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Biomedical subjects

S Ganesan

Publications and source records attributed to S Ganesan.

At least 19 recordsLinked to original sources
PubMed2006

Dose distribution for endovascular brachytherapy using Ir-192 sources: comparison of Monte Carlo calculations with radiochromic film measurements.

An analysis of Ir-192 source distribution using the Monte Carlo method and radiochromic film experiments for endovascular brachytherapy is presented. Three different source possibilities, namely, mHDR Ir-192 sources with 5 mm and 2.5 mm step sizes and Ir-192 seed sources with 1 mm air gap are investigated to obtain uniform radial dose distribution throughout the treatment area. From this study, it is inferred that mHDR Ir-192 sources with 2.5 mm step size are effective for getting dose uniformity. Hence, different restenosis geometries, namely, linear, dumb bell and hairpin, are simulated with 2.5 mm step size, 15 mHDR Ir-192 sources using the Monte Carlo technique and the results are compared experimentally by using radiochromic films. The results from both methods agreed to within 7%. Further, it is also inferred that for the dosimetry of endovascular brachytherapy, the film dosimetry may be considered adequate, even if the film calibration is time consuming and requires adequate dosimetric procedures.

Brachytherapy↗
PubMed2006

Ultrasound spectrum in intraductal papillary neoplasms of breast.

Intraductal papillary neoplasms (IPNs) of breast form a wide spectrum of pathological changes with benign intraductal papilloma occupying one end of the spectrum and papillary carcinoma at the other end. Intraductal papillomas are known to occur anywhere within the ductal system and are broadly classified into central and peripheral types. Intraductal papillary carcinoma is an uncommon ductal malignancy forming papillary structures, and these lesions characteristically lack the myoepithelial layer present in benign papillary neoplasms. Three basic patterns of IPNs are recognized on ultrasound - intraductal mass with or without ductal dilatation, intracystic mass and a predominantly solid pattern with the intraductal mass totally filling the duct. Benign papillomas are known to exhibit calcifications which tend to be extremely dense and coarse. IPNs are highly vascular tumours and have a propensity to bleed spontaneously. A distinct vascular pedicle is identified within the central core of IPNs, with branching vessels arborising within the mass. In an older age group, presence of a large solid component and evidence of spontaneous intracystic bleed are more suggestive of papillary carcinomas than benign papillomas. We have serially studied 42 cases of intraductal papillary neoplasms with sonomammography and mammography from 2001 to 2004.

Adult↗
PubMed2005

Abnormalities of the inactive X chromosome are a common feature of BRCA1 mutant and sporadic basal-like breast cancer.

As a clinical entity, breast cancer appears to be a series of subforms, each with a relatively specific molecular phenotype. Among the characteristics that differentiate these subforms are sex hormone receptor expression, HER2 expression, p53 mutation, high-grade histopathology, and particular gene expression array patterns. Sporadic basal-like breast cancer is one such form. It is a relatively common, high-grade, hormone receptor and HER2-expression-negative, p53 mutation-bearing tumor and is particularly lethal. Although wild type for BRCA1, it is a sporadic phenocopy of most cases of BRCA1(/) breast cancer. Not only do the cells of the two tumors resemble one another with respect to the above-noted characteristics, they also share a defect in the maintenance of an intact, inactive X chromosome (Xi). Other high-grade and most low-grade tumors are rarely defective at Xi. This evidence suggests that an Xi defect contributes to the evolution of both sporadic and BRCA1(/) basal-like breast tumors.

Breast Neoplasms↗
PubMed2003

Study on dosimetric parameters for stereotactic radiosurgery and intensity-modulated radiotherapy.

This study is an attempt to compare the dosimetric parameters of intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS) using patient data. Radiosurgery was delivered through circular tertiary collimators attached to a linear accelerator. Six patients who were treated with SRS were replanned and evaluated with the IMRT planning system. Contouring of all structures, including target volume, was done on the IMRT system to closely match the SRS system. Treatment plans were generated after specifying the goals in the prescription module. The NOMOS BEAK collimator attached to the NOMOS MIMiC delivery device was chosen for treatment delivery. Various parameters such as conformity index, homogeneity index, target volume coverage, nontarget tissue, and brainstem doses were calculated and compared between the IMRT and SRS systems. Patient data were divided into 2 groups based on the complexity of the lesion and the number of isocenters used for radiosurgery. Analysis was done for each group and for the cumulative data. Superior conformality and homogeneous dose distribution in IMRT for multiple isocenter cases were observed. In addition, critical structure volumes for 50%, 70%, and 90% of the prescribed dose were lower in IMRT compared to SRS treatment. However, nontarget tissue received significantly higher doses with IMRT plans. Results show that IMRT treatment modality produces similar results as radiosurgery for small, spherical lesions, whereas it is found to be superior to SRS for irregular lesions in terms of critical structure sparing and better dose homogeneity.

Brain Neoplasms↗
PubMed2003

Native fluorescence spectroscopy of blood plasma in the characterization of oral malignancy.

Native fluorescence characteristics of blood plasma were studied in the visible spectral region, at two different excitation wavelengths, 405 and 420 nm, to discriminate patients with different stages of oral malignancy from healthy subjects. The fluorescence spectra of blood plasma of oral malignant subjects exhibit characteristic spectral differences with respect to normal subjects. Different ratios were calculated using the fluorescence intensity values at those emission wavelengths that give characteristic spectral features of each group of experimental subjects studied. These fluorescence intensity ratios were used as input variables for a multiple linear discriminant analysis across different groups. Leave-one out cross-validation was used to check the reliability of each discriminant analysis performed. The discriminant analysis performed across normal and oral cancerous subjects classified 94.7% of the original grouped cases and 93.7% of the cross-validated grouped cases. A classification algorithm was developed on the basis of the score of the discriminant functions (discriminant score) resulted in the analyses. The diagnostic potentiality of the present technique was also estimated in the discrimination of malignant subjects from normal and nonmalignant diseased subjects such as liver diseases. In the discriminant analysis performed across the three groups, normal, oral malignancy (including early and advanced stages) and liver diseases, 99% of the original grouped cases and 95.9% of the cross-validated grouped cases were correctly classified. Similar analysis performed across normal, early stage of oral malignancy, advanced oral malignancy and liver diseases correctly classified 94.9% of the original grouped cases and 91.8% of the cross-validated grouped cases.

Blood Chemical Analysis↗
PubMed2003

In vitro and in vivo investigations on the photodynamic activity of core-modified expanded porphyrin--ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin.

The core modification of expanded porphyrins has been proved to have better photochemical properties, which are favorable for photodynamic therapy (PDT) applications. In this context, this study was aimed to investigate the in vitro and in vivo photodynamic activity of one such core-modified expanded porphyrin, namely, ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin. For the in vitro studies, human erythrocytes were used as a membrane semimodel system to investigate the partitioning ability and drug-uptake characteristics. The partition studies on the membrane semimodel system revealed that maximum partitioning occurs at 12 microgm/mL concentration, and from the drug-uptake studies it is observed that maximum amount of the sensitizer is bound to the erythrocyte membranes during a 45 min incubation period. Photohemolysis studies at different concentrations of the sensitizer and exposure time showed maximum damage at 5 microgm/mL and 30 min exposure time. In vivo studies were performed on 7,12-dimethylbenz(a)nthracene-induced superficial squamous cell carcinoma on mouse skin. The sensitizer at a concentration of 2.5% in 2.0% dimethyl sulfoxide was applied topically on the tumor spot. After 1 h incubation the tumor spot was exposed to laser irradiation from Nd-YAG laser at its second harmonic wavelength of 532 nm. The photodynamic efficacy was estimated by tumor volume measurements at regular intervals after the treatment. One month after PDT exposure a 3.9-fold decrease in the tumor volume was observed with respect to the tumor volume before treatment. The treatment efficacy was further confirmed by histological and fluorescence spectroscopic evaluations of the tissue biopsy sample from the treated area. The results of our study suggest that the ammonium salt of 5,10,15,20-tetrakis-(meso-p-sulfonato phenyl)-25,27,29-trithia sapphyrin may find possible applications in the new modality of cancer treatment.

Journal Article↗
PubMed2002

Porphyrins in photodynamic therapy - a search for ideal photosensitizers.

The utility of light as a therapeutic agent can be traced back over thousands of years when it was used in Ancient Egypt, India and China to treat a variety of skin diseases like psoriasis, vitiligo, rickets, cancer and psychosis. The isolation of porphyrins and their inherent tumor localizing properties coupled with its ability to generate reactive singlet oxygen when activated by light of particular wavelength which in turn results in cytotoxicity led to the emergence of a new modality namely, photodynamic therapy (PDT) as a therapeutic tool. The higher degree of selectivity offered by this modality and fewer side effects when compared to chemotherapy and radiotherapy has prompted the researchers around the globe to generate new photosensitizers. Porphyrins and expanded porphyrins are one class of molecules under intense investigation due to their photosensitizing ability for PDT application. Expanded porphyrins result from the expansion of the phi electron conjugation by increasing the number of heterocyclic rings or bridging carbons of the existing porphyrin framework. These chromophores show strong absorptions in the red region (650-800 nm) compared to that of normal 18phi porphyrins. The strong absorption of light by a water soluble nontoxic photosensitizing molecule in the therapeutic window resulting in maximum penetration of light into the tissues coupled with high singlet oxygen production will conceptualize an ideal photosensitizer. This review highlights various porphyrinoid sensitizers reported till date and their photosensitizing ability both in vitro and in vivo studies. Furthermore, the urgent need for developing ideal photosensitizer for PDT will also be highlighted.

Animals↗
PubMed2001

Tumorigenesis in mice carrying a truncating Brca1 mutation.

We generated mouse mutants carrying in the Brca1 locus a modification (Brca1(tr)) that eliminates the C-terminal half of the protein product and obtained results indicating that, depending on genetic background, the missing BRCT and/or other domains are dispensable for survival, but essential for tumor suppression. Most of the apparently hypomorphic Brca1(tr/tr) mutants developed various tumors. Lymphomas were detected at all ages, whereas sarcomas and carcinomas, including breast cancer, appeared after a long latency. The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which the Brca1(tr/tr) mutation was apparently a late participant.

Animals↗
PubMed2001

BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.

BRCA1 interacts in vivo with a novel protein, BACH1, a member of the DEAH helicase family. BACH1 binds directly to the BRCT repeats of BRCA1. A BACH1 derivative, bearing a mutation in a residue that was essential for catalytic function in other helicases, interfered with normal double-strand break repair in a manner that was dependent on its BRCA1 binding function. Thus, BACH1/BRCA1 complex formation contributes to a key BRCA1 activity. In addition, germline BACH1 mutations affecting the helicase domain were detected in two early-onset breast cancer patients and not in 200 matched controls. Thus, it is conceivable that, like BRCA1, BACH1 is a target of germline cancer-inducing mutations.

Adult↗
PubMed2001

Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.

Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and ionizing radiation. Although six FA genes (for subtypes A, C, D2, E, F, and G) have been cloned, their relationship to DNA repair remains unknown. In the current study, we show that a nuclear complex containing the FANCA, FANCC, FANCF, and FANCG proteins is required for the activation of the FANCD2 protein to a monoubiquitinated isoform. In normal (non-FA) cells, FANCD2 is monoubiquitinated in response to DNA damage and is targeted to nuclear foci (dots). Activated FANCD2 protein colocalizes with the breast cancer susceptibility protein, BRCA1, in ionizing radiation-induced foci and in synaptonemal complexes of meiotic chromosomes. The FANCD2 protein, therefore, provides the missing link between the FA protein complex and the cellular BRCA1 repair machinery. Disruption of this pathway results in the cellular and clinical phenotype common to all FA subtypes.

Active Transport, Cell Nucleus↗
PubMed2001

Self-efficacy as a moderator of information-seeking effectiveness.

The authors assessed previously unexplored processes by which information seeking and self-efficacy contribute to self-regulatory effectiveness in industrial selling. They assessed the synergistic interaction of inquiry and monitoring with respect to role clarity and tested whether this interaction was further moderated by self-efficacy. Results indicated that the role-clarifying effects of feedback inquiry and monitoring were contingent rather than independent. Role clarity increased as the combination of inquiry and monitoring increased. Furthermore, these joint effects were moderated by self-efficacy, such that high-self-efficacy employees were able to effectively use the combination of inquiry and monitoring to clarify role expectations, whereas low-self-efficacy employees were not. Implications for theory, practice, and future research are discussed.

Adult↗
PubMed2000

An integrated model of feedback-seeking behavior: disposition, context, and cognition.

This study replicates, integrates, and extends prior research on the dispositional, contextual, and cognitive antecedents of feedback-seeking behavior. Regression analysis was used to analyze data collected from a sample of salespeople (N = 310) from 2 Fortune 500 companies. The study hypotheses were supported with the following results. First, the individual disposition of learning goal orientation and the contextual factors of leader consideration and leader initiation of structure influenced cognitions about the perceived cost and value of feedback seeking. Second, the strength of the relationship of learning goal orientation with the cost and value perceptions was moderated by the leadership style of the supervisor.

Adult↗
PubMed2000

Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation.

Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining (NHEJ). Here we used the telomerase-deficient mouse, null for the essential telomerase RNA gene (Terc), to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc-/- mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic, cellular and organismal response to ionizing radiation.

Animals↗
PubMed2000

Dual infection with atypical mycobacteria and Mycobacterium tuberculosis causing cervical lymphadenopathy in a child.

The most common presentation of mycobacterial infection encountered in otolaryngological practice is cervical lymphadenitis. We report a child with an unusual cause of cervical lymphadenopathy, i.e. dual tuberculous infections. This had clinical ramifications as, initially Mycobacterium avium-intracellulare was grown in culture and was resistant to standard anti-tuberculous agents, and hence treated with excision of the lymph node. However, the cultures from the excised lymph node grew out Mycobacterium tuberculosis that was sensitive to standard anti-tuberculous drugs. To our knowledge, no such presentation has been reported previously. We also review the literature on cervical lymphadenitis due to atypical mycobacteria and Mycobacterium tuberculosis, with particular emphasis on clinical presentation, diagnosis and management.

Antibiotics, Antitubercular↗
PubMed2000

Unexpected overnight admissions following day-case surgery: an analysis of a dedicated ENT day care unit.

Day-case surgery is an integral part of otolaryngology, and many procedures can be performed as day-cases provided strict criteria are applied in the selection of patients. We reviewed patients who required unexpected admission from the day-case unit at the Royal National Throat, Nose and Ear Hospital, London between April 1997 and March 1998. The total number of patients undergoing surgery was 1642. Of the total, 29 (1.8%) had to be admitted unexpectedly for overnight stay: 24 of these patients had undergone nasal surgery, representing 5.4% of all the nasal procedures performed--and the cause of all these admissions was haemorrhage. Further analysis revealed 22 of these 24 nasal operations had included a septoplasty. The total number of septoplasties performed was 163; thus, septoplasty had an unexpected admission rate of 13.4%. This information has been used to formulate stricter guidelines for day-case septoplasty admissions in our unit.

Ambulatory Surgical Procedures↗
PubMed1999

Genetic analysis of BRCA1 function in a defined tumor cell line.

Retrovirally expressed, wild-type BRCA1 decreased the gamma radiation (IR) sensitivity and increased the efficiency of double-strand DNA break repair (DSBR) of the BRCA1-/- human breast cancer line, HCC1937. It also reduced its susceptibility to DSB generation by IR. By contrast, multiple, clinically validated, missense mutant BRCA1 products were nonfunctional in these assays. These data constitute the basis for a BRCA1 functional assay and suggest that efficient repair of double-strand DNA breaks is linked to BRCA1 tumor suppression function.

BRCA1 Protein↗
PubMed1999

The impact of breastfeeding practices on respiratory and diarrhoeal disease in infancy: a study from Sri Lanka.

A hospital-based descriptive recall study was conducted to assess the relationship, if any, between breastfeeding practices and morbidity from respiratory and diarrhoeal diseases in infants. A total of 343 infants (285 admitted patients and 58 controls) were recruited. Clinical and sociodemographic data and details regarding breastfeeding practices, timing of the first respiratory or diarrhoeal illness, and the timing of the first admission for a respiratory or diarrhoeal illness, were carefully documented. Three broad groups of those who were exclusively breastfed for 3 months or less, 4 months or more, and those who were never breastfed were identified. There was no significant difference in the numbers of infants who developed a respiratory or diarrhoeal illness or were admitted to hospital with a respiratory or diarrhoeal illness during the period of exclusive breastfeeding, irrespective of the period of exclusive breastfeeding. However, significant numbers of patients who were breastfed for 3 months or less developed the first respiratory infection, the first episode of diarrhoea, and the first hospital admission for respiratory or diarrhoeal disease during the first 3 months following the introduction of other foods and in the subsequent 3 months following this period. Those who were never breastfed showed the worst results. Significantly fewer of those who were breastfed for 4 months or more fulfilled the same criteria. Identical findings were noted whether the additional feeds used to terminate exclusive breastfeeding were water, herbal tea, native medicines, or formula milk. Similar results were obtained in the control group. This study reiterates the extended protective effects of exclusive breastfeeding for periods of over 4 months against respiratory and diarrhoeal diseases using a novel set of outcome measures.

Breast Feeding↗