Differential transforming growth factor-beta secretion in adenocarcinoma and squamous cell carcinoma of the uterine cervix.

Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-beta (TGF-beta) in vitro. All fresh adenocarcinomas secreted significant levels of TGF-beta (mean 397, range between 207 and 782 pg/ml/10(5) cells/48 hr). In contrast, no detectable TGF-beta was present in the supernatants from the four fresh squamous carcinoma cultures (P < 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-beta exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.

Effects of cytokines combined with high-dose gamma irradiation on the expression of major histocompatibility complex molecules and intercellular adhesion molecule-1 in human ovarian cancers.

Tumor cells from 7 freshly isolated human ovarian tumors and 2 continuous human ovarian cancer cell lines were analyzed for their surface expression of MHC class-1, class 11 and ICAM-1 surface antigens before and after exposure to gamma-irradiation and/or the cytokines TNF-alpha plus IFN-gamma. All 7 fresh tumors expressed high levels of MHC class 1 and 1CAM-1 antigens, and levels were markedly up-regulated after exposure to TNF-alpha plus IFN-gamma Similarly, class-11 antigens were either induced (3 out of 7 tumors) or significantly up-regulated by TNF-alpha plus IFN-gamma. Exposure to high doses of gamma-irradiation also increased the expression of MHC class-1 and ICAM-1 antigens, albeit to a modest degree. MHC class 1 and ICAM-1 antigens expression was much lower on continuous human ovarian cell lines than on the fresh tumors. Exposure of these cells to TNF-alpha plus IFN-gamma markedly up-regulated antigen expression to levels comparable to those expressed on the freshly isolated tumors. With the established ovarian cell lines, removal of cytokines caused a rapid down-regulation of antigen expression to basal levels within 6 days, while in the fresh tumors a low level of up-regulation was still present at this time. In contrast, exposure to cytokines followed by high-dose gamma-irradiation resulted in a highly significant and long-lasting expression of each surface antigen which was either up-regulated or induced by the cytokines. These data indicated that the combination of these modalities may be beneficial in generating optimal antigen expression for use of tumor cells in vaccine studies.

The effects of nicotinamide and glimepiride on diabetes prevention in BB rats.

Glimepiride is an oral sulfonylurea drug; nicotinamide is an inhibitor of poly (ADP-ribose) synthetase and a precursor of NAD. Three studies were carried out to determine whether glimepiride and/or nicotinamide could prevent diabetes in BB rats. In Study I, we administered glimepiride treatment 200 mg/kg/day orally from the 35th to 143rd day of age. The incidence of diabetes in the glimepiride group was lower than in the control group (32% vs 55%, p < 0.02). In Study II, the treatment period was from the 35th to 147th day of age, and rats received glimepiride combined with nicotinamide (500 mg/kg/day IP). The treatment group showed a 22% incidence of diabetes compared to 53 in controls (p < 0.03). In Study III, nicotinamide treatment alone (1000 mg/kg/day orally) and combined with glimepiride were compared to untreated controls. The treatment period was from the 35th to 167th day of age. Nicotinamide-treated rats showed a 42% incidence of diabetes compared to 60% in controls (p = NS). In the nicotinamide combined with glimepiride treatment group, a lower incidence (28%) was observed when compared to the controls (60%, p < 0.05). These findings suggest that glimepiride can prevent diabetes in BB rats; however, nicotinamide when used in young animals shows only a trend to lower the incidence of diabetes, and when combined with glimepiride, no significant effect is observed.

Prognostic significance of the heterogenous expression of IgG Fc receptors in B-cell chronic lymphocytic leukemia.

Receptors for the Fc part of IgG (Fc gamma R) are expressed in three forms on peripheral blood lymphocytes. The presence of the releasable form (Fc gamma R(REL.)) as well as of the two nonreleasable forms with lower (Fc gamma R(LOW)) and higher (Fc gamma R(HIGH)) cellular avidity was correlated with survival in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL). High percentage of cells with Fc gamma R(LOW) as well as high "absolute" number of cells carrying the two nonreleasable forms of Fc gamma R were connected to unfavorable prognosis. Combining these three parameters, an Fc gamma R constellation was defined which pointed to a favorable prognosis (in 24 patients) when all three parameters were low, but detected short survivors when all three data were high (in 14 patients). The Fc gamma R constellation was capable of identifying patients with better or worse prognosis within groups that were homogeneous regarding some other known prognostic factors. Fc gamma R constellation as a prognostic factor was shown to be independent of age, sex, and Rai and Binet stages, but it was found to be connected with the total tumor mass score (TTM). The three forms of Fc gamma R on B cells might reflect stages of B-cell activation. Differences in Fc gamma R constellations between patients with B-CLL would thus correspond to differently activated B-cell clones with variable prognosis.

[Connection between the expression of IgG Fc receptors and other immunologic and clinical parameters in chronic B-cell lymphoid leukemia. A multiple regression model of Fc receptor expression]. / Az IgG Fc receptorok expressziójának összefüggése más immunológiai és klinikai paraméterekkel B-sejtes chronicus lymphoid leukémiás betegekben. Az Fc receptor expresszió multiplex regressziós modellezése.

In 63 patients with B-cell chronic lymphocytic leukemia the expression of three recently described forms of the IgG Fc receptor (FcR) was correlated with other cell surface structures detected by rosetting or monoclonal antibodies. In 7.4% of the more than ten thousand statistical investigations paired linear or non-linear correlations were found. Partial correlation technique eliminating the effects of the varying lymphocyte count still resulted in a high number (169) of correlations fulfilling the unusually strict criteria applied. Using a stepwise multiple regression method to create mathematical models describing the expression of the different forms of FcR it was shown that (1) expression is predominantly a function of certain B-cell markers, (2) models change with the progression of the disease, and (3) B cells in B-CLL have an activated phenotype shown by the presence of the releaseable form of FcRII, an early activation marker of B cells.

[Prognostic value of expression of IgG Fc receptors in patients with chronic B-cell lymphoid leukemia]. / Az IgG Fc receptorok expressziójának prognosztikai jelentösége B-sejtes chronicus lymphoid leukémiás betegekben.

In 63 patients with B-cell chronic lymphocytic leukemia the expression of three recently described forms of the IgG Fc receptor (FcR) on peripheral blood lymphocytes was correlated with survival. High percentage of cells with FcRa as well as high "absolute" number of cells carrying FcRa or FcRc was connected to unfavourable prognosis. Combining these three parameters and FcR-constellation was defined which pointed to a favourable prognosis (in 24 patients) when all three parameters were low, but detected short-survivors when all three data were high (in 14 patients). FcR-constellation was capable of identifying patients with better or worse prognosis within groups that were homogenous regarding some other known prognostic factors. FcR-constellation as a prognostic factor was shown to be independent of age, sex, Rai and Binet stages, but was found to be connected with the total tumour mass score (TTM).

[Following and using the scientific literature on a home computer with the REPRINT program system]. / A tudományos irodalom követése és felhasználása házi számítógépen, a REPRINT programrendszerrel.

REPRINT, running on the Commodore 64 home computer, and originally meant to manage a file containing several thousand reprints, has capabilities exceeding this simple task considerably. Bibliographic data can be entered into REPRINT through a word processor or a special input program which automatically corrects usage of capital letters. Code numbers referring to the contents of a reprint can be added to the bibliographic data. Thus, scientific information not contained in the title can also be stored. Searches can be done on code numbers or on any term in the title, authors or source. REPRINT is able to read the text of an article from a disk and automatically construct the list of references to it in the format used by the periodical which the author wants to publish it. While there is no need for any computer knowledge for its application, the speed of REPRINT seems to be satisfactory: search by a code number on 600 reprints takes 48 seconds. Five years of using REPRINT have proven its capabilities to efficiently support usage of a growing personal reprint file in different phases of the process of publication.

Monoclonal antibodies: new diagnostic and therapeutic means in acute leukaemias.

The monoclonal antibodies have had a major role in the recent years' development of the diagnostic methods of acute leukaemia. It was by means of these antibodies that the exact mechanism of the differentiation of the different cell lines could be learned a new therapy- and prognosis-orientated leukaemic classifications could be worked out. With the reasonable application of the monoclonal antibodies in more than 99% of the cases the cell line-age and maturity of the dominant cell type of acute leukaemia may be identified today even in cases of aberrant antigen expression. By means of these antibodies clinical relapse may be forecasted in certain cases and minimal residual disease may be demonstrated as well. The therapeutic systemic application of the monoclonal antibodies has yielded only temporary results but in case of bone marrow transplantation their in vitro application is promising since they are capable of eliminating both the T cells and the residual leukaemic cells of the transplant and, as a result, have a role in the prevention of the development of "graft versus host" disease and leukaemic relapse. Monoclonal antibodies are used in acute leukaemia as a routine diagnostic method while their therapeutic application is still at an early stage of investigation.

The expression of CD 15 antigen on myeloid leukaemia cells--a new prognostic index for complete remission and for survival.

377 untreated acute leukaemia patients were categorized according to FAB and cytochemical criterials and simultaneously phenotyped with the use of 6-21 monoclonal antibodies (MoAb) of VI series (W. Knapp, Vienna). The leukaemia phenotype was compared with the patients outcome after treatment. In adult ANLL patients a positive relationships was proved statistically between the expression of the CD 15 cell differentiation antigen on leukaemic blasts and the CR rate (p less than 0.01, chi 2 test). Also a comparison of the Kaplan-Meier survival curves revealed that the CD 15 positive group of ANLL patients has a better outcome than the CD 15 negative one (p less than 0.01, by Wilcoxon and Log-rank tests). Thus, examination of cell differentiation antigens could be a useful addition to existing risk assignment in acute leukaemia.

CD-15 antigen detected by the VIM-D5 monoclonal antibody for prediction of ability to achieve complete remission in acute nonlymphocytic leukemia.

The prognostic value of cell differentiation antigens detected with the monoclonal antibodies of VI series was studied in 242 cases of acute nonlymphoblastic leukemia (ANLL) treated in 7 cooperating centers. A significantly higher complete remission rate was observed in patients with a higher expression of CD-15 antigen detected by VIM-D5 antibody than in those with lower values. These significant differences were proved when comparing subgroups with VIM-D5 positivity of blastic cells less than 15 and much greater than 15% (p less than 0.01) as well as in the subgroups with values less than 50% (median value) and greater than or equal to 50% (p less than 0.02). Our studies suggest the VIM-D5 positivity of ANLL cells to be favourable prognostic factor predicting the ability to achieve complete remission. Further studies are needed to establish whether the expression of the VIM-D5-defined antigen may serve as a prognostic factor related to survival.

Interaction of human lymphocytes and viruses in vitro.

Interaction between phytohaemagglutinin (PHA) stimulated human lymphocytes and two DNA viruses (adenovirus type 5 and herpes simplex virus type 1) considered to be closely connected with lymphoid tissues has been studied. The fate of the same viruses was investigated also in non-stimulated separated lymphocytes for comparative purposes. To elicit this interaction infectivity titrations, immunofluorescent technique and electron microscopy were used. The production of viral antigens was investigated by complement fixation. It has been shown that in PHA-stimulated lymphocytes from peripheral blood of healthy donors adenovirus type 5 is capable to replicate in its infectious form. Prolongation of the interval between stimulation and infection of cells significantly influenced the dynamics of replication. Non-stimulated lymphocytes produced antigens but no infectious particles.