Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations

Mycotic aneurysm is a rare but life-threatening disease that warrants an integrated therapeutic approach involving surgical intervention and prolonged antibiotic use. However, the causative organisms are often unidentified because antibiotics started empirically render blood and tissue cultures negative. Molecular diagnosis has been reported to be useful in such culture-negative cases. We report a case of a culture-negative mycotic aortic aneurysm due to Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed type b, and PCR and sequencing of the ftsI gene revealed alterations in penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus sequence typing demonstrated that the isolate belonged to sequence type 54.     

Detection of hepatitis B virus X gene protein and antibody in type B chronic liver disease

The genome of the hepatitis B virus contains a sequence (X gene) whose role is unclear. The almost complete region of the hepatitis B virus X gene was expressed in Escherichia coli, with the resulting protein being approximately 17 kilodaltons in molecular weight. Sera from 139 subjects were analyzed by Western blot analysis. Of the hepatitis B surface antigen-positive patients, anti-X was not found in 4 patients with acute hepatitis and in 12 healthy carriers, but was present in 41% (21/51) of the patients with chronic hepatitis, 63% (15/24) of those with liver cirrhosis, and 46% (12/26) of those with hepatocellular carcinoma. The expression of the X product in the liver tissues (43 hepatitis B surface antigen-positive patients) was investigated using an indirect immunohistochemical method. The X protein was observed in 64% (21/33) of the patients with chronic hepatitis and 50% (5/10) of those with liver cirrhosis, and was found when the serum was negative for anti-X. Hepatitis B core antigen was frequently expressed together with the X protein in the liver. The conclusions reached were that the frequency of anti-X increases with the length of chronic hepatitis B virus infection, that anti-X may suppress the expression of the X protein in the liver, and that the X protein may be related to hepatitis B virus replication.     

Transient liver injury caused by gefitinib]

Gefitinib blocks epidermal growth factor receptor autophosphorylation and subsequently the signal transduction pathways implicated in proliferation, metastasis, invasion, and angiogenesis. Reported adverse reactions to gefitinib include liver injury that is not fully understood. Liver injury was observed in 5 (12.2%) of 41 patients with non-small cell lung cancer who received gefinitib monotherapy. Onset of liver injury was seen between 28 and 56 days after initiation of administration. Two patients had Grade 2 liver injury and 3 patients, Grade 3. In 4 patients, liver injury was temporary, lasting during a period of continuous gefitinib administration. In another patient, gefitinib was discontinued because of the onset of liver injury, which improved when gefitinib administration was restarted. Gefitinib is necessary in most patients whose lung cancer is refractory to cytotoxic chemotherapy, because no other treatment regimens are available at present. The rate of liver injury in cases treated with gefitinib is high, and so it is necessary to observe liver function carefully, but the liver injury due to this drug is often transient. However, the use of gefitinib in many cases appears to be a necessity.     

A Japanese patient with familial Mediterranean fever associated with compound heterozygosity for pyrin variant E148Q/M694I

Familial Mediterranean fever (FMF) is an inherited inflammatory disease occurring mainly in Mediterranean and Middle Eastern populations. FMF is caused by mutations in the MEFV gene that encodes pyrin/marenostrin. Here, we report a Japanese female FMF patient with heterozygosity for the compound pyrin E148Q/M694I showing recurrent fever, serositis or delay in skin wound healing. Her father and elder sister were heterozygous for pyrin variant M694I alone and sometimes suffered from mild fever or delay in wound healing, but her mother was heterozygous for pyrin variant E148Q alone and had no symptoms. This suggested that the inheritance of FMF occurred not only in an autosomal recessive manner but also in an autosomal dominant manner in this Japanese family, and the severity of the disease differed among the family members in relation to the mutation. In the treatment of FMF, colchicine, reserpine or prazosin hydrochloride have been reported to prevent the attacks, but, in our patient such drugs were ineffective or caused side effects, and only the anti-allergic drug azelastine was of benefit in relieving the attacks.     

Role of immunoproteasomes and thymoproteasomes in health and disease

The proteasome is a multisubunit protease that degrades intracellular proteins into small peptides. Besides playing a pivotal role in many cellular processes indispensable for survival, it is involved in the production of peptides presented by major histocompatibility complex class I molecules. In addition to the standard proteasome shared in all eukaryotes, jawed vertebrates have two specialized forms of proteasome known as immunoproteasomes and thymoproteasomes. The immunoproteasome, which contains cytokine-inducible catalytic subunits with distinct cleavage specificities, produces peptides presented by class I molecules more efficiently than the standard proteasome. The thymoproteasome, which contains a unique catalytic subunit β5t, is a tissue-specific proteasome expressed exclusively in cortical thymic epithelial cells. It plays a critical role in CD8⁺ cytotoxic T cell development via positive selection. This review provides a brief overview on the structure and function of these specialized forms of proteasome and their involvement in human disease.     

Stenosing ureteritis in Henoch–Schönlein purpura: Report of two cases

Stenosing ureteritis (SU), a rare complication of Henoch–Schönlein purpura (HSP), typically presents with severe symptoms. We report the cases of two HSP patients presenting with gross hematuria, blood clotting, and colicky flank pain, followed by purpura on the lower extremities. Early‐stage ultrasonography indicated hydronephrosis, thickened renal pelvic mucous membrane, and ureteral dilatation (UD), suggesting HSP complicated with SU. After early SU treatment with prednisolone, kidney function, thickened renal pelvic mucous membrane, and UD progressively normalized and the pain gradually disappeared. Regular ultrasonography of HSP patients from the onset of gross hematuria can be useful to detect early SU and facilitate conservative therapy with prednisolone. Diagnosis of SU can be easily missed by assuming HSP nephritis, particularly owing to the non‐specific symptoms. Common characteristics as well as treatment methods and prognosis of SU are given in the literature review.