Expression of CD163 in the liver of patients with viral hepatitis

CD163 is a marker of activated macrophages, and increased levels of soluble CD163 have been detected in sera obtained from patients with hepatitis. The aim of this study was to detect the expression of CD163 in the liver from patients with viral hepatitis. Frozen sections of liver specimens were obtained from 5 patients with acute viral hepatitis (AH) and from 23 patients with chronic viral hepatitis (CH). The expression of CD163 in the liver was determined immunohistochemically using monoclonal antibody to human CD163. Double immunostaining was done to assess those cell types that express CD163 in the liver. The frequencies of CD163-positive cells were significantly higher both in the portal areas and in the hepatic lobules in the liver of patients with AH compared to those with CH (p < 0.05). Double immunostaining revealed that most of the CD163-positive cells were macrophages and Kupffer cells, because they expressed CD68. The expression of CD163 was very low in endothelial cells and liver stellate cells. This study shows that macrophages are activated in hepatitis liver.     

Binocular visual function after surgery for detached retina

Binocular visual function after surgery for detached retina was examined in 100 patients with a visual acuity of less than 0.3 in the reattached retina and with a visual acuity of more than 1.0 in the non-detached retina:1) There was no significant sex difference in binocular visual function.2) There was no significant difference in binocular visual function according to postoperative interval.3) Maintenance of postoperative binocular visual function was best in patients under 19 years of age, and grew worse with age.4) In patients with a visual acuity of more than 0.1 in the reattached retina, simultaneous perception was good in 100%, and fusion in more than 80%. However, stereopsis was worse in most cases.5) In patients with a visual acuity of less than 0.1 in the reattached retina, all aspects of binocular visual function were worse, except in those under 19 years of age.6) There was no significant difference in binocular visual function between patients with and without temporary amputation of extrinsic ocular muscles at operation.7) There was no significant difference in binocular visual function between patients with and without macular detachment before operation.8) In the patients who had had an encircling operation, binocular visual function was worse than in those operated on with other procedures, because the former had the severest retinal detachment.     

Roles of metabolic and endocrinological alterations in atherosclerosis and cardiovascular disease in renal failure: another form of metabolic syndrome

Patients with end-stage renal disease have markedly increased risk for death from cardiovascular disease. Renal failure is associated with multiple metabolic and endocrinologic abnormalities, and these alterations are involved in advanced atherosclerosis and high cardiovascular risk. Increased insulin resistance index by homeostasis model assessment (HOMA-IR), a simple index of insulin resistance, was an independent predictor of cardiovascular mortality in nondiabetic patients on maintenance hemodialysis. Renal failure impairs lipoprotein metabolism leading to the atherogenic lipoprotein profile characterized by increased triglyceride-rich remnant lipoproteins such as intermediate-density lipoprotein, an independent factor of increased aortic stiffness. Non-high-density lipoprotein cholesterol, the sum of cholesterol of intermediate-density lipoprotein and other apoB-containing lipoproteins, is an independent factor associated with increased arterial thickness and a predictor of cardiovascular death in hemodialysis patients. The risk for cardiovascular death in hemodialysis patients is associated closely with hypertension and malnutrition, but not with obesity. The constellation of insulin resistance, dyslipidemia, hypertension, and malnutrition in renal failure suggests the presence of another type of metabolic syndrome promoting cardiovascular disease. In addition, vitamin D deficiency and abnormalities in calcium, phosphate, and parathyroid hormone levels increase the death risk from cardiovascular disease in renal failure. It is expected that treatment of these metabolic and endocrinologic alterations would improve the survival of patients with renal failure.     

Severe hyperreninemic hypertension associated with spontaneous renal cholesterol crystal embolization

A 70-year-old man was admitted because of severe hypertension and renal insufficiency. Marked elevation in plasma renin activity (PRA; 34.2ng/ml per h) was noted. Five days later, the patient developed hemorrhagic duodenal ulcers and panperitonitis, went into shock, and died. An autopsy revealed severe atherosclerosis with marked ulceration in the abdominal aorta. Renal histology showed multiple cholesterol crystal embolization (CCE) associated with infarction. Cholesterol crystals were also detected in the vessels of the gastrointestinal system, including the liver, stomach, colon, and pancreas. Although not common, spontaneous CCE should be considered in elderly patients who present with abrupt onset of severe hypertension associated with renal insufficiency. The most important finding in this patient was severe hyperreninemia. Although potentiation of the renin-angiotensin-aldosterone system is the suggested mechanism for the hypertension in renal CCE, we could not find any reported case of renal CCE with hyperreninemia. It is reasonable to consider that severe hyperreninemia might be overlooked in renal CCE. PRA should be measured in patients with renal CCE, because it may give important information for selecting antihypertensive agents and improving the prognosis. To clarify this possibility, an accumulation of similar cases is necessary.     

Death receptor 3 (DR3) gene duplication in a chromosome region 1p36.3: gene duplication is more prevalent in rheumatoid arthritis

The death receptor 3 (DR3) gene is a member of the apoptosis-inducing Fas gene family. In the current study, fluorescence in situ hybridization (FISH) and Fiber-FISH revealed the existence of a second DR3 gene approximately 200 kb upstream of the original DR3 gene. The existence of the duplicated DR3 gene was confirmed by sequencing the corresponding human artificial chromosome clones as well as with quantitative PCR that measured the ratio of the DR3 gene mutation (Rm), intrinsic to rheumatoid arthritis (RA) patients, by simultaneous amplification of the normal and mutated DR3 sequences. The DR3 gene duplication measured by FISH was found to be more frequent in patients with RA as compared to healthy individuals. We therefore surmise that the human DR3 gene can be duplicated and that this gene duplication is more prevalent in patients with RA.     

Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus

The phosphorylation of calcium/calmodulin-dependent protein kinase (CaMK) II, induced by an increase in the intracellular Ca2+ concentration, is involved in the alteration of brain functions such as memory formation. In the present study, we examined the influence of various immobilization stress paradigms on the phosphorylation of CaMKII (phospho-CaMKII) and CaMKII levels in the rat hippocampus. Immunoblot and immunohistochemical analyses were performed to examine the levels of CaMKII and phospho-CaMKII. Real-time quantitative polymerase chain reaction (PCR) was performed to analyse the mRNA levels of N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subtypes. Acute (single) and repeated (4 d), but not chronic (14 d), stress exposure of 45 min or longer duration significantly increased phospho-CaMKII levels without affecting the levels of CaMKII. Pre-treatment with NBQX, a selective AMPA receptor antagonist, significantly prevented this stress-induced increase. In contrast, two NMDA receptor antagonists, LY235959 and MK-801, showed no inhibitory effect on phospho-CaMKII levels during acute stress. Neither acute nor chronic stress changed mRNA levels of NMDA and AMPA receptors. These results demonstrate that immobilization stress promotes the phosphorylation of CaMKII. The increase in the intracellular Ca2+ concentration by the activation of AMPA receptors may play a role in the stress-induced phospho-CaMKII in the rat hippocampus.     

Evaluation of immunotoxic and immunodisruptive effects of inorganic arsenite on human monocytes/macrophages

A trivalent inorganic arsenic, arsenite, has been causing chronic inflammation in humans through the consumption of contaminated well water. The total peripheral blood arsenic concentrations of chronic arsenic-exposed patients, who had inflammatory-like immune responses, are less than 1 microM, thus, nM concentrations may be very important regarding the chronic inflammatory effects by arsenite. However, there are few reports about the biological effects of low concentrations of arsenite in mammalian cells, especially in normal immune effector cells. In this study, we examined whether arsenite has any biological and/or toxicological effects on the differentiation of human peripheral blood monocytes into macrophages using the colony-stimulating factor (CSF) in vitro compared with that of other metallic compounds, and found that arsenite sensitively inhibited the CSF-induced in vitro maturation of monocytes into macrophages at nM levels, and it also induced small, nonadhesive and CD14-positive abnormal macrophage generation from monocytes with granulocyte-macrophage CSF (GM-CSF) at 50-500 nM without cell death. The addition of other metallic compounds, including chromium, selenium, mercury, cadmium, nickel, copper, zinc, cobalt, manganese and other human pentavalent arsenic metabolites, such as inorganic arsenate, monomethylarsonic acid and dimethylarsinic acid, could not induce the same abnormal cell generation from monocytes with CSFs at any concentration and any additional time schedules; they showed only simple cytolethality in monocytes and macrophages at n-mM levels accompanied by cell death. This work may have implications in the arsenic-induced chronic inflammation in humans.