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Biomedical subjects

S Anand

Publications and source records attributed to S Anand.

At least 91 records · Page 5Linked to original sources
PubMed1993

Phase I clinical trial of an injectable contraceptive for the male.

Earlier studies on the rat and the monkey had demonstrated that an injection of styrene maleic anhydride (SMA) in a solvent vehicle of dimethyl sulphoxide (DMSO) into the lumen of the vas deferens is toxicologically safe and has contraceptive action. Phase I clinical trial was therefore undertaken on 38 male volunteers giving varying doses of SMA, ranging between 5 mg and 140 mg, into each vas deferens. A dose of 70 mg is the predicted therapeutic dose based on animal data. That the compound is within the vas deferens lumen during the period of the safety assessment is inferred from the effect on the spermatozoa count in ejaculates which reach azoospermic levels in the higher dose ranges. The treatment is well tolerated with only minimal side effects in a few cases and no long-term adverse effects.

Adult↗
PubMed1993

Inner clot diffusion and permeation during fibrinolysis.

A model of fibrinolysis was developed using multicomponent convection-diffusion equations with homogeneous reaction and heterogeneous adsorption and reaction. Fibrin is the dissolving stationary phase and plasminogen, tissue plasminogen activator (tPA), urokinase (uPA), and plasmin are the soluble mobile species. The model is based on an accurate molecular description of the fibrin fiber and protofibril structure and contains no adjustable parameters and one phenomenological parameter estimated from experiment. The model can predict lysis fronts moving across fibrin clots (fine or coarse fibers) of various densities under different administration regimes using uPA and tPA. We predict that pressure-driven permeation is the major mode of transport that allows for kinetically significant thrombolysis during clinical situations. Without permeation, clot lysis would be severely diffusion limited and would require hundreds of minutes. Adsorption of tPA to fibrin under conditions of permeation was a nonequilibrium process that tended to front load clots with tPA. Protein engineering efforts to design optimal thrombolytics will likely be affected by the permeation processes that occur during thrombolysis.

Animals↗
PubMed1993

Intracranial compensatory mechanisms for volume perturbations: a theoretical analysis.

The proposed mathematical formulation accounts for the role of the absorption and production mechanisms of the intracranial cavity. The transport barrier conduction is governed by the pressure gradients across them and hence by the instantaneous flow rates. The above mentioned mechanisms have now been incorporated into a previous model for static changes in the cranial cavity. The integrated model now evolved is simulated for a constant, bolus and sinusoidal infusion. The output has been correlated to experimentally observed trends. The results that emerge, point to a system whose response is sensitive to the nature of CSF volume perturbations. The production and absorption mechanisms function in a relay configuration, whose primary objective is to maintain the base line CSF pressure values when deviations in pressure occur. These mechanisms have a finite activation time which is dependent on the nature of the volume variation.

Absorption↗
PubMed1993

Alternating prism exposure causes dual adaptation and generalization to a novel displacement.

In two experiments, we examined the hypothesis that repeatedly adapting and readapting to two mutually conflicting sensory environments fosters the development of a separate adaptation to each situation (dual adaptation) as well as an increased ability to adapt to a novel displacement (adaptive generalization). In the preliminary study, subjects alternated between adapting their visuomotor coordination to 30-diopter prismatic displacement and readapting to normal vision. Dual adaptation was observed by the end of 10 alternation cycles. However, an unconfounded test of adaptive generalization was prevented by an unexpected prism-adaptive shift in preexposure baselines for the dual-adapted subjects. In the primary experiment, the subjects adapted and readapted to opposite 15-diopter displacements for a total of 12 cycles. Both dual adaptation and adaptive generalization to a 30-diopter displacement were obtained. These findings may be understood in terms of serial reversal learning and "learning to learn."

Adaptation, Psychological↗
PubMed1993

Hemophilia B carrier determination based on family-specific mutation detection by DNA single-strand conformation analysis.

Single-strand conformation (SSC) analysis can distinguish normal from variant DNA fragments containing single point mutations by conformation-induced electrophoretic mobility shifts in non-denaturing polyacrylamide gels. We studied 25 hemophilia B kindreds by using SSC analysis after polymerase chain reaction (PCR) amplification of the eight factor IX exons and their intron boundaries. Variant SSC fragments were unambiguously identified in 24 kindreds, and direct DNA sequencing of variant PCR fragments identified 20 different hemophilia B mutations. This technique was used for rapid and accurate carrier determination in female family members without the need for additional sequencing studies, because carriers have both normal and hemophilia family-specific SSC fragments. Of 25 obligate carriers from 15 kindreds, 24 were confirmed to carry variant fragments. The exception, a patient's daughter homozygous for the normal allele, was demonstrated by subsequent PCR genotyping to be the result of non-paternity. In the additional 32 at-risk females from 16 kindreds studied, 19 were identified as carriers and 13 as non-carriers. Eleven of the unique mutations affected restriction enzyme digestion sites, and carriers could then be identified by appropriate restriction enzyme digestion of amplified DNA. Our study, with hemophilia B as a model system, demonstrates the accuracy and efficiency of SSC analysis in screening and tracking unknown mutations in monogenic inherited disorders with known gene sequences.

Base Sequence↗
PubMed1992

Cerebral venous system mechanics during a constant infusion in subarachanoid space: a model study.

A model has been developed to explain the development of stress under a constant infusion of fluid into the subarachanoid space. When the regulatory mechanism operates, the infused fluid is accommodated by the venous system and hence the tissue 'give' mechanism is under minimal stress. The necessity of maintaining a constant blood flow causes the blood vessel to dilate at higher CSF pressures. This puts the tissue 'give' mechanism under dual pressures, since it has to make room for the expanding ventricle as well as the dilating venous system. The theoretical model developed has been validated by experimental observations.

Animals↗
PubMed1992

Computer as a group teaching aid for persons who are blind.

A concept has been formulated whereby a teacher in a classroom for students who are blind can communicate line diagrams and text directly to the students. This approach is based upon a single computer placed on the teacher's desk, with monitors on the students' desks. Access to the information displayed on the monitors is obtained by means of an optoelectronic sensor and vibrotactile output. Two versions of the sensor have been made--one for sensing line diagrams, and the other for Braille text. A simple, low-cost arrangement has also been designed by which students who are blind can prepare a hard copy of the diagrams from the monitor display. The special feature of the system is that it allows the teacher to convey information directly to the students, that is, diagrams and text that have been entered into the computer while the students are in the classroom. Information previously stored on floppy disks may also be communicated in this way. This methodology will overcome the current limitation where the teacher is able to hand out only embossed diagrams and text that have been previously prepared. Learning to use the new system can be accomplished in a short time, with the added advantage that the system is relatively inexpensive.

Blindness↗
PubMed1992

Hemophilia A carrier detection by restriction fragment length polymorphism analysis and discriminant analysis based on ELISA of factor VIII and vWf.

We performed carrier determination on female subjects from 32 hemophilia A kindreds with a combination of restriction fragment length polymorphism analysis and discriminant analysis of factor VIII antigen and von Willebrand factor antigen analyzed by enzyme-linked immunosorbent assay. Subjects included 25 obligate carriers, 30 at-risk female subjects from 19 kindreds each with two or more male subjects, with hemophilia and 28 at-risk female subjects from 13 kindreds each with a single sporadic case. Deoxyribonucleic acid (DNA) analysis with factor VIII intragenic probes clarified the carrier status of 15 female subjects, and extragenic probes classified an additional 14. Discriminant analysis, which identified 24 of 25 (96%) obligate carriers with carrier probabilities greater than or equal to 0.71 and 37 of 39 (95.0%) normal female subjects with probabilities less than or equal to 0.30, was useful for clarifying the carrier status of the female subjects who were not helped by DNA analysis and those that were classified by extragenic probes alone. Twenty-nine female subjects could not be categorized by restriction fragment length polymorphism analysis because DNA was unavailable from the subject or from key family members, key female subjects were noninformative, or carriership could not be excluded by restriction fragment length polymorphism in kindreds with sporadic cases. We studied 28 of these female subjects by discriminant analysis; 15 had carrier probabilities of greater than or equal to 0.71, 12 less than or equal to 0.30, and 1 = 0.35. All carriers by extragenic probes had carrier probability values greater than or equal to 0.71, whereas all noncarriers had values less than or equal to 0.30. In some families, particularly those in which gonadal mosaicism was a possibility, extensive family studies together with DNA and discriminant analyses were required for clarifying the source of the mutation, and hence the carrier status of the at-risk female subjects. Thus DNA and discriminant analyses complement each other, and when combined with careful pedigree analysis, the power of carrier determination is increased in some families.

DNA↗
PubMed1992

Genetic probing of the yeast plasma membrane H(+)-ATPase.

The H(+)-ATPase from Saccharomyces cerevisiae has been probed by a random genetic approach that has led to the isolation of primary and secondary site mutations. These H(+)-ATPase (PMA1) mutants help define specific functional, as well as interacting, regions of the H(+)-ATPase. Cellular resistance to hygromycin B has been an important selection tool for the isolation of pmal mutants. One prominent hygromycin B-resistant mutant, pmal-105, was found to have a S368F mutation near the site of phosphorylation (D378) in the catalytic core. This mutation prevents growth in low pH or NH(4+)-containing medium and induces an acid-sensitive Vmax for ATP hydrolysis, as well as a pronounced insensitivity to vanadate. The prominent cellular and biochemical phenotypes of this strain facilitated a detailed revertant analysis to identify protein structure domains that interact directly or indirectly with the localized region defined by the F368 mutation. Partial revertants were isolated which were resistant to low pH or NH4+ but retained hygromycin resistance. Second site mutations were found within the first and second cytoplasmic loop domains, as well as in transmembrane segments 1-3 & 7. All of the revertant enzymes have a stable Vmax but some show changes in the pH optimum for ATP hydrolysis; all display vanadate sensitivities ranging between the insensitive F368 mutant and the fully-sensitive wild type enzyme. Revertant analyses have also been performed on two other pma1 mutants which carry the mutations A135V and G158D in transmembrane segments 1 and 2, respectively. Compensating second site mutations to these mutations were identified in transmembrane segments 1, 2, 4 & 7, as well as within the central catalytic domain. These analyses have helped identify interacting protein structure domains that may participate in coupling ATP hydrolysis to proton transport. Furthermore, they facilitate the construction of structural models to account for these interactions.

Cell Membrane↗
PubMed1990

Time-controlled injectable occlusion of the vas deferens.

An injectable method of obtaining vas deferens occlusion is presented. The agent used is styrene maleic anhydride (SMA) with dimethyl sulphoxide as the solvent. The special feature of the approach is that after a period of time, spermatozoa passage is spontaneously reestablished. By varying the dose of SMA administered, the interval between injection and restoration of spermatozoa flow can be regulated from as short a period as about 3 months to more than five years.

Animals↗
PubMed1989

Rise in intracellular pH is concurrent with 'start' progression of Saccharomyces cerevisiae.

Intracellular pH (pHi) was determined during arrest and recovery of temperature sensitive-cell division cycle mutants of Saccharomyces cerevisiae. In all mutants, pHi decreased during arrest; but when the mutants were released from arrest a rapid increase in pHi ensued in only cdc28- and cdc37-arrested cells. Both of these mutations cause arrest at 'start', the sole regulatory point in the S. cerevisiae cell cycle. In cells with cdc4 or cdc7 mutations, which arrest past start, pHi remained constant and exhibited a decrease, respectively, upon recovery of growth. The activity of plasma membrane ATPase decreased during the first 30 min of recovery of cdc28-arrested cells, concomitant with the rise in pHi. During the same period, there was no significant change in activity in cdc4-bearing cells, whereas an increase was observed for cdc7-bearing cells. Increase in pHi may be used as a specific signal by S. cerevisiae for start traversal and commitment to a new cycle.

Cell Cycle↗
PubMed1989

Study of the inhibitory effect of lead acetate on duodenal contractility in rat.

1. Abdominal colic and constipation are symptoms of lead poisoning in man, but mechanisms of these effects are not yet fully understood. In this study the effect of lead acetate on contractility of rat duodenum was determined in vivo in 70 rats. 2. Rats were orally dosed with 44 mg/kg per day lead as 53 mmol/L lead acetate, for 4 weeks. Motility of the duodenum was recorded with an electrical impedance probe. 3. A significant decrease in the amplitude of contraction waves in case of treated rats was observed compared with controls which received an equal volume of saline. The number of contractions increased from 26 per min in controls to 33 per min in treated rats. Gastrointestinal transit rate decreased by 64% and 69% after 9 and 15 days of lead exposure, respectively.

Animals↗
PubMed1989

A new stretcher design for easy manoeuvreability on narrow staircases and rough ground for developing countries.

Rough terrains with obstacles, narrow staircases and inadequate space to position the ambulance conveniently in relation to the exit door of houses, often encountered in developing countries like India, make it difficult if not impossible to carry patients using conventional stretchers. A novel two-wheeled stretcher to overcome the limitations has been designed, fabricated and tested for a decade. The special features allow even one stretcher operator to transport a patient over all types of ground, down staircases with landings so small as not to provide space for a regular stretcher to turn into and out from the ambulance. This wide range of facilities has been obtained by incorporating very simple and low-cost devices such as a metal guard over two wheels, friction belts and an ergonomically designed tie bar system. Usage in handling various medical and surgical emergency cases has proven the efficacy and acceptability of the design.

Ambulances↗