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L Baldini

Publications and source records attributed to L Baldini.

At least 55 records · Page 3Linked to original sources
PubMed1998

Stimulation of rat peritoneal mast cells induces phagocytosis of adriamycin by rat peritoneal macrophages.

Rat and beige mouse peritoneal mast cells, induced to exocytose with the antineoplastic agent adriamycin, extrude their granule remnants in the extracellular medium. These granules are loaded with the fluorescent drug adriamycin and exhibit intense yellow-reddish fluorescent staining. Granules extruded from mast cells were ultimately phagocytosed and could be observed inside the macrophages by fluorescence microscopy. All stages of the internalization process could be followed by electron microscopy. Granules adhering to the cell surface of macrophages were first embraced by short superficial projections, then enveloped by deep surface infoldings, and finally engulfed into the macrophage cytoplasm. Phagocytosis occurred exclusively in macrophages; granules were observed also on the surface of eosinophils and lymphocytes, but never inside these cells. The concentrations of adriamycin in macrophages, measured by spectrofluorimetry, were significantly higher when these cells were incubated with adriamycin and granule remnants in comparison with adriamycin alone. Preincubation with the endocytosis inhibitor cytochalasin B significantly reduced the granule mediated adriamycin uptake. As a consequence of the phagocytosis of adriamycin loaded mast cell granules, macrophages can concentrate the antineoplastic drug. These cells act as reservoirs of adriamycin and could have an important role in both the antitumor and toxic effects of the drug.

Animals↗
PubMed1998

Plasmablastic lymphoma of the stomach. A case report.

We report the case of a 53 year-old woman with a gastric tumor showing morphological, phenotypical and molecular features of a plasmablastic lymphoma, a recently recognized subtype of diffuse large B-cell lymphoma. The tumor was composed of plasmablast-like cells, lacked CD45 and B-cell associated antigens, expressed the plasma cell-associated antigen CD38, and showed clonally rearranged IgH genes in the absence of bcl-2 and bcl-6 genes rearrangement.

Female↗
PubMed1998

Handling of doxorubicin by the LLC-PK1 kidney epithelial cell line.

The characteristics of doxorubicin handling have been studied in the cultured kidney epithelial cell line LLC-PK1, which has structure and function similar to those of renal tubular cells and expresses P-glycoprotein. The uptake of doxorubicin by LLC-PK1 cells was time dependent, reaching a steady state at about 4 hr, and reduced at low temperature; the initial uptake was saturable. The efflux of doxorubicin from LLC-PK1 cells was also temperature dependent but, even at 37 degrees C, a significant percentage of the drug remained associated with the cells after 180 min, which suggests a strong cellular binding, and the fluorescence microscopy revealed that the drug was concentrated in intracellular organelles. Substances that are substrates for P-glycoprotein, such as verapamil, vinblastine, vincristine and quinidine, significantly increased doxorubicin concentrations in LLC-PK1 cells. Similar results were obtained with the metabolic inhibitors sodium metavanadate and 2,4-dinitrophenol. On the other hand, the uptake was not affected by the classic organic cation transport drugs cimetidine, decynium 22 or decynium 24, nor by the organic anion drug probenecid. These results indicate that, in LLC-PK1 cells, doxorubicin enters by passive diffusion, is trapped in intracellular organelles and then is extruded from cells by a mechanism that probably involves P-glycoprotein. On the contrary, substances that interfere with the renal organic cation or anion secretory system have no effect on doxorubicin net accumulation in these cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL.

BACKGROUND AND OBJECTIVE: To compare the efficacy of ProME(Epidoxorubicin)CE-CytaBOM (PE-C) and ProMI(Idarubicin)CE-CytaBOM (PI-C) in the treatment of adult patients with aggressive non Hodgkin's lymphoma in a multicenter randomized controlled trial performed by 18 centers of the Italian Lymphoma Study Group (GISL). DESIGN AND METHODS: One hundred and twenty-eight and 122 patients were randomly assigned to receive either 6 courses of PE-C or PI-C, respectively. Some patients achieving complete remission with induction therapy participated in another randomized study comparing no further therapy versus maintenance therapy consisting of four blocks of two drugs. RESULTS: The rate of CRs was 62% and 64% for patients treated with PE-C and PI-C, respectively (p = 0.51). The 5-year relapse-free survival was 60% for PE-C and 53% for PI-C (p = 0.29). The estimated relapse-free disease survival rates at 4 years were 75% for patients in the consolidation group and 57% for those in the observation group (p = 0.11). Patients alive in first complete remission 4 years after study entry were estimated to be 39% in the PE-C arm and 38% in the PI-C arm (p = 0.90). The 3-year and 5-year estimated survival rates were 61% and 55% for the PE-C group and 56% and 47% for the PI-C group (p = 0.26). Fatal toxicities occurred in 7 patients (2.9%) with active disease and in 4 patients (1.7%) in complete remission. Stage (p = 0.04), bulky disease (p = 0.02), serum LDH (p = 0.0006), serum albumin (p = 0.0051), hemoglobin (p = 0.0011), performance status (p = 0.0001), International prognostic index (p < 0.0001) and the index proposed by the French group G.E.L.A. (p < 0.0001) were of prognostic value. In a multivariate analysis (Cox regression model) alternatively IPI alone or G.E.L.A. index plus performance status emerged as independent prognostic factors. INTERPRETATION AND CONCLUSIONS: The present study indicates that epirubicin and idarubicin in a combined chemotherapy regimen, have similar activities. The toxic profile also indicates the safety of both anthracyclines at the dosages employed, suggesting their possible dose escalation in a combined chemotherapy setting. PE-C and PI-C were both effective and feasible regimens in an outpatient setting, with acceptable cardiovascular toxicity. The trend toward a better outcome in patients undergoing consolidation therapy after the achievement of a complete remission, warrants further investigation.

Adolescent↗
PubMed1998

Retrospective analysis of mantle cell lymphoma: experience of the "Gruppo Italiano per lo Studio dei Linfomi" (GISL).

BACKGROUND AND OBJECTIVE: Mantle cell lymphoma is a recently recognized histologic entity with specific biological and clinical features. Clinically, the reported unfavorable outcome of these patients has focused attention on this category of non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: The slide specimens of 69 NHL patients, originally classified as Working Formulation (WF) group B and E, were reviewed. The clinical features at presentation, response to therapy, response duration and survival were analyzed in cases reclassified as MCL. The correlation between clinical and histologic characteristics and the final outcome was evaluated. RESULTS: Out of 69 cases, 34 specimens were reclassified as MCL; in 6 patients, previously classified as WF group B, the nodular pattern was confirmed; in 2 instances the blastoid form was recognized. After a median follow-up of 35.7 months, the entire series displayed a median overall survival of 41.2 months; a significantly longer survival was associated with the nodular histologic pattern, IPI score < 2, response achievement, and a higher Hb level. The vast majority of patients received anthracycline-containing combination chemotherapy. Complete remission rate was 38.8% and overall response rate was 67.6%; response achievement was significantly influenced only by Hb level. Median response duration was 23.3 months. INTERPRETATION AND CONCLUSIONS: The present study confirms the unfavorable clinical course of MCL and the possible need for an alternative therapeutic strategy for this NHL category. Therefore, the correct identification of MCL at diagnosis appears of relevance.

Adult↗
PubMed1997

A novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene.

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), the most consistent chromosomal abnormality is the 14q+ marker, which originates in one third of cases through a t(11; 14)(q13; q32) chromosomal translocation; in the remaining cases, the identity of the partner chromosomes has not been well established. We used a Southern blot approach based on the linkage analysis of the joining (J) and the constant (C) mu, alpha, and gamma regions to detect cases bearing IGH switch-mediated chromosomal translocations. We evaluated DNA of 88 nonkaryotyped patients with MM (78 cases) or plasma cell leukemia (PCL) (10 cases) and found the presence of "illegitimate" rearranged IGH fragments (no comigration between the J and C regions) in 21 cases. To confirm this analysis, we cloned the illegitimate rearranged fragments from three samples, and the molecular and fluorescent in situ hybridization (FISH) analyses indicated the presence of chromosomal translocations juxtaposing a switch IGH region to sequences from chromosomes 11q13 (one PCL case) or 4p16.3 (two MM cases). Interestingly, the breakpoints on 4p16.3 occurred about 14 kb apart in a genomic region located approximately 50 kb centromeric to the fibroblast growth-factor receptor 3 (FGFR3) gene. Moreover, Southern blot analysis using 4p16.3 genomic probes detected a rearrangement in an additional MM tumor. FISH analysis of the MM-derived KMS-11 cell line, reported to be associated with a t(4; 14)(p16.3; q32), showed that the FGFR3 gene was translocated on 14q32. High levels of FGFR3 mRNA expression were observed in the cloned MM tumors and KMS-11 cell line, but not in the cases that were apparently negative for this lesion. Furthermore, a point mutation at codon 373 in the transmembrane domain of the FGFR3 gene resulting in an amino acid substitution (Tyr --> Cys) was detected in the KMS-11 cell line. These findings indicate that the t(4; 14)(p16.3; q32) represents a novel, recurrent chromosomal translocation in MM, and suggest that the FGFR3 gene may be the target of this abnormality and thus contribute to tumorigenesis in MM.

Base Sequence↗
PubMed1997

A pilot study on the use of the ProMACE-CytaBOM regimen as a first-line treatment of advanced follicular non-Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND: The role of intensive conventional dose chemotherapy in advanced low grade non-Hodgkin's lymphomas is a matter of debate. The Gruppo Italiano per lo Studio dei Linfomi conducted a study to evaluate the efficacy and toxicity of a third-generation polychemotherapeutic regimen, ProMACE-CytaBOM, as a first-line therapy in a selected group of patients with advanced follicular non-Hodgkin's lymphoma (Fo-NHL) who were younger than 60 years. METHODS: Thirty-nine patients were included in the study (14 males, 25 females; median age, 44 years; age range, 22-60 years). Their WF histotypes were B (9 patients), C (23 patients), and D (7 patients). All of the patients had disease in an advanced clinical stage (Stage III, 15 patients; Stage IV, 24 patients), and 9 patients had B symptoms. According to the age-adjusted International Prognostic Index (IPI), 20 patients exhibited low-intermediate risk, 14 high-intermediate risk, and 5 high risk. Three of the patients were not considered evaluable because they withdrew their consent after three (one patient) and four (two patients) cycles of therapy (one of these patients was in complete remission [CR], and two were in partial remission [PR]). Of the 36 evaluable patients, 4 received IF-RT after the 6 planned cycles of therapy. RESULTS: CR was achieved in 20 patients (55.5%) and PR in 14 (38.8%). One patient (2.7%) experienced disease progression during the treatment program. Eight of the 20 patients with CR (40%) relapsed. Eight patients (22.2%) died: 6 died of disease progression, 1 died of therapy consequences, and 1 died of an unrelated cause. With a median follow-up of 49 months (range, 28-79 months), the disease free survival rate was 60%. The overall survival rate was 80% after a median follow-up of 44 months (range, 3-79 months). The IPI stratification of patients showed a borderline statistical difference in terms of time to treatment failure and overall survival. The main hematologic toxicity was neutropenia (Grade 3 in approximately 10% of patients). One patient died of sepsis. Cotrimoxazole prophylaxis was always given. Cardiac toxicity (Grade 3) was observed in 1 patient at the end of the planned therapy. The average relative dose intensity of the drugs was 89% of the projected dose, without the regular use of growth factors. CONCLUSIONS: This study indicates that ProMACE-CytaBOM could be a suitable regimen for adult patients with advanced Fo-NHL, allowing a good CR rate and very good disease free survival rate. However, the occurrence of severe, albeit limited, adverse effects suggests that this regimen should first be used in controlled therapeutic protocols to verify its efficacy with respect to less intensive approaches.

Adult↗
PubMed1997

Identification of a tumor-associated mutant form of the NF-kappaB RelA gene with reduced DNA-binding and transactivating activities.

Alterations of NF-kappaB family members have been found to be associated with various forms of lymphoid malignancies. In order to determine whether alterations of the RelA gene are involved in lymphomagenesis, we analysed a large and representative panel (200 cases) of such tumors. Southern blot analysis did not reveal any rearrangements or locus amplification, suggesting that structural alterations of the RelA gene may represent rare events in lymphoid neoplasia. By means of PCR-SSCP analysis, we were able to identify a single point mutation leading to amino acid substitution (codon 494, Glu-Asp) in the transactivating (TA) domain in one case of multiple myeloma. The mutated allele was expressed in the pathological bone marrow sample but not in the peripheral blood cells of the patient. We demonstrate that the RelA protein carrying this specific mutation (called RelA494D) has less transactivating ability than the normal RelA protein. Interestingly, the mutated protein has a lower affinity for kappaB binding sites both as a homodimer or in association with the NFKB1/p50 subunit. Transfection experiments using a Gal4-RelA494D fusion protein indicated that the mutation does not alter the intrinsic transactivating ability of the TA domain of RelA. Furthermore, in vitro translated RelA494D is able to dimerize efficiently with other NF-kappaB members, such as p50, cREL and Ikappa Balpha. Our data therefore suggest that this mutation may alter the specific structural conformation needed for the DNA interaction of RelA, and provide insights into the amino acid sequences involved in mediating the biological activities of RelA.

Animals↗
PubMed1997

The physical and genetic map surrounding the Lyst gene on mouse chromosome 13.

During the recent cloning of the mouse Lyst gene we developed both a high-resolution genetic map and a complete YAC and BAC contig of the Lyst critical region on mouse Chromosome 13. We also report the mapping of the human homologue of the mouse Lyst gene (LYST) to 1q43. These data are consistent with LYST being the gene for the human Chediak-Higashi Syndrome and strengthen the synteny relationship between MMU13 and human 1q43.

Animals↗
PubMed1997

Adriamycin-induced histamine release from heart tissue in vitro.

It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells. As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the clinically employed formulation.

Animals↗
PubMed1997

Population-based survey of hepatitis A virus infection in the Republic of San Marino.

In 1990-1991, the prevalence of antibodies to hepatitis A virus infection (anti-HAV) was assayed by the ELISA method among 1528 apparently healthy subjects, 20-85 years old in the Republic of San Marino. Subjects were selected from the list of residents by a random stratified sampling procedure with a proportional allocation by age, sex and district of residence. The overall anti-HAV prevalence was 64.7%; it increased from 28.6% in subjects 20-30 years old to 97% in those > 60 years (p < 0.01). No gender difference was observed. At the multivariate analysis age > 40 years (OR: 39.5; 95% CI: 12.4-126) and lowest level of schooling (OR: 1.8; 95% CI: 1.1-2.9), which is a good indirect indicator of socio-economic status, resulted both independent predictors of anti-HAV seropositivity. These findings reflect the improved sanitation standards in this area and indicate that the proportion of non-immune adults is increasing with a higher risk of symptomatic infection in the near future.

Adult↗
PubMed1997

Poor prognosis in non-villous splenic marginal zone cell lymphoma is associated with p53 mutations.

We have recently reported a series of 15 non-villous splenic marginal zone lymphoma patients, six of whom showed p53 mutations (40%). This molecular alteration did not correlate with any particular clinico-pathologic feature at diagnosis. After a median follow-up of 56 months, four cases evolved into aggressive fatal non-Hodgkin's lymphoma (NHL) and two had refractory progressive disease; interestingly, p53 mutations were demonstrated in five of these patients at diagnosis. As the patients with wild-type p53 presented responsive or indolent disease, this genetic alteration may be an early marker of aggressive transformation or refractoriness. p53 evaluation at diagnosis could be advisable in this particular subset of NHL.

Adolescent↗
PubMed1997

Seroprevalence of hepatitis A virus and Helicobacter pylori infections in the general population of a developed European country (the San Marino study): evidence for similar pattern of spread.

OBJECTIVE: To evaluate the role of faecal-oral transmission in the spread of Helicobacter pylori. DESIGN: A cross-sectional comparison of the patterns of hepatitis A and H. pylori seropositivity. METHODS: At interview, blood samples and questionnaire data were collected from a random sample of 1528 healthy subjects aged 20-85 years from the Republic of San Marino. Serum samples from each subject were then tested for anti-H. pylori and anti-hepatitis A antibodies. RESULTS: Overall, 529 of 670 H. pylori-seropositive subjects (78.9%) and 460 of 858 H. pylori-seronegative subjects (53.6%) were hepatitis A seropositive (P<0.01; odds ratio=3.2; confidence interval 95%=2.6-4.1). This association remained after adjustment by a multiple logistic regression analysis for the confounding effect of age and length of schooling, as surrogate for socio-economic status (OR=2.0; CI 95%=1.3-3.3). The age-specific prevalence curves for H. pylori and hepatitis A infections showed a parallel increase by age, although to a lesser extent for H. pylori. CONCLUSION: These findings provide evidence that in the community studied H. pylori may have spread in a manner similar to that of hepatitis A.

Adult↗
PubMed1997

Adriamycin binds to the matrix of secretory granules during mast cell exocytosis.

The antineoplastic drug adriamycin induces exocytosis in rat peritoneal mast cells followed by a significant uptake of the drug into the secretory granules. The drug is fluorescent, allowing visualization of its accumulation and binding to mast cell granules by fluorescence microscopy. At the same time, the well known inorganic dye ruthenium red was used as a probe because of its great affinity for heparin in the mast cell secretory granules as visualized by bright field microscopy. Competition between adriamycin and ruthenium red for binding to the negatively charged matrix of granules was demonstrated. Biochemical studies were also performed to confirm microscopic observations. Adriamycin may be of interest for studying mast cell secretion; it is not only a strong fluorescent dye for mast cell granules that are in communication with the extracellular space, but it also induces mast cell exocytosis.

Animals↗
PubMed1997

Anti-CagA antibodies are associated with atrophic gastritis in a population at high gastric cancer risk: a morphometric study by computerized image analysis.

BACKGROUND: CagA-positive Helicobacter pylori strains appear to increase the risk for atrophic gastritis. AIM: To verify the association between CagA status and atrophic gastritis in the general population by means of computerized image analysis. SUBJECTS: Forty-five subjects were chosen out of a representative sample of a population at high gastric cancer risk. METHODS: Helicobacter pylori status was assessed by IgG ELISA, rapid urease test and histology. Serum anti-CagA antibodies were detected by western blotting. Subjects were subdivided into 3 groups: 15 subjects Helicobacter pylori positive CagA-positive, 15 Helicobacter pylori positive CagA-negative and 15 controls Helicobacter pylori negative. Biopsies were studied using the Sydney System score. A computerized image analysis was used to count inflammatory cells in the lamina propria and to measure the area of the gastric glands. RESULTS: Anti-CagA antibodies were associated with reduction of gland area (126,671 +/- 81,032 mu 2/mm2 vs 231,384 +/- 54,159; p = 0.0001), with increasing both of polymorphonuclear cells (426 +/- 238 cell/mm2 vs 136 +/- 69; p = 0.0001) and mononuclear cells (8675 +/- 1304 cell/mm2 vs 7141 +/- 1230; p = 0.003). CONCLUSIONS: The association of anti-CagA antibodies with a high grade of gastric atrophy further supports the hypothesis that Helicobacter pylori CagA-positive strains can promote the multifactorial process of gastric carcinogenesis.

Adult↗
PubMed1996

Identification and characterization of the mouse obesity gene tubby: a member of a novel gene family.

The mutated gene responsible for the tubby obesity phenotype has been identified by positional cloning. A single base change within a splice donor site results in the incorrect retention of a single intron in the mature tub mRNA transcript. The consequence of this mutation is the substitution of the carboxy-terminal 44 amino acids with 24 intron-encoded amino acids. The normal transcript appears to be abundantly expressed in the hypothalamus, a region of the brain involved in body weight regulation. Variation in the relative abundance of alternative splice products is observed between inbred mouse strains and appears to correlate with an intron length polymorphism. This allele of tub is a candidate for a previously reported diet-induced obesity quantitative trait locus on mouse chromosome 7.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy.

The presenting clinico-hematologic features of 386 patients with nonmyelomatous monoclonal gammopathy (MG) were correlated with the frequency of malignant transformation to evaluate the most important variables conditioning its evolution into multiple myeloma (MM) or Waldenström macroglobulinemia (WM). Most of the patients (335) had monoclonal gammopathy of undetermined significance (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG) fulfilled all of the MGUS diagnostic criteria (according to Durie) except that bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined as having monoclonal gammopathy of borderline significance (MGBS). There were no significant differences between the MGUS and MGBS groups in terms of age, sex, or median follow-up. After a median follow-up of 70 and 53 months, respectively, 23 of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution. Univariate analysis of the IgA and IgG patients showed that the cumulative probability of the disease evolving into MM correlated with diagnostic definition (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced serum polyclonal Ig. In the IgG cases, there was also a significant correlation with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the same variables remained in the Cox model where the BMPC percentage was considered after natural logarithmic transformation and the monoclonal component as g/dL value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1 for a reduction in one or two polyclonal Ig. In conclusion, our study allows the identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at very low-risk of evolution, who can be considered as having benign monoclonal gammopathies. We also describe a previously undefined group of MG patients (with monoclonal gammopathy of borderline significance) who are at high-risk of malignant evolution. These findings could have a considerable impact on the cost/benefit ratio of monitoring programs in these patients.

Aged↗