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PubMed2026

Pathogen local adaptation shapes Pierce's disease of grapevines outcomes under field conditions.

Climate change is broadly expected to increase the range of many plant diseases, yet the current status of local thermal adaptation in many pathogens is poorly understood. Xylella fastidiosa (Xf) is a global bacterial plant pathogen that causes Pierce's disease (PD) of grapevines and infects over 700 other host plant species, impacting both agricultural and natural ecosystems. In a common garden experiment with 477 vines in the field, we compared PD outcomes from a local (colder climate in CA) vs non-local (warmer climate in CA) bacterial strain in 13 Mediterranean grapevine varieties over 3 years. Relative to the local strain, there was 77% lower overwinter survival in the non-local strain from a warmer climate, strongly indicating local adaptation in these CA Xf populations. Host genotype also had a significant effect on pathogen winter survival, and grapevine varieties differed in PD susceptibility. Additionally, we assessed in planta evolution of the two pathogen strains over 3 years by whole-genome sequencing 58 field-derived isolates. There were convergent loss-of-function mutations in genes encoding minor Type IV pilin (T4P) proteins, which control twitching motility and other virulence phenotypes, suggesting rapid adaptive evolution. Our results suggest local adaptation to cold temperatures in a bacterial plant pathogen and a possible role for minor Type IV pilins in thermal adaptation. These findings demonstrate the urgent need to incorporate X. fastidiosa evolution and local thermal adaptation into global models of PD spread. Differentiating pathotypes with distinct thermal adaptations will improve disease forecasting and inform quarantine decisions.IMPORTANCEForecasting the movement of plant pathogens is a critical issue under global warming to effectively manage future plant disease outbreaks. Yet, current plant pathogen local thermal adaptation is often unaccounted for, especially in bacterial pathogens. Our study examines local adaptation to temperature in a bacterial plant pathogen, Xylella fastidiosa, that causes disease in grapevines in addition to infecting 700 other plant species. In a large-scale field experiment across 13 grapevine varieties, we demonstrate local adaptation in pathogen winter survival in distinct Xylella fastidiosa strains. Additionally, we found evidence of adaptive evolution in just 3 years, as we observed convergent mutations after resequencing strains that evolved in the field. Our results suggest that X. fastidiosa populations-even within a small geographic area-have distinct adaptations to winter temperatures and may exhibit differential responses to warming winters.

Type IV pili↗
PubMed2006

Gene expression profiles of primary breast carcinomas from patients at high risk for local recurrence after breast-conserving therapy.

PURPOSE: Several risk factors for local recurrence of breast cancer after breast-conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also in improving understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence. EXPERIMENTAL DESIGN: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients, 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9 of 19 patients, the local recurrence was also available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences. RESULTS: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from nonrecurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences. CONCLUSIONS: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after BCT were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy.

Adult↗
PubMed2005

Local anesthetics inhibit priming of neutrophils by lipopolysaccharide for enhanced release of superoxide: suppression of cytochrome b558 expression by disparate mechanisms.

Local anesthetics have anti-inflammatory effects in vivo and inhibit neutrophil functions in vitro, but how these agents act on neutrophils remains unclear. Phagocytosis and bactericidal activity of neutrophils are enhanced by exposure to bacterial components such as lipopolysaccharide (LPS); this process is termed priming, which for enhanced release of superoxide (O2-) causes mobilization of intracellular granules that contain cytochrome b558, a component of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We studied whether local anesthetics affected LPS priming for enhanced release of O2- in response to triggering by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP), and we investigated which element in the LPS signaling pathway might be the target of local anesthetics. Neutrophils were incubated with 10 ng/ml LPS and 1% plasma+/-local anesthetics, washed, and triggered with fMLP. Local anesthetics all inhibited LPS priming, and 50% inhibition was at 0.1 mM tetracaine, 0.5 mM bupivacaine, 3.0 mM lidocaine, or 4.0 mM procaine. Local anesthetics inhibited LPS-induced mobilization of specific granules and secretory vesicles. Local anesthetics inhibited LPS-induced up-regulation of cytochrome b558 but not LPS-induced translocation of p47phox. Inhibition of priming by local anesthetics was reversed by washing and incubating for 5 min. Tetracaine alone, but not the other local anesthetics, inhibited LPS activation of p38 mitogen-activated protein kinase (MAPK) and MAPK kinase 3 (kinases in the LPS signaling pathway). The p38 MAPK inhibitors SB203580 and PD169316 also blocked LPS priming. Thus, tetracaine and the other local anesthetics inhibit by disparate mechanisms, but all the local anesthetics impaired up-regulation of cytochrome b558 and all impaired priming of NADPH oxidase by LPS.

Anesthetics, Local↗
PubMed2004

Clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision with or without preoperative radiotherapy.

PURPOSE: To document the clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision (TME) with or without 5 x 5 Gy preoperative radiotherapy (PRT) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after local recurrence. PATIENTS AND METHODS: For 96 Dutch patients with a local recurrence who participated in a multicenter randomized clinical trial, data on treatments and follow-up were gathered from surgeons and radiation and medical oncologists. Twenty-three patients (24%) had previously been treated with PRT plus TME, and 73 patients (76%) had been treated with TME alone. Eighty-one patients (84%) were followed until death; median follow-up time of the alive patients after local recurrence was 21 months (range, 5 to 48 months). RESULTS: Survival after local recurrence in the PRT + TME group was significantly shorter than in the TME group (median survival, 6.1 v 15.9 months; hazard ratio for death, 2.1; P =.008). Patients with a local recurrence in the PRT + TME group had distant metastases more often (74% v 40%; P =.004), underwent surgical resection of local recurrence less often (17% v 35%; P =.11), and received radiotherapy for local recurrence at a total dose >/= 45 Gy less often (4% v 42%; P =.001) than patients without PRT. In a multivariate analysis, the difference in survival after local recurrence between randomization groups was no longer statistically significant (hazard ratio for death of PRT, 1.53; P =.16). CONCLUSION: The clinical nature and prognosis of patients with locally recurrent rectal cancer has changed since the introduction of PRT. The majority of patients who present with a local recurrence after previous PRT have simultaneous distant metastases, and median survival has decreased to 6 months.

Colectomy↗
PubMed2004

The effect of local anesthetics on monocyte mCD14 and human leukocyte antigen-DR expression.

UNLABELLED: It has been demonstrated that local anesthetics have several effects on the immune system. Monocytes and macrophages are essential components of the host response to microbial infection; however, the effect of local anesthetics on monocyte surface receptor expression remains unclear. We designed this study to investigate the effects of local anesthetics on monocyte mCD14 and human leukocyte antigen (HLA)-DR expression and lipopolysaccharide (LPS)-induced or staphylococcal enterotoxin B (SEB)-induced tumor necrosis factor (TNF)-alpha production. Blood samples were obtained from 10 healthy volunteers. The effects of local anesthetics on LPS- or SEB-induced TNF-alpha production were determined by using an enzyme-linked immunosorbent assay. After different doses of local anesthetics were added, the blood was stimulated with LPS (10 ng/mL) or SEB (10 micro g/mL) for 4 h. The effects of local anesthetics on monocyte mCD14 and HLA-DR expression were measured by dual monoclonal antibody staining and flow cytometry. Local anesthetics showed no effect on LPS- or SEB-induced TNF-alpha production in human whole blood. Local anesthetics suppressed monocyte HLA-DR expression in a dose-dependent manner (P < 0.05) but had no effect on monocyte mCD14 expression. This study demonstrated that local anesthetics suppress HLA-DR expression on the surface of human monocytes. IMPLICATIONS: Monocyte surface receptors have a crucial role in the host response to microbial infection. We investigated the effects of local anesthetics on monocyte mCD14 and human leukocyte antigen (HLA)-DR expression. Our results show that local anesthetics suppress HLA-DR expression on the surface of human monocytes.

Adult↗
PubMed2006

Local anesthetic-induced protection against lipopolysaccharide-induced injury in endothelial cells: the role of mitochondrial adenosine triphosphate-sensitive potassium channels.

Lidocaine attenuates cell injury induced by ischemic-reperfusion and inflammation, although the protective mechanisms are not understood. We hypothesized that lidocaine and other amide local anesthetics protect against endothelial cell injury through activation of the mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels. We determined the effects of amide local anesthetics (lidocaine, ropivacaine, and bupivacaine), ester local anesthetics (tetracaine and procaine), one amide analog (YWI), and two non-amide local anesthetic analogs (JDA and ICM) on viability of human microvascular endothelial cells after exposure to lipopolysaccharide (LPS) in the absence or presence of the mitoK(ATP) channel antagonist 5-hydroxydecaonate. Flavoprotein fluorescence was used to investigate the effects of local anesthetics on diazoxide-induced activation of mitoK(ATP) channels. Lidocaine, ropivacaine, bupivicaine, YWI, JDA, and ICM attenuated by 60% to 70% the decrease in cell viability caused by LPS. Amide local anesthetics and YWI protection was inhibited by 5-hydroxydecaonate, whereas the protection induced by JDA and ICM was not. Tetracaine and procaine did not protect against LPS-induced injury. The amide local anesthetics and the amide analog (YWI) enhanced diazoxide-induced flavoprotein fluorescence by 5% to 20%, whereas ester local anesthetics decreased diazoxide-induced flavoprotein fluorescence by 5% to 60% and the non-amide local anesthetic analogs had no effect. In conclusion, amide local anesthetics and the amide analog (YWI) attenuate LPS-induced cell injury, in part, through activation of mitoK(ATP) channels. In contrast, tetracaine and procaine had no protective effects and inhibited activation of mitoK(ATP) channels. The non-amide local anesthetic analogs induced protection but through mechanisms independent of mitoK(ATP) channels.

Adenosine Triphosphate↗
PubMed2006

[The long-term prognosis of locally recurrent breast cancer after breast conserving treatment].

OBJECTIVE: To study the long-term prognosis of patients with locally recurrent breast cancer following breast-conserving treatment. DESIGN: Descriptive. METHOD: Data were collected on 266 patients in 11 Dutch centres; in these patients, an isolated local recurrence of an infiltrating mammary carcinoma for which they had received breast-conserving treatment was diagnosed before January 1st, 1994. The median age was 45 years (range 16-81) at the time of treatment of the primary tumour and 49 years (range 17-82) at the time of diagnosis of the local recurrence. The patients were followed through December 2002. The median follow-up after local recurrence of those patients who were still alive was 11.2 years. RESULTS: Of the 226 patients with an infiltrating local recurrence, 148 (65%) had died and 145 (64%) had developed distant metastases. Of the metastases, 61% appeared within 2.5 years and 87% within 5 years after treatment of the local recurrence. 10 years after treatment of the local recurrence, the overall survival rate was 39% (95% CI: 32-46) and the distant metastasis-free survival rate was 36% (95% CI: 29-42). The prognosis of patients with a local recurrence occurring at a different site in the breast was the same as that of patients with a local recurrence < or = 1 cm in diameter occurring at or near the original tumour site. Both of these groups had a better prognosis than patients with a recurrence larger than 1 cm at the site of the original tumour or patients with a diffuse recurrence. CONCLUSION: Almost two-thirds of the patients with an invasive local recurrence following breast-conserving surgery for invasive breast cancer developed distant metastases. Both the exact location in the breast and the size of the local recurrence appeared to be predictors of the risk of subsequent metastatic disease.

Adolescent↗
PubMed1990

[Local anesthetic mixtures in various regional anesthesia procedures].

The use of local anaesthetic mixtures in regional anaesthesia has been discussed controversially. This assumption led us to conduct an inquiry on anaesthesiologist opinion on local anaesthetic mixtures. The study was performed on 131 anaesthesiologists answering a questionnaire. It was asked how often and how many procedures of regional anaesthesia were performed, whether local anaesthetic mixtures were used or not, and what were the most common mixtures. Other questions were in what kind of regional anaesthesia mixtures were applied, and which causes led to the use of local anaesthetic mixtures. Local anaesthetic mixtures were used by 70.2% of the anaesthesiologists who responded. Generally, however, parent components were preferred (88.3%). The types of regional anaesthesia in which mixtures were applied, were blockades of plexus brachialis (50.4%), spinal anaesthesia (29.0%), and epidural anaesthesia (28.4%). Locally applied anaesthetic mixtures - in 40.5% a mixture of bupivacaine and prilocaine and in 38.2% a mixture of bupivacaine and mepivacaine - were used in 58.0% because of their short latency and their long duration. In 27.5% the reply was that the anaesthesiologists used such combinations since in these the maximal doses of the parent components were not exceeded. In 22.9% it was argued that mixtures were less toxic than the parent components. On the other hand, the application of local anaesthetic mixtures was rejected because of their unpredictable effect (33.6%), and also to avoid local anaesthetic interactions (13.7%). The results of the inquiry demonstrate that the use of local anaesthetic mixtures in regional anaesthesia is common practice. However, mixing local anaesthetics may produce unpredictable interactions. We conclude that mixtures of local anaesthetics should be used only in exceptional cases.

Anesthesia, Conduction↗
PubMedDate not supplied

Local recurrence in the conservatively treated breast cancer patient: a correlation with age and family history.

BACKGROUND: The purpose of this study was to evaluate the relationships among young age at diagnosis, family history status, and local recurrence in breast cancer patients treated with lumpectomy and radiation therapy. METHODS: Between January 1970 and December 1990, 984 early-stage breast cancer patients were treated with conservative surgery and radiation therapy at Yale-New Haven Hospital. All patient data, including demographics, staging information, treatment, and outcome variables were entered into a computerized database. The current study focused on the relationships between young age, family history, and local relapse. A group of 52 patients who experienced a local recurrence in the conservatively treated breast and 52 matched control patients who had not experienced a local recurrence were asked to participate in a study to determine whether local recurrence was associated with family history. Detailed family history interviews were conducted, and pedigrees were analyzed by a genetic counselor who was blind to the clinical history of the patients. RESULTS: As of September 1997, with a median follow-up of 12.3 years for the 984 patients in the database, the overall actuarial 10-year survival is 73%, and the 10-year distant metastasis-free survival is 78%. Of the 984 patients, 112 have experienced a local relapse in the conservatively treated breast, resulting in a 10-year actuarial breast relapse rate of 15%. The 10-year survival after breast relapse is 69%. Patient age tested as a continuous variable correlated strongly with ipsilateral breast tumor relapse. Using age 40 as a cutpoint, patients aged 40 years or less had a significantly higher local relapse rate than patients older than 40 years (P < 0.001). Although the relationship between local relapse and young age was strong, no association was found between family history and local relapse in the detailed family history study. CONCLUSIONS: Young age at diagnosis was a significant prognostic factor for local relapse. In a detailed family history study using a case-control design, no significant differences in family history status were found between patients who had experienced a local relapse and patients who had not.

Adult↗
PubMed1997

Tumor localization of a radiolabeled bombesin analogue in mice bearing human ovarian tumors induced to express the gastrin-releasing peptide receptor by an adenoviral vector.

BACKGROUND: The adenoviral vector, AdCMVGRPr, has been used to induce the expression of the murine gastrin-releasing peptide receptor (GRPr) both in vitro and in vivo. A bombesin analogue ([125I]-mIP-bombesin) has been shown to bind with high affinity to GRPr and to localize to intraperitoneal (i.p.) ovarian tumors 2 days after induction of GRPr in an athymic nude mouse model. The present study was conducted to determine the level of localization of [(125/131)I]-mIP-bombesin in the tumors at 2, 4, and 7 days after AdCMVGRPr administration and to determine the feasibility of giving multiple doses of [131I]-mIP-bombesin for therapy. METHODS: Human ovarian cancer cells (SKOV3.ip1) were infected in vitro with AdCMVGRPr and were assayed for receptor expression at 2, 4, and 7 days after infection by using a radiolabeled bombesin-binding assay. Biodistribution studies utilized athymic nude mice inoculated i.p. with SKOV3.ip1 cells. The tumors were induced to express GRPr with an i.p. injection of AdCMVGRPr followed by administration of [125I]-mIP-bombesin 2 days later (AdCMVLacZ or saline was used for negative controls). In addition, the tumor localization of [125I]-mIP-bombesin was determined 4 and 7 days after AdCMVGRPr administration. The tumor localization of [131I]-mIP-bombesin was compared with [125I]-mIP-bombesin in this in vivo model. RESULTS: SKOV3.ip1 cells infected with AdCMVGRPr resulted in 80.3 +/- 5.9% binding of [125I]-Tyr4-bombesin at 2 days after infection, which decreased to 46.8 +/- 0.4% at 4 days and to 17.7 +/- 0.1% at 7 days. The biodistribution study showed that the tumor localization (14.9 +/- 8.2% injected dose/gram; ID/g) of [125I]-mIP-bombesin 2 days after administration of AdCMVGRPr was significantly greater than its localization in other organs (P < 0.003) and was significantly greater than in AcCMVLacZ- and saline-treated mice (P < 0.003). Injections of [125I]-mIP-bombesin at 4 and 7 days after a single AdCMVGRPr administration showed tumor localization of 4.5 +/- 3.0% ID/g at Day 4 and 3.9 +/- 3.5% ID/g at Day 7. The decreased localization at longer times after AdCMVGRPr infection correlated with in vitro results. The tumor uptake of [125I]-mIP-bombesin was comparable to the uptake of [131I]-mIP-bombesin (21.2 +/- 8.3% ID/g versus 15.4 +/- 5.6% ID/g, respectively), as was the normal tissue biodistribution. CONCLUSIONS: The expression of GRPr in human ovarian cancer cells can be accomplished both in vitro and in vivo by using AdCMVGRPr, with the in vivo tumor localization of [125I]-mIP-bombesin being significantly greater than in control animals. The tumor localization of [125I]-mIP-bombesin and [131I]-mIP-bombesin at 2 days after AdCMVGRPr was comparable in a mouse model of human ovarian carcinoma. Injections of [125I]-mIP-bombesin at Days 4 and 7 after AdCMVGRPr infection resulted in tumor localization of [125I]-mIP-bombesin but at a level lower than 2 days. Thus, the total amount of radioactivity delivered to the tumor should be increased by multiple injections of [131I]-mIP-bombesin, which would be required for a therapeutic effect.

Adenoviridae↗
PubMed1987

Local therapy in stage I clear cell adenocarcinoma of the vagina.

Of the 219 cases of Stage I vaginal clear cell adenocarcinoma reviewed, 176 had conventional therapy and 43 underwent local therapy. The two groups appear to be similar with respect to symptoms, stage, location of the lesion in the vagina, greatest tumor diameter, surface area, depth of invasion, predominant histologic pattern, grade, and number of mitoses; nonetheless, firm conclusions cannot be drawn because of missing data. Actuarial survival rates at 5 and 10 years for the local therapy group (92% and 88%, respectively) were essentially equivalent to those for the conventional therapy group (92% and 90%, respectively), however, the recurrence experience after local therapy was less favorable. Local therapy consisted of vaginectomy in nine cases, local excision alone in 17 cases, and local irradiation (with or without local excision) in 17 cases. The subgroup of patients receiving local irradiation had a recurrence experience as favorable as that of the conventional therapy group and more favorable than that of either the subgroup treated with vaginectomy or local excision alone. The data suggest that when employed, local therapy should include local irradiation.

Adenocarcinoma↗
PubMed2003

Parameters that predict local control after definitive radiotherapy for squamous cell carcinoma of the head and neck.

PURPOSE: To analyze parameters that may influence the likelihood of local control after definitive radiotherapy for head and neck cancer. METHODS: Between April 1980 and January 2000, 404 patients were treated with definitive RT alone (358 patients) or combined with adjuvant chemotherapy (46 patients) at our institution and were followed up for 0.25 to 20.25 years (median, 3.5 years.) All living patients were followed up for at least 2 years. All patients had the primary tumor volume calculated on pretreatment CT. End points were local control after RT and local control after RT without a severe late complication. Parameters evaluated in multivariate analyses of these end points included primary site, T stage, primary tumor volume, N stage, histologic differentiation, fractionation schedule, adjuvant chemotherapy, and gender. RESULTS: The rates of local control and local control without a severe late complication after RT were significantly influenced by primary tumor volume for patients with cancer of the supraglottic larynx and true vocal cord. In contrast, the rates of local control and local control without severe complications for patients with tumors of the oropharynx and hypopharynx were less influenced by tumor volume. Multivariate analysis of the overall population revealed that the only parameter that was significantly related to the probability of local control after RT was T stage. Multivariate analyses stratified by primary site revealed that tumor volume significantly influenced local control for patients with cancers of the supraglottis (p =.0220) and glottis (p =.0042) but not for those with lesions of the tonsillar fossa/posterior tonsillar pillar (p =.0892), base of tongue (p =.9493), anterior tonsillar pillar/soft palate (p =.5909), and hypopharynx (p =.2282). CONCLUSIONS: The most important parameter that has an impact on local control after RT is T stage. Primary tumor volume also significantly influences the probability of local control in cancers of the supraglottis and glottis.

Adolescent↗
PubMed2004

Effect of local heating and vasodilation on the cutaneous venoarteriolar response.

The cutaneous venoarteriolar response (CVAR) is a local non-adrenergic vasoconstrictor reflex that is engaged via increases in local transmural pressure. The purpose of this study was to determine if local temperature alters the vasoconstrictor ability of the CVAR. Twelve (5 male, 7 female) subjects performed a CVAR maneuver at local temperatures of 30+/-1, 34, 38, and 42 degrees C. CVAR was also engaged after vasodilation via intradermal perfusion of sodium nitroprusside or the attenuation of local heating-induced vasodilation via intradermal perfusion of N(G)-nitro-L: -arginine methyl ester (L: -NAME) in five subjects (2 male, 3 female). CVAR was elicited by rapid cuff inflation to 45mmHg proximal to two dorsal forearm sites for 2 min in both protocols. Local heating caused a progressive increase in skin blood flow (8+/-1, 18+/-4, 43+/-11, and 78+/-2% maximal skin blood flow for 30+/-1, 34, 38, and 42 degrees C, respectively). Engagement of the CVAR decreased skin blood flow by 53+/-2, 57+/-3, and 51+/-4%, for 30+/-1, 34, and 38 degrees C, respectively. In contrast, local heating to 42 degrees C significantly attenuated the CVAR (16+/-11 %). Local administration of sodium nitroprusside during neutral temperature and L: -NAME during local heating also significantly attenuated the vasoconstrictor response of the CVAR by 27+/-8 and 38+/-4%, respectively. These data indicate that CVAR is attenuated at high (42 degrees C) local skin temperatures and that this attenuation is likely due to an effect of both local heating-induced vasodilation and a direct temperature effect.

Adult↗
PubMed1993

On the time course and accuracy of spatial localization: basic data and a two-process model.

This article addresses the question how fast and accurate the location of a single stimulus can be perceived. In Experiment 1, we measured localization performance in a task which required subjects to perceive and report the location of a single target stimulus ('*' sign) presented in one square of an imaginary 25 x 19 grid. Two factors were varied: stimulus duration and stimulus eccentricity. Stimulus duration was manipulated by employing a backward masking stimulus. Ten intervals (stimulus onset asynchronies) separated target and masking stimulus: 25, 50, 75, 100, 125, 150, 200, 250, 300, and 350 ms. Stimulus eccentricity was manipulated by presenting the target stimulus at five different distances from the fixation point. The observer localized the target stimulus by moving the cursor from the middle of the grid (the initial fixation point) to the perceived target location by pressing the 'arrow' keys on the keyboard. Localization performance showed to be typically related to stimulus duration. That is, two components could be distinguished: The first component represented an initial steep rise in localization performance during the first 50 ms of stimulus duration; the second component represented a gradual rise in localization performance after 50 ms, reaching maximal performance at about 300 ms. We interpreted these two localization performance functions as reflecting the operation of two systems, namely the attentional system for the initial strong increase and the eye movement system for the subsequent gradual increase. In Experiment 2, we measured saccadic eye response latencies to clarify the role of eye movements in localization performance. It was found that in 98.4% of all trials saccades were executed, and, moreover, that saccadic eye response latency decreased with increasing stimulus duration. In Experiment 3, we compared localization performance in the absence and presence of eye movements and demonstrated that localization performance for stimulus durations up to 50 ms was independent of eye movements. Overall, the present findings were interpreted as evidence in support of a two-process model of localization performance in which a shift of attention is followed by a rapid eye movement toward the target location. In line with a continuous flow conception of visual information processing, our model assumes that location information takes time to develop in the visual system; hence, an observer's localization response may be based on qualitatively different processes operating on qualitatively different kinds of information. In case of short duration stimuli, information conveyed by transient cells is used by the attentional system to shift attention toward the target location; this results in course location information being available.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

Radiotherapy for regionally localized hormone refractory prostate cancer.

PURPOSE: Patients with regionally localized hormone refractory adenocarcinoma of the prostate are often referred for radiotherapy to relieve local symptoms, prevent further local progression, or prevent impending urinary tract obstruction. However, the merits of radiotherapy for this patient population have not been documented. In this retrospective series, the results of 29 such patients treated at our institution between 1987-1992 are reviewed. METHODS AND MATERIALS: Prior to androgen ablation, the majority of these patients (79%) had Stage D0 or D1 disease. After androgen ablation, radiotherapy was given to 16 (55%) for progressive symptoms (mostly urinary obstructive), 11 (38%) for palpable local progression in the absence of symptoms, and 2 for a rising prostate specific antigen (PSA) profile without palpable disease. None of the patients had distant metastasis at the time of radiotherapy. The median dose to the prostate was 66 Gy and the median follow-up after radiotherapy was 43 months. RESULTS: Following local-regional radiotherapy, the actuarial rate of local failure at 4 years was only 39%. However, 80% had disease progression or a rising PSA in this time period. The actuarial survival at 4 years following radiotherapy was 39%. Univariate analyses of potential prognostic factors revealed that preandrogen ablation Gleason score, preradiotherapy PSA, and preradiotherapy prostatic acid phosphatase (PAP) were predictive of patient outcome. Most importantly, doses above 60 Gy to the prostate at standard fractionation were associated with symptom-free local control in 90% of patients at 3 years. The majority of the patients were treated using limited fields (n = 20). CONCLUSIONS: The regionally localized hormone refractory prostate cancer patients described benefited from high dose, continuous course, local radiotherapy in that excellent local control rates were obtained for an extended period. Because the majority of these patients fail with distant metastasis within 4 years, this treatment represents an aggressive approach to palliation that is justified by the maintenance of freedom from local symptoms.

Acid Phosphatase↗
PubMed2003

Local people's attitudes towards conservation and wildlife tourism around Sariska Tiger Reserve, India.

Conservationists in the recent years view local peoples' support for protected areas management as an important element of biodiversity conservation. This is often linked to the direct benefits, which local communities get from the protected areas. These benefits could be in the form of biomass resources, park funds diverted to local villages by state agencies and revenue from wildlife tourism. There are a very few studies which have attempted to study the direct relationship between benefits from wildlife tourism and local support for conservation. In India, wildlife tourism is restricted, and mostly controlled by state and private agencies. Wildlife conservation policy does not view tourism in protected areas as a source of revenue for the local communities. The present study examines the local people's attitudes towards wildlife tourism and the impact of benefits from tourism on the local support for Sariska Tiger Reserve (STR), India. STR is a flagship for tourism where protected areas are increasingly being visited and where local support for wildlife tourism has not been studied adequately. Results indicate that two-thirds of the respondents were positive towards tourism and support for conservation. The respondents were aware that more tourism benefits are possible from a well-conserved protected area. There appears to be correlation between benefits obtained by local people from wildlife tourism and other sources, and support for protected area existence, suggesting that benefits impact people's attitudes towards conservation. Some of the main problems are the unequal distribution of tourism benefits, lack of locals' involvement in tourism and development. There is a need to clearly address these issues, so that protected areas may get the support of local people, which may lead to sustainable development.

Animals↗
PubMed2004

How hematopoietic stem cells know and act in cardiac microenvironment for stem cell plasticity? Impact of local renin-angiotensin systems.

Bone marrow-derived hematopoietic stem cells (HSC) can exhibit tremendous differentiation activity in numerous non-hematopoietic organs. This enigmatic process is called as 'stem cell plasticity' (SCP). HSC may promote structural and functional repair in several organs such as heart, liver, brain, and skeletal muscle via the SCP. The differentiation capacity of HSC is dependent on the specific signals present in the local tissue microenvironment. Those specific molecular signals required for the interactions of HSC and host tissues are currently unknown. The aim of this report is to propose a hypothesis on how HSC reach, recognize, and function in cardiac tissues in the context of SCP. Locally signaling cardiac microenvironment is essential for the seeding, expansion, and 'cardiomyocyte differentiation' of the HSC in the heart. Our hypothesis is that the receptors, ligands, and signaling pathways of the tissue renin-angiotensin system (RAS) serve as the link between HSC and local cardiac microenvironment in SCP. The RAS is considered as a 'tissue-based system' exhibiting paracrine functions within many organs. The presence of local hematopoietic bone marrow RAS and local cardiac RAS have been suggested. Both local tissue RASs share similar angiotensin peptide-signaling pathways such as JAK-STAT and mitogen-activated protein kinases. HSC have angiotensin type I (AT1a) receptors for the binding of angiotensin II, the active component of the RAS. Binding of angiotensin II to AT1a can increase hematopoietic progenitor cell proliferation. Local cardiac RAS has critical (patho)biological functions in the cardiomyocyte survival, renewal, and growth, as well as in cardiac remodeling. Therefore, the components of the local cardiac RAS and hematopoietic RAS could interact with each other during the SCP through myocardial tissue repair. Activation of the local myocardial RAS after injury may be related to homing and engraftment of the HSC to the cardiac tissue. Regenerating myocardial tissue may exert regulatory functions on circulating or resident HSC via the locally active RAS. Understanding the exact molecular basis of SCP in relation to local tissue RAS could offer new frontiers in the better management of ischemic cardiac diseases.

Adaptation, Physiological↗
PubMed2006

Surgical treatment of rectal cancer: local resection.

Local treatment of rectal cancer aims to decrease the morbidity and the functional sequela associated with radical surgery without compromising local tumor control and long-term survival. Local excision is associated with a higher rate of local recurrence compared with radical surgery, and salvage radical surgery cannot guarantee equivalent long-term survival compared with radical surgery as the primary form of therapy. Therefore, strict criteria for patient selection are critical for local excision to be successful. Selecting the optimal therapy for an individual patient with rectal cancer is crucial and requires consideration of both tumor and patient characteristics. Endorectal ultrasonography is essential for the accurate assessment of rectal wall invasion and nodal metastasis. Only patients with well- or moderately differentiated T1 tumors without blood vessel or lymphatic vessel invasion are candidates for curative local excision as the only form of treatment. Tumors penetrating the muscularis propria should not be treated by local excision alone. These patients can be asked to participate in a trial of chemoradiation followed by local excision. Otherwise, they should undergo radical surgery. The tumor should be removed by full-thickness local excision with an adequate normal margin for pathologic evaluation. Final decisions regarding the treatment strategy should be based on the pathology of the surgical specimen. Intense, close follow-up is critical for early diagnosis of local recurrences as many of them may be surgically salvaged by radical resection. Local treatment can also be used for palliation of patients with histological unfavorable or advanced tumors, and those who are medically unfit for radical surgery.

Colectomy↗