bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma from patients with thrombotic thrombocytopenic purpura induces activation of human monocytes and polymorphonuclear neutrophils
Authors: Alvarez‐Larrán Alberto , Petriz Jordi , Martínez Antonio , Sanz Cristina , Pereira Arturo
Published: March 2003

Summary. Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disorder characterized by microangiopathic haemolytic anaemia, consumptive thrombocytopenia, neurological involvement and formation of platelet thrombi in the small vessels. The aetiopathology of TTP and the mechanism behind the beneficial effect of plasma exchange with plasma infusion have not yet been fully elucidated. We have studied the effect of plasma from four patients with TTP on human blood phagocyte activation, as measured by reactive oxygen species (ROS) production and CD11b expression. TTP plasma obtained in the acute phase of the disease induced ROS production by human monocytes and enhanced CD11b expression on neutrophils. This activation effect remained in the cryosupernatant but not in the cryoprecipitate made from TTP plasma, and disappeared when a complete response was achieved by plasma exchange. These findings suggest that activated blood phagocytes may be involved in the pathophysiology of TTP.
Anti‐thymocyte globulin treatment of marrow aplasia associated with paroxysmal nocturnal haemoglobinuria (PNH) resulted in haematological improvement due to an expansion of the PNH clone
Authors: Cheung W. C. , Lam C. C. K. , Kwong Y. L.
Published: March 2003

Summary. A patient with aplastic anaemia developed paroxysmal nocturnal haemoglobinuria (PNH) 4 years after diagnosis, with an ensuing haematopoietic improvement. The PNH clone subsequently declined, leading to pancytopenia again. Anti‐thymocyte globulin had to be administered 14 years later, which resulted in haematopoietic improvement once more. Flow cytometric analysis showed that this was attributable to expansion of the PNH clone, owing probably to alleviation of its suppression by immune‐mediated mechanisms. PIG‐A gene analysis showed that the same PNH clone had waned and waxed in the clinical course. Our results suggest that the PNH clone might rarely be an immune target as well.
Novel translocations that disrupt the platelet‐derived growth factor receptor β (PDGFRB) gene in BCR–ABL‐negative chronic myeloproliferative disorders
Authors: Baxter E. Joanna , Kulkarni Shashikant , Vizmanos José‐Luis , Jaju Rina , Martinelli Giovanni , Testoni Nicoletta , Hughes George , Salamanchuk Zoryana , Calasanz Maria José , Lahortiga Idoya , Pocock Christopher F. , Dang Raymond , Fidler Carrie , Wainscoat James S. , Boultwood Jacqueline , Cross Nicholas C. P.
Published: March 2003

The BCR–ABL‐negative chronic myeloproliferative disorders (CMPD) and myelodysplastic/myeloproliferative diseases (MDS/MPD) are a spectrum of related conditions for which the molecular pathogenesis is poorly understood. Translocations that disrupt and constitutively activate the platelet‐derived growth factor receptor β(PDGFRB) gene at chromosome band 5q33 have been described in some patients, the most common being the t(5;12)(q33;p13). An accurate molecular diagnosis of PDGFRB‐rearranged patients has become increasingly important since recent data have indicated that they respond very well to imatinib mesylate therapy. In this study, we have tested nine patients with a CMPD or MDS/MPD and a translocation involving 5q31–33 for disruption of PDGFRB by two‐colour fluorescence in situ hybridization (FISH) using differentially labelled, closely flanking probes. Normal control interphase cells gave a false positive rate of 3% (signals more than one signal width apart). Six patients showed a pattern of one fused signal (from the normal allele) and one pair of signals separated by more than one signal width in > 85% of interphase cells, indicating that PDGFRB was disrupted. These individuals had a t(1;5)(q21;q33), t(1;5)(q22;q31), t(1;3;5)(p36;p21;q33), t(2;12;5)(q37;q22;q33), t(3;5) (p21;q31) and t(5;14)(q33;q24) respectively. The remaining three patients with a t(1;5)(q21;q31), t(2;5)(p21;q33) and t(5;6)(q33;q24–25) showed a normal pattern of hybridization, with ≥ 97% interphase cells with two fusion signals. We conclude that two‐colour FISH is useful to determine the presence of a PDGFRB rearrangement, although, as we have shown previously, this technique may not detect subtle complex translocations at this locus. Our data indicate that several PDGFRB partner genes remain to be characterized.
Tandem transplants with different high‐dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Ósea phase II trial
Authors: Lahuerta Juan José , Grande Carlos , Martínez‐Lopez Joaquín , De La Serna Javier , Toscano Rosa , Ortiz María Cruz , Larregla Santiago , Conde Eulogio , Insunza Andrés , Gonzalez‐San Miguel José David , Bargay Juan , Cabrera Rafael , García‐Ruiz Juan Carlos , Albó Carmen , García‐Alonso Luis , Solano Fernando , Vivancos Pilar , León Angel , San Miguel Jesús ,   for the Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Ósea
Published: March 2003

Summary. Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200‐ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV‐ASCT2). All patients were in response after MEL200‐ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200‐ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV‐ASCT2. The final CR rate was 48%. The 5‐year survival (OS) was 55%[95% confidence interval (CI) 43–67%] while the event‐free survival (EFS) was 28% (95% CI 15–39%). CR status after CBV‐ASCT2 was the most important prognostic factor for OS and EFS (P = 0·00001), although no differences in outcomes were detected when the patients in CR after MEL200‐ASCT1 were compared with those who obtained CR after CBV‐ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200‐ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high‐dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.
Mutational analysis of class III receptor tyrosine kinases (C‐KIT, C‐FMS, FLT3) in idiopathic myelofibrosis
Authors: Abu‐Duhier Faisel M. , Goodeve Anne C. , Care Rory S. , Gari Mamdooh , Wilson Gill A. , Peake Ian R. , Reilly John T.
Published: March 2003

Summary. Genomic DNA from patients with idiopathic myelofibrosis (IMF) was screened by polymerase chain reaction (PCR) and conformation sensitive gel electrophoresis (CSGE) for mutations in the C‐KIT gene (60 patients), as well as the C‐FMS and FLT3 genes (40 patients). Intronic primers were used to amplify the entire coding region of both the C‐KIT and C‐FMS genes, and selected regions of the FLT3 gene. CSGE and direct DNA sequencing detected all previously reported as well as several novel polymorphisms in each of the genes. A novel c‐fms exon 9 mutation (Gly413Ser) was detected in two patients. Its functional significance remains to be determined. The c‐kit mutation Asp52Asn, previously described in two of six IMF patients in Japan, was not detected in this study. In addition, the reported c‐fms mutations involving codons 301 and 969 were not identified. Therefore, in contrast to acute myeloid leukaemia, mutations in RTKs class III do not appear to play a significant pathogenetic role in idiopathic myelofibrosis.
Endothelial stimulation by small lymphocytic lymphoma correlates with secreted levels of basic fibroblastic growth factor
Authors: Rimsza Lisa , Pastos Karen , Massey Kenneth , Braylan Raul
Published: March 2003

Summary. Lymph nodes (LN) involved with small lympho‐ cytic lymphoma (SLL) reportedly contain increased numbers of microvessels that may constitute a therapeutic target in this disease. We investigated the secretion of the angiogenic growth factor, basic fibroblastic growth factor (bFGF), from primary tissue cultures of 15 LN with SLL and 10 reactive LN. bFGF was detected from the resulting conditioned media (CM) in 13/15 SLL samples (mean 92 ± 30, range 5–420 pg/ml) but was undetectable in CM from all reactive lymph nodes. CM was also used in a 72‐h human umbilical vein endothelial cell (HUVEC) proliferation assay. HUVEC proliferation increased in the presence of SLL CM (70 ± 17%, range −4–194%), proportional to secreted levels of bFGF (R2 = 0·95), and was reversed by depleting bFGF from CM. Previous SLL studies have examined either patient serum samples or paraffin‐embedded lymph node tissue sections. This is the first study to examine the secretion of an angiogenic growth factor from primary cultures of lymph node cells. Our results indicate that bFGF is probably the primary mediator responsible for increased angiogenesis in involved nodes. These findings may be pertinent to future investigation into the mechanisms of increased angiogenesis in SLL.
Flt3‐ligand induces adhesion of haematopoietic progenitor cells via a very late antigen (VLA)‐4‐ and VLA‐5‐dependent mechanism
Authors: Solanilla Anne , Grosset Christophe , Duchez Pascale , Legembre Patrick , Pitard Vincent , Dupouy Maryse , Belloc Françis , Viallard Jean‐François , Reiffers Josy , Boiron Jean‐Michel , Coulombel Laure , Ripoche Jean
Published: March 2003

Summary. The adhesion of haematopoietic progenitor cells (HPC) to the bone marrow microenvironment is a process regulated by cytokines. In this study, we have shown that flt3‐ligand (FL), a growth factor that controls early haematopoiesis, regulated the function and expression of the beta‐1 integrins, very late antigen (VLA)‐4 and VLA‐5 on HPC. The modulation of the adhesiveness of HPC by FL was studied by adhesion assays on umbilical vein endothelial cells (HUVEC). Stimulation by FL induced two peaks of increased adhesiveness of HPC. The first peak was at around 30 min and was mechanistically related to an activation of the beta‐1 integrins, mainly VLA‐4 and VLA‐5. The second peak was at around 12 h and was related to increased expression of VLA‐4 and VLA‐5. The control of HPC adhesiveness by FL is a previously unreported property of FL that may be important for the homing and the retention of flt3‐expressing HPC within the bone marrow microenvironment.
Extragastric mucosa‐associated lymphoid tissue lymphoma showing the regression by Helicobacter pylori eradication therapy
Authors: Arima Nobuyoshi , Tsudo Mitsuru
Published: March 2003

Summary. A 69‐year‐old man presented with right neck tumour. Primary thyroid MALT lymphoma occurring in Hasimoto's thyroiditis was diagnosed. He was also diagnosed to have gastric cancer with Helicobacter pylori infection. After subtotal gastrectomy by itself, thyroid lymphoma became smaller transiently. Then the patient was treated with H. pylori eradication therapy, resulting in the complete disappearance of lymphoma. Although H. pylori organisms were not detected in the lymphoma tissue by polymerase chain reaction (PCR), it might be implicated in the pathogenesis of extragastric MALT lymphomas.
Abdominal lymphangioma in adults and children
Authors: de Perrot M , Rostan O , Morel P , LE Coultre C
Published: March 2003

Background

Abdominal lymphangioma is a rare tumour usually classified with mesenteric and retroperitoneal cysts. This experience of abdominal lymphangiomas contrasts the differences between tumours in children and adults.

Methods

Between 1970 and 1996, six patients had surgical resection of an abdominal lymphangioma.

Results

There were three children aged 4 years or less and three adults aged 36–76 years. Two children presented with an acute abdomen and one with a rapidly enlarging abdominal girth. Lymphangiomas were located in the mesentery and gastrointestinal tract. In adults, symptoms lasted from months to years and lymphangiomas were found in the pancreas, spleen and retroperitoneum.

Conclusion

In this series, abdominal lymphangioma presented more acutely in children and usually involved the mesentery, whereas in adults the history was longer and the tumour was found in the retroperitoneum.
Clinical study of adjuvant photodynamic therapy to reduce restenosis following femoral angioplasty
Authors: Jenkins M P , Buonaccorsi G A , Raphael M , Nyamekye I , McEwan J R , Bown S G , Bishop C C R
Published: March 2003

Background

Photodynamic therapy (PDT) reduces neointimal hyperplasia and negative remodelling following balloon injury in small and large animal models. This clinical study investigated the role of adjuvant PDT following femoral percutaneous transluminal angioplasty (PTA).

Methods

Eight PTAs in seven patients (two women) with a median age of 70 (range 59–86) years were performed with adjuvant PDT. All patients had previously undergone conventional angioplasty at the same site which resulted in symptomatic restenosis or occlusion between 2 and 6 months. Each was sensitized with oral 5-aminolaevulinic acid 60 mg/kg, 5–7 h before the procedure. Following a second femoral angioplasty, up to 50 J/cm2 red light (635 nm) was delivered to the angioplasty site via a laser fibre within the angioplasty balloon. Patients were kept in subdued light overnight and discharged the following day. Outcome was assessed by duplex imaging at 24 h, 1, 3 and 6 months and by intravenous digital subtraction angiography at 6 months. A peak systolic velocity ratio (PSVR) of more than 2·0 at the angioplasty site was taken to represent restenosis.

Results

All patients tolerated the procedure well without adverse complications or death. All were rendered asymptomatic which was sustained throughout the study interval. All vessels remained patent and no lesion attained the duplex definition of restenosis. Median (interquartile range) PSVR across stenotic segments was 4·7 (3·7–5·7) before angioplasty, 1·1 (0·9–1·3) at 24 h and 1·4 (1·0–1·8) at 6 months after intervention (P = 0·04 compared with preoperative value).

Conclusion

This pilot study suggests that endovascular PDT is safe and may reduce restenosis following angioplasty. The data justify a randomized controlled trial.
Levels of the chemokines growth-related oncogene α and epithelial neutrophil-activating protein 78 are raised in patients with severe acute pancreatitis
Authors: Shokuhi S , Bhatia M , Christmas S , Sutton R , Neoptolemos J P , Slavin J
Published: March 2003

Background

Multiple organ dysfunction syndrome secondary to systemic leucocyte activation is the major cause of death following an attack of acute pancreatitis. Although plasma levels of interleukin (IL) 8 are known to be raised in acute pancreatitis, levels of other CXC chemokines such as growth-related oncogene (GRO) α and epithelial neutrophil-activating protein (ENA) 78, which are also potent neutrophil chemoattractants and activators, have not been measured.

Methods

Timed plasma samples were obtained from 51 patients with acute pancreatitis, 27 with a severe attack and 24 with mild disease according to the Atlanta classification. Samples were analysed to determine levels of C-reactive protein (CRP), IL-8, GRO-α and ENA-78.

Results

Plasma levels of IL-8, GRO-α and ENA-78 were increased in patients with severe as opposed to mild acute pancreatitis as early as 24 h following disease onset. Using cut-off levels of 7 pg/ml for IL-8, 70 pg/ml for GRO-α and 930 pg/ml for ENA-78, peak levels within the first 24 h of admission had an accuracy of 81, 71 and 87 per cent respectively in predicting the severity of an attack of acute pancreatitis.

Conclusion

In patients with severe acute pancreatitis plasma levels of GRO-α and ENA-78 were raised in addition to those of IL-8, suggesting that all three chemokines are involved in the inflammatory response in this condition.
Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer
Authors: Yachida S , Fukushima N , Sakamoto M , Matsuno Y , Kosuge T , Hirohashi S
Published: March 2003

Background

The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer.

Methods

Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated.

Results

One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0·001) and more advanced (P = 0·022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0·347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence.

Conclusion

Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.
Renal transplant fibrosis correlates with intragraft expression of tissue inhibitor of metalloproteinase messenger RNA
Authors: Nicholson M L , Waller J R , Bicknell G R
Published: March 2003

Background

Chronic renal allograft nephropathy is characterized by an abnormal accumulation of extracellular matrix proteins in the glomeruli and tubulo-interstitium. The aim of this study was to determine the relationship between intragraft expression of the genes controlling the accumulation of extracellular matrix and the development of chronic renal allograft nephropathy in human renal transplants.

Methods

Forty renal allografts with stable renal function were biopsied 6 months after transplantation. Single glomeruli were plucked from the surface of these protocol biopsies and total messenger RNA (mRNA) was extracted. Reverse transcriptase–polymerase chain reaction was used to study the intragraft expression of several fibrosis-associated genes (collagen III, collagen IVα2, matrix metalloproteinase (MMP) 2, tissue inhibitors of metalloproteinases (TIMPs) 1 and 2, tenascin and transforming growth factor (TGF) β). The level of tubulo-interstitial fibrosis was measured by quantitative immunostaining of collagen III.

Results

There were positive correlations between the level of tubulo-interstitial collagen III immunostaining and intragraft expression of the genes for TIMP-1 (rs = 0·70, P < 0·02) and TIMP-2 (rs = 0·59, P < 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF-β mRNA (rs = 0·67, P < 0·002). Finally, TIMP-1 expression increased with TGF-β expression (rs = 0·77, P < 0·002).

Conclusion

Failure of extracellular matrix degradation may be an important molecular mechanism in the pathogenesis of chronic renal allograft damage.
A meta-analysis of 50 years of ruptured abdominal aortic aneurysm repair
Authors: Bown M J , Sutton A J , Bell P R F , Sayers R D
Published: March 2003

Background

Operative repair of ruptured abdominal aortic aneurysm (RAAA) is associated with a high mortality rate but reported figures vary widely. The aim of this study was to estimate the operative mortality of RAAA repair and determine how it has changed over time.

Methods

A meta-analysis of all English language literature quoting figures for operative mortality of RAAA repair.

Results

The pooled estimate for the overall operative mortality rate of RAAA repair from 1955 to 1998 was 48 (95 per cent confidence interval 46 to 50) per cent. Meta-regression analysis of operative mortality over time demonstrated a constant reduction of approximately 3·5 per cent per decade (1954–1997) with an operative mortality rate estimate for the year 2000 of 41 per cent. Seventy-seven studies reported intraoperative mortality but, while this appears to have remained constant over time, there was evidence of the presence of publication bias in the subgroup of papers reporting this outcome. There was no evidence of publication bias for the overall operative mortality outcome.

Conclusion

Contrary to the conclusion of recent studies, this paper demonstrates a gradual reduction with time in the operative mortality rate of RAAA repair.
Retrospective study of acute toxicity following short-course preoperative radiotherapy
Authors: Hartley A , Giridharan S , Gray L , Billingham L , Ismail T , Geh J I
Published: March 2003

Background

The use of short-course preoperative radiotherapy (25 Gy in five fractions over 1 week) in resectable rectal cancer reduces local recurrence but is associated with an increased risk of postoperative complications and late toxicity. This study aimed to identify those patients who are unlikely to benefit from short-course preoperative radiotherapy and the factors associated with acute toxicity.

Methods

All patients who received short-course preoperative radiotherapy at a university hospital in 1998 and 1999 were included in this retrospective study. The association between complications occurring within 3 months and patient demographics, radiotherapy technique, surgical details and overall treatment time (OTT) was assessed by univariate and multivariate analysis.

Results

The mortality rate at 30 days was 6 per cent in the 177 patients identified. Thirty-seven per cent of patients had either Dukes' A tumours, surgically incurable disease or positive circumferential margins. One or more complications occurred in 38 per cent of patients. On multivariate analysis an OTT of more than 13 days (P = 0·03), age (P = 0·02) and length of the radiotherapy field (P = 0·05) were associated with an increased risk of complications.

Conclusion

Surgery within 1 week of completing short-course preoperative radiotherapy improved preoperative staging and use of an optimal radiotherapy technique will result in fewer patients at risk of acute toxicity.
New insight into bile flow dynamics in anomalous arrangement of the pancreaticobiliary duct
Authors: Fumino S , Tokiwa K , Katoh T , Ono S , Iwai N
Published: March 2003

Background

In an anomalous arrangement of the pancreaticobiliary duct (AAPBD), two-way regurgitation, including pancreaticobiliary reflux and biliopancreatic reflux (BPR), might occur. Although pancreaticobiliary reflux has been shown by high levels of pancreatic enzymes in bile, there have been few reports of clinical evidence of BPR in AAPBD. Recently, spiral computed tomography combined with intravenous infusion cholangiography (IVC–SCT) has been reported to be useful for visualizing the biliary anatomy, which may allow a new insight into bile flow dynamics in AAPBD.

Methods

Fifteen paediatric patients with AAPBD were examined before operation using both IVC–SCT and endoscopic retrograde cholangiopancreatography. Visualization of the main pancreatic duct on IVC–SCT defined the presence of BPR. Blood samples were also analysed when the initial symptom was strongly present.

Results

BPR was observed in six of 15 patients. Pancreatic enlargement and hyperamylasaemia were significantly more frequent in patients without BPR than in those with BPR. Levels of enzyme markers of cholestasis were also higher in the former group.

Conclusion

The present study, using IVC–SCT, has identified clinical evidence of BPR in AAPBD. Further studies are necessary to determine the correlation between BPR and clinical manifestations.
The c‐myc gene regulates the polyamine pathway in DMSO‐induced apoptosis.
Authors: Potten Christopher , Darzynkiewicz Zbigniew , Sasaki Kohsuke , Trubiani O. , Pieri C. , Rapino M. , Di Primio R.
Published: March 2003

Abstract. It is accepted that apoptosis is a gene‐controlled process of cellular self‐destruction. It occurs during physiological regulation and in pathological situations in the life of a cell. In the immune system, several different intracellular and extracellular factors have been associated with the induction of apoptosis, and the final responses depend on the cell system and the acquired signals. In lymphoid cells, dexamethasone‐induced apoptosis is associated with c‐myc downregulation in cells that remain in G0–G1 until the point of death. Ornithine decarboxylase (ODC), a key enzyme involved in polyamine biosynthesis, is regulated by c‐myc, which is a transcriptional activator implicated not only in the control of cell proliferation and differentiation but also in programmed cell death. As dimethylsulphoxide (DMSO) induces apoptosis in the RPMI‐8402 human pre‐T cell line, the present study analysed the involvement of the c‐myc proto‐oncogene and polyamine pathway as mediators of apoptosis. Cell growth, programmed cell death, c‐myc expression, ODC activity and intracellular polyamine content were detected after DMSO and difluoromethylornithine (DFMO) treatment. DMSO‐treated cells exhibit a decrease in ODC activity and polyamine levels associated with cell growth arrest and programmed cell death induction. The expression of c‐myc proto‐oncogene, as its mRNA or protein, is specifically down‐regulated. DFMO, a well defined polyamine biosynthesis inhibitor, completely blocks ODC activity, resulting in growth inhibition but not apoptosis. Moreover, in these samples no evidence of changes of c‐myc expression were found. The results obtained suggest that, in RPMI‐8402 cells, DMSO provokes a c‐myc‐dependent decrease of ODC activity followed by a depletion of intracellular polyamine levels, associated with programmed cell death and cell growth arrest.
Comparison between differentcell kinetic variables in human breast cancer
Authors: Barzanti F. , Dal Susino M. , Volpi A. , Amadori D. , Riccobon A. , Scarpi E. , Medri L. , Bernardi L. , Naldi S. , Aldi M. , Gaudio M. , Zoli W.
Published: March 2003

Cell kinetics holds a prominent role among biological factors in predicting clinical outcome and response to treatment in neoplastic patients. Different cell kinetic variables are often considered as valid alternatives to each other, but the limited size of case series analysed in several studies and the lack of simultaneous determinations of all the variables on the same tumours do not justify this conclusion. In the present study, the correlation between [3H]thymidine labelling index ([3H]dT LI), flow cytometric S phase cell fraction (FCM‐S) and Ki‐67 immunoreactivity (Ki‐67/MIB‐1) was verified and the type of correlation with the most important clinical, pathological and biological patient and tumour characteristics was investigated in a very large series of breast cancer patients. Ki‐67/MIB‐1, FCM‐S and [3H]dT LI were determined in 609, 526 and 485 patients, respectively, and all three cell proliferation indices were evaluated in parallel on the same tumour in a series of 330 breast cancer patients. All the cell kinetic determinations were performed within the context of National Quality Control Programmes. Very poor correlation coefficients (ranging from 0.37 to 0.18) were observed between the different cell kinetic variables determined in parallel on the same series of breast cancers. Moreover, Ki‐67/MIB‐1 and FCM‐S showed a significant relationship with histological type, grade and tumour size, whereas statistically significant correlations were not observed for [3H]dT LI. In conclusion, the results show that the different cell kinetic variables provide different biological information and cannot be considered as alternatives to each other.
Dietary fibre on cell proliferation in large bowel mucosal crypts near or away from lymphoid nodules and on mineral bioavailability
Authors: Cameron I. L. , Hardman W. E. , Heitman D. W. , Carter J. W.
Published: March 2003

The effect of consumption for 24 weeks of different amounts (0%, 5% or 10% w/w) of fermentable (pectin and guar gum) or nonfermentable (cellulose and lignin) dietary fibres on cell proliferation and other parameters in large bowel mucosal crypts was studied in rats. In all 12 dietary groups, the crypts located over the distal aggregate of lymphoid nodules (ALN) had more colchicine arrested metaphase figures per midaxial crypt section (MC) and a longer crypt column height than crypts located three to four cm away from this ALN. These differences are attributed to the tropic influence of nodular cells in the ALN. Consumption of fermentable fibre decreased pH in the lumen of the caecum, and glucose, Zn and Cu in serum but increased Ca and Mg in serum. The decrease in caecal pH and serum glucose was significantly correlated with a decrease in MC. Increased intake of the nonfermentable fibre types increased faecal bulk but had no significant correlation with the other measured crypt parameters. Multiple regression analyses was used to model the relationships between the mucosal crypt criterion variables and the two measured predictor variables, caecal pH and serum glucose. Relationships between dietary fibre, ALN, MC, bioavailability of dietary minerals and risk of colorectal cancer are discussed.
MCF‐7 mammary tumour cells express the myeloid cell differentiation controlling factor, serine protease3/myeloblastin
Authors: Horman S. , Fokan D. , Galand P.
Published: March 2003

Our previous data indicated that HSP27 plays a role in MCF‐7 cell differentiation similar to that it has in HL‐60 cells. In the latter case, this involves a control of its levels by proteinase 3/myeloblastin (PR3/Mbn), a serine proteinase hitherto considered specific of the myeloid lineage. Having observed that the treatment of MCF‐7 cells with the serine protease inhibitor N‐tosyl‐l‐phenylalanine‐chloromethyl ketone (TPCK) increased their content in HSP27 and induced them to acquire a secretory phenotype, we undertook this work to test the assumption that an enzyme similar or identical to PR3/Mbn might be expressed in this cell line. The data show that MCF‐7 cells exhibited specific immunopositivity for a monoclonal antibody against PR3/Mbn. Western blot analysis of immunoprecipitates from MCF‐7 cell extracts, obtained and checked with PR3/Mbn monoclonal antibodies, confirmed the presence of the 35 kDa glycosylated and 29 kDa mature forms of the protein. Finally, Northern blot analysis confirmed the expression of the corresponding mRNA. Together with our data with TPCK, this substantiates our hypothesis that, as in HL‐60 cells, regulation of MCF‐7 cells differentiation might involve a postranslation control on HSP27 levels by a serine protease.
Heterogeneity in nuclear transport does not affect the timing of DNA synthesis in quiescent mammalian nuclei induced to replicate in Xenopus egg extracts
Authors: Sun W.‐H. , Hola M. , Baldwin N. , Pedley K. , Brooks R.F.
Published: March 2003

Intact G0 nuclei from quiescent mammalian cells initiate DNA synthesis asynchronously in Xenopus egg extracts, despite exposure to the same concentration of replication factors. This indicates that individual nuclei differ in their ability to respond to the inducers of DNA replication. Since the induction of DNA synthesis requires the accumulation of replication factors by active nuclear transport, any variation in the rate of transport among nuclei could contribute to the variability of DNA replication. Using the naturally fluorescent protein allophycocyanin (APC) coupled with the nuclear localization sequence (NLS) of SV40 T antigen, as a marker of nuclear uptake, we show here that individual G0 nuclei differ in their rate of transport over a range of more than 20‐fold. Surprisingly, this variation has no direct influence on the timing or extent of DNA synthesis. Similar results were obtained by monitoring the uptake of nucleoplasmin, a nuclear protein present at high levels in egg extracts. These experiments show that the initiation of DNA synthesis is not driven merely by the accumulation of replication factors to some threshold concentration. Instead, some other explanation is needed to account for the timing of initiation.
Establishment of a tetraploid Meth‐A cell line through polyploidization by demecolcine but not by staurosporine, K‐252A and paclitaxel
Authors: Fujikawa‐Yamamoto K. , Wang S. , Yamagishi H. , Ohdoi C. , Murano H. , Ikeda T.
Published: March 2003

Polyploid cells are made by DNA reduplication without cell division, however, it is not easy to establish polyploid mammalian cell lines. It is worth studying the difference in cell character between hyperploid and parent cell lines. Meth‐A cells were polyploidized by demecolcine, K‐252a, staurosporine and paclitaxel. The cell‐cycle responses of highly polyploid Meth‐A cells after the removal of the drugs were examined by flow cytometry (FCM). Meth‐A cells were highly polyploidized by these drugs. The polyploid Meth‐A cells gradually decreased in ploidy after the drug release. A tetraploid Meth‐A cell line was established only from the demecolcine‐induced polyploid Meth‐A cells. The duration of G1, S and G2/M phases of the tetraploid cell line were mostly the same as those of the parent diploid cells, except that the G2/M phase was 1.5 h longer. The chromosome number of tetraploid Meth‐A cell line was about twice of the diploidy. A tetraploid Meth‐A cell line was established.
Use of real time leukaemia data to validate model predictions based on analyses and computer simulations
Authors: Afenya E. K.
Published: March 2003

Predictions arising out of a mathematical model that describes the expansion of leukaemia from a diffusion‐orientated perspective are critiqued and validated by employing available real time data. Based on agreements found between model predictions and the data, but mindful of the limitations it presents, it is concluded that the model could be used to describe the dynamics of normal and abnormal cells in leukaemia. It is suggested that further studies of the behaviour of certain normal cell types in contrast to abnormal cells during leukaemic development could engender additional insights into leukaemia and its treatment.
Stimulation of DNA synthesis, activation of mitogen‐activated protein kinase ERK2 and nuclear accumulation of c‐fos in human aortic smooth muscle cells by ketamine
Authors: Boulom V. , Lee H.‐W. , Zhao L. , Eghbali‐Webb M.
Published: March 2003

Abstract. Proliferation of vascular smooth muscle cells is known to be regulated by autocrine and paracrine stimuli, including extracellular matrix, reactive oxygen species, lipids, and biomechanical forces. The effect of many pharmacological agents to which smooth muscle cells may be exposed, however, is widely unexplored. Ketamine, an intravenous anaesthetic and a phencyclidine derivative, regulates diverse intracellular signalling pathways in smooth muscle cells, several of which are known to affect cell proliferation. The effect of ketamine on proliferative response of smooth muscle cells, however, is not determined. We tested the hypothesis that ketamine may regulate proliferation of smooth muscle cells, and investigated the effects of pharmacological doses of ketamine on their proliferative capacity by measuring DNA synthesis and activation of mitogen‐activated protein (MAP) kinase signalling pathway in human aortic smooth muscle cells. DNA synthesis, as determined by incorporation of 3H‐thymidine into DNA, was enhanced by 73% (P < 0.0001) and 130% (P < 0.0001) with 10 and 100 µm ketamine, respectively. Ketamine‐induced DNA synthesis was dependent on de novo protein synthesis, as it was abolished by an inhibitor of protein synthesis, cycloheximide. A synthetic inhibitor of MAP kinase pathway, PD98059, decreased 50% (P < 0.0001) of ketamine‐induced DNA synthesis, suggesting that the activation of MAP kinase pathway was partially responsible for ketamine‐induced effects. Consistently, in‐gel kinase assay and in vitro kinase assay of cell lysates showed ketamine‐induced MAP kinase activation and expression of ERK2 (extracellular signal‐regulated kinase) in smooth muscle cells. This effect of ketamine was not dependent on de novo protein synthesis. Immunofluorescent light microscopy showed ketamine‐induced nuclear accumulation of c‐fos, a downstream effect of MAP kinase activation, in smooth muscle cells. In conclusion, these data support the hypothesis of the study and demonstrate that ketamine, by stimulating DNA synthesis in human aortic smooth muscle cells, may have an impact on proliferative capacity of these cells. The present results also demonstrate that ketamine induces the activation of MAP kinase pathway and nuclear accumulation of transcription factor c‐fos in smooth muscle cells. They further demonstrate that the activation of MAP kinases is partially responsible for ketamine‐induced DNA synthesis in human aortic smooth muscle cells. Together, these findings suggest that ketamine may play a role as a pharmacological regulator of mechanisms involved in proliferation of smooth muscle cells.
Proliferation of glial cells induced by lithium in the neural lobe of the rat pituitary is enhanced by dehydration
Authors: Levine S. , Saltzman A. , Katof B. , Meister A. , Cooper T. B.
Published: March 2003

Abstract. Rats dehydrated by 6 days of water deprivation had a low level of mitotic activity in the astrocytes (‘pituicytes’) of the neural lobe of the pituitary. Mitotic activity in the pituicytes was greatly increased when isotonic lithium was administered in the last 3 days of water deprivation. Rehydration on the last day of the experiment produced a further increase in mitoses. Isotonic solutions of sodium, potassium or rubidium chloride did not increase mitoses. This model of cell proliferation is of interest because the mitotic activity is related to a physiological attempt to maintain homeostasis rather than a response to injury or the development of neoplasia.
Supporting families of origin: an exploration of the influence of the Children Act 1948
Authors: James Ann N.
Published: March 2003

The 50th anniversary of the Children Act 1948 is an opportunity to look back at the evolution of child care practice in England and Wales. This paper traces the development of social work practice aimed at supporting families of origin. It highlights the transition of the concept of prevention from a narrow focus on the prevention of admission to care, to the wider understanding of family support reflected in the Children Act 1989. Some of the challenges to policy and practice supporting families are identified and it is argued that the retreat from prevention in the 1970s is most evident in the subsequent investment in the child rescue ideology of the ‘permanence movement’. The paper draws attention to the intentions of the Children Act 1989 to redress the failures and deficiencies of earlier practice by its emphasis on supporting families of children in need. It highlights current concerns that practice aimed at supporting families of origin continues to be marginalized by an emphasis on child protection and argues for a renewed commitment to section 17, Children Act 1989.
Responding to child sexual abuse: an evaluation of social work by children and their carers
Authors: Prior  , Lynch  , Glaser
Published: March 2003

This paper presents the views and perceptions of 35 children and their current carers regarding the social work response to child sexual abuse. Interviews with the children and carers, including foster carers and residential carers, were carried out 2–4 years following disclosure, thus the nature of social work support in the longer term, as well as the initial response, is assessed and described. Three evaluations of social work support are presented: the child‐ren’s evaluations of social workers known since disclosure, and two evaluations from the carers, one focusing on the child’s needs, and one focusing on their own as carers. All three evaluations perceived the majority of social workers as having helped. Aspects of social work considered essential included providing emotional support and reassurance, providing information and explanation and arrang‐ing and coordinating services, including counselling or therapy.

 Carers of children who were abused by someone outside the family were less likely to receive social work support. The frustra‐tion and disappointment expressed by some of these carers reaffirms the importance of assessing needs even when the child is considered protected from further abuse. The findings of this study support the need to refocus responses to abused children and their families.
Parenting stress and anger: the Hong Kong experience
Authors: Lam
Published: March 2003

This paper examines the relationship between parenting stress and anger. A study was done on parenting stress and anger and its form of expression among Hong Kong Chinese parents. Three measures were used in the study: Abidin’s Parental Stress Index/Short Form (PSI/SF; 1990), the Maternal Social Support Index (Pascoe et al. 1981) and Spielberger’s State Trait Anger Expression Inventory (STAXI; 1991). A total of 475 parents of children in a primary school participated in the study. The Chinese PSI/SF and the STAXI showed good inter‐item reliability. The study helped to provide a profile of the parenting stress and the style of anger expression of Hong Kong Chinese parents. Stress was not found to be related to the year of the children in school or the general socio‐economic conditions of the family. But stress correlated positively with anger expression. Multiple regression showed that anger expression was most strongly related to Trait Anger, the Difficult Child scores and the social support available to respondents. Rather than blaming the parent or the child, it is suggested more services should be provided to enhance the anger management, problem‐solving skills and social support of the parents.
Quality social work with children and families
Authors: Morris  , Shepherd
Published: March 2003

The paper explores some of the current issues and dilemmas in providing services to children and families. Existing value bases are considered, as well as the effect of these on the type and quality of services received by children and families. The structures are also discussed and the relationship to services critically commented upon. The conclusion describes an alternative model that combines service structure with core skills.
Socio‐genealogical connectedness: on the role of gender and same‐gender parenting in mitigating the effects of parental divorce
Authors: Owusu‐Bempah  , Howitt
Published: March 2003

Guided by the idea of socio‐genealogical connectedness (i.e. knowledge, and belief in, one’s biological and social roots), the present study explored the relationship between a number of the characteristics of lone‐parent families and the well‐being of children in these families. Since it is well established that develop‐mental difficulties do not emerge in all children of divorced/separated families, there is a need to understand those factors which mitigate against the adverse influences of divorce on children. Evidence suggests that socio‐genealogical connectedness is one of the possible mitigating factors. However, the present study, which involved a variety of multivariate statistical techniques, indicates academic attainment to be the most important mitigating factor. This implies that children with greater intellectual resources to deal with problems are less vulnerable than others to the long‐term effects of divorce and separation. Nonetheless, the results support the hypothesis derived from the concept of socio‐genealogical connectedness; it was the second most important predictor.
The day fostering scheme: a service for children in need and their parents
Authors: Steele L.
Published: March 2003

This paper summarizes a new scheme, set up initially as a pilot project, which has now become Children and Families Social Services provision, in the Metropolitan Borough of Stockport. The pilot project ran for a 6‐month period, in order to establish whether a day fostering service would be a useful and effective way of working in partnership with birth families. The paper discusses the philosophy behind the Children Act 1989 (England and Wales), and some research findings on the consequences of poor parenting for children, to examine the need for a day fostering scheme. Finally, the scheme itself is described, with an evaluation of the referrals for the 6‐month pilot period, and a discussion of the future of the project.
The transition of Israeli men to fatherhood: a comparison between new fathers of pre‐term/full‐term infants
Authors: Rimmerman Arie , Sheran Haviva
Published: March 2003

The study compared a group of 62 new Israeli fathers of pre‐term infants with a comparison group of 58 new fathers of full‐term infants with respect to parental stress, depression symptoms, mastery, self‐esteem and involvement with the child. Findings indicated that fathers of pre‐term infants had significantly greater stress and depression scores and lower involvement rate with the child compared with fathers of the matching group. No differences were found with respect to the fathers' mastery and self‐esteem. New fathers of full‐term infants, aged 30 years and more, had significantly higher self‐esteem compared with fathers aged less than 30 years. Findings are discussed with respect to practice in neonatal units.
Promoting children's rights through the use of relationship
Authors: Bell Margaret
Published: March 2003

This paper reports on a research study exploring the views of 27 children and young people on their involvement in a child protection investigation. Their perspectives on the personal and professional qualities of the professionals involved and on the choice, influence and representation they experienced and prefer are discussed. One of the most striking findings is that most of the children and young people had experienced a positive relationship with a social worker. Overall, many reported improvements at home, at school and in their health and behaviour. Their responses to different aspects of the intervention are discussed within the context of their rights to participation, choice and representation. It is acknowledged that children lack agency in promoting these rights in child protection work and concluded that these are best promoted through the development and maintenance of a relationship of trust, offered by a key professional in their network. Drawing upon Heard & Lake's (1997) work on attachment theory, it is suggested, further, that relationships and processes which embody supportive and companionable interactions are more likely to offer opportunities for representation and participation than those which are dominant and submissive. Finally, it is argued that children's services should be based on a human rights perspective, the discourse of which has more in common with the values of respect and honesty than with cost effectiveness and business management.
Social welfare services for single parent families in Hong Kong: a paradox
Authors: King Lau Yuk
Published: March 2003

This paper argues that researchers and social workers, whose work aims at empowering single parent families, have inadvertently participated in a social construction process that reinforces a pathological perspective on these families. The process has paradoxically caused single parent families to be disempowered through a welfare service system that pinpoints their difficulties and vulnerabilities. To address the paradox, the author recommends a ‘both–and’ perspective that takes into account both the needs and difficulties, and the strengths and successes, of these families.