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G Martinelli

Publications and source records attributed to G Martinelli.

At least 217 records · Page 12Linked to original sources
PubMed1994

The HLA class I-CML association revisited taking into account the two forms of gene fusion in the Philadelphia chromosome. A multicenter study.

CML patients possess either a b3-a2 or a b2-a2 fusion between the BCR and ABL genes. Depending on the type of fusion, two different series of non-self potentially immunogenic peptides may be produced. If they are presented by HLA class I molecules and recognized by cytotoxic CD8 lymphocytes, individuals could be more susceptible or resistant to leukemic cells bearing one or the other form of fusion according to their HLA class I phenotype. To test this point, the frequencies of HLA-A and HLA-B alleles were compared between b3-a2 and the b2-a2 CML patients. In essence, no difference was found whose significance could withstand correction for multiple comparisons.

Base Sequence↗
PubMed1994

[Discrepancy between histopathological diagnosis based on guided biopsy and cone biopsy of the cervix uteri: analysis of 346 cases of laser conization].

The conservative management of cervical intraepithelial neoplasia (CIN) essentially depended on the introduction and improvement of colposcopy. This technique, allowing to locate the lesion, to estimate its extension and to perform multiple punch biopsies, becomes discriminant in therapeutic choice. Whether colposcopy reveals endocervical involvement or abnormal transformation zone (ANTZ) may be only partially explored, excisional conization should be preferred to ablative therapy since the former advantageously can verify histopathologic diagnosis, confirm completely excision of lesion and rule out invasive carcinoma. The literature shows that cases of invasive lesions can be underestimated and therefore inadequately treated by ablative therapy, emphasizing colposcopy and punch biopsy limitations about suspect and diagnosis of microinvasion. We analyzed data concerning preliminary diagnostic investigations and results of 346 CO2 laser excisional conizations performed between 1984 and 1993. Histopathologic diagnosis on punch biopsy, performed in 111 cases of ANTZ1 and in 235 cases of ANTZ2, shows an agreement with cone biopsy in 30.8% of the cases of CIN1, of 40.9% in cases of CIN2 and of 66.3% in cases of CIN3. Whereas the lesion is overestimated in 30.6% of cases, in which it is likely that punch biopsy has removed the epicenter of the lesion or the lesion in toto, we had an underestimation in 15% of cases, particularly in 4 cases of CIN2, in 38 cases of CIN3 and in all microinvasive processes. The rate of invasive lesions previously ignored and detected only by histopathologic diagnosis on cone biopsy is 2.9%. In only one of these cases colposcopy, even if attributing to each of these the higher grading, shows the suspicion of invasion, whereas the detection of invasive processes is missed in every case by punch biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Molecular analysis of six variant Philadelphia chromosome translocations in chronic myeloid leukemia.

In 420 Philadelphia positive (Ph+) chronic myeloid leukemia (CML) patients karyotyped at diagnosis in our laboratory, 26 Ph variants (6.2%) were observed. Twelve of them are reported. Five cases are "simple" variants without detectable involvement of band 9q34, and seven are "complex," since a third chromosomal band is involved in the Ph formation. Two translocations [t(7;22)(q36;q11) and t(9;22;12)(q34;q11;q11)] are reported for the first time. Six cases were characterized molecularly, and bcr-abl rearrangement was demonstrated, confirming involvement of 9q34 band also in the cases in which chromosomes 9 appear cytogenically normal. Chimeric mRNAs in which M-BCR exon 3 is joined to abl exon 2 (type b3-a2) were detected in four of six cases; one case showed a DNA breakpoint in zone III, which may also give rise to the same transcript. In one case, mRNA junction was b2-a2. The frequency of the b3-a2 junction occurs more frequently in CML patients with a Ph variant than in patients with the standard translocation, suggesting a preferential correlation between this type of transcript and the involvement of other chromosomes in Ph formation.

Adult↗
PubMed1993

t(8;14)(q11;q32) in acute lymphoid leukemia: description of two cases.

An 8;14 chromosome translocation with breakpoints at q11 and q32, respectively, is described as the sole abnormality in bone marrow cells of two adult patients with common acute lymphoblastic leukemia (ALL). The Southern blot analysis revealed a rearrangement after BamHI and HindIII digestion and hybridization with a JH probe, thus demonstrating the involvement of the gene coding for the heavy chains of the immunoglobulins (IgH). Therefore, a pathogenetic mechanism similar to that observed in Burkitt's lymphoma and its variants, or in other lymphomas with t(11;14) or t(14;18), may be hypothesized. In all these cases IgH is juxtaposed to an oncogene (c-MYC, BCL-1, and BCL-2, respectively). A similar structure, with oncogene type potential, could be present on 8q11. The patients underwent a complete remission after induction therapy.

Adult↗
PubMed1993

Chronic oral etoposide in small-cell lung cancer: clinical and pharmacokinetic results.

AIMS: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of chronic oral etoposide (E) in patients (pts) with small-cell lung cancer (SCLC) previously untreated with chemotherapy. PATIENTS AND METHODS: Twenty-seven (14 extensive-, 13 limited-stage) pts receiving 100 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 microgram/ml) with evaluation during the first cycle of weekly 24-hour drug concentrations. RESULTS: Among 25 evaluable pts, 60% (95% CI: 39%-79%) overall response, 144 and 217 days of median PFS and survival. Dose-limiting non-cumulative neutropenia of high interpatient variability. Linear reduction (30% per week) of absolute neutrophil counts (ANC) up to the 3rd week, recovering the following week. Risk factors for neutropenia (age, PS, serum creatinine and albumin) not identified. High inter-patient variability of 24-hour E plasma levels. A weak correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC, but higher relative decrease of ANC in pts with 24-hour E plasma levels of > 0.32 microgram/ml. CONCLUSIONS: Chronic oral E is effective in SCLC pts previously untreated with chemotherapy. Careful hematological monitoring is essential to avoid severe myelosuppression. The degree of neutropenia might be related to the maintenance of a critical drug concentration level for a critical period of time.

Administration, Oral↗
PubMed1993

Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation.

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially alpha 1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex "lytic" state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.

Adolescent↗
PubMed1993

The type of BCR/ABL junction does not predict the survival of patients with Ph1-positive chronic myeloid leukaemia.

The prognostic value of the location of the breakpoint on chromosome 22 in patients with Ph1+ chronic myeloid leukaemia (CML) is still controversial. We analysed both DNA rearrangement and transcript type in a new continuous series of CML patients. By Southern blotting analysis, we found that, out of 72 patients, 43 had a 5' rearrangement and 29 a 3' one, of the 43 5'-rearranged patients, 35 carried an a2b2 transcript and eight an a2b3 one, while, of the 29 patients rearranged in the 3' part of the M-BCR area, 26 had an a2b3 transcript, one had an a2b2 transcript and two carried both types of transcript. Thus, mRNA studies allow to detect an a2b3 transcript in 17.7% of 5' rearranged patients. However, no correlation was observed between type of transcript and survival, as after DNA studies.

Adolescent↗
PubMed1993

Structural organization of BCR-ABL gene in chronic phase and blast transformation in chronic myeloid leukemia patients.

We studied 36 DNA samples of 18 patients affected with chronic myeloid leukemia (CML) for the presence of mutations in the first exon of the BCR gene was divided into four regions amplified by polymerase chain reaction (PCR). By single strand conformation polymorphism analysis (SSCP) and direct sequencing of amplified fragments, we found different banding profiles in 9 out of 18 patients in the PCR fragment spanning nucleotide 506-826. In one patient, sequence analysis revealed the presence of a point mutation at nucleotide 669 (A-T; Gln-Leu). No difference was found between DNA samples collected during the chronic phase and the blastic transformation. No different mobility shifts of single stranded PCR products were found in the other amplified fragments. The activation of BCR-ABL involves direct interaction between BCR first exon sequences and the tyrosine kinase regulatory domains of ABL. In the first BCR exon, and around the mutated sequences two SH-2-binding sites, are retained. These domains are essential for BCR-ABL-mediated transformation. Our results demonstrate the presence of point mutation in this regulatory region, which may suggest a role for the altered BCR sequence in activation of the BCR-ABL oncogene.

Base Sequence↗
PubMed1993

Will molecular biology contribute to refine prognosis and to select treatment? The Molecular Biology Committee. Italian Cooperative Study Group on Chronic Myeloid Leukemia.

The possible prognostic value of the position of the breakpoint within the M-BCR in patients with Ph1+ CML is still being debated. We analyzed the DNA rearrangements and the transcript types of 244 patients and tried to correlate the data obtained with prognostic features, defined according to Sokal's risk index, and with chronic phase and/or survival duration. The exact location of the breakpoint, either 5' or 3' to the Hind III restriction site within the M-BCR was identified. Moreover, the exact M-BCR subregion was also identified. As a whole, 150 pts were rearranged in the 5' part and 94 in the 3' part of the M-BCR. No correlation was observed between the site of rearrangement on the one hand and the Sokal's prognostic index and survival, on the other. Transcript analysis was performed in 130 patients; 59 carried an a2b2 and 69 an a2b3 pattern. Two patients carried both transcripts. Of the patients rearranged in the 5' area, according to Southern blotting, 29.2% showed an a2b3 transcript. Therefore, RT-PCR analysis allowed a better definition of the breakpoint. However, also the type of transcript did not show any correlation either with risk categories or survival. No difference in response to therapy, either chemotherapy or alpha interferon, was observed between 5' and 3' rearranged patients.

Antineoplastic Agents↗
PubMed1993

Hemoperfusion--state of art.

The authors make a general review of the state of art in HP with particular reference to the history, the main field of application, and the development of specific and selective sorbents. In this text, attention is paid to the application in the immunological field comparing the therapeutical removal of toxins with different sorbents. Next, the authors describe their experimental study with hemoperfusion using coated anion exchange resins for the treatment of acute respiratory insufficiency, the correction of metabolic alkalosis in pyloric stenosis, the removal of a high dosage of antiblastic agent in conjunction with the study of heparin subtraction by coated resins and finally the development of a particular type of resin for phosphates removal in uremia. These different fields of research recognize the necessity to look for a selective exchange by hemoperfusion because the concept of the "magic filter" that removes everything is not scientifically acceptable. Some explanations are given for the behaviour of the strong anion exchange resins regarding simple or complex ions and the influence of the chemical composition of the matrix. In conclusion, the authors underline that selective removal by HP is actually underutilized considering its potency.

Alkalosis↗
PubMed1993

[Blastoma of the lung--a rare malignancy. Case report].

Pulmonary blastoma--so called because of its histological resemblance to fetal lung--is a rare malignant neoplasm, which tends to relapse locally and metastasize mainly in the first years, has a poor 5-year prognosis, and shows a potential radio-chemosensitivity. We report our findings and therapeutic approach in a case of a 64-year-old male.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT.

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.

Adult↗
PubMed1993

New strategies for selection of unrelated bone marrow donors.

An important problem in the selection of unrelated donors for bone marrow transplantation (UD-BMT), is HLA matching, between selected donor and recipient. Serological screening, mixed lymphocyte culture (MLC), and sequence specific oligonucleotide genotyping (PCR-SSO) are the methods commonly used for typing of HLA-genes. These ways to select donor candidates are time-expensive. We set up new applications of the "fingerprinting-PCR" technique, to analyse the polymorphic second exon of DRB, DQB, DQA, DPB of HLA Class II and second exon A, B, C HLA-Class I genes, and to search for identity between patient and serologically selected unrelated donors. In an assessment of the technique, 50 normal samples, and 4 unrelated HLA-A and HLA-B serological matched patient-donor pairs were analysed for HLA polymorphic regions. In 3 of the 4 cases (UD-BMT) at least HLA-DRB mismatched different donor-transplanted patterns were identified. In all cases PCR-SSO analysis was performed as control. Based on our data, we suggest that identification of UD for allogeneic BMT should follow these steps: 1) serological HLA-Class I and II genes screening; 2) HLA-Class II DRB gene PCR fingerprinting; 3) confirmation by SSO analysis in case of fingerprinting identity. 4) HLA-Class II DQA, DQB, DPB PCR fingerprinting. Moreover, confirmation by PCR fingerprinting or protein isoelectrofocusing of HLA-Class I identity is recommended. This "strategy" may contribute to rapid and specific selection of unrelated marrow donors.

Base Sequence↗
PubMed1992

[Pericardial effusion in patients with malignant neoplasms].

Pericardial effusions are often present in patients suffering from tumoral diseases, especially lung and breast cancers. Between September 1984 and February 1991 we observed 21 patients with "malignant pericarditis", of whom 57% had carcinoma of the bronchus and 33% a carcinoma of the breast. The symptoms most frequently seen were dyspnea (in 76% of the patients) and tachycardia (67%), accompanied by enlargement of the heart on chest radiograph. The effusions were bloody in all the patients, and the pericardial fluid cytology was positive in 9 of 10 of the lung cancer patients. 16 patients were treated by pericardiocentesis and in 10 of these thiotepa and hydrocortisone were instilled intrapericardially. In this manner it was possible to avoid recurrences of major effusion. The survival of the patients who received the intrapericardial instillation seems to be longer than that of the remaining patients.

Adult↗