PubMed Health⌕ Search

Biomedical subjects

S Sasu

Publications and source records attributed to S Sasu.

6 recordsLinked to original sources
PubMed2004

Index of potential contamination: Schistosoma haematobium infections in school children in the Ashanti Region of Ghana.

BACKGROUND: Children are acknowledged as the most vulnerable group to urinary schistosomiasis. OBJECTIVE: To determine the age group(s) of school children considered as the major contributor(s) to the spread of the disease. DESIGN: Observational/Prospective (concurrent) studies. SETTING: Barekuma, Aninkroma and Hiawo Besease, riparian communities in the Ashanti Region of Ghana. SUBJECTS: Hundred children each were randomly selected from Barekuma and Hiawo Besease basic schools with population age profiles between 4 and 18 years. They were then categorised into 4-6, 7-9, 10-12, 13-15 and 16-18 years, respectively. However, at Aninkroma, the entire school population of 119 pupils, aged between 4 and 15 years were used. They were similarly grouped into 4-6, 7-9, 10-12 and 13-15 years, respectively. Urine filtration method was used for isolation and enumeration of S. haematobium eggs from the subjects. The subjects were monitored through repetition of the experiment at fortnightly intervals over four weeks. MAIN OUTCOME MEASURES: Corrected relative Index of Potential Contamination (IPC) expressed as percentage after calculating the crude IPC. RESULTS: The age groups with the highest relative IPCs at Barekuma, Aninkroma and Hiawo Besease were 7-9, 10-12 and 13-15 years, registering 35.6%, 53.9% and 57.7%, respectively. The age group 4-6 years consistently had the lowest IPC in all the communities. CONCLUSION: The age groups 7-9,10-12 and 13-15 years were considered to be the major transmitters of the disease in the communities.

Adolescent↗
PubMed2001

Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation.

An early component of atherogenesis is abnormal vascular smooth muscle cell (VSMC) proliferation. The presence of Chlamydia pneumoniae in many atherosclerotic lesions raises the possibility that this organism plays a causal role in atherogenesis. In this study, C pneumoniae elementary bodies (EBs) rapidly activated p44/p42 mitogen-activated protein kinases (MAPKs) and stimulated proliferation of VSMCs in vitro. Exposure of VSMCs derived from human saphenous vein to C pneumoniae EBs (3x10(7) inclusion forming units/mL) enhanced bromodeoxyuridine (BrdU) incorporation 12+/-3-fold. UV- and heat-inactivated C pneumoniae EBs also stimulated VSMC proliferation, indicating a role of direct stimulation by chlamydial antigens. However, the mitogenic activity of C pneumoniae was heat-labile, thus excluding a role of lipopolysaccharide. Chlamydial hsp60 (25 microg/mL) replicated the effect of C pneumoniae, stimulating BrdU incorporation 7+/-3-fold. Exposure to C pneumoniae or chlamydial hsp60 rapidly activated p44/p42 MAPK, within 5 to 10 minutes of exposure. In addition, PD98059 and U0126, which are two distinct inhibitors of upstream MAPK kinase 1/2 (MEK1/2), abolished the mitogenic effect of C pneumoniae and chlamydial hsp60. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the p44/p42 MAPK pathway. Human VSMCs were shown to express TLR4 mRNA and protein, and a TLR4 antagonist abolished chlamydial hsp60-induced VSMC proliferation and attenuated C pneumoniae-induced MAPK activation and VSMC proliferation. Together these results indicate that C pneumoniae and chlamydial hsp60 are potent inducers of human VSMC proliferation and that these effects are mediated, at least in part, by rapid TLR4-mediated activation of p44/p42 MAPK.

Bacterial Proteins↗
PubMed2001

Juxtacrine effects of IL-1 alpha precursor promote iNOS expression in vascular smooth muscle cells.

After injury to the blood vessel wall, vascular smooth muscle cells (SMC) synthesize interleukin (IL)-1 and inducible nitric oxide (NO) synthase (iNOS). The present study tested whether endogenous production of IL-1 alpha stimulates iNOS expression in vascular SMC, and assessed whether IL-1 alpha exerts autocrine effects on the cells producing IL-1 alpha or juxtacrine effects on cells that contact the IL-1 alpha producing cells. Rat aortic SMC were transiently transfected with expression plasmids encoding either IL-1 alpha precursor, which localizes to the plasma membrane, or mature IL-1 alpha, which remains cytosolic. iNOS mRNA levels, determined by RT-PCR, and production of nitrite, a stable oxidation product of NO, were markedly elevated in SMC overexpressing IL-1 alpha precursor, and modestly elevated in SMC overexpressing mature IL-1 alpha, relative to SMC transfected with vector alone. Exposure to exogenous IL-1 beta or TNF-alpha further stimulated iNOS gene expression in SMC producing IL-1 alpha; low levels of IL-1 beta (20 pg/ml) were effective in SMC transfected with IL-1 alpha precursor plasmid, whereas SMC transfected with mature IL-1 alpha plasmid or vector alone required higher concentrations of IL-1 beta (200 and 2,000 pg/ml, respectively). The increases in iNOS mRNA levels and NO production in SMC overexpressing IL-1 alpha precursor were prevented by exogenous IL-1 receptor antagonist, suggesting that these effects were mediated by the type I IL-1 receptor. Immunostaining studies indicated that IL-1 alpha precursor stimulates iNOS gene expression via cell-cell contact. Expression of iNOS was enhanced in cells that were in contact with a cell overexpressing IL-1 alpha precursor (identified by coexpression of green fluorescent protein), and in cells that were overexpressing IL-1 alpha themselves, but only when the cell contacted another cell. Together these results indicate that IL-1 alpha precursor acts by cell-cell contact as an autocrine and juxtacrine enhancer of iNOS gene expression, inducing moderate iNOS expression on its own, and markedly augmenting the responsiveness of rat aortic SMC to exogenous cytokines.

Animals↗
PubMed2000

Essential roles of IkappaB kinases alpha and beta in serum- and IL-1-induced human VSMC proliferation.

Interleukin-1 (IL-1) is a potent vascular smooth muscle cell (VSMC) mitogen, which can stimulate cells via activation of nuclear factor-kappaB (NF-kappaB) following phosphorylation of its inhibitory subunit (IkappaB). Because the proliferative effect of IL-1 is additive with that of serum, the present studies assessed the role of IkappaB kinases (IKKs) and NF-kappaB in both IL-1- and serum-induced VSMC proliferation. IL-1beta (1 ng/ml) induced marked and persistent NF-kappaB activation in VSMC that was maximal at 1 h and persisted for 3 days. There was a 3-fold increase in DNA synthesis after acute IL-1 exposure (24-96 h) and a 12-fold increase after chronic IL-1 exposure (>7 days). Electrophoretic mobility shift assay and supershift analysis indicated that IL-1-induced NF-kappaB complexes consisted of p65/p50 heterodimers and p50 homodimers. Human saphenous vein smooth muscle cells (HSVSMC) were transiently cotransfected with expression plasmids encoding a dominant negative mutant form of either IKKalpha or IKKbeta, in which K(44) was mutated to A (K44A), and a green fluorescent protein expression plasmid that allows identification of transfected cells. IL-1 induced nuclear localization of p65 in 95% of cells transfected with vector alone but in only 69% and 26% of cells expressing IKKalpha (K44A) or IKKbeta (K44A), respectively. Likewise, proliferation increased 3.2-fold in IL-1-treated HSVSMC which had been transfected with vector alone, but only 2.2- and 1.5-fold proliferation in HSVSMC expressing IKKalpha (K44A) or IKKbeta (K44A), respectively. Although serum activated NF-kappaB transiently, serum-induced proliferation was markedly attenuated in HSVSMC expressing IKKalpha (K44A) and IKKbeta (K44A) compared with HSVSMC transfected with vector alone. The results support an essential role of IKKs in the proliferative response of HSVSMC to IL-1 and to serum.

Animals↗