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Biomedical subjects

G Berger

Publications and source records attributed to G Berger.

At least 19 recordsLinked to original sources

HPA axis functioning associated with transition to psychosis: combined DEX/CRH test.

We investigated functioning of the hypothalamic-pituitary-adrenal (HPA) axis in 12 young people at ultra high risk for developing psychosis, using the combined dexamethasone corticotrophin releasing hormone (DEX/CRH) test. Over a two year period, three of the 12 participants developed an acute psychosis. Descriptive analysis of the data indicated that contrary to expectations, participants who did not make the transition to psychosis had on average higher cortisol levels at the latter stages of the test, as well as a greater severity of depression and anxiety symptoms, than participants who subsequently developed psychosis. These preliminary results suggest that dysregulated HPA-axis functioning in individuals at high risk for psychosis may be associated more with comorbid depression symptoms than factors specifically related to the process of emerging psychosis illness.

Acute Disease↗

Clinical features, classification and prognosis of migraine and tension-type headache in children and adolescents: a long-term follow-up study.

We performed a long-term follow-up examination in children and adolescents with migraine and tension-type headache (TTH) in order to investigate the evolution of clinical features and headache diagnoses, to compare International Classification of Headache Disorders (ICHD)-I and ICHD-II criteria and to identify prognostic factors. We re-examined 227 patients (52.4% female, age 17.6 +/- 3.1 years) 6.6 +/- 1.6 years after their first presentation to a headache centre using identical semistructured questionnaires. Of 140 patients initially diagnosed with migraine, 25.7% were headache free, 48.6% still had migraine and 25.7% had TTH at follow-up. Of 87 patients with TTH, 37.9% were headache free, 41.4% still had TTH and 20.7% had migraine. The number of subjects with definite migraine was higher in ICHD-II than in ICHD-I at baseline and at follow-up. The likelihood of a decrease in headache frequency decreased with a changing headache location at baseline (P < 0.0001), with the time between baseline and follow-up (P = 0.0019), and with an initial diagnosis of migraine (P = 0.014). Female gender and a longer time between headache onset and first examination tended to have an unfavourable impact. In conclusion, 30% of the children and adolescents presenting to a headache centre because of migraine or TTH become headache-free in the long-term. Another 20-25% shift from migraine to TTH or vice versa. ICHD-II criteria are superior to those of ICHD-I in identifying definite migraine in children and adolescents presenting to a headache centre. The prognosis is adversely affected by an initial diagnosis of migraine and by changing headache location, and it tends to be affected by an increasing time between headache onset and first presentation.

Adolescent↗

Bioceramics composition modulate resorption of human osteoclasts.

Biomaterials used in bone regeneration are designed to be gradually resorbed by the osteoclast and replaced by new bone formed through osteoblastic activity. The aim of the present study is to analyze the role of osteoclasts in the resorption process. The attachment of human osteoclasts and the appearance of their resorption lacunae, when cultured on either the resorbable crystalline, calcium orthophosphate materials or on the long-term stable bioceramic material was investigated. The resorbable materials contain Ca10[K,Na](PO4)7 (AW-Si) and Ca2KNa(PO4)2 (GB14, GB9 & D9/25) as their main crystal phases, however they differ in their total solubility. These differences result from small variations in the composition. The long-term stable material consist of about 30% fluorapatite beside calcium zirconium phosphate (Ca5(PO4)3F + CaZr4(PO4)6) and shows a very small solubility. AW-Si has an alkali containing crystalline phase, Ca10[K,Na](PO4). While GB14, GB9 and D9/25 contain the crystalline phase Ca2KNa(PO4)2 with small additions of crystalline and amorphous diphosphates and/or magnesium potassium phosphate (GB14). D9/25 and AW-Si is less soluble compared to GB14, and GB9 among the resorbable materials. Resorbable and long-term stable materials vary in their chemical compositions, solubility, and surface morphology. Osteoclasts modified the surface in their attempts to resorb the materials irrespective of the differences in their physical and chemical properties. The depth and morphology of the resorption imprints were different depending on the type of material. These changes in the surface structure created by osteoclasts are likely to affect the way osteoblasts interact with the materials and how bone is subsequently formed.

Biocompatible Materials↗

Impaired niacin sensitivity in acute first-episode but not in multi-episode schizophrenia.

Niacin (vitamin B3) flushing--a marker of altered prostaglandin signaling--is indirectly linked to the phospholipid-prostaglandin metabolism. Diminished skin flushing was repeatedly found in schizophrenia, but has not been systematically investigated at different stages of disorder as yet. We compared niacin sensitivity of 32 first-episode and 32 multi-episode patients (mainly on stable medication) with age and gender matched healthy controls. Methylnicotinate was applied in three concentrations onto the inner forearm skin. Flush response was assessed in 3 min intervals over 15 min using optical reflection spectroscopy. Whereas first-episode patients showed significantly diminished flush response as compared to controls, comparable differences were not found between multi-episode patients and controls. Comparison of niacin sensitivity at different stages of schizophrenia support the notion of altered prostaglandin signaling primarily at the onset of disorder. Longitudinal studies have to rule out possible long-term effects of neuroleptic medication.

Acute Disease↗

Colon perforation in an adolescent after short-term diclofenac intake.

Chronic intake of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to cause side-effects distal to the duodenum. These include strictures, diaphragm-like lesions and perforations of the small and large intestines. This is the first case report on colon perforation occurring in an adolescent (16-year-old girl) after short-term diclofenac intake.

Adolescent↗

Improvement in 5-fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) concentration by 5-fluorouracil-polyethylene-glycol-liposomes in abdominal stop-flow: treatment of VX2 liver-tumor-bearing rabbits.

The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration. In abdominal stop-flow therapy, a separate partial circulation with a defined flow is realized via a roller pump under hypoxic conditions. Forty chinchilla rabbits with VX-2 liver tumors were treated either intra-aortally (stop-flow therapy) or systemically with 50 mg 5-FU or 5-FU-PEG liposomes. During therapy, pH and pO2 were measured at regular intervals. After 20 minutes, concentrations of 5-FU and its metabolite FdUrd were determined by HPLC in different organs and the liver tumor. Compared to the i.v. application of monosubstances, the combination of i.a. 5-FU-PEG liposomes and flow retardation increased the concentration in tumor tissue by a factor of 44 and even 100-fold in the para-aortal lymph nodes (LN). The concentration of 5-FU and FdUrd was increased by flow reduction, intraaortal application and liposomal encapsulation of 5-FU.

Animals↗

Effect of rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins in vitro.

The use of biodegradable bone substitutes is advantageous for alveolar ridge augmentation because it avoids second-site surgery for autograft harvesting. This study examines the effect of novel, rapidly resorbable calcium phosphates and a calcium phosphate bone cement on the expression of bone-related genes and proteins by human bone-derived cells (HBDCs) and compares this behavior to that of tricalciumphosphate (TCP). Test materials were alpha-TCP, two materials with a crystalline phase Ca(2)KNa(PO(4))(2) and with a small amorphous portion containing either magnesium potassium phosphate (material denominated GB14) or silica phosphate (material denominated GB9), and a calcium phosphate bone cement (material denominated Biocement D). HBDCs were grown on the substrata for 3, 7, 14, and 21 days, counted, and probed for various mRNAs and proteins (type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase, and bone sialoprotein). All substrates supported continuous cellular growth for 21 days. In the presence of GB14 and Biocement D specimens cell proliferation was reduced and cell differentiation increased. At day 21, the greatest number of cells was found on GB9 expressing significantly higher levels of bone-related proteins than cells grown on all other surfaces. Because all novel materials facilitated the expression of the osteoblastic phenotype at least as much as TCP and the polystyrene control, these biomaterials can be regarded as excellent candidate bone substitute materials. GB9 induced the highest proliferation and cellular differentiation after 21 days of incubation, suggesting that this material may possess a higher potency for enhancing osteogenesis than TCP.

Adolescent↗

The modulation of osteogenesis in vitro by calcium titanium phosphate coatings.

Calcium phosphate coated titanium and titanium alloy are widely used as dental and orthopaedic implants. This study examines the effect of novel calcium titanium and calcium titanium zirconium phosphates suitable for plasma-spraying onto titanium substrata on the expression of bone-related genes and proteins by human bone-derived cells (HBDC) and compares this behavior to that on native titanium and hydroxyapatite-coated titanium. Test materials were an acid etched and sand-blasted titanium surface (Ti-DPS), a plasma-sprayed hydroxyapatite coating (HA), and five materials which were created from CaTi(4)(PO(4))(6) (CTP) and CaZr(4)(PO(4))(6) (CZP): sintered CaTi(4)(PO(4))(6) (CTP-S1), sintered 46CaO.23TiO(2).31P(2)O(5) (CTP-S2), sintered CaTiZr(3)(PO(4))(6), (CTZP-S1), sintered 46CaO.23ZrO(2).31P(2)O(5) (CTZP-S2) and sintered 55CaO.20TiO(2).31P(2)O(5) (CTP-S3). HBDC were grown on the substrata for 3, 7, 14 and 21 d, counted and probed for various mRNAs and proteins (type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase and bone sialoprotein). All substrates significantly affected cellular growth and the temporal expression of an array of bone-related genes and proteins. At 14 and 21 d, cells on CTP-S3 displayed significantly enhanced expression of all osteogenic mRNAs. Surfaces of CTP-S1 and CTP-S3 had the most effect on osteoblastic differentiation inducing a greater expression of an array of osteogenic markers than recorded for cells grown on Ti-DPS and HA, suggesting that these novel materials may possess a higher potency to enhance osteogenesis.

Alkaline Phosphatase↗

Hypotheses on a germline origin of antibody diversity. Possible applications: improvement of the efficiency of immune response and autoimmune disease treatment.

In this paper, the antibody reaction is supposed to be due to the combination of a limited number of different antibodies against the epitopes of the antigen. In addition, the efficient part of the epitopes of proteins is assumed to be the size of dipeptides. The 400 different dipeptides would be distributed in two sets, those which are foreign to the host, against which would be directed antibodies, and those which are present in the proteins of the self, which would elicit no reaction. Each chain of the antibodies would recognise one aminoacid and 40 genes would be sufficient (20 for the light chains and 20 for the heavy chains) to code for the variable parts of the immunoglobulins against proteic antigens. With these hypotheses, the combination of antibodies against at least four different epitopes of the size of dipeptides can account for the main characteristics of the antibody reaction: response against any foreign proteic antigen and specificity. In fact, the epitopes have been found to be larger than dipeptides, several additional aminoacids are involved in the antibody-binding sites. Somatic mutations and VDJ recombinations are selected to give the maximal affinity for the antigens. However, these mechanisms have not been shown to create different specificities from the same V genes. Moreover, the phenomenon of heteroclisis and the decrease, due to mutations, of antigen-binding capacity of antibodies, sometimes observed, are better explained by the model proposed here than by the classical theory. The modification of the epitope subset of the self, by intrathymic injection of antibodies against particular pathogens, is proposed to improve the immune response when microorganisms develop immune escape mechanisms. On the other hand, in the case of autoimmune diseases, the displacement of autoantibodies against self-epitopes could be carried out by the injection into the thymus of specific anti-idiotypic antibodies.

Adjuvants, Immunologic↗

The functional expression of human bone-derived cells grown on rapidly resorbable calcium phosphate ceramics.

The use of biodegradable bone substitutes is advantageous for alveolar ridge augmentation, since it avoids second-site surgery for autograft harvesting. This study examines the effect of novel, rapidly resorbable calcium phosphates on the expression of bone-related genes and proteins by human bone-derived cells (HBDC) and compares this behavior to that of tricalciumphosphate (TCP). Test materials were alpha-TCP, and four materials which were created from beta-Rhenanite and its derivatives: R1-beta-Rhenanite (CaNaPO(4)); R1/M2 composed of CaNaPO(4) and MgNaPO(4); R1+SiO(2) composed of CaNaPO(4) and 9% SiO(2) (wt%); and R17-Ca(2)KNa(PO(4))(2). HBDC were grown on the substrata for 3, 5, 7, 14 and 21 days, counted and probed for various mRNAs and proteins (Type I collagen, osteocalcin, osteopontin, osteonectin, alkaline phosphatase and bone sialoprotein). All substrata supported continuous cellular growth for 21 days. At day 21, surfaces of R1+SiO(2) and R17 had the highest number of HBDC. At 14 and 21 days, cells on R1 and on R1+SiO(2) displayed significantly enhanced expression of all osteogenic proteins. Since all novel calcium phosphates supported cellular proliferation together with expression of bone-related proteins at least as much as TCP, these ceramics can be regarded as potential bone substitutes. R1 and R1+SiO(2) had the most effect on osteoblastic differentiation, thus suggesting that these materials may possess a higher potency to enhance osteogenesis than TCP.

Bone Substitutes↗

Intra-aortal therapy with 5-fluorouracil- polyethylene glycol stealth liposomes: does the metabolism of 5-fluorouracil into 5-fluoro-2'-deoxyuridine depend on ph value?. An animal study in VX-2 liver tumor-bearing rabbits.

BACKGROUND: The application of liposome-encapsulated cytostatics results in higher concentrations in tumor tissue. This effect can be further increased by blood flow retardation with longer retention time in the tumor and by arterial administration realized in abdominal stop-flow therapy, a separate partial circulation with a defined flow under hypoxic conditions. The pH changes under stop-flow therapy may affect the further metabolism of 5-fluorouracil (5-FU), used here. METHODS: The in vitro 5-fluoro-2'-deoxyuridine (5-FUrd) concentrations at increasing pH values were measured using liposomal encapsulated and free 5-FU. Subsequently, 20 chinchilla rabbits were treated intra-aortally with 5-FU or 5-FU-polyethylene glycol (PEG) liposomes. The pH value was maintained in the physiological range by continuous NaHCO3 application. After 20 min, concentrations of 5-FU and its metabolite 5-FUrd were determined in different organs, the perfusate, serum and the VX-2 tumor by HPLC. RESULTS: The in vitro 5-FUrd concentrations, which occur only in the physiological pH range, were doubled by the use of 5-FU-PEG liposomes. In the animal trial, NaHCO(3) titration doubled the 5-FUrd concentrations found in our preliminary studies. Compared to free 5-FU, 5-FU-PEG liposomes significantly increased the concentrations in the VX-2 liver tumor by 6.6-fold and in the para-aortal lymph nodes by 8.76-fold. CONCLUSION: The metabolism of 5-FU into its active metabolite 5-FUrd depends on the pH value and can be modulated. 5-FUrd concentrations can be approximately doubled with the intra-aortal application of 5-FU-PEG liposomes compared to free 5-FU.

Animals↗

Macromolecule-ligand binding studied by the Hummel and Dreyer method: current state of the methodology.

The use of the Hummel and Dreyer method to measure binding parameters of ligand-macromolecule associations is reviewed. The possibility to determine the number of binding sites and their association constants, even in the case of low affinity, and to control the free ligand concentration as an independent variable are the main advantages of the method. The conditions of the validity are rapid equilibrium kinetics, independence between ligand binding and macromolecule association, and identical retention rates between free and bound macromolecules. Initially developed on soft gels, the method has been applied to high-performance chromatography and capillary zone electrophoresis. Technical progress such as increase in resolution, detection sensitivity, and automation have improved its utilization. The binding parameters given by the Hummel and Dreyer method are in general similar to those obtained by other techniques, in comparable experimental conditions (equilibrium dialysis, ultrafiltration, frontal elution, vacancy peak method, vacancy affinity capillary electrophoresis, retention analysis, affinity chromatography and affinity capillary electrophoresis, physical methods). The choice between these methods is directed by material availability and practical constraints. Separation by new types of chromatographic columns or by capillary zone electrophoresis would enable the study of the simultaneous binding of different drugs on the same macromolecule and their competition.

Chromatography, Liquid↗

Proposition of treatment of cancer cells by nuclear protein mixtures from embryonic cells.

Several kinds of cancer cells are shown to revert to normal state by action of chemical or biochemical differentiation agents. The analogy between cancer and embryonic cells, with regard to the expression of oncogenes, and the presence, in young embryos, of regulating factors, lead to the proposition of treatment of cancer cells by extracts of nuclei from embryo cells. Preliminary experiments with these extracts, on hepatoma cells in culture, have shown growth and DNA synthesis inhibitions, without cell toxicity, and a prolongation of survival of rats injected with the treated cancer cells.

Animals↗

Use of the hummel and dreyer method for the study of nucleotide binding on chloroplast ATPase CF1.

The study of the binding of the nucleotides ADP and ATP on the exchangeable sites of chloroplast ATPase CF1 has been carried out by the Hummel and Dreyer method applied to HPLC. It has been shown that this method was well fitted to the problem: rapidity of exchange, absence of noticeable modification after binding, presence of a constant concentration of ligand during the chromatography, which stabilizes these low affinity complexes. The dissociation constants of binding of ADP, ATP and of their magnesium salt complexes have been determined. In order to measure the simultaneous binding of ADP and ATP when present in mixture, we have modified the method by using an anion-exchange column in place of the gel filtration column: the two nucleotides were easily separated, while the binding on the protein was unchanged. The extension of this method to the reversed-phase chromatography could also be considered for the binding of hydrophobic ligands.

Adenosine Diphosphate↗

Ultrasonic characterization of human cancellous bone using transmission and backscatter measurements: relationships to density and microstructure.

The present study was designed to evaluate the relationships between ultrasonic backscatter, density, and microarchitecture of cancellous bone. The slopes of the frequency-dependent attenuation coefficient (nBUA), ultrasound bone velocity (UBV), the frequency-averaged backscatter coefficient (BUB) were measured in 25 cylindrical cancellous bone cores. Bone mineral density (BMD) was determined using X-ray quantitative computed tomography. Microarchitecture was investigated with synchrotron radiation microtomography with an isotropic spatial resolution of 10 microm. Several microstructural parameters reflecting morphology, connectivity, and anisotropy of the specimens were derived from the reconstructed three-dimensional (3D) microarchitecture. The association of the ultrasonic variables with density and microarchitecture was assessed using simple and multivariate linear regression techniques. For all ultrasonic variables, a strong association was found with density (r = 0.84-0.90). We also found that, with the exception of connectivity, all microstructural parameters correlated significantly with density, with r values of 0.54-0.92. For most microstructural parameters there was a highly significant correlation with ultrasonic parameters (r = 0.33-0.91). However, the additional variance explained by microstructural parameters compared with the variance explained by BMD alone was small (Delta r(2) = 6% at best). In particular, no significant independent association was found between microstructure and backscatter coefficient (a microstructure-related ultrasonic parameter) after adjustment for density. The source for the unaccounted variance of quantitative ultrasound (QUS) parameters remains unknown.

Aged↗

Effect of articular cartilage proteoglycan depletion on high frequency ultrasound backscatter.

OBJECTIVE: To study the effect of variations of articular cartilage proteoglycans (PG) on high-frequency ultrasound backscatter. DESIGN: The study was performed on patellar cartilages of immature and mature rats (N=36). The variation of PG content was induced by enzyme digestion. Control and treated cartilages were explored in vitro using a 55MHz scanning acoustic microscopy, then assessed by histology for the fibrillar collagen organization analysis. The variations of proteoglycan and collagen content were evaluated. Thickness measurements performed on both B-scan images and histologic sections were compared. Ultrasonic radio-frequency signals reflected by the cartilage surface and backscattered from its internal matrix were processed to estimate the integrated reflection coefficient (IRC) and apparent integrated backscatter (AIB). RESULTS: Although hyaluronidase treatment of immature and mature cartilages removed approximately 50% of the proteoglycans, the echogenicity level of ultrasound images of degraded cartilages was similar to that of controls. IRC and AIB parameters did not significantly vary. Histologic sections of degraded cartilage displayed no change in collagen fiber organization. The thickness mean values measured by ultrasound in PG-depleted groups were significantly higher than in controls, whereas no significant difference in thickness was detected by histological measurement. The increase in cartilage thickness may potentially be explained by a decrease of speed of sound in PG-depleted cartilages that is more likely subsequent to an increase of water content. CONCLUSION: Current results indicate that PG depletion has no significant effect on high frequency ultrasound backscattered from rat patellar cartilage. Ultrasound may provide information about variations of PG content via speed of sound measurement.

Acoustics↗

Proposition of treatment to improve the immune response: possible application to AIDS.

The molecular similarity between certain human antigenic determinants with those of HIV has been already described. In this matter, we have previously demonstrated, by a chromatographic method, the cross reactivity of human serum albumin with HIV gp 120. The hypothesis that this similarity could be one of the reasons why the virus escapes to the immune system is presented in this paper and a treatment is proposed to enhance the efficiency of the immune response: it is based on the blocking of the determinants of the self, expressed in the thymus, which are in common with the virus. Repeated injections within the thymus of neutralizing antibodies against the pathogen, obtained from a sufficiently distant animal species and purified by affinity chromatography, would prevent the T cells of the host recognizing these epitopes, common to the host and to the virus, from clonal deletion and would improve the immune response.

AIDS Vaccines↗