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We compute the fundamental group of the "moduli space" of classical solutions of the two dimensional Euclidean $S^n$-model., 15 pages

In order to elucidate possible roles of thymic nurse cells (TNC) we isolated them as lympho-epithelial cell complexes from spontaneous thymomas of BUF/Mna rats and characterized them using immuno- and enzyme-histochemical techniques. A remarkable increase in the number of TNC was seen at 8 months of age, immediately before or in accordance with the onset of thymomas. No structural abnormality in the TNC was detected by light-microscopy compared with those from normal control thymi. Phenotypically, the TNC per se were positive for major histocompatibility complex (MHC) class I, class II, cytokeratin and thymulin, but lacked macrophage markers, indicating their epithelial origin. They also expressed some of the markers for non-epithelial components, such as Thy-1, S100 and peanut agglutinin (PNA). The majority of intra-TNC cells were MHC class 1+, Thy-1+, CD5+, CD4+ CD8+ (double positive) and PNA+, but with some heterogeneity in their phenotype. The intra-TNC cells from thymomas revealed higher proliferation indices than those from control thymi, as assessed by 5-bromo-2'-deoxyuridine (BrdU)-uptake. It was also demonstrated for the first time that, not only in thymoma rats but also in normal control rats, about 15-30% of TNC enclosed macrophage populations within them. These results may suggest that the TNC in BUF/Mna thymomas represent typical TNC populations, but they are hyperactive particularly in their number and nursing capacity, resulting in the unusual increment of thymocytes in the thymomas. This animal model lends itself greatly to studies on the regulatory roles of TNC in T-cell development.

Low-affinity (dissociation constant: Kd = 7 nM) and high-affinity (Kd = 27 pM) interleukin-2 receptors (IL-2R) were detected on rabbit T-cell lines by IL-2 binding studies. Chemical cross-linking studies using 125I-labelled IL-2 showed that rabbit low-affinity IL-2R was singly expressed alpha-chain (MW 55,000) and that high-affinity IL-2R was composed of at least alpha- and beta- (MW 75,000) chains, similar to the human and murine counterparts. The existence of an additional chain (MW 25,000) was suggested in the rabbit IL-2R. Rabbit T-cell transfectant lines were established by human IL-2R alpha-chain (IL-2R alpha) cDNA transfection. These transfectant lines possessed not only extremely large numbers of human IL-2R alpha (over 10 times more than endogenous rabbit alpha-chain) but also twice as many high-affinity sites as their parental lines. The number of high-affinity sites on the transfectants significantly decreased when human alpha-chains were blocked, indicating that these transfectants expressed high-affinity receptor consisting of the exogenous human alpha-chain and rabbit beta-chain. This was confirmed by cross-linking experiments. The observation that expression of extremely large numbers of exogenous alpha-chains lead to an increase of the total number of high-affinity sites in the apparent absence of an increase of beta-chain expression raises the possibility that not only the beta-chain but also the alpha-chain may play an important role in regulating the number of high-affinity receptors.

Various doses (1 microgram to 10 mg) of oestriol (E3) were intraperitoneally injected into mice immediately after subcutaneous inoculation of an oestrogen receptor-negative lymphoma cell line (KE-5) established from a spontaneously developed AKR thymic lymphoma. The growth of KE-5 cells was markedly promoted by E3 at the early stage of tumour growth. At this stage, 1 microgram E3 enhanced tumour growth significantly and the maximum effect was obtained with 1 mg E3. Normal female mice showed a higher incidence and shorter latency than males. However, once tumours became palpable, the tumour growth rate appeared to be unaffected. Histological observations using Alcian blue and colloidal iron revealed a marked increase of hyaluronic acid in the subcutaneous connective tissue of the tumour-injection site within 3-5 days after intraperitoneal administration of 1 mg E3. Biochemical analyses showed a rapid and marked increase in skin hyaluronic acid content to over 3 times the control levels (0.25 +/- 0.10 mg g-1 skin) within 3 days of E3 administration. Subcutaneous inoculation of KE-5 cells together with hyaluronic acid (0.2 mg) resulted in markedly enhanced tumour growth, particularly at the early stage. These results suggest that an increase in stromal hyaluronic acid content is the most likely mechanism responsible for the promoting effect of E3 on KE-5 cells. Images Figure 3 Figure 4

In an attempt to study the site and mechanism of action of estrogen in producing positive feedback control, porcine anterior pituitary slices were incubated in vitro in the presence of estradiol benzoate (EB). EB elevated pituitary cyclic AMP concentration within 5 min and augmented pituitary release of luteinizing hormone (LH). The magnitude of increase of cyclic AMP and LH release was related to the doses of EB used. Also, luteinizing hormone releasing hormone (LH-RH) elevated pituitary cyclic AMP concentration and stimulated pituitary release of LH. The magnitude of increase of cyclic AMP and LH release was inversely related to the doses of LH-RH used. EB and LH-RH were additive in increasing cyclic AMP. Progesterone and clomiphene citrate interfered with an increase of pituitary cyclic AMP produced by EB, but did not significantly affect the basal level of pituitary cyclic AMP. Testosterone propionate, human chorionic gonadotropin and hexestrol were without effect on either basal or stimulated level of pituitary cyclic AMP. Since cyclic AMP and dibutyryl cyclic AMP (DBC) stimulated LH release, it is suggested that EB directly stimulates the release of LH by augmenting cyclic AMP synthesis in the anterior pituitary.

Delayed-type hypersensitivity (DTH), primary direct and indirect PFC, memory antibody response and suppressor cell induction against sheep red blood cells (SRBC) have been examined in oestriol (E3) pretreated mice. The results showed that DTH and primary direct and indirect PFC responses were suppressed by E3 treatment. These suppressive effects could, however, be overcome when oestrogenized mice were given supra-optimal doses of SRBC for each response. On the other hand, the memory antibody response was markedly enhanced when E3 was given prior to the primary antigen stimulation. Induction of the suppressor cells for the antibody response seemed not to be affected by E3 treatment, but the characterization of the suppressor cells revealed that those obtained from E3 treated mice were surface immunoglobulin positive (sIg+) cells whereas those from control mice were not. These results were discussed in terms of the altered antigen distribution due to the activated phagocytic activity of the reticuloendothelial system (RES) after E3 treatment.

The entry of environmental antigens into the lumen of the bursa of Fabricius was prevented by ligating the bursal duct prior to hatching (BDL: bursal duct ligation). The development of 'natural' serum agglutinins for bacteria and heteroerythrocytes was markedly suppressed by BDL. The antigen-specific recovery was observed by simultaneous administration of sterile antigens into the bursal lumen at the time of BDL. These results strongly suggest that the bursa of Fabricius is a major channel through which environmental antigens stimulate the immune system and induce the formation of 'natural' serum agglutinins.