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A Greco

Publications and source records attributed to A Greco.

At least 109 records · Page 6Linked to original sources
PubMed1993

Characterization of the NTRK1 genomic region involved in chromosomal rearrangements generating TRK oncogenes.

TRK oncogenes are created by chromosomal rearrangements linking the tyrosine-kinase domain of the NTRK1 gene (encoding one of the receptors for the nerve growth factor) to foreign activating sequences. TRK oncogenes are frequently detected in human papillary thyroid carcinoma, as result of rearrangements involving at least three different activating genes. We have found that the rearrangements creating all the TRK oncogenes so far characterized fall within a 2.9-kb XbaI/SmaI restriction fragment of the NTRK1 gene. Here we report the nucleotide sequence and the exon organization of this fragment.

Base Sequence↗
PubMed1993

Biliary lipid secretion: immunolocalization and identification of a protein associated with lamellar cholesterol carriers in supersaturated rat and human bile.

Feeding a 0.5% diosgenin plus 0.02% simvastatin diet to rats increases biliary cholesterol concentration and saturation to levels generally found in human native supersaturated bile. By using preparative ultracentrifugation, gel filtration chromatography, and electron microscopy, we isolated, purified, and identified lamellar structures (unilamellar vesicles and multilamellae) as a major biliary cholesterol transport in supersaturated human and rat bile. It was estimated that more than 60% of biliary cholesterol is transported in these lamellar carriers, which were identified by transmission electron microscopy as unilamellar vesicles and multilamellar bodies within bile canaliculi of rats with cholesterol supersaturated bile. By SDS-PAGE, a characteristic and constant protein profile was found associated to the purified lamellar carriers. One of these proteins, a 130-kDa protein, was isolated from human biliary lamellae and used for preparation of a rabbit polyclonal antibody, which cross-reacted with the homologous rat protein. By Western blotting, it was established that the purified low density fraction of bile-Metrizamide gradients, containing lamellae, was enriched with the 130-kDa protein. The 130-kDa protein was characteristically detected at the canalicular membrane by Western blotting of hepatic subcellular fractions and by immunohistochemistry of rat and human liver biopsies. Amino acid sequencing of the amino terminus of the 130-kDa protein demonstrated a complete identity with aminopeptidase N, a canalicular transmembrane hydrophobic glycoprotein. These studies show that biliary lipids may acquire an ordered multilamellar structure that is present in the canaliculi of rats with supersaturated bile. These biliary lamellae are similar to lamellar bodies and surfactant-like material frequently found in other epithelia, suggesting common biogenetic, structural, and functional properties. The identification of aminopeptidase N associated with biliary lamellae is consistent with the involvement of the canalicular membrane in the secretory mechanism of biliary lipids.

Amino Acid Sequence↗
PubMed1993

Methylxanthine drug therapy in chronic heart failure associated with hypoxaemia: double-blind placebo-controlled clinical trial of doxofylline versus theophylline and bamifylline.

The effects of the methylxanthine drugs doxofylline, theophylline and bamifylline were investigated on the basis of clinical and gasometric parameters in hypoxic patients with chronic heart failure. A parallel, double-blind, randomized study was conducted in 48 in-patients with NYHA II-IV chronic heart failure with normo- or hypercapnic hypoxaemia. They were divided into three groups and then submitted to a 4-day run-in with placebo. Either doxofylline 800 mg b.i.d., theophylline slow-release 400 mg b.i.d. or bamifylline 1200 mg b.i.d. were administered orally in each group of 16 patients for 10 days. Exercise capacity was estimated through NYHA class modification. Gasometric determinations, including arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and oxygen saturation (SaO2), were measured from arterial blood samples at the time of enrollment (T-4), at the onset of xanthine therapy (T0) and at the end of the trial (T9). After 10 days' treatment, the NYHA class was found to be diminished in 50% of the doxofylline group, 50% of the bamifylline group and 44% of the theophylline group. PaO2 showed a > 15% increase in 75% of the doxofylline group, 56% of the theophylline group and 43% of the bamifylline group (responders). In all three groups the responders presented a highly significant enhancement in PaO2 and SaO2 (p < 0.01 T0 vs T9). Doxofylline exhibited the highest percent increase in PaO2 and SaO2 with respect to T0. The effects on cardiac rhythm showed a progressive heart-rate reduction in the doxofylline group, whereas patients receiving theophylline presented an increase rate of beating. In conclusion, the use of methylxanthines in patients with chronic heart failure seems to be particularly effective especially when a significant ventilatory dysfunction is present. Doxofylline appears to be specially useful because of its ability not to interfere with cardiac rhythm.

Aged↗
PubMed1993

The gene complementing a temperature-sensitive cell cycle mutant of BHK cells is the human homologue of the yeast RPC53 gene, which encodes a subunit of RNA polymerase C (III).

The temperature-sensitive BN51 cell cycle mutant of BHK cells arrests in G1 at the nonpermissive temperature (39.5 degrees C). We have previously reported cloning the gene which complements this mutation. The complementing gene encodes a highly charged protein with a basic amino-terminal domain and an acidic carboxyl-terminal domain. We have recently found that the predicted BN51 protein shows significant homology to the 53 kilodalton subunit of RNA polymerase C (III) from Saccharomyces cerevisiae. Consistent with this, antibodies raised to fusion proteins containing BN51 coding sequences and antipeptide antibodies reveal that the BN51 gene encodes a 48 kilodalton protein which appears to be located primarily in the nucleus following subcellular fractionation and by immunohistochemistry. Analysis of RNA polymerase III activity in temperature-sensitive BN51 cells by nuclear runoff transcription assay reveals a marked drop in RNA polymerase III transcription after 48 h at the nonpermissive temperature (39.5 degrees C). This is correlated with a significant decrease in low molecular weight RNAs after 48 h at 39.5 degrees C. In addition, RNA polymerase III activity in S100 extracts of BN51 cells is more sensitive to heat inactivation at 39 degrees C than control extracts from BHK cells. When the yeast gene is introduced into the BN51 cells in a mammalian expression vector, it weakly complements the BN51 mutation in that it prevents cell death at 39.5 degrees C. The mechanism by which inhibition of RNA polymerase III activity leads to arrest in G1 is unclear but is not due to a marked decrease in total protein synthesis.

Amino Acid Sequence↗
PubMed1993

Expression of TRK-T1 oncogene induces differentiation of PC12 cells.

The TRK-T1 oncogene, isolated from a human thyroid carcinoma, represents a rearranged form of the high affinity nerve growth factor (NGF) receptor encoded by the NTRK1 gene; it is created by an intrachromosomal rearrangement fusing the NTRK1 tyrosine kinase domain to the 5' portion of the TPR gene. We have investigated the effect of the TRK-T1 oncogene in PC12 cells, a model system for studying neuronal differentiation and the mechanism of action of NGF. Here, we report that, in PC12 cells, the TRK-T1 oncogene has a differentiating effect that resembles that of NGF and requires the phosphorylation of the oncoprotein. Our results are consistent with the hypothesis that TRK-T1, as well as the original TRK oncogene, induces PC12 differentiation by mimicking the action of NGF bound to its receptor.

Animals↗
PubMed1992

[Recurrent cardiac echinococcosis: a report of a case with multiple intrapericardial cysts].

A case of an isolated recurrent cardiac hydatidosis with multiple intrapericardial cysts is presented. The patient, who underwent 2 previous surgical resection of intramyocardial and pericardial hydatid cysts, presented with atypical chest pain. The ECG and the perfusion scintigraphy with 201-thallium showed a previous lateral myocardial infarction. The diagnosis of recurrent cardiac hydatidosis was made by two-dimensional echocardiography and computed tomography and was confirmed by clinical and biochemical findings.

Adult↗
PubMed1992

TRK-T1 is a novel oncogene formed by the fusion of TPR and TRK genes in human papillary thyroid carcinomas.

We have recently reported the frequent activation of the TRK oncogene in human papillary thyroid carcinoma. In this paper we describe the isolation and characterization of one of the thyroid TRK oncogenes, designated TRK-T1. A 1746-bp-long cDNA was isolated from a library derived from a primary transformant. The cDNA was able to induce foci in NIH3T3 cells. Sequence analysis revealed that TRK-T1 is created by an intrachromosomal rearrangement that juxtaposes the 5' end of the TPR gene to the TRK tyrosine kinase domain. The resulting hybrid mRNA contains 598 nucleotides of the TPR gene and 1148 nucleotides of the TRK proto-oncogene. TRK-T1 mRNA encodes a protein of 55 kDa reacting with antibodies against the carboxy terminus of the proto-TRK protein. We show also the involvement of TPR in the generation of another TRK-T oncogene.

3T3 Cells↗
PubMed1991

Prothrombin expression in the adult and fetal rabbit liver.

Plasma prothrombin levels in newborn humans are lower than in adults. The same is true of many newborn and fetal mammals, including the rabbit. To determine if the lower levels are due to less expression of the protein, we have compared mRNA for prothrombin in fetal and adult rabbit liver. Northern blots were hybridized with a cDNA for rabbit prothrombin revealing a single mRNA of approximately 2 kb in both adult and fetal animals. mRNA specific for prothrombin was quantitated by slot blotting of RNA prepared from adults and fetuses aged 21 d to term (31 d). Prothrombin-specific mRNA in fetuses was greater than 50% of that in adults even when the fetal plasma prothrombin was only 15% of the adult level. This suggests that low plasma levels in the fetuses are not the result of less transcription. Examination of liver sections revealed that the predominant tissue in the fetus is hematopoietic, not hepatic. In the youngest fetuses, less than 20% of the liver consisted of hepatocytes, yet these fetuses expressed more than 50% of the adult level of prothrombin-specific mRNA. Thus, transcription of prothrombin mRNA may be proceeding at a greater rate in the fetal hepatocyte than in the adult, or hematopoietic cells may be expressing the protein. We conclude that in fetal rabbit liver, prothrombin is expressed at a high level relative to the hepatocyte content and that the cause of the low plasma levels is posttranscriptional.

Animals↗
PubMed1991

Primary bone tumors. MR morphologic appearance correlated with pathologic examinations.

Eighty-three MR studies for primary bone tumors, performed with both spin echo and short time inversion recovery (STIR) sequences, were reviewed. Twenty-six patients underwent surgery within 10 days after MR imaging. Specimens were cut and directly compared with MR images. In the remainder, pathologic slides were compared in order to obtain a better understanding of MR pattern. All MR images were examined with a traditional morphologic approach and, upon comparison with surgical macroslides and with pathology samples, some MR distinctive patterns were identified: the bulky appearance of osteosarcoma surrounded by muscle edema, the multilobular high signal intensity (SI) chondroid lesions, the subtle infiltration of Ewing's sarcoma, rarely accompanied by muscle edema and prone to MR underestimation, the well defined "multiple shells" pattern of giant cell tumor, and the ill defined "storiform" appearance of malignant fibrous histocytoma are all typical MR features strictly corresponding to pathologic findings. The chondroid origin tumors may be identified based on the lobular high SI pattern whereas a benign fibrous lesion was the only one in this series to be distinguished relying on the SI. Peritumoral soft tissue edema was found by the STIR sequence only in malignant tumors (69%) of this series, and particularly in osteosarcoma (96%), chondrosarcoma (83%), and giant cell tumor (100%): this associate finding may further contribute to the diagnosis.

Adolescent↗
PubMed1991

[Neoplasms of the base of the tongue. Evaluation with magnetic resonance].

The authors investigated MR capabilities in evaluating the neoplasms of the base of tongue. Thirty patients were examined. The images were obtained--at INI, Grottaferrata, Rome--using a 1.5 T superconductive Gyroscan unit by Philips. On T2-weighted images, the neoplasms were always hyperintense; in 10 patients edema could be distinguished from neoplasm. On T1-weighted scans the tumor exhibited the same signal intensity as the tongue muscle in 4 patients, while in the extant 26 cases it was hypointense. This pattern proved to be aspecific and could not be correlated with a specific histology. In 3 clinically symptomatic patients, MR imaging diagnosed the invasion of the internal pterigoid muscle. MR capabilities in identifying swollen lymph nodes was also evaluated on the basis of the signal intensities of the latter, as well as on their size. The authors' conclusion is that MR imaging is to be considered the method of choice in the staging of tumors at the base of tongue thanks to its high contrast resolution and multiplanar capabilities.

Aged↗
PubMed1990

Chemotherapy for advanced thymoma. Preliminary results of an intergroup study.

OBJECTIVE: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma. DESIGN: Nonrandomized, prospective phase I-II trial. SETTING: A Cooperative Oncology Group trial involving tertiary medical centers. PATIENTS: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response. INTERVENTION: Patients were given cisplatin, 50 mg/m2 body surface area, doxorubicin, 50 mg/m2, and cyclophosphamide, 500 mg/m2, on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m2) was reached. Intravenous hydration with normal saline was administered during treatment courses. For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle. MEASUREMENTS AND MAIN RESULTS: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%). The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years. The median survival time of all eligible patients was 59 months (CI, 22 months to infinity). Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity. CONCLUSIONS: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma. Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma.

Adult↗
PubMed1990

Efficacy of almitrine-raubasine in cognitive disorders of aging: a double-blind, placebo-controlled, clinical and psychometric study.

Early treatment of age-related cognitive impairment can be decisive in enabling elderly patients to remain at home. A double-blind, placebo-controlled trial of almitrine-raubasine was conducted in 40 elderly outpatients (25 women, 15 men; mean age: 73.5 years) with moderate cognitive impairment randomized into two groups, one receiving almitrine and raubasine, the other placebo, two tablets daily for 90 days. They were assessed at T0, T45 and T90 days, using the Toulouse-Pieron test, 8 subtests from the Wechsler Adult Intelligence Scale (WAIS) and the Sandoz Clinical Assessment for Geriatrics (SCAG). End-of-study results were significantly better in the almitrine-raubasine group in all tests: Toulouse-Pieron test (p less than 0.001), WAIS (p less than 0.001), and SCAG (p less than 0.001).

Aged↗