Biomedical subjects

G Cimino

Publications and source records attributed to G Cimino.

At least 73 records · Page 4Linked to original sources

PubMed1997

Multigenetic lesions in infant acute leukaemias: correlations with ALL-1 gene status.

In this study we investigated the presence of structural lesions in the ALL-1, p53 and p16 (cyclin-dependent kinase 4 inhibitor) genes in leukaemic cells obtained from 22 patients with infant acute leukaemia (aged < 18 months). Of these, 18 cases were classified as acute lymphoblastic leukaemia (ALL) and four as acute myeloid leukaemia (AML). Tumour DNAs were analysed by a combination of Southern blot. polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequence analyses. The results showed ALL-1 gene rearrangements in 15/22 (68%) cases, p53 gene mutations in 5/22 (26%), and a homozygous deletion of p16 in a single T-ALL case. p53 and p16 alterations were all found in the group of patients with ALL-1 gene rearrangements. p53 mutations were more often associated with a myeloid phenotype (3/5). In summary, multiple molecular alterations were found in 6/15 (40%) infant acute leukaemias with ALL-1 rearrangements. As to the clinical course, patients with additional lesions had similar clinical outcome with respect to patients with ALL-1 gene rearrangement as the sole genetic aberration. This may support the hypothesis that ALL-1 alterations are genetic events per se sufficient to confer a fully malignant phenotype to the leukaemic clone.

Acute Disease↗

PubMed1997

Different serological examinations in cystic fibrosis patients: response to Pseudomonas aeruginosa St-Ag.

Crossed immunoelectrophoresis (CIE), enzyme linked immunosorbent assay (ELISA) and immunoblotting (IMB) were used to look for the presence of anti-bodies to Pseudomonas aeruginosa standard antigen in the sera of cystic fibrosis patients with intermittent (CF +/- P) and chronic (CF + P) colonization. Our results show that CIE is too complex a method to use when monitoring the infection over time, that with ELISA a correlation with the patient's clinical status may be made and that IMB can evidence an early, albeit low, reaction in the CF +/- P patient.

Adult↗

PubMed1996

Novel diterpenoid diacylglycerols from marine molluscs: potent morphogens and protein kinase C activators.

Five novel 1,2-sn-diacylglycerols with diterpenoid acyl moieties in the sn-1 position were isolated and characterized, together with the corresponding 1,3-sn-diacylglycerols, from three species of dorid nudibranchs molluscs. Their potent activity as morphogens in vivo in the Hydra tentacle regeneration assay and their parallel activity as activators of rat brain protein kinase C (PKC) in vitro are reported here. Our findings promote the use of these compounds as useful molecular probes for both in vivo and in vitro studies on the participation of PKC in cell development.

Animals↗

PubMed1996

Distribution of TP53 mutations among acute leukemias with MLL rearrangements.

Acute leukemias carrying MLL rearrangements are characterized by a high degree of clinical and immunologic heterogeneity, as demonstrated by variability in their immunophenotype, consistent with lymphoid or myeloid/monoblastic derivation, as well as their occurrence in distinct age groups from infancy to adulthood. Recently, it was shown that inactivation of the TP53 tumor suppressor gene occurs frequently in cases of acute lymphoblastic leukemia carrying MLL rearrangements. In order to assess the extent of TP53 inactivation throughout the immunophenotypic and clinical spectrum of MLL+ acute leukemias, we tested for TP53 mutations 29 cases of MLL+ acute leukemias displaying lymphoid (13 cases) or myeloid/monoblastic (16 cases) features and belonging to different age groups. Mutations were detected in 6/16 myeloid/monoblastic cases and in 3/13 lymphoid cases. Among myeloid/monoblastic leukemias, the TP53 mutations occurred in 3/4 infants, but only in 3/16 cases in other age groups. Overall, our data suggest that (1) TP53 inactivation is a relatively common event in leukemias with MLL rearrangements irrespective of the leukemic phenotype and of the patients' age; (2) at least two genetic lesions (i.e., MLL rearrangement and TP53 mutation) have accumulated in the short time (few weeks after the birth or conception of the child) corresponding to the development of acute leukemias of infancy.

Acute Disease↗

PubMed1996

Precipitating Pseudomonas aeruginosa antibodies and antimicrobial therapy in cystic fibrosis patients.

Forty patients with cystic fibrosis were studied bacteriologically and serologically. Precipitating Pseudomonas aeruginosa antibodies were monitored by crossed-immunoelectrophoresis (CIE) in order to evaluate the possibility of preventing chronic colonization by Pseudomonas aeruginosa by cycles of antimicrobial therapy. Sputum or pharyngeal aspirate and serum samples from all patients were analyzed by means of spread on selective media and CIE, respectively. Significant differences in the number of precipitins were obtained: noncolonized and intermittently colonized patients had no precipitins, whereas the number of precipitins in the chronically colonized patients varied from 11 to 44. An increase in the number of precipitins could be a good marker for initiation of therapy with antimicrobial agents that are either active against Pseudomonas aeruginosa or able to inhibit the release of virulence factors.

Adolescent↗

PubMed1996

Clinical relevance of residual disease monitoring by polymerase chain reaction in patients with ALL-1/AF-4 positive-acute lymphoblastic leukaemia.

In this study we used reverse transcriptase-polymerase chain reaction (RT-PCR) for the longitudinal monitoring of minimal residual disease in 12 patients with All-1/AF-4 positive ALL. Of these, seven also showed at presentation a typical t(4;11) cytogenetic translocation. Seven patients were infants <18 months of age and five were adults. Eleven patients were treated with high-dose intensive induction and consolidation chemotherapy without bone marrow transplantation and one received conservative treatment due to poor performance status. Three had resistant disease, four relapsed within 12 months after achieving complete remission, and five are in continuous complete remission (CCR) at 32, 39, 52, 53 and 61 months from diagnosis, respectively. The sequential analysis of the ALL-1/AF-4 hybrid transcript showed a persistently negative RT-PCR in the five CCR long-term survivors. The PCR analysis resulted persistently positive in the remaining seven cases, including the four cases who relapsed after the achievement of clinical CR. These data emphasize the clinical relevance of PCR monitoring analysis in t(4;11) ALL patients and should be considered in order to better determine variable post-remission treatment according to risk prediction.

Adult↗

PubMed1996

Inflammatory pseudotumour of the liver with malignant transformation. Report of two cases.

Inflammatory pseudotumour is a rare pathologic lesion, of unknown aetiology, rarely involving the liver. Resection seems to be the treatment of choice and it is generally associated with a good prognosis. Histologically, these processes appear to be benign, nevertheless, aggressive courses or recurrences of inflammatory pseudotumour with tumor-like deaths have been reported. The cases of two patients are described who underwent hepatic lobectomy for a liver mass that was diagnosed as liver inflammatory pseudotumour at the initial histopathological assessment: albeit a malignant course followed and both the patients died cachectic. One patient, a 39-year-old man, had an unusually aggressive clinical course and recurrence of the disease with multiple hepatic masses and extension into the thorax six years later. In the other case, in a 28-year-old woman, the hepatic lesion was identified as a low-grade hepatic sarcoma only seven years after surgery.

Adult↗

PubMed1995

Detection of homozygous deletions of the cyclin-dependent kinase 4 inhibitor (p16) gene in acute lymphoblastic leukemia and association with adverse prognostic features.

A recently described putative tumor suppressor gene, the cyclin-dependent kinase 4 inhibitor (p16), has been shown to be altered by deletions and/or point mutations in various human cancers. To assess the incidence and clinico-biologic correlations of p16 homozygous deletion in hemopoietic tumors, we studied a panel of 244 DNA samples representative of distinct acute (99 cases) and chronic (57 cases) leukemia subtypes, myelodysplastic (22 cases) and myeloproliferative (15 cases) syndromes, and lymphomas (51 cases). A 361-bp probe complementary to the p16 exon 2 gene sequences was generated by polymerase chain reaction and used in Southern blot hybridization against these tumor DNAs. Homozygous deletions of p16 (p16-/-) were detected in 10 of 58 (17%) cases of acute lymphoblastic leukemia (ALL) of either B or T lineage and in no other tumors. Single-strand conformation polymorphism analysis of p16 exons 1 and 2 was also performed in 40 of the 58 ALL cases and in 16 lymphomas. In no cases were point mutations detected. The comparison of clinical features at presentation in p16-/- and in p16 germline ALL cases showed a greater leukemic cell mass (P = .001) and higher white blood cell counts (P = .01) in the former group. Two ALL cases in which diagnostic and relapse DNA samples were available showed p16-/- in both specimens. We conclude that homozygous p16 gene deletions characterize a subset of ALL with features of aggressive disease.

Adolescent↗

PubMed1995

ALL-1 gene rearrangements in acute myeloid leukemia: association with M4-M5 French-American-British classification subtypes and young age.

We have analyzed by Southern blotting the ALL-1 (MLL, HRX, Hrtx 1) gene configuration in a series of 126 patients with acute myeloid leukemia (AML) representative of all ages and French-American-British Classification groups and correlated this genetic feature with clinical and biological features at diagnosis. ALL-1 gene rearrangements were detected in 17 of the 74 cases with M4-M5 (myelomonocytic and monocytic) AML and in 2 of the 52 cases with other leukemic subtypes (P < 0.01). Within the series of 74 M4-M5 patients, ALL-1 rearrangements were significantly associated with French-American-British Classification M5 (P = 0.009), high WBC (P = 0.002), and young age. In particular, all 5 infant (< 1.5 years) AML cases, 6 of the 19 (31%) patients between 1.5 and 18 years of age, and 6 of the 50 (12%) patients > 18 years old showed an altered ALL-1 genomic configuration (P < 0.001). Immunophenotypic characterization revealed coexpression of lymphoid and myeloid markers in 6 of 17 ALL-1 rearranged M4-M5 cases. The IgH gene configuration was studied in 77 of 126 AMLs. Five patients (6%) showed IgH clonal rearrangements and all were in the ALL-1 rearranged group (P < 0.0001). Our findings indicate that ALL-1 rearrangement is the commonest genetic alteration presently detectable in M4-M5 AML, particularly in childhood where it is found in up to one-third of all cases. The association of IgH rearrangements with ALL-1 alterations in AML, coupled to the frequent detection in this subset of lymphoid associated markers, further supports the origin of these tumors from a common multipotent precursor with bipotential lymphoid and monocytic differentiation capability.

Adolescent↗

PubMed1995

Severe case of Al Awadi/Raas-Rothschild syndrome or new, possibly autosomal recessive facio-skeleto-genital syndrome.

A Sicilian girl whose parents were first cousins had a severe tetramelic limb deficiency (amelia of lower limbs, peromelia of upper limbs) and other defects including cleft lip and palate, facial anomalies, athelia, low umbilicus, bladder exstrophy, no external genitalia, and anteriorly displaced anus. This probably represents a particularly severe case of Al Awadi/Raas-Rothschild syndrome (limb/pelvis-hypoplasia/aplasia syndrome, LPHAS), but the possibility of a new autosomal recessive facio-skeleto-genital syndrome cannot be excluded.

Abnormalities, Multiple↗

PubMed1995

Analysis of the BCL-6 gene configuration in diffuse B-cell non-Hodgkin's lymphomas and Hodgkin's disease.

BCL-6 is a novel proto-oncogene that codes for a zinc-finger protein sharing homologies with many transcription factors. It has recently been shown that BCL-6 is involved in chromosome band 3q27 aberrations in non-Hodgkin's lymphomas (NHLs) and BCL-6 rearrangements have been detected in 34-45 per cent of diffuse large cell lymphomas with B immunophenotype. We have studied the BCL-6 gene configuration by Southern blot analysis in 60 cases of B-cell NHL and in 17 cases of Hodgkin's disease (HD). BCL-6 was rearranged in 15/46 (32.6 per cent) diffuse B-large cell lymphomas, mainly with centroblastic morphology, and in 2/11 (18.2 per cent) follicular (centroblastic-centrocytic) lymphomas. Conversely, all cases of HD, including four cases of lymphocyte predominant, nodular type (nodular paragranuloma), had a germline configuration. These findings confirm that BCL-6 is rearranged in a significant percentage of diffuse B-large cell lymphomas, suggesting that this proto-oncogene might have a pathogenetic role in this subset of NHLs, but our preliminary analysis suggests that BCL-6 lesions are not involved in the pathogenesis of HD. However, further investigations using more sensitive techniques are required to confirm these findings.

Blotting, Southern↗

PubMed1995

[Morphologic and ultrastructural changes of soft palate in patients who underwent palatopharyngoplasty].

In order to clarify pathogenesis of Obstructive Sleep Apnea Syndrome (OSAS) in patients with anatomic abnormalities of upper airways, we studied soft palate and uvula of OSAS patients by means of histological and ultrastructural techniques. 38 OSAS patients, severe and moderately severe form, underwent modified Palatopharingoplasty. We evaluated only 16 OSAS patients' soft palate and uvula and observed histological changes in all of them: submucosal edema and minor salivary glandes ipertrophy and iperplasy are present. On the contrary, ultramicroscope showed normal muscle fibers. Strie Z alterations and sarcomeres disorganization, although present, have no statistical value. Very probably, ronflement and apneas determined the observed alterations through trauma on pharingeal wall. Therefore, they are not OSAS primary cause.

Humans↗

PubMed1995

p53 gene inactivation in acute lymphoblastic leukemia of B cell lineage associates with chromosomal breakpoints at 11q23 and 8q24.

The clinical heterogeneity of acute lymphoblastic leukemia (ALL) of B cell lineage reflects the presence of distinct molecular pathways leading to well-defined ALL molecular subtypes. These molecular pathways include the formation of the fusion transcripts BCR/ABL and E2A/PBX1, due to t(9;22) and t(1;19), respectively, as well as rearrangements of the MLL gene at 11q23 and of c-MYC at 8q24. Hyperdiploid ALL in the absence of chromosomal structural abnormalities is an additional ALL molecular subtype. Mutations of the RAS family genes and of the p53 tumor suppressor gene represent additional genetic lesions detected in a fraction (10-20%) of ALL cases. RAS activation in ALL may be detected in all molecular subtypes of ALL and denotes poor prognosis. Conversely, little is known regarding the clinical and biological features of ALL cases carrying p53 mutations. In order to help clarify the role of p53 inactivation in ALL development, we have determined the frequency of p53 mutations throughout the molecular spectrum of B cell lineage ALL. We report that p53 inactivation in ALL of B cell lineage is restricted to cases carrying a rearrangement of MLL or c-MYC, whereas it is consistently negative in other molecular subgroups. These data underline the molecular heterogeneity of ALL of B cell lineage and indicate that at least some of the molecular pathways involved in ALL pathogenesis require more than one genetic lesion.

Base Sequence↗

PubMed1995

Acute leukemia presenting a variant Ph chromosome with p190 expression, dup 3q and -7, developed after malignant lymphoma treated with alkylating agents and topoisomerase II inhibitors.

We describe the occurrence of a variant Ph chromosome (v-Ph) in a therapy-related acute leukemia (s-AL), developed after 8-year treatment for a NHL with alkylating agents, anthracyclines and topoisomerase II inhibitors. The v-Ph originated from a complex t(2;9;22) translocation, expressed a p190bcr-abl fusion protein, and was associated to other specific changes, such as dup(3) (q21q26) and -7. The s-AL, apparently not preceded by a dysplastic phase, presented with signs of trilineage dysplasia with 10% micromegakaryocytes; it was classified as M5 according to FAB. The complex genetic changes observed in the present case may reflect distinct leukemogenic effects by different chemotherapeutic agents.

Acute Disease↗

PubMed1995

Therapy-related acute myelomonocytic leukemia following successful treatment for acute promyelocytic leukemia.

We report a case of therapy-related acute myeloid leukemia (t-AML), M4 FAB subtype, with t(10;11)(p14;q21) chromosome abnormality developed in a patient treated for acute promyelocytic leukemia (APL) after 4 years of continuous complete remission (CCR). Two distinct forms of t-AML have been described: the classical type and the second type. Our case has many characteristics in common with the second type of t-AML such as: exposure to topoisomerase II active agents (idarubicin (IDA), mitoxantrone (MITOX), etoposide (VP16)), M4 FAB subtype, a latency period of 39 months and absence of a preleukemic phase. However, it differs in the chromosome 11 breakpoint (band q21 instead of q23) and absence of ALL-1 (Hrx, MLL, Htrx) gene involvement. This can represent the second observation of t-AML occurring after treatment for APL.

Adolescent↗

PubMed1995

Prognostic relevance of ALL-1 gene rearrangement in infant acute leukemias.

We and others have recently reported a high frequency (70-80%) of ALL-1 (MLL, HRX, HTRX) gene rearrangements in infants with acute leukemias (AL) aged less than 1 year. Preliminary observations in limited series also suggested that ALL-1 gene configuration is an important prognostic factor in this leukemic subset. We have now extended our study to a series of 45 AL patients aged between 0 and 18 months. The genomic configuration of ALL-1 in leukemic DNAs was determined by Southern blot hybridization and correlated with biological and clinical features at presentation, as well as with treatment outcome. Twenty-nine out of 45 (64%) patients showed ALL-1 rearrangements, including 4/11 (36%) infants aged between 13 and 18 months. Considering morphological types, 24/38 cases with acute lymphoblastic leukemia and 5/7 patients with acute myeloid leukemia showed ALL-1 rearrangements. The features more frequently found in association with ALL-1 rearrangements were hyperleukocytosis (P < 0.007) and CD19+/CD10- blast immunophenotype (P < 0.02). ALL-1 status was an independent prognostic marker of event-free survival (EFS) in a multivariate model including age, sex and WBC count, and maintained its statistical significance when FAB morphology was considered in the analysis by including AML patients. Considering the ALL cases the actuarial EFS was 57 and 9% for infants with germline and rearranged ALL-1 configuration, respectively (P = 0.008). A high frequency of ALL-1 gene alterations in infant AL is confirmed by this study. In addition, our results emphasize the need for extending the analysis of ALL-1 gene status to infants with AL aged > 12 months. We show that this genetic lesion is the most important variable negatively affecting prognosis in a multivariate model including other known risk factors. This latter observation should influence the choice of risk-adapted treatment strategies in this AL subset.

Chromosomes, Human, Pair 11↗

PubMed1995

[Primary microcytoma of the larynx. Case report, ultrastructural study and review of the literature].

Oat cell carcinoma of the larynx is a rare tumor. A throughout search of the literature revealed only 80 cases; the first case in literature was reported by Olofsson in 1972. The tumor often presents in the sixth and seventh decades of life and appears to be highly aggressive and metastases develop early. We have had the opportunity to study ultrastructurally a small cell carcinoma of oat cell type arising in the larynx.

Aged↗

PubMed1994

Formation and inactivation of endogenous cannabinoid anandamide in central neurons.

Anandamide (N-arachidonoyl-ethanolamine) was recently identified as a brain arachidonate derivative that binds to and activates cannabinoid receptors, yet the mechanisms underlying formation, release and inactivation of this putative messenger molecule are still unclear. Here we report that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents. Anandamide formation occurs through phosphodiesterase-mediated cleavage of a novel phospholipid precursor, N-arachidonoyl-phosphatidylethanolamine. A similar mechanism also governs the formation of a family of anandamide congeners, whose possible roles in neuronal signalling remain unknown. Our results and those of others indicate therefore that multiple biochemical pathways may participate in anandamide formation in brain tissue. The life span of extracellular anandamide is limited by a rapid and selective process of cellular uptake, which is accompanied by hydrolytic degradation to ethanolamine and arachidonate. Our results thus strongly support the proposed role of anandamide as an endogenous neuronal messenger.

Animals↗