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Biomedical subjects

C Morandi

Publications and source records attributed to C Morandi.

At least 19 recordsLinked to original sources
PubMed2000

Organization of the human gene encoding heterogeneous nuclear ribonucleoprotein type I (hnRNP I) and characterization of hnRNP I related pseudogene.

The human gene hnRNPI encoding the heterogeneous nuclear ribonucleoprotein type I, an alternative splicing modulator of tissue-specific transcripts, also known as PTB (polypyrimidine tract-binding protein), was recently mapped on chromosome 14, as well as on chromosome 19, suggesting that two closely related copies of the same gene might exist in the human genome. We report here that the gene localized on chromosome 14 corresponds to a highly homologous processed pseudogene related to hnRNPI gene (psihnRNPI). Analysis by RT-PCR and by EST database comparison indicates that psihnRNPI is not expressed. In this report we have also analyzed the organization of the actual hnRNPI gene localized on chromosome 19. The DNA sequence at the intron-exon boundaries unveiled the possible mechanism by which three isoforms of the protein (namely hnRNPI, PTB2 and PTB3) are generated by means of alternative splicing of the same hnRNPI gene transcript.

Amino Acid Sequence↗
PubMed1998

[Percutaneous positioning of port catheter in the hepatic artery for chemotherapy of metastases using the Arai technique].

INTRODUCTION: Liver metastases from colorectal, gastric and breast cancers are a very frequent event; these metastases are treated with cycles of intraarterial chemotherapy with a permanent catheter positioned in the hepatic artery or with surgical or interventional radiology techniques. We tested Arai's technique and its feasibility and evaluated the efficacy of this chemotherapy schedule. MATERIAL AND METHODS: Four patients with liver metastases from colorectal carcinoma were treated with combined systemic and locoregional chemotherapy with a permanent catheter placed in the hepatic artery according to Arai's technique. Arai's technique consists in studying the hepatic vascularization and then redistributing hepatic flow in case of multiple hepatic arteries; the vessels in which the infusion of chemotherapies could cause toxicity are then occluded and finally a catheter is positioned in the hepatic artery with subclavian artery catheterization and the connection with a subcutaneous reservoir for injection--the port-a-cath system. We planned CT examinations to study liver morphology and radiographs of the abdomen and chest to depict the catheter position and patency, respectively. RESULTS: The catheter was positioned correctly without any complications in all patients, as planned. We administered 37 cycles of combined systemic and locoregional chemotherapy in all. Two patients died of disease progression after 6 months but the other 2 are still alive and CT showed partial disease remission. We observed no catheter dislocation or occlusion at chest radiography and transport angiography, respectively. CONCLUSIONS: Infusion chemotherapy in the hepatic artery from permanent catheters is widely accepted in our country and we believe that Arai's technique could be an alternative to the more classic and established surgery. The small number of our patients and the short follow-up do not permit definitive conclusions to be drawn on the clinical efficacy of this combined systemic and intra-arterial treatment.

Adult↗
PubMed1997

Sequence determinants for hnRNP I protein nuclear localization.

hnRNP I, also referred to as polypyrimidine tract binding protein, is one of the proteins associated with nascent pre-mRNA in the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. As for all karyophilic proteins, the nuclear import of hnRNP proteins requires specific sequence determinants that in many instances differ from the canonical import signal. In order to identify the sequences responsible for the nuclear localization, various hnRNP I portions were fused to a reporter protein (bacterial chloramphenicol acetyl transferase) and used in transient transfection assay. By this approach we identified a 60-amino-acid sequence located at the amino terminus of hnRNP I (designated NLD-I) that is both necessary and sufficient for nuclear localization. NLD-I represents a novel bipartite type of nuclear localization signal that bears no resemblance to other nuclear localization determinants so far identified in hnRNP proteins.

3T3 Cells↗
PubMed1997

Four years experience of primary intra-arterial chemotherapy (PIAC) for locally advanced and recurrent breast cancer.

AIMS: To find a means of achieving operability very quickly without the additional discomfort of prolonging systemic chemotherapy. To improve the patient's quality of life by obtaining quick tumor reduction and decreasing systemic toxicity. MATERIALS AND METHODS: From January 1991 to January 1995, 13 patients with locally advanced breast cancer (LABC) and 8 patients with recurrent breast cancer (RBC), were treated by transfemoral Seldinger technique, with the catheter tip placed into the subclavian artery at the basis of the internal mammary artery. The patients received 5-fluorouracil (5FU) 1000 mg, epirubicin (EPI) 30 mg/m2, mitomycin (MMC) 7 mg/m2 over an infusion for 30 minutes. The cycle was repeated every two weeks for three times. RESULTS: The overall response rate was 62%. Stage IIIb and RBC patients had a response rate of 100% and 25% respectively. In respondent patients a measurable response was seen after the first cycle. Ten patients were radically operated. After a media follow-up of 21 months, the overall survival is 52% at 48 months (68% at 48 months and 65% at 34 months for stage IIIb and RBC patients respectively). CONCLUSIONS: PIAC is feasible and effective. In LABC patients it reaches 100% of response rate. Systemic toxicity was absent and the local one was mild. The interval between the starting of PIAC and operation is short. There was an optimal compliance of the patients.

Adult↗
PubMed1994

Analysis of the yeast NSR1 gene and protein domain comparison between Nsr1 and human hnRNP type A1.

The yeast nucleolar protein-encoding gene NSR1 was isolated by low-stringency screening of a yeast genomic library with the human heterogeneous nuclear ribonucleoprotein type A1 (hnRNP A1) cDNA probe, and was mapped to chromosome VII. RNA abundance was determined and the transcription start point and polyadenylation site were mapped. A comparison between the Nsr1 and hnRNP A1 proteins, based on homopolymer RNA binding to their structural domains in vitro, revealed a striking biochemical similarity. When the N-terminal, lysine- and arginine-rich domain of Nsr1 was removed, the truncated protein behaved similarly to hnRNP A1; furthermore, the two RRM (RNA recognition motif) domains of Nsr1 behaved in the same manner as the two RRM domains of hnRNP A1. The biochemical data, therefore, would support the hypothesis that the two RRM domains in hnRNP A1 and Nsr1 interact with RNA in a similar manner in both mammalian and yeast cells, respectively.

Base Sequence↗
PubMed1994

Intra-arterial hepatic carboplatin-based chemotherapy for ocular melanoma metastatic to the liver. Report of a phase II study.

AIMS AND BACKGROUND: ocular melanoma tends to metastasize to the liver, sparing for a long time the rest of the organism. Therefore, a regional treatment is especially indicated. METHODS: eight patients with ocular melanoma metastatic to the liver were treated with intra-arterial hepatic carboplatin-based chemotherapy at the dose of 300 mg/m2 once every two weeks at an out-patient clinic. All the patients were submitted to laparotomy with surgical implantation of an arterial port device through the gastroduodenal artery. RESULTS: the overall response rate was 38% with a median survival time of 15 months. The regimen was well tolerated and the principle toxicity was myelosuppression; any instance of hepatic and/or cholangitic damage was reported. CONCLUSIONS: Carboplatin seems suitable for intra-arterial hepatic chemotherapy and active in ocular melanoma metastatic to the liver.

Aged↗
PubMed1993

[Vulvo-vaginitis in pediatric age].

In pediatric gynecology, inflammatory vulvo-vaginitis are very common. Their diagnosis cannot be based either on the symptoms (itching or pain) or on the signs (leucoxanthorrhea) for these classifications are "non-specific". At the Consulting Room of pediatric gynecology of the Vittore Buzzi Hospital, 215 "non-specific" vulvo-vaginitis cases have been analyzed through bacteriological and microscopical examinations of vaginal secretions. The vaginal tampon resulted negative in 53% of the cases and positive in the remaining 47%. Comparing these results with microscopical examinations we obtain: 81.8% of sensibility, 77.4% of specificity, 87.8% of negative predictive value and 62.2% of positive predictive value. In particular, this last figure is influenced by the high number of false positives of the vaginal tampons, due to the growth "in vitro" of opportunist germs momentarily quiescent "in vivo". Thus it is useful to associated the microscopical examination (that will indicate all the cases in need of treatment) and the bacteriological examination (that will indicate the right cure).

Adolescent↗
PubMed1992

hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs.

Many hnRNP proteins and snRNPs interact with hnRNA in the nucleus of eukaryotic cells and affect the fate of hnRNA and its processing into mRNA. There are at least 20 abundant proteins in vertebrate cell hnRNP complexes and their structure and arrangement on specific hnRNAs is likely to be important for the processing of pre-mRNAs. hnRNP I, a basic protein of ca. 58,000 daltons by SDS-PAGE, is one of the abundant hnRNA-binding proteins. Monoclonal antibodies to hnRNP I were produced and full length cDNA clones for hnRNP I were isolated and sequenced. The sequence of hnRNP I (59,632 daltons and pI 9.86) demonstrates that it is identical to the previously described polypyrimidine tract-binding protein (PTB) and shows that it is highly related to hnRNP L. The sequences of these two proteins, I and L, define a new family of hnRNP proteins within the large superfamily of the RNP consensus RNA-binding proteins. Here we describe experiments which reveal new and unique properties on the association of hnRNP I/PTB with hnRNP complexes and on its cellular localization. Micrococcal nuclease digestions show that hnRNP I, along with hnRNP S and P, is released from hnRNP complexes by nuclease digestion more readily than most other hnRNP proteins. This nuclease hypersensitivity suggests that hnRNP I is bound to hnRNA regions that are particularly exposed in the complexes. Immunofluorescence microscopy shows that hnRNP I is found in the nucleoplasm but in addition high concentrations are detected in a discrete perinucleolar structure. Thus, the PTB is one of the major proteins that bind pre-mRNAs; it is bound to nuclease-hypersensitive regions of the hnRNA-protein complexes and shows a novel pattern of nuclear localization.

Amino Acid Sequence↗
PubMed1992

Immunohistochemistry of dihydrofolate reductase in methotrexate-sensitive and -resistant human cell lines by flow cytometry: a comparison with the cytochemical tetrazolium salt method.

Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an enzyme involved in the metabolism of nucleic acids; it is also an important target for folate antagonists such as methotrexate (MTX). The distribution and expression of DHFR both in human HeLa BU-25 cell line and in methotrexate-resistant (MTX-R) variant, deriving from the human VA2-B cell line (having the DHFR gene amplified) was studied by tetrazolium salt method and by flow cytometric analysis. The immunohistochemical labelling of DHFR was achieved by using the streptavidinbiotinilated complex technique. DHFR activity was low in the human HeLa BU-25 cell line, while it was very high in the MTX-R cell line; the activity level increased with the increasing concentration of the MTX. The results obtained with cytochemical and immunohistochemical technique were compared. These findings showed that the hyperproduction of DHFR is strictly related with the cells having the DHFR gene amplified. Since MTX resistance is a common finding in the cells of patients with acute leukaemia, these studies may be extended to tumour-bearing patients at onset and following chemotherapy with methotrexate.

Cell Line↗
PubMed1990

Modeling by homology of RNA binding domain in A1 hnRNP protein.

Eukaryotic nuclear RNA binding proteins share a common sequence motif thought to be implicated in RNA binding. One of the two domains present in A1 hnRNP protein, has been modelled by homology in order to make a prediction of the main features of the RNA binding site. Acylphosphatase (EC 3.6.1.7) was selected as template for the modeling experiment. The predicted RNA binding site is a beta-sheet containing the two RNP consensus sequences as well as lysines and arginines conserved among the family.

Acid Anhydride Hydrolases↗