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Biomedical subjects

G E Griffin

Publications and source records attributed to G E Griffin.

At least 19 recordsLinked to original sources
PubMed2004

Risk factors for atopy among school children in a rural area of Latin America.

BACKGROUND: Infection with common childhood infectious diseases including geohelminth infections may provide protection against the development of atopy and allergic disease. Few studies have investigated risk factors for atopy among children living in rural areas of Latin America. OBJECTIVE: To identify risk factors associated with atopy among school-age children in a rural area of Latin America. METHODS: Analytic cross-sectional study of school-age children conducted in seven rural schools in Pichincha Province in Ecuador. Detailed risk factor information was obtained by questionnaire, stool samples were collected for identification of geohelminth parasites, and Mantoux testing was performed to determine tuberculin sensitization. RESULTS: A total of 1002 children from seven rural schools were recruited. The prevalence of geohelminth infections was high (70.1% were infected with at least one geohelminth parasite) and the prevalence of allergic sensitization was high (20.0% had evidence of aeroallergen sensitization). Factors associated with significant protection against atopy in multivariate analyses were the presence of overcrowding in the child's home, low socio-economic level, and infection with geohelminth parasites, and the protective effects of the three factors were statistically independent. CONCLUSION: Low socio-economic level, overcrowding and geohelminth infection, are independently protective against atopy among school-age children living in a rural area of Latin America.

Adolescent↗
PubMed2003

Rapid and frequent induction of protective immunity exceeding UK recommendations for healthcare settings by MF59-adjuvated hepatitis B vaccine.

The ability of three doses of a novel MF59-adjuvanted hepatitis B virus (HBV) vaccine containing surface and pre-S2 antigens given at 0, 1, and 6 months to induce levels of HBV surface antibody (sAb) > or = 100 mIU/ml was compared with a UK licensed alum-adjuvanted yeast-derived HBV vaccine in HBV-naive healthcare workers (HCWs). One month after second immunization with HBV/MF59, 100% of HCWs had sAb > or = 100 mIU/mL, compared with only 11% and 85% after two or three immunisations with Engerix-B. The sAb GMT of the Engerix B immunised group remained below 100 mIU/mL until month seven, (compared with month one for HBV/MF59), and was 123-fold lower at this time (208,561 vs. 1,686 mIU/mL). In our subjects HBV/MF59 vaccine rapidly induced sAb to levels far in excess of those recommended by the Department of Health for high-risk situations (e.g. HCWs and patients on dialysis). It has the potential for shorter schedules and reduced need for serology and boosters.

Adjuvants, Immunologic↗
PubMed2002

Production of beta-amyloid by primary human foetal mixed brain cell cultures and its modulation by exogenous soluble beta-amyloid.

Previous studies on beta-amyloid production have been carried out using transfected cells and cell lines. We measured the 40 and 42 amino acid forms of beta-amyloid released into the culture medium by primary human foetal mixed brain cell aggregate culture over 3 months. In this model, neurones and supporting cells are maintained in serum-free defined medium. The secretion of significant amounts of beta-amyloid 40 and 42 was observed throughout culture for three separate cultures. Levels of beta-amyloid 40 and 42 closely followed the neuronal content of the cultures as estimated by cellular neurone-specific enolase. Addition of synthetic beta-amyloid 1-40 to the cultures for 1 week at 35 days in vitro resulted in a dose-related reduction in cellular neurone-specific enolase levels. Primary human aggregate brain cell cultures produced multimeric beta-amyloid, as determined by immunoassay. beta-Amyloid-treated cultures released diminishing amounts of multimeric beta-amyloid and contained increasing amounts of intracellular multimeric beta-amyloid with increasing exogenous beta-amyloid. These results suggest that release of multimeric beta-amyloid into the extracellular environment by human primary neurones can be affected by the presence of extracellular beta-amyloid. This has implications for Alzheimer's disease in that beta-amyloid released into the extracellular environment by dead/dying neurones could modulate beta-amyloid release by surrounding neurones, potentially causing amplification of toxicity. Moreover, intracellular beta-amyloid oligomer-dependent neurotoxicity may be a component of neurodegeneration in Alzheimer's disease, and other conditions with increased beta-amyloid synthesis, suggesting anti-amyloid therapies for Alzheimer's disease may have to target intracellular beta-amyloid.

Amyloid beta-Peptides↗
PubMed2001

Enhancement of Mycobacterium tuberculosis-induced tumor necrosis factor alpha production from primary human monocytes by an activated T-cell membrane-mediated mechanism.

Mycobacterium tuberculosis alone induces small, donor-variable amounts of tumor necrosis factor alpha (TNF-alpha) from primary human monocytes in vitro. However, TNF-alpha release is increased 5- to 500-fold when fixed activated T cells (FAT) or their isolated, unfixed membranes are added to this system. This FAT-induced synergy was at least as potent as that induced by gamma interferon (IFN-gamma) at 100 U/ml. FAT-enhanced TNF-alpha production is at least in part transcriptionally mediated, as reflected by quantitative changes in TNF-alpha mRNA between 2 and 6 h poststimulation. Unlike IFN-gamma-cocultured cells, FAT-treated monocytes appeared not to have enhanced TNF-alpha message stability, suggesting that de novo transcription may be involved in this effect. Furthermore, M. tuberculosis alone induced only minimal DNA binding of monocyte NF-kappaB, but cells treated with M. tuberculosis and FAT potentiated NF-kappaB activity more effectively. It is therefore possible that one mechanism by which FAT synergize with M. tuberculosis to stimulate TNF-alpha production is via NF-kappaB-enhanced transcription. These data strongly suggest that in the interaction of cells involved in the immune response to M. tuberculosis, T-cell stimulation of monocyte TNF-alpha production involves a surface membrane interaction(s) as well as soluble mediators.

Cell Membrane↗
PubMed2001

Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR.

To investigate the potential immunomodulatory effects of concurrent ascariasis on the cytokine response to a live oral vaccine, we measured cytokine responses to cholera toxin B subunit (CT-B) following vaccination with the live oral cholera vaccine CVD 103-HgR in Ascaris lumbricoides-infected subjects randomized in a double-blind study to receive two doses of either albendazole or placebo prior to vaccination and in a group of healthy U.S. controls. Postvaccination cytokine responses to CT-B were characterized by transient increases in the production of interleukin-2 (IL-2; P = 0.02) and gamma interferon (IFN-gamma; P = 0.001) in the three study groups combined; however, postvaccination increases in IFN-gamma were significant only in the albendazole-treated A. lumbricoides infection group (P = 0.008). Postvaccination levels of IL-2 were significantly greater in the albendazole-treated group compared with the placebo group (P = 0.03). No changes in levels of Th1 and Th2 cytokines in response to control ascaris antigens were observed over the same period. These findings indicate that vaccination with CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-gamma) to CT-B, that infection with A. lumbricoides diminishes the magnitude of this response, and that albendazole treatment prior to vaccination was able to partially reverse the deficit in IL-2. The potential modulation of the immune response to oral vaccines by geohelminth parasites has important implications for the design of vaccination campaigns in geohelminth-endemic areas.

Adult↗
PubMed2001

Protein and energy metabolism in chronic bacterial infection: studies in melioidosis.

Chronic infection is often accompanied by a wasting process, the metabolic basis of which is not fully understood. The aims of the present study were to measure protein and energy metabolism in patients with melioidosis (a serious and antibiotic-refractory Gram-negative bacterial infection which is endemic in South-East Asia) in order to define the metabolic abnormalities that might contribute to wasting. Whole-body protein turnover was measured using the [(13)C]leucine technique, both in the fasted state and while consuming a high-energy meal. Resting energy expenditure was measured by indirect calorimetry, and total energy expenditure by the bicarbonate/urea method. Results were normalized for fat-free mass, as estimated from skinfold thickness. Protein turnover was increased in melioidosis patients compared with healthy controls during fasting (170.9 compared with 124.1 micromol x kg(-1) x h(-1); P=0.04), but the net rate of catabolism (22.2 compared with 20.5 micromol x kg(-1) x h(-1); P=0.77) and the anabolic response to feeding were similar in the two groups. Resting energy expenditure was higher in melioidosis patients compared with controls (191.4 and 157.3 kJ x kg(-1) x day(-1) respectively; P=0.04), but total energy expenditure (measured in a separate group of eight patients with melioidosis) was low (192.1 kJ x kg(-1) x day(-1)). In conclusion, this study found no evidence of metabolic causative factors, such as accelerated net protein catabolism during fasting, a blunted anabolic response to feeding or increased daily energy expenditure, and therefore suggests that reduced energy intake is the prime cause of wasting. The observed normal response to feeding should encourage nutritional approaches to prevent wasting.

Adult↗
PubMed2000

T cell-monocyte contact enhances tumor necrosis factor-alpha production in response to Mycobacterium leprae.

Tumor necrosis factor (TNF)-alpha has been implicated as a key factor in inflammatory processes occurring in erythema nodosum leprosum (ENL). In the present study, the roles of soluble factors and contact-mediated interaction in the induction of enhanced TNF-alpha secretion in leprosy have been investigated. In vitro studies have demonstrated that Mycobacterium leprae per se is a poor stimulus for TNF-alpha production by purified monocytes obtained from normal subjects, although this could be enhanced by either exogenous interferon-gamma or cell contact with fixed activated T lymphocytes. Further investigations demonstrated that monocyte-T cell contact enhanced M. leprae-induced TNF-alpha production by peripheral blood mononuclear cells of ENL patients and was modulated by blocking antibodies to CD40L, CD69, and CD18. These results suggest that physical contact with T cells isolated from patients in a particular disease state (ENL) modulates monocyte function and may contribute to the secretion of proinflammatory cytokines described in ENL.

Adult↗
PubMed2000

Human infection with Ascaris lumbricoides is associated with a polarized cytokine response.

To define the cytokine response to Ascaris lumbricoides infection, the cellular immune response to adult and larval-stage Ascaris antigens in young adults with moderate infection intensities (n=73) was compared with that of a group of uninfected control subjects (n=40). A. lumbricoides-infected subjects had significantly greater lymphoproliferative responses to adult and larval-stage antigens, compared with uninfected control subjects (P<.01). The frequencies of parasite antigen-stimulated peripheral blood mononuclear cell (PBMC)-expressing interleukin (IL)-4 and IL-5 were significantly greater in the infected group (P<.001), whereas the frequencies of IL-10- and interferon-gamma-expressing PBMC were similar in the 2 groups studied. The ratios of Th2 to Th1 cytokine frequencies were significantly elevated in the infected group, compared with those in uninfected subjects, as was IL-5 protein production by PBMC stimulated with adult (P<.05) and L3/L4 stage (P<.001) antigens. Analysis of these data indicates that A. lumbricoides infections in endemic regions are associated with a highly polarized type 2 cytokine response.

Adolescent↗
PubMed2000

Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR.

Because concurrent infections with geohelminth parasites might impair the immune response to oral vaccines, we studied the vibriocidal antibody response to the oral cholera vaccine CVD 103-HgR in children infected with Ascaris lumbricoides and investigated the effect of albendazole pretreatment on the postvaccination response. Children with ascariasis were randomized to receive either 2 sequential doses of 400 mg of albendazole or placebo. After the second dose, CVD 103-HgR was given, and serum vibriocidal antibody levels were measured before and 10 days after vaccination. Postvaccination rates of seroconversion were greater in the treatment group that received albendazole (P=.06). Significantly greater rates of seroconversion and geometric mean titer were observed in the albendazole group in subjects with non-O ABO blood groups. A significant association was observed between vibriocidal seroconversion rates and treatment group, suggesting that A. lumbricoides infections impair the immune response to oral cholera vaccine, particularly in subjects of non-O blood groups.

Adolescent↗
PubMed2000

Acute systemic inflammation impairs endothelium-dependent dilatation in humans.

BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS: Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Acetylcholine↗
PubMed2000

Conditional lethality of the diprotic weak bases chloroquine and quinacrine against Cryptococcus neoformans.

Chloroquine at 10 microM enhances the activity of macrophages against Cryptococcus neoformans but does not directly inhibit cryptococcal growth. The antifungal activity of higher chloroquine concentrations likely to be found within the acidic cryptococcal phagosome was tested. Concentrations of >/=30 microM inhibited cryptococcal growth, and there was fungal killing at concentrations of >/=100 microM. Activity was dependent on physiologic temperature and pH. Quinacrine was 50-fold more active than chloroquine, and concentrations as low as 100 nM enhanced macrophage anticryptococcal activity. Quinacrine was concentrated within a vacuolar system within the fungal cell and highly concentrated within intracellular C. neoformans. Ammonium chloride and bafilomycin A both inhibited cryptococcal growth, suggesting that the activity of chloroquine and quinacrine may in part be due to disruption of pH-dependent processes. These findings add to the known spectrum of activity of chloroquine and quinacrine. These, and related compounds, may have utility for the treatment of cryptococcosis.

Anti-Bacterial Agents↗
PubMed2000

Human rotation-mediated fetal mixed brain cell aggregate culture: characterization and N-methyl-D-aspartate toxicity.

One difficulty in generating in vitro models of neuropathogenesis lies in maintaining stable proportions of primary neurons within a mixed brain cell population. Rotation-mediated fetal brain aggregate culture has been modified to permit growth of human primary fetal brain cells containing 50 to 60% neurons. After 12 weeks cholinesterase, neuron specific enolase and microtubule-associated protein-2 were demonstrable by biochemical assay and immunocytochemical labelling of cryostat sections of human fetal brain aggregates. Upon exposure to the glutamate agonist; N-methyl-D-aspartate for 7 days at 35 days in vitro neuron specific enolase and cholinesterase decreased to 60 to 70% of untreated levels. Glial fibrillary acidic protein did not change significantly but swollen astrocytes were seen in labelled sections of treated aggregates. This method is useful to study human neurotoxicity and degeneration in mixed glial culture without astrocyte overgrowth.

Astrocytes↗
PubMed2000

Elevated serum concentrations of soluble CD14 in HIV- and HIV+ patients with tuberculosis in Africa: prolonged elevation during anti-tuberculosis treatment.

Data are limited regarding serum concentrations of soluble CD14 (sCD14), a marker of macrophage activation, in patients with active tuberculosis (TB) and during drug treatment. In this study, concentrations of sCD14 were measured in serum samples obtained from 105 African subjects who were categorized into one of four groups: persons with pulmonary TB alone (TB+HIV-, n = 30), pulmonary TB and HIV co-infection (TB+HIV+, n = 20), or HIV infection alone (TB-HIV+, n = 25), and healthy controls (TB-HIV-, n = 30). Mean total sCD14 was significantly increased in serum of patients with newly diagnosed pulmonary TB (mean = 6.6 g/ml, s.d. = 1.6 g/ml) compared with healthy controls (mean = 3.1 g/ml, s.d. = 0.6 g/ml; P < 0.0001), and this elevation comprised proportionate increases in the alpha (2.1-fold greater, P < 0.0001) and beta (2.0-fold greater, P < 0. 0001) forms of sCD14. Total sCD14 was also increased in serum of HIV-infected patients (mean = 4.1 g/ml, s.d. = 1.9 g/ml; P < 0.01), but the highest concentrations were observed in patients with pulmonary TB and HIV co-infection (mean = 8.7 g/ml, s.d. = 3.1 g/ml; P < 0.0001). Analysis of serum samples prospectively collected from TB+HIV-patients during the first 3 months of successful anti-TB treatment demonstrated steep reductions in mean concentrations of the acute-phase protein, C-reactive protein, and the soluble lymphocyte activation marker, sCD25. In contrast, levels of sCD14 increased during the first month of treatment and slowly declined thereafter. These data indicate that the serum concentration of sCD14 is not a sensitive index of response to anti-TB treatment and suggest that cellular activation resolves more slowly in the macrophage pool compared with the lymphocyte pool during anti-TB treatment.

Adult↗
PubMed2000

Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction.

Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 microg/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 microgram/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B. recurrentis infection.

Adolescent↗
PubMed2000

Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides.

Heterosexual transmission of human immunodeficiency virus (HIV) is the most frequent mode of infection worldwide. However, the immediate events between exposure to infectious virus and establishment of infection are still poorly understood. This study investigates parameters of HIV infection of human female genital tissue in vitro using an explant culture model. In particular, we investigated the role of the epithelium and virucidal agents in protection against HIV infection. We have demonstrated that the major target cells of infection reside below the genital epithelium, and thus HIV must cross this barrier to establish infection. Immune activation enhanced HIV infection of such subepithelial cells. Furthermore, our data suggest that genital epithelial cells were not susceptible to HIV infection, appear to play no part in the transfer of infectious virus across the epithelium, and thus may provide a barrier to infection. In addition, experiments using a panel of virucidal agents demonstrated differential efficiency to block HIV infection of subepithelial cells from partial to complete inhibition. This is the first demonstration that virucidal agents designed for topical vaginal use block HIV infection of genital tissue. Such agents have major implications for world health, as they will provide women with a mechanism of personal and covert protection from HIV infection.

Antiviral Agents↗
PubMed2000

Unseen blindness, unheard deafness, and unrecorded death and disability: congenital rubella in Kumasi, Ghana.

OBJECTIVES: Although rubella serosusceptibility among women of reproductive age in West Africa ranges from 10% to 30%, congenital rubella syndrome has not been reported. In Ghana, rubella immunization and serologic testing are unavailable. Our objectives were to identify congenital rubella syndrome cases, ascertain rubella antibody seroprevalence during pregnancy, and recommend strategies for congenital rubella syndrome surveillance. METHODS: Congenital rubella syndrome cases were identified through prospective surveillance and retrospective surveys of hospital records. A rubella serosurvey of pregnant urban and rural women was performed. RESULTS: Eighteen infants born within a 5-month period met the congenital rubella syndrome case definitions, coinciding with a 9-fold increase in presentation of infantile congenital cataract. The congenital rubella syndrome rate for this otherwise unrecorded rubella epidemic was conservatively estimated to be 0.8 per 1000 live births. A postepidemic rubella immunity rate of 92.6% was documented among 405 pregnant women; susceptibility was significantly associated with younger age (P = .000) and ethnicity (northern tribes, P = .024). CONCLUSIONS: Congenital rubella syndrome occurs in Ghana but is not reported. Information about congenital rubella syndrome and rubella in sub-Saharan Africa is needed to evaluate inclusion of rubella vaccine in proposed measles control campaigns.

Adolescent↗