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Biomedical subjects

N Subramanian

Publications and source records attributed to N Subramanian.

At least 37 records · Page 2Linked to original sources

Gait before and 10 years after rhizotomy in children with cerebral palsy spasticity.

OBJECT: Selective dorsal rhizotomy is a neurosurgical procedure performed for the relief of spasticity in children with cerebral palsy, but its long-term functional efficacy is still unknown. The authors sought to address this issue by means of an objective, prospective study in which quantitative gait analysis was used. METHODS: Eleven children with spastic diplegia (mean age at initial surgery 7.8 years) were evaluated preoperatively in 1985 and then at 1, 3, and at least 10 years after surgery. For comparison, 12 age-matched healthy individuals were also studied. Retroreflective targets were placed over the hip, knee, and ankle joints, and each individual's gait was videotaped. The video data were subsequently entered into a computer for extraction and analysis of the gait parameters. An analysis of variance yielded a significant time effect (p < 0.05), and post hoc comparisons revealed differences before and after surgery and with respect to the healthy volunteers. The knee and hip ranges of motion (59 degrees and 44 degrees, respectively, for healthy volunteers) were significantly restricted in children with spastic diplegia prior to surgery (41 degrees and 41 degrees, respectively), but were within normal limits after 10 years (52 degrees and 45 degrees, respectively). The knee and hip midrange values (31 degrees and 3 degrees, respectively, for healthy volunteers), indicative of posture, were significantly elevated preoperatively (42 degrees and 15 degrees) and increased sharply at 1 year (56 degrees and 18 degrees), but by 10 years they had decreased to within normal limits (36 degrees and 9 degrees). Step length and velocity improved postoperatively but were not within the normal range after 10 years. Ten years after surgery these patients not only had increased ranges of motion, but also used that movement at approximately a normal midrange point. CONCLUSIONS: Selective dorsal rhizotomy is an effective method for alleviating spasticity. Furthermore, the authors provide evidence to show that lasting functional benefits, as measured by improved gait, can also be obtained.

Adolescent↗

A monoclonal antibody to avidin dissociates quaternary structure and curtails biotin binding to avidin and streptavidin.

An anti-avidin mAb, viz., H12G4, is shown to release bound biotin in a dose-dependent manner from holoavidin and holostreptavidin and inhibit the binding of ligand to the two apoproteins. The release of biotin by this mAb is accompanied by quenching of ligand-induced enhanced fluorescence of the FITC-avidin conjugate. In terms of mechanism of release of bound biotin, we demonstrate that on binding to the Fab fragment of the mAb, the native tetrameric holoavidin undergoes dissociation progressively with time to monomers with no bound biotin associated with the latter. Based on the immunoreactivity associated with defined overlapping fragments of avidin obtained by chemical cleavage, the epitope recognized by mAb H12G4 has been localized to residues 58-96 of the primary sequence. By pepscan method of epitope mapping, this mAb is shown to identify a minimal core sequence of 87RNGK90 in avidin and a corresponding sequence of 84RNAH87 in streptavidin.

Amino Acid Sequence↗

Mapping the common antigenic determinants in avidin and streptavidin.

An epitope scan analysis of the whole sequence of avidin and core streptavidin using polyclonal antibodies to these two antigens reveal the presence of multiple common epitopes in both the proteins. These antigenic determinants consist mostly of either identical or similar residues. The antibody recognition sites in both antigens are shown to be localized to homologous regions.

Amino Acid Sequence↗

Spontaneous, extra-dural haematoma causing spinal cord compression.

We describe a patient with acute compression of the spinal cord by a spontaneous extra-dural haematoma. This rare condition is often misdiagnosed. We believe that an urgent MRI scan is indicated in patients presenting with progressive neurological deficit following spinal trauma. This allows the diagnosis of extra-dural haematoma to be made rapidly and for prompt decompression of the cord.

Aged↗

Antigenic similarities among biotin-binding proteins.

Using polyclonal antisera to avidin, streptavidin, and biotin binding protein-II (BBP-II), the extents of immunological cross-reactivities shared by this family of biotin-binders were investigated. In Western blot analysis, varying degrees of cross-reactivities among these proteins depending on the antisera used was observed. Using liquid phase radioimmunoassay, evidence for the existence of common antigenic determinants shared by all the biotin-binders was deduced. Antibodies directed against such epitopes inhibited the binding of [3H]biotin to as well as displace the bound ligand from all the three high affinity biotin-binders in a dose dependent manner.

Animals↗

Simultaneous purification of biotin-binding proteins-I and -II from chicken egg yolk and their characterization.

Chicken egg yolk biotin-binding protein-I (BBP-I) has been purified to homogeneity along with the tetrameric BBP-II by a common protocol. The purification includes delipidation of egg yolk by butanol extraction, DEAE-Sephacel chromatography, treatment with guanidinium chloride and biotin-aminohexyl-Sepharose affinity chromatography. The identity of purified BBP-I was ascertained by its physicochemical properties as well as by its immunological cross-reactivity and precursor-product relationship with BBP-II.

Animals↗

Pharmacological characterization of tachykinin-induced intracellular calcium rise in a human NK2 receptor transfected cell line.

We have examined the effect of various natural and synthetic tachykinins on the steady state Ca(++)-rise ([Ca++]i) in transfected chinese hamster ovary cells expressing recombinant human Neurokinin 2 (NK2) receptors. The rank order of potency with natural tachykinins was NeurokininA > Neurokinin B > Eledoisin > Physaelamin > substance P. The selective NK2 agonist, [beta-Ala8]NKA(4-10) was very potent, with an EC50 value of 4.83 x 10(-9) M whereas Senktide, MePhe7NKB and Sar9, (MetO2)11 substance P, selective NK3 and NK1 agonists, respectively, did not have any effect on [Ca++]i in hrNK2CHO cells, suggesting a selective and preferential recognition and activation of NK2 receptors in these cells. (+/-) SR 48968, a selective NK2 antagonist, abolished the beta-AlaNKA-induced [Ca++]i with an IC50 value of 0.7 nM. Two other peptidic NK2 antagonists, MEN 10376 and L-658977, were less active with IC50 values of 49 nM and 5.29 microM, respectively. In contrast, (+/-) CP-96,345 and (+/-)CP-99,994 and RP 67580, all selective NK1 antagonists, did not have any effect on the beta-AlaNKA-induced [Ca++]i in hrNK2CHO cells (+/-) SR 140333, a potent and selective NK1 antagonist, had a 35% inhibition under similar conditions. These data demonstrate a high selectivity and sensitivity to NK2 receptor mediated [Ca++]i in rhNK2R-CHO cells and may be of value as a rapid, selective test of drug action at the human NK2 receptors in vitro.

Animals↗

CGP 41251, a novel protein kinase inhibitor with in vitro selectivity for protein kinase C, strongly inhibits immunological activation of human skin mast cells and human basophils.

The process of high-affinity IgE receptor (Fc epsilon RI)-mediated signal transduction in human basophils and mast cells is accompanied by activation of protein kinase C (PKC). The present study investigated the effects of a novel protein kinase inhibitor with in vitro selectivity for PKC (CGP 41251) in comparison with the potent but non-selective PKC inhibitor staurosporine on the activation of human peripheral basophilic leukocytes and enzymatically isolated human skin mast cells. CGP 41251 exerted strong concentration-dependent inhibitory effects on Fc epsilon RI-mediated histamine release from both cell populations. In addition, the IgE-mediated generation of arachidonic acid metabolites (leukotriene C4/D4 and prostaglandin E2) from human basophils was also significantly inhibited by this compound. Its action was not significantly different from the action of staurosporine. Direct activation of cellular PKC by the phorbol ester 12-o-tetradecanoyl-phorbol-13-acetate and subsequent histamine release from basophils was also inhibited by both compounds. CGP 41251 did not suppress N-formyl-met-leu-phe- or A23187-induced activation of basophils, whereas A23187-induced mediator release from human skin mast cells was inhibited in a concentration-dependent fashion. We conclude that an increase of in vitro selectivity for PKC does not significantly enhance inhibitory effects on immunological activation of histamine-containing cells. Moreover, nonimmunological pathways of signal transduction in basophils and mast cells appear to be mediated by distinct biochemical events.

Alkaloids↗

Leukotriene B4 induced steady state calcium rise and superoxide anion generation in guinea pig eosinophils are not related events.

We have examined the nature of the leukotriene B4 (LTB4) induced steady state intracellular calcium rise [Ca++]i in guinea pig eosinophils and the relationship between LTB4 induced [Ca++]i and superoxide anion (O2-). LTB4 induced a rise in intracellular Ca++ (following a Ca(++)- transient) in a dose dependent manner with an optimal increase around 50-100 nM. Depolarizing concentrations of K+ did not induce [Ca++]i in eosinophils nor did the voltage operated calcium channel inhibitor, nifedipine, inhibit the LTB4 induced Ca++ entry. In contrast, SK&F 96365 a purported receptor operated calcium channel (ROCC) inhibitor, and its parent compound SC 32849, attenuated LTB4 induced [Ca++]i. Five reference anti-asthmatics (ketotifen, formoterol, disodium-cromoglycate, theophylline and budesonide) had no influence on LTB4 induced [Ca++]i. LTB4 also induced O2- generation (a functional response) in a dose dependent manner with optimal effect around 100 nM. However, in contrast to Ca(++)- influx, LTB4 induced O2- generation was not affected by either SK&F 96365 or its analogues or reference anti-asthmatics. The results of this study suggest a) the presence of a non-voltage gated, receptor operated, calcium sequestration process in guinea pig eosinophils, b) that LTB4 induced [Ca++]i and O2- generation are apparently unrelated events in these cells, and c) that standard anti-asthmatics do not have an influence on either LTB4 induced [Ca++]i or O2- generation in these cells.

Animals↗

Predictive factors for success in surgery of the physically disabled.

The following factors influencing vocational success or failure were selected and studied for their predictive value in a Rehabilitation Centre, age, family background, educational level, work history and work level, motivation, mental ability and physical disability. Graded numerical scores from 1 to 3 were assigned to these factors according to Lane et al. A cut-off score was tested and found to distinguish the successful from the unsuccessful groups. The individual factors found to differ significantly in the two groups were work history and skill, motivation, and physical disability. Mental ability, however, could not be tested adequately.

Adolescent↗

Effect of cyproheptadine on glucose tolerance, serum insulin and structure of pancreatic islets in rats.

The effect of cyproheptadine (CPH) on glucose tolerance, serum immunoreactive insulin (IRI) and structure of pancreatic islets in albino rats has been studied. Hyperglycemia with glucose intolerance was observed after 10 days of administration of CPH (40 mg/kg, ip). There was insignificant change of fasting IRI after the treatment. Histological studies indicated degranulation and vacuolation of beta cells with enlargement of capillaries. Improvement in blood glucose, glucose tolerance and structure of islets with proliferation of small pancreatic ducts and cell cords were observed 10 days after the withdrawal of CPH.

Animals↗

Platelet activating factor (PAF) is a potent stimulator of porcine tracheal fluid secretion in vitro.

Mucus hypersecretion is a major clinical feature of chronic obstructive lung diseases such as asthma. The possible role of the inflammatory and bronchoconstrictor ether lipid PAF (platelet activating factor) has been studied in isolated porcine trachea with the tantalum 'hillock' technique used to visualize fluid production from tracheal submucosal glands. PAF caused a rapid, dose-dependent (0.001-1 nM) stimulation of fluid secretion which could be detected after 5 min and which increased with time up to at least 15 min. The PAF-induced fluid secretion was unaffected by both antagonists of histamine, acetylcholine and leukotriene D4 and inhibitors of prostaglandin and leukotrienes synthesis. A purported PAF receptor antagonist (CV 3988) inhibited the PAF responses in a dose-dependent manner implying a receptor-mediated event. These results may be of relevance to the mucus hypersecretion seen in chronic airway diseases.

Animals↗

Interleukin 1 releases histamine from human basophils and mast cells in vitro.

Interleukin (IL 1) preparations from five different sources (human monocyte, LPS-stimulated, purified IL 1 from two different laboratories) and human recombinant IL 1 (HrIL 1) were shown to be capable of directly inducing histamine (HA) release from human basophils (10 to 50% of total cellular HA, depending on the source of IL 1). The release was not due to the medium, pyrogens, or other contaminants. Il 1-induced HA release was dose dependent between 1 to 100 U/ml of IL 1 and 1 to 15 ng/ml of HrIL 1 and was rapid, with a peak release at 15 min. HA release induced by IL 1 was blocked completely by preexposure of cells to IL 1 but was not affected by prechallenge with anti-IgE. Also, preincubation of IL 1 with anti-IL 1 antibody abolished the HA-releasing activity. IL 1-induced HA release was also observed in preparations of human adenoidal mast cells. Our data indicate that it is unlikely that the HA release induced by IL 1 is due to a contamination with HA-releasing factor. This effect of IL 1 provides a mechanism for non-IgE-related local HA release and raises the possibility of a link between cellular immunity and immediate hypersensitivity of potential importance for the pathology of immuno/inflammatory diseases.

Adenoids↗