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Biomedical subjects

S Bennett

Publications and source records attributed to S Bennett.

At least 145 records · Page 8Linked to original sources

Synergistic induction of rat microsomal CYP1A1 and CYP1A2 by acetone in combination with pyridine.

The effect of exposure to acetone, pyridine or acetone in combination with pyridine on microsomal CYP1A1, CYP1A2 and CYP2E1 levels and their catalytic activities was determined in the rat. CYP1A1 and CYP1A2 in the liver and CYP1A1 in the lung were induced along with their catalytic activities by either pyridine, acetone or acetone and pyridine. The induction by acetone and pyridine was greater than the additive effect of both compounds, indicating synergism. Acetone, pyridine or both compounds induced CYP2E1 protein to the same extent in the liver and lung. However, induction of CYP2E1 protein was accompanied by induction of its catalytic activity in the liver but not in the lung. This is the first reported induction of CYP1A proteins and catalytic activities (a) by acetone and (b) synergistically by xenobiotics.

Acetone↗

In vitro replication dynamics of human culture-derived macrophages in a long term serum-free system.

Human peripheral blood monocytes maintained in a long term serum-free system were found to undergo extensive replication. Newly replicated culture-derived macrophages initially appeared as colonies of small cells on the adherent monolayer. After the appearance of these colonies, large numbers of nonadherent macrophages were observed. Using PKH26, a fluorescent tracking dye, the increase in cell number was attributed to a replicating pool of cells. Half of the monocytes present in the original monolayer were able to undergo at least one cycle of replication and of these, approximately 16% underwent three or more cycles of replication. Macrophages in the nonadherent state contained a larger proportion of cells that had undergone division compared with adherent cells. However, it appeared that only adherent macrophages were capable of replication, suggesting movement between the adherent and nonadherent states. Culture-derived macrophages were also predisposed to multinucleated giant cell formation; and in the nonadherent state, their capacity to form these cells increased. At the end of the study period, approximately 25% of the cells maintained in a nonadherent state had two or more nuclei, and 3% had 10 or more nuclei. By comparison, the adherent cells, over the same period, had 10% of cells with two or more nuclei and none had 10 or more nuclei. These multinucleated cells were found to arise through cell fusion.

Cell Adhesion↗

Anopheles albimanus (Diptera: Culicidae) host selection patterns in three ecological areas of the coastal plains of Chiapas, southern Mexico.

The host-feeding patterns of Anopheles albimanus Wiedemann were described and the effect of host availability on these patterns was assessed in three different ecological areas of coastal Chiapas, Mexico. Resting mosquitoes were collected indoors and outdoors during rainy seasons. A 20% sample of blood-fed mosquitoes was tested to determine the source of the blood meal using an ELISA. The unweighted human blood index (HBI) of An. albimanus in the three areas ranged from 0.11 to 0.21. This mosquito species fed more frequently on bovines than on any other host, but the forage ratio indicated that there was also a high preference for equines. Some females tended to rest or complete their gonotrophic cycle indoors after feeding on animals, but females also fed on man and rested outdoors. Host availability and ecological conditions appeared to be responsible for differences observed in the HBI among areas.

Animals↗

Randomized trial of umbilical arterial catheter position: clinical outcome.

In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the "high" group and nine in the "low" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis.

Catheterization↗

Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates.

In a survey of 640 human subjects, a subgroup of 356 persons without recent exposure to antibiotics demonstrated that those with a high prevalence of Hg resistance in their intestinal floras were significantly more likely to also have resistance to two or more antibiotics. This observation led us to consider the possibility that mercury released from amalgam ("silver") dental restorations might be a selective agent for both mercury- and antibiotic-resistant bacteria in the oral and intestinal floras of primates. Resistances to mercury and to several antibiotics were examined in the oral and intestinal floras of six adult monkeys prior to the installation of amalgam fillings, during the time they were in place, and after replacement of the amalgam fillings with glass ionomer fillings (in four of the monkeys). The monkeys were fed an antibiotic-free diet, and fecal mercury concentrations were monitored. There was a statistically significant increase in the incidence of mercury-resistant bacteria during the 5 weeks following installation of the amalgam fillings and during the 5 weeks immediately following their replacement with glass ionomer fillings. These peaks in incidence of mercury-resistant bacteria correlated with peaks of Hg elimination (as high as 1 mM in the feces) immediately following amalgam placement and immediately after replacement of the amalgam fillings. Representative mercury-resistant isolates of three selected bacterial families (oral streptococci, members of the family Enterobacteriaceae, and enterococci) were also resistant to one or more antibiotics, including ampicillin, tetracycline, streptomycin, kanamycin, and chloramphenicol. While such mercury- and antibiotic-resistant isolates among the staphylococci, the enterococci, and members of the family Enterobacteriaceae have been described, this is the first report of mercury resistance in the oral streptococci. Many of the enterobacterial strains were able to transfer mercury and antibiotic resistances together to laboratory bacterial recipients, suggesting that the loci for these resistances are genetically linked. Our findings indicate that mercury released from amalgam fillings can cause an enrichment of mercury resistance plasmids in the normal bacterial floras of primates. Many of these plasmids also carry antibiotic resistance, implicating the exposure to mercury from dental amalgams in an increased incidence of multiple antibiotic resistance plasmids in the normal floras of nonmedicated subjects.

Animals↗

Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children.

The aims of the present study were to describe the age-related immunoglobulin M (IgM) and IgG response to part of a 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum and to determine possible correlations of possession of these antibodies with malaria morbidity. IgM and IgG levels were measured with a recombinant fusion protein consisting of the carboxy-terminal 783 amino acids of the GLURP. Samples for the study were obtained during a longitudinal malaria morbidity survey performed in The Gambia; cross-sectional surveys were performed at the beginning of the transmission season in May and in October. Seropositivity rates increased with age to a maximum of 77% for IgM and 95% for IgG in adults. High prevalences of seropositivity were associated with certain human leukocyte antigen class II alleles (DRw8, DR9, DR7, DR4, DQw7, and DQw2) or haplotypes. The relationship between anti-GLURP489-1271 antibodies and clinical immunity is not clear; asymptomatically infected children aged 5 to 8 years had significantly higher levels of IgG than clinically ill children of the same age, suggesting that antibodies to the carboxy-terminal part of the GLURP may contribute to immunity to P. falciparum. However, this was not significant for younger children.

Adolescent↗

Within-person variation in urinary sodium, potassium and creatinine concentrations, and their relationship to changes in the blood pressure of adult male Gambians.

Variation in urinary electrolyte and creatinine concentrations was studied in untimed, casual specimens obtained from 65 adult Gambian males over a 15-month period during which up to nine specimens were obtained from each subject. Measurements of blood pressure were made at the times when specimens were collected. The within-person variation in urinary creatinine, sodium and potassium concentrations were all found to be larger than that between persons. Within individual subjects, the sodium concentration tended to be comparatively low, and the potassium concentration high, in specimens in which the creatinine concentration was high. This suggests that the excretion of sodium was reduced at times of relative dehydration while the excretion of potassium may have been unrelated to the urine flow. The data also suggest that changes in the state of hydration were associated with changes in blood pressure since an individual subject's pressure was inversely related to the creatinine concentration. The negative relationship of the sodium:potassium ratio with creatinine concentration casts doubt on the simple use of this ratio as an indicator of dietary intake. After adjusting for creatinine concentration by multiple regression, changes in systolic pressure were shown to be positively correlated with changes in sodium concentration. These observations show the importance of replicating measurements of urinary electrolyte concentrations. The demonstration of complex inter-relationships between blood pressure and urinary concentrations of creatinine, sodium and potassium emphasizes the need for care in the interpretation of findings from causal, untimed urine specimens.

Adult↗

Monocyte proliferation in a cytokine-free, serum-free system.

The aim of this study was to establish a cytokine-free, serum-free system which would enable the long-term survival and proliferation of human peripheral blood monocytes. Monocytes were isolated from peripheral blood mononuclear cells (PBMC) by adherence to untreated plastic petri dishes and maintained up to 6 weeks in serum-free medium (SFM) consisting of IMEM, insulin, transferrin, sodium selenite and BSA. Maximal cell proliferation occurred during the first 2 weeks of culture and corresponded to the appearance of large numbers of pure, nonadherent culture-derived macrophages. Monocyte maturation was characterised by the modulation of specific cell surface antigens. The percentage of cells staining for the transferrin receptor increased with time, whereas the percentages of cells expressing CD11b, CD11c and HLA-DR remained greater than 60% for the 15 days studied. The mean fluorescent intensities (MFI) of all these antibodies increased significantly with time. The only differences found between the adherent and nonadherent cells, using the above antibodies, were with the MFI for CD11b and CD11c. In both cases, the intensity of staining was significantly greater in the adherent cells. Estimation of cytokine production by cells maintained for 5 weeks in SFM found that they constitutively produced large amounts of macrophage colony-stimulating factor (M-CSF) in the absence of any exogenous stimuli. These cells were also found to secrete high levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) during the 1st week and granulocyte macrophage colony-stimulating factor (GM-CSF) during the 3rd week. However, the addition of exogenous GM-CSF (5 U/ml, S5) was found to significantly inhibit monocyte proliferation up to 17 days. This is the first report of proliferation associated with long-term survival of culture derived macrophages in a serum-free, cytokine-free system.

Antigens, Surface↗

The statistical analysis of data from immunoepidemiological studies.

Immune responses encountered in human populations display a higher level of heterogeneity than is typically seen with laboratory animals, and the expected clear distinction between responders and non-responders to particular antigens may not be apparent. In such a situation, the methods of statistical analysis traditionally used in laboratory studies may no longer be appropriate, and there is no consensus among immunologists about how such data should be analysed. Using data from a large study of lymphocyte proliferation responses to candidate antigens for a vaccine against Plasmodium falciparum malaria, we discuss questions such as the appropriateness of logarithmic transformation of the data, the use of the stimulation index versus delta--cpm, the use of the proportion of responders for comparing two groups of individuals, and the choice of threshold for defining such a responder.

Animals↗