Proximal Site (proximal + site)

Distribution by Scientific Domains


Selected Abstracts


Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients

CANCER, Issue 7 2010
Frank Sinicrope MD
Abstract BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil,based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n = 982) from 6 5-fluorouracil,based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n = 326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic = 0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n = 326), a model including proximal site, TILs (>2/high-power field), and female sex showed even better discrimination (c statistic = 0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. Cancer 2010. © 2010 American Cancer Society. [source]


Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient

PEDIATRIC TRANSPLANTATION, Issue 6 2005
Soshi Takahashi
Abstract:, Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18,22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 pm on day 6, and tacrolimus was discontinued at 9:00 pm; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case. [source]


Expression, crystallization and preliminary crystallographic analysis of RNA-binding protein Hfq (YmaH) from Bacillus subtilis in complex with an RNA aptamer

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2010
Seiki Baba
The Hfq protein is a hexameric RNA-binding protein which regulates gene expression by binding to RNA under the influence of diverse environmental stresses. Its ring structure binds various types of RNA, including mRNA and sRNA. RNA-bound structures of Hfq from Escherichia coli and Staphylococcus aureus have been revealed to have poly(A) RNA at the distal site and U-rich RNA at the proximal site, respectively. Here, crystals of a complex of the Bacillus subtilis Hfq protein with an A/G-repeat 7-mer RNA (Hfq,RNA) that were prepared using the hanging-drop vapour-diffusion technique are reported. The type 1 Hfq,RNA crystals belonged to space group I422, with unit-cell parameters a = b = 123.70, c = 119.13,Å, while the type 2 Hfq,RNA crystals belonged to space group F222, with unit-cell parameters a = 91.92, b = 92.50, c = 114.92,Å. Diffraction data were collected to a resolution of 2.20,Å from both crystal forms. The hexameric structure of the Hfq protein was clearly shown by self-rotation analysis. [source]


Model-based prediction of defective DNA mismatch repair using clinicopathological variables in sporadic colon cancer patients

CANCER, Issue 7 2010
Frank Sinicrope MD
Abstract BACKGROUND: Colon cancers with defective DNA mismatch repair (MMR) have a favorable prognosis and may lack benefit from 5-fluorouracil,based adjuvant chemotherapy. The authors developed models to predict MMR deficiency in sporadic colon cancer patients using routine clinical and pathological data. METHODS: TNM stage II and III colon carcinomas (n = 982) from 6 5-fluorouracil,based adjuvant therapy trials were analyzed for microsatellite instability and/or MMR protein expression. Tumor-infiltrating lymphocytes (TILs) were quantified (n = 326). Logistic regression and a recursive partitioning and amalgamation analysis were used to identify predictive factors for MMR status. RESULTS: Defective MMR was detected in 147 (15%) cancers. Tumor site and histologic grade were the most important predictors of MMR status. Distal tumors had a low likelihood of defective MMR (3%; 13 of 468); proximal tumors had a greater likelihood (26%; 130 of 506). By using tumor site, grade, and sex, the logistic regression model showed excellent discrimination (c statistic = 0.81). Proximal site, female sex, and poor differentiation showed a positive predictive value (PPV) of 51% for defective MMR. In a patient subset (n = 326), a model including proximal site, TILs (>2/high-power field), and female sex showed even better discrimination (c statistic = 0.86), with a PPV of 81%. CONCLUSIONS: Defective MMR is rare in distal, sporadic colon cancers, which should generally not undergo MMR testing. Proximal site, poor differentiation, and female sex detect 51% of tumors with defective MMR; substituting TILs for grade increases the PPV to 81%. These data can increase the efficiency of MMR testing to assist in clinical decisions. Cancer 2010. © 2010 American Cancer Society. [source]


UNCOORDINATED PHYLOGEOGRAPHY OF BORRELIA BURGDORFERI AND ITS TICK VECTOR, IXODES SCAPULARIS

EVOLUTION, Issue 9 2010
Parris T. Humphrey
Vector-borne microbes necessarily co-occur with their hosts and vectors, but the degree to which they share common evolutionary or biogeographic histories remains unexplored. We examine the congruity of the evolutionary and biogeographic histories of the bacterium and vector of the Lyme disease system, the most prevalent vector-borne disease in North America. In the eastern and midwestern US, Ixodes scapularis ticks are the primary vectors of Borrelia burgdorferi, the bacterium that causes Lyme disease. Our phylogeographic and demographic analyses of the 16S mitochondrial rDNA suggest that northern I. scapularis populations originated from very few migrants from the southeastern US that expanded rapidly in the Northeast and subsequently in the Midwest after the recession of the Pleistocene ice sheets. Despite this historical gene flow, current tick migration is restricted even between proximal sites within regions. In contrast, B. burgdorferi suffers no barriers to gene flow within the northeastern and midwestern regions but shows clear interregional migration barriers. Despite the intimate association of B. burgdorferi and I. scapularis, the population structure, evolutionary history, and historical biogeography of the pathogen are all contrary to its arthropod vector. In the case of Lyme disease, movements of infected vertebrate hosts may play a larger role in the contemporary expansion and homogenization of the pathogen than the movement of tick vectors whose populations continue to bear the historical signature of climate-induced range shifts. [source]


Open flap debridement with or without intentional cementum removal: a 4-month follow-up

JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2005
Antonio Wilson Sallum
Abstract Objectives: The aim of this study was to investigate the influence of cementum removal on periodontal repair. Material and Methods: Forty subjects with chronic periodontitis and presenting, at least, two proximal sites in anterior teeth (upper or lower) with probing depth 5 mm were selected. After oral hygiene instructions and ultrasonic supragingival instrumentation, the subjects were randomly assigned for one of the following groups: CIC, scaled with Gracey curettes; CIUS, scaled with ultrasonic device; CDC, calculus deattachment with Gracey curettes and brushing with saline solution; and CDUS, calculus deattachment with ultrasonic device and brushing with saline solution. Full-thickness flaps were reflected and the instrumentation was performed with a clinical microscope. Probing depth (PD), relative gingival margin level (RGML) and relative attachment level (RAL) were registered at five experimental periods: baseline and 30, 60, 90 and 120 days postoperative. Results: All the approaches were able to markedly reduce the PD values from the baseline to the other evaluation periods (p<0.0001). The increase in RGML values was statistically significant only for the CDUS group. There were no statistically significant differences between the baseline and postoperative values in all groups for the RAL changes. The changes in RAL were statistically significant only among the groups CDC and CDUS (p<0.0001). Conclusion: The conventional scaling and root planing and the calculus deattachment were effective in reducing the probing depth values, regardless of the instrumentation method. [source]


QUANTITATIVE SENSORY TESTING AND SWEAT FUNCTION IN FRIEDREICH'S ATAXIA.

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000
CORRELATION WITH CUTANEOUS INNERVATION
To evaluate small fiber function in Friedreich's Ataxia (FA), we performed in 7 patients pin-prick, thermal thresholds, and sweat test. All tests were performed in four different sites: hand dorsum, anterior thigh, lateral distal leg, and foot dorsum. The same subjects underwent 3 mm punch skin biopsy from fingertip, anterior thigh, and lateral distal leg. We used a thin needle mounted on a calibrated nylon wire for the pin-prick test, and a Medoc 2001 TSA system for thermal threshold assessment. Sweat test was performed using a silicon mold after stimulation with pilocarpine by iontophoresis. Skin specimens, cut into 100-,m-thick sections, were double-stained using primary antibodies specific for collagen and nervous fibers and secondary antibodies labeled with Cy3 and Cy5 fluorophores. Tridimensional digitized images were obtained from z-series of 2-,m-thick optical sections acquired with a confocal microscope. We found in all patients in the more distal sites definite signs of functional impairment of the small fibers. These data correlated with the skin innervation morphological findings that showed, in the same sites, a sensible loss of small fibers regarding both the epidermal free endings and the subepidermal neural plexus. Less severe morphological abnormalities were found in the proximal sites. The large fiber neuropathy in FA is well documented. Our data show a length-dependent involvement of small fibers in the pathological process. [source]