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Biomedical subjects

M Petrini

Publications and source records attributed to M Petrini.

At least 37 records · Page 2Linked to original sources

Unusual morphology in a case of large granular cell leukemia.

Large granular lymphocyte proliferative status represents a group of clonal and nonclonal lymphoproliferative disorders of natural killer (NK) or T-cell lineages with common morphological features. Cellular differences may sustain the clinical polymorphism observed in these disorders. Here we report a case of large granular lymphocyte disease unusually expressing CD4+CD8+ clonal T cells and atypical cell morphology in bone marrow.

Arthritis, Rheumatoid↗

Interferon-alpha activity in a case of severe autoimmune lymphoproliferative disease.

Autoimmune lymphoproliferative disease (ALD) is a rare familial disorder. Clinical and laboratory features of this disease include a generalized lymphadenopathy, splenomegaly, increased levels of circulating CD3+ with low levels of CD4+, CD8+ T-cells, and autoimmune phenomena, characteristics that the autoimmune lymphoproliferative syndrome (ALPS) have in common. Treatment usually consists of different supportive therapies. We report on the case of a young man affected by ALD who became resistant to steroids and was unresponsive to cyclosporine. Nevertheless, he was successfully treated with interferon (IFN)-alpha, resulting in a long-lasting, clinically complete remission.

Adolescent↗

Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: To determine the clinical activity and safety of the combination immunotherapy of the chimeric anti-CD20 antibody, Rituximab, and Interferon (IFN)- alpha 2a DESIGN AND METHODS: Sixty-four patients with relapsed low-grade or follicular B-cell non Hodgkin's lymphoma received 4 infusion of Rituximab (375 mg/m(2) x dose) after priming and simultaneous treatment with IFN- alpha 2a. RESULTS: The overall response rate was 70% with 33% complete responses. Median for duration of response is 19 months, after a median follow-up of 22 months. By univariate analysis none of the most common prognostic factors predicted for response to therapy. After treatment 10 patients become bcl-2 negative in the bone marrow, but no correlation between molecular and clinical response was found. Fifty-three patients (83%) had drug related or unknown origin adverse events. The number of adverse events per patient varied from 1 to 21. Considering all 272 events, 231 (85%) were grade 1 or 2, 36 (13%) grade 3 and 5 (2%) grade 4. Twenty-three patients required reduction in the dose and/or short discontinuation of IFN treatment, either during priming or subsequent treatment. The most frequent adverse events were leukopenia, fever, neutropenia, hypotension and thrombocytopenia. INTERPRETATION AND CONCLUSIONS: this report shows that combination immunotherapy Rituximab + IFN- alpha 2a is active and relatively well tolerated. The overall response rate of 70% and the median duration remission of 19 months compare favorable with the results obtained with Rituximab alone in similar subset of patients. Randomized trials, investigating Rituximab versus combination immunotherapy are needed.

Adult↗

Acyclic stereoselection in the reaction of nucleophilic reagents with chiral N-acyliminium ions generated from N-

Optically active N-[1-(phenylsulfonyl)alkyl]imidazolidin-2-ones react at low temperature in the presence of tin tetrachloride to give acyclic N-acyliminium ions. These electrophilic substrates give addition products upon reaction with pi-nucleophiles. Allyltrimethylsilane affords the corresponding allylated products in good yields and high diastereoselectivity. The stereochemical outcome of this process can be rationalized by taking into account the preference of the intermediate N-acyliminium ion for an E configuration that favors the attack of the nucleophile from the si-si face. Disappointing results are obtained using silyl ketene acetals; conversely trimethylsilyl enol ether of acetophenone gives the corresponding adducts in high diastereoselectivity. The utilization of trimethylsilyl enol ether of 2-acetylfuran is particularly interesting since the corresponding adducts are obtained with good diastereoselectivity and the furan ring could be amenable of further synthetic transformations.

Journal Article↗

The murine DSCR1-like (Down syndrome candidate region 1) gene family: conserved synteny with the human orthologous genes.

A recently recognized gene family, conserved from yeast to humans, includes Down syndrome candidate region 1 gene (DSCR1), Adapt78 (recognized as the hamster ortholog of the DSCR1 isoform 4), ZAKI-4 (renamed DSCR1-like 1, DSCR1L1) and DSCR1L2 (a novel gene on human chromosome 1), along with yeast and C. elegans single members (Strippoli P., Lenzi L., Petrini M., Carinci P., Zannotti M., 2000. A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member. Genomics 64, 252-263). The proposed family labels were a putative single-strand nucleic acid binding domain similar to the RNA recognition motif, and a unique, highly-conserved serine-proline motif. We have used a bioinformatics-driven molecular biology approach to characterize the murine members of DSCR1-like gene family. Systematic expressed-sequence-tags (EST) database search and reverse-transcription polymerase chain rection (RT-PCR) product sequencing allowed identification of the murine DSCR1, DSCR1L1 and DSCR1L2. The sequences of the respective protein products are of 198, 197 and 241 amino acids, respectively, and are very similar to the corresponding human proteins. The very broad expression pattern of the murine DSCR1 genes is similar to that of the human genes. Using a radiation hybrid panel, we mapped the murine DSCR1-like family members. The murine DSCR1 ortholog is located on the chromosome 16, in a region corresponding to that on human chromosome 21 just upstream of the Down syndrome candidate region. DSCR1L1 and DSCR1L2 murine genes are also located in chromosomal segments of chromosome 17 and 4, respectively, exactly corresponding to those containing the respective human homologs on chromosomes 6 and 1. Description of the mouse orthologs for DSCR1-like genes will allow knockout mice to be obtained for specific family members.

Adaptor Proteins, Signal Transducing↗

A novel route to the vinyl sulfide nine-membered macrocycle moiety of Griseoviridin.

The synthetic potentialities of cerium(III) chloride are demonstrated by the synthesis of a nine-membered ring heterocycle component of Griseoviridin (3) in optically active form. The key step involves the stereospecific formation of the alpha-carbalkoxy alkenyl sulfide moiety using a combination system of cerium(III) chloride heptahydrate and sodium iodide.

Anti-Bacterial Agents↗

An Efficient Procedure for the Diastereoselective Dehydration of beta-Hydroxy Carbonyl Compounds by CeCl(3).7H(2)O/NaI System.

The dehydration of beta-hydroxy ketones and beta-hydroxy esters is a synthetically useful method for the conversion of these compounds to the corresponding alpha,beta-unsaturated derivatives. Cerium(III) chloride heptahydrate in combination with sodium iodide in refluxing acetonitrile acts as an efficient reagent for this conversion. The present procedure, which utilizes cheap and "friendly" reagents, offers the corresponding (E)-enones in good yields as the only isolable products.

Journal Article↗

A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2).

A new gene family has been identified on the basis of in-depth bioinformatics analysis of the Down syndrome candidate region 1 (DSCR1) gene, located on 21q22.1. We have determined the complete coding sequences of similar genes in Saccharomyces cerevisiae and Caenorhabditis elegans, as well as that of a novel human gene, named DSCR1L2 (DSCR1-like 2). Peripheral blood leukocyte cDNA sequencing predicts as its product a 241-amino-acid protein highly similar to products of the human genes DSCR1 and ZAKI-4 (HGMW-approved symbol DSCR1L1). The highest level of expression of DSCR1L2 mRNA was found by Northern blot analysis in heart and skeletal muscles, liver, kidney, and peripheral blood leukocytes (three transcripts of 3.2, 5. 2, and 7.5 kb). The gene consists of four exons and spans about 22 kb on chromosome 1 (1p33-p35.3) (Human Chromosome 1, Sanger Centre). Exon/intron organization is highly conserved between DSCR1 and DSCR1L2. Two alternative DSCR1L2 mRNA splicing forms have been recognized, with one lacking 10 amino acids in the middle of the protein. Analysis of expressed sequence tags (ESTs) shows DSCR1L2 expression in fetal tissues (heart, liver, and spleen) and in adenocarcinomas. ESTs related to the murine DSCR1L2 orthologue are found in the 2-cell stage mouse embryo, in developing brain stem and spinal cord, and in thymus and T cells. The most prominent feature identified in the protein family is a central short, unique serine-proline motif (including an ISPPXSPP box), which is strongly conserved from yeast to human but is absent in bacteria. Moreover, homology with the RNA-binding domain was weakly but consistently detected in a stretch of 80 amino acids at the amino-terminus by fine sequence analysis based on tools utilizing both hidden Markov models and BLAST. The identification of this new gene family should allow a better understanding of the functions of the genes belonging to it.

Adaptor Proteins, Signal Transducing↗

Is lithium able to reverse neurological damage induced by vinca alkaloids? (Short communication).

Lithium (Li) actively antagonises the inhibiting action of vinca alkaloids on human leukocyte chemotaxis; it proved to be related to the activation of microtubular system, possibly mediated by its inhibiting effect on cyclic AMP. Vinca alkaloids induce peripheral neuropathy and muscle damage. The molecular basis of this neurotoxicity has not been fully explained, but a possible role of neurofibrillary degeneration has been reported. We studied both in animals and in humans, whether Li is able to antagonise vinca alkaloid neurotoxicity.

Adult↗

An advantageous method to evaluate IgH rearrangement and its role in minimal residual disease detection.

A sensitive, safe and cheap method to detect minimal residual disease (MRD) is here presented. The PCR-GS technique includes: (a) a fluorescent PCR for the IgH region with CDR3/JH consensus primers; (b) the electrophoresis on an automatic sequencer (ABI PRISM 310); (c) the analysis of results by the GeneScan program. A total of 72 samples were analysed: 34/49 B-cell Non-Hodgkin's Lymphoma (NHL) (69%), six out of seven Multiple Myeloma (MM) (86%), 1/2 Hodgkin's Disease (HD) and 4/4 Acute Lymphoblastic Leukaemia (ALL) were found to be positive, showing a monoclonal IgH rearrangement. The major bias of the PCR-GS method are the 21% of false negatives, but 13/15 negative patients carried t(14;18); consequently, the association of the evaluation by PCR assays of the IgH and BCL2/JH rearrangement allowed to detect a molecular marker of B-neoplasia in more than 94% of tested samples.

Adult↗

Differential activity of glycosaminoglycans on colony-forming cells from cord blood. Preliminary results.

Heparin, heparan sulfate and chondroitin sulfate were evaluated for their possible role on proliferation and differentiation of hematological precursor cells from cord blood. For these purposes, different concentrations of glycosaminoglycans were added to methyl-cellulose in colony assay performed with human cord blood derived cells. A volume of 10 microg/ml heparin induces a significant increase of both granulocyte-monocyte and granulocyte colonies, and a decrease of erythroid-colonies, more evident in the presence of 100 microg/ml. Heparan sulfate-treatment induces a significant increase of all granulocyte-monocyte colonies derived from CFU-granulocyte-monocyte, CFU-granulocyte and CFU-monocyte precursors. A significant decrease of multipotent cells was also observed. On the other hand, chondroitin sulfate induces an increase of granulocyte-colonies and a decrease of erythroid-colonies. Glycosaminoglycans with different structure may be useful to increase the number of specific colonies. The selective and differential binding of glycosaminoglycans with several growth factors and the regulation of their activities is discussed.

Fetal Blood↗

Arsenic and all-trans retinoic acid as induction therapy before autograft in a case of relapsed resistant secondary acute promyelocytic leukemia.

Arsenic trioxide has recently been reported to be successful in the treatment of promyelocytic leukemia. Several concerns about the use of this toxic agent are currently reducing its potential clinical use even in severely ill patients. In this report we describe the results achieved by As2O3 with all-trans retinoic acid in a patient suffering from secondary, relapsed, resistant promyelocytic leukemia. Several complications, including sepsis and an extensive area of skin necrosis, did not allow us to treat the patient further with chemotherapy. With As2O3 and ATRA therapy, the patient obtained a complete molecular remission without any significant toxicity and, subsequently, it was possible to perform a bone marrow autograft in a state of complete remission.

Adult↗

Clinical characteristics, treatment outcome and survival of 36 adult patients with primary anaplastic large cell lymphoma. Gruppo Italiano per lo Studio dei Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Although in recent years anaplastic large-cell lymphoma (ALCL) has emerged as a distinct clinico-pathological entity, a gold standard for treatment has still not been defined. Goals of our histologic, phenotypic and clinical study were to present clinical findings, treatment outcome and survival rates of a small, but highly homogeneously treated, series of patients. DESIGN AND METHODS: From April 1991, 36 newly diagnosed adult patients with systemic ALCL CD30+, entered a prospective non-randomized trial in one of the institutions participating in a GISL (Gruppo Italiano per lo studio dei Linfomi) study and were treated with a MOPP/EBV/CAD hybrid scheme. Chemotherapy (CHT) was administered every 28 days, for a total of 6 cycles. After CHT, 19 patients received radiation therapy (RT) to the site of previously involved fields. Kaplan and Meier and log-rank tests were used for statistical analysis. RESULTS: The overall complete remission rate was 78%, the partial remission rate was 6%. The overall survival rate at 74 months was 69%. No statistically significant differences in response or survival rates were noted comparing ALCL-HL and -CT subgroups, T+ Null- and B- subtypes, or ALCL-HL and -CT, with different phenotypes. In the analysis of patients with T+ Null phenotype treated with CHT+RT in comparison with B-ALCL patients who had the same treatment, we observed statistically significant differences in the survival rate (p=0.048). No prognostic factors predictive of response or survival were identified. INTERPRETATION AND CONCLUSIONS: Our results show that using MOPP/ABV/CAD the results, in terms of remission rate and survival, are similar to those obtained with 3rd generation CHT regimens. The diagnosis of T and Null ALCL is the most important prognostic factor, because it is associated with a very good survival, even in patients with a high prognostic index. Finally, we believe that longer follow-ups are needed to evaluate long-term survival and toxicity with different treatments.

Adolescent↗