bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency of β1‐6 N‐Acetylglucosaminyltransferase Involved in the Biosynthesis of Blood Group I Antigen in the Liver of LEC Rats
Authors: Gu Jianguo , Nishikawa Atsushi , Matsuura Nariaki , Sugiyama Toshihiro , Taniguchi Naoyuki
Published: September 2010

The activities of the β1‐6 and β1–3 N‐acetylglucosaminyltransferases, which synthesize blood group I and i antigens, respectively, were measured in various tissues of hepatitis‐ and hepatoma‐predisposed rats (LEC rats). In LEC rats the β1‐6 N‐acetylglucosaminyltransferase activity was barely detectable in the liver, while substantial enzyme activity was found in other tissues. In the control LEA rats the enzyme was expressed in most tissues, including the liver. Immunochemical studies using a monoclonal antibody which recognizes I antigen indicated that the expression of I antigen was less prominent in hepatocytes of LEC rats than in hepatocytes of LEA rats. The level of β1–3 N‐acetylglucosaminyltransferase activity was constant in most of the tissues during the development. These results indicate that the biosynthesis of I antigen does not occur in the livers of the LEC rats.
Serum midkine concentrations and gastric cancer
Authors: Obata Yuki , Kikuchi Shogo , Lin Yingsong , Yagyu Kiyoko , Muramatsu Takashi , Kumai Hideshi ,   Tokyo Research Group on Prevention of Gastric Cancer
Published: September 2010

Midkine (MK) is one of a family of heparin‐binding growth factors, and increased MK expression is reported in various types of human carcinomas. To clarify the association between serum MK (S‐MK) concentrations and gastric cancer, we examined S‐MK concentrations of gastric cancer patients (n = 275) and healthy controls (n = 275). S‐MK concentrations of all subjects were measured by enzyme‐linked immunosorbent assay (elisa). The medians (25th and 75th percentiles) of S‐MK were 192 (123 and 314) pg/mL in the cases and 170 (81 and 273) pg/mL in the controls (P < 0.01). We also compared S‐MK concentrations in each group divided by the progression stage or histological type of cancer. A difference was observed in the median S‐MK concentrations between early and advanced cancers [182 (105 and 301) pg/mLvs203 (139 and 331) pg/mL,P = 0.07], but not between intestinal and diffuse type cancers [185 (121 and 306) pg/mLvs198 (127 and 323) pg/mL,P = 0.51]. We found that those progression stages affect S‐MK concentration more strongly than the histological types in gastric cancer patients. Because S‐MK seems to reflect the progression stage of gastric cancer, it may serve as a useful marker in the clinical follow‐up of gastric cancer patients. (Cancer Sci2005; 96: 54 –57)
Generation of 8‐hydroxydeoxyguanosine from DNA using rat liver homogenates
Authors: Shi Minyi , Takeshita Haruko , Komatsu Masaharu , Xu Baohui , Aoyama Kohji , Takeuchi Toru
Published: September 2010

In relation to carcinogenesis, aging and other pathologic conditions, urinary 8‐hydroxydeoxyguanosine (8OHdG) is widely used as a marker for evaluating the effect of oxidative stress on DNA. Because no reports have described how 8OHdG is generated from DNA in vivo or by biological materials, and how it is excreted into urine, the authors investigated the generation of 8OHdG from DNA, using rat liver homogenate. Oxidatively damaged DNA samples containing different levels of 8OHdG were prepared using ultraviolet irradiation with three different concentrations of riboflavin. Following incubation of damaged DNA samples with rat liver homogenates, the generation of 8OHdG from the DNA was determined using high‐performance liquid chromatography with electrochemical detection after ultrafiltration of the incubation mixtures. The generation of 8OHdG was also tested with an anti‐8OHdG antibody. The quantity of 8OHdG generated from the DNA by rat liver homogenates was dependent on the 8OHdG levels in the DNA: almost all 8OHdG in the DNA was released as 8OHdG by rat liver homogenates. Generation of 8OHdG correlated with the degradation of DNA. Interestingly, the generated 8OHdG was stable in the presence of rat liver homogenates, whereas deoxyguanosine (dG) rapidly disappeared in the same conditions. Less than 1/10 000 of dG was converted to 8OHdG when dG was incubated with rat liver homogenate. Incubation of 8‐hydroxyguanine with rat liver homogenates did not generate 8OHdG. These findings suggest that most of the 8OHdG in DNA is released as 8OHdG during DNA degradation and that, because of its stability, 8OHdG is excreted into urine, thus providing a convenient measure of oxidative damage to DNA. (Cancer Sci 2005; 96: 13–19)
EPHA2/EFNA1 expression in human gastric cancer
Authors: Nakamura Ritsuko , Kataoka Hideki , Sato Naomi , Kanamori Masao , Ihara Megumi , Igarashi Hisaki , Ravshanov Sanjar , Wang You‐Jie , Li Zhong‐You , Shimamura Takahiro , Kobayashi Toshihiko , Konno Hiroyuki , Shinmura Kazuya , Tanaka Masamitsu , Sugimura Haruhiko
Published: September 2010

The erythropoietin‐producing hepatocellular (EPH)A2 receptor, tyrosine kinase, is overexpressed and phosphorylated in several types of human tumors and has been associated with malignant transformation. A recent report, however, indicated that stimulation of the EPHA2 receptor ligand, ephrinA1 (EFNA1), inhibits the growth of EPHA2‐expressing breast cancer. The authors examined the expression of EPHA2 and EFNA1 using semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR) in four gastric cancer cell lines and 49 primary gastric cancer samples, as well as in normal gastric tissue. EPHA2 was more highly expressed in tumor tissue than in normal tissue in 27 cases (55%). EFNA1 was overexpressed in tumor tissue in 28 cases (57%). No significant correlation was detected between the expression levels and histologic features such as tumor size, age, vessel invasion, or lymph node involvement. However, EPHA2 overexpression was more prominent in macroscopic type 3 and 4 tumors than in type 1 or 2 advanced gastric cancer. The authors observed EPHA2 expression in three of the four gastric cancer cell lines (AGS, KATO3, and MKN74) that were examined. In one cell line, TMK1, EPHA2 expression was barely detectable using northern blotting, RT‐PCR, and western blotting. In contrast, EFNA1 was detected in all cell lines. In the gastric cancer cell lines that endogenously expressed EPHA2, stimulation with ephrinA1‐Fc led to decreased EPHA2 protein expression and increased EPHA2 phosphorylation. Finally, the growth of EPHA2‐expressing cells was inhibited by repetitive stimulation with soluble ephrinA1‐Fc. Taken together, these findings suggest that EPHA2 and EFNA1 expression may influence the behavior of human gastric cancer. (Cancer Sci 2005; 96: 42–48)
Correlation of KIT and EGFR overexpression with invasive ductal breast carcinoma of the solid‐tubular subtype, nuclear grade 3, and mesenchymal or myoepithelial differentiation
Authors: Tsuda Hitoshi , Morita Daisaku , Kimura Mikihiko , Shinto Eiji , Ohtsuka Yukiko , Matsubara Osamu , Inazawa Johji , Tamaki Kuniyoshi , Mochizuki Hidetaka , Tamai Seiichi , Hiraide Hoshio
Published: September 2010

Although KIT and EGFR overexpressions are reported to occur in breast cancer, their pathological significance is still unclear. We examined KIT, EGFR, and c‐erbB‐2 overexpressions immunohistochemically in 150 cases of surgically resected breast cancer and their correlation with the histological type and grade and mesenchymal and/or myoepithelial immunophenotype of primary tumors. To facilitate the analysis, we constructed a tissue microarray comprising 2‐mm diameter tissues cored from the representative tissue block of each tumor. KIT, EGFR, and c‐erbB‐2 overexpressions were detected in 15 (10%), 12 (8%), and 23 (15%), respectively. The KIT was more frequent in the group comprising comedo‐type ductal carcinoma in situ and invasive ductal carcinomas (IDCs) of the solid‐tubular subtype than in the group of other histological types (P = 0.027), and the EGFR was more frequent in IDCs of solid‐tubular type than in other histological types (P < 0.05). KIT and EGFR overexpressions were correlated with nuclear grade 3 (P = 0.0095 and 0.0005) and tended to be concurrent (P = 0.005). KIT overexpression was correlated with vimentin and S‐100 expression (P = 0.003 and P = 0.005), and EGFR overexpression was correlated with S100 expression (P = 0.0001). These correlations with grade and mesenchymal/myoepithelial markers were not observed for c‐erbB‐2 overexpression. KIT and EGFR appeared to be indicators of high‐grade breast carcinoma groups that often contain the carcinomas with mesenchymal and/or myoepithelial differentiation, which are distinct from the group with c‐erbB‐2 overexpression. (Cancer Sci 2005; 96: 48 –53)
Retroviral insertional mutagenesis identifies oncogene cooperation
Authors: Nakamura Takuro
Published: September 2010

Retroviral insertional mutagenesis has been applied to identify oncogenes that are important for both human and rodent carcinogenesis. The method reveals not only primary oncogenes but also cooperative genes that might be affected as second or third hits in multistep carcinogenesis. The use of genetically engineered mice such as NUP98‐HOXA9 transgenic mice enabled efficient identification of cooperative genes, which provides important information for the molecular pathway in carcinogenesis/leukemogenesis. With use of the retrovirus mediated gene transfer system, retroviral insertional mutagenesis will provide invaluable information to understand genetic interaction in complex mechanisms of carcinogenesis. (Cancer Sci 2005; 96: 7–13)
Adenovirus‐mediated CD40L gene therapy induced both humoral and cellular immunity against rat model of hepatocellular carcinoma
Authors: Iida Tomonori , Shiba Hiroaki , Misawa Takeyuki , Ohashi Toya , Eto Yoshikatsu , Yanaga Katsuhiko
Published: September 2010

Adenoviral‐vector expressing CD40L (AxCAmCD40L)‐mediated gene therapy was studied for treatment of hepatocellular carcinoma (HCC) using CD40 ligand (CD40L) complementary DNA in rats. The particular focus was whether humoral immunity took part in antitumor effect. When tumor cells transduced by AxCAmCD40L were implanted into the subcutaneous tissues of syngeneic rats, the tumor growth was suppressed. Intratumoral injection of AxCAmCD40L to pre‐existing tumor in rats also led to significant reduction of tumor size. When tumor cells were re‐implanted to prevention model rats and treatment model rats, no tumor growth was observed. Many studies to date have reported that cellular immunity induces antitumor immunity. However, the present study demonstrated that not only cellular immunity but also humoral immunity plays an essential role in a HCC model. These observations suggested that CD40L‐mediated immune gene therapy for HCC was very effective treatment by activation of both cellular and humoral immune system. (Cancer Sci 2008; 99: 2097–2103)
Plasma midkine level is a prognostic factor for human neuroblastoma
Authors: Ikematsu Shinya , Nakagawara Akira , Nakamura Yohko , Ohira Miki , Shinjo Masaki , Kishida Satoshi , Kadomatsu Kenji
Published: September 2010

Neuroblastoma is the third‐most‐common solid tumor of childhood. To date, no reliable blood marker for neuroblastoma has been established. The growth factor midkine is highly expressed in human carcinomas and its knockdown leads to tumor growth suppression in animal models. The present study evaluated the plasma midkine level in human neuroblastoma patients. Plasma samples were obtained from patients found through mass screening, as well as from sporadic neuroblastoma patients. The total number of cases examined was 756. Among them, prognostic information was available for 175 sporadic cases and 287 mass‐screening cases. Midkine levels were significantly higher in neuroblastoma patients, including both mass‐screening cases and sporadic cases, than in non‐tumor controls (P < 0.0001). The midkine level was significantly correlated with the statuses of MYCN amplification, TRKA expression, ploidy, stage and age (P < 0.0001, < 0.0001, = 0.004, < 0.0001 and < 0.0001, respectively), which are known prognostic factors for neuroblastoma. There was a striking correlation between high plasma midkine level and poor prognosis (P < 0.0001). Within sporadic cases, the midkine level was also strikingly higher than in non‐tumor controls (P < 0.0001), and correlated with the statuses of MYCN amplification and stage (P = 0.0005 and = 0.003, respectively). There was a significant correlation between high plasma midkine level and poor prognosis (P = 0.04). Taken together, the present data indicate that plasma midkine level is a prognostic factor for human neuroblastoma. (Cancer Sci 2008; 99: 2070–2074)
Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case–control study
Authors: Keszthelyi D. , Jansen S. V. , Schouten G. A. , De Kort S. , Scholtes B. , Engels L. G. J. B. , Masclee A. A. M.
Published: September 2010

Aliment Pharmacol Ther 2010; 32: 1124–1128

Background  Microscopic colitis causes chronic watery diarrhoea. Recent studies have suggested an aetiological role for various medications, including proton pump inhibitors, in the pathogenesis of microscopic colitis.

Aim  To determine whether an association exists between microscopic colitis and proton pump inhibitor use in patients with documented microscopic colitis vs. age‐ and gender‐matched controls.

Methods  In this retrospective case–control study, cases of microscopic colitis from a secondary and tertiary referral medical centre diagnosed in the last 5 years were reviewed. Demographic characteristics, clinical, histological and endoscopic records, as well as exposure to PPIs and NSAIDs were assessed. Controls from the population were matched to cases by gender and by age.

Results  During the investigated period, 136 cases were identified in both hospitals. Of these, 95 cases of microscopic colitis were retrieved for detailed analysis. Exposure to proton pump inhibitors at the time of the histological diagnosis was significantly higher in patients with collagenous colitis than in controls [38% vs. 13%, P < 0.001; adjusted OR of 4.5 (95% CI 2.0–9.5)].

Conclusions  This observation confirms the presumed association between microscopic colitis and PPI use, and it supports the possible aetiological role of PPI exposure in the development of microscopic colitis.
ORIGINAL ARTICLE: The ability of anaesthetists to identify the position of the right internal jugular vein correctly using anatomical landmarks
Authors: Harber C. R. , Harvey D. J. R. , Wiles M. D. , Bogod D. G.
Published: September 2010

We performed a study of 85 consenting anaesthetists to assess their ability to locate the right internal jugular vein using a landmark technique. Initially, a questionnaire was completed ascertaining previous user experience. An ultrasound probe, using the midpoint as an ‘imaginary needle’, was placed on the neck of a healthy volunteer (with previously confirmed normal anatomy) and the image recorded. Both anaesthetist and volunteer were blinded to the screen until the image was stored. Anaesthetists were grouped into those in training before 2002 (Pre‐2002, n = 58), when National Institute for Health and Clinical Excellence guidelines recommending ultrasound guidance were published, and those training after this time point (Post‐2002, n = 27). The success rate for identifying the internal jugular vein using the landmark technique was 36/58 (62%) in the Pre‐2002 group and 6/27 (22%) in the Post‐2002 group (p < 0.001). Three participants in each group would have hit the carotid artery (5% Pre‐2002 and 11% Post‐2002 respectively; p = 0.2). The advent of routine use of ultrasound has resulted in a cohort of anaesthetists who are unable to use a landmark technique effectively or safely. This has significant training implications.
ORIGINAL ARTICLE: Can sugammadex save a patient in a simulated ‘cannot intubate, cannot ventilate’ situation?
Authors: Bisschops M. M. A. , Holleman C. , Huitink J. M.
Published: September 2010

Recent studies have shown that the use of high dose rocuronium followed by sugammadex provides a faster time to recovery from neuromuscular blockade following rapid sequence induction than suxamethonium. In a manikin‐based ‘cannot intubate, cannot ventilate’ simulation, we studied the total time taken for anaesthetic teams to prepare and administer sugammadex from the time of their initial decision to use the drug. The mean (SD) total time to administration of sugammadex was 6.7 (1.5) min, following which a further 2.2 min (giving a total 8.9 min) should be allowed to achieve a train‐of‐four ratio of 0.9. Four (22%) teams gave the correct dose, 10 (56%) teams gave a dose that was lower than recommended, four (22%) teams gave a dose that was higher than recommended, six (33%) teams administered sugammadex in a single dose, and 12 (67%) teams gave multiple doses. Our simulation highlights that sugammadex might not have saved this patient in a ‘cannot intubate, cannot ventilate’ situation, and that difficulties and delays were encountered when identifying, preparing and administering the correct drug dose.
Basin architecture and thermal maturation in the strike‐slip Deer Lake Basin, Carboniferous of Newfoundland
Authors: Hyde RICHARD S. , Miller HUGH G. , Hiscott RICHARD N. , Wright JAMES A.
Published: September 2010

Abstract The Deer Lake Basin is an entirely non‐marine basin associated with the Cabot fault zone. Structural and stratigraphic evidence strongly suggest dextral strike‐slip movements along the fault zone during Tournaisian‐Visean time. Two elongated, end‐on structural blocks (probable positive flower structures) contain fold axes and second‐order faults oriented obliquely to fault traces bounding the blocks, in a manner implying dextral movements. In one part of the basin, the stratigraphic thickness of a long homoclinal section of later basin‐fill sediment (Deer Lake Group) greatly exceeds the suggested depth to basement based on gravity measurements, a situation common to strike‐slip basins. Formations representing basin fill can be arranged into megasequences (from oldest to youngest: Anguille Group, Wetstone Point and Wigwam Brook Formations, Deer Lake Group, Howley Formation) corresponding to lateral growth stages of the basin.

Gravity, magnetic, and seismic data show that depths to basement on either side of the end‐on flower structures are comparable, so that the youngest strata in the basin (Howley Formation) are not underlain by earlier basin fill. These geophysical data, therefore, corroborate the geological conclusion of onlapping stratigraphic relations. The geophysical data suggest participation of basement in Carboniferous gravity faulting and show the location of the subsurface extension of the Taylors Brook Fault in the western part of the Deer Lake Basin.

Thermal maturation of the Anguille and Deer Lake Groups, as measured by vitrinite reflectance, clay mineral assemblages, illite crystallinity, and Rock‐Eval pyrolysis, indicate a much higher level of maturation for the Anguille than for the Deer Lake Group. Palaeotemperatures for the Anguille and Deer Lake Groups are estimated to be around 200 and 100oC, respectively, suggesting that Anguille Group rocks are overmature whereas Deer Lake Group strata are within the oil‐generating window. Onlapping stratigraphic relations and areally homogeneous time/temperature effects, however, have created a situation in which the Deer Lake Group and Howley Formation have similar maturation levels.
Rates of active deformation in the Aegean Sea and surrounding regions
Authors: Jackson JAMES , McKenzie DAN
Published: September 2010

Abstract Average strain rates are calculated from earthquakes in the period 1908‐81 that occurred in the Aegean Sea extensional region, and in the convergent zone associated with the Hellenic Trench. In spite of large uncertainties resulting from the use of an MS:Mo relationship, seismic N‐S extensional rates in the Aegean are in the region 20–60 mm yr‐1 whereas seismic shortening rates in the Hellenic Trench are less than about 15 mm yr‐1. This is surprising because Africa and Eurasia are known to be converging, not separating. This apparent anomaly is caused by most of the convergence in the Hellenic Trench occurring aseismically. By contrast, the seismic extensional rates in the Aegean agree quite well with those expected from other arguments. The present day extensional rates are sufficiently high for McKenzie's instantaneous stretching model to be applicable. There is some evidence that these high extensional rates have operated throughout the last 5 Myr.
Structural development of Neogene basins in western Greece
Authors: Brooks M. , Clews J. E. , Melis N. S. , Underhill J. R.
Published: September 2010

Abstract An account is given of the structural setting of the various Neogene sedimentary basins of western Greece. Compressional basins are attributable to foreland loading by the Alpine fold and thrust belt of the Outer Hellenides, and to active subduction in the adjacent western Hellenic arc. Late extensional basins are related to N‐S crustal extension in the Aegean marginal basin and, in western Greece, are superimposed on the earlier compressional structures. The local seismicity provides evidence that the main E‐W‐trending basin‐bounding faults of the extensional basins form a linked system that includes NW‐SE‐ and NE‐SW‐trending transfer zones of transtension. The transfer zones are themselves the sites of small extensional basins.
Normal fault displacement characteristics, with particular reference to synthetic transfer zones, Mae Moh mine, northern Thailand
Authors: Morley C. K. , Wonganan N.
Published: September 2010

Normal faults in middle Miocene sedimentary rocks of the Mae Moh mine have their geometries and displacement patterns well constrained by outcrop and subsurface data. Seventeen of the largest faults are described and analysed. The 17 faults have very different displacement profiles, with differences between the profiles being explicable in terms of the linkage of initially separate faults. Lateral tip gradients show a large range from 0.035 to 0.6. Fault displacement–length (D–L) relationships plot with considerable scatter. Following previous studies, data points with relatively high D–L ratios are attributed to displacement transfer between overlapping faults; faults with relatively low D–L ratios display linkage of two or more faults. In transfer zones conservation of displacement between the faults ranges from high (> 70%) to low (10–40%). This appears to depend upon whether the faults propagated relatively early (high displacement transfer) or late (low displacement transfer) into overlapping configurations. Where displacement transfer is low, extension appears to be conserved in a broader zone on adjacent mappable faults, with little increase in ductile deformation.
River response to lateral ground tilting: a synthesis and some implications for the modelling of alluvial architecture in extensional basins
Authors: Peakall J. , Leeder M. , Best J. , Ashworth P.
Published: September 2010

This paper reviews and synthesizes several Holocene field examples of river response to lateral ground tilting. Key aspects of alluvial architecture modelling in extensional basins are addressed, including the nature of gradual lateral migration, the spatial and temporal history of avulsive sequences, and the underlying controls that determine whether a river responds to lateral tilting through gradual migration or avulsion. A new conceptual model for gradual lateral migration is proposed that unifies previously disparate models. Tilt‐induced avulsion in several field examples is associated with sequences that move towards and away from the locus of subsidence during active and quiescent tectonic periods, respectively. These avulsion sequences closely correspond to those produced by several 2D and 3D alluvial architecture models. The rate of lateral tilt appears to control the style of channel movement, with gradual migration occurring at low tilt rates, and avulsion at higher rates. This apparent dependence on tilt rate suggests the mode of channel movement, and also the avulsion frequency, may in part be a function of the imposed tectonic regime.
Evolution of the Congo rift basin, West Africa: an inorganic geochemical record in lacustrine shales
Authors: Harris N. B.
Published: September 2010

The inorganic geochemistry and mineralogy of synrift lacustrine shales from the Early Cretaceous Congo rift basin provide insight into source terrane, palaeoclimate and evolution of rift topography. The basin formed in a Late Proterozoic metamorphic belt as South America and Africa began to separate. Within the synrift section, a late rift sequence (Marnes Noires and Argilles Vertes Formations) can be distinguished from an underlying active rift sequence (Vandji, Sialivakou and Djeno Formations), based on diminished faulting and more uniform subsidence.

Provenance did not vary significantly until deposition of the youngest part of the rift sequence. Al2O3/TiO2 and K2O/Na2O ratios, generally constant, rise sharply in upper Marnes Noires and Argilles Vertes, demonstrating decreased contribution from Proterozoic volcanic sources. Parameters including (quartz+feldspar)/total clay and SiO2/Al2O3 suggest that depositional systems reorganized during lower Djeno deposition, possibly due to rejuvenation of faulting. Grain size decreases in the late rift section; however, the parameter SiO2/Al2O3 increases. This is attributed to chemical or biogenic deposition of silica.

The proportion of chemical sedimentation increases upward in the synrift section, peaking in the Marnes Noires Formation, where the concentrations of organic carbon and carbonate and the proportion of SiO2 to siliciclastic‐associated elements reach a maximum. This is interpreted as resulting from input of high dissolved chemical load in the late rift stage and is attributed to increased chemical weathering in the basin as rift topography diminishes. The slower flow of ground and surface water to the rift lakes enhanced weathering and dissolution of minerals in rocks and sediments surrounding the rift lake. The carbon isotopic composition of carbonate decreases from +6 at the base of the rift section, associated with carbon from Late Proterozoic carbonates, to 0, indicating increasing contribution of light carbon; the source of light carbon is interpreted as vegetation, which increases as rift topography degrades.
Propagation history and passive rotation of mesoscale normal faults: implications for synrift stratigraphic development
Authors: Sharp I. R. , Gawthorpe R. L. , Armstrong B. , Underhill J. R.
Published: September 2010

Field data from onshore exposures of the Oligo‐Miocene Gulf of Suez Rift in the Sinai document the passive rotation of early formed mesoscale synthetic and antithetic faults and associated half‐graben due to long‐lived activity on large displacement (2–5 km) block‐bounding faults. Early formed small‐displacement (<350 m) mesoscale antithetic faults and half‐graben within regional‐scale fault blocks underwent progressive steepening due to footwall uplift, rotational faulting and footwall flexing on large‐displacement, block‐bounding faults. In contrast, mesoscale synthetic faults were progressively rotated to shallower angles. Analysis of palaeohorizontal surfaces within synrift sediments deposited in half‐graben adjacent to the mesoscale faults indicate passive rotations of up to 25° about horizontal axes since deposition. Passive burial and in‐filling of early formed mesoscale faults and half‐graben by synrift sediments is consistent with extension being transferred from numerous mesoscale faults to few block‐bounding macroscale faults as extension preceded. Furthermore, this transfer of extension appears to be associated with a marked change in basin configuration, synrift sediment dispersal patterns and facies development. Identification of early formed, passively rotated normal faults and half‐graben is important for correctly reconstructing the early stages of basin palaeogeography and sediment dispersal, and for addressing models of rift basin evolution.
Burial/exhumation histories for the Cooper–Eromanga Basins and implications for hydrocarbon exploration, Eastern Australia
Authors: Mavromatidis Angelos
Published: September 2010

The Cooper–Eromanga Basins of South Australia and Queensland are not at their maximum burial depth due to Late Cretaceous–Tertiary, and Late Triassic–Early Jurassic exhumation. Apparent exhumation (maximum burial depth–present burial depth) for the Cooper Basin has been quantified using the compaction methodology. The results show that exhumation of the Cooper Basin for the majority of the wells is greater than the exhumation of the Eromanga Basin. Using the compaction methodology, apparent exhumation of Early to Middle Triassic age Arrabury and Tinchoo Formatios has been quantified. Both units yield similar results and do not support that the Arrabury/Tinchoo boundary represents the Cooper–Eromanga boundary. Hence, the Cooper Basin is believed to have reached its maximum burial depth in Late Triassic times. Sonic log data are not available for the units overlying the Late Cretaceous Winton Formation; thus, it is not possible to date exhumation beyond the Late Cretaceous–Tertiary using the compaction methodology. Tertiary sequences as are preserved are relatively thin and separated by marked unconformities and weathered surfaces; hence, exhumation rather than sedimentation dominated the Tertiary, and in exhumed areas, maximum burial depth was attained in Late Cretaceous times. The burial/exhumation history of representative wells was synthesized using sediment decompaction and establishing porosity/depth relations for the Cooper–Eromanga units. Considering the relative significance of the major periods of exhumation in the Cooper/Eromanga Basins, three broad types of burial/exhumation histories can be distinguished. Maximum burial depth of the Cooper Basin sequence was attained before the deposition of the Eromanga Basin sequence, i.e. Late Triassic–Early Jurassic times; maximum burial depth of the Cooper and Eromanga Basin sequences attained in Late Cretaceous times; and Cooper and Eromanga Basin sequences are currently at maximum burial‐depth. Incorporation of exhumation into burial history has major implications for hydrocarbon exploration.
Lithological control on thrust‐related deformation in the Sassa‐Guardistallo Basin (Northern Apennines hinterland, Italy)
Authors: Feroni Andrea Cerrina , Bonini Marco , Martinelli Patrizia , Moratti Giovanna , Sani Federico , Montanari Domenico , Ventisette Chiara Del
Published: September 2010

The Sassa‐Guardistallo Basin (SGB) is located close to the Tyrrhenian Sea and represents one of the most internal Neogene–Quaternary hinterland basins of the Northern Apennines fold‐and‐thrust belt. Its sedimentary succession consists of ca. 400‐m‐thick Late Tortonian–Messinian continental – largely conglomeratic – units overstepping a mainly shaly substratum (Palombini Shales) and overlain by Late Messinian evaporites and marine to continental Pliocene–Pleistocene sediments. This stratigraphic succession can be approximated to a composite rheological multilayer that dictated the style of basin deformation. Detailed geological mapping and structural analysis revealed that basin deposits were affected by compressional deformations that can be found both at map and outcrop scales. Decametric splay thrusts emanating from the substratum–conglomerate interface locally double the continental succession and are bounded by a roof thrust along the Late Messinian evaporite décollement, defining a deformation pattern consistent with a duplex‐like structure. The time–space structural evolution of the basin inferred from the fieldwork was addressed and tested by analogue modelling that approximated the rheological stratification of the study area to a layered brittle–ductile system. The model results support the hypothesis that the evolution of the thrust system affecting the SGB started as an early floor imbricate fan thrust system that successively evolved to a duplex structure as the link thrusts propagated into the upper décollement layer that resulted from the deposition of the Late Messinian evaporites. Models display many structural features that may be compared with the natural prototype, and highlight the importance of syntectonic sedimentation in the development and evolution of tectonic structures. The results of this study retain relevant implications for the Neogene evolution of the Tyrrhenian Basin–Northern Apennines system. This study also supports that combining between field structural analyses and analogue modelling can give useful hints into the evolutionary history of tectonically complex areas.
Submarine slope failure primed and triggered by silica and its diagenesis
Authors: Davies Richard J. , Clark Ian R.
Published: September 2010

Three‐dimensional seismic analysis of a submarine palaeo‐translational slope failure on the northeast Atlantic margin indicates that it was ‘primed’ and probably ‘triggered’ as a result of diagenesis at a silica chemical reaction front, where biogenic silica (opal A) is being converted to opal CT (Cristobalite/Tridymite). Conversion of opal A to opal CT is a thermochemical dehydration reaction that causes rapid compaction. It therefore is a potential overpressure generation mechanism, usually once sediment has been buried to depths of 300–800 m below the contemporaneous seabed. The overpressure reduces the sediment shear strength, making it susceptible to failure. In this example, the translated succession (volume of 25 km3 and area of 110 km2) was coherent and rigid but the detachment unit was a liquified sediment mass. After failure, the translated succession broke up into a series of faulted‐bounded blocks, which differentially subsided into this underlying sediment‐fluid mass. Sediment‐fluid intrusions utilized the faults bounding the blocks, intruding 200–400 m of the overburden stratigraphy to expel a fluid–sediment mix into the water column and onto the palaeoseabed. Pore pressure decreased and sediment strength within the detachment unit was re‐established. Key factors for the initiation of this failure mechanism are (a) the rate of the reaction front advancement (ROFA), (b) the magnitude of the porosity reduction at the reaction front, (c) the sealing capabilities of the overburden and (d) the low shear strength of opal A. Given that the reaction front normally forms at depths of 300–800 m, the mechanism is more likely to induce deep and therefore large volume detachments, which should be more common in high latitude and equatorial regions where biogenic silica production is high.
announcement: Non‐malignant haematology research in the UK: looking forward to new opportunities
Authors: Collins P. W. , Baglin T. P. , Dang R. , Evans G. , Greaves M. , Laffan M. , Pasi K. J. , Rose P. , Stanworth S. , Toh C. H. , Gower J. ,   on behalf of the UK Non‐Malignant Haematology Speciality Group
Published: September 2010

Over the last few years there has been rapid and radical change in the way clinical research in the UK is funded and supported within the NHS. This has resulted from restructuring and major new investment in research infrastructure, co‐ordinated through Clinical Local Research Networks (CLRNs) and equivalent organisations in the devolved nations. CLRNs have resources to support local researchers undertake studies that have been adopted on to the national research portfolio. For example, CLRNs can help with gaining local approvals or provide research nurses to recruit patients, undertake study procedures and perform data entry. CLRNs can establish Local Speciality Groups in a number of areas of medicine, including non‐malignant haematology. These new networks offer non‐malignant haematology access to significant new resources and a major opportunity to support clinical research for the benefit of our patients.
Changes In the Dna Labelling Index After β Irradiation of the Mouse Epidermis
Authors: Hansen L. S. , Coggle J. E. , Wells J. , Charles M. W.
Published: September 2010

This study looked at the changes in the interfollicular DNA labelling index (LI) with time after strontium‐90/yttrium‐90 β irradiation of approximately 100 mm2 of mouse flank skin, after a dose of 100 Gy which produces transitory moist desquamation. Within 24 hr of such a dose the LI of the irradiated area was essentionally zero (0.07 ± 0.03%), whilst those of the side area and of the control area were 15.0 ± 2.6% and 21.4 ± 2.7%, respectively. the LI of the side and the control areas then fell within 3–5 days to approximately 4% and approximately 2% respectively, whilst that of the irradiated area rose rapidly to a peak value of 30.2 ± 1.7% at 10 days post‐irradiation. There was a 20% reduction in the diameter of the area with detectable radiation damage within 5 days, and this is primarily due to cell proliferation and migration from the unirradiated margins of the field. In contrast, between days 10 and 20 the major source of repopulation is probably derived from local migration and proliferation of surviving hair follicle basal cells within the irradiated field.
Differential Calcium Requirements For Growth of Mouse Skin Epithelial and Fibroblast Cells
Authors: Kulesz‐Martin M. F. , Fabian D. , Bertram J. S.
Published: September 2010

Concentrations of extracellular Ca++ optimum for growth of cell types of mesodermal origin have been reported to be up to 100‐fold higher than concentrations optimal for epidermal or other epithelial lining cells. In order to examine Ca++ requirements of epithelial v. fibroblastic cells derived from a common tissue source, prior to prolonged culture, freshly isolated mouse epidermal keratinocytes, hair follicle cells and dermal fibroblasts were plated at high density or at clonal density in medium ranging from 0.014 to 1.4 mM Ca++. Epithelial skin cells grew best at Ca++ levels below 0.1 mM while dermal fibroblasts grew best at a Ca++ concentration of 1.4 mM. the epithelial cell types exhibited marked morphologic changes in response to Ca++, while the fibroblasts did not. These results suggest that the variations in Ca++ response between lining epithelium and mesenchymal cells resulted from inherent differences in these cell types, but a mechanism for such differential effects has not yet been defined.
Identification of genes deregulated during serum‐free medium adaptation of a Burkitt's lymphoma cell line
Authors: Zander L. , Bemark M.
Published: September 2010

Abstract.  Objective: Serum is usually added to growth media when mammalian cells are cultured in vitro to supply the cells with growth factors, hormones, nutrients and trace elements. Defined proteins and metal ions, such as insulin, growth factors, transferrin and sodium selenite, are sometimes also included and can in some cases substitute serum components. How adaptation to serum free media influences cells has not been studied in detail. Materials and Methods: We have adapted the Burkitt's lymphoma line Ramos to a serum‐free medium that supports long‐term survival and studied gene expression changes that occurred during the adaptation process. Results and Conclusions: The adaptation process was characterized by initial cell population growth arrest, and after that extensive cell death, followed by proliferation and long‐term survival of clonal cultures. Proliferation and cell cycle progression of the serum‐free cultures closely mimicked that of serum‐dependent cells. Affymetrix micro‐array technology was used to identify gene expression alterations that had occurred during the adaptation. Most changes were subtle, but frequently the genes with altered expression were involved in basal cellular functions such as cell division, cell cycle regulation, apoptosis and cell signalling. Some alterations were restored when the cells were transferred back to serum‐containing medium, indicating that expression of these genes was controlled by components in serum. Others were not, and may represent changes that were selected during the adaptation process. Among these were, for example, several genes within the Wnt signalling pathway.
A quantitative study of growth variability of tumour cell clones in vitro
Authors: Tomelleri C. , Milotti E. , Dalla Pellegrina C. , Perbellini O. , Del Fabbro A. , Scupoli M. T. , Chignola R.
Published: September 2010

Abstract.  Objectives: In this study, we quantify growth variability of tumour cell clones from a human leukaemia cell line. Materials and methods: We have used microplate spectrophotometry to measure growth kinetics of hundreds of individual cell clones from the Molt3 cell line. Growth rate of each clonal population has been estimated by fitting experimental data with the logistic equation. Results: Growth rates were observed to vary between different clones. Up to six clones with growth rates above or below mean growth rate of the parent population were further cloned and growth rates of their offspring were measured. Distribution of growth rates of the subclones did not significantly differ from that of the parent population, thus suggesting that growth variability has an epigenetic origin. To explain observed distributions of clonal growth rates, we have developed a probabilistic model, assuming that fluctuation in the number of mitochondria through successive cell cycles is the leading cause of growth variability. For fitting purposes, we have estimated experimentally by flow cytometry the average maximum number of mitochondria in Molt3 cells. The model fits nicely observed distributions in growth rates; however, cells in which mitochondria were rendered non‐functional (ρ0 cells) showed only 30% reduction in clonal growth variability with respect to normal cells. Conclusions: A tumour cell population is a dynamic ensemble of clones with highly variable growth rates. At least part of this variability is due to fluctuations in the initial number of mitochondria in daughter cells.
Melatonin and vitamin C administration ameliorate diazepam‐induced oxidative stress and cell proliferation in the liver of rats
Authors: El‐Sokkary G. H.
Published: September 2010

Abstract. Objective: Oxidative stress is a likely molecular mechanism in long‐term diazepam administration. The benefits of antioxidants (melatonin and vitamin C) against diazepam‐induced cell proliferation, DNA synthesis and oxidative damage were investigated in this study.Materials & methods: Four equal‐sized groups of male rats [control, diazepam (3 mg/kg), diazepam plus melatonin (5 mg/kg) and diazepam plus vitamin C (50 mg/kg)] were used. Levels of lipid peroxides (LPO), superoxide dismutase (SOD) activity and glutathione (GSH) concentration were measured in tissue homogenates. Cell proliferation and rate of DNA synthesis were detected by autoradiography.Results: Results documented increased labelling index,3H‐thymidine incorporation (DNA synthesis), LPO plus decrease in GSH levels and SOD activity in livers of diazepam‐administered rats versus those of controls. When melatonin and vitamin C were given to diazepam‐administered rats, they almost attenuated the increase of labelling index, DNA synthesis and LPO, and restored the levels of GSH and SOD activity.Conclusion: These results suggest long‐term hazard in use of drugs such as diazepam; they may be toxic and damage terminates in complex liver damage. Furthermore, melatonin and vitamin C may be useful in combating free radical‐induced liver injury resulting from hazard and/or repeated diazepam administration.
Inhibition of transient receptor potential canonical channels impairs cytokinesis in human malignant gliomas
Authors: Bomben V. C. , Sontheimer H. W.
Published: September 2010

Abstract.  Objectives: Glial‐derived primary brain tumours, gliomas, are among the fastest growing malignancies and present a huge clinical challenge. Research suggests an important, yet poorly understood, role of ion channels in growth control of normal and malignant cells. In this study, we sought to functionally characterize Transient Receptor Potential Canoncial (TRPC) channels in glioma cell proliferation. TRPC channels form non‐selective cation channels that have been suggested to represent a Ca2+ influx pathway impacting cellular growth. Materials and Methods: Employing a combination of molecular, biochemical and biophysical techniques, we characterized TRPC channels in glioma cells. Results: We showed consistent expression of four channel family members (TRPC‐1, ‐3, ‐5, ‐6) in glioma cell lines and acute patient‐derived tissues. These channels gave rise to small, non‐voltage‐dependent cation currents that were blocked by the TRPC inhibitors GdCl3, 2‐APB, or SKF96365. Importantly, TRPC channels contributed to the resting conductance of glioma cells and their acute pharmacological inhibition caused an ~10 mV hyperpolarization of the cells’ resting potential. Additionally, chronic application of the TRPC inhibitor SKF96365 caused near complete growth arrest. A detailed analysis, by fluorescence‐activated cell sorting and time‐lapse microscopy, showed that growth inhibition occurred at the G2+ M phase of the cell cycle with cytokinesis defects. Cells underwent incomplete cell divisions and became multinucleate, enlarged cells. Conclusions: Nuclear atypia and enlarged cells are histopathological hallmarks for glioblastoma multiforme, the highest grade glioma, suggesting that a defect in TRPC channel function may contribute to cellular abnormalities in these tumours.
Source of cell injected is a critical factors for short and long engraftment in xeno‐transplantation
Authors: Noia G. , Ligato M. S. , Cesari E. , Visconti D. , Fortunato G. , Tintoni M. , Mappa I. , Greco C. , Caristo M. E. , Bonanno G. , Corallo M. , Minafra L. , Perillo A. , Terzano M. , Rutella S. , Leone G. , Scambia G. , Michejda M. , Mancuso S.
Published: September 2010

Abstract. This study aims to investigate engraftment of human cord blood and foetal bone marrow stem cells after in utero transplantation via the intracoelomic route in the sheep. Here, we performed transplantation in 14 single and 1 twin sheep foetuses at 40–47 days of development, using a novel schedule for injection. (i) Single injection of CD34+ human cord blood stem cells via the coelomic route (from 10 to 50 × 104) in seven single foetuses. (ii) Single injection of CD34+ foetal bone marrow stem cells via the intracoelomic route with further numbers of cells (20 × 105 and 8 × 105, respectively) in three single and in one twin foetuses. (iii) Double fractioned injection (20–30 × 106) via the coelomic route and 20 × 106 postnatally, intravenously, shortly after birth of CD3‐depleted cord blood stem cells in four single foetuses. In the first group, three single foetuses showed human/sheep chimaerism at 1, 8 and 14 months after birth. In the second group, the twin foetuses showed human/sheep chimaerism at 1 month after birth. In the third group, only two out of four single foetuses that underwent transplantation showed chimaerism at 1 month. While foetal bone marrow stem cells showed good short‐term engraftment (1 month after birth), cord blood stem cells were able to persist longer in the ovine recipients (at 1, 8 and 14 months after birth).