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A Bigotti

Publications and source records attributed to A Bigotti.

At least 55 records · Page 3Linked to original sources

Distribution of laminin and collagen type-IV in benign and malignant lesions of melanocytic origin.

Using antisera for two specific basement membrane (b.m.) antigens such as laminin and collagen type-IV, together with electron microscopy, we have shown that fully antigenic b.m. and morphologically typical basal lamina (b.l.) are associated with normal and transformed cells of the melanocyte lineage in different ways. Thus, while b.m. and b.l. surround individual choroidal melanocytes, intradermal nevus cells and cells of blue nevi are not detectable at the periphery of resting and proliferating epidermal melanocytes. They have a low degree of expression with a heterogeneous pattern of distribution in primary and metastatic melanoma. This heterogeneity is present within single metastases and among autologous metastases. These findings indicate that the presence of b.m. can be an additional marker for cells of the melanocyte lineage and should be considered when applying serological means for the detection and control of neoplasms of melanocytic origin.

Basement Membrane↗

Distribution of a cross-species melanoma-associated antigen in normal and neoplastic human tissues.

In previous studies the monoclonal antibody (MoAb) M2590 elicited in C57/BL6 mice with the syngeneic melanoma cell line B16 has been shown to recognize a 31K glycoprotein expressed by human melanoma cell lines. The present study has shown that the MoAb M2590 cross-reacts with surgically removed benign and malignant lesions of melanocyte origin. The reactivity pattern of the MoAb M2590 with these lesions is different from that of the anti-high-molecular weight-melanoma associated antigen (HMW-MAA) MoAb 225.28S, of the anti-115K MAA MoAb 345.134S, and of the anti-100K MAA MoAb 376.96S, which were elicited with human melanoma cell lines. In particular, the MoAb M2590 reacts with blue nevi. The MoAb M2590-defined MAA, like other types of MAA, is heterogeneous in lesions removed from different patients, in autologous lesions removed from different anatomic sites, and in cells within a lesion. The distribution of the MoAb M2590-defined MAA in normal tissues and in tumors of nonmelanocyte origin is broader than that of the HMW-MAA, but is similar to that of the 115K MAA and of the 100K MAA. The results of this investigation suggest that immunization with xenogeneic melanoma cells may broaden the range of specificity of antihuman MAA MoAbs and provide information about the phylogenetic evolution of MAAs.

Adult↗

Heterogeneous expression of melanoma-associated antigens and HLA antigens by primary and multiple metastatic lesions removed from patients with melanoma.

Indirect immunofluorescence staining with a large battery of monoclonal antibodies of primary and autologous metastatic lesions removed from seven patients with melanoma has detected heterogeneity in the expression of various types of melanoma-associated antigens (MAAs), of distinct determinants of the high molecular weight melanoma-associated antigen (HMW-MAA), of the two subunits of Class I HLA antigens, and of the gene products of the HLA-D region. Among the 10 MAAs tested, the HMW-MAA had the highest frequency and the Mr 87,000 MAA the lowest. Furthermore, the HMW-MAA displayed the lowest heterogeneity. These findings, in conjunction with the restricted tissue distribution of the HMW-MAA, its lack of susceptibility to antibody-mediated modulation, and the high affinity of the available anti-HMW-MAA monoclonal antibodies, indicate that this antigen may be a useful marker for radioimaging and immunotherapy in patients with melanoma. The common acute lymphoblastic leukemia antigen was detected only in five lesions. Class I HLA antigens were detected in a larger number of lesions than HLA-DR antigens, which had a significantly higher frequency than HLA-DQ antigens. The degree of antigenic heterogeneity did not appear to correlate with the histopathological features of the lesions and/or with the clinical course of the disease. The results of the present study indicate that immunodiagnostic and immunotherapeutic approaches to melanoma should rely on the use of combinations of monoclonal antibodies to distinct MAAs.

Animals↗

Phenotyping of lesions of melanocyte origin with monoclonal antibodies to melanoma-associated antigens and to HLA antigens.

The antigenic profiles of a large number of surgically removed human benign and malignant lesions of melanocyte origin have been analyzed with the use of monoclonal antibodies (MoAb) against la antigens, against the HLA-A,B,C-beta 2-microglobulin molecular complex, against a cytoplasmic melanoma-associated antigen (MAA), and against membrane-bound MAA. Membrane-bound MAA include a high-molecular-weight MAA (HMW-MAA), a 115K MAA, and a 100K MAA. Appearance of the HMW-MAA and of the cytoplasmic MAA, as well as cytoplasmic distribution or loss of HLA-A,B,C antigens, occurs in benign lesions. Additional appearance of Ia antigens is associated with malignant transformation of melanocytes. The antigenic profile defined by the battery of MoAb used displays differences among benign lesions of different histogenesis, between benign and malignant lesions, and among malignant lesions with different histopathologic properties. These results suggest that phenotyping of surgically removed lesions with anti-MAA and anti-HLA MoAb may contribute to the understanding of the steps involved in tumor progression of melanocytes and may aid in the diagnosis of lesions with unusual histopathologic features.

Antibodies, Monoclonal↗

Distribution of human Class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin.

Indirect immunofluorescence and immunoperoxidase staining of surgically removed tissues of nonlymphoid origin with monoclonal antibodies to the heavy and light chain of HLA-A,B,C antigens have shown that they have a more restricted tissue distribution than previously assumed. HLA-A,B,C antigens were not detected in brain cortex, cerebellum, sympathetic ganglia, hypophysis, parathyroid gland, thyroid, exocrine pancreas, hepatocytes, sperm, seminiferous tubules, or skeletal or smooth muscle. Malignant transformation of cells may be associated with appearance, changes in cellular distribution of HLA-A,B,C antigens, and/or dissociation in the expression of the two subunits. Analysis of primary tumors and of autologous metastases showed heterogeneity in the expression of HLA-A,B,C antigens among lesions removed from different sites. The degree of heterogeneity did not correlate with the site of origin of metastases.

Female↗

Heterogeneity in the expression of HLA and tumor-associated antigens by surgically removed and cultured breast carcinoma cells.

Surgically removed normal and malignant mammary tissues and human breast carcinoma cell lines were tested in binding assays with monoclonal antibodies to HLA-A,B,C antigens, beta 2-microglobulin, HLA-DR antigens, and tumor-associated antigens; the latter included a Mr 280,000, a Mr 94,000, and a Mr 85,000 membrane-bound glycoprotein and a cytoplasmic antigen. HLA-A,B antigens, beta 2-microglobulin, HLA-DR antigens, and the cytoplasmic antigen are expressed by normal mammary cells. Their malignant transformation may be associated with quantitative changes in the expression of these antigens and with the appearance of Mr 94,000 and Mr 85,000 glycoproteins. The Mr 280,000 glycoprotein was detected on only one of the breast carcinoma cell lines tested. Analysis of primary tumors and autologous axillary lymph node metastasis from 13 patients has shown differences in the expression of all the antigens tested between primary and metastatic lesions.

Adult↗

Antigenic heterogeneity of skin tumors of nonmelanocyte origin: analysis with monoclonal antibodies to tumor-associated antigens and to histocompatibility antigens.

Surgically removed benign and malignant human skin lesions of nonmelanocyte origin have been tested with monoclonal antibodies to la antigens, to the HLA-A,B antigenic molecular complex, and to melanoma-associated antigen(s) (MAA). MAA include a high-molecular-weight (HMW) MAA, a 115,000-molecular-weight MAA, a 94,000-molecular-weight MAA, and a cytoplasmic MAA. Indirect immunofluorescence was used as the assay system because of the limited amount of tissue available. When the amount of tissue available was sufficient, double determinant immunoassays (DDIA) were used to quantitate the level of the HMW MAA and of the cytoplasmic MAA. The results of the DDIA were in agreement with those of indirect immunofluorescence in more than 75% of the cases. Malignant skin tumors of various histiotypes displayed three types of changes: 1) appearance of la antigens and cytoplasmic MAA, 2) increase in the level of the HMW MAA, of a 115,000- and a 100,000-molecular-weight MAA, and 3) reduction in the level of HLA-A,B antigens and beta 2-microglobulin. A significant heterogeneity was found in the antigenic profile among various lesions of a given histiotype as well as among tumor cells within a given lesion.

Aged↗

Antigenic heterogeneity of surgically removed primary and autologous metastatic human melanoma lesions.

The antigenic heterogeneity of primary and metastatic lesions surgically removed from nine patients with nodular melanoma was investigated by using monoclonal antibodies to HLA-A, B antigens, to beta 2-microglobulin, to Ia antigens, and to melanoma-associated antigens (MAA). The latter include three types of membrane-bound MAA and a cytoplasmic MAA. In spite of an homogeneous morphologic appearance, multiple lesions removed from the same patient differed significantly in their reactivity with the panel of monoclonal antibodies in indirect immunofluorescence test. The extent of antigenic heterogeneity did not correlate with melanin synthesis, site of origin of the primary tumor, site of metastatic foci, or treatment, but was less marked in patients carrying the primary tumor. The antigenic heterogeneity of multiple lesions removed from one patient and the independent expression of the various types of MAA investigated suggest that combinations of monoclonal antibodies to MAA may be more effective than single antibodies for radioimaging and immunotherapy.

Antibodies, Monoclonal↗

Tissue distribution, molecular profile, and shedding of a cytoplasmic antigen identified by the monoclonal antibody 465.12S to human melanoma cells.

The mouse immunoglobulin G2 monoclonal antibody (MoAb) 465.12S reacts with a cytoplasmic antigen present in human melanoma cells but not detectable in melanocytes. Indirect immunofluorescent staining of a large number of surgically removed normal adult and fetal tissues with the MoAb 465.12S detected the cytoplasmic antigen in epithelial cells from several organs. The intensity of staining was greater in adult tissues than in the corresponding fetal tissues. Furthermore, the MoAb 465.12S stained nearly all of the surgically removed tumors tested but did not stain many of the normal tissues from which they originated. In almost all cases, the intensity and frequency of staining wa greater for tumor cells than for corresponding normal tissues. From cultured carcinoma and melanoma cells, the MoAb 465.12S immunoprecipitated four glycopolypeptides with molecular weights of 94,000, 75,000, 70,000, and 25,000. Incorporation of 3H-labeled sugars into the various components of the cytoplasmic antigen revealed that the M.W. 75,000 component was unusual in that it contained only glucosamine and mannose. The antigenic determinant defined by the MoAb 465.12S appears to be protein rather than carbohydrate in nature since it is heat sensitive and is expressed on the antigens synthesized by cells in presence of tunicamycin. Analysis of the spent culture medium of carcinoma and melanoma cell lines revealed that the cytoplasmic antigen is readily shed by these cells and consists of a major M.W. 94,000 and a minor M.W. 72,000 component. Treatment of cultured melanoma cells with the antibiotic tunicamycin showed that glycosylation of the cytoplasmic antigen is required for its shedding and/or stability in the spent culture medium.

Antibodies, Monoclonal↗

A 94,000-dalton glycoprotein expressed by human melanoma and carcinoma cells.

The IgG2a monoclonal antibody (MoAb) 376.96S, secreted by a hybridoma derived from a mouse immunized with cultured human melanoma cells COLO 38, reacts with a single 94,000-dalton glycoprotein that is peripherally associated with the plasma cell membrane of cultured melanoma cells. Indirect immunofluorescence analysis with cryostat thin sections of human tissues showed that this antigen is absent from a large variety of normal tissues but is readily detectable on melanomas, nevi, and several different carcinomas. The MoAb 376.96S binds with cultured melanoma and carcinoma cell lines to a similar extent and can mediate both complement-dependent and cell-dependent lysis of these cells. The 94,000-dalton glycoprotein detected by MoAb 376.96S is distinct in its tissue distribution, antigenicity, and molecular profile from several structures previously identified with monoclonal antibodies that have similar molecular weights.

Antibodies, Monoclonal↗

The central-nervous-system toxicity of long-term oral administration of L-tryptophan to porto-caval-shunted rats.

In a previous paper we have reported that the oral long-term administration of 200 mg/kd of L-tryptophan to rats with a porto-caval shunt causes significant loss of body weight, muscular hypertonicity and aggressivity, as well as marked alteration of the liver structure. We now report that tryptophan administered at the same dosage for the same length of time also induces significant alteration of the central nervous system. These results further demonstrate that high plasma levels of tryptophan are quite well tolerated by control animals but are quite toxic to rats with a porto-caval shunt. We also claim that the brain alterations observed in such animals are not secondary to liver dysfunction but to high levels of plasma tryptophan per se.

Animals↗

Cystic lymphangioma of stomach and jejunum: report of one case.

A case of cystic lymphangioma of stomach and jejunum is reported. The patient, a woman aged 58, was referred to the hospital for a melena of 4 days duration, which was interpreted as related to an old history of hypertrophic gastritis and duodenal ulcer. A conservative treatment with transfusions, cimetidine i.v., and gastric washout with antacids was started, but the hemorrhage appeared unresponsive, so an explorative laparotomy was performed. At the operation a soft pliable cystic mass in the anterior wall of the stomach was found; a smaller one was felt in the second jejunal loop. A Billroth II gastroduodenal resection was performed. The diagnosis of nature was only microscopic. At 9 months follow-up the patient is well, free of the disease.

Female↗

Malignant lentigo-melanoma--a comparative histological and electron microscopy study.

We examined, by light and electron microscopy, three cases of malignant lentigo, one of which was in the vertical growth phase. The purpose of our work was to compare the diverse patterns between superficial spreading melanoma and malignant lentigo. The observations suggest the following major findings: 1) the cells of malignant lentigo differ from normal melanocytes, and in the same specimen they differ from one another; 2) in malignant lentigo, melanosomes at stage II-IV are visible; and 3) in spreading melanoma, the melanosomes do not attain complete maturation. These morphological features explain the different behaviour of these two types of tumors.

Cell Nucleus↗

Structural properties and tissue distribution of the antigen recognized by the monoclonal antibody 653.40S to human melanoma cells.

The hybridoma 653.40S, constructed with splenocytes from an inbred BALB/c mouse immunized with cultured human melanoma cells, secreted an antibody that had been shown to recognize an antigenic determinant restricted to human melanoma cell lines. The monoclonal antibody (MoAb) 653.40S showed immunoprecipitation of two glycopolypeptides synthesized by melanoma cells, one with the apparent molecular weight of 280,000 and the other one with a molecular weight larger than 500.000. These two glycopolypeptides were not bridged by disulfide bonds and were peripheral rather than integral to the plasma cell membrane. Comparison of the reactivity of cells of the melanocyte lineage with the MoAb 653.40S and with the MoAb Q5/13 to human Ia-like antigens showed that the former reacted with proliferating melanocytes and melanoma cells, whereas the latter reacted only with melanoma cells. The MoAb 653.40S did not react with a large variety of surgically removed normal and tumor tissues except for some instances of basal cell and squamous cell carcinomas. These results suggested that double staining of pigmented skin lesions with the MoAb 653.40S and with an MoAb to Ia-like antigens may help to solve controversial diagnosis of melanoma. Furthermore, the MoAb 653.40S may be useful for radioimaging and immunotherapy of melanoma.

Animals↗

Nonfunctional preaortic paraganglioma: report of one case.

A case of nonfunctional benign preaortic paraganglioma is reported. The patient, a woman aged 50, complained of vague mesogastric pain irradiated posteriorly, occasional nausea and vomiting, related to a tender pulsatile mesogastric mass fixed to the posterior wall of the abdomen. Preoperative diagnostic examinations showed a severe anemia, a severe mechanical impairment of renal function as shown at IVP, a doubt of aortic aneurism at echography, not confirmed by selective arteriography. The mass was removed radically. The diagnosis of nature was only microscopic. Since from 15 days after surgery IVP improved significantly. At three months follow-up the patient is well with no sign of recurrence.

Female↗