Hematoma Size in Deep Intracerebral Hemorrhage and its Correlation with Dot-Like Hemosiderin Spots on Gradient Echo T2*-Weighted MRI

BACKGROUND AND PURPOSE: Dot-like low intensity spots (dot-like hemosiderin spots: dotHSs) on gradient echo T2*-weighted MRI have been histologically diagnosed to represent old cerebral microbleeds associated with microangiopathies. They have also been correlated to the fragility of small vessels and the tendency to bleed. Therefore, a substantial number of dotHSs might be associated with a large-sized, deep intracerebral hematoma (ICH). On the other hand, dotHSs may reflect old microbleeds that did not enlarge to symptomatic size. METHODS: To investigate how dotHSs are related to the size (maximal diameter) of primary deep ICH, we analyzed the diameter and the number of dotHSs in 151 patients with deep ICH not associated with subarachnoid hemorrhage or intraventricular hemorrhage (75 males and 76 females, age ranged from 37 to 90 [65.7 +/- 11.3 years old] who were consecutively admitted to Hakodate Municipal Hospital. The hazard ratio (HR) for a maximal diameter of deep ICH < or =2 cm was estimated, using the number of dotHSs and risk factors for stroke. RESULTS: The number of dotHSs associated with the diameter < or =2 cm was 9.2 +/- 11.5, significantly larger than that with the diameter > or =2 cm (4.7 +/- 7.0, P= .012). Multivariate analysis revealed that a maximal diameter of deep ICH of < or =2 cm was found in patients with dotHS (HR, 3.7; 95% confidence interval [CI], 1.4-10.1; P= .009). CONCLUSION: Though small sample size limited the power of our analyses, these findings suggest that the number of dotHSs may be associated with a small diameter of deep ICH.     

Monoclonal antibody analysis of glomerular, tubulo-interstitial infiltrating immune cells in various glomerulonephritis

To investigate the role of cell-mediated immunity (CMI) in glomerulonephritis (GN), we identified the infiltrating immune cells both within the glomerulus and in the interstitium. Frozen sections from 103 patients with various forms of GN: 10 with minor glomerular abnormality (MGA) as control, 10 with minimal change nephrotic syndrome (MCNS), 10 with membranous nephropathy (MN), 9 with focal glomerulosclerosis (FGS), 30 with IgA nephropathy (IgAN), 22 with acute post streptococcal glomerulonephritis (APSGN), and 2 with rapidly progressive glomerulonephritis (RPGN) were examined using monoclonal antibodies (MoAb) by indirect immunoalkaline-phosphatase labelling. In most glomerulonephritis, monocyte/M phi and helper/inducer T cells were predominantly infiltrating in the interstitium, but intraglomerular infiltration was rare, except for APSGN. This interstitial infiltration increased proportionally to the level of serum creatinine, and was most prominent in RPGN. Apparently different distribution was seen in APSGN, that is, prominent increase in total number of intra-glomerular monocyte/M phi infiltration with slightly increased T cells. The change was correlated with time after onset; namely the more leucocytic infiltration was observed when the tissue was taken earlier. These data suggest that in APSGN, monocyte/M phi accumulate in glomeruli via cell mediated immunity in addition to humoral immune mechanism resulting in glomerular hypercellularity, whereas in most chronic glomerulonephritis interstitial leucocyte infiltration, particularly helper T cells and monocyte/M phi may play an important role in the progression of glomerulonephritis.     

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.     

Effects of cepharanthin on neutrophil chemotaxis, phagocytosis, and reactive oxygen species generation.

The effects of cepharanthin on inflammatory parameters such as neutrophil chemotaxis, phagocytosis and reactive oxygen species (ROS) generation, were examined. Cepharanthin significantly decreased the levels of O2-, H2O2, and OH. generated by neutrophils. H2O2 and OH. generated in a cell-free, xanthine-xanthine oxidase system were also reduced in the presence of cepharanthin. However, the drug did not affect neutrophil chemotaxis or phagocytosis. The present study indicates that cepharanthin is an effective ROS scavenger, exerting its anti-inflammatory action by reducing the potent ROS species excessively generated in tissues and organs, especially at the sites of inflammation.     

Prevention of Restenosis after Coronary Angioplasty with Low-Density Lipoprotein Apheresis

Abstract: A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.     

Immunohistochemical detection of imidazolone, a novel advanced glycation end product, in kidneys and aortas of diabetic patients.

To investigate the role of the Maillard reaction in the pathogenesis of diabetic complications, we produced several clones of monoclonal antibodies against advanced glycation end products (AGEs) by immunizing mice with AGE-modified keyhole limpet hemocyanin, and found that one clone (AG-1) of the anti-AGE antibodies reacted specifically with imidazolones A and B, novel AGEs. Thus, the imidazolones, which are the reaction products of the guanidino group of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, were found to be common epitopes of AGE-modified proteins produced in vitro. We determined the erythrocyte levels of imidazolone in diabetic patients using ELISA with the monoclonal anti-imidazolone antibody. The imidazolone levels in the erythrocytes of diabetic patients were found to be significantly increased as compared with those of healthy subjects. Then we studied the localization of imidazolone in the kidneys and aortas obtained from diabetic patients by immunohistochemistry using the antibody. Specific imidazolone immunoreactivity was detected in nodular lesions and expanded mesangial matrix of glomeruli, and renal arteries in an advanced stage of diabetic nephropathy, as well as in atherosclerotic lesions of aortas. This study first demonstrates the localization of imidazolone in the characteristic lesions of diabetic nephropathy and atherosclerosis. These results, taken together with a recent demonstration of increased serum 3-DG levels in diabetes, strongly suggest that imidazolone produced by 3-DG may contribute to the progression of long-term diabetic complications such as nephropathy and atherosclerosis.     

Oscillator mechanism of Notch pathway in the segmentation clock.

Somites are formed by periodic segmentation of the presomitic mesoderm (PSM). This periodic event is controlled by the segmentation clock, where Notch signaling plays an essential role. The basic helix-loop-helix factor Hes7, a Notch effector, is cyclically expressed by negative feedback and regulates cyclic expression of Lunatic fringe (Lfng), a Notch modulator. Lfng then seems to periodically inhibit Notch, leading to oscillation in Notch activity. It is thought that these coupled negative feedback loops by Hes7 and Lfng are important for sustained and synchronized oscillations in the PSM. Of interest, another Notch effector, Hes1, is cyclically expressed by many cell types such as neuroblasts, suggesting that this clock is widely distributed and regulates many biological events. This review summarizes the recent finding about roles and mechanism of Notch signaling in the segmentation clock and discusses the significance of Hes1 oscillation in non-PSM cells.     

Dotlike Hemosiderin Spots Are Associated With Past Hemorrhagic Strokes in Patients With Lacunar Infarcts

BACKGROUND AND PURPOSE: Dotlike hemosiderin spots ongradient-echo T2(*)-weighted magnetic resonance imaging of the brain have been histologically diagnosed as old microbleeds associated with small vessel disease (SVD). The authors hypothesize that the presence of many dotHSs may be correlated with the fragility of small vessels and the recurrence of SVD, including lacunar infarction and deep intracerebral hemorrhage (ICH). METHODS: To investigate how dotHSs are related to past history of SVD, the number of subcortical or deep dotHSs was investigated in 146 patients with lacunar infarctions (95 men, 51 women, age 38 to 90 [66.6+/-9.4] years). They were divided into 2 subgroups according to history of deep ICHs or lacunar infarctions. The odds ratio (OR) for past history was estimated from logistic regression analyses with the number of subcortical or deep dotHSs as well as other factors. RESULTS: Of 146 patients with lacunar infarctions, 11 had past symptomatic ICHs and 19 had past symptomatic lacunar infarctions. An elevated rate of history of ICH was found for lacunar infarction patients with many deep dotHSs (>or=3; OR, 9.1; 95% confidence interval, 1.6-51, P=.015). However, history of lacunar infarction was not significantly associated with the number of subcortical or deep dotHSs. CONCLUSIONS: Our findings suggest that many deep dotHSs on T2(*)-weighted magnetic resonance imaging may be correlated with deep ICH-lacunar infarction type of SVD recurrence but not lacunar infarction-lacunar infarction type.