Type III hyperlipoproteinema with apolipoprotein E2/2 genotype in Japan

Limited information is available concerning type III hyperlipoproteinemia (HLP) in the Asian population. Therefore, clinical and biochemical characteristics of type III HLP were examined in 16 Japanese patients. Mean plasma triglyceride (TG) and total cholesterol (chol) levels were 381 mg/dl and 253 mg/dl, respectively, and the mean very low density lipoprotein (VLDL)-chol/plasma TG ratio was 0.27, which were lower than those reported in Western countries. Eighty percent of the patients had high plasma remnant-like particles (RLP)-chol levels above 50 mg/dl and a high RLP-chol/plasma TG ratio above 0.1. Twelve patients (75.0%) were obese. Seven patients (43.8%) had type 2 diabetes mellitus and four patients (25.0%) had impaired glucose tolerance. Six patients (37.5%) had coronary heart disease (CHD), but none had peripheral vascular disease or xanthomas. TG-rich lipoproteins from type III HLP patients with diabetes mellitus stimulated cholesteryl ester synthesis by human macrophages significantly (p < 0.001) more than those from type III HLP patients without diabetes mellitus. In conclusion, the Japanese type III HLP patients had lower plasma TG and total chol levels and a lower VLDL-chol/plasma TG ratio, but CHD was more common. The patients were characterized by a high frequency of obesity and/or glucose intolerance. The TG-rich lipoproteins from type III HLP patients with diabetes mellitus were more atherogenic.     

Mild emphysema: a novel method using formalin-fixed lungs for computed tomography and pathological analyses

We evaluated a novel method of computed tomography (CT) analysis using formalin-fixed lungs of autopsy cases with mild emphysema. Eight formalin-inflated lungs (FILs) obtained at autopsy were examined using CT after draining off the formalin and air inflation with an air pump, and subjected to pathological study including pathological scoring of emphysema and microscopic image analysis (MIA). Satisfactory CT examination was carried out within 5 h of lung fixation. The mean alveolar area determined by MIA correlated highly with the lung volume (r=0.845) and CT score (r=0.722). This method is simple compared with conventional polyethylene glycol fixation for CT and enables CT examination of resected lungs without anxiety about biohazards. Mild emphysema can be detected by MIA.     

The pathogenesis of hyaline globules in liver cells after partial hepatectomy in rats

To clarify the pathogenesis of hyaline globules in liver cells after partial hepatectomy, the present study was undertaken in rats. When partial hepatectomy was performed by the surgical procedure of Higgins and Anderson, the inferior vena cava pressure was raised, and many hyaline globules, which are very similar to those caused by condensation of the contents of vacuoles in liver cells after temporary pressure elevation of the inferior vena cava, were induced in liver cells. On the other hand, when the median lobe and the left lateral lobe were removed carefully one at a time to avoid operative narrowing of the inferior vena cava, the inferior vena cava pressure was not elevated, and only very few hyaline globules were formed. This suggests that hyaline globules in liver cells following partial hepatectomy in rats may be caused by elevation of inferior vena cava pressure due to narrowing of the inferior vena cava by surgical procedure.     

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/- 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.     

A study of endotoxin-associated hepatotoxicity on proliferating hepatocytes.

It is thought that regeneration of the liver provides a state of preparedness for the Shwartzman reaction and contributes to the development of endotoxin-associated massive hepatic necrosis following partial hepatectomy. Therefore we examined endotoxin hepatotoxicity in rats with hepatic regeneration after 35% hepatectomy and in rats with liver cell proliferation induced by lead nitrate. Biochemical and histopathological studies showed no enhanced endotoxin hepatotoxicity in either partially hepatectomized rats or in rats with lead nitrate-induced liver cell proliferation. These results indicate that the development of endotoxin-associated hepatic damage after partial hepatectomy may not relate to regeneration and proliferation of the liver.     

Characterization of serum antibody responses to natural rotavirus infections in children by VP7-specific epitope-blocking assays.

Knowledge of the immune response to rotavirus is crucial for vaccine development. We compared an epitope-blocking assay (EBA) that uses VP7-specific monoclonal antibodies with neutralization assays (NAs) with polyclonal antisera for detecting serum antibody responses after natural rotavirus infection in children. Twenty-six serum pairs from children living in an orphanage with and without symptoms during two rotavirus outbreaks were evaluated for VP7 type 1-, 2-, 3-, and 4-specific antibody responses. In the first outbreak, which was caused by a VP7 type 3 strain, homotypic antibody responses were detected in 11 of 11 symptomatic children by NA and in 10 of 11 symptomatic children by EBA. Heterotypic antibody responses were detected more frequently (12 of 15 children) by NA than by EBA, and the heterotypic epitope-blocking antibody responses occurred in children older than 14 months of age. Antibody responses in asymptomatic children were more commonly detected by EBA than by NA. EBA results from the sera of children in the second outbreak indicated that it was caused by VP7 type 4, whereas NA results suggested it was caused by VP7 type 3. Our results confirm that EBA is a sensitive and specific method for determining VP7 type-specific immune responses after natural rotavirus infections.     

Extracellular vesicles released from irradiated neonatal mouse cheek tissue increased cell survival after radiation

Alopecia is one of the common symptoms after high-dose radiation exposure. In our experiments, neonatal mice that received 7 Gy X-ray exhibited defects in overall hair growth, except for their cheeks. This phenomenon might suggest that some substances were secreted and prevented hair follicle loss in the infant tissues around their cheeks after radiation damage. In this study, we focused on exosome-like vesicles (ELV) secreted from cheek skin tissues and back skin tissues, as control, and examined their radiation protective effects on mouse fibroblast cell lines. We observed that ELV from irradiated cheek skin showed protective effects from radiation. Our results suggest that ELV from radiation-exposed cheek skin tissue is one of the secreted factors that prevent hair follicle loss after high-dose radiation.     

Are bladder washing samples suitable for investigation of HPV infection in urinary bladder? Comparison in HPV prevalence between urine and washing samples

Although urine and bladder washing samples are commonly used for the cytological evaluation of the bladder mucosa, it has been unknown whether these samples are likely suitable to investigate human papillomavirus (HPV) prevalence in the urinary bladder. The present study aimed to elucidate the appropriateness of spontaneously voided urine or bladder washing in screening HPV infection in the urinary bladder. Urine and bladder washing samples were obtained from 201 patients who underwent transurethral bladder tumor resection. After extracting DNA from both samples, HPV-DNA was examined using a nested polymerase chain reaction with GP5+/6+ and MY09/11 primers. HPV genotyping was performed in the HPV-positive samples. In situ hybridization (ISH) was performed to observe the HPV-DNA localization in urothelial cells among cytological samples and paraffin-embedded tumor tissues in HPV-positive washing samples. HPV prevalence in urine and washing samples were 9.5% and 7.0%, respectively. High-risk HPV prevalence in urine and washing samples was 7.5% and 4.0%, respectively. The most common HPV type was HPV 16, followed by HPV 52 and HPV 18 in both samples. HPV type distribution in both samples was not in agreement (κ = −0.431). The ISH analysis revealed that HPV-DNA signal was observed in urothelial cells of five (55.7%) of nine detectable HPV-positive cytological samples. Six (66.7%) of nine HPV-positive cases had HPV-DNA signals in tumor tissue. The use of washing samples was likely applicable for investigating HPV prevalence in the urinary bladder. HPV-DNA detected in washing samples might be frequently derived from the urinary bladder.