bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure and chiroptical properties of supramolecular flower pigments
Authors: Ellestad George A.
Published: December 2005

Research over the last 30 years has shown that at physiological concentrations of ca. 5 × 10−3 M, flower pigments composed of anthocyanins, either alone or complexed with flavone copigments, and frequently with metals, are self‐assembled into non‐covalent, chiral supramolecular complexes. This serves several biological functions including color stability, protection against UV radiation and provision for specific colors to attract insects for pollination. Self‐association of the monomers takes place under conditions of molecular crowding by precise matching of the π–π stacking interactions of the aromatic chromophores and intermolecular hydrogen bonding between the attached sugars. The resulting handedness is controlled by the chiral information provided by the sugars joined glycosidically at certain positions around the periphery of the aromatic nuclei. This review gives an overview of (i) the physicochemical evidence including circular dichroism, 1H NMR, and X‐ray analysis for the structure and supramolecular chirality of these amphiphilic complexes, (ii) the role of the sugars on directing the chirality of the resulting supramolecules, (iii) the energetics of monomer association, and (iv) the possible influence of stacking chirality on insect pollination. © 2005 Wiley‐Liss, Inc. Chirality 18:134–144, 2006.
Robert Boyle's chiral crystal chemistry: Computational re‐evaluation of enantioselective adsorption on quartz
Authors: Kahr Bart , Chittenden Brianne , Rohl Andrew
Published: December 2005

While searching for early examples of interactions of organic chromophores with minerals in the context of a systematic study of the process of dyeing crystals, we came across Robert Boyle's description of an experiment that may have been evidence of the enantioselective adsorption of a natural product, carminic acid (7‐β‐d‐glucopyranosyl‐9,10‐dihydro‐3,5,6,8‐tetrahydroxy‐1‐methyl‐9,10‐dioxo‐2‐anthracenecarboxylic acid), to the chiral surfaces of α‐quartz, three centuries before such interactions became the subject of active chemical investigations. In order to determine whether Boyle did indeed observe enantioselective adsorption—albeit unbeknownst to him—we attempted to dye quartz with carminic acid according to his recipe. Quartz adsorbs carminic acid only because on heating it develops a network of microfissures that adsorb dye. This process depends on capillarity, not on specific non‐covalent interactions; there is no evidence of enantioselectivity adsorption to heated crystals or enantioselective epitaxy to unheated crystals. These failures changed the focus of our inquiry: Why have almost all attempts to demonstrate the enantioselective adsorption of additives to quartz crystal surfaces been generally confounding and equivocal? In order to answer this question, we complement our experimental historical re‐investigation with contemporary computational techniques for modeling crystal surface structure and the adsorption of additives. Minimizations of the energies associated with the adsorption of carminic acid to relaxed, hydrated d‐ and l‐quartz {10&1macr;0} surfaces are analyzed in light of quartz's abysmal record as an enantioselective stationary phase. © 2005 Wiley‐Liss, Inc. Chirality 18:127–133, 2006.
Incidence of esophageal and gastric carcinomas among American Asians/Pacific Islanders, whites, and blacks
Authors: Wu Xiaocheng , Chen Vivien W. , Ruiz Bernado , Andrews Patricia , Su L. Joseph , Correa Pelayo
Published: December 2005

BACKGROUND

The authors examined subsite‐specific and histology‐specific esophageal and gastric carcinoma incidence patterns among the Asians/Pacific Islander (API) population in the United States and compared them with those among whites and blacks.

METHODS

Data on newly diagnosed esophageal and gastric carcinomas during 1996–2000 were obtained from 24 population‐based central cancer registries, representing approximately 80% of the API population in the United States. Age‐adjusted rates, using the 2000 United States standard population, and age‐specific rates were computed by anatomic subsite, histology, race, and gender. The difference in the age‐adjusted rates between APIs and other races were examined using the two‐tailed z statistic.

RESULTS

Greater than 75% of esophageal carcinomas among APIs, both males and females, were squamous cell carcinoma. Adenocarcinoma accounted for < 20% of all esophageal carcinomas. This pattern was similar to that among blacks but was completely opposite to that among whites. The rate of esophageal squamous cell carcinoma was 81% higher among API males compared with white males, but it was 64% less compared with black males. The rates of esophageal adenocarcinoma were significantly lower among APIs than among both whites and blacks both males and females. The majority of gastric carcinomas among APIs were noncardia adenocarcinoma, whereas cardia adenocarcinoma accounted for only 11% of gastric carcinomas among API males and 6% of gastric carcinomas among API females. The age‐adjusted incidence rate of cardia adenocarcinoma was 23% lower among API males compared with white males, but it was 26% higher compared with black males. In contrast, the rates of noncardia adenocarcinoma among APIs were approximately 3.7 times the rate among whites for both males and females and 33% higher than the rate among blacks.

CONCLUSIONS

Subsite‐specific and histology‐specific incidence patterns of esophagogastric carcinoma among APIs differ from those among whites and blacks. The reasons for significantly higher rates of noncardia adenocarcinoma among APIs compared with whites and blacks need further investigation. Cancer 2006. © 2005 American Cancer Society.
Correlations of telomere length, telomerase activity, and telomeric‐repeat binding factor 1 expression in colorectal carcinoma
Authors: Garcia‐Aranda Cristina , de Juan Carmen , Diaz‐Lopez Antonio , Sanchez‐Pernaute Andres , Torres Antonio‐Jose , Diaz‐Rubio Eduardo , Balibrea Jose‐Luis , Benito Manuel , Iniesta Pilar
Published: December 2005

BACKGROUND

Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.

METHODS

Ninety‐one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric‐repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors.

RESULTS

Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P = 0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P = 0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P = 0.04; relative risk, 6.48). Among patients with tumors classified as telomerase‐positive, telomere length ratios (the ratio of tumor tissues to normal tissues) ≤ 0.66 or TRF1 over‐expression conferred a favorable outcome (P = 0.03 and P = 0.05, respectively).

CONCLUSIONS

The majority of CRC specimens in the current study displayed telomerase reactivation. However, only those tumors that displayed telomere elongation conferred a poor prognosis. Conversely, colorectal tumors that over‐expressed TRF1 demonstrated telomere shortening, and patients with those tumors had a better clinical course. Cancer 2006. © 2005 American Cancer Society.
Molecular mechanism of phenoxodiol‐induced apoptosis in ovarian carcinoma cells
Authors: Alvero Ayesha B. , O'Malley David , Brown David , Kelly Graham , Garg Manish , Chen Wei , Rutherford Thomas , Mor Gil
Published: December 2005

BACKGROUND

Previously, it was demonstrated that phenoxodiol induces apoptosis in epithelial ovarian carcinoma (EOC) cells and that it is capable of sensitizing these cells to Fas‐mediated apoptosis. The objectives of this study were to determine whether phenoxodiol can also act as chemosensitizer to chemotherapeutic agents and to characterize the molecular mechanism behind its sensitizing effect.

METHODS

Ten EOC cell lines were used in this study. The effect of phenoxodiol on the inhibitory concentration 50% (IC50) of carboplatin, paclitaxel, and gemcitabine was determined by the CellTiter 96 Assay. The in vivo effect of combination treatments with phenoxodiol and the above‐mentioned agents was determined in animal xenograft models. Apoptosis was measured using the Caspase‐Glo Assay and the apoptotic cascade was characterized by Western blot analyses.

RESULTS

The results showed that phenoxodiol is able to sensitize EOC cells to carboplatin, paclitaxel, and gemcitabine both in vitro and in vivo. In addition, it was demonstrated that phenoxodiol is capable of inducing apoptosis by: 1) the activation of the mitochondrial pathway through caspase‐2 and Bid signaling, and 2) the proteasomal degradation of the anti‐apoptotic protein XIAP.

CONCLUSION

Understanding the components of the apoptotic pathway activated by phenoxodiol, which allows it to sensitize EOC cells to chemotherapeutic agents, will provide valuable information on the characteristic mode of action of a chemosensitizer. This will help in the identification of novel drugs and in the design of better strategies for combination therapy in patients with recurrent ovarian carcinoma. Cancer 2006. © 2005 American Cancer Society.
Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen‐deprivation therapy
Authors: Basaria Shehzad , Muller Denis C. , Carducci Michael A. , Egan Josephine , Dobs Adrian S.
Published: December 2005

BACKGROUND

Prostate carcinoma (PCa) is one of the most common malignancies in men. Androgen‐deprivation therapy (ADT) is used frequently in the treatment of recurrent and metastatic PCa, rendering these men hypogonadal. Because male hypogonadism is associated with an unfavorable metabolic profile, and men with PCa have high cardiovascular mortality, the authors evaluated the effects of long‐term ADT on fasting glucose levels, insulin levels, and insulin resistance.

METHODS

To evaluate the long‐term effects of ADT on fasting glucose and insulin resistance in men with PCa who received ADT and to determine whether these metabolic alterations are a result of hypogonadism, the authors conducted a cross‐sectional study at a university‐based research institution in the United States. In total, 53 men were evaluated, including 18 men with PCa who received ADT for at least 12 months prior to the onset of the study (the ADT group), 17 age‐matched men with nonmetastatic PCa who had undergone prostatectomy and/or received radiotherapy and who were not receiving ADT (the non‐ADT group), and 18 age‐matched controls (the control group). None of the men had a known history of diabetes mellitus.

RESULTS

The mean age was similar in all 3 groups (P = 0.33). Serum total testosterone levels (P < 0.0001) and free testosterone levels (P < 0.0001) were significantly lower in the ADT group compared with the other groups. Men in the ADT group had a higher BMI compared with the other groups (overall P = 0.005). After adjustment for age and BMI, men in the ADT group had significantly higher fasting levels of the following parameters: 1) Glucose levels were 131.0 ± 7.43 mg/dL in the ADT group compared with 103.0 ± 7.42 mg/dL in the non‐ADT group (P = 0.01) and 99.0 ± 7.58 mg/dL in the control group (P < 0.01). 2) Insulin levels were 45.0 ± 7.25 uU/mL in the ADT group compared with 24.0 ± 7.24 uU/mL in the non‐ADT group (P = 0.05) and 19.0 ± 7.39 uU/mL in the control group (P = 0.02). 3) Leptin levels were 25.0 ± 2.57 ng/mL in the ADT group compared with 12.0 ± 2.56 ng/mL in the non‐ADT group (P < 0.01) and 6.0 ± 2.62 ng/mL in the control group (P < 0.01). 4) The homeostatic model assessment for insulin resistance (HOMAIR) = 17.0 ± 2.78 in the ADT group compared with HOMAIR = 6.0 ± 2.77 in the non‐ADT group (P < 0.01) and HOMAIR = 5.0 ± 2.83 in the control group (P = 0.01). There was a significant negative correlation between total and free testosterone levels with fasting glucose, insulin, leptin, and HOMAIR.

CONCLUSIONS

The current data suggested that men with PCa who are receiving long‐term ADT are at risk for developing insulin resistance and hyperglycemia, thus leading to their increased risk of cardiovascular disease. This adverse metabolic profile developed independent of age and BMI and appeared to be a direct result of androgen deprivation. Cancer 2006. © 2005 American Cancer Society.
Gonadotropin‐releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma
Authors: Recchia Francesco , Saggio Gaetano , Amiconi Giovanna , Blasio Anna Di , Cesta Alisia , Candeloro Giampiero , Rea Silvio
Published: December 2005

BACKGROUND

The objective of the current study was a retrospective evaluation of 100 consecutive premenopausal women with high‐risk, early breast carcinoma who received a gonadotropin‐releasing hormone (Gn‐RH) analogue as ovarian protection during adjuvant chemotherapy.

METHODS

After surgery, patients received a Gn‐RH analogue and adjuvant chemotherapy, which was tailored to their peculiar biologic features. The median patient age was 43 years (range, 27–50 yrs). Fifty‐two women had positive estrogen receptor (ER) status, and 48 women had negative ER status. There were 64 women with Stage II breast carcinoma and 36 women with UICC Stage III breast carcinoma. All patients had their serum estradiol suppressed to values < 40 pg/mL. The chemotherapy regimens administered included cyclophosphamide, methotrexate, and 5‐fluorouracil (n = 26 patients) and anthracycline‐based regimens (n = 74 patients, including 9 patients who had > 10 positive axillary lymph nodes, who also received high‐dose chemotherapy with autologous peripheral blood progenitor cell transplantation). Patients with positive c‐erb‐2 status also received a taxane. Eighty patients received radiation therapy. During therapy with the Gn‐RH analogue, patients who had a positive ER status after chemotherapy received an aromatase inhibitor.

RESULTS

After a median follow‐up of 75 months, normal menses were resumed by all patients younger than age 40 years and by 56% of patients older than age 40 years. Three pregnancies were observed that resulted in two normal deliveries and one voluntary abortion. The projected recurrence‐free survival rates at 5 years and 10 years were 84% and 76%, respectively; and the projected overall survival rates at 5 years and 10 years were 96% and 91%, respectively.

CONCLUSIONS

The current data showed that, in premenopausal women with early breast carcinoma, the addition of a Gn‐RH analogue to adjuvant therapy and temporary total estrogen suppression in patients with ER‐positive disease was tolerated well, protected long‐term ovarian function, and appeared to improve the expected clinical outcome. Cancer 2006. © 2005 American Cancer Society.
Racial/ethnic patterns in lifetime and age‐conditional risk estimates for selected cancers
Authors: Miller Barry A. , Scoppa Steven M. , Feuer Eric J.
Published: December 2005

BACKGROUND

Estimates of the probability of developing or dying from cancer, either over a lifetime or over a specified number of years, are useful summary measures of the burden of cancer in a population.

METHODS

The authors used publicly available DevCan software and new, detailed, racial/ethnic data bases that were developed in the Surveillance Research Program of the National Cancer Institute to produce risk estimates for selected major cancers among American Indian/Aleut/Eskimo, black, Chinese, Filipino, native Hawaiian, Japanese, white (total, non‐Hispanic), and Hispanic populations.

RESULTS

Japanese and non‐Hispanic white men had the highest lifetime risk for developing cancer (47.94% and 47.41%, respectively), and the American Indian/Eskimo/Aleut population (excluding Alaska) had the lowest lifetime risk among men (24.30%). Among women, white and American Indian/Eskimo/Aleut (in Alaska) populations had higher lifetime risks than Japanese women, whereas American Indian/Eskimo/Aleut (excluding Alaska) women had the lowest risk. The age‐conditional probabilities of developing cancer within the next 10 years among men and women age 60 years and the lifetime probabilities of dying from cancer also were reported by racial/ethnic group.

CONCLUSIONS

Racial/ethnic disparities in the lifetime risk of cancer may be because of differences in cancer incidence rates, but they also may reflect differential mortality rates from causes other than the cancer of interest. Furthermore, because cross‐sectional incidence and mortality rates are used in calculating the DevCan lifetime risk estimates, results must be interpreted with caution when events, such as the widespread and rapid implementation of a new screening test, are known to have influenced disease rates. Cancer 2006. © 2005 American Cancer Society.
Elevated serum heparanase‐1 levels in patients with pancreatic carcinoma are associated with poor survival
Authors: Quiros Roderick M. , Rao Geetha , Plate Janet , Harris Jules E. , Brunn Gregory J. , Platt Jeffrey L. , Gattuso Paolo , Prinz Richard A. , Xu Xiulong
Published: December 2005

BACKGROUND

It has previously been shown that heparanase‐1 (HPR1), an endoglycosidase, is up‐regulated in pancreatic carcinoma. The purpose of this study was to test whether serum HPR1 levels in pancreatic carcinoma patients are elevated, and whether higher serum HPR1 levels are associated with a shortened survival.

METHODS

Serum HPR1 levels in 40 healthy donors, 31 pancreatic carcinoma patients, and 11 patients treated with gemcitabine were measured by a novel enzyme‐linked immunoadsorbent assay. HPR1 expression in tumors was analyzed by immunohistochemical staining. Patient overall survival time was determined according to the Kaplan–Meier method, and their difference was evaluated by the log‐rank test. A P value < 0.05 was considered statistically significant.

RESULTS

The mean serum HPR1 activity in pancreatic carcinoma patients was 439 ± 14 units/mL, compared with 190 ± 4 units/mL in the control serum samples from healthy donors. Serum HPR1 levels were significantly higher in patients with HPR1‐positive tumors (660 ± 62 units/mL) compared with those with HPR1‐negative tumors (241 ± 14 units/mL). The mean survival of 19 pancreatic carcinoma patients with serum HPR1 activity > 300 units/mL was 7.9 ± 0.2 months, whereas the mean survival of 12 patients with serum HPR1 activity < 300 units/mL was 13.3 ± 0.6 months. A Kaplan–Meier plot of the patient survival curve followed by log‐rank test revealed that patients in the high serum HPR1 group had a significantly shorter survival compared with those in the low serum HPR1 group. Mean serum HPR1 activity decreased by 64% in 11 pancreatic carcinoma patients after 2 weeks of treatment with gemcitabine.

CONCLUSIONS

Serum HPR1 activity in pancreatic carcinoma patients was found to be significantly elevated, in particular in those with HPR1‐positive tumors. Increased serum HPR1 activity was associated with a shorter survival in patients with pancreatic carcinoma patients. Cancer 2006. © 2005 American Cancer Society.
Solid tumors “melt” from the inside after successful CD8 T cell attack
Authors: Blohm Ulrike , Potthoff Dan , van der Kogel Albert J. , Pircher Hanspeter
Published: December 2005

Adoptive transfer of tumor‐specific T cells represents a promising approach for cancer immunotherapy. Here, we visualized the anti‐tumor response of CD8 T cells from P14 TCR‐transgenic mice specific for the model antigen GP33 by immunohistology. P14 T cells, adoptively transferred into tumor‐bearing hosts, induced regression of established 3LL‐A9GP33 and MCA102GP33 tumors that express GP33 as a tumor‐associated model antigen. Strikingly, the visible effects of P14 T cell attack, such as the destruction of the tumor vasculature and accumulation of granulocytes, were predominantly detected inside the tumor mass. In regressing tumors, P14 T cells were found in the intact rim zone but not in central areas that were infiltrated with granulocytes and lacked CD31+ endothelial cells. The rim of P14 T cell‐treated tumors showed an increase in vascular density and decrease in hypoxia compared to untreated tumors. Hypoxic areas of tumors are known to exhibit decreased sensitivity to radiation therapy or chemotherapy. Thus, our data also imply that adoptive transfer of tumor‐specific CD8 T cells might synergize with radiation therapy or chemotherapy in the elimination of solid tumors in vivo.
Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine
Authors: García‐Piñeres Alfonso J. , Hildesheim Allan , Trivett Matthew , Williams Marcus , Wu Li , KewalRamani Vineet N. , Pinto Ligia A.
Published: December 2005

Dendritic cell‐specific intercellular adhesion molecule‐grabbing non‐integrin (DC‐SIGN), a specific C‐type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC‐SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus‐like particles (VLP) bind to DC‐SIGN expressed on transfected Raji cells and that antibodies against DC‐SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/chemokines. Although our results indicate that DC‐SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF‐α, IL‐6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC‐SIGN was blocked by anti‐DC‐SIGN antibodies. These results suggest that DC‐SIGN has a functional role in DC activation induced by HPV‐16 L1‐VLP, and thus highlight new aspects of DC interactions with HPV VLP.
Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy
Authors: Jakobsen Håvard , Hannesdottir Solveig , Bjarnarson Stefania P. , Schulz Dominique , Trannoy Emanuelle , Siegrist Claire‐Anne , Jonsdottir Ingileif
Published: December 2005

Immunization with a tetanus‐protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1‐TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti‐PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1‐TT responded with proliferation and IFN‐γ secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2‐cytokine responses were observed in mice immunized with Pnc1‐TT. Impaired IFN‐γ production upon TT‐stimulation in vitro was also reflected in reduced IFN‐γ/IL‐5 ratio. The IL‐‐5 response correlated with IgG anti‐PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier‐specific IL‐5 production. These results show that immunization with Pnc1‐TT induces carrier‐specific T cell responses that increase with age and determine the levels of PPS‐specific Ab elicited. Whereas a weak and Th2‐biased response was observed in neonatal mice, infant mice showed a mixed Th1‐Th2 response as observed in adults.
Mechanism of pathogen‐specific TLR4 activation in the mucosa: Fimbriae, recognition receptors and adaptor protein selection
Authors: Fischer Hans , Yamamoto Masahiro , Akira Shizuo , Beutler Bruce , Svanborg Catharina
Published: December 2005

The mucosal host defence discriminates pathogens from commensals, and prevents infection while allowing the normal flora to persist. Paradoxically, Toll‐like receptors (TLR) control the mucosal defence against pathogens, even though the TLR recognise conserved molecules like LPS, which are shared between pathogens and commensals. This study proposes a mechanism of pathogen‐specific mucosal TLR4 activation, involving adhesive ligands and their host cell receptors. TLR4 signalling was activated in CD14‐negative, LPS‐unresponsive epithelial cells by P fimbriated, uropathogenic Escherichia coli but not by a mutant lacking fimbriae. Epithelial TLR4 signalling in vivo involved the glycosphingolipid receptors for P fimbriae and the adaptor proteins Toll/IL‐1R (TIR) domain‐containing adaptor inducing IFN‐β (TRIF)/TRIF‐related adaptor molecule (TRAM), but myeloid differentiation protein 88 (MyD88)/TIR domain‐containing adaptor protein were not required for the epithelial response. Substituting the P fimbriae with type 1 fimbriae changed TLR4 signalling from the TRIF to the MyD88 adaptor pathway. In addition, the adaptor proteins and the fimbrial type were found to influence bacterial clearance. Trif–/– and Tram–/– mice remained infected with P fimbriated E. coli but cleared the type 1 fimbriated strain, while Myd88–/– mice became carriers of both the P and the type 1 fimbriated bacteria. Thus, TLR4 may be engaged specifically by pathogens, when the proper cell surface receptors are engaged by virulence ligands.

See accompanying commentary: http://dx.doi.org/10.1002/eji.200535777
HIV‐1 down‐regulates the expression of CD1d via Nef
Authors: Chen Nan , McCarthy Corinna , Drakesmith Hal , Li Demin , Cerundolo Vincenzo , McMichael Andrew J. , Screaton Gavin R. , Xu Xiao‐Ning
Published: December 2005

HIV‐1 has evolved several strategies to subvert host immune responses to the infected cells. One is to inhibit CTL recognition by HIV‐1 Nef‐mediated down‐regulation of MHC‐I expression on the surface of infected cells. Here we report that Nef also reduces the expression of the non‐classical MHC‐I like CD1d molecule, a third lineage of antigen‐presenting molecule, which presents lipid antigens. Nef achieves this by increasing internalization of CD1d molecules from the cell surface and retaining CD1d in the trans‐Golgi‐network (TGN). This effect depends on a tyrosine‐based motif present in CD1 cytoplasmic tail as well as the actions of four Nef motifs, which are known to be involved in the down‐regulation of MHC‐I or CD4. These results suggest that Nef regulates intracellular trafficking of CD1d via a distinct but shared pathway with MHC‐I and CD4. Thus, HIV‐1 reduces the visibility of its infected cells not only to MHC‐I‐restricted T cells but also to CD1d‐restricted NKT cells. Given that CD1d‐restricted T cells have unique effector and regulatory functions in innate and adapted immune responses as compared with their counterpart MHC‐restricted T cells, our data provide additional new insights into molecular basis of HIV‐1‐mediated damage to the immune system.
Differential effects of the tryptophan metabolite3‐hydroxyanthranilic acid on the proliferation of human CD8+ T cells induced by TCR triggering or homeostatic cytokines
Authors: Weber Walter P. , Feder‐Mengus Chantal , Chiarugi Alberto , Rosenthal Rachel , Reschner Anca , Schumacher Reto , Zajac Paul , Misteli Heidi , Frey Daniel M. , Oertli Daniel , Heberer Michael , Spagnoli Giulio C.
Published: December 2005

Production of indoleamine 2,3‐dioxygenase (IDO) by tumor cells, leading to tryptophan depletion and production of immunosuppressive metabolites, may facilitate immune tolerance of cancer. IDO gene is also expressed in dendritic cells (DC) upon maturation induced by lipopolysaccarides or IFN. We investigated IDO gene expression in melanoma cell lines and clinical specimens as compared to mature DC (mDC). Furthermore, we explored effects of L‐kynurenine (L‐kyn) and 3‐hydroxyanthranilic acid (3‐HAA) on survival and antigen‐dependent and independent proliferation of CD8+ cells. We observed that IDO gene expression in cultured tumor cells and freshly excised samples is orders of magnitude lower than in mDC, providing highly efficient antigen presentation to CD8+ T cells. Non toxic concentrations of L‐kyn or 3‐HAA did not significantly inhibit antigen‐specific CTL responses. However, 3‐HAA, but not L‐kyn markedly inhibited antigen‐independent proliferation of CD8+ T cells induced by common receptor γ‐chain cytokines IL‐2, ‐7 and ‐15. Our data suggest that CD8+ T cell activation induced by antigenic stimulation, a function exquisitely fulfilled by mDC, is unaffected by tryptophan metabolites. Instead, in the absence of effective T cell receptor triggering, 3‐HAA profoundly affects homeostatic proliferation of CD8+ T cells.
A New Access to Enantiopure syn‐ and anti‐2‐Methyl‐1,3‐diol Moieties from Chiral Nonracemic α‐Bromo α′‐Sulfinyl Ketones Promoted by Samarium Diiodide
Authors: Colobert Françoise , Obringer Michel , Solladié Guy
Published: December 2005

syn‐ and anti‐2‐Methyl‐1,3‐diols have been prepared by a two‐step sequence that involves a SmI2‐promoted stereoselective Reformatsky addition of chiral nonracemic α‐bromo α′‐sulfinyl ketones to various aldehydes followed by stereoselective reduction of the Reformatsky adduct. The absolute configuration of the products was determined by comparison with literature data and by 1H NMR NOESY experiments. The observed stereoselectivities can be explained in terms of a boat transition state. Functionalization of the aldehyde and removal or transformation of the chiral sulfoxide will allow this methodology to be applied to the total synthesis of biologically active molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Diastereoselective Synthesis of New P‐Stereogenic (ortho‐Hydroxyaryl)diazaphospholidine–Borane Complexes by a Totally Stereoselective P–O to P–C Migration Rearrangement
Authors: Ngono Christian J. , Constantieux Thierry , Buono Gérard
Published: December 2005

The totally diastereoselective synthesis of new P‐stereogenic (o‐hydroxyaryl)diazaphospholidines, in the form of their borane complexes 4a–4h, is described. The efficiency of this procedure is based both, on a one‐pot and totally diastereoselective synthesis of the precursors (ortho‐bromoaryloxy)diazaphosphospholidine–borane complexes 3a–3h, and on a stereoselective P–O to P–C migration rearrangement. A X‐ray diffraction study of the structures of the product 4f and his precursor 3f shows unambiguously the totally stereoselectivity of the P–O to P–C rearrangement with clean retention of the phosphorus configuration.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Effective Debye length in closed nanoscopic systems: A competition between two length scales
Authors: Tessier Frédéric , Slater Gary W.
Published: December 2005

The Poisson‐Boltzmann equation (PBE) is widely employed in fields where the thermal motion of free ions is relevant, in particular in situations involving electrolytes in the vicinity of charged surfaces. The applications of this non‐linear differential equation usually concern open systems (in osmotic equilibrium with an electrolyte reservoir, a semi‐grand canonical ensemble), while solutions for closed systems (where the number of ions is fixed, a canonical ensemble) are either not appropriately distinguished from the former or are dismissed as a numerical calculation exercise. We consider herein the PBE for a confined, symmetric, univalent electrolyte and quantify how, in addition to the Debye length, its solution also depends on a second length scale, which embodies the contribution of ions by the surface (which may be significant in high surface‐to‐volume ratio micro‐ or nanofluidic capillaries). We thus establish that there are four distinct regimes for such systems, corresponding to the limits of the two parameters. We also show how the PBE in this case can be formulated in a familiar way by simply replacing the traditional Debye length by an effective Debye length, the value of which is obtained numerically from conservation conditions. But we also show that a simple expression for the value of the effective Debye length, obtained within a crude approximation, remains accurate even as the system size is reduced to nanoscopic dimensions, and well beyond the validity range typically associated with the solution of the PBE.
Continuous separation of microparticles by size with Direct current‐dielectrophoresis
Authors: Kang Kwan Hyoung , Kang Yuejun , Xuan Xiangchun , Li Dongqing
Published: December 2005

Direct current‐dielectrophoresis (DC‐DEP), the induced motion of the dielectric particles in a spatially nonuniform DC electric field, is demonstrated to be a highly efficient method to separate the microparticles by size. The locally nonuniform electric field is generated by an insulating block fabricated inside a polydimethylsiloxane microchannel. The particle experiences a negative DEP (accordingly a repulsive force) at the corners of the block, where the local electric‐field strength is the strongest. Thus, the particle deviates from the streamline and the degree of deviation is dependent on the DEP force (i.e., the particle size). Combined with the electrokinetic flow, mixed polystyrene particles of a few micrometers difference in diameter can be continuously separated into distinct reservoirs. For separating target particles of a specific size, it is required to simply adjust the voltage outputs of the electrodes. A numerical model based on the Lagrangian tracking method is developed to simulate the particle motion and the results showed a reasonable agreement with the experimental data.
Electrophoresis of soft particles: Analytic approximations
Authors: Ohshima Hiroyuki
Published: December 2005

An approximate analytic expression is derived for the electrophoretic mobility of a weakly charged spherical soft particle (i.e., a hard particle covered with a weakly charged polyelectrolyte layer) on the basis of the general mobility expression for soft particles (Ohshima, H., J. Colloid Interface Sci. 2000, 228, 190–193). The obtained mobility expression, which reproduces various approximate results so far derived and gives some new mobility formulas, covers all types of weakly charged soft particles with arbitrary values of the thickness of polymer layer, the radius of the particle core, the electrophoretic softness, and the Debye length, including spherical polyelectrolytes with no particle core as well as spherical hard particles with no polyelectrolyte layer.
A new type of migrating zone boundary in electrophoresis: 2. Transient sample zone shapes
Authors: Gebauer Petr , Malá Zdena , Boček Petr
Published: December 2005

A new type of migrating zone boundary in electrophoresis is presented theoretically and evidenced experimentally. This type of the boundary (called hybrid boundary) shows simultaneously a steady‐state part with self‐sharpening properties and an unsteady‐state part with time‐dependent electromigration dispersion. It is shown that a sample zone may possess a hybrid boundary both as its front and rear one simultaneously. In such a case, the evolution of a sample zone injected originally as a rectangular pulse exhibits very complex transient shapes before it reaches the well‐known fronting or tailing triangular shape. Depending on the stage at which detection of such a sample zone occurs, variable and peculiar‐shape peaks may appear in the electropherogram. Based on theoretical predictions, experimental examples of the above‐mentioned phenomena are presented in this contribution for direct and indirect UV absorbance detection of sample zones. Excellent agreement of theoretical predictions with the experiments has been found. The knowledge of hybrid boundaries is of key significance for correct interpretation of records of CE analyses in practice.
Origin of peak asymmetry and isotherm nonlinearity in micellar electrokinetic chromatography: Variation of peak shape with buffer concentration
Authors: Williamson Yuping , Davis Joe M.
Published: December 2005

The diffuse fronts and sharp rears of peaks of nitrobenzene (nbz) solubilized at high concentrations in 50 mM SDS and 2.5, 25, and 50 mM sodium tetraborate buffers were modeled in MEKC by measurements of, and fits to, concave upward isotherms, and by numerical solution of the continuity equation. The isotherms varied with buffer concentration, with the smallest limiting slope and largest curvature found for the 50 mM tetraborate buffer. The Brunauer, Emmett, and Teller isotherm described the peak profiles in all buffers, with symmetrical peaks observed at sub‐ and low‐mM levels of nbz, anti‐Langmuirian peaks observed at 10–20 mM levels, and aquiline peaks resembling curved noses observed at 20–30 mM levels. The variation of the partition coefficient with nbz and buffer concentrations was shown to result from nonideal thermodynamics. High‐buffer concentrations salt out nbz from the mobile phase, as quantified by a mobile‐phase activity coefficient related to the Setchenov constant of nbz in sodium tetraborate. The activity coefficient of nbz in SDS micelles was shown to resemble that measured by other researchers for benzene in micelles of sodium octyl sulfate, i.e. it decreases with increasing solute concentration and increases with electrolyte concentration. Many examples from the literature are discussed, in which the variation of the intramicellar activity coefficient with solute mole fraction is consistent with peaks having diffuse fronts and sharp rears.
The piscine micronucleus test to assess the impact of pollution on the Japaratuba river in Brazil
Authors: de Moraes Pantaleão Silmara , Alcântara Ayda Vera , Alves José do Patrocínio Hora , Spanó Mário Antônio
Published: December 2005

In situ investigations of the effects of mutagenic pollutants (environmental monitoring) have increasingly used bioindicators, and fish often have been used in these studies as sentinel organisms. In the present study, we have used the piscine micronucleus test (MNT) as an in situ biological indicator of chemical contamination in two fresh water fish species (Astyanax bimaculatus and Hoplias malabaricus). The fish were collected from two sites (Sites 1 and 2) in the Japaratuba River (Sergipe, Brazil), in an area impacted by a petrochemical industrial complex which indirectly contributes treated effluent (produced water) to the river. Responses in fish from these sites were compared to fish from a clean reference site (Jacarecica River ‐ Sergipe, Brazil). The results indicated an enhanced frequency of micronuclei (MN) in peripheral red blood cells of A. bimaculatus collected at Sites 1 and 2 when compared to their respective negative control (A. bimaculatus collected from the Jacarecica River). H. malabaricus collected at Sites 1 and 2 did not have a significant increase in MN. The results of this study indicate that the piscine MNT is a useful in vivo technique for the detection of chemical contaminants in the aquatic environment and that the assay shows potential for in situ monitoring of water quality. Nevertheless, the results also demonstrated differential sensitivity of A. bimaculatus and H. malabaricus to the induction of MN. Environ. Mol. Mutagen., 2006. © 2005 Wiley‐Liss, Inc.
Prevalence and risk factors for primary hyperparathyroidism in hyperthyroid patients
Authors: Abboud Bassam , Sleilaty Ghassan , Mansour Eid , El Ghoul Rawad , Tohme Cyril , Noun Roger , Sarkis Riad
Published: December 2005

Background.

Coexistence of hyperthyroidism and primary hyperparathyroidism may be more prevalent than previously recognized. We report 13 cases of concomitant occurrence of both diseases to estimate their combined prevalence and its factors.

Methods.

Ninety‐six unselected patients admitted for elective hyperthyroidism surgery were retrospectively included. Eighty‐three patients were initially seen for hyperthyroidism with normocalcemia (group 1), and 13 patients were initially seen for hyperthyroidism with associated primary hyperparathyroidism (group 2). Patients' characteristics, examinations, and pathology reports were reviewed. Risk factors were identified using a logistic regression model.

Results.

The prevalence of concomitant hyperparathyroidism was 13.5%. No patients manifested hypercalcemia in the absence of organic parathyroid disease. Eleven patients had a parathyroid adenoma, and two patients had parathyroid hyperplasia. Group 2 patients were older (median 61 vs 43 years, p = .006). Thyroid‐stimulating hormone levels were more depressed in group 2 (median 0.01 vs 0.032 UI/L, p = .034). On multivariate analysis, age was the unique factor significantly different between groups (odds ratio, 1.05; 95% confidence interval, 1.008–1.098; p = .020).

Conclusions.

Hypercalcemia in patients with hyperthyroidism, particularly older patients, should warrant a thorough investigation for concomitant primary hyperparathyroidism that would dictate a combined thyroidectomy and parathyroidectomy. © 2005 Wiley Periodicals, Inc. Head Neck 27: 420–426, 2006
Superficial ulnar artery: Curse or blessing in harvesting fasciocutaneous forearm flaps
Authors: Sieg Peter , Jacobsen Hans‐Christian , Hakim Samer G. , Hermes Dirk
Published: December 2005

Background.

Superficial ulnar artery is a well‐known vascular anomaly that may cause special risks because of possible impairment of the vessel by mistake during harvesting fasciocutaneous forearm flaps.

Methods.

The charts of patients who had undergone forearm flap transfer were reviewed for vascular anomalies. When a superficial ulnar artery was present, a superficial ulnar artery flap was raised and arteriography was performed postoperatively to figure out the vascular pattern in the contralateral arm.

Results.

Four superficial ulnar arteries were found during dissection of ulnar forearm flaps (n = 107). We were unable to identify any superficial ulnar artery when preparing the radial pendant (n = 27), and we did not notice any impairment of such an artery. The four superficial ulnar artery flaps healed uneventfully. Postoperative arteriography revealed a bilateral vascular anomaly in one of the four cases.

Conclusion.

The superficial ulnar artery is a calculable anatomic variation as long as its possible presence is considered during flap harvesting. In these cases, the use of the superficial ulnar artery flap was found to be an easy and safe alternative. © 2005 Wiley Periodicals, Inc. Head Neck 27: 447–452, 2006
Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT‐11
Authors: Kim Seungwon , Yazici Yasemin D. , Barber Samantha E. , Jasser Samar A. , Mandal Mahitosh , Bekele B. Nebiyou , Myers Jeffrey N.
Published: December 2005

Background.

A preclinical evaluation of CPT‐1 (Camptosar, irinotecan) and PTK787/ZK222584, a vascular endothelial growth factor receptor (VEGFR‐2) tyrosine kinase inhibitor, as therapeutic agents against anaplastic thyroid carcinoma (ATC) was performed in vitro and in an orthotopic model of ATC in nude mice.

Methods.

The cytotoxic and cytostatic effects of CPT‐11 on ATC cell lines were evaluated. The antitumor effects of CPT‐11 in combination with PTK787/ZK222584 on orthotopic ATC xenografts in nude mice were also studied.

Results.

CPT‐11 demonstrated significant antiproliferative effects on ATC cell lines. In vivo, PTK787/ZK222584, CPT‐11, and the two agents together produced 61%, 82%, and 89% decrease in tumor growth, respectively. The differences in tumor volume between CPT‐11 and CPT‐11 + PTK787/ZK222584 groups were not statistically significant. PTK787/ZK222584 inhibited the phosphorylation of VEGFR‐2 on tumor endothelium and decrease the tumor microvessel density.

Conclusions.

The camptothecin class of chemotherapeutic agents and antiangiogenic agents such as PTK787/ZK222584 warrant further study as novel therapeutic agents against ATC. © 2005 Wiley Periodicals, Inc. Head Neck 27: 389–399, 2006
Emodin inhibits vascular endothelial growth factor‐A‐induced angiogenesis by blocking receptor‐2 (KDR/Flk‐1) phosphorylation
Authors: Kwak Hee‐Jin , Park Myung‐Jin , Park Chang‐Min , Moon Sang‐Ik , Yoo Doo‐Hyun , Lee Hyung‐Chahn , Lee Seung‐Hoon , Kim Mi‐Suk , Lee Hyean‐Woo , Shin Woon‐Seob , Park In‐Chul , Rhee Chang Hun , Hong Seok‐Il
Published: December 2005

Emodin (1,3,8‐trihydroxy‐6‐methylanthraquinone), an active component in the root and rhizome of Rheum palmatum, is a tyrosine kinase inhibitor with a number of biological activities, including antitumor effects. Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)‐A‐induced angiogenesis, both in vitro and in vivo. In vitro, emodin dose‐dependently inhibits proliferation, migration into the denuded area, invasion through a layer of Matrigel and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated with VEGF‐A. Emodin also inhibits basic fibroblast growth factor‐induced proliferation and migration of HUVECs and VEGF‐A‐induced tube formation of human dermal microvascular endothelial cells. Specifically, emodin induces the cell cycle arrest of HUVECs in the G0/G1 phase by suppressing cyclin D1 and E expression and retinoblastoma protein phosphorylation, and suppresses Matrigel invasion by inhibiting the basal secretion of matrix metalloproteinase‐2 and VEGF‐A‐stimulated urokinase plasminogen activator receptor expression. Additionally, emodin effectively inhibits phosphorylation of VEGF‐A receptor‐2 (KDR/Flk‐1) and downstream effector molecules, including focal adhesion kinase, extracellular signal‐regulated kinase 1/2, p38 mitogen‐activated protein kinase, Akt and endothelial nitric oxide synthase. In vivo, emodin strongly suppresses neovessel formation in the chorioallantoic membrane of chick and VEGF‐A‐induced angiogenesis of the Matrigel plug in mice. Our data collectively demonstrate that emodin effectively inhibits VEGF‐A‐induced angiogenesis in vitro and in vivo. Moreover, inhibition of phosphorylation of KDR/Flk‐1 and downstream effector molecules is a possible underlying mechanism of the anti‐angiogenic activity of emodin. Based on these data, we propose that an interaction of emodin with KDR/Flk‐1 may be involved in the inhibitory function of emodin toward VEGF‐A‐induced angiogenesis in vitro and responsible for its potent anti‐angiogenic in vivo. © 2006 Wiley‐Liss, Inc.