bluuebunny/crossref_metadata_2025 huggingface dataset:
Bullous amyloidosis: the mechanism of blister formation revealed by electron microscopy
Authors: Ochiai Toyoko , Morishima Takafumi , Hao Takako , Takayama Atsuko
Published: March 2003

Background: Few electron microscopic studies of blister lesions in bullous amyloidosis have been reported, and the mechanism of blister formation remains to be elucidated. This study was designed to examine the nature of bullous amyloidosis ultrastructurally, and clarify the pathogenesis of blister formation.

Methods: We examined a 47‐year‐old woman with IgD‐lambda type myeloma, suffering from bullous lesions on her hands and feet caused by trauma or rubbing. Light and electron microscopic studies were performed.

Result: Ultrastructurally, amyloid deposits aggregated under the lamina densa. Keratinocyte protrusions penetrated the dermis through the gap in the lamina densa and enfolded amyloid deposits. Amyloid globules were found in enlarged intercellular spaces of keratinocytes. Desmosomes were sparsely distributed in some areas of the epidermis.

Conclusion: These results indicate that keratinocytes enfold the amyloid globules and take them in the intercellular space of epidermis, and that the breakdown of the lamina densa and widening of the intercellular space between keratinocytes induce skin fragility. Trauma or rubbing of her hands and feet appears to act as the localized precipitating factor of blister formation in bullous amyloidosis.
Sweet’s syndrome in the setting of CD34‐positive acute myelogenous leukemia treated with granulocyte colony stimulating factor: evidence for a clonal neutrophilic dermatosis
Authors: Magro Cynthia M. , De Moraes Edward , Burns Frank
Published: March 2003

Background: Sweet’s syndrome in the setting of hematologic dyscrasias can be categorized into paraneoplastic‐associated SS, drug‐induced SS, and SS with leukemia cutis. Apart from those cases demonstrating concomitant leukemic infiltrates, it has been surmised that SS is a reactive phenomenon induced by a specific cytokine milieu.

Methods: The authors present a patient with CD34+ acute myelogenous leukemia (AAML) who developed SS in the setting granulocyte colony stimulating factor (GCSF) therapy. Routine light microscopy and molecular studies were carried on the patient’s skin biopsy specimen and post‐treatment marrow. An X inactivation assay for clonality was employed.

Results: Routine light microscopic examination revealed differentiated myeloid precursors including myelocytes and metamyelocytes within the subcutis; myeloblasts were not identified. In addition, in the overlying skin, features typical of SS were observed. The neutrophils demonstrated dysplastic features including hypolobation compatible with a Pseudo Pelger‐Huet anomaly. X inactivation studies showed clonality both within her post‐treatment marrow and skin biopsy specimen.

Conclusions: Sweet’s syndrome developing in CD34+ AML patients following GCSF therapy likely reflects therapy induced differentiation of sequestered leukemic cells, hence indicative of a clonal neutrophilic dermatosis.
Epidemiology and microbiology of cellulitis and bacterial soft tissue infection during HIV disease: a 10‐year survey
Authors: Manfredi Roberto , Calza Leonardo , Chiodo Francesco
Published: March 2003

Background: Cellulitis and soft tissue infection are underestimated complications of HIV disease.

Patients and methods:  Sixty‐seven bacteriologically proven consecutive episodes were identified among 2221 HIV‐infected patients hospitalized in a 10‐year period, and assessed according to several epidemiological, microbiological and clinical variables.

Results:  Staphylococcus aureus was the most frequently cultured pathogen (50% of 92 isolates), followed by Pseudomonas spp., Escherichia coli and Streptococcus pyogenes; a polymicrobial infection was present in 38.1% of episodes. Drug addiction (p < 0.003) and male gender (p < 0.04) were significantly associated with the occurrence of these complications, which were community‐acquired in 83.6% of cases. While a remarkable variation in the severity of underlying immunodeficiency was shown, hematogenous dissemination occurred in 25.4% of episodes, and proved significantly related to a low CD4+ lymphocyte count, and neutropenia. A 21.7% methicillin‐resistance rate was shown among S. aureus isolates. All episodes were favorably treated in 5–16 days, in over 60% of cases with associated β‐lactam‐aminglycoside antibiotics; a recurrence of staphylococcal cellulitis occurred in four patients only.

Conclusion:  Skin and soft tissue infections are continuing causes of morbidity in HIV‐infected patients, even in the highly active antiretroviral therapy era.
Expression of syndecan‐1 is a sensitive marker for cutaneous plasmacytoma
Authors: Bayer‐Garner Ilene B. , Joseph Lija , Sanderson Ralph D. , Smoller Bruce R.
Published: March 2003

Background:  Cutaneous plasmacytoma is a well‐recognized, yet infrequent, occurrence in multiple myeloma (MM). There are limitations in the morphologic assessment, and as such, the diagnosis presents some difficulty, particularly with the plasmablastic type.

Methods:  Pathology reports of 2357 patients with a diagnosis of MM were reviewed. Twenty patients yielded a total of 25 plasmacytomas, 10 of which were analyzed for syndecan‐1 immunoreactivity. Bartl grade of bone marrow and cutaneous plasmacytoma was compared and immunoglobulin secretory status of the patients was assessed.

Results:  The incidence of cutaneous plasmacytoma was found to be 1 in 118 patients with MM. Immunoglobulin secretion was found to be predominantly IgG. There was a trend for the plasmacytoma Bartl grade to be equal to or greater than that of the corresponding bone marrow Bartl grade, suggesting a more aggressive phenotype in the metastatic lesion.

Conclusion:  Syndecan‐1 was found to be a sensitive marker for plasmacytomas, independent of cytologic differentiation.
Testing of fine motor skills in dental students
Authors: Luck Olaf , Reitemeier Bernd , Scheuch Klaus
Published: March 2003

Manual skills form only a part of the capabilities required of future dentists, but they are a very important component, which should be tested. With regard to the dental specialities, the present study tested speciality‐independent fine motor skills. No objective, practical solution has been found up to now. 88 dental students and, as a control group, 23 medical students were examined in the longitudinal study. In the course of the analysis, 4 fine motor tests were carried out at the beginning of the 2nd and 6th semesters. The tests comprised the tremometer test, the tremometer test with a mirror, the 2‐hand sinusoid test and archery using the Game Gear by SEGA. The test devices facilitate primarily the testing of components of accuracy of movements, indirect working methods, and eye‐hand coordination. In the comparison of performances on test day A, the medical students’ performance was noticeably better. As testing progressed, results showed stagnation in the performance of the medical students and a significant improvement in the performance of the dental students. That means that the test system can be used for a test over the course of study, but not as an initial test.
The admission of students to UK Dental Schools – Recent trends (1983–1998)
Authors: Duguid R. , Drummond J. R.
Published: March 2003

Details of student applications and admissions to UK Dental Schools from 1983 to 1998 have been recorded and analyzed. Trends observed include a rise in the proportion of female dental students, a drop in real numbers of male dental students, a recent drop in the proportion of mature students and an increase in the number of EU and overseas entrant dental students. Some implications of these and other factors on workforce planning in the UK are discussed.
Recording and understanding social histories by dental undergraduates in a community‐based clinical programme
Authors: Harris R. V. , Dailey Y. , Lennon M. A.
Published: March 2003

Although social inequalities are known to account for large differences in dental health, attitudes to dental attendance and the type of treatment received by the patient, the taking of a patient's social history receives little emphasis in dental undergraduate teaching. Social history is defined as recording the social and family circumstances of the patient. An exercise undertaken by undergraduate dental students on clinical placements in the Community Dental Service (CDS) is described. Students write a profile of the community in which the clinic is situated, write case histories for two of their patients and then highlight issues illustrated by the case histories with reference to information on the wider community and published literature on inequalities in health and barriers to care. Students completing the exercise in April 2000 and their tutors were given additional information, including a checklist to help in the completion of the social histories of the two patients. A comparison with the reports submitted in the previous year showed that this significantly improved the recording and understanding of social history. This exercise provides a means whereby dental public health issues can be taught to undergraduates whilst maintaining relevance to the clinical setting.
2.3 Towards global convergence of education, training, quality, outcome and assessment
Authors: Reed Mike , Claffey Noel , Allen Bill , Beeley Josie , Beemsterboer Phyllis , Carrassi Antonio , Filippi Enrico , Licari Frank , Munck Claus , Nagy Gábor , Rass Marwan Abou , Sanz Mariano , Sekiguchi Eugene , Townsend Grant
Published: March 2003

The purpose of this section's report is to propose strategies which will help those committed to promoting and implementing higher standards in dental education. There is a wide variety of systems throughout the world. These systems are developed, governed, operated and applied differently. Their standards, whether they are controlled by governments (federal and/or state), councils, universities or professional organizations are frequently determined cooperatively with dental educators, so that there is often some agreement among interested constituencies as to the content and application of the standards. These standards, whether they be called ‘accreditation standards’‘requirements’ or ‘guidelines’ (formal or informal), or written as laws or statutes reflect a region's history, traditions, culture and socio‐economic realities. The emphasis in this report will be on the development of an organic or growing electronic database containing worldwide information relating to standards in dental education. This database might contain or be linked with similar sources detailing, inter alia, best practices, innovations and core values as they relate to the convergence of standards in education, professional training, continuous quality analysis, assessment and outcome. The linking of such a database to others containing electronic curricular modules, clinical management and practice information needs to be further developed.
3.1 Scholarship and the university
Authors: Tedesco Lisa , Martin Muir , Banday Ninette , Clarke Mary , DeChamplain Richard , Fazekas Andras , Giuliani Michele , Guglielmotti Maria Beatriz , Kotowic William , Martinez Concha , Nakata Minoru , Radnai Marta , Robinson Peter J. , Saporito Robert , Stenvik Arild , Tansy Martin
Published: March 2003

Universities now exist in an environment of increasing accountability for their academic performance, both in teaching and research. Dental schools are expected to meet the academic expectations of their parent university and, in addition, to contribute to the health‐care needs of the community. Individual staff members must achieve collectively the performance targets required of their school and individually must develop skills and expertise in their academic and clinical activities to merit tenure and promotion. This discussion examines the issues which impact on current problems of recruitment and retention of academic staff in dental schools internationally. The essential issue is career development in a manner which maintains the values that will ensure the credibility of dentistry as a scientifically based discipline and profession, while balancing the achievable academic needs with the added demands of achieving specialist clinical skills. Central to this balance is recognition that scholarship, which provides the bridge between research and teaching, can be broadly defined and that different individuals can be scholarly in a range of ways. Increasingly, schools are recognizing the importance of providing structured opportunities and guidance for career development of younger staff and of the need for flexibility in their criteria for tenure and promotion, recognizing that a diversity of individual strengths and teamworking are necessary both for the collective performance of the institution and the morale and development of the individual.
3.3 Human resource management
Authors: Ferrillo Pat , Jonas Irmtrud , Gundersen Sverre , Jones Malcolm , Whitehouse Norman , Wierzbicka Maria , Wochna‐Sobanska Magdalena , Mario Carlo , Yen Ed , Boari Antonia , Frithiof Lars
Published: March 2003

The most valuable of all resources in a dental teaching hospital are human intelligence and wisdom. Increasingly, universities recognize that their mission to become a centre of academic (and clinical) excellence is dependent on the most constructive and empowering use of their staff and faculty. The appropriate management and empowerment of individuals will help to maximize intellectual potential, research abilities, educational, clinical and management skills to the mutual benefit of all.
4.3 Towards a global superstore of quality‐assured modularized learning programmes
Authors: Oliver Richard , Paganelli Corrado , Cerny Daniel , Gravert Christian , Klinge Bjorn , Kordass Bernd , Johnson Lynn , O'Keefe John , Onisei Doina , Podestá Marie Therese Camilleri , Schleyer Titus , Spallek Heikko
Published: March 2003

Our section's assignment entails exploration of the current challenges to develop criteria for quality assurance of dental e‐learning material. Our work has involved comparison of current methods of assessment, the identification of best practice and the formulation of guidelines and criteria for producers and assessors. We anticipate the need for a standing international body responsible for the revision and refinement of guidelines and criteria and that might award a ‘Seal of Approval’.
2.1 Evolving methods of assessment
Authors: Manogue Michael , Kelly Mary , Bartakova Masaryk Sonia , Brown George , Catalanotto Frank , Choo‐Soo Teo , Delap Elis , Godoroja Pavel , Morio Ikuko , Rotgans Jerome , Saag Mare
Published: March 2003

This Working Section is concerned with evolving methods of assessment in dental education. It focuses on newer methods of assessment that might have relevance for broader application. Although it cannot provide answers to all the questions it raises, it is hoped that the contribution it makes is of value in the process of the development of a global network in dental education.
Insect community organisation in estuaries: the role of the physical environment
Authors: Williams D. Dudley , Hamm Tanya
Published: March 2003

Insects are reportedly uncommon in marine habitats and, from a spatial/temporal intercomparison perspective, estuaries are among the least studied. We examined the natural variability seen among insect community organisation in estuaries on both sides of the North Atlantic, and evaluated the role of their physical environments. Community composition was found to be strongly influenced by three physical factors: estuary size, the degree of inundation by incoming tides, and substrate size/stability. Insects formed a significant proportion (17–54%, by numbers) of the benthic community of coarse‐grained‐substratum estuaries, and species richness increased with estuary size. Nymphs/larvae of mayflies, stoneflies, caddisflies, elmid beetles and chironomids dominated channel sites inundated by up to 25% of all incoming tides, but a gradual loss in species richness occurred downstream. However, even the most seaward sites supported high insect densities (up to 25 016 and 5433 m−2, supporting 26 and 4 species, at sites inundated by 75 and 100% of all incoming tides, respectively). Sites covered by tides for between 3 and 5 h twice daily were dominated by orthocladine chironomids, especially of the genusOrthocladius. Chironomid larvae contribute significantly to the diets of some coastal fish species, particularly juvenile flounder and sticklebacks. We present a schematic model summarising the relationships between estuary size, degree of inundation by salt water and insect community structure.
The declining spadefoot toad Pelobates fuscus: calling site choice and conservation
Authors: Nyström Per , Birkedal Linda , Dahlberg Christina , Brönmark Christer
Published: March 2003

We investigated whether local biotic and abiotic conditions could explain the occurrence of calling males of the declining spadefoot toad Pelobates fuscus in 72 ponds in southern Sweden. The ponds covered the entire distribution range of P. fuscus and were monitored during the breeding season in 2000. Calling males were found in 33 ponds, representing ca 50% of all known ponds for the species in Sweden. They had a non‐random distribution and a discriminant analysis including 19 environmental variables successfully classified 86% of the ponds as with or without calling males. A stepwise discriminant analysis selected eight of these variables and classified 85% of the ponds correctly. Ponds with calling males were classified mainly on characteristics of the ponds, whereas composition of the terrestrial habitat close to the ponds and traffic load within 500 m had little influence on the distribution of calling males. Ponds with P. fuscus were large, permanent and eutrophic with high concentrations of oxygen and high spring temperatures. They also had a high proportion of shoreline with steep banks. Permanent ponds with calling males typically had a low abundance of predatory fish and crayfish; only two of the ponds with P. fuscus contained predatory fish. The results of this study indicate that interactions between physical factors (e.g. pond drying) and predation determine the presence of P. fuscus. Because P. fuscus has specific habitat requirements necessary for its survival and high site fidelity, it is particularly vulnerable to local changes in the condition of its natural breeding ponds. The situation is particularly serious for this species because the majority of the ponds that are within its dispersal range do not seem to be suitable for P. fuscus because of physical constraints.
Illustrations and guidelines for selecting statistical methods for quantifying spatial pattern in ecological data
Authors: Perry J. N. , Liebhold A. M. , Rosenberg M. S. , Dungan J. , Miriti M. , Jakomulska A. , Citron‐Pousty S.
Published: March 2003

This paper aims to provide guidance to ecologists with limited experience in spatial analysis to help in their choice of techniques. It uses examples to compare methods of spatial analysis for ecological field data. A taxonomy of different data types is presented, including point‐ and area‐referenced data, with and without attributes. Spatially and non‐spatially explicit data are distinguished. The effects of sampling and other transformations that convert one data type to another are discussed; the possible loss of spatial information is considered.  Techniques for analyzing spatial pattern, developed in plant ecology, animal ecology, landscape ecology, geostatistics and applied statistics are reviewed briefly and their overlap in methodology and philosophy noted. The techniques are categorized according to their output and the inferences that may be drawn from them, in a discursive style without formulae. Methods are compared for four case studies with field data covering a range of types. These are: 1) percentage cover of three shrubs along a line transect; 2) locations and volume of a desert plant in a 1 ha area; 3) a remotely‐sensed spectral index and elevation from 105km2of a mountainous region; and 4) land cover from three rangeland types within 800 km2of a coastal region. Initial approaches utilize mapping, frequency distributions and variance‐mean indices. Analysis techniques we compare include: local quadrat variance, block quadrat variance, correlograms, variograms, angular correlation, directional variograms, wavelets, SADIE, nearest neighbour methods, Ripley's(t), and various landscape ecology metrics.  Our advice to ecologists is to use simple visualization techniques for initial analysis, and subsequently to select methods that are appropriate for the data type and that answer their specific questions of interest. It is usually prudent to employ several different techniques.
Selective toxicity of vincristine against chronic lymphocytic leukemia cells in vitro
Authors: Vilpo Juhani A. , Koski Tomi , Vilpo Leena M.
Published: March 2003

Abstract: The cytotoxicity of vincristine in vitro was investigated in B chronic lymphocytic leukemia (CLL) cells and in normal peripheral blood mononuclear cells. An approximately 25‐fold selectivity towards leukemic vs. normal lymphocytes was demonstrated. Cells from patients having a mature subtype (CLL or CLL/mix) or a slowly progressing form of CLL were significantly more sensitive to vincristine in vitro than the cases with a CLL/PL phenotype or faster‐progressing disease. Depending on the vincristine dose, the number of dead CLL cells accumulated slowly during the 4‐d observation period. Our data indicate a marked individual variation in vincristine susceptibility among individual CLL cells. Vincristine induced annexin positivity, nuclear blebbing and DNA fragmentation in CLL cells. These indicate an “apoptosis‐like” cell death. Since CLL cells are in the G0/G1 phase of the cell cycle, the only known mode of anticancer action of vinca alkaloids, i.e. anti‐mitotic action, cannot explain the death of CLL cells. Furthermore, similar cellular uptake and efflux of vincristine by normal and CLL cells excluded pharmacokinetic differences as a cause of selectivity of vincristine towards leukemic lymphocytes. Immunostaining of filamentous structures of CLL cells revealed that vincristine brings about selective changes in α‐tubulin but not in β‐actin or vimentin. Although the antitubulin action of vinca alkaloids in the biochemical sense is well demonstrated, this kind of anticancer effect has not previously been shown. Vincristine is used in several regimens for CLL, but its efficacy in CLL has never been demonstrated in a clinical context and its value in routine CLL chemotherapy has been questioned. The present data strongly support the need for further evaluation of the role and mode of action of vincristine in chemotherapy of CLL and other cancers as well.
Organ specificity of c‐kit+ lymphoid precursors in the liver, thymus, andbone marrow
Authors: Shimizu Takao , Bannai Makoto , Kawamura Hiroki , Yamamoto Satoshi , Oya Hiroshi , Maruyama Satoshi , Minagawa Masahiro , Kawamura Toshihiko , Watanabe Hisami , Hatakeyama Katsuyoshi , Abo Toru
Published: March 2003

Abstract: c‐kit+Lin− cells are present in various immune organs, including the liver, thymus, and bone marrow, where lymphoid, myeloid, or erythroid cells are generated. To compare their properties as lymphoid precursors, c‐kit+Lin− cells purified from various organs of B6.Ly5.1 mice were injected into 6.5 Gy‐irradiated B6.Ly5.2 mice. Depending on the source of the c‐kit+ cells, the degree of entrance and expansion of lymphoid cells differed in the liver and thymus of recipient mice. c‐kit+ cells isolated from the bone marrow entered and expanded prominently in both the liver and thymus, whereas c‐kit+ cells from the thymus did not do so at all. On the other hand, c‐kit+ cells isolated from the liver and spleen showed an intermediate pattern, namely, they took a long time to enter and expand in the liver and thymus of recipient mice. All of these c‐kit+ cells had the potential to give rise to lymphoid cells, which were specific to the liver and thymus, respectively. We previously showed that progenitor cells for extrathymic T cells in the liver and those for conventional T cells in the thymus are not always supplied by the bone marrow, as shown by experiments using parabiosis. Taken together with those previous data, the present results suggest that c‐kit+Lin− cells isolated from various immune organs have organ specific properties.
Serum levels of IL‐6 and its soluble receptor (sIL‐6R) in Waldenström's macroglobulinemia
Authors: Hatzimichael Eleftheria ChR. , Christou Leonidas , Bai Maria , Kolios George , Kefala Lambrini , Bourantas Konstantinos L.
Published: March 2003

Abstract: Background: Interleukin‐6 (IL‐6) is a multifunctional cytokine that plays roles in the immune response, inflammation and hematopoiesis. Serum IL‐6 levels have reported to reflect disease severity and high tumor burden in multiple myeloma (MM) patients and to correlate with several other laboratory parameters. Serum‐soluble IL‐6 receptor (sIL‐6R) plays an agonist role in IL‐6 signaling, enhancing its biological activity tenfold. Purpose–Methods: We measured IL‐6 and sIL‐6R levels in 11 patients (7 male, 4 female, mean age 66.9 yr) with Waldenström's macrobulinemia (WM) using a commercially available enzyme‐linked immunoassay in order to investigate their biological role and to find any possible relationship with disease severity, tumor burden or response to treatment. Results: Serum IL‐6 and sIL‐6R concentrations at diagnosis were significantly higher than in healthy controls (Mann–Whitney U‐test, p<0.001 and p<0.01, respectively). Patients who were effectively treated had a significant reduction in IL‐6 levels (p=0.017). With regard to sIL‐6R levels, no specific tendency was observed. In some of the responsive patients the levels increased whereas in others they decreased. No correlation was found between IL‐6 and sIL‐6R levels at diagnosis (p=0.9, r=0.036) or after treatment (p=0.083, r=0.3). Conclusions: Our results suggest that IL‐6 may be a marker reflecting tumor burden, disease severity and response to treatment in WM. With regard to sIL‐6R, we believe that it does not seem to be of much value, and its role remains to be clarified. However, future studies are needed to confirm and further extend the present results.
Long‐term administration of high‐dose deferoxamine 2 days per week in thalassemic patients
Authors: Hagège Isabelle , Becker Annie , Kerdaffrec Thierry , Kanfer Alain , Girot Robert
Published: March 2003

Abstract: Objective: Compliance with parenteral administration of deferoxamine is often poor in thalassemic patients with iron overload. We tested the efficacy and tolerance of the drug at high dosage 2 d per week for 24 months in two adult thalassemic patients with permanently high serum ferritin using a portable pump and an implanted chamber. Methods: Deferoxamine was administered using a pressure‐operated portable pump through an implanted chamber. The patients were infused over 48 h every week with 198 mg/kg/d (patient 1) and 170 mg/kg/d (patient 2). Serum ferritin levels were measured at regular intervals. Results: Serum ferritin decreased progressively from 2967 to 457 µg/L in patient 1 and from 6476 to 1951 µg/L in patient 2. Compliance and tolerance to treatment were excellent in the two patients. Conclusion: Intravenous administration of high‐dose deferoxamine over 48 h per week using a portable pump and implanted chamber improved compliance in two thalassemic adult patients, resulting in a significant decrease in iron overload. We suggest that high‐dose chelation therapy should be assessed in selected groups of iron‐overload thalassemic patients receiving regular blood transfusions.
Doxorubicin and a butyric acid derivative effectively reduce levels of BCL‐2 protein in the cells of chronic lymphocytic leukemia patient
Authors: Rabizadeh E. , Bairey O. , Aviram A. , Ben‐Dror I. , Shaklai M. , Zimra Y.
Published: March 2003

Abstract: B‐chronic lymphocytic leukemia (B‐CLL) is a disease caused primarily by defects in the apoptosis mechanism. AN‐9, a butyric acid (BA) derivative, is a potent differentiating and an anti‐cancer drug that induces apoptosis in HL‐60 cells. Herein we show the affect of AN‐9, alone and in combination with doxorubicin, on cell cultures from B‐CLL patients. Cells from 17 patients were cultured and tested for viability, apoptosis, bcl‐2 and bax protein expression. Exposure of B‐CLL cell cultures to AN‐9 was accompanied by apoptosis and a marked viability loss (up to 46%, p=0.0017). AN‐9 reduced up to 51% (p=0.0017) the levels of bcl‐2 in 57% of the cultures that express bcl‐2. The combination of low concentrations of AN‐9 and doxorubicin more than additively enhanced apoptosis and reduced bcl‐2 levels in B‐CLL cultures which were resistant to AN‐9. AN‐9 enhanced bax expression up to 58%(p=0.008) in cultures from 53% of the patients, but had no effect on bax levels when combined with doxorubicin.

In conclusion, AN‐9 alone reduced bcl‐2 and enhanced bax expression in cultures from B‐CLL patients, and the reduction of bcl‐2 levels in combination with doxorubicin was greater than additive. These results may be beneficial in possible future combination therapy with AN‐9 in B‐CLL.
Increased risk for acute myeloid leukaemia in individuals with glutathione S‐transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defects
Authors: Arruda Valder Roberval , Lima Carmen Silvia Passos , Grignoli Carlos Roberto Escrivão , De Melo Mônica Barbosa , Lorand‐Metze Irene , Alberto Fernando Lopes , Saad Sara Teresinha Ollala , Costa Fernando Ferreira
Published: March 2003

Abstract: Objectives: Glutathione S‐transferases (GST) modulate the effects of exposure to various cytotoxic and genotoxic agents, including those associated with increased risks of the myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and aplastic anemia (AA). Both the GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. In this study, we tested whether null genotypes for the GSTM1 and GSTT1 genes altered the risks for MDS, AML and AA. Methods: Genomic DNA from 49 MDS, 38 AML and 37 AA patients and 276 controls was analysed using the polymerase chain reaction (PCR). Results: The frequencies of GSTM1 (73.6%) and GSTT1 (34.2%) null genotypes were significantly higher in AML patients than in the controls (36.9 and 18.1%, respectively). A higher frequency of the combined null genotype for both genes was also observed in patients with AML (26.3% compared with 5.0% in the controls). In contrast, no differences in the frequencies of the null genotypes were found among MDS patients, AA patients and the controls. Conclusion: Our observation of a 4.7‐fold (95% CI: 2.1–11.0) and 2.3‐fold (95% CI: 1.0–5.2) increased risk associated with the GSTM1 and GSTT1 null genotypes, respectively, and a 6.6‐fold (95% CI: 2.4–7.9) increased risk associated with the combined null genotype presents preliminary evidence that the inherited absence of this carcinogen detoxification pathway may be an important determinant of AML.
Modulators of intraplatelet calcium concentration affect the binding of thrombospondin to blood platelets in healthy donors and patients with type 2 diabetes mellitus
Authors: Wieclawska Boguslawa , Rozalski Marcin , Trojanowski Zygmunt , Watala Cezary
Published: March 2003

Abstract: Thrombospondin (TSP), which is secreted from α‐granules of activated platelets, binds to its surface receptor (CD36) in the presence of Ca2+. Objectives: We monitored how the modulation of intraplatelet Ca2+ affects TSP binding to CD36 on platelets from healthy donors and patients with type 2 diabetes mellitus. We also aimed to verify whether the impaired Ca2+ mobilisation in diabetes influences TSP binding upon the pharmacological modulation of calcium transport. Methods: Whole blood cytometry was used to monitor TSP release/binding and CD36 presentation in platelets from 28 type 2 patients and 33 healthy donors. Results: No significant changes in TSP and CD36 levels were revealed between the groups in circulating platelets and TRAP‐, collagen‐ or thrombin‐activated platelets. In healthy donors, 1 µM thapsigargin (TG) elevated the TRAP‐activated TSP binding (by up to 50%, p<0.001), 5 mM EGTA reversed the effect (by up to 85%, p<0.001), and overcame the effect of TG when used together. Less profoundly expressed effects occurred in the NIDDM group. In both groups TG increased the presentation of CD36 in TRAP‐stimulated platelets (p<0.05), whereas EGTA lowered the TRAP‐stimulated increase in CD36 (p<0.001). The inhibition of CD36 by EGTA was stronger in healthy volunteers (41% vs. 32%, respectively, p<0.05), whereas the activation by TG was higher in the NIDDM group (11% vs. 27%, p<0.05). When acting together the suppressive effects of EGTA on TG‐dependent Ca2+ mobilisation were much attenuated in diabetic subjects (p<0.05). Conclusion: Both the release of TSP and CD36 presentation are under the influence of agents modulating intracellular Ca2+. Diabetic platelets seem more vulnerable to the releasers of cytosolic [Ca2+] and more resistant to the blockers of cytosolic [Ca2+] mobilisation.
The splenic form of mantle cell lymphoma
Authors: Angelopoulou Maria K. , Siakantariz Marina P. , Vassilakopoulos Theodoros P. , Kontopidou Flora N. , Rassidakis George Z. , Dimopoulou Maria N. , Kittas Christos , Pangalis Gerassimos A.
Published: March 2003

Abstract: Objectives: To describe the clinical, immunophenotypic and molecular features, as well as the clinical course of patients with unusual presentation of mantle cell lymphoma (MCL) purely located to the spleen. Patients and methods: We describe seven patients presented with splenomegaly and a leukemic picture without lymphadenopathy, fulfilling the diagnostic criteria of MCL. In addition to clinical and pathologic features, patients were studied with respect to surface immunophenotype, including adhesion molecule profile, immunohistochemical expression of cyclin‐D1 and bcl‐1 rearrangement by polymerase chain reaction. Results: Four patients were male and three female. The median palpable spleen size was 15 cm. A preliminary diagnosis of MCL was made, based on blood cell morphology and immunophenotype. All patients underwent splenectomy for therapeutic purposes. Studies done in blood and splenic lymphocytes revealed the following: 7/7 patients were CD19/CD5, CD20 and CD38 positive; CD10 negative and 6/7 CD23 negative. The adhesion molecule expression pattern was consistent in all patients: L‐Selectin and CD11c were negative, CD11α and CD18 weakly positive and CD54 strongly positive. The median spleen weight was 1775 g. Histology disclosed a cytologic and architectural pattern consistent with MCL. Cyclin‐D1 was positive in 6/6 studied patients. Bcl‐1 rearrangement was found in 5/7 patients. Splenectomy was applied as the sole treatment and was beneficial in all patients, with median blood values as following: prior to splenectomy, Ht 29.5%, platelets 110 × 109/l, lymphoma cells 5.0 × 109/L, and at 6 months post‐splenectomy, Ht 43%, platelets 311 × 109/l and lymphoma cells 3.0 × 109/L. Of the seven patients, two developed progressive disease 11 and 26 months post‐splenectomy. The remaining five are in improving clinical and hematological condition without chemotherapy at a median follow up of 20 months. Conclusions: We conclude that this presentation represents a separate form of MCL which requires splenectomy. It remains to be seen whether it carries a better prognosis than classical MCL.
Iron deficiency anaemia in young women
Authors: Carlsson Lena E. , Hempel Susanne , Greinacher Andreas
Published: March 2003

Abstract:  Objectives
: The expression density of GPIaIIa, the primary platelet collagen receptor (integrin α2β1), is linked to two polymorphisms (GPIa‐807C/T and HPA‐5a/b). During evolution a gene shift from the genotypes GPIa‐807CC‐HPA‐5bb to the genotypes GPIa‐807CT‐HPA‐5aa has taken place. The aim of the study was to assess whether iron deficiency anaemia (e.g. increased blood loss) in young women could be associated with a specific genotype, indicating a role as potential evolutionary selection factor.
Study design
: Women between 18 and 40 yr of age presenting for their first blood donation were asked about alimentary habits and use of oral contraception. Haemoglobin and serum ferritin were measured and the GPIa‐C807T and HPA‐5 genotypes were determined.
Results
: Two hundred women were included and grouped according to the WHO definition for iron deficiency anaemia (haemoglobin <121 g L
−1
and ferritin <15 µg L
−1
). Eight women fulfilled both WHO‐criteria for iron deficiency anaemia, 145 women fulfilled none. No differences regarding age, use of oral contraceptives, alimentary habits, and HPA‐5 were found between the groups. The GPIa‐807CC genotype was strongly over‐represented in the WHO‐anaemic women as compared to the non‐WHO‐anaemic women (87.5% vs. 33.1%,
P
=0.003).
Conclusion : Iron deficiency anaemia in young women might have been the evolutionary disadvantage causing the gene shift from GPIa‐807CC to 807CT.
The comprehensive care of sickle cell disease
Authors: Okpala Iheanyi , Thomas Veronica , Westerdale Neil , Jegede Tina , Raj Kavita , Daley Sadie , Costello‐Binger Hilda , Mullen Jean , Rochester‐Peart Collis , Helps Sarah , Tulloch Emense , Akpala Mary , Dick Moira , Bewley Susan , Davies Mark , Abbs Ian
Published: March 2003

Abstract: Millions of people across the world have sickle cell disease (SCD). Although the true prevalence of SCD in Europe is not certain, London (UK) alone had an estimated 9000 people with the disorder in 1997. People affected by SCD are best managed by a multidisciplinary team of professionals who deliver comprehensive care: a model of healthcare based on interaction of medical and non‐medical services with the affected persons. The components of comprehensive care include patient/parent information, genetic counselling, social services, prevention of infections, dietary advice and supplementation, psychotherapy, renal and other specialist medical care, maternal and child health, orthopaedic and general surgery, pain control, physiotherapy, dental and eye care, drug dependency services and specialist sickle cell nursing. The traditional role of haematologists remains to co‐ordinate overall management and liase with other specialities as necessary. Co‐operation from the affected persons is indispensable to the delivery of comprehensive care. Working in partnership with the hospital or community health service administration and voluntary agencies enhances the success of the multidisciplinary team. Holistic care improves the quality of life of people affected by SCD, and reduces the number as well as length of hospital admissions. Disease‐related morbidity is reduced by early detection and treatment of chronic complications. Comprehensive care promotes awareness of SCD among affected persons who are encouraged to take greater control of their own lives, and achieves better patient management than the solo efforts of any single group of professionals. This cost‐effective model of care is an option for taking haemoglobinopathy services forward in the new millennium.
Simultaneous elevation of the serum concentrations of vascular endothelial growth factor and interleukin‐6 as independent predictors of prognosis in aggressive non‐Hodgkin's lymphoma
Authors: Niitsu Nozomi , Okamoto Masataka , Nakamine Hirokazu , Yoshino Tadashi , Tamaru Jun‐ichi , Nakamura Shigeo , Higashihara Masaaki , Hirano Masami
Published: March 2003

Abstract:Therapeutic approaches for non‐Hodgkin's lymphoma (NHL) are currently based on the International Prognostic Index (IPI). Research on biological prognostic factors has been actively pursued in recent years, with serum vascular endothelial growth factor (VEGF) and interleukin‐6 (IL‐6) being identified as prognostic factors for NHL. Here, we determined that serum VEGF and IL‐6 levels are independent prognostic factors for aggressive lymphoma. Compared with normal controls, serum VEGF and IL‐6 levels were significantly higher in patients with aggressive lymphoma or adult T‐cell leukemia/lymphoma. Furthermore, overall and disease‐free survival rates for patients with high levels of VEGF or IL‐6 were significantly poorer than for patients with low levels. In addition, the prognosis for patients with high levels of both serum VEGF and IL‐6 was significantly poorer than that for patients with high levels of either VEGF or IL‐6 or with low levels of both VEGF and IL‐6. Multivariate analyses of a variety of prognostic factors, including the five IPI factors, revealed that serum VEGF and IL‐6 were both independent prognostic factors for overall survival of aggressive lymphoma. Therefore, a combination of VEGF and IL‐6 represents a useful prognostic factor for aggressive lymphoma.
GM‐CSF induces expression of gp91phox and stimulates retinoic acid‐induced p47phox expression in human myeloblastic leukemia cells
Authors: Shimizu Takahisa , Kodama Reiko , Tsunawaki Shohko , Takeda Ken
Published: March 2003

Abstract:  All‐trans retinoic acid (ATRA) combined with granulocyte macrophage colony‐stimulating factor (GM‐CSF) synergistically increases superoxide‐generating activity in human myeloblastic leukemia ML‐1 cells. ATRA is known to increase the expression of some NADPH components; however, little is known about the effect of GM‐CSF on the expression of these components. We examined the expression of NADPH oxidase components in ML‐1 cells treated with ATRA, GM‐CSF, or a combination of ATRA and GM‐CSF. Expression of p47phox and gp91phox proteins increased markedly after treatment with both reagents. p47phox expression was increased by ATRA alone, and the expression was increased synergistically by the combination of ATRA with GM‐CSF. gp91phox was increased by ATRA or GM‐CSF alone. The expression of p47phox and gp91phox mRNA underwent similar changes to those seen in protein level. These results indicate that GM‐CSF induces expression of gp91phox and enhances ATRA‐induced p47phox expression. We speculate that the remarkable induction of gp91phox and p47phox protein is associated with an increase in superoxide‐generating activity due to the synergistic effect of ATRA plus GM‐CSF.
Acute myeloid leukaemia arising from a patient with untreated essential thrombocythaemia
Authors: Bolaños‐Meade Javier , López‐Arvizu Carmen , Cobos Everardo
Published: March 2003

Abstract:  Acute myeloid leukaemia (AML) is an uncommon complication of patients with essential thrombocythaemia (ET). We report a patient with ET which progressed into AML and who had only received a few days of therapy with hydroxyurea (HU) when diagnosed with ET. This is extremely rare, as in large series no patients who were left untreated for their ET developed this complication. This case supports the theory that AML transformation can be part of the natural history of ET in some cases.
Low levels of mannose‐binding lectin do not affect occurrence of severe infections or duration of fever in acute myeloid leukaemia during remission induction therapy
Authors: Bergmann Olav J. , Christiansen Michael , Laursen Inga , Bang Peter , Hansen Niels Ebbe , Ellegaard Jørgen , Koch Claus , Andersen Vagn
Published: March 2003

Abstract: Purpose: To estimate the clinical significance of low serum concentrations of mannose‐binding lectin (MBL) in patients with acute myeloid leukaemia (AML) during initial cancer chemotherapy. Patients and methods: 80 consecutive, newly diagnosed, and unselected AML patients (age 18–77 yr) undergoing remission induction chemotherapy. The patients were examined for 28 d. Main findings: Low levels of serum MBL (<1000 μg/L) were found in 16/80 patients at diagnosis. This frequency is similar to what is found in the general population. In the remaining 64 patients, MBL concentrations were significantly higher than in controls and showed only a slight rise during the period of antineoplastic chemotherapy with its associated infectious complications. Low levels of MBL did not affect overall survival or morbidity in terms of incidence or duration of fever, or occurrence of septicaemia or pneumonia. Long‐term survival was likewise independent of MBL concentration. Conclusion: MBL levels have no discernible influence on the occurrence or course of infections in AML patients during the initial hospitalisation. The predominant immunodeficiency during this phase is the profound granulocytopenia, which also compromises important effector functions of MBL. The finding in most AML patients of elevated MBL concentrations on admission is most likely because of the role of MBL as an acute phase reactant.
Expression of genes regulating angiogenesis in human circulating hematopoietic cord blood CD34+/CD133+ cells
Authors: Pomyje Jiří , Živný Jan , Šefc Luděk , Plašilová Magdalena , Pytlík Robert , Nečas Emanuel
Published: March 2003

Objectives: Human CD34+ cells represent a heterogeneous population of immature cells which may differentiate to various cell types. The aim of the study was to determine angiogenesis regulating genes expression in CD34+ cells, their subpopulations, and during their differentiation induced by hematopoietic growth factors.

Material and methods: We have measured the expression of angiogenesis regulating genes angiopoietin‐1 (Ang‐1), angiopoietin‐1 (Ang‐2) and their receptor Tie‐2, vascular endothelial growth factor (VEGF) and its receptors VEGFR‐1 and VEGFR‐2 in sorted population of CD34+ and CD34+/CD133+ cells from human cord blood and bone marrow, and in their differentiating progeny, using real time reverse transcriptase polymerase chain reaction. The hematopoietic differentiation of CD34+ cells was induced in semisolid or liquid differentiation supporting media containing appropriate hematopoietic growth factors.

Results: A higher expression of Ang‐1, Ang‐2, and Tie‐2 mRNAs was detected in CD34+/CD133+ cord blood cells as compared with CD34−/CD133− fraction, but no expression of these genes was detected in burst‐forming unit erythroid (BFU‐E) nor colony‐forming unit granulocyte macrophage (CFU‐GM) colonies. The level of Ang‐1 and Tie‐2 mRNAs, but not that of Ang‐2 mRNA gradually decreased during a 14‐d incubation of cord blood CD34+ cells in a liquid culture. A significantly higher expression of VEGF mRNA was in BFU‐E as compared with CFU‐GM cell colonies and CD34+/CD133+ cells. VEGFR‐1 mRNA was equally expressed in CD34+/CD133+ and CD34−/CD133− cells as well as in BFU‐E and CFU‐GM colonies. Expression of VEGFR‐2 mRNA was detected at the borderline of method sensitivity only in CD34+/CD133+ cells.

Conclusion: CD34+/CD133+ cord blood cells express Ang‐1, Ang‐2 and VEGF as well as their receptor mRNAs, suggesting a role of these cells in regulation both angiopoiesis and hematopoiesis.