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Biomedical subjects

S Anand

Publications and source records attributed to S Anand.

At least 73 records · Page 4Linked to original sources
PubMed1997

Multiple transcripts of the murine immunoglobulin epsilon membrane locus are generated by alternative splicing and differential usage of two polyadenylation sites.

The human C epsilon gene produces a number of alternatively spliced heavy chain transcripts of which some encode functional IgE isoforms. We now show that differentially processed epsilon mRNA variants also exist in the mouse and are generated by differential polyadenylation and alternative splicing of primary epsilon chain transcripts. The two poly(A) sites of the mouse membrane transcripts were identified in the present study by RACE-PCR analysis. The first poly(A) site is located 743 nt downstream from the beginning of the second membrane exon (M2) and contains the same non-consensus AGTAAA signal sequence as the single poly(A) site of the human membrane transcripts. The second poly(A) site is located almost 500nt further downstream and is characterized by an AAGAAA hexamer. This poly(A) site contains a (G+T) rich element downstream to the site of cleavage and polyadenylation and is preferentially utilized by the membrane epsilon transcripts. Additional diversity of epsilon transcripts is generated by alternative splicing between the last constant region exon (CH4) and the two membrane exons (M1 and M2). The alternatively spliced transcripts include two variants that skip the first membrane exon and encode epsilon heavy chains that lack the transmembrane domain. The third variant is generated by splicing to an internal site in M2 and codes for a membrane isoform that is 10 amino acids shorter in the cytoplasmic domain than the classical membrane IgE. Although little amino-acid sequence homology exists between the murine epsilon chain isoforms and their human counterparts, the pattern of splicing is rather conserved between the two species.

Alternative Splicing↗
PubMed1997

Disability-adjusted life years: a critical review.

The disability-adjusted life year (DALY) has emerged in the international health policy lexicon as a new measure of the 'burden of disease'. We argue that the conceptual and technical basis for DALYs is flawed, and its assumptions and value judgements are open to serious question. In particular, the implications of age-weighting and discounting are found to be unacceptable. Moreover, the proponents of DALYs do not distinguish between the exercises of measuring the burden of disease and of allocating resources. But the appropriate information sets for the two exercises are quite different. Allocating resources by aggregate DALY-minimization is shown to be inequitable.

Age Factors↗
PubMed1997

Rapid-rate transcranial magnetic stimulation of human frontal cortex can evoke saccades under facilitating conditions.

Rapid-rate transcranial magnetic stimulation (rTMS) of a localized area within premotor frontal cortex elicited short-latency, multistep eye movements during a double-step saccade task in 3 of 9 subjects. These evoked saccades occurred in 14-32% of trials when rTMS was delivered over premotor regions located 5-7 cm lateral and 2-4 cm anterior to the vertex. In trials without rTMS or when rTMS was delivered medial or posterior to these sites, multistep saccades occurred in less than 2% of trials. In two subjects, rTMS of the right premotor cortex evoked contraversive saccades. In a third subject, rTMS of the left premotor cortex evoked saccades whose trajectory depended on the direction of the double-step targets. The amplitude and likelihood of occurrence of evoked saccades varied between rTMS trials. The intervals between evoked saccades were proportional to the intervals between rTMS pulses delivered at 16, 20 or 25 Hz. rTMS did not elicit saccades during fixation on a stationary target or during straight-ahead gaze in darkness, suggesting that the double-step saccade task facilitated the activation of a discrete premotor area consistent with the human frontal eye fields.

Adolescent↗
PubMed1997

Evanescent wave fibre optic sensor for detection of L. donovani specific antibodies in sera of kala azar patients.

An easy-to-use technique for detection of antibodies specific for the parasite L. donovani in human serum sample has been developed. The method is based on an evanescent wave generated from a tapered configuration of decladded optical fibre and does not require any volumetric measurement. Tapered fibres are immobilized with the purified cell surface protein of L. donovani by covalent bonding. Treated fibres are incubated with the patient serum for 10 min followed by incubation with goat anti human IgG tagged FITC. Fluorescent intensity from the fibre has been shown to be proportional to L. donovani specific antibodies present in the test sera. Direct readings can be obtained after signal enhancement through a photomultiplier tube within 5 min. The system, when tested on 12 positive sera, did not show any false negative result. Also, no false positive result was obtained with serum samples of patients infected with leprosy, tuberculosis, typhoid and malaria, showing the specificity of the sensor and efficacy of the technique.

Animals↗
PubMed1997

Classifying ethnicity utilizing the Canadian Mortality Data Base.

UNLABELLED: The study of ethnic differences in disease is a methodological challenge as ethnicity is often not identified in existing datasets and surrogate measures need to be used. We have developed a novel methodology combining last name and country of birth to study mortality patterns of Canadians of South Asian (SA) and Chinese (CH) ethnic origin and have compared death rates among SA, CH, and White (WH) Canadians. METHODS: SA and CH were identified in the Canadian Mortality Data Base (CMDB) using the last name and country of birth of the deceased. Records of people who had been born in countries with large South Asian and Chinese populations (e.g. India, Pakistan, China, Hong Kong) were selected and manually screened by last name. A name directory was then created of distinct South Asian and Chinese names and this directory was used to search all other records in the CMDB for SA and CH deaths. Where necessary, other identifying characteristics such as first name and parents' last name were also used. Population counts were obtained from the Census self-reported question on ethnicity for SA and CH. WH were identified as non-immigrant Canadians who were neither SA nor CH. The method of assigning ethnicity in the CMDB and Census were assessed for comparability and issues of validity and reliability were addressed. RESULTS: Using this method, 10,989 SA and 21,548 CH deaths were identified. There was marked heterogeneity in birthplace, with only 56% of SA born in South Asia and only 74% of CH born in Greater China. Last names had high validity for self-reported ethnicity in a population sample of SA and were highly reproducible. Mortality rates varied dramatically between groups studied. SA and WH had high rates of ischemic heart disease while stroke mortality was similar among all three groups. Cancer death rates were high in CH and WH and much lower in SA. CONCLUSION: Last names and country of birth can be used to determined ethnicity of SA and CH with validity and reliability, and leads to a more accurate classification than country of birth alone. The contrasting patterns observed in mortality from major causes of death suggest many interesting hypotheses for further study.

Adult↗
PubMed1997

Tri-axial recording of event-related potentials during passive cognitive tasks in patients with Alzheimer's disease.

Standard methods used to assess cognitive function in patients with Alzheimer's Disease (AD) often use instructions to direct attention and gauge task difficulty, and measure only the output of processing, i.e., the patient's behavioral response. Because this may focus assessment on functions that are observable and to periods when patient comprehension is not compromised, the present study presented stimuli without instruction, manipulated task difficulty by varying stimulus factors, and used the brain's electrical response as the dependent variable. Because the recording electrode's position on the scalp may limit full examination of the voltage distribution of these responses, a Tri-Axial method of recording electrical activity within a Cartesian coordinate system was used. Results suggest attention may inhibit habituation so that inputs can be represented, discriminated and consolidated. For the control group, the levels of task difficulty modulated electrical peaks presumed to reflect the brain's ability to perform these functions. In the AD group, these responses were attenuated or absent, suggesting that dysfunctional attentional processing may underlie response errors often attributed to memory.

Aged↗
PubMed1997

Interaction of cognitive and sensorimotor maps of visual space.

Studies of saccadic suppression and induced motion have suggested separate representations of visual space for perception and visually guided behavior. Because these methods required stimulus motion, subjects might have confounded motion and position. We separated cognitive and sensorimotor maps without motion of target, background, or eye, with an "induced Roelofs effects": a target inside an off-center frame appears biased opposite the direction of the frame. A frame displayed to the left of a subject's center line, for example, will make a target inside the frame appear farther to the right than its actual position. The effect always influences perception, but in half of our subjects it did not influence pointing. Cognitive and sensorimotor maps interacted when the motor response was delayed; all subjects now showed a Roelofs effect for pointing, suggesting that the motor system was being fed from the biased cognitive map. A second experiment showed similar results when subjects made an open-ended cognitive response instead of a five-alternative forced choice. Experiment 3 showed that the results were not due to shifts in subjects' perception of the felt straight-ahead position. In Experiment 4, subjects pointed to the target and judged its location on the same trail. Both measures showed a Roelofs effect, indicating that each trial was treated as a single event and that the cognitive representation was accessed to localize this event in both response modes.

Cognition↗
PubMed1996

The two membrane isoforms of human IgE assemble into functionally distinct B cell antigen receptors.

The human C epsilon gene expresses two membrane IgE heavy chain mRNAs which differ in the sequence that encodes their extracellular membrane-proximal domain. In the long IgE isoform (mLIgE), this domain contains a stretch of 52 amino acids which are absent in the short variant (mSIgE). We have now generated B cell transfectoma cell lines that express these two isoforms and show that both types of mIgE form functional B cell antigen receptors (BCR). Both receptors associate with the Ig-alpha/Ig-beta heterodimer, as well as with protein kinases that are capable of phosphorylating this complex. Upon their cross-linking, both receptors can activate protein tyrosine kinases that phosphorylate the same substrate proteins. Both IgE receptors also associate with two novel proteins that do not bind to mIgM. Apart from these similarities, the two IgE-BCRs show several differences of which some are analogous to the differences between the IgM- and IgD-BCRs. First, the mSIgE is transported to the cell surface at a higher rate than the mLIgE. Second, the two IgE-BCRs associate with differently glycosylated Ig-alpha proteins, the mLIgE associates with the completely glycosylated form, whereas the mSIgE associates with an Ig-alpha glycoform that is partially sensitive to endoglycosidase H. Third, the kinetics of protein tyrosine phosphorylation induced by receptor cross-linking is significantly different for the two IgE-BCRs. Finally, cross-linking of the mSIgE-BCR leads to growth inhibition of the B cell transfectoma, whereas signaling through the mLIgE-BCR does not affect the cellular proliferation. These data show that the two human membrane IgE isoforms assemble into functionally distinct antigen receptors which can induce different cellular responses.

Amino Acid Sequence↗
PubMed1996

Computer simulation of systemic circulation and clot lysis dynamics during thrombolytic therapy that accounts for inner clot transport and reaction.

BACKGROUND: We developed a computer model to predict lysis rates of thrombi for intravenous thrombolytic regimens based on the convective/diffusive penetration of reacting and adsorbing fibrinolytic species from the circulation into the proximal face of a dissolving clot. METHODS AND RESULTS: Solution of a one-compartment plasma model provided the dynamic concentrations of fibrinolytic species that served as inlet conditions for stimulation of the one-dimensional spatiodynamics within a dissolving fibrin clot of defined composition. The model predicted the circulating levels of tissue plasminogen activator (TPA) and plasminogen levels found in clinical trials for various intravenous therapies. To test the model predictions under in vitro conditions, plasma clots were perfused with TPA (0.1 mumol/L) and plasminogen (1.0 mumol/L) delivered at constant permeation velocity of 0.1 or 0.2 mm/min. The model provided an accurate prediction of the measured lysis front movement. For TPA administration regimens used clinically, simulations predicted clot dissolution rates that were consistent with observed reperfusion times. For unidirectional permeation, the continual accumulation of adsorbing species at the moving lysis front due to prior rounds of solubilization and rebinding was predicted to provide for a marked concentration of TPA and plasmin and the eventual depletion of antiplasmin and macroglobulin in an advancing (approximately 0.25 mm thick) lysis zone. CONCLUSIONS: Pressure-driven permeation greatly enhances and is a primary determinant of the overall rate of clot lysis and creates a complex local reaction environment at the plasma/clot interface. With simulation of reaction and transport, it becomes possible to quantitatively link the administration regimen, plasminogena activator properties, and thrombolytic outcome.

Clot Retraction↗
PubMed1996

Treatment for acute myocardial infarction. Overview of randomized clinical trials.

This review summarizes the results of several pharmacological interventions that have been evaluated in the management of acute myocardial infarction. Of these, thrombolytic therapy, aspirin, beta-blockers and angiotensin converting enzyme inhibitors have all been proven to reduce mortality risk and the latter three classes of drugs have also been shown to reduce morbidity. Routine use of heparin or nitrates is not recommended although they may be useful in specific circumstances such as post-infarction angina or large infarcts. Drugs that have as yet not been shown to have a role in the routine management of acute myocardial infarction include Class I antiarrhythmic agents, magnesium and calcium antagonists. Management of patients with acute myocardial infarction can now be appropriately based on the evidence generated from well conducted randomized clinical trials and appropriate therapeutic choices based on such information can be expected to reduce their morbidity and mortality risks.

Evaluation Studies as Topic↗
PubMed1995

Mutations of G158 and their second-site revertants in the plasma membrane H(+)-ATPase gene (pma1) in Saccharomyces cerevisiae.

A G158D mutation residing near the cytoplasmic end of transmembrane segment 2 of the H(+)-ATPase from Saccharomyces cerevisiae appears to alter electrogenic proton transport by the proton pump (Perlin et al. (1988) J. Biol. Chem. 263, 18118-18122.) The mutation confers upon whole cells a pronounced growth sensitivity to low pH and a resistance to the antibiotic hygromycin B. The isolated enzyme retains high activity (70% of wild type) but is inefficient at pumping protons in a reconstituted vesicle system, suggesting that this enzyme may be partially uncoupled (Perlin et al. (1989) J. Biol. Chem. 264, 21857-21864). In this study, the acid-sensitive growth phenotype of the pma1-D158 mutant was utilized to isolate second site suppressor mutations in an attempt to probe structural interactions involving amino acid 158. Site-directed mutagenesis of the G158 locus was also performed to explore its local environment. Nineteen independent revertants of pma1-G158D were selected as low pH-resistant colonies. Four were full phenotypic revertants showing both low pH resistance and hygromycin B sensitivity. Of three full revertants analyzed further, one restored the original glycine residue at position 158 while the other two carried compensatory mutations V336A or F830S, in transmembrane segments 4 and 7, respectively. Partial revertants, which could grow on low pH medium but still retained hygromycin B resistance, were identified in transmembrane segments 1 (V127A) and 2 (C148T, G156C), as well as in the cytoplasmic N-terminal domain (E110K) and in the cytoplasmic loop between transmembrane segments 2 and 3 (D170N, L275S). Relative to the G158D mutant, all revertants showed enhanced net proton transport in whole-cell medium acidification assays and/or improved ATP hydrolysis activity. Small polar amino acids (Asp and Ser) could be substituted for glycine at the 158 position to produce active, albeit somewhat defective, enzymes; larger hydrophobic residues (Leu and Val) produced more severe phenotypes. These results suggest that G158 is likely to reside in a tightly packed polar environment which interacts, either directly or indirectly, with transmembrane segments 1, 4 and 7. The revertant data are consistent with transmembrane segments 1 and 2 forming a conformationally sensitive helical hairpin structure.

Cell Membrane↗
PubMed1995

Induction of apoptosis in chronic myelogenous leukemia lymphocytes by hydroxyurea and adriamycin.

The nature of the cytotoxic effects of the anticancer drugs hydroxyurea, adriamycin, cisplatin and interferon, was studied on lymphocytes obtained from chronic myelogenous leukemia (CML) subjects prior to the commencement of chemotherapy. These drugs appeared to mediate their cytotoxic effects by the process of apoptosis as observed from the morphological changes, i.e., cell shrinkage, chromatin condensation, cell membrane blebbing, and also from the cellular damage and DNA fragmentation into oligonucleosomal ladder of 180-bp multiples, which are all characteristics of apoptotic cell death. The effect was much more marked by hydroxyurea and adriamycin. Maximum sensitivity was seen at 24 h post treatment. Untreated CML lymphocytes cultured for 24 h also showed some apoptosis.

Adult↗
PubMed1995

Apoptosis in health and disease.

Two distinct forms of cell death are known, necrosis which results from physical or chemical insult and apoptosis or programmed cell death results from programming within the cell for self destruction in response to internal and external stimuli. Apoptosis is a genetically governed process of cell death occurring in development and maintenance of multicellular organisms. It occurs to get rid of individual cells that become unwanted for various reasons or that present a threat to the organism. It is accompanied by distinct morphological changes. DNA fragmentation in most cases, and appears to be caused by the activities of specific genes. Its defective regulation may play a part in the aetiology of cancer, AIDS, autoimmune and degenerative diseases. Apoptosis offers potential for prevention and therapeutic modulation of these disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cell death by apoptosis.

Apoptosis has been the focus of considerable attention in recent years. Apoptosis/programmed cell death, is a morphologically distinct process of cell death in which cells die in a controlled manner, in response to specific stimuli, following an intrinsic programme. Apoptosis is a greek work which means "falling off", as of leaves from trees. So occurs in plants suggesting that apoptosis originated very early in biological evolution. This wide spread active process of self destruction is seen in a wide variety of tissues, and is an essential feature in both development and maintenance of multicellular animals. It is ascribed roles in the process of embryogenesis, differentiation, metamorphosis, neural development, epithelial turnover, aging, regulation of cell population of the immune system and tumor regression.

Apoptosis↗