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M Gobbi

Publications and source records attributed to M Gobbi.

At least 19 recordsLinked to original sources
PubMed1992

Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains.

In this study, we have evaluated 14 large granular lymphocyte (LGL) expansions, 11 of which were CD8+. Analysis of the membrane expression of the alpha and beta chains of the CD8 antigen, using specific monoclonal antibodies (MoAbs), has shown that LGL expansions with the CD3+, CD4+, CD8+, CD57+ T-cell receptor (TcR) alpha beta phenotype bear the CD8 alpha/alpha isoform, while the CD3+, CD4-, CD8+, CD57+ TcR alpha beta samples were positive for both the CD8 alpha and CD8 beta chains. These data were confirmed also by messenger RNA analysis. One additional case, with a peculiar phenotype (CD3-, CD2-, CD4-, CD8+, CD57-) and a germline configuration of the TcR beta and gamma chain genes, expressed only the CD8 alpha chain. After additional phenotypic analysis with a wider panel of MoAbs, it was found that the beta chain of the interleukin-2 receptor was constitutively expressed on the majority of the samples tested, and that most of the monoclonal samples coexpressed CD45RA/R0 antigens. Using MoAbs directed against the variable regions of the TcR beta chain, we could show a preferential V beta region restriction in the CD8+ monoclonal cases. This more extensive characterization of CD8+ LGL expansions has further documented the marked heterogeneity within this rare condition and allowed a better phenotypic dissection between the monoclonal and polyclonal cases.

Adult↗
PubMed1992

Releasing activities of d-fenfluramine and fluoxetine on rat hippocampal synaptosomes preloaded with [3H]serotonin.

Rat hippocampal synaptosomes preloaded with [3H]serotonin and maintained in a superfusion apparatus were exposed for 3 min to d-fenfluramine or fluoxetine. Both drugs evoked a tritium overflow which was reserpine-sensitive requiring the presence of intact synaptic vesicles. However the two drugs displayed different characteristics: 1) the overflow was immediate with d-fenfluramine whereas the releasing activity of fluoxetine showed a delay of about 2 min; 2) d-fenfluramine-induced overflow was already apparent at 0.15 mumol/l whereas the minimal effective concentration of fluoxetine was 2.5 mumol/l. Their concentration-effect curves were differently shaped, the effect of d-fenfluramine being saturable at 5-20 mumol/l (EC50 about 1 mumol/l) while no saturation was observed with fluoxetine up to 10 mumol/l; 3) only 19% of the tritium overflow evoked by fluoxetine (2.5-10 mumol/l) consisted of true [3H]serotonin, compared with 70% when 0.5 mumol/l d-fenfluramine was used; 4) the releasing action of 0.5 mumol/l d-fenfluramine was completely Ca(++)-dependent, while at higher d-fenfluramine concentrations the Ca(++)-independent overflow became more important. The fluoxetine induced overflow was mainly (70%) Ca(++)-independent; 5) the releasing activity of d-fenfluramine was mainly (80%) blocked by the serotonin uptake blockers indalpine, midalcipram and also fluoxetine whereas fluoxetine-induced overflow was insensitive to inhibition of the serotonin carrier. In conclusion, the releasing activity of d-fenfluramine is already present at a very low concentration (0.5 mumol/l) and at this concentration its mechanism of action was Ca(++)-dependent, together with the requirement of a functional serotonin carrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

B-B10 (anti-CD25)-saporin immunotoxin--a possible tool in graft-versus-host disease treatment.

An immunotoxin containing the B-B10 MoAb, directed against the CD25 determinant, and the ribosome-inactivating protein saporin, inhibits 3H-TdR incorporation in phytohemagglutin, allogeneic-stimulated lymphocytes (primary and secondary mixed-lymphocyte reaction), and in an alloreactive T cell clone. A lower degree of inhibition was obtained with the B-B10 MoAb, which is known to inhibit IL-2 activity, as well as with the unconjugated compounds. These results suggest that the in vivo administration of the conjugate might be a more effective tool in the treatment of patients affected by graft-versus-host disease than B-B10 alone, by inducing an efficient killing of allogeneic-reacting T lymphocytes.

Antibodies, Monoclonal↗
PubMed1992

Ber-H2 (anti-CD30)-saporin immunotoxin: a new tool for the treatment of Hodgkin's disease and CD30+ lymphoma: in vitro evaluation.

An immunotoxin containing an anti-CD30 monoclonal antibody (Ber-H2) and saporin, a ribosome-inactivating protein type 1, is described. It specifically inhibits protein synthesis by Hodgkin derived target cell lines with a very high efficiency (IC50 ranging from 5 x 10(-12) M to 5 x 10(-14) M, as saporin), while irrelevant immunotoxins do not. Present results suggest that this immunotoxin could be used for in vivo therapy as well as for ex vivo bone marrow purging in Hodgkin's disease and CD30+ lymphomas.

Animals↗
PubMed1992

A comparison of anti-lymphocyte immunotoxins containing different ribosome-inactivating proteins and antibodies.

Immunotoxins were prepared with several single-chain ribosome-inactivating proteins (RIPs type 1) and with the A-chain of ricin linked to the F(ab')2 fragment of sheep anti-mouse IgG. The cytotoxic activity of these conjugates was tested on human lymphocytes pretreated with an anti-CD3 murine MoAb. The immunotoxins inhibited DNA synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes with IC50S (concentrations causing 50% inhibition) ranging from 8.9 x 10(-13) to 5.7 x 10(-11) M (immunotoxins containing dianthin 32, saporin, pokeweed antiviral protein from seeds (PAP-S), bryodin, momordin, momorcochin, and trichokirin), 1 x 10(-8) M (immunotoxin containing gelonin) and 5 x 10(-9) M (immunotoxin containing ricin A-chain). The immunotoxin containing saporin linked to the anti-mouse IgG F(ab')2 fragment was also highly toxic to human lymphocytes pretreated with anti-CD2, -CD3, -CD5 and -CD45 MoAbs, with IC50S less than or equal to 10(-11) M. Immunotoxins were prepared also with saporin linked to MoAbs against various CD antigens. The immunotoxin prepared with the anti-CD3 antibody had the highest specific cytotoxicity to human lymphocytes.

Antibodies↗
PubMed1991

Ubiquitous pollution by n-hexane and reference biological levels in the general population.

n-Hexane levels were determined by gas chromatography and mass spectrometry in environmental air and in the alveolar air, blood and urine of a group of subjects aged on average of 38 years who had not been occupationally exposed to this hydrocarbon. n-Hexane was found in all environmental air samples examined (n = 49), with the mean concentration being 104 ng/l (limit values, 1-279 ng/l). It was also found in all 49 samples of alveolar air, with the mean concentration being 50 ng/l (variation limit, 1-304 ng/l). In 64 samples of urine, n-hexane was found in only 50 samples, with the mean concentration being 1,417 ng/l (limit values, 34-8,820 ng/l). In 77 of the 90 blood samples taken, a mean concentration of 608 ng/l was detected (variation limit, 15-7,684 ng/l). Particularly the haematic and urinary concentration showed significant differences among the nine groups of individuals classified according to their work activity. The lowest levels were found in the blood and urine of farmers: 270 and 298 ng/l, respectively. The highest values were found for chemical workers (1,377 and 411 ng/l), respectively printers (585 and 2,691 ng/l respectively), and traffic wardens (740 and 8,820 ng/l, respectively). In all, 95% of the determinations of n-hexane yielded values of less than 255 ng/l in environmental samples, less than 105 ng/l in alveolar air, less than 1,475 ng/l in blood and less than 5,875 ng/l in urine. A comparison of these data revealed a significant correlation between environmental levels and alveolar (r/s = 0.769; P less than 0.00001), haematic (r/s = 0.624; P less than 0.0002), and urinary (r/s = 0.597; P less than 0.0005) values for n-hexane.

Adult↗
PubMed1991

Acute noise stress in rats increases the levels of diazepam binding inhibitor (DBI) in hippocampus and adrenal gland.

We investigated the effect of acute noise-induced stress on the concentrations of diazepam binding inhibitor (DBI) and its processing products in brain regions and adrenal glands of rats. DBI levels in hippocampus began to increase at 15 and 30 min and became significantly higher (+100%) at 90 and 120 min after stress; they returned to normal values at 360 min. While basal DBI levels were similar in the left and right hippocampus, the stress-induced increase of DBI levels was significantly higher in the left compared to the right side. A significant increase was also detected in the adrenals; here, the time course of DBI increase paralleled that of previously reported plasma corticosterone in stressed rats, being significantly higher 30 min after stress, and recovering to normal values at 60 and 90 min. After acute noise-induced stress, no significant change of DBI levels was detectable in cerebral cortex, striatum, hypothalamus and cerebellum. The present study reports for the first time the occurrence of a modification of DBI and its processing products (ODN-like immunoreactivity) in an experimental model of stress, and suggests a role for these neuropeptides in emotional responses.

Adrenal Glands↗
PubMed1991

Effect of acute and chronic administration of buspirone on serotonin and benzodiazepine receptor subtypes in the rat brain: an autoradiographic study.

The affinity of buspirone and its main metabolite 1-(2-pyrimidinyl)piperazine (PmP) for serotonin1 (5-HT1) and benzodiazepine receptors was first evaluated by computerized receptor autoradiography. The results confirmed that buspirone is a selective 5-HT1A ligand, since it inhibited the binding of [3H]5-HT with lower IC50 values (about 100 nM) in regions of the brain of the rat where this receptor subtype is predominant (such as hippocampal areas). Larger IC50 values than 3 microM were found in areas of the brain richer in 5-HT1 receptors, other than the 5-HT1A subtype (e.g. striatum, substantia nigra and the ventricles). The PmP was not selective, inhibiting the binding of [3H]5-HT with similar affinity (about 4-10 microM) in all the regions of the brain examined. Neither buspirone nor PmP, up to 100 microM, were active on benzodiazepine receptors. The autoradiographic technique was therefore used to evaluate the effects of acute (10 mg/kg, p.o., 1 hr before killing) and chronic (10 mg/kg, i.p., twice a day for 21 days, 24 hr washout) treatment with buspirone in male rats. Acute treatment reduced the binding of [3H]5-HT in all the regions of the brain studied, including those with low levels of 5-HT1A receptors, indicating the occupancy of 5-HT1 receptors by either buspirone or its metabolite. The binding of [3H]flunitrazepam was decreased (16%) only in the substantia nigra.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Diazepam binding inhibitor (DBI) increases after acute stress in rat.

Diazepam binding inhibitor (DBI) acts in brain by binding to GABAA/benzodiazepine receptors (GBR) and to mitochondrial benzodiazepine receptors (MBR). Because DBI acting at MBR, has been shown to be an effector of ACTH-induced steroidogenesis and stress is known to change the level of GBR and MBR, the model of acute noise stress in rats was used to study modifications of DBI and GRB or the content of MBR in various areas of the brain and adrenal gland. It was found that, in the brain of stressed rats, DBI and its processing products (ODN-like immunoreactivity), increased selectively in the hippocampus. This increase in the content of DBI was preceded and followed by a net decrease of GBR and an increase of MBR. Similarly, in adrenal cortex, the content of DBI and MBR increased during the first hour, following acute stress and this increase paralleled the increase in plasma corticosterone. These data suggest that DBI, acting on MBR may regulate steroidogenic function in stress.

Adrenal Glands↗
PubMed1991

Immunohistochemical detection of the multidrug transport protein P170 in human normal tissues and malignant lymphomas.

Two monoclonal antibodies, MRK16 and C219, both directed at the 170 kDa P-glycoprotein multidrug resistance agent, were applied to frozen sections or cytospin preparations from normal human tissues and 60 non-Hodgkin's malignant lymphomas. Adrenal gland, kidney, liver and pancreas were always stained by the reagents, albeit with slightly different patterns. Brain capillaries as well as macrophages and some elements of the bone marrow, peripheral blood, ovarian stroma and colonic, gastric and jejunal mucosa were positive in all examined preparations. There were differences in the staining patterns with the two antibodies. Among the 60 non-Hodgkin's lymphomas, 25 contained a number of positive cells, which ranged from 2% to 100%. No correlation was seen between the expression of P170 and histological type, stage, clinical symptoms or growth fraction. A close relationship was shown between the presence of P170 positive elements and the clinical course of the disease (P less than 0.001).

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

CD34 or S313 positive cells selection by avidin-biotin immunoadsorption.

A column immunoadsorption method, based on the high affinity between the protein Avidin and the vitamin Biotin has been used to obtain positive CD34+ or S313+ marrow cells selection. Cell suspensions from marrow samples of six healthy subjects were incubated either the monoclonal antibody S313 or HPCA 1 (My 10-like) and a biotinilated goat anti-mouse Immunoglobulins antiserum, passed over a column containing an Avidin coated Polyacrylamide matrix, at the flow rate of 1 ml/min. The phenotype and the clonogenic efficiency of the recovered adherent cell fraction were studied by cytofluorimetric analysis and haemopoietic progenitors short term cultures. The results obtained show a mean CD34+ and S313+ cells recovery greater than 50% with a lower stem cells enrichment. Although these data could not considered optimal for clinical application in haematologic neoplasias, these preliminary studies demonstrate the possible use of the method for autologous bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1990

CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report.

Between March 1987 and December 1988, 30 previously untreated patients with low-grade non-Hodgkin's lymphomas (NHL), according to the Kiel classification, were treated by a combination of therapy including cyclophosphamide, epirubicin, vincristine, and prednisone (CEOP). Eighteen patients (60%) achieved a complete pathologic remission, and 8 patients (26.6%) had a partial response with a reduction of more than 50% of tumor-related manifestations. Four patients (13.4%) were primary resistant to CEOP. The overall survival was 96.6% with a median follow-up of 25 months from the diagnosis; none of the patients who achieved complete response relapsed at a median follow-up of 21 months from the completion of treatment. Clinical and hematologic toxicities were irrelevant. This regimen was effective in inducing a good remission rate of low-grade NHL, but a longer follow-up for definitive conclusions is warranted.

Adult↗