bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of cyclin E in resting and activated B‐chronic lymphocytic leukaemia cells: cyclin E/cdk2 as a potential therapeutic target
Authors: Decker Thomas , Hipp Susanne , Hahntow Ines , Schneller Folker , Peschel Christian 
Published: December 2004

SummaryDisease progression in B‐cell chronic lymphocytic leukaemia (B‐CLL) is determined by the interplay between proliferation kinetics in the proliferating compartment and cell death in the accumulating compartment. Improving our knowledge of cell cycle regulation in B‐CLL cells might therefore be important for identifying therapeutic targets. Cyclin E was detected by Western blotting in purified B‐CLL cells from peripheral blood samples of all 12 patient tested but not in normal peripheral blood B cells. While cyclin‐dependent kinase 2 (cdk2) expression was similar in different samples, p27 and cyclin E expression was highly variable. We further investigated the regulation of p27, cyclin E and cdk2 in an in vitro model of cycling B‐CLL cells. Cyclin E and cdk2 expression was increased in B‐CLL cells stimulated with a CpG‐oligodeoxynucleotide and interleukin‐2, while p27 expression rapidly declined. This was accompanied by the increased formation of cyclin E–cdk2 complexes, which were able to phosphorylate Histone H1 in vitro. Pharmacological inhibition of cdk2 activity with Roscovitine‐inhibited thymidine incorporation and Histone H1 phosphorylation. We conclude that further evaluation of cyclin E and p27 in peripheral blood cells might help to identify prognostic subgroups. In addition, inhibition of Cyclin E–cdk2 activity by Roscovitine might be a new therapeutic strategy in B‐CLL.
B‐prolymphocytic leukaemia with t(11;14) revisited: a splenomegalic form of mantle cell lymphoma evolving with leukaemia
Authors: Ruchlemer Rosa , Parry‐Jones Nilima , Brito‐Babapulle Vasantha , Attolico Imma , Wotherspoon Andrew C. , Matutes Estella , Catovsky Daniel 
Published: December 2004

SummaryWe reviewed eight cases that were diagnosed before 1995 with B‐prolymphocytic leukaemia (B‐PLL) harbouring t(11;14)(q13;q32) and/or cyclin D1 staining. Thirteen B‐PLL patients without t(11;14) were selected as controls. Peripheral blood, bone marrow and histological sections were re‐examined without cytogenetic information. Final diagnosis was made using morphology, cytogenetics, immunophenotype and immunohistochemistry. Clinical characteristics were similar for both groups except for younger age, male predominance and extranodal involvement in cases with t(11;14). CD5 was more frequently positive in the t(11;14)+ group (80%) than in the t(11;14)− group (31%). Surface membrane immunoglobulin was strongly expressed by all t(11;14)+ cases, but only 45% of t(11;14)− cases. Histopathological and cytological review of cases with t(11;14) showed an infiltrate with a mixture of cells, some resembling prolymphocytes and others with mantle cell lymphoma (MCL) morphology. Blood films of cases with t(11;14) showed features suggestive of B‐PLL in three, and in others, a mixture of cells resembling MCL and nucleolated ones; none corresponded to the blastoid form of MCL. We suggest that ‘B‐PLL’ with t(11;14) may represent a splenomegalic form of MCL evolving with leukaemia. These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B‐cell leukaemia with prolymphocytic features.
Clinical and molecular cytogenetic studies in seven patients with myeloid diseases characterized by i(20q−)
Authors: Li Tianyu , Xue Yongquan , Wu Yafang , Pan Jinlan 
Published: December 2004

SummaryWe report on seven patients with myeloid diseases characterized by i(20q−) anomaly. Four patients were male and three were female, their median age was 57 years. The diagnosis at presentation was myelodysplastic syndrome in six patients, acute myeloid leukaemia in one patient. Four died but three survived and remain anaemic. The survivals were 6 months for patient 1, 7 months for patient 2, 17 d for patient 4 and 28 d for patient 5. Chromosome specimens were prepared by direct and/or short‐term culture of bone marrow cells. Karyotype analysis was performed by R‐ and G‐banding technique, which showed that one of the normal chromosomes 20 was substituted by one or two small metacentric chromosomes in all seven patients. The karyotype was ider(20)(q10)del(20)(q11q13), i.e. i(20q−) in six patients by dual‐colour fluorescence in situ hybridization assay using two probes (a subtelomeric probe for 20q and an unique probe for 20q12). As far as we know, this anomaly has not been reported previously. Thus, we consider that i(20q−) is a novel and rare recurrent chromosomal abnormality that is specifically associated with myeloid diseases and may indicate a poor prognosis.
The effects of folic acid supplements on coagulation status in pregnancy
Authors: Deol Paramjeet S. , Barnes Tim A. , Dampier Karen , John Pasi K. , Oppenheimer Christina , Pavord Sue R. 
Published: December 2004

SummaryThromboembolic disease remains the leading cause of maternal death in the UK. Recent literature has proposed that folate status is a strong predictor for venous thrombosis. Using thrombelastography (TEG®), we tested the hypothesis that folic acid supplementation is associated with a reduction in whole blood coagulability. Blood samples and questionnaire data were obtained at a mean gestation of 13·6 weeks (SD: 3·8, range: 6–38 weeks) from unselected consecutive women attending for their antenatal booking scan. Of 588 patients, 439 (74·7%) took folic acid. All TEG® parameters were less hypercoagulable in women that had taken folic acid compared with those that had not: mean maximum amplitude (MA) 60·3 versus 62·1; mean difference 1·8; 95% confidence interval 0·8, 2·8; P = 0·0001; mean coagulation index (CI) 0·54 versus 0·85; mean difference 0·31; 95% confidence interval 0·11, 0·5; P = 0·002. There was no difference in the incidence of the homozygous MTHFR mutation in patients taking folic acid (5·53%) compared with those that were not (4·08%). This study suggests that benefit may be derived from longer‐term treatment, although large multicentre studies are required to determine whether the relative hypocoagulability is associated with a reduction in risk of venous thrombosis.
Low intensity warfarin: is it clinically useful in venous thromboembolism management?
Authors: Bauer Kenneth A. 
Published: December 2004

SummaryTherapy for a first episode of venous thromboembolism (VTE) typically includes a vitamin K antagonist, such as warfarin, for 3–6 months at an international normalized ratio (INR) of 2–3. After the cessation of warfarin therapy, unprovoked VTE is associated with a recurrence rate of 5–15% per year. Prolonging initial therapy does not reduce the recurrence risk once warfarin is discontinued and is not routinely recommended for such patients. The Prevention of Recurrent Venous Thromboembolism (PREVENT) and Extended Low‐Intensity Anticoagulation for Thromboembolism (ELATE) trials were undertaken to evaluate the efficacy and safety of low‐intensity warfarin (INR 5–2) in this population. While both trials demonstrated that low‐intensity warfarin offers substantial protection against recurrent VTE, only the ELATE trial included a standard intensity arm; this arm showed a significantly lower recurrence rate and a major bleed rate that, surprisingly, was similar to the low‐intensity arm. There still remains no consensus that long‐term warfarin at an INR of 2–3 should be recommended for all patients who sustain a first unprovoked venous thromboembolic event, which largely stems from our current inability to reliably identify those patients most likely to develop recurrences. Given that an individualized approach is required in deciding the duration of anticoagulation, it is the author's belief that low‐intensity warfarin, which the PREVENT trial demonstrated could be monitored every other month, is a useful option for some patients with a first episode of VTE.
Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the ‘cutaneous variant’1
Authors: Ferreri Andrés J. M. , Campo Elías , Seymour John F. , Willemze Rein , Ilariucci Fiorella , Ambrosetti Achille , Zucca Emanuele , Rossi Giuseppe , López‐Guillermo Armando , Pavlovsky Miguel A. , Geerts Marie‐Louise , Candoni Anna , Lestani Maurizio , Asioli Silvia , Milani Mario , Piris Miguel A. , Pileri Stefano , Facchetti Fabio , Cavalli Franco , Ponzoni Maurilio ,   the International Extranodal Lymphoma Study Group (IELSG)
Published: December 2004

SummaryDespite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico‐pathological characteristics of 38 human immunodeficiency virus‐negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34–90; male:female ratio 0·9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG‐PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin (‘cutaneous variant’; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG‐PS >1, ‘cutaneous variant’, stage I and chemotherapy use were independently associated with improved survival.
A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma
Authors: Jagannath S. , Barlogie B. , Berenson J. , Siegel D. , Irwin D. , Richardson P. G. , Niesvizky R. , Alexanian R. , Limentani S. A. , Alsina M. , Adams J. , Kauffman M. , Esseltine D.‐L. , Schenkein D. P. , Anderson K. C. 
Published: December 2004

SummaryIn a phase 2 open‐label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1·0 or 1·3 mg/m2 bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15·7–47·1] and 38% (90% CI, 22·6–56·4) in the 1·0 mg/m2 (8 of 27 patients) and 1·3 mg/m2 (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1·0 and 1·3 mg/m2 cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.
Ex vivo evaluation of erythrocytosis‐enhanced platelet thrombus formation using the cone and plate(let) analyzer: effect of platelet antagonists
Authors: Peerschke Ellinor I. B. , Silver Richard T. , Weksler Babette , Grigg Sage E. , Savion Naphtali , Varon David 
Published: December 2004

SummaryRed blood cells (RBC) contribute significantly to haemostasis and thrombosis under oscillatory flow conditions, and erythrocytosis has been associated with increased thrombotic risk. To measure the dynamic influences of RBC on platelets, we used a recently described cone and plate(let) analyzer (CPA), evaluating the effect of haematocrit (Hct) on platelet function in whole blood under arterial flow conditions (1800/s, 2 min, 25°C). Anticoagulated blood, reconstituted to varying haematocrits with autologous RBC, demonstrated a significant increase in adherent platelet aggregate formation at Hct levels >45%. This increase was not affected by pretreatment of blood with 0·05 mmol/l aspirin, but was prevented by antagonists of P2Y1, P2Y12, or P2X1, ADP and ATP receptors, and by converting exogenous ADP to ATP with creatine phosphate/creatine phosphokinase. As negligible platelet granule secretion was measured during CPA analysis, but metabolic inhibition of RBC with sodium azide or glutaraldehyde fixation inhibited erythrocytosis‐enhanced increases in platelet aggregate size, adenine nucleotides contributing to shear‐induced platelet aggregate formation appear to be derived from erythrocytes. These findings support the use of CPA for ex vivo evaluation of the contribution of RBC to platelet function and its inhibition under physiological shear conditions.
Recurrent abdominal pain, anxiety, and depression in primary care
Authors: Ramchandani Paul 
Published: December 2004

.

Campo JV,
Bridge J,
Ehmann M,
Altman S,
Luca A,
Birmaher B,
Di Lorenzo C,
Iyengar S &
Brent D.

(
2004
)
Pediatrics
,
113
,
817
–
824
.
ObjectiveThe prevalence of psychiatric disorder in children and adolescents with functional recurrent abdominal pain (RAP) is unknown. Our aim was to determine whether RAP is associated with psychiatric symptoms and disorders, anxious temperament and functional impairment in paediatric primary care.MethodsChildren and adolescents who were 8–15 years of age, inclusive, and presented with RAP (n = 42) or for routine care in the absence of recurrent pain (n = 38) were identified by a screening procedure in paediatric primary care office waiting rooms and recruited to participate in a case–control study. Outcome measures were psychiatric diagnoses generated by standardized psychiatric interview administered blind to subject status and self, parent and clinician ratings of child psychiatric symptoms, temperamental traits and functional status.ResultsRAP patients were significantly more likely to receive a diagnosis of a psychiatric disorder, with a categorical anxiety disorder in 33 (79%) and a depressive disorder in 18 patients (43%), and higher levels of anxiety and depressive symptoms, temperamental harm avoidance and functional impairment than control subjects. Anxiety disorders [mean age of onset: 6.25 (standard deviation: 2.17) years] were significantly more likely to precede RAP [mean age of onset: 9.17 (standard deviation: 2.75) years] in patients with associated anxiety.ConclusionsYouths who present with RAP in primary care deserve careful assessment for anxiety and depressive disorders. Future studies should examine treatments that are proved to be efficacious for paediatric anxiety and/or depressive disorders as potential interventions for RAP. Longitudinal, family and psychobiological studies are needed to illuminate the nature of observed associations among RAP, anxiety and depression.
Impact of a general practice based group parenting programme: quantitative and qualitative results from a controlled trial at 12 months
Authors: Reading Richard 
Published: December 2004

.

Stewart‐Brown S,
Patterson J,
Mockford C,
Barlow J,
Klimes I &
Pyper C.

(
2004
)
Archives of Disease in Childhood
,
89
,
519
–
525
.
AimsTo test the effectiveness at 1 year of the Webster Stratton Parents and Children Series group parenting programme in a population sample of parents.MethodsIn a multicentre block randomized controlled trial, parents of children aged 2–8 years in 116 families who scored in the upper 50% on a validated behaviour inventory, took part in Webster‐Stratton's 10 weeks parenting programme led by trained and supervised health visitors. The following outcome measures were used: Eyberg Child Behaviour Inventory, Goodman Strengths and Difficulties Questionnaire, General Health Questionnaire, Parenting Stress Index, Rosenberg Self Esteem Scale.ResultsThe intervention significantly reduced child behaviour problems and improved mental health at immediate and 6 months follow ups. One year differences between control and intervention groups were not significant. Qualitative results suggest that these findings might be attributable in part to either Hawthorne effects or contamination of control group. At interview parents described ways in which the programme had improved their mental health. They reported gains in confidence and feeling less stressed. Some also reported beneficial changes in their own and their children's behaviour and improved relationships with their children. Some spoke of a need for further sessions to support the behaviour changes they had managed to make, and some the desire for attendance by both parents.ConclusionsParenting programmes have the potential to promote mental health and reduce social inequalities, but further work is needed to improve long‐term effectiveness.
Causal association between cannabis and psychosis: examination of the evidence
Authors: Reading Richard 
Published: December 2004

.

Arseneault L,
Cannon M,
Witton J &
Murray RM
. (
2004
)

,
184
,
110
–
117
.
Background  Controversy remains as to whether cannabis acts as a causal risk factor for schizophrenia or other functional psychotic illnesses.Aims  To examine critically the evidence that cannabis causes psychosis using established criteria of causality.Methods  We identified five studies that included a well‐defined sample drawn from population‐based registers or cohorts and used prospective measures of cannabis use and adult psychosis.Results  On an individual level, cannabis use confers an overall twofold increase in the relative risk for later schizophrenia. At the population level, elimination of cannabis use would reduce the incidence of schizophrenia by approximately 8%, assuming a causal relationship. Cannabis use appears to be neither a sufficient nor a necessary cause for psychosis. It is a component cause, part of a complex constellation of factors leading to psychosis.Conclusions  Cases of psychotic disorder could be prevented by discouraging cannabis use among vulnerable youths. Research is needed to understand the mechanisms by which cannabis causes psychosis.
Changes in monocytic expression of aminopeptidase N/CD13 after major trauma
Authors: HUSCHAK G , ZUR NIEDEN K , STUTTMANN R , RIEMANN D 
Published: December 2004

SUMMARYHLA-DR expression on monocytes as marker for monocytic function is severely depressed after major trauma. The membrane enzyme aminopeptidase N/CD13 can trigger help in antigen processing by MHC class II molecules of antigen-presenting cells. We determined the simultaneous expression of HLA-DR and CD13 on peripheral blood monocytes of patients with major trauma (injury severity score of ≥16). 1 : 1 conjugates of phycoerythrin (PE)-to-monoclonal antibody were used in combination with QuantiBRITETM PE beads for a standardized quantification in terms of antibodies bound per cell (ABC). The very low expression of HLA-DR antigen on monocytes of patients at day 1 after major trauma confirmed previous results in the literature. Monocytic HLA-DR expression increased slowly to reach values in the lower range of healthy volunteers at day 14. Monocytic CD13 expression at day 1 showed values in the range of healthy volunteers, and a strong rise afterwards. Fourteen days after trauma, the monocytic expression of CD13 was still much higher than in the control group. Because lipopolysaccharide (LPS) and the anti-inflammatory cytokine interleukin (IL)-10 have been shown to be involved in the depressed HLA-DR expression on monocytes in trauma patients, we studied the in vitro effects of LPS and interleukin (IL)-10 on the expression of CD13 on monocytes prepared from the peripheral blood of healthy volunteers. Whereas a 3-day IL-10 treatment resulted in a down-regulation of both HLA-DR and CD13 expression on monocytes, LPS caused a down-regulation of HLA-DR but a rapid up-regulation of CD13 levels. Therefore we suggest that, with respect to monocytic CD13 expression, LPS rather than IL-10 could well be the explanation for monocytic surface molecules after severe injury, although other mediators with a CD13 regulating function have to be considered.
Pleiotropic effects of CXC chemokines in gastric carcinoma: differences in CXCL8 and CXCL1 expression between diffuse and intestinal types of gastric carcinoma
Authors: ECK M , SCHMAUßER B , SCHELLER K , BRÄNdlein S , MÜLLER-HERMELINK H K 
Published: December 2004

SUMMARYCXC chemokines modulate host immunity, neovascularization, growth and invasive behaviour of tumours. Despite their relevance in tumour biology, chemokine expression in intestinal- and diffuse-type gastric carcinoma, which exhibit a completely different growth pattern, has not been investigated in detail. In this study, expression of the CXC chemokines CXCL8 [interleukin (IL)-8], CXCL1 [growth-related oncogene alpha (Groα)], CXCL9 [monokine induced by interferon (IFN)-γ] and CXCL10 [IFN-γ-inducible protein-10 (IP-10)] and the corresponding chemokine receptors CXCR1–3 was investigated by immunohistochemistry in intestinal- and diffuse-type gastric carcinoma. Tumour cells of all patients expressed CXCL8. CXCL8 expression was significantly stronger in tumour cells of diffuse- rather than intestinal-type gastric carcinoma (P &lt; 0·01) as determined by a semiquantitative score. CXCL1 was expressed almost exclusively by diffuse- but not intestinal-type carcinoma cells. The corresponding chemokine receptors, CXCR1 and CXCR2, were found on carcinoma cells. Furthermore, CXCL8 expression correlated with number of tumour vessels (P &lt; 0·01), suggesting an angiogenetic function in gastric carcinoma not only in vitro but also in vivo. CXCL10 and CXCL9, attractants for T cells, were expressed by peritumorous macrophages in close proximity to IFN-γ-producing CXCR3-positive T cells in both tumour types. These chemokines may attract gastric carcinoma-infiltrating T cells via an IFN-γ-mediated pathway and enhance host immunity against the tumour. In gastric carcinoma a complex interplay between CXC-chemokine signals derived from both tumour cells and tumour-infiltrating immune cells may exhibit pleiotropic effects in tumour biology that go far beyond their originally described functions as leucocyte chemoattractants. Because CXCL8 and CXCL1, which are known to increase growth and invasive behaviour of malignant tumours, are significantly stronger expressed in diffuse- than intestinal-type gastric carcinoma, one may speculate that these chemokines influence the different growth pattern of gastric carcinoma types.