bluuebunny/crossref_metadata_2025 huggingface dataset:
Type I, but not type II, interferon is critical in liver injury induced after ischemia and reperfusion
Authors: Zhai Yuan , Qiao Bo , Gao Feng , Shen Xiuda , Vardanian Andrew , Busuttil Ronald W. , Kupiec-Weglinski Jerzy W.
Published: October 2007

We have documented the key role of toll-like receptor 4 (TLR4) activation and its signaling pathway mediated by interferon (IFN) regulatory factor 3, in the induction of inflammation leading to the hepatocellular damage during liver ischemia/reperfusion injury (IRI). Because type I IFN is the major downstream activation product of that pathway, we studied its role in comparison with IFN-γ. Groups of type I (IFNAR), type II (IFNGR) IFN receptor–deficient mice, along with wild-type (WT) controls were subjected to partial liver warm ischemia (90 minutes) followed by reperfusion (1-6 hours). Interestingly, IFNAR knockout (KO) but not IFNGR KO mice were protected from IR-induced liver damage, as evidenced by decreased serum alanine aminotransferase and preservation of tissue architecture. IR-triggered intrahepatic pro-inflammatory response, assessed by tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and chemokine (C-X-C motif) ligand 10 (CXCL-10) expression, was diminished selectively in IFNAR KO mice. Consistent with these findings, our

in vitro

cell culture studies have shown that: (1) although hepatocytes alone failed to respond to lipopolysaccharide (LPS), when co-cultured with macrophages they did respond to LPS via macrophage-derived IFN-β; (2) macrophages required type I IFN to sustain CXCL10 production in response to LPS. This study documents that type I, but not type II, IFN pathway is required for IR-triggered liver inflammation/damage. Type I IFN mediates potential synergy between nonparenchyma and parenchyma cells in response to TLR4 activation. (Hepatology 2007.)
Long‐term precipitation and slide activity in south‐eastern Norway, autumn 2000
Authors: Jaedicke Christian , Kleven Arne
Published: October 2007

In autumn 2000 high amounts of precipitation caused a large number of landslides in south‐eastern Norway. The precipitation reached more than 400% of the normal monthly values in November. In addition to the precipitation, groundwater monitoring showed unusual high levels. High air temperatures in the mountains caused the precipitation to fall as rain instead of snow, causing additional runoff in the catchments. In this paper, 90 landslides are presented that were studied and evaluated by the Norwegian Geotechnical Institute (NGI) in the counties effected by the slide activity. The landslide database serves as start point for an analysis of the connection between slide activity and precipitation. The analysis shows a high variability of the observed precipitation just a few days before the slides. This variability decreases significantly around 50 days prior to the slides when the results stabilize at about 400% of normal precipitation in a 50‐day period. Comparison of these results to long time observations gives an estimate of return periods for the precipitation events. The 53 days accumulated precipitation has the highest return period of 132 years. This suggests that the high landslide activity in autumn 2000 in south‐eastern Norway was caused by a long‐term infiltration of large amounts of precipitation rather than high rainfall intensities during a short period. Copyright © 2007 John Wiley & Sons, Ltd.
Phosphoinositide 3‐kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death
Authors: Yu Hong‐Gang , Ai Yao‐Wei , Yu Liang‐Liang , Zhou Xiao‐Dong , Liu Jin , Li Jun‐Hua , Xu Xi‐Ming , Liu Song , Chen Jing , Liu Fen , Qi Yuan‐Ling , Deng Quanjun , Cao Jun , Liu Shi‐Quan , Luo He‐Sheng , Yu Jie‐Ping
Published: October 2007

The major obstacle to successful treatment of gastric cancer is chemotherapy resistance. Our study was designed to investigate the role of phosphoinositide 3‐kinase (PI3K)/Akt pathway in the development of chemoresistance in gastric cancer. In the present study, elevated Akt expression and Akt phosphorylation (Ser 473), as well as decreased PTEN expression were observed in 28 cases of gastric cancer tissues. Etoposide and doxorubicin stimulated Akt and PI3K activities in 2 gastric cancer cell lines (BGC‐823 and SGC‐7901), and the activities were concentration and time‐dependent. Up‐regulation of PTEN expression in BGC‐823 cells by PEAK8‐PTEN transient transfection obviously decreased the basal and anticancer drugs induced Akt activities, then sensitized BGC‐823 cells to etoposide and doxorubicin. Pretreatment of BGC‐823 and SGC‐7901 cells with wortmannin, a PI3K inhibitor, attenuated cells's resistance to etoposide and doxorubicin. In addition, pretreatment of wortmannin blocked etoposide and doxorubicin induced IkappaB‐α degradation, NFkappaB activation, phosphorylation of Akt, MDM‐2 and forkhead transcription factors. Wortmannin pretreatment also promoted the accumulation of p27/Kip, but inhibited the Mcl‐1 expression. Furthermore, wortmannin promoted etoposide and doxorubicin induced caspase‐3, caspase‐9 activation and poly ADP‐ribose polymerase cleavage. Taken together, the observations indicate the PI3K/Akt pathway plays an important role in the chemoresistance of gastric cancer cells. A new strategy for combined chemotherapy of gastric cancer should be designed to more specifically block PI3K/Akt pathway and then decrease the amount of resistant cells. © 2007 Wiley‐Liss, Inc.
Diagnostic performance of stereotactic large core needle biopsy for nonpalpable breast lesions in routine clinical practice
Authors: Peters Nicky , Hoorntje Lidewij , Mali Willem , Borel Rinkes Inne , Peeters Petra
Published: October 2007

The COBRA (COre Biopsy after RAdiological localization) study showed that in a controlled study setting, stereotactic large core needle biopsy (LCNB) is as reliable for diagnosing nonpalpable breast lesions as open surgical biopsy. In the present study, we evaluated the diagnostic performance of stereotactic LCNB in routine clinical practice. Between February 2000 and June 2002, data on all patients (n = 955) with nonpalpable breast lesions referred for LCNB were collected. High risk underestimate rate, ductal carcinoma in situ (DCIS) underestimate rate and sensitivity rate after 2 years were calculated. The usefulness of the COBRA guidelines in clinical practice was determined. Nine hundred five successful biopsies were performed in 874 patients. Of the high‐risk lesions, 27% were found to be carcinomas on open biopsy, which is comparable to the results of the COBRA study (23%). The DCIS underestimate rate (28%) was higher than found in the COBRA study (17%). No carcinomas were missed after a follow‐up period of 2 years. Ninety‐six percent of patients were treated according to the COBRA guidelines. The diagnostic performance of stereotactic LCNB in patients with nonpalpable breast lesions seems to be comparable in a controlled study setting and routine clinical practice. © 2007 Wiley‐Liss, Inc.
Protein kinase CK2 is a key activator of histone deacetylase in hypoxia‐associated tumors
Authors: Pluemsampant Sireerat , Safronova Olga S. , Nakahama Ken‐ichi , Morita Ikuo
Published: October 2007

Increasing evidence points to a link between histone deacetylases (HDACs) and tumorigenesis. Although several HDAC inhibitors have been tested in clinical trials for cancer therapies, the mechanisms of HDAC activation in tumors remain unknown. In this study, we investigated the pathway of HDAC activation in the context of hypoxia and inflammation, common features of solid tumors. In HeLa cells, hypoxia was a more potent activator of HDAC than IL‐1β. As HDAC protein expression did not change during treatment, we hypothesized that hypoxia regulated HDAC activity through post‐translational modification. We observed that hypoxia induced HDAC1 and HDAC2 protein phosphorylation both in the presence and absence of IL‐1β. Using TBB, an inhibitor of protein kinase CK2, we showed that CK2 was required for hypoxia‐induced HDAC activation. We also observed that CK2 activity was induced by hypoxia but not by IL‐1β alone. While CK2β subunits were retained in the cytoplasm upon hypoxic treatment, CK2α and CK2α′ subunits were shuttled to the nucleus, where HDAC1 and HDAC2 are predominantly localized. Knockdown of catalytic and regulatory subunits of CK2 revealed that formation of heterotetramic complex was not required for HDAC phosphorylation. von Hippel‐Lindau protein (pVHL) inactivation and hypoxia inducible factor‐1α (HIF‐1α) activation are associated with tumor growth and vasculogenesis. Use of Apicidin (an HDAC inhibitor) and TBB revealed that CK2‐dependent HDAC activation contributed to pVHL downregulation and HIF‐1α stabilization under hypoxia. Our findings that CK2 may be a key mediator for HDAC activation under hypoxia support the future application of CK2 inhibitors in cancer therapy. © 2007 Wiley‐Liss, Inc.
Alpha‐6 integrin is necessary for the tumourigenicity of a stem cell‐like subpopulation within the MCF7 breast cancer cell line
Authors: Cariati Massimiliano , Naderi Ali , Brown John P. , Smalley Matthew J. , Pinder Sarah E. , Caldas Carlos , Purushotham Anand D.
Published: October 2007

The identification of mammary epithelial stem cells raises the hypothesis that these cells may be crucial in the pathogenesis of breast cancer. To further support this, a highly tumourigenic sub‐population of cancer cells has recently been identified in primary and metastatic breast cancer samples. In this study, a sub‐population of cells displaying features normally attributed to stem cells was identified within the breast cancer cell line MCF‐7. This sub‐population is capable of growth in anchorage‐independent conditions as spherical organoids, displays resistance to proapoptotic agents and significantly greater tumourigenicity than its parental line, with as few as 1,000 cells able to form tumours in immunodeficient mice. Cells within this sub‐population can be enriched by serial passages in anchorage‐independence, and are characterized by over‐expression of the adhesion molecule α6‐integrin. Alpha‐6 integrin proves to be required for the growth and survival of these cells, as the knockdown of ITGA6 causes mammosphere‐derived cells to lose their ability to grow as mammospheres and abrogates their tumourigenicity in mice. These findings support the existence of a highly tumourigenic sub‐population in breast cancer cells. Furthermore, it shows α6‐integrin as a potential therapeutic target aimed at tumour‐generating subsets of breast cancer cells. © 2007 Wiley‐Liss, Inc.
Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis
Authors: Zhang Yu , Feng Yan‐Bin , Shen Xiao‐Ming , Chen Bao‐Sheng , Du Xiao‐Li , Luo Man‐Li , Cai Yan , Han Ya‐Ling , Xu Xin , Zhan Qi‐Min , Wang Ming‐Rong
Published: October 2007

Esophagin/SPRR3 is one of the cornified‐envelope structural precursor proteins, which is expressed during epithelia cell differentiation. In 1996, another research group discovered, and our own laboratory subsequently confirmed, frequent and dramatic decreased Esophagin/SPRR3 expression in esophageal squamous cell carcinoma (ESCC). However, the role of Esophagin/SPRR3 in tumorigenesis of esophageal epithelium remains undetermined. In this study, we demonstrate that expression of Esophagin/SPRR3 is frequently downregulated in ESCC. In contrast, no correlations between downregulation of Esophagin/SPRR3 expression and clinicopathologic characteristics were observed. Diminished Esophagin/SPRR3 expression was present in dysplastic epithelia, suggesting that Esophagin/SPRR3 alteration could represent an early event in squamous carcinogenesis of the esophagus. Exogenous expression of Esophagin/SPRR3 significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar, as well as tumor formation in vivo. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end label assay and immunofluorescence analysis of the active form of Caspase 3 indicated that dysregulated apoptosis might contribute to reduced tumorigenicity. In particular, upregulation of CDK11p46 protein was observed in ESCC cells expressing Esophagin/SPRR3, but not in control cells, indicating that Esophagin/SPRR3‐induced apoptosis may be due, at least in part, to increased expression of CDK11p46 protein. These findings suggest that Esophagin/SPRR3 may play a role in the maintenance of normal esophageal epithelial homeostasis, and that aberrant expression of Esophagin/SPRR3 may contribute to the tumorigenesis of ESCC. © 2007 Wiley‐Liss, Inc.
Gankyrin oncoprotein overexpression as a critical factor for tumor growth in human esophageal squamous cell carcinoma and its clinical significance
Authors: Ortiz Cristian M. , Ito Tetsuo , Tanaka Eiji , Tsunoda Shigeru , Nagayama Satoshi , Sakai Yoshiharu , Higashitsuji Hiroaki , Fujita Jun , Shimada Yutaka
Published: October 2007

To elucidate the possible involvement of gankyrin in ESCC progression and the effect of its down‐regulation in ESCC, we investigated the expression of gankyrin in ESCC tissues comparing it with the corresponding normal esophageal epithelia and tested a short‐hairpin RNA (shRNA) expression vector for gankyrin in ESCC cell lines. Gankyrin protein expression in 11 ESCC cell lines (KYSE series) was examined by RT‐PCR and western blot. The expression of gankyrin mRNA in 30 ESCC tissues was compared with the corresponding normal epithelia by Real‐time PCR. Expression of gankyrin protein was immunohistochemically analyzed in the ESCC of 103 patients. A gankyrin‐shRNA vector was stably transfected into KYSE 170 cells to assess the role of gankyrin in cell motility, invasion and proliferation in vitro and tumor formation in vivo. Gankyrin expression increased in all 11 ESCC cell lines. Real‐time PCR revealed that gankyrin expression was higher in the cancerous tissue for all 30 patients. In immunohistochemistry, gankyrin overexpression was correlated with lower survival rate (p = 0.0001), extent of the primary tumor, lymph node metastasis, distant lymph node metastasis and stage (p = 0.0072, p = 0.0004, p = 0.0172 and p = 0.0002, respectively). A shRNA vector against gankyrin repressed growth, cell motility, invasiveness in vitro and tumor formation in vivo. Gankyrin overexpression is associated with poor prognosis. It may play an important role in ESCC tumor progression and could be a potentially important therapeutic gene target in ESCC. © 2007 Wiley‐Liss, Inc.
Retracted: Immunotherapy of metastatic breast cancer patients with vitamin D‐binding protein‐derived macrophage activating factor (GcMAF)
Authors: Yamamoto Nobuto , Suyama Hirofumi , Yamamoto Nobuyuki , Ushijima Naofumi
Published: October 2007

The above article from the International Journal of Cancer, published online on 12 October 2007 in Wiley Online Library and in Volume 122, Issue 2, pp 461–467, has been retracted by agreement between the journal Editor‐in‐Chief Peter Lichter and Wiley Periodicals, Inc. due to irregularities in the documentation for institutional review board approval.
Cutaneous human papillomavirus 88: Remarkable differences in viral load
Authors: Kullander Johanna , Handisurya Alessandra , Forslund Ola , Geusau Alexandra , Kirnbauer Reinhard , Dillner Joakim
Published: October 2007

A human papillomavirus (HPV) was cloned from a patient with multiple squamous cell carcinomas (SCCs) and identified as HPV88, recently categorized into a new species within the genus Gamma. The HPV88 viral load in an SCC of the index patient exceeded 1 million copies/cell. By contrast, a survey of 447 skin lesions (79 actinic keratoses, 73 seborrhoeic keratoses, 169 basal cell carcinomas and 126 SCCs) and 362 healthy skin biopsies found detectable HPV88 DNA in only 7 specimens. All these had very low viral loads (<1 copy/103 cells) implying extreme biological variability in viral load. © 2007 Wiley‐Liss, Inc.
Passive smoking and lung cancer in Japanese non‐smoking women: A prospective study
Authors: Kurahashi Norie , Inoue Manami , Liu Ying , Iwasaki Motoki , Sasazuki Shizuka , Sobue Tomotaka , Tsugane Shoichiro ,   for the JPHC Study Group
Published: October 2007

Although smoking is a major cause of lung cancer, the proportion of lung cancer cases among Japanese women who never smoked is high. As the prevalence of smoking in Japan is relatively high in men but low in women, the development of lung cancer in non‐smoking Japanese women may be significantly impacted by passive smoking. We conducted a population‐based prospective study established in 1990 for Cohort I and in 1993 for Cohort II. The study population was defined as all residents aged 40–69 years at the baseline survey. 28,414 lifelong non‐smoking women provided baseline information on exposure to tobacco smoke from their husband, at the workplace and during childhood. Over 13 years of follow‐up, 109 women were newly diagnosed with lung cancer, of whom 82 developed adenocarcinoma. Compared with women married to never smokers, hazard ratio (HR) [95% confidence interval (CI)] for all lung cancer incidence in women who lived with a smoking husband was 1.34 (95% CI 0.81–2.21). An association was clearly identified for adenocarcinoma (HR 2.03, 95% CI 1.07–3.86), for which dose‐response relationships were seen for both the intensity (p for trend = 0.02) and amount (p for trend = 0.03) of the husband's smoking. Passive smoking at the workplace also increased the risk of lung cancer (HR 1.32, 95% CI 0.85–2.04). Moreover, a higher risk of adenocarcinoma was seen for combined husband and workplace exposure (HR 1.93, 95% CI 0.88–4.23). These findings confirm that passive smoking is a risk factor for lung cancer, especially for adenocarcinoma among Japanese women. © 2007 Wiley‐Liss, Inc.
2‐Methoxyestradiol modulates β‐catenin in prostate cancer cells: A possible mediator of 2‐methoxyestradiol‐induced inhibition of cell growth
Authors: Van Veldhuizen Peter J. , Ray Gibanananda , Banerjee Snigdha , Dhar Gopal , Kambhampati Suman , Dhar Animesh , Banerjee Sushanta K.
Published: October 2007

2‐Methoxyestradiol (2‐ME2) is a novel anticancer agent because of its ability to potentiate apoptotic cell death and inhibit cancer cell growth and angiogenesis. The modes of action of this agent, however, have not yet been fully elucidated. In our study, we have investigated whether 2‐ME2 is able to modulate β‐catenin signaling in prostate cancer cells, which is one of the major players in cell–cell adhesion, proliferation, apoptosis and carcinogenesis. We found that β‐catenin levels were significantly upregulated by 2‐ME2 in a dose‐dependent manner in androgen dependent and independent prostate cancer total cellular extracts. We further show that β‐catenin levels were significantly increased in the membrane fraction, while nuclear fractions of β‐catenin were downregulated in the 2‐ME2‐treated cells. Accumulation of dephospho‐β‐catenin (nondegraded form) parallel with Bcl‐2 and Cyclin D1 downregulation was also achieved after 2‐ME2 treatment. Moreover, we demonstrate that the β‐catenin production by 2‐ME2 is mediated through the MEK/ERK‐2 signaling pathway. Collectively, these results suggest that the cytostatic effect of 2‐ME2 may be mediated through the prevention of the translocation of β‐catenin to the nucleus parallel with an increase in cell–cell adhesion by increasing membrane β‐catenin production, eventually preventing cell migration. Moreover, dephospho‐β‐catenin accumulation by 2ME2 in the cytoplasm may contribute to the induction of apoptosis of these cells. Finally, studies testing the efficacy of 2‐ME2 in human prostate cancer are warranted to determine whether the inhibition of the expected loss of membranous β‐catenin and the upregulation of nuclear β‐catenin can prevent prostate cancer development and progression. © 2007 Wiley‐Liss, Inc.
Cost‐effectiveness of primary cytology and HPV DNA cervical screening
Authors: Bistoletti Peter , Sennfält Karin , Dillner Joakim
Published: October 2007

Because cost‐effectiveness of different cervical cytology screening strategies with and without human papillomavirus (HPV) DNA testing is unclear, we used a Markov model to estimate life expectancy and health care cost per woman during the remaining lifetime for 4 screening strategies: (i) cervical cytology screening at age 32, 35, 38, 41, 44, 47, 50, 55 and 60, (ii) same strategy with addition of testing for HPV DNA persistence at age 32, (iii) screening with combined cytology and testing for HPV DNA persistence at age 32, 41 and 50, iv) no screening. Input data were derived from population‐based screening registries, health‐service costs and from a population‐based HPV screening trial. Impact of parameter uncertainty was addressed using probabilistic multivariate sensitivity analysis. Cytology screening between 32 and 60 years of age in 3–5 year intervals increased life expectancy and life‐time costs were reduced from 533 to 248 US Dollars per woman compared to no screening. Addition of HPV DNA testing, at age 32 increased costs from 248 to 284 US Dollars without benefit on life expectancy. Screening with both cytology and HPV DNA testing, at ages 32, 41 and 50 reduced costs from 248 to 210 US Dollars with slightly increased life expectancy. In conclusion, population‐based, organized cervical cytology screening between ages 32 to 60 is highly cost‐efficient for cervical cancer prevention. If screening intervals are increased to at least 9 years, combined cytology and HPV DNA screening appeared to be still more effective and less costly. © 2007 Wiley‐Liss, Inc.
Assessment of causes of death in a prostate cancer screening trial
Authors: Mäkinen Tuukka , Karhunen Pekka , Aro Jussi , Lahtela Jorma , Määttänen Liisa , Auvinen Anssi
Published: October 2007

Accurate assessment of the causes of death is crucial for a conclusive evaluation of the ongoing prostate cancer screening trials. Here, we report the validity of the official causes of death as compared with an independent expert review in the Finnish prostate cancer screening trial. Because nearly 80,000 men were involved, death‐cause evaluation was restricted to men diagnosed for prostate cancer. Medical charts were retrieved and the cause of death was assigned by an expert review panel for all deaths among men with prostate cancer during the study period, 1996–2003. The panel decision was compared with both death certificates and the official causes of death as assigned by Statistics Finland. Of a total of 315 deaths, the review panel attributed 127 (41%) to prostate cancer and 184 (59%) to other causes, the corresponding figures in death certificates being 124 (40%) and 187 (60%). Four cases were excluded because of insufficient information. The death‐certificate data were in agreement with the panel's assessment in 305 out of 311 cases (overall agreement 97.7%, κ = 0.95). The overall agreement between the official causes of death and the panel's decision was 97.4% (304/311, κ = 0.95). The sensitivity of the certificates in identifying prostate cancer deaths was 96.1% (panel as golden standard). Correspondingly, specificity was 98.9%. The official causes of death thus provide an accurate means for evaluating disease‐specific mortality in a large population‐based prostate‐cancer screening trial in Finland. © 2007 Wiley‐Liss, Inc.
Haplotypes of the estrogen receptor beta gene and breast cancer risk
Authors:   Breast and Prostate Cancer Cohort Consortium
Published: October 2007

Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07–1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women. © 2007 Wiley‐Liss, Inc.
Effects of two whole blood systems (DALI and Liposorber D) for LDL apheresis on lipids and cardiovascular risk markers in severe hypercholesterolemia
Authors: Otto Carsten , Berster Jutta , Otto Bärbel , Parhofer Klaus G.
Published: October 2007

LDL apheresis is an extracorporal modality to lower the concentration of atherogenic lipoproteins, e.g., LDL cholesterol. We compared two recently introduced whole‐blood LDL apheresis systems inpatients with hypercholesterolemia in a randomized cross‐over trial with respect to their effects on lipoproteins as well as on other cardiovascular risk markers. Six patients (4 women, 2 men, median age 62.5 years, median BMI 25.9 kg/m2) on regular LDL apheresis were randomly assigned to receive six weekly treatments with either DALI (Fresenius) or Liposorber D (Kaneka). After 6 weeks, the patients were switched to the other device (again six weekly treatments). Blood was drawn before and immediately after LDL apheresis at three time points (last regular apheresis before the study; after six treatments with DALI and after six treatments with Liposorber D). LDL cholesterol concentration before the sixth apheresis (DALI 129 mg/dL, Liposorber D 132 mg/dL) as well as LDL cholesterol reduction during the sixth apheresis (DALI 68.3% and Liposorber D 68.4%) were similar with the two systems. CRP and fibrinogen concentrations were lower but interleukin‐6, myeloperoxidase, and resistin concentrations were higher after the last Liposorber treatment compared with DALI (P < 0.05, respectively). No differences were observed concerning adiponectin, ghrelin, and PYY levels. In conclusion, both devices were highly effective in eliminating atherogenic lipoproteins. CRP and fibrinogen were better eliminated with Liposorber D. However, following Liposorber D, interleukin‐6 levels were higher than after DALI possibly indicating an increased inflammatory activation. J. Clin. Apheresis, 2007. © 2007 Wiley‐Liss, Inc.
“Non‐heart‐beating,” or “cardiac death,” organ donation: Why we should care
Authors: Rady Mohamed Y. , Verheijde Joseph L. , McGregor Joan
Published: October 2007

BACKGROUND

Organ donation after cessation of cardiac pump activity is referred to as non‐heart‐beating organ donation (NHBOD). NHBOD donors can be neurologically intact; they do not fulfill the brain death criteria prior to cessation of cardiac pump activity. For hospitals to participate in NHBOD, they must comply with a newly introduced federal requirement for ICU patients whose deaths are considered imminent after withdrawal of life support. This report describes issues related to NHBOD.

METHODS

A nonstructured review of selected publications and Web sites was undertaken.

RESULTS

Scientific evidence from autoresuscitation and extracorporeal perfusion suggests that verifying cardiorespiratory arrest lasting 2–5 minutes does not uniformly comply with the dead donor rule, so that the process of organ procurement can be the irreversible event defining death in organ donors. The interest of organ procurement organizations and affiliates in maximizing recovery of transplantable organs introduces self‐serving bias in gaining consent for organ donation and abandons the basic tenet of obtaining true informed consent. The impact of donor management and procurement protocols on end‐of‐life (EOL) care and the potential trade‐off are not disclosed, raising concern about whether potential donors and their families are fully informed before consenting to donation.

CONCLUSIONS

The use of comprehensive quality indicators for EOL care can determine the impact of NHBOD on care offered to donors and the effects on families and health care providers. Detailed evaluation of NHBOD will enable the public to make informed decisions about participating in this type of organ donation. Journal of Hospital Medicine 2007;2:324–334. © 2007 Society of Hospital Medicine.
Barriers to mobility during hospitalization from the perspectives of older patients and their nurses and physicians
Authors: Brown Cynthia J. , Williams Beverly R. , Woodby Lesa L. , Davis Linda L. , Allman Richard M.
Published: October 2007

BACKGROUND

Low mobility is common during hospitalization and is associated with adverse outcomes. Understanding barriers to the maintenance or improvement of mobility is important to the development of successful interventions.

OBJECTIVES

To identify barriers to mobility during hospitalization from the perspectives of older patients and their primary nurses and physicians, to compare and contrast the perceived barriers among these groups, and to make a conceptual model.

DESIGN

Qualitative interviews analyzed and interpreted using a grounded theory approach.

SETTING

Medical wards of a university hospital.

PARTICIPANTS

Twenty‐nine participants—10 patients ≥ 75 years, 10 nurses, and 9 resident physicians.

MEASUREMENTS

Participants were interviewed using a semistructured interview guide, with similar questions for patients and health care providers. Interviews were audiotaped, transcribed, and reviewed for common themes by independent reviewers. Perceived barriers to mobility were identified, and their nature and frequency were examined for each respondent group.

RESULTS

Content analysis identified 31 perceived barriers to increased mobility during hospitalization. Barriers most frequently described by all 3 groups were: having symptoms (97%), especially weakness (59%), pain (55%), and fatigue (34%); having an intravenous line (69%) or urinary catheter (59%); and being concerned about falls (79%). Lack of staff to assist with out‐of‐bed activity was mentioned by patients (20%), nurses (70%), and physicians (67%). Unlike patients, health care providers attributed low mobility among hospitalized older adults to lack of patient motivation and lack of ambulatory devices.

CONCLUSIONS

Recognizing and understanding perceived barriers to mobility during hospitalization of older patients is an important first step toward developing successful interventions to minimize low mobility. Journal of Hospital Medicine 2007;2:305–313. © 2007 Society of Hospital Medicine.
Promoting effective transitions of care at hospital discharge: A review of key issues for hospitalists
Authors: Kripalani Sunil , Jackson Amy T. , Schnipper Jeffrey L. , Coleman Eric A.
Published: October 2007

The period following discharge from the hospital is a vulnerable time for patients. About half of adults experience a medical error after hospital discharge, and 19%–23% suffer an adverse event, most commonly an adverse drug event. This article reviews several important challenges to providing high‐quality care as patients leave the hospital. These include the discontinuity between hospitalists and primary care physicians, changes to the medication regimen, new self‐care responsibilities that may stress available resources, and complex discharge instructions. We also discuss approaches to promoting more effective transitions of care, including improvements in communication between inpatient and outpatient physicians, effective reconciliation of prescribed medication regimens, adequate education of patients about medication use, closer medical follow‐up, engagement with social support systems, and greater clarity in physician–patient communication. By understanding the key challenges and adopting strategies to improve patient care in the transition from hospital to home, hospitalists could significantly reduce medical errors in the postdischarge period. Journal of Hospital Medicine 2007;2:314–323. © 2007 Society of Hospital Medicine.
Vitamin D receptor distribution in intestines of domesticated sheep Ovis ammon f. aries
Authors: Riner Katharina , Boos Alois , Hässig Michael , Liesegang Annette
Published: October 2007

The biologically active form of vitamin D, i.e., 1,25‐dihydroxycholecalciferol or calcitriol, plays an important role in bone metabolism and calcium homeostasis, which is often disturbed at the onset of lactation in high milk‐yielding domestic ruminants. Gene transcription is modulated via vitamin D receptors, but nongenomic effects of vitamin D via membrane receptors have also been described. In the intestines, vitamin D promotes calcium absorption via vitamin D receptors. Vitamin D receptors are of clinical relevance, but have not been systematically assessed within all segments of the intestine in any species. Thus, we present for the first time an immunohistochemical study of the distribution patterns of the vitamin D receptor protein in sheep, which may be the basis for present and future investigations on mineral homeostasis in domestic ruminants. Tissue probes of the intestines were collected from five lambs and five nonlactating and nonpregnant dams, fixed in formalin, embedded in paraffin, and used for the assessment of vitamin D receptor protein. Nuclear vitamin D receptor immunoreaction was scored semiquantitatively and exhibited a segment‐specific distribution pattern. Goblet cells always were devoid of any vitamin D receptor immunoreaction. Surface epithelial cells and enterocytes of the crypt openings generally demonstrated only a weak immunoreaction. Basally and/or intermediately located crypt epithelial cells exhibited stronger immunoreactions in duodenum, jejunum, and colon descendens. This basal/intermediate to superficial gradient was most pronounced in the duodenum and less evident in jejunum and colon descendens and not observed in ileum and cecum. There were no age‐dependent variations in vitamin D receptor protein expression. Results demonstrate that intestinal vitamin D receptor distribution patterns are segment‐specific and strongest immunoreactions correlate with highest intestinal calcium absorptive activities, as reported in literature. Strong expression of vitamin D receptors within the lower half of crypts also suggests a role for calcitriol in epithelial differentiation and cellular homeostasis. J. Morphol., 2008. © 2007 Wiley‐Liss, Inc.
The peristomatic structures of Lithobiomorpha (Myriapoda, Chilopoda): Comparative morphology and phylogenetic significance
Authors: Koch Markus , Edgecombe Gregory D.
Published: October 2007

A comparative survey of the epipharynx and hypopharynx of lithobiomorph centipedes by light and scanning electron microscopy examines 18 species that sample the major groups of both families, the Lithobiidae and Henicopidae. Cladistic analysis of 11 characters of the peristomatic structures together with 29 additional morphological characters serves as a basis for interpreting the evolution of the lithobiomorph peristomatic structures. Scutigeromorpha is used for outgroup comparison in the framework of a homology scheme for the basic components of the epi‐ and hypopharynx. Compared to other chilopods, the monophyly of Lithobiomorpha is supported by a row of distinctive bottle‐shaped gland openings at the border between the labral and clypeal parts of the epipharynx, as well as by a distinctive shape of the hypopharynx. Paired rows of elongate spines on the clypeal part of the epipharynx are an apomorphic character of Lithobiidae. The transformation of these spine rows into a few groups of branching spines is characteristic for the Monotarsobius group sensu Verhoeff. Similar groups of branching clypeal spines characterize the Anopsobiinae within Henicopidae, whereas Henicopinae possess a dense cluster of short, simple spines instead. The recently described genus Dzhungaria is resolved closer to Henicopinae than to Anopsobiinae, a hypothesis supported by a field of grooves on the medial labral part of the epipharynx. Monophyly of Henicopidae does not receive unique support from the peristomatic structures although two homoplastic characters contribute to this node; among these, the reduction of a median spine field between clypeal and labral parts of the epipharynx to a narrow transverse band also supports a close relationship between the Ezembius group and Hessebius within Lithobiidae. An Ezembius + Hessebius clade is additionally supported by the absence of a transverse bulge between the clypeal and labral parts of the epipharynx, a character otherwise present in all lithobiomorph species studied so far. Lithobius is resolved as polyphyletic, with different species being most closely related to such genera as Australobius, Hessebius and Pleurolithobius. J. Morphol., 2008. © 2007 Wiley‐Liss, Inc.
Comparative trophic morphology in eight species of damselfishes (Pomacentridae)
Authors: Frédérich Bruno , Pilet Arnaud , Parmentier Eric , Vandewalle Pierre
Published: October 2007

Damselfishes show significant biodiversity in the coral reefs. To better understand such diversity, an ecomorphological approach was investigated in the trophic morphology of eight species of Pomacentridae (Chromis acares, C. margaritifer, Dascyllus aruanus, D. flavicaudus, Pomacentrus pavo, Plectroglyphidodon johnstonianus, Pl. lacrymatus and Stegastes nigricans) belonging to different trophic guilds (zooplankton, algal, coral polyp feeders and omnivores). Geometric morphometrics were used to quantify size and shape variations in four skeletal units: (1) neurocranium, (2) suspensorium and opercle, (3) mandible and (4) premaxilla. This method allowed us to reveal shape and size differences correlated to functional diversity both within and between trophic guilds. Among zooplanktivores, C. margaritifer, D. aruanus and D. flavicaudus have a high and long supraoccipital crest, short mandibles forming a small mouth and high suspensoria and opercles. These three species can be considered to be suction feeders. In the same guild, C. acares shows opposite characteristics (long and thin mandibles, lengthened neurocranium and suspensorium) and can be considered as a ram feeder. Among herbivores and corallivores, the two species of Plectroglyphidodon and S. nigricans can be considered as grazers. Differences in skeletal shape are mainly related to improving the robustness of some skeletal parts (broad hyomandibular, short and high mandibles). The shapes of P. pavo, which feeds largely on algae, strongly differ from that of the other three grazers exhibiting similar morphological characteristics to C. acares (e.g., long and shallow suspensorium, lengthened neurocranium). This highlights likely differences concerning cutting or scraping method. Finally, no strong correlations exist between size and shapes in the eight studied species. Size difference among species having a very similar shape could be viewed as a factor optimizing resource partitioning. J. Morphol., 2008. © 2007 Wiley‐Liss, Inc.
Sperm aggregations in female Agkistrodon piscivorus (Reptilia:Squamata): A histological and ultrastructural investigation
Authors: Siegel Dustin S. , Sever David M.
Published: October 2007

Upon copulation in female Agkistrodon piscivorus, sperm migrate up the oviduct to sperm storage tubules (SSTs) in the posterior infundibulum. The epithelium of the SSTs is composed of ciliated and secretory cells and differs ultrastructurally from that of the epithelium lining the lumen of the posterior infundibulum. Sperm pass through an area composed primarily of ciliated cells at the opening of each gland before aligning themselves in parallel arrays with their nuclei facing an area composed primarily of secretory cells at the base of the tubules. Sperm are also found embedded inter‐ and intracellularly in the SSTs. The secretory vacuoles in the SSTs become highly electron dense after the start of the fall mating season along with the synthesis of lipid droplets. Histochemical analysis reveals that the alteration in secretory material density is caused by the production of neutral carbohydrates. Some sperm remain in aggregates in the nonglandular section of the posterior uterus until the time of ovulation. However, ultrastructural evidence indicates these sperm degrade before ovulation. Therefore, sperm in posterior aggregates have no role in fertilization of ovulated ova. The data presented here support the hypothesis that infundibular sperm storage is the mode that snakes utilize to sequester viable sperm until ovulation. J. Morphol., 2008. © 2007 Wiley‐Liss, Inc.
Successful treatment of an entecavir‐resistant hepatitis B virus variant
Authors: Yatsuji Hiromi , Hiraga Nobuhiko , Mori Nami , Hatakeyama Tsuyoshi , Tsuge Masataka , Imamura Michio , Takahashi Shoichi , Fujimoto Yoshifumi , Ochi Hidenori , Abe Hiromi , Maekawa Toshiro , Suzuki Fumitaka , Kumada Hiromitsu , Chayama Kazuaki
Published: October 2007

Emergence of a lamivudine (LAM)‐resistant hepatitis B virus (HBV) with amino acid substitutions in the YMDD motif is a well‐documented problem during long‐term LAM therapy. Entecavir (ETV) is a new drug approved for treatment of HBV infection with or without LAM‐resistant mutants. This report describes an ETV‐resistant strain of HBV, which emerged after prolonged ETV therapy in a patient who did not respond to LAM therapy. Direct sequence analysis of the ETV‐resistant strain showed appearance of amino acid substitution rtS202G in the reverse transcriptase (RT) domain, together with rtL180M + M204V substitution that had developed at the emergence of LAM‐resistant mutant. In vitro analysis demonstrated that the rtL180M + M204V + S202G mutant strain displayed a 200‐fold and a 5‐fold reduction in susceptibility to ETV compared with the wild‐ type and the rtL180M + M204V mutant strain, respectively. Adefovir was effective against the ETV‐resistant strain both in vitro and during the clinical course. In conclusion, this study showed that virological and biochemical breakthrough due to ETV could occur in patients infected with LAM‐resistant HBV and confirmed that the addition of rtS202G substitution to the rtL180M + M204V mutant strain is responsible for ETV resistance and we could treat the resistant mutant successfully. J. Med. Virol. 79:1811–1817, 2007. © 2007 Wiley‐Liss, Inc.
Comparison of strain‐specific antibody responses during primary and secondary infections with respiratory syncytial virus
Authors: Scott Paul D. , Ochola Rachel , Sande Charles , Ngama Mwanajuma , Okiro Emelda A. , Medley Graham F. , Nokes D. James , Cane Patricia A.
Published: October 2007

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infants. RSV repeatedly reinfects individuals: this may be due in part to the variability of the attachment (G) glycoprotein and changes in this protein have been shown to be under positive selection. Infants experiencing their primary infection show a genotype‐specific antibody response with respect to the variable regions of the G protein. A prospective study of RSV infections in a birth cohort in rural Kenya identified infants experiencing repeat infections with RSV. The serum antibody responses of these infants were investigated with respect to their anti‐RSV reactions in an enzyme‐linked immunosorbent assay (ELISA) and the specificity of the response to a variable region of the G protein by ELISA and immunoblotting using bacterially expressed polypeptides representative of the currently circulating strains of RSV. The results presented here confirm that the primary antibody response to the variable regions of the G protein is generally genotype‐specific, but show that the response may become cross‐reactive (at least within group A viruses) during secondary infections even where the secondary infection is of the same genotype as the initial infection. Also, some infants who did not mount a detectable antibody response to whole RSV antigens during their primary infection nevertheless showed genotype‐specific responses to the G protein. In conclusion, the strain‐specific nature of the serum antibody response to the variable regions of the G protein of RSV observed in primary infections can become cross‐reactive in subsequent reinfections. J. Med. Virol. 79:1943–1950, 2007. © 2007 Wiley‐Liss, Inc.
Influence of enteric viruses on gastroenteritis in Albania: Epidemiological and molecular analysis
Authors: Fabiana Arrivi , Donia Domenica , Gabrieli Rosanna , Petrinca Anna Rita , Cenko Fabian , Bebeci Durim , Altan Anna Maria Doro , Buonomo Ersilia , Divizia Maurizio
Published: October 2007

Gastroenteritis is one of the most important diseases in developing country and viral infections are well documented. To understand better the epidemiological aspect of gastroenteritis in Albania and especially viral gastroenteritis, one‐year study was carried out with the cooperation of physicians working in the Paediatric Hospital in University Hospital Center “Mother Thereza” in Tirana. Three hundred thirteen stool samples were collected from children with diarrhoea and a questionnaire was filled by the health personnel for each child. Analysis of the questionnaires revealed that overcrowding families and the limited availability of drinking water at home were risk factors for gastroenteritis. All the tests for enteroviruses were carried out using the molecular methods. One hundred and forty‐seven out of three hundred thirteen stool samples showed a specific amplification band for one of the enteric viruses: astrovirus, adenovirus, rotavirus, and norovirus with an overall positive specimen rate of 46.9%. Rotavirus was the most frequent virus identified in 105 out of 147 samples (71.4%), astrovirus in 5 (3.4%), norovirus in 19 (12.9%), and enteric adenovirus in 18 (12.3%) samples. Double infection was present only in 14 samples (9.5%). The data suggest an evident circulation of viruses involved in gastroenteritis with a higher prevalence of rotavirus. J. Med. Virol. 79:1844–1849, 2007. © Wiley‐Liss, Inc.