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Biomedical subjects

S Pradhan

Publications and source records attributed to S Pradhan.

At least 55 records · Page 3Linked to original sources

Parkinsonism due to predominant involvement of substantia nigra in Japanese encephalitis.

OBJECTIVE: To study the clinical correlates of lesions seen predominantly in the substantia nigra in some patients with Japanese encephalitis (JE). BACKGROUND: JE typically involves thalamus, brainstem, spinal cord, and cerebral cortex. Rarely, basal ganglia and cerebellum may be affected. Lesions are often widespread and discrete. Predominant involvement of substantia nigra in JE has not been previously reported. METHODS: Of 52 patients with JE seen in an endemic zone, five were selected on the basis of isolated lesions in the substantia nigra on MRI; all were subjected to detailed clinical and laboratory evaluation. RESULTS: Presenting symptoms were fever, alteration of consciousness, neck stiffness, and decreased body movements. Examination during acute illness revealed restricted eye movements, opsoclonus, upbeating nystagmus, and cogwheel rigidity. There was early and complete recovery of consciousness and eye signs. Parkinsonian features such as positive glabellar tap sign, masklike face, bradykinesia, tremors, and postural instability became apparent as these patients started walking. Reversible mutism was observed in three patients during the acute phase. Response to levodopa, amantadine, and trihexiphenedyl was partial. Three patients were followed for more than 1 year, during which time their parkinsonian features recovered completely. Substantial recovery was also observed in the two other patients 2 months after regaining consciousness. CONCLUSIONS: Some patients with Japanese encephalitis may have lesions predominantly in the substantia nigra. After recovery from acute encephalitic illness, they manifest clinically with typical parkinsonian features. Although several viruses are known to cause parkinsonism, this is the first demonstration of a virus producing lesions predominantly in the substantia nigra and causing parkinsonism.

Adolescent↗

Effect of CWG methylation on expression of plant genes.

The presence of two DNA methyltransferases in Pisum raises the possibility that they serve different functions. In vitro methylation of CWG sequences in the strong cauliflower mosaic virus 35S promoter had no effect on reporter gene expression. In contrast, in vitro methylation of CWG sequences in the relatively weak, CG-deficient Phaseolus vulgaris rbcS2 promoter inhibited transcription. Expression of both constructs was strongly inhibited by extensive CG methylation. A search of published plant promoter sequences revealed that the CG content of promoters is very variable, with some promoters having typical CG islands. In contrast, the distribution of CWG sequences is more even with little evidence for CWG islands.

Chloramphenicol O-Acetyltransferase↗

Intravenous immunoglobulin therapy in acute disseminated encephalomyelitis.

We describe 4 patients with acute disseminated encephalomyelitis (ADEM) who were treated with intravenous immunoglobulins (IVIg) after getting no immediate response from a 3-5 day course of high dose intravenous methylprednisolone. All had clinical features to suggest poor prognosis and MRI findings to indicate extensive white matter changes in the brain. Two patients who had spinal cord involvement as well, required ventilatory support during acute phase of the illness. All the 4 patients recovered dramatically. Recovery pattern suggested that IVIg might be useful in fulminant ADEM. Further trials are needed to look for the efficacy of IVIg alone and in combination with methylprednisolone in the treatment of ADEM.

Adolescent↗

Inhibition of early DNA-damage and chromosomal aberrations by Trianthema portulacastruml. In carbon tetrachloride-induced mouse liver damage.

The underlying molecular mechanisms of the antihepatotoxic activity of Trianthema portulacastrum by monitoring its effect on mouse liver DNA-chain break, sugar-base damage and chromosomal aberrations, during chronic or acute treatment with carbon tetrachloride (CCl(4)) have been studied. Daily oral feeding with the ethanolic extract (150 mg/kg basal diet, per os) was given 2 weeks before CCl(4)treatment and continued until the end of the experiment (13 weeks). T. portulacastrum extract offer unique protection (P< 0.05-0. 001) against the induction of liver-specific structural-type chromosomal anomalies 15, 30 or 45 days after the last CCl(4)insult, compared to control mice. This was further evidenced by extract-mediated protection (15 days prior feeding following a single necrogenic dose of CCl(4)) of the generation of DNA chain-break and Fe-sugar-base damage assays. The observed hepatoprotective mechanism could be due to its ability to counteract oxidative injury to DNA in the liver of mouse.

Acute Disease↗

5-Fluorouracil induces defects in platelet function.

Platelet factor-3 (PF(3)) availability and platelet aggregation to ADP (4 micromol/l) and adrenaline (1.2 micromol/l) were evaluated in patients being treated with 5-fluorouracil (5-FU) for gastrointestinal malignancy. It produced a significant reduction in platelet aggregation and platelet factor-3 (PF(3)) availability ( P < 0.001) without being associated with thrombocytopenia. The changes in platelet aggregation occurred during the first week of chemotherapy and continued with subsequent courses. This acquired abnormality may be responsible for a haemorrhagic diathesis even without obvious thrombocytopenia. Study of platelet function is important and may be considered to assess the haematological toxicity in patients being treated with systemic 5-FU therapy.

Journal Article↗

Magnetization transfer MR imaging in CNS tuberculosis.

BACKGROUND AND PURPOSE: CNS tuberculosis may simulate other granulomas and meningitis on MR images. The purpose of this study was to improve the characterization of lesions in CNS tuberculosis and to assess the disease load using magnetization transfer (MT) imaging. METHODS: A total of 107 tuberculomas in seven patients with or without meningitis and 15 patients with tuberculosis meningitis alone were studied. Fifteen patients with cysticercus granulomas with T2 hypointensity, five patients each with viral and pyogenic meningitis, and two patients with cryptococcal meningitis were also studied. The MT ratios were calculated from tuberculomas, cysticercus granulomas, and thickened meninges in tuberculous, viral, pyogenic, and cryptococcal meningitis and were compared within each pathologic group and with the MT ratio of different regions of normal brain parenchyma. Detectability of lesions on T1-weighted MT spin-echo (SE) images was compared with that on conventional SE and postcontrast MT-SE images. RESULTS: Thickened meninges appeared hyperintense relative to surrounding brain parenchyma in the basal and supratentorial cisterns on precontrast MT-SE images in all 18 patients with tuberculosis meningitis. These meninges were not seen or were barely visible on conventional SE images, and enhanced on postcontrast MT-SE images. The MT ratio from the thickened meninges of tuberculous meningitis was significantly lower than that from the meninges in cryptococcal and pyogenic disease and significantly higher than the meninges in viral meningoencephalitis. The MT ratio from T2 visible and invisible tuberculomas appeared to be significantly lower than that of normal white matter. The MT ratio of T2 hypointense cysticercus granuloma was significantly higher than that of T2 hypointense tuberculoma. CONCLUSION: Precontrast MT-SE imaging helps to better assess the disease load in CNS tuberculosis by improving the detectability of the lesions. With the use of MT ratios, it may be possible to differentiate tuberculosis from similar-appearing infective lesions on MR images.

Adolescent↗

Parainfectious conus myelitis.

We describe electroclinical and imaging features of a peculiar type of parainfectious myelitis that selectively involves the conus/epiconus region of the spinal cord. Twelve patients of parainfectious myelitis with MRI evidence of inflammatory lesions in the conus/epiconus region of the spinal cord were studied. All patients underwent full clinical and electrophysiological evaluation along with MRI of the spine. MRI included axial images at the site of lesion. All patients had a unique clinical presentation with urinary symptoms. Careful clinical examination revealed minimal sensorimotor dysfunction in the lower lumbar and sacral segments, which remained unnoticed by most of the patients; three female patients had no sensorimotor deficit. The motor paralysis recorded in four patients was flaccid and areflexic. The sensory level was inconspicuous as it was in the leg area corresponding to the lumbar and sacral spinal segments. Sensory loss was significantly more in the perineal region in those seven patients who had MRI evidence of inflammatory lesion in conus medullaris; two patients had maximum sensory loss in lumbar dermatomal distribution, which corresponded with the focal segmental myelitis involving 'epiconus'. MRI done in the sagittal plane was either normal or only 'suggestive' of myelitis in most of the patients and the inflammatory lesions were much more visible in the axial plane. The lesions predominantly involved central gray matter with spread to adjoining white matter in nine patients; in three patients with pure bladder involvement, lesions were confined to lateral gray matter of the conus medullaris. Our findings indicate that parainfectious myelitis (PIM) selectively involving conus medullaris is an important cause of unexplained acute or sub-acute urinary symptoms in adolescent and adult patients. In suspected cases, MRI must include axial images of the conus-epiconus region, as sagittal images may not always reveal the lesion. Due to initial presentation with urinary symptoms, absent or minimal sensory-motor signs, no transverse level over the trunk and unique MRI features, this condition may be called parainfectious conus myelitis (PICM).

Acute Disease↗

Isolation, characterization and baculovirus-mediated expression of the cDNA encoding cytosine DNA methyltransferase from Pisum sativum.

A series of overlapping clones complementary to the Arabidopsis cytosine-5 DNA methyltransferase (C-5 MTase) has been isolated from pea cDNA libraries. The assembled nucleic acid sequence contains an open reading frame of 4761 bp encoding a protein of 1554 amino acids. Like other eukaryotic C-5 MTases, the inferred protein has a presumed regulatory N-terminal region linked to a catalytic C-terminal domain, which has eight of the ten conserved motifs found in prokaryotic C-5 MTases. The pea C-5 MTase has 65% identity at the nucleotide level and 61% identity at the protein level, with the Arabidopsis C-5 MTase. The catalytic domain of the pea enzyme shares 78% identity with Arabidopsis and approximately 52% identity with murine and human C-5 MTases, including the relative position of the proline-cysteine dipeptides of the catalytic centre. Using the conserved region of the cDNA as a probe, we have identified a transcript of 5 kb. Southern blot analysis of pea genomic DNA with the above probe indicates the presence of a single gene. Using poly(A)+ RNA from different developmental stages and different tissues, we have observed that expression is confined mostly to the rapidly dividing tissues of the plant. Expression of this assembled cDNA in a baculovirus system gives a protein of approximately 174 kDa. The expressed protein can be cross-linked, in an AdoMet-dependent manner, to duplex oligonucleotide substrates containing FdC in place of target cytosines in either CG or CAG/CTG sequences.

Amino Acid Sequence↗

Kluver Bucy syndrome in young children.

For the first time, Kluver Bucy syndrome (KBS) is described in young children who had no environmental learning of sex. The syndrome has so far been noted only in adults after bilateral temporal lobe affection. A few of its components, especially the hypersexuality and hypermetamorphosis, are likely to manifest differently in very young children. Seven patients in the pre-pubertal age group, who developed KBS as a post-encephalitic sequelae, are described. The patients, 2.5-6 years old, suffered from acute herpes simplex encephalitis (HSE) at 10 months-5.5 years of age and developed KBS on regaining consciousness and ambulation. Altered emotional behaviour, changes in dietary habits, hyperorality and hypersexuality were present in all, while psychic blindness and hypermetamorphosis were noted in a few of the patients. All showed marked indifference and lack of emotional attachment towards their close relatives. Apathy and easy distractibility were rare. Bulimia and strong urge to put non-food items into the mouth were common. Hypersexuality manifested as frequent holding of genitals, intermittent pelvic thrusting movements and rubbing of genitals to the bed on lying prone. Due to lack of environmental learning of sex and also, due to emotional and physical dependence on parents, the manifestations in young children showed modification over those of adults.

Brain Damage, Chronic↗

Carcinoma of the gallbladder presenting as scalp tumour.

Carcinoma of the gallbladder is characterized by rapid tumour growth associated with lymphatic and local tumour invasion. The peritoneum, GIT and lungs are common sites of seeding. Distant metastasis to bone rarely occurs. Here we document a case of silent gallbladder carcinoma presenting as scalp tumour with improved survival.

Carcinoma↗

Time dependent selective recurrent discharge of motor units in F-response.

The interaction among the recurrent discharge of motor units is studied in surface recorded composite F-response. In the first experiment, 200 serially elicited polyphasic F-responses from foot muscles of patients with different lower motor neurone (LMN) disorders were rearranged to understand the behaviour of individual negative and positive peaks. These peaks were considered on the basis of simultaneous recording with a single fibre EMG needle, to be the partial expression of either a single motor unit potential (MUP) or more than one MUP generated simultaneously. In another experiment, two serially averaged F-responses (50 each) were superimposed over each other to look for their similarities at 15 min intervals 6 times. Result analysis indicated interaction of MUPs by in-phase summation and out-of-phase subtraction. Less affected MUPs recurred as negative or positive peaks in morphologically different F-responses. Certain peaks were observed more frequently than the others. Two serially averaged F-responses were nearly identical on superimposition over each other but their morphologies differed at different time intervals. The study suggests more frequent generation of F-response in a specific group of alpha motoneurones at one point of time, which is replaced by another group at another point of time. The characteristic variation in F parameters is, however, mainly due to the interaction of these frequently generated F-response MUPs with other sporadically generated ones. This interaction can be appreciated on visual screening of F-responses in patients with lower motor neurone disorders, perhaps because of a reduction in the number of participating MUPs.

Adolescent↗

Chemosensitivity of advanced larynx carcinoma cells in vitro and significance of multidrug resistance markers in these tumors.

Thirty cases of previously untreated advanced larynx carcinoma were checked for in vitro chemosensitivity and presence of the resistance markers viz. P-glycoprotein (P-gp) glutathione-S-transferase-pi (GST-pi) and protein kinase C (PKC) overexpression. The cytotoxicity testing was done using MTT assay and the resistance markers were checked by immunohistochemical methods using monoclonal antibodies. The drug combinations employed in MIT assay were 5FU* + MTX*, 5FU + cisPt*, 5FU + Mito*, cisPt + Mito and MTX + Mito (*5FU = 5Fluorouracil, MTX-methotrexate, cisPt-cisplatin and Mito = mitomycin C). No statistically significant correlation was observed between resistance to the above drug combinations and presence of the resistance markers under consideration. A statistically significant correlation was observed between node positivity and expression of resistance markers which indicates that presence of one or more of these markers in these tumors may be considered as a negative prognosis marker. CisPt-Mito was found to be the most effective drug combination in vitro, in the cases studied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Comparison of low molecular weight heparin (Fragmin) with sodium heparin for prophylaxis against postoperative thrombosis in women undergoing major gynaecological surgery.

A randomized controlled trial was undertaken comparing the efficacy and safety of low molecular weight (LMW) heparin (Fragmin) with sodium heparin for prophylaxis against postoperative thromboembolic disease after major gynaecological surgery. Women were randomized to receive subcutaneous injections of 5,000 U of either once daily LMW heparin or twice daily sodium heparin. A total of 566 women were recruited, of whom 552 completed the study. Most women (461) had malignant disease and 430 of these underwent radical surgery. The remainder underwent major, but not radical surgery. There were 5 thromboembolic events in the LMW heparin group and 2 in the sodium heparin group, with no significant difference between these groups. No significant difference was found in the incidence of intraoperative or postoperative transfusion in the 2 groups. The decision of which heparin to use in routine practice cannot be made on clinical grounds.

Anticoagulants↗

"Extensor toe sign" by various methods in spastic children with cerebral palsy.

Upper motor neuron lesion in adults is usually associated with spasticity and "extensor toe sign" on plantar stimulation (extensor plantar response). There are various methods of eliciting this sign including the classic method by Babinski. Other methods produce this response when the area of reflexogenic zone is increased due to upper motor neuron lesion. There are varying reports of Babinski positivity in spastic cerebral palsy. This study was undertaken to assess the sensitivity of different methods of eliciting "extensor toe sign." An attempt has also been made to correlate the severity of spasticity with the combined "extensor toe sign" positivity by various methods and with the increase in reflexogenic zone. Eighty-one children with spastic cerebral palsy were examined. Twelve had hemiplegia; therefore, a total of 150 limbs were tested. "Extensor toe sign" was elicited by 12 different methods in each patient. The sensitivity of each method was calculated and compared with each other one. The assessment of spasticity was done using the Ashworth Tone Scale. The severity of spasticity was correlated with "extensor toe sign" positivity using various methods. Classic Babinski reflex was positive in 75% of cases, whereas Gonda-Allen sign was positive in 90% of cases followed by Allen-Cleckley (82%), Chaddock (74%), and Cornell (54%). All other signs had sensitivity of less than 30%. There was no increase in sensitivity after combining them. There was significant negative correlation between the spasticity and the combined "extensor toe sign" positivity (by all the methods). This study, therefore, suggests that the majority of patients with spastic cerebral palsy have positive "extensor toe sign." The Gonda-Allen method is more sensitive than the classic Babinski method. A positive "extensor toe sign" is negatively correlated to the degree of spasticity.

Adolescent↗

Baculovirus-mediated expression and characterization of the full-length murine DNA methyltransferase.

The original cDNA sequence reported for the murine DNA methyltransferase (MTase) was not full length. Recently, additional cDNA sequences have been reported that lie upstream of the original and contain an extended open reading frame with three additional ATGs in frame with the coding region [Tucker et al . (1996) Proc. Natl. Acad. Sci. USA , 93, 12920-12925; Yoder et al . (1996) J. Biol. Chem . 271, 31092-31097]. Genomic DNA upstream of this ATG contains two more ATGs in frame and no obvious splice site. We have constructed, and expressed in baculovirus, MTase clones that begin at each of these four ATGs and examined their properties. Constructs beginning with any of the first three ATGs as their initiator methionines give a predominant DNA MTase band of approximately 185 kDa on SDS-PAGE corresponding to translational initiation at the third ATG. The fourth ATG construct gives a much smaller protein band of 173 kDa. The 185 kDa protein was purified by HPLC, characterized by mass spectrometry and has a measured molecular mass of 184 +/- 0.5 kDa. All of these MTases were functional in vitro and steady state kinetic analysis showed that the recombinant proteins exhibit similar kinetic properties irrespective of their length. The homogeneous recombinant enzyme from the fourth ATG construct shows a 2.5-fold preference for a hemi-methylated DNA substrate as compared to an unmethylated substrate, whereas the 185 kDa protein is equally active on both substrates. The kinetic properties of the recombinant enzyme are similar to those reported for the native MTase derived from murine erythroleukemia cells. The new clones are capable of yielding large quantities of intact MTases for further structural and functional studies.

Amino Acid Sequence↗

Selective involvement of basal ganglia and occipital cortex in a patient with acute endosulfan poisoning.

We report a teenage girl with acute endosulfan poisoning who developed psychosis, generalized tonic-clonic seizures, myoclonic jerks, cortical blindness and limb rigidity. Serial magnetic resonance imaging (MRI) showed bilateral reversible lesions localized to caudate nucleus, putamen and occipital cortex; internal capsule and thalamus were spared. This selective involvement may have a bearing on mechanisms underlying endosulfan toxicity.

Adolescent↗

Magnetic resonance imaging in juvenile asymmetric segmental spinal muscular atrophy.

Magnetic resonance imaging (MRI) of cervical spine was performed in 16 patients of juvenile asymmetric segmental spinal muscular atrophy (JASSMA) in neutral and flexed positions to look for abnormalities in the spinal cord and the surrounding structures. The study included 5 normal individuals and 5 disease-negative controls who had spinal cord atrophy due to amyotrophic lateral sclerosis. In normal and disease-negative controls, lower cervical spinal cord moved forward and got mildly flattened against the vertebral bodies during flexion. The subarachnoid space increased behind the cord with no significant forward movement of the posterior dura mater; epidural space was just visible. The patients of JASSMA showed spinal cord atrophy in a small vertical segment in front of cervical 4 to 7 vertebral bodies. In addition, 9 patients had high cord signal on T2 weighted images, mainly localized to anterior and lateral horns of the grey matter. In flexion, there was marked anterior displacement and anteroposterior flattening of lower cervical cord against the vertebral bodies; posterior dura mater also moved forward obliterating subarachnoid space in all the patients. A large posterior epidural space was visible which showed enhancement after gadolinium-DTPA administration. Twelve patients had prominent blood vessels in this epidural space. These findings suggest that MRI done in neck flexion may have diagnostic significance in JASSMA.

Adult↗