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Biomedical subjects

M Gobbi

Publications and source records attributed to M Gobbi.

At least 199 records · Page 11Linked to original sources

Malignant histiocytosis (true histiocytic lymphoma) clinicopathological study of 25 cases.

Twenty-five cases originally diagnosed as malignant histiocytosis/true histiocytic lymphoma were reviewed according to both pathological and clinical criteria. Microscopically, they were characterized by large, pleomorphic tumour cells showing variable degrees of atypia and phagocytic activity. The growth more often appeared as diffuse, being limited to the sinuses in only two cases. Cytochemistry on touch imprints showed tumour cells strongly positive for acid phosphatase and alpha-naphthyl-acetate esterase in all the samples tested. Immunohistochemistry on paraffin embedded sections using specific antisera showed tumour cell positivity for lysozyme in 12 of 25 cases, for alpha 1-antitrypsin in 24 of 25 cases and for alpha 1-antichymotrypsin in all 25 cases. Immunophenotyping on frozen-sections in three cases displayed a clear-cut reactivity of the neoplastic cells with the monoclonal antibody OKM1. Clinically, the disease more often presented with B-symptoms, lymphadenopathy and mediastinal involvement. In the majority of the patients (18/25) it had a fatal and rapid course, despite therapy (median survival: 9 months; mean survival: 12 months). The presence of B-symptoms and bulky disease appeared as the only factors influencing the prognosis, both suggesting a more aggressive course of the tumour.

Adolescent↗

Nonsecretory multiple myeloma. Presenting findings, clinical course and prognosis.

The present report gives information both on the clinical features at presentation and the clinical course of 7 consecutive patients with nonsecretory multiple myeloma. It provides evidence that the nonsecretory variant was closely associated with high tumor cell mass, as determined by severe anemia and/or multiple areas of bone destruction. The marked depression of normal immunoglobulins and the absence of both renal failure and hypercalcemia differentiated nonsecretory from typical myelomatosis. Finally, the survival length of patients with nonsecretory myeloma appeared to be similar to that of comparably staged patients with secretory myeloma.

Actuarial Analysis↗

Meningeal leukemia complicating prolymphocytoid transformation of B-chronic lymphocytic leukemia.

A patient who developed a meningeal leukemia during prolymphocytoid transformation of B-chronic lymphocytic leukemia is described. The central nervous system (CNS) complication occurred after 5 years of relatively benign course. Almost all CNS mononuclear cells showed the typical morphology and immunology of prolymphocytic leukemia cells, whereas a mixture of prolymphocytoid elements and small-sized lymphoid cells was observed in peripheral blood. In this case the more aggressive component was present at diagnosis and showed an uncommonly slow progression allowing the occurrence of the CNS involvement.

B-Lymphocytes↗

Phorbol ester induces abnormal chronic lymphocytic leukemia cells to express features of hairy cell leukemia.

We have investigated the relationship between chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and different normal B cell subsets: Mrbc+, T1+ and slgM+ tonsil cells; germinal center; mantle zone; and peripheral blood B lymphocytes. Both malignant and normal cells were incubated in vitro with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 72 hours and the morphology, cytochemical profile, and surface markers were evaluated. The results show that CLL cells TPA-induced become indistinguishable from HCL by four independent criteria: the morphology; the cytoplasmic tartrate resistant acid phosphatase (TRAP) enzyme activity; the membrane positivity with anti-Leu M5 (SHCL3); and anti-Tac monoclonal antibodies which, in the uninduced state, react only with HCL. The features of TRAP and Tac positivity are also expressed (though in variable degree) by different normal B cell populations activated with TPA or pokeweed mitogen (PWM). It is concluded that HCL might represent an aberrantly activated variant of CLL (or of a CLL-related disorder).

Acid Phosphatase↗

Stimulation of serotonin synthesis in rat brain after antiepilepsirine, an antiepileptic piperine derivative.

Piperine and two of its derivatives, antiepilepsirine (AE or 3,4-methylendioxycynnamoylpiperine) and compound 7448 (N-isopropyl 3 (4 chloro-phenyl) propenoylamide) are very effective in stimulating serotonin (5HT) synthesis. AE raises the ratio of free-to-bound tryptophan (TP) in plasma and induces a long-lasting increase of this aminoacid in brain. At the same time in striatum and limbic area it causes a lasting increase in 5 hydroxyindolacetic acid (5HIAA) a 5HT metabolite and to a lesser extent, an increase in the levels of the monoamine itself. Together with this action on 5HT metabolism we found that AE caused release of 3H-5HT from an in vitro synaptosomal preparation. It thus appears that piperine and its derivatives AE and compound 7148 affect the central serotonergic system.

Animals↗

Effects of denzimol on benzodiazepine receptors in the CNS: relationship between the enhancement of diazepam activity and benzodiazepine binding sites induced by denzimol in the rat.

Denzimol, a new anticonvulsant drug with a pharmacological profile similar to that of phenytoin, enhances the ataxic and antimetrazol activity of diazepam in rats without affecting its activity against picrotoxin-induced seizures. In vivo and ex vivo denzimol enhances the binding of 3H-flunitrazepam in cortex and in hippocampus but not in cerebellum. The possibility of this increase in the number of benzodiazepine binding sites contributing in some way to enhancement of the depressive and anticonvulsant activity of diazepam is discussed.

Animals↗

Lineage relationship of chronic lymphocytic leukemia and hairy cell leukemia: studies with TPA.

The tumor promoting agent TPA (phorbol ester; 1.6 X 10(-8)M) was used to induce the differentiation in vitro of B-chronic lymphocytic leukemia (B-CLL) cells from 14 untreated patients. The uninduced phenotype was SIg+, Mrbc+, RFT-1+, RFA-4-, FMC7-. After 72 h incubation with TPA, B-CLL cells became RFA-4+, FMC7+ and lost the capability of Mrbc rosetting. Large proportions of the "induced" cells also showed morphological and ultrastructural changes, such as undulating membranes and bleblike protusions and became strongly positive for tartrate resistant acid phosphatase (TRAP+) and also contained cytoplasmic immunoglobulins. These features are very similar to the features of hairy cell leukemia (HCL). These observations confirm previous clinical findings that B-CLL and HCL are related disorders of the B lineage. The development of "hairy" features in induced B-CLL and in HCL seems to be a malignancy-associated feature because the Mrbc+ normal B cells (B-CLL-equivalent cells) isolated from tonsil also develop TRAP positivity but no membrane aberrations.

B-Lymphocytes↗

Prognostic significance of lymphography in stage IIIs Hodgkin's disease (HD).

Ninety-six patients with pathological stage IIIs Hodgkin's disease, uniformly treated with six cycles of MOPP and TNI, were retrospectively analysed in an effort to determine whether the lymphographic aspect of lymph nodes influence the prognosis. Case material was grouped according to the presence of lymph nodes less than 3 cm in diameter or larger at lymphography. Five-year survival and disease-free survival were 85 and 78% for patients with small lymph node involvement, compared to 48 and 30% for patients with larger lymph nodes. The comparative analysis between the lymphographic aspect and other prognostic factors shows that large lymphographic involvement is strongly correlated with the presence of large spleen involvement (P less than 0.0000029), followed by stage III2 (P less than 0.000612), followed by greater than or equal to 5 involved sites (P less than 0.012), followed by age greater than 40 yr (P less than 0.047). Conversely, no significant correlation was found with symptoms, histology and mediastinal involvement. Modifications of current treatment for both large and small lymph node involvement are discussed.

Adult↗

B-chronic lymphocytic leukaemia patients with stable benign disease show a distinctive membrane phenotype.

The circulating B cells of 98 patients with B-CLL were analysed with a panel of conventional markers and monoclonal antibodies including RFA-1 and RFA-4. A subgroup of patients was defined with a distinctive double membrane marker phenotype (RFA-1+, RFA-4+). These patients showed features of clinical stability. Their physical signs, haematological features and lymphocyte counts remained unchanged for 5-10 years: therefore, the RFA-1+, RFA-4+ membrane phenotype appears to identify a subgroup of B-CLL patients with a particularly non-progressive disease.

Aged↗

Immunohistological study of transferrin receptor expression in non-Hodgkin's lymphoma.

Lyophilized frozen sections of 24 lymph nodes from patients with different types of non-Hodgkin's malignant lymphoma, diagnosed according to the Kiel Classification, were tested by an immunoperoxidase-ABC-method, in order to assess the expression of the transferrin receptors, recognized by the OKT9 monoclonal antibody. Our results support the hypothesis that OKT9 reactivity of lymphomatous tissues might reflect the histological grading, offering a new important prognostic parameter, and stress the concept that immunological studies in frozen sections allow a more precise definition of the lymphoma phenotype.

Antibodies, Monoclonal↗

Increased number of brain benzodiazepine receptors after in-vivo administration of estazolam to rats.

Estazolam significantly increased the Kd of [3H]flunitrazepam in-vitro, like other benzodiazepines (BDZs) acting competitively at the receptor site. At variance with other BDZs, estazolam significantly raised the Bmax for [3H]flunitrazepam, at concentrations lower than its Ki for BDZ receptors. This effect may be responsible for the observed increase in [3H]diazepam binding after in-vivo administration of estazolam to rats.

Animals↗

Hairy-cell leukemia complicating coeliac disease: report of a case and discussion of possible pathogenetic mechanisms.

10-28% of the patients with chronic coeliac disease develop a second malignancy, such as non-Hodgkin's lymphomas, particularly of the histiocytic type, and adenocarcinomas. The second tumor may arise in the intestinal tract or in other organs. We describe here a patient who developed a tartrate-resistant, acid phosphatase-positive, hairy-cell leukemia after a history of chronic coeliac disease. In the literature, no similar case has been described as yet.

Celiac Disease↗

Lonidamine in the treatment of chronic lymphoid leukemia.

Blood and/or bone marrow cells from patients with hematological malignancies, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia in blastic phase, acute lymphoid leukemia, acute myeloid leukemia, prolymphocytic leukemia, multiple myeloma and myelofibrosis, were incubated with Lonidamine at different concentrations (50, 100 and 160 micrograms/ml) for 1-2 h. B lymphocytes of CLL had the highest sensitivity to the drug: a decrease of more than 30% in the viable nucleated cells was recorded in 8 out of 10 experiments. Subsequent in vivo studies were performed to investigate the effectiveness of Lonidamine in the treatment of CLL. The drug was administered orally for a period of 7 days to 19 selected patients, both previously treated and untreated, in different stages of the disease. Only 5 patients responded: 2 of them had a significant decrease (greater than 30%) in the lymphocyte count, and the remaining 3 showed an appreciable reduction of the spleen (1 case) and of the lymph node size (2 cases). Generalized myalgia was the most common side effect induced by Lonidamine.

Antineoplastic Agents↗

Membrane phenotype and functional behaviour of T lymphocytes in multiple myeloma: correlation with clinical stages of the disease.

The distribution of T lymphocyte subsets was assessed using monoclonal antibodies (MoAbs) in 44 untreated patients with multiple myeloma (MM) subdivided according to the clinical stage of the disease. A significant reduction (P less than 0.001) of T lymphocytes was observed only in stage II and III patients. The proportion and absolute number of OKT4 positive cells (helper/inducer phenotype) were significantly reduced in all stages of the disease; this quantitative abnormality was more pronounced in advanced disease. While the proportion of OKT8 positive cells (suppressor/cytotoxic phenotype) was increased above normal in all stages, the absolute number (of OKT8 positive cells) was high only in stage I patients; on the contrary in stage II-III patients the total OKT8 count was reduced compared with normal controls. A significantly reduced OKT4/OKT8 ratio was found in both groups of patients (P less than 0.005). Functional studies, carried out on the unfractionated T cells of patients with MM, demonstrated a consistent helper defect in the ability to induce the differentiation of normal B lymphocytes into antibody producing cells in a pokeweed mitogen driven system. However, the removal of OKT8 positive cells produces a significant increase in helper capacity, suggesting that the reduced helper function of T lymphocytes in toto is probably due to excessive suppressor activity. The possible immunoregulatory role of MM T cell disease is discussed.

Antibodies, Monoclonal↗

Functional behaviour and immunological phenotype of circulating B lymphocytes in multiple myeloma. Studies with pokeweed mitogen.

Peripheral blood B lymphocytes, depleted of adherent cells, from 10 patients with multiple myeloma were cultured in the presence of PWM with autologous or donor T lymphocytes. The results show that: (1) co-cultures with allogeneic T lymphocytes produced more plasma cells than those with autologous ones; (2) the kappa/lambda ratio overlapped the values obtained in normal controls, irrespective of the light chain produced by the neoplastic plasma cells and (3) the immunological phenotype of plasma cells obtained from PWM stimulated peripheral B cells (RFA2+, RFA3+, A10+) was clearly different from that one of myelomatous plasma cells (RFA2-, RFA3-, A10+). These data confirm the T cell imbalance already seen in myeloma patients; moreover they show that PWM responsive B cell are functionally normal and phenotypically different from bone marrow myeloma cells. These results support the view that most of the peripheral B lymphocytes, previously identified as monoclonal are in fact normal cells bearing adherent monoclonal Ig molecules.

Antibodies, Monoclonal↗

Increased proportion of suppressor/cytotoxic (OKT8+) cells in patients with Hodgkin's disease in long-lasting remission.

The distribution of T-lymphocyte subsets in patients with Hodgkin's disease (HD) at diagnosis and in those disease-free off-therapy for over 5 years, was assessed with OKT monoclonal antibodies. In patients at diagnosis, T-cell subsets appeared substantially balanced with only a moderate reduction in the proportion and absolute number of OKT4 (helper/inducer) positive cells, suggesting that the lymphopenia, constantly associated with HD at diagnosis, is mainly due to a reduction in the helper/inducer T-cell subpopulation. In patients off-therapy, a reduced proportion, but normal absolute number, of OKT4+ cells was constantly accompanied by a significant increase in the proportion and absolute number of OKT8+ cells, compared with patients at diagnosis and normal controls (40% +/- 11 versus 24% +/- 7 and versus 23 +/- 6, respectively). Consequently the OKT4/OKT8 ratio, normal or near normal in patients at diagnosis (1.70 versus 2.00), was significantly reduced in patients off-therapy (0.78 versus 2.00, P less than 0.001). These data suggest that in patients with HD at diagnosis, T-cell subpopulations are substantially normal, while a significant abnormality was observed in patients with HD off-therapy and potentially "cured." Further investigations will better elucidate these findings probably related to the cytotoxic radiotherapy and chemotherapy.

Adolescent↗

E-rosette positive acute lymphoblastic leukaemia in adolescents and adults.

E-rosetting of leukaemic blast cells is one of the markers of T-cell acute lymphoblastic leukaemia (ALL). In children, E+ ALL has a bad prognosis. In adults, data are scarce. This report provides information on 25 E+ ALL adult patients who have a minimum follow-up time of 36 months. Twenty-two of 25 patients (88%) achieved complete remission (CR) (median duration 16 months), and six of them were alive, relapse-free, and off therapy after 36-81 months, with a 26% projected 6-year relapse-free survival. In 97 patients with E-SmIg- ALL, who were treated at the same Institutions, over the same period of time, and by the same modalities, the outcome of therapy was almost identical: CR 80%, median duration of first CR 15 months, projected 6-year relapse-free survival 15%. The white blood cell (WBC) count at presentation influenced significantly and to the same degree first CR length in both E+ and E- cases. In this adult series, WBC count was not as high as in children. Moreover, a high Hb concentration, a very high WBC count, lymphadenomegaly, and mediastinal involvement, were found more frequently in adolescents and young adults than in adults. Based on these data, it is suggested that in adults E-rosetting as such is not a marker of a poorer prognosis, that some of the typical features of children E+ ALL weaken with age, and that in adults the disease can have a less aggressive character.

Adolescent↗