bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAG‐1 expression in human breast cancer: interrelationship between BAG‐1 RNA, protein, HSC70 expression and clinico‐pathological data
Authors: Townsend P. A. , Dublin E. , Hart I. R. , Kao R.‐H. , Hanby A. M. , Cutress R. I. , Poulsom R. , Ryder K. , Barnes D. M. , Packham G. 
Published: October 2002

AbstractBAG‐1 (BCL‐2 athanogene‐1), a multifunctional protein which associates with steroid hormone receptors (including the oestrogen receptor) and the anti‐apoptotic BCL‐2 protein, regulates steroid hormone‐dependent transcription and apoptosis. Direct interaction with 70 kD heat‐shock proteins, HSC70 and HSP70, may mediate the diverse functions of BAG‐1. Immunohistochemistry was used to examine the expression of BAG‐1 and HSC70 in 160 cases of invasive breast cancer. BAG‐1 was expressed in 92% of cases; most tumours exhibited cytoplasmic BAG‐1, while a smaller proportion also had nuclear immunostaining. There was a significant inverse correlation between histological grade and nuclear BAG‐1 expression, with higher‐grade tumours tending to have reduced nuclear BAG‐1 expression, but there was no association with cytoplasmic BAG‐1. There was also no significant correlation between nuclear or cytoplasmic BAG‐1 expression and oestrogen receptor positivity. Since BAG‐1 may be influenced by hormonal background, the relationship between grade and oestrogen receptor was examined separately in pre‐menopausal and post‐menopausal women. The statistically significant correlation between nuclear BAG‐1 expression and low tumour grade was strong in pre‐menopausal, but not apparent in post‐menopausal women. A statistically significant correlation was observed between cytoplasmic, but not nuclear, BAG‐1 expression and oestrogen receptor status in pre‐menopausal, but not post‐menopausal, women. There was no correlation between BAG‐1 protein expression and RNA, suggesting that important post‐transcriptional mechanisms control BAG‐1 expression in vivo. HSC70 was also detected in the majority (97%) of cases, although expression was not correlated with BAG‐1 levels, oestrogen receptor status or tumour grade. Overall survival in cases with high levels of nuclear BAG‐1 expression was improved, though not significantly. These results are consistent with the hypothesis that BAG‐1 plays an important but variable role in breast cancers developing in pre‐menopausal and post‐menopausal women. Copyright © 2002 John Wiley & Sons, Ltd.
The glomerulo‐tubular junction: a target in renal diseases
Authors: Lindop G. B. M. , Gibson I. W. , Downie T. T. , Vass D. , Cohen E. P. 
Published: October 2002

AbstractBoth global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo‐tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of the Duffy antigen/receptor for chemokines (DARC) by the inflamed synovial endothelium
Authors: Patterson Angela M. , Siddall Hilary , Chamberlain Giselle , Gardner Lucy , Middleton Jim 
Published: October 2002

AbstractThe expression of chemokine binding sites on the endothelial cells of venules in inflamed synovia was examined and whether the Duffy antigen/receptor for chemokines (DARC) was involved. Insitu binding assays were performed to determine the expression of chemokine binding sites from rheumatoid (n=10) and non‐rheumatoid (n=10) synovia. The expression of DARC protein and mRNA was examined by immunohistochemistry and northern blotting. The involvement of DARC in chemokine binding was studied by incubating sections with blocking antibodies to DARC (Fy3and 6), to find out if these reduced 125I‐IL‐8 binding. Binding of radiolabelled chemokines IL‐8, RANTES, MCP‐1, but not MIP‐1α, was found on venular endothelial cells in inflamed synovia from both rheumatoid and non‐rheumatoid patients. Excess homologous unlabelled chemokine displaced binding and excess unlabelled RANTES could displace radiolabelled IL‐8 binding. DARC protein expression was demonstrated on venular endothelial cells in all samples and DARC mRNA could be detected in extracts from synovia. There was downregulation of DARC protein and mRNA in rheumatoid samples. Binding of IL‐8 to both rheumatoid and non‐rheumatoid synovia was significantly reduced in the presence of anti‐DARC Fy3 and Fy6 monoclonal antibodies. These findings show the expression of a multispecific chemokine binding site on the inflamed synovial endothelium, with evidence for involvement of DARC. This suggests a potential role for DARC in the inflammatory processes involved in synovitis. Copyright © 2002 John Wiley & Sons, Ltd.
Nerve growth factor expression and innervation of the painful intervertebral disc
Authors: Freemont A. J. , Watkins A. , Le Maitre C. , Baird P. , Jeziorska M. , Knight M. T. N. , Ross E. R. S. , O'Brien J. P. , Hoyland J. A. 
Published: October 2002

AbstractFollowing a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high‐ and low‐affinity receptors trk‐A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non‐pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high‐affinity NGF receptor trk‐A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non‐pain level or control IVD. Some non‐pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies. Copyright © 2002 John Wiley & Sons, Ltd.
Robotic telepathology: efficacy and usability in pulmonary pathology
Authors: Leong F. J. W.‐M. , Nicholson A. G. , McGee J. O'D. 
Published: October 2002

AbstractRobotic telepathology is well established in the USA as a method of case referral, but is less frequently used in the UK. Using cases covering a broad spectrum of pulmonary pathology, this study assessed its application in primary diagnosis and its functionality in terms of accuracy of diagnosis and time per case, for both small biopsies and open lung biopsies/resections. Forty cases (20 bronchoscopic and 20 surgical lung biopsy/resection specimens) were reviewed in blinded fashion by a single pathologist using robotic telepathology. Connection between the John Radcliffe and Royal Brompton Hospitals was via 10 Mb/s LAN to the Internet (supported by the Joint Academic Network). The cases were then randomized and reviewed a second time with conventional light microscopy. Diagnosis, initial time to reach diagnosis, and overall time per case were recorded. In two bronchoscopic biopsy cases, there were clinically significant differences between telepathology and conventional light microscopy, one probably attributable to user inexperience and the other to either speed of image capture or digital image quality. In the surgical lung biopsies and resections, there was one variation of opinion: with telepathology a case was considered to be probably mesothelioma, whereas this was thought less likely on light microscopy. In both instances, immunohistochemistry was requested prior to clinical management. Telepathology was 14 times slower than conventional light microscopy when examining bronchoscopic biopsies. The average time spent per slide was 7 min 21 s, compared with 32 s per slide with conventional light microscopy. When assessing open lung biopsies and resections, telepathology was five times slower, at 6 min 13 s compared with 1 min 10 s with conventional light microscopy. This study showed that robotic telepathology is accurate for primary diagnosis in pulmonary histopathology, but modifications in both laboratory protocols and telepathology hardware are needed to decrease the time difference between telepathology and conventional light microscopy, for telepathology to be usable within the framework of a busy referral practice. Copyright © 2002 John Wiley & Sons, Ltd.
Induction of PDX‐1‐positive cells in the main duct during regeneration after acute necrotizing pancreatitis in rats
Authors: Taguchi Masashi , Yamaguchi Taizo , Otsuki Makoto 
Published: October 2002

AbstractPancreatic regeneration involves two pathways; proliferation and differentiation of pancreatic progenitor cells, which probably exist in pancreatic ductal epithelium, and replication of pre‐existing differentiated acinar, islet, and ductal epithelial cells. During pancreatic development, differentiated cells arise from the ductal progenitor cells expressing the pancreatic/duodenal homeobox‐1 (PDX‐1) homeodomain transcription factor. The aims of this study were to characterize cell proliferation and differentiation during regeneration after acute necrotizing pancreatitis and to evaluate the role of PDX‐1‐positive stem cells. Necrotizing pancreatitis was induced in rats by retrograde intraductal infusion of sodium taurocholate. Cell types were classified into five categories: main, large, and small ductal epithelial cells, tubular complexes and acinar cells. Each category was scored using a 5‐bromo‐2′‐deoxyuridine (BrdU) labelling index (LI) at various time points after induction of pancreatitis. Tissue sections were also immunostained for PDX‐1 to determine the source of pancreatic stem cells. Acinar necrosis was observed at 24 h after induction of pancreatitis and most lobules were filled with tubular complexes on day 5. Subsequently, newly formed acinar cells were observed on day 7, but the lobular architecture returned to normal appearance on day 28. Proliferation started in the main and large ducts at 24 h; marked mitotic activity was evident in small ductal epithelial cells and tubular complexes on day 3, and in acinar cells on day 7. At 24 h after induction of pancreatitis, epithelial cells of the main duct with PDX‐1‐positive nuclei were greatly increased, simultaneously with the peak LI of BrdU. These results suggest that regeneration after necrotizing pancreatitis involves proliferation and differentiation of pancreatic progenitor cells, and that ductal epithelial cells with PDX‐1‐positive nuclei may contribute to the differentiation of pancreatic stem cells in the main duct. Copyright © 2002 John Wiley & Sons, Ltd.
Activated status of tumour‐infiltrating lymphocytes and apoptosis in testicular seminoma
Authors: Yakirevich Evgeny , Lefel Oleg , Sova Yanina , Stein Avi , Cohen Oded , Ben Izhak Ofer , Resnick Murray B. 
Published: October 2002

AbstractTesticular seminoma is characterized by a prominent lymphoid infiltrate and an excellent prognosis. Cytotoxic T‐lymphocytes (CTLs) infiltrating seminoma tumour nests constitute a major subset of the lymphoid infiltrate. The objective of this study was to determine whether CTLs express markers of cytotoxic potential and activity and whether the number of activated CTLs correlates with the extent of apoptosis in testicular seminomas, as opposed to non‐seminomatous testicular germ cell tumours (NSTGCTs). Twenty cases of pure seminoma as well as 20 cases of NSTGCTs including 16 mixed germ cell tumours (MGCTs) were studied. Immunohistochemistry for the cytotoxic markers TIA‐1 (cytotoxic potential) and granzyme B (cytotoxic activity) and the T‐cell markers CD3 and CD8 was performed on formalin‐fixed, paraffin‐embedded sections. The apoptotic index (AI) was determined by the TUNEL method. The number of CD3+, CD8+, TIA‐1+, and granzyme B+ cells in tumour cell nests was markedly increased in testicular seminomas, compared with NSTGCTs (p<0.01). Activated granzyme B+ cells numbered 25.6±5.2 per high power field in seminomas and 8.9±3.2, 8.1±3.9, and 0.4±0.2 for embryonal carcinomas, yolk sac tumours, and immature teratomas, respectively. Double immunohistochemical staining for granzyme B and CD8 revealed that 82.6±8.5% of granzyme B‐expressing cells were CD8+. The tumour cell AI was significantly increased in embryonal carcinoma, compared with the seminoma, yolk sac tumour, and immature teratoma subgroups (6.7±1.3, 2.3±0.3, 3.0±1.1, and 2.3±1.1, respectively, p<0.001). TUNEL/CD3 double immunostaining revealed that a significant proportion of the apoptotic seminomatous tumour cells were in direct contact with one or more CD3+ lymphocytes (47.2±6.2%). The number of activated granzyme B+ CTLs showed a strong linear correlation with the AI in the seminoma group (r=0.71, p<0.0001) but not in other subgroups. TUNEL/granzyme B double immunolabelling revealed that a proportion of activated granzyme B+ lymphocytes (20%) were often seen in close contact with apoptotic tumour cells. The presence of increased numbers of activated cytotoxic lymphocytes in testicular seminomas suggests that apoptotic tumour cell death in this neoplasm may be triggered by cytotoxic granule effectors. This phenomenon may be one of the key host immune mechanisms leading to the excellent prognosis in this tumour. Copyright © 2001 John Wiley & Sons, Ltd.
Pallister‐Killian syndrome: difficulties of prenatal diagnosis
Authors: Doray Bérénice , Girard‐Lemaire Françoise , Gasser Bernard , Baldauf Jean‐Jacques , de Geeter Bernard , Spizzo Michèle , Zeidan Charles , Flori Elisabeth 
Published: October 2002

AbstractThe first prenatal diagnosis of Pallister‐Killian syndrome (PKS) was reported by Gilgenkrantz et al. in1985. Since this report, about 60 prenatal cases have been reported but both sonographic and cytogenetic diagnoses remain difficult. Although ultrasound anomalies such as congenital diaphragmatic hernia, polyhydramnios and rhizomelic micromelia in association with fetal overgrowth are very suggestive of the syndrome, they are inconstant and they may even be absent. The mosaic distribution of the supernumerary isochromosome 12p greatly increases these difficulties. No prenatal cytogenetic technique is sensitive enough to ensure prenatal diagnosis and false‐negative results have been described on fetal blood, chorionic villi and amniocentesis. We report here two prenatal cases of PKS which illustrate the great variability of the fetal phenotype. In reviewing the 63 reported cases, we attempt to determine ultrasound indicators of the syndrome and to define a cytogenetic strategy. In cases where ultrasound indicators are present, our proposal is first to perform chorionic villus or placental sampling and then amniocentesis when the first cytogenetic result is normal. Fetal blood sampling is the least indicated method because of the low frequency of the isochromosome in lymphocytes. In this cytogenetic strategy, fluorescent in situ hybridization (FISH) and especially interphase FISH on non‐cultured cells increases the probability or identifying the isochromosome. A misdiagnosis remains possible when ultrasound is not contributory; the identification of new discriminating ultrasound indicators would be very helpful in this context. Copyright © 2002 John Wiley & Sons, Ltd.
Prenatal prediction of childhood‐onset spinal muscular atrophy (SMA) in Turkish families
Authors: Savas S. , Eraslan S. , Kantarci S. , Karaman B. , Acarsoz D. , Tükel T. , Cogulu O. , Ozkinay F. , Basaran S. , Aydınlı K. , Yuksel‐Apak M. , Kirdar B. 
Published: October 2002

AbstractChildhood‐onset spinal muscular atrophy (SMA) is one of the most common neurodegenerative genetic disorders. SMN1 is the SMA‐determining gene deleted or mutated in the majority of SMA cases. There is no effective cure or treatment for this disease yet. Thus, the availability of prenatal testing is important. Here we report prenatal prediction for 68 fetuses in 63 Turkish SMA families using direct deletion analysis of the SMN1 gene by restriction digestion. The genotype of the index case was known in 40 families (Group A) but unknown in the remaining 23 families (Group B). A total of ten fetuses were predicted to be affected. Eight of these fetuses were derived from Group A and two of these fetuses were from Group B families. Two fetuses from the same family in Group A had the SMNhyb1 gene in addition to homozygous deletion of the NAIP gene. One fetus from Group A was homozygously deleted for only exon 8 of the SMN2 gene, and further analysis showed the presence of both the SMN1 and SMNhyb1 genes but not the SMN2 gene. In addition, one carrier with a homozygous deletion of only exon 8 of the SMN1 gene was detected to have a SMNhyb2 gene, which was also found in the fetus. To our knowledge, these are the first prenatal cases with SMNhyb genes. Follow‐up studies demonstrated that the prenatal predictions and the phenotype of the fetuses correlated well in 33 type I pregnancies demonstrating that a careful molecular analysis of the SMN genes is very useful in predicting the phenotype of the fetus in families at risk for SMA. Copyright © 2002 John Wiley & Sons, Ltd.
Novel mutation and prenatal sonographic findings of glutaric aciduria (type I) in two Taiwanese families
Authors: Lin S. K. , Hsu S. G. , Ho E. S. C. , Tsai C. R. , Hseih Y. T. , Lo F. C. , Lai H. Y. , Chen M. H. 
Published: October 2002

AbstractGlutaric aciduria type I (GA I) is an autosomal recessively inherited inborn error with a defect of the enzyme glutaryl‐CoA dehydrogenase (GCDH), which has never been diagnosed prenatally in Taiwanese patients. We present the prenatal sonographic findings and mutational analysis data of three children in two Taiwanese families. One patient from each family was diagnosed postnatally due to macrocephaly and neurological deterioration at 4 months and 10 months, respectively. The third child, sister of the first patient, was diagnosed prenatally at 11 weeks' gestation through chorionic villus sampling (CVS). Molecular analysis revealed that the fetus and child in Family 1 were homozygous for a common mutation, IVS10 ‐2A>C, which has not been reported in the Caucasian population. The patient in Family 2 was a compound heterozygote for IVS10 ‐2A>C and a novel mutation 749T>C (L238P). After genetic counseling, the couple decided to continue the second pregnancy. However, dilatation of quadrigeminal cistern (QC) and suspicious macrocephaly were noted at 30 weeks. Progressive dilatation of the QC associated with macrocephaly, fronto‐temporal atrophy and wide space of perisylvian fissure were found in the follow‐up scans. The affected girl was delivered at 37 weeks' gestation by cesarean section. Postnatal magnetic resonance imaging (MRI) studies confirmed the prenatal sonographic findings. With prenatal sonographic findings and mutational analysis presented in the present cases, the feasibility of prenatal diagnosis of GA I in high‐risk pregnancy can not be overlooked. Copyright © 2002 John Wiley & Sons, Ltd.
Ability to handle, and patient preference for, insulin delivery devices in visually impaired patients with type 2 diabetes
Authors: Fox Charles , McKinnon Carol , Wall Anthony , Lawton Simon A 
Published: October 2002

AbstractIn this comparative study, 86 patients with type 2 diabetes and visual impairment were evaluated on their preference for, and ability to operate, three different insulin delivery systems— InnoLet® (NovoNordisk), Humulin® NPH Pen (Eli Lilly) and vial and syringe (Becton Dickinson). Patients found the clocklike dose scale on InnoLet® significantly easier to read than that of the other systems (92% were able to read four doses, versus 45% and 61% with Humulin® Pen and syringe respectively, both p < 0.001), and showed greater ability to set and dispense a 20 unit dose without instruction. After reading the packaging information leaflet and brief verbal instruction, 99% of patients were able to correctly set and dispense three consecutive insulin doses with InnoLet® compared with 85% with Humulin® Pen and 64% with syringe (p = 0.001 and p > 0.001, respectively). Ability to set and deliver insulin was not however clearly related to visual acuity. On questionnaire, 87% of patients expressed an overall preference for InnoLet®, and 13% for Humulin® Pen (p < 0.001); no patients preferred the syringe. In conclusion, insulin delivery systems designed to simplify accurate, reliable insulin delivery for people with visual impairment can improve the ability of such patients to repeatedly set and deliver the correct insulin dose. Copyright © 2002 John Wiley & Sons, Ltd.
Variations in prescribing atypical antipsychotic drugs in primary care: cross‐sectional study
Authors: Ashcroft Darren M. , Frischer Martin , Lockett Joanne , Chapman Stephen R. 
Published: October 2002

AbstractBackgroundSide‐effects from conventional antipsychotic drugs, in particular extrapyramidal side‐effects, limit their use for some patients, lead to non‐compliance and may adversely affect the quality of life of others. Newer, more expensive, ‘atypical’ antipsychotics have been developed in attempts to address these problems, although debate about the most appropriate role for these medications remains.ObjectivesTo examine variations in prescribing of the ‘atypical’ antipsychotics in primary care, over a 5‐year period.SettingAll 13 health authorities within the West Midlands region.MethodCross‐sectional analysis of prescribing analysis and cost (PACT) data for atypical antipsychotic drugs (amisulpride, clozapine, olanzapine, risperidone, sertindole, and zotepine) was performed using one‐way analysis of variance. To test whether the differences reflected variation in local population need, the prescribing data were adjusted using Mental Illness Needs Index scores. Regression analysis was used to examine the relationship between the overall levels of prescribing and local population need.ResultsThe total volume of prescribing of atypical antipsychotic drugs in primary care increased nearly six‐fold from 1996/97 to 2000/01 in the West Midlands region. Olanzapine was the most commonly prescribed drug during 1999/2000, accounting for 45% of defined daily doses, while risperidone accounted for 38% of the total. In 1996/97, a four‐fold variation in rates of atypical antipsychotic prescribing between health authorities was found, compared with a three‐fold variation in 2000/01, after adjusting for measures of local population need.ConclusionsThere has been a substantial increase in the prescription of atypical antipsychotics in primary care over the last 5 years, but the rate of increase has varied widely between health authorities. Further studies are needed to determine the factors that have led to these differences in uptake, and the likely impact of national guidance on future prescribing patterns. Copyright © 2002 John Wiley & Sons, Ltd.