants in a universal testing machine under quasistatic conditions according to DIN ISO 14801. Comparative analysis included a 2 × 2 format: prefabricated titanium abutments using proprietary bonding bases (group A) vs nonproprietary bonding bases (group B), and customized zirconia abutments using proprietary Straumann CARES (group C) vs nonproprietary Astra Atlantis (group D) material. Stiffness and strength were assessed and calculated statistically with the Wilcoxon rank sum test. Cross-sections of each tested group were inspected microscopically. RESULTS Loaded LS2 crowns, implants, and abutment screws in all tested specimens (groups A, B, C, and D) did not show any visible fractures. For an analysis of titanium abutments (groups A and B), stiffness and strength showed equally high stability. In contrast, proprietary and nonproprietary customized zirconia abutments exhibited statistically significant differences with a mean strength of 366 N (Astra) and 541 N (CARES) (P < .05); as well as a mean stiffness of 884 N/mm (Astra) and 1,751 N/mm (CARES) (P < .05), respectively. Microscopic cross-sections revealed cracks in all zirconia abutments (groups C and D) below the implant shoulder. CONCLUSION Depending on the abutment design, prefabricated titanium abutment and proprietary customized zirconia implant-abutment connections in conjunction with monolithic LS2 crowns had the best results in this laboratory investigation.

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Sixty-three samples representing 379 m of sheeted dikes from Deep Sea Drilling Project/Ocean Drilling Program Site 504B have been analyzed for major and selected trace elements by X-ray fluorescence. The samples range from microcrystalline aphyric basalts to moderately phyric (2%-10% phenocrysts) diabase that are typically multiply saturated with plagioclase, olivine, and clinopyroxene, in order of relative abundance. All analyzed samples are classified as Group D compositions with moderate to slightly elevated compatible elements (MgÆ-value = 0.65% ± 0.03%; Al2O3 = 15.5% ± 0.8%; CaO = 13.0% ± 0.3%; Ni = 114 ± 29 ppm), and unusually depleted levels of moderate to highly incompatible elements (Nb < 1 ppm; Zr = 44 ± 7 ppm; Rb < 0.5 ppm; Ba ~ 1 ppm; P2O5 = 0.07% ± 0.02%). These compositions are consistent with a multistage melting of a normal ocean ridge basaltic mantle source followed by extensive fractionation of olivine, plagioclase, and clinopyroxene. Leg 140 aphyric to sparsely phyric (0%-2% phenocrysts) basalts and diabases are compositionally indistinguishable from similarly phyric samples at higher levels in the hole. An examination of the entire crustal section, from the overlying volcanics through the sheeted dikes observed in Leg 140, reveals no significant trends indicating the enrichment or depletion of Costa Rica Rift Zone source magmas over time. Similarly, significant trends toward increased or decreased differentiation cannot be identified, although compositional patterns reflecting variable amounts of phenocryst addition are apparent at various depths. Below ? 1700 mbsf to the bottom of the Leg 140 section, there is a broadly systematic pattern of Zn depletion with depth, the result of high-temperature hydrothermal leaching. This zone of depletion is thought to be a significant source of Zn for the hydrothermal fluids depositing metal sulfides at ridge-crest hydrothermal vents and the sulfide-mineralization zone, located in the transition between pillow lavas and sheeted dikes. Localized zones of intense alteration (60%-95% recrystallization) are present on a centimeter to meter scale in many lithologic units. Within these zones, normally immobile elements Ti, Zr, Y, and rare-earth elements are strongly depleted compared with "fresher" samples centimeters away. The extent of compositional variability of these elements tends to obscure primary igneous trends if the highly altered samples are not identified or removed. At levels up to 40% (or possibly 60%) recrystallization, Ti, Zr, and Y retain their primary signatures. Although the mechanisms are unclear, it is possible that these intense alteration zones are a source of Y and rare-earth elements for the typically rare-earth-element-enriched hydrothermal vent fluids of mid-ocean ridges.

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The study of radiolarian assemblages from Core MD 962086 provides new information on the variability in the upwelling intensity and origin of upwelled water masses over the past 350 ky in one of the major filamentous regions of the Benguela Upwelling System (BUS), located off Lüderitz, Namibia. The use of key radiolarian species to trace the source of upwelled waters, and the use of a radiolarian-based upwelling index (URI) to reconstruct the upwelling intensity represent the first use of radiolarians for paleoceanographic reconstructions in the BUS. These radiolarian-based proxies indicate strongest upwelling during Marine Isotope Stages (MIS) 3, 5, and 8, which compares well with other studies. While during MIS 3 and 8, the radiolarian-based proxies indicate the influx of waters of Southern Ocean origin, they also point to the increased influence of tropical waters during the lower portion of MIS 5. During MIS 2, 4 and 6 the radiolarian assemblages indicate generally lower upwelling intensities, although this signal is complicated by the increased occurrence of organic carbon in the sediments during these intervals. During MIS 2 there appears to be less of an input of Southern Ocean waters to the BUS, although during the also glacial MIS 4 and 6, there is evidence for an increased influence of cold Antarctic waters. The comparison of the results from Core MD 962086 with other studies in the BUS area indicates a non-uniform pattern of upwelling intensity and advection of cold, southern waters into this system during MIS 2. Weaker upwelling signaled by the radiolarian-based proxy in MIS 4 is in contrast to other studies that indicate higher productivity during this time period. In general, the data show that there is a strong spatiotemporal complexity in upwelling intensity in the BUS and that the advection of water into it is not strongly tied to glacial-interglacial variations in climate.

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Petrography and isotope geochemical characteristics of H, O, S, Sr, and Nd have been described for basalts recovered from Hole 504B during Leg 111 of the Ocean Drilling Program. The petrographic and chemical features of the recovered basalts are similar to those obtained previously (DSDP Legs 69, 70, and 83); they can be divided into phyric (plagioclase-rich) and aphyric (Plagioclase- and clinopyroxene-rich) basalts and show low abundances of TiO2, Na2O, K2O, and Sr. This indicates that the basalts belong to Group D, comprising the majority of the upper section of the Hole 504B. The diopside-rich nature of the clinopyroxene phenocrysts and Ca-rich nature of the Plagioclase phenocrysts are also consistent with the preceding statement. The Sr and Nd isotope systematics (average 87Sr/86Sr = 0.70267 ± 0.00007 and average 143Nd/144Nd = 0.513157 ± 0.000041) indicate that the magma sources are isotopically heterogeneous, although the analyzed samples represent only the lowermost 200-m section of Hole 504B. The rocks were subjected to moderate hydrothermal alteration throughout the section recovered during Leg 111. Alteration is limited to interstices, microfractures, and grain boundaries of the primary minerals, forming chlorite, actinolite, talc, smectite, quartz, sphene, and pyrite. In harmony with the moderate alteration, the following alteration-sensitive parameters show rather limited ranges of variation: H2O = 1.1 ±0.2 wt%, dD = - 38 per mil ± 4 per mil, d180 = 5.4 per mil ± 0.3 per mil, total S = 562 ± 181 ppm, and d34S = 0.8 per mil ± 0.3 per mil. Based on these data, it was estimated that the hydrothermal fluids had dD and d180 values only slightly higher than those of seawater, the water/rock ratios were as low as 0.02-0.2, and the temperature of alteration was 300°-400°C. Sulfur exists predominantly as pyrite and in minor quantities as chalcopyrite. No primary monosulfide was detected. This and the d34S values of pyrite (d34S = 0.8 per mil) suggest that primary pyrrhotite was almost completely oxidized to pyrite by reaction with hydrothermal fluids containing very little sulfate.

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Chemical compositions and 1-atm. phase relations were determined for basalts drilled from Holes 501, 504A, 504B, 505, and 505B on Legs 68, 69, and 70 of the Deep Sea Drilling Project. Chemical, experimental, and petrographic data indicate that these basalts are moderately evolved (Mg' values from 0.60 to 0.70), with olivine plus Plagioclase and often clinopyroxene on the liquidus. Chemical stratigraphy was used to infer that sequential influxes of magma into a differentiating magma chamber or separate flows from different magma chambers or both had occurred. Two major types of basalt were found to be inter layered: Group M, a rarely occurring type with major element chemistry and magmaphile element abundances within the range of the majority of ocean-floor basalts (TiO2 = 1.3%, Na2O 2.5%, Zr = 103 ppm, Nb = 2.5 ppm, and Y = 31 ppm); and Group D, a highly unusual series of basalt compositions that exhibit much lower magmaphile element abundances (TiO2 = 0.75-1.2%, Na2O = 1.7-2.3%, Zr = 34-60 ppm, Nb = 0.5-1.2 ppm, and Y = 16-27 ppm). The liquidus temperatures of the Group D basalts are high (1230- 1260°C) compared with those of other ocean-floor basalts of similar Mg' values. They have high CaO/Na2O ratios (5-8) and are calculated to be in equilibrium with unusually calcic Plagioclase (An78-84). The two basalt groups cannot be related by fractionation processes. However, constant Zr/Nb ratios (>40) for the two groups suggest a single mantle source, with differences in magmaphile element abundances and other element ratios (e.g., Zr/Ti, Zr/Y, Ce/Yb) arising through sequential melting of the same source. Magmas similar to Group D, if mixed with more typical mid-ocean-ridge basalt (MORB) magmas in shallow magma chambers, could provide a source for the highly calcic Plagioclase phenocrysts that appear in more common (i.e., less depleted) phyric ocean-floor basalts.

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At Sites 689 and 690, drilled during ODP (Ocean Drilling Program) Leg 113 on the Maud Rise (southeast Weddell Sea), moderately to well preserved radiolarian assemblages were obtained from continuously recovered upper Oligocene and Neogene sequences. Based on radiolarian investigations, a biostratigraphic zonation for a time interval covering the late Oligocene to the middle Miocene is proposed. The radiolarian zonation comprises 10 zones. Five zones are new, and five zones previously defined by Chen (1975) were modified. The zones and the ranges of the nominate species are directly calibrated with a geomagnetic polarity record. This is the first attempt at a direct correlation of late Oligocene to middle Miocene radiolarian zones with the geomagnetic time scale. Six hiatuses were delineated in the studied upper Oligocene to middle Miocene sections. One major hiatus, spanning ca. 6 m.y., is between the upper Oligocene and the lower Miocene sequences. Another important hiatus separates the lower and middle Miocene sediments. As a base for the biostratigraphic investigations, a detailed taxonomic study of the recovered radiolarian taxa is achieved. Three new radiolarian species that occur in upper Oligocene and lower Miocene sediments are described (Cycladophora antiqua, Cyrtocapsella robusta, and Velicucullus altus).

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Basalts from Hole 504B, Leg 83, exhibit remarkable uniformity in major and trace element composition throughout the 1075.5 m of basement drilled. The majority of the basalts, Group D', have unusual compositions relative to normal (Type I) mid-ocean ridge basalts (MORB). These basalts have relatively high mg values (0.60-0.70) and CaO abundances (11.7-13.7%; Ca/Al = 0.78-0.89), but exhibit a marked depletion in compatible trace elements (Cr and Ni); moderately incompatible trace elements (Zr, Y, Ti, etc.); and highly incompatible trace elements (Nb, LREE, etc.). Petrographic and compositional data indicate that most of these basalts are evolved, having fractionated significant amounts of plagioclase, olivine, and clinopyroxene. Melting experiments on similar basalt compositions from the upper portion of Hole 504B (Leg 70; Autio and Rhodes, 1983) indicate that the basalts are co-saturated with olivine and plagioclase and often clinopyroxene on the 1-atm. liquidus. Two rarely occurring groups, M' and T, are compositionally distinct from Group D' basalts. Group T is strongly depleted in all magmaphile elements except the highly incompatible ones (Nb, La, etc.), while Group M' has moderate concentrations of both moderately and highly incompatible trace elements and is similar to Type I MORB. Groups M' and T cannot be related to Group D' nor to each other by crystal fractionation, crystal accumulation, or magma mixing. The large differences in magmaphile element ratios (Zr/Nb, La/Yb) among these three chemical groups may be accounted for by complex melting models and/or local heterogeneity of the mantle beneath the Costa Rica Ridge. Xenocrysts and xenoliths of plagioclase and clinopyroxene similar in texture and mineral composition to crystals in coarse-grained basalts from the lower portion of the hole are common in Hole 504B basalts. These suggest that addition of solid components either from conduit or magma chamber walls has occurred and may be a common source of disequilibrium crystals in these basalts. However, mixing of plagioclase-laden depleted melts (similar to the Costa Rica Ridge Zone basalts) with normal MORB magmas could provide an alternate source for some refractory plagioclase crystals found out of equilibrium in many phyric MORB. The uniformity of major element compositions in Hole 504B basalts affords an ideal situation for investigating the effects of alteration on some major and trace elements in oceanic basalts. Alteration observed in whole-rock samples records primarily two events - a high-temperature and a low-temperature phase. High-temperature phases include: chlorite, talc, albite, actinolite, sphene, quartz, and pyrite. The low-temperature phases include smectite (saponite), epistilbite or laumontite, and minor calcite. Laumontite may actually straddle the gap between the low- and high-temperature mineral assemblages. Alteration is restricted primarily to partial replacement of primary phases. Metamorphic grade, in general, increases from the top to the bottom of Hole 504B (Legs 69, 70, and 83) as seen in the change from a smectiteto- chlorite-dominated secondary mineral assemblage. However, a systematic progression for the interval recovered during Leg 83 is not apparent. Rather, the extent of alteration appears to be a function of the initial texture and fracture density. Variations in whole-rock major and trace element concentrations cannot be attributed convincingly to any differences in alteration observed. Compositional characteristics of the secondary minerals indicated that extensive remobilization of elements has not occurred; local redistribution is suggested in most cases. Thus, the major and trace element signature of these basalts remains effectively the same as the original composition prior to alteration.

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Mineral and whole-rock geochemical data are presented for chilled dike margins from the lower sheeted dike complex of Deep Sea Drilling Project/Ocean Drilling Program (DSDP/ODP) Hole 504B. Compositions of phenocrystic plagioclase (An80-89); olivine (Fo82-86); clinopyroxene (Wo52En40Fs8, with Cr2O3 up to 1.2%); and rare chromian spinel (Cr# 43) are consistent with those from the lavas and the upper dike complex recovered previously (DSDP Legs 69, 70, 83, and ODP Leg 111). Major and trace element compositions fall in group D of Autio and Rhodes (1983) and have high CaO/Na2O, and low TiO2, K2O, and (La/Sm)N values consistent with previous analyses from this site.