Detection of non-HLA-DR determinants by alloreactive lymphocyte clones

Using the soft-agar colony assay, we have generated three MT3-associated clones: HJ1, HJ13, and HJ39, from an MLR combination of two unrelated individuals. Another clone, HJ37, appeared to recognize a novel HLA-D determinant. PLT inhibition studies with monoclonal anti-Ia-like antibodies (Mab) were conducted on clones HJ1, HJ39, and HJ37. Five different anti-DR Mab had no significant inhibitory effect on these clones. On the other hand, two Mab SG171 and Q5/13 which appear to react with DR and MT3 (I-A like) molecules strongly inhibited the two MT3-specific PLT clones. While SG171 and Q5/13 had little effect on HJ37, it was observed that a polymorphic Mab 17.15 had a strong inhibitory effect. These results, in concordance with biochemical data on Ia molecules precipitated by these Mab, suggest that these alloreactive clones may recognize non-DR PLT determinants. They also provide further indirect support that MT3 molecules represent the human homologue of murine I-A molecules.     

Specific and non-specific components in the triggering of proliferative and cytotoxic responses of T lymphocytes with different cell density

We hve analyzed the functional behavior of lymphocyte subsets separated on the basis of cell density. Low and high density subpopulations were cultured in FCS, alone or with allogeneic irradiated PBL, and then examined for proliferation and cytotoxic activity against autologous (responder) and allogeneic (stimulator) PHA-induced blasts, K562 and Daudi. In the high density subset proliferation and generation of anti-K562 and anti-Daudi effects were induced by FCS and to higher extent by allospecific stimulation. Exposure to alloantigens induced allospecific cytotoxicity. Autologous PHA blasts were not affected. The results with the low density subset differed. Independently of the type of stimulus imposed, the low density fraction showed little if any proliferation, but its cytotoxic activity was stronger against all targets tested. In some of the experiments, anti-alloblast cytotoxicity was generated in the control cultures. Thus, polyclonal activation induced by FCS triggered in this fraction allospecific cytotoxicity. In this subset, the effect against allogeneic PHA blasts comprised a specific and a non-specific component because autologous PHA blasts were also lysed. Limiting dilution analysis involving allostimulation showed higher frequency of cytotoxic precursors in the low density subset. Split minicultures were tested for lysis of auto- and allogeneic blasts. Alloreactive cultures that did not lyse the autologous target were more frequent in the cultures initiated with the high density cells. There was no conclusive evidence for the existence of autoreactive cultures that did not lyse the allogeneic blasts.     

A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases

Renal disease with distinctive pathologic features developed in two young women who had placental site trophoblastic tumors. The renal abnormalities were manifested by proteinuria in both cases and by hematuria in one case; blood pressure was elevated in one of the patients. Pathologic examination of the kidneys showed distinctive glomerular abnormalities, characterized mainly by the presence of occlusive eosinophilic deposits in many of the glomerular capillary lumina, most of which stained for fibrinogen-related antigens and IgM by immunohistochemical techniques. Ultrastructural examination showed the deposits to consist mainly of granular material that contained packets of fibrillar material with the appearance of fibrin. The uterine tumors were composed of mononucleated and multinucleated cells with abundant cytoplasm that infiltrated between the muscle bundles of the myometrium; in both tumors there was prominent deposition of eosinophilic material that had the tinctorial properties of fibrin and that stained for fibrinogen and IgM in immunoperoxidase studies. The renal abnormalities disappeared after hysterectomy in one case; the other patient, who was receiving chemotherapy and had disseminated intravascular coagulation, died with leukopenia and sepsis. The clinical and pathologic features in these cases suggest that the renal abnormalities were related to the uterine tumors and that the production of immune complexes and/or the activation of intravascular coagulation by the tumors were pathogenetic mechanisms.     

A cell-free model of the encephalomyocarditis virus-induced inhibition of host cell protein synthesis.

When preincubated extracts from Krebs-II cells were supplemented with total poly(A)-containing RNA isolated from encephalomyocarditis virus-infected Krebs-II cells, two phenomena characteristic of EMC virus infection of these cells in vivo were observed: (i) preferential translation of viral rather than cellular, mRNA, and (ii) a general inhibition of protein synthesis, relative to the synthesis in samples where the poly(A)-containing RNA from uninfected cells served as the template. The first effect could not be explained by an irreversible functional inactivation of cellular templates and seemed to result from a direct interference of viral RNA with the translation of cellular mRNA. The second effect was due primarily to the presence of double-stranded RNA.     

Cross-reactive antigens and immunity to diseases caused by encapsulated bacteria.

Antigenic structures may be shared among naturally occurring polymers, including proteins and polysaccharides. Proteins are polymers of amino acids. Cross-reactions between proteins are due to similarities in their overall shape rather than their individual amino acid components. Cross-reactions have been demonstrated among proteins with similar evolutionary development and structure, such as serum albumins or immunoglobulins. Polysaccharides are polymers of monosaccharides. In contrast to proteins, antigenic specificities may be conferred by mono-, di-, and trisaccharides. Since there are about 150 known naturally occurring monosaccharides, it is not unexpected that cross-reactions are demonstrable between polysaccharides from widely divergent sources.     

Study of the HLA system in Burkitt's lymphoma

Seventy-eight patients with Burkitt's lymphoma and seventy controls from Ghana were typed for HLA-A, B, C and DR antigens, to determine whether there is an association between the HLA system and Burkitt's lymphoma. Increased relative risk was observed in Burkitt's lymphoma patients with DR7, HLA-A1 and B12 (BW44).     

Ellis‐van Creveld syndrome in a patient from Tanzania

We report an African infant with Ellis‐van Creveld (EVC) syndrome. EVC syndrome is a chondral and ectodermal dysplasia with autosomal recessive transmission. The baby presented with polydactyly, short limbs and atrioventricular septal defect, but was withdrawn from clinical follow up for the first year of life. Initial hematological abnormalities could not be explained and normalized later. EVC syndrome was confirmed by genetic analysis that showed two pathogenic mutations in the EVC2 gene, c.653_654del, p.Val218Glyfs*12 in exon 5, and c.2710C>T, p.Gln904* in exon 16. The variant c.653_654del; p.Val218Glyfs*12 in exon 5 has not been described before. Our review of medical literature suggested this is the first molecularly confirmed case of EVC syndrome in sub‐Saharan Africa.     

Immunologic mechanisms in hypersensitivity pneumonitis: I. Evidence for cell-mediated immunity and complement fixation in pigeon breeders' disease

Immunologic studies were performed on 5 patients with pigeon breeders' disease. Intradermal injection of pigeon serum produced an immediate wheal-and-flare reaction within 15 minutes and a secondary Arthus-type reaction within 4 to 8 hours. Immunofluorescent studies of the secondary reaction site showed IgG, C3, and C4 in 2 patients. Patients' sera produced multiple precipitin bands with pigeon serum when reacted by double diffusion in gel. IgG antibody isolated from each of the patients' serum formed precipitating immune complexes that fixed large amounts of complement (C4) when added to fresh human serum. Peripheral blood lymphocytes from 4 of the 5 patients produced macrophage migration inhibitory factor (MIF) when challenged with dilute pigeon serum. These studies are the first to show complement fixing antibodies and macrophage MIF production by lymphocytes from patients with hypersensitivity lung disease and suggest that both humoral and cellular immunity may be important in the pathogenesis of these disorders.     

Synthesis and Optical Properties of a New Series of Side‐Chain Poly(amic acid)s With p‐π Conjugation

Summary: After the condensation polymerization of benzoguanamine (BGA) and pyromellitic dianhydride (PMDA) under microwave irradiation, the resulting p‐π conjugate poly(amic acid) was grafted via the azo coupling reaction. The obtained side‐chain polymers were further grafted with TDI‐aliphatic alcohol derivatives and TDI‐aniline derivatives. The third‐order NLO coefficient and response time of PAA and graft polymers were measured by degenerated four wave mixing (DFWM) technique and their fluorescent properties were also investigated. All of the graft polymers have larger NLO coefficients and film‐formability than PAA. Their fluorescent properties were also changed by the different electronic effect of the side‐chains. The influences of the introduction of side‐chains, the side‐chain length and the electronic effect of the substituting groups on the azobenzol side‐chain to both optical properties of the polymers by varying the conjugation degree were investigated.

     

Involvement of E-cadherin and beta-catenin in germ cell tumours and in normal male fetal germ cell development

Intercellular contacts, mediated by E-cadherin, are essential for germ cell migration and maturation. Furthermore, it has been suggested that decrease or loss of E-cadherin correlates with tumour progression and invasive behaviour. beta-catenin is involved in a number of different processes, including cell--cell interaction when bound to cadherins, and determination of cell fate in pluripotent cells when activated via the Wnt signal-transduction pathway. To shed more light on the role of these factors in normal fetal germ cell development and the pathogenesis of germ cell tumours (GCTs), the present study investigated the presence and localization of E-cadherin and beta-catenin by immunohistochemistry. E-cadherin was only weakly expressed in or absent from fetal germ cells of the second and third trimesters, and was not expressed in carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/ITGCNU) and gonadoblastoma, the precursor of an invasive GCT in dysgenetic gonads. In GCTs, it was generally not expressed in seminoma and dysgerminoma, but was found in the vast majority of non-seminoma cells. beta-catenin was found in the cytoplasm of fetal germ cells at all gestational ages and in spermatogenesis in post-pubertal testes. It was also present in CIS/ITGCNU and gonadoblastoma. Whereas seminomas and dysgerminoma were negative, non-seminoma cells were frequently found to express beta-catenin. Expression of both factors therefore reflects the degree of differentiation of these tumours. No differences for either E-cadherin or beta-catenin were observed between samples of tumours resistant or sensitive to chemotherapy, and E-cadherin expression did not correlate with vascular invasion. E-cadherin and beta-catenin therefore play a role in both normal and malignant germ cell development and differentiation that warrants further investigation, but they seem to be of limited value as predictive or prognostic factors in GCTs.