Expression of CD4-like structure on murine egg vitelline membrane and its signal transductive roles through p56lck in fertilization.

Expression of CD4-like molecule on vitelline membrane of murine eggs was demonstrated by indirect immunofluorescence (IIF) test and immunoprecipitation corresponding to the expression of major histocompatibility complex (MHC) class II molecule on murine sperm detected by immunoblotting. This molecule showed slightly larger size than that of the authentic CD4 molecule from T-cells on SDS-PAGE. This molecule was suggested to bind to MHC class II structure on sperm during fertilization because anti-CD4 monoclonal antibody (mAb) blocked in vitro fertilization (IVF). In addition, src-related tyrosine protein kinase (p56lck) was demonstrated in the inner vitelline membrane of eggs by means of IIF with anti-p56lck mAb and immune-complex kinase assay. This molecule was suggested to be associated with CD4-like molecule.     

Over-expression of TATA binding protein (TBP) and p53 and autoantibodies to these antigens are features of systemic sclerosis, systemic lupus erythematosus and overlap syndromes

The aim of this study was to determine the expression levels of p53 and TATA binding protein (TBP) and the presence of autoantibodies to these antigens in Asian Indian patients with systemic sclerosis (SSc), overlap syndromes (OS) and systemic lupus erythematosus (SLE). Fifty patients with SSc, 20 with OS, including mixed connective tissue diseases (MCTD), 20 with SLE, 10 disease controls (DC) and 25 controls (C) were studied. The over-expression of p53 and TBP antigen was determined quantitatively by sandwich enzyme-linked immunosorbent assay (ELISA), varies between four- and sevenfold higher in patients with SSc, OS and SLE, in comparison to DC and C. The expressed protein antigens were not present as free antigens but as immune-complexes. Autoantibodies to p53 were detected by ELISA in 78% subjects with SSc, 100% with OS and 80% with SLE. Autoantibodies to TBP were observed in 28% patients with SSc, 25% with OS and 15% with SLE. In comparison to healthy controls, the titre of antibodies to p53 was significantly higher in patients with SSc (P = 0.00001) than the patients with OS (P = 0.00279) and SLE (P = 0.00289), whereas the titre of antibodies to TBP was higher in patients with OS (P = 0.00185) than the SLE (P = 0.00673) and the SSc (P = 0.00986) patients. Autoantibodies to p53 and TBP were detected in all these patients and the levels of these two autoantibodies showed weak negative correlation with each other. We propose that the over-expression of these antigens might be due to hyperactive regulatory regions in the p53 and TBP gene.     

Structure of the functional interleukin-2 receptor: Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line

The structural basis of the high affinity interleukin-2 receptorwhich was previously reconstituted in a cultured murine T cellline, EL4 by expressing either wild-type Tac antigen complementaryDNA (cDNA) or a chimeric cDNA was characterized. The chimericcDNA encodes a membrane portion whose extracellular portionconsists of that of Tac antigen whereas transmembrane and cytoplasmicportions consists of those the human insulin beta chain. TheTac antigen/anti-Tac antibody complex was treated by chemicalcrosslinking reagents, purified by goat anti-mouse immunoglobulin(lg), and was analysed by SDS–PAGE. We here demonstrated the presence in mouse EL4 transfectantsof a novel membrane protein which is closely associated withthe products of transfected cDNAs in the absence of interleukln-2.The protein is 75 kDa in size and is detected in cells whichexpress high affinity interieukln-2 receptor but not in cellswhich only express low affinity interleukin-2 receptor. Thetransmembrane region and the cytoplasmic region of Tac antigenis not necessary for the formation of the complex consistingof Tac antigen and 75 kDa molecule, indicating that a murine75 kDa molecule associates with Tac antigen extra-cellularly.     

Distribution of house dust mite allergen: comparing house dust mite allergen levels in dust samples collected from different sites on living room floors with smooth coverings

BACKGROUND: The distribution of house dust mite allergen (Der p1) in living rooms with smooth floor coverings, as measured in the middle compared with the border of the floor was investigated. It was hypothesized that activity causes displacement of Der p1, from the middle towards the border. METHODS: Dust samples from the middle and border of 50 floors with smooth coverings were collected and analysed on Der p1 content in a standardized way. RESULTS: The Der p1 exposure expressed as per unit area (ng/m2) showed that border samples contained significantly more Der p1 compared with middle samples (median: 2.57 vs 0.27, respectively, P = 0.023). Presence of pets and presence of more than two inhabitants increased the difference. When expressed as per unit weight of dust (ng/g), significant differences were only detected when comparing Der p1 content of samples collected in households with three or more inhabitants [median: 2 (border) vs 53 (middle), respectively; P = 0.035]. CONCLUSIONS: The Der p1 is unequally distributed on living room floors with smooth coverings, most likely because of displacement of dust from the middle towards the border due to activity. Expression as ng/g of dust and ng/m2 could not obviously be interchangeable.     

Overexpression of p53 protein and Ki67 proliferative index in hepatocellular carcinoma:

The overexpression of p53 protein and the Ki67 proliferative index was evaluated in 96 hepatocellular carcinomas (HCC), 67 in cirrhotic livers and 29 in non-cirrhotic ones, and in 13 non-carcinomatous lesions, all surgically resected from Italian patients. Overexpression of p53 was detected only in carcinomatous lesions, and was significantly related to the grade of HCC ( P < 0.001). In fact, p53 was observed in 7/7 (100%) cases of grade IV, 13/43 (30.3%) of grade III, and 10/ 46 (21.7%) of grade II. The relationship between p53 and Ki67 scores was determined in serial sections from corresponding areas of both diffuse and patchy immunoreactivity. In the overall population, p53-positive tumors showed a significantly higher Ki67 score (15.9 ± 5.5% vs 9.2 ± 4.3% [ P < 0.001]). This observation was evident in all grades of HCC.     

Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon

Summary Interferon is currently being evaluated for the treatment of disseminated cancer and viral diseases. Alpha interferons have shown to be effective in the treatment of a number of malignancies. Recombinant leukocyte A interferon (rIFN-A) is an alpha interferon produced by recombinant DNA techniques. A kinetic evaluation of rIFN-A following intravenous and intramuscular administration has not been adequately defined. The present study was designed to evaluate the kinetics of rIFN-A following intravenous and intramuscular administration of 3, 9 or 18×10⁶ units to patients with disseminated cancer.A preliminary report of this study was presented at the meeting of the American Society for Clinical Pharmacology and Therapeutics in San Diego, March 1983 (1).     

The distribution of (-)-propranolol in the isolated rabbit iris

It has been postulated that propranolol lowers the intraocular pressure by adrenergic neurone block. However, in the isolated iris of albino rabbits, there was only a small degree of cocaine-sensitive (i.e., neuronal) accumulation of ³H-(-)-propranolol, and none at all after pretreatment of the animals with reserpine. Moreover, after preloading of the iris with ³H-(-)-propranolol, veratridine failed to release any labelled material. Hence, any adrenergic neurone blocking action of propranolol is highly unlikely.Albino and pigmented irides were first exposed to ³H-(-)-propranolol and then washed out. The results and their compartmental analysis indicated an extensive binding of ³H-(-)-propranolol in or at pigment cells; the binding is characterized by a low dissociation constant. It is very likely that the initial binding and the subsequent slow dissociation from pigment cells explains the long duration of action of beta-adrenoceptor antagonists in human therapy.     

Sodium regulation of agonist and antagonist binding to β-adrenoceptors in intact and Ns-deficient membranes

Summary Agonist binding to various hormone receptors mediating adenylate cyclase inhibition is decreased by sodium ions. We studied the influence of Na⁺ on agonist and antagonist binding to -adrenoceptors in membrane preparations of guinea pig lung, S49 lymphoma wild-type cells (WT) and their N_s-deficient cyc^– variants by measuring binding of the antagonist, [¹²⁵I]iodocyanopindolol ([¹²⁵I]CYP). At 37° C, sodium decreased the receptor affinity for the agonist, isoproterenol, in all three membrane preparations. In lung and WT membranes, Na⁺ steepened the shallow agonist competition curves in a manner similar to and synergistic with guanine nucleotides. When binding was performend at 4° C, sodium regulation but not guanine nucleotide regulation of agonist binding was preserved. At the low temperature, [¹²⁵I]CYP affinity was reduced, and sodium increased [¹²⁵I]CYP binding in both N_s-containing and N_s-deficient membranes by increasing the antagonist affinity without significant change in total receptor number. Compared to Na⁺, Li⁺ and K⁺ were much less potent and efficient in decreasing agonist and increasing antagonist binding. Na⁺ and Mg²⁺ had opposite effects on agonist binding in the N_s-containing lung and WT membranes but not in the N_s-deficient cyc^– membranes. The data indicate that sodium not only regulates binding of inhibitory hormone receptors but also agonist and antagonist binding to the adenylate cyclase stimulatory -adrenoceptor. The finding that sodium regulation of -adrenoceptor binding is also observed in the N_{s 2} cyc^– membranes, furthermore, indicates that the target of sodium is not the -subunit of N_s but possibly a component common to both types of receptor systems regulating adenylate cyclase activity.