Spontaneous arterial baroreflex control of the heart rate during head-down tilt in heat-stressed humans

The purpose of this study was to elucidate the effect of raised body temperature per se during acute heat stress on the spontaneous arterial baroreflex control of heart rate (f _c) in humans. To investigate whether unloading of cardiopulmonary baroreceptors during whole-body heating would alter the arterial baroreflex control of f _c, we controlled loading of the cardiopulmonary baroreceptors by head-down tilt (HDT) at angles of 5°, 10°, 15°, and 30° during heat stress produced by hot-water-perfused suits. The sensitivity of the arterial baroreceptor-cardiac reflex was calculated from the spontaneous changes in beat-to-beat arterial pressure and f _c. As an index of cardiopulmonary baroreceptor loading, the left atrial diameter (LAD) was measured by echocardiography. During whole-body heating, the LAD decreased with the rising body core temperature and increased with the HDT. The decreased LAD during heating almost recovered to the normothermic control level by 10° HDT. In the supine position, cardiac baroreflex sensitivity remained unchanged during heating. Arterial pressure, f _c and cardiac baroreflex sensitivity were not changed by HDT ranging from 5° to 30° during heating. These results suggest that cardiac baroreflex sensitivity remain unchanged during graded loading of the cardiopulmonary baroreceptors in heat-stressed humans. Also, we conclude that the sensitivity of the spontaneous arterial baroreflex controlling the f _c is not influenced by raised body temperature per se during acute heat stress. Electronic Publication     

Long-term outcomes using vascular grafts sealed with fragmented autologous adipose tissue for aortoiliac occlusive disease

The aim of this study was to test the safety and efficacy of fragmented autologous adipose tissue (FAT) grafts for revascularization in aortoiliac occlusive disease. Twenty-seven patients with atherosclerotic aortoiliac occlusive disease underwent surgical treatment using FAT grafts. A piece of adipose connective tissue was obtained from the operative wound, cut into small pieces, and pressed into the wall of a fabric vascular prosthesis. Cumulative primary patency rates were 92% at 1 year, 92% at 3 years, and 86% at 6 years. Cumulative secondary patency rates were 96%, 96%, and 90% for the same intervals. In this clinical study, the FAT grafts demonstrated good long-term patency rates and no particular problems. This is the first clinical report of long-term outcomes using FAT grafts for aortofemoral or aortoiliac bypasses. FAT grafts are thus safe for revascularization in aortoiliac occlusive disease.     

Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.     

CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress exogenous FIV replication of their peripheral blood mononuclear cells in vitro

Summary.  Feline immunodeficiency virus (FIV) isolates from domestic cats have been classified into five subtypes, designated A, B, C, D and E. Although many FIV-infected cats may have frequent contact with multiple strains of FIV, they usually become infected with a single FIV subtype. In the present study, we demonstrate that peripheral blood mononuclear cells (PBMC) of FIV infected cats were resistant to exogenous FIV (second virus) replication in vitro and that the resistance of these PBMC was mediated by CD8⁺ T cells. In cats with a low anti-FIV activity of CD8⁺ T cells, the proviral DNA of the second virus inoculated into PBMC was detected intracellularly, and both the second and the originally infecting strain (original virus) were produced in the culture supernatant. In contrast, in cats with a high anti-FIV activity of CD8⁺ T cells, both the proviral DNA of the second virus and the original virus were detected in PBMC intracellularly, but neither virus was produced in the culture supernatant. However, when PBMCs from these cats were depleted of CD8⁺ T cells, the RNA of both viruses was detected in the culture supernatant. These results suggest that CD8⁺ T cells inhibit the late phase of FIV replication after viral integration. Moreover, the inhibition was also effective against FIV strains of different subtypes from that of the original strain. It appears that the CD8⁺ T cell-mediated immune response plays important roles in the maintenance of an asymptomatic state in FIV-infected cats and their resistance to superinfection. Received December 11, 2001; accepted March 22, 2002 Published online June 21, 2002     

Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimer''s disease. An immunoelectron microscopic study.

The fine structure of cerebral amyloid angiopathy, especially in small and presumably early deposits, was examined by immunolabeling of the beta/A4 protein in semithin and ultrathin sections from brains with Alzheimer's disease. The following findings emerged: 1) in large leptomeningeal arteries, small, focal amyloid deposits appear to consist of clusters of delicate (approximately 8 nm diameter) amyloid fibrils, not previously described, in the outermost part of the basement membrane (BM) at the media-adventitia junction; 2) in small leptomeningeal arteries and perforating cortical arterioles, small foci of delicate amyloid fibrils were observed within the BM. They appeared mostly in the outer portion of the BM, around intact smooth muscle cells, rather than in the subendothelial region. In larger and presumably more advanced deposits, coarse amyloid fibrils (approximately 10 nm) occupied the abluminal BM, and adjacent smooth muscle cells showed degeneration; and 3) in capillaries, small amounts of delicate (approximately 8 nm) amyloid fibrils, not previously described, were seen within the BM in the smallest discernible deposits. The BM at these sites was abnormally folded and layered. In larger deposits, amyloid fibrils appeared to extravasate from the outer BM of the capillary into the neuropil and were surrounded by astrocytic foot processes and/or microglia. Our results suggest that vascular amyloid fibrils may first be formed within the abluminal vascular BM, that is, outside of cells. The BM may trap degradative intermediates of the amyloid precursor protein that contain the beta/A4 region, and local proteases may then cleave them further to yield amyloidogenic fragments.     

Defective interleukin-1 production in a familial monocyte disorder with a combined abnormality of mobility and phagocytosis-killing.

Monocytes in a familial monocyte disorder, a recently recognized primary immunodeficiency syndrome, with impaired phagocytic functions were studied for their ability to produce interleukin 1 (IL-1) as well as the surface property. Monocytes from two children (siblings) with the disorder possessed CD11b, CD13, CD14, CD33, Ia and LFA-1/Mac-1/p150,95 beta subunit antigens as determined by flow cytometry. Electron microscopic cytochemistry showed that the monocytes had surface glycoproteins reactive with four representative lectins. The IL-1 production by monocytes was assayed in the two patients and compared with that in six children with primary immunodeficiency syndromes and some monocyte abnormalities; three had congenital neutropenia, two had hyper-IgE syndrome, and one had defective monocyte chemotaxis. Monocyte culture supernatants were prepared with stimulation by lipopolysaccharide or silica, and their IL-1 activity was measured by the mouse thymocyte-proliferation assay. The patients' monocytes were defective in IL-1 production: the values were less than 1.0% of the control monocyte values (n = 12) and were in contrast with those of congenital neutropenia monocytes of 186.2% to 204.3%. These results demonstrate a familial monocyte disorder which is characteristic among the immunodeficiency syndromes with regard to the defective IL-1 production and the impaired phagocytic functions.