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A Kahn

Publications and source records attributed to A Kahn.

At least 19 recordsLinked to original sources
PubMed2005

Direct determination of the hole density of states in undoped and doped amorphous organic films with high lateral resolution.

We investigate the density of states (DOS) for hole transport in undoped and doped amorphous organic films using high lateral resolution Kelvin probe force microscopy. Measurements are done on field effect transistors made of N,N1-diphenyl-N, N1-bis(1-naphthyl)-1,10-biphenyl-4,4II-diamine undoped or p doped with tetrafluoro-tetracyanoquinodimethane. We determine the DOS structure of the undoped material, including an anomalous peak related to interfaces between regions of different surface potential, the DOS doping-induced broadening, and doping-induced sharp peaks on the main DOS distribution.

Journal Article↗
PubMed2005

Apnea, glial apoptosis and neuronal plasticity in the arousal pathway of victims of SIDS.

Of 27,000 infants whose sleep-wake characteristics were studied under the age of 6 months, 38 died unexpectedly 2-12 weeks after the sleep recording in a pediatric sleep laboratory. Of these infants, 26 died of sudden infant death syndrome (SIDS), and 12 of definitely identified causes. The frequency and duration of sleep apneas were analysed. Sleep recordings and brainstem histopathology were studied to elucidate the possible relationship between sleep apnea and neuropathological changes within the arousal system. Immunohistochemical analyses were conducted using tryptophan hydroxylase (TrypH), a serotonin synthesizing enzyme, and growth-associated phosphoprotein 43 (GAP43), a marker of synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used for apoptosis. The pathological and physiological data were correlated for each infant. In the SIDS victims, statistically significant positive correlations were seen between the number of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apneas (p = 0.03), between the number of TUNEL-positive glial cells in the pedunculopontine tegmental nucleus (PPTN) and the average number of spines in GAP43-positive neurons in the PPTN (p = 0.04). These findings in the dorsal raphe nucleus of the midbrain and PPTN, that play important roles in the arousal pathway suggest a possible link between changes in arousal and SIDS.

Apoptosis↗
PubMed2005

[The pain of the newborn: between reality and perception].

UNLABELLED: A newborn hospitalized in neonatology suffers a lot of painful and fully perceived procedures. However this pain is not enough taken into consideration. There are various reasons for this failure. The objective of our study was to analyze the perception of 3 groups of participants (parents, nurses and doctors) about newborns'pain. We wanted to compare these perceptions with pain scales (EDIN and BBdol scale) and to study their connection with newborn illness severity and mortality risk scores (SNAP and CRIB). POPULATION AND METHOD: We have led a prospective study involving 80 newborns. Questionnaires assessing, with the help of a visual analogic scale, the pains' perception and the efficiency of the treatment of this pain were given to the 3 groups of participants. RESULTS: Parents assessed that their newborn feels an important pain (median: 5/10), that was not correlated with pain scales. Nurses and doctors assessed a lower level of pain (median: 2/10), greatly correlated with the pain scales. Parents assessed that the treatment of pain was better when the newborn was severely ill. The nurses, and even more the doctors, assessed the opposite effect. The nurses appeared to hold an intermediate position between parents and doctors. Nurses underlined moreover some lack of communication of the doctors about the newborns' pain. This communication problem is a major hindrance to the adequate treatment of pain.

Attitude of Health Personnel↗
PubMed2004

Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas.

Although inappropriate activation of the Wnt/beta-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apc(lox/lox), in which exon 14 of the tumor-suppressor gene adenomatous polyposis coli (Apc) is flanked by loxP sequences. i.v. injection of adenovirus encoding Cre recombinase (AdCre) at high multiplicity [10(9) plaque-forming units (pfu) per mouse] inactivated the Apc gene in the liver and resulted in marked hepatomegaly, hepatocyte hyperplasia, and rapid mortality. beta-Catenin signaling activation was demonstrated by nuclear and cytoplasmic accumulation of beta-catenin in the hepatocytes and by the induction of beta-catenin target genes (glutamine synthetase, glutamate transporter 1, ornithine aminotransferase, and leukocyte cell-derived chemotaxin 2) in the liver. To test a long-term oncogenic effect, we inoculated mice with lower doses of AdCre (0.5 x 10(9) pfu per mouse), compatible with both survival and persistence of beta-catenin-activated cells. In these conditions, 67% of mice developed HCC. beta-Catenin signaling was strongly activated in these Apc-inactivated HCCs. The HCCs were well, moderately, or poorly differentiated. Indeed, their histological and molecular features mimicked human HCC. Thus, deletion of Apc in the liver provides a valuable model of human HCC, and, in this model, activation of the Wnt/beta-catenin pathway by invalidation of Apc is required for liver tumorigenesis.

Animals↗
PubMed2003

Child victims of dog bites treated in emergency departments: a prospective survey.

UNLABELLED: The study was conducted to determine the characteristics of child victims of dog bite accidents. Pediatricians and nurses prospectively collected standardized information on all child victims of dog bites brought in for treatment to six hospital emergency departments (three urban university teaching hospitals and three rural hospitals). One hundred completed questionnaires were collected and analyzed. The frequency of dog bites brought for care to the emergency departments was equivalent to about one-quarter of all road traffic casualties and one-third of burns at home. Of the 100 victims, 65 were bitten at home, and 35 in a public place. The bite accidents that occurred at home concerned children with a median age of 5 years, who were without adult supervision at the time of the accident. The children who were bitten by dogs in public places had a median age of 9 years. For 77 bites, the dog was not familiar to the child. Based on the history, it appeared that 56 out of 65 accidents at home and 11 out of 35 in public places resulted mainly from the children's or adult's behavior. CONCLUSION: To reduce the frequency of dog bites both at home and in public places, education could be the preventive measure with the highest priority. Out of 100 accidents, 67 children might not have been bitten had they and their parents been adequately educated on safe conduct towards dogs.

Accidents, Home↗
PubMed2003

Sudden infant deaths: stress, arousal and SIDS.

The prevalence of the Sudden Infant Death Syndrome (SIDS) has dropped in most countries following the development of education campaigns on the avoidance of preventable risk factors for SIDS. These include factors in the infant's micro environment, such as prenatal passive smoking, administration of sedative drugs, prone sleep, high ambient temperature or sleeping with the face covered. Sleep laboratory studies have shown that these risk conditions contribute to the development of respiratory and autonomic disorders and reduce the child's arousability. The opposite effects were seen when studying factors protective from SIDS, such as breastfeeding or the use of a pacifier. In victims of SIDS, similar breathing, autonomic and arousal characteristics were recorded days or weeks before their death. It is concluded that in some infants, already immature control mechanisms can be aggravated by environmental factors.

Arousal↗
PubMed2003

[The use of autogenous block graft for augmentation of the atrophic alveolar ridge].

The use of osseointegrated implants has become a standard treatment option in modern dental rehabilitation. Adequate bone quantity and quality is a prerequisite for good esthetic and biomechanical result. Alveolar ridge defects can be the result of trauma, periodontal diseases or other pathologic conditions. In these cases, alveolar ridge augmentation is needed if endosseous implants are to be used. While xenografts, alloplastic bone grafts and allografts have been proposed for alveolar ridge augmentation, the use of autogenous bone grafts represents the "gold standard" for bone augmentation procedures. Either intraoral or extraoral sites may be considered for donor sites. Although the iliac crest is the most common donor site in maxillofacial reconstruction, the mandibular symphysis or ramus offer important advantages like avoidance of general anesthesia, convenience due to the proximity between the donor site and the augmentation site and avoidance of cutaneous scar. Bone harvested from intraoral donor site is less associated with resorption when compared with iliac bone because membranous grafts revascularize more quickly than endocondral bone grafts. The main disadvantage of the intraoral donor sites is the limited amount of available bone. Alveolar ridge augmentation using autologous bone block, can be done during implant placement or staged with implant placement, after bone graft healing. In the staged technique, a better implant positioning and the use of wide diameter implants are possible. The overall implant success is higher in the staged technique. Alveolar ridge augmentation using autogenous block graft is a predictable way of treatment, for the atrophic alveolar ridge before implant placement.

Alveolar Bone Loss↗
PubMed2002

Sudden infant deaths: from epidemiology to physiology.

The incidence of sudden infant death syndrome (SIDS) has dropped significantly in most countries following the development of education campaigns on the avoidance of risk factors for SIDS. However, questions have been raised about the physiological mechanism responsible for the effects of these environmental risk factors. Since 1985, a series of prospective, multicentric studies have been developed to address these questions; over 20,000 infants were recorded during one night in a sleep laboratory and among these, 40 infants eventually died of SIDS. In this review, the following methods were employed: sleep recordings and analysis, monitoring procedure, data analysis of sleep stages, cardiorespiratory and oxygen saturation, scoring of arousals, spectral analysis of the heart rate and the determination of arousal thresholds, and statistical analysis and the results including sleep apneas, arousals and heart rate and autonomic controls in both future SIDS victims and normal infants were introduced separately. In addition, the physiological effect of prenatal risk factors (maternal smoking during gestation) and postnatal risk factors (administration of sedative drugs, prone sleeping position, ambient temperature, sleeping with the face covered by a bed sheet, pacifiers and breastfeeding) in normal infants were analyzed. In conclusion, the physiological studies undertaken on the basis of epidemiological findings provide some clues about the physiological mechanisms linked with SIDS. Although the description of the mechanisms responsible for SIDS is still far from complete, it appears to involve both arousal responses and cardiac autonomic controls during sleep-wake processes.

Autonomic Nervous System↗
PubMed2002

Muscle as a putative producer of acid alpha-glucosidase for glycogenosis type II gene therapy.

Glycogenosis type II (GSD II) is a lysosomal disorder affecting skeletal and cardiac muscle. In the infantile form of the disease, patients display cardiac impairment, which is fatal before 2 years of life. Patients with juvenile or adult forms can present diaphragm involvement leading to respiratory failure. The enzymatic defect in GSD II results from mutations in the acid alpha-glucosidase (GAA) gene, which encodes a 76 kDa protein involved in intralysosomal glycogen hydrolysis. We previously reported the use of an adenovirus vector expressing GAA (AdGAA) for the transduction of myoblasts and myotubes cultures from GSD II patients. Transduced cells secreted GAA in the medium, and GAA was internalized by receptor-mediated capture, allowing glycogen hydrolysis in untransduced cells. In this study, using a GSD II mouse model, we evaluated the feasibility of GSD II gene therapy using muscle as a secretary organ. Adenovirus vector encoding AdGAA was injected in the gastrocnemius of neonates. We detected a strong expression of GAA in the injected muscle, secretion into plasma, and uptake by peripheral skeletal muscle and the heart. Moreover, glycogen content was decreased in these tissues. Electron microscopy demonstrated the disappearance of destruction foci, normally present in untreated mice. We thus demonstrate for the first time that muscle can be considered as a safe and easily accessible organ for GSD II gene therapy.

Adenoviridae↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

Altered myosin isoform expression in rat skeletal muscles induced by a changed thyroid state.

The aim of our study was to find out, which are the thyroid linked mechanisms responsible for the changes in myosin isoform composition which accompany endurance training (ET) in rodents. We studied the interaction between ET and altered sedentary group with no thyroid treatment or Se group. Six groups of rats were compared: (1) a trained group with no thyroid treatment or T group; (2) a thyroid state in rats; (3) a sedentary group rendered hypothyroid with 6-n-propyl thio uracil (H); (4) a sedentary group rendered hyperthyroid with T3 (150 microg kg(-1) every other day for 4 weeks) (St); (5) trained rats rendered hyperthyroid with T3 (150 microg kg(-1) every other day for 4 weeks) (Tt) and (6) a trained group kept euthyroid with T3 (150 ng kg(-1) every other day for 4 weeks) (Te). In each group myosin isoform composition was determined in five muscles, three locomotor muscles: (1) extensor digitorum longus, (2) superficial lateral gastrocnemius, (3) deep medial gastrocnemius, (4) an antigravity muscle, the soleus and (5) a rhytmic respiratory muscle, the crural diaphragm. Different muscles responded in a specific way to variations of the thyroid state and training.

Animals↗
PubMed2001

Developmental characteristics of apnea in infants who succumb to sudden infant death syndrome.

We compared the breathing characteristics of 40 infants who subsequently died of sudden infant death syndrome (SIDS) with those of 607 healthy infants matched for sex and age. The infants were between 2 and 19 wk old at the time of recording. Compared with the control group, the infants who died of SIDS experienced significantly more frequent episodes of obstructive and mixed sleep apnea. The duration of the apneic episodes did not exceed 15 s. Moreover, the SIDS group had a greater proportion of infants with obstructive and mixed apneic episodes than did the control group. In both groups, the frequency of episodes among male infants with apnea was greater than that among female infants. After the age of 9 wk, the proportion of male infants with episodes of obstructive apnea was greater in the SIDS group than in the control group. The frequency of apneic episodes decreased with age. The rate of decrease was significantly greater in the control subjects than in the SIDS group. This finding was made mainly in male infants. The present study provides further indirect evidence for a slower maturation of respiratory control in some infants who ultimately die of SIDS.

Female↗
PubMed2001

Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene.

Autosomal dominant polycystic kidney disease (ADPKD) is common and is a major cause of renal failure. Although the genetics of ADPKD are well known and have led to the discovery of polycystins, a new protein family, the pathogenesis of the disease remains largely unknown. Recent studies have indicated that the beta-catenin signaling pathway is one of the targets of the transduction pathway controlled by the polycystins. We have generated transgenic mice that overproduce an oncogenic form of beta-catenin in the epithelial cells of the kidney. These mice developed severe polycystic lesions soon after birth that affected the glomeruli, proximal, distal tubules and collecting ducts. The phenotype of these mice mimicked the human ADPKD phenotype. Cyst formation was associated with an increase in cell proliferation and apoptosis. The cell proliferation and apoptotic indexes was increased 4-5-fold and 3-4-fold, respectively, in cystic tubules of the transgenic mice compared to that of littermate controls. Our findings provide experimental genetic evidence that activation of the Wnt/beta-catenin signaling pathway causes polycystic kidney disease and support the view that dysregulation of the Wnt/beta-catenin signaling is involved in its pathogenesis.

Animals↗
PubMed2001

Cancer incidence in New York State acquired immunodeficiency syndrome patients.

To identify cancers that occur at higher rates in acquired immunodeficiency syndrome (AIDS) patients, the cancer experience of New York State (NYS) AIDS patients aged 15-69 years who were diagnosed between 1981 and 1994 was compared with that of the NYS general population. Sex and HIV risk group-specific standardized incidence ratios (SIRs), post-AIDS relative risks, and trends of relative risks were calculated to determine cancer risk. Among non-AIDS-related cancers, elevated SIRs were found for Hodgkin's disease (male, 8.0; female, 6.4; heterosexually infected males, 31.3); cancer of the rectum, rectosigmoid, and anus (male, 3.3; female, 3.0); trachea, bronchus, and lung (male, 3.3; female, 7.5); and brain and central nervous system (male, 3.1; female, 3.4; heterosexually infected females, 23.8) cancers. Moreover, significant trends of increasing relative risks from the pre-AIDS to the post-AIDS period were found for cancers of the rectum, rectosigmoid, and anus; trachea, bronchus, and lung; skin; and connective tissues (all sites, p < 0.05) among males. For AIDS-related cancers in women, invasive cervical cancer had an overall SIR of 9.1 (95% confidence interval: 6.9, 10.8) and a post-AIDS relative risk of 6.5 (95% confidence interval: 4.1, 9.7). This population-based registry linkage analysis evaluates cancer risk in AIDS patients by sex and risk factors and adds evidence that HIV-associated immunosuppression increases the risks of specific types of cancer.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Protective effects of cardiotrophin-1 adenoviral gene transfer on neuromuscular degeneration in transgenic ALS mice.

Amyotrophic lateral sclerosis (ALS) is mainly a sporadic neurodegenerative disorder characterized by loss of cortical and spinal motoneurons. Some familial ALS cases (FALS) have been linked to dominant mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Transgenic mice overexpressing a mutated form of human SOD1 with a Gly93Ala substitution develop progressive muscle wasting and paralysis as a result of spinal motoneuron loss and die at 5 to 6 months. We investigated the effects of neurotrophic factor gene delivery in this FALS model. Intramuscular injection of an adenoviral vector encoding cardiotrophin-1 (CT-1) in SOD1G93A newborn mice resulted in systemic delivery of CT-1, supplying motoneurons with a continuous source of trophic factor. CT-1 delayed the onset of motor impairment as assessed in the rotarod test. Axonal degeneration was slowed and skeletal muscle atrophy was largely reduced by CT-1 treatment. By monitoring the amplitude of the evoked motor response, we showed that the time-course of motor impairment was significantly decreased by CT-1 treatment. Thus, adenovirus-mediated gene transfer of neurotrophic factors might delay neurogenic muscular atrophy and progressive neuromuscular deficiency in ALS patients.

Adenoviridae↗
PubMed2001

Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice.

We previously reported the disruption of the murine gene encoding the transcription factor USF2 and its consequences on glucose-dependent gene regulation in the liver. We report here a peculiar phenotype of Usf2(-/-) mice that progressively develop multivisceral iron overload; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart. In contrast, the splenic iron content is strikingly lower in knockout animals than in controls. To identify genes that may account for the abnormalities of iron homeostasis in Usf2(-/-) mice, we used suppressive subtractive hybridization between livers from Usf2(-/-) and wild-type mice. We isolated a cDNA encoding a peptide, hepcidin (also referred to as LEAP-1, for liver-expressed antimicrobial peptide), that was very recently purified from human blood ultrafiltrate and from urine as a disulfide-bonded peptide exhibiting antimicrobial activity. Accumulation of iron in the liver has been recently reported to up-regulate hepcidin expression, whereas our data clearly show that a complete defect in hepcidin expression is responsible for progressive tissue iron overload. The striking similarity of the alterations in iron metabolism between HFE knockout mice, a murine model of hereditary hemochromatosis, and the Usf2(-/-) hepcidin-deficient mice suggests that hepcidin may function in the same regulatory pathway as HFE. We propose that hepcidin acts as a signaling molecule that is required in conjunction with HFE to regulate both intestinal iron absorption and iron storage in macrophages.

Animals↗
PubMed2001

Bidirectional activity and orientation-dependent specificity of the rat aldolase C promoter in transgenic mice.

We previously reported that the rat aldolase C 115 bp promoter is sufficient to ensure the brain specific expression of the chloramphenicol acetyltransferase reporter gene in transgenic mice. We identify in a further reduced 84 bp promoter several putative binding sites for the transcriptional factors Sp1, USF, AP1, and AP2. Deletion or mutation of these partially overlapping binding sites results in inactivation of the cognate transgenes. Moreover, we show that the 115 bp sequence is able to direct bidirectional transcription in vivo but, surprisingly, transcriptional activity in the opposite direction is no more brain specific.

Animals↗