[Optimal management of patients with stress fractures and the role of the orthopedic surgeon in reducing the risk of new fractures].
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Bone Density↗
Biomedical subjects
L Tosi
Publications and source records attributed to L Tosi.
Phosphorous acid residues in apples after foliar fertilization: results of field trials.
The levels of phosphorous acid residues in apples after foliar fertilization with P fertilizers and after treatment with a phosphonate fungicide (Fosetyl-Al) were determined and compared. Two field trials and a glasshouse experiment, using different genotypes and plants of different age, were carried out and monitored over a three-year period. Phosphorous acid residues were found in apples after application of foliar P fertilizers. Concentrations of the residues ranged between 0.02 and 14 mg kg(-1) depending on the phosphorous acid content in the fertilizer used and the plant size and yield. The treatments induced an accumulation of the residue in the course of the experiments, which in some cases reached a level exceeding the maximum limit set by EU legislation. Residues were also detected in other plant organs, i.e., roots and buds. Plants treated with Fosetyl-Al contained phosphorous acid residues in their fruits and buds two years after the suspension of the treatment, suggesting a long-term persistence of the substance in plant storage organs. A second experiment, involving treatment of trees with seven foliar fertilizers of different composition, also induced accumulation of phosphorous acid residues in fruits. It is concluded that a wide array of foliar products containing phosphorous acid, even as a minor component, could mimic the residue effect of phosphonate fungicide treatments.
Drug Residues↗
Titanium-cell interaction: analysis of gene expression profiling.
Titanium and its alloys are used worldwide in surgery. Dental implants, screws and plates, prostheses, and surgical instruments are made with titanium-based metals. The favorable characteristics that make this material desirable for implantation are (a) mechanical proprieties and (b) biocompatibility. The latter has been demonstrated by in vivo studies with animal models and clinical trials over a 40-year period. However, the exact effect of titanium on cells is still not well characterized. Expression profiling by DNA microarray is a new molecular technology that allows the analysis of gene expression in a cell system. Several genes whose expression was significantly up- or downregulated in an osteoblast-like cell line (MG-63) on titanium were identified with the use of DNA microarrays containing 19,200 genes. The differentially expressed genes are associated with a broad range of functional activities, including apoptosis, vesicular transport, and structural function. It was also possible to detect some genes whose function is unknown. The data reported are, to the author's knowledge, the first genetic portrait of titanium-cell interaction. They may help to provide a better understanding of the molecular mechanisms of titanium biocompatibility and serve as a model for studying the biocompatibility of other materials.
Animals↗
Genetic portrait of malignant granular cell odontogenic tumour.
Odontogenic tumours are rare neoplasms whose classification is sometime controversial. Among these entities, granular cell odontogenic tumour (GCOT) is extremely rare and usually has a benign clinical behaviour. While the histogenesis of GCOT remains to be clarified, we documented the existence of a malignant counterpart of this neoplasm and proposed the name of malignant GCOT. Expression profiling by cDNA microarrays is a molecular technology that enables a global gene expression analysis. By using cDNA microarrays, we identified in malignant GCOT several genes with significantly differentially regulated genes when compared to non neoplastic tissues. These cancer specific genes include a range of functional activities: (1) transcription, (2) signaling transduction, (3) cell-cycle regulation, (4) apoptosis, (5) differentiation and (6) angiogenesis. In conclusion, we show that cDNA microarrays is a useful approach to investigate the biology of tumours. Moreover, this technology might lead to identification of gene targets for cancer therapy and to molecular classification of odontogenic tumours.
Adult↗
Genetic expression profiling of six odontogenic tumors.
Odontogenic tumors are rare neoplasms arising from the odontogenic apparatus. We aimed to identify molecular characteristics associated with odontogenic tumorigenesis and malignancy. To this end, we investigated the expression level of human genes by using, for the first time in odontogenic tumors, the technique of expression profiling. Gene expression alterations common to all six odontogenic tumors were identified by the use of cDNA microarrays containing 19,000 human cDNAs. Statistical analysis on a subset of 4974 cDNAs present in the biopsies identified 506 distinct genes associated with the tumors (p-value < 0.01). Gene ontology analysis of the cellular processes which were differentially regulated in odontogenic tumors was accomplished by the use of a subset of 1409 annotated genes. Finally, 43 cDNAs differentiated the three malignant odontogenic tumors (ameloblastic carcinoma, clear cell odontogenic tumor, granular cell odontogenic tumor) from the three benign ameloblastoma biopsies (p < 0.01). The identified genes might help us better classify borderline odontogenic tumors.
Ameloblastoma↗
Marie Meurdrac: Paracelsian chemist and feminist.
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Alchemy↗
Supra-agonist peptides enhance the reactivation of memory CTL responses.
Single amino acid substitutions at TCR contacts may transform a natural peptide Ag in CTL ligands with partial agonist, antagonist, or null activity. We obtained peptide variants by changing nonanchor amino acid residues involved in MHC class I binding. These peptides were derived from a subdominant HLA-A2-presented, latent membrane protein 2-derived epitope expressed in EBV-infected cells and in EBV-associated tumors. We found that small structural changes produced ligands with vastly different activities. In particular, the variants that associated more stably to HLA-A2/molecules did not activate any CTL function, behaving as null ligands. Interestingly, T cell stimulations performed with the combination of null ligands and the natural epitope produced significantly higher specific CTL reactivation than reactivation of CTLs induced by the wild-type epitope alone. In addition, these particular variants activated memory CTL responses in the presence of concentrations of natural epitope that per se did not induce T cell responses. We show here that null ligands increased ZAP-70 tyrosine kinase activation induced by the natural epitope. Our results demonstrate for the first time that particular peptide variants, apparently behaving as null ligands, interact with the TCR, showing a supra-agonist activity. These variant peptides did not affect the effector T cell functions activated by the natural epitope. Supra-agonist peptides represent the counterpart of antagonists and may have important applications in the development of therapeutic peptides.
Adjuvants, Immunologic↗
Developmental dysplasia of the hip. American College of Radiology. ACR Appropriateness Criteria.
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Acetabulum↗
Isolation and characterization of phytotoxic compounds produced by Phomopsis helianthi.
The isolation, chemical characterization and biological activity of two phytotoxic metabolites of Phomopsis helianthi Munt-Cvet et al. is reported. These compounds were identified by spectroscopic methods (UV, IR, 1H and 13C NMR, and MS) as trans-4,6-dihydroxymellein (trans-3-methyl-4,6,8-trihydroxy-3,4-dihyroisocoumarin) and cis-4,6-dihydroxymellein (cis-3-methyl-4,6,8-trihydroxy-3,4-dihydroisocoumarin). This is the first report of the isolation of trans-4,6-dihydroxymellein from fungal cultures and of the production of cis- and trans-4,6-dihydroxymelleins by P. helianthi. Rice was found to be a good substrate for the production of the dihydroxymelleins. Culture extracts of some Italian and French strains of P. helianthi showed different degrees of phytotoxicity towards sunflower leaves and seedlings. The minimum effective doses of trans- and cis-4,6-dihydroxymelleins with different bioassays were 76 and 135 microg per spot (leaf puncture bioassay), 3 and 5 micromol g(-1) fresh tissue (absorption by leaf cutting) and 5 and 2 micromol g(-1) fresh tissue (absorption by cut seedlings), respectively. These compounds may contribute to the severity of the sunflower disease caused by P. helianthi.
Helianthus↗
Exogenous spermidine modulates glycosaminoglycan accumulation and epithelial differentiation in chick embryonic skin.
We have previously shown that feather formation in chick embryonic skin depends on accumulation of sulphated glycosaminoglycans in the underlying mesenchyme, and that addition of spermidine to chick embryo fibroblasts increases the extracellular sulphated glycosaminoglycans. In the present work, using histological, histochemical and biochemical procedures, we have investigated the effects on glycosaminoglycan accumulation and on epithelial differentiation of adding spermidine and bis-cyclohexylammonium sulphate, a spermidine inhibitor, to embryonic chick skin cultures. Our results demonstrate that spermidine induces an accumulation of sulphated glycosaminoglycan and an increase in feather formation, suggesting that the morphogenetic effect of spermidine may be dependent on specific glycosaminoglycan accumulation.
Animals↗
A type II phosphoinositide 3-kinase is stimulated via activated integrin in platelets. A source of phosphatidylinositol 3-phosphate.
We have observed that aggregation of human platelets, caused by activation of integrin alphaIIb beta3 and its consequent binding of fibrinogen, stimulates a novel pathway for synthesis of phosphatidylinositol 3,4bisphosphate, thereby activating protein kinase B/Akt. Such synthesis depends upon both the generation of phosphatidylinositol 3-phosphate (PtdIns3P), which is sensitive to wortmannin (IC50 7 nM) and calpain inhibitors, and the phosphorylation of PtdIns3P by PtdIns3P 4-kinase. We now report that a recently characterized C2 domain-containing phosphoinositide 3-kinase isoform (HsC2-PI3K) is present in platelets and a leukemic cell line (CHRF-288) derived from megakaryoblasts, and is likely to be responsible for the stimulated synthesis of PtdIns3P observed in platelets. HsC2-PI3K, identifiable by Western blotting and immunoprecipitatable activity, is sensitive to wortmannin (IC50 6-10 nM), requires Mg2+, and shows strong preference for PtdIns over PtdIns4P or phosphatidylinositol 4,5-bisphosphate as substrate. HsC2-PI3K is activated severalfold when platelets aggregate in an alphaIIb beta3-dependent manner or when platelet or CHRF-288 lysates are incubated with Ca2+. Activation is prevented by calpain inhibitors. CHRF-288, which cannot undergo activation of alphaIIb beta3 and thereby aggregate in response to platelet agonists, do not generate PtdIns3P or activate HsC2-PI3K under conditions that stimulate other phosphoinositide 3-kinases. HsC2-PI3K may thus be an important effector for integrin-dependent signaling.
Androstadienes↗
Three novel type I collagen mutations in osteogenesis imperfecta type IV probands are associated with discrepancies between electrophoretic migration of osteoblast and fibroblast collagen.
In three cases of type IV osteogenesis imperfecta (OI), we identified unique point mutations in type I collagen alpha1(I) cDNA. In two cases, the appearance of dimers indicated the presence of cysteine substitutions in the alpha1(I) protein chain. Cyanogen bromide digestion localized these cross-links to CB8 and 3, respectively. In the third case, the overmodification pattern of the CNBr peptides was compatible with a substitution in the aa 123-402 region of either type I collagen chain. We identified a unique point mutation in each proband, which resulted in substitutions for glycine residues in a 300-aa region of the alpha1(I) helix, specifically, Gly to Ala at codon 220 (GGT-->GCT), Gly to Cys at codon 349 (GGT-->TGT) and Gly to Cys at codon 523 (GGT-->TGT). We compared each proband's fibroblast and osteoblast collagen directly, as well as with fibroblast and osteoblast controls. For all cases, the OI osteoblast collagen was more electrophoretically delayed than OI fibroblast collagen. In the patient with G349C, OI fibroblast and osteoblast collagen synthesized in the presence of alpha,alpha'-dipyridyl co-migrated on gels, demonstrating that the electrophoretic discrepancy resulted from differences in post-translational modification. Melting temperature curves for stability of the collagen helix yielded an identical Tm for control fibroblast and osteoblast collagen (41.2 degrees C). By contrast, for collagen with the gly349-->cys substitution, the Tm of the fibroblast collagen was 1 degree C lower than the Tm of the osteoblast collagen. These data indicate that the metabolism of mutant collagen might be cell-specific and has significant implications for understanding the phenotype/genotype correlations and the pathophysiology of OI.
Adolescent↗
A single focus of multiple sclerosis in the cervical spinal cord mimicking a radiculopathy.
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Cervical Vertebrae↗
Transient global amnesia and migraine in young people.
Two cases of transient global amnesia (TGA) in a 16-year-old boy and in a 13-year-old girl are reported; both occurred during competitive sport and were associated with migraine. TGA in young people could provide crucial information on the still equivocal pathogenesis, a vascular thromboembolic hypothesis being untenable in such cases. A migrainous mechanism is likely to underlie TGA in young people and "pure' TGA in general. TIA or stroke, like epilepsy or other pathological conditions, should concern the differential diagnosis of transient amnestic episodes rather than the pathogenesis of TGA.
Adolescent↗
An experimental pilot study of tacalcitol activities during modulation of parakeratotic skin features.
Establishing guidelines and experimental models preclinical and clinical evaluations of new agents for treatment, and/or prevention of human diseases has become a task of crucial importance. Psoriasis is such one disease holding great interest for dermatology owing to its high rate of incidence and complexity of treatment. However the absence of psoriatic lesions in animals and the inability to induce them, calls for experimental techniques both in vitro and in vivo. The purpose of this study was to evaluate experimentally the effects of tacalcitol on cell proliferation and differentiation process. Thereafter a human pilot study on psoriatic patients has been developed.
Administration, Topical↗
Dermatomal somatosensory evoked potentials in the diagnosis of lumbosacral radiculopathies.
The diagnostic sensitivity of dermatomal somatosensory evoked potentials (DSEPs) was evaluated in a homogeneous group of fifteen patients with low back pain due to isolated lumbosacral radiculopathy. The normative values from L3 to S1 were defined, as were the parameters of abnormality. In seven patients with pseudoradicular or referred leg pain, a negative neurological examination and images indicative of protrusion or paramedian disc hernia, the DSEPs were normal in six cases and slightly altered in one. In eight patients with deafferentation leg pain, clinical signs of root damage and images indicative of an intraforaminal hernia, the DSEPs showed varying degrees of alteration which could generally be correlated to the severity of the clinical picture. This method can therefore be useful in differentiating pain due to stimulation of the receptors of the osteoarticular structures or the root sheath, in which the DSEPs are normal, from pain due to direct root damage, in which the DSEPs are altered. This functional evaluation of anatomical damage provides further information which may help to achieve a better therapeutic approach.
Adult↗
Fibrocartilaginous embolism of the spinal cord: a clinical and pathogenetic reconsideration.
A 16 year old girl did a handstand for fun, returned to her feet, experienced a sudden pain in her back, and became progressively paraplegic within 30 hours. MRI showed lumbar cord swelling, multiple Schmorl's nodes, a collapsed T11-T12 disc space, and intraspongious disc prolapse into the T12 vertebral body. These findings, related to the initial manoeuvre, suggested that an acute vertical disc herniation could have occurred as the first step in a process leading to spinal cord infarction due to fibrocartilaginous emboli from the nucleus pulposus of the intervertebral disc. The medical literature so far reports 32 cases of fibrocartilaginous embolism (FCE) of the spinal cord, all at necropsy, with the exception of one histologically demonstrated in a living patient. A clinical diagnosis of FCE would be desirable for many important reasons, but was never made. This causes severe limitations in the knowledge of the disease and precludes any therapeutic possibility. On the basis of the clinical features and findings in the present case, compared with data from the reported cases, a first attempt is made to identify the clinical context within which new information obtainable through MRI examination can lead to a reliable clinical diagnosis of FCE. The vexed question of the pathogenesis has been reviewed. An increased intraosseous pressure within the vertebral body, due to acute vertical disc herniation, seems to offer a consistent pathogenetic explanation and some therapeutic prospects.
Adolescent↗
DNA methyltransferase activity in the early stages of a sea urchin embryo. Evidence of differential control.
The specific activity of DNA methyltransferase increases in the nuclei of Sphaerechinus granularis sea urchin embryos at increasing stages of development. The activity reaches maximal value at about 20 h of growth, when embryos are at the mesenchyme blastula stage, then abruptly decreases and is essentially zero at about 35 h of development, when embryos are at the early gastrula stage. Both the increase and the drop of the activity are faster than embryonic cell duplication indicating that the enzyme is under strict control during development and that, in the more advanced embryo, a mechanism is activated to specifically block its activity.
Animals↗