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R Sankaranarayanan

Publications and source records attributed to R Sankaranarayanan.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones as new analgesic and anti-inflammatory agents.

A new series of 3-(2-pyridyl)-2-substituted-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 2-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material 2-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one was synthesized from 2-aminopyridine. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. While the test compounds exhibited significant activity, compound 2-(1-ethylpropylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS2) showed moderate analgesic activity and compound 2-(1-methylbutylidene)-hydrazino-3-(2-pyridyl)-quinazolin-4(3H)-one (AS3) showed realistic anti-inflammatory activity when compared to the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic side effect when compared to aspirin.

Analgesics↗
PubMed2006

A novel lysine-rich domain and GTP binding motifs regulate the nucleolar retention of human guanine nucleotide binding protein, GNL3L.

A variety of G-proteins and GTPases are known to be involved in nucleolar function. We describe here a new evolutionarily conserved putative human GTPase, guanine nucleotide binding protein-like 3-like (GNL3L). Genes encoding proteins related to GNL3L are present in bacteria and yeast to metazoa and suggests its critical role in development. Conserved domain search analysis revealed that the GNL3L contains a circularly permuted G-motif described by a G5-G4-G1-G2-G3 pattern similar to the HSR1/MMR1 GTP-binding protein subfamily. Highly conserved and critical residues were identified from a three-dimensional structural model obtained for GNL3L using the crystal structure of an Ylqf GTPase from Bacillus subtilis. We demonstrate here that GNL3L is transported into the nucleolus by a novel lysine-rich nucleolar localization signal (NoLS) residing within 1-50 amino acid residues. NoLS identified here is necessary and sufficient to target the heterologous proteins to the nucleolus. We show for the first time that the lysine-rich targeting signal interacts with the nuclear transport receptor, importin-beta and transports GNL3L into the nucleolus. Interestingly, depletion of intracellular GTP blocks GNL3L accumulation into the nucleolar compartment. Furthermore, mutations within the G-domains alter the GTP binding ability of GNL3L and abrogate wild-type nucleolar retention even in the presence of functional NoLS, suggesting that the efficient nucleolar retention of GNL3L involves activities of both basic NoLS and GTP-binding domains. Collectively, these data suggest that GNL3L is composed of distinct modules, each of which plays a specific role in molecular interactions for its nucleolar retention and subsequent function(s) within the nucleolus.

Active Transport, Cell Nucleus↗
PubMed2006

Chapter 8: Screening for cervical cancer in developing countries.

Organised and quality assured cytology-based screening programmes have substantially reduced cervical cancer incidence in many developed countries. However, there are considerable barriers to setting up cytology-based screening programs, particularly in developing countries. This has stimulated the search for novel and alternative approaches to cytology for cervical cancer prevention. These approaches generally perform as well as cytology, and sometimes better, although many of them have a lower specificity, resulting in higher false-positive rates. The possibility of linking screening to treatment in a one- or two-visit strategy appears to be safe, feasible and effective. Barriers to establishing screening programs and the pitfalls encountered differ from one country to the next. Country-specific solutions need to be found, while being cognizant of the criteria that have enabled successful screening programmes.

Developing Countries↗
PubMed2006

Association between diabetes mellitus and pre-malignant oral diseases: a cross sectional study in Kerala, India.

Recent studies have suggested role of diabetes mellitus in the development of periodontal diseases, oral inflammatory and neoplastic lesions. We analysed data from randomised oral cancer screening trial in Kerala, India, to study the association between chronic diseases in general, diabetes mellitus in particular, and pre-malignant oral lesions and conditions. A total of 927 subjects with oral leukoplakia, 170 with oral submucous fibrosis, 100 with erythroplakia lesions and 47,773 apparently healthy subjects constituted the cases and controls respectively for our present study. The odds ratio (OR) for oral leukoplakia among women with a history of diabetes mellitus was found to be 2.0 (95% confidence interval (CI) = 1.4-2.9) whereas that for erythroplakia was 3.2 (95% CI = 1.3-7.9), after adjusting for potential confounders. No statistically significant association between diabetes mellitus and oral submucous fibrosis and pre-cancerous lesions/conditions in men was found. An association between diabetes mellitus and pre-malignant oral lesions among women has been observed in our study, although the underlying mechanisms are not clear. This needs to be further evaluated in other settings.

Adult↗
PubMed2005

Worldwide burden of gynaecological cancer: the size of the problem.

The estimation of cancer burden is valuable to set up priorities for disease control. The comprehensive global cancer statistics from the International Agency for Research on Cancer indicate that gynaecological cancers accounted for 19% of the 5.1 million estimated new cancer cases, 2.9 million cancer deaths and 13 million 5-year prevalent cancer cases among women in the world in 2002. Cervical cancer accounted for 493 000 new cases and 273 000 deaths; uterine body cancer for 199 000 new cases and 50 000 deaths; ovarian cancer for 204 000 new cases and 125 000 deaths; cancers of the vagina, vulva and choriocarcinoma together constituted 45 900 cases. More than 80% of the cervical cancer cases occurred in developing countries and two-thirds of corpus uteri cases occurred in the developed world. Political will and advocacy to invest in healthcare infrastructure and human resources to improve service delivery and accessibility are vital to reduce the current burden in low- and medium-resource countries.

Developing Countries↗
PubMed2005

Tobacco associated mortality in Mumbai (Bombay) India. Results of the Bombay Cohort Study.

BACKGROUND: Little is known about the excess mortality from forms of tobacco use other than cigarette smoking that are widely prevalent in India, such as bidi smoking and the various forms of smokeless tobacco use. We report on absolute and relative risks of mortality among various kinds of ever tobacco users vs never-users in the city of Mumbai, India. METHODS: Using the Mumbai voters' list as the selection frame, 99 570 individuals aged > or = 35 years were interviewed at their homes during 1992-94. At active follow-up (during 1997-99) after 5.5 years, 97 244 (97.7%) were traced. Among these, 7531 deaths (4119 men, 3412 women) were recorded, of which 89% died within study area. It was possible to abstract cause of death information from the records of the municipal corporation for 5470 deaths. These were coded using ICD 10. RESULTS: The adjusted relative risk was 1.37 (95% CI 1.23-1.53) for (men) cigarette smokers and 1.64 (95% CI 1.47-1.81) for bidi smokers, with a significant dose-response relationship for number of bidis or cigarettes smoked. Women were essentially smokeless tobacco users; the adjusted relative risk was 1.25 (95% CI 1.15-1.35). The risk of deaths from respiratory diseases (RR 2.12, 95% CI 1.57-2.87), tuberculosis (RR 2.30, 95% CI 1.68-3.15), and neoplasms (RR 2.60, 95% CI 1.78-3.80) were significantly high in male smokers than never tobacco users. CONCLUSIONS: Bidi is no less hazardous than cigarette smoking, and smokeless tobacco use may also result in significantly increased mortality.

Adult↗
PubMed2005

A new relaxed state in horse methemoglobin characterized by crystallographic studies.

A new relaxed state has been characterized in the crystals of horse methemoglobin grown at neutral pH at low ionic concentration and their low humidity variants. The crystals provide an example for improvement in X-ray diffraction quality with reduced solvent content. Only the classical R state has been so far observed in liganded horse hemoglobin. The state characterized in the present study lies in between the R state and the R2 state characterized earlier in liganded human hemoglobin. The results presented here, along with those of earlier studies, suggest that relaxed and tense hemoglobin can access ensembles of states.

Animals↗
PubMed2005

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India.

OBJECTIVE: Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. METHODS: Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. RESULTS: The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. CONCLUSION: As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

Adult↗
PubMed2005

Papillomavirus infection in rural women in southern India.

To investigate the prevalence of, and the risk factors for, cervical infection with 44 types of human papillomavirus (HPV) in a rural area in the Dindigul District, Tamil Nadu, India, we interviewed and obtained cervical cell samples from 1891 married women aged 16-59 years. HPV prevalence was 16.9% overall and 14.0% among women without cervical abnormalities, or 17.7 and 15.2%, respectively, age-standardised to the world standard population. In all, 21.9% of infections involved more than one HPV type. High-risk HPV types predominated, particularly HPV 16 (22.5% of women infected), followed by HPV 56, HPV 31, HPV 33 and HPV 18. Unlike most populations studied in developed countries, HPV prevalence was constant across the age groups. HPV positivity was inversely associated with education level (odds ratio (OR) among women with high school vs no education=0.6) and positively associated with widowhood and divorce (OR=1.7), nulligravidity (OR=2.3), and condom use (OR=2.6). It is unclear how much low clearance of, or frequent reinfection with HPV accounted for the study prevalence of infection in different age groups.

Adolescent↗
PubMed2005

A critical assessment of screening methods for cervical neoplasia.

The objective of cervical cancer screening is to reduce cervical cancer incidence and mortality by detecting and treating precancerous lesions. Conventional cytology is the most widely used cervical cancer screening test. Although cytology has been effective in reducing the incidence of and mortality from cervical cancer in developed countries in both opportunistic and--more dramatically--organized national programs, it has been less successful and largely ineffective in reducing disease burden in low-resource settings where it has been implemented. Liquid-based cytology, testing for infection with oncogenic types of human papillomaviruses, visual inspection with 3-5% acetic acid, magnified visual inspection with acetic acid, and visual inspection with Lugol's iodine have been evaluated as alternative tests. Their test characteristics, and the applications and limitations in screening, are discussed with an emphasis on the work of the Alliance for Cervical Cancer Prevention over the past 5 years.

Cytological Techniques↗
PubMed2005

Training for cervical cancer prevention programs in low-resource settings: focus on visual inspection with acetic acid and cryotherapy.

The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

Acetic Acid↗
PubMed2005

Major histocompatibility complex class I polymorphism in Asiatic lions.

Asiatic lions (Panthera leo persica), whose only natural habitat in the world is the Gir forest sanctuary of Gujarat State in India, are highly endangered and are considered to be highly inbred with narrow genetic diversity. An objective assessment of genetic diversity in their immune loci will help in assessing their survivability and may provide vital clues in designing strategies for their scientific management and conservation. We analyzed the comparative sequence polymorphism at exon 2 and exon 3 of major histocompatibility complex (MHC) class I in three groups of lions, i.e. wild Asiatic (from Gir forest), captive-bred Asiatic (from zoological parks in India), and Afro-Asiatic hybrid groups (from zoological parks in India) through polymorphism chain reaction-assisted sequence-based typing. The two exons were amplified, cloned, sequenced, and analyzed for polymorphism at nucleotide and putative translated product level. The analysis revealed extensive sequence polymorphism not only between clones derived from different lions but also the clones derived from a single lion. Furthermore, the wild Asiatic lions of Gir forest exhibited abundant sequence polymorphism at MHC class I comparable with that of Afro-Asiatic hybrid lions and significantly higher than that of captive-bred Asiatic lions. We hypothesize that Asiatic lions of Gir forest are not highly inbred as thought earlier and they possess abundant sequence polymorphism at MHC class I loci. During this study, 52 new sequences of the multigene MHC class I family were also identified among Asiatic lions.

Amino Acid Sequence↗
PubMed2004

Do younger female breast cancer patients have a poorer prognosis? Results from a population-based survival analysis.

Younger women who develop breast cancer are hypothesized to have poorer survival rates than women who develop it at a later stage in life. Several studies have suggested that differences in biologic characteristics of breast cancer in younger (premenopausal) and older (postmenopausal) women may account for the prognostic variation. This population-based cohort study reports on survival rates of breast cancer in Singapore and examines the hypothesis that younger breast cancer patients have a poorer prognosis. A total of 6,397 breast cancer patients diagnosed from 1968 to 1992 were identified from the population-based cancer registry and followed up through 1997. Outcome measures were relative survival rates (RSRs) calculated using Hakulinen's method and excess hazards ratios (HRs) derived from a regression model based on relative survival. The 2-, 5- and 10-year RSRs were worse among those aged > 75 (65%, 48% and 39%, respectively). The best survival rates were seen among those aged 40-44 (84%, 67% and 56%). Patients younger than 35 years faired reasonably well (79%, 60% and 50%). When the data were stratified according to clinical stage and calendar year, the highest risk of excess deaths was found in women > or = 75 years old. In patients with localized cancer and/or regional metastases, those in the 35-39 age group had the lowest excess risk. In patients with distant metastases, those younger than 35 years of age had the lowest excess risk of death. At the population level, younger women (< 45 years) with breast cancer in Singapore have higher relative survival rates.

Adult↗
PubMed2004

Accuracy of conventional cytology: results from a multicentre screening study in India.

OBJECTIVE: We conducted a multi-centre cross-sectional study in India to evaluate the accuracy of conventional cytology to detect high-grade squamous intraepithelial lesions (HSIL). SETTING: Cross-sectional studies in Jaipur, Kolkata, Mumbai and Trivandrum, India, during 1999-2003. METHODS: A common protocol and questionnaire were used to test 22,663 women aged 25-65 years with conventional cytology in five cross-sectional studies. Three thresholds were used to define test positivity: atypical squamous cells of uncertain significance (ASCUS), low-grade squamous intra-epithelial lesion (LSIL), or HSIL. All screened women were investigated with colposcopy, and biopsies were taken when necessary. The reference standard for final disease status was histology or negative colposcopy. Data from the studies were pooled to evaluate the test characteristics for the detection of histologically confirmed HSIL. RESULTS: The test positivity rates of cytology were 8.8% at ASCUS, 6.2% at LSIL and 1.8% at HSIL thresholds, and 355 women had histologically confirmed HSIL while 74 had invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values at ASCUS threshold were 64.5%, 92.3%, 11.8% and 99.4% respectively. The corresponding values at LSIL threshold were 58.0%, 94.9%, 15.2% and 99.3%, while at the HSIL threshold they were 45.4%, 99.2%, 46.3% and 99.1%. The sensitivity varied between 37.8-81.3% at ASCUS, 28.9-76.9% at LSIL and 24.4-72.3% at HSIL thresholds. A significantly low sensitivity was observed in women aged 25-39 years (p<0.001). The wide variation in sensitivity across study sites persisted even after age standardisation. CONCLUSION: The sensitivity of cytology varied widely between the study sites. Findings from our study and other reviews indicate that sustained efforts in improving sampling, preparation and reading of cytological specimens and improvements in clinical judgement are essential to achieve concurrently high sensitivity and specificity.

Adult↗
PubMed2003

Recurrence of fidelity in nearly integrable systems.

Within the framework of simple perturbation theory, recurrence time of quantum fidelity is related to the period of the classical motion. This indicates the possibility of recurrence in nearly integrable systems. We have studied such possibility in detail with the kicked rotor as an example. In accordance with the correspondence principle, recurrence is observed when the underlying classical dynamics is well approximated by the harmonic oscillator. Quantum revival of fidelity is noted in the interior of resonances, while classical-quantum correspondence of fidelity is seen to be very short for states initially in the rotational Kolmogorov-Arnold-Moser region.

Journal Article↗
PubMed2003

Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India.

A cluster randomized controlled oral cancer screening trial is on-going in the Trivandrum district, India, to evaluate the efficacy of screening in reducing oral cancer mortality. Subjects, aged 35 years and above, in 13 clusters in the Trivandrum district, India, were randomized to the intervention (screening) group (7 clusters, 78969 subjects) to receive three rounds of screening by oral visual inspection by trained health workers at 3-year intervals or to a control group (6 clusters, 74739 subjects). Two rounds of screening were completed between 1995 and 2002 during which 69896 (88.5%) subjects were screened at least once, and 59.7% of the 4408 screen-positive subjects were further investigated. In the intervention group, 344404 person-years were accrued and 329326 person-years were in the control group. In the intervention group, 149 incident oral cancer cases and 65 deaths from oral cancer were observed, and 106 incident cases and 62 deaths from oral cancer were observed in the control group. The programme sensitivity for detection of oral precancerous lesions and cancer was 81.5% and the programme specificity was 84.8%; the programme positive predictive value was 39.6%. In the intervention group 37.6% of the cases were in stages I-II, as opposed to 18.9% in the control group. The 3 year survival rate was 57.5% in the intervention and 38.8% in the control group (P<0.05). The age standardized oral cancer mortality rates were 21.2/100000 person-years in the intervention and 21.3/100000 in the control group. After completing two rounds of screening, oral cancer mortality rates were similar in both study groups.

Adult↗
PubMed2003

Survival from glottic and supraglottic laryngeal carcinoma in Mumbai (Bombay), India.

The survival experience of patients with cancer of the larynx (ICD 10) registered by the Bombay population-based cancer registry India, during the years 1992-1994, is described. The vital status of these subjects were established by matching with death certificates from the Bombay Municipal death register and by active methods such as reply-paid postal enquiries, telephone enquiries, scrutiny of case records and house visits. Of the 675 eligible cases for analysis, 458 (67.9%) were dead and 217 (32.1%) were alive at last follow-up. The 5-year observed and relative survival rates were 29.1 and 38.2%, respectively; these were 52.1 and 58.5% for glottic laryngeal cancer and 24.2 and 31.4% for supraglottic laryngeal cancer, respectively. The 5-year observed survival was 53.1% for those with localised cancer and 17.8% for those with regional extension. Advancing age, regional and metastatic disease and supraglottic cancers were associated with significantly reduced survival. Early detection and prompt treatment should improve overall survival from laryngeal cancer.

Adult↗