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Biomedical subjects

J Shoham

Publications and source records attributed to J Shoham.

52 records · Page 3Linked to original sources
PubMed1982

Anti-thyroid drugs and lymphocyte function. I. The in vitro effect on blastogenesis and suppressor cell activity.

The in vitro effect of the anti-thyroid drugs (ATD), propylthiouracil (PTU) and methimazole (MMI) on blastogenesis of peripheral blood mononuclear cells (PBMC) from healthy subjects was studied in 72 hr PHA stimulated cultures. PTU in therapeutic concentrations (10 micrograms/ml) suppressed blastogenesis only when added at the last 18 hr of culture, while at 100 micrograms/ml significant suppression (25%) was recorded also for PTU present throughout culture. PTU had no cytotoxic effect on Raji cells as tested by 51Cr release assay and 3H-thymidine incorporation. Moreover, strong and irreversible suppression (33%) was induced in resting PBMC on 1 hr pre-incubation with PTU. These findings and the fact that suppression was recorded only in cultures exposed to suboptimal concentration of PHA (0.5 micrograms/ml) speak against a direct anti-metabolic effect. MMI in therapeutic concentration (1 microgram/ml) and tri-iodothyronine (T3) in pharmacological concentration (10(-7)M) were much less active. Suppression of blastogenesis by PTU appeared to be mediated through suppressor cell enhancement as indicated by: (a) the augmented blastogenesis following 24 hr pre-incubation, commonly ascribed to suppressor cell depletion, was blunted by pre-incubation with PTU; (b) mixing PTU pre-treated with untreated cells reduced the expected response to PHA and (c) PTU pre-incubated, mitomycin treated cells suppressed blastogenesis of autologous or allogeneic responder cells.

Adult↗
PubMed1982

Feedback inhibition of thymic secretory activity in mice treated by the thymic extract TP-1 (thymostimulin).

The ultrastructural changes occurring in the medullary epithelium of the thymus of young mice, as a result of repeated injections of thymic extract, TP-1 (thymostimulin) was investigated. After daily injection of TP-1 for 3 weeks, no changes in thymus architecture could be observed by light microscopy. However, by electron microscopy, specific changes were noticed in the epithelial cells. The secretory granules became dilated and engorged; diameter of granules in normal control thymus was approximately 200-250 nm, but reached 1000 nm in treated mice. Degenerative changes appeared in some of these granules, including myelin bodies, distorted configuration and fat droplets. Signs of involution of whole cells and presence of cellular debri within macrophages were observed. Acid phosphatase staining disclosed many lysosomes containing ingested granules. No such findings were observed in control untreated mice, or in mice treated by a heart extract similarly prepared to TP-1. All these findings can be taken as ultrastructural evidence for feedback inhibition of thymic secretory activity, in analogy to the changes occurring other feedback inhibited, peptide hormone secreting glands. The data indicate that (i) the thymus respond to feedback inhibitory stimuli, as other endocrine glands do; (ii)TP-1, the thymic extract under study, contains a physiologically significant thymic hormone, which, when introduced in high doses can exert specific feedback inhibition. This can be taken as an additional, new criterion for the definition of thymic hormones.

Animals↗
PubMed1981

Effect of the thymic factor, thymostimulin (TP-1), on the survival rate of tumor-bearing mice.

The effect of treatment with the thymic factor thymostimulin (TP-1) on the survival rate of tumor-bearing mice was studied, using C57BL/6 mice inoculated with 1 x 10(5) Lewis lung carcinoma (3LL) cells. TP-1 given from inoculation day (4 mg/kg, twice weekly) caused a delay in the appearance of primary tumor [14.4 +/- 1.1 (S.E.) days in control; 18.5 +/- 1.4 days in TP-1-treated animals; p less than 0.05], without changing ultimate survival rate. When primary tumor was resected, the incidence of fatal lung metastasis increased as a function of tumor size on resection day. TP-1 given after resection (same dose schedule) significantly increased survival rate as compared to resection only, provided that resected tumor diameter was less than 1.7 mm. The combination of TP-1 and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; single i.p. injection, 50 mg/kg) was effective in either resected or nonresected primary tumor. Without resection, TP-1 with CCNU cured (more than 6 months free of tumor; untreated animals died within 30 to 44 days) 55% of the animals, as compared to 23% cured by CCNU alone (p less than 0.01). With resection animal cure rates were: resection (resected tumor diameter, 0.7 to 1.7 mm) alone, 42% cured; resection with CCNU, 47% cured; resection with TP-1, 70% cured; resection with CCNU and TP-1, 100% cured (last two groups significantly different from resection only). The results indicate a profound effect of TP-1 in prolonging life and increasing cure of tumor-bearing mice. This effect was manifested when tumor load was small and was apparently more pronounced on metastatic than on primary tumor.

Animals↗
PubMed1980

Thymic hormonal effect on human peripheral blood lymphocytes in vitro. III. Conditions for mixed lymphocyte-tumor culture assay.

Conditions for the reproducible measurement of thymic hormonal effect on the functional activity of human peripheral blood lymphocytes (PBL) were determined using a mixed lymphocyte-tumor culture assay. Three thymic hormonal preparations (thymopoietin, thymic humoral factor and TP-1) were tested by this assay and found to have a significant enhancing effect on the blastogenic response. Essential for the demonstration of the hormonal effect was the selection of suboptimal stimulation conditions, with the appropriate cell lines, including the number of stimulating cells and the time in culture. The most reproducible results were achieved when 1 x 10(5) PBL were co-cultured for 4 days with 1 x 10(4) mitomycin-C treated Raji lymphoma cells, after 1 h preincubation with one of the thymic preparations. However, strong enhancing effects of the thymic preparations could also be demonstrated with other tumor cel lines, especially IgR3 melanoma cells.

Adenocarcinoma↗
PubMed1980

Thymic hormonal activity on human peripheral blood lymphocytes in vitro. II. Enhancement of the production of immune interferon by activated cells.

The thymic extract TP-1 significantly enhanced the production of immune interferon (IF) by human peripheral blood mononuclear cells in Con A- or Raji- but not PHA-induced cultures. TP-1 effect was more pronounced under conditions of low IF production. The effect was evident before cell proliferation took place and without necessary concurrent effect of TP-1 on the blastogenic response. TP-1 had no detectable effect on nonactivated cultures. The enhancement of IF production by TP-1 to the degree demonstrated here necessitates consideration of its possible effects in every assay of thymic hormones that involves lectin or allogeneic stimulation of lymphocytes.

Antiviral Agents↗
PubMed1980

Tight junctions in epithelial cells of human fetal hindgut, normal colon, and colon adenocarcinoma.

The structural patterns of tight junctions in normal human colon mucosa, colon adenocarcinomas, and fetal colon were studied and compared by the freeze-fracturing technique. The zonula occludens of the normal colon cells at the upper, more differentiated part of the crypts of Lieberkühn appeared as continuous belts made of about eight parallel strands. At the less differentiated bases of the crypts, the zonula occludens was less regular and contained fewer, mostly beaded strands. In the colons of 10-week fetuses, early stages of tight junction assembly were observed. At the same time, vesicles bearing remnants of tight junction elements were observed within the cytoplasm. This finding suggested that during the early development and organization of the fetal gut, mechanisms of assembly and disassembly of tight junctions are operating concomitantly. In well-differentiated adenocarcinomas, the cells in the luminal region retained their polarity and had seven or eight parallel junctional elements. In infiltrating cells, however, tight junctions appeared as fascia occludens and resembled the junctional organization of 10-week fetuses.

Adenocarcinoma↗
PubMed1980

Thymic hormonal activity on human peripheral blood lymphocytes, in vitro. I. Reciprocal effect on T and B rosette formation.

One hour incubation with the thymic extract TP-1 induced reciprocal effect on B and T rosette formation in lymphocytes of human peripheral blood. The percentage of mouse erythrocyte rosette-forming cells among lymphocytes of chronic lymphatic leukaemia was decreased by TP-1 from 54.5% to 27.1% (P < 0.001). No such effect was observed in healthy adult or cord blood lymphocytes. On the other hand, the percentage of sheep erythrocyte rosette forming cells increased significantly after TP-1 treatment, but only under conditions of active rosette formation and not in the total rosette assay. This increase was highly significant in three conditions with relative deficiency of cell-mediated immunity: newborns (17.1 to 28.3%), cancer patients (24.5 to 31.7%) and patients with lepromatous leprosy (19.8 to 31.8%). Only a small increase was noticed in healthy adults. A similarly prepared spleen extract was not active in either B or T rosette assays.

Adult↗
PubMed1979

A newly designed whole microplate automatic harvester for lymphocyte stimulation assays.

A unique automated sampling manifold designed to recover cells grown in standard 96 well microplates from their culture medium is described. Cells are recovered and washed on fiber glass filter discs. Incorporation of radioisotopes into cells, can then be measured by appropriate counting of the filter discs. Typical applications include termination of mixed lymphocyte cultures, assays of mitogen stimulation of lymphocytes and antigen-specific lymphocyte transformation and assays of interferon activity. The harvester can also be used in other biological systems where collection and washing of precipitates is desired.

Autoanalysis↗
PubMed1979

Antibody-dependent cellular cytotoxicity to human colon-tumour cells. I. Lack of tumour specificity in a population study.

The humoral and cellular components of the antibody-dependent cellular cytotoxicity (ADCC) against allogeneic human colonic tumour cell lines were evaluated. The 2 colon cell lines used in this study (HT-29 and ACC-20) were found by immunofluorescence to have carcinoembryonic antigen (CEA) on their surface, and to become sensitive to the lytic effect of unstimulated lymphocytes after coating with heterologous anti-CEA. This reaction was used to evaluate the ADCC activity of mononuclear cells from the peripheral blood of patients with gastrointestinal cancer (mostly local extensive colo-rectal). Remarkable variability was found in the lytic capability (2-50% specific lysis) of both cancer and non-cancer mononuclear cells, with no significant difference between them. Sera from 127 cancer patients and 91 non-cancer patients were tested, using the reaction with heterologous anti-CEA as positive control and as a reference point. In 46 cases (21%) the sera were reactive in this system, and 43 of them were of Blood Group O. However, there was no difference between the cancer patients and the normal controls. The antigenic determinant involved in this reaction is not the Blood Group A specificity but, most probably, a polypeptide common to CEA and A (as shown in the following publication). In addition, trials for the elimination of the non-tumour-specific reaction, by absorption or inhibition, failed to disclose a tumour-specific one. The value of the ADCC assay in monitoring human tumour immunity, and possible ways of eliminating reactivity to normal antigens in this system, are discussed in the light of these findings.

ABO Blood-Group System↗
PubMed1979

Antibody-dependent cellular cytotoxicity to human colon-tumour cells. II. Analysis of the antigens involved.

The relationship between carcinoembryonic antigen (CEA) and A antigenic determinants on the cell surface of colon-tumour cells was studied by the ADCC assay. Antiserum prepared in 2 rabbits to an undecapeptide analogous to the amino terminal of CEA(1-11) was found by us either to participate in (Rabbit 2) or specifically inhibit (Rabbit 1) ADCC. The binding spectra of these two antisera and of antiserum to the whole CEA molecule were similar. All of them react with A and non-A colon-tumour cells as well as red blood cells of Type A (RBC-A) and their activity was completely absorbed on RBC-A but not on B or O. O-type, ADCC-reactive human sera always react with A-type colon-tumour cells and RBC-A, and some of them with non-A colon-tumour cells also. The degree of inhibition of their reactivity by anti-CEA(1-11) R1 varied between sera, from none to almost a complete inhibition, and is not related to whether the serum is of cancer or non-cancer origin. Non-reactive O-type sera contain anti-A activity demonstrable by haemagglutination and immunofluorescence. However, they cannot participate in ADCC reaction nor inhibit it. The sera, which contain lymphocyte-dependent antibody to A-type colon-tumour cells, lysed RBC-A, without the addition of lymphocytes or complement, in an immunologically specific way. It is concluded that the reactivity seen in our ADCC system is related to a determinant common to A and CEA (and maybe to other normal cross-reacting antigens) which most probably resides in the amino terminal part of these molecules. This determinant elicits the production of lymphocyte-dependent antibodies in about 50% of people with blood group O. Thus, the amino terminal part of CEA is not a tumour-specific part of the CEA molecule. No specific anti-tumour activity was found in patients' serum by this method, and claims for its demonstration by other methods may well be related to the non-specific activity observed here.

ABO Blood-Group System↗
PubMed1972

Differences in the binding of fluorescent concanavalin A to the surface membrane of normal and transformed cells.

The binding of fluorescein-conjugated Concanavalin A to the cell surface has been studied in normal and transformed cells in interphase and mitosis. Binding to the cell surface was in the form of an incomplete ring of fluorescence, and the binding was inhibited by alpha-methyl-D-mannopyranoside. All the cells were fluorescent when treated with 25-250 mug/ml of fluorescent Concanavalin A. With 10 mug, the cells were all fluorescent after 30 min of binding, but after 0.5-5 min with 10 mug or 30 min with 1 or 2.5 mug, transformed interphase cells showed a higher percentage of cells with surface fluorescence than did normal interphase cells. Trypsinized normal and transformed interphase cells showed the same fluorescence. Binding with 2.5 mug at 4 degrees instead of at 24 degrees , gave a higher percentage of fluorescent cells with trypsinized than with untrypsinized transformed cells. Mitotic normal cells were similar to transformed interphase cells, whereas mitotic transformed cells were intermediate between normal and transformed interphase cells. The results indicate that the use of low concentrations of fluorescent Concanavalin A can show differences in surface fluorescence between normal and transformed, interphase and mitotic, and trypsinized and untrypsinized cells. It is suggested that the observed differences in fluorescence can be explained by differences in affinity of the lectin binding sites and/or differences in the clustering of sites.

Animals↗