Search PubMed⌕ Search

Biomedical subjects

A L Jones

Publications and source records attributed to A L Jones.

At least 55 records · Page 3Linked to original sources
PubMed2000

Polymorphism of human mucin genes in chest disease: possible significance of MUC2.

Most of the genes that encode epithelial mucins are highly polymorphic due to variations in the length of domains of tandemly repeated (TR) coding sequence, the part of the apomucin that is heavily glycosylated. We report here for the first time a difference in the distribution of MUC TR length alleles in chest disease. We examined the distribution of the length alleles of those MUC genes whose expression we have confirmed in the bronchial tree in an age- and sex-matched series of 50 pairs of atopic patients with and without asthma. There was no significant difference in the distribution of alleles of MUC1, MUC4, MUC5AC, and MUC5B. MUC2, however, showed a highly significant difference in distribution. The atopic, nonasthmatic individuals showed an allele distribution that was very different from all our other patient and control groups, this group showing a longer mean allele length. The observations suggest that longer MUC2 alleles may help protect atopic individuals from developing asthma, though the effect may be due to a linked gene. The biological significance of this variation with respect to susceptibility to asthma will merit further investigation, and it will also be important to substantiate this finding on an independent data set.

Alleles↗
PubMed2000

Expression of epidermal growth factor and its receptor in cirrhotic liver disease.

Polypeptide growth factors, including epidermal growth factor (EGF), play a central role in regulating hepatocyte growth both in vivo and in primary culture. To characterize EGF gene expression in the pathogenesis of regenerative cirrhotic fibrosis, we employed biotinylated antisense oligonucleotide probes to localize hepatic mRNA transcripts in situ. In control tissue and regenerative hepatic nodules, EGF receptor (EGFR) mRNA transcripts were expressed constitutively. In contrast, oligonucleotide probes targeting the human EGF coding region showed that EGF transcription was extremely low in control liver but was highly elevated and localized to regenerative hepatic nodules and bile duct epithelia of cirrhotic liver. To determine whether EGF mRNA accumulation accompanied a comparable increase in the EGF peptide, we performed immunohistochemistry using an antibody specific for the nonprocessed peptide aminoterminus. We observed that positive localized EGF staining paralleled its mRNA transcript. These results indicate that EGF upregulation is a characteristic of cirrhotic liver disease and suggest that persistent de novo ligand synthesis and its signaling contribute to an autocrine-mediated hepatocyte proliferation within the regenerative nodule.

Biotin↗
PubMed1999

The localization and interactions of huntingtin.

Huntingtin was localized by using a series of antibodies that detected different areas of the protein from the immediate N-terminus to the C-terminal region of the protein. The more C-terminal antibodies gave a cytoplasmic localization in neurons of the brain in controls and cases of Huntington's disease (HD). The N-terminal antibody, however, gave a distinctive pattern of immunoreactivity in the HD brain, with marked staining of axon tracts and white matter and the detection of densely staining intranuclear inclusions. This implies some processing differences between mutated and normal huntingtin. We have also localized two interacting proteins, cystathionine beta-synthase and the nuclear receptor co-repressor (N-CoR), in brain. Cystathionine beta-synthase was not relocalized in HD brain, but the N-CoR was excluded from neuronal nuclei in HD brain, and a further protein that exists in the same repression complex, mSin3, was similarly excluded. We conclude that the co-repressor might have a part in HD pathology.

Animals↗
PubMed1999

Localization of rabbit huntingtin using a new panel of monoclonal antibodies.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG repeat which is expressed as a polyglutamine tract near the N-terminus of the gene product, huntingtin. N-terminal huntingtin fragments form intranuclear aggregates in HD patients and these may be involved in the pathogenesis. Monoclonal antibodies (mAbs) against three different regions of huntingtin (amino acids 997-1276, 1844-2131 and 2703-2911) have been produced and two of the epitopes have been identified using phage displayed peptide libraries. All mAbs reacted with 350 kDa huntingtin on Western blots and one mAb from each region was selected for further study by strong immunoreactivity with neurons in different regions of rabbit brain and by ability to immunoprecipitate native huntingtin. Subcellular fractionation and sucrose density centrifugation of rabbit brain extract showed that most of the huntingtin exists as a high molecular weight complex in the cytoplasm. Two outstanding problems have been addressed; the location of huntingtin in tissues outside the central nervous system and whether huntingtin is present in the nucleus of normal cells. We conclude that huntingtin is present at low levels in most non-neuronal cells though we have identified an interstitial cell type in skin with very high immunoreactivity. Using both immunolocalization and nuclear purification methods, we were unable to exclude the possibility that a small proportion of full-length huntingtin is present in the nucleus.

Animals↗
PubMed1999

Elevated immunoglobulin E (IgE) levels in children with exposure to environmental lead.

Lead has been reported to be an immunosuppressive agent in animal systems at levels far below those recognized as overtly toxic. Little data exist on lead's effects on the human immune system, especially in young children who are at greatest risk for exposure to this environmental hazard. The effects of environmental lead exposure on the human immune system were examined in a population of young children, age 9 months-6 years, from the urban population of Springfield-Greene County, Missouri. Reported here are data from 279 children with blood lead levels ranging from 1 to 45 microg/dl. White blood cell populations have been enumerated and examined for cell surface expression of activation markers. Serum has been analyzed for IgE, specific titers to Rubella vaccine, sCD25 (the soluble form of the IL2 receptor), sCD27 (the soluble form of the lymphocyte specific member of the tumor necrosis factor receptor family), and IL4 (the cytokine interleukin 4). Variation of these assays with age of the child was considered in statistical analysis of data. A statistically significant relationship of IgE and blood lead level was found in this population; as blood lead (PbB) level increases, IgE level increases. No other statistically significant differences between risk categories or other associations with blood lead level were found. The exact mechanism for this apparent stimulus of IgE-producing B cells remains to be elucidated. The development of allergic symptoms is often preceded by an increase in IgE. These data indicate that ingested lead could play a role in this process by stimulating IgE production.

Age Factors↗
PubMed1999

Differential expression of apolipoprotein E messenger RNA within the rat liver lobule determined by in situ hybridization.

Apolipoprotein (Apo) E plays a key role in the metabolism of lipoproteins. It also modulates immunoregulation, cell growth and differentiation and the response to nerve injury. The liver is a major site of ApoE synthesis. Most of the circulating ApoE is thought to be of hepatic origin with most synthesized in hepatocytes. We showed that total liver ApoE messenger RNA (mRNA) levels were greater in normal adult female rats than in male and that gender-specific patterns of liver ApoE mRNA expression were present by in situ hybridization. In the male liver, the signal was strongest in the portal area, decreasing toward the central vein with the weakest signal in pericentral hepatocytes, resulting in a hepatic lobular gradient of expression. In female liver, a strong periportal signal also was observed that decreased in Zone 2, similar to that in males, but which then increased in pericentral hepatocytes resulting in a bowl-like distribution in marked contrast with that of the male. The results suggest that ApoE mRNA level is regulated differentially in hepatocytes within the liver plate and that the regulation is gender-dependent. Further, the results suggest that in males, hepatocytes in the portal area are the major contributors of ApoE to the plasma and/or sinusoidal pool, whereas in females, both portal and central area hepatocytes play an equal role.

Animals↗
PubMed1999

An analysis of first-time enquirers to the CancerBACUP information service: variations with cancer site, demographic status and geographical location.

A retrospective comparison of cancer incidence data and, where relevant, population data with 16,955 first-time users (patients, relatives and friends) of a national cancer information service (CancerBACUP) during the period April 1995 to March 1996 is presented. The number of events observed was compared with the number of events expected, were the national rates of cancer incidence and population demographics apply. Standardized incidence ratios (SIRs) (observed - expected ratios) were used to indicate any differences. Statistically significant differences (P < 0.001) in the observed and expected sex, age and primary site distribution of patients enquired about were found. Statistically significant differences (P < 0.001) were also identified for the age, employment status, socioeconomic class and geographical location of first-time enquirers (patients, relatives and friends). Enquiries about brain, testis and breast cancers and non-Hodgkin's lymphoma (NHL) were substantially higher than expected; enquiries about bladder, lung, stomach and colorectal cancers were much lower than expected. As the service is provided via a freephone number, it is available to all, and users might be expected to be randomly distributed across the variables listed. The underlying reasons for the differences identified need to be investigated, and the role of information in the care of cancer patients should be formally evaluated.

Adult↗
PubMed1999

Review article: mechanisms and management of hepatotoxicity in ecstasy (MDMA) and amphetamine intoxications.

The social use of ecstasy (methylenedioxymethampheta-mine, MDMA) and amphetamines is widespread in the UK and Europe, and they are popularly considered as 'safe'. However, deaths have occurred and hepatotoxicity has featured in many cases of intoxication with amphetamine or its methylenedioxy analogues such as ecstasy. Recreational use of these drugs presents an important but often concealed cause of hepatitis or acute liver failure, particularly in young people. The patterns of liver damage and multiple putative mechanisms of injury are discussed. Recognition of the aetiological agent requires a high index of suspicion. Optimum management of the resultant liver damage, including the controversial role of liver transplantation for fulminant hepatic failure, is also discussed.

Amphetamine↗
PubMed1999

Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin.

We detected an interaction of the N-terminus of huntingtin (htt171) with the C-terminal region of the nuclear receptor co-repressor (N-CoR) using the yeast two-hybrid system. This interaction was repeat length dependent and specific to htt171; the co-repressor did not interact with the repeat carrying a section of atrophin 1 nor with the androgen receptor or polyglutamine alone. The interaction was confirmed using His-tagged Escherichia coli -expressed C-terminal human and rat co-repressor protein which pulled full-length huntingtin out of homogenized rat brain and in pull-down assays. The N-CoR represses transcription from sequence-specific ligand-activated receptors such as the retinoid X-thyroid hormone receptor dimers and other nuclear receptors including Mad-Max receptor dimers. The mechanism of this repression appears to be through the formation of a complex of repressor proteins including the N-CoR, mSin3 and histone deacetylases. We have used N-CoR and mSin3A antibodies in immunohistochemical studies and find that in Huntington's disease (HD) cortex and caudate, the cellular localization of these proteins is exclusively cytoplasmic whilst in control brain they are localized in the nucleus as well as the cytoplasm; mSin3A immunoreactivity also occurred in a subset of huntingtin positive intranuclear inclusions. The relocalization of repressor proteins in HD brain may alter transcription and be involved in the pathology of the disease.

Acetyltransferases↗
PubMed1999

Glycopeptide tolerance in bacteria causing endocarditis.

Glycopeptides have been recommended as therapy for endocarditis. MICs and MBCs of vancomycin and teicoplanin were compared for 100 isolates from patients with proven bacterial endocarditis. MICs were generally lower for teicoplanin and tolerance to both agents was common. Almost all isolates of enterococci were tolerant to both glycopeptides. Among the streptococci, 78% were tolerant to teicoplanin and 57% to vancomycin. Similar findings were demonstrated for staphylococci. Although isolates appear sensitive to glycopeptides, bactericidal activity cannot always be predicted. If a glycopeptide is indicated for treatment of endocarditis, combination therapy with a suitable aminoglycoside should be considered unless MBC testing can be performed.

Anti-Bacterial Agents↗
PubMed1999

Multiple logistic regression analysis of plasma paraquat concentrations as a predictor of outcome in 375 cases of paraquat poisoning.

Successful prediction of who may survive paraquat poisoning can prevent inappropriately aggressive treatment in those who have little hope of survival and those only minimally poisoned. We examined case records of patients admitted to one poisoning treatment unit over the last 5 years, and the English and French language literature on paraquat poisoning. Data were recorded from all patients where outcome and timed plasma paraquat concentrations were present. Of 375 patients (113 M, 62 F, 200 unknown), mean age 38.3 years (range 1-87 years), 49 had evidence of renal toxicity, and 41 received haemodialysis or charcoal haemoperfusion; 61 developed pulmonary sequelae; and 44 had lesions in the upper gastrointestinal tract. Median time from ingestion to death in the 241 deaths reported was 270 h (range 3-720 h). We plotted log(plasma paraquat concentration) against log(h since ingestion). The predicted probability of survival for any specified time and concentration was exp(logit)/[1 + exp(logit)], where logit = 0.58-2.33 x log(plasma paraquat)-1.15 x log(h since ingestion). This equation may be helpful in predicting who will survive after ingestion of paraquat up to at least 200 h after ingestion, and can now be used as a research tool for studies on efficacy of treatment of paraquat poisoning.

Adolescent↗
PubMed1999

The continuous assessment of cerebrovascular reactivity: a validation of the method in healthy volunteers.

UNLABELLED: Using transcranial Doppler ultrasonography, we investigated the moving correlation between slow waves in arterial blood pressure (ABP) and blood flow velocity (FV) at different levels of cerebrovascular vasodilation provoked by changing PETCO2. Fourteen healthy volunteers were examined. The FV in middle cerebral arteries, PETCO2, and ABP were recorded during normocapnia, hypercapnia, and hypocapnia. The moving correlation coefficients between ABP and mean FV (FVm) or systolic FV (FVs) during spontaneous fluctuations in ABP were calculated for 3-min epochs and averaged for each investigation, thus yielding the mean index (Mx) and systolic index (Sx). As a reference method, Aaslid's cuff tests were performed to obtain the rate of regulation (RoR). RoR, Mx, and Sx significantly depended on PETCO2 (analysis of variance, P < 0.00001). At high PETCO2, cerebrovascular reactivity was disturbed as reflected in RoR values of < 0.17/s for all volunteers and increased values of Mx (> 0.4 in 86% of volunteers) and Sx (> 0.2 in 79% of volunteers). Overall, there was a reasonably good correlation of both Mx and Sx with RoR (R2 = 0.65 and 0.58, respectively). IMPLICATIONS: Indices derived from the correlation between spontaneous fluctuations of blood flow velocity wave form and arterial blood pressure may be used for the noninvasive continuous monitoring of cerebrovascular reactivity.

Adult↗
PubMed1999

The "swashbuckler": a modified anterior approach for fractures of the distal femur.

A modified anterior approach to the distal femur is presented. The approach allows surgical exposure of the entire articular surface of the distal femur. The quadriceps muscle bellies are spared during the approach. The skin incision used will not interfere with subsequent total knee arthroplasty, if posttraumatic arthritis develops and arthroplasty is necessary.

Femoral Fractures↗
PubMed1999

Distribution of tetracycline resistance genes and transposons among phylloplane bacteria in Michigan apple orchards.

The extent and nature of tetracycline resistance in bacterial populations of two apple orchards with no or a limited history of oxytetracycline usage were assessed. Tetracycline-resistant (Tc(r)) bacteria were mostly gram negative and represented from 0 to 47% of the total bacterial population on blossoms and leaves (versus 26 to 84% for streptomycin-resistant bacteria). A total of 87 isolates were screened for the presence of specific Tc(r) determinants. Tc(r) was determined to be due to the presence of Tet B in Pantoea agglomerans and other members of the family Enterobacteriacae and Tet A, Tet C, or Tet G in most Pseudomonas isolates. The cause of Tc(r) was not identified in 16% of the isolates studied. The Tc(r) genes were almost always found on large plasmids which also carried the streptomycin resistance transposon Tn5393. Transposable elements with Tc(r) determinants were detected by entrapment following introduction into Escherichia coli. Tet B was found within Tn10. Two of eighteen Tet B-containing isolates had an insertion sequence within Tn10; one had IS911 located within IS10-R and one had Tn1000 located upstream of Tet B. Tet A was found within a novel variant of Tn1721, named Tn1720, which lacks the left-end orfI of Tn1721. Tet C was located within a 19-kb transposon, Tn1404, with transposition genes similar to those of Tn501, streptomycin (aadA2) and sulfonamide (sulI) resistance genes within an integron, Tet C flanked by direct repeats of IS26, and four open reading frames, one of which may encode a sulfate permease. Two variants of Tet G with 92% sequence identity were detected.

Base Sequence↗
PubMed1999

ABC medium, a new chromogenic agar for selective isolation of Salmonella spp.

We describe a new chromogenic agar medium, ABC medium (alphabeta-chromogenic medium), which includes two substrates, 3, 4-cyclohexenoesculetin-beta-D-galactoside and 5-bromo-4-chloro-3-indolyl-alpha-D-galactopyranoside, to facilitate the selective isolation of Salmonella spp. This medium exploits the fact that Salmonella spp. may be distinguished from other members of the family Enterobacteriaceae by the presence of alpha-galactosidase activity in the absence of beta-galactosidase activity. A total of 1, 022 strains of Salmonella spp. and 300 other gram-negative strains were inoculated onto this medium. Of these, 1,019 (99.7%) strains of Salmonella spp. produced a characteristic green colony, whereas only 1 strain (0.33%) of non-Salmonella produced a green colony. A total of 283 stool samples were cultured onto desoxycholate citrate (DC) agar and ABC medium by direct inoculation and after selective enrichment in selenite broth. Overall, the sensitivity and specificity were superior for ABC medium (100 and 90.5%, respectively) than for DC agar (88 and 26.9%, respectively). We conclude that ABC medium offers a high degree of specificity for the detection of Salmonella spp. in stool samples.

Agar↗
PubMed1999

Age of onset in Huntington disease: sex specific influence of apolipoprotein E genotype and normal CAG repeat length.

Age of onset (AO) of Huntington disease (HD) is known to be correlated with the length of an expanded CAG repeat in the HD gene. Apolipoprotein E (APOE) genotype, in turn, is known to influence AO in Alzheimer disease, rendering the APOE gene a likely candidate to affect AO in other neurological diseases too. We therefore determined APOE genotype and normal CAG repeat length in the HD gene for 138 HD patients who were previously analysed with respect to CAG repeat length. Genotyping for APOE was performed blind to clinical information. In addition to highlighting the effect of the normal repeat length upon AO in maternally inherited HD and in male patients, we show that the APOE epsilon2epsilon3 genotype is associated with significantly earlier AO in males than in females. Such a sex difference in AO was not apparent for any of the other APOE genotypes. Our findings suggest that subtle differences in the course of the neurodegeneration in HD may allow interacting genes to exert gender specific effects upon AO.

Age of Onset↗