Search PubMed⌕ Search

Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 145 records · Page 8Linked to original sources
PubMed1999

The parahippocampal place area: recognition, navigation, or encoding?

The parahippocampal place area (PPA) has been demonstrated to respond more strongly in fMRI to scenes depicting places than to other kinds of visual stimuli. Here, we test several hypotheses about the function of the PPA. We find that PPA activity (1) is not affected by the subjects' familiarity with the place depicted, (2) does not increase when subjects experience a sense of motion through the scene, and (3) is greater when viewing novel versus repeated scenes but not novel versus repeated faces. Thus, we find no evidence that the PPA is involved in matching perceptual information to stored representations in memory, in planning routes, or in monitoring locomotion through the local or distal environment but some evidence that it is involved in encoding new perceptual information about the appearance and layout of scenes.

Adolescent↗
PubMed1999

Color doppler imaging of the central retinal artery in premature infants undergoing examination for retinopathy of prematurity.

PURPOSE: Recent attempts have been made to quantify blood flow velocity in the central retinal artery (CRA) of adults using color Doppler imaging (CDI). Although retinal vascular abnormalities are the hallmark of severe retinopathy of prematurity (ROP), normal values have not been established for CRA blood flow velocity in premature infants. METHODS: CDI of the CRA was successfully performed on 43 eyes in 22 infants (postconceptional ages 32 to 39 weeks) before the infants underwent examination for ROP. Peak systolic velocity (PSV) and end diastolic velocity were recorded from at least 1 eye of each patient. Pourcelot's resistive index was then calculated for each eye studied. RESULTS: Mean PSV for patients with no ROP (n = 6) was 7.2 +/- 1.5 cm/s, whereas those with any degree of ROP excluding plus disease (n = 9) had a mean PSV of 8.9 +/- 1.8 cm/s. Of the patients with ROP and plus disease (n = 7), the mean PSV was 7.0 +/- 1.6 cm/s. There were no statistically significant differences among these 3 groups (P= .08). CONCLUSIONS: CDI can be successfully performed on preterm infants and yields values lower than those previously reported in healthy adult subjects. PSV in the CRA may be higher in subjects with ROP in the absence of plus disease; however, further study is needed to determine whether these differences are significant.

Blood Flow Velocity↗
PubMed1999

Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration.

New technologies have facilitated the study of the ocular circulation. These modalities and analysis techniques facilitate very precise and comprehensive study of retinal, choroidal, and retrobulbar circulations. These techniques include: 1. Vessel caliber assessment; 2. Scanning laser ophthalmoscopic fluorescein angiography and indocyanine green angiography to image and evaluate the retinal circulation and choroidal circulation respectively; 3. Laser Doppler flowmetry and confocal scanning laser Doppler flowmetry to measure blood flow in the optic nerve head and retinal capillary beds; 4. Ocular pulse measurement; and 5. color Doppler imaging to measure blood flow velocities in the central retinal artery, the ciliary arteries and the ophthalmic artery. These technique have greatly enhanced the ability to quantify ocular perfusion defects in many disorders, including glaucoma and age-related macular degeneration, two of the most prevalent causes of blindness in the industrialized world. Recently it has become clear, in animal models of glaucoma, that retinal ganglion cells die via apoptosis. The factors that initiate apoptosis in these cells remain obscure, but ischemia may play a central role. Patients with either primary open-angle glaucoma or normal-tension glaucoma experience various ocular blood flow deficits. With regard to age-related macular degeneration, the etiology remains unknown although some theories include primary retinal pigment epithelial senescence, genetic defects such as those found in the ABCR gene which is also defective in Stargardt's disease and ocular perfusion abnormalities. As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD. Vascular defects have been identified in both nonexudative and exudative AMD patients using new technologies. This paper is a comprehensive update describing modalities available for the measurement of all new ocular blood flow in human and the clinical use.

Animals↗
PubMed1999

Prevalence of cholelithiasis: results of an epidemiologic investigation in Vidauban, southeast France. General Practitioner's Group of Vidauban.

Cholelithiasis leads to 80,000 cholecystectomies being performed every year in France, but its prevalence is still unknown. The aim of this study was to assess the prevalence and risk factors of cholelithiasis in a random population of 1027 women and 727 men over the age of 30 in a small town in the southeast of France. Detailed clinical history, dietary investigation, and gallbladder ultrasound were collected for each subject and assessed by univariate analysis. A regression model was used in the multivariate analysis to detect the relative risk of cholelithiasis. Cholelithiasis was found in 130 individuals (global prevalence 13.9%). The relative risk for lithiasis was higher in women compared to men (1.89). Age (P<0.0001) and body mass index (BMI) >25 (P = 0.013) were also significant risk factors. Neither pregnancy nor oral contraceptive use proved to be risk factors. Typical biliary colic pain was the only symptom significantly associated with cholelithiasis (P<0.0001). These results show that the prevalence of gallstones in France is similar to that in Denmark and Italy.

Adult↗
PubMed1999

X-inactivation and marker studies in three families with incontinentia pigmenti: implications for counselling and gene localisation.

Familial incontinentia pigmenti (IP) is an X-linked dominant disorder with an extremely variable clinical presentation. Ambiguous diagnosis can complicate genetic counselling and attempts to refine the gene location in Xq28. Marked skewing of X-inactivation patterns is a hallmark of IP and provides a means for investigating uncertain cases. We have conducted X-inactivation studies in three families where Xq28 marker studies were at odds with the original clinical assessment. The results indicate that no recombination between the disease locus and Xq28 loci has occurred and suggest that mosaicism is responsible for the discrepancy in one family.

Chromosome Mapping↗
PubMed1999

Human cultured dendritic cells show differential sensitivity to chemotherapy agents as assessed by the MTS assay.

Assessment of the chemosensitivity of dendritic cells (DC) may allow more rational development of combined chemotherapy and immunotherapy protocols. Human monocyte-derived DC generated reproducible results in the MTS (Owen's reagent) assay, which was then used to study DC survival after treatment with four different chemotherapy agents. DC preparations from three different donors were used per drug. DC were sensitive to doxorubicin (concentration range 0.1-50 microM) with variation in sensitivity between donors (IC50 244-1100 nM). The most extreme variation was seen for vinblastine (concentration range 250-0.025 microM with IC50 0.15-17.25 microM). In contrast, there was relative resistance to etoposide (concentration range 0.2-200 microM) and 5-fluorouracil (concentration range 0.7-7700 microM) with no toxicity seen until 50 microM and 770 microM respectively. The function of DC in allogeneic mixed leucocyte reactions closely paralleled results from the MTS assays. The differential sensitivity to chemotherapy agents did not appear to be due to expression of P-glycoprotein. These results suggest that etoposide or 5-fluorouracil is less likely to reduce the immunotherapeutic potential of DC and may be valuable in the design of prodrug activation therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Analysis of a DNase I hypersensitive site located -20.9 kb upstream of the CFTR gene.

The cystic fibrosis transmembrane conductance regulator gene (CFTR) shows a tightly regulated pattern of expression with spatial and temporal control. The regulatory elements achieving this appear to lie outside the basal promoter of the gene. We previously identified DNase I hypersensitive sites (DHSs) at -79.5 kb and -20.5 kb with respect to the CFTR translational start site which may contain important regulatory elements. We have now investigated further the DHS at -20.5 kb to evaluate its potential function in the regulation of CFTR expression. Finer mapping revealed that the DHS lies at -20.9 kb. Deletion of the DHS from a 310-kb yeast artificial chromosome (YAC) containing the human CFTR gene has shown that this site may be responsible for about 60% of wild-type levels of transcription from the YAC transgene when expressed in Caco2 cells. DNase I footprinting showed several regions of protection within the -20.9 kb region with nuclear extracts from Caco2 cells, but not with extracts from lymphoblastoid cells, which do not show the DHS. Matches to several transcription factor-binding sites were found, but supershift analysis with specific antibodies did not identify the transcription factors involved. Two purine/pyrimidine mirror repeat elements within the -20.9-kb DHS were shown not to adopt non-B-DNA conformations. Thus, we provide evidence for a role for the -20.9 kb DHS in the transcriptional regulation of the CFTR gene, although the mechanisms mediating this effect remain unclear.

Amino Acid Motifs↗
PubMed1999

Meta-analysis of antibiotic prophylaxis in endoscopic retrograde cholangiopancreatography (ERCP).

BACKGROUND AND STUDY AIMS: Considerable controversy exists regarding the role of antibiotic prophylaxis prior to endoscopic retrograde cholangiopancreatography (ERCP), in that various studies of antibiotic prophylaxis have reached conflicting conclusions. The aim of this meta-analysis is to synthesize the data in order to determine whether antibiotic prophylaxis reduces the rate of occurrence of bacteremia and/or the rate of sepsis/cholangitis among patients undergoing ERCP. PATIENTS AND METHODS: Clinical trials were selected via Medline and Pubmed using subject words and textwords "ERCP", "antibiotic" and "antibiotic prophylaxis". Summary estimates of the risk ratios for the outcomes of bacteremia and sepsis/cholangitis were calculated. RESULTS: After 49 abstracts had been reviewed, seven randomized placebo-controlled trials of antibiotic prophylaxis prior to ERCP were identified. Upon further review, two studies were excluded because patients received antibiotics before and after the ERCP. Four studies reported on the clinical outcome of bacteremia. Five studies reported on the clinical outcome of sepsis/cholangitis. The summary relative risk of the association between antibiotic prophylaxis and bacteremia was 0.39 (95% CI, 0.12-1.29). For sepsis/cholangitis the summary relative risk was 0.91 (95 % CI, 0.39-2.15). CONCLUSIONS: Antibiotic prophylaxis prior to ERCP may reduce the incidence of bacteremia but this has little clinical relevance. Prophylaxis does not substantially reduce the incidence of sepsis/cholangitis and thus the routine use of antibiotic prophylaxis cannot be recommended.

Antibiotic Prophylaxis↗
PubMed1999

Epidemiology and clinical outcomes of patients with multiresistant Pseudomonas aeruginosa.

We conducted a case-series study of multiresistant Pseudomonas aeruginosa in patients who did not have cystic fibrosis. Patient characteristics, antibiotic exposures, time course of emergence of resistance, and clinical outcomes were examined. Twenty-two patients were identified from whom P. aeruginosa resistant to ciprofloxacin, imipenem, ceftazidime, and piperacillin was isolated. Nineteen (86%) had clinical infection. Patients received prolonged courses of antipseudomonal antibiotics before isolation of multiresistant P. aeruginosa. Nine of 11 patients with soft-tissue infection exhibited resolution of clinical infection but usually required surgical removal of infected tissue with or without revascularization. Overall, three patients died. In two instances in which multiple isolates with different susceptibility profiles from the same patient were available, pulsed-field gel electrophoresis profiles of serial isolates were indistinguishable or closely related. This study illustrates that multiresistant P. aeruginosa emerges in a stepwise manner after exposure to antipseudomonal antibiotics and results in adverse outcomes.

Aged↗
PubMed1999

Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma.

The purpose of this study was to determine how a topical carbonic anhydrase inhibitor, dorzolamide, alters visual function and ocular blood flow in persons with normal-tension glaucoma. Eighteen normal tension glaucoma patients, after washout of other ocular medications, were treated for four weeks with 2% dorzolamide, three times daily. A control group of eleven other normal-tension glaucoma patients received placebo eye drops. Patients were studied before treatment, and after two and four weeks of treatment. Each study included assessment of central visual function (contrast sensitivity), intraocular pressure (IOP), and several aspects of ocular hemodynamics, including measures of retinal arteriovenous passage time, retinal arterial and venous diameters, and flow velocities in the ophthalmic, central retinal, and posterior ciliary arteries. Dorzolamide significantly reduced IOP at two and four weeks (each p<0.01), and at the same time increased contrast sensitivity at both three and six cycles per degree (each p<0.05). Neither of these variables changed significantly in the control group. Dorzolamide also accelerated retinal arteriovenous passage time of fluorescein dye, at constant retinal arterial and venous diameters (p<0.05), but failed to change flow velocities in any retrobulbar vessel. The ability of dorzolamide to improve contrast sensitivity in persons with normal-tension glaucoma may be related to either IOP reduction or altered ocular perfusion.

Blood Pressure↗
PubMed1999

Ginkgo biloba extract increases ocular blood flow velocity.

We evaluated a possible therapeutic effect of Ginkgo biloba extract (GBE) on glaucoma patients that may benefit from improvements in ocular blood flow. A Phase I cross-over trial of GBE with placebo control in 11 healthy volunteers (8 women, 3 men: Age; 34 +/- 3 years, mean +/- SE) was performed. Patients were treated with either GBE 40 mg or placebo three times daily orally, for 2 days. Color Doppler imaging (Siemens Quantum 2000) was used to measure ocular blood flow before and after treatment. There was a two week washout period between GBE and placebo treatment. Ginkgo biloba extract significantly increased end diastolic velocity (EDV) in the ophthalmic artery (OA) (baseline vs GBE-treatment; 6.5 +/- 0.5 vs 7.7 +/- 0.5 cm/sec, 23% change, p=0.023), with no change seen in placebo (baseline vs GBE-treatment; 7.2 +/- 0.6 vs 7.1 +/- 0.5 cm/sec, 3% change, p=0.892). No side effects related to GBE were found. Ginkgo biloba extract did not alter arterial blood pressure, heart rate, or IOP. Ginkgo biloba extract significantly increased EDV in the OA and deserves further investigation in ocular blood flow and neuroprotection for possible application to the treatment of glaucomatous optic neuropathy as well as other ischemic ocular diseases.

Adult↗
PubMed1999

Primary open-angle glaucoma patients characterized by ocular vasospasm demonstrate a different ocular vascular response to timolol versus betaxolol.

We evaluated the retrobulbar response to a selective versus nonselective beta blocker in a subgroup of primary open-angle glaucoma patients (POAG) characterized by ocular vasospasm. Eleven patients who exhibited ocular vasospasm (i.e. a significant increase in ophthalmic artery blood flow velocity or a significant decrease in ophthalmic artery resistance index during hypercapnia) underwent medication washout for 4 weeks and were enrolled in a double-masked cross-over study (betaxolol versus timolol). Patients were evaluated for blood flow velocity of the retrobulbar vessels using color Doppler imaging, intraocular pressure, visual field sensitivity and contrast sensitivity at the beginning and end of each 4 week treatment period. Timolol treatment caused a significant reduction in IOP (p = .007), but no change in retrobulbar hemodynamics or visual function. After betaxolol treatment, resistance index fell significantly (p = .040) in the ophthalmic artery and increased significantly in both the central retinal (p = .003) and temporal posterior ciliary arteries (p = .030). Also following betaxolol treatment, contrast sensitivity improved significantly (p = .006), and a significant positive correlation was shown between change in contrast sensitivity and change in resistance index (r = .70; p = .015) of the ciliary arteries. POAG patients characterized by ocular vasospasm display a significant hemodynamic response to betaxolol, but not to timolol.

Adrenergic beta-Antagonists↗
PubMed1999

CFTR expression does not influence glycosylation of an epitope-tagged MUC1 mucin in colon carcinoma cell lines.

The cause of the mucus clearance problems associated with cystic fibrosis remains poorly understood though it has been suggested that mucin hypersecretion, dehydration of mucins, and biochemical abnormalities in the glycosylation of mucins may be responsible. Since the biochemical and biophysical properties of a mucin are dependent on O-glycosylation, our aim was to evaluate the O-glycosylation of a single mucin gene product in matched pairs of cells that differed with respect to CFTR expression. An epitope-tagged MUC1 mucin cDNA (MUC1F) was used to detect variation in mucin glycosylation in stably transfected colon carcinoma cell lines HT29 and Caco2. The glycosylation of MUC1F mucin was evaluated in matched pairs of Caco2 cell lines that either express wild-type CFTR or have spontaneously lost CFTR expression. The general glycosylation pattern of MUC1F was evaluated by determining its reactivity with a series of monoclonal antibodies against known blood group and tumor-associated carbohydrate antigens. Metabolic labeling experiments were used to estimate the gross levels of glycosylation and sulfation of MUC1F mucin in these matched pairs of cell lines. Expression of CFTR in this experimental system did not affect the gross levels of glycosylation or sulfation of the MUC1F mucin nor the types of carbohydrates structures attached to the MUC1F protein.

Caco-2 Cells↗
PubMed1999

Critical review of GABA-ergic drugs in the treatment of schizophrenia.

GABA-ergic medications may have a potential role in the treatment of schizophrenia. Laboratory evidence has generally supported the ability of gamma-aminobutyric acid (GABA) to reduce dopaminergic activity and has suggested that GABA may be effective in combating hypofrontality by acting on mesoprefrontocortical tracts in patients resistant to treatment with antipsychotic drugs. Although the results of clinical trials of several GABA-ergic compounds have been inconclusive because of methodologic limitations and drug toxicity, benzodiazepines and valproate seem to be associated with favorable treatment outcomes, especially when combined with typical antipsychotic agents. This study concludes that further investigation of the use of GABA in schizophrenia is likely to improve the understanding of the psychopathology of this illness and to expand our treatment alternatives. Also provided are suggestions to enhance the design of future studies, improve the potential for favorable treatment outcomes, and assist in predicting patients' responses to GABA-ergic medications.

Anti-Anxiety Agents↗
PubMed1999

Cholecystokinin A and B receptor mRNA expression in human pancreas.

Little information is available on the expression of cholecystokinin (CCK) receptors in the human pancreas, especially in the developing pancreas. We evaluated expression patterns for the CCK receptors in human pancreas at three different ages: fetus, infant, and adult. Expressions of CCK-A and CCK-B receptor messenger RNA (mRNA) were studied in human midtrimester fetus (14-15 weeks' gestation), infant (50 days old), and adult pancreas by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Expression levels of mRNA for both receptors also were evaluated by Northern blot analysis of adult pancreas. Northern blot analysis showed a strong signal for CCK-B receptor mRNA in adult pancreas, but no detectable signal for CCK-A receptor mRNA. However, RT-PCR/Southern blotting showed the presence of CCK-A receptor mRNA in adult pancreas. This was confirmed by sequencing of the complementary DNA (cDNA). RT-PCR/Southern blot analysis also showed CCK-A and CCK-B receptor mRNA expression in fetal and infant pancreas. These results show that the both CCK receptor types are expressed in human pancreas at stages of early gestation, but there is predominant expression of CCK-B receptor in adult pancreas.

Adult↗
PubMed1999

Structural similarities between influenza virus matrix protein M1 and human immunodeficiency virus matrix and capsid proteins: an evolutionary link between negative-stranded RNA viruses and retroviruses.

The evolutionary relationship of retroviruses to the negative-stranded RNA virus superfamily was examined by comparing protein structures. Since protein structures are more conserved over time than primary protein sequences, three-dimensional structural comparisons permit the identification of evolutionary relationships that were previously undetected. Human immunodeficiency virus (HIV) and influenza virus were used as representatives of the virus groups, and proteins with similar functions were compared. Since M1 of influenza virus has membrane- and RNA nucleocapsid-binding activities that are functionally analogous to those of the HIV matrix and capsid proteins, the structural similarities between these proteins were determined. Sequence alignments were based on superimposition of the three-dimensional structures. Helices 2, 2', 3 and 4 of the HIV matrix protein aligned and superimposed with the four-helix bundle of the membrane-binding N domain of M1 with a root mean square (RMS) of 3.48 A. Helices A, B and C of the HIV N-terminal capsid protein aligned and superimposed with three helices of the four-helix bundle of the RNA-binding N domain of M1 with an RMS of 2.63 A. The HIV Gag protein and influenza virus matrix protein may have evolved from a common ancestor protein. The similarities between influenza virus M1 and HIV matrix and capsid proteins may indicate an evolutionary link between retroviruses and negative-sense RNA viruses.

Amino Acid Sequence↗