Identification of trypsin-degrading commensals in the large intestine.

Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1-3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.

Factors contributing to discrepant estimated glomerular filtration values measured by creatinine and cystatin C in patients with rheumatoid arthritis.

This study aimed to clarify the factors underlying the discrepancy that has been noted between estimated glomerular filtration ratio (eGFR) measured using serum creatinine (Cr) and eGFR using serum cystatin C (CysC) in patients with rheumatoid arthritis (RA) and to identify those patients whose renal function should be evaluated using CysC. We retrospectively evaluated clinical features, disease activity, Steinbrocker radiological staging, and co-morbidities (diabetes mellitus, hypertension, dyslipidemia) in 238 RA patients. eGFR using serum creatinine (eGFR-Cr) and eGFR using serum cystatin C (eGFR-CysC) were calculated using the new Japanese coefficient-modified Modification of Diet in Renal Disease study equation. To clarify the cause(s) of differences of 20% or more between the two eGFRs, we divided our RA patients into Group A (eGFR-Cr/eGFR-CysC ≥ 1.2) and Group B (eGFR-Cr/eGFR-CysC < 1.2), and searched for factors independently related to Group A. Forty-five patients (18.9%) were assigned to Group A, and 193 (81.1%) to Group B. BMI (Odds Ratio [OR] 0.820, 95% confidence interval [CI] 0.675-0.996), Hb (OR 0.633, 95% CI 0.433-0.926), CK (OR 0.773 per 10 units, 95% CI 0.644-0.933), NSAID use (OR 0.099, 95% CI 0.020-0.494), diabetes mellitus (OR 6.024, 95% CI 1.508-24.390) and stage 4 Steinbrocker radiological stage (OR 10.309, 95% CI 2.994-35.714) were identified as independent relevant factors for Group A by a multifactorial analysis. Renal function in RA patients with low BMI, diabetes, anemia and low CK may be overestimated using eGFR-Cr alone, and such patients need to be evaluated using eGFR-CysC.

A case report of progressive multifocal leukoencephalopathy during steroid treatment for ANCA-associated renal vasculitis.

CASE REPORT: an 80-year-old woman presented with rapidly progressive glomerulonephritis and was admitted to our hospital. Myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA) was positive. We diagnosed ANCA-associated renal vasculitis (ANCA-RV). Treatment was initiated with intravenous methylprednisolone pulse therapy, followed by prednisolone (PSL) at 30 mg/day. We gradually reduced the PSL dose to 7.5 mg/day over 6 months. At that time, the patient developed disturbances of consciousness which progressed subacutely. MRI revealed regions of patchy white matter with an increased signal on T2-weighted, fluid attenuated inversion recovery (FLAIR) sequences and diffusion-weighted sequences. JC virus DNA was detected in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), leading to a diagnosis of progressive multifocal leukoencephalopathy (PML). PML is a rare infectious demyelinating disease of the central nervous system caused by JC virus infection, occurring in highly immunosuppressed individuals such as HIV-infected patients and patients using some biological agents, and having a very poor prognosis. In the present case, PML may have been associated with steroid use, although there are very few case reports of PML in patients taking only steroids. We report progressive multifocal leukoencephalopathy during steroid treatment of ANCA-RV. When patients show progressive disturbance of consciousness during treatment for ANCA-RV, we need to take PML into consideration for differential diagnosis.

[Carcinoma of the gallbladder which progress on the mucosa of choledochocolonic fistula].

A 70-year-old man was admitted to our hospital for further examination of pneumobilia and atrophy in the gallbladder. Abdominal CT scan and EUS revealed that the atrophic gallbladder was occupied by a tumor lesion. In addition, ERCP showed choledochocolonic fistula. Colonoscopy revealed an elevated lesion in the colonic side of fistula, and biopsy of the elevated lesion revealed adenocarcinoma. Cholecystectomy and right hemicolectomy was performed under a preoperative diagnosis of gallbladder carcinoma with choledochocolonic fistula. Pathologically, most of the tumor was localized in the gallbladder, and grew along the mucosa of choledchocolonic fistula. This case was of interest with regard to the relationship between the choledochocolonic fistula and gallbladder carcinoma.

Recurrence of primary hepatic carcinoid tumor in the remnant liver 13 yr after resection.

We report here a case of primary hepatic carcinoid tumor (PHCT) recurring in the remnant liver 13 yr and 10 mo after first resection. A 70-yr-old man developed four hypervascular tumors in the liver in December 2003. He had undergone curative left-lobe hepatectomy for PHCT in February 1990. Histopathological examination of the tumor biopsy specimen showed that the tumor was composed of uniform round-to-oval cells with solid arrangement and the tumor cells stained positive for chromogranin A, synaptophysin, and neuron-specific enolase. We diagnosed this case as an intrahepatic metastasis of PHCT with a long latency period, based on the fact that no primary site of carcinoid tumor could be found despite intensive examination and the immunohistochemical findings of the resected tumors were essentially same as those of PHCT in 1990. Although PHCT is reported to have a more favorable prognosis than other hepatic cancer or metastatic carcinoid tumor in the liver, long-term observation is recommended.

A pancreatic abscess 7 years after a pancreatojejunostomy for calcifying chronic pancreatitis.

We present herein a case of a 75-year-old Japanese man who had developed a pancreatic abscess 7 years after a longitudinal pancreatojejunostomy for chronic pancreatitis. The patient, a heavy drinker of alcohol, underwent surgical decompression of a ductal obstruction to relieve persistent abdominal pain due to severely calcifying chronic pancreatitis. After the surgery, he stopped drinking alcohol and was treated with insulin to control secondary diabetes mellitus. Thereafter, his symptoms disappeared. Seven years after the surgery, however, he was hospitalized due to obstructive jaundice, high-grade fever, and right hypochondria pain. Ultrasound and computed tomographic scans of the abdomen both disclosed a cystic mass, approximately 6 cm in size, in the pancreatic head. Magnetic resonance imaging strongly suggested a pancreatic abscess with necrotic fluid and debris. First, percutaneous transhepatic cholangiodrainage (PTCD) was done to treat the progressively obstructive jaundice. Subsequently, fine-needle aspiration of the pancreatic abscess was performed under ultrasound guidance. Enterococcus avium and Klebsiella oxytoca were revealed by culture of abscess aspirates. He was successfully cured by treatment with both appropriate antibiotic and continuous PTCD for the obstructive jaundice.

[A case of gastric mucosal bridge with Behçet's disease].

A 69-year-old man visiting our hospital with an epigastralgia and tarry stool was diagnosed as having Behçet's disease on the basis of repetitious aphthous stomatitis, erythema nodosum and arthralgia in 1991. The next year, he suffered from double active ulcers in the antrum of the stomach, and he had been operated on for intestinal perforation. In 1994, endoscopic examination revealed the gastric mucosal bridge between the double ulcers. The double ulcer healed after an eradication therapy of H. pylori, but the gastric mucosal bridge has remained there on the gastrointestinal endoscopy. The gastric mucosal bridge with Behçet's disease has not been reported in Japan, being considered to be very rare.

Measurements of the micro/beta ERD and gamma ERS during the imagination of body parts movement.

In recent years, many studies shows that the ERS (event-related synchronization) in the gamma band is associated with cortical activation during the imagination of body parts movement. It is also known that the ERD (event-related desynchronization) in the micro and beta band are caused by the imagination of body parts movement. In this study, we investigated the relationship between the gamma ERS and micro/beta ERDs. We recorded 64-channel EEG in order to obtain the power map of the gamma component. Furthermore, we compared the characteristics of the gamma waveform and micro/beta waveforms at the locations where the gamma ERS appeared clearly. As a result, we obtained three conclusions. Firstly, gamma ERS caused by the imagination of body parts movement appears at near somatosensory area and motor area. Gamma ERS caused by the imagination of right arm movement appears at the left side of the somatosensory area, that of left arm movement appears at the right side of the somatosensory area, and that of the foot movement appears at the center of the motor area. Secondly, micro/beta ERDs appear simultaneously with the preparation of the imagination, and they continue during the imagination. However, gamma ERS appeared simultaneously with the imagination of body parts movement. Finally, the power of the micro/beta component decrease gradually, but that of the gamma component increases significantly.