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Biomedical subjects

A Anand

Publications and source records attributed to A Anand.

At least 19 recordsLinked to original sources
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

Association analysis of CAG repeats at the KCNN3 locus in Indian patients with bipolar disorder and schizophrenia.

Bipolar affective disorder and schizophrenia are severe behavioral disorders with a lifetime risk of approximately 1% in the population worldwide. There is evidence that these diseases may manifest the phenomenon of anticipation similar to that seen in diseases caused by trinucleotide repeat expansions. A recent report has implicated a potassium channel-coding gene, KCNN3, which contains a polymorphic CAG repeat in its coding region, in schizophrenia and bipolar disorder. We have tried to confirm these findings in Indian patients suffering from bipolar disorder and schizophrenia. No statistically significant evidence for the presence of an excess of longer alleles in the patient population, as compared to ethnically matched controls, was found. However, an analysis of the difference of allele sizes revealed a significantly greater number of patients with schizophrenia having differences of allele sizes > or = 5 when compared to normal controls. This finding may be of functional significance as the KCNN3 protein is thought to act as a tetramer, and a large difference in allele sizes would result in an asymmetric molecule with a different number of glutamine residues in each monomer. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:744-748, 2000.

Adult↗
PubMed2000

Antidepressant effects of ketamine in depressed patients.

BACKGROUND: A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression. METHODS: Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions. RESULTS: Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 +/- SD 10 points vs. 0 +/- 12 points, respectively during active and sham treatment). CONCLUSIONS: These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.

Adult↗
PubMed2000

Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists.

BACKGROUND: The cognitive, behavioral, and mood effects of N-methyl-D-aspartate (NMDA) receptor antagonists, such as phencyclidine and ketamine, have been used to study the effects of NMDA receptor dysfunction. Pharmacological modulation of the effects of NMDA receptor antagonists, such as ketamine, may lead to development of novel therapeutic agents for psychiatric illnesses such as schizophrenia. Preclinical studies indicate that some ketamine effects may be mediated through increased glutamate release. In this study, we tested the hypothesis that lamotrigine, a drug reported to inhibit glutamate release, will reduce the neuropsychiatric effects of ketamine in humans. METHOD: Healthy subjects (n = 16) completed 4 test days involving the administration of lamotrigine, 300 mg by mouth, or placebo 2 hours prior to administration of ketamine (0.26 mg/kg by intravenous bolus and 0.65 mg/kg per hour by intravenous infusion) or placebo in a randomized order under double-blind conditions. Behavioral and cognitive assessments were performed at baseline and after administration of the medications. RESULTS: Lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001); positive symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale positive symptoms subscale (P<.001); negative symptoms as assessed by the Brief Psychiatric Rating Scale negative symptoms subscale (P<.05); and learning and memory impairment as assessed by the Hopkins Verbal Learning Test (P<.05). However, lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05). CONCLUSIONS: Glutamate release-inhibiting drugs may reduce the hyperglutamatergic consequences of NMDA receptor dysfunction implicated in the pathophysiologic processes of neuropsychiatric illnesses such as schizophrenia. Further study is needed.

Adult↗
PubMed2000

The present status of the mechanical hypothesis for chemoreceptor stimulation.

Reasons are given to show why the transmitter based hypothesis for the stimulation of chemoreceptors needs to be reviewed. On the other hand evidence is presented to show that chemoreceptors can be stimulated by various mechanical stimuli and how the local PO2 can be sensed by the type II cell which by getting mechanically deformed causes this cell to shrink. This shrinkage is transmitted to the generator region of the nerve terminal thereby leading to the production of propagated impulses at the regenerative region thus making the whole process of generation of information about the local PO2, similar to the generation of sensory information by other sensory receptors.

Animals↗
PubMed2000

Influence of bronchial C fibre receptors on respiration in cats: possible role in humans.

In order to find out whether the bronchial C fibre receptors influence respiration in cats, as the J receptors do, two drugs known to stimulate them consistently, i.e. phenyl diguanide (PDG) and capsaicin were injected into the left atrium (LA). The influence of these drugs, in suprathreshold doses, was seen on the intrapleural pressure (IPP), frequency of respiration (f(R)), systemic blood pressure (BP) and cardiac frequency (f(H)). PDG LA produced an inhibitory influence on respiration of a majority of cats, accompanied by a fall in BP and f(H). With capsaicin, a stimulation of respiration and a notable increase in BP (sometimes preceded by a fall also of f(H)) was seen. After blocking the epicardial/cardiac receptors with xylocaine, a local anaesthetic, the effects of PDG LA on the above variables were blocked, whereas, those of capsaicin survived--which they did, also after a bilateral vagotomy. Similar responses were obtained from injecting the drugs into the distal part of the aorta i.e. a notable stimulation of respiration by capsaicin, which survived vagotomy and hardly any effect, by PDG. It is concluded that activation of bronchial C fibre receptors does not influence respiration or BP in cats.

Anesthetics, Local↗
PubMed2000

In vivo modulation of Hmgic reduces obesity.

The HMGI family of proteins consists of three members, HMGIC, HMGI and HMGI(Y), that function as architectural factors and are essential components of the enhancesome. HMGIC is predominantly expressed in proliferating, undifferentiated mesenchymal cells and is not detected in adult tissues. It is disrupted and misexpressed in a number of mesenchymal tumour cell types, including fat-cell tumours (lipomas). In addition Hmgic-/- mice have a deficiency in fat tissue. To study its role in adipogenesis and obesity, we examined Hmgic expression in the adipose tissue of adult, obese mice. Mice with a partial or complete deficiency of Hmgic resisted diet-induced obesity. Disruption of Hmgic caused a reduction in the obesity induced by leptin deficiency (Lepob/Lepob) in a gene-dose-dependent manner. Our studies implicate a role for HMGIC in fat-cell proliferation, indicating that it may be an adipose-specific target for the treatment of obesity.

Adipose Tissue↗