Biomedical subjects

V Chandra

Publications and source records attributed to V Chandra.

At least 19 recordsLinked to original sources

PubMed2001

Regulation of catalytic function by molecular association: structure of phospholipase A2 from Daboia russelli pulchella (DPLA2) at 1.9 A resolution.

The crystal structure of phospholipase A(2) from the venom of Daboia russelli pulchella has been refined to an R factor of 0.216 using 17,922 reflections to 1.9 A resolution. The structure contains two crystallographically independent molecules in the asymmetric unit. The overall conformations of the two molecules are essentially the same except for three regions, namely the calcium-binding loop including Trp31, the beta-wing and the C-terminal residues 119-131. Although these differences have apparently been caused by molecular packing, they seem to have functional relevance. Particularly noteworthy is the conformation of Trp31, which is favourable for substrate binding in one molecule as it is aligned with one of the side walls of the hydrophobic channel, whereas in the other molecule it is located at the mouth of the channel, thereby blocking the entry of substrates leading to loss of activity. This feature is unique to the present structure and does not occur in the dimers and trimers of other PLA(2)s.

Animals↗

PubMed2001

Purification, crystallization and preliminary X-ray diffraction studies of disintegrin (schistatin) from saw-scaled viper (Echis carinatus).

This is the first report of crystallographic data on a disintegrin molecule from any source. The heterodimeric disintegrin with a molecular weight of 14 kDa from Echis carinatus venom is a potent antagonist of alpha4 integrins. The intact disintegrin, containing two subunits A and B, was isolated and purified using affinity and ion-exchange columns. It has been crystallized using 1.6 M ammonium sulfate as a precipitating agent. The crystals grew to dimensions of 0.25 x 0.20 x 0.20 mm and diffracted to 2.5 A resolution. The crystals belong to space group I4(1)22, with unit-cell parameters a = b = 91.7, c = 55.1 A. Assuming a molecular weight of 14 kDa, a V(M) of 2.1 A(3) Da(-1) is obtained for one molecule of disintegrin in the asymmetric unit.

Animals↗

PubMed2001

Preliminary X-ray diffraction studies of the external functional unit RtH2-e from the Rapana thomasiana.

The 'external' oxygenated functional unit RtH2-e of the Rapana hemocyanin subunit RHSS2 was isolated and crystallized. X-ray intensity data to 3.3 A resolution have been collected at 100 K and the structure has been solved using the molecular-replacement method. The space group is assigned to be the tetragonal P4(3)2(1)2, with unit-cell parameters a = b = 105.5, c = 375.0 A.

Animals↗

PubMed2001

Incidence of Alzheimer's disease in a rural community in India: the Indo-US study.

OBJECTIVE: To determine overall and age-specific incidence rates of AD in a rural, population-based cohort in Ballabgarh, India, and to compare them with those of a reference US population in the Monongahela Valley of Pennsylvania. METHODS: A 2-year, prospective, epidemiologic study of subjects aged > or =55 years utilizing repeated cognitive and functional ability screening, followed by standardized clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for the diagnosis, and the Clinical Dementia Rating scale for the staging, of dementia and AD. RESULTS: Incidence rates per 1000 person-years for AD with CDR > or =0.5 were 3.24 (95% CI: 1.48-6.14) for those aged > or =65 years and 1.74 (95% CI: 0.84-3.20) for those aged > or =55 years. Standardized against the age distribution of the 1990 US Census, the overall incidence rate in those aged > or =65 years was 4.7 per 1000 person-years, substantially lower than the corresponding rate of 17.5 per 1000 person-years in the Monongahela Valley. CONCLUSION: These are the first AD incidence rates to be reported from the Indian subcontinent, and they appear to be among the lowest ever reported. However, the relatively short duration of follow-up, cultural factors, and other potential confounders suggest caution in interpreting this finding.

Age Factors↗

PubMed2001

APOE polymorphism in a rural older population-based sample in India.

Allele frequencies are most often reported from small convenience samples of unknown demographics and limited generalizability. We determined the distribution of apolipoprotein E genotype (APOE) and allele frequencies for a large, well-defined, representative, rural, population-based sample (n = 4450) aged 55-95 years in Ballabgarh, in the northern Indian state of Haryana. The overall APOE E*2, E*3, and E*4 allele frequencies were 0.039, 0.887, and 0.073, respectively; frequencies are also reported by age, sex, and religious/caste groups. The APOE*4 frequency is among the lowest reported anywhere in the world. APOE allele frequencies did not vary significantly by age or sex in this study. To our knowledge, this is the largest Indian sample ever genotyped for the APOE polymorphism. The representativeness of the sample and its known demographics provide a much-needed normative background for studies of gene-disease associations.

Age Distribution↗

PubMed2001

Detection of gastrointestinal tract events from multichannel intraluminal impedance measurements.

Investigation of Gastrointestinal tract (GIT) using multichannel intraluminal impedance technique (MII) is presented. The MII traces have large variations which correspond to the occurrence of certain activity that causes the impedance to change. A technique to detect the tract events from MII data is developed using wavelet transform. The resulting transformed signals are used to detect the occurrence of GIT events and to classify the events as swallow, reflux, or gas reflux. The technique is also used in estimating reflux event duration and the bolus velocity.

Electric Impedance↗

PubMed2000

Three-dimensional structure of a presynaptic neurotoxic phospholipase A2 from Daboia russelli pulchella at 2.4 A resolution.

The phospholipase A(2 )from Daboia russelli pulchella (DPLA(2)) is the only known member of subclass II of group IIA. The three-dimensional structure of this presynaptic neurotoxic DPLA(2) enzyme has been determined at 2.4 A resolution. The structure was determined by the molecular replacement method using the model Crotalus atrox, and refined using X-PLOR to a final R-factor of 18.8 % for all data in the resolution range 20.0 A-2.4 A. The final refined model comprises 1888 atoms from two crystallographically independent protein molecules and 160 water oxygen atoms. The overall folding of DPLA(2), with three long helices and two short antiparallel beta-strands is grossly similar to those observed for other PLA(2)s. In the present structure, the calcium binding site is empty but the conformation of the calcium binding loop is similar to those observed in the calcium bound states. Two spatially adjacent regions of residues 55-61 (a typical beta-turn I) and 83-94 (a well defined loop) are remarkably different in conformation, electrostatic characteristics and inter-segmental interactions from those found in non-neurotoxic PLA(2)s. Yet another striking structural feature in DPLA(2 )pertains to the stretch of residues 53-77, which has a series of positively charged residues protruding outwardly. The above segment is presumed to be involved in the anticoagulant activity. A unique hydrophobic patch including residues Leu17, Ala18, Ile19, Pro20, Phe106 and Leu110 is found on the surface together with an equally emphatic region of -OH groups containing residues such as Ser21, Tyr22, Ser23, Ser24, Tyr25 and Tyr28. The interactions between two molecules of DPLA(2) in the asymmetric unit are remarkably different from those observed in the standard dimers and trimers of PLA(2)s, leaving the enzyme's active site fully exposed for enzyme-substrate reactions, it makes this structure one of the most favourable examples for structure-based drug design through soaking experiments.

Amino Acid Sequence↗

PubMed2000

Apolipoprotein E polymorphism and Alzheimer disease: The Indo-US Cross-National Dementia Study.

BACKGROUND: The APOE*E4 allele of the gene for apolipoprotein E (APOE) has been reported as a risk factor for Alzheimer disease (AD) to varying degrees in different ethnic groups. OBJECTIVE: To compare APOE*E4-AD epidemiological associations in India and the United States in a cross-national epidemiological study. DESIGN: Case-control design within 2 cohort studies, using standardized cognitive screening and clinical evaluation to identify AD and other dementias and polymerase chain reaction to identify APOE genotyping. PARTICIPANTS: Rural community samples, aged 55 years or older (n=4450) in Ballabgarh, India, and 70 years or older (n=886) in the Monongahela Valley region of southwestern Pennsylvania. MAIN OUTCOME MEASURES: Criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable and possible AD and Clinical Dementia Rating (CDR) scale for dementia staging. RESULTS: Frequency of APOE*E4 was significantly lower (P<.001) in Ballabgarh vs the Monongahela Valley (0.07 vs 0.11). Frequency of probable or possible AD, with CDR of at least 1.0, in the Indian vs US samples, was as follows: aged 55 to 69 years, 0.1% (Indian sample only); aged 70 to 79 years, 0.7% vs 3.1%; aged 80 years or older, 4.0% vs 15.7%. Among those aged 70 years or older, adjusted odds ratios (95% confidence interval) for AD among carriers of APOE*E4 vs noncarriers were 3.4 (1.2-9.3) and 2.3 (1.3-4.0) in the Indian and US samples, respectively, and not significantly different between cohorts (P=. 20). CONCLUSION: This first report of APOE*E4 and AD from the Indian subcontinent shows very low prevalence of AD in Ballabgarh, India, but association of APOE*E4 with AD at similar strength in Indian and US samples. Arch Neurol. 2000.

Aged↗

PubMed1999

Development of an activities of daily living scale to screen for dementia in an illiterate rural older population in India.

OBJECTIVE: to develop a measure of activities of daily living appropriate for use in assessing the presence of dementia in illiterate rural elderly people in India. DESIGN: identification of relevant items, pre-testing of items and refinement of administrative procedures and scoring in four successive groups of 30 subjects each, pilot testing in a group of 100 subjects comparable to those for whom the measure is intended, administration to a representative sample of 387 people aged 55 and older, and assessment of the reliability of the final measure. SETTING AND SUBJECTS: age-stratified random sample of older men and women in rural areas of Ballabgarh, Northern India. RESULTS: the original pool of 35 items covering mobility, instrumental and personal care activities was reduced to an 11-item unidimensional scale (to which an additional item on mobility was added) with internal consistency (Cronbach's alpha)=0.82, perfect inter- and intra-rater reliability, test-retest reliability (intraclass correlation)=0.82 (any disability) and 0.92 (unable to perform for 'mental' reasons). Women, older subjects, the totally illiterate and subjects with poorer cognitive function performed significantly more poorly (P < or = 0.02 for all). PRODUCT: a brief, reliable and valid activities of daily living measure, with norms, which is appropriate for use in assessing dementia in illiterate rural elderly people in India.

Activities of Daily Living↗

PubMed1999

Purification, crystallization and preliminary x-ray crystallographic analysis of a phospholipase A2 from Daboia russelli pulchella.

Phospholipases are esterolytic enzymes which hydrolyze glycerophospholipids. The pharmacological efficiency of phospholipase A2 (PLA2) enzymes is reflected by their specificity towards a tissue or organ. The Russell's viper has been classified into two classes. Class 1 contains Viper russelli russelli, Viper russelli siamensis and Viper russelli formosensis, whereas class 2 contains Daboia russelli pulchella. The sequence identity between the PLA2s from these two classes is 47%. The novel PLA2 from Daboia russelli pulchella has been crystallized using the hanging-drop vapour-diffusion method with ammonium sulfate as precipitating agent. Crystals belong to the orthorhombic space group C2221 with unit-cell parameters a = 77.01, b = 92.29, c = 76.90 A and two molecules in the asymmetric unit. These crystals diffract to about 2. 49 A resolution using a rotating-anode source.

Amino Acid Sequence↗

PubMed1999

Purification, crystallization and preliminary crystallographic analysis of a natural complex of phospholipase A2 from Echis carinatus (saw-scaled viper).

A novel complex of phospholipase A2 complexed with another venom protein has been isolated and purified from saw-scaled viper (Echis carinatus) venom. The molecular weights of the two components are 16 and 14 kDa, respectively. The complex was purified using an Affigel blue column and an anion-exchange (DEAE Sephacel) column. Long diamond-shaped crystals were obtained by hanging-drop vapour diffusion. The protein complex was dissolved at a concentration of 10 mg ml-1 in 20 mM sodium cacodylate, 1 mM CaCl2 and 2% dioxane at pH 6.0. The reservoir contained the same buffer with 7%(w/v) PEG 4000. Crystals appeared within 2-3 weeks. Native data to 2.9 A resolution have been obtained at 291 K. The crystals belong to the monoclinic space group P21 with unit-cell parameters a = 74.47, b = 47.87, c = 106.39 A, beta = 104.5 degrees and contain two molecules per asymmetric unit. Structure determination by molecular replacement is in progress.

Amino Acid Sequence↗

PubMed1999

Depressive symptoms, cognitive impairment and functional impairment in a rural elderly population in India: a Hindi version of the geriatric depression scale (GDS-H).

OBJECTIVE: To measure depressive symptomatology in a largely illiterate elderly population in India, using a new Hindi version of the Geriatric Depression Scale (GDS-H), and to examine its distribution and associations with age, gender, literacy, cognitive impairment and functional impairment. DESIGN: A Hindi version of the Geriatric Depression Scale was developed and administered to participants along with measures of demographic characteristics, cognitive functioning and functional ability. SETTING: The rural community of Ballabgarh in northern India. PARTICIPANTS: A community sample of 1554 mostly illiterate Hindi-speaking residents of Ballabgarh aged 55+. MEASURES: The Hindi version of the Geriatric Depression Scale (GDS-H); the Hindi Mental State Exam (HMSE); the Everyday Abilities Scale for India (EASI); age, gender and literacy. RESULTS: The GDS-H had high internal consistency and a factor structure comparable to the original English language version. The overall distribution of scores was higher than reported from other populations. Greater numbers of depressive symptoms, as measured by higher scores on the GDS-H, were associated with older age and illiteracy. Among the illiterate, there was no gender difference while among the literate, higher GDS-H scores were found among women. Cognitive impairment and functional disability were independently associated with higher scores on the GDS-H after adjustment for age, gender and literacy. CONCLUSION: A reliable and valid Hindi version of the GDS has been developed. Depressive symptoms as measured by the GDS-H were prominent in this elderly illiterate northern Indian population and strongly associated with both cognitive and functional impairment.

Activities of Daily Living↗

PubMed1999

Delirium episodes during the course of clinically diagnosed Alzheimer's disease.

A retrospective review was conducted of 122 charts of patients with clinically diagnosed Alzheimer's disease (CDAD) who had participated in a longitudinal dementia study at the Mayo Clinic from 1965 to 1970. DSM-III-R diagnoses were assigned based on the longitudinal description of symptoms detailed in the Mayo Clinic medical records of the hospitalizations; clinic, home, and nursing home visits; and state hospital admissions. Thirty patients (25%) were found to have a delirium episode during their course of CDAD that occurred during inpatient admissions; 50% (15 of 30) of the delirium episode occurred in patients ages 80 to 89. Among patients with a delirium episode, 50% died within one year of the delirium episode and 64% died within two years. Of 13 patients, 10 (77%) had multiple delirium episodes within two years. Admitting diagnoses were mainly primary degenerative dementia of the Alzheimer's type (PDDAT) or PDDAT with delirium. Only 3 (10%) demented patients experienced delirium episodes during a medical admission. No deaths occurred during hospitalization for the years covered by this study. A psychiatric consultation was requested in only 17 (14%) patients; 88% of these patients received diagnoses involving PDDAT, late onset. An additional diagnosis included depressive disorders. Psychopharmacology was the major management strategy (82% of patients with a delirium episode received medication) with a resolution of symptoms within 48 hours. At discharge, only 2 (7%) patients failed to clear the increased degree of confusion.

Aged↗

PubMed1998

Effects of literacy and education on measures of word fluency.

As part of a cross-national study of dementia epidemiology, two types of verbal fluency tasks were administered to three groups of subjects, varying in level of literacy and education, recruited from the rural district of Ballabgarh in northern India. Subjects were asked to list items in a given semantic category (animals; fruits) or words beginning with a given sound (the phonemes /p/ and /s/) the latter being a minor modification of the more familiar initial letter fluency task in view of the high prevalence of illiteracy in Ballabgarh. Analysis of variance revealed main effects of education and task with a task by education interaction such that education had a greater effect on initial sound fluency than on category fluency. The results are discussed in terms of their implication for the design of cross-cultural studies and the evidence that the ability to segment speech into phonemic units is dependent on literacy.

Adult↗

PubMed1998

Practical issues in cognitive screening of elderly illiterate populations in developing countries. The Indo-US Cross-National Dementia Epidemiology Study.

The study of the epidemiology of dementia, specifically Alzheimer's disease, in developing countries requires specialized instruments and personnel. Cultural and sub-cultural differences among populations are highly relevant to the design of such instruments. Over and above the cultural issues, it is widely recognized that low education and illiteracy pose considerable challenges to reliable and valid cognitive screening. The overall objectives of the Indo-US Cross-National Dementia Epidemiology Study were: a) to determine the prevalence and incidence of, and risk factors for, Alzheimer's and other dementias in a defined Indian community; and b) to compare these results with those found in a defined American community. To achieve these epidemiological objectives, our first task was to develop, systematically and empirically, suitable cognitive and activities assessment screening instruments for use in India, which would 1) be culturally fair, psychometrically sound, and valid for a population with little or no education; 2) be optimally sensitive and specific for dementia; and 3) allow not only the identification but also the more detailed characterization of dementia, and of normal and abnormal cognitive aging. In this paper we address the practical issues involved in the development and administration of the modified cognitive screening battery in our rural Indian context.

Aging↗

PubMed1998

Gene-environment interaction in Alzheimer's disease: a potential role for cholesterol.

Alzheimer's disease is probably a complex disease caused by an interaction of multiple environmental and genetic factors. Genetic defects include 'causative' genes which are rare and a 'susceptibility' gene (sigma4 allele of apolipoprotein E) which is more common in cases. Recent research suggests that environmental factors may interact with a genetic predisposition to modify the risk of Alzheimer's disease. An interaction between serum cholesterol levels and sigma4 genotype is proposed. The evidence for this gene-environment interaction is discussed.

Aged↗

PubMed1998

Neurologic factors associated with cognitive impairment in a rural elderly population in India: the Indo-US Cross-National Dementia Epidemiology Study.

Few reports exist of cognitive impairment and associated factors in developing countries. An age-stratified random sample of 388 men and women, 55 years and older, was drawn from a community-based population in the rural area of Ballabgarh in northern India. We classified as "cognitively impaired" those subjects who had scores below the 10th percentile of the population on a general mental status test (the Hindi Mental State Exam, HMSE) and, separately, on a memory test (Delayed Recall of a 10-Item Word List, DRWL). Three hundred seventy-six subjects also underwent a standardized neurologic history and examination. Neurologic factors associated with cognitive impairment, after adjusting for age, gender, and literacy, were history of impaired consciousness and findings of gait disturbance, diminished deep tendon reflexes, and the presence of at least one primitive reflex. We speculate that there may be unique risk factors in developing countries such as nutritional deficiencies leading to focal deficits and cognitive impairment.

Aged↗

PubMed1998

Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-US study.

OBJECTIVE: To determine the prevalence of AD and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.

Aged↗