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We have previously isolated the hpttg proto-oncogene, which is expressed in normal tissues containing proliferating cells and in several kinds of tumors. In fact, expression of hPTTG correlates with cell proliferation in a cell cycle-dependent manner. Recently it was reported that PTTG is a vertebrate analog of the yeast securins Pds1 and Cut2, which are involved in sister chromatid separation. Here we show that hPTTG binds to Ku, the regulatory subunit of the DNA-dependent protein kinase (DNA-PK). hPTTG and Ku associate both in vitro and in vivo and the DNA-PK catalytic subunit phosphorylates hPTTG in vitro. Furthermore, DNA double-strand breaks prevent hPTTG-Ku association and disrupt the hPTTG-Ku complexes, indicating that genome damaging events, which result in the induction of pathways that activate DNA repair mechanisms and halt cell cycle progression, might inhibit hPTTG-Ku interaction in vivo. We propose that hPTTG might connect DNA damage-response pathways with sister chromatid separation, delaying the onset of mitosis while DNA repair occurs.

The serum from a patient with Sjögren's syndrome (RM serum) was used to screen a human testis cDNA expression library. A cDNA of 865 base pairs containing the entire coding sequence for a novel protein was isolated. The 14-kDa predicted protein contains an acidic domain (amino acids 6-80) with a high frequency of heptad repeats characteristic of alpha-helices that form dimeric coiled-coil structures and an alkaline carboxyl-terminal domain (amino acids 81-119). It seems to be widely expressed, but its expression level varies depending on tissues. A protein of apparent molecular mass of 14 kDa was immunoprecipitated from cell lysates by the autoimmune serum, and it was recognized by rabbit antibodies raised to a recombinant bacterial fusion protein generated from the cDNA clone. Conventional and confocal immunofluorescence microscopy on HeLa and 3T3 cells transiently transfected with a tagged form of the protein showed numerous punctate structures scattered throughout the nucleus. This novel protein has been termed NA14 for Nuclear Autoantigen of 14 kDa.

Grb2 is an adaptor molecule comprising one Src homology (SH) 2 and two SH3 domains. This protein has a natural isoform named Grb3-3 with a deletion within the SH2 domain. Numerous evidence points to a functional connection between SH2- and SH3-containing proteins and molecules implicated in RNA biogenesis. In this context, we have examined the binding of Grb2 and Grb3-3 to heterogeneous nuclear ribonucleoprotein (hnRNP) C. By the use of an in vivo genetic approach and through in vitro experiments, we furnish evidence that both Grb2 and Grb3-3 interact with hnRNP C proteins. Subcellular fractionation studies clearly show that Grb2 is partially localized in the nucleus. In addition, coimmunoprecipitation experiments demonstrate that Grb2.hnRNP C complexes exist in intact hematopoietic cells. The carboxyl-terminal SH3 domains of Grb2 and Grb3-3 are primarily responsible for the association with hnRNP C. However, although the proline-rich motif of hnRNP C is involved in the interaction with Grb2, it is not in the binding to Grb3-3. Furthermore, poly(U) RNA inhibits the association of Grb2 with hnRNP C, whereas it enhances the interaction between Grb3-3 and hnRNP C. These findings suggest that the Grb2/Grb3-3-hnRNP C interactions might fulfill different biological functions.

Although research on the leptospiroses was initiated in 1886 with Weil's report on the clinical picture of a disease suspected to be a separate entity, it was not until 1910 that the first cases of what appeared to be meningitis of leptospiral origin were reported in the French medical literature.1-4 In 1915, Inada and Ido, in Japan, and Uhlenhuth and Fromme, in Germany, proved that Weil's disease was caused by a spirochete, which was later classified as Leptospira by Noguchi.1,2,5 Conclusive experimental evidence in support of the role of the Leptospira icterohaemorrhagiae in the production of meningeal manifestations, which frequently accompany the leptospiroses in the icteric and anicteric forms, appeared in 1916.6,7 Physical signs and symptoms of meningitis have been reported in 10% to 33% of large series of cases in the European medical literature.8,9 However, even in the absence of clinical signs pointing to meningeal involvement, significant alterations of

The proper evaluation of the effectiveness of therapy in schistosomiasis is rendered difficult by the protean clinical manifestations of the disease, the invariable tendency toward chronicity, and the lack of accurate information pertaining to the natural course of the disease. From the outset a pessimistic attitude is assumed in view of the failure to discover drugs of definite efficacy. A review of the voluminous medical literature dealing with this subject fails to reveal a single medication that can effectively control the ravages of the disease. Thus, after maturation of the parasite and oviposition, progressive, and at times irreversible, tissue changes occur, emphasizing the early recognition of the disease as the most important governing factor in the determination of the degree of possible therapeutic success in the future. However, it appears as if the direct contact of the adult parasites and their eggs with the host's tissues leads to pathological alterations

Infiltrative eosinophilia is a condition characterized by a marked relative and absolute increase in the circulating mature eosinophiles and an inflammatory reaction with a profuse infiltration of this cell. It has been reported in the literature under these various names: Loeffler's syndrome,* tropical eosinophilia,† acute febrile eosinophilic asthma,21 pulmonary eosinophilia,21 pulmonary eosinophiliosis,‡ eosinophilic infiltration of the lungs,§ eosinophilic asthma,40 Weingarten's syndrome,17 pseudotuberculosis of the lungs,∥ benign eosinophilic leukemia,¶ familial eosinophilia,# pulmonary acariasis,* lecithinophil eosinophilia,†grande eosinophilié sanguinaire,68 eosinophile lung,‡ eosinophilia with splenomegaly,§ eosinophilic pneumopaty,∥ and pulmonary infiltration with eosinophilia (P. I. E.).61Since all the reported cases present many traits in common, differing only in the degree of severity of the symptoms and their duration, it seems convenient to group them under the term infiltrative eosinophilia. Although Loeffler's syndrome implies a short clinical course with transitory roentgenological pulmonary alterations, some of Loeffler's cases showed a tendency to chronicity, and