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Biomedical subjects

M Gobbi

Publications and source records attributed to M Gobbi.

At least 181 records · Page 10Linked to original sources
PubMed1987

Immunohistochemical determination of growth fractions in human permanent cell lines and lymphoid tumours: a critical comparison of the monoclonal antibodies OKT9 and Ki-67.

OKT9 and Ki-67 monoclonal antibodies have recently been proposed as useful tools for evaluating the growth fraction in malignant tumours, with special reference to non-Hodgkin's lymphomas. In particular, while the former is commonly thought to detect a transferrin receptor present on the cytoplasmic membrane of proliferating cells, the latter recognizes a nuclear antigen, which is expressed in G1, S, G2 and M phase of continuously cycling elements. To further verify their reliability, OKT9 and Ki-67 were applied to seven permanent cell lines (four myeloid and three B-lymphoblastoid) and 100 lymphoid tumours (70 non-Hodgkin's and 30 Hodgkin's lymphomas) phenotypically characterized on frozen sections. The results obtained showed that OKT9 and Ki-67 cannot be employed as equivalent means in assessing the growth fraction. In fact, OKT9 is directed to a transferrin receptor which is not only expressed by proliferating cells, but also by some resting elements. On the other hand, Ki-67 provides a nuclear, easily detectable positivity which is restricted to proliferating cells only. Therefore, it seems to represent the only monoclonal which can confidently be employed in the assessment of the growth fraction. Furthermore, the present study underlines that the immunocytochemical analysis of the proliferation rate in tumours gives similar information to the radionucleide uptake assay, while it represents a more sensitive method than the cytofluorimetric evaluation of the DNA content.

Antibodies, Monoclonal↗
PubMed1987

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis). Morphological and immunohistochemical study of eight cases.

Eight examples of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis) are described. They occurred in young or middle-aged women who usually complained of latero-cervical lymphadenopathy. Serology revealed significant titres for Epstein-Barr virus and Yersinia enterocolitica serogroup 9 in one of eight and one of six tested. All patients fully recovered within 2 months. On histological examination of the lymph nodes large foci of infiltration were observed in the cortex and/or paracortex: they consisted of variable numbers of small lymphocytes, immunoblasts, macrophages and so-called plasmacytoid T-cells; granulocytes were absent. Necrotic changes varied from single pyknotic cells to extensive areas of necrosis. Immunohistochemistry showed that within the lesion the number of macrophages was inversely proportional to the number of peripheral T-lymphocytes and 'plasmacytoid T-cells'. The latter displayed a phenotype (CD4+, CD10+, CD45+) which, in the absence of macrophage-associated antigens, seemed in keeping with their supposed lymphoid nature. In seven cases peripheral T-lymphocytes predominantly expressed the cytotoxic/suppressor phenotype, while in one remaining case a mild predominance of the helper/inducer subset was observed. In the areas with less extensive tissue necrosis, numerous T-immunoblasts expressed both markers of activation and the proliferation-associated nuclear antigen Ki-67. The results of the present study expand the spectrum of our knowledge and allow speculation as to the biology of this disease.

Adolescent↗
PubMed1987

Diazepam and desmethyldiazepam differ in their affinities and efficacies at 'central' and 'peripheral' benzodiazepine receptors.

The in-vitro binding characteristics of three different ligands ([ 3H]Ro 15-1788, [3H]Ro 5-4864 and [3H]flunitrazepam) and the structural requirements for binding to 'central' and 'peripheral' benzodiazepine receptors have been evaluated in rat cerebral cortex, cerebellum and adrenal glands. [3H]Ro 15-1788 binding was detectable only in the brain. Clonazepam was the most potent inhibitor followed by diazepam and desmethyldiazepam, which showed the same affinity, and by premazepam; Ro 5-4864 did not show appreciable affinity. The same pattern was seen for [3H] flunitrazepam binding in brain areas while in adrenal gland the inhibition pattern was exactly superimposable on that with [3H]Ro 5-4864 in all the areas considered (Ro 5-4864 greater than diazepam greater than desmethyldiazepam greater than clonazepam greater than premazepam). These data confirm and extend previous reports. A methyl group in position 1 enhances the affinity for peripheral benzodiazepine binding sites which are labelled in the adrenal gland by [3H]Ro 5-4864 and [3H]flunitrazepam; in brain areas, [3H]flunitrazepam, like [3H]Ro 15-1788, selectively labels central binding sites. Methylation in position 1 did not change the affinity for these sites. Desmethyldiazepam is less active than diazepam as an anticonvulsant and in other tests. In-vivo experiments were therefore carried out to assess the 'intrinsic activity' of desmethyldiazepam: it appeared that this compound acts as a partial agonist at central benzodiazepine receptors.

Adrenal Glands↗
PubMed1987

Normal and neoplastic plasma cell membrane phenotype: studies with new monoclonal antibodies.

Three monoclonal antibodies (MoAb), named 8A, 8F6 and 62B1, reacting with plasma cell-associated antigens, were characterized. 8A was found to be positive throughout the B cell lineage maturation steps from the immature B-committed CD10+ cell to the plasma cells. 8F6 and 62B1 reactivity is restricted to more mature cells and related lymphoid malignancies. In particular 62B1 appears to be limited to hairy cells and plasma cells. The results show that it is possible to obtain reagents reacting with plasma cells by immunizing mice with cells derived from human multiple myelomas. Furthermore, the obtained results suggest that it is possible to elicit antibodies against antigens which are present throughout all the differentiation steps of the B cell lineage. These new MoAb could help in elucidating the phenotype of the plasma cells and the relationships of multiple myelomas with other B cell proliferative disorders.

Animals↗
PubMed1986

Localization of GABAA and GABAB receptor subtypes on serotonergic neurons.

The effect of selective destruction of serotonin (5-HT)-containing neurons with 5,7-dihydroxytryptamine (5,7-DHT) on [3H] muscimol and (-)-[3H]baclofen binding was investigated in various rat brain regions. Ten days after intracerebroventricular 5,7-DHT, serotonin levels and [3H]imipramine binding were markedly decreased. 5,7-DHT reduced [3H]muscimol binding only in the mesencephalon, and (-)-[3H]baclofen binding was unmodified in all the areas considered. These results suggest that except in the mesencephalon GABA receptors may not be localized on serotonergic nerve terminals.

5,7-Dihydroxytryptamine↗
PubMed1986

Vimentin and keratin intermediate filaments expression by K562 leukemic cell line.

The expression of intermediate filaments (IMF) by K562 leukemic cell line has been studied by the use of polyclonal and monoclonal antibodies. These cells exhibited an extremely rich network of IMF reacting with both anti-vimentin and anti-keratin antibodies. Although these results need to be confirmed by different techniques, such as immunoblotting, they suggest the possibility that leukemic cell lines can express different types of IMF similarly to other cultured cells.

Actins↗
PubMed1986

Hodgkin's disease (HD): a historical perspective.

Five hundred and seven patients with Hodgkin's lymphoma (HL), forming the basis of our 18 years experience, are retrospectively analyzed. Four therapeutic periods are recognizable: The 1966-1970 period was characterized by the absence of treatment and management policy. The 55 patients entered in this period experienced 70 and 56% survival at 5 and 10 yr, respectively, from diagnosis. The 1971-1974 period was characterized by the increasing knowledge of staging relevance and therapeutic approaches. The 153 patients who were treated in this period experienced 72 and 60% survival at 5 and 10 yr, respectively. The 1975-1980 period was characterized by a large combination of MOPP and radiotherapy. The 216 patients who entered this period observed 80 and 72.5% survival at 5 and 10 yr, respectively. The last therapeutic period (1980 to present time) is characterized by the increasing relevance of prognostic factors and alternating use of MOPP and ABVD as non-cross resistant regimen. The 83 patients who entered this period showed 90% survival at 5 yr. Both survival and disease-free survival were positively influenced by the change of therapeutic strategies during the four periods (P less than 0.005). Although better results have been recorded moving from one to the next therapeutic period, the present policy has been also based on the recognition of a high number of late complications due to the therapy. Preliminary results about the present therapeutic experience seem to indicate both a good remission rate and low incidence of complications.

Adult↗
PubMed1986

The value of lymph node biopsy in patients with the acquired immunodeficiency syndrome (AIDS) and the AIDS-related complex (ARC): a morphological and immunohistochemical study of 90 cases.

The morphological and immunohistochemical findings in lymph nodes of nine patients with the acquired immunodeficiency syndrome (AIDS) and 81 patients with the AIDS-related complex (ARC) are presented. Three basic histological patterns were observed: follicular hyperplasia (29 cases), mixed hyperplasia (49 cases) and lymphocyte depletion (12 cases). While the first two variants were detected in typical ARC patients, lymphocyte depletion was always associated with AIDS. Immunohistochemistry on frozen sections showed that the number of B-cells varied throughout the series, being higher in the follicular type and significantly lower in the lymphocyte depletion nodes. The content of T-lymphocytes of the helper/inducer (T4) phenotype was reduced in all instances; this reduction was more pronounced in the germinal centres in follicular hyperplasia, while it involved all compartments of the node in the mixed and lymphocyte depletion types. In contrast the cytotoxic/suppressor (T8) subset was increased in the follicular and mixed hyperplasias only. Partial disintegration of the dendritic network in at least some of the follicles could be demonstrated in all lymph nodes. In the follicular and mixed hyperplasias there was a high number of proliferating B-cells in the germinal centres. Our data indicate the usefulness of grading the changes occurring in lymph nodes of patients with ARC and AIDS, and allow speculation as to the pathophysiology of these conditions.

AIDS-Related Complex↗
PubMed1986

Effect of long term amineptine treatment on pre- and postsynaptic mechanisms in rat brain.

The effect of amineptine and its two metabolites on monoamine uptake, release and receptor binding was studied in vitro. Amineptine and its two metabolites did not displace labelled ligands for known neurotransmitters and drug receptor sites. Amineptine and its two metabolites did not influence [3H]-5-hydroxytryptamine ([3H]-5-HT) uptake or release by rat brain synaptosomes. Amineptine inhibited [3H]-dopamine and [3H]-noradrenaline ([3H]-NA) accumulation, with IC50 values of 1.4 and 10 microM, respectively. The effect was retained, though with lower efficacy, by the two metabolites. Amineptine released [3H]-dopamine from preloaded synaptosomes. Metabolite 1 had no effect on catecholamine release, and metabolite 2 was about half as active as the parent compound on [3H]-dopamine release. The releasing effect of amineptine on [3H]-dopamine was potentiated by reserpine pretreatment, suggesting that the drug acts on the cytoplasmic neurotransmitter pool. Chronic treatment with amineptine (20 mg kg-1, twice daily for 15 days followed by a 3 days drug withdrawal period) resulted in a decrease of [3H]-spiperone binding sites in striatum, and of [3H]-dihyroalprenolol and [3H]-clonidine in cortex. Chronic treatment with amineptine reduced basal [3H]-dopamine accumulation in striatal synaptosomes, without affecting [3H]-NA or [3H]-5-HT accumulation. The adaptive changes in the pre- and postsynaptic dopamine mechanisms observed after long term treatment with amineptine are consistent with the drug acting as an indirect dopamine agonist. The down regulation of beta- and alpha 2-noradrenoceptors observed after long term amineptine treatment may play a role in the antidepressant activity of the drug.

Animals↗
PubMed1986

Bone marrow transplantation in multiple myeloma.

We report 3 cases of allogeneic bone marrow transplantation in multiple myeloma that we have recently performed. Following conditioning treatment with i.v. cyclophosphamide (60 mg/kg/d, for 2 d), oral melphalan (1.0 mg/kg/d, for 5 d), i.v. BCNU (5.5 mg/kg, in a single dose) and total body irradiation (10 Gy in a single fraction) we observed in all 3 cases the disappearance both of serum M component and of monoclonal bone marrow plasma cells. 1 patient died of acute GVH disease, grade IV, at 2 months, while the other 2 patients are in good health and in unmaintained complete remission at 4 and 20 months, respectively. The usefulness of allogeneic bone marrow transplantation in the management of multiple myeloma is emphasized.

Adult↗
PubMed1986

Allosteric inhibition as a model to explain flatter displacement curves in binding experiments: application to "heterogeneous" serotonin receptors.

Flattened or biphasic inhibition curves are usually interpreted by postulating the presence of two sites which are labelled with the same affinity by the ligand and can be recognized using the appropriate inhibitor with different selective affinities. We found that a priori this type of curve, can be equally fitted by another model, the allosteric model, on account of the mathematical equivalence of the two model functions when the 3H-ligand concentration is kept constant (i.e. inhibition experiments). A new approach consisting of three-dimensional analysis of the experimental data (3H-ligand binding as a function of ligand and inhibitor concentrations, simultaneously) permitted a statistical discrimination between the two models. The examples, used as tool for the present study, are the flattened or biphasic inhibition curves obtained by displacing 3H-serotonin with the neuroleptic spiperone. The results are discussed in relation to the general interpretation of this type of "anomalous" binding data and to the specific field of serotonergic receptor subtypes.

Allosteric Regulation↗
PubMed1986

Neurochemical effects of buspirone in rat hippocampus: evidence for selective activation of 5HT neurons.

The effect of buspirone on neurotransmitter systems in rat hippocampus has been evaluated in vitro and in vivo. In vitro buspirone does not affect the specific binding of 3H-flunitrazepam, 3H-GABA, 3H-dexetimide, but displaces 3H-5HT binding with nanomolar affinity. Oral administration of buspirone does not modify the hippocampal concentrations of GABA, acetylcholine, choline and of 3H-flunitrazepam specifically bound in vivo, but results in a dose-dependent reduction of 5HIAA and noradrenaline concentrations. While the effect on noradrenaline is also obtained in striatum of buspirone-treated animals, the effect on 5HIAA shows a regional specificity. The in vitro and in vivo data suggest that buspirone specifically activates 5HT neurons in hippocampus, and are compared with those obtained with diazepam.

Animals↗
PubMed1986

Renal failure in multiple myeloma. A study of the presenting findings, response to treatment and prognosis in 26 patients.

The presenting clinical features, response to treatment and survival duration of 26 consecutive multiple myeloma patients with renal failure at diagnosis were investigated. All but 1 of the patients had high tumour cell mass stage, as identified by one (3 cases) or more (22 cases) of the criteria defined by Durie and Salmon. Survival length of azotaemic patients was significantly shorter than that of stage III patients with normal renal function (median: 4 months vs 41 months, respectively, P less than 0.0005), and was positively affected by reversal of renal failure following treatment (P less than 0.0005). Of the 26 patients, 56% achieved reversal of renal failure. Recovery of normal renal function was prompt in most of the cases and appeared to be independent from both M component type and pretreatment serum creatinine levels. Finally, it was shown that patients with reversible renal impairment but with myeloma unresponsive to alkylating agents had early recurrence of impaired renal function and a shorter life expectancy than patients with a significant decrease in tumour cell mass.

Adrenal Cortex Hormones↗
PubMed1985

In vivo interaction of premazepam with benzodiazepine receptors: relation to its pharmacological effects.

The study of in vivo occupancy of benzodiazepine receptors in rat hippocampus and cerebellum indicates that premazepam reaches only about 70% and 80% occupancy respectively within the dose range used for pharmacological tests in rats. Moreover, at equiactive doses (antileptazol ED50), more brain receptors are occupied by premazepam than by other benzodiazepines, suggesting that premazepam may act as a partial agonist at benzodiazepine receptors, with intrinsic activity lower in cerebellum than in hippocampus. These results may explain the lack of sedative and ataxic properties of premazepam.

Animals↗
PubMed1985

Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.

A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.

Acute Disease↗