The Pregnant Smoker Stigma Scale - Self Stigma (P3S-SS): development and validation in pregnant smoking women in France.

Pregnancy smoking self-stigma may be associated with mental health and smoking cessation. This study aims to validate the Pregnant Smoker Stigma Scale - Self-Stigma (P3S-SS) assessing perceived and internalized stigma. Between May 2021 and May 2022, French pregnant smokers recruited online (n = 143) took the P3S-SS and other scales assessing depressive symptoms (EPDS), social inclusion (SIS), dissimulation, dependence (CDS-5), cessation self-efficacy (SEQ), and intention. The two versions of the scale include four dimensions: derogatory cognitions ("People think/I feel I am selfish"), negative emotions and behaviors ("People make me feel/smoking makes me feel guilty"), personal distress ("People/I feel sorry for me/myself"), and information provision ("People tell me/I think about the risks of smoking"). Confirmatory factor analyses and multiple regressions have been computed. Model fit was good for perceived stigma and internalized stigma (X2/df = 3.06, RMSEA = .124, AGFI = .982, SRMR = .068, CFI = .986, NNFI = .985; X2/df = 3.31, RMSEA = .14, AGFI = .977, SRMR = .087, CFI = .981, NNFI = .979). Controlling for dependence, cessation intention was positively predicted by perceived and internalized personal distress and negatively predicted by perceived negative emotions and behaviors (Adj R2 = .143, F(8,115) = 3.567, p = .001). Controlling for dependence, dissimulation was positively predicted by internalized negative cognitions and perceived personal distress and negatively predicted by internalized personal distress (Adj R2 = .19, F(9,98) = 3.785, p = .000). The P3S-SS opens up exciting avenues for further research. Stigma does not motivate women to stop smoking but increases distress and dissimulation.

Screening Beyond Postpartum Depression: Occluded Anxiety Component in the EPDS (EPDS-3A) in French Mothers.

INTRODUCTION: According to many studies, anxiety in the perinatal period is widespread and has many detrimental effects. Thus, screening measures should not be limited to assessing depression symptoms. The widely used Edinburgh Postnatal Depression Scale (EPDS) might assess depression but also anxiety symptoms. This study explores whether an anxiety dimension (EPDS-3A) was found and valid in French women during pregnancy and the postpartum period. METHODS: French women were followed-up at late pregnancy and 2 and 4 months postpartum (N = 144, 138 and 129). They completed the EPDS and the Hospital Anxiety and Depression Scale (HADS-A). Exploratory factor analyses were performed. Then to test its validity, the EPDS-3A was correlated with anxiety (HADS-A) and depression (EPDS-D) scores. Finally, prevalence estimates were computed according to recommended cut off. RESULTS: The anxiety dimension assessed through the EPDS-3A was observed during the postpartum period but not during pregnancy. A two-factor structure (depression and anxiety) increases the variance explained at 2 and 4 months postpartum (respectively 6 and 12%). The EPDS-3A shows good internal consistency (≥ .70) and was more strongly associated with anxiety scores (HADS-A) (.48-.57) than with depression scores (EPDS-D) (.30-.39). Nearly 28% of mothers had scores that exceeded the EPDS-3A cut off (≥ 4) but not the full EPDS cut off (≥ 13 or more). DISCUSSION: The EPDS contains an anxiety component (EPDS-3A) that can be found in French women during the postnatal period but not during pregnancy. It shows signs of internal consistency and validity. The EPDS-3A could be considered when screening for postpartum anxiety.

The copulatory plug delays ejaculation by rival males and affects sperm competition outcome in house mice.

Females of many species mate with multiple males (polyandry), resulting in male-male competition extending to post-copulation (sperm competition). Males adapt to such post-copulatory sexual selection by altering features of their ejaculate that increase its competitiveness and/or by decreasing the risk of sperm competition through female manipulation or interference with rival male behaviour. At ejaculation, males of many species deposit copulatory plugs, which are commonly interpreted as a male adaptation to post-copulatory competition and are thought to reduce or delay female remating. Here, we used a vertebrate model species, the house mouse, to study the consequences of copulatory plugs for post-copulatory competition. We experimentally manipulated plugs after a female's first mating and investigated the consequences for rival male behaviour and paternity outcome. We found that even intact copulatory plugs were ineffective at preventing female remating, but that plugs influenced the rival male copulatory behaviour. Rivals facing intact copulatory plugs performed more but shorter copulations and ejaculated later than when the plug had been fully or partially removed. This suggests that the copulatory plug represents a considerable physical barrier to rival males. The paternity share of first males increased with a longer delay between the first and second males' ejaculations, indicative of fitness consequences of copulatory plugs. However, when males provided little copulatory stimulation, the incidence of pregnancy failure increased, representing a potential benefit of intense and repeated copulation besides plug removal. We discuss the potential mechanisms of how plugs influence sperm competition outcome and consequences for male copulatory behaviour.

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Sex-specific clines support incipient speciation in a common European mammal.

Hybrid zones provide excellent opportunities to study processes and mechanisms underlying reproductive isolation and speciation. Here we investigated sex-specific clines of molecular markers in hybrid zones of morphologically cryptic yet genetically highly-diverged evolutionary lineages of the European common vole (Microtus arvalis). We analyzed the position and width of four secondary contact zones along three independent transects in the region of the Alps using maternally (mitochondrial DNA) and paternally (Y-chromosome) inherited genetic markers. Given male-biased dispersal in the common vole, a selectively neutral secondary contact would show broader paternal marker clines than maternal ones. In a selective case, for example, involving a form of Haldane's rule, Y-chromosomal clines would not be expected to be broader than maternal markers because they are transmitted by the heterogametic sex and thus gene flow would be restricted. Consistent with the selective case, paternal clines were significantly narrower or at most equal in width to maternal clines in all contact zones. In addition, analyses using maximum likelihood cline-fitting detected a shift of paternal relative to maternal clines in three of four contact zones. These patterns suggest that processes at the contact zones in the common vole are not selectively neutral, and that partial reproductive isolation is already established between these evolutionary lineages. We conclude that hybrid zone movement, sexual selection and/or genetic incompatibilities are likely associated with an unusual unidirectional manifestation of Haldane's rule in this common European mammal.

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.

Achievements of the Belgian Antibiotic Policy Coordination Committee (BAPCOC).

A Belgian Antibiotic Policy Coordination Committee (BAPCOC) was officially established in 1999 by Royal Decree. The overall objective of BAPCOC is to promote judicious use of antibiotics in humans and animals and to promote infection control and hospital hygiene, with the overall aim to reduce antibiotic resistance. BAPCOC fostered strong and interdisciplinary public health, scientific and political leadership, which led to many evidence-based interventions such as multimedia campaigns to promote the prudent use of antibiotics in the community, national campaigns to promote hand hygiene in hospitals, publication of clinical practice guidelines, staffing and technical support for establishment of antibiotic management teams in all Belgian hospitals, surveillance programmes on antibiotic use and resistance in humans and animals and the promotion of research. These activities and interventions resulted in a measurable decrease in antibiotic use and resistance in the community and hospitals.

Effects of social crowding on emotionality and expression of hippocampal nociceptin/orphanin FQ system transcripts in mice.

The novel nociceptin/orphanin FQ (N/OFQ) system was proposed to be an important component of neural circuits involved in stress-coping behaviour and fear. This study investigated whether variations between the mouse strains in vulnerability to social crowding stress might be linked to different regulation of N/OFQ system transcripts in mice. Three weeks old C57BL/6J (B6), BALB/cByJ (CBy) and 129S2/SvPas (129S2) male mice were housed individually or in crowded (7/cage) conditions and then tested as adults in a battery of anxiety tests (open field, elevated plus-maze and acoustic startle reflex tests). Both 129S2 and B6 mice displayed increased signs of anxiety under crowded housing, while CBy mice tended to show the opposite profile. Analysis of gene expression revealed a 10-fold increase of nociceptin precursor and 4-fold increase of the NOP receptor mRNAs contents in the hippocampus of CBy mice kept in crowded conditions compared to those housed individually. In B6 mice, mRNA level of the peptide precursor remained unchanged, while that of the receptor was increased by 2-fold under crowding compared to individual housing. No significant changes were detected in 129S2 mice. These findings show that social housing may be important environmental stress factor in mice depending on the strain. The possible involvement of central nociceptin mechanisms in behavioural resilience to social crowding stress is discussed.

Women with symptoms of a urinary tract infection but a negative urine culture: PCR-based quantification of Escherichia coli suggests infection in most cases.

OBJECTIVES: Our objective was to examine whether or not women with symptoms of a urinary tract infection but with a negative culture (20%-30%) do have an infection. METHODS: We performed quantitative PCR (qPCR) for Escherichia coli and Staphylococcus saprophyticus, on top of a standard culture, in urine samples from 220 women with dysuria and/or frequency and/or urgency and from 86 women without symptoms. For symptomatic women, qPCR was also carried out for four sexually transmitted agents. RESULTS: In the symptomatic group, 80.9% (178/220) of the urine cultures were positive for any uropathogen and 95.9% (211/220) were E. coli qPCR-positive. For the control group, cultures for E. coli and E. coli qPCR were positive in, respectively, 10.5% (9/86) and 11.6% (10/86). In the symptomatic group, qPCR yielded 19 positive samples for S. saprophyticus qPCR, one positive sample for Mycoplasma genitalium and one for Trichomonas vaginalis. CONCLUSIONS: These findings suggest that almost all women with typical urinary complaints and a negative culture still have an infection with E. coli.

Decreased brain tryptophan availability as a partial determinant of post-partum blues.

BACKGROUND: The post-partum blues is a transient mood alteration affecting most women a few days after delivery. Its stereotypic pattern of symptoms and time course, peaking on post-partum day 3-5, is suggestive of biological determinants superimposed on psycho-social factors. This study was designed to evaluate the possible role of the serotonin system during this period through assessment of brain tryptophan availability. METHODS: Blood samples from 50 women were collected just before (D0) and 3 days after (D3) delivery. Based on plasma concentration of tryptophan, amino acids competing with tryptophan for transport across the blood-brain barrier and on their respective affinities for this transporter, a brain tryptophan availability index (BTAI) was calculated and its variation correlated with the intensity of post-partum blues evaluated through the Kennerley and Gath score at D3. RESULTS: The BTAI showed a -15% decrease between D0 and D3 (p < 0.01, paired t-test). This decrease was not supported by a drop in plasma tryptophan since its level rather increased (+19%). There was no evidence for change in placental indoleamine-2,3-dioxygenase activity since the variation in plasma l-kynurenine (+12%) paralleled the change in tryptophan level. The decreased BTAI appeared the consequence of a dramatic increase in plasma levels of most amino acids, particularly the competitor aminoacids leucine, isoleucine, valine and tyrosine, during the early post-partum. This decrease in brain tryptophan availability was concomitant to the post-partum blues, whose intensity significantly correlated with the amplitude of BTAI variation (Pearson's coefficient -0.283, p < 0.05). CONCLUSION: This study suggests that generalized, large amplitude metabolic and/or nutritional changes occurring in the early post-partum result in a transient decrease in brain tryptophan availability, partly accounting for the mood alteration referred to as the post-partum blues, a model for the triggering of puerperal mood disorder in vulnerable women.

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.

[Baby blues: characterization and influence of psycho-social factors]. / Le baby blues: caractérisation clinique et influence de variables psycho-sociales.

BACKGROUND: Within days following birth, most women are showing signs of mood changes, commonly named baby blues. Due to the frequency of this condition, baby blues is considered as a physiological state probably associated to biological modifications. Some studies have shown an existing link between the intensity of the baby blues and post-partum mood disorder. Therefore, it seems important to report and explore in more details the clinical background related the condition. The aim of this study was to demonstrate the possibility of a link between the intensity of the baby blues and some specific factors like maternal self-esteem, maternal childcare stress and social background, and also to define the symptoms of the baby blues from core dimensions in mood disorders. METHOD: Mothers were recruited few hours before giving birth in a teaching hospital. At the third day following birth, an appointment was made to obtain the necessary information (past medical history and social history) and history of previous mood disorders. The mood was evaluated from the scale of the intensity of baby blues from Kennerly and Gath (1989). Moreover, evaluations at day 3 and week 6 post birth of self-esteem in relation to motherhood (Maternal self-report Inventory from Shea and Tronick, 1988), stress in relation with the care of the baby (Childcare Stress Inventory from Cutrona, 1983) and the social support (Social Support scale from Bruchon-Schweitzer, 1998) were undertaken. RESULTS: 95 women were included in the final sample. The intensity of the baby blues was explained by the type of pregnancy (p=0.002), a low maternal self-esteem (p=0.025), high levels of stress in relation to the care of the baby (p=0.074). The basic clinical characteristic of the baby blues seems to be due to an increase in the emotional reaction with a sharp feelings, leading to a lability rather than an affect sad tonality. CONCLUSION: The baby blues seems to be a physiological process whereby the intensity is influenced by psychological factors. Consequently the diminution of self-esteem with motherhood and the increase of stress in relation to the care of the baby appeared to be significant factors in the intensity of the baby blues. Moreover, the clinical characteristics found in this study implies that the baby blues is more related to hypomania rather than to depression syndrome. This non-pathological state could be the first stage leading to a puerperal psychosis in predisposed women, which is mainly characterized by manic symptoms.

Clinical outcomes and costs associated with in-hospital biliary complications after liver transplantation: a cross-sectional analysis.

INTRODUCTION: In-hospital biliary complications (BCs) after liver transplantation (LT) are reported in up to 20 % of patients and contribute to poor outcomes and increased costs. Existing single-center outcome and cost analyses studies are limited in scope. METHODS: This is a cross-sectional analysis of national data involving 7,967 patients transplanted between 2011 and 2012 with the primary aim of determining the association between BCs and clinical outcomes and costs. Age, race, diagnosis, and severity of illness are associated with the development of BCs. RESULTS: BCs develop in 14.6 % of LT recipients and have substantial implications for perioperative outcomes, including length of hospital and ICU stay (27.9 vs 19.6 mean days, p < 0.001 and 12.0 vs 8.3 mean days, p < 0.001, respectively), in-hospital morbidity (39 vs 27 %, p < 0.001), 30-day readmissions (14.8 vs 11.2 %, p < 0.001), and in-hospital mortality (5.8 vs 4.0 %, p < 0.001). BCs contributed to a mean increase in in-hospital costs of $36,212 (p < 0.001), due to increases in accommodations ($9,539, p < 0.001), surgical services ($3,988, p < 0.001), and pharmacy services ($8,445, p < 0.001). DISCUSSION: BCs are a predominant etiology for in-hospital morbidity and mortality, while contributing significantly to the high cost of LT. Efforts should be focused on understanding salient and modifiable risk factors, while developing innovative strategies to reduce BCs.

Assessment of mechanisms driving non-linear dose-response relationships in genotoxicity testing.

In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose mechanisms, this review aims to clarify which mechanistic data are required to support the use of non-linear dose-response models in risk assessment. Such key experiments are presented and discussed for alkylating agents, oxidants, particulate matter, nucleoside analogues, topoisomerase inhibitors and aneugens and exemplify the use of gene knockout models or transgenic models as well as chemical modulators of key effectors of relevant pathways and their impact on dose-response relationships. In vitro studies are particularly valuable to elucidate mechanisms of low-dose protection or lack thereof, while in vivo experiments are most appropriate for deriving a safe dose. In order to evaluate the existence of non-linear dose-response relationships for genotoxicants, we suggest that careful attention should be given to the mode of genotoxic action, relevant biomarkers of exposure, as well as to the existence and impact of potential cytoprotective mechanisms like detoxifying metabolism and DNA repair.

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.

Nerve growth factor (NGF) receptor expression in chicken cranial development.

In order to map the expression of receptors for nerve growth factor (NGF) during brain and cranial ganglia development, iodinated NGF (125I beta NGF) was used as a probe in an autoradiographical analysis performed between embryonic day 3 (E3) and posthatching day 3 (P3) of chicken development. Heavy autoradiographic labelling was observed at the classical NGF target sites, the proximal cranial sensory ganglia and the sympathetic superior cervical ganglion, throughout development and after hatching. In contrast, only weak labelling could be detected during a restricted time span in the vestibulocochlear (E4-E8) and the distal cranial sensory ganglia (E4-E10), the neurons of which originate from the otic and epibranchial placodes. Specific 125I beta NGF binding was also observed in various brain regions during early brain development. NGF receptor expression there followed a characteristic pattern. The neuroepithelial layer displayed very low levels of specific 125I beta NGF binding, while strong 125I beta NGF labelling was found in the mantle layer. Brainstem somatomotor nuclei, visceromotor columns, brainstem alar plate, cerebellar anlage, tectum, and basal forebrain (epithalamus, striatum) were found to be transiently labelled by 125I beta NGF in early development (E4-E12). Non-nervous tissues such as parts of the otic vesicle epithelium and skeletal muscle anlagen of the head were also labelled. These results, showing specific binding of 125I beta NGF to cranial cells of different origin (neural tube, neural crest, placode, and possibly mesoderm) strengthen the concept that NGF may have diverse functions in growth and differentiation of various tissues and cell types.

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.

[Effects of methamphetamine and enriched experience on behavioral recovery after brain damage (author's transl)]. / Effets de la méthamphétamine et d'un environnement complexe sur la récupération comportementale aprés atteinte cérébrale

Two factorial experiments (brain status x environment x drug) were designed to measure the effects of methamphetamine and enriched experience on recovery after bilateral cortical lesions. Fisher male rats were operated or sham operated when 30 days old and thereafter raised in either an enriched (EC) or impoverished (IC) condition while daily injected with either methampheteamine (2 mg/kg) or saline. In EC, 12 rats lived together in a large cage with stimulus objects that were changed daily. In IC, a rat was kept alone in a small cage. The animals' performance was measured on a standard series of problems in a Hebb-Williams maze. The animals' scores were impaired by removal of tissue from the occipital cortex. Enriched experience, on the contrary, helped significantly in overcoming, at least partially, the effects of brain damage on problem-solving behavior regardless of whether this experience was given, for 2 h per day over a 60-day period (Expt. 1), or for 2 h per day over only a 30-day period (EXPT. 2). No drug effect was found in any of these experiments.

Nerve growth factor receptors: analysis of the interaction of beta NGF with membranes of chick embryo dorsal root ganglia.

The binding of the beta subunit of Nerve Growth Factor (beta NGF) to membrane preparations of 8-day chick embryo dorsal root ganglia (DRG) has been investigated under conditions similar to those used to study the binding of beta NGF to intact single cell dissociates of DRG. The equilibrium binding data reveal heterogeneityy of binding that is more complex than that seen with intact cells. Binding is not saturable up to 125I beta NGF concentrations of 10(-8) M. Steady-state and kinetic binding data show two sites with dissociation constants similar to those found on DRG cells. In addition, displacement data reveal a binding component with lower affinity (Kd = 10(-6) M) which is not found on intact cells. As with intact cells, the difference in the affinities of the two high affinity sites has been shown to be due to different rate constants of dissociation. The kinetics of dissociation of NGF are slower with membranes than with cells, and dissociation characteristics of 125I beta NGF change with increasing time of exposure to membranes. Degradation of 125I beta NGF during incubation with membranes is minimal and does not complicate the analysis of steady-state binding. Insulin does not bind to either of the two high affinity sites. Heterogeneity of the 125I beta NGF preparation and cooperativity of binding as a cause for the heterogeneity of the binding of NGF has been ruled out. Although there was an apparent increase in the rate of dissociation of 125I beta NGF in the presence of unlabelled NGF, a finding previously interpreted as evidence for negative cooperativity, this was shown to be independent of receptor site occupancy by NGF, and in part due to isotopic dilution within a diffusion barrier around the membranes.

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.