Takahiro Sakai

The presence of collagenase in Kupffer cells of the rat liver

Abstract Collagenase was first demonstrated as an active form in the Kupffer cells of the rat liver. The cells were isolated by the method of protease digestion and bovine serum albumin floatation. The activity was approximately three to five times higher than that of the rat granulocytes.

Demonstration of collagenase activity in rat liver homogenate.

Abstract Collagenase activity became detectable in rat liver homogenate by washing liver tissue repeatedly with buffered saline before homogenization. This enzyme activity was inhibited by adding minute quantities of serum. These data suggest that collagenase is active in situ in the liver, but is made inactive during the homogenization by forming a complex with contaminating serum factors.

Collagenase-like peptidase activity in fibrotic liver tissue

Abstract Activities of an enzyme capable of digesting carbobenzoxy-glycyl-prolyl-leucyl-glycyl-proline proved to be significantly elevated in fibrotic and cirrhotic human liver tissues, as well as in experimentally induced fibrotic rat liver tissues. Hydroxyproline content was also elevated.

Elastogenesis in the liver

It has been well established that Increase of elastic fibers Is a prominent feature In chronic liver diseases, especially in liver cirrhosis. Little is known, however, about the mechanism of the elastogenesis in liver tissue. As a result of histological examination of the pattern of elastic fiber formation in various kinds of liver diseases, it was concluded that elastogenesis in the liver tissue can be divided into two stages: first stage is proliferation of thin elastic fibers and second step Is remodeling of newly formed and preexistent elastic fibers. It seemed reasonable to conclude that the formation of thin elastic fibers was mainly related to proliferation of arteries and arterioles, from the observation of specimens, which were injected dye from the A. hepatlca. On the other hand, thick elastic fibers found in advanced liver cirrhosis, were supposed as the result of fusion and deformation of preexistent or newly formed thin elastic fibers. Chemical analysis of collagen and elastin of the liver tissues of various conditions showed that the ratio of elastin to collagen increased with the progress of liver fibrosis. These results suggested that elastic fibers in chronic liver diseases were not teleologlcally formed to some pathological condition, but were formed and accumulated as the result of some process.

A clinicopathologic study of fulminant hepatitis

We have carried out a clinicopathologic study of 59 patients with fulminant hepatitis who ranged in age from 18 to 80 years (male 25, female 34). Fifty-nine percent of the patients were above the age of 40 and the age distribution of the 34 women showed an increased incidence in both the younger and older age groups. Furthermore, significant preexisting disease or complication was present in 30 of 59 patients. The development of the disease may relate to host factors such as age, sex, hormonal status and general resistence. The etiology of the disease was presumed to be viral in 47 patients who included 17 following blood transfusion within the preceding six months and drug reaction in the remaining 12. The value of different laboratory data was analysed for early diagnosis of fulminant hepatitis. Most patients had progressive elevations of total bilirubin with a relative increase of unconjugated bilirubin, fluctuating levels of G O T and G P T ( G O T < G P T ) with abrupt falls of the serum transaminase near the coma, lowered concentrations of albumin and cholinesterase, slightly to striking elevations of alkaline phosphatase and LDH, leucocytosis and hypoglycemia. However, the most consistent markers of the severity or early diagnosis of the disease were prothrombin time, eFetoprotein and acute rapid turnover proteins such as Haptoglobin, cq-acidglycoprotein with short half-life time which were produced in the liver cells really. In liver-biopsy specimens of 6 patients surviving fulminant hepatitis, 2 patients showed subacute hepatic necrosis, but the other patients had mild liver damage without remarkable necrosis. Although the pathologic features of the disease are basically characterized by acute or subacute hepatic necrosis, there is fulminant hepatitis in part which the histological alterations do not necessary correlate well with the clinical features of the desease.

Biochemical Analysis of The Collagen from Cirrhotic Human Liver

ヒトの乙型硬変肝のコラーゲンを1M食塩(中性溶性コラーゲン),および0.5M酢酸(酸溶性コラーゲン)で抽出し,そのアミノ酸組成,糖含量および分子量を測定した.1) ヒトの硬変肝から抽出されたコラーゲンもカルボキシメチルセルロースクロマトグラフィーによりα1,α2およびβ12鎖に分離出来る.2) α1,α2鎖のアミノ酸組成は,ハイドロオキシプロリン,メチオニンが少なく,ハイドロオキシリジン,ヒスチジンが多い.α2鎖により多く塩基性アミノ酸が含まれている.3) α1,α2,β12鎖ともに糖含量が著しく多く,糖を介する基質との結合が,ヒトの硬変肝のコラーゲンの抽出を困難にしているものと考えられる.4) α1,α2鎖の分子量は103,000, 106,000と推定される.

Effect of 3,5,3’triiodothyropropionic acid on fibrotic rat liver

ConclusionThyroxine derivative, 3,5,3′-triiodothyropropionic acid, has some effect on collagen degradation and showed an inhibitory effect on development of rat liver fibrosis induced by swine serum injection.