bluuebunny/crossref_metadata_2025 huggingface dataset:
An ecosystem model of the global ocean including Fe, Si, P colimitations
Authors: Aumont Olivier , Maier‐Reimer Ernst , Blain Stéphane , Monfray P.
Published: June 2003

Observations have shown that large areas of the world ocean are characterized by lower than expected chlorophyll concentrations given the ambient phosphate and nitrate levels. In these High Nutrient‐Low Chlorophyll regions, limitations of phytoplankton growth by other nutrients like silicate or iron have been hypothesized and further evidenced by in situ experiments. To explore these limitations, a nine‐component ecosystem model has been embedded in the Hamburg model of the oceanic carbon cycle (HAMOCC5). This model includes phosphate, silicate, dissolved iron, two phytoplankton size fractions (nanophytoplankton and diatoms), two zooplankton size fractions (microzooplankton and mesozooplankton), one detritus and semilabile dissolved organic matter. The model is able to reproduce the main characteristics of two of the three main HNLC areas, i.e., the Southern Ocean and the equatorial Pacific. In the subarctic Pacific, silicate and phosphate surface concentrations are largely underestimated because of deficiencies in ocean dynamics. The low chlorophyll concentrations in HNLC areas are explained by the traditional hypothesis of a simultaneous iron‐grazing limitation: Diatoms are limited by iron whereas nanophytoplankton is controlled by very efficient grazing by microzooplankton. Phytoplankton assimilates 18 × 109 mol Fe yr−1 of which 73% is supplied by regeneration within the euphotic zone. The model predicts that the ocean carries with it about 75% of the phytoplankton demand for new iron, assuming a 1% solubility for atmospheric iron. Finally, it is shown that a higher supply of iron to surface water leads to a higher export production but paradoxically to a lower primary productivity.
Application of eddy covariance measurements to the temperature dependence of soil organic matter mean residence time
Authors: Sanderman Jonathan , Amundson Ronald G. , Baldocchi Dennis D.
Published: June 2003

The micrometeorological technique of eddy covariance is a powerful tool for characterizing the carbon (C) budget of terrestrial ecosystems. However, few attempts have been made to link canopy‐scale eddy exchange to soil C processes. Here we develop a simple means of using calculations derived from a global database of eddy flux measurements to examine the role of climate on soil C decomposition rates. We then compare the results of the eddy covariance calculations to the temperature dependence of soil C residence times determined by four common methods: laboratory incubations, direct soil respiration measurements, radiocarbon uptake, and stable C isotope change following land conversion. In all five methods, the soil organic C turnover time decreases exponentially with increasing mean annual temperature. The similar slopes and intercepts of the eddy flux and chamber measurements lend support for the robustness of micrometeorological techniques in measuring respiration. The similarities in the response of soil C turnover to temperature for the eddy flux and 14C‐derived turnover times is especially encouraging in that bomb‐14C measurements do not rely on any of the assumptions that were used to calculate soil C turnover from eddy flux data. However, the 13C isotope method yields a significantly different slope and intercept than the other three techniques. The results of this work reinforce the recognized temperature dependence of soil C turnover and suggest that eddy flux experiments are a useful and additional approach for studying the soil C budget.
Effect of H2 on the Martian ionosphere: Implications for atmospheric evolution
Authors: Fox J. L.
Published: June 2003

Because H2 reacts efficiently with O+, CO2+, CO+, and N2+, the molecular hydrogen abundance assumed in models of the Martian ionosphere greatly affects the high altitude density profiles of these ions. We have found that models of the low solar activity Martian ionosphere exhibit much smaller O+ densities than the measured values if the adopted H2 abundance is of the order of 40 ppm, the value proposed in a 1998 model of the Martian atmosphere. For a model based on the recently measured H2 abundance of 15 ppm [Krasnopolsky and Feldman, 2001a, 2001b], the O+ densities are closer to, but still somewhat less than the Viking densities. The O+ peak densities of ∼600–750 cm−3 measured by the retarding potential analyzers on Vikings 1 and 2 [Hanson et al., 1977] are best reproduced with H2 abundances less than ∼4 ppm. We have investigated the effect of various H2 mixing ratios at the lower boundary of our model, and we find that the high altitude densities of O+, CO2+, CO+, and N2+ ions decrease as the H2 abundance increases, and are much less for H2 mixing ratios greater than 4 ppm than previous models have shown. Moreover, the photochemical escape rates of heavy atoms, such as C and N that are due to reactions of these ions, are also reduced. The Martian atmosphere was probably more reducing in past epochs, and therefore consisted of a larger fraction of H2. As the abundance of H2 increases, the composition of the exosphere will also be altered, and the altitude of the exobase will rise. At very large mixing ratios, H and H2 could potentially dominate the absorption of EUV radiation. Thus the escape of species by other photochemical mechanisms such as photodissociation and photodissociative ionization could also be reduced. If so, the nonthermal escape rates of heavy atoms in past epochs may have been much lower than previous estimates in which it is assumed that the oxidation state of the Martian atmosphere has remained constant over time.
Persistence of Gulf Stream separation during the Last Glacial Period: Implications for current separation theories
Authors: Matsumoto Katsumi , Lynch‐Stieglitz Jean
Published: June 2003

We present stable oxygen isotope ratio (δ18O) measurements on deep‐dwelling planktonic foraminifera from the western margin of the North Atlantic in order to reconstruct the latitude at which the Gulf Stream separated from the western boundary of the Atlantic Ocean in the past. The modern separation latitude can be reconstructed within one degree from δ18O measured on the fossil shells of deep‐dwelling planktonic foraminifera Globorotalia truncatulinoides from the Holocene sediments representing the past 10,000 years of mild climate conditions similar to today. The separation latitude is captured in a sharp δ18O gradient, which reflects the prominent hydrographic change across the boundary between the warm waters south and east of the Gulf Stream and the cold Slope Water to the north. The latitudinal δ18O profile from approximately the Last Glacial Maximum shows that the Gulf Stream separated from the coast near Cape Hatteras at almost the same latitude as it does today. We assess our finding in light of existing Gulf Stream separation theories and conclude that one of the theories, the wind‐induced separation mechanism, is not consistent with our paleoceanographic reconstruction.
Parameterization of the Mueller matrix of oceanic waters
Authors: Kokhanovsky Alexander A.
Published: June 2003

This paper is devoted to the parameterization of the Mueller matrix of oceanic water measured by Voss and Fry [1984]. Their matrix was obtained as an average of many observations in different parts of the world ocean, including the Gulf of Mexico and the Pacific and Atlantic Oceans. The results presented here can be used as input data for the theoretical polarized radiative transfer studies in oceanic waters.
Late Holocene surface ocean conditions of the Norwegian Sea (Vøring Plateau)
Authors: Andersson Carin , Risebrobakken Bjørg , Jansen Eystein , Dahl Svein Olaf
Published: June 2003

Late Holocene sea surface ocean conditions of the eastern Norwegian Sea (Vøring Plateau) are inferred from planktic stable isotopes and planktic foraminiferal assemblage changes in cores JM97‐948/2A and MD95‐2011 (66.97°N, 7.64°E). Strong covariance between the planktic stable oxygen isotopic record and abundance changes of N. pachyderma (sin) show that major changes in surface ocean conditions are reflected both in the geochemical composition of the foraminiferal tests as well as in the composition of the foraminiferal fauna. Surface ocean conditions warmer than present were common during the past 3000 years. During the so‐called Medieval Warm Period, surface conditions were highly variable with marked changes in sea surface temperature. The warmest sea surface temperatures during this period occurred between 800 and 550 years BP (0 BP = AD 2000). Climatic deterioration, recorded as decreases in sea surface temperature, occurred at about 2750, 1550, 400, and 100 years BP. The cooling events at about 2750 and 1550 years BP appear to correlate with increases in ice‐rafted debris in the North Atlantic. Based on the results from JM97‐948/2A and MD95‐2011, the onset of the Little Ice Age cooling trend seems to have occurred around 700–600 years BP. Faunal changes indicate two cooling events during the Little Ice Age (at 400 and 100 years BP) that correspond to decreases in Fennoscandian summer temperatures and increases in ice‐rafted debris in the eastern North Atlantic.
Expansion ofJuniperus virginianaL. in the Great Plains: Changes in soil organic carbon dynamics
Authors: Smith Dixie L. , Johnson Loretta C.
Published: June 2003

Woody encroachment byJuniperus virginianainto Great Plains grasslands allowed us to answer: Does changing the type of plant input to soils alter soil organic carbon (SOC) distribution or soil carbon (C) storage? The answer is critical because woody encroachment may alter C cycling over millions of hectares in the Great Plains and Midwest. We predicted that (1) forest SOC would become concentrated in shallow soil layers compared to SOC distribution in grassland, (2) woody expansion would increase soil C storage, and (3) forest C would be apparent in the larger soil organic matter fractions. Using δ13C signatures of SOC, 1/5 of the C from 0 to 25 cm in juniper forest soils was derived from C3juniper trees. Forest C3input occurred primarily in shallow surface layers: Forest soils developed over former C4prairie contained 42% C3‐SOC from 0 to 2.5 cm depth, and decreased to 6% at 25 cm. Isotopic analysis of SOC size fractions revealed that at 0–2.5 cm, the forest soil fraction >212 μm was −25.7‰. The fraction <2 μm had a13C isotope ratio of −17.0‰ at the same depth, reflecting the predominance of residual prairie C in the smallest fraction. In spite of fast dynamics of soil C turnover, there was no net change in SOC amounts over 40–60 years (cumulative mineral and organic SOC in forest, 8782 g C/m2± 810; in grassland, 7699 ± 1004). Thus as junipers expand into mesic areas of the Great Plains, juniper forests will provide little additional soil C storage.
Surface ocean‐lower atmosphere interactions in the Northeast Pacific Ocean Gyre: Aerosols, iron, and the ecosystem response
Authors: Johnson Kenneth S. , Elrod Virginia A. , Fitzwater Steve E. , Plant Joshua N. , Chavez Francisco P. , Tanner Sara J. , Gordon R. Michael , Westphal Douglas L. , Perry Kevin D. , Wu Jingfeng , Karl David M.
Published: June 2003

Here we report measurements of iron and aluminum in surface and subsurface waters during late March and late May of 2001 on transects between central California and Hawaii. A large cloud of Asian dust was detected during April 2001, and there was a clear signal in surface water iron due to aerosol deposition on the May transect. Iron and aluminum concentrations increased synchronously by 0.5 and 2 nM along the southern portion of the transect, which includes the Hawaii Ocean Time series (HOT) station, from background values in March (0.1 to 0.2 nM Fe). These changes occurred in a ratio that is close to the crustal abundance ratio of the metals, which indicates a soil aerosol source. A vertical profile of dissolved iron was also measured at the HOT station in late April and this profile also shows a large increase near the surface. Direct observations of aerosol iron concentration at Mauna Loa Observatory on Hawaii indicate that aerosol concentrations were significantly lower than climatological values during this period. Soil aerosol concentrations along the transect were estimated using the real‐time Navy Aerosol Analysis and Prediction System (NAAPS). The NAAPS results show a large meridional gradient with maximum concentrations in the boundary layer north of 30°N. However, the deposition of iron and aluminum to surface waters was highest south of 25°N, near Hawaii. There were only weak signals in the ecosystem response to the aerosol deposition.
Dehydration potential of ultrathin clouds at the tropical tropopause
Authors: Luo B. P. , Peter T. , Fueglistaler S. , Wernli H. , Wirth M. , Kiemle C. , Flentje H. , Yushkov V. A. , Khattatov V. , Rudakov V. , Thomas A. , Borrmann S. , Toci G. , Mazzinghi P. , Beuermann J. , Schiller C. , Cairo F. , Di Donfrancesco G. , Adriani A. , Volk C. M. , Strom J. , Noone K. , Mitev V. , MacKenzie R. A. , Carslaw K. S. , Trautmann T. , Santacesaria V. , Stefanutti L.
Published: June 2003

We report on the first simultaneous in situ and remote measurements of subvisible cirrus in the uppermost tropical troposphere. The observed cirrus, called UTTCs (ultrathin tropical tropopause clouds), are the geometrically (200–300 m) and optically (τ ≈ 10−4) thinnest large‐scale clouds ever sampled (≈105 km2). UTTCs consist of only a few ice particles per liter with mean radius ≈5 μm, containing only 1–5 % of the total water. Yet, brief adiabatic cooling events only 1–2 K below mean ambient temperature destabilize UTTCs, leading to large sedimenting particles (r ≈ 25 μm). Due to their extreme altitude above 17 km and low particle number density, UTTCs may efficiently dehydrate air during its last encounter with the ice phase before entering the stratosphere.
Theoretical results on the latitude dependence of the Kelvin‐Helmholtz instability at the dayside magnetopause for northward interplanetary magnetic fields
Authors: Contin Julia E. , Gratton Fausto T. , Farrugia Charles J.
Published: June 2003

We study the Kelvin‐Helmholtz (KH) instability at the dayside magnetopause, modeling the flow, the magnetic field, and the density profiles in the transition from magnetosheath to magnetosphere with hyperbolic tangent functions. The strength and the direction of the fields on the sunward sides of the magnetopause are obtained from a MHD simulation code of the magnetosheath, which includes the magnetic tension forces on the plasma in the plasma depletion layer. The theory is applied to strongly northward interplanetary magnetic fields. We work at slightly off‐noon local times and compute at three different latitudes. We find that as the latitude increases the instability growth rate becomes negligible due to the increasing local magnetic shear, which reaches ∼21° at the highest latitude examined. The KH growth rates for the most unstable modes are given as functions of λ/Δ, the ratio of the wavelength to the width of the transition. The KH perturbation tends to be localized on the magnetospheric side when the configuration is most unstable, whereas it shifts increasingly toward the magnetosheath side of the velocity gradient region as the latitude increases and the growth rate diminishes substantially. Growth rates for a tangential discontinuity model are within a 10% of those corresponding to continuous profiles when λ > 15Δ. The influence of temporary (sunward or earthward) accelerations of the magnetopause on the KH modes is examined. The effect of a difference between the scale length of the density profile and the width of the current sheath on the KH instability, as in pristine magnetopauses, is also studied.
Remote sensing the magnetosheath by the spin modulation of terrestrial continuum radiation
Authors: Nagano I. , Wu X.‐Y. , Takano H. , Yagitani S. , Matsumoto H. , Hashimoto K. , Kasaba Y.
Published: June 2003

Using the Plasma Wave Instrument (PWI) data from the GEOTAIL satellite, we show that the angular intensity distribution of the Continuum Radiation (CR) received in the magnetotail regions changes from isotropic to anisotropic above a specific frequency. The transition frequency where this change occurs is primarily controlled by the upstream solar wind plasma frequency measured with IMP 8 satellite. We interpret the transition as evidence of the magnetosheath cavity trapping of terrestrial radiation. The transition frequency, strongly associated with the electron density in the tail bow shock regions, can be used as a new approach of remote sensing the global scale magnetosheath dynamics. Two preliminary case studies reveal the complex nonlinear responses of the tail magnetosheath to the steady and the transient solar wind variations. The 0–3 hour time delay of the variation in the transition frequency (corresponding to the magnetosheath electron density) relative to the upstream solar wind density variation may suggest that the magnetosheath plasma relaxes at the local Alfven speed, rather than the solar wind convection speed.
On the geocentric micrometeor velocity distribution
Authors: Janches Diego , Nolan Michael C. , Meisel David D. , Mathews John D. , Zhou Qihou H. , Moser Danielle E.
Published: June 2003

We report micrometeor velocity distributions measured with unprecedented velocity and radiant resolution using the dual‐beam 430 MHz Arecibo (AO) radar in Puerto Rico. The AO radar detects over 10,000 events daily inside its 300 m radar beam that are produced mainly by particles in the size range 0.5–100 microns. During the observations reported here, the line feed antenna is pointed vertically while the Gregorian feed is pointed at an angle of 15 degrees from zenith. The off‐vertical radar beam is initially placed pointing north and every 30 min is rotated 180 degrees, allowing observation of three different regions of the Earth's ionosphere. Results from the observations performed on 21 January and 25 June 2002 are presented and discussed. We observe that the meteoroid population detected by AO is smaller in particle size and faster in velocity and thus entirely different from the one observed by conventional lower‐frequency meteor radars that use a different scattering mechanism. We observe qualitative difference in the shape of the meteor velocity distribution for the different pointing directions. Preliminary analysis of these distributions indicates that we detect at least four particle populations characterized by their geocentric velocities: A slow one with a “classical” value (∼15 km/sec), an intermediate velocity population (∼30 km/sec) the presence of which depends on ecliptic latitude and longitude, and two fast and dominant (at sunrise) populations (∼45 km/sec and ∼50 km/sec). Finally, we explore the possibility of observational biases in our technique and find no evidence for large effects.
AKR disappearance during magnetic storms
Authors: Morioka A. , Miyoshi Y. , Seki T. , Tsuchiya F. , Misawa H. , Oya H. , Matsumoto H. , Hashimoto K. , Mukai T. , Yumoto K. , Nagatsuma T.
Published: June 2003

It is well known that auroral kilometric radiation (AKR) is intensified during substorms and has a good correlation with AE index. In the case of the magnetic storms, however, AKR characteristics have not been investigated. In this paper we report unexpected behavior of the storm‐time AKR and its related particle precipitation: (1) AKR often disappears in the initial and main phases of the magnetic storms in spite of the large enhancement of AE index and field‐aligned current; (2) At that time, the energy spectra of precipitating electrons do not show signature of the field‐aligned acceleration but hot electron injection; (3) The radiation activates strongly in the recovery phase; and (4) AKR tends to disappear in larger storms. These results suggest that the field‐aligned electric field which accelerates precipitating electrons and drives field‐aligned currents is not formed in the initial and main phases of magnetic storms.
A comparison of a two‐dimensional variational analysis method and a median filter for NSCAT ambiguity removal
Authors: Henderson J. M. , Hoffman R. N. , Leidner S. M. , Atlas R. , Brin E. , Ardizzone J. V.
Published: June 2003

The ocean surface vector wind can be measured from space by scatterometers. For a set of measurements observed from several viewing directions and collocated in space and time, there will usually exist two, three, or four consistent wind vectors. These multiple wind solutions are known as ambiguities. Ambiguity removal procedures select one ambiguity at each location. We compare results of two different ambiguity removal algorithms, the operational median filter (MF) used by the Jet Propulsion Laboratory (JPL) and a two‐dimensional variational analysis method (2d‐VAR). We applied 2d‐VAR to the entire NASA Scatterometer (NSCAT) mission, orbit by orbit, using European Centre for Medium‐Range Weather Forecasts (ECMWF) 10‐m wind analyses as background fields. We also applied 2d‐VAR to a 51‐day subset of the NSCAT mission using National Centers for Environmental Prediction (NCEP) 1000‐hPa wind analyses as background fields. This second data set uses the same background fields as the MF data set. When both methods use the same NCEP background fields as a starting point for ambiguity removal, agreement is very good: Approximately only 3% of the wind vector cells (WVCs) have different ambiguity selections; however, most of the WVCs with changes occur in coherent patches. Since at least one of the selections is in error, this implies that errors due to ambiguity selection are not isolated, but are horizontally correlated. When we examine ambiguity selection differences at synoptic scales, we often find that the 2d‐VAR selections are more meteorologically reasonable and more consistent with cloud imagery.
Temperature inversions in the open Gulf of Mexico
Authors: Weatherly Georges , Wienders Nicolas , Harkema Reinard
Published: June 2003

Some ∼1500 PALACE float temperature profiles obtained throughout the Gulf of Mexico between April 1998 and March 2002 indicate that temperature inversions are rather common. Most are seen near the surface, but some are seen at essentially all depths down to the deepest measurement at about 1000 m. The inversions are associated with layers of relatively cool, and presumed fresher, riverine and coastal waters. Most are attributed to the Mississippi River and Mexican rivers discharging into the Campeche Bay, and a few are thought to have drifted in from the Caribbean Sea.
Atmospheric CO2 flux from mangrove surrounding waters
Authors: Borges A. V. , Djenidi S. , Lacroix G. , Théate J. , Delille B. , Frankignoulle M.
Published: June 2003

The partial pressure of CO2 (pCO2) was measured at daily and weekly time scales in the waters surrounding mangrove forests in Papua New Guinea, the Bahamas and India. The pCO2 values range from 380 to 4800 μatm. These data, together with previously published data, suggest that overall oversaturation of CO2 with respect to atmospheric equilibrium in surface waters is a general feature of mangrove forests, though the entire ecosystems (sediment, water and vegetation) are probably sinks for atmospheric CO2. The computed CO2 fluxes converge to about +50 mmolC m−2 day−1. If this conservative value is extrapolated for worldwide mangrove ecosystems, the global emission of CO2 to the atmosphere is about 50 106 tC year−1. Based on this tentative estimate, mangrove waters appear to be regionally a significant source of CO2 to the atmosphere and should be more thoroughly investigated, especially at seasonal time scale.
In‐situ observations of a neutral gas torus at Europa
Authors: Lagg A. , Krupp N. , Woch J. , Williams D. J.
Published: June 2003

A persistent pattern in the pitch angle distributions of energetic protons near the orbit of Europa has been observed with the Energetic Particles Detector (EPD) on board the Galileo spacecraft during each of the Europa orbit crossings in the last 7 years. The proton fluxes at energies larger than 220 keV peak at equatorial pitch angles of 90° whereas fluxes of lower energy protons (80–220 keV) at this pitch angle are depleted. We propose that a Jupiter‐surrounding neutral gas torus in the vicinity of the orbit of Europa is responsible for the depletion of energetic particle fluxes by charge exchange collisions. In order to reproduce the observed depletion signature an average neutral number density of 20 to 50 cm−3 is required.
A novel syndrome of combined immunodeficiency, autoimmunity and spondylometaphyseal dysplasia
Authors: Roifman CM , Melamed I
Published: June 2003

We describe here four patients who appear to have similar clinical and immunological features which constitute a novel syndrome. The patients present with short stature owing to spondylometaphyseal dysplasia and with severe infections as the result of a combined humoral and cellular immune deficiency. Presumably because of dysregulation of the immune system, all patients also developed autoimmune manifestations.
Analysis of splice‐site mutations of the α‐galactosidase A gene in Fabry disease
Authors: Lai L‐W , Whitehair O , Wu M‐J , O'Meara M , Lien Y‐HH
Published: June 2003

Fabry disease is an X‐linked disease caused by a defective lysosomal enzyme, α‐galactosidase A, and characterized by skin lesions and multiorgan involvement, including kidney, heart, and the central nervous system. Currently more than 200 genotypes have been identified, including several aberrant splicing. However, most of the mutation analyses were performed using genomic sequencing only, and therefore some of the splicing mutations were misclassified as missense mutations. In order to predict the splicing event caused by each mutation, we conducted a literature search for all published mutations located near the splice sites, including exonic point mutations, and performed a splice‐site score (SSS) analysis. The literature search identified 13 donor‐site mutations, including four exonic mutations (S65T, D183S, K213N, and M267I), located at the end of exons 1, 3, 4, and 5, respectively, six acceptor‐site mutations, and one new exon creation. All mutated splice sites, except for the one associated with the new exon creation, had a lower SSS than their respective natural sites. Cryptic or newly created sites were identified with SSS from 0.09 to 1.0. The predictions, based on SSS analysis, are in agreement with all six mutations with known cDNA sequence from the literature, including five mutations with exon skipping and one mutation with creation of a new acceptor site. For the S65T genotype, we performed reverse transcription–polymerase chain reaction (RT–PCR) analysis using RNA isolated from the whole‐blood sample. We verified that a weak cryptic site (SSS = 0.09) 14 nucleotides downstream was activated and resulted in an insertion of 14 bp and a frameshift stop at codon 106. This change is more consistent with the clinical presentation of the patient, the classical Fabry disease, than the amino acid substitution (S65T), which does not affect the enzyme function. In conclusion, the SSS analysis is very useful for predicting splicing events and genotype/phenotype correlation in Fabry disease. As different mechanisms may be involved in pre‐mRNA splicing, it is important to obtain cDNA sequencing for molecular diagnosis.
Genetic epidemiology of alpha‐1 antitrypsin deficiency in southern Europe: France, Italy, Portugal and Spain
Authors: De Serres FJ , Blanco I , Fernández‐Bustillo E
Published: June 2003

Alpha‐1‐antitrypsin deficiency (AAT deficiency) is one of the most common serious hereditary disorders in the world because it affects all major racial subgroups worldwide and there are at least 120.5 million carriers and deficient subjects worldwide. This genetic disease is related to a high risk for development of jaundice in infants, liver disease in children and adults, and pulmonary emphysema in adults. Moreover, AAT‐deficiency carrier phenotypes (PiMS and PiMZ) and deficiency‐allele phenotypes (PiSS, PiSZ, and PiZZ) are suspected to make subjects susceptible to a variety of other adverse health effects. As there is a limited database on the number of individuals affected by this disease worldwide, the authors of the present report collected data on control cohorts in genetic epidemiological studies published in the peer‐reviewed literature worldwide. The data collected were used to estimate the numbers of carriers and deficiency‐allele combinations for the two most common defective alleles, namely PiS and PiZ, in over 58 countries worldwide. The present report focuses on the distribution of the PiS and PiZ deficiency alleles in France, Italy, Portugal, and Spain. The total number of individuals at risk for adverse health effects were as follows: 9, 101, 739 in France; 4, 289, 566 in Italy; 2, 659, 241 in Portugal; and 8, 903, 773 in Spain. The geographical distribution of individual control cohorts and estimates of the numbers of carriers and deficiency‐allele phenotypes in each of these four southern European countries are shown in individual tables and maps. This report will be followed by other reports on the remaining countries in Europe, as well as worldwide.
Endoglin gene mutations and polymorphisms in Italian patients with hereditary haemorrhagic telangiectasia
Authors: Lastella P , Sabbà C , Lenato GM , Resta N , Lattanzi W , Gallitelli M , Cirulli A , Guanti G
Published: June 2003

Autosomal‐dominant hereditary haemorrhagic telangiectasia (HHT) is a genetically heterogeneous disease caused by mutations in at least two different loci. We screened for mutations in four Italian families where segregation studies showed clear evidence of linkage to the endoglin (ENG) locus. In addition, one sporadic case and three patients with pulmonary arteriovenous malformations, belonging to small nuclear families unsuitable for linkage analysis, were included in the screening. The proband from each family was investigated using single‐strand conformation polymorphism and heteroduplex analysis; potential variants were sequenced. Four novel and one previously reported mutation were detected, as well as three new polymorphisms. The novel mutations included deletions in exon 1 (patient 581/02), exon 5 (patient 780/01) and exon 7 (patient 700/01), and a C→T229 substitution in exon 3 (patient 462/02). When analysing patient 700/01 and his affected daughter, we encountered a mutant ENG allele with two mutations – a deletion in exon 7 and a substitution in exon 12 – which converts isoleucine 575 into threonine, in a non‐conserved region. Both mutations were absent in the two healthy sons of the patient, while the polymorphic variant in exon 12 was present in his healthy father. These results and haplotype‐segregation studies suggest that a de novo deletion had occurred in the gamete of paternal origin. For the first time the parental germline in which a de novo HHT mutation occurred has been identified.
Intact fetal cell isolation from maternal blood: improved isolation using a simple whole blood progenitor cell enrichment approach (RosetteSep™)
Authors: Bischoff FZ , Marquéz‐Do DA , Martinez DI , Dang D , Horne C , Lewis D , Simpson JL
Published: June 2003

Isolation and analysis of intact fetal cells in maternal blood is an attractive method of non‐invasive prenatal diagnosis; however, detection levels are not optimal. The poor sensitivity and inconsistent recovery of fetal cells is compounded by small numbers of circulating fetal cells and loss of fetal cells during enrichment procedures. Optimizing selection criteria by utilizing less complicated methods for target cell enrichment is essential. We report here salutary results using a simple density‐based depletion method that requires neither MACS (magnetic‐activated cell sorting) nor flow cytometric separation for enrichment of progenitor cells. Maternal blood samples (n = 81) were obtained from women prior to invasive prenatal genetic diagnostic procedures and processed randomly within 24 h using one of two density‐based enrichment methods. For progenitor cell enrichment, samples (n = 49) were labeled with a RosetteSep™ progenitor antibody cocktail to remove unwanted mature T‐cells, B‐cells, granulocytes, natural killer cells, neutrophils and myelomonocytic cells. For CD45‐negative cell enrichment, samples (n = 14) were labeled with RosetteSep™ CD45 antibody to remove unwanted maternal white cells. The desired cellular fraction was collected and analyzed by either fluorescent in situ hybridization (FISH) or real‐time PCR for the presence of intact fetal cells and to quantify Y‐chromosome‐specific DYS1 sequences, respectively. Overall, FISH and real‐time PCR correct detection rates for the progenitor cell enrichment approach were 53% and 89% with 3% (1 out of 30 cases) and 0% false–positive detection, respectively. Fetal sequences were detected in the range from 0.067 to 1.167 genome equivalents per milliliter of blood. No fetal cells were detected using the CD45‐negative enrichment method. Flow cytometric analysis of cord blood showed that a unique myeloid population of cells was recovered using RosetteSep™ progenitor enrichment compared with the CD45‐negative enrichment method. Sensitivity of the RosetteSep™ progenitor enrichment approach for detection of fetal cells in this pilot study shows great promise with recovery of cells that are suitable for FISH and automated microscope scanning. This simple and rapid method may also allow expansion in culture and characterization of the fetal cell type(s) that circulate in maternal blood, hence, greatly improving reliability of non‐invasive prenatal diagnosis.
Development of the thyroid gland: lessons from congenitally hypothyroid mice and men
Authors: Vliet G Van
Published: June 2003

Congenital hypothyroidism is the most common congenital endocrine disorder (one newborn in 3000) and represents the most common cause of preventable mental retardation. In 10–20% of cases, it is due to autosomal recessive functional disorders leading to goiter formation (thyroid dyshormonogenesis). In the remainder, it is due to thyroid dysgenesis, which comprises usually isolated defects in: (1) migration of the median thyroid anlage, leading to a round cluster of ectopic cells (usually in a sublingual position) with no other thyroid tissue present; (2) differentiation or survival of the thyroid follicular cells leading to athyreosis; and (3) growth of a thyroid with the normal bilobed shape and in the normal cervical position (orthotopic hypoplasia). Mouse knock‐outs have demonstrated that thyroid transcription factor‐1 (TTF‐1) and PAX8 are required for the survival and proliferation of thyroid follicular cell precursors, TTF‐2 for their downward migration and the thyrotropin receptor (TSHR) for post‐natal thyroid growth. In humans, thyroid dysgenesis is generally a sporadic malformation but an affected relative is found in 2% of cases, a figure 15‐fold higher than by chance alone. Pedigree analysis is most compatible with dominant inheritance with variable penetrance. However, mutations in TTF‐1, TTF‐2, PAX8 and TSHR are found in <10% of patients with congenital hypothyroidism and these predominantly have orthotopic thyroid hypoplasia, often associated with other malformations. This low yield and the discordance of >90% of monozygotic twin pairs suggests that isolated thyroid ectopy or athyreosis most often results from early somatic mutations, epigenetic modifications or stochastic developmental events.
The molecular genetics of Usher syndrome
Authors: Ahmed ZM , Riazuddin S , Riazuddin S , Wilcox ER
Published: June 2003

Association of sensorineural deafness and progressive retinitis pigmentosa with and without a vestibular abnormality is the hallmark of Usher syndrome and involves at least 12 loci among three different clinical subtypes. Genes identified for the more commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts from all these genes are found in many tissues/cell types other than the inner ear and retina, but all are uniquely critical for retinal and cochlear cell function. Many of these protein products have been demonstrated to have direct interactions with each other and perform an essential role in stereocilia homeostasis.
Prognostic factors in laryngeal carcinoma: the role of apoptosis, p53, proliferation (Ki‐67) and angiogenesis
Authors: TEPPO HEIKKI , SOINI YLERMI , MELKKO JUKKA , KOIVUNEN PETRI , ALHO OLLI‐PEKKA
Published: May 2003

Even though the roles of different known or suggested prognostic factors in laryngeal cancer have been studied in detail, clinical stage at time of diagnosis and anatomic subsite of the tumour remain the only practical predictors of clinical outcome and offer the only guidelines in the planning of treatment. In this study, the relative roles of known demographic and clinical prognostic factors, in addition to four histopathological factors, were evaluated in a sample of 100 laryngeal carcinoma patients with multivariate analysis using the Cox regression model. In addition to advanced stage (stage III‐IV) (relative hazard of death (HR) 8.9, p=0.01) and supraglottic disease (HR 5.6, p=0.02), high apoptotic index (HR 11.1, p=0.05) was significantly associated with poor survival. Cell proliferation, p53 and angiogenesis did not significantly affect the prognosis. In the future, high degree of apoptosis could be used to identify patients with poor prognosis in laryngeal cancer.
VEGF in 105 pheochromocytomas: enhanced expression correlates with malignant outcome
Authors: SALMENKIVI KAISA , HEIKKIL PÄIVI , LIU JIANQI , HAGLUND CAJ , AROLA JOHANNA
Published: May 2003

Pheochromocytomas are rare sympathoadrenal tumors that are highly vascular. Their malignancy is extremely difficult to estimate on the basis of histopathological features. Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors involved in both tumor growth and metastasis. In our search for new prognostic markers, we investigated the expression of VEGF in normal adrenal gland, in 105 primary pheochromocytomas, and in 6 metastases by using immunohistochemistry and Northern blot analysis. We also calculated the microvessel density of these tumors by staining the endothelial cells with monoclonal CD34 antibody.

VEGF messenger ribonucleic acid was found in all pheochromocytomas studied. Immunohistochemically, VEGF was not found in normal adrenal medullary cells. Interestingly, all malignant pheochromocytomas (n=8), regardless of their primary location, had strong or moderate VEGF immunoreactivity, while most benign adrenal pheochromocytomas (26 of 37, 70.3%) were either negative or only weakly positive. The staining was heterogenous in extraadrenal pheochromocytomas as well as in a group of tumors that had histologically suspicious features but had not metastasized, here called borderline tumors (n=29). The microvessel density varied greatly in all of the tumor groups, and no statistical difference was found between these groups.

Here we report moderate to strong VEGF expression in malignant pheochromocytomas, and negative or weak expression in benign adrenal pheochromocytomas. Normal medullary cells are immunohistochemically negative. Thus, low VEGF expression in pheochromocytomas favors a benign diagnosis.
Genetic alterations of the HCCS1 gene in Korean hepatocellular carcinoma
Authors: XIAO WENHUA , PARK CHEOL KEUN , PARK JIK YOUNG , LEE JONG HEUN , KIM HONG SUG , CHO YONG GOO , KIM CHANG JAE , AHN YOUNG MIN , LEE JONG HOO , SONG YOUNG HWA , LEE SUG HYUNG , YOO NAM JIN , LEE JUNG YOUNG , PARK WON SANG
Published: May 2003

We analyzed the gene mutations and loss of heterozygosity (LOH) of the HCCS1 gene using intragenic polymorphic markers in a series of 88 primary HCCs. We found two sequence variations at exon 5 and 14 in both normal and tumor DNAs of case 50 and 51, respectively. The variation in case 50 led to a reading frameshift and a premature stop (TGA) at codon 125 and case 51 showed amino acid change at codon 448 (Val→Ala, GTG→GCG). Interestingly, these variations were not found in peripheral lymphocytes of 69 normal individuals and 227 cancer patients (86 HCC, 75 unselected gastric cancer, and 66 breast cancer), suggesting that these two variations are mutation, not polymorphism. In addition, we found 14 novel intragenic polymorphic sites in the HCCS1 gene. Thirty‐two (47%) of sixty‐eight informative cases showed allelic loss at at least one or more intragenic polymorphic sites, but there was no significant relationship between the frequency of LOH and clinicopathologic parameters. These results suggest that mutation of the HCCS1 gene might not be a main inactivation mechanism in the development of Korean HCC and that the HCCS1 gene might be involved in acceleration of the tumorigenic process in Korean HCC.
Comamonas testosteroni meningitis in a patient with recurrent cholesteatoma
Authors: ARDA BILGIN , AYDEMIR SOHRET , YAMAZHAN TANSU , HASSAN ABDULLAHI , TÜNGER ALPER , SERTER DEMIR
Published: May 2003

Comamonas testosteroni, a lesser‐known member of the genus, has shown little apparent capacity for causing infections in humans. We here present a case of purulent meningitis due to C. testosteroni, which occurred in a patient who had recurrent cholesteatoma. Ceftriaxone treatment was not effective in this patient even though in vitro the bacteria were susceptible to the drug. The patient responded well to meropenem therapy.
Effects of Ocimum gratissimum L. essential oil at subinhibitory concentrations on virulent and multidrug‐resistant Shigella strains from Lagos, Nigeria
Authors: IWALOKUN B. A. , GBENLE G. O. , ADEWOLE T. A. , SMITH S. I. , AKINSINDE K. A. , OMONIGBEHIN E. O.
Published: May 2003

Ocimum gratissimum leaf extracts have been extensively demonstrated to be effective against the various aetiologic agents of diarrhoea, including Shigellae. However, the mechanism of the shigellocidal action of this plant remains to be understood. This study investigated the effects of O. gratissimum essential oil (EO) at subinhibitory concentrations of 0.75 and 1.0 μg/ml on virulence and multidrug‐resistant strains of 22 Shigella isolates from Nigeria. Compared with untreated Shigella strains, O. gratissimum EO caused significant decreases (p<0.01) in extracellular protease activity, o‐lipopolysaccharide rhamnose content and incidence of invasiveness mediated as keratoconjunctivitis in guinea pig. The disparity in extracellular protease activity and o‐lipopolysacharide rhamnose between the two treatment groups was also found to be significant (p<0.05), suggesting greater anti‐virulent effects of O. gratissimum oil at 1.0 μg/ml. Antibiotic susceptibility testing revealed that the EO of O. gratissimum reduced the MICs of antibiotics to which Shigellae showed resistance by 9.8–53.1% and fluoroquinolones by 18.2–45.5%. The results of this study strongly suggest inhibition of extracellular protease and expression of O‐LPS rhamnose in Shigellae by O. gratissimum EO. The future use of O. gratissimum– antibiotic combinations as a therapeutic measure against shigellosis is discussed.
Tumour‐type‐specific capillary endothelial cell stainability in malignant B‐cell lymphomas using antibodies against CD31, CD34 and Factor VIII
Authors: NORRBY KLAS , RIDELL BÖRJE
Published: May 2003

The microvessel density (MVD) was assessed in lymph nodes infiltrated by diffuse large B‐cell lymphomas, mantle cell lymphomas, chronic lymphatic leukemia and follicular lymphomas, and in lymphadenitis. Serial sections of formalin‐fixed and paraffin‐embedded tissue were stained with antibodies against CD31, CD34 or Factor VIII. Using light microscopy and computerised image analysis, the number and size of individual immunostained vessel profiles within a preselected area size range corresponding to capillaries, postcapillary venules, small collecting venules and small arterioles were determined. A significantly larger number of vessels were registered following staining with anti‐CD34 than with anti‐CD31 or anti‐Factor VIII. Moreover, among the smallest capillary‐sized vessel profiles in all lesion types, there was a selective relative loss of stainability of anti‐CD31 and anti‐Factor VIII, resulting in a substantial total loss of visualised capillary‐sized vessels compared with anti‐CD34. In fact, the number of non‐detected capillaries following staining with anti‐CD31 and anti‐Factor VIII was significantly tumour type specific. These findings influence how we evaluate MVD data in B‐cell lymphomas and possibly also other tumour types, as well as data relating to capillary endothelium‐related functional variables of proliferation, apoptosis and maturation when different double‐labelling immunohistochemical techniques are used and different tumour types are analysed.
Mutational analysis of Fas ligand gene in human non‐Hodgkin lymphoma
Authors: KIM HONG SUG , LEE SUG HYUNG , LEE JONG WOO , SOUNG YOUNG HWA , LEE JONG HEUN , PARK JIK YOUNG , CHO YONG GU , KIM CHANG JAE , KIM SU YOUNG , LEE YUN‐SIL , PARK WON SANG , KIM SANG HO , LEE JUNG YOUNG , YOO NAM JIN
Published: May 2003

Among the systems triggering apoptosis, the Fas‐Fas ligand (FasL) system is recognized as a major pathway for the induction of apoptosis in cells and tissues. Ligation of Fas by either an agonistic antibody or FasL transmits a ‘death signal’ to the target cell, potentially triggering apoptosis. Alterations of genes along the Fas‐mediated apoptosis pathway have been reported in many human cancers. However, there have been no data regarding FasL gene mutations in human cancers. We hypothesized that FasL gene mutation might be involved in the development of non‐Hodgkin lymphoma (NHL). In this study, we analyzed the entire coding region of the FasL gene for the detection of somatic mutations in a series of 111 NHLs and found that one tumor had a FasL gene mutation in the cytoplasmic domain. To evaluate the functional alterations of the mutant in apoptosis, we overexpressed the mutant in 293T cells, but couldn't find any significant loss of cell death compared to the wild‐type FasL. Together, these data suggest that FasL is occasionally mutated in human NHL and that FasL mutations appear to play no role in the pathogenesis of the vast majority of NHLs.