Localization of prosaposin in rat cochlea

Prosaposin, the precursor of the sphingolipid hydrolase activator proteins called saposins A, B, C, and D, is abundant in the nervous system and muscles. Besides its role as the precursor of saposins, prosaposin is reported to function as a neurotrophic factor, initiating neural differentiation and preventing neuronal cell death in vivo and in vitro. In this study, we examined the localization and synthesis of prosaposin in the rat cochlea. Intense prosaposin immunoreactivity was observed in the organ of Corti, stria vascularis, and spiral ganglion. In an immuno-electron microscopic study, prosaposin immunoreactivity was found mainly in lysosomal granules of the cells in these regions. In the lysosome, prosaposin does not always colocalize with cathepsin D, but was localized mainly in the dark area of the lysosome. Prosaposin mRNA was observed in these same regions. Our results suggest that prosaposin plays a role in homeostasis in the peripheral auditory system.     

Pneumo- and neurotropism of avian origin Italian highly pathogenic avian influenza H7N1 isolates in experimentally infected mice

An experimental infection of mice was performed in order to investigate the potential for interspecies transmission in mammals of Italian HPAI viruses of the H7N1 subtype. Three avian origin isolates were selected, two strains obtained from ostrich (one of which contained a PB2-627 Lysine residue) and one from a chicken. Following intranasal infection of mice, clinical signs and mortality were recorded in the experimental groups challenged with the two ostrich isolates, while only weight loss was observed in those receiving the chicken strain. Viruses were recovered to a varying extent from respiratory and nervous tissues of infected animals. These results suggest that HPAI viruses, other than H5N1 and H7N7, may have zoonotic implications, and support the consensus that AI infections in poultry are to be eradicated rather than contained.     

Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice

Ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27 mediated by SCF-Skp2 ubiquitin ligase is involved in cell cycle regulation. Proliferation of tubular cells is a characteristic feature in obstructed kidneys of unilateral ureteral obstruction. Comparing Skp2(+/+) mice with Skp2(-/-) mice, we investigated the involvement of Skp2, a component of SCF-Skp2 ubiquitin ligase for p27, in the progression of renal lesions in unilateral ureteral obstructed kidneys. mRNA expression of Skp2 was markedly increased in the obstructed kidneys from Skp2(+/+) mice and peaked 3 days after unilateral ureteral obstruction. Renal atrophy, tubular dilatation, tubulointerstitial fibrosis, and increases in alpha-smooth muscle actin expression, the number of tubular cells, and proliferating tubular cells positive for Ki67 were observed in the obstructed kidneys from Skp2(+/+) mice; however, these findings were significantly attenuated in Skp2(-/-) mice. The p27 protein level was increased in the obstructed kidneys but was significantly greater in Skp2(-/-) mice. The number of Ki67-positive p27-negative cells was lower in obstructed kidneys from Skp2(-/-) mice than Skp2(+/+) mice, whereas that of Ki67-negative p27-positive cells was greater in Skp2(-/-) mice. These findings suggest that p27 accumulation, which results from SCF-Skp2 ubiquitin ligase deficiency in Skp2(-/-) mice, is involved in the amelioration of renal damage induced by obstructive nephropathy.     

Perception thresholds for electrical stimulation of the palatal mucosa

PURPOSE: To define the normative ranges of the Current Perception Threshold (CPT) of the palatal mucosa and to correlate it with the subjects' attributes. MATERIALS AND METHODS: A group of 129 informed healthy subjects consented to participate in the study. A Neurometer NS3000 device was used to evaluate the CPTs of the nasopalatine nerve (NPN) and the greater palatine nerve (GPN) by using 2000-, 250-, and 5-Hz stimulations. After confirming the relationships with regard to gender, age, weight, height, alcohol consumption, duration of sleep, weight percentage of water content, smoking, and CPT, the normative ranges of the CPT measurements were obtained. RESULTS: Correlations were observed between age and CPTs obtained with the 2000- and 250-Hz stimulations of the GPN. The CPTs of the GPN were higher than those of the NPN. With the exception of the 5-Hz stimulation of the NPN, the CPTs in men were higher than those in women; however, the within- and between-site ratios exhibited no differences between the male and female subjects. No significant effects of smoking and alcohol consumption on CPT were observed. Range analysis revealed an increase in the CPTs as the frequency increased from 5 to 250 to 2,000 Hz. Within-site ratio analysis revealed increasing and spreading CPT ratios in the following order: 250/5 Hz, 2000/250 Hz, and 2,000/5 Hz. In the order of 5-, 250-, and 2000-Hz stimulations, decreasing ratios were observed for the between-site ratio analysis. CONCLUSION: This study provides useful diagnostic criteria for CPTs in the palatal mucosa.     

Circadian rhythm of serum concentration of small dense low-density lipoprotein cholesterol

BACKGROUND: The atherogenicity of small dense low-density lipoprotein (sdLDL) has been reported and recently a new easy-handling method for measuring serum concentration of sdLDL cholesterol (sdLDLC) has been developed. Using this method, we observed the circadian rhythm of sdLDLC to determine the adequacy of fasting measurement of it and to seek the modulator of the atherogenic lipoprotein. METHODS: Study population was consisted of 20 healthy volunteers (10 women and 10 men, mean age 28 y). They had 3 meals per day and blood samples were taken before and 2 h after every meal and next morning. Serum concentrations of sdLDLC and other valuables including triglyceride (TG) and remnant-like particles cholesterol (RLPC) were determined. RESULTS: Serum concentration of sdLDLC had a unique circadian rhythm that was highest before breakfast (fasting status), decreased after each meal, hit the bottom after dinner and then increased during at night. Fasting sdLDLC was highly correlated with TG levels. The sum of the 6 TG values during a day (i.e., average TG level) had higher correlation coefficient with sdLDLC than fasting TG or fasting RLPC. CONCLUSIONS: From the observation of the unique circadian rhythm, measuring sdLDLC at fasting status is exactly reasonable because it never underestimate the risk of atherosclerotic diseases. Measuring sdLDLC can also be used as a marker for average TG levels regardless of the existence of postprandial hyperlipidemia.     

Girl with a PRRT2 mutation and infantile focal epilepsy with bilateral spikes

This paper documents the case of a female Japanese patient with infantile focal epilepsy, which was different from benign infantile seizures, and a family history of infantile convulsion and paroxysmal choreoathetosis. The patient developed partial seizures (e.g., psychomotor arrest) at age 14 months. At the time of onset, interictal electroencephalography (EEG) showed bilateral parietotemporal spikes, but the results of neurologic examination and brain magnetic resonance imaging were normal. Her seizures were well controlled with carbamazepine, and she had a normal developmental outcome. EEG abnormalities, however, persisted for more than 6 years, and the spikes moved transiently to the occipital area and began to resemble the rolandic spikes recognized in benign childhood epilepsy. Her father had paroxysmal kinesigenic dyskinesia, with an onset age of 6 years, and her youngest sister had typical benign infantile seizures. Genetic analysis demonstrated that all affected members had a heterozygous mutation of c.649_650insC in the proline-rich transmembrane protein-2 (PRRT2) gene. This case indicates that the phenotypic spectrum of infantile seizures or epilepsy with PRRT2-related pathology may be larger than previously expected, and that genetic investigation of the effect of PRRT2 mutations on idiopathic seizures or epilepsy in childhood may help elucidate the pathological backgrounds of benign childhood epilepsy.     

Prevalence and risk factor analysis of nephrosclerosis and ischemic nephropathy in the Japanese general population

Background

Nephrosclerosis/ischemic nephropathy (NS/IN) ranks third among renal diseases requiring dialysis in Japan. Although it is an important renal disease in terms of frequency, its prevalence, new incidence, and risk factors are not fully elucidated.

Methods

We analyzed the prevalence, incidence, concurrent diseases, and risk factors of NS/IN by using data from specific health checkups of Kumamoto citizens between 2008 and 2010.

Results

Although the prevalence of NS/IN was 1?2 % in people in their 40s, it increased sharply with age, reaching 17.6 % in people aged 70–74 years. The incidence of new NS/IN was 0.4?0.5 % per year. In multivariate logistic regression analysis, factors such as age, male gender, body mass index (BMI), hyperuricemia, hypertension, and dyslipidemia correlated with NS/IN. When risk factors associated with NS/IN progress were evaluated by multivariate logistic regression analysis, four factors—male gender, hypertension, BMI, and current smoking—significantly correlated.

Conclusion

The analysis of Kumamoto citizens aged 40–74 years receiving specific health checkups showed that in addition to hypertension and age that were considered important, male gender and obesity are also risk factors for NS/IS independent from hypertension.     

Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer

BACKGROUND: Helicobacter pylori affects gastric epithelium integrity by acceleration of apoptosis. However, it remains unclear what product of the bacteria causes apoptosis, or whether or not the apoptosis is involved in the development of ulcers. AIMS: To elucidate the factor from H pylori that causes acceleration of apoptosis and the role of apoptosis in the development of duodenal ulcer in H pylori infection. PATIENTS: Five H pylori negative healthy volunteers, 47 H pylori positive patients with duodenal ulcer, and 35 H pylori positive patients with gastric ulcer. METHODS: An endoscopic examination was carried out to diagnose ulcers and determine their clinical stage. To analyse apoptosis, a cell cycle analysis was performed using biopsy specimens. RESULTS: There was a significant correlation between the urease activity of the H pylori strain and the level of apoptosis induced by this bacterial strain. Moreover, in duodenal ulcer patients infected with H pylori, the patients with an active ulcer exhibited a significantly higher level of apoptosis than those with ulcers at both the healing and scarring stages. CONCLUSION: These findings suggest that acceleration of apoptosis in the antral mucosa caused by the urease of H pylori plays a crucial role in the development of ulcers in the duodenum.