bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary chondroid melanoma
Authors: Ackley Christopher D. , Prieto Victor G. , Bentley Rex C. , Horenstein Marcelo G. , Seigler Hilliard F. , Shea Christopher R.
Published: March 2003

Background: Malignant melanoma is notorious for the wide range of histologic patterns it can assume, among the least frequent of which is chondroid melamona.

Methods: Two cases of primary chondroid melanoma of the distal lower extremity were studied. Tissue for light microscopy was fixed in formalin, embedded in paraffin, and processed routinely. In one case, transmission electron microscopy and immunohistochemical evaluation were performed.

Results: Both cases exhibited melanoma in‐situ, a conventional (non‐chondroid) invasive component, and areas of chondroid differentiation, as confirmed by strongly positive staining with Alcian blue at pH 2.5 and Safranin O. Immunohistochemically, one case expressed S‐100 protein and vimentin, and did not express gp100 (HMB‐45), tyrosinase, MART‐1, the Mel‐5 antigen, the NKI/C3 antigen, CD45Ro, cytokeratin, or desmin. Electron microscopy of the chondroid component revealed occasional tumor cells with rare, membrane‐bound, electron‐dense organelles; the extracellular compartment showed amorphous ground substance consistent with cartilaginous differentiation.

Conclusions: Chondroid change in the absence of osteogenic differentiation is extremely rare in malignant melanoma. Melanoma should be considered in the differential diagnosis of primary cutaneous neoplasms exhibiting cartilaginous differentiation.
Absence of Borrelia burgdorferi DNA in cutaneous B‐cell lymphomas from the United States
Authors: Wood Gary S. , Kamath Nandan V. , Guitart Joan , Heald Peter , Kohler Sabine , Smoller Bruce R. , Cerroni Lorenzo
Published: March 2003

Background: An association between Borrelia burgdorferi and cutaneous B‐cell lymphoma (CBCL) has been made in several European countries. The evidence in favor of such an association has recently been based on more definitive tests for the pathogenetic role of B. burgdorferi in CBCL, including positive cultures or polymerase chain reaction (PCR) amplification of borrelial DNA from lesional skin. However, there is only one report of B. burgdorferi in four North American cases of B‐cell lymphoma.

Methods: We retrieved 38 cases of primary and secondary CBCL from different geographic regions of the United States. Two separate techniques were used to detect borrelial DNA by PCR, a nested PCR method to amplify a B. burgdorferi‐specific gene as well as a borrelial chromosomal Ly‐1 clone amplification method. Southern blot hybridization was used for confirmation of the PCR results.

Results: No B. burgdorferi‐specific DNA was detected in any of the 38 CBCL cases, whereas detectable PCR products were obtained with our positive controls.

Conclusions: Our findings, in light of previous studies, suggest that B. burgdorferi plays a minimal role in the development or pathogenesis of CBCL in the United States. The findings also suggest that the geographic variations in the clinical manifestations of B. burgdorferi are indeed real and may be secondary to the genetic and phenotypic differences between B. burgdorferi strains present in Europe and North America.
CD‐34 and Ki‐67 staining patterns of basaloid follicular hamartoma are different from those in fibroepithelioma of Pinkus and other variants of basal cell carcinoma
Authors: Naeyaert J. M. , Pauwels C. , Geerts M. L. , Verplancke P.
Published: March 2003

Background and aims: Basaloid follicular hamartoma is a rare disorder regarded as a developmental malformation. It may be solitary or generalized, linear or regionalized, and is sometimes associated with myasthenia gravis or alopecia. We compared immunohistochemical staining patterns of selected markers in order to differentiate this hamartoma from fibroepithelioma of Pinkus, a basal cell carcinoma variant it can be confused with.

Methods: The expression of three immunohistochemical markers – CD‐34, Ki‐67, bcl‐2 – was studied in a basaloid follicular hamartoma and in a fibroepithelioma of Pinkus. Two basal cell carcinomas, a nodular and a fibrosing type, and a trichoepithelioma were included as controls.

Results: Basaloid follicular hamartoma shows a low proliferation index and an at least focally circumferential expression of CD‐34 around the epithelial strands. This compares to the findings in trichoepithelioma. In contrast, fibroepithelial tumor of Pinkus and two other basal cell carcinoma subtypes display a high proliferative index and an absence of CD‐34 expression around the epithelium. These findings support the non‐neoplastic nature of basaloid follicular hamartoma.
Primary cutaneous lymphoblastic lymphoma presenting in an 8‐week old infant
Authors: Trupiano Jacqueline K. , Bringelsen Karen , Hsi Eric D.
Published: March 2003

Background:  We report a case of primary cutaneous lymphoblastic lymphoma (LBL) presenting in an 8‐week‐old infant.

Methods:  Histopathology and flow cytometric analysis confirmed the diagnosis of a lymphoblastic lymphoma. The cells expressed CD19, CD20, CD34 and surface immunoglobulin (sIg).

Results:  The cells were negative for TdT and CD99. This unusual immunophenotype has been described as “transitional pre‐B‐cell”, in that the cells express both immature markers (CD34) and mature markers (sIg).

Conclusions:  To our knowledge, only five other cases of sIg positive precursor B‐cell LBL have been reported in the literature. This may represent the youngest reported case of primary cutaneous LBL, occurring at 8 weeks of age.
Simultaneous detection of receptor mRNA and ligand protein in human skin tissues
Authors: Fischer Tanja C. , Dinh Q. Thai , Peiser Christian , Löser Christoph , Fischer Axel , Groneberg David A.
Published: March 2003

Background:  In situ hybridization techniques allow a cell‐type‐specific messenger RNA (mRNA) analysis in complex tissues such as human skin.

Methods: To evaluate both the expression of mRNA and protein within the same tissue section, we developed a protocol of combined non‐radioactive in situ hybridization and immunohistochemistry for use in dermatohistopathology. To validate the technique, we assessed the distribution of vasoactive intestinal polypeptide (VIP) protein and its receptor, VPAC2 mRNA, in human skin samples.

Results: Simultaneous detection of VPAC2 mRNA and VIP immunoreactivity led to abundant staining for both signals in a variety of cell types. There was marked staining for VPAC2 mRNA in epidermal cells, with most pronounced hybridization signals found in keratinocytes of the basal layer and in glandular cells surrounded by VIP‐immunoreactive nerve fibers. Hair follicle cells next to VIP‐positive fibers also exhibited hybridization signals. Specific staining was also detected in endothelial and mononuclear cells. The findings of simultaneous in situ hybridization and immunohistochemistry were identical to results obtained by the single application of both methods.

Conclusions:  The combination of in situ hybridization and immunohistochemistry appears to be a promising technique to assess the expression of both protein and mRNA in skin samples and may be used for various purposes in experimental and clinical dermatopathology.
Cutaneous Destombes–Rosai–Dorfman disease: absence of detection of HHV‐6 and HHV‐8 in skin
Authors: Ortonne N. , Fillet A. M. , Kosuge H. , Bagot M. , Frances C. ,   Janine Wechsler
Published: March 2003

Background:  We report three new cases of cutaneous Destombes–Rosai–Dorfman disease (DRDD). Two were skin‐limited, and one was associated with systemic involvement. In all cases typical large S100 positive macrophages with emperipolesis were present, but different patterns were seen. A viral etiology has long been suspected in DRDD.

Methods:  Thus, all cases were investigated for presence of HHV‐6 major capcid protein gene by polymersae chain reaction (PCR), and for presence of HHV‐8 latency‐associated nuclear antigen 1 by immunohistochemistry.

Results:  All results were negative. HHV‐6 antibody tests were positive for IgG but not for IgM in one case. With regard to HHV‐6, previous studies supplied inconclusive results while, to our knowledge, HHV‐8 has never been investigated in DRDD.

Conclusion:  This study suggests that HHV‐8 is not involved in the pathogenesis of cutaneous DRDD. However, this should be confirmed by further studies. We can postulate three hypotheses in regard to HHV‐6 role in DRDD pathogenesis: 1) its presence in lesionnal tissues is fortuitous, 2) HHV‐6 plays a role in promoting more agressive diseases and 3) various causes, including HHV‐6, are implicated in the pathogenesis of DRDD.
Benign lichenoid keratoses with histologic features of mycosis fungoides: clinicopathologic description of a clinically significant histologic pattern
Authors: Al‐Hoqail Ibrahim A. , Crawford Richard I.
Published: March 2003

Background: Benign lichenoid keratosis (BLK) is a well‐known clinicopathologic entity and several histopathologic patterns havebeen described. Features mimicking mycosis fungoides (MF) in clinically typical BLKs have not yet been emphasized. The aim of this study was to confirm the occurrence of an MF‐like pattern of BLK.

Methods: A retrospective survey was conducted on cases diagnosed as BLK over a 9‐month period in a regional dermatopathology service. Seven histologic parameters, previously confirmed as diagnostically suggestive of MF, were applied. Inclusion criteria were: three or more MF‐related histologic features and a size less than 2 cm. The clinical features were reviewed.

Results: Fifteen cases of MF‐pattern BLK were identified. The number of MF‐like parameters present in individual cases exceeded the inclusion criteria by variable amounts. Pautrier microabscesses and alignment of lymphocytes along the basal layer were the most frequent (14/15). The age of the patients ranged from 28 to 83 years, with a mean of 50. The size of the lesions ranged from 0.2 to 1.8 cm, with a mean of 0.6 cm. The upper trunk was the favored site. Most of the lesions had been removed because of suspicion of cutaneous malignancy; basal cell carcinoma was the most frequent clinical diagnosis.

Conclusion: We describe an MF‐like histologic pattern of BLK. Pathologists and dermatopathologists should be aware of this novel histologic pattern to facilitate distinction between the two disorders.
The value of molecular analysis by PCR in the diagnosis of cutaneous lymphocytic infiltrates
Authors: Holm Niels , Flaig Michael J. , Yazdi Amir S. , Sander Christian A.
Published: March 2003

The diagnosis and classification of cutaneous lymphomas remain a challenge for the clinician and dermatopathologist. This diagnostic dilemma is mainly encountered in the distinction between an early malignant lymphoma and a benign reactive lymphocytic infiltrate (pseudolymphoma). Until the beginning of the 1980s, our diagnostic tools were limited to the clinical presentation, course, and histopathology in diagnosis and classification of lymphocytic infiltrates. Advances in immunology and, in particular, in molecular genetics with the introduction of the Southern blot technique and the polymerase chain reaction (PCR) have revolutionized the diagnosis of lymphocytic infiltrates by determination of clonality. In some series, more than 90% of cutaneous T‐cell lymphomas have a clonal rearrangement of the T‐cell receptor γ‐chain gene, as opposed to very low percentages of rearrangement in T‐cell pseudolymphomas.

However, the presence of clonality does not necessarily imply malignancy. Cases of pseudolymphomas, lichen planus and pityriasis lichenoides et varioliformis acuta were reported with clonal lymphocytic proliferations. Therefore, care should be exercised in the evaluation of the results of molecular analysis, and these should always be correlated with the clinical, histological and immunophenotypic picture to arrive at the correct diagnosis. It may be expected that the molecular methods for diagnosis of lymphocytic infiltrates will be improved and refined in future, and that sensitivity and specificity will increase.
Physician Referral Patterns and Race Differences in Receipt of Coronary Angiography
Authors: LaVeist Thomas A. , Morgan Athol , Arthur Melanie , Plantholt Stephen , Rubinstein Michael
Published: March 2003

Objective. This study addresses the following research questions: (1) Is race a predictor of obtaining a referral for coronary angiography (CA) among patients who are appropriate candidates for the procedure? (2) Is there a race disparity in obtaining CA among patients who obtain a referral for the procedure?

Study Setting. Three community hospitals in Baltimore, Maryland.

Study Design. We abstracted hospital records of 7,927 patients from three hospitals to identify 2,653 patients who were candidates for CA. Patients were contacted by telephone to determine if they received a referral for CA. Logistic regression was used to assess whether racial differences in obtaining a referral were affected by adjustment for several potential confounders. A second set of analyses examined race differences in use of the procedure among a subsample of patients that obtained a referral.

Principal Findings. After controlling for having been hospitalized at a hospital with in‐house catheterization facilities, ACC/AHA (American College of Cardiology/American Heart Association) classification, sex, age, and health insurance status, race remained a significant determinant of referral (OR=3.0, p<.05). Additionally, we found no significant race differences in receipt of the procedure among patients who obtained a referral.

Conclusions. Our results demonstrate that race differences in utilization of CA tend to occur during the process of determining the course of treatment. Once a referral is obtained, African American patients are not less likely than white patients to follow through with the procedure. Thus, future research should seek to better understand the process by which the decision is made to refer or not refer patients.
A retrospective study of shared learning on the BMedSci Dental Technology course at The University of Sheffield
Authors: Cannavina Giuseppe , Wood Duncan , Winstanley Raymond B. , Walsh Trevor F.
Published: March 2003

The aim of this study was to identify the level of shared learning on a Bachelor of Medical Science in Dental Technology (BMedSci) course at the University of Sheffield, School of Clinical Dentistry. A summative evaluation of the course was carried out, using semi‐structured nominal group interviews. BMedSci students, BDS students and recent graduates were questioned and their answers analysed to identify shared learning activities. The results revealed that different levels of shared learning opportunities occurred within the different departments which delivered the course modules. Shared learning was viewed favourably by the students. It has the potential to maximise the use of resources and offers the opportunity for developing an integrated dental team.
English language education in Japanese dental schools
Authors: Morse Zac , Nakahara Sen
Published: March 2003

English is the common language of international scientific and cultural exchange. As the world becomes more globalized and with increasing dependence on the Internet, English becomes increasingly important as a second language. English is the official language for all international associations, societies, organizations etc and their meetings and publications. High quality international collaboration usually requires a high standard of English language proficiency. There is very little information regarding English language education in dentistry on a global basis, particularly in Japan. In 1999 we undertook a comprehensive survey of English education in all 29 Japanese dental schools in the form of a questionnaire. Few schools had native‐speaking educators or those at native speaker level and most did not have a background in dentistry or the health sciences. There are no ideal textbooks for dental students studying English. Most disciplines within dentistry have a professional society or an association with meetings and publications. Currently there is no such group for English‐language education in dentistry. Closer collaboration amongst those concerned may help improve the quality of education. The level of English‐language ability of current dental students will affect the quality of future dental educators and researchers.
Instructional multimedia programs for self‐directed learning in undergraduate and postgraduate training in orthodontics
Authors: Aly M. , Willems G. , Carels C. , Elen J.
Published: March 2003

Objectives:  The objectives of this study were to develop and evaluate an interactive multimedia courseware package in orthodontics and to provide dental undergraduate and postgraduate students with an interactive means of self‐study and self‐evaluation.

Methods:  A commercially available software authoring system was used to develop the courseware package. The courseware was presented for evaluation through a questionnaire to four different groups of undergraduate and postgraduate students. Each group consisted of 25 students. The first three groups were third, fourth, and fifth year of dental curriculum at the Katholieke Universiteit Leuven, Belgium. The fourth group comprised postgraduate students. A one‐way ANOVA was carried out in order to check for statistical differences, whereas a Scheffe's test was used in order to locate the statistical differences between groups. The p value was set at 0.05.

Results:  The majority of undergraduate and postgraduate students in this study were very enthusiastic about this form of educational approach (74/100) because it was experienced as very helpful in understanding the orthodontic curriculum more efficiently (98/100).

Conclusions:  The program provides both undergraduate and postgraduate dental students with a useful interactive means of self‐study and self‐evaluation.
Distributions of forest birds and butterflies in the Andaman islands, Bay of Bengal: nested patterns and processes
Authors: Davidar Priya , Yogananad K. , Ganesh T. , Devy Soubadra
Published: March 2003

The distributional patterns of forest birds and butterflies in the Andaman islands, an oceanic chain located off SE Asia, were tested for nestedness. Both taxa were highly nested. Nestedness could be due to colonization or extinction processes, area or distance effects or nestedness of habitats. Nestedness in forest bird distributions were strongly influenced by area and habitat related factors. Habitats were significantly nested in all three island groups, however most strongly for the North Andamans. However forest bird distributions in the North Andamans, as indicated by row order in the packed matrix, was not correlated with habitat diversity, suggesting that habitat related factors alone cannot account for these patterns. Other causal influences could be passive sampling, where common and abundant species and habitats are more likely to have a widespread distribution than rare species and habitats. The nested subset pattern seen in two unrelated taxa suggests that the Andamans are extinction dominated and that the protection of forests on large islands is critical for the conservation of its biodiversity.
Global patterns of environmental synchrony and the Moran effect
Authors: Koenig Walter D.
Published: March 2003

There is considerable debate over the relative importance of dispersal and environmental disturbances (the Moran effect) as causes of spatial synchrony in fluctuations of animal populations. If environmental factors generally exhibit high levels of spatial autocorrelation, they may be playing a more important role in synchronizing animal populations than sometimes recognized. Here I examine this issue by analyzing spatial autocorrelation in annual rainfall and mean annual temperatures from sites throughout the world using the database maintained by the Global Historical Climatology Network. Both annual precipitation and mean annual temperatures exhibit high synchrony declining with distance and are statistically significant over large distance, often on a continental scale. In general, synchrony was slightly higher in annual precipitation at short distances, but greater in mean annual temperatures at long distances. No latitudinal gradient in synchrony of either variable was detected. The high overall synchrony observed in these environmental variables combined with a pattern of decline with distance similar to that observed in many animal populations suggest that the Moran effect can potentially play an important role in driving synchrony in a wide variety of ecological phenomena regardless of scale.
CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) regimen with granulocyte colony‐stimulating factor (G‐CSF) for patients with aggressive non‐Hodgkin's lymphoma: a pilot study
Authors: Niitsu Nozomi , Okamoto Masataka , Kuraishi Yasuaki , Nakamura Shinobu , Kodama Fumio , Hirano Masami
Published: March 2003

Abstract: We conducted a multi‐institutional collaborative study to examine the usefulness and safety of third‐generation chemotherapy CyclOBEAP (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) combined with granulocyte colony‐stimulating factor (G‐CSF) in the treatment of aggressive non‐Hodgkin's lymphoma (NHL). Subjects included patients with aggressive NHL who were 60 yr of age or younger and had been diagnosed as having a low–intermediate, high–intermediate, or high risk using the International Prognostic Index (IPI). A total of 24 patients were enrolled in the study between May 1997 and March 1998, including 9 low–intermediate‐risk cases, 13 high–intermediate‐risk cases and 2 high‐risk cases. Although all 24 patients were originally enrolled in the study, one adult T‐cell leukemia/lymphoma case was subsequently excluded. Thus, in the end, 23 cases were evaluated. Evaluation of the efficacy of therapy revealed complete remission in 20 patients (87%). Of these 20 patients, 8 were low–intermediate‐risk cases (89%) and 12 were either high–intermediate‐ or high‐risk cases (86%). Partial remission was achieved in 2 patients (8.7%). The 2‐yr survival rate was 91.3%, and the 2‐yr disease‐free survival rate was 81.8%. Grade 3 or higher adverse reactions were granulocytopenia (87%), thrombocytopenia (17.4%) and liver dysfunction (4.3%).

 CyclOBEAP therapy has been associated with a high remission rate for aggressive NHL. When combined with G‐CSF, a high relative dose intensity was maintained for each drug administered (0.94–0.97). Furthermore, although the observation period was short, both the survival rate and disease‐free survival rate were good. Hence, we concluded that there were no problems associated with the procedure in terms of safety.
Arterial thrombosis associated with anticardiolipin and anti‐β2‐glycoprotein‐Iantibodies in patients with non‐Hodgkin's lymphoma: a report of two cases
Authors: Genvresse I. , Buttgereit F. , Späth‐Schwalbe E. , Ziemer S. , Eucker J. , Possinger K.
Published: March 2003

Abstract: Autoimmune phenomena in lymphoid malignancies are often observed. However, clinical manifestations such as a secondary antiphospholipid syndrome in the presence of antiphospholipid antibodies are rarely reported. Furthermore, in the few cases of lymphomas so far reported with thrombosis associated with elevated antiphospholipid antibodies, the anti‐β2‐glycoprotein‐I antibodies have not been studied. We report on two cases of arterial thrombosis occuring in patients with B‐cell lymphoma who presented with positive anti‐cardiolipin and anti‐β2‐glycoprotein‐I antibodies. Our observation suggests that patients with non‐Hodgkin's lymphoma and both anti‐cardiolipin and anti‐β2‐glycoprotein‐I antibodies may be, similar to lupus patients, at considerable risk towards thrombosis, especially towards arterial thrombosis.
CD34+ cells derived from fetal liver contained a high proportion of immature megakaryocytic progenitor cells
Authors: Ma Dong‐Chu , Sun Ying‐Hui , Zuo Wei , Chang Kui‐Zhong , Chu Jun‐Jie , Liu Ya‐Ge
Published: March 2003

Abstract: Endoreplication and maturation of the megakaryocyte (MK) may be retarded or delayed during ontogenesis. In this study, CD34+ cells were isolated from both human fetal liver and adult bone marrow and incubated with thrombopoietin (TPO). The cell number, morphological characteristics, platelet‐associated antigen phenotype, maturation stage and DNA ploidy of CD41+cells were examined from day 0 to day 12 in culture. 1) TPO stimulated the proliferation of fetal liver (FL)‐derived CD34+ cells with a mean 73.14‐fold increase of CD41+ cells after 12 d in culture. Adult BM‐derived CD34+ cells increased only slightly, with a mean 8.18‐fold increase of CD41+ cells. 2) Although the membrane phenotype of both FL CD34+‐derived MKs and BM CD34+‐derived MKs analyzed with CD41a, CD42a, CD61 and CD34 were similar, all FL CD34+‐derived MKs were in maturation stage I and II and in low ploidy (<4N) class. By comparison, BM CD34+ MKs possessed 15% MKs in maturation stage III and IV and with 23% MKs in high ploidy class (>4N). 3) Most of cultured FL‐derived CD34+ cells did not have a well developed demarcation system (DM) and numerous α‐granules after 12 d incubation. von Willebrand factor (vWF) appeared earlier on the cultured BM‐derived CD34+ cells than on FL‐derived CD34+ cells. 4) The expression of both cyclin E and cyclin B1 progressively increased in FL CD34+cells induced by TPO during 12 d in culture. 5) The expression of cyclin D1 gradually decreased in FL CD34+cells induced by TPO over 12 d incubation. 6) Immunocytochemical analysis showed that cyclin D3 was detected only in cytoplasm of cultured FL‐derived CD34+ cells, whereas in both cytoplasm and nuclei of cultured BM‐derived CD34+ cells. These data suggest that FL‐derived CD34+ cells contain a high proportion of immature megakaryocytic progenitor cells. It further suggests that TPO can push these progenitor cells into proliferation by upregulating the expression of cyclins B1 and E, and drive a high proportion of cells into megakaryocytic lineage.
CD34/QBEND10 immunostaining in bone marrow biopsies: an additional parameterfor the diagnosis and classification of myelodysplastic syndromes
Authors: Baur Audrey S. , Meugé‐Moraw Christiane , Schmidt Pierre‐Michel , Parlier Valérie , Jotterand Martine , Delacrétaz Françoise
Published: March 2003

CD34/QBEND10 immunostaining has been assessed in 150 bone marrow biopsies (BMB) including 91 myelodysplastic syndromes (MDS), 16 MDS‐related AML, 25 reactive BMB, and 18 cases where RA could neither be established nor ruled out. All cases were reviewed and classified according to the clinical and morphological FAB criteria. The percentage of CD34‐positive (CD34+) hematopoietic cells and the number of clusters of CD34+ cells in 10 HPF were determined. In most cases the CD34+ cell count was similar to the blast percentage determined morphologically. In RA, however, not only typical blasts but also less immature hemopoietic cells laying morphologically between blasts and promyelocytes were stained with CD34. The CD34+ cell count and cluster values were significantly higher in RA than in BMB with reactive changes (p<0.0001 for both), in RAEB than in RA (p=0.0006 and p=0.0189, respectively), in RAEBt than in RAEB (p=0.0001 and p=0.0038), and in MDS‐AML than in RAEBt (p<0.0001 and p=0.0007). Presence of CD34+ cell clusters in RA correlated with increased risk of progression of the disease. We conclude that CD34 immunostaining in BMB is a useful tool for distinguishing RA from other anemias, assessing blast percentage in MDS cases, classifying them according to FAB, and following their evolution.
Characteristics of haemopoietic progenitor cells related to CD34 epitope class expression
Authors: Steen Rita , Tjønnfjord Geir E. , Grøseth Lill Anny Gunnes , Egeland Torstein
Published: March 2003

Abstract: Haemopoietic progenitor cells (HPCs) express the CD34 molecule, a heavily glycosylated transmembrane protein displaying three main classes of epitopes. The CD34 epitope class expression may vary between different subsets of HPCs. The aim of this study was to characterise the subsets of HPCs expressing CD34 class II and III epitopes. The cells were studied for coexpression of activation‐, lineage‐ and adhesion‐associated molecules, and their clonogenic ability and morphological features were examined.

CD34+ HPCs expressing class III epitopes outnumbered those expressing class II. Class III expressing HPCs were enriched for CFU‐GM and BFU‐E and cells coexpressing CD13, CD33, c‐kit and CD71 compared to class II expressing HPCs. CD34+ cells exclusively expressing class III epitopes uniformly displayed CD13 and CD33; they had a high clonogenic capacity and morphological characteristics of promyelocytes and myelocytes.

The data show that class III epitopes are distributed more broadly on CD34+ HPCs than are class II epitopes, and that lack of class II epitopes is confined to CD34+ HPCs at a late stage of myeloid differentiation. The higher number of class III expressing HPCs coexpressing c‐kit and CD71 suggests that these cells exhibit a higher proliferative or differential potential than do HPCs expressing class II epitopes.
Hydroxyurea treatment reduces haematopoietic progenitor growth and CD34 positive cells in polycythaemia vera and essential thrombocythaemia
Authors: Andréasson Björn , Swolin Birgitta , Kutti Jack
Published: March 2003

Abstract: The aim of the present work was to investigate the effect of hydroxyurea (HU) treatment on haematopoietic progenitors and CD34 positive (CD34+) cells in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). Of the PV patients were 10 treated with phlebotomy only and 10 were on HU therapy. Seven ET patients were untreated and 10 received HU. In each subject peripheral blood was obtained for in vitro colony growth, determination of CD34+ cells and plasma ertythropoietin (EPO) concentration. The mean number of EPO independent erythroid colonies (EEC) was higher in the group of PV patients on phlebotomy therapy compared to the PV patients treated with HU (74.4 and 8.0 colonies/105 cells, respectively) but the difference did not reach statistical significance. The corresponding means for the untreated ET patients and ET patients treated with HU were 13.0 and 1.3 colonies/105 cells, respectively, this difference being statistically significant (p=0.012). The mean EEC for combined groups of PV and ET without myelosuppressive treatment were compared with the results for PV and ET patients on HU therapy; this difference was statistically significant (p=0.014). The same pattern was observed for total erythroid growth with EPO. The relationship between the concentration of CD34+ cells and total EEC in peripheral blood was statistically significant for both PV (p<0.005) and ET (p<0.01). This finding supports the hypothesis that the level of CD34+ cells in peripheral blood could be used as a proliferation marker in these two myeloproliferative entities. No relationship between plasma EPO and EEC was present. It therefore appears that the reported differences in plasma/serum EPO concentrations between PV patients on phlebotomy treatment compared to patients on myelosuppressive treatment are not likely to be found at the production site for erythrocytes.
Indirect study of thrombopoiesis(TPO, reticulated platelets, glycocalicin)in patients with hereditary macrothrombocytopenia
Authors: Fabris F. , Cordiano I. , Steffana A. , Ramon R. , Scandellari R. , Nichol J. L. , Girolami A.
Published: March 2003

Abstract: Chronic isolated hereditary macrothrombocytopenia (CHMT) is a congenital form of macrothrombocytopenia that seems to be due to defective production secondary to a disturbance in megakaryocyte fragmentation. To better understand the pathogenesis of thrombopoiesis in this hereditary thrombocytopenic disorder, we determined the percentage of reticulated platelets (RP), plasma glycocalicin (GC) and thrombopoietin (TPO) levels in 29 patients with CHMT, 23 patients with immune thrombocytopenic purpura (ITP), and 17 patients with thrombocytopenia secondary to decreased bone marrow megakaryocytes (hypoplasia). The % RP was similar in CHMT (2.27±1.33) and hypoplasia (1.98±1.35) patients and markedly lower than that in ITP patients (8.80±7.97; p<0.001), suggesting that the production of new platelets is reduced in CHMT. Plasma GC was within the normal range (0.84±0.16 μg/mL) both in patients with CHMT (0.63±0.20 μg/mL) and ITP (0.82±0.90 μg/mL), while it was significantly decreased in patients with hypoplasia (0.16±0.04 μg/mL; p<0.001). When the GC value was normalized for platelet count, the GC index was normal in CHMT patients (2.05±1.1) and in patients with hypoplasia (0.85±0.10) while it was significantly increased in ITP patients (10.88±18.00; p<0.001); thus, patients with CHMT seem to have a normal platelet turnover. TPO was significantly increased in CHMT (195±72 pg/ml) as compared with normal (80±53 pg/ml; p<0.002); however, the mean level was not as high as in ITP patients (345±167 pg/mL; p<0.001). This finding suggests that CHMT syndrome is not secondary to a defective production of TPO and that megakaryocyte mass is nearly normal.
A quantitative reverse transcriptase polymerase chain reaction method for the detection of leukaemic cells with t(8;21) in peripheral blood
Authors: Fujimaki S. , Funato T. , Harigae H. , Imaizumi M. , Suzuki H. , Kaneko Y. , Miura Y. , Sasaki T.
Published: March 2003

Abstract: We evaluated the usefulness of a recently developed real‐time reverse transcriptase polymerase chain reaction (RT‐PCR) system to detect minimal residual diseases (MRD) in patients with acute myelogenous leukaemia (AML) with chromosomal translocation t(8:21). The method was simple, rapid and reproducible for the quantity of chimeric AML1‐ETO (MTG8) transcripts. The ratio of the absolute copy number of a target gene (AML1‐ETO) to a control gene (glyceraldehyde‐3‐phosphate dehydrogenase, GAPDH) was calculated by using a fluorescence curve prepared from amplicons of serially diluted standard RNA. The relative points of MRD in bone marrow (BM) of 8 patients in the acute phase of the disease was from 0.85 to 3.0, whereas those of MRD in complete remission (CR) decreased to below 6.4×10−3. This method was also applied to evaluate chimeric transcripts in peripheral blood (PB) samples. The values in patients with t(8;21) AML were from 0.97 to 2.0 in the acute phase, whereas those in CR showed less than 2.2×10−4. There was 10−5‐fold difference in AML1‐ETO mRNA expression between PB samples in the acute phase and those in CR. The results suggest that we may easily monitor MRD in patients with t(8;21) AML through quantitative analysis of AML1‐ETO transcripts in blood samples.
Relation of ferritin levels to pulmonary function in patients with thalassemia major and the acute effects of transfusion
Authors: Kanj Nadim , Shamseddine Ali , Gharzeddine Walid , Kanj Mohamed , Abi Nasr Therese , Koussa Susan , Jibrail Julie , Taher Ali
Published: March 2003

Abstract: We studied 36 patients (17 males and 19 females) with thalassemia major by performing pulmonary function testing (PFT), arterial blood gas analysis (ABG), as well as determining the serum ferritin level. In addition, 19 of these patients were transfused with two units of packed cells, and a repeat ABG and PFT were performed. Twenty‐three patients had normal PFTs, eleven patients (30.6%) showed a restrictive pattern (significant decrease in both TLC and DLCO), and only two patients (5.6%) showed an obstructive pattern. A significant negative correlation was found between serum ferritin and restrictive parameters, DLCO and TLC (p=0.01 and p=0.03, respectively). This correlation was even stronger after transfusion. Controlling for age, ferritin was still negatively correlated with DLCO (p=0.04), but no longer with TLC. There was no correlation between age and DLCO or age and TLC; however, there was a statistically significant negative correlation between age and FVC (p=0.003). Analysis of patients who were transfused revealed a significant decrease in forced vital capacity (89±4% vs. 74±5% of predicted; p‐value<0.001) and in maximum midexpiratory flow rate (79±4% vs. 67±5% of predicted; p‐value=0.004). For patients older than 15 yr of age, there was a statistically significant decrease in FEV1/FVC (84±2 vs. 83±2%; p‐value=0.04). The ABGs showed no significant change post‐ transfusion. In this study, PFT findings in thalassemia major were restrictive and correlated with serum ferritin level. Transfusion had an acute effect on the obstructive parameters of PFT.
Lactacystin activates FLICE (caspase 8) protease and induces apoptosis in Fas‐ resistant adult T‐cell leukemia cell lines
Authors: Yamada Yasuaki , Sugahara Kazuyuki , Tsuruda Kazuto , Nohda Kazuo , Mori Naoki , Hata Tomoko , Maeda Takahiro , Hayashibara Toshihisa , Joh Tatsuroh , Honda Miyuki , Tawara Masayuki , Tomonaga Masao , Miyazaki Yoshitsugu , Kamihira Shimeru
Published: March 2003

Abstract: Lactacystin (LC) is a specific inhibitor of the proteasome, and has recently been shown to induce apoptosis in certain cell lines. In the present study, we established Fas‐resistant adult T‐cell leukemia (ATL) cell subclones RSO4 and RST1 from their parental Fas‐sensitive cell lines SO4 and ST1, and examined whether LC can overcome Fas resistance. LC completely inhibited proteasome function as determined by a peptidyl‐MCA substrate (LLVY‐MCA and LLE‐MCA), and induced apoptosis in these cell lines irrespective of Fas sensitivity at low concentrations (∼10μM). LC induced the activation of caspase 3 (CPP32/Yama) and caspase 6 proteases in an identical manner to Fas‐mediated apoptosis. Moreover, LC induced the activation of caspase 8 (FLICE) protease, which is the initiator of the Fas‐mediated apoptotic cascade. Synthesized proteasome inhibitory peptide MG‐115 (ZLLnV‐CHO) also induced apoptosis in these cell lines. These results indicated that proteasome inhibitors overcome Fas‐resistance by bypassing the proximal part of the Fas signal. Inhibition of the proteasome function may be a new strategy for the treatment of ATL.
The MEK inhibitor, PD98059, reduces survival but does not block acute myeloid leukemia blast maturation in vitro
Authors: Baines Paul , Fisher Janet , Truran Louise , Davies Eryl , Hallett Maurice , Hoy Terry , Burnett Alan K.
Published: March 2003

Abstract: The appearance of blasts in acute myeloid leukemia (AML) reflects a shift from cellular processes inducing maturation and cell death to those favouring survival and accumulation. We have monitored changes in the growth factor signalling molecule MAPKinase, in the cytoprotective protein Bcl‐2 and in the cell death protein Bax, during maturation of proliferating and non‐proliferating AML blasts in vitro. Eighteen AML samples were cultured for 7 d in serum‐free medium with or without a supplement of recombinant cytokines comprising c‐kit ligand, IL3 and GMCSF. Maturation of AML blasts, as assessed by morphology on Romanowsky‐stained slides of 7/18 samples and by changes in surface CD markers on all 18 leukemias, occurred in both the absence and presence of cytokines. Cell numbers decreased to a mean of 71% after 7 d of cytokine‐free culture, but increased to 210% in cytokine‐supplemented cultures. The proportion of CD15‐positive cells, assessed by flow cytometry, increased over 7 d in 17/18 samples, from a mean of 22% to 68% in cytokine‐free cultures and to 72% in cytokine‐supplemented cultures (p=<0.0001 for both). By immunofluorescence/flow cytometry, there was no significant change in Bcl‐2 over 7 d of culture, while Bax increased, particularly in cytokine‐free cultures (2.2‐fold), which led to a significant decrease in the Bcl‐2/Bax ratio. Immunoblotting demonstrated that ERK was briefly phosphorylated after seeding AML blasts into culture. PD98059, an inhibitor of MAPKinase kinase (MEK) which activates MAPKinase, inhibited this transient ERK phosphorylation but was unable to block maturation as measured by acquisition of CD15 in samples from 12 patients with low starting numbers of CD15‐positive cells. PD98059, however, reduced cell numbers in 7‐d liquid culture and, in cytokine‐supplemented cultures, this was associated with a 1.3‐fold increase in Bcl‐2 (p=0.012) and a 1.4‐fold increase in Bax (p=0.02). Overall, these data demonstrate that most leukemic populations can partially differentiate in vitro without the need for cytokines or inducers. The MAPKinase pathway is not required for this maturation, but it does maintain cell viability in the absence or presence of cytokines. A rise in Bcl‐2 may not protect AML blasts in the face of elevated Bax.
Immunophenotypic discrepancies between granulocytic and erythroid lineages in peripheral blood of patients with paroxysmal nocturnal haemoglobinuria
Authors: Pakdeesuwan Kriangsak , Wanachiwanawin Wanchai , Siripanyaphinyo Uamporn , Pattanapanyasat Kovit , Wilairat Prapon , Issaragrisil Surapol
Published: March 2003

Abstract: In paroxysmal nocturnal haemoglobinuria (PNH), somatic mutation of the PIG‐A gene is thought to result in altered expression of glycosylphosphatidylinositol (GPI)‐anchored proteins. This study was performed to determine if there were any heterogeneities of cellular phenotypes between two major peripheral blood cells, erythrocytes and granulocytes. Using CD59‐based immunocytometry, the patterns of CD59 expression were shown to be conserved in the circulating erythroid cells (reticulocytes and mature erythrocytes) in all 29 patients with PNH. Twenty‐one patients had distinct combinations of PNH type I, II, and III cells in different lineages. Only eight patients exhibited similar patterns of CD59 expression between the two lineages. Approximately one third of the patients had PNH type II cells in either or both of the two lineages indicating variable lineage involvement. The proportion of abnormal granulocutes was higher than those of abnormal reticulocytes and erythrocytes. In patients with appropriate erythropoietic responses to haemolysis (RPI>2.0), shift reticulocytes display predominantly PNH phenotypes. These immature erythroid cells with altered expression of GPI‐anchored proteins may dominate the peripheral blood during periods of increased marrow activity resulting in greater phenotypic mosaicism in such patients. Discrepancies in expression of GPI‐anchored proteins in PNH which are highly variable between the two lineages may be the result of their different life spans and the influence of complement‐mediated cytolysis. The phenomena also indicated the possible occurrence of more than one PNH clones with variable clonal dominance.
Sweet's syndrome and Pneumocystis carinii pneumonia: two sequelae of low‐dose cytosine arabinoside therapy in a patient with acute myeloid leukemia
Authors: Chowdhary V. , Nityanand S. , Prasad K. N. , Pandey R. , Dabadghao S.
Published: March 2003

Abstract: Cytosine arabinoside in low dose is sometimes employed for treating acute myeloid leukaemia. We report here a case of acute myeloid leukemia, treated with low‐dose cytosine arabinoside, who developed acute febrile neutrophilic dermatosis and Pneumocytsis cariniipneumonia after attainment of remission. A direct effect of cytosine arabinoside on neurophil function and an immunosuppressive potential in lower doses could be speculated.
Molecular and cytogenetic remission in a case of subtype M4E acute myelogenous leukemia with minimal monochemotherapy: high sensitivity or spontaneous remission?
Authors: Martelli Maria Paola , Latagliata Roberto , Spadea Antonio , Avvisati Giuseppe , Mancini Marco , Romano Atelda , Luzi Giovanni , Petti Maria Concetta
Published: March 2003

Abstract: Complete remission was observed in an adult patient with acute myelogenous leukemia after minimal monochemotherapy. Remission occurred after a severe febrile pneumonia and was accompanied by cytogenetic and molecular remission. The hypothesis of spontaneous remission was raised, even if a high sensitivity to low‐dose cytostatics cannot be excluded. Such spontaneous complete remissions, often associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors is discussed.
Multiple myeloma in elderly patients: presenting features and outcome
Authors: Rodon Philippe , Linassier Claude , Gauvain Jean‐Bernard , Benboubker Lotfi , Goupille Philippe , Maigre Michel , Luthier François , Dugay Jacqueline , Lucas Virginie , Colombat Philippe
Published: March 2003

Abstract: Few studies have been performed regarding multiple myeloma (MM) in elderly patients. We report a retrospective series of 130 unselected patients with MM aged 75 yr or more at diagnosis. Presenting features were identical to those reported in younger patients, except for a higher rate of infection. Heavy comorbidity was characteristic of unselected geriatric patients. Ninety‐four patients received conventional chemotherapy. The response rate was 62%. Treatment toxicity was mild. Median survival was 22 months. Durie–Salmon (DS) clinical stages II and III MM were severe and often led to death, while significantly more patients with DS stage I MM died from unrelated causes (p<0.0001). Univariate analysis showed that age 85 yr, performance status 2, creatinine level 120 µmol/l, beta 2 microglobulin level >4 mg/l, C‐reactive protein level >6 mg/l, platelet count <100×109/l, presence of infection and lack of response to chemotherapy were adverse prognostic factors for survival. In Cox multivariate regression analysis, age 85 yr (p<0.0001), performance status 2 (p<0.0001) and creatinine level 120 µmol/l (p<0.0001) were independent factors in predicting short survival. This study provides evidence that in patients with symptomatic MM age should not be considered as a major obstacle to active treatment. Prospective clinical trials are needed in this population of patients and should include an assessment of quality of life.
Non‐immune chronic idiopathic neutropenia of adult: an overview
Authors: Papadaki Helen A. , Palmblad Jan , Eliopoulos George D.
Published: March 2003

Abstract: There is strong evidence that non‐immune chronic idiopathic neutropenia of adult is a cytokine‐mediated syndrome characterized by (a) neutropenia of varying degree associated with a low number of lineage‐specific CD34+ cells and increased production of inhibitors of hematopoiesis, including transforming growth factor‐β1 and tumor necrosis factor‐α; (b) lymphopenia due to selective loss of primed/memory T‐cells and NK cells; (c) increased splenic volume on ultrasonography in 48.1% of patients; (d) osteopenia and/or osteoporosis in 60.0% of patients; (e) anemia, mostly of the type of anemia of chronic disease, in 15.6% of patients; (f) features of chronic antigenic stimulation, including increased proportion of bone marrow plasma cells, increased serum levels of IgG1 and/or IgA, increased frequency of monoclonal gammopathy of undetermined significance, increased frequency of antinuclear antibodies with specific reactivity, and increased serum levels of circulating immune complexes; and (g) increased concentrations of a variety of macrophage‐derived pro‐inflammatory cytokines and chemokines capable of affecting bone metabolism, bone marrow function, and leukocyte trafficking. All these findings are suggestive of the existence of an unrecognized low‐grade chronic inflammatory process which may be involved in the pathogenesis of the disorder. Neutropenia in these patients is probably the result of a combination of at least three factors, reduced neutrophil production in bone marrow, enhanced neutrophil extravasation, and increased sequestration and/or extravasation of neutrophils into the spleen.