[A case of myositis ossificans: what is the real diagnostic value of magnetic resonance?].
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Adult↗
Biomedical subjects
F Fiore
Publications and source records attributed to F Fiore.
Interaction between Cdc37 and Cdk4 in human cells.
Using the yeast two-hybrid system we have identified novel potential Cdk4 interacting proteins. Here we described the interaction of Cdk4 with a human homologue of the yeast Drosophila CDC37 gene products. Cdc37 protein specifically interacts with Cdk4 and Cdk6, but not with Cdc2, Cdk2, Cdk3, Cdk5 and any of a number of cyclins tested. Cdc37 is not an inhibitor nor an activator of the Cdk4/cyclin D1 kinase, while it appears to facilitate complex assembly between Cdk4, and cyclin D1 in vitro. Cdc37 competes with p16 for binding to Cdk4, suggesting that p16 might exert part of its inhibitory function by affecting the formation of Cdk4/cyclin D1 complexes via Cdc37.
Amino Acid Sequence↗
Interaction of the phosphotyrosine interaction/phosphotyrosine binding-related domains of Fe65 with wild-type and mutant Alzheimer's beta-amyloid precursor proteins.
The two tandem phosphotyrosine interaction/phosphotyrosine binding (PID/PTB) domains of the Fe65 protein interact with the intracellular region of the Alzheimer's beta-amyloid precursor protein (APP). This interaction, previously demonstrated in vitro and in the yeast two hybrid system, also takes place in vivo in mammalian cells, as demonstrated here by anti-Fe65 co-immunoprecipitation experiments. This interaction differs from that occurring between other PID/PTB domain-containing proteins, such as Shc and insulin receptor substrate 1, and activated growth factor receptors as follows: (i) the Fe65-APP interaction is phosphorylation-independent; (ii) the region of the APP intracellular domain involved in the binding is larger than that of the growth factor receptor necessary for the formation of the complex with Shc; and (iii) despite a significant similarity the carboxyl-terminal regions of PID/PTB of Fe65 and of Shc are not functionally interchangeable in terms of binding cognate ligands. A role for Fe65 in the pathogenesis of familial Alzheimer's disease is suggested by the finding that mutant APP, responsible for some cases of familial Alzheimer's disease, shows an altered in vivo interaction with Fe65.
Alzheimer Disease↗
Fotemustine and dacarbazine plus recombinant interferon alpha 2a in thetreatment of advanced melanoma.
Forty-three consecutive patients with advanced melanoma not previously treated with cytotoxic drugs (22 of them had already received adjuvant recombinant interferon alpha 2a (rIFN alpha 2a)) were given a combination of intravenous (i.v.) fotemustine (FM), 100 mg/m2 on day 1, and dacarbazine (DTIC), 250 mg/m2 i.v. on days 2-5, every 3 weeks. rIFN alpha 2a was administered at the dosage of 3 MIU subcutaneously 3 times a week until progression. Four complete and 13 partial responses were registered, for an overall response rate of 40% (95% CI, 25-56%). Activity of this regimen was similar in patients with mainly visceral (10/22, 45%) or soft tissue (6/13, 46%) involvement. The median duration of responses was 24 weeks. Median survival time was 40 weeks, with a 13% 2 year survival rate. Neutropenia and thrombocytopenia affected 67% and 51% of patients, but were of WHO grade 4 in only 2% and 5% of them, respectively. Side-effects attributable to rIFN alpha 2a were mild and manageable. In conclusion, the combination of FM + DTIC and rIFN alpha 2a seemed well tolerated and relatively active in patients with advanced melanoma. However, the role of rIFN alpha 2a in affecting the long-term outcome of patients is still questionable.
Adult↗
Tc-99m MIBI scintigraphy in patients with lung cancer. Comparison with CT and fluorine-18 FDG PET imaging.
Tc-99m MIBI imaging has been used to evaluate patients with different neoplastic disorders, but its role in nuclear oncology has not been definitely established. In this study, we compared the results of Tc-99m MIBI (planar and SPECT imaging) with those of F-18 FDG PET radionuclide studies in 19 patients who had proven lung cancer. One patient was studied in follow-up. All patients underwent chest CT scans. MIBI and FDG images were qualitatively and quantitatively analyzed using region of interest analysis. Quantitative evaluation of MIBI and FDG activities in lung-tumor lesions was performed calculating tumor/nontumor ratios. On CT, 18 lung tumors were detected, while one patient was disease free. For lung lesions, the diagnostic sensitivity of planar MIBI imaging was 83%, while those of MIBI SPECT and FDG PET were both 100%. The quantitative analysis of lung-tumor MIBI and FDG activities showed that FDG uptake was significantly (P < 0.001) higher compared with MIBI uptake (5.5 +/- 3.1 vs 2.1 +/- 0.6); concordant MIBI and FDG images were found in 4 lesions in terms of central activity defect showing central necrotic tumor tissue. For lymph node abnormalities, planar MIBI scan only detected 3 lesions in 3 patients, whereas MIBI SPECT identified 9 lesions in 5 patients. FDG PET showed 13 lymph node abnormalities in 5 patients. This study shows similar results of Tc-99m MIBI SPECT and F-18 FDG PET in the diagnostic evaluation of patients with lung tumors. However, FDG lung tumor uptake was significantly higher compared with MIBI accumulation, suggesting a high glucose tumor metabolism. Thus, MIBI SPECT imaging may be useful to evaluate such patients and may be considered an alternative when PET is not available.
Adenocarcinoma↗
Oestradiol and testosterone blood levels in patients with viral cirrhosis and hepatocellular carcinoma.
BACKGROUND: Patients with alcoholic cirrhosis show hypogonadism and feminization associated with sex hormone imbalance due to enhanced aromatization of testosterone and subsequent reduced testosterone and increased oestradiol blood levels. Because oestrogens modulate hepatocyte proliferation and oestrogen receptors are present in liver cirrhosis and hepatocellular carcinoma, it has been proposed that sex hormone imbalance can play a role in liver carcinogenesis. Trials with the oestrogen receptor antagonist tamoxifen have been performed with conflicting results. OBJECTIVES: To investigate oestradiol and testosterone blood levels in men with viral cirrhosis and hepatocellular carcinoma and also to investigate changes in sex hormone circulating levels induced by tamoxifen treatment. PATIENTS AND METHODS: Oestradiol and testosterone blood levels were evaluated in 32 male patients with postviral cirrhosis and hepatocellular carcinoma at the time of diagnosis and during the follow-up, and in 20 healthy controls. In eight patients, hormone levels were also assayed during treatment with tamoxifen (40 mg/day). No patient had a history of high alcohol intake. RESULTS: Oestradiol values observed at the time of diagnosis were 56.1 +/- 54.5 pmol/l, while testosterone values were 13.6 +/- 8.0 pmol/l. There was no relationship between oestrogen values and age, while higher oestradiol values were observed in patients with advanced cirrhosis (Child B and C); conversely, testosterone levels progressively and significantly decreased from cirrhosis Child A (15.1 +/- 9.7) to C (7.7 +/- 7.1) (P < 0.05). Tamoxifen treatment (40mg/day) for 1 month in eight patients increased oestradiol values (62.2 +/- 77.0 vs. 156.4 +/- 83 pmol/l, P < 0.05), while testosterone levels decreased (15.1 +/- 6.8 vs. 8.5 +/- 10.6 pmol/l). However, these changes were not associated with clinical signs or symptoms of feminization. Oestrogen levels decreased after 6 months of tamoxifen treatment. No significant change in hormone levels was observed in patients not treated with tamoxifen. Unlike patients with alcoholic cirrhosis, in male patients with viral cirrhosis and hepatocellular carcinoma there were no significant alterations in blood oestradiol and testosterone levels, although a certain degree of sex hormone imbalance was observed in those with advanced cirrhosis. Treatment with tamoxifen (40 mg/day) did not induce clinical manifestations of sex hormone imbalance.
Age Factors↗
Weekly paclitaxel and cisplatin with concurrent radiotherapy in locally advanced non-small-cell lung cancer: a phase I study.
PURPOSE: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. RESULTS: Overall, 25 patients were recruited through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue treatment because of severe esophagitis and one of these died of complications related to grade 4 esophagitis. However, keeping the same doses of chemotherapy and replacing hyperfractionation with a standard single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only four courses. Substantial pulmonary or neurologic toxicity was not observed in this study. Two complete responses (CRs) and 13 partial responses (PRs) were observed, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-year survival probability. CONCLUSION: CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occurrence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will elucidate which of these two approaches (standard or hyperfractionated RT) is the better option to improve the outcome of patients with locally advanced NSCLC.
Adult↗
Apparent normal phenotype of Fgf6-/- mice.
To study the role of the sixth member of the FGF (fibroblast growth factor) family whose expression is restricted to skeletal muscle, we have derived mouse mutants with a homozygous disruption of the Fgf6 gene. The animals are viable, fertile and apparently normal, indicating that FGF6 is not required for vital functions in the laboratory mouse.
Animals↗
Weekly paclitaxel/cisplatin with concurrent radiotherapy in patients with locally advanced non-small cell lung cancer: a phase I study.
We designed a phase I study to determine the maximum tolerated doses of weekly cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (doses escalated alternately) when given concurrently with standard or hyperfractionated radiotherapy (RT) and to define the nature of the dose-limiting toxicity. Chemotherapy-naive patients with locally advanced non-small cell lung cancer received weekly combination cisplatin/paclitaxel with concurrent local RT. Radiation therapy was initially given at the dose of 1.2 Gy twice daily x 5 d/wk x 5 weeks (total dose, 60 Gy). In the last two patient cohorts, the single daily dose was decreased to 2 Gy x 5 d/wk x 6 weeks. Overall, 25 patients were recruited into five different cohorts. Esophagitis was the main nonhematologic toxicity, occurring in 16 of 25 patients (64%; grade 3 or 4 in five). Neutropenia was the most prevalent hematologic toxicity, occurring in 33 of 141 weekly courses, but grade 4 neutropenia was seen in only four courses. Cisplatin/paclitaxel doses of 35 mg/m2/wk and 45 mg/m2/wk, respectively, were safe when standard RT was used, while the cisplatin dose had to be decreased to 30 mg/m2/wk in patients receiving bifractionation. Two complete and 13 partial responses were observed, for a 60% overall response rate (95% confidence interval, 39% to 79%). Median survival was 16 months, with a 66% 1-year actuarial probability. We thus conclude that the cisplatin/paclitaxel combination given weekly can be safely administered concurrent with both standard or hyperfractionated RT. Hyperfractionation is associated with a higher incidence of severe esophagitis and required a slight reduction in cisplatin dose. To verify whether the use of a daily schedule translates into a better therapeutic index, a new phase I study is under way, testing twice-daily cisplatin/paclitaxel concurrently with hyperfractionated RT.
Adult↗
[Cystic nephroma vs a partially differentiated nephroblastoma originating in the renal hilus. Apropos a case].
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Adolescent↗
Power Doppler sonography to evaluate response to percutaneous ethanol injection in hepatocellular carcinoma.
BACKGROUND AND AIMS: The aim of the present study was to compare power Doppler imaging with traditional color Doppler imaging and with contrast enhanced computer tomography in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and in response to percutaneous ethanol injection. PATIENTS AND METHODS: Sixteen patients with hepatocellular carcinoma underwent colour Doppler, power Doppler and computed tomography at diagnosis. Seventeen patients were studied by the three techniques one month after percutaneous ethanol injection treatment. RESULTS: At baseline evaluation, power Doppler and color Doppler were always in agreement and, with the exception of one case, were also in agreement with the computerized tomography scan. On the contrary, power Doppler and computerized tomography are more sensitive than color Doppler in the evaluation of residual vascularized tumoral tissue after percutaneous ethanol injection. In 3 patients, residual vascularity was demonstrated only by computerized tomography while color and power Doppler were negative. In another 3 cases, a positive power Doppler signal, with a typical arterial Doppler spectrum, was observed while color Doppler and computerized tomography were negative. In these patients, cancer relapse was clinically evident after a few months and treatment was repeated to obtain complete necrosis. CONCLUSIONS: We conclude that only the integration of the results of all these techniques can reliably evaluate tumoral vascularity after percutaneous ethanol injection.
Adult↗
The regions of the Fe65 protein homologous to the phosphotyrosine interaction/phosphotyrosine binding domain of Shc bind the intracellular domain of the Alzheimer's amyloid precursor protein.
Fe65 is a protein mainly expressed in several districts of the mammalian nervous system. The search of protein sequence data banks revealed that Fe65 contains two phosphotyrosine interaction (PID) or phosphotyrosine binding (PTB) domains, previously identified in the Shc adaptor molecule. The two putative PID/PTB domains of Fe65 were used to construct glutathione S-transferase-Fe65 fusion proteins. Co-precipitation experiments demonstrated that the Fe65 PID/PTB domains interacted with several proteins of apparent molecular mass 135, 115, 105, and 51 kDa. The region of Fe65 containing the PID/PTB domains was used as a bait to screen a human brain cDNA library in yeast by the two-hybrid system. Three different cDNA clones were isolated, two of which contain overlapping segments of the cDNA encoding the COOH terminus of the Alzheimer's beta-amyloid-precursor protein (APP), that represents the short intracellular domain of this membrane protein. The third clone contains a cDNA fragment coding for the COOH terminus of the human counterpart of a mouse beta-amyloid-like precursor protein. The alignment of the three APP encoding cDNA fragments found in the screening suggests that the region of APP involved in the binding is centered on the NPTY sequence, which is analogous to that present in the intracellular domains of the growth factor receptors interacting with the PID/PTB domain of Shc.
Alzheimer Disease↗
Differentially expressed mRNAs as a consequence of oxidative stress in intact cells.
Intracellular redox conditions influence the activity of several transcription factors leading to a modulation of the expression of the genes controlled by these factors. We examined the changes in cell transcription patterns after oxidative stress induced by diethylmaleate (DEM). Using the differential display technique we identified several differentially expressed sequence tags, four of which are identical or highly homologous to sequences contained in the human cDNAs encoding vimentin, c-fos, cytochrome oxidase IV and ribosomal protein L4; another one corresponds to a transcript of the mitochondrial genome of unknown function. The remaining five cDNAs are not recorded in any sequence data bank. One of these, named Rox3, lights up two mRNA species of approximately 3400 and 3600 bp, significantly increased after treatment with DEM or with other oxidizing agents. This increase appears precociously after exposure to DEM and it is completely prevented by pretreatment with N-acetylcysteine. The Rox3 fragment was used to screen a cDNA library; one fully sequenced clone showed 100% homology with the putative human guanine nucleotide regulatory protein nep1.
Cell Line↗
[Coronary disease in heart transplantation].
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Coronary Disease↗
Expression of the neuron-specific FE65 gene marks the development of embryo ganglionic derivatives.
The major transcript of the FE65 gene is a neuron-specific mRNA that encodes a nuclear protein whose aminoterminal domain strongly activates the transcription of a reporter gene when fused to a heterologous DNA-binding domain. FE65 gene expression is regulated during neuronal differentiation of the NTERA-2 cell line, and it is temporally and spatially restricted during mouse embryo development. It is first detected around day 10 of gestation in the basal plate of the neural tube, and then, at the subsequent stages of development and in the newborn animals, it is found solely in neural structures. Its expression is most abundant in the neural crest derivatives (e.g. spinal and encephalic ganglia), ganglionic structures of sense organs (ganglionic layer of the retina and olfactory epithelium), as well as the ganglionic structures of the autonomic nervous system. Thus FE65 gene expression can be considered a marker of the development of embryo ganglionic derivatives.
Animals↗
A new device for self-adjustment of colposuspension.
One of the major problems with the colposuspension technique is the tension applied to the stitches which is usually adjusted on the basis of experience or by means of endoscopic observation of the bladder neck with the patients immobile and under anesthesia. The outcome of the procedures may be different during active life and in an upright position resulting in under- or overcorrection. Therefore, the authors developed a device to be applied on the 4th to 5th postoperative day after standard Gittes or Raz-Pereyra procedures and checked continence during walking and voiding. Up to November 1993, 13 females with recurrent incontinence had been treated with this method; good results were obtained in 12 cases. The authors advocate the use of this device as a solution in cases with imperfect outcome due to assessment of colposuspension during surgery.
Aged↗
Immortalization of a cell line showing some characteristics of the oligodendrocyte phenotype.
We have used the polyoma middle T oncogene to immortalize cells from rat embryo encephalon. Immunostaining experiments with monoclonal antibodies demonstrated that the cells of one of the obtained lines, named CEINGE CL3, are stained by anti-vimentin and anti-S100 antibodies, are not stained by anti-neurofilaments (NF) or anti-glial fibrillary acidic-protein (GFAP) antibodies. Only a subset of the CEINGE CL3 cells (20-30%) is stained by an anti-galactocerebroside antibody. Northern blot analysis demonstrated that these cells express low levels of proteolipid protein mRNA, whereas polymerase chain reaction (PCR) amplification failed to evidentiate the presence of both NF and GFAP mRNAs. Either retinoic acid or forskolin treatments or a combination of them are able to induce morphological changes that are accompanied by a complete growth arrest.
Animals↗
Isolation and structural characterization of the rat gene encoding the brain specific snRNP-associated polypeptide "N".
We isolated the gene encoding the brain specific snRNP-associated polypeptide "N" from a rat genomic library. Some intronless genes have previously been reported for this polypeptide in the rat. In contrast, our gene consists of at least nine exons (the last exon(s) encoding the 3'-end of the mRNA has not been isolated). The second intron of the gene is probably so long as to hamper the cloning of the complete gene into a single phage vector. Therefore, we used polymerase chain reaction amplification of the rat genome with oligonucleotides designed on the basis of known cDNA sequences that allowed us to isolate and clone the first two exons at the 5'-end of the gene. Primer extension studies revealed multiple transcription start sites, all of them contained within the first exon. The intron/exon organization coincides with the alternative splicing events suggested by the sequences of the various cDNA species isolated so far. As also reported by others, genomic Southern analysis suggests the presence of other genomic regions containing sequences strongly hybridizing to the cDNA. We isolated and characterized two of these regions. They contain sequences very similar to the cDNA, not interrupted by introns and flanked by a polyA tail at their 3'-ends; hence they are considered two different pseudogenes.
Amino Acid Sequence↗