A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020

Clinical and Experimental Nephrology -     

Oxidized low-density lipoprotein levels circulating in plasma and deposited in the tissues: comparison between Helicobacter pylori-associated gastritis and acute myocardial infarction

Background

Oxidized low-density lipoprotein (ox-LDL) is a key factor in the progression of atherosclerosis. We developed a sensitive method for measuring plasma ox-LDL levels using a novel anti-ox-LDL antibody. Recently, several studies have shown positive associations between Helicobacter pylori (H pylori) infection and coronary heart disease. Thus the question arises whether an increase in the plasma levels of ox-LDL occurs in patients with H pylori gastritis.

Methods

We measured plasma ox-LDL levels in patients with H pylori gastritis (n = 27) and compared them with those in patients with acute myocardial infarction (AMI) (n = 62) and stable angina pectoris (SAP; n = 63) and those in control subjects (n = 64). In addition, ox-LDL localization and the presence of macrophages and neutrophils were studied immunohistochemically in gastritis specimens and in coronary culprit lesions obtained from patients with AMI.

Results

Plasma ox-LDL levels in patients with AMI were significantly higher than those in patients with SAP (P <.0001), patients with H pylori gastritis (P <.0001), or in control subjects (P <.0001; AMI, 1.34 ± 0.95; SAP, 0.61 ± 0.29; Gastritis, 0.53 ± 0.17; control, 0.57 ± 0.23 ng/5μg LDL protein). Immunohistochemically, H pylori gastritis specimens showed distinct infiltration of macrophages and myeloperoxidase-positive neutrophils; however, ox-LDL localization was not detected. In contrast, coronary culprit plaques revealed strong positivity for ox-LDL in ruptured lipid cores with abundant macrophage-derived foam cells, and these plaques also contained myeloperoxidase-positive neutrophils.

Conclusion

Our results suggest that plasma ox-LDL levels do not seem to be associated with H pylori infection, but do relate to coronary plaque instability in AMI.     

Stable expression of FRET biosensors: a new light in cancer research

The constituents of the oncogene signal transduction pathway are promising targets for anticancer drugs. Despite the wealth of available knowledge regarding their molecular properties, the spatiotemporal regulation of the signaling molecules remains elusive. Biosensors based on the principle of FRET have been developed to visualize the activities of the signaling molecules in living cells. However, difficulties in the development of sensitive FRET biosensors have prevented their widespread use in cancer research. The lack of cell lines constitutively expressing a FRET biosensor has also limited their use. In this review, we will introduce the principle of FRET-based biosensors, describe an optimized backbone of the FRET biosensors, techniques to express FRET biosensors stably in the cells, and discuss the future perspectives of FRET biosensors in cancer research.     

Androgen receptor expression in breast cancer: relationship with clinicopathological factors and biomarkers

Background  Breast cancer is a hormone-dependent tumor. Most breast cancer cells have an androgen receptor (AR), but the clinical value of AR expression is unclear. Methods  AR expression was evaluated in 227 primary breast cancers using immunohistochemistry. The relation of AR expression to clinicopathological factors and biomarkers was analyzed. AR expression was assessed semiquantitatively, and tumors with more than 10% of stained cells were regarded as positive. Results  The AR-positive rate was higher in smaller tumors (P = 0.045), tumors with negative lymph node metastasis (P = 0.045), scirrhous-type tumors (P < 0.0001), tumors of low histological grade (P = 0.0001), and p53-negative tumors (P = 0.0097). Although AR had no relation to menopausal status, 79% of cases of high AR expression (>50% stained cells) were in postmenopausal women. AR was related to estrogen receptor (ER; P = 0.027) and progesterone receptor (PR; P = 0.016) expression, but showed no relation to human epidermal growth factor receptor type 2 (Her2) expression. Regarding the coexpression of these receptors, 18 of the 42 cases of triple-negative (ER/ PR/ Her2-negative) tumors (43%) were AR-positive. Conclusion  AR expression is related to low malignancy in breast cancer. The assessment of AR expression may lead to new treatment strategies for breast cancer, especially in postmenopausal women and in women with tumors that show triple negativity for hormone receptors.     

Gastric duplication cyst: Evaluation by endoscopic ultrasonography and magnetic resonance imaging

Endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) are becoming popular methods for examining tumorous lesions along the upper gastrointestinal tract. Though duplication cysts are uncommon. EUS findings from gastric duplication cysts have accumulated and proven very useful for preoperative diagnosis. There have been few reports, however, concerning MRI findings from these cysts. We report herein the case of a 25-year-old man with a gastric duplication cyst. EUS demonstrated a cystic mass adjacent to the fourth layer of the stomach wall. MRI revealed a cyst containing low signalintensity fluid and high signal-intensity fluid separated by levels. In addition to the characteristic findings from preoperative examinations, the unique histological findings from the cyst are also described.     

Primary effusion lymphoma complicating cardiac tamponade: a case report

A 76-year-old woman was admitted to our hospital because of exertional dyspnea and leg edema during the previous month. Her systolic blood pressure on admission was 80 mmHg with 12 mmHg of pulsus paradoxous, and her pulse rate was 110 beats/min. Chest radiography revealed marked cardiomegaly and echocardiography showed massive pericardial effusion mainly behind the left ventricle and collapse of the right ventricle. The initial diagnosis was pericardial tamponade. Pericardiocentesis and pericardial drainage revealed bloody pericardial effusion. After drainage, her vital signs improved and her symptoms immediately disappeared. The cytological analysis of the pericardial effusion revealed numerous lymphoma cells. Computed tomography of the neck, chest and abdomen showed no evidence of tumor masses, lymph node enlargement, or hepatosplenomegaly. Infectious disease, collagen disease and aortic dissection were excluded. The final diagnosis was primary effusion lymphoma. The prognosis of primary effusion lymphoma is generally unfavorable because it is frequently accompanied by immunodeficiency disease. However, there was no human immunodeficiency virus infection in this patient. Fortunately, the effect of chemotherapy was excellent and the patient is doing well 1 year after the diagnosis.     

A case of 5-FU-resistant recurrent colon cancer treated with low-dose CPT-11/CDDP on an outpatient basis

We report a case of recurrent colon cancer resistant to 5-FU, whose QOL and PS has been well maintained with low-dose CPT-11/CDDP administered on an outpatient basis for more than 28 months. A 42-year-old male had lymph node recurrence 27 months after curative resection of colon cancer. He had been administered pharmacokinetic modulating chemotherapy (PMC, oral tegafur/uracil plus fluorouracil infusion) after surgery. Combined treatment with CPT-11 (50 mg/m2)/CDDP (6 mg/m2) was performed on an outpatient basis. Nine months of NC was obtained without any severe side effect. Modified administration of this treatment with 5'-DFUR and TS-1 lead to further maintenance of quality of life and performance status. This case suggests the efficacy of low-dose CPT-11/CDDP for cases of 5-FU-resistant colon cancer in terms of QOL and PS.     

Alterations of endothelin-converting enzyme expression in early and advanced stages of human coronary atherosclerosis

Endothelin-1 is a potent vasoconstrictor and exhibits a mitogenic activity on vascular smooth muscle cells (SMCs). Endothelin-converting enzyme (ECE) is the final key enzyme of endothelin-1 processing. We studied the immunolocalization of ECE in human coronary atherosclerotic lesions with different disease stages. Frozen sections of normal coronary arteries with diffuse intimal thickening (n=13) and those of coronary arteries with early (n=10) or advanced atherosclerotic plaques (n=13) were studied. Monoclonal antibodies used were directed against SMCs, macrophages, endothelial cells, and ECE. For the identification of cell types that express ECE, double immunostaining analysis was also used. In normal coronary arteries, ECE immunoreactivity was observed in luminal endothelial cells and medial SMCs. Early atherosclerotic plaques, which consisted predominantly of SMCs, showed enhanced ECE expression in luminal endothelial cells and intimal SMCs. In advanced atherosclerotic plaques, distinct ECE expression was found in accumulated macrophages and in endothelial cells of intraplaque microvessels, while luminal endothelial cells showed relatively weak immunoreactivity for ECE. In conclusion, the present study demonstrates that the major cell types expressing ECE within the plaques are different between early and advanced stages of human coronary atherosclerosis. Enhanced ECE expression and possible endothelin-1 generation may contribute to SMC proliferation and vasoconstriction in early atherosclerotic stages, and may promote plaque destabilization in advanced atherosclerotic stages.