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Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 307 records · Page 17Linked to original sources
PubMed1998

Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis.

Hereditary haemochromatosis is an inherited disorder of iron absorption that leads to excessive iron storage in the liver and other organs. A candidate disease gene HFE has been identified that encodes a novel MHC class I like protein. We report the development of a monoclonal antibody (HFE-JB1) specific for recombinant refolded HFE protein. The antibody immunoprecipitates a 49 kD protein from the cell line U937, a histiocytic lymphoma. It binds HFE but does not recognize other recombinant non-classic MHC class I proteins (HLA-E, F and G), nor does it react with a variety of recombinant classic class I MHC molecules. COS cells transfected with HFE in culture are stained specifically. The immunohistochemical staining pattern in human tissues is unique and can be defined as a subset of the transferrin receptor positive cells. In the liver HFE protein was shown to be present on Kupffer cells and endothelium (sinusoidal lining cells), but absent from the parenchyma. Kupffer cells from an untreated C282Y HH patient failed to stain with the antibody. In the normal gut scattered cells in the crypts are stained. HFE was also present on capillary endothelium in the brain (a site of high levels of transferrin receptor) and on scattered cells in the cerebellum and cortex. These results raise interesting questions concerning the function of HFE in the control of body iron content and distribution.

Animals↗
PubMed1998

Surface-catalysed disinfection of thick Pseudomonas aeruginosa biofilms.

Transition metal catalysts were incorporated into polymers which formed the surface for bacterial attachment and biofilm formation in a constant depth film fermenter (100 microns thickness), flow chamber (about 30 microns thickness) and in batch culture (< 30 microns thickness). The catalysts drive the breakdown of persulphates to reactive oxygen species. When Pseudomonas aeruginosa biofilms were exposed to dilute solutions of potassium monopersulphate (20 micrograms ml-1-1 mg ml-1), significant enhancement of killing was notable for catalyst-containing surfaces over that of controls. The degree of enhancement was greatest for thin films, but was nevertheless significant for the 100 microns thick biofilms. Fluorescence probes and viability staining, in conjunction with laser confocal microscopy, showed that reactive species were generated at the biofilm-substratum interface and killed the biofilm from the inside. Reaction-diffusion limitation now concentrates the active species within the biofilm rather than protecting it, and a diffusion bump is established whereby further treatment agent is drawn to the substratum enabling relatively thick biofilms to be disinfected.

Biofilms↗
PubMed1998

Outbreak of sterile peritonitis among continuous cycling peritoneal dialysis patients.

BACKGROUND: Approximately 30,000 patients receive peritoneal dialysis in the United States. In August 1996, several dialysis centers from different states reported sterile peritonitis among CCPD patients using sterile peritoneal dialysis solution (PDS) from a single manufacturer. The manufacturer recalled 53 lots of PDS that had passed established industry guidelines and Food and Drug Administration (FDA) approved quality control tests [including endotoxin levels <0.5 endotoxin units (EU)/ml], but had pre-sterilization bacterial colony counts >1 cfu/ml. METHODS: At one outpatient dialysis center, Hospital of the University of Pennsylvania (HUP), we conducted a retrospective cohort study of all CCPD patients treated during July 15 to August 30, 1996. A case-patient was defined as any HUP patient with culture-negative peritoneal fluid with a white blood cell count >100/mm3, cloudy peritoneal fluid, and/or abdominal pain. PDS and tubing were cultured for bacteria and assayed for endotoxin. RESULTS: Overall, 14 of 28 patients had sterile peritonitis. The only risk factor identified was exposure to > or =1 lot of recalled PDS (14 of 22 vs. 0/6, P = 0.02); the more recalled lots received, the higher the attack rate (P = 0.0001). Five of 47 PDS bags had detectable endotoxin; recalled lots were more likely to have measurable endotoxin than nonrecalled lots (5/19 vs. 0/17, P = 0.05). When case-patients resumed CCPD using PDS from non-recalled lots, no further cases were reported. CONCLUSIONS: Our results suggest that this outbreak was caused by intrinsic PDS contamination with endotoxin. Pre-sterilization colony counts may be an important quality control indicator for CCPD fluids in conjunction with endotoxin levels.

Adult↗
PubMed1998

Use of a live attenuated varicella vaccine to boost varicella-specific immune responses in seropositive people 55 years of age and older: duration of booster effect.

Varicella-zoster virus (VZV)-specific T cell immunity was measured in 130 persons > or = 55 years of age 6 years after they received a live attenuated VZV vaccine. Circulating T cells, which proliferated in vitro in response to VZV antigen, were enumerated (VZV responder cell frequency assay). Six years after the booster vaccination, the VZV-responding cell frequency (1/61,000 circulating cells) was still significantly (P < .05) improved over the baseline measurements (1/70,000) and appears to have diminished the expected decline in frequency as these vaccinees aged (to 1/86,000). Ten herpes-zoster--like clinical events were recorded. Although the frequency of these events, approximately 1/100 patient-years, is within the expected range of such events for this age cohort, the number of lesions was small, there was very little pain, and there was no postherpetic neuralgia. These results support the development of a vaccine to prevent or attenuate herpes zoster.

Aged↗
PubMed1998

Cytokine production in varicella-zoster virus-stimulated cultures of human blood lymphocytes.

Estimates of responder cell frequency (RCF) based on limiting dilution analyses are laborious, and alternative means to quantitate cell-mediated immunity to immunogens are desirable. It was shown that levels of interleukin (IL)-2 in the supernatant of varicella-zoster virus-stimulated blood lymphocytes from immune adults peaked at 48 h of culture and correlated partially with estimates of RCF (r = .74, P = .003). Levels of gamma-interferon, IL-4, and IL-10 increased through the first 4 days of culture, and gamma-interferon levels showed some correlation with peak IL-2 levels (r = .48, P = .03). Nevertheless, correlations between levels of these cytokines and RCF did not reach statistically significant levels.

Adult↗
PubMed1998

Intraventricular injection of human immunodeficiency virus type 1 (HIV-1) tat protein causes inflammation, gliosis, apoptosis, and ventricular enlargement.

To determine the role of the Tat protein of the human immunodeficiency virus type 1 (HIV-1) in the pathogenesis of HIV-1 associated dementia, recombinant Tat was injected intraventricularly as a single or repeated dose into male Sprague-Dawley rats. Histopathological evaluation showed an initial infiltration of neutrophils one day after Tat injection, followed by macrophages and lymphocytes by 7 days. Tat-injected brains also exhibited astrocytosis, apoptotic cells, and ventricular enlargement 7 days following the last injection. Nuclear magnetic resonance spectroscopic analysis of tissue extracts of hippocampi from Tat-injected rats showed a decrease in the glutamate/g aminobutyric acid ratio. We conclude that the transient extracellular exposure of the central nervous system to Tat protein of HIV can cause a cascade of events leading to the influx of inflammatory cells, glial cell activation, and neurotoxicity.

Animals↗
PubMed1998

Erk-independent partial activation of AP-1 sites by the hepatitis B virus HBx protein.

The hepatitis B virus X protein (HBx) is suggested to regulate transcription by stimulation of intracellular signalling pathways. We have analysed the effects of HBx on activation of the MAP kinase (Erk) and JNK/SAPK signalling pathways and confirm a stimulation of the Erk/MAP kinase in quiescent cells. However, a substantial Erk-independent activation of AP-1, and phosphorylation of c-Jun (serine-63), but not Erk-2, was induced by HBx in dividing, serum-maintained cells. These data suggest that HBx promiscuously activates Erk and JNK responsive pathways and that its overall effect on signalling may be influenced by external mitogenic stimuli.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Opportunistic sampling from early childhood centres: a substitute for random sampling to determine lead and iron status of pre-school children?

This report compares the results from two sampling strategies used to determine the prevalence of elevated blood lead concentrations and iron status in 12-36 month old children in Central Sydney. The two methods were stratified random sampling using census collector districts and an opportunistic sampling strategy using client registers at Early Childhood Centres (ECCs). The response rates were 75.3% (n = 718 of whom 198 were aged 12-36 months) and 24.1% (n = 304) respectively. The geometric mean blood lead concentrations were 0.40 and 0.34 mumol/L respectively (p = 0.001). The traditional random sampling prevalence survey identified a significantly higher proportion of children with blood lead concentrations greater than 0.48 (OR = 0.61, 95% CI 0.40-0.93) and 0.72 mumol/L (OR = 0.44, 95% CI 0.21-0.92) compared to the simpler opportunistic survey. The median plasma ferritin concentration for both studies was 19 micrograms/L (p = 0.4). The prevalence of iron depletion, iron deficiency and iron deficiency anaemia was not significantly different between the two studies. In conclusion, opportunistic sampling through ECCs does not appear to be a substitute for the traditional random sampling prevalence surveys of determine the prevalence of elevated blood lead concentrations in pre-school children in Central Sydney. However, opportunistic sampling through ECCs may be an appropriate method for monitoring iron status, in particular iron depletion, in pre-school children in Central Sydney.

Anemia, Iron-Deficiency↗
PubMed1998

Does gestational hypertension become pre-eclampsia?

OBJECTIVE: To determine the likelihood of progression from gestational hypertension (GH) to pre-eclampsia (PE) in hypertensive pregnant women and whether this change can be identified in advance by available clinical and laboratory measures. DESIGN: A retrospective analysis and a prospective study. SETTING: St George Hospital, Sydney, a teaching hospital of the University of New South Wales delivering 2500 women per year. POPULATION: Eight hundred and forty-five women with new hypertension in the second half of pregnancy, managed by a uniform protocol (661 in the retrospective analysis, 184 in the prospective study). METHODS: Clinical and laboratory data at initial presentation were compared among women with GH who developed PE and those who remained with a diagnosis of GH until delivery. Data predictive for progression from GH to PE were analysed by logistic regression analysis. MAIN OUTCOME MEASURED: Progression from GH to PE. RESULTS: In the retrospective analysis, 416 women initially presented as having GH and 62 (15%) progressed to PE. In the prospective study, 112 women initially presented with GH and 29 (26%) progressed to PE, giving an overall progression of 17%. In both studies, women who developed PE from GH presented earlier than those who remained with GH until delivery. In multiple logistic regression analyses prior miscarriage and early gestation at presentation were associated with increased likelihood of progressing from GH to PE. CONCLUSION: Approximately 15-25% of women initially diagnosed with GH will develop PE and this is more likely with earlier presentation or if the woman has had a prior miscarriage. Women with gestational hypertension diagnosed after 36 weeks of gestation have only about 10% risk of developing PE. These data should help stratify the risks of mildly hypertensive pregnant women being managed as outpatients in their third trimester.

Abortion, Spontaneous↗
PubMed1998

Self-reported rectal bleeding in a United States community: prevalence, risk factors, and health care seeking.

OBJECTIVE: Little data on rectal bleeding in the U.S. population are available. We therefore sought to assess the prevalence of different types of rectal bleeding, their association with potential risk factors including other colonic symptoms, and predictors of health care seeking in a U.S. community. METHODS: We used a crossectional survey by mail, applying a previously validated self-report symptom questionnaire. Our population comprised an age- and gender-stratified random sample of Olmsted County, Minnesota residents aged 20-64 yr. RESULTS: In total, 1643 responded (77%). Rectal bleeding was reported by 235 subjects (age- and gender-adjusted prevalence, 15.5 per 100; 95% confidence interval [CI], 13.6-17.4); 218 found blood on wiping, 74 noted blood coating the stools, and 46 reported dark blood mixed in the stools. The prevalence of rectal bleeding was significantly higher in younger persons (18.9%, 20-40 yr vs 11.3% > 40 yr; p < 0.001). By stepwise logistic regression analysis, constipation (odds ratio [OR] = 3.03; 95% CI, 2.09-4.41) and diarrhea (OR = 1.90; 95% CI, 1.25-2.84) were independent predictors of rectal bleeding. Among those with rectal bleeding, 13.9% (95% CI, 9.6-19.1%) had visited a physician for bowel problems in the prior yr; only a history of abdominal surgery was an independent predictor of physician visits but this explained just 15.9% of the deviance. CONCLUSIONS: In otherwise healthy young and middle-aged persons, approximately one in seven have a history of rectal bleeding and this is more frequent in younger people; only a minority seek health care and this is not related to symptom status.

Adult↗
PubMed1998

Requirement of CD40-CD40 ligand interaction for elimination of Cryptosporidium parvum from mice.

Mice with disrupted genes for CD40 and CD40 ligand (CD40L) are unable to clear infection with Cryptosporidium parvum and develop cholangitis. Parasites are present in the gut, gall bladder, and biliary tree, and biliary epithelial cells express CD40 on the cell surface. SCID mice infected with C. parvum for >1 month can clear the infection after reconstitution with spleen cells from CD40, but not CD40L, knockout mice. In an in vitro model, C. parvum-infected HepG2 cells were triggered to apoptosis when incubated with a CD40L-CD8 fusion protein. The requirement for CD40-CD40L interactions for immunity to C. parvum indicated by our results may entail the triggering of apoptosis in infected cells, in addition to the known role of CD40L-CD40 interactions in stimulating cytokine production and promoting T-cell responses.

Animals↗
PubMed1998

Age-dependent Neisseria meningitidis serogroup C class-specific antibody concentrations and bactericidal titers in sera from young children from Montana immunized with a licensed polysaccharide vaccine.

Neisseria meningitidis serogroup C bactericidal titers and class-specific enzyme-linked immunosorbent assay (ELISA) antibody concentrations were measured in sera from 173 children (1 to 5 years old) before and 6 weeks and 7 months following vaccination with a quadrivalent (A/C/Y/W-135) polysaccharide vaccine. The immune responses of the children were compared with those of 40 adults 6 weeks postvaccination. Both bactericidal titers and ELISA antibody concentrations were significantly higher in the adults than in the children (P < 0.05). In addition, the ratio of immunoglobulin G (IgG) to IgM was higher in the children than in the adults. With an ELISA total antibody concentration of >/=2 microg/ml used as a measure of seroconversion, >/=84% of the individuals from each age group responded to the serogroup C polysaccharide. However, with a >/=4-fold-increase in bactericidal titer used, only 18% of 1-year-olds, 32% of 2-year-olds, and 50 to 60% of 3-, 4-, and 5-year-olds seroconverted. The ELISA results suggest that >50% of all children retained >/=2 microg of total antibody per ml at 7 months postimmunization. However, the bactericidal titers suggest that <10% of children <4 years old retained a >/=4-fold increase at 7 months following vaccination. Of particular note, 59 of 79 sera (75%) from the 1- and 2-year-olds had high ELISA antibody concentrations (2 to 20 microg/ml) with no associated bactericidal titer (<1:8). Discordant results between bactericidal titers and ELISA antibody concentrations were not explained by the presence of IgA blocking antibody or relative levels of IgG and IgM. The bactericidal results show age-dependent differences in the production and retention of antibody in young children immunized with serogroup C polysaccharide; these differences are not evident with the ELISA data.

Adult↗
PubMed1998

The 30-base-pair deletion in Chinese variants of the Epstein-Barr virus LMP1 gene is not the major effector of functional differences between variant LMP1 genes in human lymphocytes.

One group of sequence variants of Epstein-Barr virus is characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this deletion upon LMP1 function in four human lymphoid cell lines by using three natural variants of LMP1: the prototype B95.8 gene and the CAO and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted. These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8-LMP1 in two lines and was only slightly impaired in the other two lines. Activation of NF-kappaB by CAO-LMP1 was not impaired in any of the lines; rather, activation of an NF-kappaB reporter by CAO-LMP1 was consistently about twofold greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes, the 10-amino-acid deletion appears not to be directly responsible. This conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the distinct functional characteristics of CAO-LMP1 in human lymphoid cells.

Amino Acid Sequence↗
PubMed1998

Is the association between irritable bowel syndrome and abuse explained by neuroticism? A population based study.

BACKGROUND: In outpatients and the community, an association between abuse (particularly sexual abuse) and irritable bowel syndrome (IBS) has been observed, but whether there is a causal link continues to be disputed. AIMS: To test the hypothesis that psychological factors explain the apparent association between abuse and IBS. METHODS: A sample of residents of Penrith (a Sydney suburb sociodemographically similar to the Australian population) selected randomly from the electoral rolls (that by law include the entire population of age 18 years and above) was mailed a validated self report questionnaire. Measured were gastrointestinal (GI) symptoms including the Rome criteria for IBS, abuse (including the standardised Drossman questions), neuroticism (Eysenck Personality Questionnaire), and psychological morbidity (General Health Questionnaire). RESULTS: The response rate was 64% (n = 730); 12% fulfilled the Rome criteria for IBS. Overall abuse in childhood (odds ratio (OR) = 2.02, 95% confidence interval (CI) 1.29 to 3.15) but not adulthood (OR = 1.39, 95% CI 0.88 to 2.19) was associated with IBS univariately. Neuroticism and psychological morbidity were also univariately associated with abuse in childhood, abuse in adulthood and IBS, respectively. However, by logistic regression, abuse in childhood was not associated with IBS after controlling for age, gender, and psychological factors (OR = 1.34, 95% CI 0.83 to 2.17). The results were not altered by restricting the analyses to more severe forms of abuse, and were not explained by interactions between abuse and psychological variables. CONCLUSION: There is an association between abuse and IBS in the community, but this may be explained in part by other psychological factors. Based on a path analysis, we postulate that abuse may induce the expression of neuroticism that in turn leads to IBS.

Adult↗
PubMed1998

Identification of distinct upper and lower gastrointestinal symptom groupings in an urban population.

BACKGROUND: The current classification dividing patients with functional gastrointestinal symptoms into subgroups remains controversial. AIMS: To determine whether distinct symptom groupings exist in the community. METHODS: A random sample of Sydney residents in Penrith, Australia was mailed a validated self report questionnaire. Gastrointestinal symptoms including the Rome criteria for irritable bowel syndrome (IBS) and dyspepsia were measured. RESULTS: Among 730 respondents, the 12 month age and gender adjusted prevalence (adjusted to the Australian population) of IBS, dyspepsia, and gastro-oesophageal reflux were 11.8% (95% confidence interval (CI) 9.3 to 14.3%), 11.5% (95% CI 9.6 to 14.6%), and 17.5% (95% CI 14.2 to 19.9%), respectively. In total, 60% of the population reported four or more gastrointestinal symptoms. There was considerable overlap of IBS with dyspepsia and among the dyspepsia subgroups by application of the Rome criteria. Independently, 10 symptom groupings were identified by factor analysis. The underlying constructs measured by these factors were generally the major abdominal syndromes recognised by the Rome classification: dyspepsia, IBS, reflux, painless constipation, painless diarrhoea, and bloating, in addition to a number of more specific symptom groupings. CONCLUSION: Gastrointestinal symptoms are common and overlap in the community, but distinct upper and lower abdominal symptom groupings can be identified.

Adult↗
PubMed1998

Predicting operative risk for coronary artery surgery in the United Kingdom: a comparison of various risk prediction algorithms.

OBJECTIVE: To compare the ability of four risk models to predict operative mortality after coronary artery bypass graft surgery (CABG) in the United Kingdom. DESIGN: Prospective study. SETTING: Two cardiothoracic centres in the United Kingdom. SUBJECTS: 1774 patients having CABG. MAIN OUTCOME MEASURES: Risk factors were recorded for all patients, along with in-hospital mortality. Predicted mortality was derived from the American Society of Thoracic Surgeons (STS) risk program, Ontario Province risk score (PACCN), Parsonnet score, and the UK Society of Cardiothoracic Surgeons risk algorithm. RESULTS: There were significant differences (p < 0.05) between the British and American populations from which the STS risk algorithm was derived with respect to most variables. The observed mortality in the British population was 3.7% (65 of 1774). The mean predicted mortality by STS score, PACCN, Parsonnet score, and UK algorithms were 1.1%, 1.6%, 4.6%, and 4.7% respectively. The overall predictive ability of the models as measured by the area under the receiver operating characteristic curve were 0.64, 0.60, 0.73, and 0.75, respectively. CONCLUSIONS: There are differences between the British and American populations for CABG and the North American algorithms are not useful for predicting mortality in the United Kingdom. The UK Society of Cardiothoracic Surgeons algorithm is the best of the models tested but still only has limited predictive ability. Great care must be exercised when using methods of this type for comparisons of units and surgeons.

Aged↗