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Biomedical subjects

L Baldini

Publications and source records attributed to L Baldini.

At least 91 records · Page 5Linked to original sources
PubMed1992

Peripheral neuropathy in monoclonal gammopathy of undetermined significance: prevalence and immunopathogenetic studies.

In an unselected series of patients with monoclonal gammopathy of undetermined significance (MGUS) we found neuropathy in 2 of 34 patients with IgG (6%), 2 of 14 with IgA (14%), and 8 of 26 with IgM MGUS (31%). The neuropathy was subclinical in 6 patients (1 IgG, 1 IgA, and 4 IgM). Patients with IgG or IgA MGUS had a prominent motor impairment with electrophysiologic and morphologic findings suggestive of predominant axonal degeneration. No deposit of the M-protein in sural nerve and no reactivity of the M-protein with nerve was detected in these patients. Patients with IgM MGUS had a prominent sensory impairment with evidence of predominant demyelination. In 6 of these patients the M-protein reacted with the myelin-associated glycoprotein (MAG). The higher prevalence of neuropathy in patients with IgM MGUS may be related to the frequent reactivity of IgM M-proteins with MAG.

Adult↗
PubMed1992

[Role of endoscopy in the diagnosis and follow-up of bleeding lesions of the colon].

Considering the results of the centre of colonoscopy we can draw some considerations about the irreplaceable role of endoscopy in the diagnosis of bleeding colonic lesions and about its greater security in comparison with the traditional radiologic exam, about its possibilities to be sometimes resolutive even for the therapy and about its great importance in the follow-up of patients treated for lesions of this kind.

Angiodysplasia↗
PubMed1991

No correlation between response and survival in patients with multiple myeloma treated with vincristine, melphalan, cyclophosphamide, and prednisone.

A vincristine, melphalan, cyclophosphamide, and prednisone (VMCP) multi-drug regimen was used in 85 previously untreated patients with multiple myeloma (MM) (symptomatic Durie Stages II and III) until they became refractory. The prognostic significance of various pretreatment characteristics was evaluated in terms of therapeutic response (according to Southwest Oncology Group [SWOG] and Chronic Leukemia-Myeloma Task Force [TF] criteria) and survival. Therapeutic responses, obtained in 31.2% (SWOG) and 68.7% (TF) of patients, had a significant inverse correlation with myeloma cell mass, serum calcium, and bone status. Median survival time of Stage II and Stage III patients was 39 and 34 months, respectively. Serum B2 microglobulin greater than or equal to 6 micrograms/ml was the only variable correlating unfavorably with survival duration after multi-variate analysis (increased risk = 2.79), although therapeutic response as a time-dependent variable had no effect on survival. These data suggest no correlation between response and survival, partially because of inadequate response assessment criteria and partially because no existing treatment is curative (although current therapeutic approaches may prevent death from complications).

Adult↗
PubMed1991

Analysis of tumor-specific immunoglobulin gene rearrangement in peripheral blood B-cells of multiple myeloma patients.

The search for bone marrow clone neoplastic precursors in the peripheral blood of multiple myeloma (MM) patients has been the subject of a number of studies which, using different methodological approaches, have led to conflicting results. With the aim of contributing toward resolving this controversy, immunoglobulin (Ig) gene rearrangement in the bone marrow mononuclear cells (BMMC) and B-lymphocyte enriched peripheral cells (BePBC) of 11 appropriately selected advanced MM patients was studied by means of Southern blotting. Peripheral mononuclear cells (PBMC) and BePBC were studied immunophenotypically by evaluating the presence of cytoplasmic Ig positive cells (CyIg+) and CD19/PCA-1 reactivity. A pattern of Ig gene rearrangement identical to that observed in the respective BMMC was found in only two patients who, moreover, had a significant number of CyIg+ cells. Ig gene rearrangement was not found in any of the remaining patients who showed no evidence of the presence of CyIg+ cells, although there were CD19/PCA-1 positive cells. Consequently, the significance of the presence of malignant pre-plasma cell peripheral B-lymphocytes needs to be reconsidered and, in any case, these cells should be looked for in cell populations greatly enriched in B-lymphocytes and, above all, completely lacking in plasma cells or CyIg+ cells.

Aged↗
PubMed1991

Effect of the carboxylic ionophore monensin on histamine release from rat peritoneal mast cells.

The effect of the monovalent carboxylic ionophore monensin, which mediates a one-for-one exchange of intracellular H+ for extracellular Na+, was investigated in purified rat peritoneal mast cells. Monensin inhibited histamine secretion induced by compound 48/80, adriamycin and the calcium ionophore A23187; the inhibitory effect was maximal when the compound was added at least 10 min before the secretagogues. Washing of cells before addition of the secretagogues did not abolish the inhibitory effect of monensin. On the contrary the carboxylic ionophore was completely ineffective in preventing concanavalin A-induced histamine release. When rat peritoneal mast cells were incubated in the presence of monensin for longer period (up to 5 hours), the substance induced a slow, progressive and dose dependent histamine release, which, at least for lower doses was noncytotoxic. The secretory effect of monensin was still present if the ionophore was washed away after 10 min of incubation, and the incubation continued in drug-free medium. Monensin stimulated histamine secretion was strictly dependent on extracellular Na+ concentrations, and independent on extracellular Ca++.

Animals↗
PubMed1991

Evidence of an adriamycin binding site in the secretory granules of the mast cell.

Adriamycin induced significant non-cytotoxic histamine release from rat peritoneal mast cells to which the drug showed a very high affinity. The relationship between adriamycin-induced exocytosis and its uptake by purified rat peritoneal mast cells was studied. Adriamycin induced histamine release and was highly concentrated in mast cells at 37 degrees C but not at 0 degrees C. However, if exocytosis was provoked by other secretagogues like compound 48/80, protamine, concanavalin A, and ionophore A23187, and cells were then treated with adriamycin at 0 degrees C, the concentrations of the antineoplastic drug significantly increased. Adriamycin binding to purified granular material was similar to that of intact cells treated at 37 degrees C, but was not modified by metabolic inhibitors, extremes of temperature (0 or 45 degrees C) or by the carboxylic ionophore monensin. On the contrary, sodium cromoglycate limited adriamycin binding to granular materials as well. In addition, sodium cromoglycate, but not monensin, displaced the antineoplastic drug from mast cells, even when added after adriamycin. We conclude that the high affinity of adriamycin for mast cells is ascribable to the externalization of a granular binding site, as a consequence of the exocytotic process. The experiments with sodium cromoglycate suggest that this binding site could be in common with the antiallergic drug.

Animals↗
PubMed1990

Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings.

This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of "classical" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/-, 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease.

Adult↗
PubMed1989

Ras oncogene mutation in multiple myeloma.

The frequency of ras (H-, K-, and N-ras) and c-myc oncogenes was investigated in multiple myeloma (MM). By means of the polymerase chain reaction (PCR)/oligonucleotide hybridization method, DNA from 56 tumor biopsies was analyzed for the presence of activating mutations involving codons 12 and 61 of the H-, K-, and N-ras genes and codon 13 of the N-ras gene. Mutations, involving the N- or K-ras genes, were detected in 18 of 56 (32%) cases of which 12/43 (27%) were at diagnosis and 6/13 (46%) were after treatment. In some cases, multiple mutations affecting different ras alleles were detected. Direct nucleotide sequence analysis of PCR products indicated that a more heterogeneous nature of the base pair changes than previously shown for other tumors along with a preferential involvement of N-ras codon 61. The heterogeneity of MM cases with respect to the presence of ras oncogenes prompted an analysis of possible correlations with different clinico-pathologic characteristics of MM from which a correlation between the presence of ras oncogenes and a partial or complete lack of response to therapy emerged. The frequency of activating rearrangements or mutations of the c-myc gene were studied by Southern blot analysis and PCR sequencing, respectively. However, contrary to previous reports involving mostly MM cell lines, no structural alterations of the c-myc gene were found. These results indicate that ras, but not c-myc, oncogenes are activated in vivo in MM cells, representing the first oncogene alteration that has been associated at appreciable frequency with this type of malignancy. While the mechanism of occurrence and biological role of ras activation in MM remains to be elucidated, the preliminary correlations observed in this study between the presence of ras oncogenes and poor therapeutic response suggest that further investigations of the possible prognostic significance of these alterations are necessary.

Base Sequence↗
PubMed1989

Uptake of adriamycin by rat and mouse mast cells and correlation with histamine release.

It has been shown recently that anthracyclines induce an important, noncytotoxic histamine release from rat and mouse peritoneal mast cells. In the present study we evaluate if histamine release is related to Adriamycin uptake; in addition the uptake of this antineoplastic drug is studied in other normal or tumor cells. In rat and mouse peritoneal mast cells, Adriamycin-induced histamine release is quantitatively related to its intracellular concentrations. Significant differences in Adriamycin uptake are observed among mast cells and other cells. In mast cells, both the uptake of the antineoplastic drug and histamine release are greatly limited by the antiallergic drug sodium cromoglycate; on the contrary, in other normal or neoplastic cells, sodium cromoglycate only slightly reduces Adriamycin intracellular concentrations. When tested on KB cells in culture, sodium cromoglycate does not interfere with Adriamycin cytotoxicity. In mast cells, Adriamycin uptake is temperature dependent, with an optimum at 37 degrees C, and slower than histamine release; histamine release was in fact completed in 30 s, whereas the uptake reached its maximum in 30 min. The influx is pH dependent, with a maximum at pH 6.8, and is blocked by the metabolic inhibitor antimycin A and omission of glucose. It is also possible to limit Adriamycin uptake and histamine release with the calmodulin inhibitors chlorpromazine and trifluoperazine and with the calcium antagonist nicardipine. Adriamycin efflux from mast cells is extremely rapid, temperature dependent (very slow at 0 degrees C), but pH independent, and not modified by metabolic inhibitors. These findings suggest that Adriamycin accumulation in mast cells involves an active transport system which can be inhibited by several agents, among which are sodium cromoglycate, and calmodulin and calcium antagonists.

Animals↗
PubMed1989

Anti-myelin-associated glycoprotein IgM antibody titers in neuropathy associated with macroglobulinemia.

Twenty-seven patients with neuropathy and IgM monoclonal gammopathy were tested for antigen specificity of the M-protein and for anti-myelin-associated glycoprotein (MAG) IgM levels by immunoblot. In 16 patients (59.2%) the M-protein reacted with MAG and with cross-reactive glycoconjugates. Anti-MAG IgM titers in these patients ranged between 1:12,800 and 1:100,000. A fainter IgM reactivity with MAG and related glycoconjugates was detected in 3 additional patients with neuropathy, but also in 8 of 24 patients with IgM M-protein without neuropathy (33.3%). This reactivity was not due to the M-protein and corresponded to antibody titers of 1:400 or less in all but 1 patient with a titer of 1:3,200. Low titers of anti-MAG IgM (1:200 or less) were also detected in 17 of 101 control patients without IgM M-proteins (16.8%), while 1 patient with neuropathy of unknown cause had anti-MAG IgMK titers of 1:25,600. In 1 patient with neuropathy and IgM M-protein that was not anti-MAG, the M-protein bound to other antigens in nerve, while in 6, other possible causes or mechanisms for the neuropathy were found. In this study, high titers of anti-MAG IgM antibodies were always associated with neuropathy. The presence of low levels of anti-MAG IgM in a significant proportion of controls suggests that monoclonal expansion of naturally occurring B-cell clones secreting anti-MAG IgM may be responsible for the high incidence of this antigen specificity of the M-protein.

Adult↗
PubMed1989

Interaction of adriamycin with rat and mouse mast cells: histamine release and cellular uptake.

In the present study, we evaluated in mouse and rat mast cells if adriamycin uptake is related to histamine release. In addition, the uptake of the antineoplastic drug and histamine release were studied in other normal and neoplastic cell lines. The effect of sodium cromoglycate was also examined. Adriamycin induced histamine release from mixed or purified mast cells of the mouse and rat. This exocytotic response was quantitatively related to intracellular concentrations of adriamycin. Significant differences in adriamycin uptake were observed between mast cells and other normal and neoplastic cells. When peritoneal mast cells were treated with sodium cromoglycate, histamine release and adriamycin uptake were significantly reduced. In contrast, incubation of other cells with cromoglycate only slightly reduced the cellular concentration of the antineoplastic drug.

Animals↗
PubMed1989

Amelioration of 4'-epidoxorubicin-induced cardiotoxicity by sodium cromoglycate.

Epirubicin induces an important noncytotoxic release of histamine from rat peritoneal cells in vitro. This exocytotic response is inhibited by sodium cromoglycate, similarly to that elicited by the classic mast cell secretagogue, compound 48/80. Mast cells obtained from the peritoneal cavities of rats treated with epirubicin in vivo were extensively degranulated; in contrast, samples obtained from rats pretreated with sodium cromoglycate showed normal appearing mast cells. When injected i.p., immediately before the antineoplastic agent, cromolyn significantly improved the survival time and the microscopic appearance of myocardial tissues of epirubicin-treated mice. The results indicate that histamine release could play an important role in the pathogenesis of anthracycline-induced cardiotoxicity.

Animals↗
PubMed1989

VMCP chemotherapy with or without interferon-alpha-2 in newly diagnosed patients with multiple myeloma.

Fifty-two previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon (rIFN) alpha-2 and chemotherapy or chemotherapy alone. Patients were treated with vincristine, melphalan, cyclophosphamide and prednisolone every 4-6 weeks. In the combined treatment arm rIFN was administered concurrently with chemotherapy as well as during chemotherapy free intervals. The combined regimen effected 17/21 (80.9%) responses as compared to 19/27 (70.4%) responses in VMCP treated patients. Addition of rIFN to chemotherapy did not enhance hematologic toxicity. These findings suggest a somewhat higher rate of objective response in the VPMC + rIFN group, although a significant improvement in median survival by adding rIFN to conventional first line polychemotherapy in myeloma patients has not yet been achieved.

Adult↗
PubMed1989

Combined alpha-2C-interferon/VMCP polychemotherapy versus VMCP polychemotherapy as induction therapy in multiple myeloma: a prospective randomized trial.

Thirty-three previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon-alpha-2C (rIFN-alpha-2C) plus vincristine/melphalan/cyclophosphamide and prednisone (VMCP) or VMCP chemotherapy alone. The combined regimen effected 67% responses and 26% minor responses, while 35 and 47% of VMCP-treated patients had a pathologically documented remission, respectively. Despite the somewhat earlier achievement and duration (12.0 vs. 8.0 months) of objective response, and the marginal survival benefit observed in the rIFN-alpha-2C + VMCP treatment arm, a significant improvement in therapeutic gain by adding a biologic response modifier to conventional first-line polychemotherapeutic drug treatment in myeloma patients has not yet been achieved. The combined regimen was well tolerated without unusual or unexpected toxic effects.

Adult↗
PubMed1988

Treatment of patients with neuropathy and anti-MAG IgM M-proteins.

Five patients with neuropathy and IgM M-proteins that reacted with myelin-associated glycoprotein (MAG) were treated for 10 to 20 months with cytostatic agents. In 2 patients, a decrease in serum M-protein and in anti-MAG IgM levels coincided with a progressive improvement of neuropathy. No clinical improvement and no decrease of anti-MAG IgM were observed in the other patients. The close relationship between the decrease of anti-MAG M-proteins and clinical improvement in these patients supports the pathogenetic role of the M-protein in the neuropathy.

Aged↗
PubMed1988

Evidence for the lack of involvement of free radicals in adriamycin-induced histamine release from rat peritoneal cells.

The antineoplastic drug adriamycin, at a concentration of 100 micrograms/ml, caused a significant histamine release from rat peritoneal mast cells. This exocytotic process was unaffected by pretreatment with various concentrations of catalase, superoxide-dismutase, D-mannitol, alpha-tocopherol and reduced glutathione. Only very high concentrations of n-acetylcysteine significantly limited this release; this substance was also active in limiting histamine secretion induced by a classic mast cell secretagogue, compound 48/80.

Acetylcysteine↗