Chronic persistent Epstein-Barr virus infection of natural killer cells and B cells associated with granular lymphocytes expansion

B lymphocytes and epithelial cells are the only cell types known to be infected with Epstein-Barr virus (EBV) in normal individuals. Rarely, EBV also infects other cells, including natural killer (NK) cells, almost always in the context of fatal leukaemias or lymphoproliferative disorders. We report on a 6-year-old previously healthy girl who developed fevers and liver function abnormalities for 3 months. The peripheral blood revealed an abnormal expansion of large granular lymphocytes, comprising 24% of the white blood cells. Flow cytometric analysis of the peripheral blood mononuclear cells showed an abnormal increase of CD16-positive NK cells, 62% of which were EBV-infected by in situ EBER-1 hybridization. The circulating B cells were normal in number, but 18% were infected with EBV by in situ EBER-1 hybridization. Approximately 2 years after resolution of all symptoms and continued good health, 35% of the circulating mononuclear cells were EBV-infected, indicative of persistent expansion of EBV-infected cells. We conclude that abnormal expansions of EBV-infected NK and B cells can be associated with a chronic benign course.     

Lipopolysaccharide-Induced Depressive-Like Behavior is Associated with α1-Adrenoceptor Dependent Downregulation of the Membrane GluR1 Subunit in the Mouse Medial Prefrontal Cortex and Ventral Tegmental Area

Background:

Chronic stress-induced depressive-like behavior is relevant to inflammatory immune activation. However, the neurobiological alterations in the brain following the central inflammatory immune activation remain elusive.

Methods:

Therefore, we investigated the neurobiological alterations during depressive-like behavior induced in mice by systemic administration of lipopolysaccharide (LPS; 1.2mg/kg administered twice at a 30-min interval via intraperitoneal injection).

Results:

At 24h after the second administration of LPS, an increased immobility time in the tail suspension test and the forced swimming test were observed, as well as reduced sucrose preference. Protein levels of the AMPA receptor GluR1 were significantly decreased at the plasma membrane in the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA), while levels of the GluR2 were increased at the plasma membrane in the nucleus accumbens (NAc) at 24h after LPS. However, total GluR1 and GluR2 protein levels in the mPFC, VTA, and NAc were not affected by LPS. Moreover, LPS facilitated release of noradrenaline in the mPFC and VTA, but not in the NAc. Consistently, systemic administration of prazosin, an α₁-adrenoceptor antagonist, blocked the LPS-induced downregulation of the membrane GluR1 subunit in both the mPFC and VTA and also blocked the upregulation of the membrane GluR2 subunit in the NAc. Intracerebroventricular administration of prazosin 30min before LPS injection abrogated the LPS-induced depressive-like behaviors. In opposition, administration of propranolol, a β-adrenoceptor antagonist, did not affect the LPS-induced downregulation of GluR1, the upregulation of GluR2, or the depressive-like behavior.

Conclusions:

These results suggest that LPS-activated α₁-adrenoceptor-induced downregulation of membrane GluR1 in the mPFC and VTA is associated with inflammation-induced depressive-like behavior.     

Asymptomatic chronic intestinal ischemia caused by idiopathic phlebosclerosis of mesenteric vein

Phlebosclerosis of the mesenteric vein is a rare condition causing chronic intestinal ischemia, it has only been reported in Japan. A 56-year-old man with liver cirrhosis and hepatic tumor presented with phlebosclerosis of mesenteric vein without any abdominal symptoms. He was admitted for examination of suspected hepatic tumor. Abdominal plain x-ray films and computed tomography revealed calcification of the mesenteric vein. Barium enema revealed narrowing and thumbprinting from the cecum to transverse colon. On colonoscopic examination, blue-black vessels were visible in the terminal ileum, and hyperemic nodular mucosa with small irregular ulcers surrounded by dark purple mucosa was found from the cecum to transverse colon. The etiology of mesenteric vein phlebosclerosis is unknown, although a physical mechanism rather than inflammatory changes appear to be involved in this rare and usually progressive condition of chronic intestinal ischemia.     

Effects of putrescine on D-galactosamine-induced acute liver failure in rats

We studied the effect of putrescine on acute liver failure caused in rats by two injections of 1 gm/kg D-galactosamine. The hepatic polyamine level rose only slightly in the D-galactosamine-injected rats treated with glucagon and insulin, and [3H]thymidine incorporation into DNA increased little; these hormones did not improve the survival rate. When D-galactosamine-injected rats were given putrescine, the putrescine concentration in the liver increased and the survival rate of the rats was significantly higher than that of control rats given only D-galactosamine. Putrescine administration tended to lower the serum level of alanine aminotransferase in rats injected with D-galactosamine, so the polyamine might have a protective effect on hepatocytes. Putrescine significantly increased [3H]thymidine incorporation in the liver; thus it accelerated liver regeneration. Difluoromethylornithine decreased the level of putrescine in the liver, decreasing both [3H]thymidine uptake and the survival rate. In the rats treated with D-galactosamine, in which liver damage was so severe that treatment with glucagon and insulin was ineffective, the intraperitoneal administration of putrescine increased the survival rate in acute liver failure. This probably resulted mainly from activation of liver regeneration and possibly from a protective effect of putrescine on the liver.     

An experimentally-induced acute hepatic failure model in various strains of mice

When BALB/cAJcl mice are intravenously injected with heat-killedPropionibacterium acnes (P. acnes) followed by an intravenous injection of lipopolysaccharide (LPS) 7 days later, massive necrosis is induced in the liver tissue and most of the mice die within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced in various strains of mice and the difference in the response was studied. As a result, as in BALB/cAJcl mice, acut hepatic failure was also induced in BALB/ cAJcl-nu, AKR/J, C3H/HeNJcl, C57BL/6NJcl and DDy mice. However, as an exception, hepatic cell necrosis was hardly seen and the survival rate was remarkable high in C3H/HeJ mice, which genetically do not respond to LPS stimulation. These results indicate that for this experimental induction of acute hepatic failure, macrophages must be activated by the two-step stimulation ofP. acnes and LPS.     

Immunohistochemical analysis of retinoblastoma gene product (pRB) expression in malignant and non-malignant liver diseases

ABSTRACT: The retinoblastoma gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To analyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene product and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene product were found in undamaged, nonregenerating liver tissues, whereas many hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distribution patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant positive correlation was found between the number of hepatocyte nuclei stained for retinoblastoma gene product per 1000 nuclei examined (R-LI) and the number of hepatocyte nuclei stained for DPA per 1000 nuclei examined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellular carcinoma specimens, R-LI was proportional to D-LI. Thus in both nonmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carcinoma cells.     

A Cross-sectional Survey of Patients with Suspected Diabetic Peripheral Neuropathic Pain in Japan

Objective The burden of diabetic peripheral neuropathic pain (DPNP) is poorly understood. The present study reported on the current status of DPNP in Japan, to improve our understanding of this condition among healthcare providers and inform future clinical research on its prevalence, diagnosis, and management. Methods A cross-sectional, observational study (UMIN000037023) was conducted via a web-based survey. The primary endpoints were the frequency of patients with bilateral foot symptoms, consulting a doctor, understanding DPNP, and reporting problems in daily life, as well as the treatment awareness of patients. Patients Adults ≥20 years old who were registered in the Rakuten Insight Disease Panel and receiving anti-diabetic therapy in Japan were included. Results Bilateral foot pain symptoms were reported by 1,768/7,754 (22.8%) respondents, most commonly intense numbness (13.0%). Of those with symptoms, 55.3% consulted a doctor; the most common reason for not seeking consultation was feeling that symptoms were insufficiently severe to bother their doctor (89.4%). Nearly 60% reported understanding the causes of their symptoms, with diabetes-associated neurologic deficits (58.8%) most commonly identified. About one-quarter reported daily life problems, including an inability to walk for long periods (58.3%) and feeling anxious (58.1%). Treatment awareness was reported by 18.2%; oral medications were commonly recognized (64.6%). Conclusion In Japan, 22.8% of patients with diabetes have bilateral foot pain symptoms; some experience problems in their daily life without understanding the causes of their symptoms. This supports the importance of actions to increase awareness and minimize DPNP-associated impairment of daily life in patients with diabetes.