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Biomedical subjects

S Narayanan

Publications and source records attributed to S Narayanan.

At least 91 records · Page 5Linked to original sources
PubMed1997

Structural analysis of a missense mutation (Val414Phe) in the catalytic core domain of the factor XIII(A) subunit.

Molecular analysis has been performed on a Malaysian patient with a severe bleeding disorder due to factor XIII(A) subunit deficiency. Total mRNA was isolated from the patient's leucocytes and four overlapping segments corresponding to the entire coding region of the A subunit cDNA were amplified by RT-PCR. The cDNA segments amplified efficiently and were of expected size. Direct sequencing of the complete reading frame revealed a single homozygous base change (nt 1327G-T) in exon 10 corresponding to a missense mutation, Val414Phe, in the catalytic core domain of the A subunit monomer. The mutation eliminates a BsaJ1 restriction site and family screening showed that both parents were heterozygous for the defect. The base substitution was absent in 55 normal individuals. Val414 is a highly conserved residue in the calcium-dependent transglutaminase enzyme family. Computer modelling based on 3D crystallographic data predicts that the bulky aromatic side chain of the substituted phenylalanine residue distorts protein folding and destabilizes the molecule. In addition, conformation changes in the adjacent catalytic and calcium binding regions of the A subunit are likely to impair the enzymatic activity of any protein synthesized.

Adult↗
PubMed1997

Toward articulatory-acoustic models for liquid approximants based on MRI and EPG data. Part II. The rhotics.

Magnetic resonance images of the vocal tract during sustained production of [symbol: see text] by four native American English talkers are employed for measuring vocal-tract dimensions and for morphological analysis of the 3D vocal tract and tongue shapes. Electropalatography contact profiles are used for studying inter- and intra-talker variabilities. The vocal tract during the production of [symbol: see text] appears to be characterized by three cavities due to the presence of two supraglottal constrictions: the primary one in the oral cavity, and a secondary one in the pharyngeal cavity. All subjects show a large volume anterior to the oral constriction, which results from an inward-drawn tongue body, an anterior tongue body that is characterized by convex cross sections, and a concave posterior tongue body shape. Inter-subject variabilities are observed in the oral-constriction location and the way the constriction is formed. No systematic differences are found between the 3-D vocal tract and tongue shapes of word-initial and syllabic [symbol: see text]s. Tongue-shaping mechanisms for these sounds and their acoustic implications are discussed.

Adult↗
PubMed1997

Ribotyping to compare Fusobacterium necrophorum isolates from bovine liver abscesses, ruminal walls, and ruminal contents.

Restriction fragment length polymorphism analysis of rRNA genes was employed to genetically compare Fusobacterium necrophorum subsp. necrophorum and F. necrophorum subsp. funduliforme isolates from multiple abscesses of the same liver and isolates from liver abscesses, the ruminal wall, and ruminal contents from the same animal. Four livers with multiple abscesses and samples of ruminal contents, ruminal walls, and liver abscesses were collected from 11 cattle at slaughter. F. necrophorum was isolated from all liver abscesses, nine ruminal walls, and six ruminal content samples. Chromosomal DNA of the isolates was extracted and single or double digested with restriction endonucleases (EcoRI, EcoRV, SalI, and HaeIII); then restriction fragments were hybridized with a digoxigenin-labeled cDNA probe transcribed from a mixture of 16S and 23S rRNAs from Escherichia coli. EcoRI alone or in combination with EcoRV yielded the most discriminating ribopatterns for comparison. Within the subspecies multiple isolates from the same liver were indistinguishable based on the ribopattern obtained with EcoRI. The hybridization patterns of liver abscess isolates were concordant with those of the corresponding isolates from ruminal walls in eight of nine sets of samples. None of the six ruminal content isolates matched either the liver abscess isolates or the ruminal wall isolates. The genetic similarity between the isolates from liver abscesses and ruminal walls supports the hypothesis that F. necrophorum isolates of liver abscesses originate from the rumen.

Animal Feed↗
PubMed1997

Axonal dysfunction and disability in a relapse of multiple sclerosis: longitudinal study of a patient.

In a 6-year longitudinal study of a patient with relapsing progressive multiple sclerosis (MS), we used proton magnetic resonance spectroscopy to assess N-acetylaspartate (NAA) from a large central brain volume to evaluate the relationship between this marker of neuronal integrity and clinical disability. During the follow-up period, there was one major relapse and its subsequent partial remission. Changes in the brain NAA to creatine ratio correlated strongly with clinical disability (Spearman rank coefficient = -0.73, p < 0.001). We interpret this as evidence that axonal dysfunction or loss contributes to functional impairment of patients with MS. Because the NAA signal in the large volume of interest originated predominantly from white matter that appeared normal on conventional MRI, these results also suggest that some degree of axonal dysfunction may be widespread in acute, severe relapses.

Adult↗
PubMed1997

Restriction fragment length polymorphism of Mycobacterium tuberculosis strains from various regions of India, using direct repeat probe.

Intraspecies differentiation was studied on 68 M. tuberculosis strains obtained from 6 states of India by restriction fragment length polymorphism (RFLP) using a direct repeat probe (DR probe) hybridised with Alu I digest of DNA. Most strains showed polymorphism based patterns that comprised between 2 to 7 bands and were grouped into 26 RFLP types. Of the 11 strains tested from Amritsar, 8 were RFLP type 5; the remaining 3 were of type 11 and were exclusively confined to this region. The strains from other regions were more heterogeneous. We confirm that DR-associated RFLP can be an excellent tool for the differentiation of M. tuberculosis strains. Depending on their geographical origin, these strains can be differentiated to a large extent by DR fingerprinting.

DNA Fingerprinting↗
PubMed1996

Statistics for investigation of multimodal MR imaging data and an application to multiple sclerosis patients.

Magnetic resonance spectroscopy can image axonal damage specifically based on changes in N-acetyl aspartate (NAA), a neuronal marker. We have developed statistical methods for multimodal analysis of MR spectroscopic images. These methods, which are extensions of mixed-effect models, have allowed us to quantify differences in images from different subgroups of patients with multiple sclerosis (MS) and to determine the dependence of chemical pathology on clinical disability, duration of disease and lesions on T2-weighted MRI. Statistical power was improved by using all reliable resonance intensities in the spectroscopic images while taking into consideration the intra-subject correlations. We studied 17 normal subjects, 14 patients with relapsing remitting (RR) MS and 21 patients with chronic progressive (CP) MS. The ratio of resonance intensities of N-acetylaspartate over creatine (Cr) was found to be significantly lower than normal in normal appearing white matter (NAWM) of both RR and CP patients (19.6% in RR, 28.8% in CP), NAA/Cr was decreased even more in MS plaques than in NAWM (44.2% in RR, 17.7% in CP), NAA/Cr was correlated with clinical disability (p < 0.02) and disease duration (p < 0.1). Our results suggest that, in this setting, MRS reflects accumulated neuronal loss or damage and can be used as a measure of disease severity. The methods developed provide opportunities to evaluate the relationship between inflammation, demyelination, axonal loss and clinical disability in future studies.

Aspartic Acid↗
PubMed1996

Role of dopaminergic mechanisms in the stimulatory effects of MK-801 injected into the ventral tegmental area and the nucleus accumbens.

The bilateral administration of 10 micrograms of (+)MK-801, but not (-)MK-801, into either the VTA or the N.Ac. stimulated locomotor activity. The stimulation induced by (+)MK-801 at both sites was inhibited by reserpine (5 mg/kg, SC) and the D1 antagonist, SCH 23390 (0.1 mg/kg, SC). Eticlopride (0.03 mg/kg, SC), a D2 antagonist, inhibited the stimulation produced by MK-801 in the VTA but not in the N.Ac. Baclofen (32 ng), a GABAB receptor agonist, injected into the VTA inhibited the stimulatory response to MK-801 injected systemically, into the VTA, or into the N.Ac., but did not significantly inhibit spontaneous locomotion or the stimulatory response to apomorphine (5 mg/kg, SC). These observations suggest that the stimulatory effects of MK-801 in the VTA and the N.Ac. are dependent on endogenous dopamine. In addition, the effects produced by MK-801 injected into the VTA closely resemble those produced by the systemic administration of low doses of MK-801, suggesting that this is the primary site of action of MK-801.

Adrenergic Uptake Inhibitors↗
PubMed1996

Concepts, principles, and applications of selected molecular biology techniques in clinical biochemistry.

The myriad molecular techniques that have been developed and are undergoing refinement have advanced our knowledge of disease processes and made available strategies for detection. While the greatest impact of molecular techniques in the diagnostic laboratory has been in the realm of infectious diseases, techniques such as flow cytometry, FISH, and multiplex-nested PCR followed by direct DNA sequencing are increasing the scope of cancer detection and treatment. The facile typing of HLA-class II genes is a major advance in the matching of donors to recipients of organ transplantation. With advances in genosensor technology and robotic automation, molecular biology techniques are clearly poised to enter the diagnostic clinical biochemistry laboratory for multiple applications.

Animals↗
PubMed1996

Assessment of lesion pathology in multiple sclerosis using quantitative MRI morphometry and magnetic resonance spectroscopy.

Quantitative measurement of MRI-defined brain lesions can provide an index of the extent and activity of disease in multiple sclerosis patients. However, the relationships between these indices and clinical features are not well-understood. Heterogeneity of the pathological changes underlying MRI lesions may be an important factor determining the correlation between MRI lesion volumes and clinical measures. Recent studies have suggested that with magnetic resonance spectroscopy (MRS), it may be possible to define chemical changes that better reflect the pathological changes in multiple sclerosis. Here we report results of combined quantitative brain T2-weighted MRI lesion volume and proton MRS examinations that demonstrate heterogeneity of the chemical pathology underlying brain lesions in patients selected on the basis of similar clinical disability but differing with respect to the presence or absence of clinical relapses. We examined 29 patients with disease characterized by either clear relapses with at least partial remissions (RR) or secondary, chronic progression after an earlier history of a more relapsing and remitting course (SP). Total hemispheric lesion volume was greater (P < 0.04) in the RR (32.5 +/- 20.9 cm3) than in the SP (16.2 +/- 9.0 cm3) patients, despite the longer duration of disease in the latter group. Central brain N-acetyl aspartate: creatine (NAA:Cr) ratios were reduced relative to normal controls (4.0 +/- 0.3, n = 19) by similar amounts in the two patients groups (RR, 3.1 +/- 0.5; SP, 3.2 +/- 0.4; P < 0.0001). The ratio lesion volume:(NAA:Cr) was greater for the RR group (11.7 +/- 9.3 cm3) than for the SP group (5.4 +/- 3.3 cm3, P < 0.05), implying a greater average degree of axonal loss per unit lesion volume defined by MRI for subjects in the SP group or, alternatively, a greater proportion of lesions without axonal damage or loss in the RR group. Our results emphasize a limitation of using T2-weighted MRI lesion volume alone and suggest that combined analysis of MR-based chemical and imaging data might allow improved non-invasive assessment of lesion pathology in order to better understand its relationship to clinical features of multiple sclerosis.

Adult↗
PubMed1996

Spontaneous and drug-stimulated locomotor activity after the administration of pertussis toxin into the ventral tegmental area.

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) produces an enhanced locomotor response to amphetamine. In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergic agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomotor activity with a latency of 4 d. This activity was markedly increased by day 6 and remained elevated for at least 28 d after PTX treatment. This increased spontaneous locomotor activity of PTX-treated animals was antagonized by the administration of the D1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D2 receptor antagonist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomotor cages, the animals showed a markedly enhanced motor response to amphetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc). The heightened locomotor responses to these dopaminergic agonists could be elicited for at least 2 mo after PTX administration. The enhanced response to amphetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), but not by eticlopride (0.1 mg/kg). The increased response to apomorphine in PTX-treated animals was inhibited by SCH23390 (0.1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc). Both of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an increase in spontaneous and drug-induced locomotor activity in which D1 receptors seem to play an important role.

Animals↗
PubMed1996

Considerations in the application of selected molecular biology techniques in the clinical laboratory: preanalytical and analytical issues.

As a prerequisite to the utilization of molecular biology techniques in the clinical laboratory one must be aware of preanalytical pitfalls associated with these techniques. Procedures for the identification of restriction fragment length polymorphism (RFLP) resulting from variation in the number of tandem repeats (VNTR) of a short DNA segment, or even simple tandem repeats (STRs) such as dinucleotide repeats require scrutiny to understand both the strengths and limitations of these techniques. In terms of minimizing analytical pitfalls particular attention should be given to the composition of DNA probes. Many variables affect PCR (polymerase chain reaction). These include cycling temperatures chosen for denaturation of synthesized DNA strands, annealing and primer extension steps, the type of thermocyclers used to achieve temperature cycling, requirements for primers, to name just a few. Particular attention should be given for trouble shooting PCR products. A multiplicity of kits are currently available for the isolation of DNA and RNA. These kits while simplifying the isolation procedure could in some instances introduce a preanalytical variable depending on the type of detergent used in cell lysis which may impact on the amplification of DNA by techniques such as the polymerase chain reaction (PCR). The anticoagulants used for blood collection could also affect digestion with restriction enzymes and amplification reactions, such as been reported with heparin under certain conditions. Residual red blood cells can inhibit taq polymerase enzyme used in PCR amplification. The type of tissue fixative and the duration of fixation can affect the efficiency of amplification reactions. Finally, contamination from the working environment should be controlled to minimize both preanalytical and postanalytical error.

DNA↗
PubMed1995

Restriction fragment length polymorphism typing of clinical isolates of Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Madras, India, by use of direct-repeat probe.

Large numbers of Mycobacterium tuberculosis isolates that were obtained from patients' sputa on diagnosis and during follow-up after short-course chemotherapy in Madras, India, have either no copy or only a single copy of IS6110. This poses a limitation for DNA fingerprinting with an IS6110-based probe to determine the frequency of exogenous reinfection versus that of endogenous reactivation. In the present study, we overcame this limitation by using an alternate probe, the direct-repeat element. Comparison of pre- and posttreatment isolates by direct-repeat restriction fragment length polymorphism analysis indicated a high degree of endogenous reactivation among patients who have relapses after the successful completion of chemotherapy.

Bacterial Typing Techniques↗
PubMed1993

The role of dopamine and AMPA/kainate receptors in the nucleus accumbens in the hypermotility response to MK801.

The purpose of this study was to evaluate the role of endogenous dopamine in the hypermotility response to MK801. The administration of MK801 (0.1 mg/kg, SC) to rats produced an intense stimulation of coordinated locomotor activity, which was not associated with stereotyped behavior. This stimulatory response was inhibited by pretreatment with either reserpine (5 mg/kg, IP) or alpha-methyl-p-tyrosine (2 doses of 250 mg/kg, IP). Similarly, pretreatment with the D2 antagonist eticlopride (0.03 mg/kg, SC) or the D1 antagonist SCH23390 (0.1 mg/kg, SC) produced a marked inhibition of MK801-stimulated hypermotility, and the combination of eticlopride (0.03 mg/kg, SC) and SCH23390 (0.03 mg/kg, SC) produced a greater inhibition of MK801-stimulated locomotion than either agent alone. The administration of SCH23390 or eticlopride directly into the nucleus accumbens inhibited the locomotor response to MK801, with the combination of both drugs producing a greater inhibition than either agent alone. The intra-accumbens administration of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor antagonists DNQX or GAMS also inhibited the locomotor response produced by MK801. These data suggest that the activation of D1 and D2 dopaminergic receptors and AMPA/kainate excitatory amino acid receptors in the nucleus accumbens is required for the stimulation of locomotor activity produced by MK801.

Animals↗
PubMed1991

Human tuberculosis sera show prominent antibody responses to particulate fractions of Mycobacterium tuberculosis.

Sera from smear-positive pulmonary tuberculosis patients and normal control subjects in Madras were analyzed by Western blotting for their reactivity with soluble and particulate (membrane-rich and cell wall-rich) antigen fractions extracted by sonication from Mycobacterium tuberculosis H37Rv. Discrimination between patient and control sera was best with particulate antigen fractions: 60% of patient sera reacted with a 38-kD antigen band and 90% reacted with a 55-kD band. Reactions of control sera with the 38- and 55-kD bands were infrequent and faint. The results suggest that a serodiagnostic test might be based on quantitation of responses to these two antigens.

Adolescent↗
PubMed1990

Knowledge and attitudes regarding smoking: a health education experiment with Malay college students.

This study investigated whether knowledge and attitudes of Malay college students regarding smoking can be positively influenced by educational intervention. The experiment included a pretest to assess the students knowledge and attitudes regarding smoking, a lecture on the health risks associated with smoking, and a posttest given six weeks later to assess whether any changes had occurred. A profile of the typical Malay student smoker was also elicited. Twenty-seven percent of the study population were smokers. Of the men in the sample, 44% were smokers, while less than 4% of the women were smokers. T-tests indicated that knowledge of the health risks associated with smoking was significantly improved for most groups, while attitudes towards smoking were essentially unchanged.

Adult↗