PubMed Health⌕ Search

Biomedical subjects

S Panchalingam

Publications and source records attributed to S Panchalingam.

9 recordsLinked to original sources
PubMed2002

Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway.

Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. These experiments of nature demonstrate that IL-12-dependent IFNgamma production is critical for granuloma formation and therefore host immunity against such pathogens. The essential role of granuloma formation for protective immunity to these organisms is emphasized by the differing granuloma forming capabilities and resultant clinical sequelae observed in these patients which seems to reflect their ability to produce or respond to IFNgamma (Fig. 9). At one pole of this spectrum, represented by the complete IFNgammaR1/2 deficient patients, there is a complete absence of mature granuloma formation, whereas with the less severe mutations (i.e. partial IFNgammaR1/2, complete IL-12p40 and complete IL-12Rbeta1 deficiency), granuloma formation is very heterogenous with wide variations in composition being observed. This suggests that in the latter individuals, who produce partial but suboptimal IFNgamma responses, other influences, including pathogen virulence and host genotype may also affect the type and scale of the cellular response elicited.

Genetic Predisposition to Disease↗
PubMed2001

SKF83959 exhibits biochemical agonism by stimulating [(35)S]GTP gamma S binding and phosphoinositide hydrolysis in rat and monkey brain.

SKF83959, a benzazepine with high affinity for aminergic receptors, elicits behaviors such as grooming and vacuous chewing that are characteristic of dopamine D(1)-like receptor stimulation in rodents. Unlike classical D(1) agonists, however, SKF83959 does not stimulate adenylyl cyclase. Knowing that some D(1)-like receptors are coupled to phospholipase C-mediated signaling cascades in the brain, the present study aimed to determine whether SKF83959 exhibits an agonistic action at the biochemical level and also whether this benzazepine can modulate phosphoinositide hydrolysis in a manner that would be consistent with the behavioral effects of the drug. Similar to dopamine and the selective D(1)-like agonist SKF38393, SKF83959 competitively displaced the receptor binding of [(3)H]dopamine in an agonist-like manner, significantly stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate binding, and potently enhanced phospholipase C-mediated phosphoinositide hydrolysis in rat and monkey brain tissues. SKF83959 was generally more potent than SKF38393, whereas SKF38393 consistently exhibited greater pharmacological efficacy. These findings may implicate a role for the phospholipase C signaling cascade in the agonistic behavioral and antiparkinsonian activity of SKF83959. Dopamine-sensitive phospholipase C signaling should probably be considered in subsequent formulations of mechanisms and models of dopaminergic function in the normal or diseased brain.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2000

Optimized binding of [35S]GTPgammaS to Gq-like proteins stimulated with dopamine D1-like receptor agonists.

Subtypes of dopamine D1-like receptors are coupled through the G proteins Gs or Gq to stimulate either adenylate cyclase or phospholipase C signaling cascades. In the present study, we have uncovered the marked enhancement by sodium deoxycholate of D1-like agonist-stimulated [35S]GTPgammaS binding to Gq-like G proteins in brain membranes, and determined the optimal experimental conditions for assessing agonist effects on [35S]GTPgammaS binding in the presence of the detergent. Factors and their optimal levels that were found to significantly enhance the sensitivity and robustness of the agonist-stimulated [35S]GTPyS binding reaction include protein concentration at 40 microg/ml, cationic concentrations of 120 mM Na+, 1.8 mM K+, and 20 mM Mg(2+), a molar guanine nucleotide ratio of 100,000 GDP to [35S]GTPgammaS, the presence of 1 mM deoxycholate, and an overall incubation duration of 30-120 min. Under the optimized conditions, the D1-like agonist SKF38393 induced potent and highly efficacious (up to 1000%) stimulation of [35S]GTPgammaS binding in membrane preparations from the striatum and other rat brain regions. In striatal membranes incubated with drug for 2 h, immunoprecipitation of the [35S]GTPgammaS-bound proteins with specific Galpha antibodies showed that at least 70% of SKF38393-stimulated [35S]GTPgammaS binding was to Galphaq. The present reaction parameters are consistent with conditions previously found to support dopaminergic stimulation of phospholipase C-mediated signaling in brain slice preparations. These results imply that different but equally physiologically relevant conditions can be obtained under which subtypes of dopaminergic receptors may couple preferentially to Galphas and the adenylate cyclase pathway or to Galphaq and the phospholipase C pathway.

Animals↗
PubMed1997

ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors.

The death of BCG-infected human macrophages induced in vitro by ligation of surface CD95 (Fas), CD69, or complement-mediated lysis was shown not to result in the death of intracellular mycobacteria, whereas exposure to extracellular ATP initiated both macrophage death and killed the intracellular bacteria. ATP acted via P2Z receptors because these effects were mimicked by benzoylbenzoic ATP (a known agonist of P2Z receptors) and blocked by oxidized ATP, DIDS, suramin, amiloride, and KN62 (known inhibitors of P2Z-mediated responses). ATP-mediated bacterial killing was independent of reactive nitrogen and oxygen intermediates and of actinomycin D or cycloheximide inhibition. ATP-induced macrophage cell death, BCG killing, and lucifer yellow dye incorporation were minimal in 2 out of 19 healthy donors. The results suggest possible genetic heterogeneity of this mechanism of mycobacterial killing associated with P2Z-mediated pore formation.

Adenosine Triphosphate↗
PubMed1996

Simple method for pretreatment of tissue sections for the detection of apoptosis by in situ end-labelling and in situ nick translation.

Aims-To overcome the problems associated with proteolytic pretreatment of tissue sections for the detection of apoptosis.Methods-Formalin fixed, paraffin wax embedded tissue sections of reactive lymph nodes and biopsy specimens of Burkitt lymphoma were pretreated by pressure cooking for the detection of apoptosis using the in situ end-labelling and in situ nick translation methods.Results-The results achieved with the in situ end-labelling and nick translations methods were compared with those obtained using a novel anti-apoptosis specific protein (ASP) antibody. The staining patterns generated using the three methods were similar and consistent, although the ASP antibody seemed to be more sensitive and detected higher numbers of apoptotic cells within sections.Conclusions-Pressure cooking is advocated as an alternative method to proteolytic enzyme digestion for pretreating paraffin wax sections. It is reliable, inexpensive, reduces the need to optimise pretreatment variables for different tissues, and permits double immunostaining of sections.

Journal Article↗
PubMed1977

A new look at an old technique: sterilization by infundibulectomy.

Removal of the fimbriated portion of the fallopian tube is, theoretically, quite an effective method of sterilization that has received scant attention in the recent medical literature. In this study 310 cases of infundibulectomy via laparotomy performed at the Castle Street Hospital for Women in Colombo, Sri Lanka, were analyzed. Most of the patients (88.4%) were sterilized within 10 days of the vaginal term delivery whereas the remainder were sterilized in the immediate postabortion period. General anesthetic was used in 93.9% of the procedures. Difficulties at surgery which prevented infundibulectomy were encountered in three cases (1.1%). Infection and other incision problems were the primary complications. Incision infection was noted prior to discharge in four postpartum cases (1.5%) and in no postabortion cases. At the time of the first follow-up visit, seven to 21 days after sterilization, this complication was noted in eight postpartum women (3.1%) and in one woman (2.8%) who had had an abortion. No pregnancies have been reported among the 169 patients who have already been seen at the six-month follow-up visit. The results of this study indicate that infundibulectomy is a safe and effective method of tubal occlusion for postpartum patients.

Adult↗