bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid, accurate genotyping of the common −α4.2thalassaemia deletion based on the use of denaturing HPLC
Authors: Ou-Yang H , Hua L , Mo Q H , Xu X M 
Published: January 2004

Aims:To develop an alternative assay for specific genotyping of the −α4.2thalassaemia deletion based on the DNA sequence features surrounding the breakpoint.Methods:The 5′ and 3′ ends of the breakpoint regions of the −α4.2allele and the normal homologous segments were sequenced in Chinese individuals. A sequence haplotype composed of four single nucleotide variations within the X2/X1 box of the −α4.2breakpoint region was found in all of the 10 Chinese −α4.2thalassaemia alleles studied. Based on these findings, a novel polymerase chain reaction (PCR)/denaturing high performance liquid chromatography (DHPLC) assay was developed for rapid genotyping of the −α4.2allele instead of traditional Southern blotting or Gap-PCR. This method involves amplification of the α globin target sequence encompassing these four polymorphic sites, followed by a partially denaturing HPLC analysis using the transgenomic WAVE DNA fragment analysis system.Results:The three major genotypes (−α4.2/αα, −α4.2/--SEA, and αα/αα) could be distinguished through the characteristic chromatograms generated by the WAVE system. The accuracy of this technique was evaluated blindly, and the results were 100% (40 of 40) concordant with the genotypes previously characterised by Southern blotting or Gap-PCR.Conclusions:This study validates the PCR/DHPLC approach as a simple, rapid, highly accurate, and cost effective method, potentially adaptable for use in epidemiological surveys, genetic screening, and diagnosis of silent α+thalassaemia and Hb H disease.
Lack of vascular adventitial fibroblastic cells in tumour stroma of intestinal-type and solid-type gastric carcinomas
Authors: Nakayama H , Enzan H , Miyazaki E , Kuroda N , Toi M , Hiroi M , Yasui W 
Published: January 2004

Aims:To investigate the roles of vascular adventitial fibroblastic cells in tumour stroma, the distribution of vascular adventitial fibroblastic cells was studied in gastric carcinomas.Methods:In total, 50 surgically resected gastric carcinomas (43 intestinal type, and seven solid type) and their normal tissues were examined. Vascular adventitial fibroblastic cells are positive for CD34 but negative for CD31. To differentiate vascular adventitial fibroblastic cells from vascular endothelial cells, immunostaining for CD34 and CD31 was performed. Immunostaining for high molecular weight caldesmon was also performed to recognise vascular media.Results:In normal gastric tissues, CD34 positive fibroblastic cells were found just outside the vascular media, namely vascular adventitial fibroblastic cells. In contrast, all of the 43 intestinal-type and seven solid-type gastric carcinomas had no vascular adventitial fibroblastic cells in the tumour stroma.Conclusions:These results suggest that a lack of vascular adventitial fibroblastic cells is associated with tumour stroma formation in intestinal-type and solid-type gastric carcinomas.
Gastrin releasing peptide and gastrin releasing peptide receptor expression in gastrointestinal carcinoid tumours
Authors: Scott N , Millward E , Cartwright E J , Preston S R , Coletta P L 
Published: January 2004

Aims:To establish whether gastrin releasing peptide (GRP) and the GRP receptor (GRPR) are expressed together in gastrointestinal carcinoid tumours.Methods:Twenty six carcinoid tumours from the stomach, small intestine, appendix, and colorectum were investigated by immunohistochemistry for GRP and GRPR.Results:GRP was detected in nine of 19 tumours and GRPR in 22 of 26. Coexpression of both the ligand and receptor was seen in six of 19 cases. GRPR but not GRP was more strongly expressed in appendix and colonic tumours.Conclusions:GRP and GRPR are produced by a large number of gastrointestinal carcinoid tumours. An autocrine/paracrine pathway may exist for GRP stimulated cell proliferation in some of these neoplasms, analogous to that seen in small cell anaplastic carcinoma of the lung.
Clinical evaluation of the COBAS Amplicor HBV monitor test for measuring serum HBV DNA and comparison with the Quantiplex branched DNA signal amplification assay in Taiwan
Authors: Dai C-Y , Yu M-L , Chen S-C , Lin Z-Y , Hsieh M-Y , Wang L-Y , Tsai J-F , Chuang W-L , Chang W-Y 
Published: January 2004

Aims:To evaluate the performance characteristics and clinical usefulness of the COBAS Amplicor HBV monitor (COBAS-AM) test in Taiwan and to examine its correlation with the Quantiplex branched DNA signal amplification (bDNA) assay for measuring serum hepatitis B virus (HBV) DNA concentrations.Methods:HBV DNA was measured by the COBAS-AM test in 149 sera from chronic HBV infected patients that had previously been analysed by the bDNA assay.Results:The COBAS-AM test showed good reproducibility, with acceptable intra-assay and interassay coefficients of variation (1.6% and 0.9%, respectively) and good linearity (r2 =  0.98). The overall sensitivity of the COBAS-AM test was significantly higher than that of the bDNA assay (95.3%v83.2%): 69.6% of samples with HBV DNA below the detection limit of the bDNA assay could be measured by the COBAS-AM test. There was a significant correlation between the results of the two assays (r =  0.901; p < 0.0001). On average, the results derived from the COBAS-AM test were 0.55 log lower than those of the bDNA assay. HBV DNA concentrations were significantly higher among HBV e antigen (HBeAg) positive patients than negative ones, and higher among patients with abnormal alanine aminotransferase (ALT) concentrations than those with normal ALT concentrations (p  =  0.0003).Conclusions:The COBAS-AM assay, more sensitive in HBeAg negative samples than the bDNA assay, can effectively measure HBV DNA concentrations in Taiwanese patients. HBV DNA values measured by the COBAS-AM test and bDNA assay correlate significantly.
Hepatic myospherulosis complicating portal vein embolisation
Authors: Lui P C W , Luk I S C , Lee C K L , Lui Y H , Leung C Y , Choi C H 
Published: January 2004

Aims:Myospherulosis is a rare condition characterised by sac-like structures containing spheroid bodies in cysts or cystic spaces in the tissue. This condition has not previously been reported in the liver. The association with previous portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil and the proposed mechanism of pathogenesis are discussed.Methods:Samples from 8 patients treated by hepatectomy after portal vein embolisation using a mixture of butyl 2-cyanoacrylate and ethiodised oil were retrieved from the archives of the United Christian Hospital, Hong Kong. The histological specimens were reviewed. A panel of histochemical and immunohistochemical stains was used.Results:All cases showed hepatic myospherulosis within the veins. The veins were denuded of endothelium, which was replaced by granulation tissue and fibrous tissue with a lymphoplasmacytic infiltrate. Foreign body-type giant cells (six cases) and eosinophilic infiltrates (seven cases) were noted in most cases. Both parent bodies and endobodies were stained red by Papanicolaou and Masson’s trichrome and stained blue by solochrome cyanine. The endobodies showed immunoreactivity towards glycophorin A. They were negative for Alcian blue, periodic acid Schiff, Grocott, and Ziehl-Neelsen stains.Conclusions:The endobodies of myospherulosis may be misdiagnosed as fungi or algae by the unwary. The clinical history, intravascular location, lack of staining with periodic acid Schiff and Grocott stains, and positive glycophorin A staining are generally sufficient for a confident diagnosis of myospherulosis.
Demographic study of leukaemia presenting within the first 3 months of life in the Northern Health Region of England: Table 1
Authors: Bajwa R P S , Skinner R , Windebank K P , Reid M M 
Published: January 2004

Aims:To determine the incidence and outcome of congenital leukaemia.Methods:Retrospective population based study of putative leukaemia arising during the first 3 months of life over an 18 year period within the Northern Health Region of England.Results:Nine infants with putative leukaemia were identified. Five had acute leukaemia and four had transient myeloproliferative disorder (TMD). Trisomy 21, either as Down’s syndrome or perhaps restricted to proliferating marrow cells, was present in all four infants with TMD. The incidence of congenital acute leukaemia was 8.6/106live births/year, but would be less than half this value if only patients presenting within 4 weeks of birth were counted. Remission was induced in three of the five patients with acute leukaemia. One patient, who presented at birth, remains well five years after diagnosis. All four patients with TMD survive.Conclusions:Congenital leukaemia is very rare but is not inevitably fatal. Finding trisomy 21 in spontaneously dividing blood or bone marrow cells of an infant with putative acute leukaemia, particularly within 3 months of birth, should encourage a cautious clinical approach and suggests that the diagnosis might be TMD.
The diagnostic value and cost effectiveness of routine fungal stains in a dermatopathology service of a district general hospital: Table 1
Authors: Murphy J K , O’Donohue L 
Published: January 2004

Aims:To evaluate the use and effectiveness of fungal stains in a dermatopathology service of a district general hospital.Methods:A retrospective analysis of skin biopsies submitted over three years, where fungal stains were used; the results were correlated with clinical history and case notes.Results:In total, 99 cases were studied for fungi with the periodic acid Schiff stain with diastase. Fungi were present in seven cases; fungi had been suggested in the differential diagnosis of three of these cases but were an unexpected finding in four cases.Conclusion:Non-specific clinical details should prompt early fungal staining and non-specific microscopic findings or inappropriate well recognised skin reaction patterns should warrant the exclusion of fungal infection. The finding of at least one case of unexpected fungal infection is justified financially and for patient best management where clinical and microscopic findings are non-specific or inappropriate.
α0Thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated α globin genes
Authors: Jia S-Q , Li J , Mo Q-H , Liao C , Li L-Y , Xu X-M 
Published: January 2004

Aims:To characterise a novel 11.1 kb deletion that eliminated both of the duplicated α globin genes, giving rise to a typical α0thalassaemia phenotype in four carriers from a Chinese family.Methods:Haematological investigations were carried out on all family members. The seven common forms of α thalassaemia were screened for by the polymerase chain reaction (PCR) and Southern blotting was used to analyse the α globin gene cluster. DNA sequence analysis of the entire α1 and α1 globin gene region was carried out and reverse transcription (RT)-PCR was used to investigate the transcription levels of the α and β globin genes.Results:The breakpoints were found to lie between coordinates 31695–31724 and 42846–42867 of the α globin gene cluster (NG_000006), with a total of about 11 135 nucleotides deleted. These sequences are involved in (CA)nrepeats, suggesting a homologous recombination event. RT-PCR analysis gave a transcription level of the α globin gene in heterozygotes comparable with that of SEA deletion heterozygotes, confirming no output of α globin from the linked pair of α globin genes. The heterozygosity for this novel deletion was confirmed by PCR diagnosis in all four carriers from this family.Conclusions:This rare mutation constitutes an additional heterogeneous defect causing α thalassaemia in the Chinese population.
Agreement between preoperative core needle biopsy and postoperative invasive breast cancer histopathology is not dependent on the amount of clinical material obtained
Authors: O’Leary R , Hawkins K , Beazley J C S , Lansdown M R J , Hanby A M 
Published: January 2004

Aims:To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer.Methods:The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression.Results:Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade—nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)—agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined.Conclusion:Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.
A study of public opinion on the use of tissue samples from living subjects for clinical research
Authors: Goodson M L , Vernon B G 
Published: January 2004

Aims:To assess public opinion on the use of tissue samples from living adults and children for clinical research.Methods:A questionnaire study of 100 healthy volunteers (100% response rate) from a Newcastle NHS dental practice. The issues investigated were the types of tissues that individuals were prepared to donate for research, the type of research donors would be prepared to consent to, and attitudes to research on children’s tissues.Results:Eighteen per cent of the participants said that they would not give consent for research to be carried out on their tissues, 50% would not give consent for the donation of a child’s tissues. Only 26% of subjects said that they would give consent for research on genetic cloning compared with 82% for cancer research. Sex differences existed in the responses.Conclusions:Greater research attention needs to be given to public opinion on the use of tissue from living subjects for medical research to facilitate drafting of new legislation.
CATEGORIES AS ALGEBRA, II
Authors: STEINBERG BENJAMIN , TILSON BRET 
Published: January 2004

A theory of the semidirect product of categories and the derived category of a category morphism is presented. In order to include division (≺) in this theory, the traditional setting of these constructions is expanded to include relational arrows. In this expanded setting, a relational morphism φ : M → N of categories determines an optimal decomposition [Formula: see text] where [Formula: see text] denotes semidirect product and D(φ) is the derived category of φ.The theory of the semidirect product of varieties of categories, V * W, is developed. Associated with each variety V of categories is the collection [Formula: see text] of relational morphisms whose derived category belongs to V. The semidirect product of varieties and the composition of classes of the form [Formula: see text] are shown to stand in the relationship [Formula: see text] The associativity of the semidirect product of varieties follows from this result.Finally, it is demonstrated that all the results in the article concerning varieties of categories have pseudovariety and monoidal versions. This allows us to furnish a straightforward proof that [Formula: see text] for both varieties and pseudovarieties of monoids.
Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice
Authors: Ni Weihua , Kitamoto Shiro , Ishibashi Minako , Usui Makoto , Inoue Shujiro , Hiasa Ken-ichi , Zhao Qingwei , Nishida Ken-ichi , Takeshita Akira , Egashira Kensuke 
Published: January 2004

Objective—Chronic inflammatory processes might be involved in the progression and destabilization of atherosclerotic plaques. Therefore, identification of the mechanism underlying arterial inflammatory function might lead to the development of novel therapeutic strategies. Angiotensin II (AngII) is implicated in atherogenesis by activating the vascular inflammation system, mainly through monocyte chemotaxis. Therefore, we hypothesized that AngII increases plaque size and promotes destabilization of established atheromas by activating the monocyte chemoattractant protein-1 (MCP-1) pathway.Methods and Results—We report here that 4-week infusion of AngII not only increased plaque size but also induced a destabilization phenotype (ie, increased macrophages and lipids and decreased collagen and smooth muscle cells) of pre-existing atherosclerotic lesions of hypercholesterolemic mice. AngII also enhanced the gene expression of inflammatory cytokines (TNFα, IL-6, etc.) and chemokines (MCP-1, CCR2, etc). Blockade of MCP-1, by transfecting the deletion mutant of the human MCP-1 gene into the skeletal muscles, limited AngII-induced progression and destabilization of established atherosclerotic lesions and suppressed the induction of proinflammatory genes.Conclusions—These data suggest that MCP-1 functions as a central inflammatory mediator in the AngII-induced progression and changes in plaque composition of established atheroma.
Inhibition of Plasmin Activity by Tranexamic Acid Does Not Influence Inflammatory Pathways During Human Endotoxemia
Authors: Renckens Rosemarijn , Weijer Sebastiaan , de Vos Alex F. , Pater Jennie M. , Meijers Joost C. , Hack C. Erik , Levi Marcel , van der Poll Tom 
Published: January 2004

Objective—Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.Methods and Results—To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (fromEscherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n=8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-α2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (bothP<0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-α1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.Conclusion—These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.
Pericapillary hemorrhage as criterion of severe human digestive graft-versus-host disease
Authors: Ertault-Daneshpouy Marjan , Leboeuf Christophe , Lemann Marc , Bouhidel Fatiha , Ades Lionel , Gluckman Eliane , Socié Gérard , Janin Anne 
Published: January 2004

AbstractIn an experimental model we demonstrated that endothelial cells of all organs are targets of the alloimmune reaction. Here, in 68 digestive biopsies, we found endothelial lesions by immunohistochemistry and ultrastructure in patients with severe acute graft-versus-host disease (GVHD). In contrast, no such endothelial cell alterations were found either in patients without GVHD or in nongrafted controls. In the biopsies with severe GVHD lesions, ultrastructure showed rupture of the capillary basal membrane and extravased red blood cells. These pericapillary hemorrhages were highly correlated with GVHD severity. In a separate cohort of 39 patients who underwent an allogeneic transplantation after a nonmyeloablative conditioning, 8 patients had intestinal biopsies. Three of these latter patients had both severe pathologic lesions of GVHD and similar endothelial lesions, thus, strengthening the concept that endothelial lesions are linked to GVHD severity and not to the intensity of the conditioning regimen. (Blood. 2004;103:4681-4684)
The granzyme B–serglycin complex from cytotoxic granules requires dynamin for endocytosis
Authors: Veugelers Kirstin , Motyka Bruce , Frantz Christine , Shostak Irene , Sawchuk Tracy , Bleackley R. Chris 
Published: January 2004

AbstractCytotoxic T lymphocytes and natural killer cells destroy target cells via the directed exocytosis of lytic effector molecules such as perforin and granzymes. The mechanism by which these proteins enter targets is uncertain. There is ongoing debate over whether the most important endocytic mechanism is nonspecific or is dependent on the cation-independent mannose 6-phosphate receptor. This study tested whether granzyme B endocytosis is facilitated by dynamin, a key factor in many endocytic pathways. Uptake of and killing by the purified granzyme B molecule occurred by both dynamin-dependent and -independent mechanisms. However most importantly, serglycin-bound granzyme B in high-molecular-weight degranulate material from cytotoxic T lymphocytes predominantly followed a dynamin-dependent pathway to kill target cells. Similarly, killing by live cytotoxic T lymphocytes was attenuated by a defect in the dynamin endocytic pathway, and in particular, the pathways characteristically activated by granzyme B were affected. We therefore propose a model where degranulated serglycin-bound granzymes require dynamin for uptake.
Identification and characterization of a very low density lipoprotein receptor-binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity
Authors: Hembrough Todd A. , Ruiz Jose F. , Swerdlow Bonnie M. , Swartz Glenn M. , Hammers Hans J. , Zhang Li , Plum Stacy M. , Williams Mark S. , Strickland Dudley K. , Pribluda Victor S. 
Published: January 2004

AbstractTissue factor pathway inhibitor (TFPI) is the major physiologic inhibitor of the extrinsic coagulation pathway. We have previously shown that TFPI is also a potent inhibitor of endothelial proliferation in vitro and of primary and metastatic tumor growth in vivo. Surprisingly, the antitumor activity of TFPI was demonstrated to be independent of its anticoagulant activity, suggesting a possible nonhemostatic mechanism of action for TFPI in these models. This antitumor mechanism may involve the very low density lipoprotein (VLDL) receptor because the in vitro antiproliferative activity of TFPI is mediated through interaction with the VLDL receptor. In the current study, we identify a 23-amino acid fragment of TFPI (TFPIc23) localized to the C-terminus, which mediates binding to the VLDL receptor. The TFPIc23 peptide inhibits endothelial cell proliferation through an apoptotic mechanism and blocks vessel outgrowth in the in vitro assays, and this activity is mediated through interaction with the VLDL receptor. In vivo, this peptide potently inhibits angiogenesis in Matrigel and chick chorioallantoic membrane models and also inhibits metastatic tumor growth. Our data demonstrate that this VLDL receptor-binding fragment of the TFPI molecule has apoptotic, antiangiogenic, and antitumor activity and suggests a possible mechanism whereby TFPI can regulate angiogenesis and tumor growth independently of its anticoagulant activity. (Blood. 2004;103: 3374-3380)