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ABSTRACT: In this study we aimed to develop a habituation paradigm that allows the investigation of response decrement and response recovery and examine its applicability for measuring the habituation of the visually evoked responses (VERs) in neonatal and fetal magnetoencephalographic recordings. Two paradigms, one with a long and one with a short inter-train interval (ITI), were developed and tested in separate studies. Both paradigms consisted of a train of four light flashes; each train being followed by a 500Hz burst tone. Healthy pregnant women underwent two prenatal measurements and returned with their babies for a neonatal investigation. The amplitudes of the neonatal VERs in the long-ITI condition showed within-train response decrement. An increased response to the auditory dishabituator was found confirming response recovery. In the short-ITI condition, neonatal amplitude decrement could not be demonstrated while response recovery was present. In both ITI conditions, the response rate of the cortical responses was much lower in the fetuses than in the neonates. Fetal VERs in the long-ITI condition indicate amplitude decline from the first to the second flash with no further decrease. The long-ITI paradigm might be useful to investigate habituation of the VERs in neonates and fetuses, although the latter requires precaution.
Developmental cognitive neuroscience. 03/2012; 2(3):303-16.
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ABSTRACT: Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC.
A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival.
There were 112 males and 219 females with a median age of 44 years (range 11-87). The median follow-up time for the series was 71.5 months (range 12.7-148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease-free survival (p=0.0005) on bivariate Cox regression.
US of the central compartment is an age-independent predictor for survival and CNC recurrence-free survival in PTC. Prophylactic neck dissection of the central compartment does not improve long-term disease control, regardless of the histopathological status of the lymph nodes retrieved. Our findings emphasize the ability of US to clinically detect relevant nodal disease and support conservative management of the CNC in the absence of abnormal findings.
Thyroid: official journal of the American Thyroid Association 01/2012; 22(4):347-55. · 2.60 Impact Factor
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ABSTRACT: Classification algorithms can be used to predict risks and responses of patients based on genomic and other high-dimensional data. While there is optimism for using these algorithms to improve the treatment of diseases, they have yet to demonstrate sufficient predictive ability for routine clinical practice. They generally classify all patients according to the same criteria, under an implicit assumption of population homogeneity. The objective here is to allow for population heterogeneity, possibly unrecognized, in order to increase classification accuracy and further the goal of tailoring therapies on an individualized basis.
A new selective-voting algorithm is developed in the context of a classifier ensemble of two-dimensional convex hulls of positive and negative training samples. Individual classifiers in the ensemble are allowed to vote on test samples only if those samples are located within or behind pruned convex hulls of training samples that define the classifiers.
Validation of the new algorithm's increased accuracy is carried out using two publicly available datasets having cancer as the outcome variable and expression levels of thousands of genes as predictors. Selective voting leads to statistically significant increases in accuracy from 86.0% to 89.8% (p<0.001) and 63.2% to 67.8% (p<0.003) compared to the original algorithm.
Selective voting by members of convex-hull classifier ensembles significantly increases classification accuracy compared to one-size-fits-all approaches.
Artificial intelligence in medicine 11/2011; 54(3):171-9. · 1.65 Impact Factor
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ABSTRACT: Using non-invasive fetal magnetoencephalography (fMEG), we investigated spontaneous brain activity in 28 fetuses diagnosed with intrauterine growth restriction (IUGR) and compared the results to 47 normal-growth fetuses. The fetal gestational age ranged from 28 to 39 weeks with post-natal recordings obtained on 17 of the IUGR fetuses. Power spectrum was computed and was divided into four frequency bands. A significant difference in the relative spectral power in delta, theta and beta bands (P<0.01) was observed only in the 28-32 week gestation age group with alpha band showing a similar trend (P=0.054). This observation suggests that growth restriction may have a more pronounced effect on the fetal brain in early gestation. Larger population studies could reveal the potential value of fMEG as an additional surveillance tool for growth-restricted fetuses.
Early human development 10/2011; 88(6):451-4. · 2.12 Impact Factor
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Craig A Cooney,
Fariba Jousheghany,
Aiwei Yao-Borengasser,
Bounleut Phanavanh,
Tina Gomes,
Ann Marie Kieber-Emmons, Eric R Siegel,
Larry J Suva,
Soldano Ferrone,
Thomas Kieber-Emmons,
Behjatolah Monzavi-Karbassi
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ABSTRACT: We have previously demonstrated that chondroitin sulfate glycosaminoglycans (CS-GAGs) on breast cancer cells function as P-selectin ligands. This study was performed to identify the carrier proteoglycan (PG) and the sulfotransferase gene involved in synthesis of the surface P-selectin-reactive CS-GAGs in human breast cancer cells with high metastatic capacity, as well as to determine a direct role for CS-GAGs in metastatic spread.
Quantitative real-time PCR (qRT-PCR) and flow cytometry assays were used to detect the expression of genes involved in the sulfation and presentation of chondroitin in several human breast cancer cell lines. Transient transfection of the human breast cancer cell line MDA-MB-231 with the siRNAs for carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) and chondroitin sulfate proteoglycan 4 (CSPG4 ) was used to investigate the involvement of these genes in expression of surface P-selectin ligands. The expression of CSPG4 and CHST11 in 15 primary invasive breast cancer clinical specimens was assessed by qRT-PCR. The role of CS-GAGs in metastasis was tested using the 4T1 murine mammary cell line (10 mice per group).
The CHST11 gene was highly expressed in aggressive breast cancer cells but significantly less so in less aggressive breast cancer cell lines. A positive correlation was observed between the expression levels of CHST11 and P-selectin binding to cells (P < 0.0001). Blocking the expression of CHST11 with siRNA inhibited CS-A expression and P-selectin binding to MDA-MB-231 cells. The carrier proteoglycan CSPG4 was highly expressed on the aggressive breast cancer cell lines and contributed to the P-selectin binding and CS-A expression. In addition, CSPG4 and CHST11 were over-expressed in tumor-containing clinical tissue specimens compared with normal tissues. Enzymatic removal of tumor-cell surface CS-GAGs significantly inhibited lung colonization of the 4T1 murine mammary cell line (P = 0.0002).
Cell surface P-selectin binding depends on CHST11 gene expression. CSPG4 serves as a P-selectin ligand through its CS chain and participates in P-selectin binding to the highly metastatic breast cancer cells. Removal of CS-GAGs greatly reduces metastatic lung colonization by 4T1 cells. The data strongly indicate that CS-GAGs and their biosynthetic pathways are promising targets for the development of anti-metastatic therapies.
Breast cancer research: BCR 06/2011; 13(3):R58. · 5.24 Impact Factor
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ABSTRACT: It is well accepted that near-infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light penetrates deep (3-5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore [indocyanine green (ICG), dye] can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7-9 mm) were irradiated with a 808-nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG-treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69-70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular-targeted ICG-NIR laser therapy appears to have potential for treating superficial tumors.
International Journal of Cancer 04/2011; 130(5):1208-15. · 5.44 Impact Factor
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ABSTRACT: To evaluate the long-term outcomes and prognostic value of our sonographically based surgical approach to the lateral neck for recurrences in papillary thyroid cancer (PTC).
Retrospective medical chart review.
Tertiary cancer institution.
The study population comprised 331 consecutive patients primarily treated for papillary thyroid carcinoma (PTC) at a tertiary cancer institution between 1996 and 2003. The lateral neck compartments were surgically addressed only in the presence of abnormalities on ultrasonography (US).
Recurrence-free interval and overall, disease-specific, and recurrence-free survival.
There were 112 male and 219 female patients, with a median age of 44.7 years (range, 11-87 years). The median follow-up time for the series was 77.9 months (range, 12.7-148.7 months). Preoperative US abnormalities were found in the right neck in 13.3%, in the left neck in 12.3%, and bilaterally in 11.2%; all of these patients underwent a lateral neck dissection at the time of the thyroidectomy. There were 11 recurrences in the series (0.3%), with a median time to presentation of 22.8 months (range, 6.0-55.3 months). Predictors of lateral neck disease-free interval were T stage and distant disease at presentation (P = .01 and P < .001, respectively) and the sonographic status of the ipsilateral and central neck (P = .001 and P < .001). The number of abnormal neck compartments in US correlated with the risk of regional failure (P = .01). The presence of US abnormalities in the lateral neck decreased the 10-year disease-specific survival from 98.3% to 66.9% (P < .001).
Preoperative US is an excellent outcome predictor for lateral neck disease-free interval and for disease-specific survival in PTC. Sonographically based surgical approach provides excellent long-term regional control and validates current treatment guidelines.
Archives of otolaryngology--head & neck surgery 02/2011; 137(2):157-62. · 1.92 Impact Factor
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Behjatolah Monzavi-Karbassi,
R Jean Hine,
Joseph S Stanley,
Vishnu Prakash Ramani,
Jaime Carcel-Trullols,
Tracy L Whitehead,
Thomas Kelly, Eric R Siegel,
Cecile Artaud,
Saeid Shaaf,
Rinku Saha,
Fariba Jousheghany,
Ronda Henry-Tillman,
Thomas Kieber-Emmons
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ABSTRACT: Aberrant glycosylation is a universal feature of cancer cells, and certain glycan structures are well-known markers for tumor progression. Availability and composition of sugars in the microenvironment may affect cell glycosylation. Recent studies of human breast tumor cell lines indicate their ability to take up and utilize fructose. Here we tested the hypothesis that adding fructose to culture as a carbon source induces phenotypic changes in cultured human breast tumor cells that are associated with metastatic disease. MDA-MB-468 cells were adapted to culture media in which fructose was substituted for glucose. Changes in cell surface glycan structures, expression of genes related to glycan assembly, cytoskeleton F-actin, migration, adhesion and invasion were determined. Cells cultured in fructose expressed distinct cell-surface glycans. The addition of fructose affected sialylation and fucosylation patterns. Fructose feeding also increased binding of leukoagglutinating Phaseolus vulgaris isolectin, suggesting a possible rise in expression of branching beta-1, 6 GlcNAc structures. Rhodamine-phalloidin staining revealed an altered F-actin cytoskeletal system. Fructose accelerated cellular migration and increased invasion. These data suggest that changing the carbon source of the less aggressive MDA-MB-468 cell line induced characteristics associated with more aggressive phenotypes. These data could be of fundamental importance due to the markedly increased consumption of sweeteners containing free fructose in recent years, as they suggest that the presence of fructose in nutritional microenvironment of tumor cells may negatively affect the outcome for some breast cancer patients.
International Journal of Oncology 09/2010; 37(3):615-22. · 2.40 Impact Factor
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ABSTRACT: We sought to identify effective chemotherapy regimens against uterine serous papillary adenocarcinoma (USPC).
Six USPC, half of which overexpress HER-2/neu at 3+ level, were evaluated for growth rate and in vitro sensitivity to 14 single-agent chemotherapies and 5 combinations by ChemoFx (Precision Therapeutics Inc, Pittsburgh, PA).
Cell lines overexpressing HER-2/neu showed higher proliferation when compared to low HER-2/neu-expressing cell lines and a lower half maximum inhibitory concentration (IC(50)) when exposed to the majority of single-agent chemotherapies. High HER-2/neu expressors were more sensitive to platinum compounds, manifesting a 5.22-fold decrease in carboplatin-IC(50) (P = .005) and a 5.37-fold decrease in cisplatin-IC(50) (P = .02). When all cell lines were analyzed as a group, chemotherapy agents tested demonstrated lower IC(50) when used in combination than as individual agents.
USPC overexpressing HER-2/neu display greater in vitro sensitivity to platinum compounds when compared to low HER-2/neu expressors. Higher proliferative capability rather than increased drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in USPC.
American journal of obstetrics and gynecology 08/2010; 203(2):162.e1-8. · 3.28 Impact Factor
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ABSTRACT: The processing of rapidly presented stimuli has been shown to be a precursor for the perception of speech in infants, long before they learn to speak. However, the onset and early development of rapid temporal processing (RTP) skills is not yet well understood. The main goal of this study was to assess the development of RTP skills during the prenatal and early postnatal stages of life.
Tone pairs were presented in two difficulties (long and short) and event-related magnetic fields were recorded using MEG. Pregnant women (22) (gestational ages between 29 and 38 weeks') participated in the fetal study and 15 returned for a neonatal follow-up study between 2 and 38 days after delivery or 38 and 44 weeks gestational age (GA).
In the postnatal follow-up study, a trend towards two peaks with increasing chronological and gestational age was observed in the longer tone pair. However, no such trend was evident in neonatal responses to the short tone pairs or in fetal recordings.
Neonates showed a gradual trend to successful processing of the longer tone pair with increasing age. By 22 days of chronological age, the infants processed this tone pair successfully, as indicated by two-peak waveforms. Therefore, the first 3 weeks of life could be critical for the development of RTP.
This study is a first approach towards the assessment of early RTP development. The results provide promising indications for future studies, which might lead to an early detection of deficits in speech perception and therefore prevent further language impairments.
Brain & development 11/2009; 32(8):642-57. · 1.74 Impact Factor
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ABSTRACT: A key factor for a successful outcome after hemiarthroplasty for a 4-part proximal humerus fracture is accurately restoring humeral length. Our hypothesis was that the pectoralis major insertion is not at a constant distance on the humerus, as has been previously suggested, but varies depending on the length of the humerus, and our goal was to determine if a consistent ratio exists for the insertion as it relates to total humeral length. Thirty-eight cadaver arms were dissected to expose the pectoralis major insertion. Using a digital caliper, measurements were made from the top of the humeral head to the superior aspect of the pectoralis major insertion (HP), and from the pectoralis insertion to the lateral epicondyle (PL). The predictive ability of PL for HP was examined via regression, and the average prediction error was computed. The final predictive regression model had the following formula: pHP=0.2323xPL, where pHP is predicted HP. This equation had an average prediction error of 4.11 mm. The PL can be measured intraoperatively during hemiarthroplasty for proximal humerus fractures. The proportionality relationship can then be used to predict HP with an average prediction error <5 mm. This relationship may facilitate accurate intraoperative reconstruction of prosthetic head height and enhance existing techniques for assessment of implant positioning.
Orthopedics 10/2009; 32(10). · 2.66 Impact Factor
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ABSTRACT: Coat-color proportions and patterns in mice are used as assays for many processes such as transgene expression, chimerism, and epigenetics. In many studies, coat-color readouts are estimated from subjective scoring of individual mice. Here we show a method by which mouse coat color is quantified as the proportion of coat shown in one or more digital images. We use the yellow-agouti mouse model of epigenetic variegation to demonstrate this method. We apply this method to live mice using a conventional digital camera for data collection. We use a raster graphics editing program to convert agouti regions of the coat to a standard, uniform, brown color and the yellow regions of the coat to a standard, uniform, yellow color. We use a second program to quantify the proportions of these standard colors. This method provides quantification that relates directly to the visual appearance of the live animal. It also provides an objective analysis with a traceable record, and it should allow for precise comparisons of mouse coats and mouse cohorts within and between studies.
PLoS ONE 02/2009; 4(4):e5414. · 4.09 Impact Factor
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ABSTRACT: Early diagnosis of the onset of osteoporosis is key to the delivery of effective therapy. Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of BMD by DXA. Conventional clinical measurements of bone turnover, primarily the estimation of collagen and its breakdown products in the blood or urine, lack both sensitivity and specificity as a reliable diagnostic tool. As a result, improved tests are needed to augment the use of BMD measurements as the principle diagnostic modality. In this study, the serum proteome of 58 postmenopausal women with high or low/normal bone turnover (training set) was analyzed by surface enhanced laser-desorption/ionization time-of-flight mass spectrometry, and a diagnostic fingerprint was identified using a variety of statistical and machine learning tools. The diagnostic fingerprint was validated in a separate distinct test set, consisting of serum samples from an additional 59 postmenopausal women obtained from the same Mayo cohort, with a gap of 2 yr. Specific protein peaks that discriminate between postmenopausal patients with high or low/normal bone turnover were identified and validated. Multiple supervised learning approaches were able to classify the level of bone turnover in the training set with 80% sensitivity and 100% specificity. In addition, the individual protein peaks were also significantly correlated with BMD measurements in these patients. Four of the major discriminatory peaks in the diagnostic profile were identified as fragments of interalpha-trypsin-inhibitor heavy chain H4 precursor (ITIH4), a plasma kallikrein-sensitive glycoprotein that is a component of the host response system. These data suggest that these serum protein fragments are the serum-borne reflection of the increased osteoclast activity, leading to the increased bone turnover that is associated with decreasing BMD and presumably an increased risk of fracture. In conjunction with the identification of the individual proteins, this protein fingerprint may provide a novel approach to evaluate high bone turnover states.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2008; 23(7):1106-17. · 6.04 Impact Factor
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ABSTRACT: DNA methylation at cytosines is a widely studied epigenetic modification. Methylation is commonly detected using bisulfite modification of DNA followed by PCR and additional techniques such as restriction digestion or sequencing. These additional techniques are either laborious, require specialized equipment, or are not quantitative. Here we describe a simple algorithm that yields quantitative results from analysis of conventional four-dye-trace sequencing. We call this method Mquant and we compare it with the established laboratory method of combined bisulfite restriction assay (COBRA). This analysis of sequencing electropherograms provides a simple, easily applied method to quantify DNA methylation at specific CpG sites.
Nucleic Acids Research 07/2008; 36(11):e64. · 8.03 Impact Factor
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ABSTRACT: To investigate the response decrements of visual evoked responses (VER) in newborns and assess the applicability of this paradigm to fetuses in magnetoencephalographic (MEG) recordings.
Twelve newborns with no known risks or complications participated at chronological ages between 6 and 22days. They constituted the follow-up group to a prenatal study conducted on a sample of 25 fetuses whose gestational age (GA) varied between 29 and 37weeks at the time of recording. Trains of four light flashes with an interstimulus interval of 2s followed by 10s without stimulation were delivered to record VER.
Nine of the 12 newborns responded to the stimulation and showed response decrements in amplitude from the first to the last light flash. Furthermore, the response latency increased significantly from the first to the last stimulus. The remaining three recordings were discontinued early. Even though the prenatal visual evoked response rate was only 29%, the fetuses exhibited a response decrement after the first stimulus.
The amplitude of VERs can be used to elicit a response decrement in newborns and, with limitations, even in fetuses. This paradigm might be a useful tool for a direct non-invasive assessment of neonatal and prenatal brain development and CNS functioning.
The proposed method might be a first step towards an early detection of developmental deficits in newborns and fetuses.
Clinical Neurophysiology 05/2008; 119(4):796-804. · 3.41 Impact Factor
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ABSTRACT: Mitochondria are key organelles for apoptosis, and mitochondrial DNA (mtDNA) content can regulate cancer progression. Increases in mtDNA mutations and deletions have been reported in cancer; however, a detailed investigation of mtDNA content in cancer cells has not yet been conducted.
Quantitative real-time PCR and improved extraction method were established to investigate the mtDNA content in a single prostate cell.
The heterogeneity of mtDNA content was demonstrated between the clones of prostate cancer cell line LNCaP and individual cells in each clone. To investigate whether large distributional variance of mtDNA content is associated with cancer initiation and/or progression, we first compared PZ-HPV-7, an HPV-transformed normal prostate epithelial cell line, with CA-HPV-10, transformed from prostate cancer cells derived from the same donor. We found an enhanced distributional variance of mtDNA content in CA-HPV-10. Then, we investigated mtDNA content in individual cells in laser microdisssected cancer and adjacent normal cells from prostate cancer tissue specimens using quantitative real-time PCR method. Results showed that the mtDNA content per cell follows a higher skewed distribution in cancer cells as compared in normal cells. We also observed that mtDNA content was increased in seven of nine (78%) of prostate cancers compared to normal prostate tissue.
These results indicate that prostate carcinogenesis may involve dysregulation of mtDNA content.
The Prostate 04/2008; 68(4):408-17. · 3.48 Impact Factor
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ABSTRACT: The safety and immunogenicity of the human papillomavirus type 16 (HPV16) or HPV18 (HPV16/18) E7 antigen-pulsed mature dendritic cell (DC) vaccination were evaluated for patients with stage IB or IIA cervical cancer. Escalating doses of autologous DC (5, 10, and 15 x 10(6) cells for injection) were pulsed with recombinant HPV16/18 E7 antigens and keyhole limpet hemocyanin (KLH; an immunological tracer molecule) and delivered in five subcutaneous injections at 21-day intervals to 10 cervical cancer patients with no evidence of disease after they underwent radical surgery. Safety, toxicity, delayed-type hypersensitivity (DTH) reaction, and induction of serological and cellular immunity against HPV16/18 E7 and KLH were monitored. DC vaccination was well tolerated, and no significant toxicities were recorded. All patients developed CD4(+) T-cell and antibody responses to DC vaccination, as detected by enzyme-linked immunosorbent spot (ELISpot) and enzyme-linked immunosorbent assays (ELISA), respectively, and 8 out of 10 patients demonstrated levels of E7-specific CD8(+) T-cell counts, detected by ELISpot during or immediately after immunization, that were increased compared to prevaccination baseline levels. The vaccine dose did not predict the magnitude of the antibody or T-cell response or the time to detection of HPV16/18 E7-specific immunity. DTH responses to intradermal injections of HPV E7 antigen and KLH were detected for all patients after vaccination. We conclude that HPV E7-loaded DC vaccination is safe and immunogenic for stage IB or IIA cervical cancer patients. Phase II E7-pulsed DC-based vaccination trials with cervical cancer patients harboring a limited tumor burden, or who are at significant risk of tumor recurrence, are warranted.
Journal of Virology 03/2008; 82(4):1968-79. · 5.40 Impact Factor
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ABSTRACT: Tissue factor (TF), apart from its established role in hemostasis, has been implicated in promoting angiogenesis and metastasis in a wide array of tumors including prostate cancer. Expression of TF was evaluated in freshly-resected prostate specimens obtained from patients with localized (n=9) and androgen ablated (n=6) disease using real-time reverse transcription-polymerase chain reaction and Western blot analysis. TF was detected in all specimens in both stages of the disease. We further analyzed for correlations between TF expression and those of several angiogenic growth factors and their receptors. TF RNA expression correlated significantly with expression of vascular endothelial growth factor-A in these specimens (s=0.621, P=0.013). Eighty-one prostate specimens from patients with benign prostatic hyperplasia (n=27), localized prostate cancer (ES, n=32), and advanced disease (n=22) were also evaluated using immunohistochemistry and findings were correlated with clinical parameters. TF expression was detected on epithelial cells of the malignant glands. Furthermore, its expression levels correlated significantly with Gleason score (s=0.58, P=0.0001) and with the stage of the disease (s=0.441, P=0.0001) in these specimens. These data support the role of TF in angiogenesis and disease progression.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 02/2008; 16(1):1-6. · 1.63 Impact Factor
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ABSTRACT: Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.
We compared the genome-wide distribution of DSB peaks to that of polyadenylated ncRNA molecules of the prl class. DSB peaks map to ncRNA loci that may be situated within ORFs, near the boundaries of ORFs and intergenic regions, or most often within intergenic regions. Unconditional statistical tests revealed that this colocalization is non-random and robust (P<or=5.5 x 10(-8)). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.
Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes.
PLoS ONE 02/2008; 3(8):e2887. · 4.09 Impact Factor
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ABSTRACT: Utilizing a MEG-based device specifically designed to study the fetus, we investigated the presence of salient patterns in spontaneous fetal brain activity.
We performed 91 MEG recordings from 30 fetuses at various gestational ages. The tracings were evaluated and compared to the well-established electroencephalographic (EEG) features in premature infants. Also, we looked at the correlation of the gestational age (GA) on the occurrence of these patterns and complexes.
We were able to identify specific patterns and track changes in fetal brain activity starting at 28 weeks of gestation. The patterns and trends were similar to the established EEG features in premature infants at comparable ages. Of the 30 fetuses, 18 (60%) had at least one recording with discontinuity, 7 (23%) had sharp transients, and 8 (27%) had delta brush activity. Further there was a decrease in the presence of discontinuous patterns after 35 weeks.
We have shown that fetal spontaneous brain activity features can be recorded and identified using MEG technique. The observation of more discontinuity at early gestational ages is consistent with the overall pattern of maturation seen in EEGs of premature infants.
With refinements, this method can aid in understanding the maturation process of fetal brain activity and further develop as a tool for fetal neurological evaluation.
Clinical Neurophysiology 10/2007; 118(9):1940-6. · 3.41 Impact Factor
