bluuebunny/crossref_metadata_2025 huggingface dataset:
Graft and patient survival after adult live donor liver transplantation compared to a matched cohort who received a deceased donor transplantation
Authors: Thuluvath Paul J. , Yoo Hwan Y.
Published: September 2004

Live donor liver transplantation (LDLT) has become increasingly common in the United States and around the world. In this study, we compared the outcome of 764 patients who received LDLT in the United States and compared the results with a matched population that received deceased donor transplantation (DDLT) using the United Network for Organ Sharing (UNOS) database. For each LDLT recipient (n = 764), two DDLT recipients (n = 1,470), matched for age, gender, race, diagnosis, and year of transplantation, were selected from the UNOS data after excluding multiple organ transplantation or retransplantation, children, and those with incomplete data. Despite our matching, recipients of LDLT had more stable liver disease, as shown by fewer patients with UNOS status 1 or 2A, in an intensive care unit, or on life support. Creatinine and cold ischemia time were also lower in the LDLT group. Primary graft nonfunction, hyperacute rejection rates, and patient survival by Kaplan-Meier analysis were similar in both groups (2-year survival was 79.0% in LDLT vs. 80.7% in case-controls; P = .5), but graft survival was significantly lower in LDLT (2-year graft survival was 64.4% vs. 73.3%; P < .001). Cox regression (after adjusting for confounding variables) analysis showed that LDLT recipients were 60% more likely to lose their graft compared to DDLT recipients (hazard ratio [HR] 1.6; confidence interval 1.1-2.5). Among hepatitis C virus (HCV) patients, LDLT recipients showed lower graft survival when compared to those who received DDLT. In conclusion, short-term patient survival in LDLT is similar to that in the DDLT group, but graft survival is significantly lower in LDLT recipients. LDLT is a reasonable option for patients who are unlikely to receive DDLT in a timely fashion. (Liver Transpl 2004;10:1263-1268.)
Liver transplantation from non-heart-beating donors: Current status and future prospects
Authors: Reddy Srikanth , Zilvetti Miguel , Brockmann Jens , McLaren Andrew , Friend Peter
Published: September 2004

Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non-heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). To increase organ availability, there is now a resurgence of interest in NHBD liver transplantation. This review explores the basis for this and considers some of the published results. (Liver Transpl 2004;10:1223-1232.)
Split-liver transplantation: Coming of age
Authors: Cronin David C. , Millis Michael J.
Published: September 2004

Objective

To identify predictors of graft and recipient survival from a single-institution series of in situ split-liver transplantations and compare outcomes to living donor and whole organs for adults and children.

Summary Background Data

Split-liver transplantation is a surgical technique that creates 2 allografts from a single cadaver donor. We have applied split-liver transplantation to all indications and categories of medical urgency for initial as well as retransplantation to expand the current donor pool and decrease reliance upon living donation.

Methods

A retrospective analysis was conducted of 100 consecutive in situ split-liver transplantations yielding a left lateral segment and right trisegment graft that were performed at the University of California Los Angeles between 9/91 and 02/03. These 100 transplantations generated 190 allografts for transplantation into 105 children and 60 adults, with the sharing of 25 allografts among transplant centers across the United States. Outcomes and incidence of complications were compared with living donor and whole organ recipients receiving liver transplantation during the same time period with independent predictors of split-liver graft and recipient survival identified by multivariate analysis.

Results

The incidence of biliary and vascular complications observed in recipients of left lateral segment grafts created by split-liver transplantation was not statistically different from recipients of left lateral segment grafts created from living donation or children receiving whole-organ grafts from pediatric donors. Kaplan-Meier survival estimations of left lateral segment graft and recipient survival also demonstrated no statistical difference among split-liver, living donor, and whole-organ recipients. Right trisegment grafts from split-liver transplantation demonstrated a 10% incidence of biliary and 7% incidence of vascular complications. Long-term graft function was excellent with patient and graft survival equal to 1086 recipients of cadaver whole-organ grafts from donors ages 10-40 years who underwent transplant operations during the same time period. Predictors of split-liver transplantation graft and recipient survival included United Network for Organ Sharing status at transplantation, indication, occurrence of a complication, donor creatinine, and donor length of hospitalization.

Conclusions

Split-liver transplantation is an effective mechanism for immediate expansion of the cadaver donor pool that can reduce dependence upon living donation in adults and children. (Ann Surg 2003;238:496-507).
Survival among pediatric liver transplant recipients: Impact of segmental grafts
Authors: Abt Peter L. , Rapaport-Kelz Rachel , Desai Niraj M. , Frank Adam , Sonnad Seema , Rand Elizabeth , Markmann James F. , Shaked Abraham , Olthoff Kim M.
Published: September 2004

Segmental liver transplantation with living donor (LD), reduced cadaveric (Reduced), and split cadaveric (Split) allografts has expanded the availability of size-appropriate organs for pediatric recipients. The relevance of recipient age to the selection of graft type has not been fully explored, but could offer the potential to maximize recipient outcome and donor utilization. We conducted a retrospective cohort study among children 12 years of age or less utilizing the United Network of Organ Sharing (UNOS) database. Cox proportional-hazards analysis was used to explore the association of recipient age and graft type to graft and patient survival. Among children <1 year of age and those 1 to 2 years of age, 3-year LD graft survival was superior to whole cadaveric (CAD) organs, Split grafts, and Reduced grafts (for children <1 year of age: 79.4 vs. 61.5, 66.0, and 61.1%, respectively, P = .0003; and for children 1-2 years of age: 79.2 vs 66.9, 57.1, and 63.9%, respectively, P = .02). However, in children 3 to 12 years of age, after controlling for multiple donor and recipient factors, LD grafts failed to offer a survival advantage (hazard ratio = .61; 95% confidence interval = .37-1.02) compared to CAD organs. In an adjusted analysis examining patient survival, there appeared to be minimal association between recipient age and graft type. Much of the difference in graft survival could be attributed to events in the perioperative period. In conclusion, LD liver transplantation provides improved graft survival in children 2 years of age or less. (Liver Transpl 2004;10:1287-1293.)
Prospective highlights of functional skin proteomics
Authors: Huang Chun‐Ming , Elmets Craig A. , van Kampen Kent R. , DeSilva Tivanka S. , Barnes Stephen , Kim Helen , Tang De‐chu C.
Published: September 2004

Although a wide variety of protein profiles have been extensively constructed via proteomic analysis, the comprehensive proteomic profiling of the skin, which is considered to be the largest organ of the human body, is still far from complete. Our efforts to establish the functional skin proteome, a protein database describing the protein networks that underlie biological processes, has set in motion the identification and characterization of proteins expressed in the epidermis and dermis of the BALB/c mice. In this review, we will highlight various cutaneous proteins we have characterized and discuss their biological functions associated with skin distress, immunity, and cancer. This type of research into functional skin proteomics will provide a critical step toward understanding disease and developing successful therapeutic strategies. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:647–660, 2005
Gas chromatographic–mass spectrometric urinary metabolome analysis to study mutations of inborn errors of metabolism
Authors: Kuhara Tomiko
Published: September 2004

Urine contains numerous metabolites, and can provide evidence for the screening or molecular diagnosis of many inborn errors of metabolism (IEMs). The metabolomic analysis of urine by the combined use of urease pretreatment, stable‐isotope dilution, and capillary gas chromatography/mass spectrometry offers reliable and quantitative data for the simultaneous screening or molecular diagnosis of more than 130 IEMs. Those IEMs include hyperammonemias and lactic acidemias, and the IEMs of amino acids, pyrimidines, purines, carbohydrates, and others including primary hyperoxalurias, hereditary fructose intolerance, propionic acidemia, and methylmalonic acidemia. Metabolite analysis is comprehensive for mutant genotypes. Enzyme dysfunction—either by the abnormal structure of an enzyme/apoenzyme, the reduced quantity of a normal enzyme/apoenzyme, or the lack of a coenzyme—is involved. Enzyme dysfunction—either by an abnormal regulatory gene, abnormal sub‐cellular localization, or by abnormal post‐transcriptional or post‐translational modification—is included. Mutations—either known or unknown, common or uncommon—are involved. If the urine metabolome approach can accurately observe quantitative abnormality for hundreds of metabolites, reflecting 100 different disease‐causing reactions in a body, then it is possible to simultaneously detect different mutant genotypes of far more than tens of thousands. © 2004 Wiley Periodicals, Inc., Mass Spec Rev 24:814–827, 2005
The chemokines CCL11, CCL20, CCL21, and CCL24 are preferentially expressed in polarized human secondary lymphoid follicles
Authors: Buri Caroline , Gutersohn Andreas , Hauser Chantal , Kappeler Andreas , Mueller Christoph
Published: September 2004

Chemokines regulate cellular trafficking to and from lymphoid follicles. Here, the distribution pattern of four CCL chemokines is defined by in situ hybridization in human lymphoid follicles from tonsils and lymph nodes (LNs) of newborns and adults. Cells expressing CCL11 (eotaxin) and CCL20 (Exodus) were preferentially located within follicles, while cells expressing CCL21 (secondary lymphoid‐tissue chemokine) and CCL24 (eotaxin‐2) mRNA were almost exclusively found in the perifollicular areas. Hence, the two CCR3‐binding chemokines, CCL11 and CCL24, showed a mutually exclusive expression pattern in the intra‐ and extra‐follicular areas, respectively. Chemokine gene expression paralleled follicular maturation: in tonsils, where approximately 80% of follicles are polarized, CCL11 and CCL20 mRNA‐positive cells were detected more frequently than in lymph nodes from adults, where about half of follicles are non‐polarized. No intrafollicular chemokine expression was detectable in the primary follicles from newborns. Extrafollicular cells expressing CCL21 and CCL24 were again more frequent in tonsils than in LNs from adults. The observed preferential presence of cells expressing CC chemokines in polarized human lymphoid follicles indicates that chemokines are not only instrumental in the induction of follicle formation, but may also be involved in their further differentiation. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Chromosomal instability and APC gene mutations in human sporadic colorectal adenomas
Authors: Giaretti Walter , Venesio Tiziana , Prevosto Claudia , Lombardo Federica , Ceccarelli Jenny , Molinu Silvia , Risio Mauro
Published: September 2004

The mechanisms by which adenomatous polyposis coli (APC) gene mutations contribute to colorectal tumourigenesis and progression are still not fully understood. Using in vitro mouse embryonic stem cells, APC mutations have been proposed to dysregulate the interactions between kinetochores and microtubules during mitosis, leading to chromosomal instability (CIN) and aneuploidy. A link between APC mutations and aneuploidy in vivo among human sporadic colorectal adenomas has not been reported previously and was therefore investigated in the present series of 61 adenomas. Multi‐parameter flow cytometry, based on scattering and fluorescence from the DNA‐specific 4,6‐diamidino‐2‐phenylindole‐2‐hydrochloride (DAPI) dye, which separates epithelial from stromal lymphocyte nuclei, was used to evaluate the DNA index (DI) and to sort epithelial nuclei. Additionally, DNA extracted from these sorted nuclei was used to analyse APC mutations by DNA sequencing. Aneuploidy was present in 20 of 61 adenomas (33%), with 15 of these 20 cases (75%) having a near‐diploid DI (DI different from 1 and less than 1.3). APC mutations were detected in 19 adenomas (31%): 12 were within or downstream of the mutation cluster region (MCR), roughly defined by codons 1200–1500, and seven were upstream of the MCR. Overall, the prevalence of aneuploidy in APC wild‐type and mutated adenomas was 26% and 47%, respectively, and no statistically significant association was found between APC status and DI (p = 0.142). However, when APC mutations were subdivided into two groups, ie occurring within/downstream of the MCR and upstream of the MCR, the association of APC mutations within and downstream of the MCR with aneuploidy was statistically significant (p = 0.017). In conclusion, the present data suggest that the type of APC mutation may play a role in the origin of CIN in vivo in human sporadic colorectal adenomas and that APC mutations within and downstream of the MCR, and large‐scale chromosomal alterations, may co‐operate in the progression of a subgroup of adenomas. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
p53 overexpression and mutation in metaplastic carcinoma of the breast: genetic evidence for a monoclonal origin of both the carcinomatous and the heterogeneous sarcomatous components
Authors: Lien Huang‐Chun , Lin Chung‐Wu , Mao Tsui‐Lien , Kuo Sung‐Hsin , Hsiao Cheng‐Hsiang , Huang Chiun‐Sheng
Published: September 2004

Metaplastic carcinoma of the breast (MCB) is characterized by the biphasic presence of both a carcinomatous component (CC) and heterogeneous sarcomatous components (HSCs). Although an epithelial or myoepithelial origin of the HSCs has been suggested, molecular evidence for a common origin for the CC and HSCs is limited and the mechanism underlying the sarcomatous or metaplastic change is unknown. The present study investigated the frequency and nature of p53 expression and mutation in 11 biphasic and three monophasic MCBs by immunohistochemistry and either needle‐assisted or laser‐capture microdissection, followed by PCR and direct sequencing. In all 11 biphasic MBCs, staining for p53 was concordant in the CC and HSCs (8/11 positive and 3/11 negative), consistent with a monoclonal origin of both components. Significantly, whenever a component of carcinoma in situ was present (5/11), the p53 staining was always concordant with that in the CC and HSCs. Screening of the 14 cases for p53 mutation identified four mutants, each in a single case of biphasic MCB with concordant p53 overexpression. Both the CC and each of the HSCs revealed identical p53 mutation in all four cases; in addition, one of the four cases also had an in situ component and the same mutant was found simultaneously in the in situ, invasive, and sarcomatous components. The concordant pattern of p53 alteration (overexpression or mutation) implies that early p53 mutation, occurring prior to invasion, was maintained throughout tumour progression and metaplastic change. The findings therefore support a monoclonal histogenesis of the various components, but are neutral regarding the role of p53 alteration in the development of metaplastic change in MCBs. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Geminin predicts adverse clinical outcome in breast cancer by reflecting cell‐cycle progression
Authors: Gonzalez Michael A , Tachibana Kiku‐e K , Chin Suet‐Feung , Callagy Grace , Madine Mark A , Vowler Sarah L , Pinder Sarah E , Laskey Ronald A , Coleman Nicholas
Published: September 2004

Geminin inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance (MCM) proteins onto DNA. The present study has investigated whether the frequency of geminin expression predicts clinical outcome in breast cancer. Immunohistochemistry was used first to examine geminin expression in normal and malignant breast tissue (n = 67). Correlations with cell‐cycle parameters, pathological features, and clinical outcome were then determined using an invasive breast carcinoma tissue microarray (n = 165). Breast carcinomas were scanned for mutations (n = 61) and copy number imbalances (n = 241) of the geminin gene. Finally, the cell cycle distribution of geminin in breast cancer cells was investigated in vivo and in vitro. Despite a putative tumour suppressor function, it was found that increased geminin expression is a powerful independent indicator of adverse prognosis in invasive breast cancer. Both poor overall survival (p = 0.0002) and the development of distant metastases (p = 0.005) are predicted by high geminin expression, which performs better in this patient cohort than traditional factors currently used to determine prognosis and appropriate therapy. No mutations or deletions of the geminin gene and no evidence that a high frequency of protein expression is related to gene amplification were found. It is shown that geminin is expressed from S to M phase in breast carcinoma tissue and cell lines, disappearing at the metaphase–anaphase transition. While MCM proteins identify all non‐quiescent cells, geminin identifies the sub‐fraction that have entered S phase, but not exited mitosis, thereby indicating the rate of cell‐cycle progression. It is suggested that this explains its unexpected value as a prognostic marker in breast cancer. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Angiogenesis and VEGF expression in pre‐invasive lesions of the human breast
Authors: Viacava Paolo , Naccarato Antonio Giuseppe , Bocci Guido , Fanelli Giovanni , Aretini Paolo , Lonobile Antonino , Evangelista Giuseppe , Montruccoli Giancarlo , Bevilacqua Generoso
Published: September 2004

Angiogenesis (as microvascular density—MVD) and vascular endothelial growth factor (VEGF) expression were evaluated by immunohistochemistry in all types of human pre‐invasive breast lesion, un‐associated with invasive carcinoma, including florid ductal hyperplasia of usual type (FDHUT, 40 cases), atypical ductal hyperplasia (ADH, 10), well‐differentiated intraductal carcinoma (WDIC, 16), intermediately differentiated intraductal carcinoma (IDIC, 25), poorly differentiated intraductal carcinoma (PDIC, 20), atypical lobular hyperplasia (ALH, 13), and lobular carcinoma in situ (LCIS, 12). Both parameters were also studied in normal glandular structures obtained from normal breasts or from breasts containing pre‐invasive lesions. Increased vascularization was present in all lesion types (MVD mean values (expressed as vessel number/mm2): 115 ± 8 in normal lobules, 146 ± 26 in lesions; p < 0.05) and increased with lesion severity. In ductal lesions, MVDs were significantly higher in PDIC (190 ± 65) and IDIC (167 ± 61) than in FDHUT (123 ± 40) and ADH (122 ± 47); MVD was much higher in PDIC than in WDIC (p < 0.001). WDIC showed peculiar features, with a degree of vascularization closer to hyperplasia than to the other histological types of in situ ductal cancer; this observation is in line with the hypothesis that IDIC and PDIC may originate ‘de novo’, without a mandatory transition through WDIC. LCIS was more vascularized than ALH (168 ± 50 and 125 ± 40, respectively; p < 0.05), showing MVD values similar to those of PDIC and IDIC. The vascularization of normal lobules was constant, regardless of their association with lesions. VEGF expression in normal glandular structures was lower than in lesions, with the highest levels found in ductal lesions when compared with lobular lesions. No correlation was found between VEGF expression and the degree and/or type of vascularization. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Analysis of microsatellite alterations in gastric carcinoma using the crypt isolation technique
Authors: Jiao Yu‐Fei , Sugai Tamotsu , Habano Wataru , Suzuki Masamichi , Takagane Akinori , Nakamura Shin‐ichi
Published: September 2004

The crypt isolation technique was used to analyse loss of heterozygosity (LOH) and microsatellite instability (MSI) in gastric carcinomas (36 intestinal type, 17 solid type, and 23 diffuse type) using a polymerase chain reaction assay. Increased LOH frequencies and fractional allelic losses (FAL) were observed in samples prepared using the crypt isolation technique compared with those isolated by the conventional method. A significant increase in LOH was found at several chromosomal loci, and significant differences in FAL were found in patients with intestinal‐ and solid‐type tumours. There was no difference in the frequency of MSI using either technique. In samples prepared by the crypt isolation technique, significant allelic losses (≥50%) were observed at most loci tested in intestinal‐ and solid‐type tumours, but not in diffuse‐type tumours. Significant losses of some of these loci are novel findings for gastric cancer. FAL values were significantly higher in intestinal‐ and solid‐type tumours than in diffuse‐type tumours. MSI‐high was observed in intestinal‐ (17%) and solid‐type (12%) tumours. The results suggest that the crypt isolation technique is useful for accurate allelic loss analysis in gastric carcinoma and that LOH and MSI are more common in intestinal‐ and solid‐type tumours than in diffuse‐type tumors. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Caspase‐3 expression is reduced, in the absence of cleavage, in terminally differentiated normal oral epithelium but is increased in oral squamous cell carcinomas and correlates with tumour stage
Authors: Hague Angela , Eveson John W , MacFarlane Marion , Huntley Suzanne , Janghra Nari , Thavaraj Selvam
Published: September 2004

Oral carcinomas are known to have a greater apoptotic index than normal oral epithelium, evident as shrinking cells with condensed chromatin. In this study, these morphologically apoptotic cells stained positively for cleaved (active) caspase‐3. In normal oral epithelium, cleaved caspase‐3 positive‐cells were only rarely detected. The terminally differentiated surface epithelial layers did not express cleaved caspase‐3. The caspase‐3 pro‐enzyme showed a gradient of expression in normal oral epithelium, decreasing with differentiation. No expression was detectable in surface epithelial layers. Lack of expression of the major ‘executioner’ caspase‐3 may, at least in part, explain differences in morphology between terminally differentiated and apoptotic cells. In cancers of different tissue origins, caspase‐3 pro‐enzyme expression can be either increased or decreased compared with normal tissue counterparts. To determine how caspase‐3 expression alters during oral carcinogenesis, caspase‐3 expression was compared in 39 samples of normal oral epithelium and 54 oral squamous cell carcinomas. Squamous cell carcinomas had more intense caspase‐3 staining than normal epithelium (p < 0.001). Moreover, within the oral squamous cell carcinoma series, there was significantly more intense nuclear and cytoplasmic staining with increasing STNMP stage (p = 0.017 and 0.03, respectively). This was a reflection of significant associations with site (S), palpable lymph nodes (N), and differentiation (P). Both caspase‐3 staining intensity and the percentage of cells positive for caspase‐3 were inversely associated with differentiation. Studies of the mechanisms by which high levels of caspase‐3 expression are tolerated in oral carcinoma cells may identify targets that can be used to harness caspase‐3 overexpression for therapeutic benefit. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Expression of the hepatic endothelin system in human cirrhotic livers
Authors: Ikura Yoshihiro , Ohsawa Masahiko , Naruko Takahiko , Muraguchi Takashi , Hirayama Michihiko , Suekane Takehisa , Fukushima Hiroko , Sugama Yoshimi , Shirai Nobuyuki , Kayo Soichiro , Yoshimi Noriko , Ehara Shoichi , Tanzawa Kazuhiko , Ueda Makiko
Published: September 2004

It is considered that endothelin‐1 participates in the development of liver cirrhosis and it has been recognized that every component of the endothelin system is upregulated in cirrhotic livers. However, the expression pattern of this system, including interaction between its components, is not fully understood in human livers. In this study, the expression pattern of the endothelin system was examined. Immunohistochemical analysis for endothelin‐1, endothelin receptors and endothelin‐converting enzyme was performed in 16 cirrhotic and 17 normal human liver tissues. Peptides, proteins, and RNAs extracted from the livers were also investigated using quantitative assays for the components of the hepatic endothelin system. Hepatic endothelin‐1 levels were significantly higher in cirrhotic livers (0.084 ± 0.052 pg/mg wet liver) than in normal livers (0.041 ± 0.032 pg/mg; p < 0.01), and were closely related to the severity of liver fibrosis and portal hypertension. Immunoreactivity for endothelin‐1, endothelin receptors, and endothelin‐converting enzyme was detected mainly in fibrous areas and in the hepatic vasculature, and was enhanced in cirrhosis. Although there was a negative correlation between the expression of receptor mRNA and the hepatic endothelin‐1 level, the amounts of the mRNAs were greater in cirrhotic livers than in normal livers. However, expression of endothelin‐converting enzyme in cirrhotic livers was increased at the protein level but was relatively reduced at the mRNA level. These findings suggest that the hepatic endothelin system is activated in human cirrhotic livers in association with worsening of the disease, but that the regulation of the components of this system in this disorder is complex. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cytokeratin 5/6 in normal human breast: lack of evidence for a stem cell phenotype
Authors: Clarke Catherine L , Sandle Jennifer , Parry Suzanne C , Reis‐Filho Jorge S , O'Hare Michael J , Lakhani Sunil R
Published: September 2004

In recent studies, Böcker and colleagues described a population of cells in paraffin wax sections of normal human breast that express cytokeratins (CK) 5/6 without expression of CK8/18 or smooth muscle actin (SMA). They proposed that these represent stem cells that give rise to differentiated luminal and myoepithelial cells. The data have been used to generate a model for breast cancer progression and classification with associated implications for management of pre‐invasive disease. In this study, the expression of CK5/6, CK8/18, and SMA was investigated using multiple immunofluorescence on matched pairs of paraffin wax‐embedded and frozen breast specimens. The staining patterns reported previously in antigen‐retrieved paraffin wax‐embedded sections were confirmed but no CK5/6‐only cells were found in frozen sections of normal breast. There were cells with low levels of CK8/18 expression in frozen sections that may correspond to the CK8/18 ‘negative’ cells seen in paraffin wax sections. This study brings into question the previously described profile of breast ‘stem cells’ based on CK5/6 staining and hence the breast cancer progression model and classification based on this phenotype. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Atypical antipsychotic drugs and diabetes mellitus in a large outpatient population: a retrospective cohort study
Authors: Østbye Truls , Curtis Lesley H. , Masselink Leah E. , Hutchison Steve , Wright Alan , Dans Peter E. , Schulman Kevin A. , Krishnan Ranga R.
Published: September 2004

Purpose

Previous research has suggested an association between use of atypical antipsychotics and onset of diabetes mellitus. We sought to compare the incidence of new onset diabetes among patients receiving atypical antipsychotics, traditional antipsychotics or antidepressants.

Methods

Retrospective cohort study of outpatients with claims for atypical antipsychotics (n = 10 265) compared to controls with claims for traditional antipsychotics (n = 4607), antidepressants (n = 60 856) or antibiotics (n = 59 878) in the administrative claims database of a large pharmaceutical benefit manager between June 2000 and May 2002. Main outcome measures were adjusted and unadjusted incidence rates of diabetes (new cases per 1000 per year) in a 12‐month period, as measured using new prescriptions for antidiabetic drugs after a 6‐month lead‐in period.

Results

Annual unadjusted incidence rates of diabetes (new cases per 1000 per year) were 7.5 for atypical antipsychotics, 11.3 for traditional antipsychotics, 7.8 for antidepressants and 5.1 for antibiotics. In multivariable analyses, age, male sex and Chronic Disease Score were associated with greater odds of diabetes onset. There were no statistically significant differences in outcome between the atypical antipsychotic, traditional antipsychotic and antidepressant groups. Multivariable comparisons among specific agents showed increased odds of diabetes for clozapine, olanzapine, ziprasidone and thioridazine (relative to risperidone), but these comparisons did not reach statistical significance.

Conclusions

In a large prescription claims database, outpatients taking atypical antipsychotics did not have higher rates of diabetes onset, compared to subjects taking traditional antipsychotics or antidepressants. Copyright © 2004 John Wiley & Sons, Ltd.
Stereocontrolled anionic alternating copolymerization of ethylphenylketene with benzaldehyde by a bisoxazoline ligand
Authors: Nagai Daisuke , Sudo Atsushi , Endo Takeshi
Published: September 2004

Anionic copolymerization of ethylphenylketene with benzaldehyde with butyllithium or diethylzinc as the initiator proceeded in a perfect 1:1 alternating manner to produce the corresponding polyester, whose repeating unit had two adjacent chiral centers. The relative stereochemistry between these two chiral centers was successfully controlled by the addition of (S,S)‐(‐)‐2,2′‐isopropylidenebis(4‐tert‐butyl‐2‐oxazoline), producing the corresponding polyester that had excellent diastereoselectivity (erythro‐configuration : threo‐configuration = 4:96). The diastereomeric ratio was determined by high‐performance liquid chromatography analysis of the diol, which was obtained by reductive degradation of the polyester while maintaining the configuration of the repeating unit. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5384–5388, 2004
Computer modeling of radical copolymerization under unusual conditions
Authors: Khokhlov Alexei R. , Berezkin Anatoly V. , Khalatur Pavel G.
Published: September 2004

Although recent years have witnessed an impressive confluence of experiments and kinetic and statistical theories, presently there is no comprehensive understanding of the interrelation between chemical sequences in synthetic copolymers and the conditions of synthesis. For this problem, numerical simulations in conjunction with simple models provide a rather detailed answer. A survey is given of the simulation methods as applied to the design of nontrivial chemical sequences in copolymers obtained via heterogeneous radical polymerization. This review is focused on a recently developed approach, called conformation‐dependent sequence design, which takes into account a strong coupling between the conformation and primary structure of copolymers during their synthesis. We consider some applications of this technique, including the following problems and systems: (1) the design of sequences with long‐range correlations via solution radical copolymerization with simultaneous globule formation, (2) radical copolymerization near a chemically homogeneous surface leading to a copolymer with a gradient primary structure, and (3) template copolymerization near chemically patterned surfaces. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5339–5353, 2004
Glass transition and relaxation behavior of epoxy nanocomposites
Authors: Sun Yangyang , Zhang Zhuqing , Moon Kyoung‐Sik , Wong C. P.
Published: September 2004

With advances in nanoscience and nanotechnology, there is increasing interest in polymer nanocomposites, both in scientific research and for engineering applications. Because of the small size of nanoparticles, the polymer–filler interface property becomes a dominant factor in determining the macroscopic material properties of the nanocomposites. The glass‐transition behaviors of several epoxy nanocomposites have been investigated with modulated differential scanning calorimetry. The effect of the filler size, filler loading, and dispersion conditions of the nanofillers on the glass‐transition temperature (Tg) have been studied. In comparison with their counterparts with micrometer‐sized fillers, the nanocomposites show a Tg depression. For the determination of the reason for the Tg depression, the thermomechanical and dielectric relaxation processes of the silica nanocomposites have been investigated with dynamic mechanical analysis and dielectric analysis. The Tg depression is related to the enhanced polymer dynamics due to the extra free volume at the resin–filler interface. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3849–3858, 2004
Severe hemoptysis from dilated systemic aberrant arteries supplying normal lung segments
Authors: Abdulhamid Ibrahim , Forbes Thomas
Published: September 2004

Hemoptysis is an uncommon presentation in children. It can be caused by several systemic and pulmonary disorders. Bleeding from an anomalous arterial supply to normal lung segments with no underlying pulmonary or cardiovascular disorders was widely reported in adults but is extremely rare in the pediatric age group. Here we describe 4 previously normal children and one girl with chronic lung disease, secondary to bronchopumonary dysplasia, with acute and significant hemoptysis of variable severity. Extensive clinical and laboratory investigations did not identify any reasonable causes for their symptoms. Cardiac catheterization showed dilated anomalous systemic arteries that supplied a pulmonary arteriovenous malformation in one case and normal basal lung segments in the other 4 cases. Embolization of the anomalous arterial collaterals led to occlusion of these arteries and the cessation of further hemoptysis. © 2004 Wiley‐Liss, Inc.
Ontogenesis of myosin light chain kinase mRNA and protein content in guinea pig tracheal smooth muscle
Authors: Chitano Pasquale , Voynow Judith A. , Pozzato Valeria , Cantillana Viviana , Burch Lauranell H. , Wang Lu , Murphy Thomas M.
Published: September 2004

We previously reported in guinea pig tracheal smooth muscle that maximal shortening velocity decreases from 3 weeks of age to adulthood. It is not known whether myosin light chain kinase (MLCK), a key enzyme determining the velocity of smooth muscle contraction, undergoes maturational changes. In the present work, we investigated MLCK protein content and mRNA expression in 1‐week‐old, 3‐week‐old, and adult guinea pigs. We extracted either proteins or RNA from isolated tracheal smooth muscle. The content of MLCK was assessed by Western immunoblots. MLCK mRNA was evaluated by Northern analysis and by quantitative real time reverse transcriptase‐polymerase chain reaction (RT‐PCR). The content of MLCK increased 3‐fold at 3 weeks of age and then decreased in adults, being 0.116 ± 0.042, 0.330 ± 0.125 (P < 0.05), and 0.153 ± 0.054 μg/mg of total protein, respectively, in 1‐week, 3‐week, and adult animals. Quantitative RT‐PCR revealed that MLCK mRNA increased with age to 135 ± 35% and 177 ± 23% (P < 0.01) in 3‐week and adult animals, respectively, compared to 1‐week animals. The transient increase of MLCK content in juvenile guinea pig tracheal smooth muscle may contribute to the increased shortening velocity at this age. We suggest that this increased content of MLCK is one of the mechanisms leading to maturation of airway smooth muscle contractility, which in turn contributes to the airway hyperresponsiveness reported in children and young animals. © 2004 Wiley‐Liss, Inc.
Expansile pneumonia in children caused by Mycobacterium tuberculosis: Clinical, radiological, and bronchoscopic appearances
Authors: Goussard P. , Gie R.P. , Kling S. , Beyers N.
Published: September 2004

A cohort of 24 children with expansile pneumonia caused by Mycobacterium tuberculosis is described in mostly HIV‐noninfected children (n = 22). The children presented with nonresolving pneumonia and a swinging fever (83%). On chest radiography, they had dense opacification with bulging fissures mainly in the upper lobes (75%). On computed tomography, the lobes are consolidated, with areas of liquefacation. Other features visible are enlarged mediastinal lymph adenopathy with ring enhancement (100%), cavities (63%), and tracheal compression (71%). On bronchoscopy, bronchi were obstructed by more than 75% in 20 (83%) of cases. Lymph gland enucleation was required in 42% of cases. Phrenic nerve palsy was present in 3 children, of whom 2 underwent diaphragmatic plication. The children received standard antituberculous therapy, to which prednisone (2 mg/kg/day) was added for 1 month. The mortality was 4% after 6 months of therapy. © 2004 Wiley‐Liss, Inc.
Superstring orientifolds with torsion: O5 orientifolds of torus fibrations and their massless spectra
Authors: Schulz M.B.
Published: September 2004

Using a “Superstrings with Torsion” type description, we study a class of IIB orientifolds in which spacefilling O5 planes and D5 branes wrap theT2fiber in a warped modification of the product of 4D Minkowski space and aT2fibration. For the case that the base isT4, we provide examples that preserve 4D 𝒩 = 1, 2, and 3 supersymmetry, both with internal RR flux, and with a combination of internal RR and NS flux. In these examples, the internal geometries admit integrable complex structure; however, the almost complex structure selected by the supersymmetry conditions is nonintegrable in the case that there is NS flux. We indicate explicitly the massless spectrum of gauge fields and moduli in each example. In a previous investigation, this class of orientifolds was studied using T‐duality. Here, we extend the previous analysis, first by providing an intrinsic description that does not rely on duality, and then by elaborating on details of the T‐duality map, which we use to check our results.
Linking transnational migrants and transnationalism
Authors: Smith Darren P. , Bailey Adrian J.
Published: September 2004

This paper introduces a special issue on transnational migrants. It provides a brief discussion of the need to rethink ways of conceptualising the links between transnational migrants and transnationalism. In doing so, we point to some recent work by population and social and cultural geographers which provides a valuable exemplar for reconfiguring conceptualisations of migration, migrancy and difference. This introductory paper, and the other papers selected for this special issue, contribute to the debate of problematising the meaning of transnational migrants, and the processes by which transnationalism is increasingly forming multidimensional spaces, reproduced by complex networks, circuits and flows of people, commodities and socio‐cultural exchanges. Copyright © 2004 John Wiley & Sons, Ltd.
Transnational migration theory in population geography: gendered practices in networks linking Canada and India
Authors: Walton‐Roberts Margaret
Published: September 2004

Geographers have recently suggested that transnational migration theory can contribute to the development of a critical population geography. What might such a critical population geography look like? In this paper I explore this in three ways. Firstly I offer some comments on why geographers have been slow to adopt a transnational focus on migration, and secondly I examine how gender has been underplayed in transnational literature. Thirdly I draw upon some examples from research on transnational immigrant networks between Canada and India. I focus on the specifics of Punjabi marriage migration networks to demonstrate how the practice of spousal selection has become globalised for certain diasporic communities. These examples offer a preliminary illustration of what a critical population geography, attuned to issues of gendered transnational processes, might contribute to current debates. Copyright © 2004 John Wiley & Sons, Ltd.
Transnational exchanges amongst skilled British migrants in Paris
Authors: Scott Sam
Published: September 2004

The transnational literature encompasses a bewildering array of immigrant groups and covers a diverse range of issues. Having said this, migration researchers have tended to ignore skilled immigrants and the everyday transnational communities and networks that they form. The paper addresses this research gap through an in‐depth, qualitative analysis of British expatriates in Ile‐de‐France – based upon 36 semi‐structured interviews and ten months of Paris‐based fieldwork. The paper draws attention to a number of different transnational lifestyles and advances a six‐pronged typology to encapsulate this diversity. It then highlights three prominent themes that appear to underpin transnational social and cultural exchange, relating to a ‘concern’ amongst expatriates with key events in the UK, to a desire to keep in ‘contact’ with friends and relatives still living there, and to the need for the occasional British cultural ‘comfort’. The paper then goes on to explore the world city lifestyle typology in greater depth. It shows how transnationalism is contingent upon a variety of social fissures, including gender, generation, life‐stage, socio‐professional status and length of stay overseas. These variables impact upon the scale, scope, nature and importance of transnational exchange, and in recognition of such diversity the paper calls for a nuanced view of skilled transmigrants. More particularly, it argues that the term expatriate may actually only apply to a particular economic‐based migrant community rather than skilled world city populations as a whole. Copyright © 2004 John Wiley & Sons, Ltd.
First‐principles calculations of the electronic structure and magnetic properties of the IrFe3N nitride
Authors: Paduani C.
Published: September 2004

The iron nitride IrFe3N is investigated by ab initio calculations of the electronic structure. The full potential– linearized augmented plane wave (FP‐LAPW) method is employed with the generalized gradient approximation for the treatment of the exchange‐correlation interactions. The dependence of the magnetic moments and hyperfine fields on volume are investigated. The substitution of Ir for Fe at corner sites has a small effect on the magnetic moment at the face‐centered Fe sites, whereas the hyperfine field changes appreciably. A ferromagnetic ordering at the equilibrium volume is predicted and the binding character for the iron– nitrogen bonds is mainly covalent. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dipolar interaction energy for a system of magnetic nanoparticles
Authors: Lamba Subhalakshmi
Published: September 2004

The long range dipolar interaction energy of a system of single domain magnetic particles with randomly oriented spins and easy axes is calculated by a direct space summation method based on the Lekner formalism. The method is useful for the numerical simulations of positionally disordered nanomagnetic arrays which are being widely used for these systems and is easily adapted for any geometry of the simulation cell. The summations are rapidly convergent, requiring only a few terms. This method is an alternative to the commonly used Ewald summation methods and can also be used for the quasi two – dimensional (2D + h) systems where the Ewald summation method does not give correct results. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Symmetry of electron states and optical transitions in GaN/AlN hexagonal quantum dots
Authors: Tronc P. , Smirnov V. P. , Zhuravlev K. S.
Published: September 2004

The exact symmetry of hexagonal quantum dots (QDs) made of materials with the wurtzite structure such as GaN/AlN QDs for example, is described by the C3v point group and does not depend on the existence of a wetting layer. We have determined the possible exact symmetries of electron states and vibration modes in the dots and derived the optical selection rules. The vibration modes involved in the Frölich interaction are totally symmetric with respect to the C3v group and can induce transitions only between states with the same symmetry. The not totally symmetric modes provide other channels for lowering the energy of excited carriers and excitons by connecting states with symmetries different one from another. The rapid decay of created polarons, due to the short lifetime of vibration modes, releases the carriers and excitons into ground levels. In the envelope function approximation (EFA), the symmetry of the dots is represented by the C6v point group. Interband transitions are allowed only between states whose envelope functions have the same symmetry. EFA artificially increases the number of dark exciton symmetries. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Photoinduced splitting of bipolarons in polymers
Authors: Shen Xiao , Tang Fei , George Thomas F. , Sun Xin
Published: September 2004

In conducting polymers, a polaron carries charge with spin and a bipolaron carries charge without spin. Hence, the polaron is a spin carrier but the bipolaron is not. Through a dynamical simulation, our study of photoinduced phenomena shows that, by absorbing a photon, a bipolaron is split into two polarons. This photoinduced splitting converts a charge carrier (bipolaron) into two spin carriers (polarons). (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin dependent momentum density and Fermi surface of ferromagnetic Ni obtained by positron annihilation experiments
Authors: Hamid A. S. , Uedono A.
Published: September 2004

The spin‐dependent momentum density and Fermi surface of ferromagnetic Ni have been obtained through positron annihilation experiments. The measurements were carried out through 2D angular correlation of annihilation radiation (ACAR) using longitudinally polarized positrons. The magnetic field direction was reversed in order to study the effect of the spin‐dependent positron–electron momentum space density on the Fermi surface of Ni. The results showed that ferromagnetic Ni had different Fermi surfaces for the majority‐spin and minority‐spin states. The differences due to the spin‐states were studied in the momentum space and in the wave vector space. In general, the experimental results showed good agreement with previous theoretical calculations. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)