Crystal structure and reaction mechanism of a bacterial Mg-dechelatase homolog from the Chloroflexi Anaerolineae.

Chlorophyll degradation plays a myriad of physiological roles in photosynthetic organisms, including acclimation to light environment and nutrient remobilization during senescence. Mg extraction from chlorophyll a is the first and committed step of the chlorophyll degradation pathway. This reaction is catalyzed by the Mg-dechelatase enzyme encoded by Stay-Green (SGR). The reaction mechanism of SGR protein remains elusive since metal ion extraction from organic molecules is not a common enzymatic reaction. Additionally, experimentally derived structural information about SGR or its homologs has not yet been reported. In this study, the crystal structure of the SGR homolog from Anaerolineae bacterium was determined using the molecular replacement method at 1.85 Å resolution. Our previous study showed that three residues-H32, D34, and D62 are essential for the catalytic activity of the enzyme. Biochemical analysis involving mutants of D34 residue further strengthened its importance in the functioning of the dechelatase. Docking simulation also revealed the interaction between the D34 side chain and central Mg ion of chlorophyll a. Structural analysis showed the arrangement of D34/H32/D62 in the form of a catalytic triad that is generally found in hydrolases. The probable reaction mechanism suggests that deprotonated D34 side chain coordinates and destabilizes Mg, resulting in Mg extraction. Besides, H32 possibly acts as a general base catalyst and D62 facilitates H32 to be a better proton acceptor. Taken together, the reaction mechanism of SGR partially mirrors the one observed in hydrolases.

Pembrolizumab-related cholangitis with multiple fatal liver abscesses after endoscopic biliary drainage: a case report and review of the literature.

A 60-year-old male with cStage IVB lung cancer was treated with pembrolizumab. However, after five courses of pembrolizumab, he developed pembrolizumab-related cholangitis. Imaging studies showed enlargement and diffuse wall thickening of the gallbladder and mild dilation of the bile ducts without any obvious obstruction. As the patient experienced severe abdominal pain, we suspected bile stasis and performed biliary drainage. However, his condition did not improve, and he developed multiple liver abscesses and died during immunosuppressive therapy. Our case suggests that in ir-cholangitis, the indication and method of endoscopic retrograde cholangiopancreatography should be carefully judged.

Clinical analysis of 71 spontaneous pneumomediastinum cases: an observational study from a tertiary care hospital in Japan.

BACKGROUND: Spontaneous pneumomediastinum is characterized by the presence of interstitial air in the mediastinum without any underlying disease. Some cases of spontaneous pneumomediastinum have been reported in the past, although only few reports are available, and its management remains uncertain. This study reviewed our experience in the diagnosis and treatment of spontaneous pneumomediastinum. METHODS: A retrospective study of 71 cases treated for spontaneous pneumomediastinum at the Yodogawa Christian Hospital between April 2005 and March 2020 was conducted. RESULTS: The patients' mean age was 19.3 years (range, 7-48 years). A triggering event was noted in 69% of the cases. Seventy-six percent of the patients were admitted to the hospital, and 24% were outpatients. Treatment included analgesia, rest, antibiotics, and/or oxygen therapy. Thirty-six patients (51%) were treated with antibiotics. None of the cases presented any complications, including mediastinitis or worsening respiratory condition. Two patients (3%) had a recurrence of spontaneous pneumomediastinum. CONCLUSIONS: All the patients, with or without antimicrobial treatment and hospitalization, had favorable outcomes. We should therefore reconsider the need for hospitalization and antimicrobial therapy for patients with mediastinitis prophylaxis.

Nuclear Protein in Testis Carcinoma of the Thorax.

Nuclear protein in testis (NUT) carcinoma (NUT-C) is an exceedingly rare and aggressive neoplasm. We herein report a case of a 57-year-old man with a rapidly progressing tumor of the thorax and left pleural effusion. The pathological features and immunohistochemical staining of specimens obtained by a transbronchial lung biopsy initially indicated poorly differentiated squamous cell carcinoma. However, given the clinical presentation along with the additional histopathologic features, NUT-C was considered. Immunohistochemical staining for NUT was positive in the pleural fluid cell block, confirming the diagnosis of NUT-C. This report indicates the utility of immunohistochemical staining for diagnosing NUT in the pleural fluid cell block.

Campylobacter fetus bacteremia with purulent pleurisy in a young adult with primary hypogammaglobulinemia.

A 24-year-old man presented with fever and pleural effusion predominantly containing lymphocytes. Cultures of the pleural effusion and blood revealed Campylobacter fetus, and laboratory studies showed a low serum level of immunoglobulin. The patient was diagnosed with C. fetus pleuritis, bacteremia and primary hypogammaglobulinemia, and subsequent treatment with meropenem and immunoglobulin improved his condition. Although the underlying cause of the primary hypogammaglobulinemia remains unclear, the patient's status improved under immunoglobulin replacement therapy. C. fetus pleuritis is a rare infectious disease usually observed in immunocompromised hosts. We herein describe the first report of C. fetus pleuritis in a young adult with primary hypogammaglobulinemia.

[A case of a septic pulmonary embolism-related implanted central venous port].

We report a case of a 32-year-old woman with a septic pulmonary embolism-related implanted central venous port. She was treated with S-1/cisplatin(CDDP)chemotherapy for recurrent gastric cancer. Her disease was progressive after five courses of S-1/CDDP combination therapy. Because of peritonitis carcinomatosa, her oral intake was poor, so we placed an implanted central venous port in her right subclavian vein. We administered 5-FU/Leucovorin/paclitaxel combination therapy and total parenteral nutrition from the port. Chemotherapy was effective, so we stopped total parenteral nutrition after one month. Two months later, multiple nodular shadows appeared in her left lung fields without apparent symptoms. Because we suspected septic pulmonary embolism related to the venous port, we removed the venous port promptly and administered antibiotics with a broad spectrum. Pulmonary shadows disappeared immediately, and no recurrence was observed afterward.

Pulmonary and gastric metastatic calcification due to milk-alkali syndrome: a case report.

The incidence of metastatic calcification is influenced by high serum calcium and phosphate concentrations and local physicochemical conditions, such as pH. A high pH accelerates tissue calcification. Patients with milk-alkali syndrome typically present with renal failure, hypercalcemia, and metabolic alkalosis, which are caused by the ingestion of calcium and absorbable alkali. Among patients with impairment of renal function, milk-alkali syndrome is a major cause of hypercalcemia. Long-term use of furosemide will lead to hypokalemia, metabolic alkalosis, and eventually renal failure (i.e., pseudo-Bartter syndrome). Even if the level of calcium ingestion is relatively low, the renal failure caused by long-term furosemide use can readily lead to milk-alkali syndrome. We describe a case of a 45-year-old woman who was admitted with cough and dyspnea and presented with pulmonary and gastric metastatic calcification. She had been taking alfacalcidol and oral alkaline medications such as sodium bicarbonate and calcium carbonate as well as oral furosemide for a long time. The patient was found to have hypercalcemia, chronic renal failure, and metabolic alkalosis, so milk-alkali syndrome was diagnosed. Saline was administered and oral medications were discontinued. Serum creatinine levels subsequently decreased, but pulmonary metastatic calcification was not diminished. In this case, the milk-alkali syndrome that caused the severe metastatic calcification was exacerbated by multiple factors, including oral alkaline medications such as sodium bicarbonate and calcium carbonate. In addition, metabolic alkalosis and renal failure were affected by long-term furosemide use (i.e., pseudo-Bartter syndrome).

[A case of Wegener's granulomatosis with pachymeningitis].

A 49-year-old man was admitted to our hospital because of headache, rhinorrhea, and general fatigue. Chest CT revealed some lung nodules bilaterally, and laboratory data were positive for C-ANCA. Brain MRI revealed the findings of pachymeningitis. Wegener's granulomatosis (WG) was diagnosed by the pathological findings of his paranasal sinuses and kidneys. Most of his symptoms remarkably improved with oral corticosteroids and cyclophosphamide. A MEDLINE search about WG with pachymeningitis obtained only 15 cases previously reported in Japan. Considering those reports about WG with pachymeningitis in both Japan and overseas, in some cases pachymeningitis preceded WG, and relatively more cases than normal WG were negative for C-ANCA, furthermore the pathological findings of pachymeningitis were mainly necrotizing granuloma. Therefore pachymeningitis with WG might be mainly composed of granuloma rather than angitis and which might be a expansion of granulomatous inflammation of upper respiratory tract.

[Case of Toxocara canis larva migrans cured by additional treatment with albendazole].

A 42-year-old man presented at our emergency department with fever, sputum, and dyspnea. His chest X-ray films showed ground-glass opacities mainly in the upper and middle lung fields. We diagnosed pneumonia, gave antibiotic treatment, and his symptoms improved. However he later showed eosinophilia. We performed additional workup, and diagnosed Toxocara canis larva migrans. We treated him with albendazole for four weeks, but his eosinophil count rose again from the end of treatment one month later. Therefore we performed additional treatment with albendazole for 8 weeks, after which the clinical imaging findings and serum antibody titer improved. There are few reports about additional treatment for Toxocara canis larva migrans, and there is not yet a consensus. We think that we should consider additional treatment in cases that do not show improvement on initial treatment.

[A case of pulmonary amebiasis].

A 57-year-old man was admitted to our hospital because of dyspnea and right abdominal pain. Chest X-ray radiogram showed right massive pleural effusion. Ultrasonic echogram of abdomen showed a unilocular liver cyst. He was treated with intravenous infusion of meropenem, and percutaneous pleural and liver drainage were performed. At the time of drainage, we injected contrast medium into the liver cyst and confirmed a fistula connecting to the right pleural space. Initially we made a diagnosis of bacterial empyema and liver abscess, yet there was no response to the initial treatment. Cultures of pleural effusion and liver abscess were confirmed to be negative. A few days after admission, the patient stated that he was a homosexual. Liver amebiasis and its perforation became the most likely diagnosis, and metronidazole was administered. On admission day 21, tests for anti-amebic antibody were positive. Finally he fully recovered. We must be aware of the rare pulmonary manifestation of amebiasis. We report this case and review the literature.