bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of two missense mutations causing factor XIIIA deficiency
Authors: Kangsadalampai Sasichai , Chelvanayagam Gareth , Baker Rohan , Tiedemann Karin , Kuperan Ponnudurai , Board Philip G. 
Published: March 2003

In this study, two amino acid substitutions, Arg260His and Val414Phe, have been identified in the factor XIIIA subunits of factor XIII deficient patients of Syrian and Indian descent, respectively. To confirm the deleterious effects of these substitutions, both variant sequences have been engineered into cDNA clones and the mutant enzymes expressed in yeast. Determination of the transglutaminase activity and immuno detection of the mutant enzymes together with mRNA hybridization revealed that the mutations dramatically reduce both the catalytic activity and the level of enzyme expressed in yeast.The mutations Arg260His and Val414Phe occur within the ‘core’ domain of the enzyme. Computer modelling of the mutant enzymes reveals that the substitution of the Arg260 by His results in the loss of a conserved electrostatic interaction whereas the effect of the Val414Phe substitution is a consequence of the large increase in side‐chain volume. Although both mutations do not effect the active site directly, they are predicted to reduce the stability of the enzyme.The effects of these two amino acid substitutions on enzyme expression and three‐dimensional structure strongly confirm that residues which are located outside of the active site can have a significant effect on protein stability and function.
Cyclin D2 promoter disrupted by t(12;22)(p13;q11.2) during transformation of chronic lymphocytic leukaemia to non‐Hodgkin's lymphoma
Authors: Qian L. , Gong J. , Liu J. , Broome J. D. , Koduru P. R. K. 
Published: March 2003

In a unique case of chronic lymphocytic leukaemia (CLL) we performed a longitudinal cytogenetic and molecular genetic study of tumour cells from diagnosis through progression and transformation to non‐Hodgkin's lymphoma (NHL) and lymphomatous meningitis. CLL cells at diagnosis had trisomy 12 and a t(14;19)(q32;q13.3). At relapse, the leukaemic cells had a subclone carrying a t(12;22)(p13;q11.2) in addition to the initial changes.We cloned reciprocal translocation junctions at the 22q11.2− chromosome and the 12p13+ chromosome and the corresponding germline DNA fragments. Restriction map analysis and nucleotide sequence analysis of the cloned DNA fragment from the 22q11.2− chromosome mapped the translocation break within the immunoglobulin (Ig)‐λ‐C complex at the nt3889; nts 3890, 3891 were lost from the translocation site. A probe from the 3′‐end of the clone derived from the 22q11.2− chromosome showed single copy hybridization which was different from the Ig‐λ probe. Nucleotide sequence analysis of the exact junction region and the corresponding germline DNA showed that the translocation at 12p13 occurred in the negative regulatory region of the cyclin D2 gene at the nt −1602, and a pentamer consisting of nts −1603 to −1599 was lost at the break site. We sequenced another 227 bp upstream of the known 5′‐end of the promoter and did not find any open reading frame. From these results we hypothesize that, in this patient, the t(12;22) disrupted the negative regulator in the promoter of cyclin D2 which in turn might have deregulated cyclin D2.
Cyclin D1 and E2F‐1 immunoreactivity in bone marrow biopsy specimens of multiple myeloma: relationship to proliferative activity, cytogenetic abnormalities and DNA ploidy
Authors: Wilson CarlA. S. , Butch AnthonY. W. , Lai Raymond , Medeiros L. Jeffrey , Sawyer JeffreY. R. , Barlogie Bart , McCourty Althea , Kelly Kathy , Brynes RusselL. K. 
Published: March 2003

Cyclin D1, encoded by the CCND1 gene, is immunohistochemically detectable in up to one‐third of cases of multiple myeloma (MM). To examine the mechanism of cyclin D1 overexpression, we compared cyclin D1 immunoreactivity with the results of conventional cytogenetics to determine if the t(11;14)(q13;q32) or other abnormalities of 11q11–14 explained cyclin D1 overexpression. Karyotypic abnormalities were found in 45 out of 67 (67%) MM cases; the t(11;14) was present in seven cases (10%). Additional 11q11–14 abnormalities were not identified. The t(11;14) correlated with cyclin D1 upregulation in low to intermediately proliferative MM, but was not present in highly proliferative tumours (assessed using bromodeoxyuridine labelling index). Cyclin D1 indirectly activates the transcription factor E2F‐1. In the bone marrow biopsy specimens of MM cases, E2F‐1 was concurrently expressed with cyclin D1 (P = 0·001), indicating that cyclin D1 is functional. However, as neither E2F‐1 nor cyclin D1 expression correlated with proliferative activity, the speculation that t(11;14) upregulates the CCND1 gene to induce higher proliferation and possibly more aggressive disease is not supported. We conclude that in low to intermediately proliferative MM cases, cyclin D1 is probably upregulated by t(11;14), but an alternative mechanism is more probable in highly proliferative MM.
Effect of chemotherapy and stem cell transplantation on T lymphocyte clones in familial haemophagocytic lymphohistiocytosis
Authors: Kimura Nobuhiro , Ishii Eiichi , Sako Masahiro , Yoshida Tetsuya , Nagano Mitsuyuki , Takada Hidetoshi , Imashuku Shinsaku , Tamura Kazuo 
Published: March 2003

Familial haemophagocytic lymphohistiocytosis (FHL) is a rare disorder in infancy, curative only by an allogeneic stem cell transplantation (SCT). We recently confirmed the clonal evidence of T cells in FHL. To confirm the effect of chemotherapy and SCT in FHL, the change of T‐cell clones was analysed in two patients using inverse reverse transcription‐polymerase chain reaction (RT‐PCR) of the T‐cell receptor variable region (TCR V) gene, followed by PCR for the junctional region (Jβ‐PCR), a single‐strand conformation polymorphism (SSCP) and sequencing analysis at diagnosis, after chemotherapy and after SCT. A high frequency (> 15%) of αβ T‐cell clones and a predominant bias (Jβ1:Jβ2, 85:15) for the Jβ1 subgroup were observed in the two patients at diagnosis. In one patient, however, an inverted predominant bias (Jβ1:Jβ2, 9:91) for the Jβ2 subgroup and oligoclonal expansion were observed at relapse after chemotherapy. In the other patient, correction of both restricted Jβ cluster usage and variation of TCR were observed after chemotherapy and SCT. Using sequence analysis, the clonal T cells detected at diagnosis were found to be substituted at low frequency (< 0.75%) by several new clones after chemotherapy and SCT. These results indicate that any genetic defect could influence the regulation of the T‐cell network, and normalization of both the variation in each Vβ repertoire and the Jβ1/Jβ2 ratio is needed to achieve remission, and might support the rationale that the only acceptable curative therapy of FHL is allogeneic SCT.
Prospective monitoring of the Epstein–Barr virus DNA by a real‐time quantitative polymerase chain reaction after allogenic stem cell transplantation
Authors: Hoshino Yo , Kimura Hiroshi , Tanaka Naoko , Tsuge Ikuya , Kudo Kazuko , Horibe Keizo , Kato Koji , Matsuyama Takaharu , Kikuta Atsushi , Kojima Seiji , Morishima Tsuneo 
Published: March 2003

Epstein‐Barr virus (EBV)‐related lymphoproliferative disorder (LPD) is a serious complication of haematopoietic stem cell transplantation (HSCT). To clarify the frequency, natural course and risk factors for LPD, we prospectively monitored 38 allogeneic (allo)‐HSCT patients, focusing on the use of anti‐thymocyte globulin (ATG). We used a recently developed real‐time polymerase chain reaction assay to monitor EBV genome load. The subjects consisted of 19 patients given ATG for conditioning and 19 patients not given ATG. Of the 19 patients given ATG, 47·4% (nine patients) had a significant increase in EBV genome load (102·5copies/µg DNA). Of these nine patients, two developed LPD. Therefore, 10·5% of the patients receiving allo‐HSCT with ATG developed LPD. In contrast, none of the 19 patients without ATG had a significantly increased EBV load. The increases in viral load were observed in the second or third month after HSCT. We found that the peak viral loads of LPD patients were > 104·0copies/µg DNA. On the other hand, the viral loads of most patients with no symptoms were < 102·5copies/µg DNA. In conclusion, routine monitoring of EBV load during the second and third months after transplantation may benefit patients undergoing HSCT with ATG. We propose that an EBV load > 102·5copies/µg DNA is the reactivation of EBV, and that an EBV load > 104·0copies/µg DNA is indicative of developing LPD.
Abdominal lymphangioma in adults and children
Authors: de Perrot M , Rostan O , Morel P , LE Coultre C 
Published: March 2003

Abstract

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

Abstract

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

AbstractBackgroundMultiple 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.MethodsTimed 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.ResultsPlasma 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.ConclusionIn 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

Abstract

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 &lt; 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

Abstract

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 &lt; 0·02) and TIMP-2 (rs = 0·59, P &lt; 0·02). Interstitial fibrosis was also strongly correlated with the levels of TGF-β mRNA (rs = 0·67, P &lt; 0·002). Finally, TIMP-1 expression increased with TGF-β expression (rs = 0·77, P &lt; 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

AbstractBackgroundOperative 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.MethodsA meta-analysis of all English language literature quoting figures for operative mortality of RAAA repair.ResultsThe 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.ConclusionContrary 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

Abstract

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

AbstractBackgroundIn 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.MethodsFifteen 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.ResultsBPR 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.ConclusionThe 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.
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

AbstractThe 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.