bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleation events in the continental boundary layer: Long‐term statistical analyses of aerosol relevant characteristics
Authors: Boy M. , Rannik Ü. , Lehtinen K. E. J. , Tarvainen V. , Hakola H. , Kulmala M.
Published: November 2003

This paper reflects intensive data analyses from the Station for Measuring Forest Ecosystem‐Atmosphere Relations (SMEAR II) field measurement station in Hyytiälä, Finland, for the years 2000 and 2001. The results can be divided into two main parts: first, a study about common trends and correlation between concentration of particles with Dp = 3–6 nm and different parameters; and second, the calculation of different aerosol relevant characteristics. The first section of this work showed that we can differentiate between two kinds of variables: Solar radiation and the reciprocal condensation sink values correlate in their daily profiles with the number concentrations of the nucleation mode particles. Also, the daytime mean values (0900 to 1500 LT) of these parameters correlate during the 2 years with the small particles. Particle flux, vertical wind variance, or ozone are marginal correlated with the particle concentrations during single event days; however, they show the same yearly behavior as solar radiation or the reciprocal condensation sink values. In the second part the condensing vapor source rates and concentrations and the growth and the nucleation rates were calculated on the basis of measured monoterpenes and sulphur dioxide concentrations. Afterward, these values were compared with results obtained using measured particle number concentrations. The estimated oxidation products of monoterpenes are able to explain 8–50% from observed growth rates.
Upstream dams and downstream water allocation: The case of the Hadejia‐Jama'are floodplain, northern Nigeria
Authors: Barbier Edward B.
Published: November 2003

This paper models the economic and hydrological impacts of upstream water diversion on downstream floodplain activities. The model is illustrated and applied to the example of the Hadejia‐Jama'are River Basin, northern Nigeria. Full implementation of all the upstream dams and large‐scale irrigation schemes in the river basin would produce losses of US$20.2–20.9 million in present value terms in terms of flooplain agriculture, forestry, and fishing. The associated annual losses from declining groundwater levels in surrounding areas would be around $1.2 million for tube well irrigation and $4.76 million for domestic water consumption. The introduction of a regulated flooding regime for upstream dams would probably protect the groundwater recharge function of the downstream floodplain and reduce substantially the losses to agriculture, forestry, and fishing to around $15.4–16.5 million.
The domestic chicken in the Tylos burials of Bahrain
Authors: MacDonald Kevin C.
Published: November 2003

Four out of fifteen burials from the Tylos period (c.200 BC – AD 200), presented by Toft Jensen in this number of AAE, contained bones of the domestic chicken (Gallus gallus) and represent the earliest remains of that species found on the island of Bahrain.
Tectonic control of fan size: the importance of spatially variable subsidence rates
Authors: Whipple Kelin X. , Trayler Carolyn R.
Published: November 2003

We study the geophysical controls on the size of alluvial fans. Simple relationships between catchment characteristics, sediment yield, subsidence patterns and fan size are developed. As predicting fan size is essentially a conservation of mass problem, our analysis is general, applying to all types of fan landform. The importance of spatially variable subsidence rates has gone largely unrecognized in previous studies of modern fans. Here we stress that the distribution of subsidence rates in the depositional basin is a primary control on relative fan size. Both free coefficients in the oft‐cited power‐law correlation of fan area and catchment area can be shown to be set primarily by the tectonic setting, taken to include source area uplift rate and the subsidence distribution in the depositional basin. In the case of a steady‐state landscape, relative fan size is shown to be independent of both climate and source lithology; only during times of significant departure from steady state can relative fan size be expected to vary with either climate or source lithology. Transients associated with (1) a sudden increase in rock uplift rate, (2) a sudden change in climate and (3) the unroofing of strata with greatly differing erodibilities may produce variation of relative fan areas with both climate and source lithology. Variation of relative fan size with climate or lithology, however, requires that catchment–fan system response to perturbations away from steady state is sensitive to climate and lithology. Neither the strength of transient system responses nor their sensitivity to climate or lithology are known at present. Furthermore, internal feedbacks can significantly dampen any climatic or lithological effect. Thus theoretical considerations of the importance of climatic and lithological variables are inconclusive, but suggest that climatic and lithological effects are probably of secondary importance to tectonic effects. Field data from an unsteady landscape in Owens Valley, California, support and illustrate theoretical predictions regarding tectonic control of fan size. Field data from Owens Valley allow, but do not prove, a secondary dependence on source lithology. In addition, the Owens Valley field data indicate no relationship between relative fan size and climate. Headward catchment growth and enhanced sediment bypassing of fans during times of increased sediment yield (glacial) are put forward as plausible explanations.
Estimating palaeorelief from detrital mineral age ranges
Authors: Stock Jonathan D. , Montgomery David R.
Published: November 2003

We propose a method that uses the increase in mineral age with elevation in some bedrock landscapes to quantify palaeotopographic relief from the age range of detrital minerals in coeval sediment. We use the rate at which mineral age changes with elevation (its age‐gradient, dt/dz) and its age range (Δt) in the sediment to invert for relief: Δz=Δt/(dt/dz). Relief inversion requires a single‐grain dating precision high enough that detrital grains originate from resolvably different elevations (e.g. laser microprobe 40Ar/39Ar fusion). The technique assumes that there is no change in mineral age during erosion and transport, that sediment is mixed well enough and (or) sampled sufficiently to capture the extrema of mineral ages, and that isochrons were horizontal during erosion. Subject to these constraints, inversion of the age range of individual grains in synorogenic sedimentary sequences allows quantitative estimation of relief development for eroded mountain ranges. This method provides the only direct quantitative measure of palaeorelief, a poorly constrained, but important aspect of many geological, geomorphological and geodynamic models.
Axial–transverse fluvial interactions in half‐graben: Plio‐Pleistocene Palomas Basin, southern Rio Grande Rift, New Mexico, USA
Authors: Leeder M. R. , Mack G. H. , Salyards S. L.
Published: November 2003

Accurate magnetostratigraphic dating of Plio‐Pleistocene alluvium in the Palomas half‐graben permits correlation of transverse and axial deposits, thus enabling analysis of the movement of alluvial facies belts in time and space for the first time. Northern areas show evidence for basinward progradation of footwall‐sourced Matuyama‐age alluvial fan deposits over axial channel belt deposits of the ancestral Rio Grande, despite both deposits having similar deposition rates. This gradual ‘forced’ westward migration of the axial belt was in opposition to ongoing eastward growth of hangingwall‐sourced fans and tectonic tilt imposed by the bounding Caballo normal fault. Fan growth was coincident with a recently proposed gradual climatic shift that may have increased sediment flux out of transverse catchments. It is also possible that continuing tectonic footwall uplift and divided retreat caused catchment areas to increase, contributing to these trends.

Southern areas of the Palomas half‐graben feature late Gilbert/early Gauss deposits indicative of rapid westwards progradation of large low‐gradient, footwall‐sourced fans over axial deposits. This ‘forced’ migration of the ancestral Rio Grande may have occurred due to footwall catchment and fan growth consequent upon initiation and growth of the Red Hills Fault. Subsequent eastward movement of the axial channel belt in late Gauss and Matuyama times overwhelmed these large fans. We attribute this to continued tilting on the Red Hills Fault and to development of the Jornada Fault to the south‐east, the axial river belt avulsing north and eastwards through a developing Red Hills/Jornada crossover transfer zone.

We conclude generally that facies architecture of axial and transverse elements in half‐graben must reflect both climatic influences and the effects of fault development. Careful field mapping, accurate dating and palaeoclimatic studies are all necessary to determine the relative importance of these controls. Although adequate as broad guides, previous purely ‘fixist’ tectonosedimentary models allow for no fault growth, decay or climatic modulation of facies trends and are thus generally inadequate to explain important aspects rift basin stratigraphy.
Palaeohydraulics revisited: palaeoslope estimation in coarse‐grained braided rivers
Authors: Paola Chris , Mohrig David
Published: November 2003

Methods for estimating palaeoslope from fluvial deposits have been available for some time, but new data and improved understanding of the relevant physical processes afford the possibility of improving existing methods, and the emerging field of quantitative stratigraphy provides a new context for the results. Here we focus on deriving palaeoslope estimates for coarse‐grained fluvial deposits. These estimates can be used in basin analyses to constrain the magnitude of the slope change necessary for a given deflection of palaeocurrents, to constrain temporal and spatial variation in basin subsidence rate, and to provide a surface datum for use in sediment‐backstripping calculations. The algorithm we derive to estimate palaeoslope applies to rivers that self‐adjust through variations in channel width to maintain a temporally and spatially averaged bed shear stress equal to some constant multiple of the critical shear stress for initial motion of bed sediment. Data from modern coarse‐grained rivers with minimal bank cohesion and form resistance suggest that this boundary shear stress is equal to about 1.4 times the critical shear stress for movement of the median‐sized clast of the surface layer. The key sedimentological criteria for recognition of systems appropriate for this type of analysis are: (1) field relations suggesting that channel banks formed in effectively noncohesive gravel (i.e. free of clay‐size sediment and plant roots); (2) absence of significant volumes of dune‐derived cross‐stratification; and (3) absence of indicators of extremely rapid, flash‐flood‐type deposition. The basic input data for a palaeoslope calculation are spatially averaged estimates of palaeodepth and median grain size. The most important aspect of data collection is that the depth and grain‐size estimates should be determined independently by random sampling over the whole outcrop. Joint analysis of data from appropriate modern rivers and of errors associated with palaeodepth and grain‐size estimates indicates that in coarse‐grained braided‐river deposits, palaeoslope can be estimated to within a factor of 2.
The kinematics and pattern of escarpment retreat across the rifted continental margin of SE Australia
Authors: Seidl Michele A. , Weissel Jeffrey K. , Pratson Lincoln F.
Published: November 2003

Rifted continental margins generally display an interior, low‐relief, highly weathered upland area and a deeply incised, high‐relief coastal area. The boundary between the two zones is commonly demarcated by an abrupt, seaward‐facing escarpment. We investigate the rate and pattern of escarpment erosion and landscape evolution along the passive margin of south‐east Australia, in the region of the New England Tableland. The process of rifting is shown to initiate an escarpment across which rivers flow, resulting in an escarpment that takes the form of dramatic, elongated gorges. Using a mass balance approach, we estimate the volume/unit length of continental material eroded seaward of the escarpment to be between 41 and 68 km2, approximately an order of magnitude less than the 339 km2 of terrigenous sediments calculated to have been deposited offshore, but consistent with earlier denudation estimates based on apatite fission track data. On the bedrock rivers draining the New England Tableland region, the escarpment is manifested as a series of sharp knickpoints punctuating the river longitudinal profiles. The knickpoints are situated the same distance upstream along the different channels and uniform escarpment retreat rates on the order of 2 km Myr−1 are estimated, despite some differences in bedrock lithologies. Gorge head migration appears to be very important as a bedrock incision mechanism. Field observations indicate a coupling between escarpment retreat and knickpoint propagation, bedrock channel incision, and hillslope development.
Plan‐view curvature of foreland basins and its implications for the palaeostrength of the lithosphere underlying the western Alps
Authors: Sinclair H. D.
Published: November 2003

In zones of continental collision, three methods can be used to calculate the strength of the underthrust lithosphere: (1) a forward model approach to the Bouguer gravity field, (2) an inverse model of the gravity and topography using admittance techniques, or (3) a forward model of the stratigraphic infill of the foreland basin to estimate the cross‐sectional profile of the downflexed plate. The use of reconstructed stratigraphy has the potential to yield values for the equivalent elastic thickness (Te) of the cratonic lithosphere at varying slices in geological time, and hence enable an insight into the longer term (10–50 Myr) mechanical behaviour of the continental lithosphere.

Calculations of Te based on isopachs of foreland basin stratigraphy use sea level as a reference line to estimate the basement deflection, and therefore are limited to using stratigraphy which records shallow marine or coastal sedimentation. A new empirical approach is applied to evaluating ancient Te values using the reconstructed palaeocurvature of the basin in plan view. The radius of curvature of 12 curvilinear foreland basins is plotted against their documented Te values and shows a linear relationship. The maximum Te value for a given radius of curvature can also be plotted as a straight line. The palaeocurvature of reconstructed basins can then be compared with the plots, and estimates of likely maximum Te values may be obtained.

During Eocene times, the underfilled foreland basin of the Alps was characterized on its cratonic edge by the deposition of Nummulite‐rich limestones. Palaeogeographical reconstructions of the Nummulitic Limestones enable estimates of the palaeocurvature of the cratonic margin of the Alpine foreland basin during the Eocene. By comparing this value with the curvature of documented basins, it is possible to suggest that the European lithosphere underlying the western Alps had an effective elastic thickness of no greater than 17 km during the Eocene. It has been suggested that the transition in the depositional state of the Alpine foreland basin from an underfilled to a filled state during middle Oligocene times was linked to a thickening of the continental lithosphere associated with the effective ramp of the Tethyan passive margin. The Te value of less than 17 km during the underfilled stage combined with a value of 10±5 km for the later filled stage at 17 Ma does not lend support to this hypothesis.
Tectonic geomorphology of the Ash Hill fault, Panamint Valley, California
Authors: Densmore Alexander L. , Anderson Robert S.
Published: November 2003

ABSTRACT

Panamint Valley, in eastern California, is an extensional basin currently bounded by active, dextral‐normal oblique‐slip faults. There is considerable debate over the tectonic and topographic evolution of the valley. The least‐studied structure, the Ash Hill fault, runs for some 50 km along the valley’s western edge, and active strands of the fault continue south into the neighbouring Slate Range. Vertical displacement on the fault is valley‐side up, creating topography that conflicts with the gross morphology of the valley itself. We use this topography, along with kinematic and geological markers, to constrain the Quaternary slip rate and orientation of the Ash Hill fault. The fault offsets all but the active channel deposits in the valley, and slickenlines indicate a strike‐slip to dip‐slip ratio of 3.5:1. An offset volcanic unit dated at 4 Ma provides a minimum slip rate of 0.3±0.1 mm yr−1, and a long‐term strike‐slip to dip‐slip ratio of 5.2:1. Slip on the fault has warped a palaeolake shoreline within the valley. Simple elastic dislocation modelling of the vertical deformation of the shoreline suggests total fault slip of ≈60 m, valley‐side up. The shoreline probably dates to 120–150 ka, implying a late Quaternary slip rate of 0.4–0.5 mm yr−1. We suggest two possible mechanisms for the apparently anomalous slip behaviour of the Ash Hill fault. The fault may be a listric structure related to the proposed low‐angle fault underlying Panamint Valley. Alternatively, the Ash Hill fault is a high‐angle fault, implying that the valley is currently bounded by high‐angle dextral‐slip faults. Lack of detailed subsurface information precludes any knowledge of the true relationships between the presently active faults.
The Rioja Trough (N Spain): tectosedimentary evolution of a symmetric foreland basin
Authors: Muñoz‐Jiménez A. , Casas‐Sainz A. M.
Published: November 2003

ABSTRACT

The Rioja Trough is the foreland basin of the western Pyrenees (to the north) and the Cameros‐Demanda Massif (to the south). This E–W elongated trough is about 120×35 km. It was filled with Tertiary continental deposits (upper Eocene to upper Miocene), reaching thicknesses between 2500 and 5000 m. Both margins of the Rioja Trough are large thrusts with horizontal displacements of more than 20 km basinward. Rocks that fill the basin originated in alluvial fan and playa‐lake environments, with conglomerates in the proximal sectors grading into sandstones, mudstones, lacustrine limestones and evaporites in distal sectors. The Tertiary series are horizontal in the central parts of the basin, with several E–W monoclines caused by north‐verging thrusts in the basement of the basin. Near the basin margins, the Tertiary units are folded and thrusted, with several syntectonic unconformities. Calculated velocities for the Cameros‐Demanda thrust range from 0.02 to1.1 mm yr−1 (average 0.7 mm yr−1). The sedimentation rate near the southern basin margin varies between 2 and 20 cm 1000 yr−1 (average 10 cm 1000 yr−1). Deposition in the Rioja Trough was strongly controlled by tectonic activity throughout the Tertiary. Eight tectosedimentary units (R1 to R8) have been characterized. These are bounded by angular unconformities at the margins and breaks in the vertical trend of the sedimentary record toward the basin centre. Every tectosedimentary unit (except R6 and R8) shows a fining‐upward/coarsening‐upward trend, corresponding to tectonic retrogradations and progradations, respectively. The main source area during the Palaeogene was the Cameros‐Demanda Massif, whose unroofing sequence was strongly dependent on tectonic activity. During the Neogene a longitudinal WNW–ESE drainage system, with short alluvial fans in the northern and southern margins, developed. The final shape and the evolution of the Rioja Trough are the result of crustal flexure in the northern border of the Iberian plate, linked to the emplacement of the southern Pyrenean thrust system, and intraplate thrusting with basement uplift at its southern margin.
Tectonic modelling of the Middle Jurassic synrift stratigraphy in the Oseberg–Brage area, northern Viking Graben
Authors: Ter Voorde M. , Ravnås R. , Færseth R. , Cloetingh S.
Published: November 2003

A finite difference model, allowing for episodic movements along different faults, is used to examine the effect of tectonics on the stratigraphic signature in the Oseberg–Brage area in the northern Viking Graben. Constraints are provided by local exploration and production well data and 3‐D seismic coverage, and a regional depth‐converted seismic line.

In the modelling, we focus on the influence of varying rates of fault movement on stratigraphic signatures such as upflank unconformities and changes in layer thickness. We couple the basinwide features of the northern Viking Graben with the fault‐block‐scale features of the Oseberg–Brage area by using parameter constraints derived by large‐scale modelling as input for the local‐scale model. In addition, subsidence patterns resulting from the basinwide model were used as background subsidence for the fault block model of the Oseberg–Brage area.

The model results indicate that the alternating activation of different faults with varying extension rates can cause stratigraphic features such as unconformities, condensation and onlap/offlap patterns. Onlap occurs during periods of low extension rates. An increase in extension rate along a fault causes footwall uplift, resulting in condensation or upflank erosion yielding unconformities. This influence can also affect sub‐basins further away from the fault. Downdip layer thickening reflects the local tilting of fault blocks.

The coupling of the local and regional scales turns out to be essential in explaining the stratigraphy of the Oseberg–Brage area: basinward and, notably, updip layer thickening as observed on some of the fault blocks can only be explained by activity of the boundary fault on the opposing, western margin of the northern Viking Graben.
Thermal effects of intrusion below the Taranaki Basin (New Zealand): evidence from combined apatite fission track age and vitrinite reflectance data
Authors: Armstrong P. A. , Kamp P. J. J. , Allis R. G. , Chapman D. S.
Published: November 2003

A high surface heat‐flow anomaly on the northern Taranaki Peninsula in the Taranaki Basin (New Zealand) coincides spatially with Quaternary volcanic edifices, but the temporal aspects of heating of the sedimentary column associated with volcanism and any related plutonism have been unclear. A combined analysis of fission track age and vitrinite reflectance data, in particular comparing data from within the high heat‐flow anomaly to calibration wells elsewhere in the Taranaki Basin, provides important new constraints. Within the high heat‐flow region, apatite fission track (AFT) ages are older and vitrinite reflectance (Ro) values are lower than in samples from elsewhere in the basin that have undergone similar burial histories. Modelled AFT ages and Ro values suggest gradual heating to within about 20 °C of maximum temperature followed by rapid heating of sedimentary strata in the last 1 Myr, perhaps as recently as the last 0.1 Myr. The inferred age of this heating event is younger than the age of the volcanic edifice on which it is centred, suggesting that volcanism precedes heating that may be related to plutonism under the northern peninsula. These results suggest that, if the heating is caused by intrusion, then the intrusion is probably in the upper crust.
Architecture and controls on Bathonian–Kimmeridgian shallow‐marine synrift wedges of the Oseberg–Brage area, northern North Sea
Authors: Ravnås R. , Bondevik K.
Published: November 2003

The Oseberg Fault‐Block, situated along the eastern flank of the northern Viking Graben in the North Sea, was affected by Middle–Late Jurassic rifting initiated in Bajocian–Bathonian times. Temporal variations in stretching rates exerted the major control on the depositional infill patterns of the Bathonian–Kimmeridgian Heather Formation and its intercalated Middle Callovian to Early Oxfordian Fensfjord and Late Oxfordian to Kimmeridgian Sognefjord Formations. Three shallow‐marine, regressive–transgressive synrift wedges are recognized, and are interpreted in terms of discrete rift phases. The lower, regressive segments of the synrift wedges were deposited during periods of relatively low tectonic activity, whereas the upper, overall transgressive segments correspond to extensional pulses or stages during which significant fault‐related subsidence and fault‐block rotation occurred. These rotational tilt stages are further subdivided into an early, a climax and a late synrotational substage.

The lower, regressive segments consist of stacked, shallowing‐upward units, which reflect the advance of wide shallow‐marine, rift‐marginal shorelines during the tectonically quiescent periods. During the intervening rotational tilt stages renewed basin floor tilting and increased basinal subsidence led to retreat of the rift‐marginal depositional systems, renewal of the half‐graben topography, formation of intrabasinal sediment sources (footwall islands) and the re‐establishment of localized footwall, hangingwall and axial depositional systems. These localized depositional systems generally have an overall forestepping‐to‐backstepping character superimposed on the larger‐scale transgressive trend. There was an associated shift from a wave‐ and storm‐dominated environment during deposition of the lower, regressive segment to a more protected, partly current‐(?tidally) influenced environment in the upper, transgressive segment. This reflects a shift from a broad open basin in tectonically quiescent periods to smaller subbasins (embayments or estuaries) during periods with increased rates of rifting.

The footwall highs which formed intrabasinal sediment sources were of limited size compared with the volume of the adjacent depositional sinks. As a consequence, complete infilling of individual half‐grabens were not achieved during the synrotational stages, leaving the subbasins underfilled at the end of each successive rift phase. Mudstone drapes represent periods with deprivation of clastic material and basinal condensation during the latest synrotational to early tectonic quiescence substages, when footwall islands were small or completely submerged and there was a large distance to the (then progradational) rift‐marginal shoreline.
Slope basins, headless canyons, and submarine palaeoseismology of the Cascadia accretionary complex
Authors: McAdoo Brian G. , Orange Daniel L. , Screaton Elizabeth , Lee Homa , Kayen Robert
Published: November 2003

A combination of geomorphological, seismic reflection and geotechnical data constrains this study of sediment erosion and deposition at the toe of the Cascadia accretionary prism. We conducted a series of ALVIN dives in a region south of Astoria Canyon to examine the interrelationship of fluid flow and slope failure in a series of headless submarine canyons. Elevated head gradients at the inflection point of canyons have been inferred to assist in localized failures that feed sediment into a closed slope basin. Measured head gradients are an order of magnitude too low to cause seepage‐induced slope failure alone; we therefore propose transient slope failure mechanisms. Intercanyon slopes are uniformly unscarred and smooth, although consolidation tests indicate that up to several metres of material may have been removed. A sheet‐like failure would remove sediment uniformly, preserving the observed smooth intercanyon slope. Earthquake‐induced liquefaction is a likely trigger for this type of sheet failure as the slope is too steep and short for sediment flow to organize itself into channels. Bathymetric and seismic reflection data suggest sediment in a trench slope basin between the second and third ridges from the prism’s deformation is derived locally. A comparison of the amounts of material removed from the slopes and that in the basin shows that the amount of material removed from the slopes may slightly exceed the amount of material in the basin, implying that a small amount of sediment has escaped the basin, perhaps when the second ridge was too low to form a sufficient dam, or through a gap in the second ridge to the south. Regardless, almost 80% of the material shed off the slopes around the basin is deposited locally, whereas the remaining 20% is redeposited on the incoming section and will be re‐accreted.
SUCCESSFUL TREATMENT OF ACUTE PROMYELOCYTIC LEUKAEMIA WITH ALL‐TRANS‐RETINOIC‐ACID DURING LATE PREGNANCY
Authors: Lipovsky M. M. , Biesma D. H. , Christiaens G. C. M. L. , Petersen E. J.
Published: November 2003

We describe a patient with acute promyelocytic leukaemia (PML) diagnosed in the third trimester of pregnancy who presented with coagulopathy and prolonged bleeding time. Treatment with all‐trans‐retinoic‐acid (ATRA) resulted in rapid normalization of the coagulopathy and complete remission of PML within 2 weeks. Induced labour resulted in an uneventful vaginal delivery without major blood loss with no signs of neonatal ATRA‐induced embryopathy. ATRA therapy for PML during late pregnancy was effective in reversing the maternal bleeding tendency and inducing a complete remission of the PML without evidence of teratogenicity. Careful monitoring of bleeding time is important, even after normalization of clotting parameters and thrombocyte count, for determining the moment of induction of labour.
Acute myeloid leukaemia with t(8;16)(p11;p13) in a child after intrauterine X‐ray exposure
Authors: Savaşan Süreyya , Mohamed Anwar N. , Lucas David R. , Dugan Michael C. , Ryan James R. , R avindranath Yaddanapudi
Published: November 2003

We describe t(8;16)(p11;p13) acute myeloid leukaemia (AML‐M4) in a 12‐year‐old white male with a history of prenatal X‐ray exposure. He had skin and bone involvement and some of the leukaemic blasts showed haemophagocytosis, characteristic features seen in t(8;16) AML. 20% of the reported cases of t(8;16)(p11;p13) AML are therapy‐related and this case further supports the possible role of the ionizing radiation in the development of this disorder.
The effect of the chemokine rhMIP‐1α, and a non‐aggregating variant BB‐10010, on blast cells from patients with acute myeloid leukaemia
Authors: Owen‐Lynch P. Jane , Adams Julie A. , Brereton Michelle L. , Czaplewski Lloyd G. , Whetton Anthony D. , Liu Yin John A.
Published: November 2003

The effects of recombinant macrophage inflammatory protein 1α (rhMIP‐1α) on the proliferation of leukaemic blast cells from patients with acute myeloid leukaemia was assessed. Using the previously described [3H]thymidine incorporation index assay, the response of autonomous and growth factor responsive AML blast cells to the chemokine rhMIP‐1 was measured. In the case of autonomous proliferators, rhMIP‐1α had no inhibitory effect  on [3H]thymidine incorporation and in 4/6 cases [3H]‐thymidine incorporation was stimulated by rhMIP‐1α. In the presence of stem cell factor (SCF), a majority (8/9) of the samples which responded to this growth factor were inhibited when rhMIP‐1α was included in the assay medium. Similar results were obtained with GM‐CSF‐responsive samples; however, when these two cytokines were combined, only 3/14 were significantly inhibited. In the presence of human placental conditioned medium (HPCM), rhMIP‐1α significantly inhibited [3H]thymidine incorporation in only 2/10 of HPCM‐responsive samples. In methylcellulose assays rhMIP‐1α had no consistent effect on colony/cluster formation in the presence of either GM‐CSF + SCF or HPCM. Similar results were obtained with BB‐10010, a mutant of rhMIP‐1α which has defined aggregation properties in solution. These data suggest that autonomously proliferating AML cells, and also some AML samples which require cytokines to proliferate, are non‐responsive to the growth inhibitors rhMIP‐1α and BB‐10010 in the presence of multiple growth factors.
Progenitor cell yield in sequential blood stem cell mobilization in the same patients: insights into chemotherapy dose escalation and combination of haemopoietic growth factor and chemotherapy
Authors: Lie Albert K. W. , Rawling Trevor P. , Bayly Joanne L. , To L. Bik
Published: November 2003

Between April 1988 and March 1994 a total of 23 patients with haematological or non‐haematological malignancies received serial peripheral blood stem cell (PBSC) mobilization to attain sufficient harvest for PBSC transplant at our institution. There was no improvement in yield with the second mobilization for group A patients (n = 12) who had the same dose of cyclophosphamide twice as mobilizing agent. For group B patients (n = 6), who had a higher dose of cyclophosphamide with the second mobilization, there was significant increase in CFU‐GM yield. CD34+ cell yield was not measured. For group C patients, who received interleukin‐3 plus granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) with the first mobilization and chemotherapy plus GM‐CSF with the second, there was significant increase in CFU‐GM as well as CD34+ cell yield.  Our results demonstrate that, at the doses studied, chemotherapy dose escalation and combining haemopoietic growth factor with chemotherapy improve progenitor cell yield in PBSC mobilization.
High prevalence of autoimmune phenomena in hepatitis C virus antibody positive patients with lymphoproliferative and connective tissue disorders
Authors: Pivetti Sonia , Novarino Anna , Merico Franca , Tiziana Bertero M. , Brunetto Maurizia R. , Bonino Ferruccio , Caligaris‐Cappio Federico
Published: November 2003

The aim of this study was to investigate whether hepatitis C virus (HCV) may perturb the immune system towards autoreactivity. We studied the relationship between the prevalence of anti‐HCV and the presence of laboratory and/or clinical autoimmune features in 300 patients: lymphoid malignancies (167) and autoimmune disorders (connective tissue diseases 100; idiopathic thrombocytopenic purpura (ITP) 33). As a control, hepatitis B surface antigen (HBV) and anti‐hepatitis B core antigen (anti‐HBc) were related to the same parameters.  Anti‐HCV and anti‐HBV were detected in 68/300 (22.6%) and 70/300 (24.6%) patients, respectively. HCV prevalence was 18% in lymphoproliferative disorders (anti‐HBc 28.1%) and 26% in connective tissue disease (anti‐HBc 16.3%). Among ITP cases, 12/33 (36.4%) were anti‐HCV+ and 10/33 (30.3%) anti‐HBc+. In 24/30 (80%) anti‐HCV+ patients with lymphoproliferative disorders at least one serologic or clinical autoimmune abnormality was detected. To the contrary, only 10/45 (22.2%) anti‐HBc+ patients with lymphoproliferative disorders had at least one serologic or clinical abnormality (P < 0.0001). A statistically significant correlation was observed between HCV prevalence and the number of autoimmune alterations in both lymphoproliferative and connective tissue disorders, which was not found for anti‐HBc.  These data suggest that HCV may skew the immune system toward the production of autoantibodies and also support the possibility that some cases of ITP may be linked to both HCV and HBV infection.
A common frameshift mutation in von Willebrand factor does not alter mRNA stability but interferes with normal propeptide processing
Authors: Mohlke Karen L. , Nichols William C. , Rehemtulla Alnawaz , Kaufman Randal J. , Fagerström Heidi M. , Ritvanen K. L. Annukka , Kekomäki Riitta , Ginsburg David
Published: November 2003

Quantitative defects in von Willebrand factor (VWF) result in type 1 and type 3 von Willebrand disease (VWD). This study characterizes the defect in VWF expression resulting from a single nucleotide deletion in VWF exon 18, a mutation previously reported to be common among type 3 VWD patients. A severely affected (type 3) VWD patient in the current pedigree is homozygous for the mutation, whereas heterozygous individuals exhibit variable expression of type 1 VWD. In contrast to the previously reported high frequency of the exon 18 deletion in Sweden and Germany, this mutation appears to be infrequent among type 3 VWD patients in the United States. Although this frameshift mutation results in proximal premature termination of VWF translation, the abnormal VWF mRNA is stable. The mutant truncated recombinant VWF protein is retained within the transfected cell, and no propeptide processing is observed, suggesting a defect in protein folding. Cotransfection of mutant and wild‐type recombinant VWF fails to demonstrate a dominant effect of the mutant on the normal allele. Consistent with these results, plasma VWF propeptide of the homozygous individual was markedly reduced whereas heterozygotes exhibited moderately reduced levels. In contrast to type 2A VWD (group 1), the misfolded mutant protein does not appear to exert a dominant‐negative effect on normal VWF subunits expressed from the wild‐type allele.
CMV iNFECTION AFTER ALLOGENEIC BONE MARROW TRANSPLANTATION IS ASSOCIATED WITH THE OCCURRENCE OF VARIOUS AUTOANTIBODIES AND MONOCLONAL GAMMOPATHIES
Authors: Hebart Holger , Einsele Hermann , Klein Reinhild , Fischer Ina , Bühler Sonja , Dietz Klaus , Jahn Gerhard , Berg Peter A. , Kanz Lothar , Müller Claudia A.
Published: November 2003

Recent findings indicate that the kinetics of B‐cell reconstitution after marrow transplantation mimic normal ontogeny. The early B‐cell repertoire during ontogeny is characterized by a high degree of autoreactivity and interconnectivity. Therefore, in a prospective analysis, 95 consecutive recipients of an allogeneic marrow transplant were screened for the occurrence of various autoantibodies and 47 of these 95 were also screened for monoclonal gammopathies. None of the patients developed antibodies specific for systemic autoimmune disorders. In contrast, a high prevalence of natural antibodies (79/95) was found early post‐transplant, with 58 of these 79 patients developing two or more autoantibodies. According to multiple regression, the mean number of natural antibodies (95% confidence limits in parentheses) depends significantly (P = 0.006) on the status of CMV infection: 0.9 (0.4; 1.6) CMV‐negative; 2.0 (1.0; 3.3) asymptomatic CMV infection; 3.1 (1.7; 5.0) CMV disease. Sex, age, underlying disease, conditioning therapy, acute graft‐versus‐host disease and CMV serology of donor and recipient pretransplant did not affect the number of natural autoantibodies. Monoclonal gammopathies were detected in 12/47 patients with a predominance of the IgG‐kappa subtype. All these 12 patients suffered from a viral infection (CMV, n = 11; influenza strain A, n = 1). The high degree of self‐reactivity post‐transplant further supports the hypothesis that B‐cell reconstitution mimics ontogeny. Moreover, these data indicate nonspecific polyclonal, CMV‐mediated, presumably T‐cell independent B‐cell stimulation and disturbed T‐cell regulatory function following allogeneic BMT.
Establishment of human granulocyte‐macrophage colony stimulating factor producing transgenic SCID mice
Authors: Miyakawa Yoshitaka , Fukuchi Yumi , Ito Mamoru , Kobayashi Kimio , Kuramochi Takashi , Ikeda Yasuo , Takebe Yutaka , Tanaka Toshiyuki , Miyasaka Masayuki , Nakahata Tatsutoshi , Tamaoki Norikazu , Nomura Tatsuji , Ueyama Yoshito , Shimamura Kazuo
Published: November 2003

Previous work has shown the usefulness of severe combined immunodeficient (SCID) mice as in vivo models for the growth of normal human haemopoietic cells and leukaemic cells. Many approaches have been made to improve the engraftment of human haemopoietic cells in SCID mice. We established transgenic mice producing human granulocyte‐macrophage colony stimulating factor (hGM‐CSF) with the homozygote of the scid gene. Endogenous serum hGM‐CSF levels were detected by ELISA [mean 9585 pg/ml (line A, n = 4); mean 1610 pg/ml (line B, n = 4)]. Expression of hGM‐CSF was observed in all organs tested including the heart, lung, liver, kidney, spleen, thymus, bone marrow and brain of hGM‐CSF transgenic (hGMTg) mice. Morphological analysis of organs and peripheral blood cell counts showed no differences between hGMTg mice and their littermates. Murine Ba/F3 cells expressing functional hGM‐CSF αβ receptor (BAF/αβ cells) could be successfully engrafted in hGMTg SCID mice. The cells invaded multiple organs and caused death within a few weeks of transplantation, although they infiltrated only the spleen of their littermates. These results showed that these hGM‐CSF‐producing SCID mice are useful as an in vivo assay system for investigating leukaemogenesis.
Plasma exchange with solvent/detergent‐treated plasma of resistant thrombotic thrombocytopenic purpura
Authors: Harrison C. N. , Lawrie A. S. , Iqbal A. , Hunter A. , Machin S. J.
Published: November 2003

A patient with unremitting thrombotic thrombocytopenic purpura (TTP), with circulating von Willebrand factor (VWF) multimers of unusually high molecular weight, and refractory to standard plasma exchange therapy, was treated with solvent detergent (S/D) plasma. The patient achieved a sustained clinical and haematological remission, with normal VWF multimeric profile. Spontaneous remission of this patient's condition could not be excluded but would appear unlikely. S/D plasma was efficacious and potentially safe for repeated large‐volume plasma exchange with respect to viral safety and reduction of anaphylactoid reactions. We have assayed coagulation factors and physiological inhibitors of haemostasis in S/D plasma, which were comparable to normal plasma except in the distribution of VWF multimers.

The use of S/D plasma, previously reported in paediatric chronic relapsing TTP, should be assessed in further cases of adult TTP in the context of a clinical trial.
Diamond‐Blackfan anaemia in the U.K.: analysis of 80 cases from a 20‐year birth cohort
Authors: Ball S. E. , McGuckin C. P. , Jenkins G. , Gordon‐Smith E. C.
Published: November 2003

The U.K. Diamond‐Blackfan Anaemia (DBA) Registry was established with the aim of providing a representative database for studies on the aetiology, pathophysiology and treatment of DBA. We have analysed retrospective data from 80 cases (33 male, 47 female) born in the U.K. in a 20‐year period (1975–94), representing an annual incidence of 5 per million live births. Ten children from seven families had an apparently familial disorder. 13% were anaemic at birth, and 72.5% had presented by the age of 3 months. 67% had macrocytosis at presentation. 72% responded initially to steroids, and at the time of study 61% were transfusion‐independent (45% steroid‐dependent) and 39% required regular transfusions. Unequivocal physical anomalies, predominantly craniofacial, were present in 37%, and were more likely in boys (52%) than girls (25%). 18% had thumb abnormalities. Height was below the third centile for age in 28%, and 31% had neither short stature nor physical anomalies. Four children without physical abnormalities had normal red cell indices, and achieved steroid‐independent remission, suggesting transient erythroblastopenia of childhood rather than DBA. The birth month distribution of children with sporadic DBA and craniofacial dysmorphism showed a possible seasonality, consistent with a viral aetiology.
Haemoglobin Lleida: a new α2‐globin variant (12 bp deletion) with mild thalassaemic phenotype
Authors: Ayala S. , Colomer D. , Pujades A. , Aymerich M. , Vives Corrons J. Ll
Published: November 2003

Molecular studies of α‐thalassaemias have revealed defects at different steps in the process of α‐gene expression. It is not surprising, therefore, that in some cases a single mutation or small deletion can result in a structurally abnormal haemoglobin that produces the α‐thalassaemia phenotype. In this report we describe a new unstable α‐globin variant, Hb Lleida, in a Spanish patient with α‐thalassaemia trait. The mutation was detected by single‐strand conformation polymorphism in the third exon of the α2‐globin gene. Direct sequence analysis of the α‐globin gene showed a 12 bp deletion as the only defect of the α2‐ and α1‐globin genes. The propositus was revealed to be a heterozygous carrier, and two alleles were separated by electrophoresis. This deletion causes the loss of four aminoacid residues (from codon 113 to 116) and would be expected to produce an unstable haemoglobin, as a shorter α‐globin chain variant is created with 137 amino acids instead of 141 amino acids present in a normal α‐globin chain. However, no abnormal haemoglobin was found by either isoelectric focusing or haemoglobin electrophoresis. Since the deletion affects an aminoacid residue (114 Pro) involved in α1‐β1‐globin chain contacts, the interaction required for efficient Hb assembly is also compromised. The resulting unstable α‐globin chain is rapidly catabolized and unsuitable for haemoglobin tetramer formation, causing an α‐thalassaemia trait phenotype in the heterozygous patient.
The CDKN2 gene alterations in various types of adult T‐cell leukaemia
Authors: Uchida Toshiki , Kinoshita Tomohiro , Watanabe Takashi , Nagai Hirokazu , Murate Takashi , Saito Hidehiko , Hotta Tomomitsu
Published: November 2003

The CDKN2 gene, encoding the cyclin‐dependent kinase‐4 inhibitor p16, is a putative tumour‐suppressor gene because it is frequently altered in many malignant tumours. We analysed the CDKN2 gene in 44 cases of adult T‐cell leukaemia (ATL) by Southern blot analysis, polymerase chain reaction‐mediated single‐strand conformation polymorphism (PCR‐SSCP) analysis, and direct sequencing. Southern blot analysis detected a homozygous deletion of the CDKN2 gene in 5/44 patients (11.4%). Mutational analysis by the PCR‐SSCP method and direct sequencing showed one nonsense mutation at codon 72 (nucleotide 232), and two missense mutations at codon 43 (nucleotide 146) and codon 97 (nucleotide 309, 3/44, 6.8%). Therefore we found changes in the CDKN2 gene, including point mutations, in 18.2% of the patients with ATL. Interestingly, most of these patients had acute type ATL. Our results suggest that the CDKN2 gene is inactivated not only by homozygous deletion but also by point mutation, and these alterations contribute to the aggressiveness of ATL.
Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy‐induced thrombocytopenia
Authors: Akahori Hiromichi , Shibuya Kazunori , Obuchi Masako , Nishizawa Yoshito , Tsuji Akio , Kabaya Koji , Kusaka Masaru , Ohashi Hideya , Tsumura Haruhiko , Kato Takashi , Miyazaki Hiroshi
Published: November 2003

We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy‐induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 μg/kg/d or monkey’s serum once each day from day 1 to day 28. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose‐dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTPO‐treated animals exhibited no significant changes in several serum parameters, C‐reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy‐induced thrombocytopenia.