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Biomedical subjects

M Natarajan

Publications and source records attributed to M Natarajan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neonatal hypothalamic c-fos expression in an excitotoxicity-induced model of precocious puberty.

We have used immunocytochemical detection of c-fos expression (FOS-like immunoreactivity, FLI) to establish the site of action of monosodium glutamate (MSG) in neonatal rats in a model of lesion-induced precocious puberty. The primary target appears to be the hypothalamic arcuate nucleus (ARC) but other circumventricular organs (CVO) are also affected (e.g. subfornical organ). Single injections of MSG (1-4 mg/g single dose, postnatal day 2 (P2)) which result in precocious puberty induce an area of edema, surrounded by a ring of FLI in the basal hypothalamus. In contrast, a maximal sub-lethal dose of NMDA (N-methyl-D-aspartate; 3 mg/kg) which produces a different pattern of ARC FLI, without edema, has no effect on puberty. Multiple doses of MSG (4 mg/g P2, P4, P6, P8), consistent with severe ARC damage and resultant sterility, markedly attenuates the FLI response by P8, with no visible edematous reaction following the final injection. In efforts to block the effect of MSG, pretreatment with the NMDA receptor-specific antagonist MK-801 (dizocilpine maleate) prevented the appearance of edema, as well as the onset of precocious puberty. However, MK-801 did not completely eliminate the FLI, but transformed the pattern of staining so that the original edematous area now contained many FOS-positive cells. This remaining MSG-induced FLI could not be eliminated by higher doses of MK-801 or by the non-NMDA antagonist DNQX (6,7-dinitroquinoxaline-2,3-dione). The combination of MK-801 and DNQX was also ineffective. MK-801 or DNQX had no effect on FLI when injected alone (i.e., without MSG) or in combination. The receptor which mediates MSG-induced c-fos expression, in the presence of MK-801 or DNQX, needs to be identified. We conclude, in conjunction with our previous work, that MSG induces precocious sexual maturation via an MK-801-sensitive mechanism associated with an edematous response of the basal hypothalamus. Whether the appearance of edema is indicative of an excitotoxic action of MSG, resulting in the removal of neurons inhibitory to sexual maturation, remains to be established.

Animals↗
PubMed1997

Recovery of hypothalamic NMDA-induced c-fos expression following neonatal glutamate (MSG) lesions.

The neonatal brain is susceptible to neurotoxic insult. In a previous report we showed that a single neonatal injection of MSG, known to cause damage in the arcuate nucleus (ARC), induces a precocious yet otherwise normal puberty in female rats. We have examined this ability of the medial basal hypothalamus (MBH) to recover from an excitotoxic insult using the immediate-early gene c-fos as a developmental marker of ARC response to glutamate receptor stimulation with N-methyl-D-aspartate (NMDA). Groups of neonatal (postnatal day (PD) 2) pups were injected with MSG, then stimulated on subsequent days (PD 3-29) with NMDA, known to induce c-fos expression in ARC. Computer-assisted densitometry was used to quantify Fos-like immunoreactivity (FLI) profiles in ARC. Pups treated neonatally with saline (PD 2) showed a robust, age-specific expression of FLI in the ARC following NMDA treatment. The FLI response was absent in the days immediately following an MSG lesion but subsequently recovered up to 75% of maximum by PD 16. Almost full recovery was seen by PD 29. We also examined the ability of the ARC to recover following chronic MSG treatment (PD 2-8), known to induce extensive hypothalamic damage. These pups displayed an unusual response to subsequent NMDA injection, consisting of 5 min cycles of hyper- and hypoactivity. Stimulation with NMDA revealed only a 50% recovery of FLI even at PD 29. In both treatment groups (acute vs. chronic MSG) the zone of recovery (i.e., reappearance of FLI) was initiated close to the third ventricle and with time radiated towards the periphery of the ARC. Some cells which reacquired FLI in the ARC following lesions presented a highly irregular condensed nuclear morphology. We conclude that the recovery of hypothalamic function (i.e., onset of puberty) after a neonatal MSG lesion is coincident with the reappearance of a normal pattern of c-fos expression in response to NMDA stimulation.

Animals↗
PubMed1997

Viability determination of M.leprae: comparison of normal mouse foot pad and bacillary ATP bioluminescence assay.

Correlation between viability assessment by mouse foot pad and ATP bioluminescence was studied in biopsy specimens from multibacillary leprosy cases. Biopsies were processed for inoculation into mouse foot pad and estimation of bacillary ATP levels by bioluminescent assay by earlier established procedures. ATP content as pg/million bacilli was estimated and correlation was assessed with growth in the mouse foot pad. It was observed that when the ATP content was > 36 pg/million bacterial cells, (> 1% probable viables) there was growth in the mouse foot pad from all the specimens. Similar results were observed when the ATP content was in the range of 3.6 to 35.99 pg/million cells (0.1 to 1% probable viables). The positivity rates in the mouse foot pad decreased when the ATP content decreased further. No positive growth in the specimens below 0.04 pg/million bacilli (< 0.001% viable organisms) was observed. These findings show an overall correlation between viability assessed by mouse foot pad and ATP bioluminescence. These observations validate the concept of ATP content of viable unit of M.leprae being in the order of 10(-15) g/live cell which is in the same order of magnitude as a colony forming unit of cultivable mycobacteria.

Adenosine Triphosphate↗
PubMed1996

Adhesion of sickle red blood cells and damage to interleukin-1 beta stimulated endothelial cells under flow in vitro.

Two factors that are hypothesized to contribute to vasoocclusive crises in sickle cell anemia are increased sickle red blood cell-endothelial cell interactions and damage to endothelium. Despite considerable study, the mechanisms by which erythrocyte-endothelial interactions occur and the role of endothelial damage have not yet been fully elucidated. In this report, we demonstrate that adhesion and damage may be related in a model of vasoocclusion in sickle cell anemia. Phase contrast microscopy coupled to digital image processing was used to determine the adhesion of sickle red blood cells to 1-, 4-, and 24-hour interleukin-I beta (IL-1 beta) stimulated endothelial calls in a parallel plate flow chamber. Morphological alterations to activated endothelial cells after the perfusion of sickle erythrocytes were also identified. Pretreatment of monolayers with 50 pg/mL of IL-1 beta for 1, 4, and 24 hours caused approximately 16-fold increases in adhesion of sickle cells to activated endothelium at all time points. Results with an Arginine-glycine aspartic acid (RGD) peptide and monoclonal antibodies indicated a role for three different endothelial cell receptors: alpha v beta 3 after 1 hour of IL-1 beta stimulation; E-selectin after 4 hours of IL-1 beta stimulation; and vascular cell adhesion molecule-1 after prolonged exposure to cytokines. Perfusion of sickle, but not normal, erythrocytes resulted in alteration of endothelial morphology. Approximately 6% to 8% damage was observed on 4- and 24-hour IL-1 beta stimulated endothelial cells after the perfusion of sickle cells. Damage to 24-hour activated endothelial cells showed a positive correlation (r = .899) with the number of adherent sickle erythrocytes.

Amino Acid Sequence↗
PubMed1995

Biomechanics and head injury outcome.

On the basis of biomechanical principles, common head injuries can be classified into acceleration injuries characterised by a predominant diffuse cerebral injury and contact injuries characterised by a predominant focal injury. In a follow-up of 174 head injured patients, it was found that patients with acceleration injuries evinced a longer duration of coma, lengthier post-traumatic amnesia, and less number of skull fractures. Organic behaviour syndromes were seen mostly in acceleration injuries. During the prospective follow-up of 141 patients for a period of 18 months, there were differences in cognitive recovery. But, late behaviour changes and psychosocial outcome were not different in both groups.

Adult↗
PubMed1993

Long-term outcome following head injury.

In a perspective study of follow-up of 141 head-injured patients, neurological, behavioural, neuropsychological and psychosocial parameters of outcome were used to measure the patient's functional status for 18 months. Neurophysical sequelae including seizure disorders were seen in 29 patients. Cortical functional disturbances observed were nominal difficulties in 5 patients, perseveration in 5 patients, disturbed kinetic melodies in 9 patients, frontal acalculia in 4 patients, constructional apraxia in one patient and left side neglect in one patient. These deficits were reversed except in 13 cases. Only 32 patients (22.7%) did not suffer from any behavioural changes. The role of compensation as an aetiologic factor was found in 5 patients. Out of 94 patients in whom scores in memory test was done, 11 patients performed better than their age and education-related norms. Scores in Raven's matrices for level of intellectual performance were done in 71 patients. The score was below 25th percentile in majority (58 cases). Among 130 patients with some jobs, 56 patients (43%) were fully restored. Out of 105 married patients, 45 patients (43%) had disturbed relations after head injury. Seven patients had separation of marriage. Compared to neurological deficits, behavioural and neuropsychological impairments were more prevalent and disabling. Psychosocial outcome, particularly vocational restoration was adversely affected by behavioural changes and cognitive deficits. Need for a multidisciplinary intervention to minimise the avoidable morbidity is emphasised.

Craniocerebral Trauma↗
PubMed1992

Histological changes with combined chemotherapy and immunotherapy in highly bacillated lepromatous leprosy.

Highly bacillated untreated lepromatous cases with an initial BI 4+ of to 6+ were treated with combined multidrug treatment (MDT) and immunotherapy with heat killed Mycobacterium w or BCG. The vaccines were administered intradermally every six months. It was observed that majority of cases on immunotherapy showed increased lymphocytic infiltration (both at local and distant sites) and some cases showed epithelioid cells as well. The lymphocytic infiltration was (slightly) more vigorous in those vaccinated with Mycobacterium w. Such changes were not seen in the patients on MDT alone. Also, the granuloma fraction reduced much faster in cases who were on additional immunotherapy as compared to those on MDT alone. These changes along with evidence of clinical and bacteriological improvements suggest that immunotherapy may have an important supportive role specially in the therapy of anergic lepromatous cases.

Antitubercular Agents↗
PubMed1992

Immune response to purified chick embryo cell culture rabies vaccine manufactured in India.

The immunogenic efficacy of the first batch of indigenous purified chick embryo cell culture grown (PCEC) rabies virus vaccine has been measured in ten subjects. All of them were immunologically naive to rabies virus, and were given 5 doses of the vaccine in the post-exposure regime of injections on days 0, 3, 7, 14 and 30. On day 7, four subjects had developed very low levels of rabies virus neutralizing antibody, as detected and measured in the suckling mouse neutralization test. On day 14, all subjects had protective levels of antibody, which were maintained or enhanced by day 30. With the limited data presented here, the immunogenic efficacy of this batch of vaccine appeared similar to that of a batch of imported PCEC vaccine investigated earlier.

Animals↗
PubMed1991

Clinical and bacteriological progress of highly bacillated BL-LL patients discontinuing treatment after different periods of MDT.

Highly bacillated lepromatous patients (BL/LL) with an initial bacterial index (BI) of 4 to 6+ are being treated with a modified World Health Organization-recommended multiple-drug therapy (WHO/MDT) regimen consisting of rifampin 600 mg once a month, clofazimine 100 mg on alternate days, and dapsone 100 mg daily. The clinical and bacteriological profiles of the patients who had discontinued treatment at different durations have been compared with patients who took the same treatment until attainment of smear negativity. All six of the patients who had discontinued treatment at 12-18 months had worsened clinically and bacteriologically, and viable bacilli could be demonstrated in those tested for ATP. In four patients who had stopped treatment at 24-30 months, the BI continued to fall and there was no clinical or bacteriological worsening in 1 to 2 years of follow-up. The fall in the BI in five cases who had discontinued treatment at 36-44 months was comparable to those on continuous treatment, and there was no worsening. These observations indicate that with the conventional MDT regimen it is not advisable to stop treatment at 12 and 18 months. It appears that treatment should be continued for at least 2 years, and longer in the untreated highly bacillated cases. Prospective clinical trials with a sufficient number of cases and long-term follow-up need to be carried out to ascertain the optimum duration.

Adolescent↗
PubMed1989

Sexual behavior after head injury in Indian men and women.

Disorders in sexual function constitute one of the most prevalent and least discussed problems following head injury. The disorders are often the outcome of an interaction between the neurological sequelae, the psychological makeup of the individual, and the sociocultural context of the couple. In a study of 34 head-injured patients, only 13 reached their premorbid level of sexual functioning over a period of 1 year. Deviant behavior, total loss of sexual function, and sexual dysfunction were noted in the rest. Deviant behavior was consistently associated with frontal lobe damage. Otherwise, neurological indices of head injury in the dysfunctional group were not different from those of the clinically recovered group. Associated psychiatric disturbances, gender-role differences, the impact on the marital harmony of the couple, and the role of sociocultural beliefs in the etiology of the disorders are analyzed and discussed, with a particular emphasis on Indian culture.

Adolescent↗
PubMed1989

CD1-positive epidermal Langerhans cells in skin reactions to autologous peripheral-blood-derived mononuclear cells in leprosy patients.

A comparison was made on the characteristics of the infiltrates, the number and distribution of CD1-positive epidermal Langerhans cells (LC) at the sites of skin reaction induced by autologous peripheral-blood-derived mononuclear cells (PBMC) in leprosy patients. Clinically and histologically, the skin reaction was well expressed in tuberculoid patients as compared to lepromatous patients, erythema nodosum leprosum (ENL) patients and contacts. The quantum of lymphocytes in the infiltrates was maximal in the tuberculoid patients and it was minimal in lepromatous and ENL patients. The number and distribution of LC in the tuberculoid patients was significantly higher in the PBMC-inoculated sites as compared to control sites over 24 h. In contrast, no difference in the number and distribution of LC was noticed in the lepromatous and ENL patients. These observations indicate that the lymphocytes of tuberculoid patients in contrast to lepromatous leprosy patients are capable of sustenance in the local micro-environments of the skin and an effective interaction may be possible between LC and PBMC.

Antigens, CD1↗
PubMed1989

Usefulness of exploratory burr holes in the management of severe head injury.

The authors performed burr hole exploration for the diagnosis of intracranial haematomas in 110 consecutive patients with severe head injury. Burr hole revealed extra-axial mass lesions in 61 patients and 49 patients had negative exploration. Post-mortem study showed that only a very few clots were missed by routine burr holes. The study indicated that diagnostic burr hole exploration was a sensitive method for detecting extracerebral mass lesions in centres where CT scanning facilities were not available.

Adolescent↗