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Biomedical subjects

A Ravindran

Publications and source records attributed to A Ravindran.

36 records · Page 2Linked to original sources
PubMed1990

Jack fruit lectin binding pattern in carcinoma of the uterine cervix.

A lectin was isolated and purified from the seeds of Jack Fruit (Artocarpus integrifolia) using a column of immobilized N-acetyl D-Galactosamine. The Jack Fruit lectin (JFL) was conjugated to horse radish peroxidase (HRP). The purified conjugate was used to study the binding properties of tissues from carcinomas of the uterine cervix. The binding to cancer tissues was compared with that of normal controls. The carcinomatous cells showed varying degrees of binding towards JFL in contrast to normal controls which generally had uniform binding. The nature and intensity of binding of the lectin with the cancer tissues suggest that this lectin may be used as a diagnostic marker in carcinoma of uterine cervix.

Carcinoma, Papillary↗
PubMed1990

Chromosome abnormalities in squamous cell carcinoma of the human oral cavity.

Cytogenetic studies carried out in tissues of 75 patients with squamous cell carcinoma of the oral cavity gave satisfactory results in 12 cases. Remarkable variation characterized the modal chromosome numbers of these tumors, ranging from marked hypodiploidy to tetraploidy. Chromosomes which were lost belonged to group A whereas chromosomes which were gained belonged to groups C, D, E, F and G. Marker chromosomes were present in three cases. There was no correlation between the chromosome abnormalities observed and the clinical stages of the disease. The pattern of chromosome abnormalities ranging from marked hypodiploidy to tetraploidy observed in oral cancer tissues suggests an association of DNA oncogenic virus possibly Herpes simplex virus Type I (HSV-1) with oral cancer.

Adult↗
PubMed1989

Analysis of the blocking activity of charybdotoxin homologs and iodinated derivatives against Ca2+-activated K+ channels.

Two charybdotoxin peptides were purified from venom of the Israeli scorpion, Leiurus quinquestriatus hebraeus. Microsequencing of the most abundant toxin, ChTX-Lq1, revealed identity with the 37-residue peptide previously sequenced by Gimenez-Gallego et al. [Gimenez-Gallego, G., et al., Proc. Natl. Acad. Sci. USA 85:3329-3333 (1988)]. Sequence data on the minor peptide, ChTX-Lq2, showed substantial homology to ChTX-Lq1 with differences observed at eight positions. These two charybdotoxin sequences, along with that of noxiustoxin, define a distinct family of scorpion peptide toxins with activity against K+ channels. Both charybdotoxin homologs inhibited Ca2+-dependent K+ efflux from human erythrocytes with similar potency, K0.5 approximately 40 nM. In planar bilayer assays of single K(Ca) channels from rat muscle, ChTX-Lq1 and ChTX-Lq2 blocked with intrinsic Kd's of 1.3 and 43 nM, respectively, in the presence of 50 mM external KCl. A new application of dwell-time histogram analysis of single-channel blocking events was used to characterize the kinetic homogeneity of toxin samples and the blocking kinetics of ChTX derivatives. The lower blocking affinity of ChTX-Lq2 was the combined result of a faster dissociation rate and a slower association rate as compared to ChTX-Lq1. The blocking activity of two mono-iodinated derivatives of ChTX-Lq1 was also analyzed. Blocked dwell-time histograms of the iodinated peptides were characterized by predominately brief (0.2-2 sec) blocking events in comparison to the native toxin (20 sec). Histogram analysis revealed that mono-iodination of ChTX-Lq1 impairs blocking activity by adverse effects on both dissociation and association rate constants. Frequency density histograms of single channel blocking events provide a sensitive assay of toxin purity suitable for quantitating structure-activity relationships of charybdotoxin derivatives.

Amino Acid Sequence↗
PubMed1989

Influence of negative surface charge on toxin binding to canine heart Na channels in planar bilayers.

The presence of negative surface charge near the tetrodotoxin/saxitoxin binding site of canine heart Na channels was revealed by analysis of the kinetics of toxin block of single batrachotoxin-activated Na channels in planar bilayers as a function of [NaCl]. The voltage-dependence of toxin binding and the toxin dissociation rate are nearly constant as [NaCl] is varied from 0.05 to 3 M. In contrast, the association rate constant of the toxins is inversely dependent on [NaCl], with the rate for the divalent toxin, saxitoxin2+, affected more steeply than that of the monovalent toxin, tetrodotoxin1+. These results for toxin-insensitive Na channels from canine heart parallel previous findings for toxin-sensitive Na channels from canine brain. The model of Green et al. (Green, W. N., L. B. Weiss, and O. S. Anderson. 1987. J. Gen. Physiol. 89:873-903), which includes Na+ competition and Gouy-Chapman screening of surface charge, provided an excellent fit to the data. The results suggest that the two canine Na channel subtypes have a similar density of negative surface charge (1 e-/400 A2) and a similar dissociation constant for Na+ competition (0.5 M) at the toxin binding site. Thus, negative surface charge is a conserved feature of channel function of these two subtypes. The difference in toxin binding affinities arises from small differences in intrinsic association and dissociation rates.

Animals↗
PubMed1988

An emerging pharmacology of peptide toxins targeted against potassium channels.

Voltage-dependent ion channels are a difficult class of proteins to approach biochemically. Many such channels are present at low density in relevant tissues and exist as multiple subtypes that can be distinguished electrophysiologically. In particular, K channels appear to be a diverse family of proteins characterized by many different conductance properties, gating behaviors and regulatory phenomena. Fortunately, specific peptide toxins for K channels are present in the venoms of insects, scorpions, snakes and possibly other species. The available sequences of these peptides define several different families of toxins. Electrophysiological and radioligand binding studies suggest that these toxins can be used to distinguish subclasses of K channels that share similar toxin binding sites. The growing databank of sequence homologies for both toxins and channels is, in essence, a codebook for identifying common elements of structure and function. The continuing development of toxins as biochemical probes should help to uncover the molecular basis and physiological significance of K-channel diversity.

Animals↗
PubMed1988

Multiple saxitoxin-binding sites in bullfrog muscle: tetrodotoxin-sensitive sodium channels and tetrodotoxin-insensitive sites of unknown function.

The possible presence of multiple sodium channel subtypes in bullfrog skeletal muscle was investigated in binding experiments with [3H]saxitoxin and in single-channel studies using planar lipid bilayers. Two classes of [3H]saxitoxin-binding sites were identified in membrane preparations. One class displayed a toxin specificity characteristic of voltage-dependent sodium channels: high affinity for saxitoxin (KD approximately equal to 0.5 nM), neosaxitoxin (KD approximately equal to 0.1 nM), and tetrodotoxin (KD approximately equal to 1.3 nM). A second class of membrane-associated binding sites exhibited high affinity for saxitoxin (KD approximately equal to 0.1 nM), lower affinity for neosaxitoxin (KD approximately equal to 25 nM), and complete insensitivity to tetrodotoxin at concentrations up to 32 microM. The first class corresponded to functional tetrodotoxin-sensitive sodium channels that could be incorporated and observed in planar bilayers in the presence of batrachotoxin. Similar attempts to incorporate tetrodotoxin-insensitive sodium channels from bullfrog muscle and heart membranes were unsuccessful. The unusual, tetrodotoxin-insensitive binding activity for [3H]saxitoxin was also found at nM levels in the high speed supernatant of homogenized skeletal muscle without the addition of detergents. This soluble class of sites exhibited low affinity for neosaxitoxin (KD approximately equal to 60 nM) and a very slow dissociation rate of [3H]saxitoxin (t0.5 approximately equal to 90 min), properties nearly identical to those of the tetrodotoxin-insensitive sites in membranes. The soluble saxitoxin-binding activity is also characterized by a more basic pH dependence and a complete lack of binding competition between saxitoxin and alkali cations. Bullfrog muscle appears to be a good tissue source for the purification of this soluble saxitoxin-binding protein.

Amphibian Proteins↗
PubMed1987

Kinetic basis for insensitivity to tetrodotoxin and saxitoxin in sodium channels of canine heart and denervated rat skeletal muscle.

The single-channel blocking kinetics of tetrodotoxin (TTX), saxitoxin (STX), and several STX derivatives were measured for various Na-channel subtypes incorporated into planar lipid bilayers in the presence of batrachotoxin. The subtypes studied include Na channels from rat skeletal muscle and rat brain, which have high affinity for TTX/STX, and Na channels from denervated rat skeletal muscle and canine heart, which have about 20-60-fold lower affinity for these toxins at 22 degrees C. The equilibrium dissociation constant of toxin binding is an exponential function of voltage (e-fold per 40 mV) in the range of -60 to +60 mV. This voltage dependence is similar for all channel subtypes and toxins, indicating that this property is a conserved feature of channel function for batrachotoxin-activated channels. The decrease in binding affinity for TTX and STX in low-affinity subtypes is due to a 3-9-fold decrease in the association rate constant and a 4-8-fold increase in the dissociation rate constant. For a series of STX derivatives, the association rate constant for toxin binding is approximately an exponential function of net toxin charge in membranes of neutral lipids, implying that there is a negative surface potential due to fixed negative charges in the vicinity of the toxin receptor. The magnitude of this surface potential (-35 to -43 mV at 0.2 M NaCl) is similar for both high- and low-affinity subtypes, suggesting that the lower association rate of toxin binding to toxin-insensitive subtypes is not due to decreased surface charge but rather to a slower protein conformational step. The increased rates of toxin dissociation from insensitive subtypes can be attributed to the loss of a few specific bonding interactions in the binding site such as loss of a hydrogen bond with the N-1 hydroxyl group of neosaxitoxin, which contributes about 1 kcal/mol of intrinsic binding energy.

Animals↗
PubMed1982

Thiamine, riboflavin and pyridoxine deficiency in psychiatric in-patients.

One hundred and seventy-two successive admissions to a district general hospital psychiatric unit were examined. Routine psychiatric, drug and dietary histories were taken and signs of avitaminosis B specifically noted. Red cell transketolase (for thiamine deficiency), glutathione reductase (for riboflavin deficiency) and aspartate transaminase (for pyridoxine deficiency) were measured. Of the patients, 53 per cent were deficient in at least one vitamin, 12 per cent in more than one (30 per cent in thiamine, 27 per cent in riboflavin and 9 per cent in pyridoxine). Schizophrenics and alcoholics were significantly over-represent in those patients low in thiamine and in more than one vitamin. Patients with an affective disorder had low riboflavin and low pyridoxine. It is suggested that affective changes are characteristic of riboflavin and pyridoxine deficiency.

Aspartate Aminotransferases↗
PubMed1980

Systemic lupus erythematosus presenting as morbid jealousy.

A patient fulfilling the diagnostic criteria for systemic lupus erythematosus and presenting with morbid jealousy is described. There was evidence of cerebral lupus. Her physical and mental symptoms responded to a combination of chlorpromazine and steroids. The morbid mental process was probably caused by her physical condition while the content of her disordered thought and behaviour was determined by her introverted premorbid personality, religiosity, unhappy childhood experiences and frustrated desire for children.

Brain Diseases↗
PubMed1978

Two-tone suppression in auditory nerve of the cat: rate-intensity and temporal analyses.

Responses to two-tone stimuli were recorded from auditory-nerve fibers in anesthetized cats. One tone, the suppressor, was set at a frequency above characteristic frequency and was fixed in intensity. A second tone was set at an excitatory frequency and was varied in intensity. The suppressor tone, when set at a sufficient level, always reduced the response to the excitatory tone by an amount equivalent to a fixed number of decibels, regardless of the excitatory tone's intensity. Estimates of suppression magnitude were derived from shifts in rate-intensity function obtained when the suppressor tone was present relative to the functions obtained for the excitatory tone alone. When suppressor-tone intensity was increased, suppression magnitude likewise increased. When the two tones were increasingly separated in frequency, either by varying the excitor or by varying the suppressor, suppression magnitude decreased monotonically. Suppression behaved in the same manner regardless of whether suppresor tone was excitatory or nonexcitatory. When frequency separation was small enough and when both tones were above the neuron's characteristic frequency, responses synchronized to low-order combination tones could be elicited. These responses usually possessed different rate-intensity characteristics and resulted in estimates of suppression magnitude which were spuriously low. When frequency separation is normalized with regard to position of traveling wave maxima within the cochlear duct, the magnitude of two-tone suppression for a given suppressor-tone intensity is seen to be frequency independent.

Acoustic Stimulation↗
PubMedDate not supplied

A time series aggregation model for predicting the incidence of syphilis.

The incidence of infectious syphilis is much different from the number of reported cases in any given year; therefore, an estimate of the incidence is needed to formulate effective control programs for the future. A time series aggregation model that predicts the incidence of syphilis was developed. The model accounts for the number of treated but unreported cases, and it provides estimates of incidence for different age and racial groups. As an illustration the model was applied for estimation of the incidence of syphilis in the city of Chicago, Illinois. A sensitivity analysis revealed that a 10% variation in input parameters would cause an error of smaller than or equal to 4.1% in the estimates of incidence.

Age Factors↗