Biomedicine / [publiee pour l'A.A.I.C.I.G.]最新文献

We have isolated from normal and regenerating rat liver a protein fraction 80,000 molecular weight which inhibits the multiplication of LF hepatoma cells in culture and decreased the 3H-thymidine incorporation into liver DNA in two thirds hepatectomized rats. In the present work, we have shown that this factor possess some immunosuppressive properties. It inhibits the blastogenic response to mitogens for both splenic and thymic cells, in vitro as well as in vivo; the synthesis of SRBC-antibodies is also impaired. Thus this factor which acts upon liver homeostasis seems to play a role as modulator of the immune response.

Conventional blind randomized trials involve obtaining consent for treatment prior to randomization into control or treatment groups. When the trial is of necessity an open one, obtaining consent to treatment and then assigning the patient to a control group may lead to undesirable consequences. When consent is required prior to randomization, inability to obtain it diminishes both control and treatment numbers. Obtaining consent after randomization enhances the power of the study since refusal affects only treatment numbers thus making more efficient use of patient material. We propose to analyze the outcome of patients allocated to treatment, but refusing experimental therapy, as a separate group. Comparison of this group with the control population will permit validation of the efficacy of the randomization process and allow testing of the hypothesis that refusers of consent react the same as the control population. If no difference occurs we propose that the refuser and control groups be combined and compared with those patients who receive experimental treatment.

A microspectrofluorometer has been used for kinetic studies of the decrease of benzo(a)pyrene and benzo(k)fluoranthene fluorescence. This decrease is observed for single living cells: L cells and human peripheral blood monocytes, after their incubation which culture medium containing these compounds and washing the petri dish with fresh medium. The entire fluorescence spectra is recorded at given time intervals in order to watch at some eventual spectral modification. The fluorescence decrease is monoexponential and its parameters are computed with a program based on the least squares fit method. Such determination shows no difference between the calculated rate constants of metabolisation for B(a)P and B(k)F and, as long as we consider L cells with a similar morphological shape, only statistical fluctuations of the rate constants of metabolism are observed. As compared, monocytes show faster kinetics of the decrease of the B(a)P intracellular fluorescence due to B(a)P metabolism, and also a more reached dispersion of the values of the rate constant than the one observed for L cells indicating some heterogeneity in the monocyte population of each donor.

The influence of the thymus on its bone marrow precursors was investigated: T cell differentiation was studied in irradiated mice reconstituted with bone marrow from thymectomized donors. Up to twelve months after TX the influx of precursors and differentiation into T cells were not changed in the recipients. CFU-s determination of bone marrow and spleen from thymectomized animals did not show a change in numbers but during ageing a shift of the E/G ratio was observed in thymectomized as well as control donors.

A study was made of the number of T lymphocytes and thier functional activity in 16 patients with pemphigus vulgaris, 5 with involvement of the mucosa, 3 with involvement of the skin and 8 with involvement of both; 2 patients had been suffering from the disease for 7 years, one for one year and the remainder for one to 6 months prior to this investigation. Patients were tested prior to institution of treatment, while receiving initially high doses of steroids and subsequently on maintenance doses. T lymphocyte number was determined by the E rosette technique and their functional activity by a local xenogeneic graft-versus-host reaction (GVHR) developed in our laboratories. Prior to therapy 50% of the patients showed impairment in T cell function, with no improvement during intensive steroid therapy; subsequently, when the disease was under control, there was a clear tendency for function to return to normal. There was no correlation between duration of the disease and immune competence but there appeared to be a partial correlation between the latter and the degree of involvement. Our study indicates that long-term steroid therapy not only benefits the clinical condition of the patient but is associated with an improvement in the immunological status.

Red blood cells from normal subjects and subjects with heterocellular hereditary persistence of fatal haemoglobin and beta-thalassaemia were fractionated according to density by centrifugation on a discontinuous gradient of Stractan II. F-cells were studied by immunofluorescence and their proportion was evaluated in each separated population. This approach has permitted to show that F-cells were preferentially distributed among high density erythrocytes. This phenomenon reflects a peculiar characteristic of F-cells.

The effect of hydrocortisone on blood CFU-C has been studied in six normal subjects through a double layer agar culture system. Increased numbers of CFU-C appeared in the peripheral blood reaching a maximum 366% to 631% increase 5-8 hours after the i.v. administration of the hormone. Contemporary lymphopenia caused a 4 to 10 fold enrichment in the proportion of CFU-C to lymphocytes. Hydrocortisone added in vitro somewhat inhibited the colony growth. The results suggest that the increase of blood CFU-C is due to mobilization from the bone marrow. Hydrocortisone, when compared to other agents, appears to offer some advantages in increasing the blood CFU-C for clinical purposes.

Histamine metabolism of a transplantable syngeneic spontaneous murine mammary adenocarcinoma with a high degree of undifferentiation was studied. The endogenous histamine content is significantly higher than in normal intestine and lung. This is not due to an increase of the histamine biosynthetic capacity, which is lower than in the lung. The administration of histamine, 0.1 mg per kg body, for 7 days, decreased significantly the biosynthesis of histamine in the tumor, but not its endogenous histamine content; in the intestine and in the lung no significant modification of histamine biosynthesis was observed. It has also be shown that the proportion of radioactivity in the purified nuclear fraction of the tumor is significantly higher than in the intestine, after incubating either tissue with 3H-histamine. Since the mast-cell content of the tumor has been found to be low, our results should be considered as a specific alteration of the function of histamine in these tumor cells.

Protein kinase activity and histone kinase isozyme distribution have been determined in soluble extracts of adenocarcinoma of the human colon and compared to adjacent normal mucosa. The results show an enhancement in endogenous protein kinase activity and the presence of an additional isozyme (PKI) for histone kinase activity in the tumour tissue. PKI activity exhibited a peculiar behaviour in comparison to the isozyme. PKII present in both carcinoma and normal mucosa after dialysis of the soluble extracts. It is suggested that alteration of intracellular regulatory processes involved in PKI activity might be related to the maintenance of the proliferate state in human colon carcinoma.