Late onset type I familial amyloidotic polyneuropathy: Presentation of three autopsy cases in comparison with 19 autopsy cases of the ordinary type

Clinicopathological features of three autopsy cases of extremely rare late onset type I familial amyloldotic polyneuropathy were presented and compared with 19 autopsy cases of the ordinary type. In the late onset cases, the ages at onset and at death were 27.5 and 24.5 years older, respectively, compared with the ordinary type. Also, duration of the total clinical course form onset to death was 3.7 years less than in the late onset cases. The degree of amyloid deposition was more marked in the heart of the late onset cases, causing prominent cardiac hypertrophy. It was also marked In the kidneys or thyroid of two cases, but slight to moderate in the peripheral or autonomic nervous tissues in all cases. Immunohistochemical Investigation demonstrated the presence of transthyretin (TTR) as an amyloid precursor protein and of serum amyloid P-component in amyloid deposits in various organs and tissues of the late onset type. These findings, as well as serum levels of variant TTR, were similar to those of the ordinary type. These results suggest that there are some factors other than the amyloid precursor protein that effect the degree of amyloid deposition.     

Dynamics of gastrin-producing cells in the rat after truncal vagotomy. Evaluation by double immunostaining for bromodeoxyuridine and little gastrin.

The mechanism of hyperplasia of gastrin-producing cells (G-cells) in the rat antral mucosa after truncal vagotomy was studied using double immunostaining for bromodeoxyuridine (BrdU) and little gastrin (G17). With single labeling of BrdU, a few G-cells (less than 1%) showed positive immunostaining for BrdU in the nucleus throughout the experimental period in both vagotomized rats and those given a sham operation. The labeled cells in both groups demonstrated a linear increase of BrdU labeling in an identical number of cells for each experimental time-point. The labeling index of the G-cells increased rapidly from day 2 to day 6 and attained a maximum level of 44.0% on day 10 in the vagotomized group after cumulative labeling. Even in this group, however, many G-cells showed no BrdU immunoreactivity throughout the experimental period. These cells did not replicate during the experimental period, but showed an intense reaction product for G17 in their cytoplasm after vagotomy. The present study indicates that the most important factor involved in G-cell hyperplasia observed after truncal vagotomy is the activation of pre-existing G-cells to synthesize and release hormone, together with the rapid maturation of progenitor cells to mature G-cells.     

Direct measurement of phagosomal reactive oxygen by luminol-binding microspheres

A new method, utilizing microsphere-bound luminol, which makes possible the direct measurement of highly reactive oxygen within phagosomes, was studied. When Freund's complete adjuvant-elicited mouse peritoneal macrophages and luminol-binding microspheres were mixed, the microspheres were engulfed in macrophages and enclosed in phagosomes, where chemiluminescence (CL) was generated, showing the generation of highly reactive oxygen. The reactive oxygen could be quantitatively assayed by measuring the intensity of CL. The addition of cytochalasin B inhibited the CL. CL production by the thioglycollate-elicited macrophages was found to be only a ninth of that by Freund's complete adjuvant-elicited macrophages, though the phagocytic activities were almost equivalent in both cases.     

Overexpression of the Del1 gene causes dendritic branching in the mouse mesentery

In the present study, we established transgenic mice overexpressing Del1, a ligand of integrins, to examine the effect of overexpression of Del1 on vascular morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes consisting of a long stalk and short branches at the periphery. In contrast, those in transgenic mice showed typical dendritic architecture consisting of a few large primary branches with smaller spreading branches. The phenotype of mice overexpressing Del1 suggests the existence of a tissue-specific mechanism for branching morphogenesis in the mesentery.     

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats

The copper and Iron status in the liver of non-tumor bearing Long-Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely-bound copper and iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA-chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA-chelatable free copper was also higher in LEC rats than In LEA rats (P<0.05). But for the free iron level there was no signiflcant difference between the two rat groups (P>0.05). The formation of thiobarbituric acid-reactive substances was higher In LEC rats than In LEA rats (P<0.01). The 4–hydroxy-2–nonenal (HNE)-modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect In the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor-induction nor preneo-plastic lesions in the experimental LEC rats were observed. Therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important translation metals In the body, may participate In the Induction of DNA damage and oncogenesls     

The relationship of VEGF and PGE2 expression to extracellular matrix remodelling of the tenosynovium in the carpal tunnel syndrome

Tenosynovial thickening within the confined space of the carpal tunnel is thought to be the cause of the carpal tunnel syndrome (CTS). However, little is known about the pathological mechanism of tenosynovial thickening. In this study, the role of prostaglandin E(2) (PGE(2)) and vascular endothelial growth factor (VEGF) (two representative molecules that can induce oedema by increasing vascular permeability) was analysed in CTS by using immunohistochemistry and enzyme-linked immunosorptive assay (ELISA). Expression of these molecules was compared with the patients' clinical histories and a temporary increase in production of these molecules was found in cells within the vessels and synovial lining during the intermediate phase of the syndrome when the histology of the tenosynovium changes from oedematous to fibrotic. Statistical analysis clearly demonstrated that there is a close correlation between the expression of PGE(2) and VEGF. Furthermore, immunohistochemical analysis with anti-proliferating cell nuclear antigen (PCNA) revealed that the area with distinct VEGF expression closely matched the area where endothelial cells, vascular smooth muscle cells, and synovial lining cells proliferate. In contrast, despite marked alteration in the extracellular matrix (ECM) component of the tenosynovium, the fibroblasts responsible for most ECM framework production do not proliferate during any phase of CTS. Histological analysis demonstrated that angiogenesis takes place only during the intermediate phase. Since clusters of capillaries and arterioles are often surrounded by type III collagen-rich, disorganized, degenerate connective tissue, which contains fewer fibroblasts than normal, angiogenesis appears to take place as a part of a regenerative reaction that results in fibrosis. These findings strongly indicate that both PGE(2) and VEGF are expressed in the tenosynovium in CTS during the intermediate phase and induce the histological changes seen in the tenosynovium.     

Protective role of heme oxygenase-1 in renal ischemia

Oxidative stress, which has been implicated in the pathogenesis of ischemic renal injury, degrades heme proteins, such as cytochrome P450, and causes the elevation in the level of cellular free heme, which can catalyze the formation of reactive oxygen species. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is induced not only by its substrate, heme, but also by oxidative stress. In various models of oxidative tissue injuries, the induction of HO-1 confers protection on tissues from further damages by removing the prooxidant heme, or by virtue of the antioxidative, antiinflammatory, and/or antiapoptotic actions of one or more of the three products, i.e., carbon monoxide, biliverdin IXalpha, and iron by HO reaction. In contrast, the abrogation of HO-1 induction, or chemical inhibition of HO activity, abolishes its beneficial effect on the protection of tissues from oxidative damages. In this article, we review the protective role of HO-1 in renal ischemic injury, and its potential therapeutic applications. In addition, we summarize recent findings in the regulatory mechanism of ho-1 gene expression.