A Case of Mediastinal Tuberculous Lymphadenitis in a Chronic Dialysis Patient Diagnosed by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA).

A 54-year-old woman on dialysis due to chronic renal failure had a fever lasting 2 weeks and was referred to a hospital. Non-enhanced CT and blood tests showed no remarkable findings. She was hospitalized and received an antibacterial drug. Although she was discharged after the fever subsided, she was hospitalized again due to a fever a few days later. A contrast-enhanced CT revealed mediastinal lymphadenopathy, and she was transferred to our hospital for a bronchoscopy. Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration (EBUS-TBNA) for subcarinal lymph nodes was performed in our hospital. The Polymerase Chain Reaction (PCR) test of the obtained specimen was positive for mycobacterium tuberculosis, and histologically, caseous granulomas were found in the specimen. She was diagnosed with mediastinal tuberculous lymphadenitis, and HREZ (isoniazid, rifampicin, ethambutol, and pyrazinamide) treatment was started. The fever subsided immediately, and she was discharged from our hospital 2 weeks after the initiation of treatment. Thereafter, she received treatment as an outpatient. Since the use of a contrast medium was complicated by dialysis, a non-enhanced CT was performed at first, and it was difficult to make a diagnosis from this. We report this as an informative case that could be diagnosed with EBUS-TBNA, which was easily performed on a patient weakened by prolonged fever and dialysis.

High-resolution crystal structure of peptidyl-tRNA hydrolase from Thermus thermophilus.

Peptidyl-tRNA hydrolase (Pth) cleaves the ester bond between the peptide and the tRNA of peptidyl-tRNA molecules, which are the products of defective translation, to recycle the tRNA for further rounds of protein synthesis. Pth is ubiquitous in nature, and its activity is essential for bacterial viability. Here, we have determined the crystal structure of Pth from Thermus thermophilus (TtPth) at 1.00 Å resolution. This is the first structure of a Pth from a thermophilic bacterium and the highest resolution Pth structure reported so far. The present atomic resolution data enabled the calculation of anisotropic displacement parameters for all atoms, which revealed the directionality of the fluctuations of key regions for the substrate recognition. Comparisons between TtPth and mesophilic bacterial Pths revealed that their structures are similar overall. However, the structures of the N- and C-terminal, loop-helix α4, and helix α6 regions are different. In addition, the helix α1 to strand ß4 region of TtPth is remarkably different from those of the mesophilic bacterial Pths, because this region is 9 or 10 amino acid residues shorter than those of the mesophilic bacterial Pths. This shortening seems to contribute to the thermostability of TtPth. To further understand the determinants for the thermostability of TtPth, we compared various structural factors of TtPth with those of mesophilic bacterial Pths. The data suggest that the decreases in accessible surface area and thermolabile amino acid residues, and the increases in ion pairs, hydrogen bonds, and proline residues cooperatively contribute to the thermostability of TtPth.

Orexin neurons are indispensable for prostaglandin E2-induced fever and defence against environmental cooling in mice.

We recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron-ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin peptides per se, are indispensable for stress-induced thermogenesis. To examine whether orexin neurons are more generally involved in central thermoregulatory mechanisms, we applied other forms of thermogenic perturbations, including brain prostaglandin E2 (PGE2) injections which mimic inflammatory fever and environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT) litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE2-induced fever and intolerance to cold (5°C) exposure, and these findings were similar to the results previously obtained with stress-induced thermogenesis. PGE2-induced shivering was also attenuated in ORX-AB mice. Both mutants responded similarly to environmental heating (39°C). In WT and ORX-KO mice, the administration of PGE2 and cold exposure activated orexin neurons, as revealed by increased levels of expression of c-fos. Injection of retrograde tracer into the medullary raphe nucleus revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. In addition, we found that glutamate receptor antagonists (D-(-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE2-induced fever in WT mice. These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. In addition, these results indicate the possible involvement of glutamate in orexin neurons implicated in PGE2-induced fever.

Crystallization and preliminary X-ray analysis of peptidyl-tRNA hydrolase from Thermus thermophilus HB8.

Peptidyl-tRNA is produced from the ribosome as a result of aborted translation. Peptidyl-tRNA hydrolase cleaves the ester bond between the peptide and the tRNA of peptidyl-tRNA molecules, to recycle tRNA for further rounds of protein synthesis. In this study, peptidyl-tRNA hydrolase from Thermus thermophilus HB8 (TthPth) was crystallized using 2-methyl-2,4-pentanediol as a precipitant. The crystals belonged to the orthorhombic space group P212121, with unit-cell parameters a=47.45, b=53.92, c=58.67 Å, and diffracted X-rays to atomic resolution (beyond 1.0 Šresolution). The asymmetric unit is expected to contain one TthPth molecule, with a solvent content of 27.13% (VM=1.69 Å3 Da(-1)). The structure is being solved by molecular replacement.

A case of bone marrow involvement in sarcoidosis with crescentic glomerular lesions.

Renal and bone marrow involvements in sarcoidosis are rare. We experienced the case of a 67-year-old man with systemic sarcoidosis, with bone marrow involvement, hepatic involvement and a unique constellation of renal lesion with cellular crescent formation. Immunosuppressive therapy was helpful for maintaining the stability of his pancytopenia, hepatic function and renal function. To the best of our knowledge, the association between sarcoidosis, bone marrow involvement and crescentic glomerulonephritis has been reported in only few cases in literature.