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O Cohen

Publications and source records attributed to O Cohen.

At least 19 recordsLinked to original sources

Random-phase solitons in nonlinear periodic lattices.

We predict the existence of random phase solitons in nonlinear periodic lattices. These solitons exist when the nonlinear response time is much longer than the characteristic time of random phase fluctuations. The intensity profiles, power spectra, and statistical (coherence) properties of these stationary waves conform to the periodicity of the lattice. The general phenomenon of such solitons is analyzed in the context of nonlinear photonic lattices.

Journal Article↗

Enhanced glucose-dependent glucagon-like peptide-1 and insulin secretion in Crohn patients with terminal ileum disease is unrelated to disease activity or ileal resection.

BACKGROUND: Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been reported in patients with Crohn disease (CD). However, the correlation between the enteropancreatic axis and the activity of CD remains unclear. METHODS: Plasma glucose, insulin, GLP-1 levels and insulin sensitivity were determined before and after oral glucose tolerance tests in 13 patients with CD of the terminal ileum, in 13 patients after resection of the terminal ileum and in 7 healthy controls. Basal and stimulated insulin sensitivities were determined using the homeostasis model assessment (HOMA) and the insulin sensitivity index (ISI) methods, respectively. RESULTS: Basal and stimulated glucose levels were comparable in patients and controls. The peak stimulated GLP-1 secretion was significantly higher in the patient group compared to controls: 12.2 +/- 1.24 pM/L and 8.1 +/- 1.72 pM/L, respectively, P=0.03. This was associated with 52% increased overall insulin secretion in the patients' group as compared to controls (P=0.007) and a higher peak insulin response: 63.5 +/- 9.69 mU/L and 41.5 +/- 6.85 mU/L for patients and controls, respectively, P=0.04. Operated patients had similar GLP-1 levels but higher peak and overall insulin secretions compared with those in non-operated patients (P=0.01). Fasting and stimulated insulin sensitivities were reduced only in patients with ileal resection as compared to controls: P=0.01 and P=0.05, respectively. No correlation was found between the CD activity index and GLP-1 or insulin secretion. CONCLUSIONS: CD of the terminal ileum is associated with enhanced glucose-dependent GLP-1 secretion, which is unrelated to disease activity or ileal resection.

Adult↗

[Ductal carcinoma in situ].

Ductal carcinoma in situ (DCIS) is now found far more frequently because of mammograms, appearing with microcalcifications. Actually, it is probably very common. Premalignant lesions such as ductal carcinoma in situ are demonstrating the truth of a major concept: that there are lesions within the breast that may be locally removed and controlled before the development of metastatic disease. This article, presents the current management of ductal carcinoma in situ.

Breast Neoplasms↗

The clinical impact of 18F-FDG gamma PET in patients with recurrent well differentiated thyroid carcinoma.

The therapeutic approach to recurrent well-differentiated thyroid cancer is based on the detection of active disease. While a measured increase of thyroglobulin level in an ablated patient is highly suggestive of recurrence, localization of the tumour is necessary for adequate treatment planning. A whole body scan with 131I yields false negative results in the presence of non-iodophyllic foci of disease. Hypermetabolic foci of differentiated thyroid carcinoma can be detected by gamma PET with 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG). This study retrospectively evaluated the therapeutic impact of the 18F-FDG scan in patients with suspected recurrent thyroid carcinoma in whom the iodine scan was negative. Twenty patients (five male, 15 female) aged 19-77 years, were suspected of having recurrent thyroid carcinoma due to elevated thyroglobulin levels and/or palpable neck findings. All whole body iodine scans obtained with diagnostic doses (74-148 MBq (2-4 mCi) of 131I), were reported normal, i.e., no iodophyllic foci were detected. Whole body gamma positron emission tomography (PET) imaging was performed in fasting patients following i.v. administration of 370 MBq (10 mCi) 18F-FDG, with a strict 1 h immobilization post-injection. Gamma PET results were validated either by anatomical imaging, repeat iodine scanning after administration of a therapeutic dose (at least 3,700 MBq (100 mCi) of 131I) or surgery. The impact of the FDG scan on patient management was evaluated by the referring physicians. Positive gamma PET results confirmed the presence of active disease in 14/15 patients. One false positive finding (fibrosis) and one false negative (carcinoid) were reported. Localization of hypermetabolic foci supported treatment decisions in 10 patients, and significantly altered therapeutic management in six others. Treatment was withheld in four patients with negative findings. The clinical impact of the scan in this patient group is similar to that reported in the literature and justifies its future implementation.

Adult↗

Use of hormone replacement therapy by menopausal women in six family-practice teaching clinics in Israel.

BACKGROUND: The necessity of hormone replacement therapy (HRT) remains a controversial subject, but guidelines suggest that the subject be discussed with all menopausal women. AIM: To determine the rate of HRT use among women cared for in family-practice, university-affiliated teaching clinics. METHODS: Physicians from six family-practice teaching clinics enrolled all menopausal patients, aged between 50 and 70 years, registered in their practice. A detailed questionnaire was completed regarding demographic and health variables, gynecological history and the nature of HRT use. RESULTS: In total, 682 women were invited to participate in the study; 587 (86%) participated. Some 74% of the women were married, 64% were secular and 43% stated that they performed regular exercise. Current HRT use was reported by 156 women (26.6%). Most women (83%) had been treated for over 1 year. Common indications for starting treatment were hot flushes (75%), and routine recommendation by their physician (68%). Eighty-three (14%) women were past HRT users. It was stated by 45% of never-users that HRT had never been offered to them. Current users of HRT were found to be younger than non-users (mean age 58.2 years vs. 61.5 years, p < 0.0001), more secular than traditional or religious (p < 0.0001) with more years of formal education (p < 0.0001), and more likely to be of Western or European ("Ashkenazi") origin (p < 0.0001). Current HRT users reported fewer chronic illnesses than did non-users (p = 0.001); they were more likely to report being engaged in regular exercise (p < 0.002) and were less likely to be obese (p < 0.005). In a multiple regression model, HRT use was associated with more years of formal education and a secular identity. CONCLUSION: Our study found a higher proportion of women using HRT than in other Israeli studies. HRT use was more prevalent among women with improved health status and higher socioeconomic status. The most common reason given for not using HRT was that a physician had not raised the subject, indicating that physician-related factors might contribute to using HRT. Thus, comparing HRT prescribing rates in non-teaching clinics should clarify this factor.

Aged↗

Neuronal overexpression of "readthrough" acetylcholinesterase is associated with antisense-suppressible behavioral impairments.

Molecular origin(s) of the diverse behavioral responses to anticholinesterases were explored in behaviorally impaired transgenic (Tg) FVB/N mice expressing synaptic human acetylcholinesterase (hAChE-S). Untreated hAChE-S Tg, unlike naïve FVB/N mice, presented variably intense neuronal overexpression of the alternatively spliced, stress-induced mouse "readthrough" mAChE-R mRNA. Both strains displayed similar diurnal patterns of locomotor activity that were impaired 3 days after a day-to-night switch. However, hAChE-S Tg, but not FVB/N mice responded to the circadian switch with irregular, diverse bursts of increased locomotor activity. In social recognition tests, controls displayed short-term recognition, reflected by decreased exploration of a familiar, compared to a novel juvenile conspecific as well as inverse correlation between social recognition and cortical and hippocampal AChE specific activities. In contrast, transgenics presented poor recognition, retrievable by tetrahydroaminoacridine (tacrine, 1.5 mg kg(-1)). Tacrine's effect was short-lived (24 h) suppression of the abnormal social recognition pattern in transgenics. Efficacy of antisense treatment was directly correlated with AChE-R levels and the severity of the impaired phenotype, being most apparent in transgenics presenting highly abnormal pre-treatment behavior. These findings demonstrate that neuronal AChE-R overproduction is involved in various behavioral impairments and anticholinesterase responses, and point to the antisense strategy as a potential approach for re-establishing cholinergic balance.

Acetylcholinesterase↗

Vancomycin versus cefazolin prophylaxis for cardiac surgery in the setting of a high prevalence of methicillin-resistant staphylococcal infections.

OBJECTIVE: This study was undertaken to compare the efficacy of vancomycin prophylaxis with that of cefazolin in preventing surgical site infections in a tertiary medical center with a high prevalence of methicillin-resistant staphylococcal infections. METHODS: All adult patients (> or = 18 years) scheduled for cardiac surgery requiring sternotomy were randomly assigned to receive vancomycin (1 g every 12 hours) or cefazolin (1 g every 8 hours). Prophylaxis was started during the induction of anesthesia and continued for only 24 hours. Patients were followed up for at least 30 days (1 year for those receiving a cardiac implant). Surgical site infections were stratified according to the National Nosocomial Infections Surveillance System risk index. RESULTS: Of the 885 patients included in the study, 452 received vancomycin and 433 received cefazolin. The overall surgical site infection rates were similar in the two groups (43 cases in the vancomycin group, 9.5%, vs 39 cases in the cefazolin group, 9.0%, P =.8). Superficial and deep incisional surgical site infection rates were also similar in the two groups. There was a trend toward more frequent organ-space infections and infections with beta-lactam-resistant organisms among patients receiving cefazolin, but this trend did not reach statistical significance. In contrast, surgical site infections caused by methicillin-susceptible staphylococci were significantly more common in the vancomycin group (17 cases, 3.7%, vs 6 cases, 1.3%, P =.04). The durations of postoperative hospitalization and the mortalities were similar in the two groups. CONCLUSIONS: This trial suggests that vancomycin and cefazolin have similar efficacy in preventing surgical site infections in cardiac surgery.

Adult↗

The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism.

Death-associated protein kinase is a calcium/calmodulin serine/threonine kinase, which positively mediates programmed cell death in a variety of systems. Here we addressed its mode of regulation and identified a mechanism that restrains its apoptotic function in growing cells and enables its activation during cell death. It involves autophosphorylation of Ser(308) within the calmodulin (CaM)-regulatory domain, which occurs at basal state, in the absence of Ca(2+)/CaM, and is inversely correlated with substrate phosphorylation. This type of phosphorylation takes place in growing cells and is strongly reduced upon their exposure to the apoptotic stimulus of C(6)-ceramide. The substitution of Ser(308) to alanine, which mimics the ceramide-induced dephosphorylation at this site, increases Ca(2+)/CaM-independent substrate phosphorylation as well as binding and overall sensitivity of the kinase to CaM. At the cellular level, it strongly enhances the death-promoting activity of the kinase. Conversely, mutation to aspartic acid reduces the binding of the protein to CaM and abrogates almost completely the death-promoting function of the protein. These results are consistent with a molecular model in which phosphorylation on Ser(308) stabilizes a locked conformation of the CaM-regulatory domain within the catalytic cleft and simultaneously also interferes with CaM binding. We propose that this unique mechanism of auto-inhibition evolved to impose a locking device, which keeps death-associated protein kinase silent in healthy cells and ensures its activation only in response to apoptotic signals.

Amino Acid Motifs↗

Effect of chemical modification of recombinant human acetylcholinesterase by polyethylene glycol on its circulatory longevity.

Post-translational modifications were recently shown to be responsible for the short circulatory mean residence time (MRT) of recombinant human acetylcholinesterase (rHuAChE) [Kronman, Velan, Marcus, Ordentlich, Reuveny and Shafferman (1995) Biochem. J. 311, 959--967; Chitlaru, Kronman, Zeevi, Kam, Harel, Ordentlich, Velan and Shafferman (1998) Biochem. J. 336, 647--658; Chitlaru, Kronman, Velan and Shafferman (2001) Biochem. J. 354, 613--625], which is one of the major obstacles to the fulfilment of its therapeutic potential as a bioscavenger. In the present study we demonstrate that the MRT of rHuAChE can be significantly increased by the controlled attachment of polyethylene glycol (PEG) side chains to lysine residues. Attachment of as many as four PEG molecules to monomeric rHuAChE had minimal effects, if any, on either the catalytic activity (K(m)=0.09 mM and k(cat)=3.9 x 10(5) min(-1)) or the reactivity of the modified enzyme towards active-centre inhibitors, such as edrophonium and di-isopropyl fluorophosphate, or to peripheral-site ligands, such as propidium, BW284C51 and even the bulky snake-venom toxin fasciculin-II. The increase in MRT of the PEG-modified monomeric enzyme is linearly dependent, in the tested range, on the number of attached PEG molecules, as well as on their size. It appears that even low level PEG-conjugation can overcome the deleterious effect of under-sialylation on the pharmacokinetic performance of rHuAChE. At the highest tested ratio of attached PEG-20000/rHuAChE (4:1), an MRT of over 2100 min was attained, a value unmatched by any other known form of recombinant or native serum-derived AChE reported to date.

Acetylcholinesterase↗

HC Forum: a web site based on an international human cytogenetic database.

Familial structural rearrangements of chromosomes represent a factor of malformation risk that could vary over a large range, making genetic counseling difficult. However, they also represent a powerful tool for increasing knowledge of the genome, particularly by studying breakpoints and viable imbalances of the genome. We have developed a collaborative database that now includes data on more than 4100 families, from which we have developed a web site called HC Forum (http://HCForum.imag.fr). It offers geneticists assistance in diagnosis and in genetic counseling by assessing the malformation risk with statistical models. For researchers, interactive interfaces exhibit the distribution of chromosomal breakpoints and of the genome regions observed at birth in trisomy or in monosomy. Dedicated tools including an interactive pedigree allow electronic submission of data, which will be anonymously shown in a forum for discussions. After validation, data are definitively registered in the database with the email of the sender, allowing direct location of biological material. Thus HC Forum constitutes a link between diagnosis laboratories and genome research centers, and after 1 year, more than 700 users from about 40 different countries already exist.

Chromosome Aberrations↗

Recurrence of acute disseminated encephalomyelitis at the previously affected brain site.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a usually monophasic demyelinating disorder of the central nervous system. Recurrences pose a diagnostic challenge because they can be overlooked or suggest an alternative diagnosis. OBJECTIVE: To examine the frequency, nature, and outcome of recurrent ADEM. DESIGN: Review of the medical records of patients diagnosed in our institution as having ADEM between January 1, 1983, and May 31, 1998. Recurrences were defined as appearance of new symptoms and signs at least 1 month after the previous episode. RESULTS: Five (24%) of 21 patients with ADEM developed recurrent disease episodes. In all, diagnosis was confirmed by brain biopsy. One patient had 4 disease episodes, 2 had 3, and the other 2 each had 2. Recurrence appeared 1.5 to 32 months after initial presentation and involved the same brain territory in 6 of 9 recurrences in 3 of 5 patients. In 2 patients, recurrences included neuropsychiatric signs. A good response to corticosteroid therapy was observed in 10 of 13 of treated ADEM attacks: in 3 of the 4 treated initial events and in 7 of 9 recurrences. CONCLUSIONS: Recurrent ADEM may be more prevalent than previously recognized. Patients who relapse tend to have more than 1 recurrence that usually involves, clinically and radiologically, a brain territory that was affected before and can simulate a space-occupying lesion that requires histologic diagnosis. Neuropsychiatric features may be the main presentation of a relapse. Since recurrent ADEM is a corticosteroid-responsive condition, awareness and early diagnosis are mandatory.

Adolescent↗

DAP-kinase: from functional gene cloning to establishment of its role in apoptosis and cancer.

DAP-kinase is a pro-apoptotic Ca(2+) calmodulin-regulated serine/threonine kinase that participates in a wide array of apoptotic systems initiated by interferon-gamma, TNF-alpha, activated Fas, and detachment from extracellular matrix. It was isolated by an unbiased functional approach to gene cloning aimed at hitting central mediators of the apoptotic process. This 160 Kd protein kinase is localized to actin microfilaments and carries interesting modules such as ankyrin repeats and the death domain. The death promoting effects of DAP-kinase depend on its intact catalytic activity, the correct intracellular localization, and on the presence of the death domain. A few mechanisms restrain the killing effects of the protein in healthy cells. The enzyme's active site is negatively controlled by an adjacent CaM regulatory domain whose effect is relieved by binding to Ca(2+)-activated calmodulin. A second mode of autoinhibition engages the serine-rich C-terminal tail, spanning the last 17 amino acids of the protein. A link between DAP-kinase and cancer has been established. It was found that the mRNA and protein expression is frequently lost in various human cancer cell lines. Analysis of the methylation status of DAP-kinase's 5' UTR in DNA extracted from fresh tumor samples, showed high incidence of hypermethylation in several human carcinomas and B cell malignancies. The anti-tumorigenic effect of DAP-kinase was also studied experimentally in mouse model systems where the re-introduction of DAP-kinase into highly metastatic mouse lung carcinoma cells who had lost the protein, strongly reduced their metastatic capacity. Thus, it appears that loss of DAP-kinase confers a selective advantage to cancer cells and may play a causative role in tumor progression. A few novel kinases sharing high homology in their catalytic domains with DAP-kinase have been recently identified constituting altogether a novel family of death promoting serine/threonine kinases.

Animals↗

[The influence of the presence of students on the consultation--attitudes of tutors in family medicine clinics].

BACKGROUND: The consultation is the pivot of clinical teaching in ambulatory care. It is therefore essential that students observe the consultation. The students' presence itself influences the consultation and also requires the patients' consent. Moreover the introduction in Israel of the "Patients' Rights Act" in 1996 has made us more acutely aware of the place of the patient in teaching especially with regard to the consent to be part of the teaching process. AIM: This study was undertaken in order to investigate how tutors in family medicine perceive changes in the consultation caused by the presence of students. METHODS: An anonymous physician questionnaire was distributed on the first day of the 6th year clinical clerkship in family medicine. The questions pertained to perceived influence on length and content of the consultation. In addition physician and patient background information was gathered; and the physicians were asked to estimate the patients' willingness to be part of the teaching process. RESULTS: 46 tutors in family medicine participated, 70% of whom were female. Sixty four percent of the doctors thought that the student's presence had an influence on the consultation. Ninety one percent thought that it increased consultation length, especially of the physical part (93%). More than half thought that the student's presence might interfere with asking intimate questions. The majority held the opinion that the patient's gender and socioeconomic background were inconsequential. Ninety two percent of physicians estimated that 5% or less of the patients would refuse the presence of a student. IN CONCLUSION: Tutors in family medicine think that the presence of a student affects the consultation. Those involved in and responsible for teaching should take this into account. Further research of these changes with objective measurements is needed.

Adult↗

Patients' attitudes towards the presence of medical students in family practice consultations.

BACKGROUND: Patients' consent to being part of medical education is often taken for granted, both in primary and secondary care. Formal consent procedures are not used routinely during teaching and patients are not always aware of teaching activities. OBJECTIVE: To investigate patients' attitudes and expectations on issues of consent regarding participation in teaching in general practice, and the influence of a student's presence on the consultation. METHODS: The study took place in 46 teaching practices during the sixth year clinical internship in family medicine. Patients completed questionnaires at the end of 10 consecutive eligible consultations. The questionnaire contained data on the willingness to participate in teaching, the preferred consent procedure and the effects of the student's presence. The doctors were asked to estimate the sociodemographic level in their clinic area. RESULTS: A total of 375 questionnaires were returned; the response rate was not affected by the clinic's sociodemographic level. Overall, 67% of the patients had come into contact with students in the past; 3.2% of the participants objected to the presence of a student during the consultation; 15% would insist on advance notification of the presence of a student, and another 13.9% would request it; 4% stated that the presence of students had a detrimental influence on the physical examination and history; and 33.6% would refuse to be examined by a student without the doctor's presence. CONCLUSION: Most patients agreed to have a student present during the consultation; some would like prior notification; a minority refused the student's presence. A large minority would refuse to be examined without the tutor's presence. Our findings need to be taken into account when planning clinical clerkships.

Attitude to Health↗

Distillation of Greenberger-Horne-Zeilinger states by selective information manipulation.

Methods for distilling Greenberger-Horne-Zeilinger (GHZ) states from arbitrary entangled tripartite pure states are described. These techniques work for virtually any input state. Each technique has two stages which we call primary and secondary distillations. Primary distillation produces a GHZ state with some probability, so that when applied to an ensemble of systems a certain percentage is discarded. Secondary distillation produces further GHZs from the discarded systems. These protocols are developed with the help of an approach to quantum information theory based on absolutely selective information, which has other potential applications.

Information Theory↗

Implantation of rat insulinoma cell line into cyclosporine treated rats. Effect of the in vivo environment on beta-cell specific gene expression.

BACKGROUND: Transplantation of engineered beta cell-derived lines is a promising modality for cell-based therapy of diabetes mellitus. The in vivo environment and antirejection and other medications may have significant effects on the differentiation and proliferation of the transplanted beta cells, thus affecting their function. The effect of the in vivo environment on expression of genes encoding proteins involved in insulin production, secretion, and glucose sensing were analyzed in the RIN 104638 cell line. METHODS: RIN 104638 cells, were used for s.c. implantation in cyclosporine treated rats and for parallel in vitro culture. The differential expression of the insulin, PDX-1, GLUT-2, and glucokinase genes were assessed by quantitative reverse transcription polymerase chain reaction. RESULTS: The in vivo environment of cyclosporine-treated rats, preserved most of the differentiated characteristics of the implanted cells. Insulin and glucokinase gene expression were maintained at high levels, although GLUT-2 expression decreased. This was in contrast to the substantial decrease of all the three genes expression when cultured in vitro. Cyclosporine treatment reduced insulin and GLUT-2 gene expression in in vitro culture. CONCLUSIONS: Beta cell implantation in cyclosporine-treated rats induces alteration in expression of genes pivotal to insulin production and secretion and the glucose sensing abilities. The normal in vivo environment improves the implanted b cell function by increasing the insulin gene expression and content. Furthermore, it reverses some of the dedifferentiating changes caused by the in vitro culture. This may have a positive effect on the therapeutic efficiency of this cell line.

Actins↗

Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases.

Human brain ageing is associated with reductions in a variety of nicotinic receptors subtypes, whereas changes in age-related disorders including Alzheimer's disease or Parkinson's disease are more selective. In Alzheimer's disease, in the cortex there is a selective loss of the alpha4 (but not alpha3 or 7) subunit immunoreactivity and of nicotine or epibatidine binding but not alpha-bungarotoxin binding. Epibatidine binding is inversely correlated with clinical dementia ratings and with the level of Abeta1-42, but not related to plaque or tangle densities. In contrast, alpha-bungarotoxin binding is positively correlated with plaque densities in the entorhinal cortex. In human temporal cortex loss of acetylcholinesterase catalytic activity is positively correlated with decreased epibatidine binding and in a transgenic mouse model over expressing acetylcholinesterase, epibatidine binding is elevated. In Parkinson's disease, loss of striatal nicotine binding appears to occur early but is not associated with a loss of alpha4 subunit immunoreactivity. Tobacco use in normal elderly individuals is associated with increased alpha4 immunoreactivity in the cortex and lower densities of amyloid-beta plaques, and with greater numbers of dopaminergic neurons in the substantia nigra pars compacta. These findings indicate an early involvement of the alpha4 subunit in beta-amyloidosis but not in nigro-striatal dopaminergic degeneration.

Acetylcholinesterase↗