bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel genetic variants in microRNA genes and familial breast cancer
Authors: Shen Jie , Ambrosone Christine B. , Zhao Hua 
Published: September 2008

AbstractMicroRNA (miRNA) plays an important role in tumorigenesis, but whether miRNA is a cancer predisposition factor or not is still unknown. Considering the fact that miRNA regulates a number of tumor suppressor genes (TSGs) and oncogenes, genetic variations in miRNA genes could affect the levels of expression of TSGs or oncogenes and, thereby, cancer risk. To test this hypothesis, we screened genetic variants in 17 selected miRNA genes, which are predicted to regulate key breast cancer genes, in 42 patients with familial breast cancer. Seven novel genetic variants were observed in 7 primary or precursor miRNA genes. Among them, 1 rare variant in the precursor of miR‐30c‐1 and 1 rare variant in the primary precursor of miR‐17 were only observed in noncarriers of BRCA1/2 mutations. In functional assays, these 2 variants resulted in conformational changes in the predicted secondary structures, and consequently altered the expression of mature miR‐30c‐1 and miR‐17. In the target in vitro assay, we observed that miR‐17 could bind to the 3′UTR of BRCA1 mRNAs, which is predicted to be a target for miR‐17. Our findings suggest that functional genetic variants in miRNA genes can potentially alter the regulation of key breast cancer genes. Whether they confer genetic susceptibility to breast cancer remains to be determined. © 2008 Wiley‐Liss, Inc.
Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older
Authors: Meijer Chris J.L.M. , Berkhof Johannes , Castle Philip E. , Hesselink Albertus T. , Franco Eduardo L. , Ronco Guglielmo , Arbyn Marc , Bosch F. Xavier , Cuzick Jack , Dillner Joakim , Heideman Daniëlle A.M. , Snijders Peter J.F. 
Published: September 2008

AbstractGiven the strong etiologic link between high‐risk HPV infection and cervical cancer high‐risk HPV testing is now being considered as an alternative for cytology‐based cervical cancer screening. Many test systems have been developed that can detect the broad spectrum of hrHPV types in one assay. However, for screening purposes the detection of high‐risk HPV is not inherently useful unless it is informative for the presence of high‐grade cervical intraepithelial neoplasia (CIN 2/3) or cancer. Candidate high‐risk HPV tests to be used for screening should reach an optimal balance between clinical sensitivity and specificity for detection of high‐grade CIN and cervical cancer to minimize redundant or excessive follow‐up procedures for high‐risk HPV positive women without cervical lesions. Data from various large screening studies have shown that high‐risk HPV testing by hybrid capture 2 and GP5+/6+‐PCR yields considerably better results in the detection of CIN 2/3 than cytology. The data from these studies can be used to guide the translation of high‐risk HPV testing into clinical practice by setting standards of test performance and characteristics. On the basis of these data we have developed guidelines for high‐risk HPV test requirements for primary cervical screening and validation guidelines for candidate HPV assays. © 2008 Wiley‐Liss, Inc.
Population differences in immune marker profiles associated with human T‐lymphotropic virus type I infection in Japan and Jamaica
Authors: Birmann Brenda M. , Breen Elizabeth C. , Stuver Sherri , Cranston Beverly , Martínez‐Maza Otoniel , Falk Kerstin I. , Okayama Akihiko , Hanchard Barrie , Mueller Nancy , Hisada Michie 
Published: September 2008

AbstractThe natural history of human T‐lymphotropic virus type I (HTLV‐I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T‐cell lymphoma (ATL) and HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV‐I‐endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)—i.e., 51 HTLV‐I‐positive (“carriers”) and 51 HTLV‐I‐negative individuals (“noncarriers”) from each population—by age, sex and blood collection year. We compared plasma concentrations of markers of T‐cell‐mediated (antigen‐specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV‐I noncarriers, Japanese noncarriers had higher covariate‐adjusted mean levels of T‐cell activation markers, including antibody to Epstein‐Barr virus nuclear antigen‐1 (reciprocal titer 27 vs. 71, respectively, p = 0.005), soluble interleukin‐2 receptor‐α (477 vs. 623 pg/mL, p = 0.0008) and soluble CD30 (34 vs. 46 U/mL, p = 0.0001) and lower levels of C‐reactive protein (1.1 vs. 0.43 μg/mL, p = 0.0004). HTLV‐I infection was associated with activated T‐cell immunity in Jamaicans but with diminished T‐cell immunity in Japanese persons. The observed population differences in background and HTLV‐I‐related host immunity correspond closely to the divergent natural histories of infection observed among HTLV‐I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk. © 2008 Wiley‐Liss, Inc.
TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis
Authors: Castillejo Adela , Rothman Nathaniel , Murta‐Nascimento Cristiane , Malats Núria , García‐Closas Montserrat , Gómez‐Martínez Angeles , Lloreta Josep , Tardón Adonina , Serra Consol , García‐Closas Reina , Chanock Stephen , Silverman Debra T. , Dosemeci Mustafa , Kogevinas Manolis , Carrato Alfredo , Soto José Luis , Real Francisco X. 
Published: September 2008

AbstractThe transforming growth factor‐beta (TGF‐β) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF‐β signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFB1 (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case‐control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan‐Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle‐invasive tumors, we found a significant association between TGFBR1‐rs868 and disease‐specific mortality with an allele dosage effect (p‐trend = 0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of TGFBR1‐rs868 with outcome should be validated in independent patient series. © 2008 Wiley‐Liss, Inc.
Comparative evaluation of FASTPlaque assay with PCR and other conventional in vitro diagnostic methods for the early detection of pulmonary tuberculosis
Authors: Singh Sarman , Saluja Taran Prit , Kaur Manjot , Khilnani G.C. 
Published: September 2008

AbstractRapid and accurate diagnosis of symptomatic patients of pulmonary tuberculosis (TB) is highly desirable to minimize the spread of the disease in the society. We, therefore, compared the usefulness of various conventional diagnostic methods, the in‐house polymerase chain reaction (PCR), and the FASTPlaque assay in this study. Laboratory data of 150 patients with clinical diagnosis of pulmonary TB and 50 controls were included in this study. The sputa from all these 200 individuals were subjected to acid‐fast staining, culture on Lowenstein–Jensen (L‐J) slants, automated BACTEC‐MGIT‐960 culture methods, and a mycobacteriophage assay. A mycobacterium genus andMycobacterium tuberculosisspecies‐specific PCRs were also done and samples positive on both PCRs were considered as standard for comparison. Of the 5 in vitro diagnostic tests, PCR method was found to be the most rapid, sensitive, and specific, detecting all the 150 cases of pulmonary TB without any false‐positive and negative result. In comparison with PCR the sensitivity of MGIT‐960 was 90%, followed by FASTPlaque assay (76.7%), L‐J culture method (73.3%), and microscopy (60%). The mean detection time for smear‐positive and smear‐negative samples was 12.5 and 14 days in MGIT‐960 and 18 and 25 days for L‐J method, respectively. The FASTPlaque failed to detect mycobacteria from the paucibacillary samples. The contamination rates for MGIT‐960, L‐J, and FASTPlaque assays were 4, 8 and 10%, respectively. The best correlation with mycobacterial load in the specimen was observed in BACTEC‐MGIT‐960 showing 66.6% detection rate in paucibacillary, 83.3% in 1+ samples, and 100% in 2+ and 3+ samples. Out of the 150 patients, 140 (93.3%) could be diagnosed by one or more nonmolecular methods. Therefore, it could be concluded that combination of three or more in vitro diagnostic methods will have acceptable detection level. J. Clin. Lab. Anal. 22:367–374, 2008. © 2008 Wiley‐Liss, Inc.
Normal blood cells reference intervals of healthy adults at the Gaza Strip—Palestine
Authors: Sirdah Mahmoud M. , Tarazi Issa S. , Jeadi Hesham El , Al Haddad Rami M. 
Published: September 2008

AbstractHematological parameters are affected by different factors that include age, sex, smoking, ethnicity, and environmental altitude. It has been justified that each population must establish its own normal reference intervals to be used in clinical assessments and interpretations. Hematological reference intervals for adults from the Gaza Strip—Palestine have never been addressed. Therefore, this study was designed and aimed at the establishment of normal blood cells reference intervals for healthy adults at the Gaza Strip—Palestine. This study involved 89,491 apparently healthy individuals (from both sexes and from the different governorates of the Gaza Strip) who were referred to the Thalassemia Central Laboratory during the period from September 2000 until February 2008. Complete blood counts were performed. Subjects were categorized into subgroups according to gender, smoking habit, and age (15–18, 19–45, and >45 years old). For each subgroup, descriptive and comparative statistical analysis was performed for hematological parameters. The results showed substantial differences between males and females, between smokers and nonsmokers, and between the different age groups. Moreover, reference intervals derived from our population are markedly shifted downward as compared with Western European and American populations. It was concluded that separate and region‐specific reference intervals based on gender, smoking, and age for the Palestinian population at the Gaza Strip should be generalized for clinical laboratories and clinical practitioners, which could help in interpreting laboratory hematological tests more specifically, and potentially develop the quality of medical care provided to patients. J. Clin. Lab. Anal. 22:353–361, 2008. © 2008 Wiley‐Liss, Inc.
Serum adipocyte‐fatty acid binding protein discriminates patients with permanent and temporary body weight loss
Authors: Stejskal D. , Karpisek M. , Bronsky J. 
Published: September 2008

AbstractAdipocyte‐fatty acid binding protein (A‐FABP) is a biomarker of adiposity and metabolic syndrome. The aim of our work was to investigate the effect of weight reduction on serum A‐FABP value. In the study, we analyzed a group of 189 probands suffering from obesity (102 women and 87 men; aged 57.3±12 years) initially, after a 3‐month low‐fat diet and once again 3 months after the termination of the diet for serum A‐FABP, insulin, glucose, total cholesterol, HDL‐cholesterol, LDL‐cholesterol, and triglycerides. Basal biomarker concentrations were typical of the metabolic syndrome, and moreover A‐FABP correlated with Quicki and BMI. We observed a reduction in BMI in 145 subjects who were divided into two subgroups: A—with persistent BMI reduction even after 6 months, B—with BMI reduction after 3 months and its regress after 6 months. Individuals with rise or no BMI difference were signed as subgroup C. In subgroup A, A‐FABP level increased and returned to the earlier level (42.3 vs 68.3 vs 37.1 µg/l) and correlated with the markers of the metabolic syndrome. In subgroup B, A‐FABP level increased less significantly, however elevated A‐FABP level persisted for 6 months (41.9 vs 53.6 vs 50.7 µg/l). Subgroup C (n=54) showed no difference in A‐FABP after 3‐month diet and after next 3 months. The A‐FABP value correlated with the some components of the metabolic syndrome. In conclusion, we describe that serum A‐FABP might be a prognostic marker of body weight loss suggesting a preventive therapeutic intervention. J. Clin. Lab. Anal. 22:380–382, 2008. © 2008 Wiley‐Liss, Inc.
Evaluation of a new commercial enzyme immunoassay for the detection of IgM antibodies to West Nile virus using a ratio method to eliminate nonspecific reactivity
Authors: Welch Ryan J. , Anderson Brian L. , Litwin Christine M. 
Published: September 2008

AbstractAs West Nile virus (WNV) has become endemic in the United States, following the first reported cases in New York during the summer of 1999, the demand for specific serology has increased. Several IgM capture ELISA assays for the detection of WNV‐specific IgM have been approved by the Food and Drug Administration for in vitro diagnostic testing, including kits from Focus Diagnostics and InBios International, Inc. The Focus Diagnostics IgM capture ELISA has a background subtraction protocol and the InBios IgM capture ELISA implements a ratio method to detect nonspecific reactivity due to rheumatoid factor, heterophile antibodies, and other interfering substances. We compared the InBios IgM capture ELISA with the Focus Diagnostics capture ELISA. Agreement, sensitivity, and specificity of the InBios IgM capture ELISA were 99, 98, and 100%, respectively. Samples that originally tested positive on the Focus Diagnostics IgM capture ELISA without the subtraction protocol and were then determined negative following the subtraction protocol agreed 100% with the InBios IgM capture ELISA. We conclude that a method to eliminate background reactivity is a necessary portion of any anti‐WNV IgM assay in order to eliminate false‐positive results. J. Clin. Lab. Anal. 22:362–366, 2008. © 2008 Wiley‐Liss, Inc.
Use of vaginal pH in diagnosis of infections and its association with reproductive manifestations
Authors: Mania‐Pramanik Jayanti , Kerkar S.C. , Mehta P.B. , Potdar S. , Salvi V.S. 
Published: September 2008

AbstractIncrease in vaginal secretion pH is an indicator of bacterial vaginosis (BV), but is yet to be in use as a diagnostic tool by clinicians. Similarly, no reports are available on the effect of cervical chlamydia infection and different reproductive manifestations on vaginal secretion pH. This study evaluated the use of vaginal pH for screening of BV, the effect of Chlamydia trachomatis (C. trachomatis) infection, and different reproductive manifestations on vaginal pH of women attending the gynecology outpatient department of a general hospital. Vaginal pH was recorded while diagnosing infections in 358 women, among which 45 were with repeated spontaneous abortion, 79 with infertility, 185 had sign and symptoms of lower genital tract infection, and 49 had no history or symptom of any complications or infections. Normal vaginal pH, BV, and C. trachomatis infection were observed in 72.6, 21.5, and 10.1% of women, respectively. BV and C. trachomatis were observed in 78.6 and 4.1% of women, respectively, with high vaginal pH; 12.3% of women with normal vaginal pH had C. trachomatis infection. C. trachomatis infection or different reproductive manifestations do not lead to change in vaginal pH but high vaginal pH correlated with BV and should be used as a simple tool for its diagnosis. J. Clin. Lab. Anal. 22:375–379, 2008. © 2008 Wiley‐Liss, Inc.
In vitro differentiation of human calvarial suture derived cells with and without dexamethasone does not induce in vivo‐like expression
Authors: Coussens Anna K. , Hughes Ian P. , Morris C. Phillip , Powell Barry C. , Anderson Peter J. 
Published: September 2008

AbstractOsteogenic supplements are a requirement for osteoblastic cell differentiation during in vitro culture of human calvarial suture‐derived cell populations. We investigated the ability of ascorbic acid and β‐glycerophosphate with and without the addition of dexamethasone to stimulate in vivo‐like osteoblastic differentiation. Cells were isolated from unfused and prematurely fused suture tissue from patients with syndromic and non‐syndromic craniosynostosis and cultured in each osteogenic medium for varying lengths of time. The effect of media supplementation was investigated with respect to the ability of cells to form mineralised bone nodules and the expression of five osteodifferentiation marker genes (COL1A1, ALP, BSP, OC and RUNX2), and five genes that are differentially expressed during human premature suture fusion (GPC3, RBP4, C1QTNF3, WIF1 and FGF2). Cells from unfused sutures responded more slowly to osteogenic media but formed comparable bone nodules to fused suture‐derived cells after 16 days of culture in either osteogenic media. However, gene expression differed between unfused and fused suture‐derived cells, as did expression in each osteogenic medium. When compared to expression in the explant tissue of origin, neither medium induced a level or profile of gene expression similar to that seen in vivo. Overall, our results demonstrate that cells from the same suture that are isolated during different stages of morphogenesis in vivo, despite being de‐differentiated to a similar level in vitro, respond uniquely and differently to each osteogenic medium. Further, we suggest that neither cell culture medium recapitulates differentiation via activation of the same genetic cascades as occurs in vivo. J. Cell. Physiol. 218: 183–191, 2009. © 2008 Wiley‐Liss, Inc.
Increased bone mass, altered trabecular architecture and modified growth plate organization in the growing skeleton of SOCS2 deficient mice
Authors: MacRae V.E. , Horvat S. , Pells S.C. , Dale H. , Collinson R.S. , Pitsillides A.A. , Ahmed S.F. , Farquharson C. 
Published: September 2008

AbstractSuppressor of cytokine signalling‐2 (SOCS2) negatively regulates the signal transduction of several cytokines. Socs2−/− mice show increased longitudinal skeletal growth associated with deregulated GH/IGF‐1 signalling. The present study examined the role of SOCS2 in endochondral ossification and trabecular and cortical bone formation, and investigated whether pro‐inflammatory cytokines associated with pediatric chronic inflammatory disorders mediate their effects through SOCS2. Seven‐week‐old Socs2−/− mice were heavier (27%; P < 0.001) and longer (6%; P < 0.001) than wild‐type mice. Socs2−/− tibiae were longer (8%; P < 0.001) and broader (18%; P < 0.001) than that of wild‐type mice, and the Socs2−/− mice had wider growth plates (24%; P < 0.001) with wider proliferative and hypertrophic zones (10% (P < 0.05) and 14% (P < 0.001) respectively). Socs2−/− mice showed increased total cross‐sectional bone area (16%: P < 0.001), coupled to increased total tissue area (17%; P < 0.05) compared to tibia from wild‐type mice. Socs2−/− mice showed increased percent bone volume (101%; P < 0.001), trabecular number (82%; P < 0.001) and trabecular thickness (11%; P < 0.001), with associated decreases in trabecular separation (19%; P < 0.001). TNFα exposure to growth plate chondrocytes for 48 h increased SOCS2 protein expression. Growth of metatarsals from 1‐day‐old Socs2−/− and Socs2+/+ mice, as well as expression of Aggrecan, Collagen Type II and Collagen Type X, were inhibited by TNFα, with no effect of genotype. Our data indicate that physiological levels of SOCS2 negatively regulate bone formation and endochondral growth. Our results further suggest that pro‐inflammatory cytokines mediate their inhibitory effects on longitudinal bone growth through a mechanism that is independent of SOCS2. J. Cell. Physiol. 218: 276–284, 2009. © 2008 Wiley‐Liss, Inc.
Sustained NF‐κB activation produces a short‐term cell proliferation block in conjunction with repressing effectors of cell cycle progression controlled by E2F or FoxM1
Authors: Penzo Marianna , Massa Paul E. , Olivotto Eleonora , Bianchi Francesca , Borzi Rosa Maria , Hanidu Adedayo , Li Xiang , Li Jun , Marcu Kenneth B. 
Published: September 2008

AbstractNF‐κB transcription factors induce a host of genes involved in pro‐inflammatory/stress‐like responses; but the collateral effects and consequences of sustained NF‐κB activation on other cellular gene expression programming remain less well understood. Here enforced expression of a constitutively active IKKβ T‐loop mutant (IKKβca) drove murine fibroblasts into transient growth arrest that subsided within 2–3 weeks of continuous culture. Proliferation arrest was associated with a G1/S phase block in immortalized and primary early passage MEFs. Molecular analysis in immortalized MEFs revealed that inhibition of cell proliferation in the initial 1–2 weeks after their IKKβca retroviral infection was linked to the transient, concerted repression of essential cell cycle effectors that are known targets of either E2F or FoxM1. Co‐expression of a phosphorylation resistant IκBα super repressor and IKKβca abrogated growth arrest and cell cycle effector repression, thereby linking IKKβca's effects to canonical NF‐κB activation. Transient growth arrest of IKKβca cells was associated with enhanced p21 (cyclin‐dependent kinase inhibitor 1A) protein expression, due in part to transcriptional activation by NF‐κB and also likely due to strong repression of Skp2 and Csk1, both of which are FoxM1 direct targets mediating proteasomal dependent p21 turnover. Ablation of p21 in immortalized MEFs reduced their IKKβca mediated growth suppression. Moreover, trichostatin A inhibition of HDACs alleviated the repression of E2F and FoxM1 targets induced by IKKβca, suggesting chromatin mediated gene silencing in IKKβca's short term repressive effects on E2F and FoxM1 target gene expression. J. Cell. Physiol. 218: 215–227, 2009. © 2008 Wiley‐Liss, Inc.