bluuebunny/crossref_metadata_2025 huggingface dataset:
A prospective study of macrophage migration inhibitory factor as a marker of inflammatory detection
Authors: Zhang Chao , Hou Guihua , Liang Ting , Song Jing , Qu Lili , Chen Fuqiang , Xu Jia , Wang Dan , Han Jiankui
Published: October 2008

This study was to evaluate whether macrophage migration inhibitory factor (MIF) can be used as a better marker of inflammatory detection through the biodistribution and inflammatory imaging study with 131I‐labelled anti‐MIF McAb and control antibody in inflammatory model mice. The mRNA and protein expression of MIF in inflammatory lesions were proved by RT‐PCR and immunohistochemistry. The model mice were injected with 3.7 MBq of each agent and killed at 24, 48 and 72 hrs after injection. Whole‐body images were obtained with storage phosphor screen. The organs, blood, abscesses muscles were removed, weighed and counted with a γ counter. The percentage of uptake by organs and per gram tissues and abscess/normal tissue (%ID/g) concentration ratios were calculated. The abscesses in mice were well visualized from 24 hrs. The target‐to‐non‐target (T/NT) ratios were 6.71 ± 1.09 (24 hrs), 8.57 ± 0.81 (48 hrs) and 11.41 ± 0.37 (72 hrs) for 131I‐labelled anti‐MIF McAb group; while in control group of 131I‐IgG, T/NT ratios were 4.65 ± 0.63 (24 hrs), 6.44 ± 0.60 (48 hrs) and 8.23 ± 0.35 (72 hrs) (P < 0.05). MIF mRNA expression was threefold increased in inflammatory tissues at 24 hrs compared with normal tissues, and twofold increased at 48 hrs. MIF protein expression was stronger in the inflammatory tissues at 48 hrs after focal inflammation occurred. Our findings suggest that the 131I‐labelled anti‐MIF McAb appears to be more specific and suitable than 131I‐labelled IgG for targeting focal inflammation, which means MIF can be used as a better marker of inflammatory detection.
Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt‐mediated HIF‐1α up‐regulation and MMP9 activation
Authors: Song Gang , Ouyang Gaoliang , Mao Yubin , Ming Yanlin , Bao Shideng , Hu Tianhui
Published: October 2008

Osteopontin (OPN) is a secreted, integrin‐binding matrix phosphorylated glycoprotein. OPN has been shown to facilitate the progression and metastasis of malignancies and has prognostic value in several types of cancer, including gastric cancer. However, the functional mechanism of OPN mediated metastatic growth in gastric cancer remains unclear. Here, using multiple in vitro and in vivo models, we report that OPN strongly promoted the progression and metastasis of gastric cancer. Immunohistochemical staining revealed that OPN, matrix metalloproteinase (MMP)9 and hypoxia‐inducible factor (HIF)‐1α have statistically significant different expression patterns between well‐ and poorly differentiated tissue samples (P < 0.05). Correlations existed between OPN and MMP9, and between OPN and HIF‐1α (r1= 0.872, p1 < 0.01 and r2= 0.878, p2 < 0.01). Furthermore, OPN dramatically increased colony formation and invasion of gastric cancer cells in vitro and promoted tumour growth and metastasis in vivo. In addition, OPN potently protected gastric cancer cells from serum depletion‐induced apoptosis. Further study shows that OPN activated phosphoinositide 3‐kinase/Akt survival pathway and up‐regulated HIF‐1αvia binding to αvβ3 integrins in gastric cancer cells. Moreover, we found that OPN could activate MMP9 and up‐regulate MMP2. Taken together, our results suggest that the survival‐promoting function is crucial for OPN to promote the development of gastric cancer, and HIF‐1α and MMP9 may play key roles during this process. Thus, targeting OPN and its related signalling network may develop an effective therapeutic approach for the management of gastric cancer.
The polyubiquitin Ubc gene modulates histone H2A monoubiquitylation in the R6/2 mouse model of Huntington's disease
Authors: Bett John S. , Benn Caroline L. , Ryu Kwon‐Yul , Kopito Ron R. , Bates Gillian P.
Published: October 2008

Huntington's disease (HD) is an inherited neurodegenerative disease caused by the expansion of a polyglutamine tract in the protein huntingtin (htt). HD brains are characterized by the presence of ubiquitin‐positive neuronal inclusion bodies, suggesting that disturbances in the distribution of cellular ubiquitin may contribute to disease pathology. The fact that several neurodegenerative diseases are caused by mutations in ubiquitin‐processing enzymes and that the polyubiquitin genes are required for resistance to cellular stress led us to investigate the effect of perturbing the ubiquitin system in HD. We crossed R6/2 transgenic HD mice with heterozygous polyubiquitin Ubc knockout mice (Ubc+/−) and assessed the effect on the R6/2 neurological phenotype. Although the R6/2 phenotype was largely unaffected, surprisingly we observed some subtle improvements in various behavioural activities correlating with heterozygous Ubc knockout. Interestingly, immunoblot analysis revealed that the levels of monoubiquitylated histone H2A (uH2A), a modification associated with gene repression, were significantly increased in the brains of R6/2 mice. Furthermore, the reduction of Ubc expression in R6/2; Ubc+/− mice largely prevented this increase in uH2A levels. However, we were not able to show by the use of a limited number of quantitative RT‐PCR assays that changes in the amount of uH2A in the R6/2‐Ubc mice had an effect on disease‐associated transcriptional abnormalities. These results suggest that the expression of aggregation‐prone mutant htt causes disturbances to the ubiquitin system, which may contribute to disease due to the diverse and important roles of ubiquitin.
Nutritional channels in breast cancer
Authors: Godoy Alejandro , Salazar Katherine , Figueroa Carlos , Smith Gary J. , de los Angeles Garcia Maria , Nualart Francisco J.
Published: October 2008

Breast cancers increase glucose uptake by increasing expression of the facilitative glucose transporters (GLUTs), mainly GLUT1. However, little is known about the relationship between GLUT1 expression and malignant potential in breast cancer. In this study, expression and subcellular localization of GLUT1 was analysed in vivo in breast cancer tissue specimens with differing malignant potential, based on the Scarff‐Bloom‐Richardson (SBRI, II, III) histological grading system, and in vitro in the breast cancer cell lines, MDA‐MB‐468 and MCF‐7, and in MDA‐MB‐468 cells grown as xenografts in nude athymic BALB/c male mice. In situ hybridization analyses demonstrated similar levels of GLUT1 mRNA expression in tissue sections from breast cancers of all histological grades. However, GLUT1 protein was expressed at higher levels in grade SBRII cancer, compared with SBRI and SBRIII, and associated with the expression of the proliferation marker PCNA. Immunolocalization analyses in SBRII cancers demonstrated a preferential localization of GLUT1 to the portions of the cellular membrane that faced neighbouring cells and formed ‘canaliculi‐like structures’, that we hypothesize could have a potential role as ‘nutritional channels’. A similar pattern of GLUT1 localization was observed in confluent cultures of MDA‐MB‐468 and MCF‐7, and in MDA‐MB‐468 cells grown as xenografts, but not in the normal breast epithelial cell line HMEC. However, no relationship between GLUT1 expression and malignant potential of human breast cancer was observed. Preferential subcellular localization of GLUT1 could represent a physiological adaptation of a subset of breast cancer cells that form infiltrative tumours with a nodular growth pattern and that therefore need a major diffusion of glucose from blood vessels.
Intracardiac injection of erythropoietin induces stem cell recruitment and improves cardiac functions in a rat myocardial infarction model
Authors: Klopsch Christian , Furlani Dario , Gäbel Ralf , Li Wenzhong , Pittermann Erik , Ugurlucan Murat , Kundt Guenther , Zingler Christiana , Titze Ulf , Wang Weiwei , Ong Lee‐Lee , Wagner Klaus , Li Ren‐Ke , Ma Nan , Steinhoff Gustav
Published: October 2008

Erythropoietin (EPO) protects the myocardium from ischaemic injury and promotes beneficial remodelling. We assessed the therapeutic efficacy of intracardiac EPO injection and EPO‐mediated stem cell homing in a rat myocardial infarction (MI) model. Following MI, EPO (3000 U/kg) or saline was delivered by intracardiac injection. Compared to myocardial infarction control group (MIC), EPO significantly improved left ventricular function (n= 11–14, P< 0.05) and decreased right ventricular wall stress (n= 8, P< 0.05) assessed by pressure‐volume loops after 6 weeks. MI‐EPO hearts exhibited smaller infarction size (20.1 ± 1.1%versus 27.8 ± 1.2%; n= 6–8, P< 0.001) and greater capillary density (338.5 ± 14.7 versus 259.8 ± 9.2 vessels per mm; n= 6–8, P< 0.001) than MIC hearts. Direct EPO injection reduced post‐MI myocardial apoptosis by approximately 41% (0.27 ± 0.03%versus 0.42 ± 0.03%; n= 6, P= 0.005). The chemoattractant SDF‐1 was up‐regulated significantly assessed by quantitative realtime PCR and immunohistology. c‐Kit+ and CD34+ stem cells were significantly more numerous in MI‐EPO than in MIC at 24 hrs in peripheral blood (n= 7, P< 0.05) and 48 hrs in the infarcted hearts (n= 6, P< 0.001). Further, the mRNAs of Akt, eNOS and EPO receptor were significantly enhanced in MI‐EPO hearts (n= 7, P< 0.05). Intracardiac EPO injection restores myocardial functions following MI, which may attribute to the improved early recruitment of c‐Kit+ and CD34+ stem cells via the enhanced expression of chemoattractant SDF‐1.
The effect of antifungal agents and human monocytes on in vitro galactomannan release by Aspergillus spp. in liquid culture medium
Authors: WINN RICHARD M. , WARRIS ADILIA , GAUSTAD PETER , ABRAHAMSEN TORE G.
Published: October 2008

Invasive pulmonary aspergillosis is increasing in incidence in immunosuppressed patients. Diagnosis of this infection is problematic, relying on clinical suspicion and computerized tomography of the thorax and sinuses. An assay capable of detecting the fungal cell wall component galactomannan (GM) as a sign of Aspergillus infection is in use in patients with hematological malignancies. The aim of this study was to investigate the release of GM during growth of two medically important species, Aspergillus fumigatus and Aspergillus terreus, in liquid medium, including interaction with fluconazole, amphotericin B, liposomal amphotericin B and itraconazole, as well as human monocytes. Our results showed that for both species, amphotericin B deoxycholate, liposomal amphotericin B and itraconazole reduced the concentrations of GM to very low levels at the lowest doses tested (1, 3 and 4 μg/L, respectively). High doses of fluconazole had negligible effect on GM release by A. terreus, as expected. However, fluconazole at 128 μg/L increased GM concentrations released by A. fumigatus without reduction in visible growth. Co‐incubation with human monocytes had no significant effect on GM release. The effects of antifungal agents on GM release may have diagnostic implications.
Mutational analysis of NOTCH1, 2, 3 and 4 genes in common solid cancers and acute leukemias
Authors: LEE SUNG HAK , JEONG EUN GOO , YOO NAM JIN , LEE SUG HYUNG
Published: October 2008

NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain‐of‐function mutations of the NOTCH1 gene in T‐cell acute lymphoblastic leukemias (ALL). To see whether NOTCH1 mutation occurs in other malignancies, we analyzed NOTCH1 for the detection of somatic mutations in 334 malignancies, including 48 lung, 48 breast, 48 colorectal and 48 gastric carcinomas, and 142 acute leukemias (105 acute myelogenous leukemias, 32 B‐ALLs and 4 T‐ALLs) by single‐strand conformation polymorphism assay. Also, to see whether other NOTCH genes harbor somatic mutations, we analyzed NOTCH2, NOTCH3 and NOTCH4 genes in the same tissue samples. Overall, we detected three NOTCH mutations in the cancers, which consisted of one NOTCH1 mutation in the T‐ALLs (25.0%), one NOTCH2 mutation in the breast carcinomas (2.1%), and one NOTCH3 mutation in the colorectal carcinomas (2.0%). There was no NOTCH mutation in other malignancies analyzed. Our data indicate that NOTCH1 is mutated in T‐ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. Despite the importance of NOTCH activation in many types of human cancers, mutation of NOTCH genes, except for NOTCH1 mutation in T‐ALL, may not play an important role in the tumorigenesis of common cancers.
CuZn‐SOD suppresses the bovine papillomavirus‐induced proliferation of fibroblasts
Authors: RAUSALU KAI , KARO‐ASTOVER LIIS , KILK ANN , USTAV MART
Published: October 2008

Eukaryotic cells continuously produce reactive oxygen species (ROS) and have mechanisms to control ROS levels. ROS have been shown to mediate cell proliferation and transformation. We studied the effect of CuZn‐superoxide dismutase (CuZnSOD) on the focus‐forming ability of bovine papillomavirus (BPV‐1) wtDNA and hypertransforming mutant of its major oncoprotein E5, E5–17S. We found that CuZnSOD suppresses the focus‐forming ability of BPV‐1 wtDNA and E5 oncoprotein. Significantly fewer foci were detected in pCGCuZnSOD‐ and BPV‐1 DNA‐cotransfected cell culture compare to BPV‐1 DNA‐transfected cell culture (p<0.001). CuZnSOD decreases the rate of cell proliferation in both non‐transformed C127 and BPV‐1‐ and E5‐transformed cell lines. CuZnSOD decelerates cell entry into the S phase of the cell cycle and has a suppressing effect on the actively dividing cells. As the transformed cells proliferate faster than normal cells when confluent, CuZnSOD inhibits the growth of foci. These results indicate that superoxide radicals may be involved in signaling for cell proliferation and that SOD suppresses cell proliferation.
Evaluation of several fluoroquinolones and beta‐lactams in terms of their capability to restrict the selection of fluoroquinolone‐resistant Salmonella: in vitro models
Authors: CEBRÍÁN L. , RODRÍGUEZ J. C. , ESCRIBANO I. , ROYO S. G.
Published: October 2008

With a view to understanding the interaction between Salmonella and the drugs used to treat it, our aim was to compare the different capacities of various antibiotics to generate mutants resistant to fluoroquinolones following repeated exposure of the microorganisms to subinhibitory concentrations of these drugs. Mutants were generated by repeated exposure to fluoroquinolones and beta‐lactams. In order to compare the different capacity to generate resistant mutants, we studied the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of the wild‐type strains and of the mutants generated. These data were compared with pharmacokinetic parameters. Mutants generated following repeated exposure to fluoroquinolones exhibit an increased MPC as compared to the wild‐type strains, both in strains that are nalidixic acid susceptible and in those that are nalidixic acid resistant, with repeated exposure to ciprofloxacin leading to the smallest increases. This increase in MPC is gradual and depends on the number of exposures the bacteria are subjected to. It results in a decrease in the AUC/MPC ratio, although the absolute values vary. Ciprofloxacin is the most active drug, both against nalidixic acid‐susceptible and nalidixic acid‐resistant strains, although in late mutants of originally nalidixic acid‐resistant strains, the AUC/MPC values are low. Repeated exposure to amoxicillin and cefotaxime also produces an increase in the MPC of fluoroquinolones, with ciprofloxacin being the least affected. Exposure to amoxicillin leads to the greatest increase in the MPC of fluoroquinolones. When the AUC/MPC ratios of these mutants are compared, the values are still seen to be high (between 25 and 75). When we compare the MPC data with the antibiotic levels in humans following administration of the usual doses, it can be seen that ciprofloxacin exhibits the highest AUC/MPC and therefore the lowest risk of therapeutic failures. In addition, administration of subinhibitory concentrations of beta‐lactams produces a decrease in fluoroquinolone susceptibility, which may lead to an increase in the risk of therapeutic failure if these compounds are subsequently used.
A new map of Qâni’ (Yemen)
Authors: Mouton Michel , Sanlaville Paul , Suire Joël
Published: October 2008

Qâni’, the main seaport for the export of goods from South Arabia, was founded by the Hadramawt kingdom in the first century BC. A geomorphological survey and a general surface reconnaissance of Qâni’ have revealed a new image of the site. Originally a royal entrepôt in a fortress on an ancient island, separated from the mainland by a silted channel lined with a mangrove forest, Qâni’ gradually grew and spread around the beach fronting the mooring place of the trade ships that arrived by sea. Sacred spaces, cemeteries, dwellings and trade quarters appear to be well‐defined areas forming a real town within the limits imposed by the surrounding sea.
The inscription of Zuhayr, the oldest Islamic inscription (24 AH/AD 644–645), the rise of the Arabic script and the nature of the early Islamic state1
Authors: Ghabban ‘Ali ibn Ibrahim ,   Translation and concluding remarks by, Hoyland Robert
Published: October 2008

This article provides an edition, translation and analysis of an inscription dated 24 AH (644 AD) discovered recently in north‐west Saudi Arabia. It is an immensely important find, since it is our earliest dated Arabic inscription; it apparently contains a reference to the caliph ‘Umar I and shows evidence of a fully‐fledged system of diacritical marks. The latter aspect is of great significance for our understanding of the development of the Arabic script and of the writing down of Arabic texts, especially the Qur’an. The text is compared with others composed in the decades shortly before and after the rise of Islam.
Early Dilmun and its rulers: new evidence of the burial mounds of the elite and the development of social complexity, c. 2200–1750 BC
Authors: Laursen Steffen Terp
Published: October 2008

This paper deals with the social organisation of early Dilmun in Bahrain based on evidence from the burial mound record. Complete aerial photography survey and mapping have documented the extensive mound fields of Bahrain in their entirety and revealed a new and rare type of burial mound encircled by an outer ring wall. From the spatial distribution and appearance of these ‘ring mounds’ it is argued that they cover the time span 2200–1750 BC. It is further argued that the ring mounds reflect the entombment of a prominent segment of early Dilmun society and thus testify to the presence of a social elite as early as the late third millennium BC. The paper offers evidence supporting the view that fundamental changes in the size of the ring wall and the encircled mound occurred over time, culminating in the colossal ‘royal’ mounds near Aali village. The increase in size of the special mounds and the exclusive appearance of the type in the Aali cemetery after the emergence of ten concentrated cemeteries around 2050 BC are correlated with the already available evidence of increasing social complexity in Dilmun. Three clusters of ring mounds in Aali are argued to reflect the appearance of one or more ruling lineages that were ultimately to found the colony on Failaka, Kuwait, and rule not only Bahrain but also the adjacent coast of Saudi Arabia.
The lithic industry of Wadi Shab, a Middle Holocene site on the coast of Oman
Authors: Usai D. , Cavallari A.
Published: October 2008

One of the most tedious stages in archaeological research is that which concerns the analytical study of the hundreds and thousands of lithic, ceramic, faunal and other remains generated during the excavation of a site. Detailed descriptions of these assemblages have the advantage of becoming a tool for theoretical work and, moreover, for studies of unstratified assemblages. This paper illustrates in detail the lithic assemblage of the Neolithic/Early Bronze Age site of Wadi Shab‐GAS 1 located on the coast of the Gulf of Oman with a partial, i.e. typologically based, interpretation of the data in comparison with the overall archaeological context as it emerged from excavation. The analysis highlights a lithic assemblage that was mainly flake‐oriented, using different core‐treatment techniques and aimed at producing a range of tools of which perforators appear to be the most common. The manufacture of beads and other soft‐stone jewellery would appear to explain such a specialised industry.
Die Petrografie himyarischer Keramik vom Jabal al ‘Awd, Jemen
Authors: Zech Janine , Weiss Christian
Published: October 2008

Early Himyarite ceramics (first century BC–third century AD) from the Jabal al ‘Awd in Yemen are classified by visual criteria into a number of ware groups. Following classification the ceramics were investigated with petrologic methods (porosity and density). Mineralogical and physical properties were determined from thin sections according to cathodo‐luminescence spectra. The ceramics are divided into six ware groups, each of which has distinctive material properties and mineralogy.
Merkel cell carcinoma within follicular cysts: report of two cases
Authors: Requena Luis , Jaqueti Gerardo , Rütten Arno , Mentzel Thomas , Kutzner Heinz
Published: October 2008

Merkel cell carcinoma is a rare cutaneous neoplasm of unknown histogenesis. Several reports have described the association of Merkel cell carcinoma of the skin with other cutaneous neoplasms within the same lesion, and there are also reports describing three examples of Merkel cell carcinoma within follicular cysts. We describe two examples of Merkel cell carcinoma developed within epithelial cysts. Neoplastic cells of Merkel cell tumor expressed immunoreactivity for chromogranin, synaptophysin, neuron‐specific enolase, CAM 5.2 and cytokeratin 20, the last two markers showing the characteristic paranuclear dot‐like pattern. In contrast, the epithelial wall lining the cyst and surrounding Merkel cell tumor only expressed immunoreactivity for cytokeratin MNF116. The description of five cases of Merkel cell carcinoma within follicular cysts, including the two cases of this report, support some relationship between Merkel cell tumor and the hair follicle.
ORIGINAL ARTICLE: Characterization of Cytokine Production by Human Term Placenta Macrophages In Vitro
Authors: Pavlov Oleg , Pavlova Oksana , Ailamazyan Edouard , Selkov Sergei
Published: October 2008

Problem  Macrophages are apparently the only immune cells within placenta villi, yet functions of these cells remain obscure. It has been postulated that placental macrophages accomplish regulatory roles at the fetal–maternal interface by means of wide variety of secreted cytokines. We attempt to analyze the patterns of cytokine production in an isolated population of placental macrophages.

Method of study  Macrophages were obtained from term placentas in the absence of spontaneous labor. The basal and lipopolysaccharide (LPS)‐stimulated levels of intracellular cytokines were detected by flow cytometry. The basal cytokine secretion was determined by BD™Cytometry Bead Array (BD Biosciences, San Diego, CA, USA).

Results  Intracellular IL‐1α, IL‐1β, IL‐6, and TNFα were detected in 31, 27, 4, and 3% CD68+ cells, respectively. Stimulation with LPS increased the proportions of cytokine‐producing CD68+ cells to 48, 50, 28, and 49%, respectively. Under basal conditions, levels of released TNFα and IL‐6, respectively, were 20‐ and 25‐fold higher when compared with IL‐1β while IL‐10 was secreted in small but detectable amounts. When a secretory activity was estimated for cytokine‐producing cells, the secretion rate for TNFα and IL‐6 overwhelmingly surpassed that for IL‐1β (TNFα:IL‐6:IL‐1β ratio was 192:145:1).

Conclusion  These results suggest functional heterogeneity of the placental macrophage population and contribute to the elucidation of regulatory roles of these cells in gestation.
The Sexual Ethics of HIV Testing and the Rights and Responsibilities of Partners
Authors: Dixon‐Mueller Ruth
Published: October 2008

The discourse of much of the international AIDS community champions the rights of individuals in low‐income countries to “just say no” to routine HIV testing in health‐care settings and, if tested and found positive, not to inform their sexual partner(s) if such disclosure could result in substantial personal harm. This study contends that the right of individuals to refuse testing ignores the right of their sexual partners—male or female, regular or casual—to be informed of the health risks to which they may be exposed on entering or continuing a sexual relationship or engaging in particular sexual acts. If, as the UN has declared, all persons have the right to decide freely and responsibly on matters relating to their sexuality, including their sexual and reproductive health, free from coercion, discrimination, and violence, then all persons have the right and the responsibility to know their own and their partner's serostatus and to protect themselves and their partner(s) from sexually transmitted infections (STIs). Support by AIDS activists for policies of routine STI/HIV testing, counseling, and disclosure between both partners in a sexual relationship would help to promote an ethic of equal rights and shared responsibility for sexual behavior and its consequences.
Confidentiality Concerns with Mapping Survey Data in Reproductive Health Research
Authors: Sherman Jill E. , Fetters Tamara L.
Published: October 2008

The increasing availability of georeferenced datasets creates new opportunities to perform spatial analysis of social science and public health survey data, but also raises ethical issues regarding the potential for unintended violation of the confidentiality of respondents. This article examines these ethical challenges by reflecting on the experience of a study mapping the facilities that provide abortion‐related services in Cambodia. The technique of masking is examined as a potential method for preventing reidentification of respondents in georeferenced surveys. Broader solutions are offered for ways to balance the potentially conflicting goals of spatial analysis and protection of confidentiality.
Using Mystery Clients to Assess Condom Negotiation in Malawi: Some Ethical Concerns
Authors: Van Den Borne Francine
Published: October 2008

To halt the HIV/AIDS epidemic in Malawi, donors supported the government in promoting safer sex among women who solicit sex with men in and around bars. In 1996, a qualitative study explored the changing dynamics of concurrent sexual partnerships, using a variety of researchers and methods. Although most international ethical research codes prescribe the informed consent of research subjects, the present author, as principal investigator for that study, included the mystery‐client method, which omits informants’consent. Five trained, pilot‐tested, and closely supervised male researchers contacted 101 bar girls and “freelancing” women in trading and urban centers to assess the women's ability to negotiate condom use. The men posed as clients but were instructed not to have sex with their informants. This approach provided important contextualized information to improve HIV transmission‐prevention programs, yet it raises ethical concerns. This article is intended to contribute to the dialogue and debate on ethical research involving mystery clients and to encourage other researchers to share their ethical dilemmas and show how they have addressed them.
Ability of heifers to discriminate between familiar herdmates and members of an unfamiliar group: preference test and operant conditioning test
Authors: KOBA Yuki , MUNKSGAARD Lene , TANIDA Hajime , PEDERSEN Lene
Published: October 2008

Using a preference test and operant conditioning in a Y‐maze, this experiment examined the ability of heifers to discriminate between their own familiar herdmates and member(s) of an unfamiliar group. Sixteen Danish Friesian heifers, eight older animals (360.6 ± 24.2 days of age) and eight younger ones (190.1 ± 14.1 days of age) were used. Each age group was further divided into two experimental groups. Members of each of these groups were housed together in small pens before the experiments began. In experiment 1, each of the 16 animals was allowed to approach either a familiar or an unfamiliar individual in the Y‐maze. The test was repeated 12 times, with a different unfamiliar subject for each test. In experiment 2, eight heifers were individually tested in a conditioning experiment to examine whether they could learn to discriminate between a group of their three herdmates and a group of three unfamiliar heifers. Test animals were rewarded when they chose their own group. In experiment 1, heifers did not show a preference between familiar and unfamiliar individuals. Interestingly the younger stimulus heifers but not the test animals showed an ability to discriminate between unfamiliar animals by vocalizing. In experiment 2, four of the eight test animals achieved the criterion for successful discrimination between the familiar and unfamiliar group (P < 0.003: binomial law). There was no age group difference in the ability to discriminate between familiar and unfamiliar animals. In conclusion, heifers did not show a preference toward familiar or unfamiliar individuals; but after conditioning, some heifers could learn to discriminate between familiar and unfamiliar groups.
Effect of cooking time on some nutrient and antinutrient components of bambaragroundnut seeds
Authors: OMOIKHOJE Stanley Omoh , ARUNA Mohammed Bashiru , BAMGBOSE Adeyemi Mustapha
Published: October 2008

The proximate composition, gross energy, mineral composition, percentage sugar, oligosaccharides and antinutrient substances of bambaragroundnut seeds subjected to different cooking times were determined. The seeds were cooked for 30, 60, 90 and 120 min. Results of the proximate analysis showed that only the ether extract and ash were significantly (P < 0.05) reduced as the cooking time increased. In contrast, gross energy values significantly (P < 0.05) increased with increased cooking time. Amongst, the mineral elements assayed, calcium, magnesium and iron were significantly (P < 0.05) increased, while phosphorous, potassium, sodium and copper were reduced significantly (P > 0.05) with inreased cooking time. Percentage sucrose and glucose of bambaragroundnut seeds were significantly (P < 0.05) lowest in the raw form, but increased progressively with increased of cooking time. Raffinose and stachyose levels were reduced significantly by increased cookinf time (P < 0.05) with the least value in seeds cooked for 120 min. Trypsin inhibitor, hemagglutinin and tannin were completely eliminated in seeds cooked for 60 min or longer, but the phytin level was reduced significantly (P < 0.05) by cooking. For a significant detoxification of antinutrient substances and for optimal bioavailability of the component nutrients of bambaragroundnut seeds, an optimum cooking time of 60 min at 100°C is therefore recommended.
Determination of angiotensin‐I converting enzyme inhibitory peptides in chicken leg bone protein hydrolysate with alcalase
Authors: CHENG Fu‐Yuan , WAN Tien‐Chun , LIU Yu‐Tse , CHEN Chi‐Ming , LIN Liang‐Chuan , SAKATA Ryoichi
Published: October 2008

This study aims to identify peptides with angiotensin‐I converting enzyme (ACE) inhibitory activity in hydrolysate from chicken leg bone protein hydrolyzed with alcalase for 4 h (A4H). The hydrolysate has demonstrated potent in vitro ACE inhibitory activity, and has been shown to attenuate the development of hypertension and cardiovascular hypertrophy in spontaneously hypertensive rats (SHR). A4H is competitive for ACE and was separated using high‐performance liquid chromatography (HPLC) with a gel filtration column (Superdex Peptide HR 10/30). The results show that A4H is a mixed non‐competitive inhibitor. Eighteen fractions were detected after separation of A4H, and most of them showed ACE inhibitory activity. Five fractions with strong ACE inhibitory activities (above 50%) were labeled from A to E. In addition, there were 10 peptides, consisting of 5–10 amino acid residues that were identified from fraction D that exhibited the strongest ACE inhibitory activity. Three of the identified peptides corresponded to peptides derived from collagen type I and chicken muscular protein. It is revealed that A4H has several peptides that possess ACE inhibitory activities.
The structure of vocalization of ewes and male lambs at pasture
Authors: NAEKAWA Hirofumi
Published: October 2008

We performed an analysis of the vocalization of 161 ewes and 50 male lambs that were pastured day and night. The vocalization structures of the phonetic notations of the opened‐mouth from closed mouth /ηaee/ and /ηnaeee/ and closed‐mouth /ηηηη/ of ewes, and the opened‐mouth from closed‐mouth /ηeee/ and /ηneeee/ and closed‐mouth /ηηηη/ of male lambs were studied in terms of their audio characteristics. The items subject to analysis included duration of each vocalization, fundamental frequency, sound pressure and first formant (F1), second formant (F2), and third formant (F3). Among the male lambs, the duration of each call type showed significant differences depending on the behavior types or the target types, and the closed‐mouth to open‐mouth sounds, /ηeee/ and /ηneeee/ showed a tendency to be longer than the closed‐mouth sound of /ηηηη/. A significant correlation (r = 0.9, P < 0.05) was observed between the fundamental frequency and F1 with the /ηeee/ type of call of the male lambs when the vocalization was targeted toward the stockperson. When the ewes' behavior pattern was grazing and moving and the calling target was an ewe, the sound pressure significantly differed between /ηηηη/ and /ηnaeee/ (P < 0.05). From the analysis of the call durations, the fundamental frequencies, the sound pressures and formants, and the particular characteristics in sound structure were shown to vary according to the vocalization conditions and the situations, and where the animals were placed, even within the same call types.
Effects of dietary glucose level during late gestation on litter performance and glucose concentration in sows
Authors: HAN Young‐Keun , WANG Qi , CHO Jin‐Ho , CHEN Ying‐Jie , YOO Joo‐Sang , SHIN Seung‐Oh , KIM In‐Ho
Published: October 2008

The effects of feeding glucose during the 5 days before parturition on litter performance and on glucose concentration in sows were studied. At day 100 of gestation, 130 multiparous sows were assigned to the treatments. Late gestating sows were fed 0 g, 150 g, 250 g, 350 g and 450 g of glucose a day, respectively. During lactation, all sows were given free access to the same lactation diet (without glucose). One day before parturition, blood samples were collected from 30 sows (6 sows per treatment) at 10 before and 20, 40, 60 and 80 min after the meal. The supply of additional dietary glucose increased piglet birth weight (P < 0.05). Feed intake in week 1 and week 1–4 of lactation was greatest in sows fed the 0% glucose diet, least by sows fed the 18% glucose diet, and intermediate by sows fed the 6, 10, 14% glucose diets (P < 0.05). Basal glucose concentration and time of maximum glucose concentration after glucose intake were not affected by dietary treatment in the last 5 days of gestation. The sows fed the 14 and 18% glucose diets had greater maximum increase in glucose concentration than sows fed diet without glucose (P < 0.05). In conclusion, feeding glucose to sows during 5 days before parturition increased birth weight of live‐born piglet and decreased sows feed intake during lactation, but did not affect the performance of sows and piglets.
Heavy metal ions inhibit molybdoenzyme activity by binding to the dithiolene moiety of molybdopterin in Escherichia coli
Authors: Neumann Meina , Leimkühler Silke
Published: October 2008

Molybdenum insertion into the dithiolene group on the 6‐alkyl side‐chain of molybdopterin is a highly specific process that is catalysed by the MoeA and MogA proteins in Escherichia coli. Ligation of molybdate to molybdopterin generates the molybdenum cofactor, which can be inserted directly into molybdoenzymes binding the molybdopterin form of the molybdenum cofactor, or is further modified in bacteria to form the dinucleotide form of the molybdenum cofactor. The ability of various metals to bind tightly to sulfur‐rich sites raised the question of whether other metal ions could be inserted in place of molybdenum at the dithiolene moiety of molybdopterin in molybdoenzymes. We used the heterologous expression systems of human sulfite oxidase and Rhodobacter sphaeroides dimethylsulfoxide reductase in E. coli to study the incorporation of different metal ions into the molybdopterin site of these enzymes. From the added metal‐containing compounds Na2MoO4, Na2WO4, NaVO3, Cu(NO3)2, CdSO4 and NaAsO2 during the growth of E. coli, only molybdate and tungstate were specifically inserted into sulfite oxidase and dimethylsulfoxide reductase. Other metals, such as copper, cadmium and arsenite, were nonspecifically inserted into sulfite oxidase, but not into dimethylsulfoxide reductase. We showed that metal insertion into molybdopterin occurs beyond the step of molybdopterin synthase and is independent of MoeA and MogA proteins. Our study shows that the activity of molybdoenzymes, such as sulfite oxidase, is inhibited by high concentrations of heavy metals in the cell, which will help to further the understanding of metal toxicity in E. coli.
A novel β‐N‐acetyl‐d‐hexosaminidase from the insect Ostrinia furnacalis (Guenée)
Authors: Yang Qing , Liu Tian , Liu Fengyi , Qu Mingbo , Qian Xuhong
Published: October 2008

Exploiting specific targets is of specific interest in developing eco‐friendly pesticides. We isolated, purified and characterized a novel β‐N‐acetyl‐d‐hexosaminidase (OfHex1) from the fifth instar larva integument of the Asian corn borer, Ostrinia furnacalis (Guenée). OfHex1 was purified 1468‐fold to homogeneity with an activity yield of 20% by four column chromatography steps. Under denaturing conditions, the molecular mass of OfHex1 was determined to be 67.0 kDa by MS and SDS/PAGE, but 128 kDa by gel filtration chromatography, suggesting that it was in the form of a homodimer. Its pI was 4.7 as determined by IEF electrophoresis. OfHex1 was shown to be an exo‐splitting enzyme, acting by cutting one β‐GlcNAc unit once from the nonreducing ends of substrates, with a preference for shorter substrates. OfHex1 could hydrolyze p‐nitrophenyl β‐GlcNAc, p‐nitrophenyl β‐GalNAc and chito‐oligosaccharides (degree of polymerization from 2 to 6), but it could not hydrolyze the complex N‐glycan substrate (GlcNAcβ‐1,2Manα‐1,6)(GlcNAcβ‐1,2Manα‐1,3)Manβ‐1,4GlcNAcβ‐1,4GlcNAc‐PA as well as the long polymer chitin. Certain structural elements of substrates, the 2‐acetamido group and the β‐glycoside bond linkage, were determined to be essential for its activity. The 2.6 kb cDNA encoding OfHex1 was obtained by RT‐PCR. Sequence analysis indicated that it was different from reported β‐N‐acetyl‐d‐hexosaminidases with N‐glycan hydrolytic activities. Real‐time PCR determined that its transcriptional level increased dramatically before the molting stage. According to its hydrolytic mode, substrate spectrum, cDNA sequence and mRNA transcriptional level, we deduced that OfHex1 could be mostly involved in insect chitin catabolism and might be a specific target for pesticide development.
Altered expression of tumor protein D52 regulates apoptosis and migration of prostate cancer cells
Authors: Ummanni Ramesh , Teller Steffen , Junker Heike , Zimmermann Uwe , Venz Simone , Scharf Christian , Giebel Jürgen , Walther Reinhard
Published: October 2008

Tumor protein D52 (TPD52) is a protein found to be overexpressed in prostate and breast cancer due to gene amplification. However, its physiological function remains under investigation. In the present study, we investigated the response of the LNCaP human prostate carcinoma cell line to deregulation of TPD52 expression. Proteomic analysis of prostate biopsies showed TPD52 overexpression at the protein level, whereas its transcriptional upregulation was demonstrated by real‐time PCR. Transfection of LNCaP cells with a specific small hairpin RNA giving efficient knockdown of TPD52 resulted in significant cell death of the carcinoma LNCaP cells. As demonstrated by activation of caspases (caspase‐3 and ‐9), and by the loss of mitochondrial membrane potential, cell death occurs due to apoptosis. The disruption of the mitochondrial membrane potential indicates that TPD52 acts upstream of the mitochondrial apoptotic reaction. To study the effect of TPD52 expression on cell proliferation, LNCaP cells were either transfected with enhanced green fluorescence protein‐TPD52 or a specific small hairpin RNA. Enhanced green fluorescence protein‐TPD52 overexpressing cells showed an increased proliferation rate, whereas TPD52‐depleted cells showed the reverse effect. Additionally, we demonstrate that exogenous expression of TPD52 promotes cell migration via αvβ3 integrin in prostate cancer cells through activation of the protein kinase B/Akt signaling pathway. From these results, we conclude that TPD52 plays an important role in various molecular events, particularly in the morphological diversification and dissemination of prostate carcinoma cells, and may be a promising target with respect to developing new therapeutic strategies to treat prostate cancer.
Preventive Effect of S‐Allylcysteine on Membrane‐Bound Enzymes and Glycoproteins in Normal and Isoproterenol‐Induced Cardiac Toxicity in Male Wistar Rats
Authors: Padmanabhan Mannangatti , Rajadurai Murugan , Prince Ponnian Stanely Mainzen
Published: October 2008

Abstract:  This study was aimed to evaluate the preventive role of S‐allylcysteine (SAC) on creatine kinase‐MB, iron, iron binding capacity, uric acid, total protein, membrane‐bound enzymes such as sodium potassium‐dependent adenosine triphosphatase, calcium‐dependent adenosine triphosphatase and magnesium‐dependent adenosine triphosphatase, and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol‐induced myocardial infarction in rats. Male albino Wistar rats were pre‐treated with SAC (50, 100 and 150 mg/kg) daily for a period of 45 days. After the treatment period, isoproterenol (150 mg/kg) was subcutaneously injected in rats at an interval of 24 hr for 2 days. Isoproterenol‐induced rats showed significantly (P < 0.05) increased activities of serum creatine kinase‐MB and calcium‐dependent adenosine triphosphatase and magnesium‐dependent adenosine triphosphatase in the heart, and the levels of iron and uric acid in serum and significantly (P < 0.05) decreased the levels of plasma iron binding capacity, plasma total protein, plasma albumin/globulin ratio and activity of sodium potassium‐dependent adenosine triphosphatase in the heart. Isoproterenol induction also showed a significant increase in the levels of glycoproteins in serum and the heart. Pre‐treatment with SAC (100 and 150 mg/kg) daily for a period of 45 days exhibited significant (P < 0.05) effect and altered these biochemical parameters positively. SAC (50, 100 and 150 mg/kg) treatment to normal rats did not exhibit any significant effect in any of the parameters studied. Thus, our study shows that SAC has a protective role in isoproterenol‐induced myocardial infarction in rats. The observed effects might be due to the free radical scavenging, antioxidant and membrane stabilizing properties of SAC.
Involvement of Regulations of Nucleophosmin and Nucleoporins in Gambogic Acid‐Induced Apoptosis in Jurkat Cells
Authors: Shu Wenxiu , Chen Yan , Li Rui , Wu Qing , Cui Guohui , Ke Wenjuan , Chen Zi
Published: October 2008

Abstract:  Gambogic acid, the main active compound of gamboge resin of Garcinia hanburryi, has recently exhibited marked antitumour potency on solid tumours of various derivations. We demonstrate here that gambogic acid also present powerful antileukaemic potency through both growth arrest and apoptosis induction in Jurkat cells, which was accompanied by typical apoptotic morphological changes and sharp decreased expression of Bcl‐xL and Bcl‐2. Furthermore, nucleophosmin, recently demonstrated to be mutated and aberrantly localized in the cytoplasm of leukaemia blasts in a high proportion of patients with acute myeloid leukaemia, was over‐expressed in Jurkat cells. As the sole site of nucleocytoplasmic communication, the protein components of nuclear pore complex, such as NUP98, NUP88, NUP214 complex, were also deregulated in Jurkat cells. Especially, NUP98 was found to distribute mainly at the cell membrane, while NUP88 and NUP214 situated not just at the nuclear envelope, but also in the cytoplasm. However, in vitro treatment with gambogic acid resulted in significantly reduced expression of nucleophosmin and all three nucleoporins in a dose‐dependent manner. Moreover, most of NUP88 and NUP214 nucleoporins were relocated to the nuclear rim in the gambogic acid‐treated cells. These results suggest that the fact that nucleophosmin and some nucleoporins might act as new targets of gambogic acid, correlates well with the sensitivity to gambogic acid, as well as the rate of apoptosis induced by gambogic acid. Mechanisms that regulate nucleocytoplasmic transport of proteins may provide novel opportunities for drug development.
In vitroCYP3A4 Metabolism: Inhibition byEchinacea purpureaand Choice of Substrate for the Evaluation of Herbal Inhibition
Authors: Hansen Torstein Schrøder , Nilsen Odd Georg
Published: October 2008

Abstract: Thein vitroCYP3A4 inhibition profiles ofEchinacea purpurea, St. John's wort and ketoconazole were evaluated by three different substrates: 7‐benzyloxy‐trifluoromethylcoumarin (BFC), 7‐benzyloxyquinoline (BQ) and testosterone. St. John's wort and ketoconazole produced similar inhibition profiles regardless of substrate. ForE. purpurea, testosterone metabolism showed a much lower CYP3A4 inhibition (IC505394 µg/ml) compared to the fluorescent substrates BFC and BQ (IC50354 and 452 mg/ml, respectively). It is suggested that the substrate/assay‐dependent effects may arise from a complex nature ofE. purpureaconstituents, involving different CYP3A4 substrate binding sites. The choice of substrate might thus be essential for evaluation of the inhibition of CYP3A4 metabolism for some herbs. A weak inhibition potential ofE. purpureatowards CYP3A4‐mediated metabolismin vitrowas confirmed by the use of three different substrates.
Cavernous Nerve Injury Using Rodent Animal Models
Authors: Canguven Onder , Burnett Arthur
Published: October 2008

Introduction

With the advance of the “nerve sparing” technique in radical pelvic surgeries, medically unaided rates of normal erectile function following surgery have improved. Precise determinations of post-surgery erection recovery, however, continue to be problematic and rates of normal erectile function range from 9% to 86%. It is understood that injury to cavernous nerves (CNs) occurs despite modern modifications of the surgery, although the precise pathophysiologic mechanisms of surgical erectile dysfunction are not completely understood.

Aim

To describe the experimental models of CN injury in small rodents, including both survival surgery (CN injury) and non-survival surgery (monitoring of intracavernosal pressure and arterial blood pressure) models. We also summarize studies on experimental procedures relating to these CN injury models and critique techniques according to their advantages and disadvantages.

Main Outcome Measure

Data from a peer review literature search on the topic of CN injury in rodent models.

Methods

A comprehensive review of the literature was performed using PubMed. “Cavernous nerve injury” and “animal model” were used as search terms, and a manual bibliographic review of cross-referenced items was performed.

Results

Assorted molecular, morphological, and physiological changes are measurable after CN injury in rodent models.

Conclusion

Various models of CN injury have been applied successfully and offer insights regarding erectile function recovery effects.