bluuebunny/crossref_metadata_2025 huggingface dataset:
Controls on sublithospheric small‐scale convection
Authors: Huang Jinshui , Zhong Shijie , van Hunen Jeroen
Published: August 2003

The Pacific upper mantle structures revealed from recent seismic studies prompt us to study the dynamics of sublithospheric small‐scale convection (SSC) derived from thermal boundary layer instabilities of cooling lithosphere. As oceanic lithosphere cools and thickens, its sublayer may go unstable, thus producing SSC in the asthenosphere. By formulating two‐dimensional (2‐D) and three‐dimensional (3‐D) numerical models with realistic mantle rheology, we examine the controls on the onset time of SSC and its dynamic consequences. The onset of SSC is mainly controlled by two parameters: activation energy and asthenospheric viscosity, which can be recast as the Frank‐Kamenetskii parameter θ and a Rayleigh number Rai, respectively. Our models show that the onset time of SSC, τc, scales as Rai−0.68θ0.74, independent of 2‐D or 3‐D geometry. Our scaling coefficient for θ is significantly smaller than that from previous studies, but the weaker dependence on activation energy confirms the result of Korenaga and Jordan [2003]. We found that thermal structure associated with age offset across fracture zones has significant effects on the onset of SSC, and it causes the SSC to occur always first near the fracture zones. Asthenospheric thickness and plate motion may also have significant effects on the onset of SSC. When the thickness of asthenosphere is sufficiently small to be comparable with the wavelength of the SSC, the onset may be delayed significantly. Plate motion also tends to delay the onset of the SSC in our 2‐D models. Although at the onset of SSC surface heat flux Q is consistent with the half‐space cooling model prediction, Q may eventually deviate from the half‐space cooling model prediction as thermal perturbations associated with SSC diffuse through the stable part of lithosphere or stagnant lid to the surface. We found that the time it takes for Q to deviate from the half‐space cooling model after the onset of SSC, Δτ, scales as Rai−0.65θ1.52, while the thickness of the stagnant lid at the onset time, δ, scales as Rai−0.33θ0.78, which is consistent with Δτ ∼ δ2 for thermal diffusion. At the onset of SSC, Q scales as Rai0.34θ−0.37 or τc−0.5 as expected from the half‐space cooling model. However, these scaling coefficients change significantly with time. After nine onset times Q scales as Rai0.28θ−0.7, which although showing the trend toward the scaling for steady state convection is still far from the predictions for steady state convection, thus suggesting a fundamentally transient nature of the SSC.
Clear‐column closure studies of aerosols and water vapor aboard the NCAR C‐130 during ACE‐Asia, 2001
Authors: Redemann J. , Masonis S. J. , Schmid B. , Anderson T. L. , Russell P. B. , Livingston J. M. , Dubovik O. , Clarke A. D.
Published: August 2003

Column closure studies are a tool to assess whether in situ and remote measurements of aerosol optical properties on a given aircraft are mutually consistent. In this paper we describe aerosol and water vapor column closure studies on the basis of instrumentation flown aboard the NCAR C‐130 aircraft in the ACE‐Asia field experiment in March–May 2001. For in situ observations, aerosol particles were sampled through a newly designed low‐turbulence inlet (LTI). In 28 profiles extending to altitudes of up to 8 km, the in situ observations of scattering and absorption were compared to measurements with the six‐channel NASA Ames Airborne Tracking Sun photometer (AATS‐6). The comparison of Sun photometer and in situ‐derived layer aerosol optical depth (AOD) at 550 nm showed agreement (closure) within the measurement uncertainties in 25 out of 28 case studies. The average difference in layer AOD derived from the two methods was 0.03, corresponding to an average difference of 11.5%. The uncertainties in AATS‐6‐derived layer AOD ranged between 5 and 59% (with a mean of 22%), and for the first time included an estimate for the uncertainty in layer AOD caused by possible horizontal variability in AOD encountered in the vertical profile. The average uncertainty in AATS‐6‐derived layer AOD due to possible horizontal variability alone was 19%. The uncertainties in in situ‐derived layer AOD were between 10 and 55% (with a mean of 19%). Stratification of the extinction closure data by ambient relative humidity (RH) revealed that in situ‐derived aerosol extinction at low ambient relative humidity (<20% RH) tended to be slightly less than Sun photometer‐derived aerosol extinction, while in situ‐derived aerosol extinction at higher relative humidity was slightly greater than the Sun photometer‐derived values. Stratification of the extinction closure data by the fine mode fraction of scattering indicated a modest enhancement of coarse mode extinction in the combined LTI/plumbing system. Analogous closure studies for layer water vapor and water vapor density showed that AATS‐6 measured these quantities with very high accuracy, with correlation coefficients of 0.989 and 0.955 (rms differences of 10% and 33%), respectively.
Limited dechlorination of sea‐salt aerosols during the last glacial period: Evidence from the European Project for Ice Coring in Antarctica (EPICA) Dome C ice core
Authors: Röthlisberger Regine , Mulvaney Robert , Wolff Eric W. , Hutterli Manuel A. , Bigler Matthias , de Angelis Martine , Hansson Margareta E. , Steffensen Jørgen P. , Udisti Roberto
Published: August 2003

Chloride (Cl−) and sodium (Na+) in ice cores originate mainly from sea salt, and one would thus expect the Cl−/Na+ ratio to reflect the seawater ratio. However, at Dome C, a low‐accumulation site in East Antarctica, this is not the case in present‐day snow. Instead, a Cl− excess relative to Na+ is observed in surface snow, and within a few meters depth the Cl− concentration decreases, and the Cl−/Na+ ratio becomes significantly lower than the seawater ratio. Aerosol studies at coastal Antarctic sites have shown that the reaction of sea‐salt aerosols with nitric and sulphuric acid leads to the formation of HCl that eventually escapes the sea‐salt aerosol. The observed decrease in Cl− concentrations in the uppermost snow layers is due to reemission of HCl from the snow. Postdepositional loss of HCl depends among other factors on the accumulation rate at the site, with lower accumulation rates leading to larger losses. During the Last Glacial Maximum (LGM) the Cl−/Na+ ratio is relatively stable and close to the seawater ratio, despite the even lower accumulation rate during that time. The likely explanation for this conflicting observation is that high levels of dust neutralized nitric and sulphuric acids during the LGM which in turn reduced the formation of HCl from sea‐salt aerosol. With less or no HCl formed, postdepositional loss would be prevented, keeping the Cl−/Na+ ratio close to that of sea water.
Constraints on the size of Martian aerosols from Thermal Emission Spectrometer observations
Authors: Wolff Michael J. , Clancy R. Todd
Published: September 2003

We combine a robust multiple‐scattering radiative transfer algorithm with the Thermal Emission Spectrometer (TES) spectral data set in order to characterize the properties of Martian aerosol particles. Because of the importance of accurate model input when performing such retrievals, we include self‐consistent and physically plausible treatments of surface emissivity and atmospheric aerosol dielectric functions, as well as gaseous absorption effects. Considerable effort is expended in the identification and discussion of potential sources of error and uncertainty. Significant results stemming from this analysis are a new dust aerosol dielectric function that appears to well represent the IR spectral behavior sampled by TES for a wide range of dust loading conditions, two distinct populations of water ice particles with reff of ∼1–2 μm and ∼3–4 μm; and distinct departures in dust particle sizes during the 2001A global dust storm from the canonical 1.6–1.7 μm values. Very consistent aerosol size distributions are obtained when 9 μm dust and 12 μm ice optical depths retrieved from this analysis are compared to visible optical depths retrieved from TES solar band emission phase function sequences [Clancy et al., 2003]. Direct comparison of our optical depths to those available from the Planetary Data System (PDS) (as provided by the TES science team) reveals a systematic bias toward τ values which are 20–30% (or more) too small. Much of this offset stems from the fact that TES PDS aerosol optical depths are actually an approximation to τabsorption, which is ∼30% lower than τextinction for Mars dust aerosols. Additional biases in TES optical depths arise from assumptions of fixed surface emissivity and temperature.
Mars aerosol studies with the MGS TES emission phase function observations: Optical depths, particle sizes, and ice cloud types versus latitude and solar longitude
Authors: Clancy R. Todd , Wolff Michael J. , Christensen Philip R.
Published: September 2003

Emission phase function (EPF) observations taken in 1999–2001 by Mars Global Surveyor Thermal Emission Spectrometer (MGS TES) support the broadest study of Martian aerosol properties to date. TES solar band and infrared (IR) spectral EPF sequences are analyzed to obtain first‐time seasonal/latitudinal distributions of visible optical depths, particle sizes, and single scattering phase functions. This combined angular and wavelength coverage enables identification of two distinct ice cloud types over 45°S–45°N. Type 1 ice clouds exhibit small particle sizes (reff = 1–2 μm) and a distinctive backscattering increase. They are most prevalent in the southern hemisphere during aphelion, but also appear more widely distributed in season and latitude as topographic and high‐altitude (≥20 km) ice hazes. Type 2 ice clouds exhibit larger particle sizes (reff = 3–4 μm), a distinct side‐scattering minimum at 90–100° phase angles (characteristic of a change in particle shape relative to the type 1), and appear most prominently in the northern subtropical aphelion cloud belt. The majority of retrieved dust visible‐to‐IR optical depth ratios are indicative of reff = 1.5 ± 0.1 μm, consistent with Pathfinder and Viking/Mariner 9 reanalyses. However, increased ratios (2.7 versus 1.7) appear frequently in the northern hemisphere over LS = 50–200°, indicating substantially smaller dust particles sizes (reff = 1.0 ± 0.2 μm) at this time. In addition, larger (reff = 1.8–2.5 μm) dust particles were observed locally in the southern hemisphere during the peak of the 2001 global dust storm. Detailed spectral modeling of the TES visible band pass indicates agreement of EPF‐derived dust single scattering albedos (0.92–0.94) with the spectrally resolved results from Pathfinder observations.
A solar system survey of forced librations in longitude
Authors: Comstock Robert L. , Bills Bruce G.
Published: September 2003

Forced librations are periodic rotational rate variations due to gravitational interactions with an orbital partner. We have developed an analytic theory capable of calculating expected amplitudes of forced librations for nonresonant rotators as well as for bodies existing in a spin‐orbit resonance. The theory has been applied to 34 solar system bodies, including terrestrial planets, planetary satellites, and the asteroid Eros. Parameters governing libration amplitude are the body's orbital eccentricity, moment difference, and the ratio of its spin rate to its orbital rate. In each case the largest libration amplitude is associated with the forcing frequency 2 (p − 1) n, where n is the orbital mean motion and p is the spin/orbit rate ratio. This dominant frequency is simply semidiurnal as seen from the position of the torquing body. The maximum libration angular amplitude is 1.3 × 10−2 radians for Thebe, and the maximum mean equatorial displacement is 1.4 km for Mimas.
Surface versus internal loading of the Tharsis rise, Mars
Authors: Lowry Anthony R. , Zhong Shijie
Published: September 2003

Two hypotheses compete to explain the remarkable topography and geoid of the Tharsis province on Mars: One attributes Tharsis to volcanically constructed surface loads, whereas the second views it as dynamic effects of single‐plume mantle convection. Both are likely to contribute, so we would like to constrain both. We introduce a method to invert load structure from geoid and topography of a viscoelastic planetary body. Estimates of the internal load contribution to Tharsis depend on assumed parameters. Buoyancy of the internal load estimate increases with increasing lithospheric thickness, crustal density, and crustal thickness, and load size increases with depth of loading. Despite parameter uncertainties, we can rule out a predominantly internal load. We cannot reject the possibility that Tharsis results from surface loading alone. Internal loads contribute at most 35% of the lithospheric force balance, 50% of the topography, and 25% of the geoid at Tharsis, for load depths ≤420 km and lithospheric thickness Te ≤ 200 km. A corollary is that any Te and reference density structure can exactly reproduce the geoid and topography if internal loading can vary as a function of harmonic degree and order. Hence Te and density estimates depend on assumptions about internal loading. If surface and internal loads are approximately uncorrelated, Te is ∼110 km with crustal density ∼2600 kg m−3. Adopting these parameters, internal buoyancy contributes 2.1% of lithospheric loading, 4.2% of topography, and 0.7% of the geoid at Tharsis for a 200 km deep load, or 4.3% of lithospheric loading, 8.5% of topography, and 2.2% of the geoid for a load at 400 km depth.
Misleading hallucinations in unrecognized narcolepsy
Authors: Szűcs A. , Janszky J. , Holló A. , Migléczi G. , Halász P.
Published: September 2003

Objective: To describe psychosis‐like hallucinatory states in unrecognized narcolepsy.

Method: Two patients with hypnagogic/hypnapompic hallucinations are presented.

Results: Both patients had realistic and complex – multi‐modal and scenic‐daytime sexual hallucinations leading, in the first case, to a legal procedure because of false accusation, and in the second, to serious workplace conflicts. Both patients were convinced of the reality of their hallucinatory experiences but later both were able to recognize their hallucinatory character. Clinical data, a multiple sleep latency test, polysomnography, and HLA typing revealed that both patients suffered from narcolepsy.

Conclusion: We suggest that in unrecognized narcolepsy with daytime hypnagogic/hypnapompic hallucinations the diagnostic procedure may mistakenly incline towards delusional psychoses. Daytime realistic hypnagogic/hypnapompic hallucinations may also have forensic consequences and mislead legal evaluation. Useful clinical features in differentiating narcolepsy from psychoses are: the presence of other narcoleptic symptoms, features of hallucinations, and response to adequate medication.
Postmaturity in a genetic subtype of schizophrenia
Authors: Chow E. W. C. , Husted J. , Weksberg R. , Bassett A. S.
Published: September 2003

Objective: To determine whether postmaturity (gestation > 41 weeks), small for gestational age (SGA), and other pregnancy and birth complications that may elevate risk for neurodevelopmental disorders, are associated with elevated risk for schizophrenia in 22q11 Deletion Syndrome (22qDS), a genetic subtype of schizophrenia.

Method: Antepartum and intrapartum features were examined in 20 adults with 22qDS‐schizophrenia and three comparison groups: newborn encephalopathy (n = 164) and healthy newborn controls (n = 400) from Badawi et al.'s (Br Med J 1998, 317: 1549) study, and 16 non‐psychotic 22qDS adults (22qDS‐NP).

Results: Postmaturity (OR 13.0, 95% CI 3.95, 42.77; P < 0.001) and SGA (OR 3.59, 95% CI 1.23, 10.5; P = 0.03) were more prevalent in 22qDS‐SZ than controls. Postmaturity was non‐significantly more prevalent in 22qDS‐SZ than in newborn encephalopathy (P = 0.06) or 22qDS‐NP (P = 0.2). SGA showed similar rates in the two 22qDS groups and newborn encephalopathy, but was more prevalent in 22qDS‐NP than controls (P = 0.05).

Conclusion: The results suggest that postmaturity may be associated with expression of schizophrenia in a 22qDS subtype of schizophrenia. SGA may be a non‐specific marker of neurodevelopmental disturbance.
Depression and subjective quality of life in chronic phase schizophrenic patients
Authors: Reine G. , Lançon C. , Di Tucci S. , Sapin C. , Auquier P.
Published: September 2003

Objective: To evaluate the influence of depression on subjective quality of life in schizophrenic patients.

Method: Sixty‐seven schizophrenic patients in a stabilized phase were included. Schizophrenic symptoms were evaluated using the Positive and Negative Symptoms Scale (PANSS). The subjective quality of life was evaluated using the short version of the Lehman quality of life scale (QoLI). Depression was evaluated using the Calgary Depression Scale for Schizophrenia (CDSS) and extrapyramidal effects with the Extrapyramidal Symptoms Rating Scale (ESRS).

Results: The PANSS total score, PANSS general psychopathology subscore, PANSS depression factor, the total CDSS and some ESRS scores were negatively correlated with the overall life satisfaction score. The CDSS score was negatively correlated with all except one QoLI score. QoLI scores were significantly lower in depressed patients, and this result remained consistent for four QoLi dimensions when adjusted on ESRS and PANSS scores. When analysing the association between high depression scores and high parkinsonism scores with reduced quality of life, multivariate analysis showed that depression was the main explanatory factor: the CDSS total score explained 22% of the variance of the overall subjective quality of life score. The patient questionnaire at the ESRS explained 10.5% of the variance of the ‘mental and physical health’ QoLI score.

Conclusion: In schizophrenic patients, depressive symptoms should be focused because of their strong association to overall subjective quality of life.
Brain morphological abnormality in schizophrenia is independent of country of origin
Authors: Chua S. E. , Lam I. W. S. , Tai K.‐S. , Cheung C. , Tang W.‐N. , Chen E. Y. H. , Lee P. W. H. , Chan F.‐L. , Lieh‐Mak F. , McKenna P. J.
Published: September 2003

Objective: The disorder schizophrenia has a worldwide prevalence of 1% and is generally associated with lateral cerebral ventricular enlargement. Whether there is a relationship between these two findings is unclear but has aetiological relevance.

Method: Consecutively admitted Chinese patients (n = 19) with first episode of schizophrenia and healthy community volunteers (n = 29) underwent magnetic resonance imaging brain scan. The groups were balanced for age, sex, best social class and handedness. These patients were similar on clinical and socio‐demographic indices to those who declined participation (n = 15). Semi‐automated volumetric analysis of whole brain volume, cortical grey matter, cerebrospinal fluid, sulci and lateral ventricles was performed.

Results: Chinese patients in their first episode of schizophrenia have significant enlargement of lateral ventricles.

Conclusion: Brain morphological abnormality in schizophrenia is present regardless of the country of origin. The importance of genes in driving normal brain development and stable prevalence suggests that aetiology may favour genes over environment.
Attention profile in schizophrenia compared with depression: differential effects of processing speed, selective attention and vigilance
Authors: Egeland J. , Rund B. R. , Sundet K. , Landrø N. I. , Asbjørnsen A. , Lund A. , Roness A. , Stordal K. I. , Hugdahl K.
Published: September 2003

Objective: The aim of the study is to investigate whether subjects with schizophrenia and major depression display attention deficits for different reasons.

Method: Subjects with schizophrenia (n = 53), recurrent major depression (n = 50) and normal controls (n = 50) were administered with 11 measures of processing speed, selective attention and vigilance. Indices of basal speed, speeded attention, non‐speeded attention and vigilance were computed.

Results: Both clinical groups were impaired on all chronometric tests. The schizophrenic subjects were also more impaired on speeded attention compared with basal processing speed. Only the schizophrenics were impaired on the non‐speeded measures of selective attention. Compared with the schizophrenics, the depressives showed a decrement in vigilance.

Conclusion: Reduced performance on attention tests in major depression is because of a non‐specific speed reduction and loss of vigilance consistent with lack of effort. In addition to generally impaired processing speed, the schizophrenic subjects exposed a deficit in selective attention, indicating executive dysfunction.
The stigma of mental illness: effects of labelling on public attitudes towards people with mental disorder
Authors: Angermeyer M. C. , Matschinger H.
Published: September 2003

Objective: Aim of the study is to examine the impact of labelling on public attitudes towards people with schizophrenia and major depression.

Method: In Spring 2001, a representative survey was carried out in Germany involving adults of German nationality (n = 5025).

Results: Labelling as mental illness has an impact on public attitudes towards people with schizophrenia, with negative effects clearly outweighing positive effects. Endorsing the stereotype of dangerousness has a strong negative effect on the way people react emotionally to someone with schizophrenia and increases the preference for social distance. By contrast, perceiving someone with schizophrenia as being in need for help evokes mixed feelings and affects people's desire for social distance both positively and negatively. Labelling has practically no effect on public attitudes towards people with major depression.

Conclusion: Our findings illustrate the need for differentiation, differentiation between the different components of stigma as well as differentiation between the various mental disorders.
The first episode of psychosis: the experience of relatives
Authors: Addington J. , Coldham E. L. , Jones B. , Ko T. , Addington D.
Published: September 2003

Objective: The aim was to determine the extent of and the correlates of the distress and impact of care families of patients with first episode psychosis were experiencing when they first came for treatment.

Method: Subjects were 238 individuals who had presented with a first episode of psychosis and their family members. Family members were assessed with the Psychological General Well‐Being Scale, and the Experience of Caregiving Inventory. Patient data included assessment of positive and negative symptoms, depression, quality of life, and substance use.

Results: Family members of these first‐episode patients were experiencing distress and difficulties. It was the family's appraisal of the impact of the illness that was associated with their psychological well‐being.

Conclusion: As the majority of these first episode families are keen to be involved early and have engaged in an intervention programme, the next step should be an evaluation of their involvement to determine if it is effective.
The Family Questionnaire (FQ): a scale for measuring symptom appraisal in relatives of schizophrenic patients
Authors: Quinn J. , Barrowclough C. , Tarrier N.
Published: September 2003

Objective: This study examined the psychometric properties of the Family Questionnaire (FQ): a self‐report measure of relatives’ perceptions of the behaviours and symptoms of schizophrenic patients in terms of three dimensions: the frequency of symptoms, the relatives’ concern (primary appraisal) and their ability to cope (secondary appraisal) with the symptoms.

Method: Factor analysis of the FQ, test–retest and inter‐rater reliability, and measures of validity were examined.

Results: Factor analysis supported the validity of five subscales labelled negative symptoms, antisocial behaviours, interpersonal problems, affective symptoms and psychotic symptoms. Test–retest reliability for all scales was good and the prediction that there would be limited correspondence between two different relatives’ scores was supported for the subscales of negative symptoms and affective symptoms. Concurrent measures of relatives’ distress, burden and patients’ symptomatology indicated that the FQ showed acceptable validity. In particular, the study showed that high expressed emotion relatives have higher scores on the appraisal dimensions of some subscales.

Conclusion: The study provides evidence that the FQ is a useful tool for measuring relatives’ perceptions of schizophrenic illness, particularly within the context of family interventions where it may be utilized to help to understand the factors mediating relatives’ burden and distress.
Behavioural management of antipsychotic‐induced weight gain: a review
Authors: Werneke U , Taylor D , Sanders T.A.B. , Wessely S
Published: September 2003

Objective: Although psychiatrists are aware of weight gain induced by atypical antipsychotics, only few studies on behavioural interventions in this patient group are published. This review aims to summarize the evidence on effectiveness of behavioural interventions for weight gain in the general population and in‐patients treated with atypical antipsychotics.

Method: Medline and Cochrane databases search for evidence on effectiveness of behavioural interventions.

Results: In general, behavioural approaches including, diet, exercise and drug treatments may be effective. There were only 13 studies of behavioural interventions for patients taking antipsychotic medication. No study met the criteria for a RCT. Calorie restriction in a controlled ward environment, structured counselling combined with cognitive behavioural therapy and counselling on life style and provision of rewards may potentially lead to weight loss.

Conclusion: Currently only limited, methodologically flawed, evidence is available that behavioural interventions in overweight patients treated with antipsychotics, although intuitively appealing, actually work.
Long‐term inter‐episode stability of syndromes underlying mania
Authors: Sato T. , Bottlender R. , Sievas M. , Schröter A. , Hecht S. , Möller H.‐J.
Published: September 2003

Objective: To explore the stability of diverse manic presentations across manic recurrences.

Method: A total of 253 bipolar patients who experienced two or more hospitalizations, because of consecutive manic (or mixed) episodes, during a 20‐year period were included. All patients had second hospitalizations with an mean interval of 773 days, while 126 and 91 patients had third and fourth hospitalizations with mean intervals of 1559 and 2237 days from the index hospitalization, respectively. Seven symptom scores, previously factor‐validated, were calculated.

Results: Depressive mood, irritable aggression, psychomotor/thought inhibition, mania, emotional lability/agitation and psychosis were moderately correlated across the index and subsequent hospitalizations.

Conclusion: A majority of diverse manic presentations were stable across manic recurrences. The stability was not restricted to two consecutive recurrences but appeared widespread over the long‐term course of bipolar disorder. The finding may serve for the development of more effective long‐term treatment strategies and a clinically more reasonable subtyping of mania.
Peripheral T‐cell lymphoma associated consecutively with hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome
Authors: Gutiérrez Antonio , Solano Carlos , Ferrández Antonio , Marugán Isabel , Terol María José , Benet Isabel , Tormo Mar , Bea María Dolores , Rodríguez José
Published: September 2003

Abstract:  Both hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome have been associated with hematologic neoplasms and are respectively related to an overproduction of the cytokines Thelper 1 (Th1) and Th2 by tumor cells or reactive cells. To our knowledge, this is the first time a case of a peripheral T‐cell lymphoma consecutively associated with both paraneoplastic conditions has been reported. Importantly, in this case when the lymphoma exclusively involved the bone marrow, severe paraneoplastic systemic damage, a CD8+ suppressor/cytotoxic phenotype and a hypereosinophilia not related to high levels of interleukin (IL)‐5 was found. Interestingly, progression of the lymphoma coincided with an increase in the serum levels of several Th2 cytokines and IL‐2, a decrease in tumor necrosis factor and granulocyte‐macrophage colony‐stimulating factor levels and the onset of a hypereosinophilic syndrome.
Molecular differences between small and large cells in patients with chronic lymphocytic leukemia
Authors: Lee Jeong N. , Giles Fancis , Huh Yang O , Manshouri Taghi , O'Brien Susan , Kantarjian Hagop M. , Keating Michael J. , Albitar Maher
Published: September 2003

Abstract: The genetic events involved in the transformation of chronic lymphocytic leukemia (CLL) to Richter's syndrome (RS) are poorly understood. Frequently large cells are seen in the bone marrows of patients with CLL and evidence of RS. Using a laser‐capture microdissection we analyzed small and large leukemic bone marrow cells from 19 patients with RS for loss of heterozygosity (LOH) on chromosome 11 (D11S2179 at the ATM gene), 17 (D17S938 and D17S1852 at the TP53 site), and 20 (Plc1, D20S96, D20S110, and D20S119). Megakaryocytes were also isolated and used as a control for normal cells. Four of 15 (27.7%) informative cases showed LOH in small cells in the ATM gene while seven (46.7%) showed LOH in large cells. Six of 15 (40%) informative cases had LOH in chromosome 17 in small cells, and eight (53%) showed LOH in large cells. Eleven of 19 informative cases (61.1%) showed LOH in chromosome 20 in large cells, and eight (42.1%) showed LOH in small cells. RS cases with LOH at chromosome 20 were associated with marginally shorter survival rates (P = 0.08). Our data suggest that there are significant molecular differences between large and small cells in patients with CLL. Further analysis of the genes on these chromosomes may provide new insight into our understanding of the transformation of small CLL cells to large (Richter) cells.
An unusual case of CD4+ CD7+ CD56+ acute leukemia with overlapping features of type 2 dendritic cell (DC2) and myeloid/NK cell precursor acute leukemia
Authors: Anargyrou K. , Paterakis G. , Boutsis D. , Politou M. , Papadhimitriou S. I. , Siakandaris M. , Vassiliadis J. , Androulakis A. , Meletis J. , Rombos J. , Tassiopoulou A. , Vaiopoulos G.
Published: September 2003

Abstract: Type 2 dendritic cell (DC2) acute leukemia has been recently described. We report here an unusual case of a 17‐yr‐old adolescent with overlapping features of DC2 and myeloid/NK cell precursor acute leukemia as defined by Suzuki et al. The patient presented with lymphadenopathy and hepatosplenomegaly without extranodal manifestations in skin or elsewhere. The morphologic, cytochemical and immunophenotypic features were compatible with those described in DC2 acute leukemia, with co‐expression of CD4, CD56 and CD123 antigens. The novel markers BDCA‐4 and BDCA‐2 considered specific for DC2s were co‐expressed. However, bright CD7 positivity along with a dim expression of CD33 (57%) and CD117 (27%) were also noted. Additionally, there was bright expression of NG2 monoclonal antibody 7.1, a frequent finding in myeloid/NK cell precursor acute leukemia. The interpretation of the immunophenotypic profile leads to the hypothesis on the existence of borderline cases between DC2 and myeloid/NK cell precursor acute leukemia. Still, other hypotheses can not be overlooked, such as the possibility for a kind of variant monoblastic leukemia or of another rare entity of acute unclassified leukemia.
Multilobated nuclei in Waldenström’ macroglobulinaemia
Authors: Metzgeroth G. , Sick Ch. , Maywald O. , Schatz M. , Kuhn Ch. , Hehlmann R. , Hastka J.
Published: September 2003

Abstract: We report a case of Waldenström’ macroglobulinaemia, where the bone marrow analysis showed an almost complete infiltration by a heterogeneous population, consisting of 80% small lymphoplasmacytoid cells and 20% large atypical cells with multilobulated nuclei. Both cell populations were CD19+ and CD38+ and contained IgM. Fluorescence in situ hybridization analysis with a chromosome 8 painting probe on interphase nuclei revealed only two signals in each cell, including in those with multiple nuclei. Our findings suggest that the multilobulated nuclear structures are diploid and originate from a single nucleus. In contrast to the published multiple myeloma cases, our patient showed good response to chemotherapy. After successful chemotherapy, the morphology of the lymphoma changed into typical lymphoplasmacytoid lymphoma. The multilobulated population was no longer detectable. Five years after the initial diagnosis, the patient is still alive and in good health.
CD7 expression by CD34+ cells in CML patients, of prognostic significance?
Authors: Normann Are P. , Egeland Torstein , Madshus Inger H. , Heim Sverre , Tjønnfjord Geir E.
Published: September 2003

Abstract:  The purpose of the study was to identify a unique immunophenotype of normal or Philadelphia chromosome positive (Ph+) CD34+ cells that might be used to purify normal CD34+ cells from chronic myelogenous leukemia (CML) patients. An immunophenotypical study of CD34+ bone marrow cells of 20 patients with CML at diagnosis and during hydroxyurea treatment, and 39 controls were performed. All patients were Ph+, two patients had variant translocations and three patients displayed cytogenetic signs of clonal evolution. The immature progenitor cell compartment (CD34+ HLA‐DR− and CD34+ CD38− cells) was comparable. The CD34+ AC133+ progenitor cell compartment was decreased in CML patients. We found no difference for any of the adhesion molecules examined except for CD62L, where the percentage of CD34+ CD62L+ cells was decreased in CML patients. The number of myeloid progenitors (CD34+ CD33+) was increased at the expense of B‐lymphoid progenitors (CD34+ CD10+ and CD34+ CD19+) in CML patients indicating that B‐lymphopoiesis is inhibited in CML. The megakaryocytic (CD34+ CD61+) and erythroid (CD34+ CD71+) progenitors were increased in CML patients. The number of CD34+ CD7+ cells was also significantly increased (mean 25.3% vs. 4.9%). However, the level of CD7 expression was quite heterogeneous, and the patients could be separated into two populations according to CD7 expression (more or less than 20% CD7+ CD34+ cells). The Sokal and Hasford risk scores did not differ between CD34+ CD7− CML and CD34+ CD7+ CML, but all patients with signs of disease progression clustered in the CD34+ CD7+ population indicating that the level of CD7 expression on CD34+ cells may be of prognostic importance in CML.
Collagen metabolism and enzymes of the urokinase plasminogen activator system in chronic myeloproliferative disorders: correlation between plasma‐soluble urokinase plasminogen activator receptor and serum markers for collagen metabolism
Authors: Jensen Morten Krogh , Riisbro Rikke , Holten‐Andersen Mads N. , Brown Peter de Nully , Junker Peter , Brünner Nils , Hasselbalch Hans C.
Published: September 2003

Abstract:  Extracellular proteolytic enzymes of the urokinase‐type plasminogen activator (uPA) system and the family of metalloproteinases (MMPs) catalyse the matrix degradation and remodelling processes characteristic of invasive malignant disorders. In a cohort of 50 patients with chronic myeloproliferative disorders (MPD) serum markers for collagen metabolism were compared to plasma levels of enzymes of the uPA and MMP system. Serum aminoterminal propeptide of type III procollagen (S‐PIIINP) (P < 0.0001) concentration was significantly higher in the patients (median 3.7 μg/L vs. 2.5 μg/L) compared with controls. In a subgroup analysis comprising patients with myelofibrosis (MF), polycythaemia vera (PV) and essential thrombocythaemia (ET), respectively, S‐PIIINP levels differed significantly with the highest values found in patients with MF (MF vs. PV vs. ET; P = 0.0027). Serum concentration of carboxyterminal telopeptide of type I collagen (S‐ICTP) (P = 0.0006), reflecting type I collagen degradation, was significantly higher in patients compared with controls (median 4.0 μg/L vs. 2.7 μg/L). When comparing S‐ICTP measurements between patient subgroups and controls there were only significantly higher values among MF and PV patients (MF vs. controls; P < 0.0001, PV vs. controls; P = 0.0016). A significant correlation between the marker for collagen synthesis (S‐PIIINP) and degradation (S‐ICTP) (r = 0.59; P < 0.0001) was demonstrated. A correlation analysis between serum markers for bone marrow remodelling processes (S‐PIIINP, S‐ICTP and S‐hyaluronan) and plasma‐soluble urokinase plasminogen receptor (suPAR) disclosed a significant relationship between suPAR and S‐PIIINP (r = 0.48; P = 0.0009), S‐hyaluronan (r = 0.56; P < 0.0001) and S‐ICTP (r = 0.47; P = 0.0013), respectively. Plasma levels of MMP‐2 and ‐9 were not correlated to serum markers for collagen metabolism. These findings suggest that enzymes of the uPA system might participate in the bone marrow remodelling processes characteristic of MPD.
Clinical features in T‐cell vs. natural killer‐cell variants of large granular lymphocyte leukemia
Authors: Neben Michelle A. , Morice William G. , Tefferi Ayalew
Published: September 2003

Objective: Standard clinical and laboratory evaluations and novel laboratory techniques were used to identify patients with T‐cell large granular lymphocyte leukemia (LGLL) and those with natural killer‐cell variants of LGLL for comprehensive clinical evaluation.

Methods: We used bone marrow histologic analysis, immunophenotypic markers of clonality, and T‐cell–receptor gene rearrangement studies to identify patients.

Results: The study identified 44 patients with T‐cell LGLL and 14 with natural killer‐cell LGLL. The two disorders were similar in sex and age distribution of patients; peripheral blood lymphocyte, neutrophil, and platelet counts; and incidence of rheumatoid arthritis. Among the two groups, patients with the T‐cell LGLL presented with significantly lower hemoglobin concentrations (P < 0.04) and a higher frequency of palpable splenomegaly (P < 0.01).

Conclusion: Overall disease progression and response to immunosuppressive therapy are similar between T‐cell and natural killer‐cell variants of LGLL.
High Th1/Th2 ratio in patients with chronic idiopathic thrombocytopenic purpura
Authors: Ogawara Hatsue , Handa Hiroshi , Morita Kimio , Hayakawa Masaki , Kojima Junko , Amagai Hatsuo , Tsumita Yuki , Kaneko Yoriaki , Tsukamoto Norifumi , Nojima Yoshihisa , Murakami Hirokazu
Published: September 2003

Abstract:  Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by increased platelet clearance because of antiplatelet antibodies. It was recently reported that the balance of T helper 1 (Th1) and T helper 2 (Th2) subsets has been implicated in the regulation of many immune responses. In this study, the intracellular interleukin‐4 and interferon‐γ production in CD4+ T‐lymphocytes activated by phorbol 12‐myristate 13‐acetate and ionomycin was assessed via flow cytometry in order to determine the clinical significance of the Th1/Th2 ratio in 42 patients with ITP. The study cohort included 28 untreated patients, seven postprednisolone therapy patients and seven postsplenectomy patients. The mean level of the Th1/Th2 ratio in the untreated group was 36.9 (95% CI 25.8–47.9), and significantly higher than in the control group (mean 12.8, 95% CI 9.5–16.1). The mean levels of the Th1/Th2 ratio in the postprednisolone therapy and postsplenectomy groups were 20.5 (95% CI 8.4–32.6) and 16.4 (95% CI 3.1–29.7), respectively, but were no significant differences as compared with control subjects. When untreated patients were divided into two subgroups by Th1/Th2 ratio, the mean level of platelet associated IgG in the high Th1/Th2 subgroup (higher than upper limit of control group) tended to be higher than in the normal Th1/Th2 subgroup. In conclusion, the high Th1/Th2 ratio was closely related to the etiology and disease status of chronic ITP.
Generation of a haptoglobin–hemoglobin complex‐specific Fab antibody blocking the binding of the complex to CD163
Authors: Horn Ivo R. , Nielsen Marianne Jensby , Madsen Mette , Jacobsen Christian , Graversen Jonas Heilskov , Moestrup Søren K. , Jacobsen C.
Published: September 2003

Abstract:  During intravascular hemolysis hemoglobin (Hb) binds to haptoglobin (Hp) leading to endocytosis of the complex by the macrophage receptor, CD163. In the present study, we used a phage‐display Fab antibody strategy to explore if the complex formation between Hp and Hb leads to exposure of antigenic epitopes specific for the complex. By Hp–Hb‐affinity screening of a phage‐Fab library, we isolated a phage clone against the ligand complex. Surface plasmon resonance analyses of the Fab part expressed as a recombinant protein revealed a high affinity binding (KD = 3.9 nm) to Hp–Hb, whereas no binding was measured for non‐complexed Hp or Hb. The Fab antibody completely inhibited the binding of 125I‐labeled Hp–Hb complexes to CD163 and blocked their uptake in CD163‐transfected cells. In conclusion, we have raised a receptor‐blocking antibody specifically recognizing the Hp–Hb complex. In addition to provide new insight into the changes occurring when Hp and Hb bind, the present study provides a new potential tool for measuring and removal of Hp–Hb complexes from plasma/serum.
Treatment of patients with advanced mycosis fungoides and Sézary syndrome with alemtuzumab
Authors: Kennedy G. A. , Seymour J. F. , Wolf M. , Januszewicz H. , Davison J. , McCormack C. , Ryan G. , Prince H. M.
Published: September 2003

Abstract:  Objectives: Alemtuzumab (anti‐CD52, Campath‐1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B‐cell chronic lymphocytic leukemia and T‐cell prolymphocytic leukemia. We undertook a phase II study to evaluate the safety, tolerability and efficacy of alemtuzumab in patients with relapsed or refractory advanced stage cutaneous T‐cell lymphoma.

Patients and methods: A total of eight patients were enrolled, seven with mycosis fungoides/Sézary syndrome (MF/SS) and one with large‐cell transformation of MF. Seven patients had disease refractory to multiple previous therapies. Alemzumab (30 mg) was administered intravenously three times per week for 12 wk or until maximum response.

Results: The overall response rate was 38%, with three patients achieving partial remission, two patients with stable disease and three patients with progressive disease (PD) during treatment. The time to progression was short, with all patients developing PD within 4 months of starting alemtuzumab. Response duration in the three PR patients was also brief, with responses lasting less than 3 months in all three cases. Significant hematological and immunosuppressive toxicity was observed, with both grade 3–4 cytopenias and significant infectious complications occurring in a majority of cases.

Conclusions: Our findings suggest that in heavily pretreated, refractory, advanced stage MF/SS, although alemtuzumab has biological activity, it is associated with significant toxicity and only modest clinical utility. As such, combination regimens incorporating alemtuzumab merit further investigation in this difficult to treat patient group.
ALK‐positive anaplastic large‐cell lymphoma: strong T and B anti‐tumour responses may cause hypocellular aspects of lymph nodes mimicking inflammatory lesions
Authors: Borisch B. , Yerly S. , Cerato Ch. , Schwaller J. , Wacker P. , Ozsahin A. H. , Brousse N. , Hoessli D. C.
Published: September 2003

Abstract: The anaplastic large cell lymphoma kinase (ALK)‐positive anaplastic large cell lymphoma (ALCL) is a rare type of non‐Hodgkin lymphoma which occurs in children mostly. The ALK protein is highly immunogenic and elicits both humoral and cellular immune responses. A 15‐yr‐old child presented with fever and adenopathy and did not respond to antibiotics. Biopsy of the enlarged lymph node contained almost no lymphoid element except for a few CD8‐positive T cells, plasma cells and isolated CD30‐positive blasts. The patient's condition improved following lymphadenectomy but relapse occurred 3 months later with multiple nodes, high fever and an abdominal mass. This time an ALK‐positive ALCL was diagnosed and the retrospective analysis of the initial biopsy revealed rare, isolated ALK+ cells. Molecular analysis showed T‐cell clones and oligoclonal B cells in both biopsies and peripheral blood of the patient. The tumour cells harbour a t(2;5) translocation, revealing a null phenotype by immunohistochemistry and no evidence for T‐cell clonality by Southern blotting. The patient's serum contained anti‐ALK antibodies. Our findings suggest that the T‐cell clones and anti‐ALK antibodies in this patient constitute an anti‐tumour response that caused the hypocellularity of the initial lymph node. Hypocellular and oedematous lymph nodes occurring in a child with evocative symptoms should be tested for the presence of ALK.
Antiphospholipid syndrome and endocrine damage: why bilateral adrenal thrombosis?
Authors: Berneis Kaspar , Buitrago‐Téllez Carlos , Müller Beat , Keller Ulrich , Tsakiris Dimitrios A.
Published: September 2003

Abstract: We describe a rare case of bilateral hemorrhagic infarction of the adrenal glands diagnosed in the context of positive antiphospholipid antibodies (aPL). The patient presented atypical clinical symptoms of adrenal insufficiency. Laboratory investigation showed complete adrenal failure and increased aPL, both manifestations persisted 1 yr after the initial event. MR imaging at baseline was compatible with bilateral hemorrhagic infarction and showed almost complete loss of viable adrenal tissue 1 yr later. Although no direct causal effect can be proved, the sequence of events and the exclusion of other common causes of bilateral adrenal hemorrhage (e.g. tuberculosis, severe coagulation disorder) support an association between aPL and adrenal hemorrhagic infarction. A unique link between particular anatomical characteristics of the adrenal fascicular zone and a novel, previously described, explanation model of aPL‐thrombosis is hypothesized. It is based on the properties of late endosomes, which are important organelles participating in cholesterol trafficking and protein sorting within cells and express epitopes recognized by aPL. It would be interesting to investigate adrenal tissue for presence of late endosomes and their aPL relevant epitopes for proof of this tempting hypothesis. Focal accumulation of aPL and isolated, simultaneous, bilateral adrenal infarctions could thus be explained.