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Biomedical subjects

R Sankaranarayanan

Publications and source records attributed to R Sankaranarayanan.

At least 55 records · Page 3Linked to original sources

Survival from head and neck cancer in Mumbai (Bombay), India.

BACKGROUND: Head and neck cancers, among the 10 most frequent cancers in the world, are common in regions with a high prevalence of tobacco and alcohol habits. They account for one-fourth of male and one-tenth of female cancers in India. The authors report and discuss the survival from these cancers in Mumbai (Bombay), India. METHODS: Follow-up information on 6311 head and neck cancer patients registered in the Bombay Population-Based Cancer Registry for the period 1987-1991 was obtained by a variety of methods, including matching with death certificates from the Bombay vital statistics registration system, postal/telephone enquiries, home visits, and scrutiny of medical records. The survival for each case was determined as the duration between the date of incidence and the date of death or date of loss to follow-up or the closing date of the study (December 31, 1996). Cumulative observed and relative survival were calculated by the Hakulinen method. For comparison of results with other populations, age-standardized relative survival (ASRS) was calculated by directly standardizing age specific relative survival to the specific age distributions of the estimated global incidence of major cancers in 1985. The log rank test was used in univariate analysis to identify the potentially important prognostic variables. The variables showing statistical significance in univariate analysis were introduced stepwise into a Cox regression model to identify the independent predictors of survival. RESULTS: The 5-year relative survival rates were 74.5% for the lip, 42.7% for the anterior tongue, 25.5% for the posterior tongue, 45.1% for the mouth, 29.7% for the oropharynx, 38.7% for the nasopharynx, 29.1% for the hypopharynx, and 41.2% for the larynx. Age, marital status, religion, and site and clinical extent of disease emerged as independent predictors of survival. Age specific 5-year relative survival declined with advancing age. Single patients had a 20% excess risk of death compared with married patients. Those with cancers of the lip, mouth, nasopharynx, and larynx had a better prognosis than those with cancer at other sites. Those with regional spread of disease experienced a threefold increased risk of death, and those with distant metastasis experienced a sixfold excess risk. Less than one-fourth of cancers were localized in the organ of origin at diagnosis; 5-year survival for localized cancers ranged from 52.9% to 80.2% depending on the subsite. CONCLUSIONS: There were significant variations in survival from cancer at individual sites within the head and neck region. Comparison with other populations revealed variations that seemed to be related to differences in detection and treatment. Tobacco and alcohol control measures and early detection linked with treatment are important measures to reduce mortality from head and neck cancer.

Adolescent↗

Cancer incidence in Karachi, Pakistan: first results from Karachi Cancer Registry.

No cancer incidence data from Pakistan have been published in the 5 decades since independence. Incidence data for the period 1995-1997 from the population of the Karachi South district (1.7 million) are presented here. A total of 4,268 new cancer cases were registered during this period: 2,160 cases in males and 2,108 cases in females. Overall, 95.3% of the incident cases were microscopically verified. The incidence rates for all cancers combined were 80.5 per 100,000 (crude) and 136.7 per 100,000 (age- standardised rates [ASR]) for males and 91.8 (crude) and 163.2 per 100,000 (ASR) for females. In males, lung cancer (ASR 20.3) was the most frequently recorded malignancy followed by oral cavity (ASR 13.8) and larynx cancer (ASR 8.6). In females, breast was the most common site of cancer, accounting for one third of female cancers (ASR 51.7), followed by oral cavity (ASR 14.1) and ovarian cancer (ASR 10.2). Karachi reports the highest incidence of breast cancer for any Asian population, except Jews in Israel. Tobacco smoking is estimated to be responsible for 40% of cancers in males and tobacco chewing for a further substantial proportion of head and neck cancers.

Adolescent↗

Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group.

BACKGROUND: Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening. The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated. The authors describe a cluster-randomized, controlled oral cancer screening trial in southern India and its early results. METHODS: Apparently healthy subjects age 35 years or older in 13 clusters called panchayaths were randomized to either an intervention group (n = 7) or a control group (n = 6). Subjects in the intervention group will receive 3 rounds of screening consisting of oral visual inspection by trained health workers at 3-year intervals. The first round of screening was carried out between October 1995 and May 1998. Participants were visited in their homes and interviewed for sociodemographic details, tobacco-smoking and alcohol-drinking habits, and personal medical history. Those with tobacco or alcohol habits were advised to stop those habits. Subjects in the intervention group were offered screening, and those with lesions suggestive of oral leukoplakia, submucous fibrosis, or oral cancer were referred for examination by physicians. Confirmed leukoplakias were excised whenever possible, others were kept on follow-up, and those with confirmed oral cancers were referred for treatment. Data on oral cancer incidence, stage distribution, survival, and mortality in the study groups are obtained by record linkage with the Trivandrum population-based cancer registry and municipal death registration systems. RESULTS: There were 59,894 eligible subjects in the intervention group and 54,707 in the control group; 31.4% of the former group reported no tobacco or alcohol habits, compared with 44.1% of the latter. The distribution of age, education, occupation, income, and socioeconomic status were similar in the two groups. Of 3585 subjects in the intervention group referred, 52.4% were examined by physicians; 36 subjects with oral cancers and 1310 with oral precancers were diagnosed. Of the 63 oral cancers recorded in the cancer registry, 47 were in the intervention group and 16 were in the control group, yielding incidence rates of 56.1 and 20.3 per 100,000 person-years in the intervention and control groups, respectively. The program sensitivity for detection of oral cancer was 76.6% and the specificity 76.2%; the positive predictive value was 1.0% for oral cancer. In the intervention group, 72.3% of the cases were in Stages I-II, as opposed to 12.5% in the control group. The 3-year case fatality rates were 14.9% (7 of 47 patients) in the intervention group and 56.3% (9 of 16 patients) in the control group. CONCLUSIONS: Though compliance with referral for confirmatory examination in the first round was lower than the 70% anticipated, intermediate end points, such as stage at diagnosis and case fatality, indicate that the trial is making fairly satisfactory progress.

Adult↗

Leads to cancer control based on cancer patterns in a rural population in South India.

OBJECTIVE: Cancer patterns and incidence rates for a rural population (359,674) resident in 384 villages spread over 2058 km2 in Palani and Oddanchathram taluks of Dindigul District, Tamil Nadu, in South India, are described in this paper. METHODS: A population-based cancer registry was established in 1995 to register incident invasive and in-situ cancers. Cases were found and details abstracted by cancer registry staff visiting 26 data sources, comprising cancer hospitals, tertiary and secondary care hospitals, pathology laboratories and death registration offices. A customized version of CANREG-3 software was used for data entry and analysis. RESULTS: During the period 1996-1998, 783 invasive cancers (310 male and 473 females) were registered, yielding an all-cancer crude incidence rate of 56.8/100,000 males and 88.5/100,000 females; the corresponding age standardized incidence rates (ASR) were 83.3 and 122.3 respectively. In males, mouth cancer (ASR 11.5) was the most frequently recorded malignancy followed by tongue (ASR 8.6), hypopharynx (ASR 7.8), esophagus (ASR 7.8) and larynx (ASR 7.8). Thus head and neck cancers accounted for half of the male cases. In females, cervical cancer (ASR 65.4) accounted for more than half of the cancers followed by breast (ASR 14.2) and mouth (ASR 10.2). Ambillikai Cancer Registry (ACR) reports the second highest incidence of cervical cancer in the world. More than four-fifths of cervical cancer cases were diagnosed in stages II B and III B; a third of these cancer patients either did not have, or did not complete, treatment. CONCLUSIONS: The observed cancer patterns in this population establish that measures directed at prevention and early detection (linked with treatment) of cervix and head and neck cancers are of paramount importance for cancer control in this and other rural populations of India where three-fourths of the total population live.

Adolescent↗

Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase.

Accurate translation of the genetic code depends on the ability of aminoacyl-tRNA synthetases to distinguish between similar amino acids. In order to investigate the basis of amino acid recognition and to understand the role played by the zinc ion present in the active site of threonyl-tRNA synthetase, we have determined the crystal structures of complexes of an active truncated form of the enzyme with a threonyl adenylate analog or threonine. The zinc ion is directly involved in threonine recognition, forming a pentacoordinate intermediate with both the amino group and the side chain hydroxyl. Amino acid activation experiments reveal that the enzyme shows no activation of isosteric valine, and activates serine at a rate 1,000-fold less than that of cognate threonine. This study demonstrates that the zinc ion is neither strictly catalytic nor structural and suggests how the zinc ion ensures that only amino acids that possess a hydroxyl group attached to the beta-position are activated.

Binding Sites↗

Chewing tobacco, alcohol, and the risk of erythroplakia.

Although chewing tobacco, smoking, and alcohol drinking have been suggested as risk factors for oral cancer, no study has examined the relationship between those factors and the risk of erythroplakia, an uncommon but severe oral premalignant lesion. In this study, we have analyzed the effects of chewing tobacco, smoking, alcohol drinking, body mass index, and vegetable, fruit, and vitamin/iron intake on the risk of erythroplakia and explored potential interactions between those factors in an Indian population. A case-control study including 100 erythroplakia cases and 47,773 controls was conducted, as part of an on-going randomized oral cancer screening trial in Kerala, India. The analysis was based on the data from the baseline screening for the intervention group, where the diagnostic information was available. The information on epidemiological risk factors was collected with interviews conducted by trained health workers. The erythroplakia cases were identified by health workers with oral visual inspections, and then confirmed by dentists and oncologists who made the final diagnosis. The odds ratios (OR) and their 95% confidence intervals (CIs) were calculated by the logistic regression model using SAS software. The adjusted OR for erythroplakia was 19.8 (95% CI, 9.8-40.0) for individuals who had ever chewed tobacco, after controlling for age, sex, education, body mass index, smoking, and drinking. The adjusted OR for ever-alcohol-drinkers was 3.0 (95% CI, 1.6-5.7) after controlling for age, sex, education, body mass index, chewing tobacco, and smoking. For ever-smokers, the adjusted OR was 1.6 (95% CI, 0.9-2.9). A more than additive interaction on the risk of erythroplakia was suggested between tobacco chewing and low vegetable intake, whereas a more than multiplicative interaction was indicated between alcohol drinking and low vegetable intake, and between drinking and low fruit intake. We concluded that tobacco chewing and alcohol drinking are strong risk factors for erythroplakia in the Indian population. Because the CIs of interaction terms were wide and overlapping with those of the main effects, only potential interactions are suggested.

Adult↗

The structure of threonyl-tRNA synthetase-tRNA(Thr) complex enlightens its repressor activity and reveals an essential zinc ion in the active site.

E. coli threonyl-tRNA synthetase (ThrRS) is a class II enzyme that represses the translation of its own mRNA. We report the crystal structure at 2.9 A resolution of the complex between tRNA(Thr) and ThrRS, whose structural features reveal novel strategies for providing specificity in tRNA selection. These include an amino-terminal domain containing a novel protein fold that makes minor groove contacts with the tRNA acceptor stem. The enzyme induces a large deformation of the anticodon loop, resulting in an interaction between two adjacent anticodon bases, which accounts for their prominent role in tRNA identity and translational regulation. A zinc ion found in the active site is implicated in amino acid recognition/discrimination.

Amino Acyl-tRNA Synthetases↗

Trends in survival rates of cancer in Cuba.

Reports of population-based survival rates of cancer from developing countries are infrequent. In Latin America, only the Cancer Registry of Puerto Rico has published population-based survival data. The National Cancer Registry of Cuba has achieved three survival studies with cases incident in 1976, 1982 and 1988-1989. This article deals with the global observed and relative survival rates estimated in the latter study. Survival time trends are analysed. In the period 1988-1989, 12,985 primary cancer cases were included from the most common cancer sites, with the exclusion of cancer in situ cases and 8900 cases reported by 'death certificate only' (DCO) (35.8%). The vital status of cases was checked up to 31 December 1994 using a mixed follow-up system with the exclusion of 2900 cases lost to follow-up (11.2%). DCO proportions are shown for the major sites and compared to those of 1982. Observed survival rates were estimated by Kaplan-Meier method using the SPSS Statistical Software. The relative rates were estimated by the Hakulinen's Computer Program Package for Cancer Survival Studies (1988) using life tables from Cuban population. Statistical comparisons of survival curves by year of diagnosis were achieved by using the Log-Rank and Pearson statistic tests. Global results are shown by year of follow-up and a comparative analysis is done in time and with internationals values. Survival rates decreased in the period 1982/1988-1989 for colon, prostate and lung cancer. Prostate cancer shows a low five years relative survival rate when compared with the USA, but its observed rate is comparable with Puerto Rico's. Figures for mouth and lung cancer were comparable with the corresponding figures of the USA and Europe. Breast and cervix cancers rates are comparable with the European mean and the blacks in USA.

Breast Neoplasms↗

Visual inspection of the uterine cervix after the application of acetic acid in the detection of cervical carcinoma and its precursors.

BACKGROUND: Organized cervical cytology screening programs are not feasible in many developing countries where cervical carcinoma is an important cause of mortality among adult women. This study compared visual inspection of the cervix after application of 3-4% acetic acid (VIA, or cervicoscopy) with cytology as methods for the detection of cervical carcinoma and its precursors. METHODS: Three thousand women were examined by both VIA and cytology. Those positive on one or both of the screening tests (n = 423) or those who had clinically suspicious lesions even if the tests were negative (n = 215) were invited for colposcopy. Directed biopsies were obtained from 277 of 573 women at colposcopy. Those with moderate dysplasia or worse lesions diagnosed by histology were considered true-positives. Those with no lesions or with reactive or reparative changes at colposcopy and those for whom histology revealed no pathology, reactive or reparative changes, atypia, or mild dysplasia were considered false-positives. The detection rate of true-positive cases and the approximate specificity of the two tests were compared. RESULTS: VIA was positive in 298 women (9.8%), and cytology was positive (for atypia or worse lesions) in 307 women (10.2%). Of the 51 true-positive cases (20 cases of moderate dysplasia, 7 of severe dysplasia, 12 of carcinoma in situ, and 12 of invasive carcinoma), VIA detected 46 (90.1%) and cytology 44 (86.2%), yielding a sensitivity ratio of 1.05. VIA detected five lesions missed by cytology, and cytology detected three missed by VIA; both missed two lesions. The approximate specificities were 92.2% for VIA and 91.3% for cytology. The positive predictive value of VIA was 17.0%, and that of cytology was 17.2%. CONCLUSIONS: These results indicate that VIA and cytology had very similar performance in detecting moderate dysplasia or more severe lesions in this study. VIA merits further evaluation as a primary screening test in low-resource settings.

Acetic Acid↗

Carbohydrate specificity and quaternary association in basic winged bean lectin: X-ray analysis of the lectin at 2.5 A resolution.

The structure of basic Winged Bean Agglutinin (WBAI) with two dimeric molecules complexed with methyl-alpha-D-galactopyranoside in the asymmetric unit, has been determined by the molecular replacement method and refined with 2.5 A X-ray intensity data. The polypeptide chain of each monomer has the characteristic legume lectin tertiary fold. The structure clearly defines the lectin-carbohydrate interactions. It reveals how the unusually long variable loop in the binding region endows the lectin with its characteristic sugar specificity. The lectin forms non-canonical dimers of the type found in Erythrina corallodendron lectin (EcorL) even though glycosylation, unlike in EcorL, does not prevent the formation of canonical dimers. The structure thus further demonstrates that the mode of dimerisation of legume lectins is not necessarily determined by the covalently bound carbohydrate but is governed by features intrinsic to the protein. The present analysis and our earlier work on peanut lectin (PNA), show that legume lectins are a family of proteins in which small alterations in essentially the same tertiary structure lead to wide variations in quaternary association. A relationship among the non-canonical modes of dimeric association in legume lectins is presented.

Amino Acid Sequence↗