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S Lele

Publications and source records attributed to S Lele.

At least 19 recordsLinked to original sources
PubMed2001

Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin.

CD40 is a member of the tumor necrosis factor receptor family and was first identified with a monoclonal antibody raised against bladder carcinoma. Recombinant human CD40L has been shown previously to have a direct antitumor effect on an ovarian cancer cell line and ovarian carcinoma cells isolated from ascites fluid. We show here that rhuCD40L inhibits the growth of several ovarian adenocarcinomas derived from surgical specimens and grown as xenografts in severe combined immunodeficient mice. Two 14-day treatment cycles were more effective than one. This effect is apparently not mediated by natural killer cells, because blocking natural killer cell activity by antiasialo GM-1 did not diminish this effect. In addition to suppression of tumor growth, treatment with rhuCD40L resulted in an increased expression of FasL, an increase in apoptosis, and histological changes including increased fibrosis and areas of tumor destruction. Using this model, we examined the efficacy of rhuCD40L in combination with chemotherapeutic agents. The antitumor effect of rhuCD40L in combination with 4 mg/kg cisplatin (CDDP) was increased over the effect of CDDP alone. Furthermore, rhuCD40L increased the efficacy of a suboptimal dose of CDDP (2mg/kg) such that it matched that of high-dose CDDP alone. These data suggest a role for rhuCD40L therapy in combination with platinum based regimens for primary treatment of epithelial ovarian tumors.

Animals↗
PubMed2001

Human ovarian cancer, lymphoma spleen, and bovine milk GlcNAc:beta1,4Gal/GalNAc transferases: two molecular species in ovarian tumor and induction of GalNAcbeta1,4Glc synthesis by alpha-lactalbumin.

Affinity Gel-UDP was utilized to purify GlcNAc:beta1,4Gal/GalNAc transferases (Ts) from human lymphoma spleen, ovarian tumor, and ovarian cancer sera. Mn(2+) was found to be an absolute requirement for activity. Two molecular species containing both beta1,4Gal/GalNAc-T activities were discernible when the purified ovarian tumor microsomal enzyme was subjected to Sephacryl S-100 HR column chromatography as well as native polyacylamide gel-electrophoresis. Acceptor specificity studies of the affinity-purified lymphoma spleen and ovarian tumor microsomal enzymes and the conventionally purified, as well as the cloned, bovine milk GlcNAc:beta1,4Gal-Ts using a number of synthetic acceptors showed that the beta(1,6)-linked GlcNAc moiety to alpha-GalNAc was the most efficient acceptor. As compared to the purified milk enzyme, the recombinant form exhibited sixfold GlcNAc:beta1,4 GalNAc-T activity and up to eightfold GlcNAc6SO3beta-:beta1,4Gal-T activity. Further, the recombinant enzyme catalyzed the transfer of GalNAc to the terminal beta-linked GlcNAc6SO3 moiety. Alpha-lactalbumin (alpha-LA) inhibited up to 85%, the transfer of Gal to the GlcNAc moiety linked either to Man or GlcNAc. On the contrary, alpha-LA had no significant influence on the transfer of GalNAc to the above acceptors. alpha-LA had no appreciable effect on the recombinant enzyme, except for the transfer of Gal or GalNAc to Glc. Both alpha- and beta-glucosides, as well as alpha-N-acetylglucosaminide, did not serve as acceptors.

Animals↗
PubMed2001

Potential benefit of lymphadenectomy for the treatment of node-negative locally advanced uterine cancers.

OBJECTIVE: The aim of this study was to examine the outcomes in patients with high-risk Stage I endometrial cancers surgically staged by complete pelvic and para-aortic lymphadenectomy, with negative nodes, and treated with postoperative brachytherapy. METHODS: From the database of patients treated for Stage I endometrial cancer, 23 patients were identified with either >50% myometrial invasion or grade 3 histology treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy. All patients had no pathologic evidence of disease in the lymph nodes. These patients were then treated with brachytherapy and followed for treatment and cost outcomes. A comparison was made of the cost of treatment between brachytherapy and external beam radiation. RESULTS: All 23 patients with either grade 3 tumor or greater than 50% myometrial invasion were treated with total abdominal hysterectomy with lymphadenectomy followed by brachytherapy for lesions that did not extend outside the uterine specimen. For all patients in this series, there were no recurrences in the follow-up period (median 25 months). This regimen is more cost efficient and spares the patient from possible complications related to whole pelvic radiation, at an average cost savings of $4100. CONCLUSION: Women undergoing hysterectomy for endometrial adenocarcinoma with high-risk node-negative disease confined to the uterus can be safely treated with brachytherapy, at a substantial cost savings, without compromising survival.

Adenocarcinoma↗
PubMed2001

Early growth response-1 gene: potential radiation response gene marker in prostate cancer.

This study was undertaken to determine whether the transcription factor EGR-1 expression: (1) in the primary tumor, correlates with radiation response in terms of complete local tumor control with no evidence of disease or recurrence and no evidence of metastasis; (2) in the postirradiated biopsies correlates with residual tumor; and (3) correlates with the expression of Egr-1 target genes such as TP53, pRB, and Bax. The authors analyzed: (1) 25 pretreated surgically resected paraffin-embedded primary adenocarcinomas of the prostate for the presence of EGR-1 expression and mutation, and correlated this with clinical endpoints such as serum prostate-specific antigen levels and current clinical status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1 expression, and correlated these findings to the residual tumor status; and (3) 12 prospective prostate tumor specimens for EGR-1 expression and its target genes. EGR-1 expression was determined by immunohistochemistry and mutations were screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain reaction-single strand conformational polymorphism analysis. Of 25 patients, 18 patients showed expression of EGR-1. EGR-1 overexpression correlated with treatment failure. No correlation with EGR-1 overexpression and its target genes was found, which may indirectly suggest that overexpressed EGR-1 may lack transactivation function. In summary, EGR-1 overexpression in the mutant form may provide an indication of clinical failure (local recurrence or metastasis).

Adenocarcinoma↗
PubMed2001

The association between extreme precipitation and waterborne disease outbreaks in the United States, 1948-1994.

OBJECTIVES: Rainfall and runoff have been implicated in site-specific waterborne disease outbreaks. Because upward trends in heavy precipitation in the United States are projected to increase with climate change, this study sought to quantify the relationship between precipitation and disease outbreaks. METHODS: The US Environmental Protection Agency waterborne disease database, totaling 548 reported outbreaks from 1948 through 1994, and precipitation data of the National Climatic Data Center were used to analyze the relationship between precipitation and waterborne diseases. Analyses were at the watershed level, stratified by groundwater and surface water contamination and controlled for effects due to season and hydrologic region. A Monte Carlo version of the Fisher exact test was used to test for statistical significance. RESULTS: Fifty-one percent of waterborne disease outbreaks were preceded by precipitation events above the 90th percentile (P = .002), and 68% by events above the 80th percentile (P = .001). Outbreaks due to surface water contamination showed the strongest association with extreme precipitation during the month of the outbreak; a 2-month lag applied to groundwater contamination events. CONCLUSIONS: The statistically significant association found between rainfall and disease in the United States is important for water managers, public health officials, and risk assessors of future climate change.

Animals↗
PubMed2001

The impact of pre-therapy extraperitoneal surgical staging on the evaluation and treatment of patients with locally advanced cervical cancer.

OBJECTIVE: The use of extraperitoneal surgical staging prior to treatment in patients with bulky or locally advanced cervical cancer allows the detection and treatment of disease beyond the standard pelvic radiation fields. This study was conducted to evaluate the impact of extraperitoneal surgical staging in the treatment and outcome of patients with locally advanced cervical cancer. METHODS: 51 patients with locally advanced cervical cancer treated between 1985 and 1998 were retrospectively reviewed. Information on morbidity, usefulness, and results of surgery and patterns of disease recurrence were obtained. Survival distributions were calculated by the Kaplan-Meier product limit method and compared with the log-rank test. RESULTS: All 51 women were surgically staged by an extra-peritoneal approach. Preoperative CT scans (n=27) when compared with surgical findings showed sensitivity for pelvic and para-aortic lymph node metastasis of 39%, specificity of 88%, positive predictive value of 39% and negative predictive value of 88%. Lymph node metastases were found in 30/51 patients (59%). There were no significant treatment delays or surgical morbidity as a result of extra-peritoneal surgical staging. In 21 patients (41%), the highest level of involved nodes was in the pelvis and they were treated with pelvic radiation. The para-aortic nodes were involved in nine patients (18%) and were treated with extended field radiation. All patients also received concurrent radiosensitization with chemotherapy. The estimated survival for the entire group was 60% at 5 years. For node negative patients, estimated 5-year survival was 67% while it was 54% for all node positive patients (p=0.17). Analysis according to anatomic site of involved nodes showed that the estimated 2-year and 5-year survival for those with pelvic nodal involvement was 81% and 64%, respectively. However, in the group of nine patients with para-aortic nodal disease, the estimated 2-year survival was 44%. Five (56%) were dead of disease with a median time to death of 16.0 months and four patients (44%) were alive with a median duration of follow up of 16.1 months. There was a statistically significant difference in survival for the group of patients with positive pelvic nodes only compared to the group with positive para-aortic nodes (p=0.03). The estimated 5-year survival by FIGO stage was 80%, 70% and 51% for stages Ib, II, III, disease, respectively. Factors that did not significantly affect survival included age, histology and type of chemotherapy. CONCLUSIONS: Pre-therapy extra-peritoneal surgical staging resulted in treatment modification in 18% of patients with locally advanced cervical cancer. The morbidity from surgery and subsequent radiation therapy was acceptable. The procedure is recommended to allow for individualization of treatment in patients with local-regional cervical cancer.

Adult↗
PubMed2000

Prospective audit following the introduction of short-course preoperative radiotherapy for rectal cancer.

BACKGROUND: The value of introducing a short course of preoperative radiotherapy before operation for rectal cancer is still subject to debate. METHODS: One hundred consecutive patients, of mean age 68 (range 29-87) years undergoing pre- operative radiotherapy for rectal cancer between January 1997 and December 1998 at two radiotherapy centres were audited prospectively. RESULTS: The time from referral to radiotherapy was 33 (11-74) days and from radiotherapy to operation 5 (1-42) days. There was a higher than expected anastomotic leak rate (15 per cent) and perineal wound infection rate (18 per cent). Patients waiting more than 7 days were more likely to suffer perineal wound breakdown: 15 per cent (n = 39) versus 30 per cent (n = 10). CONCLUSION: The high anastomotic leak and perineal wound infection rates suggest that the introduction of preoperative radiotherapy combined with total mesorectal excision should be audited carefully or performed as part of the CRO7 trial. Presented to the Association of Coloproctology of Great Britain and Ireland in St Helier, Jersey, June 1998

Adult↗
PubMed1998

Capturing data from three-dimensional surfaces using fuzzy landmarks.

Anatomical landmarks are defined as biologically meaningful loci that can be unambiguously defined and repeatedly located with a high degree of accuracy and precision. The neurocranial surface is characteristically void of such loci. We define a new class of landmarks, termed fuzzy landmarks, that will allow us to represent the form of the neurocranium. A fuzzy landmark represents the position of a biological structure that is precisely delineated, but occupies an area that is larger than a single point in the observer's reference system. In this study, we present a test case in which the cranial bosses are evaluated as fuzzy landmarks. Five fuzzy landmarks (the cranial bosses) and three traditional landmarks were placed repeatedly by a single observer on three-dimensional (3D) computed tomography (CT) surface reconstructions of pediatric dry skulls and skulls of pediatric patients, and directly on four of the same dry skulls using a 3Space digitizer. Thirty landmark digitizing trials from CT scans show an average error of 1.15 mm local to each fuzzy landmark, while the average error for the last ten trials was 0.75 mm, suggesting a learning curve. Data collected with the 3Space digitizer was comparable. Measurement error of fuzzy landmarks is larger than that of traditional landmarks, but is acceptable, especially since fuzzy landmarks allow inclusion of areas that would otherwise go unsampled. The information obtained is valuable in growth studies, clinical evaluation, and volume measurements. Our method of fuzzy landmarking is not limited to cranial bosses, and can be applied to any other anatomical features with fuzzy boundaries.

Child↗
PubMed1998

Predicting key malaria transmission factors, biting and entomological inoculation rates, using modelled soil moisture in Kenya.

While malaria transmission varies seasonally, large inter-annual heterogeneity of malaria incidence occurs. Variability in entomological parameters, biting rates and entomological inoculation rates (EIR) have been strongly associated with attack rates in children. The goal of this study was to assess the weather's impact on weekly biting and EIR in the endemic area of Kisian, Kenya. Entomological data collected by the U.S. Army from March 1986 through June 1988 at Kisian, Kenya was analysed with concurrent weather data from nearby Kisumu airport. A soil moisture model of surface-water availability was used to combine multiple weather parameters with landcover and soil features to improve disease prediction. Modelling soil moisture substantially improved prediction of biting rates compared to rainfall; soil moisture lagged two weeks explained up to 45% of An. gambiae biting variability, compared to 8% for raw precipitation. For An. funestus, soil moisture explained 32% variability, peaking after a 4-week lag. The interspecies difference in response to soil moisture was significant (P < 0.00001). A satellite normalized differential vegetation index (NDVI) of the study site yielded a similar correlation (r = 0.42 An. gambiae). Modelled soil moisture accounted for up to 56% variability of An. gambiae EIR, peaking at a lag of six weeks. The relationship between temperature and An. gambiae biting rates was less robust; maximum temperature r2 = -0.20, and minimum temperature r2 = 0.12 after lagging one week. Benefits of hydrological modelling are compared to raw weather parameters and to satellite NDVI. These findings can improve both current malaria risk assessments and those based on El Niño forecasts or global climate change model projections.

Animals↗
PubMed1995

Euclidean distance matrix analysis: confidence intervals for form and growth differences.

Analysis of biological forms using landmark data has received substantial attention recently. Much of the statistical work in this area has concentrated on the estimation of average form, average form difference, and average growth difference. From the statistical, as well as the scientific point of view, it is important that any estimate of a scientifically relevant quantity be accompanied by a statement regarding its accuracy. Such a statement is contained in a confidence interval. The purpose of this paper is to provide a method to obtain confidence intervals for form difference and growth difference estimators. The estimators are based on Euclidean distance matrix analysis. The confidence intervals are calculated using the model independent bootstrap method. We illustrate the method by using three examples: morphological differences between samples of craniofacial patients and normal controls using two dimensional data from head X-rays, sexual dimorphism of craniofacial morphology in Cebus apella, and sexual dimorphism of facial growth in Cebus apella using three-dimensional data.

Animals↗
PubMed1994

Basic fibroblast growth factor and receptor expression in human ovarian cancer.

Basic fibroblast growth factor (bFGF) and other members of the FGF family share several biological properties that have the potential to mediate neoplastic cell growth. To test the hypothesis that bFGF may play a role in human ovarian cancer cell growth, three ovarian cancer cell lines, A90, A121(P), and A121(A), were investigated for their ability to respond to bFGF as a mitogen, to express endogenous bFGF protein or message for FGF proteins, and to exhibit FGF receptor or its message. Addition of bFGF to cultures of all three cell lines maintained in chemically defined media resulted in a statistically significant increase in cell number. Cell extracts from A90, A121(P), and A121(A) contained an immunoreactive protein that comigrated with hr-bFGF by Western blot analysis. Several bands of higher molecular weight were also noted. Immunohistochemical staining for bFGF demonstrated a cytoplasmic distribution of bFGF in the three cell lines. Both high- and low-affinity binding sites for human recombinant bFGF (hr-bFGF) were expressed by all three lines. High-affinity sites varied from 2700 sites per cell (Kd = 29 pM) to 13,500 sites per cell (Kd = 71 pM). All three cell lines were screened for mRNA expression for seven FGF proteins and four FGF receptors. In all three lines, mRNA for FGF2 (bFGF) was detected by PCR analysis, and in two lines, mRNA for FGF1 (aFGF) and FGF5 were also found. The FGFR1 receptor subtype (flg) was common to all of the cell lines. Finally, suramin inhibited proliferation of A90 and A121 (P and A) with IC50's of 60 and 210 micrograms/ml, respectively. This is consistent with the A90 cell line having higher levels of endogenous bFGF and flg and therefore being more responsive to suramin inhibition than the A121 cell line. The results indicate that these ovarian cancer cell lines can produce bFGF as well as other members of the FGF family of genes and have the ability to respond to bFGF.

Base Sequence↗
PubMed1993

A coordinate-free approach to the analysis of growth patterns: models and theoretical considerations.

Developmental biology holds keys to our understanding of morphological pattern formation whether these patterns are expressed in the fossil record or among extant species. Though much is known about osseous growth at the cellular level (e.g. Hall, 1991), we have minimal understanding of the coordinated processes that combine to produce a complex, three-dimensional form. We have proposed a framework for the coordinate-free representation of form, a statistical method for comparing and modelling growth trajectories for complex morphologies, and a means for the eventual elucidation of the role of growth in the evolution of morphology. Our method uses the coordinate locations of biological landmarks to represent form as a matrix of all possible linear distances between landmarks, the form matrix. When two forms are expressed in this way, comparison of these forms is accomplished by computing the ratios of like linear distances, the form difference matrix. When the forms being compared are from a growth series, the matrix of ratios is called a growth matrix. Patterns of growth for two groups can be compared by computing the growth difference matrix. We applied growth difference matrix analysis to the study of sexual dimorphism of ontogeny in the M. fascicularis craniofacial skeleton. Growth matrices describing growth in male and female M. fascicularis were presented along with the growth difference matrix that describes sexual dimorphism of growth to underscore the detailed information available from this analytical technique. The method is quite general and can be applied to two- or three-dimensional data sets of landmark coordinates (cross-sectional or longitudinal) collected from almost any developing structure. The methods that we propose enable us to go beyond a mathematical summary of the comparison of forms and the comparison of growth patterns. We provide examples of how growth patterns might be used in the study of phylogenetic relationships. Our plans for use of this method in the study of evolutionary change assumes that morphological change in the craniofacial skeleton results from evolutionary change in developmental units (as defined by Atchley & Hall, 1991) that underlie morphological structure. We believe we have the basic tools to ultimately propose informed phylogenies based solely on developmental data. This task requires the identification of 'growth features' and the polarization of these features as primitive or derived. It is also advisable to determine a set of primitive growth features for the groups of interest. This will necessitate the inclusion of outgroups in our growth analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

On comparing biological shapes: detection of influential landmarks.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form consists of size and shape. Several approaches for comparing biological forms using landmark data are available. If the two biological forms are demonstrated to be different, the next important issue is to localize the differences by identifying those areas which differ most between the two objects. In this paper we suggest a technique to detect influential landmarks, those which contribute most to the difference between forms. We study the effectiveness of the technique using three-dimensional simulated data sets and two examples. Results suggest that the technique is useful in the study of biological form and its variation.

Acrocephalosyndactylia↗
PubMed1992

A laboratory evaluation of the Kowa laser flare-cell meter for the study of uveitis.

The Kowa FC-1000 laser flare-cell meter (LFCM) has been described as an instrument which will objectively quantify inflammation of the anterior chamber of the eye. We evaluated the LFCM using the intravenous endotoxin-induced uveitis (EIU) rabbit model of ocular inflammation. In vitro flare and cell calibration measurements utilizing bovine serum albumin (BSA) and latex particles, respectively, were also performed. A linear relationship between the flare measurements and BSA concentrations was noted. In addition, the time course of the LFCM flare count in EIU was comparable to previously published fluorophotometric data. However, the LFCM reported cells in the anterior chamber of the EIU rabbits despite negative cytology and histology results. The LFCM also recorded cells in BSA solutions which contained neither cells nor latex particles. Our results suggest that although the LFCM may be useful for evaluating flare, its cell measurements are not accurate in cases of severe uveitis.

Animals↗
PubMed1991

Some comments on coordinate-free and scale-invariant methods in morphometrics.

The unusual strategy for comparing biological shapes is to use some kind of superimposition of the two forms under study and then look at the "residuals" as the shape change. In this paper, I take a careful look at this general strategy and point out some subtle but inherent and important pitfalls. Additionally an alternative approach based on Euclidean Distance Matrix representation is presented. It is applicable to two- as well as three-dimensional objects.

Anatomy↗
PubMed1991

Euclidean distance matrix analysis: a coordinate-free approach for comparing biological shapes using landmark data.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form can be conveniently defined as consisting of size and shape. Several approaches for comparing biological shapes using landmark data are available. Lele (1991a) critically discusses these approaches and proposes a new method based on the Euclidean distance matrix representation of the form of an object. The purpose of this paper is to extend this new methodology to the comparison of groups of objects. We develop the statistical versions of various concepts introduced by Lele (1991a) and use them for developing statistical procedures for testing the hypothesis of shape difference between biological forms. We illustrate the use of this method by studying morphological differences between normal children and those affected with Crouzon and Apert syndromes and craniofacial sexual dimorphism in Cebus apella.

Acrocephalosyndactylia↗
PubMed1990

Analysis of craniofacial growth in Crouzon syndrome using landmark data.

Finite-element scaling analysis (FESA), generalized procrustes analysis (GPA), and Euclidean distance matrix analysis (EDMA) are applied in a two-dimensional study of craniofacial growth in normal children and those affected with Crouzon syndrome. Longitudinal data are used and growth is measured as change local to 10 craniofacial landmarks. Although details of the results vary among the methods, all 3 methods determine Crouzon growth to be different from normal. Nuances of the methods, especially the use of superimposition in GPA and lack of superimposition in 2 others are partly responsible for the varying results. Although Crouzon craniofacial morphology is often obvious at birth, this study demonstrates that there are general differences between normal postnatal growth patterns and those of the Crouzon individual. These patterns of malgrowth are in part responsible for the adult morphology of the Crouzon craniofacial complex.

Adolescent↗