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Biomedical subjects

A Chaudhuri

Publications and source records attributed to A Chaudhuri.

At least 19 recordsLinked to original sources

Substrate specificity of the isoprenylated protein endoprotease.

Proteins containing a CAAX motif at their carboxyl termini are subject to isoprenylation at the cysteine residue. Proteolytic trimming of isoprenylated proteins is essential in the activation of these proteins. A microsomal endopeptidase activity has been identified which cleaves all-trans farnesylated cysteine containing tetrapeptides between the modified residue and the adjacent amino acid to liberate the modified cysteine residue and an intact tripeptide. Structure/activity studies are reported here on this endopeptidase activity which are consistent with the premise that this protease is identical to the one normally involved in the cellular isoprenylation pathway. The protease only processes peptides which possess an isoprenyl moiety. Within the isoprenyl series, the enzyme hydrolyzes all-trans-farnesyl-, all-trans-geranylgeranyl-, and geranyl-containing peptides. The protease also recognizes the AAX sequence, because the protease behaves either stereospecifically or stereoselectively with respect to the individual amino acids of the tripeptide. The enzyme only measurably hydrolyzes isoprenylated peptides possessing L-amino acids at C and A. On the other hand, there is a small but measurable hydrolysis of isoprenylated peptides containing a D-amino acid at X.

Amino Acid Sequence

Heterochromatic Fusion Nystagmus: its use in estimating chromatic equiluminance in humans and monkeys.

The use of chromatic patterns that are equated for luminance has become increasingly popular in psychophysical and neurophysiological studies of visual processing. The currently available techniques for equating different colors for brightness rely upon human reports of perceptual events that are reduced at some luminance ratio. We report here the results of a study using a technique we have recently developed that produces a vivid and compelling motion percept only at isoluminance. That is, unlike previous methods, this technique relies upon a perceptual event (motion) that actually becomes more salient at isoluminance. We also observed that the optokinesis generated by the moving pattern mirrors the perceptual reports at all luminance ratios. If used in this manner, the technique can provide an estimate of chromatic isoluminance in a variety of species and can be used to corroborate a human subject's perceptual experience.

Animals

The inequality of medical expenditures for several years in a healthy, nonelderly population.

Previous studies have shown that the distribution of annual medical expenditures for a population is very unequal and remains so for periods of more than 1 year. The authors use a better measure of inequality, the Gini coefficient, to test its persistence for longer periods. This measure is applied to data collected from the Rand Health Insurance Experiment. The experiment enrolled a nonelderly population typical of those covered by employer health plans for periods up to 5 years. The distributions of annual expenditures for this population are highly unequal, in line with previous studies. Inequality declines substantially when longer periods are considered.

Adolescent

Hypothermia due to transient hypothalamic dysfunction in tuberculous meningitis with hydrocephalus.

We report two patients with tuberculous meningitis and hydrocephalus who developed hypothermia that reversed after inserting a ventricular shunt for the hydrocephalus. Pressure on the thermoregulatory centre in the posterior hypothalamus near the dilated third ventricle might have been responsible. One patient developed hypotension during the transient hypothermia, which persisted and proved fatal.

Adult

Influence of admission weight on neonatal mortality amongst hospitalised neonates in Calcutta.

The study was conducted on 785 neonates aged up to 28 days to evaluate the influence of admission weight on mortality. It was observed that there were 200 (25.5%) cases of septicaemia, 134(17.1%) of diarrhoea, 120(15.3%) each of prematurity related conditions and neonatal jaundice, 117(14.9%) of respiratory diseases and 94 (11.9%) cases of convulsion. There were total 182(23.18%) deaths comprising 70(38.5%) from prematurity related conditions, 40(22%) from diarrhoea, 35(19.2%) from respiratory diseases, 26(14.3%) from septicaemia, 8(4.4%) from neonatal jaundice and 3(1.6%) deaths from convulsion. The incidence of deaths among neonates weighing less than 2500 g on admission was 59.2% in diarrhoeal diseases, 53.4% in respiratory diseases and 44.6% in other conditions compared to those of 10%, 8.2% and 7.1% respectively in neonates having admission weight more than 2500 g. The findings are statistically significant. The results of the study indicate that low admission weight should be considered as a predictor of mortality among neonates.

Body Weight

Therapeutic guidelines for congenital complete heart block presenting in pregnancy.

Congenital complete heart block presenting for the first time in pregnancy is a therapeutic challenge. Most of the reports are from an era when pacemaker therapy was in its infancy. Although isolated case reports have appeared, there are no definite guidelines for the management of such patients. We describe three cases of congenital complete heart block presenting in pregnancy. All the patients delivered normally with temporary pacing support during labor. Two of the three women remained symptomatic during the postpartum period when they were being weaned off the pacing support, so they were discharged with permanent pacemaker implantation. The third woman remained symptom-free during pregnancy, labor, and the postpartum period and was discharged without a permanent pacemaker; she is being followed with routine and 24-hour ambulatory electrocardiography. We review the literature in an attempt to formulate a therapeutic policy for such patients.

Adult

Autocrine effects of fibroblast growth factor in repair of radiation damage in endothelial cells.

The study demonstrates that basic fibroblast growth factor (bFGF) serves as an inducer of radiation damage repair in bovine aortic endothelial cells (BAEC). Radiation dose-survival curves were generated with plateau-phase BAEC using culture dishes precoated with HR9-bFGF/extracellular matrix (ECM) for the postradiation colony formation assay. This natural basement membrane-like ECM is enriched with ECM-bound bFGF. Under these conditions the cells exhibited increased repair of radiation damage as compared to cells plated on top of the bFGF-free isotype of this extracellular matrix (the HR9/ECM). While the slopes of the curves did not differ significantly (Do 107 +/- 6.8 cGy on the HR9/ECM, compared to 112 +/- 1.3 cGy on the HR9-bFGF/ECM), there was a nearly complete elimination of the threshold shoulder in the curves generated on the bFGF-free HR9/ECM (Dq 29 +/- 19 cGy, compared to 174 +/- 22 cGy on the HR9-bFGF/ECM; P less than 0.05). Delayed plating experiments, in which the cells were irradiated under bFGF-free conditions (while adherent as contact-inhibited monolayers to the HR9/ECM in bFGF-free medium) and maintained after irradiation in the same culture for various periods of time, showed that the cells performed repair of potentially lethal damage (PLDR) and restored clonogenic ability, with a 24 h to immediate postradiation recovery ratio of 3.27. This expression of PLDR was inhibited by neutralizing monoclonal antibodies against bFGF, indicating that the irradiated cells secreted bFGF into their conditioned medium. Northern blot hybridization showed a 5.6-fold increase of the 3.7-kilobase species and a 4.7-fold increase of the 7.0-kilobase species of the bFGF-specific mRNA within 6 h after delivery of a single dose of 400 cGy. The data suggest that radiation induces a complete cycle of an autoregulated damage-repair pathway in BAEC, initiated by radiation-induced damage to cellular DNA and followed by stimulation of bFGF synthesis and its secretion into the medium. The newly synthesized bFGF stimulates the PLDR pathway, acting via an extracellular autocrine loop (inhibitable by specific anti-bFGF antibodies), leading to recovery of cells from radiation lesions and restoration of their clonogenic capacity.

Animals

Pursuit afternystagmus asymmetry in humans.

It is known that prolonged unidirectional motion of a large field induces a reflexive drift of the eyes in the same direction when the stimulus is turned off. The phenomenon, which is called optokinetic afternystagmus, is known to be stronger after upward than downward stimulus motion. It is now reported that a similar anisotropy exists in the afternystagmus associated with the smooth pursuit system (PAN). The speed of the PAN reflexive drift was found to be greater following upward tracking at all times tested during a 15 s interval when compared to the values following downward tracking. A psychophysical measure of illusory motion, presumed to be generated by suppression of PAN in order to maintain fixation upon a stationary target, also showed a significantly greater amplitude and duration for the upward direction. If the directional asymmetry is a property of a velocity integrator that is believed to generate the afternystagmus, then the results are compatible with the existence of a common integrator for both optokinetic and pursuit systems.

Eye Movements

Eye movements and the motion aftereffect: alternatives to the induced motion hypothesis.

It has been previously reported that prolonged unidirectional smooth pursuit often produces a negative motion aftereffect (MAE). This was believed to be caused by retinal image motion of stationary environmental contours during pursuit which subsequently produced a primary motion aftereffect in the tracking direction. The peripheral MAE then induced motion in the stationary tracking target resulting in illusory movement in the opposite direction. We have found that a negative MAE is also produced when the adapting field is devoid of any contours. Furthermore, the presence of a moving textured background in conjunction with smooth pursuit produced an MAE whose direction was inconsistent with the induced motion hypothesis. Since all examples of motion aftereffects in this study were associated with the pursuit aspect of the experiment rather than any interactions with background contours, it was proposed that the illusory motion had an oculomotor determinant. A scheme was tentatively outlined in which fixation suppression of an unregistered ocular drift following prolonged pursuit adaptation (pursuit after-nystagmus) produced the post-adaptive motion illusions.

Figural Aftereffect

Metastable motion anisotropy.

The phenomenon of apparent motion can arise when two spatially separated visual tokens are presented in temporal sequence. If tokens at opposite corners of a hypothetical square are presented simultaneously followed by simultaneous presentation of tokens at the remaining two corners, an apparent motion percept may occur along either the vertical or horizontal axis. The display is perceptually metastable since most observers will perceive motion along only one axis at a time. The metastable display, however, produces anisotropic results, in that with central fixation, vertical motion is seen more frequently than horizontal motion. The ratio of the vertical to horizontal length of the sides of a rectangle needed to achieve equal frequencies of motion judgments along the respective axes falls in the range of 1.18-1.92 for different observers in our experiments. It appears that signal transmission across the vertical midline is a major determinant of the vertical bias, since the anisotropic effects disappear when the fixation point is sufficiently offset along the horizontal meridian so as to cause a fully homonymous representation of all of the metastable tokens. One of the factors may be signal degradation or delay in callosal transmission which could reduce the strength of the motion signal along the horizontal axis. In addition, there appears to be a strip along the vertical midline with a width of 30-50 min arc within which reduced levels of anisotropy are found. The possibility that this strip is a consequence of a zone of naso-temporal overlap in the projection of the retina to the brain along the vertical meridian will be discussed.

Anisotropy

Evolution of messenger RNA structure and regulation in the genus Mus: the androgen-inducible RP2 mRNAs.

The RP2 gene is one of several genes that are regulated by androgens in the mouse kidney. Previous studies have demonstrated that androgen inducibility of RP2 transcription varies among species within the genus Mus, indicating extensive evolutionary modification of the participating regulatory elements. Thus, while a five-fold induction of transcription occurs in M. domesticus, none is detectable in M. hortulanus or M. caroli. In the present paper, we have sequenced cDNAs representing the RP2 mRNAs of M. caroli and M. saxicola and have compared them with each other and with M. domesticus. Several findings from the sequence comparisons indicate that the encoded 41-kD polypeptide is physiologically functional. First, divergence within noncoding regions of the mRNAs exceeds that within coding regions. Second, the 357-codon open reading frame has been maintained among the species, with approximately 90% of the amino acid replacements being conservative. Finally, substitution rates at synonymous sites within the coding regions are from twofold to threefold greater than those at nonsynonymous sites. The genetic elements responsible for variations in RP2 inducibility among species were studied by cis/trans analyses of mice heterozygous for RP2 alleles, using a primer extension assay to measure expression of species-specific mRNAs. The results show that the absence of transcriptional induction in M. hortulanus is due to a cis-acting genetic element, while that in M. caroli is due to a trans-acting element. Thus, the androgen-resistant RP2 phenotypes of these two species derive from distinct genetic events.

Animals

Changes in the testicular acid and alkaline phosphatase activities at different durations following prostatectomy: a correlative study with spermatogenesis.

The purpose of this investigation was to make a correlative study between spermatogenesis and testicular acid and alkaline phosphatase activities in mature prostatectomized animals at different post-operative periods. The results demonstrate that there was a significant augmentation in the activity of testicular acid and alkaline phosphatases subsequent to 14 and 21 days of prostatectomy. A parallel quantitative study of spermatogenesis at stage VII of the seminiferous cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), mid-pachytene spermatocytes (mPSc) and step 7 spermatids (7sd), revealed that there was a significant reduction in the number of step 7 spermatids after 14 and 21 days. No change was observed in the above testicular enzymes and spermatogenesis after 7 days of prostatectomy. Therefore, it is concluded that prostatectomy can alter the above testicular enzyme activities and spermatogenesis in chronic prostatectomized state.

Acid Phosphatase

A motion illusion generated by afternystagmus suppression.

After a period of prolonged unidirectional smooth pursuit, the tracking target is seen to drift in the opposite direction when it is stopped, even though its retinal image is stationary. If, however, the tracking target is extinguished during the post-adaptive period, the eyes continue to drift in the tracking direction, a phenomenon known as pursuit afternystagmus. It is proposed that the visual system, in an effort to maintain fixation upon the target, produces a motor signal in the opposite direction in order to offset the residual afternystagmus. The perceptual registration of this efferent signal may then produce the motion illusion.

Humans

Modulation of the motion aftereffect by selective attention.

The motion aftereffect is a much studied and well documented phenomenon. After viewing a moving visual pattern for a period of time, the same pattern appears to drift in the opposite direction when it is stopped. Psychophysical experiments involving interocular transfer, dichoptic stimulation, and motion aftereffects contingent upon other visual parameters such as colour, orientation and texture, imply that the motion aftereffect is generated at the level of the visual cortex. It has been hypothesized that cortical neurons specialized for the detection of motion along a particular direction become 'fatigued' during the adaptation period so that the resting equilibrium subsequently shifts in the opposite direction to that of the adapting stimulus, giving rise to the sensation of the aftereffect. I have found that if observers are engaged in a separate discrimination task superimposed on a moving textured background, the subsequent motion aftereffect to the background is considerably reduced. It seems that motion aftereffects are susceptible to attentional mechanisms.

Adaptation, Physiological

Effects of lithium chloride on testicular steroidogenic and gametogenic functions in mature male albino rats.

The present study was undertaken to evaluate the effects of lithium, an antimanic drug, on steroidogenic and gametogenic functions of testis in the laboratory rat. Adult male rats of Wistar strain maintained under standard laboratory conditions (L:D, 14h:10h), were injected (S.C) with lithium chloride at the dose of 0.1 mg, 0.2 mg and 0.4 mg/100 g body weight/day for 21 days. All the treated animals along with the vehicle treated controls were sacrificed 24 hours after the last injections. Testicular steroidogenic activity was evaluated by measuring the activities of two steroidogenic key enzymes, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta hydroxysteroid dehydrogenase (17 beta-HSD). Gametogenic capacity was determined by counting the number of germ cells at stage VII of seminiferous cycle. Plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and testosterone (T) were measured by radioimmunoassay (RIA). Administration of lithium chloride at a dose of 0.1 mg/100 g body wt. for 21 days led to insignificant changes of plasma FSH, LH, PRL and T along with unaltered activities of testicular delta 5-3 beta-HSD, 17 beta-HSD activities and gametogenesis. In contrast, 0.2 mg of lithium treatment for 21 days causes a significant reduction of plasma FSH (P less than 0.01), LH (P less than 0.001), PRL (P less than 0.001) and T (P less than 0.001) along with inhibition of testicular delta 5-3 beta-HSD activity (P less than 0.01) and 17 beta-HSD activity (P less than 0.001). Gametogenic activity does not exhibits any significant reduction in the number of preleptotene spermatocytes (PLSc) and midpachytene spermatocytes (mPSC) while significant reduction in the number of spermatogonia A (Asg) (P less than 0.01) and Step 7 spermatids (7Sd) (P less than 0.001) were observed at stage VII of seminiferous cycle when compared to control. The degree of detrimental effects of lithium on testicular activity became more prominent at the dose of 0.4 mg/100 g body wt. The results of our experiments suggest that lithium administration might be associated with significant adverse effects on testicular activities. Furthermore, since hormonal changes and altered gametogenic activities were evident when plasma lithium concentration was below or within the therapeutic range, our data may have some potential clinical implications.

Animals

New mammalian metabolites of sparteine.

Sparteine is reportedly metabolized in mammals with the formation of an N-oxide which undergoes dehydration to delta 2 and delta 5-dehydrosparteine. In our studies male Sprague-Dawley rats were found to metabolize sparteine and alpha-isosparteine to lupanine and alpha-isolupanine respectively in vivo. Metabolic conversion of sparteine in vitro in the presence of microsomal and 9000 x g supernatant fractions of the rat liver homogenate did not produce detectable lupanine. The in vivo studies were conducted by pretreating rats with inducers and inhibitors of microsomal enzymes. Inducers did not increase levels of lupanine in the rat urine but a significant decrease was observed in the presence of the inhibitor SFK 525A. Disulfiram reduced lupanine levels in the urine. The bioconversion of sparteine to lupanine appears to be mediated by microsomal enzymes and may proceed via an aldehyde intermediate. The conversion of sparteine to lupanine may parallel the mammalian metabolism of nicotine to cotinine.

Alkaloids