bluuebunny/crossref_metadata_2025 huggingface dataset:
Seasonal climatic effects on the hydrology of a rain garden
Authors: Muthanna T. M. , Viklander M. , Thorolfsson S. T.
Published: September 2007

This paper evaluates the performance and winter hydrology of two small‐scale rain gardens in a cold climate coastal area in Trondheim, Norway. One rain garden received runoff from a small residential watershed over a 20 month study period while the second rain garden with a shorter study period of 7 months was used as a control. The objective of the study was to investigate the extent to which cold climatic conditions would influence the hydrology and performance of the rain gardens. The hydraulic detention, storm lag time and peak flow reduction were measured and compared seasonally. No significant difference between seasonal lag time could be found, but there was a clear decreasing trend in lag time between rain, rain‐on‐snow and snowmelt. The average peak flow reduction for 44 storms in the study period was 42% compared to 27% for the winter seasons, indicating that the performance of the rain garden is reduced in the cold season (below 0 °C). The average hydraulic detention time for the rain garden was 0·84 ( ± 0·73) with runoff inflow and 1·91 ( ± 3·1) with only precipitation. A strong positive correlation was found between the time since the last wetting event and lag time, and between air temperature and hydraulic detention. This indicates that the time between events and seasonal air temperatures are key parameters in the hydraulic performance of cold climate rain gardens. The rain gardens were not used for snow storage areas, and a volume requirement for this was not evaluated in the study. Copyright © 2007 John Wiley & Sons, Ltd.
Systemic administration of a peptide that impairs the protein kinase (CK2) phosphorylation reduces solid tumor growth in mice
Authors: Perera Yasser , Farina Hernán G. , Hernández Ignacio , Mendoza Osmany , Serrano Joem M. , Reyes Osvaldo , Gómez Daniel E. , Gómez Roberto E. , Acevedo Boris E. , Alonso Daniel F. , Perea Silvio E.
Published: September 2007

The antitumor efficacy of the CK2 inhibitors so far described has not been extensively evaluated in cancer animal models. We have previously demonstrated that a proapoptotic cyclic peptide termed P15 delivered into the cells by the Tat Cell Penetrating Peptide was able to abrogate the CK2‐mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice. Here we explored the antitumor effect by systemic administration of P15‐Tat in a consecutive 5‐day schedule through either intraperitoneal or intravenous route. Importantly, significant delay of tumor growth was observed at 2 mg/kg (p < 0.05), 10 mg/kg (p < 0.01) or 40 mg/kg (p < 0.001) after P15‐Tat administration both in syngeneic murine tumors and human tumors xenografted in nude mice. In line with this, the systemic administration of P15‐Tat induced apoptosis in the tumor as evidenced by in situ DNA fragmentation. Furthermore, we evidenced that 99mTc‐labeled P15‐Tat peptide was certainly accumulated on the tumors after administration by both routes. This report becomes the first describing the antitumor effect induced by systemic administration of a peptide that targets the acidic phosphorylation domain for CK2 substrates. Also, our data reinforces the perspectives of P15‐Tat for the cancer targeted therapy. © 2007 Wiley‐Liss, Inc.
Adenovirus‐mediated expression of TIMP‐1 and TIMP‐2 in bone inhibits osteolytic degradation by human prostate cancer
Authors: Deng Xiyun , He Guangchun , Levine Andrea , Cao Ya , Mullins Chad
Published: September 2007

Matrix metalloproteinases (MMPs) are proteolytic enzymes that play critical roles in the pathogenesis of human cancers. Clinical trials using synthetic small molecule MMP inhibitors have been carried out but with little success. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that block the extracellular matrix‐degrading activity of MMPs. Here, we investigated the possibilities of genetically modifying human bones with TIMPs to create a high‐TIMP bone microenvironment, which is hostile to metastatic prostate cancer cells using adenovirus‐mediated gene transfer technology and SCID‐hu end‐organ colonization mouse model. Two strategies were used to achieve bone‐specific TIMP expression: (i) ex vivo bone adenoviral infection followed by in vivo bone implantation; and (ii) ex vivo BMS cell infection followed by injection into in vivo implanted human fetal bones. PC‐3 prostate cancer cells were injected into human fetal bones 4 weeks after implantation in SCID mice. In vitro, adenovirus‐mediated expression of TIMP‐1 or TIMP‐2 in bone fragments inhibited MMP‐2 activity, bone turnover and prostate cancer cell‐induced proteolytic degradation as determined by gelatin zymography, calcium measurement and DQ protein quenched fluorescence assay, respectively. In vivo, immunohistochemistry confirmed TIMP‐2 expression in AdTIMP‐2‐infected bone implants 4 weeks after implantation in SCID mice. Mice receiving AdTIMP‐treated bone fragments showed significantly reduced PC‐3‐induced osteolysis, osteoclast recruitment and bone turnover in the implanted bones. We propose that adenoviral gene transfer of TIMP‐1 and TIMP‐2 can prevent the proteolytic activity of prostate cancer cells in bone and that enhancing anti‐proteolytic defense mechanisms in target organs represents a promising form of prostate cancer gene therapy. © 2007 Wiley‐Liss, Inc.
K‐ras mutations and mucin profile in preneoplastic lesions and colon tumors induced in rats by 1,2‐dimethylhydrazine
Authors: Femia Angelo Pietro , Tarquini Elena , Salvadori Maddalena , Ferri Stefania , Giannini Augusto , Dolara Piero , Caderni Giovanna
Published: September 2007

K‐ras and mucin profile variations, associated with intestinal carcinogenesis, were studied in the preneoplastic lesions, mucin‐depleted foci (MDF) and aberrant crypt foci (ACF), and in colonic tumors induced in rats by 1,2‐dimethylhydrazine (DMH). The frequency of lesions with K‐ras mutations was 23% (3/13), 5.5% (1/18) and 100% (14/14) in MDF, tumors and ACF, respectively. Two of three MDF mutated in K‐ras also carried a missense mutation in Apc. We also tested the expression of MUC2, a mucin abundantly expressed in normal colon and M1/MUCA5C, up‐regulated in colon carcinogenesis, using immunohistochemistry. MDF and tumors showed a dramatic reduction in the expression of MUC2, whereas ACF showed only a slight reduction. The expression of M1/MUC5AC was almost absent in normal mucosa, but was increased in all the lesions (MDF, tumors and ACF). The expression of the intestinal trefoil factor (ITF), a marker of goblet cell lineage, was reduced in MDF and tumors compared to normal mucosa but not in ACF. In conclusion, although K‐ras mutations are present in all ACF, they are less frequent in MDF and tumors; M1/MUC5AC is a marker associated with all preneoplastic events while the reduction of MUC2 and ITF expression is selectively associated with more advanced lesions such as MDF and tumors. © 2007 Wiley‐Liss, Inc.
Organised mammography screening reduces breast cancer mortality: A cohort study from Finland
Authors: Sarkeala Tytti , Heinävaara Sirpa , Anttila Ahti
Published: September 2007

We evaluated the effectiveness and the efficacy of population‐based mammography programme in Finland, and explored associations between the screening performance and the screening efficacy. The main outcome, incidence‐based mortality from breast cancer, was estimated by invitation, participation, age at death, and screening centres categorised by recall rates. The study was based on an individual followup of screening invitees and participants from 1992 to 2003. The coverage of screening invitations was 95% among 50–59 years old women, and 20–40% among women aged 60–69 years. We compared observed deaths from breast cancer to expected breast cancer deaths without screening in ages 50–69 at death. The observed deaths were obtained from a cohort of individual invitees (n = 361,848). The expected deaths were defined by modelling breast cancer mortality from 1974 to 1985 and 1992 to 2003 at population level. The population data were derived from the same municipalities (n = 260) that were incorporated into the cohort. The breast cancer mortality among the invited women was reduced by 22% (relative risk 0.78, 95% confidence interval 0.70–0.87). After adjusting for the self‐selection, the efficacy among the participants was 28% (0.72,0.56–0.88). No clear association between the recall rates and the screening efficacy was observed. The organised mammography screening in Finland is effective. The relationship between the estimates of process and outcome of mammography is not yet straightforward: effectiveness and efficacy remain the best estimates for evaluating the success of mammography screening. © 2007 Wiley‐Liss, Inc.
Methylseleninic acid inhibits microvascular endothelial G1 cell cycle progression and decreases tumor microvessel density
Authors: Wang Zhe , Hu Hongbo , Li Guangxun , Lee Hyo‐Jeong , Jiang Cheng , Kim Sung‐Hoon , Lü Junxuan
Published: September 2007

Our previous work has shown that the cancer chemopreventive effect of selenium may in part be mediated by its antiangiogenic activities and that methylseleninic acid (MSeA) can induce G1 arrest of human umbilical vein endothelial (macrovascular) cells. The objectives of the current study are to verify MSeA‐induced G1 arrest effect in microvascular endothelial cells and to elucidate the molecular mediators and targets involved. Flow cytometric analysis after MSeA exposure (2–10 μM) of telomerase‐immortalized microvascular endothelial (TIME) cells for 24 hr showed aconcentration‐dependent increase of G1‐arrested cells. MSeA (3 μM) treatment delayed the mitogen‐stimulated progression of TIME cells from G1 to S phase. These effects of MSeA were accompanied by an early transient (6 hr) upregulation of P21/CIP1 and P27/KIP1 and a delayed modest increase of P16/INK4a (12 hr). MSeA increased P27/KIP1 mRNA transcript level and slowed the turnover of P21/CIP1 protein. MSeA‐treated cells contained elevated levels of bound P16/INK4a within the CDK4/6/cyclin D1 complexes as well as bound P21/CIP1 and P27/KIP1 within the CDK2/cyclin E complex and decreased their kinase activities. MSeA suppressed the mitogen/CDK‐driven phosphorylative inactivation of retinoblastoma (Rb) protein, diminishing E2F1 release from Rb. In vivo, daily oral MSeA treatment of nude mice bearing subcutaneously inoculated human prostate cancer DU145 xenografts inhibited tumor growth in a dose‐dependent manner. The microvessel density of the tumors in the high MSeA group was decreased by more than half from the control. An inhibition of mitogen‐stimulated proliferation of endothelial cells by MSeA may therefore contribute to the inhibition of tumor angiogenesis. © 2007 Wiley‐Liss, Inc.
Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women
Authors: Kabat Geoffrey C. , Miller Anthony B. , Rohan Thomas E.
Published: September 2007

Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk. We used data from a large cohort study of Canadian women enrolled in a randomized controlled trial of breast cancer screening to assess the association of oral contraceptive use, hormone replacement therapy and reproductive factors with risk of colorectal cancer, overall and by subsite within the colorectum. Cancer incidence and mortality were ascertained by linkage to national databases. Among 89,835 women aged 40–59 at enrollment and followed for an average of 16.4 years, we identified 1,142 incident colorectal cancer cases. Proportional hazards models were used to estimate the associations between the exposures of interest and risk of colorectal cancer. Ever use of oral contraceptives at baseline was associated with a modest reduction in the risk of colorectal cancer (hazard ratio 0.83, 95% confidence interval 0.73–0.94), with similar effects for different subsites within the colorectum. No trend was seen in the hazard ratios with increasing duration of oral contraceptive use. No associations were seen with use of hormone replacement therapy (ever use or duration of use) or reproductive factors. Our results are suggestive of an inverse association between oral contraceptive use and colorectal carcinogenesis. However, given the lack of a dose–response relationship and the potential for confounding, studies with more complete assessment of exogenous hormone use throughout the life course are needed to clarify this association. © 2007 Wiley‐Liss, Inc.
Modelling sovereign bond yield curves of the US, Japan and Germany
Authors: Tam Chi‐Sang , Yu Ip‐Wing
Published: September 2007

The movement of sovereign yields is important for both investment and risk management. This paper applies a method that was first developed by Diebold et al. (2006) to model the sovereign bond yield curves of the US, Japan and Germany. By including observable macroeconomic variables as well as the latent factors of the yield curve, we find evidence of a strong interaction between the yield curve and macro‐variables in the US and Germany but not in Japan. We also estimate the dynamic conditional correlations of the latent factors to reveal the cross‐country correlations of the bond markets. Copyright © 2007 John Wiley & Sons, Ltd.
Conventional and unconventional approaches to exchange rate modelling and assessment
Authors: Alquist Ron , Chinn Menzie D.
Published: September 2007

We examine the relative predictive power of the sticky price monetary model, uncovered interest parity, and a transformation of net exports and net foreign assets. In addition to bringing Gourinchas and Rey's new approach and more recent data to bear, we implement the Clark–West procedure for testing the significance of out‐of‐sample forecasts. The interest rate parity relation holds better at long horizons and the net exports variable does well in predicting exchange rates at short horizons in sample. In out‐of‐sample forecasts, we find evidence that our proxy for Gourinchas and Rey's measure of external imbalances outperforms a random walk at short horizons as do some of the other models, although no single model uniformly beats the random walk forecast. Copyright © 2007 John Wiley & Sons, Ltd.
Downregulation of human colon carcinoma cell (COLO‐205) proliferation through PKG‐MAP kinase mediated signaling cascade by E. coli heat stable enterotoxin (STa), a potent anti‐angiogenic and anti‐metastatic molecule
Authors: Saha Subhrajit , Chowdhury Pinki , Pal Amit , Chakrabarti Manoj K.
Published: September 2007

It was reported earlier that Escherichia coli heat stable enterotoxin (STa), a major causative agent of secretory diarrhea, can also inhibit the proliferation of colon carcinoma cells with the involvement of cGMP mediated calcium influx. In the present study it is shown that E. coli STa inhibits cell proliferation in the colonic carcinoma cell line COLO‐205 by the PKG‐ERK44/42 mediated signaling pathway. This enterotoxin negatively regulates cell proliferation by downregulating the activity of ERK44/42(MAPK) and subsequently the activity of a transcription regulatory protein cMyc. The antiproliferative effect of STa was reversed by LY83583, a guanylate cyclase (GC) inhibitor and KT5823, a PKG inhibitor. Thus suggesting the involvement of cGMP dependent protein kinase (PKG) in the downregulation of ERK44/42 and subsequent inactivation of cMyc activity. Moreover, it has been shown that a specific ERK44/42 inhibitor, PD98059, also inhibits cMyc activation and cell proliferation, which further confirms the involvement of ERK44/42 in the activation of cMyc. It is also shown that E. coli STa significantly inhibits the vascular endothelial growth factor (VEGF, a potent angiogenic factor) expression in COLO‐205 cells and also downregulates vascular cell adhesion molecule‐1 (VCAM‐1, a potent metastatic factor) expression on the COLO‐205 cell surface. So it is reported for the first time that E. coli STa inhibits the proliferation of the colonic carcinoma cell line COLO‐205 by the PKG‐ERK44/42 mediated pathway and it may have a role against the development of colon carcinoma. Copyright © 2007 John Wiley & Sons, Ltd.
Evaluation of a rapid and convenient method for determination of cytomegalovirus immunoglobulin M
Authors: Zhang Jiajun , Li Junchuan , Zhang Youshan , Zhu Hongyu , Ma Qing , Hang Gang
Published: September 2007

We evaluated a method for determination of human cytomegalovirus (hCMV) immunoglobulin M (IgM) by CLIA, and analyzed its clinical value in patients with infectious mononucleosis. Serum samples from 407 participants were measured on an automatic CLIA analyzer. At the same time the serum samples were measured by enzyme‐linked immunosorbent assay (ELISA). An assessment of technological quality (methodology) in diagnostic tests demonstrated that the sensitivity of CLIA was 1.0 AU/mL and the functional sensitivity was <1.6 AU/mL. The within‐ and between‐assay imprecision values for different concentrations were all under 5%. Recoveries for both methods were 96–110%. The linear regression equation between expected values and measured values was y=0.644+0.986x, and correlation coefficient was 0.9991 (P<0.0001). The receiver operating characteristic (ROC) curve showed that both the sensitivity and specificity of CLIA surpassed 90%. The area under the curve (AUC) was 0.990, which was significantly higher than that of ELISA (P<0.05). The results indicate that CLIA is an excellent method for hCMV IgM measurement, and thus may be useful for clinical diagnoses. J. Clin. Lab. Anal. 21:255–259, 2007. © 2007 Wiley‐Liss, Inc.
Comparison of ATP production in whole blood and lymphocyte proliferation in response to phytohemagglutinin
Authors: Augustine Nancy H. , Pasi Brian M. , Hill Harry R.
Published: September 2007

Lymphocyte proliferation in response to mitogens, phytohemagglutinin (PHA), concanavalin A, pokeweed, and/or specific antigens has been the method of choice for in vitro diagnosis of cell‐mediated immune dysfunction. Recently, an assay to measure intracellular adenosine triphosphate (ATP) production in response to PHA has been developed that requires a shorter, overnight incubation. We compared a standard 5‐ to 7‐day lymphocyte mitogen stimulation assay utilizing tritiated thymidine (3H‐thy) incorporation to one in which ATP production in response to PHA by CD4‐positive cells is measured in a luminometer that requires only 18–24 hr. A total of 20 patient samples suspected of having decreased cell‐mediated immunity submitted for mitogen induced lymphocyte proliferation and 21 normal controls were tested in both assays. A comparison of these two methods has demonstrated that the screening ATP assay has a sensitivity at 24 hr of 100% in detecting decreased PHA induced lymphocyte proliferation at 5 days and a specificity of 85% in the samples obtained from normal controls. The data indicate that the ATP assay may be a useful screening tool for more rapid detection of blood samples with decreased cell‐mediated immune responses. However, a positive screen should always be confirmed by 3H‐thy uptake using mitogens and recall antigens like candida and tetanus. J. Clin. Lab. Anal. 21:265–270, 2007. © 2007 Wiley‐Liss, Inc.
Chagas' disease: IgG isotypes against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens of Trypanosoma cruzi in chronic Chagasic patients
Authors: Verçosa A.F.A. , Lorena V.M.B. , Carvalho C.L. , Melo M.F.A.D. , Cavalcanti M.G.A. , Silva E.D. , Ferreira A.G.P. , Pereira V.R.A. , Souza W.V. , Gomes Y.M.
Published: September 2007

The wide range of clinical Chagas' disease manifestations, of which heart involvement is the most significant, because of its characteristics, frequency and consequences, and lack of treatment and cure, justify research in this area. Specific immunoglobulin G (IgG) antibody subclasses have been associated with human Chagas' disease. Thus, in this study, the profile of IgG subclasses against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive T. cruzi–specific antigens was correlated with cardiac (CARD, n=33), cardiodigestive (CD, n=7), and indeterminate (IND, n=20) forms of Chagas' disease by indirect enzyme‐linked immunosorbent assay (ELISA). IgG subclasses were detected in almost all Chagas patients studied. Nevertheless, only specific IgG2 isotype FRA was found with a significant statistical difference in CARD patients when compared to IND patients. This result suggests the potential use of this isotype for prognostic purposes, for monitoring the progression of chronic Chagas' disease, and for predicting the risk of CARD damage. This is important information, as it could help physicians to evaluate and manage the treatment of their patients. However, a follow‐up study is necessary to confirm our result. J. Clin. Lab. Anal. 21:271–276, 2007. © 2007 Wiley‐Liss, Inc.
IgM, IgG, and IgA rheumatoid factors in pigeon hypersensitivity pneumonitis
Authors: Araiza Mariana Tellez , Aguilar León Diana E. , Retana Virginia Novelo , Martínez‐Cordero Erasmo
Published: September 2007

The association of rheumatoid factor (RF) and lung disease in several immunologically mediated conditions has suggested that it may be physiopathologically relevant. Since previous reports in hypersensitivity pneumonitis (HP) have dealt mainly with the immunoglobulin M (IgM) RF measurement, we studied such antibody activity in other immunoglobulins, to determine the IgG and IgA RF levels in pigeon‐HP, and in asymptomatic breeders (AB) and rheumatoid arthritis (RA) as controls. RFs were measured in 35 HP patients, 41 AB, 31 RA controls, and 55 healthy donors by enzyme‐linked immunosorbent assay (ELISA) using human or rabbit immunoglobulin G (IgG), anti‐IgM, F(ab′)2 of IgG, and IgA F(ab′)2 conjugates. An affinity chromatography, fragment crystallizable (Fc) preparations of IgG, pepsin digestion, and Western blots were used to confirm RF specificity. We also evaluated anti‐avian antibodies (AA) and cross‐reacting antibodies. The HP group revealed positive IgM (51.4%), IgG (31.4%), and immunoglobulin A (IgA) (34.2%) RF tests, and these antibody values exceeded the AB reference levels (P<0.02). HP and RA showed a similar frequency and distribution of RFs. Possible immunoassay interferences were excluded. As in other immunologically mediated diseases, IgG and IgA RFs may play a pathogenic role in HP, amplifying the inflammatory reaction, immune‐complex formation, and complement activation. IgM‐RF producing cells that have been implicated in the presentation of self and foreign antigens, and T‐cell activation might induce the isotype switching of RFs. J. Clin. Lab. Anal. 21:315–321, 2007. © 2007 Wiley‐Liss, Inc.
Effect of infliximab on the glycosylation of IgG of patients with rheumatoid arthritis
Authors: Croce A. , Firuzi O. , Altieri F. , Eufemi M. , Agostino R. , Priori R. , Bombardieri M. , Alessandri C. , Valesini G. , Saso L.
Published: September 2007

In patients with rheumatoid arthritis (RA) a decrease in the terminal galactose content of N‐linked glycans of the Fc region of agalactosyl immunoglobulin G (IgG) (G0) occurs. The aim of this study was to evaluate, for the first time, the effect of infliximab, a new monoclonal antibody for the treatment of RA, on this phenomenon. A total of 19 patients with active RA were treated with intravenous infliximab (3 mg/kg) in combination with methotrexate (MTX) (10–20 mg). IgG was purified from their serum by caprylic acid. Analysis of IgG glycosylation was performed by lectin blotting/immunoblotting and enzyme linked lectin assay (ELLA)/enzyme linked immunosorbent assay (ELISA) using theGriffonia (bandeiraea) simplicifolialectin II and protein‐A/alkaline phosphatase. The purity of IgG samples obtained was higher than 90%. The sensitivity of the lectin/immunoblotting method was of about 0.25 µg of IgG. The inter‐ and intraassay coefficients of variation (CV) were 1.3% and 9.0% for lectin blotting, and 4.6% and 8.3% for immunoblotting, respectively. The sensitivity of the ELLA/ELISA approach was 0.025 µg/µL and the inter‐ and intraassay CV were 6.2% and 7.7% for ELLA, and 5.1% and 14.1% for ELISA, respectively. A good linear correlation (r2=0.18,P<0.05) was obtained between the two different experimental approaches. A decrease of G0 was observed in patients who clinically improved (according to the American College of Rheumatology criteria) following the pharmacological treatment. Our data indicate that infliximab can reduce the concentration of G0 in patients with active RA. J. Clin. Lab. Anal. 21:303–314, 2007. © 2007 Wiley‐Liss, Inc.
Insulin‐like growth factor I (IGF‐I) as a sensitive biomarker of catabolism in patients with gastrointestinal diseases
Authors: Nedić Olgica , Malenković Vesna , Nikolić Judith Anna , Baričević Ivona
Published: September 2007

Gastrointestinal ailments evoke changes in the hypothalamic‐pituitary‐adrenal (HPA) axis and modulation of hepatic protein synthesis. We examined the catabolic effect of certain primary gastrointestinal diseases and surgery on the concentration of insulin‐like growth factor I (IGF‐I). Blood samples from patients with gastric cancer (GC), cholecystitis (CC), or inguinal hernia (IH) were taken before and after surgery. The concentrations of IGF‐I, IGF binding protein‐1 (IGFBP‐1), insulin, cortisol, and glucose were determined. In GC patients the concentration of IGF‐I was reduced and the concentrations of IGFBP‐1 and cortisol were elevated preoperatively; after surgery, IGFBP‐1 normalized. In CC patients the concentration of IGF‐I was low and the concentration of IGFBP‐1 was high before cholecystectomy; after surgery IGFBP‐1 returned to normal and the concentration of cortisol increased. In IH patients the concentration of IGF‐I was low and the concentrations of IGFBP‐1 and cortisol were high before surgery; after laparotomy IGFBP‐1 returned to normal. The metabolic changes were present in all analyzed patient groups, regardless of the severity of disease and nutrition. The concentration of IGF‐I was reduced before surgery and remained reduced after, recommending IGF‐I as a metabolic marker in both pre and postoperative examination of patients. J. Clin. Lab. Anal. 21:335–339, 2007. © 2007 Wiley‐Liss, Inc.
Collection tubes with or without gel separator did not interfere with detection of rubella virus antibodies IgM and IgG
Authors: Oliveira L.C. , Kawasato K.H. , Otta M.S. , Lima L.P. , Okay T.S.
Published: September 2007

Rubella infection is an exanthematic disease, with high prevalence in the adult population. The only modality of disease that causes serious consequences is congenital rubella syndrome (CRS), which happens when a pregnant woman seronegative to rubella virus acquires the infection during early pregnancy. Due to the lack of signals and characteristic symptoms of disease, diagnosis of rubella is based essentially on laboratory tests: antibodies detection and/or virus isolation. Results of serologic tests should always be interpreted with caution, because they can be affected by the quality of blood samples, processing and storage of sera, the equipment and reagents used to perform tests, and finally by the technical expertise and training of biologists. The collection tubes with gel seem to facilitate serum separation, but on the other hand gels can retain and consequently decrease antibody titers. Therefore, we decided to investigate whether the use of collection tubes containing gel separator might interfere with rubella virus antibody detection in blood samples from children. We did not observe statistically significant differences with respect to rubella virus antibody detection (immunoglobulin M [IgM] and immunoglobulin G [IgG]) for samples collected in tubes with or without gel separator, from the two evaluated manufacturers. J. Clin. Lab. Anal. 21:330–334, 2007. © 2007 Wiley‐Liss, Inc.
Isotopic chemistry at Eli Lilly and Company – a look back at the past fifty years
Authors: Wheeler William J.
Published: September 2007

This review will chronicle the genesis and the next fifty years or so of the Isotopic Chemistry effort at Eli Lilly and Company. It all began from a seed planted in Bob McMahon's mind while a post‐doctoral fellow at MIT in 1949 and was later cultivated when he joined the Lilly Research Laboratories in 1954. From the humble beginnings of a few part‐time radiochemists/part time metabolism scientists (Bob McMahon and Hugh Sullivan), the group has evolved to the eleven dedicated scientists that we have today. Copyright © 2007 John Wiley & Sons, Ltd.
The Service Hospitalier Frédéric Joliot – contributions to PET chemistry over the years
Authors: Roeda Dirk , Kuhnast Bertrand , Hammadi Akli , Dollé Frédéric
Published: September 2007

The Service Hospitalier Frédéric Joliot (SHFJ) (CEA‐Orsay, France) has been a stimulating interdisciplinary research platform in medical imaging for almost half a century and particularly in the field of positron emission tomography (PET). In this context, PET chemistry, the driving force in molecular imaging, has occupied the front stage, especially where it concerns the short‐lived radioisotopes carbon‐11 and fluorine‐18. In this review, important marks left by the SHFJ actors over the years will be highlighted. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis of N‐(2,5‐dimethoxybenzyl)‐N‐(5‐fluoro‐2‐phenoxyphenyl)[carbonyl‐11C]acetamide ([carbonyl‐11C]DAA1106) and analogues using [11C]carbon monoxide and palladium(0) complex
Authors: Rahman Obaidur , Långström Bengt
Published: September 2007

N‐(2,5‐Dimethoxybenzyl)‐N‐(5‐fluoro‐2‐phenoxyphenyl)acetamide (DAA1106), a potent and selective ligand for peripheral benzodiazepine receptor, and eight structurally related analogues were labelled with 11C at the carbonyl position using a low concentration of [11C]carbon monoxide and the micro‐autoclave technique. A combinatorial approach was applied to synthesize the analogues using similar reaction conditions. Palladium‐mediated carbonylation using tetrakis(triphenylphosphine)palladium, various amines and methyl iodide or iodobenzene was employed in the synthesis. The 11C‐labelled products were obtained with 10–55% decay‐corrected radiochemical yields and the final product was more than 97% pure in all cases. Specific radioactivity was determined for the compound [carbonyl‐11C]DAA1106 using a single experiment and a 10‐µA h bombardment. The specific radioactivity, measured 36 min after end of bombardment, was 455 GBq/µmol. Synthetic routes to the precursors and reference compounds were also developed. The presented approach is a novel method for the synthesis of [carbonyl‐11C]DAA1106 and its analogues, and allows the formation of a library of 11C‐labelled DAA1106 analogues which can be used to optimize the performance as a potential positron emission tomography tracer. Copyright © 2007 John Wiley & Sons, Ltd.
The influence of rigid or flexible linkage between two ligands on the effective affinity and avidity for reversible interactions with bivalent receptors
Authors: Bobrovnik S. A.
Published: September 2007

Bivalent or polyvalent cooperative binding between ligand and receptor is much tighter and more efficient than monovalent binding of the same counterparts. Because of this, many biological processes involve polyvalent binding for realization of regulatory mechanisms. For this reason it is necessary to develop a general formalism for prediction of the relationship between the binding affinities of each ligand subunits, the length of the flexible linker between them and avidity of the interaction. Here, we consider an approach that is based on the description of the state of equilibrium for the reaction of mono‐ and multivalent ligand‐receptor binding of algebraic equation systems. This approach allows the evaluation of the avidity of bivalent binding and to determine the concentrations of ligand–receptor complexes, which will be obtained at the equilibrium state. The analysis presented here may be useful in analysing the binding behaviour of a bivalent receptor and a ligand consisting of two subunits covalently connected with a rigid or flexible linker. Copyright © 2007 John Wiley & Sons, Ltd.
A rapid, sensitive and effective quantitative method for simultaneous determination of cationic surfactant mixtures from river and municipal wastewater by direct combination of single‐drop microextraction with AP‐MALDI mass spectrometry
Authors: Shrivas Kamlesh , Wu Hui‐Fen
Published: September 2007

A rapid, simple, sensitive, and effective quantitative method for simultaneous determination of cationic surfactants (CS+) from river and municipal wastewater by direct combination of single‐drop microextraction (SDME) with atmospheric pressure (AP)‐MALDI mass spectrometry has been successfully demonstrated without the requirements of tedious sample pre‐ or post‐treatment or separation by high‐performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE). This quantitative method can greatly enhance the signal‐to‐noise ratio for analysis of small molecules of CS+ owing to the strong suppression of matrix ions by the analytes. In addition, SDME assisted in the isolation and preconcentration of CS+ from water samples, which could effectively reduce the background interferences from the matrices present in waste and river water. The SDME conditions were optimized for achieving high extraction efficiency of CS+ from aqueous samples, in terms of solvent selection, stirring speed, extraction time, exposure volume of acceptor phase, and salt addition. The enrichment factors for CS+ were found to be 40–64‐folds for 7 min of extraction time with no salt addition and at room temperature. This method was found to yield a linear calibration curve in the concentration range from 50 to 1500 µg/l CS+ with a limit of detection (LOD) of 10 µg/l. The relative recoveries in river and municipal wastewater were found to be 93.8–103.6% and 91.0–98.7%, respectively. These results indicate that the combination of SDME with AP‐MALDI/MS is effective for the simultaneous determination of CS+ from river and municipal wastewater. In addition, a comparison of enrichments and LOD values for this method with hollow‐fiber liquid phase microextraction (HF‐LPME) was also demonstrated. The present approach is easy to operate, rapid, sensitive, and suitable for high‐throughput of analysis. Copyright © 2007 John Wiley & Sons, Ltd.
The glutamate‐glutamine cycle is not stoichiometric: Fates of glutamate in brain
Authors: McKenna Mary C.
Published: September 2007

Although glutamate is usually thought of as the major excitatory neurotransmitter in brain, it is important to note that glutamate has many other fates in brain, including oxidation for energy, incorporation into proteins, and formation of glutamine, γ‐aminobutyric acid (GABA), and glutathione. The compartmentation of glutamate in brain cells is complex and modulated by the presence and concentration of glutamate per se as well as by other metabolites. Both astrocytes and neurons distinguish between exogenous glutamate and glutamate formed endogenously from glutamine via glutaminase. There is evidence of multiple subcellular compartments of glutamate within both neurons and astrocytes, and the carbon skeleton of glutamate can be derived from other amino acids and many energy substrates including glucose, lactate, and 3‐hydroxybutyrate. Both astrocytes and neurons utilize glutamate, albeit for cell‐specific metabolic fates. Glutamate is readily formed in neurons from glutamine synthesized in astrocytes, released into the extracellular space, and taken up by neurons. However, the glutamate‐glutamine cycle is not a stoichiometric cycle but rather an open pathway that interfaces with many other metabolic pathways to varying extents depending on cellular requirements and priorities. © 2007 Wiley‐Liss, Inc.
Rapid activation of ERK by 6‐hydroxydopamine promotes survival of dopaminergic cells
Authors: Lin Eva , Cavanaugh Jane E. , Leak Rehana K. , Perez Ruth G. , Zigmond Michael J.
Published: September 2007

Isoforms of the mitogen‐activated protein kinase ERK have been implicated in both cell survival and cell death. In the present study we explored their role in cell viability in response to oxidative stress. Using the dopaminergic MN9D cell line, we determined that cell death occurred in a concentration‐dependent manner after exposure to 6‐hydroxydopamine (6‐OHDA). The toxicity of 6‐OHDA was mediated through generation of reactive oxygen species and was accompanied by a large increase in phosphorylated ERK1/2 but no significant increase in phosphorylated ERK5. 6‐OHDA produced a distinct temporal pattern of ERK1/2 activation, with phosphorylated ERK1/2 peaks occurring after 10–15 min (25‐fold increase) and 6–24 hr (13‐fold increase). Inhibition of the early phosphorylated ERK1/2 peak with U0126 increased the generation of reactive oxygen species by 6‐OHDA as well as 6‐OHDA‐induced toxicity, whereas inhibition of the late peak did not affect 6‐OHDA‐induced cell death. The time course of phosphorylation of the prosurvival protein CREB mimicked the temporal profile of ERK1/2 activation after 6‐OHDA, and blocking the early phospho‐ERK1/2 peak also abolished CREB activation. In contrast, activation of caspase‐3 by 6‐OHDA was delayed, occurring after about 6 hr, and this activation was increased by inhibition of the first phosphorylated ERK1/2 peak. These results suggest that the rapid activation of ERK1/2 in dopaminergic cells by oxidative stress serves as a self‐protective response, reducing the content of reactive oxygen species and caspase‐3 activity and increasing downstream ERK1/2 substrates. © 2007 Wiley‐Liss, Inc.
Presynaptic evidence for zinc release at the mossy fiber synapse of rat hippocampus
Authors: Ketterman Joshua K. , Li Yang V.
Published: September 2007

Vesicular zinc (Zn2+) is found in a subset of glutamatergic nerve terminals throughout the mammalian forebrain and is colocalized with glutamate. Despite well‐documented neuromodulatory roles, exocytosis of endogenous Zn2+ from presynaptic terminals has never been directly demonstrated, because existing studies have measured elevated Zn2+ concentrations by examining the perfusate. Thus, the specific origin of synaptic Zn2+ remains a controversial subject. Here, we describe synaptic Zn2+ trafficking between cellular compartments at hippocampal mossy fiber synapses by using the fluorescent indicator Zinpyr‐1 to label the hippocampal mossy fiber boutons. We determined endogenous Zn2+ exocytosis by direct observation of vesicular Zn2+ as decreasing fluorescence intensity from presynaptic axonal boutons in the stratum lucidum of CA3 during neural activities induced by the stimulation of membrane depolarization. This presynaptic fluorescence gradually returned to a level near baseline after the withdrawal of moderate stimulation, indicating an endogenous mechanism to replenish vesicular Zn2+. The exocytosis of the synaptic Zn2+ was also dependent on extracellular Ca2+ and was sensitive to Zn2+‐specific chelators. Vesicular Zn2+ loading was sensitive to the vacuolar‐type H+‐ATPase inhibitor concanamycin A, and our experiments indicated that blockade of vesicular reloading with concanamycin A led to a depletion of that synaptic Zn2+. Furthermore, synaptic Zn2+ translocated to the postsynaptic cell body upon release to produce increases in the concentration of weakly bound Zn2+ within the postsynaptic cytosol, demonstrating a feature unique to ionic substances released during neurotransmission. Our data provide important evidence for Zn2+ as a substance that undergoes release in a manner similar to common neurotransmitters. © 2007 Wiley‐Liss, Inc.
Chemokine receptors and neurotrophic factors: Potential therapy against aids dementia?
Authors: Mocchetti Italo , Bachis Alessia , Masliah Eliezer
Published: September 2007

Chemokine receptors, in particular, CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV‐1) infection of immunocompetent cells and the apoptosis of these cells. However, the virus does not infect neurons. Yet through a variety of mechanisms, HIV promotes glial cell activation, synaptodendritic alterations, and neuronal loss that ultimately lead to motor and cognitive impairment. Chemokines and chemokine receptors are abundant in the adult central nervous system and play a role in neuronal apoptosis evoked by HIV proteins. Thus, reducing the availability of chemokine receptors may prevent the neuronal degeneration seen in HIV‐positive patients. In this article, we present and discuss a recent experimental approach aimed at testing effective neuroprotective therapies against HIV‐mediated neuronal degeneration. © 2007 Wiley‐Liss, Inc.
Relationship between ribosomal RNA gene transcription activity and motoneuron death: Observations of avulsion and axotomy of the facial nerve in rats
Authors: Nagasao Jun , Hayashi Yuichi , Kawazoe Yoko , Kawakami Emiko , Watabe Kazuhiko , Oyanagi Kiyomitsu
Published: September 2007

Motoneuron number and expression of cytoplasmic RNA and ribosomal RNA (rRNA) gene transcription activity in the facial nucleus were examined quantitatively and chronologically for up to 4 weeks in rats after facial nerve axotomy and avulsion in order to elucidate interrelationships in axonal changes. The right facial nerves of adult Fischer rats were avulsed at a portion of the outlet or axotomized at a portion of the foramen stylomastoideus. The number of large motoneurons in the facial nucleus was reduced by 40% 2 weeks after avulsion and by 70% 4 weeks after avulsion but displayed a 19% loss even 4 weeks after axotomy. The amount of cytoplasmic RNA decreased significantly and progressively from 1 day after avulsion. rRNA gene transcription activity in the large motoneurons of the facial nucleus decreased significantly beginning 30 min after both axotomy and avulsion, but the severity of the decrease was far more marked in the avulsion group, showing a 59% loss from the control value 4 weeks after avulsion. These findings indicate that rRNA gene transcription activity, expression of cytoplasmic RNA, and the number of motoneurons that survive are interrelated and that the decrease in rRNA gene transcription activity is a very early event in the phenomena observed in the axonal reactions of motoneurons. © 2007 Wiley‐Liss, Inc.
Mitochondrial transport proteins of the brain
Authors: Berkich D.A. , Ola M.S. , Cole J. , Sweatt A.J. , Hutson S.M. , LaNoue K.F.
Published: September 2007

In this study, cellular distribution and activity of glutamate and γ‐aminobutyric acid (GABA) transport as well as oxoglutarate transport across brain mitochondrial membranes were investigated. A goal was to establish cell‐type‐specific expression of key transporters and enzymes involved in neurotransmitter metabolism in order to estimate neurotransmitter and metabolite traffic between neurons and astrocytes. Two methods were used to isolate brain mitochondria. One method excludes synaptosomes and the organelles may therefore be enriched in astrocytic mitochondria. The other method isolates mitochondria derived from all regions of the brain. Immunological and enzymatic methods were used to measure enzymes and carriers in the different preparations, in addition to studying transport kinetics. Immunohistochemistry was also employed using brain slices to confirm cell type specificity of enzymes and carriers. The data suggest that the aspartate/glutamate carriers (AGC) are expressed predominantly in neurons, not astrocytes, and that one of two glutamate/hydroxyl carriers is expressed predominantly in astrocytes. The GABA carrier and the oxoglutarate carrier appear to be equally distributed in astrocytes and neurons. As expected, pyruvate carboxylase and branched‐chain aminotransferase were predominantly astrocytic. Insofar as the aspartate/glutamate exchange carriers are required for the malate/aspartate shuttle and for reoxidation of cytosolic NADH, the data suggest a compartmentation of glucose metabolism in which astrocytes catalyze glycolytic conversion of glucose to lactate, whereas neurons are capable of oxidizing both lactate and glucose to CO2 + H2O. © 2007 Wiley‐Liss, Inc.
Expression of the scaffolding PDZ protein glutaminase‐interacting protein in mammalian brain
Authors: Olalla Lucía , Gutiérrez Antonia , Jiménez Antonio J. , López‐Téllez Juan F. , Khan Zafar U. , Pérez Juan , Alonso Francisco J. , de la Rosa Vanessa , Campos‐Sandoval José A. , Segura Juan A. , Aledo J. Carlos , Márquez Javier
Published: September 2007

A human brain cDNA clone coding for a novel PDZ‐domain protein of 124 amino acids was previously isolated in our laboratory. The protein was termed glutaminase‐interacting protein (GIP), because it interacts with the C‐terminal region of the human L‐type glutaminase (LGA). The pattern of expression and functions of GIP in brain are completely unknown, so its significance remains undefined. Here we describe the expression of GIP mRNA and protein in mammalian brain. Northern blot analysis revealed that GIP mRNA was ubiquitous in most regions of human brain but was particularly abundant in spinal cord. The presence of the protein in rat and monkey brain was studied at the regional, cellular, and subcellular level by immunocytochemistry. The protein was found to be present in both neurons and astrocytes, with a cytosolic and mitochondrial subcellular localization. Double immunofluorescence labeling with anti‐GIP and anti‐LGA antibodies using confocal microscopy revealed colocalization of both proteins in astrocyte cell processes and their perivascular end feet. Electron microscopy of rat brain neurons revealed GIP immunoreactivity concentrated also in the nuclear envelope and the plasma membrane. The multiple locations for GIP in mammalian brain are in agreement with known protein interaction partners reported for this PDZ protein. The findings presented here support a role of GIP as an important scaffold in both astrocytes and neurons and point toward astrocytic processes and perivascular end feet as plausible anatomical substrates for interaction with glutaminase. © 2007 Wiley‐Liss, Inc.
Side pumped Nd:YAG slab laser mode-locked using multiple quantum well saturable absorbers
Authors: Kubeček V , Zendzian W , Jabczynski J K , Kwiatkowski J , Jelínková H , Stintz A , Diels J-C
Published: September 2007

Mode locking of a Nd:YAG triangle slab laser, side pumped by 600 W pulsed laser diode, using semiconductor saturable absorbers with 100 quantum wells in transmission configuration, is reported. Trains containing 6 pulses with total energy of 2 mJ and single pulse duration of 87 ps (or 0.65 mJ and duration of 65 ps) were generated. Extended trains containing 20 pulses were obtained by passive negative feedback due to beam defocusing in GaAs substrate with pulse shortening along the train.
Polarization-dependent pulse compression in an argon-filled cell through filamentation
Authors: Liu J , Chen X W , Li R X , Kobayashi T
Published: September 2007

Pulse compression through filamentation in an argon-filled cell was experimentally demonstrated by using circularly and linearly polarized pulses. A 53 fs circularly polarized pulse was successfully compressed to 15 fs. By using circularly polarized pulse input, the broadened spectrum was much wider and the incident energy in the gas cell can be increased by more than 3/2 times. Much shorter pulse could be compressed by using circularly polarized pulse input.
Quantification of normal range of inflammatory changes in morphologically normal pediatric muscle
Authors: Varsani Hemlata , Newton Katy R. , Li Charles K. , Harding Brian , Holton Janice L. , Wedderburn Lucy R.
Published: September 2007

The aim of this study was to define normal ranges of histological features in pediatric muscle in comparison with muscle demonstrating inflammatory changes. Sixteen pediatric muscle biopsy samples, considered normal by standard histology, were analyzed for the presence of inflammatory cells, and the expression of neonatal myosin and major histocompatibility complex (MHC) Class 1. Normal findings were defined for each feature. These data will facilitate quantitative analysis of inflammatory changes in pediatric muscle biopsy. Muscle Nerve, 2007