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Biomedical subjects

S Narayanan

Publications and source records attributed to S Narayanan.

At least 73 records · Page 4Linked to original sources

Acoustics of children's speech: developmental changes of temporal and spectral parameters.

Changes in magnitude and variability of duration, fundamental frequency, formant frequencies, and spectral envelope of children's speech are investigated as a function of age and gender using data obtained from 436 children, ages 5 to 17 years, and 56 adults. The results confirm that the reduction in magnitude and within-subject variability of both temporal and spectral acoustic parameters with age is a major trend associated with speech development in normal children. Between ages 9 and 12, both magnitude and variability of segmental durations decrease significantly and rapidly, converging to adult levels around age 12. Within-subject fundamental frequency and formant-frequency variability, however, may reach adult range about 2 or 3 years later. Differentiation of male and female fundamental frequency and formant frequency patterns begins at around age 11, becoming fully established around age 15. During that time period, changes in vowel formant frequencies of male speakers is approximately linear with age, while such a linear trend is less obvious for female speakers. These results support the hypothesis of uniform axial growth of the vocal tract for male speakers. The study also shows evidence for an apparent overshoot in acoustic parameter values, somewhere between ages 13 and 15, before converging to the canonical levels for adults. For instance, teenagers around age 14 differ from adults in that, on average, they show shorter segmental durations and exhibit less within-subject variability in durations, fundamental frequency, and spectral envelope measures.

Adolescent↗

Geometry, kinematics, and acoustics of Tamil liquid consonants.

Tamil is unusual among the world's languages in that some of its dialects have five contrasting liquids. This paper focuses on the characterization of these sounds in terms of articulatory geometry and kinematics, as well as their articulatory-acoustic relations. This study illustrates the use of multiple techniques--static palatography, magnetic resonance imaging (MRI), and magnetometry (EMMA)--for investigating both static and dynamic articulatory characteristics using a single native speaker of Tamil. Dialectal merger and neutralization phenomena exhibited by the liquids of Tamil are discussed. Comparisons of English /[symbol: see text]/ and /l/ with Tamil provide evidence for generality in underlying mechanisms of rhotic and lateral production. The articulatory data justify the postulation of a class of rhotics and a class of laterals in Tamil, but do not provide evidence in favor of a larger class of liquids. Such a superclass appears to have largely an acoustic basis.

Biomechanical Phenomena↗

Combined magnetization transfer and proton spectroscopic imaging in the assessment of pathologic brain lesions in multiple sclerosis.

BACKGROUND AND PURPOSE: Conventional MR imaging of multiple sclerosis (MS) provides relatively poor pathologic specificity, which has led to the investigation of more sophisticated MR techniques. The purpose of this study was to combine magnetization transfer (MT) imaging and proton MR spectroscopic imaging (MRSI) to evaluate the specific pathologic features of myelination and neuronal integrity in patients with MS and to determine the relationship between these measures within plaques. METHODS: We acquired conventional MR, MT, and proton MRSI data and evaluated clinical disability in 30 patients with MS, whose conditions were categorized as relapsing-remitting, primary progressive, or secondary progressive. The lesions were classified, using a semiautomated edge-following technique, on T2-weighted MR images, and an analysis of MT and proton MRSI data was conducted for lesion regions as well as for tissue that was categorized as normal. RESULTS: The MT ratio (MTR) of normal-appearing white matter in the patients with MS was significantly lower than in the healthy participants, whereas gray matter values were unchanged. MS lesions showed a large reduction in MTR, with old lesions exhibiting a lower MTR than new lesions. The average lesion MTR and the MR spectroscopic imaging-measured relative concentration of N-acetylaspartate, a marker of neuronal integrity, was positively correlated in patients with relapsing-remitting MS. This relationship was strengthened in regions containing new lesions. CONCLUSION: The integrated use of MT and MR spectroscopic imaging provides a more complete description of the pathologic features of MS than does conventional MR imaging alone, and our data suggest that axonal damage occurs in step with new demyelination and is not a late feature of the disease.

Adult↗

A novel bacterial reversion and forward mutation assay based on green fluorescent protein.

We report the first use of green fluorescent protein (GFP) for mutation detection. We have constructed a plasmid-based bacterial system whereby mutated cells fluoresce and non-mutated cells do not fluoresce. Fluorescence is monitored using a simple hand-help UV lamp; no additional cofactors or manipulations are necessary. To develop a reversion system, we introduced a +1 DNA frameshift mutation in the coding region of GFP and the resulting protein is not fluorescent in Escherichia coli. Treatment of bacteria containing the +1 frameshift vector with ICR-191 yields fluorescent colonies, indicating that reversion to the wild-type sequence has occurred. Site-directed mutagenesis was used to insert an additional cytosine into a native CCC sequence in the coding region of GFP in plasmid pBAD-GFPuv, expanding the sequence to CCCC. A dose-related increase in fluorescent colonies was observed when the bacteria were treated with ICR-191, an agent that induces primarily frameshift mutations. The highest dose of ICR-191 tested, 16 microg/ml, produced a mutant fraction of 16 x 10(-5) and 8.8 x 10(-5) in duplicate experiments. The reversion system did not respond to MNNG, an agent that produces mainly single-base substitutions. To develop a forward system, we used GFP under the control of the arabinose PBAD promoter; in the absence of arabinose, GFP expression is repressed and no fluorescent colonies are observed. When cells were treated with MNNG or ENNG, a dose-dependent increase in fluorescent colonies was observed, indicating that mutations had occurred in the arabinose control region that de-repressed the promoter. Treating bacteria with 100 microg/ml MNNG induced mutant fractions as high as 82 x 10(-5) and 40 x 10-5 in duplicate experiments. Treating bacteria with 150 microg/ml ENNG induced a mutant fraction of 2.1 x 10(-5) in a single experiment.

Aminacrine↗

Biochemical and biological characterizations and ribotyping of Actinomyces pyogenes and Actinomyces pyogenes-like organisms from liver abscesses in cattle.

Actinomyces pyogenes is the second most frequently encountered pathogen, next only to Fusobacterium necrophorum, in liver abscesses of feedlot cattle. Ninety-one isolates, presumptively identified as A. pyogenes, isolated from liver abscesses of cattle were studied. Biochemical characteristics determined by the API 20 Strep kit were similar to those reported previously for A. pyogenes isolated from other infections, except that 18% of isolates hydrolyzed esculin. Nine isolates that resembled A. pyogenes in morphology and in certain biochemical characteristics, but fermented mannitol and/or raffinose, were called A. pyogenes-like (APL) organisms. The five antimicrobial agents, bacitracin, chlortetracycline, oxytetracycline, tylosin, and virginiamycin were inhibitory to all strains of A. pyogenes and APLs. Generally, APL organisms had higher mean hemolytic and leukotoxic activities than A. pyogenes. All isolates of A. pyogenes and APLs produced proteases and neuraminidases. Ribotyping with endonucleases, including BstEII, ClaI, EcoRI, EcoRV, HaeIII, MboI, PvuII, SalI, and SmaI alone or in combinations, showed considerable genetic heterogeneity in both A. pyogenes and APLs. No specific ribopattern characteristic of each group was observed with any of the endonuclease used. The origin of A. pyogenes and APLs and the relative importance of APLs in causing liver abscesses in feedlot cattle are not known.

Actinomyces↗

Magnetic resonance spectroscopy guided brain tumor resection: differentiation between recurrent glioma and radiation change in two diagnostically difficult cases.

BACKGROUND: It is often difficult to differentiate a recurrent glioma from the effects of post-operative radiotherapy by means of conventional neurodiagnostic imaging. Proton magnetic resonance spectroscopic imaging (1H-MRSI), that allows in vivo measurements of the concentration of brain metabolites such as choline-containing phospholipids (Cho), may provide in vivo biochemical information helpful in distinguishing areas of tumor recurrence from areas of radiation effect. PATIENTS AND METHODS: Two patients who had undergone resection and post-operative radiotherapy for a cerebral glioma became newly symptomatic. Computed tomographic (CT) and magnetic resonance imaging (MRI) performed after the intravenous infusion of contrast material, and in one case, [18F]fluorodeoxyglucose positron emission tomography (PET), could not differentiate between the possibilities of recurrent glioma and radiation effect. The patients underwent 1H-MRSI prior to reoperation and the 1H-MRSI results were compared to histological findings originating from the same locations. RESULTS: A high Cho signal measured by 1H-MRSI was seen in areas of histologically-proven dense tumor recurrence, while low Cho signal was present where radiation changes predominated. CONCLUSIONS: The differentiation between the recurrence of a cerebral glioma and the effects of post-operative irradiation was achieved using 1H-MRSI in these two patients whose conventional neurodiagnostic imaging was equivocal for such a distinction. Where these two conditions are present, metabolite images from 1H-MRSI, such as that based on Cho, can be co-registered with other imaging modalities such as MRI and may also be integrated with functional MRI or functional PET within a multimodal imaging-guided surgical navigation system to assure maximal resection of recurrent tumor while minimizing the risk of added neurological damage.

Adult↗

Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis.

Recent magnetic resonance imaging (MRI) and magnetic resonance spectroscopic (MRS) techniques have focused the attention of the multiple sclerosis (MS) research community on reanalysis of classic pathological approaches that have suggested significant axonal injury in this demyelinating disease. There now is abundant evidence from animal work that substantial "innocent bystander" damage to axons can occur with central nervous system (CNS) inflammation. Given the close interactions between axons and glia, it is no surprise that glial damage leads to secondary axonal changes. MRI, MRS, and MRS imaging studies have emphasized that axonal loss or damage in MS can be both substantial and early. The dynamic observations that are allowed by these noninvasive measures of pathology have demonstrated direct correlations between these axonal changes and disability, making a compelling case for increased emphasis on finding treatments of MS that may limit damage to CNS axons or salvage injured axons.

Atrophy↗

Imaging axonal damage of normal-appearing white matter in multiple sclerosis.

The current study was designed to determine the relative distribution of decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA:Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA:Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA:Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.

Aspartic Acid↗

Improved correlation between scores on the expanded disability status scale and cerebral lesion load in relapsing-remitting multiple sclerosis. Results of the application of new imaging methods.

We hypothesized that a better correlation between MRI and clinical measures of neurological disability using the expanded disability status scale (EDSS) in multiple sclerosis could be obtained by assessing lesion load only in and around the corticospinal tracts, since the EDSS is weighted towards motor and ambulatory deficits. Multiple sclerosis lesions in cerebral MRIs from 39 patients with relapsing-remitting multiple sclerosis were manually painted using a three-dimensional computer display tool and mapped into a standardized three-dimensional coordinate space. Total lesion load was then measured. A mask to expose only the corticospinal tract was extracted from an MRI atlas and used to measure lesion load in the corticospinal tract. To account for the residual anatomical variability among the different MRI volumes after stereotaxic transformation, the corticospinal tract mask was dilated to various degrees and the lesion load remeasured. Spearman's rank correlation coefficient was used to calculate the correlation between the EDSS and total lesion load and corticospinal tract lesion load and between the EDSS subscores and total lesion load and corticospinal tract lesion load. Spearman's rank correlation coefficient between the EDSS and total lesion load was 0.6, probably reflecting the rather broad EDSS range represented in the study. The highest correlation of 0.67 was between the EDSS and corticospinal tract lesion load, dilated with a blurring kernel of 8-10 mm. The pyramidal subscore alone showed a weaker correlation with total lesion load, and with corticospinal tract lesion load, than did the overall EDSS, possibly reflecting the narrow range of disability in these subscores in patients with EDSS scores of 1-6.5. The imperfect correlation between the EDSS and corticospinal tract lesion load suggests that factors other than cerebral T2-weighted lesion volume are important determinants of disability.

Brain↗

Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study.

It has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course. Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate:creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate:creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetylaspartate:creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.

Aspartic Acid↗

Crohn's disease presenting as pyogenic liver abscess with review of previous case reports.

A 40-yr-old male doctor from India presented with pyogenic liver abscesses as the first manifestation of Crohn's disease. The Crohn's disease itself was limited to the appendix and the adjacent cecum and could be diagnosed only 6 months after the presentation with liver abscess. This single case highlights three unusual features of Crohn's disease, and stresses the importance of meticulous search for a cause for pyogenic liver abscess when it occurs in an otherwise healthy adult.

Adult↗

Biochemical and ribotypic comparison of Actinomyces pyogenes and A pyogenes-like organisms from liver abscesses, ruminal wall, and ruminal contents of cattle.

OBJECTIVE: To isolate Actinomyces pyogenes and A pyogenes-like (APL) organisms from the ruminal wall and ruminal contents of cattle and compare them with isolates from liver abscesses from the same animals, using ribosomal DNA restriction fragment length polymorphism analysis or ribotyping. PROCEDURE: Specimens of liver abscesses, ruminal walls, and ruminal contents were collected from 59 cattle at slaughter. All beta-hemolytic, pinpoint colonies that were gram positive, pleomorphic rod-shaped, and catalase negative, and that hydrolyzed casein and gelatin were presumptively identified as A pyogenes and were characterized biochemically, using an identification kit. The isolates that resembled A pyogenes but fermented mannitol or raffinose, or both, were called APL organisms. Isolates from the ruminal wall and ruminal contents were compared with liver abscess isolates from the same animal by use of ribotyping. RESULTS: Actinomyces pyogenes and APL organisms were isolated more frequently from the ruminal wall than from ruminal contents. Ruminal isolates of A pyogenes and APL had biochemical characteristics similar to those of the isolates from liver abscesses. Among 6 sets of isolates (4 A pyogenes and 2 APL), 2 isolates from liver abscesses had ribopatterns identical to the corresponding ruminal wall isolates. Also, the APL organisms isolated from the ruminal content matched with the corresponding liver abscess isolates for both sets of specimens tested. CONCLUSIONS: The ruminal wall may be the niche for A pyogenes and APL organisms in the rumen. The genetic similarity, on the basis of ribotyping among isolates from liver abscesses, the ruminal wall, and ruminal contents of the same animal suggests that A pyogenes and APL organisms that cause liver abscesses originate from the rumen.

Abscess↗

Preparation & standardization of the goat lung surfactant extract.

Exogenous goat lung surfactant extract (GLSE) was obtained by chloroform-methanol extraction of the centrifuged lung lavage. Four lungs provided around 250 mg of surfactant. GLSE has a phospholipid content of 50 percent, cholesterol of 1.5 percent and protein content under 1 percent. The preparation was bacteriologically sterile and had a shelf life of at least one month at 4 degrees C. Endotracheal administration of surfactant (50 mg/kg) in a rat lung model rendered surfactant deficient by saline lavage, restored the compliance characteristics to normal, thus documenting biological activity of the preparation. The cost of a course of 2 doses of surfactant replacement therapy was estimated to be as low as Rs 500/-. The study opens up the possibility of surfactant replacement therapy for the management of neonatal respiratory distress syndrome in India by an indigenous product at an affordable cost.

Animals↗

Enhancement of the locomotor response to apomorphine in pertussis toxin-treated animals depends on the site of pertussis toxin injection into the ventral tegmental area.

The locomotor stimulant response to either systemic or intra-accumbens amphetamine was enhanced 1-2 weeks after pre-treatment with pertussis toxin (PTX) into any of 3 different sites in the ventral tegmental area (VTA). An enhanced response to either systemic or intra-accumbens apomorphine occurred only after pre-treatment into the central VTA. Thus, enhanced sensitivity to drugs of either pre- or post-synaptic elements in the nucleus accumbens may develop depending on the site of the PTX pre-treatment within the VTA.

Animals↗

Imaging of axonal damage in multiple sclerosis: spatial distribution of magnetic resonance imaging lesions.

We performed magnetic resonance imaging and magnetic resonance spectroscopic imaging on 28 patients with multiple sclerosis stratified for disability and clinical course (relapsing with at least partial remissions or secondary progressive disease). Lesions were segmented on the conventional proton density and T2-weighted magnetic resonance images, and lesion distribution images were generated for, each patient. The conventional magnetic resonance and spectroscopic images were transformed into a standard brain-based stereotaxic coordinate space, allowing comparison of images from different patients on a voxel-by-voxel basis. The spatial distribution of lesions in the transformed magnetic resonance images did not differ significantly between the relapsing and the progressive disease groups. We then generated from the individual data sets, group lesion probability distribution images for the relapsing and the progressive disease groups. The spatial distribution of metabolites was characterized with respect to lesion distribution using the magnetic resonance spectroscopic images transformed into stereotaxic space and averaged. The neuronal marker N-acetylaspartate was diffusely lower in the multiple sclerosis patients than in normal control subjects. Comparison of the averaged metabolite and T2-weighted lesion probability images confirmed loss of N-acetylaspartate in regions of both high and low lesion probability. This suggests that diffuse axonal volume loss or dysfunction extends beyond the inflammatory lesions of multiple sclerosis, perhaps due to microscopic disease or wallerian degeneration along projection pathways of axons traversing the lesions.

Adult↗

Comparison of sensitization elicited by amphetamine and pertussis toxin: characterization of locomotor behavior and limbic dopamine release.

1. Male, Sprague-Dawley rats were pretreated with one of several regimens of repeated, intermittent amphetamine or with a single-dose of intra-VTA pertussis toxin (PTX). 2. An amphetamine challenge dose (0.5 mg/kg, i.p.) produced increased locomotor activity in both amphetamine and pertussis toxin-pretreated rats. 3. The magnitude of activity in PTX pretreated rats exceeded 5-fold that of the amphetamine-pretreated rats. 4. There were no significant differences in the levels of sensitized behavior elicited by 4 distinct amphetamine pretreatment protocols. 5. Neither of the drug pretreatments caused significant changes in the ability of 10 microM amphetamine to promote dopamine efflux from nucleus accumbens or striatal tissue in vitro. 6. The sensitized behaviour cannot be explained by in vitro alterations in pre-synaptic dopamine release, which may suggest an up-regulation of post-synaptic activity.

Amphetamine↗

Effect of pertussis toxin injected into the ventral tegmental area on amphetamine-induced Fos protein in the nucleus accumbens.

Amphetamine produces an enhanced locomotor stimulatory response in animals injected with pertussis toxin into the ventral tegmental area. This response is dependent on the activation of D1 receptors in the nucleus accumbens. The immediate early gene, c-Fos, has been used as a cellular marker for increases in dopamine neurotransmission in the nucleus accumbens. The purpose of the present study was to determine whether the administration of pertussis toxin into the ventral tegmental area results in an increased ability of amphetamine to induce Fos-positive immunoreactivity in the nucleus accumbens. Amphetamine (1 mg/kg and 2 mg/kg IP) produced a greater number of Fos-positive cells in the nucleus accumbens of pertussis toxin-treated animals as compared to vehicle-treated controls. However, the increase in Fos immunoreactivity at the higher amphetamine dose was not associated with a corresponding increase in locomotor activity. These data suggest that amphetamine produces an enhanced increase in dopamine neurotransmission in the nucleus accumbens of pertussis toxin-treated animals, resulting in an increased induction of Fos-related antigens.

Amphetamine↗