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Biomedical subjects

R Srinivasan

Publications and source records attributed to R Srinivasan.

At least 91 records · Page 5Linked to original sources
PubMed1998

Tumor immunity and autoimmunity induced by immunization with homologous DNA.

The immune system can recognize self antigens expressed by cancer cells. Differentiation antigens are prototypes of these self antigens, being expressed by cancer cells and their normal cell counterparts. The tyrosinase family proteins are well characterized differentiation antigens recognized by antibodies and T cells of patients with melanoma. However, immune tolerance may prevent immunity directed against these antigens. Immunity to the brown locus protein, gp75/ tyrosinase-related protein-1, was investigated in a syngeneic mouse model. C57BL/6 mice, which are tolerant to gp75, generated autoantibodies against gp75 after immunization with DNA encoding human gp75 but not syngeneic mouse gp75. Priming with human gp75 DNA broke tolerance to mouse gp75. Immunity against mouse gp75 provided significant tumor protection. Manifestations of autoimmunity were observed, characterized by coat depigmentation. Rejection of tumor challenge required CD4(+) and NK1.1(+) cells and Fc receptor gamma-chain, but depigmentation did not require these components. Thus, immunization with homologous DNA broke tolerance against mouse gp75, possibly by providing help from CD4(+) T cells. Mechanisms required for tumor protection were not necessary for autoimmunity, demonstrating that tumor immunity can be uncoupled from autoimmune manifestations.

Animals↗
PubMed1998

Investigating neural correlates of conscious perception by frequency-tagged neuromagnetic responses.

In binocular rivalry, a subject views two incongruent stimuli through each eye but consciously perceives only one stimulus at a time, with a switch in perceptual dominance every few seconds. To investigate the neural correlates of perceptual dominance in humans, seven subjects were recorded with a 148-channel magnetoencephalography array while experiencing binocular rivalry. A red vertical grating flickering at one frequency was presented to one eye through a red filter and a blue horizontal grating flickering at a different frequency was presented to the other eye through a blue filter. Steady-state neuromagnetic responses at the two frequencies were used as tags for the two stimuli and analyzed with high-resolution power spectra. It was found that a large number of channels showed peaks at both frequencies, arranged in a horseshoe pattern from posterior to anterior regions, whether or not the subject was consciously perceiving the corresponding stimulus. However, the amount of power at the stimulus frequency was modulated in relation to perceptual dominance, being lower in many channels by 50-85% when the subject was not conscious of that stimulus. Such modulation by perceptual dominance, although not global, was distributed to a large subset of regions showing stimulus-related responses, including regions outside visual cortex. The results demonstrate a correlation between the conscious perception of a visual stimulus and the synchronous activity of large populations of neurons as reflected by steady-state neuromagnetic responses.

Adult↗
PubMed1998

Expression of the c-erbB-4/HER4 protein and mRNA in normal human fetal and adult tissues and in a survey of nine solid tumour types.

The c-erbB-4/HER4 receptor belongs to the family of the type I growth factor receptors. Mouse monoclonal antibodies have been raised to the cytoplasmic domain of the c-erbB-4 receptor and characterized; the antibody HFR-1 has been used to determine the pattern of expression of the c-erbB-4 protein immunohistochemically in formalin-fixed, paraffin-embedded adult and fetal tissues. The expression of c-erbB-4 mRNA was determined by using 35S-labelled riboprobes and tissue in situ hybridization. c-erbB-4 is widely expressed in many adult and fetal tissues, including the lining epithelia of the gastrointestinal, urinary, reproductive, and respiratory tracts, as well as the skin, skeletal muscle, circulatory, endocrine, and nervous systems. The developing brain and heart notably express high levels of this receptor. The pattern of c-erbB-4 protein expression is also reported in a survey of common solid human cancers. Loss of expression was noted in 40-80 per cent of adenocarcinomas and up to 100 per cent of squamous cell carcinomas, whereas overexpression was observed in about 10-20 per cent of adenocarcinomas and astrocytomas. In general, the pattern of c-erbB-4 expression in normal tissues and cancers suggests that it tends to be associated with the differentiated compartment.

Adenocarcinoma↗
PubMed1998

The type 1 growth factor receptor family: new ligands and receptors and their role in breast cancer.

The type 1 family of growth factor receptors, which consist of the epidermal growth factor receptor, c-erbB-2, c-erbB-3, and c-erbB-4, are expressed in normal breast ductal epithelial cells and in some breast cancers. Nine genes have now been identified which code for ligands. In some cases the genes are spliced into a series of proteins which differ in structure, but all retain an EGF-like element responsible for receptor recognition. The EGF receptor is expressed in normal breast and in some cancers, but is apparently reduced in expression in other cases. Cancers with EGF receptors appear to represent a greater threat to patients as in most studies they are associated with a shorter time to relapse and overall survival. The c-erbB-2 protein is overexpressed at very high levels in about one fifth of breast cancers and is indicative of poor prognosis. Other cancers may express lesser degrees of overexpression but it is not clear if this is biologically or clinically significant. The c-erbB-3 protein is expressed in normal breast epithelial cells and has been reported to be present at high levels in some cancers but at normal levels or at lower than normal levels in some others. The limited studies to date suggest that when measured on its own c-erbB-3 expression is not predictive. c-erbB-4 is also expressed in normal breast and in some cancers but no studies have yet been performed to address whether it is associated with disease behaviour. In the future it is likely that a greater understanding of the function of this complex family of interacting proteins will assist in gaining the maximum predictive power from measurement of their expression in human breast cancer.

Amino Acid Sequence↗
PubMed1998

Spatial filtering and neocortical dynamics: estimates of EEG coherence.

The spatial statistics of scalp electroencephalogram (EEG) are usually presented as coherence in individual frequency bands. These coherences result both from correlations among neocortical sources and volume conduction through the tissues of the head. The scalp EEG is spatially low-pass filtered by the poorly conducting skull, introducing artificial correlation between the electrodes. A four concentric spheres (brain, CSF, skull, and scalp) model of the head and stochastic field theory are used here to derive an analytic estimate of the coherence at scalp electrodes due to volume conduction of uncorrelated source activity, predicting that electrodes within 10-12 cm can appear correlated. The surface Laplacian estimate of cortical surface potentials spatially bandpass filters the scalp potentials reducing this artificial coherence due to volume conduction. Examination of EEG data confirms that the coherence estimates from raw scalp potentials and Laplacians are sensitive to different spatial bandwidths and should be used in parallel in studies of neocortical dynamic function.

Algorithms↗
PubMed1998

Bayesian estimates of error bounds for EEG source imaging.

Given a set of electrical potential measurements at the surface of the head, localizing the sources of the electrical activity is an inherently ill-posed problem. Bayesian methods can be used to specify prior information to constrain the possible source solutions. We show that Bayesian analysis can also provide a means for characterizing system noise levels, estimating the "error bars" surrounding source localization results, and estimating the information about brain processes conveyed by dense sensor array electroencephalographic (EEG) recordings. This method is, in principal, applicable to any linear model of EEG or magnetoencephalographic (MEG) processes. A series of simulations demonstrated the internal consistency of our method, the robustness to noise levels, and the limitations of accurate source localization with large numbers of sources.

Artifacts↗
PubMed1998

The phosphophoryn gene family: identical domain structures at the carboxyl end.

Phosphophoryns (PPs), a family of aspartic acid and phosphoserine rich dentin proteins, are considered to be archetypal regulators of extracellular matrix biomineralization. Their very unusual composition, extensive phosphorylation, and tissue-specific heterogeneity have made their characterization a difficult task. We have recently cloned several rat incisor PP genes from our odontoblast cDNA library. The first clone, designated as DMP2, was 2.4 kb long, with an open reading frame of approximately 700 bp and an untranslated region of approximately 1.7 kb. Northern blot analysis of odontoblast mRNA showed a single message between 5 and 6 kb. When a 5' RACE technique was used to obtain the full length clone, a second approximately 2 kb DNA fragment (DMP3) was also found. Cloning and sequencing of DMP3 showed that the 3' end was highly homologous to the 3' end of DMP2, but the 5' end of this clone had 100% homology to dentin sialoprotein (DSP). DMP3 is not a typical Asp-rich phosphophoryn, but DMP2 contains a domain N-terminal to the common region which has the hallmark Asp- and Ser-rich composition of the phosphophoryns. Both DMP2 and DMP3 are closely localized on mouse chromosome 5q21, corresponding to human chromosome 4q21. The expression of these two genes is regulated differently. Thus, there may be a family of phosphophoryn-related genes coding for a common C-terminal peptide sequence domain, but involving different N-terminal domains with different functions.

Amino Acid Sequence↗
PubMed1998

When to suspect lactose intolerance. Symptomatic, ethnic, and laboratory clues.

Lactose intolerance is widespread, with adult-type hypolactasia being the predominant cause of lactose malabsorption. Daily ingestion of less than 240 mL of milk is well tolerated by most lactose-intolerant adults. Some persons with normal lactase activity may become symptomatic on consumption of products containing lactose. Lactose maldigestion may coexist in adults with irritable bowel syndrome and in children with recurrent abdominal pain. Management consists primarily of dietary changes. People who avoid dairy products should receive calcium supplementation and should be advised to read ingredient labels carefully. Several lactase replacement products are available, but their efficacy varies.

Adolescent↗
PubMed1997

Alteration by flutamide of neutrophil response to stimulation. Implications for tissue injury.

When activated, inflammatory cells such as polymorphonuclear leukocytes (PMNs) can damage isolated hepatocytes in vitro. These studies were performed to determine if flutamide activates PMNs. Flutamide (Eulexin) is an orally active, nonsteroidal antiandrogen that can cause liver injury associated with inflammation. Activation of PMNs was assessed from the production of superoxide anion and the release of myeloperoxidase in the presence or absence of flutamide and phorbol myristate acetate (PMA) or f-methionyl-leucyl-phenylalanine (fmlp). In addition, hepatocytes were cocultured with PMNs stimulated with PMA or fmlp in the presence or absence of flutamide, and cytotoxicity to hepatocytes was evaluated from the release of alanine aminotransferase into the medium. Flutamide alone did not stimulate the generation of superoxide anion by PMNs but potentiated its production in response to PMA. At lower concentrations of flutamide (i.e. 25 microM), there was a tendency toward increased release of myeloperoxidase, whereas at higher concentrations (i.e. 75-100 microM) flutamide inhibited degranulation in response to fmlp. In coculture with hepatocytes, PMNs exposed to either flutamide, fmlp, or PMA alone caused a significant increase in release of alanine aminotransferase. Hepatocellular toxicity caused by PMNs incubated with flutamide and PMA was additive and was not affected by the addition of superoxide dismutase and catalase. Flutamide had no significant effect on fmlp-induced injury in cocultures. These data indicate that flutamide alters the activation of PMNs by subsequent stimuli in vitro. In addition, in the presence of flutamide, minor PMN-mediated injury to isolated hepatocytes was observed.

Androgen Antagonists↗
PubMed1997

Modeling unfolded states of proteins and peptides. II. Backbone solvent accessibility.

Buried surface area is often used as a measure of the contribution to protein folding from the hydrophobic effect. Quantitatively, the surface buried upon folding is reckoned as the difference in area between the native and unfolded states. This calculation is well defined for a known structure but model-dependent for the unfolded state. In a previous paper [Creamer, T. P., Srinivasan, R., & Rose, G. D. (1995) Biochemistry 34, 16245-16250], we developed two models that bracket the surface area of the unfolded state between limiting extremes. Using these extrema, it was shown that earlier models, such as an extended tripeptide, overestimate the surface area of side chains in the unfolded state. In this sequel to our previous paper, we focus on backbone surface in the unfolded state, again adopting the strategy of trapping the area between limiting extrema. A principal conclusion of this present study is that most backbone surface in proteins is buried within local structure.

Amino Acids↗
PubMed1997

EEG coherency. I: Statistics, reference electrode, volume conduction, Laplacians, cortical imaging, and interpretation at multiple scales.

Several methodological issues which impact experimental design and physiological interpretations in EEG coherence studies are considered, including reference electrode and volume conduction contributions to erroneous coherence estimates. A new measure, 'reduced coherency', is introduced as the difference between measured coherency and the coherency expected from uncorrelated neocortical sources, based on simulations and analytic-statistical studies with a volume conductor model. The concept of reduced coherency is shown to be in semi-quantitative agreement with experimental EEG data. The impact of volume conduction on statistical confidence intervals for coherence estimates is discussed. Conventional reference, average reference, bipolar, Laplacian, and cortical image coherencies are shown to be partly independent measures of neocortical dynamic function at different spatial scales, due to each method's unique spatial filtering of intracranial source activity.

Action Potentials↗
PubMed1997

Probable gastrointestinal toxicity of Kombucha tea: is this beverage healthy or harmful?

Kombucha tea is a health beverage made by incubating the Kombucha "mushroom" in tea and sugar. Although therapeutic benefits have been attributed to the drink, neither its beneficial effects nor adverse side effects have been reported widely in the scientific literature. Side effects probably related to consumption of Kombucha tea are reported in four patients. Two presented with symptoms of allergic reaction, the third with jaundice, and the fourth with nausea, vomiting, and head and neck pain. In all four, use of Kombucha tea in proximity to onset of symptoms and symptom resolution on cessation of tea drinking suggest a probable etiologic association.

Basidiomycota↗