In order to assimilate iron, Acinetobacter baumannii ATCC 19606T produces a siderophore named acinetobactin (Ab) that is composed of equimolar quantities of 2,3-dihydroxybenzoic acid (DHBA), L-threonine and N-hydroxyhistamine. Application of the Fur titration assay system to A. baumannii genomic libraries, followed by further cloning of the regions surrounding the candidate genes, led to the identification of the Ab cluster, which harbours the genetic determinants necessary for the biosynthesis and transport of the siderophore. However, an entA homologue essential for DHBA biosynthesis was not found in this cluster. Functions of potential biosynthetic genes inferred by homology studies suggested that the precursors, DHBA, L-threonine and N-hydroxyhistamine, are linked in steps resembling those of bacterial non-ribosomal peptide synthesis to form Ab. Genes responsible for the two-step biosynthesis of N-hydroxyhistamine from histidine were also identified in this cluster. Their genetic organization suggests that five genes involved in the transport system of ferric Ab into the cell cytosol form an operon. Construction of disruptants of some selected genes followed by phenotypic analysis supported their predicted biological functions. Interestingly, three additional genes probably involved in the intracellular release of iron from ferric Ab and the secretion of nascent Ab are contained in this cluster. Primer extension and RT-PCR analyses suggested that the Ab cluster, which includes 18 genes, is organized in seven transcriptional units originating from respective Fur-regulated promoter-operator regions.

We report a case of VIPoma in a 72-year-old female patient who presented with excessive diarrhea, severe hypokalemia, and acidemia. She had been referred to our hospital three times because of severe diarrhea. No primary tumor site was found by conventional techniques, including contrast-enhanced CT and MRI, angiography, endoscopy, and positron emission tomography (PET), but a tumor was subsequently found in the head of the pancreas by octreotide scanning. Her diarrhea diminished dramatically after octreotide treatment, while her diarrhea has ceased without the therapy of octreotide at the first admission in the course of 2 years of her disease. Immunohistochemial analysis of the excised tumor tissue revealed the expression of both vasoactive intestinal peptide (VIP) and VIP and pituitary adenylate cyclase-activating peptide 1 (VPAC1) receptors. This is the first case report of a VIPoma that immunostains for VIP and VPAC1 receptors and indicates that abundant VIP produced by VIPoma might inhibit its growth and reduce VIP secretion via the VPAC1 receptor in vivo.

Paraneoplastic pemphigus(PNP)is an autoimmune mucocutaneous disease associated with lymphoproliferative neoplasms. We report a case of PNP associated with Castleman' s disease. A 39-year-old man showed white lesions on both edges of the tongue. The lesions were diagnosed as lichen planus, compatible on the basis of clinical features and histopathological examination. The patient was treated with steroid ointment and azulene gargle for 1 year. However, after mild common cold symptoms, he presented with extensive ulceration and erosions throughout the entire oral mucosa, conjunctivitis, and vesicles on the sole of the foot. Serological examination showed elevated immunoglobulin (Ig)G levels, extremely high titers of anti-nuclear antigen, and positive results for anti-dsDNA and anti-ssDNA. Positive results were also obtained for anti-desmoglein 3, anti-envoplakin, and anti-periplakin. Furthermore, direct immunofluorescence testing showed IgG and C3 deposition in the epidermal intercellular spaces. The past history included lymphoproliferative lesions in the mediastinal space. Castleman' s disease was therefore diagnosed. The mucocutaneous lesions were thus considered to be PNP associated with Castleman' s disease. Treatment was initiated with predonisolone, and the oral lesions, conjunctivitis, and skin lesions all improved markedly. As of the time of this writing, mediastinal lymphoproliferative lesions remain, and oral lesions have not completely disappeared. We are carefully observing the oral lesions while contiuning treatment with predonisolone.