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Biomedical subjects

A Sutter

Publications and source records attributed to A Sutter.

At least 19 recordsLinked to original sources
PubMed2002

Inhibition of the alpha-nu integrins with a cyclic RGD peptide impairs angiogenesis, growth and metastasis of solid tumours in vivo.

Anti-angiogenetic cancer therapy is a potential new form for treatment of solid tumours. The alpha(v)-integrins (alpha(v)beta3, alpha(v)beta5) mediate the contact of activated endothelial cells to proteins of the extracellular matrix during tumour angiogenesis as a prerequisite for survival of endothelial cells. The aim of this study was to investigate the effects of application of a methylated cyclic RGD-peptide as an alpha(v)-integrin antagonist on angiogenesis, microcirculation, growth and metastasis formation of a solid tumour in vivo. Experiments were performed in the dorsal skinfold preparation of Syrian Golden hamsters bearing the amelanotic hamster melanoma A-Mel-3. Animals were injected intraperitoneally with a methylated cyclic RGD-peptide every 12 h, the control group received an inactive peptide. Microcirculatory parameters of tumour angiogenesis including functional vessel density, red blood cell velocity, vessel diameter and leucocyte-endothelium interaction were analysed using intravital microscopy. In an additional study the effects on growth and metastasis of subcutaneous A-Mel-3 were quantified. Functional vessel density was markedly reduced on day 3 in treated animals compared to controls (37.2 +/- 12.1 vs 105.2 +/- 11.2 cm(-1); mean +/- s.e.m.; P<0.05) and increased subsequently in both groups. Red blood cell velocity at day 3 was below values of controls (0.026 +/- 0.01 vs 0.12 +/- 0.03 mm x s(-1); P<0.05). No differences were observed in vessel diameters and leucocyte-endothelium interaction was almost absent in both groups. Furthermore, growth and metastasis of subcutaneous tumours after administration of the cyclic RGD-peptide was significantly delayed in comparison to controls (P<0.05). Inhibition of alpha(v)-integrins by a cyclic RGD-peptide resulted in significant reduction of functional vessel density, retardation of tumour growth and metastasis in vivo. Taken together, these results implicate RGD-peptides as agents which have anti-tumour and anti-metastatic activity in vivo.

Animals↗
PubMed2001

Peptones stimulate intestinal cholecystokinin gene transcription via cyclic adenosine monophosphate response element-binding factors.

Cholecystokinin (CCK) is a potent intestinal hormone that regulates several digestive functions. Despite the physiological importance of CCK, the cellular and molecular mechanisms that govern its synthesis and secretion are not completely identified. Peptones, which are fair counterparts of the protein fraction in the intestinal lumen, are good stimulants of CCK secretion. We have previously shown that peptones activate CCK gene transcription in STC-1 enteroendocrine cells. The DNA element(s) necessary to induce the transcriptional stimulation was preliminary, localized in the first 800 bp of the CCK gene promoter. In the present study, we identify a DNA element [peptone-response element (PepRE)] essential to confer peptone-responsiveness to the CCK promoter, and we characterize the transcription factors implicated. Localization of the PepRE between -93 and -70 bp of the promoter was established using serial 5'-3'deletions. Systematic site-directed mutagenesis demonstrated that the core PepRE sequence, spanning from nucleotide -72 to -83, overlapped with the putative AP-1/CRE site. Mutations in the core sequence dramatically decreased peptone-responsiveness of CCK promoter fragments. The PepRE functioned as a low-affinity CRE consensus site, binding only transcription factors of the CREB family. Overexpression, in STC-1 cells, of a dominant-negative protein (A-CREB), that prevented the binding of CREB factors to DNA, completely abolished the peptone-induced transcriptional stimulation. Peptone treatment did not modify the nature and the abundance of proteins bound to the PepRE but led to increased phosphorylation of the CREB factors. In conclusion, the present study first demonstrates that CCK gene expression is under the control of protein-derived nutrients in the STC-1 enteroendocrine cell line.

Animals↗
PubMed2000

Normalization: contrast-gain control in simple (Fourier) and complex (non-Fourier) pathways of pattern vision.

Results from two types of texture-segregation experiments considered jointly demonstrate that the heavily-compressive intensive nonlinearity acting in static pattern vision is not a relatively early, local gain control like light adaptation in the retina or LGN. Nor can it be a late, within-channel contrast-gain control. All the results suggest that it is inhibition among channels as in a normalization network. The normalization pool affects the complex-channel (second-order, non-Fourier) pathway in the same manner in which it affects the simple-channel (first-order, Fourier) pathway, but it is not yet known whether complex channels' outputs are part of the normalization pool.

Form Perception↗
PubMed1999

A comparison of the dynamics of simple (Fourier) and complex (non-Fourier) mechanisms in texture segregation.

Models of texture segregation frequently feature two processing mechanisms: simple, linear channels (1st-order, Fourier mechanisms) and complex channels (2nd-order, non-Fourier mechanisms). Using texture patterns designed to segregate primarily as a result of activity in one set of channels or the other, we employed the method of cued response to obtain speed-accuracy tradeoff (SAT) functions measuring the time course of texture segregation processing in simple and complex channels. Here, both simple-channel and complex-channel patterns are composed of Gabor-patch texture elements, thus equating input to simple channels and the first stage of complex channels. Subjects were required to identify the orientation of a rectangular texture-region embedded in a background field of a different texture. SAT functions were obtained by requiring subjects to respond within 200 ms after an auditory cue. We found that: (1) when segregation depended primarily on activity in simple channels, performance was faster and better than when it depended primarily on complex channels; (2) in contrast to a previous study (Sutter, A., & Graham, N. (1995). Investigating simple and complex mechanisms in texture segragation using the speed-accuracy tradeoff method. Vision Research, 35, 2825-2843), simple-channel (Fourier) patterns composed of two textured regions were just as easily segregated as simple-channel patterns in which one of the regions was blank instead of textured; (3) performance with complex-channel patterns composed of diagonally oriented Gabor-patches was considerably worse than performance with complex-channel patterns composed of vertically and/or horizontally oriented Gabor-patches; (4) among simple-channel patterns containing only one region of texture (background-only or rectangle-only), there were minimal differences in performance; and (5) as in previous experiments, there were large individual differences in the segregation of complex-channel (non-Fourier) patterns. All of the above results can be explained within the framework of the simple- and complex-channels model of texture segregation.

Adult↗
PubMed1998

Spatial summation in simple (Fourier) and complex (non-Fourier) texture channels.

Complex (non-Fourier, second-order) channels have been proposed to explain aspects of texture-based region segregation and related perceptual tasks. Complex channels contain two stages of linear filtering with an intermediate pointwise nonlinearity. The intermediate nonlinearity is crucial. Without it, a complex channel is equivalent to a single linear filter (a simple channel). Here we asked whether the intermediate nonlinearity is piecewise-linear (an ordinary rectifier), or compressive, or expansive. We measured the perceptual segregation between element-arrangement textures where the contrast and area of the individual elements were systematically varied. For solid-square elements, the tradeoff between contrast and area was approximately linear, consistent with simple linear channels. For Gabor-patch elements, however, the tradeoff was highly nonlinear, consistent with complex channels in which the intermediate nonlinearity is expansive (with an exponent somewhat higher than 2). Also, substantial individual differences in certain details were explainable by differential intrusion from "off-frequency" complex channels. Lastly, the results reported here (in conjunction with those of other studies) suggest that the strongly compressive intensive nonlinearity previously known to act in texture segregation cannot be attributed to a compressive nonlinearity acting locally and relatively early (before the spatial-frequency and orientation-selective channels) but could result from inhibition among the channels (as in a normalization network).

Contrast Sensitivity↗
PubMed1997

Immunohistochemical analysis of integrin alpha vbeta3 expression on tumor-associated vessels of human carcinomas.

Expression of the alpha vbeta3 integrin is upregulated on sprouting endothelia. Systemic application of antibody or peptidic inhibitors of alpha vbeta3 function disrupts tumor angiogenesis and reduces growth and invasiveness of human tumors in animal models. We systematically investigated alpha vbeta3 expression on tumor-associated vessels of 4 different human epithelial tumors and the corresponding normal tissues by means of immunohistochemistry on frozen sections using the alpha vbeta3-complex specific monoclonal antibody LM609. Variable levels of LM609 staining were found in all carcinoma lesions. A considerable number of tumor tissues (35/50) expressed alpha vbeta3 on more than 50% of their vessels. Inflammatory infiltrates and the possibly hypoxic conditions near necrotic areas of tumors were accompanied by an increased alpha vbeta3 expression. Remarkably, the vasculature in apparently normal tissue also stained for alpha vbeta3. However, the percentages of stained vessels and their staining intensity were lower than in neoplastic tissues. Besides the vascular alpha vbeta3 expression, several extravascular cell types stained positive, in both normal and tumor specimens. Taken together, our findings show a considerable number of colon, pancreas, lung and breast carcinoma lesions with many alpha vbeta3-expressing vessels that could be targets for anti-alpha vbeta3-therapy.

Adenocarcinoma↗
PubMed1996

Effect of spatial scale and background luminance on the intensive and spatial nonlinearities in texture segregation.

Perceived segregation between element-arrangement textures is affected both by spatial scale and background luminance. The effects on the spatial nonlinearity are consistent with the proposed structure for complex (second-order) channels. The effects on the intensive nonlinearity are not consistent with an early, local nonlinearity but are consistent with either (i) a relatively early, local, nonlinearity occurring before the spatial frequency channels but after a sensitivity-setting stage, or (ii) inhibitory interaction among channels modeled as a normalization network. Thus the texture intensive nonlinearity comes after sensitivity to spatial frequency and background luminance has been determined. For six of seven observers, the texture intensive nonlinearity was compressive by 10% contrast for both increments and decrements (at high background luminance, large spatial scale.

Adaptation, Ocular↗
PubMed1996

Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization.

Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor-type integrins appears to be required for the survival and maturation of newly formed but not quiescent blood vessels in several vascular beds including the retina, blockade of this downstream adhesion receptor system was investigated. In a mouse model of hypoxia-induced retinal neovascularization twice daily administration of 1 to 20 mg cyclic alpha v-integrin antagonist peptide per kilogram of body weight reduced capillary proliferation in a dose-dependent fashion--maximum 76%--without obvious side effects. A cyclic control peptide displayed no inhibitory effect on neovascularization. These findings indicate that systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascularization and superior to cytokine-blocking strategies.

Amino Acid Sequence↗
PubMed1996

Left and right ventricular dysplasia and Uhl's anomaly. A case report.

Myocardial dysplasia involves a quasi-complete or localized absence of myocardial fibers in the right or left ventricle, with corresponding partial or complete filling by fibroadipose tissue. This disorder, in its full form called "Uhl's anomaly", was first described in 1952 as an anomaly of the heart conferring a parchment-like appearance to its walls. Incomplete forms of the disorder fall into the category of right or left arrhythmogenic ventricular dysplasia. Although approximately 50 cases of right ventricular dysplasia have been documented, only two reports concern left ventricular dysplasia. Having encountered the latter anomaly, we first present the case and our observations, and then review the etiology, pathogenesis, clinical aspects, and evolution of this disorder.

Adult↗
PubMed1995

Measuring the spatial frequency selectivity of second-order texture mechanisms.

Recent investigations of texture and motion perception suggest two early filtering stages: an initial stage of selective linear filtering followed by rectification and a second stage of linear filtering. Here we demonstrate that there are differently scaled second-stage filters, and we measure their contrast modulation sensitivity as a function of spatial frequency. Our stimuli are Gabor modulations of a suprathreshold, bandlimited, isotropic carrier noise. The subjects' task is to discriminate between two possible orientations of the Gabor. Carrier noises are filtered into four octave-wide bands, centered at m = 2, 4, 8, and 16 c/deg. The Gabor test signals are w = 0.5, 1, 2, 4 and 8 c/deg. The threshold modulation of the test signal is measured for all 20 combinations of m and w. For each carrier frequency m, the Gabor test frequency w to which subjects are maximally sensitive appears to be approximately 3-4 octaves below m. The consistent m x w interaction suggests that each second-stage spatial filter may be differentially tuned to a particular first-stage spatial frequency. The most sensitive combination is a second-stage filter of 1 c/deg with first-stage inputs of 8-16 c/deg. We conclude that second-order texture perception appears to utilize multiple channels tuned to spatial frequency and orientation, with channels tuned to low modulation frequencies appearing to be best served by carrier frequencies 8 to 16 times higher than the modulations they are tuned to detect.

Contrast Sensitivity↗
PubMed1995

Investigating simple and complex mechanisms in texture segregation using the speed-accuracy tradeoff method.

Several recent models of texture segregation have proposed two mechanisms: simple, linear channels (first-order, Fourier mechanisms) and complex channels (second-order, non-Fourier mechanisms). We used the speed-accuracy tradeoff (SAT) method to examine the time course of texture segregation processing in simple and complex channels. The stimuli were texture patterns designed to segregate primarily as a result of activity in one set of channels or the other. We presented subjects with textures that were checked or striped arrangements of either Gaussian-blob or Gabor-patch elements. Subjects were required to identify the orientation of a rectangular texture region embedded in a background field of a different texture. A range of contrasts and a control task were used to equate visibility of the Gabor and Gaussian textures. SAT functions were obtained by requiring subjects to respond within 200 msec after an auditory cue. We found that when segregation depended primarily on simple channels, performance was faster than when it depended primarily on complex channels: the 75% correct level was reached 100-200 msec sooner and this extra speed was reflected both in smaller delay and higher rate parameters.

Contrast Sensitivity↗
PubMed1995

An anti-alpha v-integrin antibody that blocks integrin function inhibits the development of a human melanoma in nude mice.

A series of murine monoclonal antibodies were raised against purified human alpha v beta 3 integrin and against M21 human melanoma cells. Five notable hybridomas were identified by ELISA on purified integrins, and the isolated antibodies bound the alpha v-chain. These antibodies, 17E6, 20A9, 23G5, 14D9.F8 and 10G2, recognised the extracellular domains of the integrin, and were shown to be reactive in FACS, immunoprecipitation, ELISA, and ELISA on fixed cells with M21, M21-L4, and UCLA-P3, but not with the alpha v-deficient M21-L or M21-L-IIb (M21-L transfected with GpIIb integrin). One antibody, 17E6, strongly perturbed cell attachment mediated by alpha v integrins, reacting at least with alpha v beta 3, alpha v beta 5, and alpha v beta 1, and strongly inhibiting cell attachment to alpha v-ligands vitronectin and fibronectin with an IC50 of approximately 0.1 microgram ml-1. Furthermore, 17E6 at this concentration could induce cell retraction from the substrate, while LM609 (anti-alpha v beta 3) and control antibody 14E2 (anti-200 kDa melanoma surface protein) at 1,000-fold higher concentrations had minimal effects on cell morphology. The action of 17E6 was reversible and was not due to toxic effects: in vitro 17E6 at 0.1 mg ml-1 did not affect either cell proliferation or DNA synthesis. In two nude-mouse tumour models, subcutaneous tumour development and a lung colonisation ('experimental metastasis') assay, injection of 17E6 strongly inhibited tumour development, while isotype-matched controls had no effect. There was no obvious mechanism of cell or of complement-mediated tumour cytotoxicity; the antibody did not mediate ADCC or AECDC, or complement fixation. The data strongly support previous studies which have indicated the importance of alpha v-integrins, and especially alpha v beta 3, in the tumour progression of human melanoma.

Animals↗
PubMed1994

Evidence for an NGF-induced autocrine neurotrophic potential of glial cells in nervous system development.

NGF receptor bearing peripheral glial cells, purified from chicken embryo dorsal root ganglia, were found to secrete neurite growth promoting activity (NGPA) but no NGF (detection limit 1 pM). If, however, minute concentrations of NGF (2 pM) were added to the glial cultures, an autocrine response was observed. Levels of NGF-like activity in the medium rose up to 50-fold. Induction of this autocrine response occured within a narrow range of NGF concentrations. NGPA production was not affected by addition of NGF. Coculture with neurons influenced the neurotrophic factor production. The data suggest that glial cells can "sense" traces of NGF and regulate its availability during neural development.

Animals↗
PubMed1993

Isérables: a Bedouin village in Switzerland?

Isérables is an alpine village--about 1000 inhabitants--which remained isolated till these recent years because of its particular geographical situation. The Isérables inhabitants call themselves "Bedjuis" (Bedouin in local dialect) and regard themselves as descendants of the Sarrazins who invaded the Alps during the VIII-X centuries. Our goal, in studying several DNA-VNTR polymorphims, in addition to some blood groups, within the Isérables community, was to see if there was any evidence supporting this popular belief. As a preliminary phase of this project, the allelic frequencies for six VNTR loci analysed for 102 individuals of the village (all descendants of nine original families) are presented. The results are compared with those reported for Swiss and white populations.

Adult↗
PubMed1993

Spatial-frequency- and orientation-selectivity of simple and complex channels in region segregation.

Models incorporating spatial-frequency- and orientation-selective channels explain many texture-segregation results, particularly when known nonlinearities are included. One such nonlinearity is complex channels. A complex channel consists of two stages of linear filtering separated by a rectification-type nonlinearity. Here we investigate the spatial-frequency- and orientation-selectivity of simple (linear) channels and of the complex channels' first stage. Observers rated the degree of segregation between two "textures" both composed of elements which were Gabor patches. When the textures differed in type of element (e.g. one composed of vertical and the other of horizontal Gabor patches), the segregation results yield bandwidth estimates for simple channels of approx. 0.5-1.0 octave on the spatial-frequency dimension and 5-20 deg of rotation on the orientation dimension. When the textures differ in the arrangement of elements (e.g. striped vs checkerboard arrangements, both of horizontal and vertical patches), the segregation results yield bandwidth estimates for the first stage of complex channels. These estimates, while differing substantially from one observer to another, were always substantially wider than those for simple channels (by at least a factor of two) but narrower than bandwidths of LGN cells (particularly on the orientation dimension where LGN cells show little selectivity at all).

Contrast Sensitivity↗
PubMed1992

Immunotherapy of human glioma xenografts with unlabeled, 131I-, or 125I-labeled monoclonal antibody 425 to epidermal growth factor receptor.

Monoclonal antibody (mAb) 425 (IgG2a) binds to the external domain of the epidermal growth factor receptor. This determinant is highly expressed by human glioma tissues but rarely by normal brain tissues, and is absent on peripheral blood lymphocytes and bone marrow cells. The mAb exerts variable cytotoxic effects against cultured human glioma cells in conjunction with human and murine effector cells. Inhibition of growth of s.c. glioma xenografts in nude mice by the mAb may be mediated by murine macrophages or may be related to the capacity of the mAb to antagonize growth stimulation of glioma cells by epidermal growth factor. In approaches to radioimmunotherapy of human glioma with mAb 425, the 125I-labeled mAb 425 exhibited more significant antitumor effects than the 131I-labeled mAb both in vitro and in vivo in xenotransplanted nude mice. These differences may be due to enhanced nuclear damage caused by 125I-labeled versus 131I-labeled fragments following their internalization into the glioma cells. Our studies provide the rationale for immunotherapy of glioma patients with either unlabeled or 125I-labeled anti-epidermal growth factor receptor mAb 425.

Animals↗
PubMed1992

Nonlinear processes in spatial-frequency channel models of perceived texture segregation: effects of sign and amount of contrast.

Observers rated the degree of segregation between two textures, each composed of the same two element types but in differing arrangements (a checkerboard arrangement in the middle region of the pattern and a striped arrangement in the top and bottom regions). The two element types in a given pattern were either both solid squares or both center-surround elements. In center-surround elements the average luminance equaled the background luminance. The two elements types were identical in size but differed in sign and/or amount of contrast. Discrepancies between the observers' ratings of perceived segregation and the predictions of simple (linear) spatial-frequency and orientation channels models of texture segregation suggested adding nonlinear processes to the model. Complex channels (a rectification-type nonlinearity between two linear-filtering stages) can explain why some patterns made of center-surround elements segregate even though there is little energy at the spatial frequencies that differentiate the two textures. Complex channels cannot, however, explain the very poor segregation of "same-sign-of-contrast" patterns (where the luminances of the two element types were both far above or both far below the background). This second result might arise from a local nonlinearity preceding the channels and might be ascribed to retinal light adaptation except that it occurs at contrasts less than or equal to 25%! Alternatively, it might arise from normalization, which may result from intracortical inhibition. Some preliminary quantitative predictions were computed from two models, one incorporating complex channels and an early local nonlinearity, the other complex channels and normalization. With suitable choices of parameters, either model could account for the results.

Contrast Sensitivity↗