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Biomedical subjects

B Simon

Publications and source records attributed to B Simon.

At least 19 recordsLinked to original sources
PubMed2001

Tumor suppressor genes in the 9p21 gene cluster are selective targets of inactivation in neuroendocrine gastroenteropancreatic tumors.

Functional inactivation of the Rb and p53 pathways appears to be a rite of passage for all cancerous cells. However, p53 and Rb alterations are rare events in neuroendocrine gastroenteropancreatic (GEP) tumors. The CDKN2 locus on chromosome 9p21 sits at the nexus of both pathways harboring tumor suppressor genes, which restrain cell growth by affecting the function of pRb and p53. Therefore, we analyzed the implication of their inactivation in 37 primary neuroendocrine GEP tumors and two cell culture models. RT-PCR analysis revealed loss of expression of at least one of the tumor suppressor genes CDKN2A/p16, CDKN2B/p15, and CDKN2D/p14 with distinct genetic profiles, most frequently in nonfunctional pancreatic tumors (57%) and small intestinal carcinoids (44%), and less commonly in insulinomas (30%) and gastrinomas (22%). DNA analysis and methylation-specific PCR attributed loss of expression to either homozygous deletion or 5'CpG island hypermethylation. 5-Aza-2-deoxycytidine treatment reversed CDKN2A/p16 and CDKN2B/p15 silencing with concurrent growth restraint. Thus, tumor suppressor genes localized in the 9p21 gene cluster are specific targets of inactivation in neuroendocrine GEP tumors, and demethylating agents might hold promise for selective therapy.

Carrier Proteins↗
PubMed2001

Synthesis of ganglioside GD3 and its comparison with bovine GD3 with regard to oligodendrocyte apoptosis mitochondrial damage.

2,3-Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2, which has a phenylthio group on the beta-side of the 3-position for anchimeric assistance and a diethyl phosphite residue as leaving group at the anomeric carbon. The known GM3 intermediate 10 was transformed into the 4b,4c,8c-O-unprotected acceptor 3, which was then allowed to react with 2 by using TMSOTf as catalyst and acetonitrile as solvent to afford the desired tetrasaccharide 12, which has an alpha(2-8)-linkage between two neuraminic acid residues. Removal of the phenylthio group gave intermediate 13, which was transformed into O-tetraosyl trichloroacetimidate 16 as glycosyl donor. Application of the azidosphingosine glycosylation procedure furnished GD3 (1) in high overall yield. Comparison of synthetic GD3 with bovine-brain-derived GD3 showed that there were similar effects in GD3-triggered uncoupling of mitochondrial respiration and in induction of apoptosis in oligodendrocytes.

Animals↗
PubMed2001

Recombinant vaccines against infectious hematopoietic necrosis virus: production by the Caulobacter crescentus S-layer protein secretion system and evaluation in laboratory trials.

We report the development of an IHNV vaccine produced by a new protein production system based on the bacterium Caulobacter crescentus. The subunit vaccines that were tested contain a 184 amino acid segment of the IHNV glycoprotein in different fusion arrangements with the C. crescentus S-layer protein. Relative percent survival of 26 to 34% was demonstrated in rainbow trout fry for a vaccine that contained the 184 amino acid segment of the IHNV glycoprotein fused to the C-terminal one-quarter of the S-layer protein. Inclusion of the universal mammalian T-cell epitopes developed from the measles fusion protein or the tetanus toxin protein did not increase the effectiveness of the IHNV-G/S-layer recombinant protein.

Adjuvants, Immunologic↗
PubMed2001

Calculation of electric fields induced in the human knee by a coil applicator.

Calculations are presented of the induced electric fields and current densities in the cartilage of the knee produced by a coil applicator developed for applying pulsed magnetic fields to osteoarthritic knees. This applicator produces a sawtooth-like magnetic field waveform composed of a series of 260-micros pulses with a peak to peak magnitude of approximately 0.12 mT in the cartilage region. The simulations were performed using a recently developed 3 dimensional finite difference frequency domain technique for solving Maxwell's equations with an equivalent circuit model. The tissue model was obtained from the anatomically segmented human body model of Gandhi. The temporal peak electric field magnitude was found to be -153 mV/m, averaged within the medial cartilage of the knee for the typical dB/dt excitation levels of this coil. The technique can be extended to analyze other excitation waveforms and applicator designs.

Bone and Bones↗
PubMed2001

Prognostic histological and immune markers of renal cell carcinoma.

Recent development on the fields of molecular genetics and immunology of human renal cell carcinoma (RCC) have resulted in more successful treatment of advanced and metastatic RCCs. Re-evaluation of the prognostic/predictive data aim the initial tumor staging of RCC patients to achieve better patient selection for immune and gene therapy. 125 RCC patients diagnosed according to the Heidelberg histological classification, graded, Robson staged, immune treated (Interferon-a a+ Vinblastine or Broncho-Waxom/Decaris) were followed-up clinically for 36 months. Tumor immunity markers by immunohistochemistry of tumor infiltrating lymphocytes (TIL) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (TIC) were visualized by fluorescent polyclonal antibodies. Histologically oncocytomas defined a better (p<0.02) and sarcomatous RCCs a worse (p<0.01) follow-up prognosis. Basically, the metastatic status (related with the stage and grade) determined the clinical outcome (p<0.00002) of the RCC patients. Tumoral immune complexes (TIC) were weak positive, while tumor infiltrating lymphocytes (TIL) weak negative predictors of the succes of Broncho-Waxom/Decaris immune therapy. Molecular genetic based histological classification, grade, stage and metastatic status parameters together with some tumor immunity parameters (TIL, TIC) can predict the success of immunotherapy of RCC patients.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Predictive genetic screening and clinical findings in multiple endocrine neoplasia type I families.

Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly inherited condition. To establish the basis for predictive family screening we evaluated the spectrum of MEN1 gene mutations in MEN-I patients treated at our institution. Relatives at risk were subjected to predictive genetic screening after genetic counseling. Gene carriers were subjected to extensive clinical screening for MEN-I, including biochemical tests for basal hormone concentrations in blood and urine, a standardized meal stimulation test and imaging procedures (ultrasonography, computed tomography, magnetic resonance imaging). Among index patients of 15 independent MEN-I kindreds, 14 heterozygous MEN1 germline mutations were identified by single-strand conformational variant analysis (SSCV) and direct DNA sequence analysis. Of 51 individuals at risk, 26 predictively tested relatives with the wild-type MEN1 gene could be excluded from further screening procedures because they had not inherited the disease. In all previously presumed unaffected relatives with the mutant gene, our extensive clinical screening program revealed at least one manifestation of MEN-I. Furthermore, 22 additional diagnoses could be established in identified MEN-I patients. We show that mutation analysis enables predictive genetic screening for MEN-I families, providing a valuable tool for genetic counseling and clinical management. An extensive clinical screening program focusing on genetically proven individuals at risk allows detection of MEN-I manifestations at an early, asymptomatic stage of the disease. Controlled, prospective studies are now required to prove whether timely appropriate treatment on the basis of predictive screening might help improve disease-related quality of life and prolong life expectancy in MEN-I kindreds.

DNA Mutational Analysis↗
PubMed2001

A TROSY relayed HCCH-COSY experiment for correlating adenine H2/H8 resonances in uniformly 13C-labeled RNA molecules.

A new TROSY relayed HCCH-COSY pulse sequence is introduced for correlating adenine H2 and H8 resonances in 13C-labeled RNA molecules. The pulse scheme provides substantial improvements in signal-to-noise compared to previously suggested experiments, and therefore will be suitable for NMR studies of larger RNA molecules. The experiment provides 13C chemical shifts for all carbon nuclei in the adenine base. This is advantageous for resolving spectral overlap in larger RNA molecules and provides a starting point for measuring additional parameters for these carbons in the adenine spin system.

Adenine↗
PubMed2001

Pediatric minor head trauma: indications for computed tomographic scanning revisited.

BACKGROUND: Although the use of computed tomographic (CT) scanning in severe head trauma is an accepted practice, the indications for its use in minor injury remain ill defined and subjective. We sought to define the incidence and identify risk factors for intracranial injury (ICI) after minor head trauma in children who did not have suspicious neurologic symptoms in the field or on presentation. METHODS: From January 1, 1992, until April 1, 2000, 569 blunt trauma patients (age < 16 years) with a Glasgow Coma Scale score of 14 or 15 triaged by American College of Surgeons Pediatric Mechanism Criteria at a Level I trauma center received head CT scan. Loss of consciousness (LOC) status was known for 429. This subgroup was retrospectively reviewed for mechanism, age, Injury Severity Score, LOC status, GCS score, associated injuries, and CT scan findings (normal, fracture only, or intracranial injury). Relative risk values for intracranial injury were generated and statistical significance was assessed. RESULTS: Fourteen percent (62 of 429) of study patients (GCS score of 14 and 15) had ICI. Sixteen percent of patients (35 of 215) with GCS score of 15 and (-)LOC (negative for LOC) had intracranial injury manifesting as subdural hematoma, epidural hematoma, subarachnoid hemorrhage, or brain contusion. Three required surgery for intracranial mass lesions. One patient deteriorated and required intubation and intensive care unit management. Neither (+)LOC (positive for LOC) nor GCS score of 14 increased the likelihood of intracranial injury over those patients without loss of consciousness or with GCS score of 15. Distant injury was also not an independent predictor of ICI for those with GCS scores of 14 or 15, as 84% of the ICI group had head injury only. Skull fracture was a risk factor for ICI but had poor negative predictive value, as 45% of patients with ICI did not have fractures. Similarly, minor craniofacial soft tissue trauma was a significant risk factor (relative risk, 11) that had marginal negative predictive value (0.95), as 14% (9 of 62) of ICI patients did not have superficial craniofacial injury. CONCLUSION: A normal neurologic exam and maintenance of consciousness does not preclude significant rates of intracranial injury in pediatric trauma patients. Contrary to convention, neither LOC nor mild altered mentation is a sensitive indicator with which to select patients for CT scanning. Skull fractures and superficial craniofacial injury are similarly unreliable. Identification of these patients is important for the occasional case requiring intervention and for the tracking of complications. A liberal policy of CT scanning is warranted for pediatric patients with a high-risk mechanism of injury despite maintenance of normal neurologic status in the field and at hospital screening.

Adolescent↗
PubMed2001

Epidemiological trends in pancreatic neoplasias.

Primary prevention is the most effective approach to reduce the incidence of pancreatic cancer. Epidemiological studies have contributed to the identification of risk factors for pancreatic cancer, suggesting an association with age, various medical conditions, environmental and lifestyle risk factors, and occupational and genetic conditions. Age is the strongest risk factor. The most consistently identified environmental risk factor is smoking, but there is less certainty concerning dietary factors. Studies have suggested a positive association with high energy intake, cholesterol and meat, while vegetable and fruit intakes are probably protective. Patients with chronic pancreatitis and new onset of diabetes mellitus have a low but increasing risk of having or developing pancreatic cancer. There is strong evidence for the association of hereditary pancreatitis or cystic diseases of the pancreas and pancreatic cancer. A family history of pancreatic cancer is an important risk factor, but only a small proportion can be linked with known familial cancer syndromes. Thus, additional yet unidentified predisposing risk factors have to be assumed.

Adult↗
PubMed2001

Politicized collective identity. A social psychological analysis.

This article develops a social psychological model of politicized collective identity that revolves around 3 conceptual triads. The 1st triad consists of collective identity, the struggle between groups for power, and the wider societal context. It is proposed that people evince politicized collective identity to the extent that they engage as self-conscious group members in a power struggle on behalf of their group knowing that it is the more inclusive societal context in which this struggle has to be fought out. Next, 3 antecedent stages leading to politicized collective identity are distinguished: awareness of shared grievances, adversarial attributions, and involvement of society at large. This sequence culminates in the final triad because the intergroup power struggle is eventually triangulated by involving society at large or representatives thereof. Consequences of politicized collective identity are discussed.

Group Processes↗
PubMed2001

Genetic repeat polymorphism in the regulating region of CYP2E1: frequency and relationship with enzymatic activity in alcoholics.

BACKGROUND: Differences in the regulatory region of the CYP2E1 gene could be responsible for the interindividual variation in the cytochrome P-450 2E1 (CYP2E1) involved in ethanol oxidation. Recently, a polymorphic repeat sequence in the human gene was described between -2178 and -1945 base pairs. Its frequency seemed to vary among different ethnic populations, and it was suspected to be related to an increased inducibility to further ethanol intake. In the study reported here, the frequency of this polymorphism was investigated in a white French population. Its relationship with the previously described PstI/RsaI or DraI CYP2E1 polymorphisms, alcoholism, alcoholic liver disease, and inducibility of CYP2E1 by ethanol was examined. METHODS: The polymorphic region was characterized by polymerase chain reaction in 103 controls, 148 alcoholic subjects without liver diseases, and 98 others with liver cirrhosis. By using in vivo chlorzoxazone (CHZ) metabolism, CYP2E1 phenotype was assessed in 36 non-ethanol-induced subjects (17 controls and 19 withdrawn alcoholics) and in 14 ethanol-induced subjects (10 controls after ingestion of 0.8 g/kg ethanol and four alcoholics with 100 g of daily intake). This phenotype was expressed as the 6-hydroxy CHZ/CHZ ratio. RESULTS: The rare allele frequency was found to be 1.58% in whites (n = 349). Neither significant association with alcoholism or alcoholic liver diseases, nor relationship with the PstI/RsaI polymorphism, was observed. But the DraI polymorphism was more frequent among the heterozygous subjects when compared with wild-type homozygous ones (p < 0.05). The CYP2E1 phenotype was similar in wild-type homozygotes and in heterozygotes at the constitutive level, as well as after induction with ethanol. CONCLUSIONS: Our data suggest that CYP2E1 repeat polymorphism does not seem to constitute a major factor for interindividual differences in CYP2E1 expression and susceptibility to alcohol-related disorders in whites.

Adult↗
PubMed2001

Individuality and group formation: the role of independence and differentiation.

This research examined the interplay of group formation and individualization processes with a particular emphasis on minority and majority groups. First, a 2-component theory of individuality that distinguishes between individuality as independence and as differentiation from other people was presented, tested, and cross-validated in 2 questionnaire studies. Next, a pilot experiment provided first support for the working assumption that the salience of the differentiation or independence components of individuality differentially affect minority and majority group formation. Finally, the main experiment demonstrated that these individuality effects on minority and majority group formation are due largely to a differential orientation toward either intergroup or intragroup comparisons. This experiment also uncovered a unique effect of relative in-group size, but this effect was limited to similarity-based group formation.

Adolescent↗
PubMed2000

Induction of mucosal and systemic antibody specific for SeMF3 of Streptococcus equi by intranasal vaccination using a sucrose acetate isobutyrate based delivery system.

Streptococcus equi causes equine strangles, a highly contagious disease of the upper respiratory tract. The antiphagocytic surface protein SeM is strongly immunogenic and evokes mucosal and systemic antibodies during convalescence. The present study investigated the potential of sucrose acetate isobutyrate (SAIB); a high viscosity excipient that provides controlled release of biologically active substances, to enhance antibody responses following intranasal immunization of horses with a 108 a.a. peptide of SeM (SeMF3). SeMF3-SAIB was administered intranasally to each of the 11 adult horses on days 0 and 28. A second group of seven horses was vaccinated with SeMF3 alone. SAIB enhanced the mucosal and systemic immunogenicity of SeMF3, whereas SeMF3 by itself stimulated only a shortlived mucosal IgA and no systemic response. Moreover, nasal mucosal responses of horses immunized with SeMF3-SAIB were qualitatively and quantitatively similar to those observed in convalescent horses and involved similar linear epitopes of SeM. Epitope analysis also suggested that the nasal response was different from that observed in serum. A booster response was obtained after the second vaccination. These results suggest that SAIB has potential as a vehicle for intranasal immunization of horses with antigenic peptides.

Administration, Intranasal↗
PubMed2000

Pulsed electromagnetic field stimulation of MG63 osteoblast-like cells affects differentiation and local factor production.

Pulsed electromagnetic field stimulation has been used to promote the healing of chronic nonunions and fractures with delayed healing, but relatively little is known about its effects on osteogenic cells or the mechanisms involved. The purpose of this study was to examine the response of osteoblast-like cells to a pulsed electromagnetic field signal used clinically and to determine if the signal modulates the production of autocrine factors associated with differentiation. Confluent cultures of MG63 human osteoblast-like cells were placed between Helmholtz coils and exposed to a pulsed electromagnetic signal consisting of a burst of 20 pulses repeating at 15 Hz for 8 hours per day for 1, 2, or 4 days. Controls were cultured under identical conditions, but no signal was applied. Treated and control cultures were alternated between two comparable incubators and, therefore, between active coils; measurement of the temperature of the incubators and the culture medium indicated that application of the signal did not generate heat above the level found in the control incubator or culture medium. The pulsed electromagnetic signal caused a reduction in cell proliferation on the basis of cell number and [3H]thymidine incorporation. Cellular alkaline phosphatase-specific activity increased in the cultures exposed to the signal, with maximum effects at day 1. In contrast, enzyme activity in the cell-layer lysates, which included alkaline phosphatase-enriched extracellular matrix vesicles, continued to increase with the time of exposure to the signal. After 1 and 2 days of exposure, collagen synthesis and osteocalcin production were greater than in the control cultures. Prostaglandin E2 in the treated cultures was significantly reduced at 1 and 2 days, whereas transforming growth factor-beta1 was increased; at 4 days of treatment, however, the levels of both local factors were similar to those in the controls. The results indicate enhanced differentiation as the net effect of pulsed electromagnetic fields on osteoblasts, as evidenced by decreased proliferation and increased alkaline phosphatase-specific activity, osteocalcin synthesis, and collagen production. Pulsed electromagnetic field stimulation appears to promote the production of matrix vesicles on the basis of higher levels of alkaline phosphatase at 4 days in the cell layers than in the isolated cells, commensurate with osteogenic differentiation in response to transforming growth factor-beta1. The results indicate that osteoblasts are sensitive to pulsed electromagnetic field stimulation, which alters cell activity through changes in local factor production.

Alkaline Phosphatase↗
PubMed2000

Strategies to optimize CAD prevention in modern cardiology. The "Marburg CAD Prevention Project".

In recent years we identified numerous cardiovascular risk factors and had been able to reduce cardiovascular events by a variety of different interventions. There is no question that we can improve the course of coronary artery disease (CAD) in patients with a high-risk profile by modifying these factors. Despite this knowledge, many patients with known CAD or myocardial infarction are not treated for secondary prevention as recommended by well established guidelines (http:¿www.chd-taskforce.com). In order to improve secondary prevention in our patients we started a project, the so called "Marburg CAD Prevention Project". By this we combine our computer data base of the CAD preventional routine laboratory with the computer program CARDDAS. Individual risk factors and the angiographic findings were analyzed. Patients as well as local physicians were informed on the need to treat the important risk factors. This approach ensures that at least all of our patients with documented CAD receive the appropriate preventional recommendations and treatment.

Adolescent↗
PubMed2000

Restenosis after percutaneous coronary interventions and infection.

Infectious agents may directly or indirectly (through the response of the host's immune system) modulate the growth of vascular cells. Local and/or systemic increase of cytokines could influence the extent of (re-)stenosis in the vascular tree. Further studies in this field may identify patients at a high risk for atherogenesis and restenosis. Their results should be helpful in treating restenosis after percutaneous coronary interventions.

Angioplasty, Balloon, Coronary↗
PubMed2000

Management of nonfunctioning islet cell carcinomas.

Tumors arising from the pancreatic islet cells are rare and represent a heterogeneous group of benign or malignant lesions. Most tumors present with well characterized syndromes, whereas others appear to be nonfunctioning. The clinical features of 11 men and 7 women with nonfunctioning islet cell carcinomas operated on between 1983 and 1998 were reviewed. The median patient age was 53.5 years (range 26-74 years). The most frequent presenting symptoms were abdominal pain (13 patients), weight loss (7 patients), and obstructive jaundice (4 patients). Gut hormone profiles were normal in all patients. Abdominal sonography and computed tomography localized the tumor in 17 patients, and correct prediction of an endocrine tumor was achieved in 12 patients. Six of seven patients showed a hypervascular tumor upon angiography, and seven of eight patients preoperatively had positive somatostatin receptor scintigraphy. At operation, regional or distant metastases were present in 15 (83%) and 6 (33%) patients, respectively. Eleven patients underwent potentially curative resections, and the remaining seven patients were managed palliatively by resection (four patients) or bypass procedures (three patients). Three patients had up to three more resection for metastases. Eight patients received postoperative octreotide, interferon alpha therapy, or both. The overall cumulative 5- and 10-year survival rates were 65.4% and 49.1%, respectively. Of the 11 patients who underwent curative resection, 10 were alive after a median follow-up of 63 months (range 7-180 months), but only 5 are free from disease. Although surgical cure is rare in nonfunctioning islet cell carcinomas, significant long-term palliation can be achieved in a large proportion of patients with an aggressive surgical approach and, when indicated, additional medical therapy.

Adult↗