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Biomedical subjects

E Elliott

Publications and source records attributed to E Elliott.

At least 37 records · Page 2Linked to original sources

Lymphohematopoietic cancers and butadiene and styrene exposure in synthetic rubber manufacture.

The described nested case-control study of lymphohematopoietic cancers occurring in a cohort of synthetic rubber production workers was conducted to determine the associations of these cancers with exposure to butadiene and styrene. Cases have been confirmed through hospital record review of 95 percent of the cancers. Exposures are based on measured values of the two chemicals from personal monitoring data in seven of the eight plants under study. The results indicate that the risk of leukemia increases with exposure to a time-weighted average butadiene measure. The odds ratio at only 1 ppm average butadiene exposure is 1.50 (95% CI 1.07, 2.10). Work in specific areas also contributes to the risk, possibly because these areas have not been completely characterized for differences in butadiene exposure. Hodgkins disease is also associated with butadiene exposure. Multiple myeloma, lymphosarcoma, and all lymphomas are associated with exposure to styrene. Since workers in this industry are apparently exposed to two carcinogenic agents, further effort must be made to distinguish the exposures to each chemical over time and to characterize their interrelationship with the risk of cancers of the lymphohematopoietic system.

Butadienes↗

Perinatal exposure to HIV in Australia, 1982-1994.

OBJECTIVE: To describe the pattern of perinatal exposure to HIV in Australia from 1 January 1982 to 31 December 1994. DESIGN: National surveillance for perinatal exposure to HIV. PARTICIPANTS AND SETTING: Women with diagnosed HIV infection in Australia whose children were exposed to HIV perinatally. OUTCOME MEASURES: Number of reported cases of women with diagnosed HIV infection who have had perinatally HIV-exposed children. RESULTS: By 31 December 1994, 91 women diagnosed with HIV infection had had 111 perinatally exposed children. While the rate of perinatal exposure to HIV was highest in the Australian Capital Territory and New South Wales, the rate was substantially lower than the rate of diagnoses of HIV and AIDS in women of child-bearing age. Before 1989, only 15% (6/39) of women knew of their HIV infection before the birth of their first perinatally exposed child: by 1989-1994, this had increased to 64% (32/52; P < 0.0005). Overall, exposure to HIV was attributed to heterosexual contact only, injecting drug use or receipt of blood or tissue by 48%, 31% and 18% of women, respectively. Source of HIV exposure changed from a history of receipt of blood in 78% of women whose first exposed child was born in 1982-1985 to heterosexual contact only in 61% of women whose first exposed child was born in 1992-1994. 38 children acquired HIV infection perinatally. The HIV transmission rate to children born to women diagnosed with HIV infection before delivery was 21.6% (11/51). CONCLUSIONS: Perinatal exposure to HIV in Australia remains rare. While the proportion of women diagnosed with HIV infection after delivery decreased, a substantial number continued to be diagnosed after delivery, precluding use of current interventions that can reduce the risk of perinatal transmission. It may be appropriate to review the application of HIV testing during pregnancy in Australia.

Adolescent↗

Anti-cathepsin D chicken IgY antibodies: characterisation, cross-species reactivity and application in immunogold labelling of human splenic neutrophils and fibroblasts.

Hyperexpression, alteration of trafficking and secretion of cathepsin D has been linked with tumour invasion and inflammation. To study these phenomena in a variety of cells large quantities of anti-cathepsin D antibodies and the appropriate immunogen are required. As the human immunogen for studies on human tissue is less easily accessed, antibodies to both human and porcine cathepsin D were raised in chickens, as high levels of antibody may be recovered from egg yolks, and the potential cross-reactivity of the anti-porcine cathepsin D IgY antibody was assessed. This preparation cross-reacted strongly with human cathepsin D, comparing favourably with the reactivity of the chicken antibody to the human immunogen. The necessity for isolating human immunogen can thus be circumvented. The cross-species-reacting chicken IgY was successfully used to localise cathepsin D in immunogold labelling of human tissues. To our knowledge, IgY antibodies have not previously been used by other researchers for this purpose. Application of the cross-reacting antibody to human splenic neutrophils (PMNs) has confirmed the presence of cathepsin D in some granules. Double labelling has shown these to be novel subpopulations of azurophil granules. Cathepsin D may, therefore, be relevant in the invasive and inflammatory activities of PMNs and a target for therapeutic strategies.

Animals↗

Effect of basic fibroblast growth factor on myocardial angiogenesis in dogs with mature collateral vessels.

OBJECTIVES: We sought to evaluate the potential of basic fibroblast growth factor (bFGF) to enhance coronary collateral perfusion in dogs with chronic single-vessel coronary occlusion. A secondary goal was to examine whether the salutary effects of bFGF treatment, previously proved effective in the short term, would be maintained in the long term (6 months). BACKGROUND: bFGF, an angiogenic growth factor, is currently the subject of a Phase I trial in patients with ischemic heart disease. It has been shown to promote collateral development in dogs with progressive coronary occlusion when given during the period of natural collateralization. The effect of bFGF on quiescent collateral vessels, a subject of significant clinical importance, is uncertain. METHODS: Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF (1.74 mg/day for 7 days), a regimen previously proved effective, or to saline solution. Maximal collateral perfusion was assessed 6 months later, and the dogs were reassigned to a course of bFGF or saline solution. Collateral perfusion was reevaluated after the second treatment course. RESULTS: At 6 months, collateral function was identical in the groups treated initially with bFGF and saline solution. The subsequent course of bFGF did not induce further collateralization. CONCLUSIONS: Although we previously demonstrated the salutary effects of this bFGF regimen in the short term (5 weeks), collateral flow in control dogs reached parity with that of bFGF-treated dogs after 6 months. bFGF did not induce further collateralization in dogs with mature collateral vessels, underscoring the priming role of ischemia for bFGF-induced collateral development.

Animals↗

Health beliefs as predictors of HIV-preventive behavior and ethnic differences in prediction.

The incidence of a variety of safer-sex behaviors was predicted, using five measures from the Health Belief Model (Janz & Becker, 1984): perceived susceptibility, perceived severity, self-efficacy, social support, and perceived barriers. The participants, 424 U.S. undergraduates at six schools, completed a written questionnaire. The results of multiple regression analyses indicated that perceived susceptibility, self-efficacy, and social support predicted many safer-sex behaviors. Although the Health Belief Model predicted more safer-sex behaviors for Euro-American students than for Hispanic American, African American, and Asian American students, the present data indicated few differences among these ethnic groups regarding the level of safer-sex behaviors.

Adolescent↗

Reductive activation markedly increases the stability of cathepsins B and L to extracellular ionic conditions.

Cathepsins B and L are thought to function extracellularly in pathological conditions. pH-Activity profiles of cathepsin B, measured in phosphate and acetate-Mes-Tris buffers of constant ionic strength, indicated that cathepsin B is sensitive to specific buffer ions, as previously reported for cathepsin L. In assessing the activity of these enzymes in vitro the influence of the buffer must therefore be taken into account. In Hank's balanced salt solution, a buffer modeling the extracellular fluid, the half-life of activated human liver cathepsin B at 37 degrees C is 245 +/- 11.3 s, at pH 7.2, and 857 +/- 50.1 s, at pH 6.8 (the peritumor pH), indicating that cathepsin B is markedly stable under these conditions. The stability was increased by the additional presence of proteins. Without immediate activation, however, the stabilities of both cathepsins B and L were markedly decreased, a large proportion of their activity being lost before it could be measured. Enzymes injected into the extracellular space in the unactivated state would therefore survive for only a very short time in their native conformation. It is proposed that the active site thiolate-imidazolium ion pair contributes substantially to the stability of cathepsins B and L to extracellular ionic conditions.

Buffers↗

Paraformaldehyde fixation of neutrophils for immunolabeling of granule antigens in cryoultrasections.

Paraformaldehyde (PFA) fixation was optimized to facilitate the immobilization and labeling of multiple granule antigens, using short fixation regimens and cryoultramicrotomy of unembedded neutrophils (PMNs). In the optimal protocol, extraction of azurophil granule antigens (especially of the abundant elastase) was obviated by manipulating the polymeric state of PFA, and hence its rate of cross-linking, by altering its concentration and pH in a multistep process. Primary fixation conditions used (4% PFA, pH 8.0, 5 min) favor fixative penetration and rapid cross-linking. Stable cross-linking of the antigen was achieved in a secondary fixation step using conditions that favor larger, more cross-linking polymeric forms of PFA (8% PFA, pH 7.2, 15 min). Immobilization of granule antigens was enhanced by flotation of cut sections on fixative (8% PFA, pH 8.0) before labeling and by using post-labeling fixation with 1% glutaraldehyde. The optimized protocol facilitated immobilization and immunolabeling of elastase, myeloperoxidase, lactoferrin, and cathepsin D in highly hydrated, unembedded PMNs.

Antibodies↗

Modulation of host response to Escherichia coli o157:H7 infection by anti-CD18 antibody in rabbits.

BACKGROUND/AIMS: Escherichia coli O157:H7 infection induces diarrhea, severe colitis, and colonic electrolyte transport abnormalities characterized by decreased Na absorption and Cl secretion. The aim of this study was to examine the role of the host inflammatory response in inducing distal colonic transport changes during infection with E. coli O157:H7. METHODS: New Zealand white rabbits aged 10 days were infected with E. coli O157:H7 strain EDL933 (plasmid+, verotoxin 1+, verotoxin 2+). Studies were performed daily from day 1 to day 5 postinfection and compared with uninfected controls (10 days old). Distal colonic ion transport was studied in vitro under short-circuited conditions in Ussing chambers, and tissue inflammation was assessed by mucosal myeloperoxidase activities and mucosal neutrophil (polymorphonuclear neutrophil [PMN]) counts. In a second study, PMN infiltration was inhibited by an anti-CD18 (leukocyte adhesion molecule) monoclonal antibody, IB4, and histology and transport were studied on day 5 postinfection. RESULTS: Infection with O157:H7 induced diarrhea and inhibition of Na absorption by day 3. CI secretion occurred on day 5, coincident with tissue infiltration with PMN. Pretreatment with IB4 prevented histological damage and tissue infiltration with PMN, and it inhibited the transport abnormalities induced by infection alone. CONCLUSIONS: Infection with O157:H7 reduces Na absorption and stimulates Cl secretion in the distal colon. Disruption of the epithelium and changes in colonic electrolyte transport during enterohemorrhagic E. coli are mediated by the host inflammatory response.

Animals↗

Regulation of glucose transport and expression of GLUT3 transporters in human circulating mononuclear cells: studies in cells from insulin-dependent diabetic and nondiabetic individuals.

We have previously shown that human circulating mononuclear cells (CMCs) respond to physiological concentrations of insulin with a rapid increase in glucose transport rate. The responding cells were found to be the monocytes, and cells derived from individuals with insulin-dependent diabetes mellitus (IDDM) had lower basal and insulin-stimulated glucose transport rates. Of interest, both cell types were found to express the GLUT1 but not the typical insulin-responsive GLUT4 transporter isoform. To further study the mechanisms responsible for stimulation of transport in these cells, we investigated (1) the response to insulin-like growth factor-I (IGF-I) and insulin-mimetic agents, and (2) the expression of other glucose transporter isoforms in CMCs of nondiabetic and IDDM individuals. The time course of insulin-stimulated glucose uptake in CMCs was rapid, reaching a plateau within 30 minutes. CMCs showed a dose-dependent and highly sensitive increase in glucose uptake to IGF-I (maximal response reached at 0.1 to 0.5 nmol/L IGF-I). The IGF-I dose-response curve was similar for CMCs of control and IDDM individuals, but both the basal and maximal response to IGF-I were lower in the diabetic group (P < .01). CMCs did not respond to vanadate, lithium, hydrogen peroxide, or short incubation (1 hour) with metformin, but glucose uptake increased in response to peroxides of vanadate and longer-duration (14 hours) metformin incubations. The glucose transporter isoforms of separated monocytes and lymphocytes were further investigated by Northern blotting of total RNA with a GLUT3-specific cDNA probe and by Western blotting of total membranes using GLUT3-specific antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Novel features of tumors that secrete both growth hormone and prolactin in acromegaly.

The most prominent previously reported clinical features of growth hormone (GH) and prolactin (PRL)-secreting pituitary adenomas associated with acromegaly have included the high incidence of galactorrhea in women and a generally more favorable response to dopamine agonist therapy. The authors analyzed a consecutive series of 62 acromegalic patients treated with transsphenoidal microsurgery. GH-PRL tumors were found in 30% of the patients. There was a significant difference in sex distribution between acromegalics with the GH-PRL tumor subtype and all other acromegalics. Women represented 73% of the GH-PRL immunostain subtype, as compared with the overall sex distribution of 33 women (53%) and 29 men (47%) for the entire series of acromegalic patients. Individuals with the GH-PRL subtype had significantly higher postoperative GH levels than those with the GH subtype, and significantly higher postoperative GH levels when compared with all other acromegalics with a variety of immunostain subtypes. Linear regression analysis of the pre- and postoperative GH data revealed that the increased postoperative GH levels in the GH-PRL immunostain subtype were independent of the invasiveness of the tumor and of sex of the subject. When the same linear regression technique was used, lower preoperative levels of thyroxine and thyroid-stimulating hormone were observed in the GH-PRL subtype. These data suggest inherent differences characteristic of tumors that secrete both growth hormone and prolactin.

Acromegaly↗

Cancer epidemiology among styrene-butadiene rubber workers.

The standardized mortality ratios for some cancers of the lymphohaematopoietic system were high in an early cohort analysis. Since the presence of large numbers of unexposed workers could conceal risks within a cohort, a case-control study was designed to examine the relationship between estimated exposures and the occurrence of these cancers. The results suggested that the risk for leukaemia was associated with exposure to butadiene and with work in specific areas. Modelling, using rank scores, indicated an increase in the risk for leukaemia with increasing exposure score. Use of cases validated by review of hospital records and selection of a new set of controls did not change the findings. The data indicated that comparison of scores within the same time frame improved the model and increased the estimated odds ratio, suggesting that exposure time or dose rate may prove to be the important variable for risk. Exact measurements from the companies involved showed significant correlations between assigned ranks and level of exposure derived from personal monitoring for butadiene but not for styrene. Thus, use of the measured values might be expected to show an association between leukaemia and exposure to butadiene. The standardized mortality ratio for leukaemia among long-term workers hired before 1960 who had worked in the three plants where the geometric mean butadiene level was three to five times higher than those in the other plants is 1.8 times higher than that of the US population. An appropriate algorithm for comparing cases and controls on the bases of the measured samples is being developed.

Butadienes↗

Improving memory and control beliefs through cognitive restructuring and self-generated strategies.

Memory problems are a major source of concern among older adults. The goal of this research was to evaluate methods for improving memory performance and beliefs about memory ability and control. Men and women between the ages of 60 and 85 were randomly assigned to one of five treatment groups: (1) cognitive restructuring to promote adaptive beliefs about memory, (2) memory skills training, (3) combined cognitive restructuring and memory skills training, (4) practice on memory tasks, and (5) a no-contact control group. Beliefs about memory (ability and control) and memory performance (working memory, recall of text materials, categorizable word list, and names and faces) were assessed at a pretest and two posttests. As predicted, those receiving the combined treatment showed the greatest increases in their sense of control and perceived ability to improve memory. Results indicated that all groups improved equally on the memory tasks, although those who had received memory training were more likely to report at the second posttest that they had begun using new strategies for remembering things.

Adaptation, Psychological↗

Age-specific sero-prevalence of amoebiasis and giardiasis in southern Indian infants and children.

The age-specific sero-prevalence of amoebiasis and giardiasis was estimated in 91 pediatric diarrhoea and in 70 non-diarrhoeal cases from Southern India. Anti-amoeba/giardia IgG assays on 20 children with inflammatory bowel disease from the UK yielded base-line levels in a non-endemic symptomatic population. IgG, IgM, and IgA levels were estimated to E. histolytica and G. lamblia using an ELISA. Concomittant faecal examinations were done for the Indian children. There was a significant correlation between acquisition of sero-positivity and age. A rise in the IgG response to both organisms was evident between 38 and 47 and 13-24 months, respectively, in diarrhoeal and non-diarrhoeal cases. An appreciable IgM response occurred predominantly in diarrhoea cases and at a younger age (less than 24 months). IgA responses were low. Anti-protozoal IgG levels in the UK children were negligible. There was no relationship between faecal excretion and sero-positivity. The study shows an age-related antibody response to E. histolytica and G. lamblia.

Age Factors↗

Anti-peptide antibodies to cathepsins B, L and D and type IV collagenase. Specific recognition and inhibition of the enzymes.

Anti-peptide antibodies were raised against synthetic peptides selected from the sequences of human cathepsins B and L, porcine cathepsin D and human type IV collagenase. Sequences were selected from the active site clefts of the cathepsins in the expectation that these would elicit immunoinhibitory antibodies. In the case of type IV collagenase a sequence unique to this metalloproteinase subclass and suitable for immunoaffinity purification, was chosen. Antibodies against the chosen cathepsin B sequence were able to recognize the peptide but were apparently unable to recognise the whole enzyme. Antibodies against the chosen cathepsin L sequence were found to recognise and inhibit the native enzyme and were also able to discriminate between denatured cathepsins L and B on Western blots. Antibodies against the chosen cathepsin D sequence recognised native cathepsin D in a competition ELISA, but did not inhibit the enzyme. Native type IV collagenase was purified from human leukocytes by immuno-affinity purification with the corresponding anti-peptide antibodies.

Amino Acid Sequence↗

Serum antibody response in children with Giardia lamblia infection and identification of an immunodominant 57-kilodalton antigen.

Giardia lamblia antigens which react with sera from children with G. lamblia infection were investigated by sodium-dodecyl polyacrylamide gel electrophoresis and immunoblotting. Serum IgG, IgM and IgA response to the antigens were immunochemically characterized. Serum antibodies from all giardiasis patients, but none of the controls, was found to react with a 57-kilodalton antigen. The 57 kDa antigen elicited IgG and IgA but not IgM antibodies. The protein nature of the 57 kDa antigen was demonstrated by loss of antibody recognition after trypsin treatment of G. lamblia trophozoites. Subcellular fractionation of G. lamblia trophozoites followed by SDS-PAGE and immunoblotting showed that the 57 kDa antigen was probably not a component of the cytoskeleton.

Animals↗