The effect of interleukin-1 on iron metabolism in rats

The effect of interleukin-1 on iron metabolism in rats was evaluated. Plasma iron decreased from 184 +/- 16 micrograms/dl (mean +/- SE) to 24 +/- 12 at 6 hours after interleukin-1 intramuscular administration in non-fasting rats and 109 +/- 6 micrograms/dl to 12 +/- 1 micrograms/dl in fasting rats, which was significantly lower than in control rats. Ferrokinetic studies showed a more rapid disappearance rate and lower iron turnover in interleukin-1-injected rats. The release of iron from the mononuclear phagocyte system to plasma was studied at 3 h after interleukin-1 administration. Although the percent of radioactivity in plasma of the total injected dose was 3.2 +/- 0.6% in interleukin-1, which was significantly lower than in the control rats (5.4 +/- 0.6%) at 9 h after intravenous injection of 59Fe chondroitin ferrous sulfate, there was no difference between the amount of 59Fe released from the mononuclear phagocyte system over the first 9 h in interleukin-1 and control rats. These data appear to imply that iron release is unimpaired but that, for some reason, there is an enhanced rate of clearance of the 59Fe once it has been released from the mononuclear phagocyte system into the plasma.     

Prostatic carcinoma in a young adult: a case report]

We report a case of carcinoma of the prostate in a 30-year-old man. Serum acid phosphatase was normal. A transrectal biopsy of the prostate demonstrated an undifferentiated carcinoma. Total prostatocystectomy was performed and subsequent pathologic report stated that the mass was an undifferentiated carcinoma of the prostate gland. Metastases to the intrapelvic lymph node were present. Although immunohistochemical prostatic acid phosphatase (PAP) activity was not demonstrated, prostatic specific antigen (PSA) staining revealed a positive reaction within the tumor cells, confirming prostatic carcinoma. The patient's course has been uneventful without any recurrence by the intermittent adjuvant chemotherapy 8 months postoperatively. Review of the literature in Japan disclosed 16 cases (including our case) of carcinoma of the prostate in patients under 40 years of age.     

Granulocyte kinetics in neutrophilia induced by recombinant human granulocyte colony-stimulating factor in mice.

To investigate the mechanisms of neutrophilic expansion induced by granulocyte colony-stimulating factor (G-CSF), granulocyte kinetics was studied by means of an autoradiographic method in G-CSF treated mice. Daily intraperitoneal injections of recombinant human G-CSF (rhG-CSF; 2.5 micrograms/day for 5 days) markedly increased the white blood cell count, especially granulocytes in circulating blood. Whole body bone marrow cellularity, quantitated using the radiodilution principle described by Donohue and Finch, increased from 30.0 x 10(7) cells/body (15.2 x 10(9) cells/kg) to 83.5 x 10(7) (41.8 x 10(9)) after the administration of rhG-CSF for 3 days. Generation time of myeloblasts, mitotic pool transit time, and post-mitotic pool transit time, assessed by autoradiography with 3H-thymidine, were significantly shortened in rhG-CSF treated mice compared with the control mice. Daily neutrophil production rates, calculated from these parameters, were 15. 61 x 10(7) cells/day in rhG-CSF mice and 1.93 x 10(7) in the controls. rhG-CSF had no significant effect on the survival time of granulocytes in the circulation, assessed by T1/2 of 3H-thymidine labeled granulocytes. Thus, neutrophilia induced by rhG-CSF is partly due to shortening of the generation time, mitotic pool transit time and post-mitotic pool transit time of myeloid cells.     

Existence of a small population of IL-2Rβhi TCRint cells in SCG and MRL-lpr/lpr mice which produce normal Fas mRNA and Fas molecules from the lpr gene

Mice carrying the lpr gene, SCG and MRL-lpr/lpr mice, were used to characterize the phenotype and lpr gene of abnormally proliferating T cells in these mice. A major population which expanded in these mice were T cells expressing intermediate (int) levels of T cell receptor (TCR) (and CD3) and the phenotype of interleukin-2 receptor (IL-2R)β^lo α^? (possibly abnormal TCR^int cells). The levels of TCR^hi cells of thymic origin (generated through the mainstream of T cell differentiation in the thymus) profoundly decreased after the onset of disease. However, a small population of normal TCR^int cells (i.e. IL-2Rβ^hi α^?) were also found to exist in all tested organs. For example, the majority of abnormal IL-2Rβ^lo TCR^int cells were CD4^?8^? CD2^?, while normal IL-2Rβ^hi TCR^int cells were a mixture of single-positive cells (mainly CD8⁺), CD4^?8^? cells and CD2⁺ cells. Moreover, normal TCR^int cells preferentially produced normal Fas mRNA and Fas molecules from the lpr gene. This phenomenon explains the leaky appearance of normal Fas mRNA and Fas molecules in mice carrying the lpr gene. It is suggested that a small population of IL-2Rβ^hiTCR^int cells are resistant to the lpr genetic abnormality.     

Extrathymic derivation of gut lymphocytes in parabiotic mice

In adult mice, c-kit+ stem cells have recently been found in their liver, intestine and appendix, where extrathymic T cells are generated. A major population of such thymus-independent subsets among intraepithelial lymphocytes is T-cell receptor (TCR)gamma delta+ CD4- CD8alpha alpha+(beta-) cells, but the origins of other lymphocyte subsets are still controversial. In this study, we examined what type of lymphocyte subsets were produced in situ by such stem cells in the small intestine, large intestine and appendix. To investigate this subject, we used parabiotic B6.Ly5.1 and B5.Ly5. 2 mice which shared the same circulation by day 3. The origin of lymphocytes was identified by anti-Ly5.1 and anti-Ly5.2 monoclonal antibodies in conjunction with immunofluorescence tests. Lymphocytes in Peyer's patches and lamina propria lymphocytes (especially B cells and CD4+ T cells) in the small intestine became a half-and-half mixture of Ly5.1+ and Ly5.2+ cells in each individual of parabiotic pairs of mice by day 14. However, the mixture was low in CD8alpha alpha+, CD8alpha beta+ and gamma delta T cells in the small and large intestines and in CD3+ CD8+ B220+ cells in the appendix. These cells might be of the in situ origin. When one individual of a pair was irradiated before parabiosis, the mixture of partner cells was accelerated. However, a low-mixture group always continued to show a lower mixture pattern than did a high-mixture group. The present results suggest that extrathymic T cells in the digestive tract may arise from their own pre-existing precursor cells and remain longer at the corresponding sites.