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Biomedical subjects

U K Misra

Publications and source records attributed to U K Misra.

At least 73 records · Page 4Linked to original sources
PubMed2001

Ligation of the alpha2M* signaling receptor regulates synthesis of cytosolic phospholipase A2.

We have studied the regulation of cytosolic phospholipase A2 (cPLA2) synthesis in macrophages stimulated with receptor-recognized forms of alpha2-macroglobulin (alpha2M*). [35S]methionine-labeled cells were stimulated with alpha2M* and [35S]cPLA2 was immunoprecipitated with a monoclonal antibody directed against cPLA2. The precipitates were electrophoresed, immunoblotted, cPLA2 detected by Enhanced Chemifluorescence, and its radioactivity determined. Stimulation of cells with alpha2M* caused a two- to threefold increase in cPLA2 synthesis compared to buffer-treated cells which was consistently maximal at 200 pM of alpha2M*. Actinomycin D or cycloheximide treatment of cells drastically reduced alpha2M*-induced cPLA2 synthesis. Likewise, inhibition of protein kinase C with chelerythrin, farnesyl transferase with manumycin A, MEK kinase with U0126, Erk1/2 kinases with PD98059, p38MAPK with SB203580, PI 3-kinase with wortmannin or LY294002, p70s6k with rapamycin, or depletion of [Ca2+]i with either BAPTA/AM or EGTA drastically reduced alpha2M* induction of cPLA2. Inhibition of NFKB activation with BAY11-7182 or PGA1 also abolished alpha2M* induction of cPLA2. We conclude that alpha2M*-induced cPLA2 synthesis is controlled by [Ca2+]i levels, tyrosine kinase activity, the p21ras-dependent MAPK and PI 3-kinase downstream signaling pathways, and regulation of NFkappaB.

Alkyl and Aryl Transferases↗
PubMed2001

Inducible expression of the alpha2-macroglobulin signaling receptor in response to antigenic stimulation: a study of second messenger generation.

Thioglycollate (TG)-elicited murine, peritoneal macrophages express two receptors for activated forms of the proteinase inhibitor alpha2-macroglobulin (alpha2M*)--namely, the low density lipoprotein receptor-related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). We now report that resident peritoneal macrophages express only 400+/-50 alpha2MSR receptors/cell compared to 5000+/-500 receptor/TG-elicited macrophage. By contrast, LRP expression is only 2-2.5-fold greater on elicited cells. The low level of alpha2MSR expression by resident cells is insufficient to trigger signal transduction in contrast to TG-elicited cells which when exposed to alpha2M* demonstrate a rapid rise in inositol 1,4,5-trisphosphate and a concomitant increase in cytosolic free Ca2+. We then studied a variety of preparations injected subcutaneously for their ability to upregulate alpha2MSR. Macroaggregated bovine serum albumin (macroBSA) injection upregulated alpha2MSR and triggered signaling responses by splenic macrophages. Nonaggregated BSA injection alone or in the presence of alum, by contrast, did not alter alpha2MSR expression. Recombivax (hepatitis B antigen adsorbed to alum) injection also upregulated alpha2MSR on splenic macrophages while the alum carrier had no effect. We conclude that macrophage alpha2M* receptors are inducible and their expression may be regulated, in part, by potential antigens.

Adjuvants, Immunologic↗
PubMed2001

Induction of cyclooxygenase-2 synthesis by ligation of the macrophage alpha(2)-macroglobulin signalling receptor.

We have studied the induction of cyclooxygenase-2 (COX-2) in macrophages consequent to ligating the alpha(2)-macroglobulin (alpha(2)M) signalling receptor (alpha(2)MSR) with receptor-recognized forms of alpha(2)M (alpha(2)M*). Macrophage stimulation with alpha(2)M* increased total cellular and nuclear COX-2 two- to threefold. The maximal increase in COX-2 occurred at a ligand concentration of 50-100 pM and after 2 h. Modulation of intracellular Ca(2+) levels or incubation of [35S] methionine-labelled macrophages with actinomycin D, prior to treatment with alpha(2)M*, markedly reduced the induction of total cellular and nuclear COX-2. Protein kinase C (PKC) or phospholipase A(2) (PLA(2)) inhibition in alpha(2)M*-stimulated macrophages or inhibition of the p21(ras)-dependent mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI 3-kinase) signalling pathways also significantly reduced alpha(2)M*-induced total cellular and nuclear COX-2 expression. Thus, COX-2 induction is dependent on cPLA(2) activity, Ca(2+) mobilization, and PKC activity and requires participation of both the p21(ras)-dependent MAPK and PI 3-kinase signalling pathways. COX-2 activation may mediate alpha(2)M*-induced mitogenesis, which we have previously observed in this and other cell types.

Animals↗
PubMed2001

Consequences of neck manipulation performed by a non-professional.

Case report. Documentation of complication of neck manipulation by an untrained person. Tertiary care referral teaching hospital at Lucknow, India. Clinical evaluation, plain radiography of cervical spine, spinal MRI.A 30-year-old man who fainted after neck manipulation by a barber and developed spinal cord and brainstem dysfunction. His MRI revealed an extramedullary, intradural dumbbell shaped mass on the right side at C1 and C2 level compressing the spinal cord. Public awareness should be increased about the danger of neck manipulation by an untrained person especially in the communities where it is commonly practiced.

Adult↗
PubMed2001

Is methyl prednisolone useful in acute transverse myelitis?

STUDY DESIGN: Hospital based observational study. OBJECTIVES: To evaluate the role of methyl prednisolone (MPS) in the management of acute transverse myelitis (ATM). METHODS: Twenty-one patients with ATM were included in a prospective hospital based study during 1992-1997. All the patients underwent neurological examination, spinal MRI, somatosensory and motor evoked potentials of both upper and lower limbs and concentric needle EMG study. Twelve consecutive patients did not receive MPS therapy who were managed during 1992-1994 and nine consecutive patients during 1995-1997 received MPS therapy in a dose of 500 mg i.v. for 5 days. The clinical and neurophysiological studies were repeated 3 months later. The outcome was defined on the basis of Barthel index (BI) score at the end of 3 months into good (BI> or =12) and poor (BI<12). RESULTS: The age of MPS group was 25.5 years (range 12-42) and three were females. The age of non MPS group was 33.5 years (range 16-70) and two were females. In the MPS group 33% had poor outcome compared to 67% in the non MPS group. In the MPS group mean admission BI score was 7.3 which improved to 14.6 after MPS therapy. In the non MPS group, the admission BI score was 3.2 which improved to 9.6 at 3 month follow-up. In patients with complete paraplegia, evidence of denervation on EMG and unrecordable central motor conduction time to lower limb and tibial SEP were associated with poor outcome irrespective of MPS treatment. Global test statistics did not suggest a beneficial role of MPS therapy in the outcome of ATM. CONCLUSION: Our results do not suggest a beneficial role of methyl prednisolone on the 3 month outcome of ATM.

Acute Disease↗
PubMed2001

A study of bone densitometry in patients with complex regional pain syndrome after stroke.

INTRODUCTION: This study was undertaken to evaluate the bone mineral density (BMD) in patients with complex regional pain syndrome type-I (CRPS-I) after stroke, and to correlate it with various clinical and neurophysiological parameters. PATIENTS AND METHODS: Twenty patients with CRPS-I after stroke were included and a detailed neurological evaluation was carried out. The severity of CRPS-I was graded on the basis of shoulder hand syndrome score. All the patients underwent bone mineral densitometry of paralysed and non-paralysed forearm by dual energy x ray absorptiometry. The BMD of paralysed forearm was also compared with that of age matched healthy controls. Neurophysiological tests included sympathetic skin response in both upper and lower limbs and median somatosensory evoked potentials. RESULTS: The mean age of patients was 57.2 (45-75) years and eight were females. Eight patients had severe weakness and 12 had moderate weakness of grade 2 on the hemiplegic side. There was significant reduction in BMD in the patients compared with controls (p<0.01). The bone density reduction correlated well with duration of illness (r = -0.673, p<0.01), shoulder hand syndrome score (r = -0.804, p<0.01), and Canadian neurological scale score (r = -0.738 p<0.01). Sympathetic skin response was not recordable bilaterally in all patients. Median somatosensory evoked potentials were not recordable in seven out of 20 patients who also had higher grade of CRPS-I. CONCLUSION: Our results show significant reduction of BMD in patients with CRPS-I after stroke. The reduction in BMD correlates with the severity of shoulder hand syndrome score, degree of weakness, duration of hemiplegia, and the severity of stroke.

Absorptiometry, Photon↗
PubMed2001

Brainstem auditory evoked potentials in tubercular meningitis and their correlation with radiological findings.

The present study has been undertaken to describe brainstem auditory evoked potential (BAEP) changes in tubercular meningitis (TBM) and correlate these with CT scan and MRI findings. 24 patients with TBM were subjected to clinical evaluation and CT scan or MRI study. Outcome was defined by 3 month Barthel index score (BI) into poor (BI<12) and good (BI>or=12). The mean age of patients was 26.4+/-14.9 (range 10-62) years, 8 of them were females. Sixteen patients were in stage III, 5 in stage II and 3 in stage I meningitis. CT scan revealed hydrocephalus in 16, exudate in 9, infarction in 12 and tuberculoma in 3 patients. Brainstem was involved in 3 patients (2 infarction and 1 granuloma). BAEPs were unrecordable in one patient and abnormal in 15. The absolute latencies and inter peak latency (IPL) however were not significantly affected. The wave V/I amplitude ratio was abnormal on 12 sides. The BAEP abnormalities were not related to the stage of meningitis, level of consciousness, any specific CT or MRI changes or outcome at 3 months.

Adolescent↗
PubMed2001

Seizures after stroke : a prospective clinical study.

Stroke is one of the most common causes of epilepsy in elderly. However, there have been very few prospective studies to define the incidence, pattern and outcome of seizures in stroke. Most studies are based on retrospective analysis of hospital records. Hence, we planned this prospective study to see the clinical, radiological and electroencephalographic characteristics of seizures in stroke and their outcome, from a north Indian tertiary care centre. Over a span of approximately 6 years, 269 consecutive patients with stroke were studied and followed up. Thirty-five (13%) of these developed seizures, primarily related to stroke, during mean follow up period of 15.9 months. Twenty of these had infarctions while 15 had haemorrhages. Involvement of the cortical region was seen in most of the patients with seizures. In these patients, 86% of the lesions involved cortical areas exclusively or in addition to subcortical areas on CT scan of the brain. Twenty-seven (77%) developed early seizures, two third of them had immediate post-stroke seizures. None of the patients with early onset seizures developed recurrent seizures or epilepsy, while 50% of late onset seizures developed epilepsy. No specific EEG pattern was found in those who later developed epilepsy. In the present study, early onset seizures after stroke were rather common and did not affect outcome and did not recur even when not treated with anti-epileptics. Late onset seizures were less common but were associated with recurrent seizures.

Adolescent↗
PubMed2001

Central motor conduction studies in patients with Guillain Barré syndrome.

To study the central nervous system involvement in Guillain Barre (GB) syndrome, 30 patients with GB syndrome were subjected to clinical evaluation, muscle testing as per Medical Research Council (MRC) scale, disability score on a 0-5 scale and central motor conduction studies to abductor digiti minimum (ADM), abductor pollicis bravis (APB) and tibialis anterior (TA) bilaterally. Outcome was defined at the end of 3 months into complete, partial and poor. Their age ranged between 12 and 61 years (mean 3.2) and 11 of them were females. At the peak of weakness, the limb muscle power was grade 0 in 8, grade I-II in 10 and grade III-IV in 12 patients. Grade 5 disability was present in 12, grade 4 in 12 and grade 3 in 6 patients. One of these patients had grade 3 muscle power. Central motor conduction time (CMCT) correlated with muscle power, disability score and outcome. Two of our patients expired during the acute stage and 23 could be followed up till 3 months. Three patients recovered completely, 15 partially and 5 had poor recovery. It can be concluded that mild prolongation of CMCT although occurs frequently in the patients with GB syndrome, however, pronounced slowing of CMCT is rare and may suggest central involvement.

Adolescent↗
PubMed2001

Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages.

Apolipoprotein E (ApoE) is a 34-kDa cholesterol transport protein that also possesses immunomodulatory properties. In this study, we demonstrate that ApoE initiates a signaling cascade in murine peritoneal macrophages that leads to increased production of inositol triphosphate with mobilization of intracellular Ca(2+) stores. This cascade is inhibited by pretreatment with receptor-associated protein and Ni(2+), and it is mediated by a pertussis toxin-sensitive G protein. These properties are characteristic of signal transduction induced via ligand binding to the cellular receptor, lipoprotein receptor-related protein. A peptide derived from the receptor-binding region of ApoE also initiates signal transduction in a manner similar to that of the intact protein, suggesting that this isolated region is sufficient for signal transduction. The ApoE-mimetic peptide competed for binding with the intact protein, confirming that they both interact with the same site. ApoE-dependent signal transduction might play a role in mediating the functional properties of this lipoprotein.

Animals↗
PubMed2001

Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis.

A prospective hospital based study was undertaken to study the effect of methyl prednisolone therapy on sensory and motor functions in tuberculous meningitis (TBM). The patients with TB meningitis seen during 1994-1998 were studied. CT scan, motor evoked potential (MEP) to upper and lower limbs; and median and tibial somatosensory evoked potentials (SEP) were carried out in all the patients. Outcome was defined at the end of 3 months into poor, partial or complete recovery on the basis of Barthel index score. Inj methyl prednisolone (MPS) 500 mg IV was given to 21 patients followed by oral tapering dose of prednisolone over one month in addition to 4 drug anti-tubercular treatment. The control group comprised of 16 patients who received 4 drugs anti-tubercular therapy without any corticosteroid. These groups were comparable with respect to their age, stage of meningitis, Glasgow coma scale score and radiological findings. In MPS group, CMCT was abnormal in 9 and SEPs in 7 patients. In the control group, these were abnormal in 9 and 5 patients respectively. Three months after the therapy the frequency of improvement, deterioration and stationary evoked potential (EP) changes were also noted in both the groups. Diversity of evoked potential changes were also noted. Evoked potential changes were neither significantly different between the groups nor there was any beneficial effect shown in MPS group at 3 months. On the contrary, the control group fared significantly better than the MPS group. Initial MEP and SEP abnormalities were however related to 3 months outcome (p<0.01).

Adult↗
PubMed2000

Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells.

Cellular binding of receptor-recognized forms of alpha2-macroglobulin (alpha2M*) is mediated by the low-density lipoprotein receptor related protein (LRP) and the alpha2M signaling receptor (alpha2MSR). In nonmalignant cells, ligation of alpha2MSR promotes DNA synthesis and cellular proliferation. Here, we report that insulin treatment of highly metastatic 1-LN human prostate carcinoma selectively increases alpha2MSR expression and binding of alpha2M* to 1-LN cells. alpha2M* induces transient increases in intracellular calcium and inositol 1,4,5-trisphosphate in insulin-treated 1-LN cells, consistent with activation of alpha2MSR. Inhibition of signaling cascades activated by insulin blocks upregulation of alpha2MSR. By contrast, alpha2M* does not bind to nor induce intracellular signaling in PC-3 cells, even though 1-LN cells were subcloned from PC-3 cells. We suggest that alpha2M* behaves like a growth factor in these highly malignant cells. The 1-LN metastatic phenotype may result, in part, from aberrant expression of alpha2MSR, indicating the possible involvement of alpha2M* in tumor progression.

Humans↗
PubMed2000

Cytosolic phospholipase A(2) activity associated with nuclei is not inhibited by arachidonyl trifluoromethyl ketone in macrophages stimulated with receptor-recognized forms of alpha(2)-macroglobulin.

We have studied the translocation of cytosolic phospholipase A(2) (cPLA(2)) to nuclei in macrophages stimulated with receptor-recognized forms of alpha(2)-macroglobulin (alpha(2)M*). Translocation of phosphorylated cPLA(2) to nuclei was determined by immunoprecipitation of cPLA(2) in (32)P(i)-labeled cells. The identity of cPLA(2) was established by comparing its mobility on gels with an authentic cPLA(2) standard. cPLA(2) activity was quantified by measuring the release of [(14)C]arachidonic acid from the substrate 1-palmitoyl-2-[1-(14)C]arachidonyl-sn-glycerophosphatidylcholine. alpha(2)M* caused a two- to threefold increase in cPLA(2) phosphorylation and its translocation to nuclei. The p38 MAPK inhibitor SB203580, PKC inhibitor chelerythrin, or depletion of intracellular Ca(2+) profoundly decreased cPLA(2) activity in nuclei isolated from agonist-stimulated cells. The requirement for Ca(2+), PKC, and p38 MAPK activation appears to be of major importance for nuclear cPLA(2) activity. In contrast to cellular cPLA(2) activity, nuclear cPLA(2) activity was not inhibited by arachidonyl trifluoromethyl ketone (AACOCF(3)) in agonist-stimulated cells. It is concluded that the association of cPLA(2) with nuclear membranes in agonist-stimulated cells modifies the activity and the sensitivity of the enzyme to inhibition by AACOCF(3) in this phospholipid environment.

Animals↗
PubMed2000

Locomotor and learning deficits in adult rats exposed to monosodium-L-glutamate during early life.

Neonatal administration of neurotoxic doses of monosodium-L-glutamate (MSG) to rats causes neuronal necrosis of the hypothalamus along with behavioral abnormalities. In the present study the behavioral effects in rats treated with subneurotoxic doses of MSG (2 mg/g, p.o., for 10 days) at the weaned stage were investigated at day 90 post-dosing. The MSG-treated rats did not show significant changes in any of the components of spontaneous locomotor activity but, after apomorphine challenge, marked decreases in the distance travelled, ambulatory and stereotypic times, and the number of stereotypic movements with an increase in the resting time were observed. Significant decrease in the active avoidance learning performance was observed in the MSG-treated rats in the learning (acquisition) phase without any changes in the extinction and relearning phases. The results indicate that exposure to MSG in early life in rats could lead to subtle behavioral aberrations in late adulthood.

Age Factors↗
PubMed2000

Comparison of CT scan and MRI findings in the diagnosis of Japanese encephalitis.

Japanese encephalitis (JE) is the commonest endemic encephalitis but there are very few studies on the radiological changes and these are based on relatively small number of patients. The present study aims at comparing the CT scan and MRI findings in JE and correlate these with the reported histopathological findings. Forty two patients with JE were subjected to detailed neurological examination. Cranial CT scan was carried out in 38 and MRI scan in 31 patients. Haemagglutination inhibition test was carried out in the acute and convalescent sera. The CT scan and MRI findings have been compared. Both CT scan and MRI were available in 28 patients. In 21 patients, CT scans were abnormal and changes included thalamic hypodensity in 15, midbrain and basal ganglia hypodensity in 1 patient each, cerebral oedema in 4 and cortical atrophy with ventricular dilatation in 2 patients. MRI however was abnormal in all 31 patients including 17 with normal CT scan. Cranial MRI revealed either mixed intensity or hypointense lesion on T(1) and hyperintense or mixed intensity lesion on T(2) in thalami in all except two patients. The MRI lesions were also noted in basal ganglia in 11, midbrain in 18, pons in 8, cerebellum and cerebral cortex in 6 patients each and subcortical white matter in 2 patients. MRI was more sensitive than CT scan in revealing thalamic and extrathalamic abnormalities. Thalamic changes may be helpful in the diagnosis of JE especially in endemic area.

Adolescent↗
PubMed2000

Markedly severe dystonia in Japanese encephalitis.

Encephalitis has been reported to be a rare cause of severe dystonia. We describe five patients with markedly severe dystonia from Japanese encephalitis. These patients with markedly severe dystonia were seen during the past 8 years as a subgroup of 50 patients with Japanese encephalitis. The diagnosis of markedly severe dystonia was based on increasingly frequent episodes of generalized dystonia with bulbar, respiratory, or metabolic derangement or leading to exhaustion or pain. The diagnosis of JE was based on clinicoradiologic features and a fourfold increase of hemagglutination-inhibiting antibody titers in paired serum. The outcome of the patients was defined as a good, partial, or poor recovery on the basis of 1-year clinical status. All the patients were males, and their ages ranged from 6 to 19 years. Movement disorders appeared 1 to 3 weeks after the illness as the level of consciousness started improving. During the next 1 to 4 weeks, patients began to experience markedly severe dystonia. It was associated with marked axial dystonia resulting in opisthotonus and retrocollis in five patients, jaw-opening dystonia in two patients, teeth clenching in one patient, and oculogyric crisis and neck deviation in another patient. The attacks of markedly severe dystonia lasted for 2 to 30 minutes and occurred as many as 20 to 30 times daily. Other developments included fixed limb dystonia in one patient, severe spasticity and rigidity in five patients, and focal muscle wasting in one patient. These patients had only a modest improvement after treatment. Markedly severe dystonia abated by 2 to 6 months in all the patients who were followed up. Cranial magnetic resonance imaging showed bilateral thalamic involvement in all patients, brainstem involvement in three patients, and basal ganglia involvement in two patients. At the 3-month follow-up, all patients had a poor outcome. At 1 year, one patient had a complete recovery; one had a partial recovery; and two were bedridden. It can be concluded that markedly severe dystonia is an important and serious sequela of Japanese encephalitis and may occur as the result of thalamus, midbrain, or basal ganglia involvement in various combinations.

Adolescent↗
PubMed2000

Neurophysiological studies in acute transverse myelitis.

A systematic evaluation of anterior horn cell, motor and sensory pathways is possible by electromyography (EMG), motor (MEPs) and somatosensory (SEPs) evoked potentials, respectively, which may provide valuable information on acute transverse myelitis (ATM). In a prospective hospital-based study, EMG, MEP and SEP studies were carried out on admission and after 3 months in 39 patients with ATM. All the patients also underwent detailed clinical evaluation, and spinal magnetic resonance imaging (MRI) was performed in 28. Outcome was defined at the end of 3 months as poor, partial or complete recovery on the basis of functional status. Spinal MRI revealed hyperintense signal changes in T2 extending for two segments to the entire spinal cord. Central motor conduction time to tibialis anterior (CMCT-TA) was more frequently abnormal (90%), followed by tibial SEP (77%). CMCT to abductor digiti minimi (ADM) was abnormal in 30% and median SEP in 15% of patients. Evidence of denervation on EMG was present in 51% of patients. The CMCT-TA improved in 48% patients and tibial SEP in 32%. Median SEP improved in all patients, and CMCT-ADM remained prolonged in two. At 3 months 2 patients had died, and 18 had poor, 10 partial and 9 complete recovery. CMCT was correlated with muscle power, tone, reflex and MRI changes. Patients' outcome of was correlated with CMCT, SEP and EMG. These results are consistent with pronounced involvement of dorsal region of spinal cord in ATM. MEP is more frequently abnormal than SEP.

Adolescent↗