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Biomedical subjects

A Anand

Publications and source records attributed to A Anand.

At least 37 records · Page 2Linked to original sources

Optical and magnetic properties of manganese-doped zinc sulfide nanoclusters.

We report the synthesis of fixed-size ZnS nanoclusters approximately 24 A in diameter with varying manganese concentrations. Various samples of Zn1-x MnxS, with x = 0, 0.02, 0.055, 0.09, and 0.13, have been prepared and characterized using X-ray diffraction, energy-dispersive analysis of X-rays, UV absorption, fluorescence emission and excitation, electron paramagnetic resonance (EPR), and magnetic susceptibility measurements. The manganese ions are found to substitute Zn randomly without giving rise to any clustering of Mn sites, as seen from EPR and magnetic susceptibility results. Our studies reveal that the band gap of the doped nanoclusters passes through a maximum as the manganese concentration is varied. Also, we observe orange emission from Mn2+ ions in the doped ZnS nanoclusters, apart from the blue emission characteristic of the ZnS defect states. The relative intensity of the orange emission compared with the blue varies with the manganese concentration in a nonmonotonic way. The inverse of susceptibility temperature plots can be plotted onto a universal curve by simple multiplicative constants, thus showing that the magnetic interactions between Mn2+ ions are weak.

Crystallization↗

Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments.

Glutamate and gamma-amino butyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. There is increasing preclinical and clinical evidence that antidepressant drugs directly or indirectly reduce N-methyl-D-aspartate glutamate receptor function. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy also suggest that unipolar, but not bipolar, depression is associated with reductions in cortical GABA levels. Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. The preponderance of available evidence suggests that glutamatergic and GABAergic modulation may be an important property of available antidepressant and mood-stabilizing agents. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.

Antidepressive Agents↗

Common psychiatric diseases and human genetic variation.

OBJECTIVE: A better understanding of human genetic variation is important in assessing disease epidemiology and phenotypic variation, and may be critical in evaluating genetic aspects of common genetic diseases, such as schizophrenia, bipolar disease and Parkinson's. These diseases are particularly difficult to investigate as there are few peripheral markers, and although a genetic aetiology has long been suspected, robust findings have been hard to establish. METHODS: Variations in alleles at 13 tri-nucleotide gene loci expressed in the brain and implicated in several neurodegenerative diseases, as well as certain other loci, were examined in the Indian population for comparison with other major ethnic groups. RESULTS AND CONCLUSION: In the Indian population, the distribution of alleles at the Machado-Joseph disease locus was similar to the Western European pattern of distribution. Analysis of haplotypes at the locus for Huntington's disease suggested multiple origins, and possible effects of population admixture because of the recent history of the country. At other alleles of neuropsychiatric interest (dopamine receptor, serotonin receptor, serotonin transporter, alcohol dehydrogenase), allele frequencies in the Indian population differed from other populations. Interspecies comparison suggests a gradual expansion in repeat size, with the exception of the CLOCK gene, which displays a contraction of CAG repeat numbers. World-wide differences in disease phenotypes need to be explored, and an appreciation of their genetic basis may provide a window of opportunity for improving our knowledge of the underlying genetic mechanisms.

Journal Article↗

Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: production of IL-4.

Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that may affect every organ or system in the body. We have shown previously that the TCR alphabeta+ subpopulation of CD3+ CD4- CD8-, DN T cells is expanded in patients with SLE and that double negative T cells express increased levels of activation markers compared both with healthy people and with patients with rheumatoid arthritis, (RA) as autoimmune controls. The aim of this study was to characterize these cells in terms of their ability to produce IL4, a Th2 cytokine, both spontaneously and after mitogen stimulation. It was found that a higher percentage of TCR alphabeta+ double negative T cells from patients with SLE contained IL4 constitutively than did the same population of cells from healthy people or from those with RA. After mitogen stimulation, there was no significant difference in the amount of IL4 produced by each of the three groups. Further study of patients producing high levels of IL4 (about one third of the patients) indicated that they had a lower percentage of alphabeta+ T cells in the double negative compartment than did patients with fewer IL4 containing cells.

Adolescent↗

Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: activation markers.

Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and the production of autoantibodies, some of which (antibodies to dsDNA) are thought to be pathogenic. T helper cells drive the production of autoantibodies and the aim of this study is to characterize phenotypically a subpopulation of T cells (the CD3+ CD4- CD8-, double negative (DN) T cells) previously identified as helping to enhance anti-DNA antibodies in patients with SLE. Data were obtained using FACS staining of DN T cells that had been purified from PBMCs by magnetic bead separation. The percentage of TCR alphabeta+ DN T cells was found to be significantly higher in patients with SLE as compared with controls (P = 0.02), although there was no significant increase in total percentage of DN T cells, which includes TCR gammadelta+ cells. Activation markers HLA-DR and CD69, the costimulatory molecule CD28 and CTLA-4 were all expressed on the surface of a higher percentage of DN T cells in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls (HC). More DN T cells from patients with SLE were of CD45RA phenotype than was found in controls, while CD45RO-expressing cells were reduced. In addition, DN T cells from patients with SLE expressed significantly higher levels of HLA-DR (P = 0.006), CD28 (P = 0.05), CTLA4 (P = 0.03) and CD45RA (P = 0.05) on the cell surface than those from the CD4/8 population. Correlation of expression of the markers measured with various parameters of disease activity and severity showed that high levels of HLA-DR expression correlated with high circulating serum C3 (> 0.9 IU/ml), indicating that an activated phenotype is consistent with severe disease.

Abatacept↗

Isolated tuberculosis of talus without ankle and subtalar joint involvement.

This case has been reported because of its rarity and atypical clinical presentation. An 8-year-old boy presented with a gradually increasing swelling localised on the antero-medial aspect of the foot haemogram, erythrocyte sedimentation rate (ESR), Mantoux and X-ray chest were normal. An irregular lytic lesion of the talus was seen on the x-ray of the affected part. Ziehl Nelson staining of the aspirated fluid revealed acid-fast bacilli. Material obtained after curettage and bone grafting was sent for histopathological examination which confirmed the diagnosis of tuberculosis. Post operatively a below knee cast was given for 12 weeks and anti tubercular treatment was given for 20 months. At the end of the treatment patient had full and painless motion at the ankle and subtalar joint. The lytic lesion had healed on X-ray.

Ankle↗

Detection of 1583 bp gene transcript in lymphocytes of muscular dystrophy patients.

DMD and BMD are X-lined recessive disorders. RAP-PCR was utilized to investigate differentially expressed gene transcripts in lymphocytes from DMD, BMD and normal individuals as possible diagnostic parameter. A 1583 bp transcript was found to be expressed in both DMD and BMD patients which was unrelated to the known dystrophin gene. This may prove helpful in determining the carrier status of DMD/BMD.

Base Sequence↗

A clinical study of patients with genetically confirmed Huntington's disease from India.

BACKGROUND: Clinical data across the globe especially in genetic diseases like Huntington's disease (HD) is most helpful when collected using standardized formats. This helps in proper comparison of clinical and genetic data. METHODS: Herein, we report clinical data on 26 genetically confirmed HD patients from 19 Indian families predominantly from South India. Clinical data and evaluation was performed using standardized formats used by the Huntington Disease Study Group. RESULTS: Adult onset HD was commonest while Juvenile HD (onset <20 years) was observed in approximately 15% of patients. Chorea was the commonest presenting symptom (n=23, 88.5%) while remaining presented with psychiatric symptoms (n=3, 11.5%). Impairment of saccades was observed in approximately 75% of patients. Mean (SD) CAG repeats in the abnormal allele was 48.4 (8.7). Total motor score but not the total behavioral score worsens with duration of symptoms. The functional checklist score correlates with total motor score rather than with duration of symptoms. CONCLUSIONS: We detail clinical characteristics in genetically confirmed HD patients from a predominantly South Indian cohort. We observed a slightly higher occurrence of Juvenile HD. Functional disabilities in our patients correlate with worsening of motor rather than behavioral symptoms.

Adolescent↗

Changes in respiratory sensations induced by lobeline after human bilateral lung transplantation.

1. The sensations evoked by the injection of lobeline into the right antecubital vein were studied in 8 subjects after bilateral lung transplantation and 10 control subjects. In control subjects, two distinct sensations were experienced. There was an early noxious sensation (onset approximately 10 s) followed by a late sensation of breathlessness (onset approximately 26 s) associated with involuntary hyperventilation. The early sensation was accompanied by respiratory and cardiovascular changes. 2. In contrast to control subjects, the early respiratory events and the noxious sensations evoked by injections of lobeline (18-60 microg kg(-1)) did not occur in subjects with recent bilateral lung transplantation. This suggests that the early respiratory sensations are mediated by the discharge of receptors in the lungs. 3. The late hyperventilation and the accompanying sensation of breathlessness occurred in both transplant and control subjects and are therefore likely to be mediated by receptors elsewhere in the body, presumably systemic arterial chemoreceptors stimulated by lobeline. 4. In control subjects, but not transplant subjects, there was a consistent decrease in mean arterial pressure associated with the lobeline injection. This suggests that pulmonary afferents mediate the hypotension. 5. For transplant subjects studied more than a year after transplantation, there was some evidence that the noxious respiratory sensations evoked by lobeline had returned. This suggests that some functional reinnervation of pulmonary afferents may occur.

Adult↗

The polyglutamine motif is highly conserved at the Clock locus in various organisms and is not polymorphic in humans.

Circadian rhythms play a central role in diverse physiological phenomena and the recent years have witnessed the identification of a number of genes responsible for the maintenance of these rhythms. One of these is the Clock gene, which was first identified in mouse and subsequently in a large number of organisms, including humans. The human Clock gene has been proposed as a possible candidate for disorders affected by alterations of circadian rhythm, including bipolar disorder and schizophrenia. This gene contains a highly conserved polyglutamine motif, that in humans is coded for by CAG repeats. In view of the involvement of CAG repeat expansion in a number of neuro-psychiatric disorders, we have sought to determine the polymorphism status of CAG repeats at the Clock locus in humans. Our analysis of 190 unrelated individuals, who included patients suffering from bipolar disorder and schizophrenia, indicated that the repeat, which consisted of 6 CAG triplets, was not polymorphic in humans. An analysis of the repeat in non-human primates and other organisms revealed that the glutamine stretch is shortest in humans and baboons, and longest in Drosophila and zebrafish. A study of various Drosophila species revealed that the repeat number is highly polymorphic, ranging from 25 to 33 pure glutamine repeats. Unlike most other microsatellites, the CAG repeat stretch at the Clock locus in humans is smaller than its homologues in non-human primates. We propose that glutamine repeat size is functionally important in this gene and thus tightly regulated. The variation in repeat number is probably deleterious to the individual, resulting in the maintenance of a short and invariable repeat structure in the human population.

Amino Acid Sequence↗

Use of polymerase chain reaction in the diagnosis of fungal endophthalmitis.

OBJECTIVE: To evaluate the usefulness of polymerase chain reaction (PCR) compared with the conventional mycologic methods in the diagnosis of fungal endophthalmitis. DESIGN: Prospective comparative validation of diagnostic testing-case-control study. PARTICIPANTS AND CONTROLS: Thirty subjects in whom fungal endophthalmitis was suspected and 20 controls with noninfections. INTERVENTION TESTING: Collection of intraocular specimens and testing for the presence of fungus by PCR and conventional methods. MAIN OUTCOME MEASURES: Detection of fungus by microscopy, growth by culture, and fungal DNA by PCR for definitive and rapid diagnosis of fungal endophthalmitis. RESULTS: None of the controls was positive by microscopy, culture, or PCR. Among the 43 intraocular specimens from 30 subjects, 24 were positive by conventional mycologic methods and 32 were positive by PCR. PCR increased the sensitivity of detection by 18.6%, which was statistically significant (McNemar test: P = 0.039). CONCLUSIONS: PCR was a more sensitive and rapid diagnostic tool compared with the conventional mycologic methods in the diagnosis of fungal endophthalmitis.

DNA Primers↗

Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless.

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal structure, the muscle of Lawrence (MOL). A preliminary investigation of several of the mutations described here showed that the fru gene also has a sex-nonspecific vital function. The fru gene produces a complex set of transcripts through the use of four promoters and alternative splicing. Only the primary transcripts produced from the most distal (P1) promoter are sex-specifically spliced under direction of the sex-determination hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis and P-element excision, to try to gain insight into the relationship of specific transcript classes to specific fru functions. Males that lack the P1-derived fru transcripts show a complete absence of sexual behavior, but no other defects besides the loss of the MOL. Both males and females that have reduced levels of transcripts from the P3 promoter develop into adults but frequently die after failing to eclose. Analysis of the morphology and behavior of adult escapers showed that P3-encoded functions are required for the proper differentiation and eversion of imaginal discs. Furthermore, the reduction in the size of the neuromuscular junctions on abdominal muscles in these animals suggests that one of fru's sex-nonspecific functions involves general aspects of neuronal differentiation. In mutants that lack all fru transcripts as well as a small number of adjacent genes, animals die at an early pupal stage, indicating that fru's function is required only during late development. Thus, fru functions both in the sex-determination regulatory hierarchy to control male sexual behavior through sex-specific transcripts and sex-nonspecifically to control the development of imaginal discs and motorneuronal synapses during adult development through sex-nonspecific transcript classes.

Alleles↗

Nitroprusside and ECS-induced retrograde amnesia.

Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.

Amnesia, Retrograde↗

Phenylephrine and ECS-induced retrograde amnesia.

Phenylephrine is a nonselective alpha-receptor agonist. This study examined whether the administration of phenylephrine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. Adult male Wistar rats received phenylephrine (0.25 mg/kg i.p.) or saline 3 min before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after the ECS course using a passive avoidance task. Phenylephrine increased seizure duration in ECS-treated rats, and also enhanced recall in both true and sham ECS groups. The latter finding suggests that phenylephrine nonspecifically improves cognitive functions, perhaps through adrenergic mechanisms that improve memory consolidation and storage. Since phenylephrine increases blood pressure, its cognitive effects also weaken the hypothesis that ECT-induced cognitive impairment results from the seizure-related hypertensive surge.

Adrenergic alpha-Agonists↗

Peripheral vascular resistance increases after termination of obstructive apneas.

The mechanisms by which obstructive apneas produce intermittent surges in arterial pressure remain poorly defined. To determine whether termination of obstructive apneas produce peripheral vasoconstriction, we assessed forearm blood flow during and after obstructive events in sleeping patients experiencing spontaneous upper airway obstructions. In all subjects, heart rate was monitored with an electrocardiogram and blood pressure was monitored continuously with digital plethysmography. In 10 patients (protocol 1), we used forearm plethysmography to assess forearm blood flow, from which we calculated forearm vascular resistance by performing venous occlusions during and after obstructive episodes. In an additional four subjects, we used simultaneous Doppler and B-mode images of the brachial artery to measure blood velocity and arterial diameter, from which we calculated brachial flow continuously during spontaneous apneas (protocol 2). In protocol 1, forearm vascular resistance increased 71% after apnea termination (29.3 +/- 15.4 to 49.8 +/- 26.5 resistance units, P < 0.05) with all patients showing an increase in resistance. In protocol 2, brachial resistance increased at apnea termination in all subjects (219.8 +/- 22.2 to 358.3 +/- 46.1 mmHg x l(-1) x min; P = 0.01). We conclude that termination of obstructive apneas is associated with peripheral vasoconstriction.

Adult↗

Value of echocardiographic findings in predicting cardiovascular complications in infective endocarditis.

Echocardiography allows the detection of vegetations and estimation of valvular dysfunction in patients with infective endocarditis. The value of echocardiographic findings in predicting cardiac and other vascular complications in infective endocarditis is not well understood. Identification of high-risk patients and early surgery may improve their prognosis. The authors reviewed echocardiographic findings and related them to the development of congestive heart failure, systemic embolism, and the need for surgery or the risk of death without surgery in patients with infective endocarditis. There were 125 episodes of endocarditis in 114 patients (84 episodes [67%] in men) with a mean age +/- standard deviation of 37 +/- 7 years. Vegetations were detected by echocardiography on at least 1 valve in 87 episodes (70%); on the mitral valve in 36 episodes (29%); on the aortic valve in 21 episodes (17%); and on the tricuspid valve in 45 episodes (36%). Severe aortic regurgitation was present in 9 episodes (7%) and severe mitral regurgitation in 4 instances (3%). In 12 of 21 episodes (57%) of vegetations on the aortic valve compared with 15 of 104 patients (14%) without vegetations on the aortic valve (p < 0.001), and in 8 of 9 instances (89%) of severe aortic regurgitation compared with 19 of 116 episodes (16%) without severe aortic regurgitation (p<0.00001), the patients developed congestive heart failure. In 18 of 55 episodes (33%) of vegetations on the aortic/mitral valve compared with 17 of 70 episodes (25%) without vegetations on the aortic valve/mitral valve (p = NS), the patients developed systemic embolism. In 13 of 21 episodes (62%) of vegetations on the aortic valve compared with 19 of 104 episodes (19%) without vegetations on the aortic valve (p < 0.001), and in 8 of 9 episodes (89%) of severe aortic regurgitation compared with 24 of 116 episodes (21%) without severe aortic regurgitation (p < 0.00001), the patients either had surgery or died without surgery. Echocardiographic findings do not reliably predict the risk of systemic embolism in patients with infective endocarditis. Vegetations on the aortic valve and severe aortic regurgitation detected by echocardiography predict a high risk of developing congestive heart failure, and for the combined outcome of requiring surgery, or dying without surgery in infective endocarditis. Early surgery may improve the outlook for survival of these patients.

Adult↗