Pyridazines,LVII: Synthesis and Cyclocondensation Reactions of (2-Aminophenyl)-(4-pyridazinyl)-ketone,a New Diaza Isoster of 2-Aminobenzophenone

A convenient approach to the new 2-aminobenzophenone analogue 4 is reported. Condensation reactions of 4 with ortho esters or amide acetals, respectively, followed by intramolecular cyclisations were found to provide smooth access to (4-pyridazinyl)-substituted quinolines 10, 13a,b , and the quinazoline derivative 15 .     

Systemic angioendotheliomatosis of the lung

Systemic angioendotheliomatosis is a very rare malignant disease characterized by intravascular neoplastic proliferation of reticuloendothelial cells. According to the clinical features three different types of prognostic value can be distinguished: Exclusive skin involvement; Progressive skin lesions disseminating to internal organs; Aggressive and lethal type affecting primarily internal organs. Until now about 60 cases of systemic angioendotheliomatosis have been reported in the literature. Here we describe the first well-documented case with almost isolated lung involvement. The presentation of morphologic and clinical signs and differential-diagnostic considerations are followed by a critical review of the literature.     

Transjugular intrahepatic cavoportal shunt for Budd–Chiari syndrome

Budd–Chiari syndrome (BCS) is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for BCS are limited. We report a case of a 21-year-old woman with protein S and C deficiency with gross ascites. Treatment with transjugular intrahepatic portosystemic shunt (TIPS) was attempted, which revealed occluded hepatic veins, so transcaval TIPS was performed. No serious procedure-related complication occurred. After successful shunt creation, the patient's symptoms subsided and she was discharged and followed up for 6 months.     

Comparison of a modified adherence assay with existing assay methods for identification of enteroaggregative Escherichia coli.

Localized, diffuse, and aggregative adherence patterns of Escherichia coli identified with specific DNA probes were compared in cell culture adherence assays by using the Center for Vaccine Development, Baltimore, method, the University of Texas Medical School, Houston (UTH), method, and a modified UTH method. Increasing postwash incubation time from 2 to 4 h in the modified UTH method allowed identification of enteroaggregative E. coli, which was otherwise not identified by the original UTH method.     

Geographical and temporal conservation of antibody recognition of Plasmodium falciparum variant surface antigens

The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSASM) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSASM-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSASM, is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.     

Localized adherence and attaching-effacing properties of nonenteropathogenic serotypes of Escherichia coli.

Traditional enteropathogenic Escherichia coli serotypes demonstrate a plasmid-mediated localized adherence in cultured HeLa or HEp-2 cells and induce an attaching-effacing intestinal lesion, both of which are considered pathognomonic and causes of diarrhea. This study describes three E. coli strains from infantile diarrhea which share these properties but belong to serotypes (O2:H2, O2:H25 and O15:H2) not considered enteropathogenic.     

Pathogenesis of Providencia alcalifaciens-induced diarrhea.

Providencia alcalifaciens is a member of the family Enterobacteriaceae. There are reports that P. alcalifaciens can cause diarrhea, but the mechanism(s) by which it causes diarrhea is known. We studied P. alcalifaciens isolated from a child and two adults with diarrhea for enteropathogenicity. The three isolates did not exhibit any characteristic adherence to cultured HEp-2 cell monolayers, and they did not produce enterotoxins, cytotoxins, or keratoconjunctivitis in the Sereny test. Two isolates invaded cultured HEp-2 cell monolayers, producing localized bacterial clusters and actin condensation. The pattern of actin condensation was different from that produced by enteropathogenic Escherichia coli but similar to that produced by Shigella flexneri. Invasion and actin condensation were poor for the third isolate. Histology of adult rabbit small intestinal loops inoculated with all three isolates revealed bacterial attachment to, penetration of, and microulcer formation on the surface epithelium and hyperemia, edema, and polymorphonuclear cell infiltration of lamina propria. All the isolates produced diarrhea in rabbits with removable intestinal ties, and some of these rabbits developed hindlimb paralysis. Intestinal histology of the rabbits with removable intestinal ties which developed diarrhea showed changes similar to that in adult rabbits on which ileal loop assays had been performed. Transmission electron microscopy of intestinal tissues also confirmed tissue penetration by the isolates. Nerve tissue histology of two rabbits that developed hindlimb paralysis showed focal mononuclear cell infiltration around peripheral nerve sheaths. It is concluded that some strains of P. alcalifaciens are enteropathogenic and that they cause diarrhea by invading the intestinal mucosal epithelium. However, the relevance to human disease of the hindlimb paralysis observed in this animal model is not clear.