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Biomedical subjects

N Mohan

Publications and source records attributed to N Mohan.

At least 37 records · Page 2Linked to original sources
PubMed2000

The posterolateral approach to the distal humerus for open reduction and internal fixation of fractures of the lateral condyle in children.

Our study describes a posterolateral approach to the distal humerus for open reduction and internal fixation of displaced fractures of the lateral condyle. A total of 20 patients had open reduction and internal fixation over a four-year period using this approach, and at a mean follow-up of 12 months had full union, range of movement and no complications, either clinical or radiological. This approach is well suited to the exact visualisation and accurate reduction of this difficult fracture with minimal dissection of tissues.

Adolescent↗
PubMed1999

Indications and outcome of liver transplantation in tyrosinaemia type 1.

UNLABELLED: A retrospective analysis was performed on 17 patients presenting with tyrosinaemia type 1 (TT1) between 1989-1997; 7 pre 1992 prior to the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and 10 post 1992. During this time, eight children (5 males) underwent orthotopic liver transplantation (OLT); six prior to the introduction of NTBC in 1992 and two on NTBC therapy. The primary indications for OLT pre-1992 were risk of hepatocellular carcinoma with evidence of hepatic dysplasia in all, associated with liver failure in two, and rise in alpha-fetoprotein (AFP) in four. Two of the ten treated with NTBC required OLT. The indications were non-response to NTBC in one child and development of hepatic dysplasia associated with poor quality of life in the second patient. Median age for OLT was 64 months (range 5-127 months) with a median weight of 24 kg (range 6-25 kg). The histology of hepatectomy specimens at transplantation showed: cirrhosis in 8, hepatic dysplasia in 6 and hepatocellular carcinoma in 1. Plasma tyrosine and AFP returned to normal in all cases. Urinary succinylacetone reduced but persisted in small amounts (median 7.7 micromol/mmol creatinine). Hypertrophic cardiomyopathy resolved in 3/3 patients. Hypoglycaemia, not responding to dietary therapy or NTBC treatment, resolved post-transplant in one patient. There were two deaths, one from primary non-function and one from chronic rejection. Late complications in survivors (n=6) include post-transplant lymphoproliferative disease of the iris in one child which resolved and renal dysfunction with a fall in glomerular filtration rate in three (50%). Median follow up post OLT is 6.7 years (range 1-7 years). Quality of life post-transplant in survivors is good with unrestricted diet in all. CONCLUSION: Liver transplantation is an effective treatment for TT1 with good quality of life. The current indications of OLT in TT1 are non-response to NTBC, risk of malignancy and poor quality of life related to dietary restriction and frequency of blood sampling.

Adolescent↗
PubMed1999

Takayasu's Arteritis.

Takayasu's arteritis is a worldwide entity that requires astuteness for early diagnosis. The challenge for the practicing physician is to document active disease, not only to justify immunosuppressive therapy but also to determine the appropriate timing for surgical intervention. No single laboratory assay or imaging modality establishes disease activity, though T2-weighted magnetic resonance imaging, magnetic resonance angiography, and spiral computed tomographic angiography have shown potential in identifying acute inflammatory changes within the vessel wall. Treatment consists primarily of glucocorticoids, but cytotoxic agents such as methotrexate and cyclophosphamide may be added to treat recalcitrant disease. New immunomodulating agents such as leflunomide and tumor necrosis factor inhibitors require further study before they can be added to the treatment armamentarium.

Journal Article↗
PubMed1999

Regulation of low shear flow-induced HAEC VCAM-1 expression and monocyte adhesion.

We recently reported that prolonged exposure of human aortic endothelial cells (HAEC) to low shear stress flow patterns is associated with a sustained increase in the activated form of the transcriptional regulator nuclear factor-kappaB (NF-kappaB). Here we investigate the hypothesis that low shear-induced activation of NF-kappaB is responsible for enhanced expression of vascular cell adhesion molecule (VCAM-1) resulting in augmented endothelial cell-monocyte (EC-Mn) adhesion and that this activation is dependent on intracellular oxidant activity. Before exposure to low shear (2 dyn/cm2) for 6 h, HAEC were preincubated with or without the antioxidants pyrrolidine dithiocarbamate (PDTC) or N-acetyl-L-cysteine (NAC). PDTC strongly inhibited low shear-induced activation of NF-kappaB, expression of VCAM-1, and EC-Mn adhesion. Paradoxically, NAC exerted a positive effect on low shear-induced VCAM-1 expression and EC-Mn adhesion and only slightly downregulated NF-kappaB activation. However, cytokine-induced NF-kappaB activation and VCAM-1 expression are blocked by both PDTC and NAC. These data suggest that NF-kappaB plays a key role in low shear-induced VCAM-1 expression and that pathways mediating low shear- and cytokine-induced EC-Mn adhesion may be differentially regulated.

Acetylcysteine↗
PubMed1999

Reversible alteration of morphology in an invertebrate erythrocyte: properties of the natural inducer and the cellular response

The normal shape of the erythrocytes of the bivalves known as blood clams is maintained by a marginal band (MB) of microtubules. When hemolymph (or "blood") is withdrawn from the animal, its erythrocytes change, within minutes, from the normal smooth-surfaced, flattened ellipsoids (N-cells) to spheroids with folded surfaces (X-cells). This alteration can be prevented by rapidly diluting the hemolymph with physiological medium, yielding N-cells for use in studying the transformation to X-cells. Bioassays showed that shape transformation was induced by a hemolymph activity (Hx) and was a function, in part, of cell responsiveness to this activity. Eventually the shape of the cells spontaneously returned to normal, at a rate dependent upon the concentration of the cells and of Hx; recovery was correlated with loss of Hx. The X-cells contained an intact but highly deformed MB, but this was not the effector of the transformation. Erythrocytes made to lack MBs still changed shape, although they did not recover as completely as did the MB-containing controls. When clams were cooled before hemolymph was withdrawn, the concentration of Hx was reduced. Hx was retained after dialysis of hemolymph, and initial filtration and chromatography indicated that its Mr was greater than 500,000. Shape transformation was blocked by EGTA, by serine protease inhibitors, and by sodium azide; the last indicates ATP-dependence. Although the mechanism responsible for shape transformation remains to be determined, the data suggest that the change is triggered by a coagulation-related activity in response to the removal of hemolymph from the animal.

Journal Article↗
PubMed1997

Proliferation and cytogenetic studies in human blood lymphocytes exposed in vitro to 2450 MHz radiofrequency radiation.

Aliquots of human peripheral blood collected from two healthy human volunteers were exposed in vitro to continuous wave 2450 MHz radiofrequency radiation (RFR), either continuously for a period of 90 min or intermittently for a total exposure period of 90 min (30 min on and 30 min off, repeated three times). Blood aliquots which were sham-exposed or exposed in vitro to 150 cGy gamma radiation served as controls. The continuous wave 2450 MHz RFR was generated with a net forward power of 34.5 W and transmitted from a standard gain rectangular antenna horn in a vertically downward direction. The mean power density at the position of the cells was 5.0 mW/cm2. The mean specific absorption rate calculated by Finite Difference Time Domain analysis was 12.46 W/kg. Immediately after exposure, lymphocytes were cultured for 48 and 72 h to determine the incidence of chromosomal aberrations and micronuclei, respectively. Proliferation indices were also recorded. There were no significant differences between RFR-exposed and sham-exposed lymphocytes with respect to; (a) mitotic indices; (b) incidence of cells showing chromosome damage; (c) exchange aberrations; (d) acentric fragments; (e) binucleate lymphocytes, and (f) micronuclei, for either the continuous or intermittent RFR exposures. In contrast, the response of positive control cells exposed to 150 cGy gamma radiation was significantly different from RFR-exposed and sham-exposed lymphocytes. Thus, there is no evidence for an effect on mitogen-stimulated proliferation kinetics or for excess genotoxicity within 72 h in human blood lymphocytes exposed in vitro to 2450 MHz RFR.

Adult↗
PubMed1997

Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments.

Endothelial cell-monocyte interaction plays an important role in atherogenesis. The expressions of some endothelial cell adhesion molecules involved in endothelial cell-monocyte interactions are regulated by transcription factor NF-kappa B. Because low shear stress has been known to influence endothelial monocyte adhesion, the differential activation of NF-kappa B under different flow regimens across time (0.5-24 h) was investigated. Nuclear proteins from flow-conditioned human aortic endothelial cells (HAEC) were analyzed by electrophoretic mobility shift assay using [gamma-32P]dATP-labeled NF-kappa B-specific oligonucleotide. Our results demonstrated that NF-kappa B activation was significantly elevated in HAEC exposed to prolonged (> 2 h) steady low shear (2 dyn/cm2) and pulsatile low shear (2 +/- 2 dyn/cm2) compared with HAEC exposed to high shear (16 dyn/cm2). In contrast, at 30 min, high shear-exposed HAEC exhibited an early, transient increase in NF-kappa B activity, relative to low shear-exposed cells, which reversed on continued exposure to high shear. Maximum activity in both low shear- and pulsatile low shear-conditioned HAEC was observed at 16 h compared with HAEC exposed to prolonged high shear. These results indicate that exposure of HAEC to prolonged low shear conditions is associated with significantly increased and prolonged NF-kappa B activity. This observation might provide a mechanism to explain the increased monocyte adhesion in atherosclerosisprone arterial sites exposed to chronic low-shear flow patterns.

Adaptation, Physiological↗
PubMed1996

Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen.

It was recently demonstrated that the pineal neurohormone melatonin is a hydroxyl radical scavenger and antioxidant, and that it plays an important role in the immune system. In studies reported herein, we have investigated the relationship of the melatonin level and the NF-kB DNA binding activity in the spleen of Sprague. Dawley rats. These in vivo results indicate that NF-kB DNA binding activity in the spleen is lower at night, when endogenous melatonin levels are elevated, than during the day, when endogenous melatonin levels are lower. Furthermore, exogenously administered melatonin (10 mg/kg) was shown to cause a significant decrease in NF-kB DNA binding activity in the spleen at 60 min after intraperitoneal injection (as compared with vehicle-treated rats). These new findings suggest that the normal night time rise which can be expected for melatonin may be associated with increased NF-kB DNA binding activity in the spleen. The melatonin, therefore, could potentially act to modulate spleen function and/or the immune system by regulating the NF-kB DNA binding activity in the spleen.

Animals↗
PubMed1995

Induction of transcription of "immediate early genes" by low-dose ionizing radiation.

The induction of transcription of specific genes after exposure to ionizing radiation has previously been reported after lethal doses of radiation (2-50 Gy). Little attention has been focused on expression of "immediate early genes" after low doses of ionizing radiation, where cell viability remains high. This dose range (0.25-2.0 Gy) is above the diagnostic dose level but at or below the doses typical for a single exposure in fractionated radiotherapy treatment of cancer. In this study, it was observed that doses in the range of 0.25-2.0 Gy induced different amounts of the mRNAs of the proto-oncogenes c-fos, c-jun, c-myc and c-Ha-ras at a given dose and time in Epstein-Barr virus-transformed human lymphoblastoid 244B cells. A maximum response was seen after a dose of 0.5 Gy for all but c-fos, which showed a maximum response after exposure to 0.25 Gy. Time-course studies demonstrated that, for all four proto-oncogenes, the induction was transient, reaching a maximum at 1 h and declining to the constitutive level at 4 h after irradiation. Using second-messenger specific inhibitors, the signaling pathways involved in the induction of these proto-oncogenes was also investigated. The results showed that all four of the proto-oncogenes induced after 0.5 Gy shared a common pathway of tyrosine kinase activation. Other signaling pathways included protein kinase C, reactive oxygen intermediates and calcium-dependent kinases; these were found to be differentially involved in the induction of transcription of the individual proto-oncogenes. In summary, this study suggests that low-dose ionizing radiation (0.25-2.0 Gy) can modulate expression of immediate early genes. Secondly, the activation of immediate early genes after low-dose exposure involves multiple second-messenger signaling pathways. Third, the magnitude of involvement of the different signaling pathways after low-dose radiation is different for each proto-oncogene expressed.

Cell Line, Transformed↗
PubMed1995

The neurohormone melatonin inhibits cytokine, mitogen and ionizing radiation induced NF-kappa B.

Recently, the neurohormone melatonin was found to be a potent endogenous hydroxyl radical scavenger. Since the activation of an important transcriptional regulator, nuclear factor-kappa B (NF-kappa B) involves free radicals as second messengers, we investigated whether melatonin alters NF-kappa B expression if present during treatment of HeLa S3 cells with known activators. The results show that upon treatment of HeLa S3 cells with tumor necrosis factor-alpha or phorbol 12-myristate 13-acetate, or with ionizing radiation, there is a profound induction of NF-kappa B binding activity. If present at the time of treatment, exogenously added melatonin, at a concentration as low as 10 microM, was found to inhibit the activation of NF-kappa B by these agents. This results leads to the hypothesis that melatonin can play a role in many physiological functions through its modulation of NF-kappa B (and possibly other) transcriptional regulators.

Base Sequence↗
PubMed1994

Induction of nuclear factor kappa B after low-dose ionizing radiation involves a reactive oxygen intermediate signaling pathway.

Reactive oxygen intermediates (ROIs) have been found to be the messengers in the activation of the kappa B transcription regulator in mitogen- or cytokine-stimulated cells, operating in conjunction with or independently of various other mechanisms; these include Ca(++)-dependent and PKC-dependent cytoplasmic signaling pathways. We have recently reported that low-dose ionizing radiation induces NF-kappa B in human lymphoblastoid 244B cells. Since ionizing radiation generates free radicals in cells, we have investigated whether the ROIs generated by ionizing radiation induce NF-kappa B activity, and also whether they do so by a similar mechanism as in cells treated with PMA or H2O2. The results not only confirm a previous observation from our laboratory that low-dose ionizing radiation (0.1-2.0 Gy) activates kappa B transcription factor transiently with a maximal induction at 0.5 Gy exposure, but also demonstrate mechanistically that the activation of NF-kappa B by low-dose ionizing radiation can be inhibited considerably by the antioxidant N-acetyl-L-cysteine, indicating that at least the major part of the activation process is mediated by ROIs. These findings support the idea that ROIs can regulate the kappa B elements which in turn can serve as response elements for oxidant stress.

Acetylcysteine↗
PubMed1994

Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation.

Nuclear factor kappa B (NF-kappa B) is a pleiotropic transcription factor which is involved in the transcriptional regulation of several specific genes. Recent reports demonstrated that ionizing radiation in the dose range of 2-50 Gy results in expression of NF-kappa B in human KG-1 myeloid leukemia cells and human B-lymphocyte precursor cells; the precise mechanism involved and the significance are not yet known. The present report demonstrates that even lower doses of ionizing radiation, 0.25-2.0 Gy, are capable of inducing expression of NF-kappa B in EBV-transformed 244B human lymphoblastoid cells. These results are in a dose range where the viability of the cells remains very high. After exposure to 137Cs gamma rays at a dose rate of 1.17 Gy/min, a maximum in expression of NF-kappa B was seen at 8 h after a 0.5-Gy exposure. Time-course studies revealed a biphasic time-dependent expression after 0.5-, 1- and 2-Gy exposures. However, for each time examined, the expression of NF-kappa B was maximum after the 0.5-Gy exposure. The expression of the p50 and p65 NF-kappa B subunits was also shown to be regulated differentially after exposures to 1.0 and 2.0 Gy.

Dose-Response Relationship, Radiation↗
PubMed1993

Production and characterization of an Mls-1-specific monoclonal antibody.

Superantigens (SAGs) represent a new class of antigens, characterized as T cell receptor (TCR) V beta-reactive elements. Bacterial toxins constitute the major group of exogenous SAGs, while the mouse mammary tumor virus (MMTV)-encoded Mls molecules represent the endogenous SAGs. Mls-1 is the prototype of the latter SAGs, because it elicits a very potent T cell stimulatory response in vitro in unprimed T cells expressing the TCR V beta 6 or 8.1 chains. In vivo, Mls-1 causes deletion of immature T cells bearing the V beta 6, 7, 8.1, or 9 chains. Although Mls-1 was functionally discovered > 20 yr ago, it has not been possible to raise antibodies against this molecule. We have previously cloned and sequenced the Mtv-7 sag gene, which encodes Mls-1. Sequence comparisons with other MMTV sag genes suggested that the polymorphic 3' end encodes the TCR V beta specificity of these SAGs. We have, therefore, immunized hamsters with a 14-amino acid peptide from the deduced COOH-terminal sequence of the Mtv-7 sag gene. We describe here the production of a monoclonal antibody (mAb), 3B12, which is peptide specific and reacts with a recombinant baculovirus product of Mtv-7 sag. This mAb blocks Mls-1-specific T cell recognition and detects the Mls-1 protein on the surface of the B cell hybridoma LBB.A, but not on LBB.11, which is an Mtv-7 loss variant of LBB.A. Transfection of the Mtv-7 sag gene into LBB.11 renders this cell functionally Mls-1+ as well as positive for 3B12 binding, confirming the specificity of this mAb. It is well documented that B cells and CD8+ T cells express T cell stimulatory Mls-1 determinants, and we show here that this functional profile correlates with the expression of MMTV-specific mRNA. However, primary lymphocytes derived from Mls-1+ mice do not stain with 3B12, even after in vitro activation with mitogens or phorbol ester.

Amino Acid Sequence↗
PubMed1993

A preliminary report on one stage open tip rhinoplasty at the time of lip repair in bilateral cleft lip and palate: the Alor Setar experience.

This paper is a preliminary report on a strategy to perform open tip rhinoplasty at the time of lip repair in bilateral cleft lip and palate deformity. This method was devised to suit unique socio-economic circumstances in the Malaysian centre of Alor Setar. Of 8 cases having surgery in 1991, 7 returned for follow-up with results being documented photographically. It is concluded that this aggressive approach is justified in severe bilateral cleft lip and palate deformity because of the cost effectiveness of limiting the number of interventions. Furthermore, it provides optimally orientated nasal tip anatomy and reduces the social stigma of cleft lip nose appearance from the earliest possible time in the child's development.

Child↗
PubMed1990

Clinicosocial aspect of osteo-articular tuberculosis.

The study constituted clinicosocial analysis of 194 cases of osteo-articular tuberculosis. The disease was common in 1st and 2nd decades of life but not rare in old age with male preponderance. Majority of the patients were from rural area belonging to lower economic classes. Lesions were usually solitary (96.4%) situated in the weight bearing bones and joints (88.66%). Spinal tuberculosis was commonest (48.97%). The onset of disease was insidious in 94.8% cases. Chronic pain, swelling, impaired movements, deformities, sinus and cold abscess were found to be salient features of disease. Negligence and secondary infection were common.

Adolescent↗