Helicobacter pylori: a human pathogen.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Biomedical subjects
A Harris
Publications and source records attributed to A Harris.
cAMP-activated chloride channels in a CFTR-transfected pancreatic adenocarcinoma-derived cell line, pANS6.
Pancreatic adenocarcinoma cell lines rarely express the CFTR gene, despite the high levels of CFTR protein that are present in primary pancreatic duct cells. We have attempted to generate a non-CF pancreatic adenocarcinoma cell line that stably produces high levels of CFTR mRNA and protein by transfecting a vector containing the CFTR cDNA, driven by a strong mammalian promoter, into the poorly differentiated pancreatic adenocarcinoma cell line, Panc-1. The pANS6 pancreatic duct cell line expresses substantial levels of CFTR mRNA, but little CFTR protein. Despite this we were able to detect low conductance chloride channels in 40% of patches, stimulated with cAMP, that have similar biophysical properties to CFTR.
Adenocarcinoma↗
Characterization of DNASE I hypersensitive sites in the 120kb 5' to the CFTR gene.
The chromatin structure of 120kb of genomic DNA 5' to the CFTR gene has been analysed in a number of CFTR expressing and non-expressing cell types, including primary genital duct epithelial cells. Novel DNAse I hypersensitive sites have been observed at -79.5kb and -20.5kb 5' to the ATG translation start codon of the CFTR coding sequence. Neither of these sites appears to show strong correlation with CFTR expression in the cell types investigated, hence they are unlikely to reflect the sites of binding of the major CFTR tissue specific regulator(s). However, they may still play an important part in the complex series of events involved in the regulation of CFTR transcription.
Base Sequence↗
Down-regulation of CFTR expression in an HT29-derived cell line by stable antisense RNA production.
In order to examine the interactions of the cAMP activated CFTR chloride ion channel with other chloride ion channels present in epithelial cells we have generated a model based on antisense mRNA down regulation of CFTR expression. The HT29-derived epithelial cell line CJC4-1 has integrated a plasmid that is constitutively expressing CFTR exons 1-6 in the antisense orientation, from the MoMULV LTR. This cell line shows a reduction in cAMP-activated chloride efflux, as measured by iodide efflux assay, in comparison to the parental HT29 cell line and a sense transfected control.
Cell Line↗
Hitting H pylori for four.
Explore the source record for details and available documents.
Anti-Ulcer Agents↗
Molecular analysis of the ovine cystic fibrosis transmembrane conductance regulator gene.
There is a need for a large-animal model to investigate the etiology and biology of cystic fibrosis (CF) lung disease and to study potential therapies. The development and electrophysiology of the sheep airway have been shown to exhibit close functional parallels with the human airway, particularly with respect to the respiratory epithelium. We have cloned and sequenced the ovine cystic fibrosis transmembrane conductance regulator (CFTR) cDNA. It shows a high degree of conservation at the DNA coding and predicted polypeptide levels with human CFTR: at the nucleic acid level there is a 90% conservation (compared with 80% between human and mouse CFTR cDNA); at the polypeptide level, the degree of similarity is 95% (compared with 88% between human and mouse). Northern blot analysis and reverse transcription-PCR have shown that the patterns of expression of the ovine CFTR gene are very similar to those seen in humans. Further, the developmental expression of CFTR in the sheep is equivalent to that observed in humans. Thus, overall a CF sheep should show lung pathology similar to that of humans with CF.
Amino Acid Sequence↗
The relationship of macular microcirculation to visual acuity in diabetic patients.
OBJECTIVE: To assess the perifoveal microcirculation in diabetic maculopathy without clinically significant macular edema and its relationship to visual acuity. DESIGN: Prospective analysis. SETTING: A teaching hospital. PATIENTS: Fifteen patients with impaired visual acuity of 20/50 or worse, a diabetic control population with unaffected visual acuity (matched age, gender, retinopathy stage), and 52 healthy controls were enrolled. INTERVENTIONS: Study consisted of video-fluorescein angiography with image analyses and hemoglobin A1c measurements. MAIN OUTCOME MEASURES: Macular capillary blood velocity, capillary density (perifoveal intercapillary area), and foveal avascular zone. RESULTS: The capillary blood velocity was significantly reduced in both diabetic groups (P < .001) when compared with healthy controls, but did not differ significantly among the two diabetic groups. The perifoveal intercapillary area and foveal avascular zone were significantly enlarged in both diabetic groups compared with healthy controls (P < .001). The foveal avascular zone (P < .01) and perifoveal intercapillary area (P = .01) were further enlarged in the diabetics with reduced visual acuity. The visual acuity correlated significantly with foveal avascular zone (R2 = .51) and perifoveal intercapillary area (R2 = .24), indicating an association between enlargement and declined visual acuity. CONCLUSIONS: Capillary blood velocity remained unchanged regardless of presence of visual impairment, whereas foveal avascular zone and perifoveal intercapillary area indicated ischemia. This may help in defining a critical hypoxic threshold for visual loss and identifying the presence of an ischemic diabetic maculopathy.
Adult↗
Detection of 12 novel mutations in the collagenous domain of the COL4A5 gene in Alport syndrome patients.
A population of 35 Alport syndrome patients, defined by strict diagnostic criteria, was screened for mutations in 23 exons of the COL4A5 gene by SSCP analysis. Mobility shifts were observed in 12 out of 35 patients and were shown to represent genuine mutations. 9 of these were glycine substitutions in the collagenous domain (in exons 20, 25, 26, 29, 31, and 41), 2 were small deletions resulting in frameshifts (in exons 21 and 31), and one was a splice site mutation (in exon 12).
Base Sequence↗
Identification of seven novel mutations associated with metachromatic leukodystrophy.
Explore the source record for details and available documents.
Base Sequence↗
Cytokine regulation of angiogenesis in breast cancer: the role of tumor-associated macrophages.
Studies over the past 20 years have established that the development of new capillaries from an existing vascular network (a process called angiogenesis) is an essential component of tumor growth. Malignant tumors do not grow beyond 2-3 mm3 in size unless they stimulate the formation of new blood vessels and thus provide a route for the increased inflow of nutrients and oxygen and outflow of waste products. Tumor angiogenesis also provides an essential exit route for metastasizing tumor cells from the tumor to the bloodstream. Indeed, extensive neovascularization is a poor prognostic factor in several forms of human cancer. Angiogenesis is a complex, multistep process driven by many local signals within the tumor. This involves the degradation of the extracellular matrix around a local venule after the release of collagenases and proteases, the proliferation and migration of capillary endothelial cells, and their differentiation into functioning capillaries. Cytokines produced by various cell types present within the microenvironment of solid tumors form a complex, dynamic network in which they have multiple effects on tumor progression. Herein we review our work on the presence, and possible regulatory influence on tumor angiogenesis, of a number of these cytokines within invasive breast carcinomas. We have combined immunocytochemistry with a single cell cytokine release assay called the reverse hemolytic plaque assay to investigate the cellular sources of the key angiogenic cytokines, vascular endothelial growth factor, basic fibroblast growth factor, and tumor necrosis factor-alpha. Tumor-associated macrophages in the stromal compartment of these tumors and/or malignant epithelial cells were seen to be a major producer cell for these cytokines, whereas tumor necrosis factor-alpha receptors were expressed by leukocytes, malignant cells, and endothelial cells in tumor blood vessels.
Antigens, CD↗
Macular capillary particle velocities: a blue field and scanning laser comparison.
BACKGROUND: Two different techniques are available for measurement of macular capillary particle velocities. The psychophysical blue field simulation technique gives data on macular leukocyte flow velocities, while the scanning laser technique provides information on capillary blood velocities of hypofluorescent segments in the macular network. Published velocity data differ considerably between the two methods. The current study was undertaken to compare the two measuring techniques in a group of healthy volunteers. METHODS: Thirty-two healthy subjects (12 man, 20 women, mean age 27 years) participated in this study. All subjects underwent entoptic leukocyte visualization by means of blue field simulation followed by fluorescein angiography using scanning laser ophthalmoscopy. RESULTS: The capillary blood velocities measured using the scanning laser technique were significantly higher (P < 0.01) than the flow velocities estimated with the blue field simulation technique (2.68 +/- 0.3 mm/s vs 0.89 +/- 0.2 mm/s). No significant correlation between the flow velocities was found (r = -0.22). CONCLUSION: The differences may be related to different measuring locations and/or measurements of different phenomena. The blue field technique estimates average leukocyte flow in the macular network, whereas the scanning laser technique quantifies the velocity of erythrocyte aggregates in the capillary lumen of the para- and perifoveal network. A combination of both techniques may be helpful in interpreting physiological responsiveness and altered velocity pattern in diseased eyes.
Adult↗
Effect of octreotide and insulin on manifest renal and glomerular hypertrophy and urinary albumin excretion in long-term experimental diabetes in rats.
Treatment of diabetic rats with octreotide can inhibit early diabetic renal hypertrophy. Octreotide administration for 6 months from the day of diabetes induction inhibits renal hypertrophy and diminishes increase in urinary albumin excretion. To investigate the effect of octreotide on manifest diabetic renal changes, octreotide treatment was given for 3 weeks after an untreated diabetic period of 3 or 6 months. In addition, following 6 months of diabetes, a group of diabetic rats was treated with insulin for 3 weeks. Renal and glomerular hypertrophy, and increased urinary albumin excretion were observed in diabetic rats compared to non-diabetic control rats from 3 months and throughout the study period. Octreotide treatment did not affect body weight, food intake, blood glucose or serum fructosamine levels. We observed no effect of octreotide treatment on renal and glomerular hypertrophy or urinary albumin excretion compared to placebo-treated diabetic rats. Insulin treatment for 3 weeks after 6 months of untreated diabetes normalized blood glucose and serum fructosamine levels, and furthermore renal hypertrophy was significantly diminished compared to the placebo-treated diabetic rats. However, insulin treatment had no effect on glomerular hypertrophy or urinary albumin excretion. In conclusion, octreotide treatment for 3 weeks following an untreated diabetic period of 3 or 6 months is unable to reduce the increased renal and glomerular volume or urinary albumin excretion. However, insulin treatment for 3 weeks with induction of euglycaemia diminishes the renal hypertrophy but has no effect on glomerular volume or urinary albumin excretion.
Albuminuria↗
Processing of the Plasmodium chabaudi chabaudi AS merozoite surface protein 1 in vivo and in vitro.
Processing of the Plasmodium merozoite surface protein 1 (MSP-1) has been described for parasites maintained under in vitro conditions. We have now demonstrated, using CBA/Ca mice infected with Plasmodium chabaudi chabaudi AS, that MSP-1 processing also occurs in vivo. The major proteolytic cleavage sites and a processing scheme were deduced from N-terminal amino-acid sequences of the MSP-1 breakdown products. Comparison of MSP-1 processing in P. falciparum and P.c. chabaudi indicates a degree of conservation and in two cases the position of protease cleavage appears identical. Significant amounts of MSP-1 polypeptides are found in plasma during schizogony. Various aspects of MSP-1 processing including immunological and physiological reactions in the host during the critical period of schizogony can now be examined in vivo.
Amino Acid Sequence↗
Retrobulbar arterial hemodynamic effects of betaxolol and timolol in normal-tension glaucoma.
PURPOSE: beta-Adrenergic blocking drugs lower intraocular pressure. The question of whether these drugs also alter, either directly or indirectly, orbital hemodynamics is potentially of great importance for patients with normal-tension glaucoma who may have some degree of reversible vasospasm. METHODS: We compared the effect of selective (betaxolol) and nonselective (timolol) beta-adrenergic blocking drugs on flow velocities (as determined by color Doppler imaging) in orbital vessels in 13 patients with normal-tension glaucoma (mean age, 62 +/- 3 years; mean intraocular pressure, 15 +/- 2 mm Hg). A one-month drug treatment double-masked crossover design, with a three-week washout before each drug, was used. RESULTS: Neither drug changed peak systolic velocity in any of the four vessels studied (ophthalmic, nasal and temporal posterior ciliary, and central retinal arteries). Additionally, timolol did not alter end-diastolic velocity or resistance index (defined as [peak systolic velocity minus end-diastolic velocity] divided by peak systolic velocity) in any of the vessels measured. In contrast, betaxolol tended to increase end-diastolic velocity and to decrease resistance index: the four-vessel average end-diastolic velocity increased 30% (P = .08), and the four-vessel average resistance index decreased significantly (P = .04). These reductions in resistance index occurred despite that betaxolol, in contrast to timolol, did not significantly decrease intraocular pressure. CONCLUSIONS: These results suggest that, in patients with normal-tension glaucoma, selective beta-adrenergic blockade (betaxolol) may have ocular vasorelaxant effects independent of any influence on intraocular pressure, whereas nonselective blockade (timolol) lowers intraocular pressure without apparently altering orbital hemodynamics.
Arteries↗
Mapping the homotypic binding sites in CD31 and the role of CD31 adhesion in the formation of interendothelial cell contacts.
CD31 is a member of the immunoglobulin superfamily consisting of six Ig-related domains. It is constitutively expressed by platelets, monocytes, and some lymphocytes, but at tenfold higher levels on vascular endothelial cells. CD31 has both homotypic and heterotypic adhesive properties. We have mapped the homotypic binding sites using a deletion series of CD31-Fc chimeras and a panel of anti-CD31 monoclonal antibodies. An extensive surface of CD31 is involved in homotypic binding with domains 2 and 3 and domains 5 and 6 playing key roles. A model consistent with the experimental data is that CD31 on one cell binds to CD31 on an apposing cell in an antiparallel interdigitating mode requiring full alignment of the six domains of each molecule. In addition to establishing intercellular homotypic contacts. CD31 binding leads to augmented adhesion via beta 1 integrins. The positive cooperation between CD31 and beta 1 integrins can occur in heterologous primate cells (COS cells). The interaction is specific to both CD31 and beta 1 integrins. Neither intercellular adhesion molecule-1 (ICAM-1)/leukocyte function-associated antigen-1 (LCAM-1) nor neural cell adhesion molecule (NCAM)/NCAM adhesion leads to recruitment of beta 1 integrin adhesion pathways. Establishment of CD31 contacts have effects on the growth and morphology of endothelial cells. CD31(D1-D6)Fc inhibits the growth of endothelial cells in culture. In addition, papain fragments of anti-CD31 antibodies (Fab fragments) disrupt interendothelial contact formation and monolayer integrity when intercellular contacts are being formed. The same reagents are without effect once these contacts have been established, suggesting that CD31-CD31 interactions are critically important only in the initial phases of intercellular adhesion.
Antigens, Differentiation, Myelomonocytic↗
The use of anti-depressants and benzodiazepines in the perpetrators and victims of accidents.
The objective of this study was to determine whether there is a greater incidence of psychotropic drugs in the blood of those 'responsible' for an accident compared with those not 'responsible' for an accident. Blood samples were taken from people involved in accidents presenting at the accident and emergency departments of two teaching hospitals over a five-month period and analysed for the presence of alcohol, tricyclic anti-depressants (TCAs) and benzodiazepines (BZs). Details of the accident were used to produce a test group (accidents where a drug may have contributed) and a control group (accidents where the presence of a drug could not have been a factor). In total, 229 samples were collected. The only criterion for inclusion in the study was that the accident was of sufficient severity to merit the routine taking of a blood sample, in which case an additional amount was taken for the purposes of this investigation. In all, 63 samples (27.5%) were positive for at least one of alcohol, TCA or BZ. Of the accidents represented by these samples, 48 could have been caused by the presence of the drug (responsible group) and 15 could not (not responsible group). There was a significantly greater representation of TCAs and BZs in the blood taken from the responsible group compared with the not responsible group (P < 0.0045).
Accidents↗
Dermatomyositis presenting in pregnancy.
We report the onset of dermatomyositis in a woman pregnant 38-weeks who subsequently delivered a healthy infant. The disease improved rapidly following delivery. The association of dermatomyositis with pregnancy is unusual, and fetal outcome may be adversely affected.
Adult↗
Vasculitis in a fixed drug eruption due to paracetamol.
A 48-year-old man presented with a history of recurrent erythematous lesions on the trunk and limbs. Examination suggested a fixed drug eruption and this was confirmed by oral challenge with paracetamol. The histology was unusual as it showed a leucocytoclastic vasculitis. Patients may have difficulty avoiding the offending drug because many drugs bought over the counter have similar names but different constituents. In addition, it may be difficult to persuade the patient that a specific drug is responsible for their skin problem.
Acetaminophen↗