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Biomedical subjects

G Fossati

Publications and source records attributed to G Fossati.

At least 109 records · Page 6Linked to original sources
PubMed1984

Low plasma cell 3(H) thymidine incorporation in monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma and remission phase myeloma: a reliable indicator of patients not requiring therapy.

The kinetics of bone marrow plasma cells were evaluated by means of in vitro 3(H)thymidine incorporation in 143 patients with monoclonal gammopathies. Fifty-three patients had symptomatic multiple myeloma (MM) at diagnosis, nine were in stable remission, six in unstable remission, and 16 in the relapse phase. Thirty-seven patients were classified has having monoclonal gammopathy of undetermined significance (MGUS) and 22 as smouldering myeloma (SM). A thymidine labelling index (LI%) of greater than 3 at initial diagnosis predicted a very short survival. High LI% values (median 2.8 +/- 1.1) were also seen at relapse. However, the major new finding was that the LI% could be used to discriminate precisely between the SM-MGUS group and the MM patients including stage I disease (P less than 0.0001). Only one patient developed MM during follow up, that being 8 months after the initial diagnosis of SM. During the unmaintained stable remission (plateau) phase a low proliferative activity was also observed (LI% = 0.6 +/- 0.2). Thus the LI% was extremely useful in identification of both poor risk groups with a LI% greater than 3 and stable patients requiring no immediate therapy with a LI% less than 1. The ability to discriminate between MGUS and SM and stage I MM should prove particularly useful clinically.

Bone Marrow↗
PubMed1983

Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells.

A monoclonal antibody (MBr1) raised against a membrane preparation (CM) of a human breast cancer line (MCF-7) and characterized as mammary gland epithelium associated (S. Mènard, E. Tagliabue, S. Canevari, G. Fossati, and M. I. Colnaghi. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res., 43:1295-1300, 1983), was used to biochemically define and partially purify its target antigen. The antigenic activity recognized by MBr1 was unaffected by treatment of MCF-7 cells with trypsin, protease K, or Vibrio cholerae neuraminidase and by heating at 100 degrees but was abolished by treatment with methanol. Since this behavior suggested a glycolipid nature of the MBr1-defined antigen, total lipids were obtained by chloroform:methanol or tetrahydrofuran:phosphate buffer extractions from crude membrane preparations of MCF-7 cells and of breast cancer surgical specimens. Total absorption of MBr1 activity was found by breast cancer lipid extracts, whereas no absorbing capability was detected with a series of highly purified acid and neutral glycolipids or with normal and neuraminidase-treated red blood cells of human, ox, and sheep species. The same pattern of inhibition of MBr1-binding activity was obtained with total lipid extract and both phases after diethyl ether partition. However, when the three extracts were chromatographed on diethylaminoethyl-Sepharose, the antigenic activity was recovered only in the neutral glycolipid fractions. Periodate oxidation of MCF-7 crude membrane preparation abolished MBr1-binding activity, suggesting that the carbohydrate portion of the molecule may constitute the antigenic determinant.

Antibodies, Monoclonal↗
PubMed1983

Generation of monoclonal antibodies reacting with normal and cancer cells of human breast.

From the fusion of the murine myeloma P3- X63-Ag8-U1 with spleen cells from a mouse immunized with the human breast cancer cell line MCF-7, 88 hybridomas producing antibodies reacting with the immunizing cells were obtained. After a first screening on human leukocytes, red blood cells, and platelets and on human and fetal calf serum, three monoclonal antibodies, MBr1, MBr2, and MBr3, with specificity for the immunizing cells were isolated and further characterized. The three monoclonals were tested by isotopic antiglobulin assay and immunofluorescence on a panel of normal cells or cell membrane preparations, including milk epithelial and foam cells; on plasma and milk proteins; on cells or cell membrane preparations from fresh surgical specimens of breast, kidney, and ovarian carcinomas; and on various tumor cell lines. MBr1 and MBr2 had a superimposable reactivity and showed specificity for a structure which seems to characterize both normal and neoplastic mammary gland epithelial cells.

Animals↗
PubMed1983

Kinetics of circulating B lymphocytes in human myeloma.

The tritiated thymidine labeling index (LI%) of peripheral B lymphocytes was studied in eight myeloma patients using simultaneous immunofluorescence and autoradiography. The LI% values were low (0.3%-5.1%), but significantly increased as compared to normal controls. In addition, there was excellent correlation between the LI% values and myeloma disease activity: lowest LI% values were observed in remission patients and the highest at the time of relapse. Simultaneous LI% evaluation of bone marrow myeloma cells in five patients gave concordant results, indicating the same kinetic behavior in both these compartments, particularly in the relapse phase. These data indicate both that circulating B lymphocytes include the neoplastic clone and that these B lymphocytes and bone marrow myeloma cells have similar kinetics.

B-Lymphocytes↗
PubMed1982

Delayed cutaneous hypersensitivity reaction to carcinoembryonic antigen in cancer patients.

The delayed cutaneous hypersensitivity reaction to carcinoembryonic antigen (CEA) was tested in 84 patients with different diseases including large bowel adenocarcinoma and breast carcinoma, with or without metastasis, liver cirrhosis and inflammatory or degenerative diseases. Positive skin test to CEA was observed in a small proportion (11%) of the patients tested. No difference in positive skin test reactions was observed in the 6 different groups of patients. Similar delayed cutaneous hypersensitivity reactions were found to various amount of CEA ranging from 0.5 to 25 micrograms. No correlation was seen between the results of skin test and blood CEA levels.

Adenocarcinoma↗
PubMed1982

Lysis of autologous human melanoma cells by in vitro allosensitized peripheral blood lymphocytes.

Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5-20 different donors. After 6-7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity.

Cytotoxicity, Immunologic↗
PubMed1981

[Glucose-1-phosphate associated with total parenteral feeding. Study of various metabolic effects and leukocyte functions].

The effects of glucose-1-phosphate (250-500 ml given by i.v. infusion over a period of 3-4 h for 3-5 days) on the quantity of exogenous insulin administered and on leukocyte adhesion and chemotaxis were studied in 4 groups of post-operative patients submitted to TPN (total parenteral nutrition), TPN + glucose-1-phosphate, standard infusion therapy and standard infusion therapy + glucose-1-phosphate respectively. With the use of glucose-1-phosphate the quantity of insulin administered could be significantly reduced (P less than 0.01) thereby an increased utilization of glucose, induced by the phosphorylated saccharide, was confirmed. Moreover, glucose-1-phosphate, through its action on intracellular sugar metabolism, increased leukocyte adhesion during TPN. This phenomenon might have a favourable effect on some of the functions carried out by these cells on the inflammatory response.

Blood Glucose↗
PubMed1979

Antibody binding to membrane of cultured melanoma cells by sera of melanoma patients.

One hundred and nine sera from 75 patients with malignant melanoma and 69 sera from as many healthy donors were assayed by isotopic antiglobulin technique (IAT) on 2 melanoma cell lines. The same picture of reactivity was observed with patients' and healthy donors' sera, and in both groups 35% of the cases were high responders on 1 line and 21% on the other one. The specificity of the reactions was analyzed by absorption experiments using 12 melanoma sera selected for their high binding activity. Pools of human erythrocytes or leukocytes did not remove, except in 1 case respectively, the activity of the sera, suggesting that it was not directed against alloantigens. Quantitative absorption experiments were done with the 2 melanoma lines and with 1 colon carcinoma line. The results, evaluated on the basis of absorption capacity per cell, indicate that the 2 melanoma lines had a similar amount of shared antigens, whereas the colon line was also effective in absorbing out the serum activity, but less frequently and less efficiently. Further experiments performed to analyze the influence of culturing the target cells in presence of fetal bovine serum (FBS), showed that the activity of sera was removed, at various degrees for different sera, by absorption with free FBS, with FBS coupled to Sepharose 4B, and with normal leukocytes cultured overnight with 10% FBS. The same positive melanoma sera became negative when assayed on the same melanoma line cultured in gamma-globulin-depleted human AB serum. In conclusion, in our experimental conditions, the activity of melanoma sera seems mostly directed against components of FBS absorbed on cell membrane during culturing.

Adenocarcinoma↗
PubMed1979

Transfer of a free lateral thoracic flap in a child.

We believe the axillary (lateral thoracic) flap should be one of the free flaps of choice in children, because it has vessels of 1.5 mm or more in diameter--thus making it possible for the donor and recipient vessels to be approximately the same diameters. This makes the suturing easier and helps to ensure a good result. The patency rate increases as the diameter of the vessels to be anastomosed increases. We present a successful case in which this flap was used in an 8-year-old boy.

Axilla↗
PubMed1976

Cellular immune reaction to human malignant melanoma and breast carcinoma cells.

An in vitro microassay was used to study cytotoxic reactivity of lymphocytes of 19 patients with malignant melanoma, 8 patients with breast carcinoma, and 18 normal subjects on cell cultures of malignant melanoma and breast carcinoma. In each of the twelve experiments, peripheral blood lymphocytes from individuals with and without cancer were tested simultaneously on two or three different target cells. Cytotoxic reactivity, evaluated by a comparison of the number of target cells remaining after incubation with lymphocytes with those incubated with medium only, was found in 20 cancer patients (74%) and 13 individuals without cancer (72%). The strength of lymphocyte reactivity of the cancer and of the non-cancer group did not differ significantly. Of the 27 cancer patients, 8 were positive only on the homologous target cells, 7 only on the opposite cells, and 5 on both types; 7 were negative. Short-term melanoma cell cultures were more lysable than were established cell lines; however, no direct correlation between the growth rate during the test period and susceptibility to lysis was seen. The blood group of the lymphocyte donors had no influence on cytotoxic reactivity.

ABO Blood-Group System↗
PubMed1975

Humoral cytotoxicity in melanoma patients and its correlation with the extent and course of the disease.

Complement-dependent cytotoxicity against melanoma cells was demonstrated with a microassay in sera from melanoma patients. The response was tumor-specific and histologic type-specific since 16 out of 52 (30%) melanoma patient sera taken before surgery reacted against melanoma cells, whereas 3 out of 43 (7%) control sera, collected from patients with unrelated tumors and from cancer-free individuals, were positive. The serum activity correlated with the clinical stage of the disease since it was detected in 15 out of 40 patients with stage I and II tumors and in 1 of the 12 patients in stage III. Twelve melanoma patients, clinically tumor-free for to 4 years after surgery, showed no humoral cytotoxicity. A follow-up study of 13 melanoma patients revealed that the cytotoxicity appeared 7-10 days after radical removal of the tumor and that it disappeared if there was no recurrence. The histologic type-specificity was further tested by assaying sera from 16 melanoma and 10 breast-cancer patients simultaneously on both melanoma and breast-cancer cells; a positive reaction was observed in 6 cases of melanoma and in 5 of breast cancer on homologous cells only, in 1 case on the opposite type of cells, and in 3 cases on both types of tumor cells.

Adolescent↗
PubMed1975

Evaluation of the cell-mediated immune response to murine sarcoma virus by (125I)iododeoxyuridine assay and comparison with chromium 51 and microcytotoxicity assays.

The cell-mediated immune response of C57BL/6 mice to murine sarcoma virus (MSV) was examined by the [125I]-iododeoxyuridine release cytotoxicity assay using MSV-induced sarcoma tissue culture cell lines as target cells. Cellular cytotoxicity was detected as early as 3 days after virus inoculation. Most mice assayed between 12 and 17 days after MSV inoculation gave positive results with maximum levels of activity present on Days 13 and 14. Reactivity was frequently detected for up to 100 days after MSV inoculation, although at low levels (5 to 10%). Additional experiments comparing the kinetics of the cellular response as measured by different in vitro cytotoxicity assays were performed. The results showed a good direct correlation between the [125I]iododeoxyuridine release assay and a 51Cr release assay. A similar pattern of reactivity was also observed when the cellular response was measured by a visual microcytotoxicity assay, although reactivity dropped off more rapidly and became undetectable in most instances by 20 days after injection of MSV. Studies on effector cell type revealed that cytotoxicity in all three assays was T-cell dependent, being eliminated by treatment with anti-theta plus complement. Macrophages did not appear to play a role, since treatment with carbonyl iron and magnet had no effect.

Animals↗