Biomedical subjects

T Sharma

Publications and source records attributed to T Sharma.

At least 37 records · Page 2Linked to original sources

PubMed2001

Butyric acid induces apoptosis by up-regulating Bax expression via stimulation of the c-Jun N-terminal kinase/activation protein-1 pathway in human colon cancer cells.

BACKGROUND & AIMS: The colonic epithelial cells near the top of the crypt have been shown to undergo apoptosis. Because butyric acid (BA) is the major short-chain fatty acid produced by fermentation of dietary fiber in the large bowel, it may be an important regulator of apoptosis in colorectal cancer. We investigated which signaling pathway is triggered by BA to undergo apoptosis in human colorectal cancer cells. METHODS: Human DiFi and FET colorectal cells were treated with BA to undergo apoptosis and were assayed for activation of c-Jun N-terminal kinase (JNK), transcription factor activation protein 1 (AP1) and NF-kappaB, and the proapoptotic molecule Bax. The contribution of specific pathways was assessed by examining the effects of dominant-negative mutants of JNK/AP1 or NF-kappaB on BA-induced Bax expression and apoptosis. RESULTS: BA-mediated DNA fragmentation and Bax induction were preceded by early stimulation of JNK, and the DNA-binding activities of AP1 and NF-kappaB. BA-induced enhancement of DNA fragmentation and stimulation of Bax promoter activity were blocked by the expression of dominant-negative mutants of JNK1 or AP1 but not NF-kappaB. CONCLUSIONS: These findings suggest that apoptosis triggered by BA involves transcriptional stimulation of the Bax gene via activation of the JNK/AP1 pathway in colonic epithelial cells.

Apoptosis↗

PubMed2001

Magnetic resonance imaging of the thalamus in first-episode psychosis.

OBJECTIVE: There is some evidence of thalamic abnormalities in schizophrenia. This study investigated thalamic volumes in patients experiencing their first episode of psychosis and nonpsychotic comparison subjects. METHOD: Magnetic resonance imaging scans were obtained for 38 patients and 29 comparison subjects. Patients' symptoms were rated by research psychiatrists using the Positive and Negative Syndrome Scale. RESULTS: Thalamic volumes were smaller in patients than in comparison subjects. There were no significant correlations between thalamic volumes and symptom scores. CONCLUSIONS: Thalamic abnormalities are present close to the onset of psychosis.

Adult↗

PubMed2001

Three-dimensional mapping of gyral shape and cortical surface asymmetries in schizophrenia: gender effects.

OBJECTIVE: People with schizophrenia exhibit abnormalities in brain structure, often in the left hemisphere. Disturbed structural lateralization is controversial, however, and effects appear mediated by gender. The authors mapped differences between schizophrenic and normal subjects in gyral asymmetries, complexity, and variability across the entire cortex. METHOD: Asymmetry and shape profiles for 25 schizophrenic patients (15 men) and 28 demographically similar normal subjects (15 men) were obtained for 38 gyral regions, including the sylvian fissure and temporal and postcentral gyri, by using magnetic resonance data and a novel surface-based mesh-modeling approach. Cortical complexity was examined for sex and diagnosis effects in lobar regions. Intragroup variability was quantified and visualized to assess regional group abnormalities at the cortical surface. RESULTS: The patients showed greater variability in frontal areas than the comparison subjects. They also had significant deviations in gyral complexity asymmetry in the superior frontal cortex. In temporoparietal regions, significant gyral asymmetries were present in both groups. Sex differences were apparent in superior temporal gyral measures, and cortical complexity in inferior frontal regions was significantly greater in men. CONCLUSIONS: Cortical variability and complexity show regional abnormalities in the frontal cortex potentially specific to schizophrenia. The results indicate highly significant temporoparietal gyral asymmetries in both diagnostic groups, contrary to reports of less lateralization in schizophrenia. Substantially larger study groups are necessary to isolate smaller deviations in surface asymmetries, if present in schizophrenia, suggesting their diagnostic value is minimal.

Adult↗

PubMed2000

The 10th Biennial Winter Workshop on Schizophrenia. A report.

The 10th Biennial Winter Workshop on Schizophrenia (5-11 February 2000), organized by Drs Tim Crow and Steven Hirsch, attracted a wide range of contributions, not only from European countries, but from all across the world, encompassing clinical, neuropsychological, cognitive, experimental, pharmacological and neuroimaging approaches to enhance the understanding of possible causes, features and the treatments of this illness. The Kongresszentrum, Davos, Switzerland was once again the venue. We present a flavour of the variety of presentations, the news and the views emerging from these presentations, and discuss their implications for further advancement in the field of schizophrenia research.

Education↗

PubMed2000

Neuropsychological functioning in first-episode psychosis--evidence of specific deficits.

Neuropsychological impairment is ubiquitous in schizophrenia even at the first presentation of psychotic symptoms. We sought to elucidate the nature of the neuropsychological profile at the onset of the illness by examining the neuropsychological functioning of 40 patients experiencing their first episode of psychosis and 22 matched controls. All participants completed a battery of neuropsychological tasks designed to assess attention, verbal learning/memory, non-verbal memory, spatial ability, psychomotor speed, and executive function. First-episode patients showed significant impairment on tasks of executive function, including those requiring the ability to form and initiate a strategy, to inhibit prepotent responses, and to shift cognitive set, and also on tasks of verbal fluency. Memory impairments were seen on verbal learning and delayed non-verbal memory only. Impairment on tasks of psychomotor speed suggests that there may be a significant amount of cognitive slowing even at the first onset of psychosis. We suggest that our patients may be experiencing difficulty in specific aspects of executive functions, including the ability to form and execute a strategy, and these difficulties may be mediating the deficits observed on tasks of verbal learning.

Adolescent↗

PubMed2000

A magnetic resonance imaging study of corpus callosum size in familial schizophrenic subjects, their relatives, and normal controls.

The corpus callosum is one of several brain regions thought to be abnormal in schizophrenia. We sought to investigate whether the size of the corpus callosum would be abnormally small in schizophrenic subjects from families with familial schizophrenia and their healthy relatives. We wished to determine whether an abnormal corpus callosum size is found in healthy relatives who are genetically at a greater risk than normal of developing or transmitting the disorder. Twenty-seven familial schizophrenics, 53 of their healthy first-degree relatives, and 35 normal volunteers underwent MRI brain scans. We defined 11 of the relatives as presumed 'obligate carriers', i.e. an individual who appears to be transmitting the schizophrenic gene(s). The mid-sagittal slice of the corpus callosum and the whole brain volume were measured blind to diagnostic and family group. We found no difference between schizophrenics, their relatives, and normal controls in the mid-sagittal area of the corpus callosum. There remained no difference when the relatives were divided into two groups comprising presumed 'obligate carriers' and 'non-obligate carriers'. Adjusting for age and whole brain area made no difference to the results. Families with several schizophrenic members are not associated with abnormality in the size of the corpus callosum.

Adult↗

PubMed2000

Prepulse inhibition of the startle response in men with schizophrenia: effects of age of onset of illness, symptoms, and medication.

BACKGROUND: Prepulse inhibition of the startle reflex response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect represents an operational index of sensorimotor gating and is found to be deficient in schizophrenia. Prepulse inhibition deficits in schizophrenia seem to be partially normalized by typical antipsychotics and more fully by some atypical antipsychotics. Early onset of schizophrenia, particularly in men, has been associated with abnormal brain maturation, profound neuropsychological deficits, and less responsiveness to antipsychotic medication. We evaluated the effects of the age of onset of illness, current positive and negative symptoms, and the type of medication (typical vs atypical) on prepulse inhibition of the startle response in schizophrenia. METHODS: Thirty-eight male schizophrenic patients and 20 healthy male controls underwent testing for prepulse inhibition of the acoustic startle response. RESULTS: Earlier onset of illness was associated with reduced prepulse inhibition, while adult onset of illness was not. No significant relationships occurred between current symptoms and prepulse inhibition. Patients given typical, but not atypical, antipsychotics exhibited less prepulse inhibition compared with healthy controls. CONCLUSION: Early onset of illness is associated with profound deficits in prepulse inhibition of the startle response in men with schizophrenia.

Acoustic Stimulation↗

PubMed2000

How good is good enough in path analysis of fMRI data?

This paper is concerned with the problem of evaluating goodness-of-fit of a path analytic model to an interregional correlation matrix derived from functional magnetic resonance imaging (fMRI) data. We argue that model evaluation based on testing the null hypothesis that the correlation matrix predicted by the model equals the population correlation matrix is problematic because P values are conditional on asymptotic distributional results (which may not be valid for fMRI data acquired in less than 10 min), as well as arbitrary specification of residual variances and effective degrees of freedom in each regional fMRI time series. We introduce an alternative approach based on an algorithm for automatic identification of the best fitting model that can be found to account for the data. The algorithm starts from the null model, in which all path coefficients are zero, and iteratively unconstrains the coefficient which has the largest Lagrangian multiplier at each step until a model is identified which has maximum goodness by a parsimonious fit index. Repeating this process after bootstrapping the data generates a confidence interval for goodness-of-fit of the best model. If the goodness of the theoretically preferred model is within this confidence interval we can empirically say that the theoretical model could be the best model. This relativistic and data-based strategy for model evaluation is illustrated by analysis of functional MR images acquired from 20 normal volunteers during periodic performance (for 5 min) of a task demanding semantic decision and subvocal rehearsal. A model including unidirectional connections from frontal to parietal cortex, designed to represent sequential engagement of rehearsal and monitoring components of the articulatory loop, is found to be irrefutable by hypothesis-testing and within confidence limits for the best model that could be fitted to the data.

Adult↗

PubMed2000

Prolonged reaction time to a verbal working memory task predicts increased power of posterior parietal cortical activation.

We used multislice functional magnetic resonance imaging (fMRI) to investigate the association between behavioral and neurophysiological measures of working memory task performance in 20 right-handed male healthy volunteers. Images were acquired over a 5-min period at 1.5 Tesla. We used a periodic design, alternating 30-s blocks of the "n-back" working memory task with 30-s blocks of a sensorimotor control task to activate verbal working memory systems. The power of functional response to the task was estimated by sinusoidal regression at each voxel. The relationship between power of fMRI response and mean reaction time over all 11 working memory trials was explored by multiple regression, with age and mean reaction time to the control task as covariates, at voxel and regional levels of analysis. All subjects were able to perform the n-back task accurately. A spatially distributed network was activated, including dorsolateral prefrontal cortex, inferior frontal gyrus, lateral premotor cortex, and supplementary motor area (SMA) in the frontal lobes. More posteriorly, there were major foci of activation in parietal and occipitoparietal cortex, precuneus, lingual, and fusiform gyri of the ventral occipital lobe, inferior temporal gyrus, and cerebellum. The power of functional response was positively correlated with reaction time in bilateral posterior parietal cortex (Talairach coordinates in x, y, z (mm) 35, -44, 37 and -32, -56, 42), indicating that subjects who found the task difficult, and responded with a slower reaction time, tended to activate these regions more powerfully. One interpretation of this regionally specific relationship between prolonged reaction time and increased power of posterior parietal activation is consistent with prior studies identifying similar areas of parietal cortex as the site of the phonological storage function in verbal working memory.

Adult↗

PubMed2000

Silencing of the Y-chromosomal gene tspy during murine evolution.

We have studied the process of tspy gene silencing in murine evolution. We have isolated functional tspy sequences from Apodemus agrarius, A. sylvaticus, A. flavicollis, and Mus platythrix (subgenus Pyromys) and nonfunctional tspy sequences from species of the subgenus Mus. We present two alternative models as to how tspy may have lost its function in the murine lineage.

Animals↗

PubMed2000

Ultrasound biomicroscopy in the diagnosis and management of pars planitis caused by caterpillar hairs.

PURPOSE: To report the use of ultrasound biomicroscopy in the detection of caterpillar hairs in the pars plana in a patient with unilateral pars planitis. METHOD: Ultrasound biomicroscopic imaging of the anterior segment of the eye. RESULTS: Ultrasound biomicroscopy located a hair in the posterior chamber at the first visit and five more in the pars plana 1 month later. This finding was confirmed intraoperatively. CONCLUSION: Ultrasound biomicroscopy is useful in the diagnosis and management of unilateral pars planitis of uncertain cause.

Animals↗

PubMed2000

Ultrasound biomicroscopy of sclerotomy sites after pars plana vitrectomy for diabetic vitreous hemorrhage.

OBJECTIVE: This study was aimed at assessing changes at the sclerotomy site using the ultrasound biomicroscope (UBM) in eyes that underwent primary pars plana vitrectomy for complications of proliferative diabetic retinopathy. DESIGN: Prospective, observational case series. PARTICIPANTS: Eighty-six eyes of 84 patients with vitreous hemorrhage caused by proliferative diabetic retinopathy. INTERVENTION: Three-port pars plana vitrectomy followed by UBM evaluation of all sclerotomy sites between 6 and 8 weeks after surgery. Correlation with intraoperative findings done in case of reoperations. Forty-one eyes had repeat UBM at 6 months. MAIN OUTCOME MEASURES: The changes at the sclerotomy site were classified into six groups: well healed, gape, plaque, vitreous incarceration, fibrovascular proliferation, and anterior hyaloidal fibrovascular proliferation (AHFVP). The UBM characteristics of each of the groups were defined. The findings at 6 months were compared with those at 6 to 8 weeks. RESULTS: At 6 to 8 weeks after surgery, most sclerotomies were well healed or had either moderate to high reflective plaques bridging the site. Wound gape was seen in 22.1% of active ports, 32.6% of light ports, and 25.6% of infusion ports. Vitreous incarceration was seen most often at the infusion port (18. 6% of eyes). Fibrovascular proliferation was seen in 9.3% of active ports, 12.8% of light ports, and 15.1% of infusion ports. Thirteen eyes had recurrent vitreous hemorrhage 6 to 8 weeks after surgery. Cases with rebleeding and no fibrovascular proliferation at the sclerotomy on UBM did well with outpatient fluid-air exchange (two eyes) or observation only (three eyes). Those with fibrovascular proliferation on UBM (eight eyes) required more extensive surgery. CONCLUSIONS: UBM is helpful in detecting complications at the sclerotomy sites after pars plana vitrectomy and is an invaluable tool in the assessment of the patient before reoperation.

Diabetic Retinopathy↗

PubMed2000

Audit of small-incision cataract surgery using an anterior chamber maintainer.

PURPOSE: To assess the results of small-incision cataract surgery with intraocular lens implantation using an anterior chamber maintainer (ACM) performed between March 1997 and December 1998. METHOD: A retrospective audit was performed of all 300 consecutive patients who underwent extracapsular cataract extraction using a 6 mm scleral tunnel incision, anterior chamber maintainer and manual fragmentation of the nucleus. RESULTS: Ninety per cent of patients had a gain in visual acuity at the end of 3 months. The rate of posterior capsule opacification was comparable to the results of the National Cataract Surgery Survey (RCO 1993), i.e. 13%, but the rate of corneal endothelial decompensation and endophthalmitis was marginally higher. CONCLUSION: Appropriate selection of cases, meticulous wound closure and subconjunctival antibiotics at the end of surgery make this an acceptable alternative small-incision closed-system low-cost procedure where phacoemulsification is not available.

Adult↗

PubMed2000

Mapping morphology of the corpus callosum in schizophrenia.

The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01).

Adult↗

PubMed2000

Endolaser around macular hole in the management of associated retinal detachment in highly myopic eyes.

PURPOSE: To analyze the role of endolaser around macular hole in managing associated retinal detachment in patients with high myopia. METHODS: Review of medical records of 25 consecutive eyes of 25 patients with at least 5.00 diopters of myopia who underwent primary pars plana vitrectomy and fluid-gas exchange. In the first half of the study period, one row of contiguous argon green endolaser was routinely applied over the retinal edge of the macular hole (EL group). In the second half of the study period, endolaser was not applied around any macular hole (NEL group). Demographic information, intraoperative and postoperative complications, and final visual acuities and retinal reattachment rates were studied. RESULTS: The mean (+/-SD) refractive error was -11.8 +/- -3.5 diopters (D) for the EL group and -11.6 +/- -5.4 D for the NEL group. The mean axial length was 29.0 +/- 1.8 mm for the EL group and 28.3 +/- 1.7 mm for the NEL group. The primary anatomic success was 62.5% (10/16) and 77.8% (7/9) in the EL and NEL groups, respectively. No statistically significant difference was found in preoperative, postoperative, or change in best-corrected visual acuities between the two groups. CONCLUSION: Endolaser around the macular hole after pars plana vitrectomy and internal gas tamponade may not affect the anatomic or visual outcome in primary retinal detachment secondary to a highly myopic macular hole.

Adult↗

PubMed2000

Sequential meiotic prophase development in the pubertal Indian pygmy field mouse: synaptic progression of the XY chromosomes, autosomal heterochromatin, and pericentric inversions.

Sequential meiotic prophase development has been followed in the pubertal male pygmy mouse Mus terricolor, with the objective to identify early meiotic prophase stages. The pygmy mouse differs from the common mouse by having large heterochromatic blocks in the X and Y chromosomes. These mice also show various chromosomal mutations; for example, fixed variations of autosomal short arms heterochromatin among different chromosomal species and pericentric inversion polymorphism. Identification of prophase stages was crucial to analyzing effects of heterozygosity for these chromosomal changes on the process of homologous synapsis. Here we describe identification of the prophase stages in M. terricolor, especially the pachytene substages, on the basis of morphology of the XY bivalent. Based on this substaging, we show delayed pairing of the heterochromatic short arms, which may be the reason for their lack of chiasmata. The identification of precise pachytene substages also reveals an early occurrence of "synaptic adjustment" in the pericentric inversion heterobivalents, a mechanism that would prevent chiasma formation in the inverted segment and thereby would abate adverse effects of such heterozygosity. The identification of pachytene substages would serve as the basis to analyze the nature of synaptic anomalies met in M. terricolor hybrids (which will be the basis of a subsequent paper).

Animals↗

PubMed2000

Dynamic of nucleolus organizer regions and karyotype evolution in Indian pygmy field mice.

Ag-NOR staining and fluorescence in situ hybridization with rDNA probes showed an unusually high number of NORs in the Indian pygmy field mice, Mus booduga and the M. terricolor complex. The chromosomal location of the NORs was also altered in terricolor, they were shifted from the proximal regions of the long arms to the tips of the perceptible heterochromatic short arms of the acrocentric autosomes. The results suggested dispersion of the NORs in the booduga-terricolor lineage probably by transposition, and relocalization of the NORs in the terricolor complex by centric reorganization during the process of replacement of the Mus musculus-related AT-rich heterochromatin with the terricolor-specific heterochromatin.

Animals↗

PubMed2000

Features of structural brain abnormality detected in first-episode psychosis.

OBJECTIVE: Structural magnetic resonance imaging (MRI) studies that focus on first-episode psychosis avoid some common confounds, such as chronicity of illness, treatment effects, and long-term substance abuse. However, such studies may select subjects with poor short-term treatment response or outcome. In this study, the authors focus on structural brain abnormalities in never or minimally treated patients who underwent MRI scanning early in their first episode of psychosis. METHOD: The authors examined 37 patients (13 medication naive, 24 previously treated) who were experiencing their first episode of psychosis; the mean duration of symptoms was short (31 weeks). These patients were comparable in age, gender, handedness, ethnicity, and parental socioeconomic status to a group of 25 healthy comparison subjects. A three-dimensional, inversion recovery prepared, fast spoiled gradient/recall in the steady state scan of the whole brain that used 1.5-mm contiguous sections was performed to acquire a T(1)-weighted data set. Human ratings of volumetric measurement of brain structures were performed with stereological techniques on three-dimensional reconstructed MRIs. RESULTS: The patient group had significant deficits in cortical gray matter, temporal lobe gray matter, and whole brain volume as well as significant enlargement of the lateral and third ventricles. Structural deviations were found in both treatment-naive and minimally treated subjects. No relationships were found between any brain matter volumes and positive or negative symptoms. CONCLUSIONS: Structural brain abnormalities were distributed throughout the cortex with particular decrement evident in gray matter. This feature is consistent with altered cell structure and disturbed neuronal connectivity, which accounts for the functional abnormality of psychosis.

Adult↗