bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for cross‐talk between M2 and M3 muscarinic acetylcholine receptors in the regulation of second messenger and extracellular signal‐regulated kinase signalling pathways in Chinese hamster ovary cells
Authors: Hornigold David C , Mistry Rajendra , Raymond Pamela D , Blank Jonathan L , John Challiss R A 
Published: April 2003

We have examined possible mechanisms of cross‐talk between the Gq/11‐linked M3 muscarinic acetylcholine (mACh) receptor and the Gi/o‐linked M2 mACh receptor by stable receptor coexpression in Chinese hamster ovary (CHO) cells. A number of second messenger (cyclic AMP, Ins(1,4,5)P3) and mitogen‐activated protein kinase (ERK and JNK) responses stimulated by the mACh receptor agonist methacholine were examined in CHO‐m2m3 cells and compared to those stimulated in CHO‐m2 and CHO‐m3 cell‐lines, expressing comparable levels of M2 or M3 mACh receptors.
Based on comparisons between cell‐lines and pertussis toxin (PTx) pretreatment to eliminate receptor‐Gi/o coupling, evidence was obtained for (i) an M2 mACh receptor‐mediated contribution to the predominantly M3 mACh receptor‐mediated Ins(1,4,5)P3 response and (ii) a facilitation of the inhibitory effect of M2 mACh receptor on forskolin‐stimulated cyclic AMP accumulation by M3 mACh receptor coactivation at low agonist concentrations (MCh 10−9–10−6 M).
The most profound cross‐talk effects were observed with respect to ERK activation. Thus, while MCh stimulated ERK activation in both CHO‐m2 and CHO‐m3 cells (pEC50 values: 5.64±0.09 and 5.57±0.16, respectively), the concentration–effect relation was approx 50‐fold left‐shifted in CHO‐m2m3 cells (pEC50: 7.17±0.07). In addition, the ERK response was greater and more sustained in CHO‐m2m3 cells. In contrast, only minor differences were seen in the time‐courses and concentration‐dependencies of JNK activation in CHO‐m3 and CHO‐m2m3 cells.
Costimulation of endogenous P2Y2 purinoceptors also caused an approx 10‐fold left‐shift in the MCh‐stimulated ERK response in CHO‐m2 cells, suggesting that the Gq/11/Gi/o interaction to affect ERK activation is not specific to muscarinic receptors.
PTx pretreatment of cells had unexpected effects on ERK activation by MCh in both CHO‐m2m3 and CHO‐m3 cells. Thus, in CHO‐m3 cells PTx pretreatment caused a marked left‐shift in the MCh concentration–effect curve, while in PTx‐treated CHO‐m2m3 cells the maximal responsiveness was decreased, but the potency of MCh was only slightly affected.
The data presented here strongly suggest that cross‐talk between M2 and M3 mACh receptors occurs at the level of both second messenger and ERK regulation. Further, these data provide novel insights into the involvement of Gi/o proteins in both positive and negative modulation of ERK responses evoked by G protein‐coupled receptors.

British Journal of Pharmacology (2003) 138, 1340–1350. doi:10.1038/sj.bjp.0705178
Breast cancer and serum organochlorine residues
Authors: Charlier C , Albert A , Herman P , Hamoir E , Gaspard U , Meurisse M , Plomteux G 
Published: April 2003

Background:Controversy still exists about the breast carcinogenic properties in humans of environmental xenoestrogens (organochlorines), justifying new investigations.Aims:To compare the blood levels of total dichlorodiphenyltrichloroethane (DDT) and hexachlorobenzene (HCB) in samples collected at the time of breast cancer discovery, in order to avoid the potential consequences of body weight change (after chemotherapy or radiotherapy) on the pesticide residue levels.Methods:Blood levels of HCB and total DDT (we calculated total DDT concentrations by adding all DDT and DDE isomers) were compared in 159 women with breast cancer and 250 presumably healthy controls. Risk of breast cancer associated with organochlorine concentration was evaluated.Results:Mean levels of total DDT and HCB were significantly higher for breast cancer patients than for controls. No differences in serum levels of total DDT or HCB were found between oestrogen receptor positive and oestrogen receptor negative patients with breast cancer.Conclusions:These results add to the growing evidence that certain persistent pollutants may occur in higher concentrations in blood samples from breast cancer patients than controls.
Increased mortality odds ratio of male liver cancer in a community contaminated by chlorinated hydrocarbons in groundwater
Authors: Lee L J-H , Chung C-W , Ma Y-C , Wang G-S , Chen P-C , Hwang Y-H , Wang J-D 
Published: April 2003

Aims:To investigate the association between cancer mortality risk and exposure to chlorinated hydrocarbons in groundwater of a downstream community near a contaminated site.Methods:Death certificates inclusive for the years 1966–97 were collected from two villages in the vicinity of an electronics factory operated between 1970 and 1992. These two villages were classified into the downstream (exposed) village and the upstream (unexposed) according to groundwater flow direction. Exposure classification was validated by the contaminant levels in 49 residential wells measured with gas chromatography/mass spectrometry. Mortality odds ratios (MORs) for cancer were calculated with cardiovascular-cerebrovascular diseases as the reference diseases. Multiple logistic regressions were performed to estimate the effects of exposure and period after adjustment for age.Results:Increased MORs were observed among males for all cancer, and liver cancer for the periods after 10 years of latency, namely, 1980–89, and 1990–97. Adjusted MOR for male liver cancer was 2.57 (95% confidence interval 1.21 to 5.46) with a significant linear trend for the period effect.Conclusion:The results suggest a link between exposure to chlorinated hydrocarbons and male liver cancer risk. However, the conclusion is limited by lack of individual information on groundwater exposure and potential confounding factors.
Study of ${\rm B^0_s}$ oscillations and measurement of the inclusive b semileptonic branching ratio in ALEPH
Authors: SCIABÀ ANDREA 
Published: April 2003

An improved search for [Formula: see text] oscillations is performed on b hadron decays collected by the ALEPH experiment during 1991-1995 with three analyses, using respectively an inclusive sample of semileptonic b decays, a sample of [Formula: see text] events and a sample of fully reconstructed [Formula: see text] decays. This update results in a significant improvement over previously published results. A precise measurement of the inclusive semileptonic b branching ratio is performed, by exploiting the correlation between the lepton charge and an inclusive charge estimator in the opposite hemisphere, thus allowing to reduce the dependence on the b-decay modelling.
Ezetimibe for Management of Hypercholesterolemia
Authors: Mauro Vincent F , Tuckerman Chad E 
Published: April 2003

OBJECTIVE: To review the primary literature describing the pharmacology of ezetimibe and clinical trials investigating its use in the management of hypercholesterolemia. DATA SOURCES: A MEDLINE search (1966–December 2002) was performed using SCH 48461, SCH 58235, ezetimibe, and 2-azetidinone as key words. English-language articles were identified and the references of these articles were used to further identify pertinent articles and abstracts. Given the paucity of published articles available on ezetimibe, many of the references cited are abstracts. STUDY SELECTION: All acquired articles that discussed the pharmacology, pharmacokinetics, chemistry, and clinical efficacy of ezetimibe were reviewed. DATA EXTRACTION: Articles were selected based on content regarding the medicinal chemistry, pharmacology, and clinical use of ezetimibe. DATA SYNTHESIS: Ezetimibe, approved for use in October 2002, belongs to a new class of antihyperlipidemic agents that uniquely inhibit the absorption of cholesterol by inhibiting the cholesterol transport system located within intestinal cell walls. In humans, ezetimibe reduced cholesterol absorption by >50%. In clinical trials, ezetimibe 10 mg/d reduced low-density lipoprotein cholesterol (LDL-C) by approximately 18% and further enhanced the LDL-C–lowering effect of statin medications by an additional 15–20%. In addition, ezetimibe lowered triglycerides about 5% and increased high-density lipoprotein cholesterol (HDL-C) approximately 3%. Ezetimibe is well tolerated. At present, no serious adverse effects have been directly attributable to ezetimibe. CONCLUSIONS: Based on the data currently available, it appears that ezetimibe has a potential role in the treatment of primary hypercholesterolemia; however further data are needed to determine its long-term tolerability and efficacy. The potential roles for ezetimibe include its concurrent use with a statin to further enhance the lowering of LDL-C. Other possible roles for ezetimibe include its concurrent use with a statin to permit a lowering of statin dosage to avoid statin-related complications or its use as monotherapy to treat hypercholesterolemia when statin use cannot be tolerated or is contraindicated. Outcome data demonstrating that cardiovascular morbidity and/or mortality are reduced by ezetimibe therapy have yet to be generated.
Holocene Relative Sea-Level History of Novaya Zemlya, Russia, and Implications for Late Weichselian Ice-Sheet Loading
Authors: Zeeberg JaapJan , Lubinski David J. , Forman Steven L. 
Published: April 2003

AbstractWe present six new radiocarbon-dated emergence curves that provide a detailed record of postglacial emergence of northern Novaya Zemlya and ages which constrain the emergence of Vaygach Island in the southern archipelago. Radiocarbon ages onHiatellasp. from a lateral moraine in Russkaya Gavan' and abundances of foraminifea in a marine core from Nordenskiold Bay, 300 km south of our study area, indicate that coastal deglaciation occurred prior to ∼10,000 cal yr B.P. However, postglacial emergence commenced ∼7000 cal yr B.P., with stabilization of global sea level. The total emergence is 13–11 m above sea level (asl) with apparent uplift rates of 1–2 mm/yr for the past 2000 yr, indicating modest glacier loads (<1 km), early (>11,000 cal yr B.P.) deglaciation, or both. The isobase pattern, showing no east–west tilt across Novaya Zemlya, and offshore moraines suggest a separate ice-dispersal center over Novaya Zemlya for the later stages of the Late Weichselian glacial cycle and possibly earlier.
Holocene Lake-Level Fluctuations of Lake Aricota, Southern Peru
Authors: Placzek Christa , Quade Jay , Betancourt Julio L. 
Published: April 2003

AbstractLacustrine deposits exposed around Lake Aricota, Peru (17° 22′S), a 7.5-km2 lake dammed by debris flows, provide a middle to late Holocene record of lake-level fluctuations. Chronological context for shoreline deposits was obtained from radiocarbon dating of vascular plant remains and other datable material with minimal 14C reservoir effects (<350 yr). Diatomites associated with highstands several meters above the modern lake level indicate wet episodes. Maximum Holocene lake level was attained before 6100 14C yr B.P. and ended ∼2700 14C yr B.P. Moderately high lake levels occurred at 1700 and 1300 14C yr B.P. The highstand at Lake Aricota during the middle Holocene is coeval with a major lowstand at Lake Titicaca (16°S), which is only 130 km to the northeast and shares a similar climatology. Comparisons with other marine and terrestrial records highlight emerging contradictions over the nature of mid-Holocene climate in the central Andes.
Raised Coral Terraces at Malakula, Vanuatu, Southwest Pacific, Indicate High Sea Level During Marine Isotope Stage 3
Authors: Cabioch Guy , Ayliffe Linda K. 
Published: April 2003

AbstractThe occurrence of a series of raised coral reefs from the uplifted island of Malakula (Vanuatu, SW Pacific) provide an opportunity to examine sea-level fluctuations over at least the past 120,000 years. Thirteen fossil coral samples from Malakula were analyzed by the thermal ionization mass spectrometry (TIMS) U/Th dating technique, yielding information on sea levels during late marine isotope stage 3 and early stage 4. Our findings are in good agreement with sea-level estimates from raised coral terraces in Papua New Guinea and the recent sea-level reconstruction from the deep-sea sedimentary δ18O records. In particular, our coral data appear to confirm that sea levels at about 45,000–50,000 yr B.P. were only 30 to 60 m below the present level. Combined with other evidence of sea-level change, our data provide a strong case for much higher sea levels and therefore markedly reduced continental ice volume at 47,000 to 49,000 years ago.
Late Quaternary Iceberg Rafting along the Antarctic Peninsula Continental Rise and in the Weddell and Scotia Seas
Authors: Ó Cofaigh Colm , Dowdeswell Julian A. , Pudsey Carol J. 
Published: April 2003

AbstractSediment cores from the continental rise west of the Antarctic Peninsula and the northern Weddell and Scotia Seas were investigated for their ice-rafted debris (IRD) content by lithofacies logging and counting of particles >0.2 cm from core x-radiographs. The objective of the study was to determine if there are iceberg-rafted units similar to the Heinrich layers of the North Atlantic that might record periodic, widespread catastrophic collapse of basins within the Antarctic Ice Sheet during the Quaternary. Cores from the Antarctic Peninsula margin contain prominent IRD-rich units, with maximum IRD concentrations in oxygen isotope stages 1, 5, and 7. However, the greater concentration of IRD in interglacial stages is the result of low sedimentation rates and current winnowing, rather than regional-scale episodes of increased iceberg rafting. This is also supported by markedly lower mass accumulation rates (MAR) during interglacial periods versus glacial periods. Furthermore, thinner IRD layers within isotope stages 2–4 and 6 cannot be correlated between individual cores along the margin. This implies that the ice sheet over the Antarctic Peninsula did not undergo widespread catastrophic collapse along its western margin during the late Quaternary (isotope stages 1–7). Sediment cores from the Weddell and Scotia Seas are characterized by low IRD concentrations throughout, and the IRD signal generally appears to be of limited regional significance with few strong peaks that can be correlated between cores. Tentatively, this argues against pervasive, rapid ice-sheet collapse around the Weddell embayment over the last few glacial cycles.
The Taylor Dome Antarctic 18O Record and Globally Synchronous Changes in Climate
Authors: Grootes Pieter M. , Steig Eric J. , Stuiver Minze , Waddington Edwin D. , Morse David L. , Nadeau Marie-Josée 
Published: April 2003

AbstractThe 18O/16O profile of a 554-m long ice core through Taylor Dome, Antarctica, shows the climate variability of the last glacial–interglacial cycle in detail and extends at least another full cycle. Taylor Dome shares the main features of the Vostok record, including the early climatic optimum with later cool phase of the last interglacial period in Antarctica. Taylor Dome δ18O fluctuations are more abrupt and larger than those at Vostok and Byrd Station, although still less pronounced than those of the Greenland GISP2 and GRIP records. The influence of the Atlantic thermohaline circulation on regional ocean heat transport explains the partly “North Atlantic” character of this Antarctic record. Under full glacial climate (marine isotope stage 4, late stage 3, and stage 2), this marine influence diminished and Taylor Dome became more like Vostok. Varying degrees of marine influence produce climate heterogeneity within Antarctica, which may account for conflicting evidence regarding the relative phasing of Northern and Southern Hemisphere climate change.
Determination of 36Cl Production Rates Derived from the Well-Dated Deglaciation Surfaces of Whidbey and Fidalgo Islands, Washington
Authors: Swanson Terry W. , Caffee Marc L. 
Published: April 2003

AbstractThe 36Cl dating method is increasingly being used to determine the surface-exposure history of Quaternary landforms. Production rates for the 36Cl isotopic system, a critical component of the dating method, have now been refined using the well-constrained radiocarbon-based deglaciation history of Whidbey and Fidalgo Islands, Washington. The calculated total production rates due to calcium and potassium are 91±5 atoms 36Cl (g Ca)−1 yr−1 and are 228±18 atoms 36Cl (g K)−1 yr−1, respectively. The calculated ground-level secondary neutron production rate in air, Pf(0), inferred from thermal neutron absorption by 35Cl is 762±28 neutrons (g air)−1 yr−1 for samples with low water content (1–2 wt.%). Neutron absorption by serpentinized harzburgite samples of the same exposure age, having higher water content (8–12 wt.%), is ∼40% greater relative to that for dry samples. These data suggest that existing models do not adequately describe thermalization and capture of neutrons for hydrous rock samples. Calculated 36Cl ages of samples collected from the surfaces of a well-dated dacite flow (10,600–12,800 cal yr B.P.) and three disparate deglaciated localities are consistent with close limiting calibrated 14C ages, thereby supporting the validity of our 36Cl production rates integrated over the last ∼15,500 cal yr between latitudes of 46.5° and 51°N. Although our production rates are internally consistent and yield reasonable exposure ages for other localities, there nevertheless are significant differences between these production rates and those of other investigators.
A 4000-Year Lacustrine Record of Environmental Change in the Southern Maya Lowlands, Petén, Guatemala
Authors: Rosenmeier Michael F. , Hodell David A. , Brenner Mark , Curtis Jason H. , Guilderson Thomas P. 
Published: April 2003

AbstractA 4000-yr sediment core record from Lake Salpetén, Guatemala, provides evidence for Maya-induced forest clearance and consequent soil erosion between ∼1700 cal yr B.C. and 850 cal yr A.D. Radiocarbon ages of wood, seeds, and charcoal support an age-depth model with average errors of ±110 cal yr. Relatively low carbonate δ18O values between 1300 and 400 cal yr B.C. coincide with pollen evidence for forest loss, consistent with increased surface and groundwater flow to the lake. Minimum δ18O values between 400 cal yr B.C. and 150 cal yr A.D. suggest a high lake level, as do 14C-dated aquatic gastropods as much as 7.5 m above the present lake stage. High lake levels resulted from reduced evaporation-to-precipitation ratios, increased hydrologic input caused by anthropogenic deforestation, or both. The Preclassic abandonment (150 A.D.) and Early Classic/Late Classic boundary (550 A.D.) are marked by relatively high δ18O values indicating reduced lake levels. Oxygen isotope composition increased further coincident with the Terminal Classic Maya demographic decline between 800 and 900 A.D. This period of high δ18O may have been caused by the greater aridity that has been documented in northern Yucatán lakes or by decreased hydrologic input to the lake as a consequence of forest recovery. Reduced soil erosion after 850 cal yr A.D. coincided with the Terminal Classic Maya demographic decline and permitted forest recovery and resumption of organic sedimentation.
Changes in the Bathymetry and Volume of Glacial Lake Agassiz between 9200 and 7700 14C yr B.P.
Authors: Leverington David W. , Mann Jason D. , Teller James T. 
Published: April 2003

AbstractComputer reconstructions of the bathymetry of the lake were used to quantify variations in the size and form of Lake Agassiz during its final two phases (the Nipigon and Ojibway phases), between about 9200 and 7700 14C yr B.P. (ca. 10,300–8400 cal yr B.P.). New bathymetric models for four Nipigon Phase stages (corresponding to the McCauleyville, Hillsboro, Burnside, and The Pas strandlines) indicate that Lake Agassiz ranged between about 19,200 and 4600 km3 in volume and 254,000 and 151,000 km2 in areal extent at those times. A bathymetric model of the last (Ponton) stage of the lake, corresponding to the period in which Lake Agassiz was combined with glacial Lake Ojbway to the east, shows that Lake Agassiz–Ojibway was about 163,000 km3 in volume and 841,000 km2 in areal extent prior to the final release of lake waters into the Tyrrell Sea. During the Nipigon Phase, a number of catastrophic releases of water from Lake Agassiz occurred as more northerly (lower) outlets were made available by the retreating southern margin of the Laurentide Ice Sheet; we estimate that each of the four newly investigated Nipigon Phase releases involved water volumes of between 1600 and 2300 km3. The final release of Lake Agassiz waters into the Tyrrell Sea at about 7700 14C yr B.P. is estimated to have been about 163,000 km3 in volume.
Holocene Climate Reconstructions from the Fennoscandian Tree-Line Area Based on Pollen Data from Toskaljavri
Authors: Seppä Heikki , Birks H.J.B 
Published: April 2003

AbstractDue to its location on the eastern North Atlantic seaboard, the Fennoscandian tree-line area is an ideal area to use biological proxies to assess the relative roles of the Scandinavian ice sheet and of oceanic, atmospheric, and astronomic forcings on regional climate history. Here we report pollen-based July mean temperature (Tjul) and annual precipitation (Pann) reconstructions from a sediment core from a high-altitude tree-line lake in northwestern Finland. The reconstructions suggest that at 9600–8300 cal yr B.P. Tjul values were low but steadily rising while Pann was high. The period of warmest summers, with Tjul values ca. 1.8°–1.6°C higher than at present, occurred at ca. 8000–6500 cal yr B.P. Since then climate has become gradually cooler. Tjul values during the “Medieval Warm Period” (ca. 1400–1000 cal yr B.P.) were ca. 0.8°C higher that at present but decreased rapidly to the low “Little Ice Age” levels at 800 cal yr B.P. We compare these results with an earlier pollen-based climate reconstruction from the same region. The reconstructions indicate a similar general Holocene Tjul pattern with lower values in the reconstruction from the high-altitude lake. However, most of the small-scale variations are not synchronous, suggesting that they may represent noise rather than signal in our data.
GnRH analogues as an adjuvant therapy for ovarian cancer patients
Authors: Rzepka‐Górska I. , Chudecka‐Glaz A. , Kosmider M. , Malecha J. 
Published: April 2003

AbstractObjectives: Lowering gonadotropin levels with gonadotropin‐releasing hormone (GnRH) analogues in patients with ovarian cancer remains open to debate. The aim of this study was to assess the results of treatment in stage III and stage IV ovarian cancer patients who had surgery supplemented with chemotherapy, radiotherapy, and GnRH analogues. Gonadotropin levels were monitored during treatment. Methods: The study group comprised 69 patients aged 27–70 years, stratified according to the type of treatment. The overall disease‐free, 5‐year survival rates and the frequency of remissions were analyzed. Hormonal tests [follicle‐stimulating hormone (FSH) and luteinizing hormone (LH)] were performed in 58 patients. Associations were checked between gonadotropin levels, clinical findings, and survival. The results were statistically compared. Results: Statistically significant differences were noted when chemotherapy was supplemented with GnRH analogues and/or radiotherapy. Administration of GnRH analogues resulted in significantly lower levels of LH than of FSH. Levels of FSH were significantly lower in patients surviving at least 5 years or in complete remission at the time of this study. Conclusions: Combined therapy can produce favorable results in late‐stage ovarian cancer, and GnRH analogues have an important role in treatment strategy.