Malignancy larynx presenting solely as pharyngo-cutaneous fistula

Malignancy larynx usually presents early, the common symptoms being hoarseness, pain thorat, cough and irritation of throat. An advanced malignancy is likely to be complicated by a pharyngo-cutaneous fistula. However it is an occurrence towards the end stage of the disease. Here we present a case of malignancy larynx primarily presenting as pharyngo-cutaneous fistula without any other symptoms.     

Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome

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Monoclonal antibody production to human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase): high-specificity recognition in whole brain acetone powders and conservation of sequence between CNP1 and CNP2

Monoclonal antibodies against human and bovine 2′:3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) were generated by fusing FOX-NY myeloma cells with spleen cells from RBF/Dn mice previously immunized with the purified brain antigens. The enzyme isolated from bovine brain was quite basic, with an isoelectric point of 9.71 and both the bovine and human enzymes consisted of a closely spaced doublet at approximately 44 and 46 kDa on SDS-PAGE. Six monoclonals were identified as strongly recognizing the enzyme on both ELISA plates and on immunoblots of whole brain protein. Four monoclonals very weakly cross-reacted with guinea pig myelin basic protein. In contrast with two previous reports, some of our monoclonal antibodies did immunostain 2 or 3 protein bands in peripheral nerve, two bands closely corresponding to those immunostained in central nervous system (CNS) myelin, the Wolfgram protein fraction and in acetone powders of whole brain. Each of the 6 monoclonals reacting strongly on immunoblots recognized the enzyme in from 2 to 5 of the species examined (human, bovine, rat, mouse and rabbit). In addition, all 6 monoclonals that immunostained the enzyme in whole brain, myelin and Wolfgram protein immunoblots recognized both CNP1 (44 kDa) and CNP2 (46 kDa). The two closely spaced protein bands observed on SDS-PAGE and previously stained on immunoblots of CNS CNPase using polyvalent rabbit anti-bovine CNPase antisera, and now different monoclonal antibodies, appear to be immunologically related and to contain highly conserved sequences.     

Identification of an early endosomal protein regulated by phosphatidylinositol 3-kinase

Phosphatidylinositol 3-kinases (PI 3-kinases) have been implicated in membrane trafficking in the secretory and endocytic pathways of yeast and mammalian cells, but the molecular mechanisms by which these lipid kinases operate are not known. Here we identify a protein of 170 kDa that is rapidly released from cell membranes in response to wortmannin, a potent inhibitor of mammalian PI 3-kinases. The amino acid sequence of peptides from p170 reveal its identity to early endosomal antigen (EEA) 1, an endosomal antigen with homology to several yeast proteins genetically implicated in membrane trafficking. Immunofluorescence analysis of 3T3-L1 adipocytes with antisera against p170/EEA1 reveal a punctate peripheral pattern that becomes diffuse in response to wortmannin. In vitro, p170/EEA1 binds specifically to liposomes containing PIns(3)P, suggesting that the effect of wortmannin on cells is due to inhibition of PIns(3)P production. Thus, p170/EEA1 may define a family of proteins that mediate the regulatory effects of 3′-phosphoinositides on membrane trafficking in yeast and mammalian cells.     

Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings

The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.