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Biomedical subjects

D Shasha

Publications and source records attributed to D Shasha.

17 recordsLinked to original sources
PubMed2003

AntiClustal: Multiple Sequence Alignment by antipole clustering and linear approximate 1-median computation.

In this paper we present a new Multiple Sequence Alignment (MSA) algorithm called AntiClusAl. The method makes use of the commonly use idea of aligning homologous sequences belonging to classes generated by some clustering algorithm, and then continue the alignment process ina bottom-up way along a suitable tree structure. The final result is then read at the root of the tree. Multiple sequence alignment in each cluster makes use of the progressive alignment with the 1-median (center) of the cluster. The 1-median of set S of sequences is the element of S which minimizes the average distance from any other sequence in S. Its exact computation requires quadratic time. The basic idea of our proposed algorithm is to make use of a simple and natural algorithmic technique based on randomized tournaments which has been successfully applied to large size search problems in general metric spaces. In particular a clustering algorithm called Antipole tree and an approximate linear 1-median computation are used. Our algorithm compared with Clustal W, a widely used tool to MSA, shows a better running time results with fully comparable alignment quality. A successful biological application showing high aminoacid conservation during evolution of Xenopus laevis SOD2 is also cited.

Algorithms↗
PubMed2001

The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas.

PURPOSE: This report presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND MATERIALS: Members of the ABS with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS: Brachytherapy used alone or in combination with external beam irradiation is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas in adults and in children. Brachytherapy options include low dose rate techniques with iridium 192 or iodine 125, fractionated high dose rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are made for patient selection, techniques, dose rates, and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed. CONCLUSION: Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biologic and dosimetric advantage in the treatment of patients with soft tissue sarcoma. The treatment approach used depends upon the institution, physician expertise, and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas in adults and in children. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as further clinical results become available.

Adult↗
PubMed2001

The negative impact of anemia on radiotherapy and chemoradiation outcomes.

In cancer patients, anemia is common and has been found to impair quality of life and reduce locoregional disease control conferred by radiotherapy. The prognostic importance of anemia in the radiation oncology setting may be related to a reduction of molecular oxygen levels, thereby attenuating radiation-induced damage and ultimate cell death. Substantially higher doses of radiation are required to eradicate malignant cells under the hypoxic conditions commonly identified in solid tumors. Consistent with this, patients with hypoxic solid tumors have been found to have shorter postradiation disease-free survival rates relative to patients with well-oxygenated tumors. An attempt to enhance intratumoral oxygenation via correction of anemia, a highly prevalent but modifiable condition, is therefore a reasonable approach to optimize radiotherapy and chemoradiation outcomes. Clinical studies investigating recombinant human erythropoietin (epoetin alfa) as an adjunct to radiotherapy have demonstrated its ability to increase and maintain hemoglobin (Hb) levels during the course of radiotherapy. In a study involving anemic patients undergoing chemoradiation for head and neck cancer, epoetin alfa extended locoregional control and survival to rates reported for patients with normal pretreatment Hb levels. Given the high prevalence and prognostic significance of anemia during radiotherapy, strategies that safely and effectively increase Hb levels may be of value for optimizing radiotherapy and chemoradiation outcomes.

Anemia↗
PubMed2001

Prevalence of anemia in cancer patients undergoing radiation therapy.

Anemia is associated with reduced local tumor control and impaired quality of life in patients with several types of solid tumors. The prevalence of anemia in patients who present at radiation oncology departments has not been well documented, and the impact of anemia on the outcome of radiation therapy is not widely appreciated in the radiation oncology setting. In an ongoing study, we are retrospectively reviewing the medical charts of patients before and after radiation therapy at our institutions to determine the magnitude of the anemia problem in this population. Preliminary data are available for 574 randomly selected patients (52% female) seen between December 1996 and June 1999. At presentation, 41% of all patients were anemic (hemoglobin < 12 g/dL); by the end of radiation therapy, this percentage increased to 54%. The most common tumor types were prostate (16%), breast (14%), head and neck (12%), colorectal (11%), lung/bronchus (11%), and uterine-cervix (9%). Anemia was most prevalent in patients with uterine-cervical tumors (75%), increasing to 79% by the end of radiation therapy. The prevalence of lung/bronchus and colorectal cancer was 55% and 44%, respectively, at baseline and increased to 77% and 63%, respectively, after radiation therapy. For nearly all tumor types, the majority of patients had or developed mild to moderate anemia (hemoglobin 10.0 to 11.9 g/dL). These data show that anemia is widespread among patients seen in radiation oncology practices. However, the anemia is usually mild and readily correctable. Because anemia and hypoxia possibly associated with anemia are obstacles to local tumor control and maintenance of quality of life, strategies to reverse anemia should receive greater attention.

Anemia↗
PubMed2001

Thermoluminescent dosimetry of the Symmetra 125I model I25.S06 interstitial brachytherapy seed.

As the efficacy of brachytherapy prostate treatment is becoming realized, new models of 125I seeds are being introduced. In this article we present thermoluminescent dosimetry (TLD) in a solid water phantom for a new design of 125I seed (UroMed/Bebig Symmetra, Model I25.S06). TLD cubes, LiF TLD-100, from Bicron (Solon, OH) with dimension 1 x 1 x 1 mm3 were irradiated at various distances from the seed at angles ranging from 0 degrees to 90 degrees in 10 degrees increments. The TLD detectors were calibrated by irradiation in a 60Co teletherapy beam. Monte Carlo simulation was used to account for TLD energy dependence and the deviation of solid water composition (as determined by chemical analysis of a sample) from liquid water. Dose rates per unit air kerma strength were determined based on calibrations traceable to the 1999 NIST standard (corrected for NIST measurement errors made in 1999) for the Symmetra seed. Dose data is presented in TG-43 format as a function of distance and angle. Values for lambda, F(r, theta), g(r), and the anisotropy constant are obtained for use in radiation treatment planning (RTP) software. The dose rate constant was determined to be 1.033+/-6.4% cGy h(-1) U(-1), which is comparable to model 6702 and higher than model 6711. We find the relative dose distributions of the Symmetra seed are similar to model 6702, and less anisotropic than model 6711. After accounting for deviation of measured solid water composition from the manufacturer's specification, good agreement between TLD results and Monte-Carlo-aided values was found.

Anisotropy↗
PubMed2001

Anemia treatment and the radiation oncologist: optimizing patient outcomes.

Anemia is a frequent complication of cancer and its associated treatment. Although its occurrence is well documented in the chemotherapy setting, the prevalence and nature of anemia in the radiation oncology setting have been inadequately characterized. Preliminary findings from an ongoing retrospective study at Beth Israel Medical Center in New York indicate that mild-to-moderate anemia (ie, hemoglobin levels of 10 to 12 g/dL) is common at presentation for radiation therapy and increases in prevalence and severity during the course of radiation treatment. The symptoms of mild-to-moderate anemia, particularly fatigue, can substantially impair the quality of life of cancer patients. Furthermore, an extensive body of literature has documented an association between low hemoglobin levels and poor locoregional tumor control and survival following curative-intent radiation therapy. Greater efforts by radiation oncologists to document and treat anemia in patients undergoing radiation therapy may provide an opportunity to improve postradiation outcomes and well-being.

Anemia↗
PubMed2000

The role of brachytherapy for palliation.

The goal of palliative radiation is to alleviate symptoms in a short amount of time and maintain an optimal functional and quality-of-life level while minimizing toxicity and patient inconvenience. Despite advances in multimodality antineoplastic therapies, failure to control the tumor at its primary site frustratingly remains the predominant source of morbidity and mortality in many patients with cancer. Escalation of doses of radiation using external beam irradiation has been shown to improve local tumor control, but limits are imposed by the tolerance of normal surrounding structures. The highly conformal nature of brachytherapy enables the radiation oncologist to accomplish safe escalation of radiation doses to the tumor while minimizing doses to normal surrounding structures. Thus, by enhancing the potential for local control, brachytherapy used alone or as a supplement to external beam radiation therapy retains a significant and important role in achieving the goals of palliation. Proper patient selection, excellent technique, and adherence to implant rules will minimize the risk of complications. The advantages realized with the use of brachytherapy include good patient tolerance, short treatment time, and high rates of sustained palliation. This article reviews various aspects of palliative brachytherapy, including patient selection criteria, implant techniques, treatment planning, dose and fractionation schedules, results, and complications of treatment. Tumors of the head and neck, trachea and bronchi, esophagus, biliary tract, and brain, all in which local failure represents the predominant cause of morbidity and mortality, are highlighted.

Brachytherapy↗
PubMed2000

Radiotherapy-associated anemia: the scope of the problem.

The impact of anemia on cancer patients undergoing chemotherapy is well established, but only recently has the prevalence of anemia in patients receiving radiotherapy received much attention. Many cancer patients present with anemia prior to radiotherapy, and even more experience anemia or a worsening of anemia at some point during treatment. However, the problem of anemia is often ignored because patients may experience only functional anemia, defined as a hemoglobin level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is discovered, efforts to correct anemia are often not made. Because hemoglobin levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of radiotherapy in a number of patient populations, ignoring even modest anemia can result in decreased locoregional control, overall survival, and quality of life (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily accomplished, there exists the potential for improving outcomes by paying greater attention to this problem. This article focuses on the prevalence of anemia, particularly functional anemia, and discusses the impact of anemia on locoregional control, overall survival, and QOL.

Anemia↗
PubMed2000

Conjunctival fibroblasts enhance the survival and functional activity of peripheral blood eosinophils in vitro.

PURPOSE: To examine the effect of human conjunctival fibroblasts on the survival and functional activity of human peripheral blood eosinophils. METHODS: Eosinophils were purified by negative immunoselection [magnetic activated cell sorter (MACS), purity > 97%] from volunteers with mild atopia. Fibroblasts were cultured from conjunctival specimens of healthy donors. Eosinophils were cultured on confluent monolayers of conjunctival fibroblasts or in culture medium alone. Eosinophil survival was evaluated by the trypan blue exclusion test. Eosinophil adherence was assessed by counting the attached cells after washing the cultures. Eosinophil viability and adherence in coculture were also assessed in the presence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF), anti-interleukin (IL)-3, and anti-IL-5 neutralizing antibodies. Cocultured eosinophils were activated by lipopolysaccharide (LPS) after 4 days in culture, and eosinophil peroxidase (EPO) release was determined as a marker of their activation. RESULTS: Eosinophils cocultured with conjunctival fibroblasts had a significantly increased viability of 35.9% (P = 0.004) and 12.8% (P = 0.003) on days 4 and 8, respectively. Fibroblast-conditioned medium did not enhance the survival of eosinophils. The increase in eosinophil survival in coculture was partially inhibited by anti-GM-CSF (P = 0.019), anti-IL-3 (P = 0.033), or anti-IL-5 (P = 0.011), whereas eosinophil adherence was reduced by anti-GM-CSF alone (P = 0.034). LPS activation of eosinophils cultured for 4 days with conjunctival fibroblasts induced higher EPO release than in freshly isolated eosinophils (P = 0.01). CONCLUSIONS: Human conjunctival fibroblasts induced prolonged survival and increased secretory function of human peripheral blood eosinophils. Increased survival is partially mediated by IL-3, IL-5, and GM-CSF. The coculture of conjunctival fibroblasts with eosinophils can serve as an in vitro system for the study of eosinophil behavior in the ocular surface and of cellular interactions in allergic eye diseases.

Adolescent↗
PubMed2000

Radiotherapy-Associated Anemia: The Scope of the Problem.

The impact of anemia on cancer patients undergoing chemotherapy is well established, but only recently has the prevalence of anemia in patients receiving radiotherapy received much attention. Many cancer patients present with anemia prior to radiotherapy, and even more experience anemia or a worsening of anemia at some point during treatment. However, the problem of anemia is often ignored because patients may experience only functional anemia, defined as a hemoglobin level less than 12 g/dl. Unless physiologic anemia (hemoglobin = 8 g/dl) is discovered, efforts to correct anemia are often not made. Because hemoglobin levels <12 g/dl seem to be associated with tumor hypoxia and poorer outcomes of radiotherapy in a number of patient populations, ignoring even modest anemia can result in decreased locoregional control, overall survival, and quality of life (QOL). Because increasing hemoglobin levels 1-2 g/dl is usually easily accomplished, there exists the potential for improving outcomes by paying greater attention to this problem. This article focuses on the prevalence of anemia, particularly functional anemia, and discusses the impact of anemia on locoregional control, overall survival, and QOL.

Journal Article↗
PubMed1999

Brachytherapy in the treatment of colorectal malignancies.

By precisely delivering a single, high dose fraction of intraoperative radiation under direct visualization while excluding surrounding normal dose-limiting tissues, IORT has improved the therapeutic ratio of tumor control to morbidity. Both IOERT and HDR-IORT represent effective means of delivering this therapy, and either may be chosen with equal confidence, depending upon the facilities available, physician preference, and the clinical situation. The extraordinary efforts often required in the management of these highly selected patients is justified by the improvement achieved in the enhanced local control rates and increased cure rates. Preoperative chemoradiation therapy followed by gross total resection and IORT affords the patient the highest likelihood of local control and survival. The importance of aggressive surgery in achieving gross total resection with pathologically negative margins is reflected by the dramatic correlation reported between margin status and local control. The high complication rate associated with this multidisciplinary therapy is, no doubt, multifactorial and may be attributed to the advanced disease state at presentation and the intensive multidisciplinary treatments administered. In an effort to eradicate disease and prolong survival, many consider these elevated complication rates acceptable, particularly in light of the complexity of these cases, as well as the morbidity and mortality associated with persistent disease in the pelvis.

Brachytherapy↗
PubMed1999

New techniques for DNA sequence classification.

DNA sequence classification is the activity of determining whether or not an unlabeled sequence S belongs to an existing class C. This paper proposes two new techniques for DNA sequence classification. The first technique works by comparing the unlabeled sequence S with a group of active motifs discovered from the elements of C and by distinction with elements outside of C. The second technique generates and matches gapped fingerprints of S with elements of C. Experimental results obtained by running these algorithms on long and well conserved Alu sequences demonstrate the good performance of the presented methods compared with FASTA. When applied to less conserved and relatively short functional sites such as splice-junctions, a variation of the second technique combining fingerprinting with consensus sequence analysis gives better results than the current classifiers employing text compression and machine learning algorithms.

Algorithms↗
PubMed1998

Elective irradiation of the N0 neck in squamous cell carcinoma of the upper aerodigestive tract.

The decision of how to optimally manage the clinically negative neck is based on the likelihood of clinically inapparent disease and the efficacy of salvage therapy. The criteria of decision for elective management of the neck takes into account the site, size, depth of infiltration, grading of the primary lesion, clinical and radiologic evaluation, and patient wishes. Diagnostic procedures currently used in evaluating head and neck cancer patients with nodal disease are reviewed. Elective irradiation of the N0 neck in patients with squamous cell carcinoma of the head and neck is an effective means of maintaining locoregional control. The impact of elective nodal treatment on disease free survival and overall survival is discussed.

Carcinoma, Squamous Cell↗
PubMed1998

The role of brachytherapy in head and neck cancer.

By precision dose delivery to a well-defined target, brachytherapy fulfills the complementary goals of delivering sufficient dose for tumor cell kill while sparing normal adjacent structures. The unique properties of this modality, either used alone or implemented in a combined modality setting with surgery or external-beam irradiation, offer an ideal means of enhancing the therapeutic ratio by exploiting the effect of local therapies while respecting normal tissue tolerance. Brachytherapy also provides an effective technique for the retreatment of patients with recurrent, persistent, or second primary head and neck malignant tumors in a previously irradiated region. The benefits of this treatment modality are reflected in excellent reported local control rates, shortened overall treatment times, reduced functional deficits, improved quality of life, and decreased costs. Successful brachytherapy relies, however, on close collaborative efforts between radiation oncologists and surgeons, careful assessment of the patient, precise planning, and technique that adheres to the rules of a system. Brachytherapy has been clearly identified as an effective, safe, and appealing modality in the treatment of head and neck malignancies.

Brachytherapy↗
PubMed1996

Complementary classification approaches for protein sequences.

We have studied five methods of protein classification and have applied them to the 768 groups of related proteins in the PROSITE catalog. Four of these methods are based on searching a database of blocks, and the other uses the frequently occurring motifs found in the protein families combined with a fingerprint technique. Our experimental results show that the block-based methods perform well when taking into account the probability of amino acids occurring in a block. Furthermore, the five methods give information that is complementary to each other. Thus, using the five methods together, one can obtain high confidence classifications (if the results agree) or suggest alternative hypotheses (if the results disagree). We also list those proteins whose current families documented in the PROSITE catalog differ from those suggested by our results. There are remarkably few of them, which is a testimony to the quality of PROSITE.

Amino Acid Sequence↗
PubMed1994

Discovering active motifs in sets of related protein sequences and using them for classification.

We describe a method for discovering active motifs in a set of related protein sequences. The method is an automatic two step process: (1) find candidate motifs in a small sample of the sequences; (2) test whether these motifs are approximately present in all the sequences. To reduce the running time, we develop two optimization heuristics based on statistical estimation and pattern matching techniques. Experimental results obtained by running these algorithms on generated data and functionally related proteins demonstrate the good performance of the presented method compared with visual method of O'Farrell and Leopold. By combining the discovered motifs with an existing fingerprint technique, we develop a protein classifier. When we apply the classifier to the 698 groups of related proteins in the PROSITE catalog, it gives information that is complementary to the BLOCKS protein classifier of Henikoff and Henikoff. Thus, using our classifier in conjunction with theirs, one can obtain high confidence classifications (if BLOCKS and our classifier agree) or suggest a new hypothesis (if the two disagree).

Algorithms↗