bluuebunny/crossref_metadata_2025 huggingface dataset:
JWA IS REQUIRED FOR THE ANTIPROLIFERATIVE AND PRO‐APOPTOTIC EFFECTS OF ALL‐TRANS RETINOIC ACID IN HELA CELLS
Authors: Mao Wen‐Ge , Liu Zu‐Long , Chen Rui , Li Ai‐Ping , Zhou Jian‐Wei
Published: August 2006

All‐trans retinoic acid (ATRA) is known to inhibit cellular proliferation and induce differentiation and apoptosis. It usually activates gene expression by binding to a nuclear receptor that interacts with retinoic acid‐response elements (RARE) and then activates the mitogen‐activated protein kinase signal pathway. JWA, a newly identified ATRA‐responsive gene, has recently been proposed as an important molecule for cellular differentiation induced by some chemicals, including ATRA.

To investigate the possible involvement of JWA in the inhibition of cellular proliferation and induction of apoptosis by ATRA, HeLa cells were stably transfected with sense or antisense JWA to establish cell lines that overexpressed or were deficient in JWA; ATRA (0.05–10 mmol/L) was used to induce cellular differentiation and apoptosis.

Western blot analysis revealed that ATRA caused increased expression of JWA in HeLa cells in a dose‐ and time‐dependent manner, accompanied by activation of extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation. However, ERK1/2 phosphorylation induced by ATRA was inhibited in JWA‐deficient HeLa cells. In JWA‐overexpressing HeLa cells, ATRA showed more significant antiproliferative effects and induced more apoptosis.

The reporter gene assay showed that ATRA (5 mmol/L) enhanced the transcriptional activity of JWA by interacting with its promoter in the region from ‐194 to +107 bp (P < 0.01). Bioinformatic analysis indicated that the JWA promoter did not contain RARE, but did contain two CCAAT boxes in this fragment spanning ‐194 to +107 bp, which may be responsive to the ATRA‐activated nuclear transcription factor CCAAT/enhancer binding proteins (C/EBP) or interacting proteins. Therefore, ATRA‐inhibited cellular proliferation and ‐induced apoptosis in HeLa cells may be dependent on JWA transactivation via its C/EBP‐binding motifs.

These data indicate that the inhibition of proliferation and the induction of apoptosis by ATRA are dependent on JWA expression in HeLa cells. The findings may represent a novel mechanism by which the effects of ATRA in regulating cellular proliferation and apoptosis are mediated, at least in part, by JWA expression.
EFFECTS OF TEA AND TEA FLAVONOIDS ON ENDOTHELIAL FUNCTION AND BLOOD PRESSURE: A BRIEF REVIEW
Authors: Hodgson JM
Published: August 2006

The consumption of tea worldwide is second only to water. Thus, any physiological effects of tea could have a significant impact on population health.

Tea is the major contributor to total flavonoid intake in many populations. Flavonoids in tea have been shown to have a range of activities and effects that could contribute to improved health. Tea intake and the intake of flavonoids found in tea have been associated with reduced risk of cardiovascular disease in several cross‐sectional and prospective population studies. A variety of possible mechanisms have been investigated. The focus of the present review is on the mounting evidence that tea flavonoids can improve endothelial function and lower blood pressure.

In vitro studies using isolated vessels have shown that tea flavonoids possess vasodilator activity. Results of human intervention trials have shown that increased flavonoid intake from tea, as well as other dietary sources, can improve endothelial function. Emerging data also suggest that the degree of benefit may be related to flavonoid metabolism.

The effects of tea flavonoids on blood pressure are less consistent. Results of animal studies and population studies are consistent with a blood pressure‐lowering effect of tea. However, short‐term intervention trials, mainly in normotensive individuals, have not demonstrated any blood pressure reduction with tea.

Overall, the available data suggest that the effects of tea flavonoids on endothelial function and, perhaps, blood pressure may be responsible, at least in part, for any benefits of drinking tea on the risk of cardiovascular disease.
Rating of CCl4‐induced rat liver fibrosis by blood serum glycomics
Authors: Desmyter Liesbeth , Fan Ye‐Dong , Praet Marleen , Jaworski Tomasz , Vervecken Wouter , De Hemptinne Bernard , Contreras Roland , Chen Cuiying
Published: August 2006

Background:  Non‐invasive staging of human liver fibrosis is a desirable objective that remains under extensive evaluation. Animal model systems are often used for studying human liver disease and screening antifibrotic compounds. The aim of the present study was to investigate the potential use of serum N‐glycan profiles to evaluate liver fibrosis in a rat model.

Methods:  Liver fibrosis and cirrhosis were induced in rats by oral administration of CCl4. Liver injury was assessed biochemically (alanine aminotransferase [ALT] activity, aspartate aminotransferase [AST] activity and total bilirubin) and histologically. The N‐glycan profile (GlycoTest) was performed using DNA sequencer‐assisted–fluorophore‐assisted carbohydrate electrophoresis technology. In parallel, the effect of cotreatment with antifibrotic interferon‐γ (IFN‐γ) was studied.

Results:  The biopsy scoring system showed that CCl4 induced early fibrosis (F < 1–2) in rats after 3 weeks of treatment, and cirrhosis (F4) after 12 weeks. Significant increases in ALT activity, AST activity and total bilirubin levels were detected only after 12 weeks of CCl4 treatment. GlycoTest showed three glycans were significantly altered in the CCl4‐goup. Peak 3 started at week 6, at an early stage in fibrosis development (F < 1–2), whereas peaks 4 and 5 occurred at week 9, at which time mild liver fibrosis (F = 1–2) had developed. The changes in the CCl4‐IFN‐γ group were intermediate between the CCl4‐ and the control groups.

Conclusion:  The GlycoTest is much more sensitive than biochemical tests for evaluating liver fibrosis/cirrhosis in the rat model. The test can also be used as a non‐invasive marker for screening and monitoring the antifibrotic activity of potential therapeutic compounds.
Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: A Chinese experience
Authors: Li Qiang , Li Huikai , Qin Yu , Wang P Peter , Hao Xishan
Published: August 2006

Background:  Although both hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are well recognized risk factors for hepatocellular carcinoma (HCC), little is known with respect to how HBV and HCV infection affect HCC recurrence in postoperative HCC Chinese patients. The objective of this study was to determine if differences exist in preoperative characteristics and postoperative HCC recurrence in patients with different HBV and HCV infection status.

Methods:  The study population consisted of 413 patients undergoing a curative resection at Tianjin Cancer Hospital for small HCC (≤3 cm) from January 1997 to December 2003. The patients were divided into four groups: HCV only (n = 75), HBV only (n = 251), HBV and HCV (n = 33), and neither HBV nor HCV (NBNC, n = 54). The preoperative status and postoperative HCC recurrence were recorded. Survival analyses were used to assess the impact of HBV/HCV status on HCC recurrence.

Results:  Patients with HCV had a significant association with older age, lower mean preoperative platelet counts and albumin levels, higher mean prothrombin time, alanine aminotransferase and total bilirubin levels and multinodular tumors during diagnosis. Patients with HCV also had significantly less differentiated tumors and a higher incidence of vascular invasion and cirrhosis when compared to the other groups. During the follow‐up, the HCV group showed a higher incidence of intrahepatic recurrence and multiple recurrent lesions than the other patients.

Conclusions:  Patients with HCV infection tended to be older, and were characterized by more severe cirrhosis and higher incidence of tumor multicentricity. The statistically significant determinants for reoccurrence in patients with small HCC were HCV infection, presence of vascular invasion and multiple tumors.
Initial site of bile regurgitation following extrahepatic biliary obstruction in living rats
Authors: Watanabe Norihito , Kojima Sei‐ichiro , Takashimizu Shinji , Nishizaki Yasuhiro , Kagawa Tatehiro , Phillips M James
Published: August 2006

Background and Aim:  The precise mechanism of bile regurgitation from the biliary system to the blood stream still remains to be elucidated. The aim of this study was to examine the initial site of bile regurgitation in vivo after common bile duct (CBD) obstruction by digitally enhanced fluorescence microscopy.

Methods:  The fluorescence excreted into bile canaliculi after the administration of sodium fluorescein was continuously observed in CBD obstruction, using video‐enhanced contrast (VEC) microscopy equipped with a silicon intensified target (SIT) camera. The liver histology and the localization of Mg2+‐ATPase were examined by light and electron microscopy.

Results:  By the continuous recording of canalicular fluorescence, the sequential regurgitation of the fluorescence from the canaliculi to the hepatocyte cytoplasm to the sinusoids was distinctively recognized after CBD obstruction. Bile canalicular fluorescence was enhanced, and then the fluorescence of the hepatocyte cytoplasm increased in intensity, followed by regurgitation of the fluorescence to the sinusoids. These in vivo sequences closely correlated with changes in CBD pressure. In zone 1, canalicular fluorescence focally burst into hepatocyte cytoplasm, thus resulting in the formation of fluorescent cells. By light and electron microscopy, the fluorescent cells were found to correspond to the liver cell injury. The reaction products of Mg2+‐ATPase were incorporated into vesicles with a decreased canalicular activity, and then were transported to the sinusoidal surface after CBD obstruction.

Conclusions:  The initial site of bile regurgitation may be transcellular, and partly involves liver cell injury in zone 1 in extrahepatic biliary obstruction, associated with increased pressure of the biliary system.
Nurses, nannies and caring work: importation, visibility and marketability
Authors: Brush Barbara L. , Vasupuram Rukmini
Published: August 2006

This paper examines nurses’ international migration within the broader context of female migration, particularly against more studied groups of women who have migrated for employment in care‐giving roles. We analyze the similarities and differences between skilled professional female migrants (nurses) and domestic workers (nannies and in‐home caretakers) and how societal expectations, meanings, and values of care and ‘women's work’, together with myriad social, cultural, economic and political processes, construct the female migrant care‐giver experience. We argue that, as the recruitment of foreign workers gains visibility, strategies are introduced to better prepare female migrant care‐givers for the marketplace. Language, specifically command of English and accent modification, is highlighted as one means to assimilate migrant care‐givers to host communities.
From perpetrator to victim in a violent situation in institutional care for elderly persons: exploring a narrative from one involved care provider
Authors: Sandvide Åsa , Fahlgren Siv , Norberg Astrid , Saveman Britt‐Inger
Published: August 2006

In order to reach a more comprehensive understanding of the dynamics in violent situations in institutional care for elderly people the aim of this study was to explore involved parties’ positions, and to illuminate forces and moves related to these positions. One involved care provider's narrative was analysed using narrative analysis and positioning theory. In the narrative the involved parties’ positions were fluid and often overlapping, and not exclusively as victim or perpetrator. Across the narrative the narrator altered the involved parties’ positions by using available discourses. We understand that the altered positions were a salient way for the care provider to make sense of her experiences. By reading the care provider's narrative we further understand that she was much more than just a perpetrator, which was the origin for her narrative. This study led us to two assumptions important for implications in nursing practice. First, it is of significance how we position ourselves and others in narratives and conversations. Second, there is a difference between being categorised in advance and getting the opportunity to narrate one's own story.
Writing place: a comparison of nursing research and health geography
Authors: Carolan Mary , Andrews Gavin J. , Hodnett Ellen
Published: August 2006

The concept of ‘place’, and general references to ‘geographies of …’ are making gradual incursions into nursing literature. Although the idea of place in nursing is not new, this recent spatial turn seems to be influenced by the increasing profile of the discipline of health geography, and the broadening of its scope to incorporate smaller and more intimate spatial scales. A wider emphasis within the social sciences on place from a social and cultural perspective, and a wider turn to ‘place’ across disciplines are probably equally important factors. This trend is raising some interesting questions for nurses, but at the same time contributes some confusion with regard to imputed meanings of ‘place’. While it is clear that most nurse clinicians and researchers certainly understand that place of care matters to their practices and patients, many diverse uses of ‘place’ are found within nursing literature, and contemporary understandings of the term ‘place’ within nursing are not immediately clear. It is in this context that this article plans to advance the discussion of place. More specifically, the aims of this paper are threefold: to critique ‘place’ as it appears in nursing literature, to explore the use of ‘place’ within health geography, whence notions of place and ‘geographies of’ have originated and, finally, to compare and contrast the use of ‘place’ in both disciplines. This critique intends to address a deficit in the literature, in this era of growing spatialization in nursing research. The specific questions of interest here are: ‘what is “place” in nursing?’ and ‘how do concepts of place in nursing compare to concepts of place in health geography?’
Investigation of rolling contact fatigue cracks in a grade 900A rail steel of a metro track
Authors: HAIDEMENOPOULOS G. N. , ZERVAKI A. D. , TEREZAKIS P. , TZANIS J. , GIANNAKOPOULOS A. E. , KOTOUZAS M. K.
Published: August 2006

Rolling contact fatigue (RCF) has been of increasing concern in the recent years in respect of the safe operation of high‐speed railway track with high traffic intensity. The present paper summarizes the results of the first investigation of RCF damage encountered in the Athens Metro. The objective of the investigation was to determine the initiation and propagation of RCF cracks and to determine their geometrical characteristics.

A thorough metallographic investigation of track regarding shelling and spalling defects showed the development of a subsurface network of cracks. An analysis of the Hertzian stress field was used to determine the conditions for first yield and shakedown limits as a function of loading.
ON THE PARTICIPATION IN MEDIUM‐ AND LONG‐DISTANCE TRAVEL: A DECOMPOSITION ANALYSIS FOR THE UK AND THE NETHERLANDS
Authors: LIMTANAKOOL NARISRA , DIJST MARTIN , SCHWANEN TIM
Published: August 2006

Social and economic benefits have accrued from medium‐ and long‐distance travel, but at the expense of the environment. Since the travel behaviour literature tends to concentrate on short‐distance trips or trips within daily urban systems, a better understanding of the factors shaping medium‐ and long‐distance travel is needed. Using the 1998 National Travel Surveys for the UK and the Netherlands, the study reported here characterises medium‐ and long‐distance travellers in terms of socio‐economic attributes, time availability, day of travel, and land‐use related factors. The results suggest that, in both countries, males and individuals with a higher socio‐economic status are more likely to engage in medium‐ and long‐distance travel. The analysis further shows that the overall structure of the urban system in combination with the size of the country and the local population density affect the participation in medium‐ and long‐distance travel. Such factors should be considered explicitly in future studies of medium‐ and long‐distance travel.
Hemicrania Continua Evolving from Episodic Paroxysmal Hemicrania
Authors: Castellanos-Pinedo F , Zurdo M , Martínez-Acebes E
Published: August 2006

A 45-year-old woman, who had been diagnosed in our unit with episodic paroxysmal hemicrania, was seen 2 years later for ipsilateral hemicrania continua in remitting form. Both types of headache had a complete response to indomethacin and did not occur simultaneously. The patient had a previous history of episodic moderate headaches that met criteria for probable migraine without aura and also had a family history of headache. The clinical course in this case suggests a pathogenic relationship between both types of primary headache.
SMART: Stroke-Like Migraine Attacks After Radiation Therapy
Authors: Black DF , Bartleson JD , Bell ML , Lachance DH
Published: August 2006

We describe two adults with stroke-like migraine attacks after radiation therapy (SMART syndrome), propose revised diagnostic criteria, and review the previously reported patients. ‘SMART’ is an acronym for a newly recognized syndrome which occurs as a delayed consequence of cerebral irradiation and consists of prolonged, unilateral, migrainous neurological symptoms with transient, dramatic cortical gadolinium enhancement of the affected cerebral hemisphere and is sometimes punctuated by generalized seizures and ipsilateral EEG slowing. Although the neurological symptoms can last for weeks, full recovery occurs. An appropriate evaluation should exclude alternative explanations.
Prognosis for the co‐twin following single‐twin death: a systematic review
Authors: Ong SSC , Zamora J , Khan KS , Kilby MD
Published: August 2006

Background  Following single‐twin death, the perinatal mortality and morbidity for the surviving co‐twin is increased but difficult to quantify. We present data on prognosis from a systematic review.

Objectives  We aimed to determine the incidence of a) co‐twin death, b) neurological abnormality and c) preterm delivery for the surviving co‐twin following single‐twin death after 14 weeks of gestation.

Search strategy  Literature was identified by searching two bibliographical databases and specialist journals between 1990 and 2005.

Selection criteria  The selected studies of ≥5 cases reported on perinatal death and/or neurodevelopmental delay of the surviving co‐twin.

Data collection and analysis  Studies were assessed for quality and data extracted to allow computation of rates. The data were inspected for heterogeneity using a Forrest plot and examined statistically using the chi‐square test. Data from individual studies were pooled within subgroups defined by prognosis.

Main results  The search strategy yielded 632 potentially relevant citations. Full manuscripts were retrieved for 54 citations and 28 studies were finally included in the review. Following the death of one twin, the risk of monochorionic and dichorionic co‐twin demise was 12% (95% CI 7–11) and 4% (95% CI 2–7), respectively. The risk of neurological abnormality in the surviving monochorionic and dichorionic co‐twin was 18% (95% CI 11–26) and 1% (95% CI 0–7), respectively. The risk of preterm delivery was 68% (95% CI 56–78) and 57% (95% CI 34–77), respectively. Where there was comparative data within studies, the odds of monochorionic co‐twin intrauterine death was six times that of dichorionic twins (OR 6.04 [95% CI 1.84–19.87]). Neurological abnormality was also higher in monochorionic compared with dichorionic pregnancies (OR 4.07 [95% CI 1.32–12.51]).

Author’s conclusions  More prospective research is required to inform decision making on this subject, especially with data that allow stratification based upon chorionicity.
Short communication: Can we improve the diagnosis of rupture of membranes? The value of insulin‐like growth factor binding protein‐1
Authors: Martinez de Tejada B , Boulvain M , Dumps P , Bischof P , Meisser A , Irion O
Published: August 2006

Our objective was to assess the value of insulin‐like growth factor binding protein‐1 (IGFBP‐1) and other tests for the diagnosis of rupture of the membranes (ROM). We included 49 women with suspected ROM. The gold standard for membranes status was defined based on clinical examination, ultrasonography, tests results (except IGFBP‐1) and labour information. Sensitivity, specificity, positive predictive value and negative predictive value of each test were as follows, respectively: IGFBP‐1 (86, 74, 73 and 87%); bromothymol (64, 100, 100 and 77%); fern test (62, 96, 93 and 75%) and ultrasonography (19, 100, 100 and 61%). The detection of IGFBP‐1 in vaginal secretions has high sensitivity for the diagnosis of ROM.
Operative laparoscopy for unruptured ectopic pregnancy in a caesarean scar
Authors: Wang Y‐L , Su T‐H , Chen H‐S
Published: August 2006

Eight women diagnosed by transvaginal ultrasonography with unruptured caesarean scar pregnancy underwent operative laparoscopy as an alternative treatment to laparotomy. The ultrasonographic diagnosis of caesarean scar pregnancy was confirmed in all women at laparoscopy. None of the women required conversion of the procedure to laparotomy. The total operative time ranged from 75 to 120 minutes. The total blood loss was limited, ranging from 50 to 200 ml. All women tolerated the operation well and had uneventful recoveries. Our results show that in the hands of a well‐trained operator, laparoscopy appears to be a reasonable alternative for the management of an unruptured caesarean scar pregnancy.
Leaving a Sexually Coercive Dating Partner: A Prospective Application of the Investment Model
Authors: Katz Jennifer , Kuffel Stephanie Washington , Brown Felisa A.
Published: August 2006

In the present study, an investment model framework was applied to identify associations between partner verbal sexual coercion and dating relationship outcomes, including relationship commitment and maintenance. Undergraduate women ( N = 180) provided self-report data on investment model variables and verbal sexual coercion within their current relationships and returned 6 to 8 weeks later to report on their relationship status. About 28% of the participants endorsed partner verbal sexual coercion. Women in sexually coercive relationships reported greater investment but did not differ from other women in satisfaction, commitment, or later relationship maintenance. Results revealed indirect effects of partner sexual coercion on relationship commitment through greater perceived investment. Sustaining verbal sexual coercion in ongoing dating relationships may represent a type of relationship investment that indirectly promotes subjective commitment. Additional studies of verbal sexual coercion in committed romantic relationships are needed.
“You can't Hustle All Your Life”: An Exploratory Investigation of the Exit Process Among Street-Level Prostituted Women
Authors: Dalla Rochelle L.
Published: August 2006

Between 1998 and 1999, 43 street-level prostituted women were interviewed regarding their developmental experiences, including prostitution entry, maintenance, and exit attempts. Three years later, 18 of the original 43 participants were located and interviewed. This exploratory follow-up investigation focused on the women's life experiences between the two points of contact, with emphasis on sex-industry exit attempts. Five women had maintained their exit efforts and had not returned to prostitution, nine had returned to both prostitution and drug use, and one had returned to prostitution only. Three additional women had violated parole and been reincarcerated. Themes evident among those who were able to stay out of prostitution and refrain from substance use are compared to those whose exit attempts had not been successful. Suggestions for intervention and outreach are presented, as are directions for future work.
How Does it End? Women Project the Outcome of a Sexual Assault Scenario
Authors: Masters N. Tatiana , Norris Jeanette , Stoner Susan A. , George William H.
Published: August 2006

Content and thematic analyses were used to examine women's written responses to a hypothetical attempted sexual assault. A community sample ( N = 371) participated in an experiment examining the effects of alcohol on sexual assault resistance. Women received a high-dose alcohol, low-dose alcohol, placebo, or control beverage and then projected themselves into a dating scenario culminating in an attempted sexual assault. Participants wrote their own endings to the story, which were analyzed qualitatively. Content analysis found that verbal and physical assertiveness were the most frequently described actions; calling out for help was less frequent. Three major themes emerged from story endings: gendered sexuality, interpersonal concerns, and empowerment. Findings included contrasting elements: Women's projected outcomes to the sexual assault scenario involved both traditional and alternative sexual scripts. Results supported the position that the current social construction of heterosexuality plays a role in high acquaintance sexual assault rates. Implications for developing effective antirape programs and for sexual assault research are discussed.
Development of microsatellite markers for the Manila clam Ruditapes philippinarum
Authors: YASUDA N. , NAGAI S. , YAMAGUCHI S. , LIAN C. L. , HAMAGUCHI M.
Published: August 2006

We isolated nine polymorphic microsatellites from the Manila clam Ruditapes philippinarum. These loci provide one class of highly variable genetic marker as the number of alleles ranged from six to 22, and the observed and expected heterozygosity ranged from 0.136 to 0.909 and from 0.553 to 0.954, respectively. We consider that these loci are potentially useful for detailing the genetic structure and gene flow among R. philippinarum populations.
IFNγ expression inhibits LHBs storage disease and ground glass hepatocyte appearance, but exacerbates inflammation and apoptosis in HBV surface protein‐accumulating transgenic livers
Authors: Reifenberg Kurt , Hildt Eberhard , Lecher Bernd , Wiese Elena , Nusser Petra , Ott Sibylle , Yamamura Ken‐Ichi , Rutter Gabriel , Löhler Jürgen
Published: August 2006

Abstract: Background/Aims: Interferon γ (IFNγ) controls hepatitis B virus replication. As systemic application may cause severe adverse effects, approaches of liver‐directed IFNγ gene therapy may represent an attractive alternative for treatment of chronic viral hepatitis B and thus needs testing in vivo in suitable animal models.

Methods: We therefore crossbred Alb‐1HBV transgenic mice overexpressing the large HBV surface protein (LHBs) in their livers and developing LHBs storage disease and ground glass hepatocyte appearance with SAP‐IFNγ transgenic animals previously shown to exhibit constitutive hepatic IFNγ expression, and analyzed the resulting double‐transgenic offspring.

Results: We found that IFNγ coexpression significantly reduced hepatic LHBs expression and thereby inhibited hepatocellular LHBs storage disease and ground glass hepatocyte appearance. The beneficial antiviral IFNγ effects as observed in Alb1‐HBV SAP‐IFNγ double‐transgenic livers were associated with significantly elevated serum ALT concentrations, massive mononuclear cell infiltrates, appearance of Councilman bodies, and increased α‐PARP (poly(ADP‐ribose) polymerase cleavage).

Conclusions: Exacerbation of hepatic necroinflammation and increased hepatocellular apoptosis rate in IFNγ‐expressing Alb1‐HBV transgenic livers suggest that special precautions be taken for testing approaches of liver‐specific IFNγ expression in patients with chronic hepatitis B.
Growth inhibitory effects of pegylated IFN α‐2b on human liver cancer cells in vitro and in vivo
Authors: Yano Hirohisa , Ogasawara Sachiko , Momosaki Seiya , Akiba Jun , Kojiro Sakiko , Fukahori Suguru , Ishizaki Hironori , Kuratomi Keitaro , Basaki Yuji , Oie Shinji , Kuwano Michihiko , Kojiro Masamichi
Published: August 2006

Abstract: Purpose: We investigated the effects of pegylated IFN‐α2b (PEG‐IFN‐α2b) on the growth of human liver cancer cells.

Methods: The effect of PEG‐IFN‐α2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN‐α receptor‐2 (IFNAR‐2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK‐1B) cultured with PEG‐IFN‐α2b. After HAK‐1B cells were transplanted into nude mice, various doses of PEG‐IFN‐α2b or IFN‐α2b were administered, and tumor volume, weight, histology, and IFNAR‐2 expression were examined.

Results: PEG‐IFN‐α2b inhibited the growth of nine cell lines with apoptosis in a dose‐ and time‐dependent manner. Continuous contact with PEG‐IFN‐α2b induced time‐dependent growth inhibition and down‐regulation of IFNAR‐2 expression. PEG‐IFN‐α2b induced a dose‐dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR‐2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG‐IFN‐α2b was significantly stronger than that of non‐PEG‐IFN‐α2b in vivo.

Conclusions: Continuous contact with PEG‐IFN‐α2b induces strong antitumor effects and the down‐regulation of IFNAR‐2 in HCC cells. The data suggest potential clinical application of PEG‐IFN‐α2b for the prevention and treatment of HCC.
Endotoxin tolerance in human intrahepatic biliary epithelial cells is induced by upregulation of IRAK‐M
Authors: Harada Kenichi , Isse Kumiko , Sato Yasunori , Ozaki Satoru , Nakanuma Yasuni
Published: August 2006

Abstract: Background/Aim: Biliary epithelial cells possess an innate immune system consisting of Toll‐like receptors (TLRs). Although the human bile contains lipopolysaccharide (LPS) in normal as well as diseased livers, LPS physiologically does not elicit an inflammatory response in the biliary tree. This absence of a response to LPS could be due to the ‘endotoxin tolerance’ speculated to maintain innate immune homeostasis in organs. Our aim here is to clarify the presence and molecular mechanisms of endotoxin tolerance of biliary epithelium.

Methods and Results: In nuclear factor‐κB (NF‐κB)‐DNA binding assays using three‐cultured human intrahepatic biliary epithelial cell (HIBEC) lines, all the cells responded to LPS (TLR4 ligand) by activating NF‐κB, but pretreatment with LPS for 24 h effectively induced tolerance against any subsequent stimulation with LPS (endotoxin tolerance). This tolerance was also induced by pretreatment with Pam3Cys‐Ser‐(Lys)4 trihydrochloride (Pam3CKS4, TLR1/2 ligand). Then, real‐time polymerase chain treaction and Western blotting revealed that LPS treatment upregulated the expression of IRAK‐M (a negative regulator of TLR signaling), but did not affect interleukin‐1 receptor‐associated kinase‐1 (IRAK‐1, an essential molecule of TLR signaling), in HIBECs. Moreover, immunohistochemistry revealed that IRAK‐M was diffusely expressed in intrahepatic bile ducts.

Conclusions: This study showed that the mechanism of endotoxin tolerance exists in the intrahepatic biliary tree and is possibly induced by the expression of IRAK‐M in the intrahepatic biliary epithelium, suggesting that the endotoxin tolerance is important in maintaining innate immune biliary homeostasis.
Anti‐irritants I: dose–response in acute irritation
Authors: Andersen Flemming , Hedegaard Kathryn , Petersen Thomas Kongstad , Bindslev‐Jensen Carsten , Fullerton Ann , Andersen Klaus Ejner
Published: August 2006

The term ‘anti‐irritant’ (AI) was coined in 1965 by Goldemberg to describe a diverse group of topical product ingredients, which were able to reduce the irritation potential of other more irritating ingredients in the same product. ‘AIs’ are being added to cosmetic formulations in order, allegedly, to benefit tolerability of the products and allow claims such as ‘soothing’ and ‘healing’ ingredients. Limited documentation in favour of the efficacy of AIs is published. We studied the dose‐related effect of 4 alleged AIs (nifedipine, (–)‐α‐bisabolol, canola oil and glycerol) on experimentally induced acute irritation in healthy volunteers. Each AI was used in 3 concentrations. Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate and 20% nonanoic acid in N‐propanol. The irritant reactions were treated twice daily with AI‐containing formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments were performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colourimetry. Only glycerol showed dose–response and effects potentially better than no treatment. There was no significant effect and no difference between the three other AIs.
Allergic contact dermatitis caused by epoxy resin systems in industrial painters
Authors: RøMyhr Olve , Nyfors Allan , Leira Håkon Lasse , Smedbold Hans Thore
Published: August 2006

A group of industrial painters employed in 6 companies of the Norwegian oil industry was followed to assess the incidence of allergic contact dermatitis (ACD) caused by exposure to epoxy resin systems. The study lasted from 1 September 1997 to 31 August 2001 and included 2236 workers, contributing 5113 person years. Commercially available patch test series were supplemented with a special study series based on known or suspected sensitizers present at the workplaces. Of 57 patch‐tested workers, 23 with ACD caused by epoxy resin systems were found, indicating an incidence rate of 4.5/1000 person years. In our study patch test series, 4 workers (17%) were identified solely by patch tests to 2,4,6‐tris‐(dimethylaminomethyl)phenol (tris‐DMP), m‐xylene‐α,α‐diamine (XAD), and/or 2,2,4 trimethylhexamethylenediamine. Positive patch tests to tris‐DMP and XAD were seen in 7 and 8 workers, respectively, indicating that the 2 chemicals are important sensitizers in industrial painters. They are, however, not classified as skin sensitizers according to the European regulations on the classification and labelling of dangerous chemicals. The results show the usefulness of including patch tests based on an investigation of known and suspected skin sensitizers present at the workplaces.
An evaluation of dose/unit area and time as key factors influencing the elicitation capacity of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in MCI/MI‐allergic patients
Authors: Zachariae Claus , Lerbæk Anne , McNamee Pauline M. , Gray John E. , Wooder Mike , Menné Torkil
Published: August 2006

Methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) contact allergy affects 1–3% of patch‐tested patients in European centres. The aim of the present study was to evaluate the importance of the factors – time and concentration (dose/per unit area) – in the elicitation capacity by means of a repeated open application test (ROAT) experimental design. The study was designed as a double‐blind, placebo‐controlled, dose–response ROAT preceded by a diagnostic patch testing. 25 subjects with confirmed MCI/MI allergy and 10 healthy, non‐MCI/MI allergic control subjects were exposed to 0.025 μg/cm2 (2 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. After a wash‐out period of at least 4 weeks, the subjects were exposed to 0.094 μg/cm2 (7.5 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. The study showed the importance of both time and exposure in the elicitation process. It demonstrated that the elicitation threshold for MCI/MI is expected to be in the proximity of 0.025 μg/cm2 although it was not possible to establish a definitive elicitation threshold for MCI/MI in this study.
Brown trout fry move inshore at night: a choice of water depth or velocity?
Authors: Bardonnet A. , Poncin P. , Roussel J.‐M.
Published: August 2006

Abstract –  The instream positions of brown trout fry differ between daylight and darkness. According to field and laboratory observations, recently emerged 0+ brown trout use shallow and slow‐flowing areas close to the bank at night and tend to move off‐shore during daylight. In laboratory channels, we tested whether the use of habitats close to the river bank could be attributed to a choice of either water depth or velocity. In two complementary experiments, emerging brown trout alevins were given the choice of using shallow‐slow or deep‐swift habitats (experiment 1), and deep‐slow or shallow‐swift habitats (experiment 2). At night, a persistent preference for the shallow habitats was displayed, regardless of velocity. It was concluded that swim‐up brown trout fry respond to shallowness rather than ambient low water velocity when selecting habitats close to the bank at night. The behavioural significance of this result and implications for river management are discussed.
1,25(OH)2Vitamin D3 induces elevated expression of the cell cycle inhibitor p18 in a squamous cell carcinoma cell line of the head and neck
Authors: Gedlicka Claudia , Hager Gudrun , Weissenböck Martina , Gedlicka Wilhelm , Knerer Birgit , Kornfehl Johannes , Formanek Michael
Published: August 2006

Background:  1α,25‐Dihydroxyvitamin D3 [1,25(OH)2 Vitamin D3] induces growth inhibition in squamous cell carcinoma (SCC) cell lines of the head and neck by arresting the cells in the G0/G1 phase of the cell cycle, probably due to an enhanced expression of p21, which could be demonstrated in other cell lines (JPPA, SCC9) before. In SCC25, a SCC cell line isolated from tongue, growth inhibition but no overexpression of p21 was detected. The retinoblastoma gene, as a direct target of G1 cyclin–CDK complexes, showed an obvious shift from the hyperphosphorylated to the hypophosphorylated form under 1,25(OH)2Vitamin D3, which indicates that the growth inhibition takes place in the G0/G1 phase. To explore the possible pathway of growth inhibition in SCC25 we investigated other cell cycle inhibitors (p18, p19, p27).

Methods:  Synchronized cells were treated with 1,25(OH)2Vitamin D3 over 96 h. The cell cycle status and expression of cell cycle‐regulating proteins was determined by fluorescence‐activated cell sorting (FACS) and Western blotting.

Results:  An overexpression of p18 in 1,25(OH)2Vitamin D3 vs. ethanol‐treated cells was determined until 30 h in SCC25. No influence was detectable on the expression of p27 and p19.

Conclusion:  One mechanism by which 1,25(OH)2Vitamin D3 controls cell growth might be the upregulation of p21. As p21 was unsusceptible to 1,25(OH)2Vitamin D3 in SCC25, other inhibiting proteins were necessary to be tested. The proven upregulation of p18 seems to be the responsible step for growth inhibition of 1,25(OH)2Vitamin D3 in SCC25.
Dyskeratosis congenita: oral hyperkeratosis in association with lichenoid reaction
Authors: Handley T. P. B. , Ogden G. R.
Published: August 2006

Dyskeratosis congenita is an inherited disorder that usually presents in males, consisting of a triad of leukoplakia of the mucous membranes, nail dystrophy and skin pigmentation. Whilst most cases are X‐linked, autosomal dominant and recessive forms have also been reported. The significance of the condition lies in premature mortality arising from either bone marrow failure or malignant change within the areas of mucosal leukoplakia. We present a case (X‐linked recessive form) where the classic triad of signs were present, along with the development of lichenoid reaction in the buccal and labial mucosa. This is believed to be the first case in which such a reaction has been noted together with the oral hyperkeratosis. The identification of a white patch within the mouth of a child, in the absence of any other obvious cause must arouse suspicion of this rare condition. All clinicians should be aware of this rare genetic disorder so that early referral can be made and appropriate management instigated.
Quantitative evaluation of tissue invasion by wild type, hyphal and SAP mutants of Candida albicans, and non‐albicans Candida species in reconstituted human oral epithelium
Authors: Jayatilake J. A. M. S. , Samaranayake Y. H. , Cheung L. K. , Samaranayake L. P.
Published: August 2006

Background:  Oral candidiasis is a common problem in compromised patients. Although several non‐albicans Candida species have emerged as pathogens the majority of candidal infections are caused by Candida albicans. Morphogenesis from the blastospore to filamentous phase, and production of secretory aspartyl proteinases (SAP) are two major virulence attributes of these opportunistic yeast. Histopathology of oral candidiasis is characterized by fungal invasion of the superficial epithelium although the invasive potentials of different Candida species vary. Computerized image analysis systems (IAS) utilizing immunohistochemistry have been successfully employed for quantification of such histopathological features. The purpose of this study was to evaluate quantitatively the in vitro invasive potential of C. albicans and its hyphal and SAP mutants, and five other non‐albicans Candida species using a computerized IAS.

Methods:  In vitro human oral candidiasis was produced using five wild type and one reference C. albicans isolates, hyphal and SAP mutants of C. albicans SC 5314, and one wild type and one reference isolate each of C. tropicalis, C. dubliniensis, C. glabrata, C. parapsilosis and C. krusei in a reconstituted human oral epithelium (RHOE) model. The infected tissues were examined histologically at 12, 24 and 48 h. Invading fungal elements were visualized by periodic acid‐Schiff (PAS) staining and quantitatively evaluated as a percentage of total tissue invasive area, using a computerized IAS.

Results:  All C. albicans isolates including hyphal mutant cph1/cph1 and SAP mutants; sap 1–3, sap 4–6 produced hyphae and differentially (P < 0.05) invaded the tissue over 48 h. The invasive potential of hyphal mutant cph1/cph1 and SAP mutants (sap 1–3, sap 4–6) were similar to the parent wild‐type isolate at 12 h although after 24 h their invasion was dissimilar (P < 0.05). Non‐albicans Candida species and hyphal mutants; efg1/efg1, efg1/efg1 cph1/cph1 were all non‐invasive.

Conclusions:  RHOE model in combination with computerized image analysis permits for the first time, the assessment of invasive potential of Candida species in a quantitative manner. The differential tissue invasive patterns of various C. albicans isolates, their mutants and other Candida species are also described.
Effects on leg muscular performance from whole‐body vibration exercise: a systematic review
Authors: Rehn B. , Lidström J. , Skoglund J. , Lindström B.
Published: August 2006

The purpose of this study was to investigate the effects on leg muscular performance from whole‐body vibration exercise. Literature search was performed on the databases Pubmed, Cinahl, ISI web of science (Sci‐expanded, SSCI) and Embase (Rehab & Physical Med). Rating of 19 relevant studies was performed (14 on long‐term exercise and five on short‐term exercise) using a score system for the methodological quality. Several randomized‐controlled trial studies of high to moderate quality show similar improvements from long‐term regimen on muscular performance in the legs after a period of whole‐body vibration exercise. As there were few studies on short‐term exercise and as they had no control groups, the same convincing improvements regarding muscular performance were not achieved. Preliminarily, there is strong to moderate evidence that long‐term whole‐body vibration exercise can have positive effects on the leg muscular performance among untrained people and elderly women. There is no clear evidence for effects on muscular performance after short‐term vibration stimuli.
Molecular Dissection of the Munc18c/Syntaxin4 Interaction: Implications for Regulation of Membrane Trafficking
Authors: Latham Catherine F. , Lopez Jamie A. , Hu Shu‐Hong , Gee Christine L. , Westbury Elizabeth , Blair Duncan H. , Armishaw Chris J. , Alewood Paul F. , Bryant Nia J. , James David E. , Martin Jennifer L.
Published: August 2006

Sec1p/Munc18 (SM) proteins are believed to play an integral role in vesicle transport through their interaction with SNAREs. Different SM proteins have been shown to interact with SNAREs via different mechanisms, leading to the conclusion that their function has diverged. To further explore this notion, in this study, we have examined the molecular interactions between Munc18c and its cognate SNAREs as these molecules are ubiquitously expressed in mammals and likely regulate a universal plasma membrane trafficking step. Thus, Munc18c binds to monomeric syntaxin4 and the N‐terminal 29 amino acids of syntaxin4 are necessary for this interaction. We identified key residues in Munc18c and syntaxin4 that determine the N‐terminal interaction and that are consistent with the N‐terminal binding mode of yeast proteins Sly1p and Sed5p. In addition, Munc18c binds to the syntaxin4/SNAP23/VAMP2 SNARE complex. Pre‐assembly of the syntaxin4/Munc18c dimer accelerates the formation of SNARE complex compared to assembly with syntaxin4 alone. These data suggest that Munc18c interacts with its cognate SNAREs in a manner that resembles the yeast proteins Sly1p and Sed5p rather than the mammalian neuronal proteins Munc18a and syntaxin1a. The Munc18c–SNARE interactions described here imply that Munc18c could play a positive regulatory role in SNARE assembly.
Genetic variation in the hypothalamic–pituitary–adrenocortical axis regulatory factor, T‐box 19, and the angry/hostility personality trait
Authors: Wasserman D. , Geijer T. , Sokolowski M. , Rozanov V. , Wasserman J.
Published: August 2006

Neurotic personality traits are important factors in several psychiatric disorders and suicidal behavior. Here, we have investigated the existence of potential relationships between neurotic personality traits and genetic variation. Non‐suicidal parents derived from trios (suicide attempter and both parents) and non‐suicidal volunteers, examined by the Neuroticism, Extraversion and Openness (NEO) Personality Inventory – Revised (NEO PI‐R), were divided into screening and replication samples. The screening sample (n= 127) was used to select potential relationships between neurotic personality traits and genetic variation among 130 single nucleotide polymorphisms (SNPs). Screening (analysis of variance) with regard to the personality dimension neuroticism indicated potential relationships at three different loci. More detailed analysis of these three SNPs at NEO PI‐R facet level indicated four potential relationships. T‐test analysis in the replication sample (n= 617) was used to retest the relationships indicated during screening. One of those relationships was confirmed in the replication sample (P= 0.0052; Bonferroni correction), indicating that genetic variation at the human T‐box 19 (TBX19) locus is related to the personality trait angry/hostility. Furthermore, using analysis of haplotypes among trios by transmission disequilibrium test and its extension, the family‐based association test, overtransmission of a haplotype GAC at the TBX19 locus was associated with increased angry/hostility scores among suicide attempters (P= 0.009; Bonferroni correction). This is to our knowledge the first report on the association of the angry hostility personality trait with genetic variation at the TBX19 locus, an important regulator of the hypothalamic–pituitary–adrenocortical axis.