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Biomedical subjects

M Boiocchi

Publications and source records attributed to M Boiocchi.

At least 199 records · Page 11Linked to original sources

Immunotherapy of mouse leukemia with monoclonal antibodies directed against type-C virus structural proteins.

The monoclonal antibody A6, isolated during a study on the natural immunoresponse of BALB/c mice against leukemia cells (4), reacts with the envelope glycoproteins gp70 of the MuLV and with the cell surface of the SL2 AKR leukemia. In the present paper, we describe the in vivo immunotherapeutic effect exerted by the A6 monoclonal antibody on the growth of the transplanted leukemia SL2. The greater therapeutic effect observed when the A6 was used with exogenous complement cooperation suggests that the immunotherapeutic activity is mediated by C'-dependent cytotoxicity.

Animals↗

Natural antilymphoma antibodies in C3Hf mice serum: lack of identity with autoimmune and anti murine leukemia virus antibodies.

Absorption experiments on C3Hf normal mouse sera followed by cytotoxic tests on EL4 lymphoma cells were done to investigate a possible identity between natural antilymphoma antibodies (NAA) and various types of autoantibodies known to be present in normal mouse sera. Single C3Hf normal sera were also tested both by cytotoxicity on EL4 cells and by radioimmune precipitation assay (RIP) on 125I-labelled AKR ecotropic virus to ascertain whether or not viral antigen are the target structures of the NAA activity. The study provides evidence that NAA coexist with autoanticorpal and antiviral activities although they are distinct entities.

Animals↗

Detection of polymorphism in BALB/c leukemia viruses with mouse antisera.

Antisera produced in mice recognize primarily type-specific antigenic determinants on both the major core protein, p30, and the major envelope proteins, gp70 and p15(E), of the endogenous leukemia viruses (MuLV) of BALB/c mice. Three different mouse sera were investigated in detail. (i) Antisera prepared in C57BL/6 mice against the AKR leukemia K36 reacted with the gp70, p15(E), and p30 proteins of MuLV. Certain pools of the C57BL/6 anti-AKR K36 serum contained antibodies which serologically distinguished the p30 proteins of N-ecotropic, B-ecotropic, and xenotropic BALB/c MuLV. (ii) Antisera prepared in BALB/c mice against the BALB/c sarcoma 1315 contained antibodies that reacted with a type-specific antigen of the 1315 MuLV gp70 that is not found on other BALB/c MuLV. (iii) The normal sera of multiparous BALB/c mice contained antibodies that reacted with gp70 and p15(E) proteins of ecotropic MuLV. Sera from some of these mice contained antibodies that serologically distinguished the gp70 of N-ecotropic and B-ecotropic BALB/c viruses. These results emphasize the utility of mouse antisera in the serological typing of MuLV. Furthermore, the antigenic differences observed in the p30 and gp70 proteins should be of particular use in the future analysis of recombinant BALB/c MuLV.

AKR murine leukemia virus↗

[Myelography as a cause of persistant cerebral vascular spasm].

A few hours after an ascending myelography with Pantopaque, a woman aged 52 presented light coma with signs of meningeal reaction, left hemiparesis and a central deficit of the left facial nerve. 24 hours later, a computer axial tomography revealed the presence of the contrast media (Pantopaque) in the basal cysterns. Three days after, the right carotid angiography indicated the presence of a diffuse spasm of the intracranial branches of the internal carotid artery, particularly a spasm of the cortical ascending parietal and descending temporal ones, without deplacements. A second CT investigation revealed a slow, but complete recovery of the neurologic functions in the following 10 days. According to the Authors, this clinical observation reproduces the experimental pattern of the cerebral spasm caused by the administration of a spasmogenic chemical factor in the basal cysterns, because of the following clinical aspects: blood absence in the liquor; T wave inversion (the electrocardiographic symptom considered as a predisposing factor); meningeal reaction owing to the irritation of the myelographic contrast and persistent vasospastic answer of the right carotid circle, as it may be seen in the angiographic control.

Angiography↗

Relationship between antigenicity and morphology of murine lung adenomata.

Thirty-six lung adenomata induced in mice by urethane followed or not by cortisone, all had an adenomatous morphology at first s.c. transplant in syngeneic hosts. Seventeen of them acquired a sarcomatous structure within a few s.c. transplant generations whilst the other 19 remained adenomatous for as long as tested, i.e. at least 10 transplant generations. The change of morphology was not dependent on s.c. growth, since tumours also transformed when allowed to grow in the lung, and was not correlated to the capacity of a tumour for growth or metastasis. The 2 types of tumours were antigenically different, since only tumours that after few transplants changed their morphology were found at the first s.c. transplant to possess tumour-associated membrane antigens as revealed by an in vitro test. In addition, only the tumours which acquired a sarcomatous morphology were found gs-positive. The majority of antigenic primary tumours arose in mice belonging to the groups of treatment which induced the strongest immunodepression. It is suggested that a predisposition to sarcoma progression is related to an immunological control, at the time of adenoma induction, of an oncornavirus, responsible for the superimposed sarcomatous change.

Adenoma↗

Genetic control of endogenous C-type virus production in pancreatic acinar cells of C57BL/He and C57BL/6J mice.

Electron microscopy revealed very active production of C-type virus particles in the pancreatic acinar cells of untreated normal adult mice of the C57BL/He strain. In C57BL/6J mice, a similar picture was observed after a single intraperitoneal injection of dexamethasone. No viruses were observed in the pancreas of untreated or dexamethasone-treated BALB/c and C3Hf mice. F1 hybrids of both C57BL strains with C3Hf mice produced viruses in the same manner and quantity as the C57BL parents, whereas hybrids with BALB/c mice were entirely negative. Approximately 50% of mice of the first backcross generation of (BALB/c times C57BL/He)F1 hybrids with C57BL/He mice were active producers of C-type particles, while the other 50% were negative. It is suggested that a regulator gene that controls C-type virus production does not function in the pancreatic cells of either C57BL strain, and that BALB/c mice can provide hybrids with an active regulator.

Animals↗

Interactions of antineoplastic chemotherapy with zidovudine pharmacokinetics in patients with HIV-related neoplasms.

To evaluate the perturbations in zidovudine (ZDV) pharmacokinetics as a consequence of antineoplastic chemotherapeutic treatments, we performed a prospective crossover study in 13 HIV-infected patients with cancer. The subjects received 2-day regimens of ZDV (250 mg x 2/day). On the first day ZDV was administered alone, whereas on the second day it was combined with antitumor chemotherapies specific for the histological type (ZDV + chemotherapy). Blood sample and urine collections were performed over a 12-hour period following oral administration of the antiretroviral agent. ZDV was measured with high-performance liquid chromatography. Pharmacokinetic parameters of ZDV were calculated by a noncompartmental model. The mean ZDV area under curve (AUC) was not significantly different in the patients treated with ZDV alone and ZDV + chemotherapy. Comparison of plasma elimination half-life (t((1/2))), apparent systemic clearance (CL/F), and apparent volume of distribution (Vd/F) of ZDV did not show any significant difference before and after chemotherapy. Conversely, some significant differences were observed for both mean peak concentration (C(max)) of ZDV and the corresponding time (T(max)). There was a 57% reduction in C(max) (p<0.05) and a 66% increase in T(max) (p<0.05) after chemotherapy compared with treatment with ZDV alone. No differences were observed in the urinary excretion of ZDV and ZDV glucuronide and urinary metabolic ratio, as a consequence of antineoplastic treatment. In conclusion, this study demonstrates that some minor perturbations in ZDV pharmacokinetics (i.e. C(max) and T(max)) derived from antineoplastic chemotherapy. Based on the observation that antineoplastic chemotherapy had no significant effect on plasma ZDV concentration expressed as AUC, the observed pharmacokinetic interaction would not warrant by itself a change in the ZDV dosage during chemotherapy.

Adolescent↗

Electron microscopic search for endogenous type C virus production in organs of dexamethasone-treated C57BL/He and C57BL/6J mice.

Several organs of newborn or adult C57BL/He and C57BL/6J mice and of infant AKR mice were examined for type-C viral particles after treatment with dexamethasone, a corticosteroid hormone that stimulates C virus replication. In both C57BL strains C particles were consistently found in the exocrine pancreas of the newborns but in smaller number than that previously observed in the adults. No C particles were observed in the submaxillary salivary glands, bones or other organs examined in adult C57BL/He and C57BL/6J mice. In infant AKR mice, few C particles were observed in the exocrine pancreas or submaxillary salivary glands whereas they were found to be produced in large number by bone cells. The results suggest that in C57BL/He and C57BL/6J mice endogenous C particle production is continuous throughout life in the exocrine pancreas and is restricted to this tissue.

Animals↗

Allelic structural genes for the expression of mature of immature endogenous type-C virus in C57BL/he and C57BL/6J mice.

Type C particles produced in a great amount by the exocrine pancreas of normal C57BL mice have been found by electron microscopy to retain their immature morphology in C57BL/6J mice and to develop into the mature form in C57BL/He mice. Examining F1, F2 and BC1 hybrids between the 2 strains, evidence of a dominant allelism for the immature phenotype was found.

Animals↗

Fc receptor-like structures on in vitro-cultured human ovarian tumor cells.

Four ovarian cystadenocarcinomas cultured in vitro were tested by a radioisotopic method with sera from cancer patients or healthy donors to search for a possible specific antitumor immune response of patients bearing ovarian tumors. However, the ovarian tumor cells were found to bear on their membrane surface structures able to bind immunoglobulins from any tested serum, thus making impossible the detection of a hypothetical specific antitumor antibody. These structures were demonstrated to bind the Fc portion of the Ig and were therefore similar to the Fc receptors described on various normal cells, particularly of the immunocompetent compartment.

Cell Membrane↗

Spontaneous mutation of cell oncogenes plays a minor role in neoplastic transformation of virus-induced murine T-cell lymphomas.

Mink cell focus-forming viruses (MCF) are slow-transforming retroviruses that are able to accelerate the appearance of T-cell lymphomas when injected in newborn AKR mice. Activation of proto-oncogenes by proviral insertion is thought to be the major mechanism by which these viruses exert their oncogenic potential. However, molecular phenomena not strictly virus-determined, such as mutations in cellular oncogenes/tumor suppressor genes or chromosome aberrations, have been hypothesized to contribute to the achievement of the fully neoplastic phenotype in MCF-infected mice. To evaluate the role of spontaneous mutagenesis phenomena in murine virus-induced lymphomagenesis, we analyzed a series of 18 MCF247-induced thymic lymphomas and derived cell lines for the presence of p53 and c-ras gene mutations. Only 1 mutation at the p53 gene and 1 mutation at the ki-ras gene were detected in our study. Our results suggest that spontaneous mutagenesis plays a minor role in virus-induced lymphomagenesis and support the notion that multiple proviral insertions could be the prevalent mechanism of transformation in this experimental system.

Animals↗

The relevance of VDJ PCR protocols in detecting B-cell clonal expansion in lymphomas and other lymphoproliferative disorders.

AIMS AND BACKGROUND: The detection of immunoglobulin heavy chain variable (VH)-diversity (DH)-joining (JH) region gene rearrangement by polymerase chain reaction (VDJ PCR) has been recently proposed as a rapid approach to assess B-cell clonality in lymphoproliferative disorders. The aim of the present study was to determine the efficacy of VDJ PCR in a wide spectrum of lymphoproliferative disorders previously characterized by immunohistochemistry and Southern blot (SB). METHODS: 83 SB-rearranged B-cell non-Hodgkin's lymphomas (NHL) of different histotype, 22 cases of SB-unrearranged classical Hodgkin's disease (HD), 18 cases of HIV-related reactive lymphadenopathy, and 4 frankly pre-lymphomatous lesions (MESA) in the course of Sjögren's syndrome were investigated by 2 different VDJ PCR protocols (FR3, FR2). RESULTS: The detection rate in NHL was 64% and 71% using the protocols FR3 and FR2, respectively. However, the overall VDJ PCR efficacy increased to 81% by combining the results of both protocols. In addition, differences in the combined, as well as in the single FR3 or FR2 protocol efficacy, were noted in the different NHL subgroups. B-cell clonality was also detected in 4/22 (18%) SB-unrearranged classical HD cases and in 2/18 (11%) reactive lymphadenopathy cases, whereas it was demonstrated in all the MESA lesions, 2 of them being SB-negative. CONCLUSIONS: VDJ PCR represents a useful and rapid technique to detect B-cell clonality in NHL, although with some differences depending on the NHL histotype and the panel of primers employed. The technique may also be of value to investigate the possible progression of early B-cell clonal expansion into frankly B-cell malignancy and to contribute to the controversy about the clonal lineage origin of the putative HD malignant cells.

AIDS-Related Complex↗

Methylenetetrahydrofolate reductase genotype in diffuse large B-cell lymphomas with and without hypermethylation of the DNA repair gene O6-methylguanine DNA methyltransferase.

C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) polymorphisms have been suggested to affect susceptibility to malignant lymphoma, possibly by altering DNA methylation. The DNA repair gene O6-methylguanine DNA methyltransferase (MGMT) is transcriptionally silenced by promoter hypermethylation in diffuse large B-cell lymphomas (DLBCL). We analyzed the MTHFR677 and MTHFR1298 genotypes in 111 DLBCL patients and 465 controls. No significant difference in the frequency of MTHFR polymorphisms between patients and controls and no significant association between MTHFR677 or MTHFR1298 genotypes and methylation of MGMT promoter were observed. These results indicate that MTHFR variants are not related to DLBCL development and MGMT hypermethylation.

Alleles↗