Hepatic histopathologic range compared with virological studies of hepatitis viruses among autopsy cases in Tokyo.

Few reports exist comparing virological studies on hepatitis viruses with histopathological studies of autopsy cases other than those of liver clinics. Relations between hepatitis virus-related markers and hepatic histopathology were studied in 1044 autopsy cases (779 men and 265 women) at the Medical Examiner's Office, Tokyo. Heart blood was obtained at the autopsy, and the sera were submitted for virus-marker detection of HBV, HCV, and HGV/GBV-C. Hematoxylin and eosin-stained paraffin sections were used for histological assessment. Histopathologically, 463 cases were determined as so-called normal liver; among them 440 cases (95.0%) were negative for all hepatitis virus-related markers, but HBV-DNA was positive in 13 cases, three cases were positive for HCV-RNA (indicating a healthy carrier rate of HCV-RNA of 4.1%), and seven cases were positive for HGV/GBV-C RNA. The incidence of these three virus-related markers was low in cases with fatty liver and micronodular cirrhosis, but in cases with chronic hepatitis, macronodular cirrhosis and hepatocellular carcinoma, the incidence of HBV-DNA and HCV-RNA increased with advancing disease. A positive rate of anti-HBs or anti-HBc (HBV-Ab) or both was found between 30 and 50% in all histopathological groups, and no noticeable relations between the positive rate and microscopical changes were detected. The presence of HGV/GBV-C RNA seemed to be unrelated to hepatic inflammation or generalized inflammatory changes or both occurring together. The decadal age incidence of the virus-related markers and their incidence in various hepatic diseases are also reported.

Syntheses of glycine and L-serine by their interconversion in the posterior silkgland of the silkworm, Bombyx mori.

It was observed by solution-state 13C NMR spectroscopy that a great portion of the 13C of [1-13C]L-serine fed to the 5th instar larvae of the silkworm, Bombyx mori was incorporated into C1 of glycine in silk fibroin. [1-13C]Glycine was detected along with [1-13C]serine in fibroin of the posterior silkgland cultured in a medium containing [1-13C]serine. This formation of [1-13C]glycine was inhibited by addition of aminopterin to the culture medium. These findings suggest that an active conversion from serine to glycine, which needs tetrahydrofolate, occurs in the posterior silkgland for fibroin synthesis. Moreover, the solid-state 13C CP/MAS spectrum of the fibroin prepared from cocoons spun by larvae fed with [13C]formate revealed that serine C3 was labelled specifically with 13C, suggesting that the reverse conversion from glycine to serine took place in the silkworm. The posterior silkgland has the ability to synthesize not only fibroin but also its major materials, glycine and serine.

Slightly elevated blood pressure as well as poor metabolic control are risk factors for the progression of retinopathy in early-onset Japanese Type 2 diabetes.

Not a few patients in Japan with early-onset type 2 (non-insulin-dependent) diabetes become blind due to proliferative diabetic retinopathy (PDR). However, the risk factors are poorly understood. The aim of this study was to determine the risk factors for background diabetic retinopathy (BDR) and PDR by following 394 Japanese patients with early-onset type 2 diabetes diagnosed before 30 years of age (mean age 27, mean blood pressure at entry 116/73 mm Hg). Of the 322 patients who were free of diabetic retinopathy at entry, 88 developed BDR, giving an incidence of 57.7 (95% CI 55.5-60. 0)/1000 person-years. Cox proportional hazard analysis revealed mean HbA(1c) and duration of diabetes to be significant predictors of development of BDR. Of the 160 patients with BDR, i.e., the 72 patients who had BDR at entry and the 88 who developed BDR during the follow-up, 50 developed PDR, giving an incidence of 17.9 (95% CI 13.6-23.6)/1000 person-years. Cox proportional hazard analysis indicated mean HbA(1c) and diastolic blood pressure to be significant predictors of the progression from BDR to PDR. In conclusion, in early-onset Japanese type 2 diabetic patients, the rates of both development of BDR and of progression from BDR to PDR appear to be potentially high. Not only lifetime exposure to glycemia but also a slightly elevated blood pressure level is an important risk factor for progression to PDR.

Chronic inhalation toxicity and carcinogenicity studies of 3-chloro-2-methylpropene in BDF1 mice.

Chronic toxicity and carcinogenicity studies of 3-chloro-2-methylpropene (CMP), which has been widely used as an insecticide and chemical intermediate, were carried out in BDF1 mice. CMP was administered to mice in groups of 50 male and 50 female mice by the inhalation route 5 days per week for 104 weeks at doses of 0, 50, 100 or 200 ppm. Male and female mice in the CMP-exposed groups had decreased body weight but no noticeable clinical signs when compared with the control group. Dose-related increases in the incidences of gastric mucosal hyperplasia and squamous cell papilloma were observed in both sexes, and squamous cell carcinoma was observed in only one male mouse in the 100 ppm group. An increased incidence of Harderian gland adenoma in female mice was also recognized. In the nasal cavity, eosinophilic exudate associated with atrophy of olfactory epithelia, respiratory metaplasia of olfactory epithelia and olfactory gland, and eosinophilic changes in respiratory and olfactory epithelia were increased in both sexes.

Liver weight of adult Japanese, especially recent weight values.

Cases of 445 adult Japanese autopsies of the Tokyo Metropolitan Medical Examiner's Office were used in this study. They were either negative for all hepatitis virus-related markers examined or had little or no histopathological hepatic changes. The maximum liver weight was observed in the fifth decade in both sexes, and after the fifth decade the liver weight decreased markedly with increasing age. The sexual difference in the liver weight was most predominant in the third to fifth decades, but the sexual difference was not marked in the older age groups. The highest liver weight to body weight ratio was observed in the fifth decade of both sexes, and a total decadal pattern of the ratio was similar to a parabola. An interesting finding was that the male liver weights in the third to fifth decades considerably increased in recent years, but the female liver weights in the third decade were almost the same despite the difference in investigation period. We suggest the data of this study may be a standard for Japanese people.

Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan.

BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis affect the incidence of diabetic vascular complications is unknown. That both type 1 and type 2 diabetes occur in the young Japanese population prompted us to investigate whether the type of diabetes and the year of diagnosis are related to the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578 (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620 (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy was analyzed in the patients according to postpubertal duration and year of diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%, 95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic patients has declined during the past two decades, whereas it has not among type 2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.

Biosynthesis of L-alanine, a major amino acid of fibroin in Samia cynthia ricini.

The derivation of alanine in fibroin was investigated using NMR and selective isotopic labelling. 2H2O infused orally into 5th instar larvae was incorporated into the proton of the methyl group of alanine in fibroin. Proton exchange among alanine, glycine and serine was also found. Incorporation of 13C from [2-(13)C]acetate into alanine C2 and C3 and glycine C2 in fibroin, and also C4 of free glutamine plus glutamate was observed in vivo. Hemolymph contained a peak for C4 of glutamate plus glutamine, and an alanine C3 peak appeared transiently. Thus, it is suggested that the C-skeleton of alanine formed was derived from L-malate via the TCA-cycle, and that this alanine is utilized in part for fibroin synthesis. Spectra of the hemolymph extract of larvae infused orally with [15N2]urea showed no 15N-compounds, whereas those of larvae injected subcutaneously showed only one peak of urea, whose intensity decreased with time, as shown in the in vivo spectra of a living larva infused with [15N2]urea. The solution NMR spectrum of fibroin showed no 15N-labelled compounds. Temporal changes in the peak intensities of six compounds in the spectra of a living larva infused with [15N]ammonium demonstrated a process in which 15N was incorporated into fibroin containing 15N-alanine through the amide group of glutamine and the amino group of glutamate. Thus, alanine biosynthesis from the TCA-cycle originates mainly from water, L-malate and ammonium. The fact that no 15N-urea was detected in the hemolymph extract of larvae infused with [15N]ammonium suggests that 15N-urea found in the above in vivo spectra may be that accumulated in the hindgut. Thus, excess ammonium in the body causes the production of urea by the urea-cycle. In Samia larvae, urea was not reutilized but excreted. The metabolic relationships between the assimilation of ammonium and the function of the urea-cycle are discussed.

Serum and urinary concentrations of heparan sulfate in patients with diabetic nephropathy.

BACKGROUND: Heparan sulfate (HS) contributes to the negative charge in the glomerular basement membrane (GBM), which may maintain the GBM charge barrier. Changes in sulfation and/or the concentration of HS may be associated with the development of diabetic nephropathy. METHODS: Using two different antibodies specific for HS chains, one that reacts with the N-sulfated sequences in HS chains (10E4) and the other that reacts with neo-epitope of HS, which occurs after heparitinase digestion of HS chains (3G10), we examined the serum and urinary concentrations of HS by enzyme-linked immunosorbent assay and performed immunohistochemical staining of glomeruli in diabetic patients with and without nephropathy. RESULTS: The level of urinary excretion of 10E4 binding HS/creatinine clearance was significantly reduced in diabetic patients when compared with that in nondiabetic subjects (P < 0.0001), and the level was more decreased in patients with overt nephropathy than in patients without overt nephropathy. No differences or only small differences were found between these groups in serum and urinary 3G10-binding HS and in serum 10E4-binding HS. Immunohistochemical staining with these antibodies was consistent with the findings in the urine. CONCLUSIONS: The results suggest that a decreased HS N-sulfation exists in the urine, which may reflect a structural change or an altered processing of HS within the GBM. Because N-sulfation plays a key role in determining the extent of sulfation within the HS chains, the decreased urinary 10E4-binding HS may have potential implications with regard to the development of diabetic nephropathy.

High incidence of diabetic nephropathy in early-onset Japanese NIDDM patients. Risk analysis.

OBJECTIVE: Because early-onset Japanese NIDDM patients (diagnosed before age 30 years) can develop diabetic end-stage renal failure (ESRF) in their thirties, this study was performed to elucidate the incidence and determinants for the development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: The incidence of diabetic nephropathy and its relationship to baseline characteristics and long-term metabolic control were determined in 426 early-onset Japanese NIDDM patients who were followed for a mean of 6.8 years. RESULTS: Of these 426 patients, 41 developed diabetic nephropathy manifested by persistent proteinuria (incidence rate [95%CI]/1,000 person-years; 14.1 [10.4-19.1]). Among patients whose mean HbA1c (measured by a high-performance chromatography method that is standardized and comparable to the one used in the Diabetes Control and Complications Trial study) was around 7% or less, few developed nephropathy. The incidence of nephropathy increased with increasing mean HbA1c level in a dose-dependent manner (chi 2 trend = 49.9, P < 0.0001). Diastolic blood pressure and duration of diabetes at entry had significant predictive effects independent of metabolic control. CONCLUSIONS: The incidence rate of diabetic nephropathy in early-onset Japanese NIDDM patients is potentially high, similar to or higher than that in Pima Indian NIDDM or Caucasian IDDM patients of comparable age. Diabetic nephropathy in NIDDM patients aged in their thirties or forties is likely to be an early feature that leads to ESRF, and this would contribute to the marked increase in the number of new patients with diabetic ESRF in Japan. NIDDM is a serious disease if near-normal glycemia is not achieved.

Infection with GB virus C, hepatitis C and B viruses in 1,044 cases autopsied at the Medical Examiner's Office in Tokyo.

Markers of GB virus C (GBV-C), hepatitis C virus (HCV) and hepatitis B virus (HBV) were sought in sera from 1,044 cases autopsied at the Medical Examiner's Office, Tokyo Metropolitan Government. GBV-C RNA was detected in 35 (3%) cases at a frequency significantly higher (P < 0.05) than in blood donors in Tokyo (4 of 448 or 1%). Three genotypes of GBV-C provisionally designated G1, G2 and G3 were determined by selective amplification with type-specific primers, and G3 (Asian type) was detected in 31 (89%), G2 (European/American type represented by the prototype hepatitis G virus) in three (9%) and G1 (West African type represented by the prototype GBV-C) in one (3%). Antibody to HCV (anti-HCV) was detected in 116 (11%) cases and accompanied by HCV RNA in 88. HCV genotypes were I/1a in one (1%), II/1b in 55 (63%), III/2a in 17 (19%) and IV/2b in 13 (15%). Antibodies to hepatitis B virus (HBV) was detected in 335 (32%) cases and hepatitis B surface antigen in 14 (1%). Subtypes were determined in 12 of them, adw was found in seven (58%), adr in four (33%) and adyr in one (8%). GBV-C RNA was detected significantly more frequently (P< 0.01) in the cases with liver disease (9 of 70 or 13%) than in those with the other causes of death (26 of 974 or 3%). Anti-HCV was more frequent in the cases with GBV-C RNA than in those without it (15 of 35 or 43% vs. 101 of 1,009 or 10%, P< 0.001). These results indicate that infection with GBV-C as well as HCV was common, while infection with HBV was not common in the Medical Examiner's autopsy cases in Tokyo.

Existence of early-onset NIDDM Japanese demonstrating severe diabetic complications.

OBJECTIVE: To identify the clinical characteristics of early-onset NIDDM patients with severe diabetic complications. RESEARCH DESIGN AND METHODS: The clinical cases of a large number of diabetic patients who visited a diabetes center within the period 1970-1990 were reviewed. Of a total of 16,842 diabetic patients, 1,065 (6.3%) had early-onset NIDDM (diabetes diagnosed before 30 years of age). These 1,065 patients were divided into two groups, those who developed proliferative retinopathy before the age of 35 (n = 135) and those who did not (n = 930). Development of proliferative retinopathy, nephropathy, renal failure, blindness, and atherosclerotic vascular disease were compared between the two groups. RESULTS: The subgroup of 135 patients was characterized by poor glycemic control, often requiring insulin therapy and a higher familial prevalence of diabetes, and contained a greater proportion of women than the subgroup of 930 patients. Of the 135 patients, 99 (67%) developed proliferative retinopathy before the first visit. The 135 patients developed severe progressive complications in contrast to the 930 patients. A total of 81 patients (60%) developed diabetic nephropathy at a mean age of 31 years, 31 (23%) developed renal failure requiring dialysis at a mean age of 35 years, 32 (24%) became blind at a mean age of 32 years, and 14 (10%) developed atherosclerotic vascular disease at a mean age of 36 years. CONCLUSIONS: Some Japanese early-onset NIDDM patients develop severe diabetic complications in their youth. Most of them had no symptoms nor regular treatment regarding diabetes until they were noticed to have developed severe diabetic complications. Although the relevant prevalence and the pathogenetic mechanism underlying the rapid onset of the complications remain to be determined, prolonged inadequate treatment of and familial predisposition to diabetes may be contributing factors. Careful diabetes care in the twenties, not only for IDDM but also for NIDDM patients, is warranted.

Alcohol-related sudden death with hepatic fatty metamorphosis: a comprehensive clinicopathological inquiry into its pathogenesis.

To clarify the pathogenesis of the widely known but obscure syndrome of sudden death with hepatic fatty metamorphosis observed in alcohol abusers, we have scrutinized both the clinical and pathological data of 11 subjects who died under such circumstances between 1987 and 1993. Death followed several days of uninterrupted drinking often with little dietary intake. The notable clinical features on arrival at the emergency room were disturbance of consciousness (11/11), hypotension (4/6), hypothermia (3/5), hypoglycaemia (8/11), metabolic acidosis (6/6), renal dysfunction (11/11), and hyperammonaemia (5/5). The common hepatic pathology was the extensive appearance of numerous microvesicular fatty droplets in the hepatocytes together with varying degrees of macrovesicular fatty change; four subjects had an underlying cirrhosis. Death undoubtedly results from a variety of metabolic disturbances triggered by the combination of massive ethanol intake and starvation. The appearance of extensive microvesicular fatty change superimposed on macrovesicular fatty change was considered to be an associated phenomenon.

Epidemiological and clinical features of Budd-Chiari syndrome in Japan.

The Japanese Ministry of Health and Welfare Research Committee on Aberrant Portal Blood Flow carried out an epidemiological survey and clinical study on Budd-Chiari syndrome in 1990. In the primary survey for determining the prevalence of the disease, a questionnaire was sent to all major hospitals throughout Japan and 160 cases seen in 1989 were compiled. More epidemiological details were obtained in 87 of these 160 cases. The number of patients with Budd-Chiari syndrome in this country was estimated to be about 300 (prevalence of 2.4/million) with about 20 new cases occurring every year. In the clinical study, 157 authentic cases of Budd-Chiari syndrome studied in 15 years (1975-89) were analyzed. There were 87 males (average age, 36.4 years) and 70 females (46.5 years), and the average period from the likely onset to the first medical consultation was 6.6 years, suggesting that these patients were mostly chronic cases. The main clinical features were hepatomegaly, leg edema, ascites and venous dilatation over the trunk. Abdominal pain was recorded in only four (2.5%). There were 16 (10.2%) with known identifiable etiologies. Of the patients 93% showed an obstructing lesion of various thickness in the hepatic portion of the inferior vena cava. Only nine (5.7%) had hepatic vein obstruction without caval lesions. Thus, the majority of Budd-Chiari syndrome patients in Japan are idiopathic, having an obstructing lesion in the inferior vena cava. The main causes of 33 deaths (21%) were liver failure, variceal bleeding and hepatocellular carcinoma. Hepatocellular carcinoma occurred in 10 (6.4%) in the 15-year period. However, the incidence of Budd-Chiari syndrome among all cases of hepatocellular carcinoma was less than 1% in the survey made by the Liver Cancer Study Group of Japan.

Successful resection of a large hepatoblastoma in a young adult: report of a case.

Hepatoblastoma (HB) rarely occurs in adults, and very few cases of successful resection have been documented. We report herein the unusual case of a 22-year-old, otherwise healthy woman with no history of liver disease who presented with upper abdominal pain and hepatomegaly. Tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative, but the AFP was mildly elevated at 77 ng/ml, the normal being < 20. There was no evidence of liver cirrhosis on either the laboratory or histologic examinations. A well-demarcated solid mass of 14 cm in diameter, which was lobulated and partly necrotic, was detected in the liver by computed tomography (CT). The lesion was echogenic on ultrasound, slightly hypodense on CT, and mildly hypervascular on arteriogram. The entire tumor was resected by extensive hepatectomy preserving only the lateral segment and part of the posterior segment of the liver. Histologically, the neoplasm was diagnosed as a pure epithelial HB of the fetal type. Following the operation, the patient has been well and free of recurrence for 38 months, maintaining low alpha-fetoprotein (AFP) levels at around 5 ng/ml. To our knowledge, this is the longest reported survival of an adult following surgical resection of an epithelial HB.

Histopathological study of intrahepatic aberrant vessels in cases of noncirrhotic portal hypertension.

Aberrant vessels, which are defined as dilated blood vessels immediately adjacent to the peripheral portal tract, appear under conditions of extrahepatic portal obstruction and nodular regenerative hyperplasia as well as idiopathic portal hypertension. Our study was undertaken to compare their morphological aspects in these three disease cases. Aberrant vessels were found in 84% of cases of idiopathic portal hypertension, 67% of cases of extrahepatic portal obstruction infantile type, 78% of cases of extrahepatic portal obstruction adult type and 83% of cases of nodular regenerative hyperplasia. They were divided into three types: type I--no communication with the portal vein, the lumen of which is normally open; type II--communication with the portal vein; and type III--no communication with the portal vein, which is occluded. The most common types of aberrant vessel were type III in idiopathic portal hypertension (51%), type I in extrahepatic portal obstruction infantile type (46%), type II in extrahepatic portal obstruction adult type (43%) and type III in nodular regenerative hyperplasia (45%). Serial sections revealed transition between types I, II and III, at frequencies between types II and III, types I and II, and types I and III of 35.7%, 33.7% and 30.6%, respectively. Aberrant vessels demonstrated the same immunoreactivity as portal veins for collagen type IV, laminin, factor VIII and ulex europaeus agglutinin-I. They were concluded to arise from the vasa septalis or inlet venules, which would be used as intrahepatic shunts draining portal blood flow blocked by stenosed portal veins. Increased portal pressure would be expected to enhance development of aberrant vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

[A national surveillance study on alcoholic liver disease in Japan (1986-1991)].

National surveillance studies on alcoholic liver disease (ALD) in Japan were performed in 1978 and 1985, by a previous Japanese study group for ALD (Takeuchi group). In the present study, a subsequent nationwide surveillance study was performed from 1986 to 1991 and the results were compared with the previous two studies. In order to clarify the etiological relationships between hepatitis C virus (HCV) infection and ALD, an analysis was also done according to the new diagnostic criteria of ALD which was proposed by this group (Takada group). By the criteria of the Takeuchi group, the incidence of ALD was not significantly different during 1986 to 1991. However, the incidence of hepatocellular carcinoma (HCC) in alcoholic cirrhosis (AL-LC) clearly increased during this period. The analysis including the results of the previous study indicate that incidence of ALD reached a plateau in 1980 and then features of ALD in Japan entered a stable stage. However, HCC in AL-LC continued to show a linear increase from 1976 to 1991. Analysis with the new criteria of the Takada group was done in cases of 1990 and 1991. Approximately 2 out of 3 cases of ALD were caused by alcohol alone, and the remaining cases were caused by a combination of alcohol and HCV. Cases caused only by HCV were very rare. The main etiology in patients with alcoholic hepatitis and fibrosis was alcohol alone and that in chronic hepatitis of heavy drinkers was a combination of alcohol and HCV. In half of the patients with AL-LC, the etiology was alcohol alone and in the other half patients, it was a combination of both factors. In most patients with HCC, the etiology was a combination of alcohol and HCV, indicating that HCV infection may be important for the development of HCC in alcoholics.

[Liver cirrhosis, its definition and classification--from a morbid anatomical point of view].

Cirrhosis of the liver is a principally a morphological entity, and it has been assumed to be an end-stage condition of all chronic active liver diseases. Morphologically, liver cirrhosis can be defined briefly as "a pathological condition characterized by diffuse pseudonodule formation throughout the entire liver". Fundamental pathogenetic changes in the cirrhotic process are hepatic necrosis, increase of connective tissue and regeneration of hepatocytes. For the sake of convenience, liver cirrhosis is classified into two groups; common and specific types. The former included postnecrotic, posthepatitic, alcoholic and mixed types of cirrhosis, and congestive, biliary, parasitic cirrhosis and Wilson disease were grouped into the latter. It should be mentioned that morphological diagnostic criteria is much more rigid for the common types than those of the specific type. Special stress has been laid on the importance of structural changes not only in the parenchymal disorganizations, but also in the stromal vascular changes in the cirrhotic process.

Pathologic analyses of non-overt necrotizing type Kikuchi and Fujimoto's disease.

Twenty-eight cases of non-overt necrotizing type Kikuchi-Fujimoto disease (KF disease, histiocytic necrotizing lymphadenitis) were investigated clinicopathologically, immunohistochemically and electron microscopically in order to analyze the nature of this disease. In addition, investigations to detect the presence of Epstein-Barr virus (EBV) using the polymerase chain reaction (PCR) and in situ hybridization (ISH) were also performed as a high incidence of positive serum immunoreactivity to EBV had been revealed in the cases examined. The clinical features were an equal male to female ratio, mean age of 26 years, mild leukopenia and about 40% association with fever over 38 degrees C. The major particular pathologic features were: (i) varying amounts of nuclear debris in the pathologic areas, identified as apoptosis by electron microscopy; (ii) presence of medium to large sized transformed lymphocytes (immunoblasts), a very small number of them positive for both UCHL1 and L26, and plasmacytoid cells, some of them positive for UCHL1; and (iii) characteristically shaped histiocytes predominant in the pathologic areas, with irregular nuclei and strongly positive for anti-lysozyme and anti-alpha 1-antitrypsin antibodies. Investigations with PCR and ISH revealed a complete absence of EBV in these cases despite excellent results for positive controls. It was therefore considered that EBV was not a causative virus for KF disease.

Human hepatic infarction: histopathological and postmortem angiological studies.

Twenty hepatic infarction cases selected from 5420 consecutive autopsy cases were investigated to clarify the pathogenetic aspects of this disease. Additional postmortem angiological studies of 24 normal human livers obtained at autopsy were also further performed to analyse the effects of blocking vascular structures on lesion development. Seventeen of the 20 cases (85%) were clinically associated with systemic circulatory insufficiency, especially hepato- and/or renal failure. Histopathologically, there was a significantly closer relationship between the location of infarcted regions and portal vein thrombosis than with either hepatic vein thrombosis or hepatic arterial damage. The borders between infarcted regions and surviving hepatic parenchyma were located around central veins, corresponding with the microcirculatory periphery of the portal venous system. Postmortem angiographic studies revealed that hepatic lobuli mainly consist of portal vein branches. Moreover, postmortem embolization studies of six normal livers using glass beads and barium-gelatin injection showed that physical occlusion of portal vein branches produced defects in broad areas of the hepatic parenchyma. Therefore, it is suggested that the development of hepatic infarction principally depends on disturbances of the portal venous system. In addition, systemic circulatory insufficiency, which reduces the intrahepatic blood flow, probably contributes greatly to the development of hepatic infarction.