Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints

OBJECTIVE: We have reported that articular cartilage showed early stage degeneration at 7 and 14 days after immobilization, moderate degeneration at 28 days, and severe degeneration at 42 days in rabbits. To test whether apoptosis occurs in association with p53 expression in chondrocytes during the process of articular cartilage degeneration, we investigated the degree of cartilage degeneration, the frequency of apoptotic cells, and the levels of p53 mRNA in rabbits and mice after knee immobilization. METHODS: Right knees of male Japanese white rabbits were immobilized in full extension with fiberglass casts for up to 42 days. Similarly, right knees of male p53 wild-type [p53 (+/+)] and p53 null [p53 (-/-)] mice were immobilized in full extension with bandage tape for up to 84 days. Apoptotic cells were confirmed by TUNEL staining on the sections of knee joints. Total RNA of articular chondrocytes obtained from Day 0 or immobilized knees was analyzed semiquantitatively by RT-PCR using specific primers for p53. RESULTS: Articular cartilage degenerated after immobilization of p53 (+/+) mouse knees, but not after immobilization of p53 (-/-) knees. Apoptotic cells were observed in articular cartilage in the femur and tibia of rabbits and p53 (+/+) mice after immobilization. However, only a few apoptotic cells were observed at the same sites in p53 (-/-) mice. In RT-PCR analysis, the levels of p53 mRNA obtained from immobilized groups were significantly higher than those of Day 0 groups in rabbit and p53 (+/+) mouse knees. CONCLUSION: Apoptosis and p53 expression in chondrocytes relate to degeneration in articular cartilage of immobilized knee joints.     

A case of Mycobacterium avium pulmonary disease detected as multiple small nodular shadows and diagnosed by CT guided transbronchial biopsy with ultrathin bronchoscopy]

A 65-year-old man was admitted to our hospital because multiple small nodular shadows measuring five to 12 mm in diameter in both lung fields were noticed on chest radiographs and CT scans during a regular checkup for pulmonary emphysema. The levels of ESR and CRP were within normal limits, but those of CEA and CYFRA were slightly elevated. Mycobacterium avium (M. avium) was detected in sputum cultures and in a sputum examination using PCR. Non-necrotizing granulomas were detected in the specimens obtained from a lesion of the right S6b by CT-guided transbronchial biopsy using an ultrathin bronchoscope after navigation with virtual bronchoscopy. On the basis of these findings, M. avium pulmonary disease was diagnosed. The patient is being followed up, but because he has no symptoms, without medication. To our knowledge, there have been no previous reports of M. avium-intracellulare complex pulmonary disease, which is characterized by multiple small nodular shadows. It is speculated that multiple centrilobular lesions developed simultaneously without extension to the bronchial walls, leading in this case to multiple small nodules in both lung fields.     

Detection and identification of pathogenic bacteria responsible for postoperative pneumonia after esophagectomy

Background

Surgical complications occur frequently after radical esophagectomy and one of its most serious complications is postoperative pneumonia. Preoperative or postoperative bacteriological assessment may be useful in predicting, preventing, and managing postoperative pneumonia.

Methods

One hundred and five consecutive patients undergoing any procedure that included subtotal esophagectomy from October 2009 to March 2011 were the subject of this study. Culture materials (pharyngeal swab, nasal swab, dental plaque, tongue coating, gastric juice, and sputum) retrieved from the 105 esophageal cancer patients before, during, and after the surgery were comprehensively investigated for an association with postoperative pneumonia.

Results

Twenty-one patients out of 105 (20%) were retrospectively diagnosed with postoperative pneumonia. The investigated culture studies were associated with the occurrence of postoperative pneumonia in only one respect: positive detection of pathogens in postoperative endotracheal sputum was associated with marginally increased pneumonia (P = 0.053). Among the 21 pneumonia patients, pathogens were frequently detected in gastric juice retrieved on the first postoperative day (8 out of 14) and postoperative endotracheal sputum (13 out of 17). The putative pathogens of postoperative pneumonia were detected in 7 out of 8 gastric juice specimens and 9 out of 11 in sputum.

Conclusions

Postoperative pneumonia could not be predicted by either preoperative or postoperative bacteriological studies. In the patients with postoperative pneumonia, the postoperative bacterial culture of the gastric juice and sputum may be useful in identifying the causative organisms of postoperative pneumonia and, thus, in selecting appropriate antibiotics.

     

Diagnostic accuracy of enhanced liver fibrosis test for nonalcoholic steatohepatitis-related fibrosis: Multicenter study

Aim

The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan.

Methods

We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the Fibrosis-4 (FIB-4) index, and combinations of these indices.

Results

In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1–4, F0–1 versus F2–4, F0–2 versus F3–4, and F0–3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cut-off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%.

Conclusions

In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate.     

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.     

Levels of Transferrin in Bronchoalveolar Lavage Fluid in Sarcoidosis

There has been only one report showing high levels of transferrin (Tf) in bronchoalveolar lavage fluid (BALF) in patients with sarcoidosis. This study was designed to assess the levels of Tf in both BALF and serum and to examine the relationship between the levels of Tf and other disease markers in sarcoidosis. Subjects were 64 sarcoidosis and 10 healthy controls. Tf in BALF and serum was measured by nephelometric assay. Median Tf levels in BALF from sarcoidosis was 0.70 (range, 0.00–3.97) mg/dl, which was significantly higher compared with controls (0.36 (range, 0.00–1.02) mg/dl; p = 0.005). In contrast, median Tf levels in serum from sarcoidosis was 258 (range, 171–383) mg/dl, which was significantly lower compared with controls (322 (range, 234–356) mg/dl; p = 0.003). Tf levels in BALF were significantly correlated with both the percentage of lymphocytes (r = 0.617, p = 0.001) and serum angiotensin-converting enzyme activity (r = 0.363, p = 0.003) and serum soluble interleukin-2 receptor (r = 0.450, p = 0.001) in sarcoidosis. Levels of Tf in BALF from patients with sarcoidosis were not influenced by smoking status. The levels of Tf in sarcoidosis are high in BALF, but low in serum. Increased levels of Tf in BALF may reflect the disease activity.     

Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria

Journal of Gastroenterology - The significance of the 2018 Japanese diagnostic criteria for acute-on-chronic liver failure (ACLF) has not yet been evaluated. A nationwide survey was performed for...