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Biomedical subjects

M Natarajan

Publications and source records attributed to M Natarajan.

At least 19 recordsLinked to original sources
PubMed2006

HEF1 is a necessary and specific downstream effector of FAK that promotes the migration of glioblastoma cells.

The highly invasive behavior of glioblastoma cells contributes to the morbidity and mortality associated with these tumors. The integrin-mediated adhesion and migration of glioblastoma cells on brain matrix proteins is enhanced by stimulation with growth factors, including platelet-derived growth factor (PDGF). As focal adhesion kinase (FAK), a nonreceptor cytoplasmic tyrosine kinase, has been shown to promote cell migration in various other cell types, we analysed its role in glioblastoma cell migration. Forced overexpression of FAK in serum-starved glioblastoma cells plated on recombinant (rec)-osteopontin resulted in a twofold enhancement of basal migration and a ninefold enhancement of PDGF-BB-stimulated migration. Both expression of mutant FAK(397F) and the downregulation of FAK with small interfering (si) RNA inhibited basal and PDGF-stimulated migration. FAK overexpression and PDGF stimulation was found to increase the phosphorylation of the Crk-associated substrate (CAS) family member human enhancer of filamentation 1 (HEF1), but not p130CAS or Src-interacting protein (Sin)/Efs, although the levels of expression of these proteins was similar. Moreover downregulation of HEF1 with siRNA, but not p130CAS, inhibited basal and PDGF-stimulated migration. The phosphorylated HEF1 colocalized with vinculin and was associated almost exclusively with 0.1% Triton X-100 insoluble material, consistent with its signaling at focal adhesions. FAK overexpression promoted invasion through normal brain homogenate and siHEF1 inhibited this invasion. Results presented here suggest that HEF1 acts as a necessary and specific downstream effector of FAK in the invasive behavior of glioblastoma cells and may be an effective target for treatment of these tumors.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Effect of millimeter waves on cyclophosphamide induced NF-kappaB.

Antiapoptotic activity of NF-Kappa B (NF-kappaB) in tumors contributes to acquisition of resistance to chemotherapy. The effect of millimeter waves (MMWs) on NF-kappaB activation induced by cyclophosphamide (CPA) was studied in the spleen of mice. CPA, an anticancer drug, caused a marked increase (58.9-fold) in NF-kappaB DNA-binding activity as compared to the control group. No significant enhancement in NF-kappaB activity (0.51-fold) was observed when the CPA group was also irradiated with MMWs. These results suggest that treatment with MMWs can inhibit activation of NF-kappaB induced by chemotherapeutic drugs.

Animals↗
PubMed2006

Nuclear translocation and DNA-binding activity of NFKB (NF-kappaB) after exposure of human monocytes to pulsed ultra-wideband electromagnetic fields (1 kV/cm) fails to transactivate kappaB-dependent gene expression.

The objective of this study was to investigate whether exposure of human monocytes to a pulsed ultra-wideband electromagnetic field (EMF) of 1 kV/cm average peak power triggers a signaling pathway responsible for the transcriptional regulation of NFKB (NF-kappaB)-dependent gene expression. Human Mono Mac 6 (MM6) cells were exposed intermittently to EMF pulses for a total of 90 min. The pulse width was 0.79+/-0.01 ns and the pulse repetition rate was 250 pps. The temperature of the medium was maintained at 37 degrees C in both sham- and EMF-exposed flasks. Total NFKB DNA-binding activity was measured in the nuclear extracts by the electrophoretic mobility shift assay. Cells exposed to the EMFs and incubated for 24 h postexposure showed a 3.5+/-0.2-fold increase in the NFKB DNA-binding activity. Since activation of NFKB was observed, the possibility of kappaB-dependent gene expression in response to exposure to the EMFs was investigated using NFKB signal-specific gene arrays. The results revealed no difference in the NFKB-dependent gene expression profiles at 8 or 24 h postexposure, indicating that activated NFKB does not lead to the differential expression of kappaB-dependent target genes. To determine whether the absence of the kappaB-dependent gene expression was due to compromised transcriptional regulation of NFKB, the functional activity of NFKB was examined in cells transiently transfected with Mercury Pathway constructs containing 4x NFKB binding sites associated either with the luciferase reporter system or a control vector. Pulsed EMF exposure did not induce NFKB-driven luciferase activity in these cells, indicating that the activation of NFKB at 24 h after the 1 kV/cm EMF exposure is functionally inactive. From these results, it is clear that the EMF-induced NFKB activation is only a transient response, with minimal or no downstream effect.

Active Transport, Cell Nucleus↗
PubMed2005

Spine revisited: principles and parlance redefined.

A revised appreciation of the evolution and the nature of bone in general and of vertebrae in particular, allows revisiting the human spine to usher in some new principles and more rational parlance, that embody spine's phylogeny, ontogeny, anatomy and physiology. Such an approach accords primacy to spine's soft-tissues, and relegates to its bones a secondary place.

Bone and Bones↗
PubMed2003

Proximal femoral reconstruction with custom mega prosthesis.

Seventy-seven patients with proximal femoral tumours underwent limb salvage surgery with custom mega prostheses between July 1989 and January 2002. We describe 44 cases with a mean follow-up of 57.8 months. Forty-one patients presented with malignant neoplasms of which 11 were malignant giant cell tumours, eight were chondrosarcoma and five were metastases. Wide margins were achieved for all malignant tumours, and marginal resection was done for all benign and metastatic lesions. Six patients died of disease and two were lost to follow-up. Mechanical complications were observed in six cases, fracture being the most common. Oncological complications occurred in five patients. Functional activity was satisfactory in 79% of patients.

Adolescent↗
PubMed2003

Protection against oxidative protein damage induced by metal-catalyzed reaction or alkylperoxyl radicals: comparative effects of melatonin and other antioxidants.

Melatonin is a well-known hydroxyl radical (*OH) scavenger that protects DNA and lipids from free radical attack. In this paper, we studied the ability of melatonin to prevent oxidative damage to bovine serum albumin (BSA) induced by two different paradigms: the metal-catalyzed oxidation (MCO) induced by Cu(2+)/H(2)O(2) and the alkoxyl and alkylperoxyl radicals formed by the azo initiator 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH, 40 mM). The protective effects of melatonin were compared with 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), glutathione (GSH), ascorbate, 3,4',5-trihydroxy-trans-stilbene (resveratrol, 0.1 microM-4 mM) and mannitol (50 microM-100 mM). Melatonin efficiently prevented protein modification induced by both models, as assayed by polyacrylamide gel electrophoresis and carbonyl content. Both trolox and ascorbate had an obvious pro-oxidant effect in the Cu(2+)/H(2)O(2) model, whereas both prevented BSA damage induced by AAPH. In the MCO model, the efficacy of GSH in terms of protein protection was higher than melatonin at relatively high concentrations (250 microM-4 mM); however, at lower concentrations (50-250 microM), the efficacy of melatonin was superior to GSH. D-Mannitol (50 microM-100 mM) and resveratrol did not protect BSA from the site-specific damage induced by Cu(2+)/H(2)O(2). On the other hand, the relative protective efficiency in the AAPH model was melatonin approximately trolox>GSH>ascorbate.

Amidines↗
PubMed2003

Hemicraniectomy for large middle cerebral artery territory infarction: outcome in 19 patients.

BACKGROUND: Large space-occupying middle cerebral artery infarction accounts for 10-15% of all supratentorial infarctions and carries a mortality of 50% to 80%. Hemicraniectomy may be useful when optimal medical management has failed. METHODS: Between June 1997 and June 2000, 19 patients who fulfilled the clinical and imaging criteria for large middle cerebral artery infarction underwent hemicraniectomy because of impending herniation despite best medical therapy. The National Institute of Health Stroke Scale (NIHSS) assessed neurological status on admission and at one week after surgery. At 3 month follow up, The Barthel Index (BI) and Rankin Scale (RS) were used to assess the functional outcome among survivors. RESULTS: There were 15 males and 4 females with a mean age of 46.5 years (range 27-76 years). Ten patients (53%) had dominant hemisphere stroke. The mean interval between stroke onset and surgery was 60.3 hours (range 20-103 hours). The mean NIHSS score before surgery was 20.5 (range 17-26) and 10.5 (range 6-22) after surgery. One patient (5.2%) died due to post-operative meningitis. At follow up, mean BI was 56.4 (range 25-90) and RS revealed severe handicap in 4 patients (21%). Patients under 50 years of age had a significantly better outcome with mean BI of 60.7 as compared to only 41.3 (p=<0.048) in older patients. Speech function, especially comprehension improved in all patients with dominant hemisphere infarction. CONCLUSION: These findings add to previous studies suggesting hemicraniectomy may be a useful procedure in patients with large middle cerebral artery territory infarction. The functional outcome is good in younger patients. A randomised controlled trial is required to substantiate these findings.

Adult↗
PubMed2003

Non-Hodgkin's lymphoma of the brainstem with atrial septal mass.

Simultaneous occurrence of cardiac and central nervous system tumors have been rarely reported. A 23 years male presented to us with right cerebello-pontine (CP) angle symptoms and signs. Cranial imaging showed a mass lesion in the right pons infiltrating into the right and middle cerebellar peduncles. There was also a cardiac-atrial septal mass. The brainstem lesion was found to be a non-Hodgkin's lymphoma where as the cardiac lesion was not accessible. Central nervous system lymphomas are reported rarely and the prognosis is poor. The chances of the cardiac lesion in this patient also being a lymphoma are high, as it was a infiltrative cardiac mass, infiltrating the atrial septum.

Adult↗
PubMed2003

Major ion correlation in groundwater of Kancheepuram Region, South India.

Groundwater samples were collected from both dugwells and borewells in an intensively irrigated area of Kancheepuram Taluk, Tamil Nadu. pH, EC and TDS of groundwater samples were measured in the site. The collected samples were analysed in the laboratory for Ca, Mg, Na, K, Cl, HCO3, CO3, SO4, NO3, P-PO4 and Si-SiO2. The results are used for inter elemental correlation analysis which indicates that most of the elements having good correlation. Piper Trilinear diagram is used to find out the hydrochemical type of groundwater which shows that most of them are CaHCO3 and the remaining are CaMgCl type. Hydrochemical characteristics of groundwater indicate that silicate weathering reaction is a probable source for high concentration of major ions.

Environmental Monitoring↗
PubMed2001

Effect of melatonin on cell growth, metabolic activity, and cell cycle distribution.

We have recently demonstrated that the pineal secretory product melatonin inhibits the key transcriptional regulator nuclear factor-kappa B (NF-kappa B). As the activation of NF-kappa B is known to regulate the expression of cellular genes associated with cell cycle progression, cell growth, and differentiation, we investigated the effect of melatonin treatment on several cellular processes. These include cell viability, metabolic activity, and cell cycle phase distribution. Human embryonic kidney (293S) cells were treated with melatonin at concentrations of 0.02, 0.2, or 2 mM. When cell viability was measured 24, 48, and 72 hr after continuous exposure to melatonin using the trypan blue dye exclusion method, no significant cell death was observed. Even after exposure to 2 mM melatonin for 72 hr, cell viability remained at 98%. In contrast, another antioxidant compound, pyrrolidine dithiocarbomate (PDTC), at a 2 mM concentration reduced cell viability to 80.7+/-2.1% as early as 24 hr compared with untreated controls (P<0.05). When the metabolic activity was determined at 24, 48, and 72 hr using the colorimetric MTT assay, no significant changes in metabolic activity were observed. Even if the cells were treated with 10 mM melatonin for 72 hr, the metabolic activity was similar to that of the control cells. When cell cycle analysis was performed by flow cytometry, no marked difference in cell cycle distribution was observed. Melatonin at a concentration of 2 mM, however, did slightly alter the cell cycle (percentage of S phase cells) at 48 hr. This study revealed that when 293S cells are treated with concentrations of melatonin up to 2 mM, no significant alterations in three important cellular functions occurred. Exogenously added melatonin appeared to have a limited influence on the normal functioning of the cells even when the exposure continued for 72 hr.

Adjuvants, Immunologic↗
PubMed2001

Circulating nucleic acids of Chlamydia pneumoniae and cytomegalovirus in patients undergoing coronary angiography.

Peripheral blood mononuclear cells from 208 consecutive patients undergoing elective coronary angiography or angioplasty were collected before, immediately after, and 4 h after the procedure. Nucleic acids of Chlamydia pneumoniae and of cytomegalovirus (CMV) were detected by PCR and confirmed by hybridization. Circulating C. pneumoniae DNA was identified in 24 patients (11.5%) and was associated with current smoking (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.6 to 12.2, P = 0.004) but not with arterial narrowing on coronary angiogram or with serological results positive for C. pneumoniae. Circulating CMV DNA was identified in 36 patients (17.3%) and was associated with anti-CMV immunoglobulin G (OR = 2.7, 95% CI = 1.2 to 6.3, P = 0.02) but not with angiographic arterial narrowing or with the need for revascularization. Neither C. pneumoniae nor CMV DNA detection increased after angioplasty, a procedure in which endothelium is disrupted. Larger prospective studies are needed to determine the prognostic significance of DNA detection.

Adult↗
PubMed2001

Low levels of p53 mutations in Indian patients with osteosarcoma and the correlation with fluoride levels in bone.

The pathogenesis of osteogenic sarcoma is not known. Recently, chronic fluoride exposure has been incriminated as having a possible etiologic role by causing a nonspecific osteoblast proliferation. We were interested in exploring the possible relationship between fluoride bone content and p53 mutations. We analyzed p53 mutations in various exons in tissue of osteosarcoma, and correlated the findings with the bone fluoride levels in Indian patients. We analyzed tissue samples from 20 osteosarcoma patients for possible genetic alterations including mutations, and we assessed the extent of fluoride accumulation in bone. Fragments displaying an altered electrophoretic mobility were confirmed as having mutated sequences. Mutation was observed in samples of two cases (10% incidence). Eighteen samples showed bone fluoride levels between 1000 and 27,000 ppm, whereas the 2 mutated samples showed fluoride levels of 64,000 and 89,000 ppm, respectively. The high levels of bone fluoride levels and the similarity of the mechanisms of action between fluoride-induced DNA damage and chemically-induced p53 mutations lead us to propose that high fluoride bone content might have been one of the major factors causing osteosarcoma.

Adolescent↗
PubMed2000

Sympathoexcitatory CVLM neurons mediate responses to caudal pressor area stimulation.

Neurons in the caudal pressor area (CPA) are a source of tonic sympathoexcitation that is dependent on activation of cardiovascular sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM). In the present study, we sought to clarify the mechanism through which CPA neurons elicit increases in RVLM neuronal discharge, vasoconstrictor sympathetic tone, and arterial pressure. In urethan-chloralose-anesthetized, paralyzed, and artificially ventilated rats, bilateral disinhibition of CPA with bicuculline (Bic) after bilateral disinhibition of caudal ventrolateral medulla (CVLM) caused increases in splanchnic sympathetic nerve activity (+277% control) and arterial pressure (+54 mmHg). Inhibition of CVLM neurons with muscimol abolished the pressor response to activation of CPA neurons, suggesting that neurons within CVLM mediate the excitatory responses from CPA. Disinhibition of CVLM and CPA with Bic enhanced the sympathoexcitatory responses to stimulation of CPA with DL-homocysteic acid, which were blocked by microinjections of kynurenic acid into CVLM. We conclude that the pathway from CPA to RVLM involves an obligatory glutamatergic activation of sympathoexcitatory neurons in the vicinity of CVLM.

Animals↗
PubMed2000

Antioxidant compounds interfere with the 3.

Antioxidants are often added to culture media as cytoprotective agents. We examined the effects of antioxidants on the results and interpretation of the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay for cell viability. Without cells, the thiol-containing antioxidant compounds beta-mercaptoethanol, dithiothreitol, pyrrolidine-dithiocarbamate, and N-acetyl-L-cysteine (acetylcysteine) reduced MTT tetrazolium salts to a blue formazan product in a dose-dependent manner. Addition of the compounds L-ascorbic acid and (+)-alpha-tocopherol acid succinate had different effects. In contrast, addition of the antioxidants N-acetyl-5-methoxytryptamine and (-)-2-oxo-4-thiazolidine carboxylic acid, which do not contain reactive thiol groups, did not result in the development of blue formazan product. These results showed that antioxidants, and potentially other chemotherapeutic compounds that contain free thiol groups or other reducing equivalents, readily reduce MTT to produce the blue formazan, irrespective of the viability of the cells present. This undescribed reaction can, therefore, significantly influence the results and interpretation of cell-viability experiments.

Acetylcysteine↗
PubMed2000

Percutaneous trigeminal ganglion balloon compression: experience in 40 patients.

Forty patients of trigeminal neuralgia were treated with percutaneous trigeminal ganglion balloon compression. Symptoms had been present since six months to twenty years. The age ranged between 23 years and 73 years. All the patients had immediate relief from pain. Two had already undergone trigeminal cistern rhizolysis. One patient had foramen ovale stenosis. After the procedure, all the patients had mild to moderate degree of ipsilateral facial sensory loss which included buccal mucosa and anterior 2/3rd of the tongue. Facial dysaesthesia (anaesthesia dolorosa) was seen in only one case, who had mild involvement lasting one week. Thirty patients had altered taste sensation, probably due to general somatic sensory loss. Five patients had herpes perioralis. In this study group, two patients had already undergone microvascular decompression. All the patients were followed for a period ranging from one to eighteen months. Balloon compression technique seems to be better than injection of alcohol, glycerol or radio frequency lesion. Recurrence of pain was noted in 3 patients after one year.

Adult↗
PubMed1999

Nocturnal and daytime panic attacks--comparison of sleep architecture, heart rate variability, and response to sodium lactate challenge.

BACKGROUND: The purpose of this study was to determine if nocturnal panic patients have greater autonomic dysregulation than patients with daytime panic. METHODS: Three groups were studied: patients who suffer from panic attacks during sleep (n = 12), those who suffer from daytime panic attacks only (n = 12), and control subjects (n = 12). Each subject underwent 24-hour holter monitoring for heart rate variability (HRV), an overnight sleep recording, and sodium lactate challenge during wakefulness. RESULTS: There was a marked subjective response to the sodium lactate challenge in the panic disorder (PD) patients but not in control subjects. Each group showed changes in HRV in response to sodium lactate challenge. The decrease in HRV measures was more marked in PD patients as a whole than in control subjects. During non-rapid eye movement (REM) sleep the value for total power (TP) was significantly higher in the nocturnal panic patients. The PD patients as a whole had higher values for TP and low-frequency (LF) power during REM sleep than control subjects. There were no significant differences between the two PD groups in sleep architecture. The PD patients as a whole had lower sleep efficiency and less stage 4 sleep than control subjects. CONCLUSIONS: These findings indicate that there are substantial differences between PD and control subjects in autonomic regulation and that there are small differences between patients with daytime panic attacks and those with sleep-related panic attacks.

Adult↗
PubMed1999

Adrenal epinephrine secretion is not regulated by sympathoinhibitory neurons in the caudal ventrolateral medulla.

By providing the principal inhibitory regulation of the discharge of sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM), neurons in the caudal ventrolateral medulla (CVLM) play a major role in regulating the level of sympathetic nerve activity (SNA) to cardiovascular targets. To determine whether adrenal medullary secretion of epinephrine (EPI) is also regulated by sympathoinhibitory inputs from the CVLM to the RVLM, we compared levels of plasma EPI obtained after disinhibition of RVLM neurons with levels obtained after inhibition of CVLM neurons, both of which result in sustained elevations in arterial blood pressure (AP), SNA, and heart rate (HR). Plasma norepinephrine (NE) concentrations were significantly elevated following bilateral microinjection either of bicuculline (BIC) into the RVLM or of muscimol into the CVLM of urethane/chloralose-anesthetized, artificially-ventilated rats. In sharp contrast, although plasma EPI concentrations were significantly elevated following disinhibition of neurons in the RVLM, they were unchanged by inhibition of neurons in the CVLM. These results demonstrate that the discharge of sympathetic premotor neurons in the RVLM regulating adrenal secretion of EPI is modulated by a tonic, GABA-ergic inhibition that arises from a source that is different from the sympathoinhibitory neurons in the CVLM that project to RVLM sympathetic premotor neurons controlling vasoconstrictor and cardiac targets.

Action Potentials↗