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Biomedical subjects

E Sutter

Publications and source records attributed to E Sutter.

At least 19 recordsLinked to original sources
PubMed2000

Connexin37 in normal and pathological development of mouse heart and great arteries.

Cx37 is a member of the connexin family of gap junction proteins, whose distribution in heart remains controversial. We have generated novel antibodies against Cx37 to investigate this distribution during normal and pathological development in mouse. Using these affinity-purified antibodies, we have detected Cx37 in hearts and aortas of mouse embryos from day 11 ed. onwards. Immunostaining revealed that during prenatal development Cx37 predominated in endothelial and endocardial cells but was also detectable in small amounts in the trabeculated and compact layers of ventricular myocardium, as well as in the mesenchyme of conotruncal ridges and atrioventricular cushions. Cx37 was also differentially expressed in the ascending and descending portions of the embryonic aorta, according to a pattern which differed in the three layers of the vessel wall. Cx37 distribution was altered in both heart and aorta of mice that had been exposed to all-trans retinoic acid at the beginning of foetal development, whether or not these animals subsequently developed a transposition of great arteries. The data indicate that Cx37 is widely distributed in multiple compartments of cardiovascular system, in patterns which are modulated during development, by retinoic acid.

Animals↗
PubMed2000

The interpretation of multifocal binary kernels.

The interpretation of binary kernels derived by means of the mulifocal ERG has frequently been the source of confusion and controversy. The aim of this paper is to provide an intuitive understanding of the concept of kernels and to demonstrate with models and examples, the relationship between the kernels and individual responses. The sample data used to illustrate the various aspects of the technique were derived and analyzed by means of the multifocal VERIS instrument using bipolar Burian-Allen contact lens electrodes. From the kernel data, response waveforms are synthesized that can be readily compared with those obtained with conventional flash, double flash and multi-flash ERG techniques. From the kernels of a single multifocal record, waveforms are synthesized that describe responses at various times after a preceding focal flash. It is shown that the observed adaptive changes in the waveforms depend not only on the flash interval but also on retinal eccentricity. Features on the response waveform exhibit independent adaptive behavior suggesting that they originate from different retinal sources. On one hand, the examples presented here illustrate the rich information on retinal dynamics contained in the kernels. On the other hand, they demonstrate how the interpretation of multifocal data can be facilitated when the kernel series is transformed into representations with more direct physiological appeal.

Adaptation, Ocular↗
PubMed2000

Continuous monitoring of the stimulated area in multifocal ERG.

INTRODUCTION: Multifocal electroretinography (MF-ERG) is widely used in the detection of local retinal dysfunction. However, the position of the stimulus on the retina and the stability of fixation are usually not directly accessible. Thus, devices have been designed for a continuous fundus visualization during recording. METHODS: MF-ERGs were recorded with a RetiScan system connected to two different Scanning-laser ophthalmoscopes (SLOs) that use either a red (633 nm) or green (415 nm) laser for stimulation, and a VERIS 4 system connected to a piggyback stimulator prototype that added the stimulus to the optical pathway of the SLO by means of a wavelength-sensitive mirror. Fundus visualization was achieved with the infrared lasers of the SLOs (780 and 835 nm). RESULTS: The most extensive study so far with a green laser stimulus in a cat model of retinal degeneration demonstrated the capability of the device to detect retinal landmarks and the different stages of degeneration. Also, the advantages of exactly reproducible stimulus positioning for averaging within and comparison between disease groups became apparent. The results with the same setup in transgenic mice suggest a pure cone origin of the responses. In humans, recordings show that fixation is sufficiently good in most subjects. It is not clear yet whether red or green laser stimulation (or both) is preferable. The results with the prototype were very similar to the MF-ERGs obtained with a standard CRT screen. CONCLUSIONS: All three devices allowed us to record MF-ERGs with continuous fundus monitoring. Although further refinements are necessary, it is obvious that fundus controlled methods will improve the reliability of MF-ERG in future research on glaucoma, transplantation studies, and evaluation of gene therapy.

Journal Article↗
PubMed2000

Continuous monitoring of the stimulated area in multifocal ERG.

INTRODUCTION: Multifocal electroretinography (MF-ERG) is widely used in the detection of local retinal dysfunction. However, the position of the stimulus on the retina and the stability of fixation are usually not directly accessible. Thus, devices have been designed for a continuous fundus visualization during recording. METHODS: MF-ERGs were recorded with a RetiScan system connected to two different Scanning-laser ophthalmoscopes (SLOs) that use either a red (633 nm) or green (415 nm) laser for stimulation, and a VERIS 4 system connected to a piggyback stimulator prototype that added the stimulus to the optical pathway of the SLO by means of a wavelength-sensitive mirror. Fundus visualization was achieved with the infrared lasers of the SLOs (780 and 835 nm). RESULTS: The most extensive study so far with a green laser stimulus in a cat model of retinal degeneration demonstrated the capability of the device to detect retinal landmarks and the different stages of degeneration. Also, the advantages of exactly reproducible stimulus positioning for averaging within and comparison between disease groups became apparent. The results with the same setup in transgenic mice suggest a pure cone origin of the responses. In humans, recordings show that fixation is sufficiently good in most subjects. It is not clear yet whether red or green laser stimulation (or both) is preferable. The results with the prototype were very similar to the MF-ERGs obtained with a standard CRT screen. CONCLUSIONS: All three devices allowed us to record MF-ERGs with continuous fundus monitoring. Although further refinements are necessary, it is obvious that fundus controlled methods will improve the reliability of MF-ERG in future research on glaucoma, transplantation studies, and evaluation of gene therapy.

Animals↗
PubMed1999

Using multi-stimulus VEP source localization to obtain a retinotopic map of human primary visual cortex.

OBJECTIVE: The goal of this study was to acquire a detailed spatial and temporal map of primary visual cortex using a novel VEP stimulus and analysis technique. METHODS: A multi-stimulus array spanning the central 18 degrees of the visual field was used where each of 60 checkerboard stimulus 'patches' was simultaneously modulated with an independent binary m-sequence (Sutter, 1992). VEPs corresponding to each patch were recorded from 3 subjects using a dense posterior electrode array. For each stimulus patch, single dipole source localization was conducted to determine the location, magnitude, and time-function of the underlying neural activation. To reduce ambiguity in the solution, a common time-function was assumed for stimulus patches at the same visual eccentricity (defining an annulus). The analysis was conducted independently for each annulus composed of 4-12 patches. RESULTS: The loci of the dipole solutions followed a smooth retinotopic pattern across annuli consistent with the classical organization of primary visual cortex. Specifically, each dipole was found contralateral to the corresponding stimulus patch and field inversion was observed for all subjects. CONCLUSIONS: Using this technique, the most detailed spatial and temporal retinotopic map of primary visual cortex to date has been obtained.

Adult↗
PubMed1998

Position-independent expression of a human nerve growth factor-luciferase reporter gene cloned on a yeast artificial chromosome vector.

Two yeast artificial chromosomes containing the entire human nerve growth factor gene were isolated and mapped. By homologous recombination a luciferase gene was precisely engineered into the coding portion of the NGF gene and a neomycin selection marker was placed adjacent to one of the YAC telomeres. Expression of the YAC-based NGF reporter gene and a plasmid-based NGF reporter gene were compared with the regulation of endogenous mouse NGF protein in mouse L929 fibroblasts. In contrast to the plasmid-based reporter gene, expression and regulation of the YAC-based reporter gene was independent of the site of integration of the transgene. Basic fibroblast growth factor and okadaic acid stimulated expression of the YAC transgene, whereas transforming growth factor-beta and dexamethasone inhibited it. Although cyclic AMP strongly stimulated production of the endogenous mouse NGF, no effect was seen on the human NGF reporter genes. Downregulation of the secretion of endogenous mouse NGF already occurred at an EC50 of 1-2 nM dexamethasone, but downregulation of the expression of NGF reporter genes occurred only at EC50 of 10 nM. This higher concentration was also required for upregulation of luciferase genes driven by the dexamethasone-inducible promoter of the mouse mammary tumor virus in L929 fibroblasts.

Animals↗
PubMed1997

Hypertension increases connexin43 in a tissue-specific manner.

BACKGROUND: Connexin43 (Cx43), a membrane protein involved in the control of cell-to-cell communication, is thought to play a role in the contractility of the vascular wall and in the electrical coupling of cardiac myocytes. The aim of this study was to investigate the effects of experimental hypertension on Cx43 expression in rat aorta and heart. METHODS AND RESULTS: Rats were made hypertensive after one renal artery was clipped (two kidney, one-clip renal model) or after the administration of deoxycorticosterone and salt (DOCA-salt model). After 4 weeks, all rats showed a similar increase in intra-arterial mean blood pressure and in the thickness of both the aortic wall and the heart. Northern blot analysis of aorta mRNA and immunolabeling for Cx43 showed that hypertensive rats expressed twice as much Cx43 in aorta as the control animals. In contrast, no difference in Cx43 mRNA or in the immunolabeled protein was observed in heart. CONCLUSIONS: The results show that rats exhibiting a similar degree of blood pressure elevation, as the result of different mechanisms, feature a comparable increase in Cx43 gene expression, which was observed in the aortic but not in the cardiac muscle. These data suggest that localized mechanical forces induced by hypertension are major tissue-specific regulators of Cx43 expression.

Animals↗
PubMed1997

International round robin tests on the measurement of carbon in diesel exhaust particulates.

OBJECT: Diesel soot has been recognized as probably carcinogenic to humans. Elemental carbon (also called black carbon) in soot is considered at the moment as the most significant surrogate to be measured for assessing the exposure to this pollutant. Its analysis is done by combustion in an oven and determination of the CO2 formed, after elimination of the organic fraction of the soot by heating and/or by solvent extraction. The analysis allows determination of both fractions of the soot: "elemental carbon" (EC) and organic carbon (OC). The sum of EC and OC is called TC (total carbon). METHOD: An informal European coordination group organized two round robin tests on filter samples collected from diluted diesel emissions. The first round (RRT1) was performed on 13 different samples analyzed by ten laboratories. The range of loading was 2.5 to 150 micrograms/cm2 of EC. No evaluation of the precision within laboratories could be made since each laboratory gave only one result per sample. Therefore a second round (RRT2) was organized with two samples and a blank filter sent in several portions to 11 laboratories. It should be stressed that each laboratory used its own method and that no standardization was planned at this stage. RESULTS: Results of RRT1 showed that the coefficient of variation between laboratories decreased with higher loading and was around 10% to 15% for EC above about 20 micrograms/cm2. Dispersion of the results varied and it appeared that the way OC is removed from the soot is probably the most important factor of influence. The correlation between the laboratories was good as a whole but some systematic differences could be detected. Besides the different techniques to remove the organic carbon, the pretreatment of the filter by HCl (either as a vapor or as a solution) to remove the inorganic carbonates (potential interference sources), is probably also a significant factor of influence in the dispersion of the results between laboratories. It is not yet clear from these results whether the "environmental" laboratories give different results from the "occupational" laboratories, but it is clear that their objectives differ since for the "environmentalists", EC is not a specific marker of diesel emmissions, in contrast to the "occupationalists". CONCLUSION: It can be concluded that, although significant differences exist between laboratories they can be attributed mainly to the narrow distribution of the results within a single laboratory, and that the overall agreement of the results for EC and TC is fairly good. These results obtained with pure diesel engine emissions, should be complemented by field samples, but they have already achieved relevant findings in the performance of the procedures used to assess exposure to diesel soot.

Air Pollutants↗
PubMed1995

Serum selenium and colonic neoplastic risk.

BACKGROUND: Selenium deficiency has been associated with cancer risk in several organs. This association was investigated in neoplasia of the colorectum. DESIGN: A case-control study is reported with two patient series, colorectal cancer and colorectal adenomatous polyps, and a control group found to be free of colorectal neoplasia. Diagnosis was determined by colonoscopy and histologic review of suspected neoplasms. Serum drawn at the time of colonoscopy was subsequently assayed for selenium content, and quartiles based on selenium were defined. Crude and adjusted odds ratios with 95 percent confidence intervals for adenoma related to selenium were calculated, controlling for known or suspected risk factors including gender, age, race, body mass index, family history, tobacco use, alcohol consumption, serum beta carotene, serum alpha tocopherol, and serum ferritin. RESULTS: There were 138 controls who had no neoplastic disease, 139 adenoma patients, and 25 cancer patients. For adenoma, comparing higher quartiles of selenium to the first (lowest selenium), the adjusted odds ratio for the second quartile was 1.7 (95 percent confidence interval, 0.8-3.7), the third quartile was 1.4 (0.7-3.2), and the fourth (highest selenium) quartile was 1.8 (0.9-4). The odds ratios for cancer patients were 0.8 for the second quartile, 1 for the third quartile, and 1.7 for the fourth quartile. CONCLUSION: No trend could be detected toward a protective effect of higher levels of serum selenium for colonic benign or malignant tumors.

Adenoma↗
PubMed1994

Body iron stores and risk of colonic neoplasia.

BACKGROUND: Body iron stores and dietary iron intake have both been shown to be positively associated with subsequent risk of colon cancer. This finding comes from a cohort study involving 14,000 men, but the positive association occurred in only 12 cases. PURPOSE: We performed a case-control study of 264 men and 98 women to test for an association between serum ferritin levels and the presence of adenoma of the colon that would be independent of other known risk factors. METHODS: Serum ferritin levels were determined in this study from sera, frozen at -80 degrees C for 5-8 years, that had been originally obtained between 1984-1987 at the Walter Reed Army Medical Center from adult male and postmenopausal female patients undergoing routine colonoscopic examination and previously enrolled in a case-control study that assessed the potential dietary and environmental risk factors for colonic neoplasia. The presence of fecal occult blood in the stool or the suggestion of colonic polyps seen on barium enema defined eligibility for the study. Patients with known preexisting colonic disease were excluded. Eligible patients had their blood drawn and serum prepared. Following colonoscopy and histologic review, the patients were classified into three groups: normal (without neoplastic disease), 159 subjects; adenoma, 145 subjects; and colon cancer, 29 subjects. Body iron stores were determined by measuring serum ferritin levels by a competitive-binding radiometric immunoassay. Ferritin levels categorized into quintiles for adenoma were defined. Crude and adjusted odds ratios (ORadj) with 95% confidence intervals (CIs) for cancer and adenoma related to ferritin were calculated, controlling for known or suspected risk factors including sex, age, race, body mass index, family history, tobacco use, and alcohol consumption. RESULTS: Statistically significant associations of adenoma risk were seen in the third ([ORadj] = 3.8; 95% CI = 1.5-9.5) and fourth (ORadj = 5.1; 95% CI = 2.0-12.7) quintiles of ferritin relative to the first quintile, for smoking history (ORadj = 2.4; 95% CI = 1.3-4.3), for male sex (ORadj = 1.9; 95% CI = 1.0-3.7), and for family history of polyps or cancer (ORadj = 1.8; 95% CI = 1.0-3.4). From a second set of analyses that excluded 36 patients with serum ferritin of greater than or equal to 399 ng/mL, the greatest effect of ferritin on adenoma risk by anatomic subsite was seen in the right colon. CONCLUSION: The apparent dose-response for serum ferritin level and adenoma risk suggest that exposure to iron may be related to adenoma formation.

Adenoma↗
PubMed1975

Effect of methylprednisolone upon arterial pressure and the renin angiotensin system in the rat.

The effect of methylprednisolone or deoxycorticosterone upon systemic arterial blood pressure and components of the renin-angiotensin system was studied in the rat. Rats maintained on regular diets given methylprednisolone suspension 20 mg/kg body wt demonstrated a significant increase in arterial pressure of + 37 plus or minus 5 mmHg, mean plus or minus SE, over a 2-wk period, whereas those treated with DOC and untreated controls showed no significant change. On normal diets, plasma renin concentration (PRC) of methylprednisolone-treated rats was significantly higher than that of DOC-treated rats. Methylprednisolone treatment also resulted in a significant elevation of plasma renin substrate concentration (PRS). Calculated plasma renin activity (PRA) was highest in methylprednisolone-treated rats, significantly above that of the DOC and no-steroid groups. NaCl supplementation resulted in a significant fall in PRC and PRA in all three groups; however, PRS remained significantly above normal in the methylprednisolone-treated rats. The pressor effect of angiotensin II was slightly increased in methylprednisolone-treated rats. Infusion of [Sar1,Ala8]angiotensin II (P-113) in methylprednisolone-treated rats resulted in a significant fall in diastolic arterial pressure. The results imply that methylprednisolone hypertension in the rat may be in part angiotensin dependent.

Angiotensin II↗