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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 199 records · Page 11Linked to original sources
PubMed1998

Developmental expression of mucin genes in the human gastrointestinal system.

BACKGROUND AND AIMS: Mucin glycoproteins play a key role in the normal function of the epithelium lining the gastrointestinal tract. The expression of mucin genes, MUC 3, 4, 5AC, 5B, 6, 7, and 8 in human fetal tissues was examined to establish the localisation and age of onset of expression of each mucin gene during human development. METHODS: Mucin gene expression was assayed by mRNA in situ hybridisation. RESULTS: Expression of MUC3 was detected in the small intestine and colon from 13 weeks gestation onwards and at low levels in the main pancreatic duct at 13 weeks only. MUC4 expression was seen at a low level in the colonic epithelium from 13 weeks of gestation but not elsewhere in the gastrointestinal tract. MUC5AC mRNA was detected in the colon at 17 weeks and at high levels in the stomach at 23 weeks. MUC6 transcripts were evident in the pancreatic ducts from 13 weeks of gestation and at high levels in the stomach at 23 weeks. MUC5B, MUC7, and MUC8 transcripts were not detected. CONCLUSIONS: Mucin genes are expressed from the early mid-trimester of gestation in the developing human fetal gastrointestinal tract.

Colon↗
PubMed1998

Development of a multiplex ARMS test for mutations in the HFE gene associated with hereditary haemochromatosis.

Genetic testing for hereditary haemochromatosis is likely to be a significant workload for diagnostic laboratories. The C282Y and H63D mutations in the HFE gene associated with hereditary haemochromatosis have previously been detected using a number of methods including alterations in the restriction digest pattern of polymerase chain reaction (PCR) amplified products. An amplification refractory mutation system (ARMS) has been developed that will simultaneously detect both hereditary haemochromatosis mutations. Comparison of the results obtained from the analysis of 46 samples referred for hereditary haemochromatosis testing showed no discrepancies between ARMS and restriction enzyme digestion. Furthermore, consistent results were obtained by ARMS from both blood and buccal mouthwash samples. The ARMS test is quicker and less expensive in terms of consumables and scientist time than restriction enzyme analysis, and is therefore suited to the routine diagnostic analysis of hereditary haemochromatosis.

Cheek↗
PubMed1998

Reproducibility of optic disk topographic measurements with the Topcon ImageNet and the Heidelberg Retina Tomograph.

OBJECTIVE: To compare the reproducibility of optic disk measurements provided by an image analyzer and a scanning laser tomograph. METHODS: Ten images of the same eye of 10 normal volunteers were taken with the Heidelberg Retina Tomograph and with the Topcon ImageNet. Intraclass correlation coefficient (ICC) and coefficient of variation (CV) were used to evaluate the reproducibility of the measurements. RESULTS: Eleven parameters were analyzed with the Topcon ImageNet. Six parameters (55%) had ICC greater than 90%. Four parameters (36%) had CV less than 10%. Twelve parameters were evaluated with the Heidelberg Retina Tomograph. Nine parameters (75%) had ICC over 90%. Nine parameters (75%) had CV less than 10%. CONCLUSION: Both systems provided reproducible data. The optic disk parameters provided by the Heidelberg Retina Tomograph had a better reproducibility than those obtained from the Topcon ImageNet.

Adult↗
PubMed1998

Antibacterial peptides in bronchoalveolar lavage fluid.

Defensins and other antimicrobial peptides act in the innate host defense of epithelial surfaces. Human beta defensin 1 (hBD-1) has recently been shown to be expressed in airway epithelial cells and so has been implicated as a primary component of antibacterial activity in human lung. We attempted to purify these molecules from bronchoalveolar lavage fluid (BALF). Extraction of BALF on SepPak C-18 cartridges, followed by continuous acid-urea polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography yielded one fraction with antibacterial activity associated with factors of < 6.5 kD. N-terminal amino acid sequencing identified these peptides as human neutrophil defensins (HD) 1 through 3. No hBD-1 was detected. Together with lysozyme, it appears that HD-1 through -3 are the most prominent antimicrobial factors in BALF. The contribution of epithelial defensins such as hBD-1 to antibacterial defense of human airway in vivo remains to be elucidated.

Anti-Bacterial Agents↗
PubMed1998

Case report of a Thai male cystic fibrosis patinet with the 1898+ 1G-->T splicing mutation in the CFTR gene: a review of East Asian cases. Mutations in brief no. 196. Online.

Cystic fibrosis (CF) is the most common fatal autosomal recessive multisystem disorder, which occurs mainly in European-derived populations. The incidence of CF varies between 1 in 2000 to 3000 live-births in various ethnic groups. The disease is rare in East Asians. Here we report a 9 year old Thai male patient, who was diagnosed to have CF based on recurrent pneumonia, a slow weight gain, pancreatic insufficiency and repeatedly elevated sweat chloride levels by two different methods. A comprehensive genetic analysis showed the splicing mutation, 1898+ 1G-->T, which was apparently of maternal origin. Literature search found 39 documented cases of CF patients in East Asians. CFTR (MIM# 602421) genotyping was performed in 14 patients including our patient and in 9 of them a CF allele was identified. The findings seem to indicate that the splicing mutations, 1898+ 1G-->T and 1898+ 5G-->T are more common in East Asian CF patients.

Alternative Splicing↗
PubMed1997

Oligosaccharides expressed on MUC1 produced by pancreatic and colon tumor cell lines.

MUC1 is expressed at the apical surface of ductal epithelia of tissues, including breast, pancreas, airway, and the gastrointestinal tract, where its functions include lubrication and protection of the epithelia. In addition, roles for MUC1 have been suggested in both adhesive and antiadhesive properties of tumor cells, and extensive O-glycosylation of the MUC1 tandem repeat domain may contribute to these functions. Little information is available on the specific O-glycosylation of MUC1. One problem in identifying different MUC1 glycoforms has been that monoclonal antibodies raised against the MUC1 core protein recognize epitopes in the tandem repeat domain, which is often glycosylated to an extent that obscures these epitopes. We developed an epitope-tagged form of MUC1 that allowed the detection of multiple MUC1 glycoforms and established the presence of a number of important blood group and tumor-associated carbohydrate antigens on MUC1 expressed by two pancreatic tumor cell lines (Panc-1 and S2-013) and two colon tumor cell lines (Caco-2 and HT-29). Antigens detected include sialyl-Lewisa, sialyl-Lewisc, sialyl-Lewisx, and sialyl-Tn.

Antibodies↗
PubMed1997

Fibronectin-fragment-induced cartilage chondrolysis is associated with release of catabolic cytokines.

Fibronectin fragments have both catabolic and anabolic activities toward articular cartilage explants in vitro. Whereas a 1 nM concentration of an N-terminal 29 kDa fibronectin fragment (Fn-f) increases the proteoglycan (PG) content of cartilage without induction of matrix metalloproteinases (MMPs), 0.1-1 microM Fn-f temporarily suppresses PG synthesis and enhances MMP release. The higher concentrations cause an initially rapid PG depletion during the first week of culture, followed by much slower PG loss and gradually increasing rates of PG synthesis. To test for the involvement of mediators, human articular cartilage was cultured with Fn-f, and conditioned media were assayed for selected cytokines and factors. With 1 nM Fn-f, the release of the anabolic factors, insulin growth factor-I and transforming growth factor beta1, from cultured cartilage was enhanced by 50-100% during the entire 28-day culture period and this was associated with both supernormal rates of PG synthesis and PG content. However, the higher concentrations of Fn-f additionally enhanced release, by at least 10-fold, of the cytokines, tumour necrosis factor alpha, interleukin-1alpha, interleukin-1beta and interleukin-6 while causing depletion of cartilage PG. Release of tumour necrosis factor alpha, interleukin 1beta and interleukin 1alpha peaked at days 2, 3 and 9 during or slightly after the period of maximal PG depletion and decreased to control levels by days 7, 7 and 21 respectively, whereas release of interleukin 6 was enhanced throughout the culture period. Neutralizing antibodies to the catabolic cytokines reduced Fn-f-mediated MMP-3 release and suppression of PG synthesis. The temporal aspects of this interplay between catabolic and anabolic factors are consistent with the kinetics of Fn-f-mediated cartilage damage and attempted repair and may be relevant to cartilage damage and repair in vivo.

Age Factors↗
PubMed1997

Identification and isolation of CD1a positive putative tumour infiltrating dendritic cells in human breast cancer.

Identification of dendritic cells (DC) in human tissues has been technically problematic due to the lack of truly specific immunohistochemical markers for DC's. Human dendritic cells express CD1a glycoprotein at certain points in their life cycle. CD1a positive cells are present in many human tumours and have been associated with improved survival. However, little information exists concerning the separation of DC from human tumours. The current study reports that human breast carcinomas have low densities of CD1a positive cells with dendritic morphology, and details are shown of a technique for successful separation of these cells from tumour tissues.

Antigen Presentation↗
PubMed1997

Hemodynamic and visual function effects of oral nifedipine in patients with normal-tension glaucoma.

PURPOSE: To investigate ocular hemodynamic and visual function changes in patients with normal-tension glaucoma after treatment with a calcium channel blocker (nifedipine). METHODS: In 21 patients with normal-tension glaucoma, color Doppler imaging of the ophthalmic, central retinal, and short posterior ciliary arteries was carried out after a 4-week washout of prior drug treatment and again after 6 months of treatment with nifedipine (30 mg per day). Visual field sensitivity, spatial contrast sensitivity, and intraocular pressure were also recorded. RESULTS: Three subjects experienced intolerable side effects from the drug and were removed from the study. In two other patients, visual function was substantially reduced after 4 months of treatment; nifedipine was discontinued. In the remaining 16 subjects, mean intraocular pressure, retrobulbar hemodynamics, visual field mean sensitivity, and contrast sensitivity at 3, 12, and 18 cycles per degree (cpd), respectively, were unchanged after nifedipine treatment. Contrast sensitivity at 6 cpd, however, improved after drug treatment (P = .004). Individuals with the greatest improvements in contrast sensitivity at 6 cpd showed the largest increases in ophthalmic arterial peak systolic velocity (r = .57; P = .02) and end-diastolic velocity (r = .65; P = .001). CONCLUSION: Nifedipine fails to provide uniform visual function or retrobulbar hemodynamic responses in patients with normal-tension glaucoma. Those patients who do show improved visual function also show improved indices of retrobulbar perfusion.

Administration, Oral↗
PubMed1997

Dorzolamide hydrochloride and visual function in normal eyes.

PURPOSE: To determine by a pilot study whether standard treatment with the topical carbonic anhydrase inhibitor dorzolamide hydrochloride influences visual function under normal breathing conditions, during carbon dioxide inhalation, or during hyperventilation, and to establish criteria for future larger-scale studies. METHODS: We enrolled 12 normal subjects into this randomized double-masked placebo-controlled crossover study. Each subject was treated with either dorzolamide 2% or placebo, three times daily, for 4 days. After a 2-week washout period, the alternative topical agent was used under identical testing conditions. On day 2 of each treatment phase, contrast sensitivities to sinusoidal gratings of 1 and 4 cycles per degree (cpd) were assessed. On day 4, mean deviation values from full-threshold 10-2 visual fields were obtained. Three sets of each visual function test were obtained before each treatment phase, and in sequence on each testing day, during normal breathing (baseline), inhalation of carbon dioxide-enriched air, and hyperventilation while intraocular pressure was monitored. RESULTS: Contrast sensitivity at 4 cpd decreased significantly (P < .01) during carbon dioxide supplementation with placebo but showed no significant change with dorzolamide. The decrease in contrast sensitivity accompanying hyperventilation was attenuated (by nearly 50% at 1 cpd) during dorzolamide treatment. Dorzolamide treatment was associated with higher perimetry mean deviation values under each treatment condition and was statistically significant (P < .05) at baseline. CONCLUSIONS: Dorzolamide appears to enhance contrast sensitivity in normal subjects during physiologic hypercapnia and hypocapnia at 4 and 1 cpd, respectively. Also, under normal breathing conditions, dorzolamide therapy increases perimetric light sensitivity.

Adult↗
PubMed1997

Stripping of failing haemodialysis catheters using the Ampltaz gooseneck snare.

The development of a fibrin sheath at the tip of a long-term haemodialysis catheter may lead to deteriorating blood flow rates, resulting in inadequate haemodialysis. Restoration of functional patency has been described using the technique of percutaneous fibrin sheath stripping (PFSS) using a wire snare device. Our purpose was to assess this technique within an established renal vascular access service. All catheters referred for the assessment of low blood flow rates on dialysis were considered for the procedure. Initial fluoroscopic assessment of the catheter was followed by stripping of the tip of the catheter using a gooseneck snare. Seventeen of 22 well-positioned catheters undergoing a single PFSS attempt were restored to function with a median prolongation of patency of 4.25 months. Two catheters underwent a second PFSS procedure providing additional patency. Nineteen of a total of 24 (79%) PFSS procedures successfully restored catheter function. Seven catheters with poorly positioned tips or a kink were not restored to functional patency using PFSS. Two patients developed a puncture site haematoma. No patient developed symptoms of pulmonary emoblism. In conclusion, PFSS restored function in 79% of attempts in well positioned catheters. The method is technically straightforward, with a low complication rate and has become a routine part of the renal vascular access service.

Catheterization, Central Venous↗
PubMed1997

The cystic fibrosis transmembrane conductance regulator as a marker of human pancreatic duct development.

BACKGROUND & AIMS: The cystic fibrosis transmembrane conductance regulator (CFTR) protein is a small conductance adenosine 3',5'-cyclic monophosphate (cAMP)-activated chloride ion channel found in the apical membranes of epithelia within the pancreas, airway, intestine, bile duct, sweat gland, and male genital ducts. Pancreatic insufficiency is a feature of about 85% of patients with cystic fibrosis and is believed to be caused by pancreatic autolysis after pancreatic duct obstruction. The aim of this study was to investigate the expression of CFTR in the pancreas from early development to postnatal life to establish whether the CFTR plays a key role in development of the pancreatic duct epithelium. METHODS: Expression of CFTR from the start of the mid-trimester of human development through term to adult life by messenger RNA (mRNA) in situ hybridization was examined. RESULTS: CFTR mRNA is detected throughout the pancreatic duct epithelium and its pattern of expression follows the differentiation of the duct system. CONCLUSIONS: CFTR is a valuable marker of human pancreatic duct cell development and differentiation.

Aging↗
PubMed1997

Color Doppler imaging of ophthalmic artery blood flow velocity: a study of repeatability and agreement.

PURPOSE: Color Doppler imaging (CDI) is a relatively new technique that allows quantification of blood flow velocity in orbital and ocular vasculature. Despite the numerous clinical studies that have used CDI, repeatability of this technique and agreement between observers have not been documented. METHODS: The authors performed a prospective investigation of the repeatability and agreement between observers on ophthalmic artery blood flow velocity measurements in 35 patients (35 eyes). RESULTS: Results on the estimated error of measurement (variability between repeated readings on the same subject) indicate good repeatability of the measurements; in fact, the measurement variances were only 5.6% for the peak systolic velocity, 11.4% for the end diastolic velocity, and 6.2% for the mean envelope velocity. The statistical analysis of repeatability showed a very narrow 95% confidence interval for both observers. The measurement of agreement between the two observers demonstrated the existence of a good concordance of the measurements taken by each observer on each subject. CONCLUSIONS: Results suggest that CDI is a reliable tool for quantitative assessment of ophthalmic artery blood flow velocity.

Aged↗