Apolipoprotein E accelerates the efflux of cholesterol from macrophages: mechanism of xanthoma formation in apolipoprotein E deficiency

A patient with congenitally deficient apolipoprotein (apo) E showed numerous tuberoerutive, tendon xanthomas and severe atherosclerosis, despite a low LDL concentration. In order to study the mechanism of xanthoma formation observed in apo E deficient patients, we evaluated the effect of VLDL and HDL from the patient on cholesterol ester (CE) accumulation in macrophages. The results showed that there was no difference in CE formation in macrophages among normal VLDL, the patient's VLDL and apo E containing VLDL, which was prepared by incubation of the patient's VLDL with recombinant apo E. On the other hand, apo E containing HDL, which was prepared by incubation of the patient's HDL with recombinant apo E, accelerated cholesterol efflux more effectively than did the patient's HDL and decreased intracellular CE content. Moreover, free apo E accelerated cholesterol efflux from lipid loaded macrophages. These results suggest that macrophages are prevented from transforming into foam cells by their secretion of apo E. This may also explain the marked atherosclerosis and xanthomatosis observed in the patient with apo E-deficiency.     

Mondini dysplasia with recurrent bacterial meningitis caused by three different pathogens

Mondini dysplasia is rare, but has an important association with recurrent bacterial meningitis. We herein describe the case of a 3‐year‐old girl with unilateral sensorineural hearing loss who presented with three independent episodes of bacterial meningitis within 8 months. Temporal bone computed tomography indicated the characteristic features of Mondini dysplasia in the right inner ear. This was treated by surgical closure of the inner ear defect via oval window and additional vaccination was administered. Appropriate vaccination might prevent the recurrent bacterial meningitis associated with Mondini dysplasia.     

CETP is a determinant of serum LDL-cholesterol but not HDL-cholesterol in healthy Japanese

Cholesteryl ester transfer protein (CETP) is one of the factors that regulate plasma levels of HDL-cholesterol. To identify the factors that may regulate CETP activity, and to determine to what extent CETP is correlated with physiologic concentrations of lipoprotein, we performed an epidemiologic study in 586 healthy volunteers (317 males and 269 females, mean age 52.2 ± 10.9 years). CETP activity in these subjects was 192.96 ± 48.73 (mean ± S.D.) nmol/ml/h and distributed to a wide range (60–450 nmol/ml/h). Using multiple regression analysis, we found significant positive correlations between CETP activity and LDL-cholesterol (P < 0.03), apolipoprotein (apo) E (P < 0.005) and LCAT activity (P < 0.001). CETP activities showed significant negative correlation with apo A-I (P < 0.03). However, CETP activity showed no significant correlation either with HDL cholesterol or with apo B. One-way layout analysis of variance showed that alcohol drinking and cigarette smoking significantly reduced CETP activity, but there was no significant association between CETP activity and body mass index. Although CETP activities were significantly higher in females than in males (P < 0.001), multiple regression analysis showed no correlation between CETP activity and age in either the males or the females. Our results suggest that CETP activity regulates the concentration of apo A-I and LDL-cholesterol, and that such activity may be influenced by gender, alcohol consumption and cigarette smoking.     

Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid‐rich hepatocellular carcinoma

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich‐hepatocellular carcinoma (HCC) was challenging. The patient was a 50‐year‐old woman in whom a 3‐cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well‐demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid‐rich type HCC because it stained positive for Hep Par1, but negative for arginase‐1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF‐1 and 3β‐HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase‐1 is to rule out the possibility of lipid‐rich HCC.     

Evaluation of a Free-Coupon Program for Cervical Cancer Screening Among the Young: A Nationally Funded Program Conducted by a Local Government in Japan

Background

Finding ways to improve the cervical cancer screening rates among young women has been seen as a critical national health problem in many countries, including Japan. The aim of the present study was to evaluate the effects of a free-coupon program for cervical cancer screening conducted by a local government under financial support from the Japanese national government.

Methods

The personal cervical cancer screening information was analyzed for all female residents of Toyonaka City, including any past screening history and clinical results since the year 2009, when a free-coupon program for screening was started. These results were compared to results from 2008, prior to implementation of the free-coupon screening program.

Results

The screening rates of women eligible for the free-coupon peaked dramatically compared to women of similar age who paid for their screening; however, the rates for the ineligible-age population also increased significantly in parallel to those in the free-coupon program, possibly by indirect peer and publicity effects. In women aged 20 to 25 years, the consecutive screening rate after a free-coupon screening was significantly lower than for those women who received a regular residential screening. After a free-coupon screening, the rate for participating in consecutive screenings depended significantly on the institution where the participant received her first screening test.

Conclusions

These results suggest that, for a generation of young women 20–25 years of age, a free-coupon program for cervical cancer screening was effective in increasing the first-time participation rate for screening; however, the increase in first-time participation did not lead to the expected increase in consecutive screenings.Key words: cervical cancer screening, free-coupon, screening rate, consecutive screening     

Acute respiratory failure due to thyroid storm developing immediately after delivery

Acute respiratory failure occurs in less than 0.1% of pregnancies. Thyroid storm should be included in the differential diagnosis of possible causes of acute respiratory failure occurring immediately after delivery, and delivery is a high risk factor for thyroid storm in pregnant women with thyrotoxicosis.     

Exploration of immobilization conditions of cellulosic lyotropic liquid crystals in monomeric solvents by in situ polymerization and achievement of dual mechanochromism at room temperature

We investigated conditions to prepare cellulosic cholesteric liquid crystalline (ChLC) films in order to accomplish dual mechanochromism, i.e., colour control and circular dichroic inversion upon mechanical stimulus, at room temperature. Flexible propionylated hydroxypropyl cellulose (PHPC) was prepared by a simple reaction and found to be capable of forming lyotropic ChLC in various monomeric solvents. The ChLC solutions were subjected to in situ polymerization to obtain PHPC/synthetic polymer composite films incorporating the ChLC structure. However, the immobilization behaviour depended on the type of original monomers. Differential scanning calorimetry and solid-state NMR measurement revealed that the ChLC structure was more highly fixed when the compatibility between PHPC and the coexisting polymers was lower. Eventually, thus obtained ChLC composite films exhibited dual mechanochromism under ambient temperature.

We obtained cellulosic/synthetic polymer composites incorporating a cholesteric liquid crystalline structure by in situ polymerization and accomplished dual mechanochromism at room temperature.     

Anti-PM/Scl Antibody-positive Systemic Sclerosis Complicated by Multiple Organ Involvement

A 40-year-old Japanese woman developed malignant-phase hypertension complicated by thrombotic microangiopathy, progressing to end-stage renal disease. Five years later, she was diagnosed with pulmonary arterial hypertension and interstitial pneumonia. Despite a lack of overt skin sclerosis, nucleolar staining in our indirect immunofluorescence analysis and nailfold capillaroscopy facilitated the diagnosis of anti-PM/Scl antibody-positive systemic sclerosis. We observed the persistent presence of anti-PM/Scl antibodies throughout the clinical course, suggesting that her kidney disease was scleroderma renal crisis. Anti-PM/Scl antibodies can be associated with multiple organ diseases. Careful attention to a patient''s antinuclear antibody pattern and dermatological findings may help clarify the etiology of undiagnosed diseases.