Two chronic myelogenous leultaemia cell lines which represent different stages of erythroid differentiation

Summary We established two cell lines, YN-1 and Y-1K. from the peripheral blood of two chronic myelogenous leukaemia patients in blastic crisis. Characterization of the YN-1 and Y-1K cells revealed that these cells expressed erythroid lineage markers. However, there was a marked difference in the level of γ-globin mRNA and haenioglobin in YN-1 and Y-1K cells. YN-1 contained approximately 1–5% benzidine-positive staining cells, whereas no benzidine-positive cells were observed in Y-1K cells. Haemoglobin production in YN-1 cells was markedly increased with various chemical inducers of erythroid differentiation, but was not in Y-1K cells. In contrast, Y-1K cells expressed CD34 stem cell antigen and CD41 megakaryocyte-specific antigen. These observations suggested that, although both cell lines were committed to the erythroid lineage. each cell line represented a distinct differentiation stage in the erythroid differentiation programme. Y-1K seemed to correspond to an early stage of cells in erythroid lineage, whereas YN-1 represented a more advanced stage in human erythropoiesis.     

Relation of long chain n-3 polyunsaturated fatty acid intake to serum high density lipoprotein cholesterol among Japanese men in Japan and Japanese-American men in Hawaii: the INTERLIPID study

Epidemiologic evidence shows an inverse relationship between fish consumption and coronary heart disease (CHD) mortality. Associations between dietary intake of long chain n-3 polyunsaturated fatty acids (PUFA) and serum high density lipoprotein (HDL) cholesterol concentration are unknown. In this study, the association between n-3 PUFA (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)) intake and serum HDL cholesterol among Japanese men and women in Japan and Hawaii was examined. The study population consisted of Japanese ancestries from five research centers of the International Study of Macronutrients and Blood Pressure (INTERMAP) study, in Japan and Hawaii (672 men and 676 women), surveyed between 1996 and 1998. Four 24-h dietary recalls and one set of serum lipid measurements were performed. For men, n-3 PUFA intake and HDL cholesterol were higher in Japan than in Hawaii (n-3 PUFA: 1.32 g/day versus 0.47 g/day, p<0.001). For women, n-3 PUFA intake was higher in Japan than in Hawaii (p<0.001) but HDL cholesterol was not significantly different (p=0.752). After adjustment for age, body mass index, physical activity, number of cigarettes per day, alcohol intake, and hormone replacement therapy (for women), n-3 PUFA intake was positively associated with serum HDL cholesterol in men (4.6 mg/dl higher HDL cholesterol with 1%kcal higher n-3 PUFA intake, p=0.011). This association was not observed in women. This positive association of dietary n-3 PUFA with serum HDL cholesterol may partially explain the low mortality from CHD among Japanese men.     

Combination of short-term prednisolone and adenine arabinoside in the treatment of chronic hepatitis B. A controlled study

The efficacy of adenine arabinoside (Ara-A) alone or in combination with prednisolone utilizing its withdrawal effect was studied in 43 patients with deoxyribonucleic acid polymerase- and hepatitis B e antigen-positive chronic hepatitis. Ten patients were treated with 10 mg/kg body wt of Ara-A alone for 4-8 wk. In 9 cases, prednisolone (40 mg/day) was given at a constant dosage for 4 wk before Ara-A treatment. Fourteen patients received oral prednisolone alone for 4 wk, and 10 patients served as untreated controls. Six of 9 patients (67%) undergoing the combination therapy became seronegative for hepatitis B e antigen, whereas only 4 of 24 patients (17%) treated either with Ara-A alone or prednisolone alone lost the antigen. Two of the 10 untreated patients became seronegative for hepatitis B e antigen during the same follow-up period of 9 mo. This prospective controlled study suggests that the combination of immunomodulation by steroid withdrawal and subsequent Ara-A is more effective in the treatment of patients with chronic liver disease and active hepatitis B virus replication than treatment with Ara-A alone.     

Daily nasal inoculation with the insulin gene ameliorates diabetes in mice

The present study examined the feasibility of liposome-mediated gene transfer via nasal administration, for treating insulin-dependent diabetes mellitus. The rat insulin gene was packed under control of the CMV promoter, complexed with DC-chol/DOPE-based liposomes and administered daily via the nasal route in mice made severely diabetic by streptozocin. Sustained expression of the insulin gene was achieved and insulinopenia, ketonuria and death were prevented. Hyperglycemia and body weight reduction were significantly suppressed without evidence of hypoglycemia throughout the experimental period. RT-PCR and FISH analysis indicated that insulin was produced in the alveolar epithelial cells of the lung. Liposome-mediated in vivo gene transfer via nasal administration may provide an efficacious route for delivery of hormonal and other gene products into the blood stream.     

Drug-induced mononucleosis-like hepatic injury in a patient with systemic lupus erythematosus

A case of systemic lupus erythematosus (SLE) with mononucleosis-like hepatic injury was described. An emergent cesarean section was performed in a 25 yr-old house wife at 34 weeks gestation, followed by administration of several antibiotics. After the surgery she complained of high fever, hepatomegaly and dull right hypochondralgia, and mild liver dysfunction was also found. The liver biopsy showed prominent mononuclear cell infiltration in the sinusoids with minimum hepatocellular necrosis and mild triaditis, resembling hepatic lesion in infectious mononucleosis (mononucleosis-like injury). There were no clinical and serological features suggestive of infectious mononucleosis. This hepatic lesion was thought to be a manifestation of allergic reaction to drugs to which the lymphocyte stimulation test was found to be positive. Immunological abnormalities inherent in SLE might be related to occurrence of such allergic drug reaction.     

Portographic Opacification of Hepatic Veins and (Anomalous) Anastomoses between the Portal and Hepatic Veins in Cirrhosis—Indication of Extensive Intrahepatic Shunts

On the premise that extensive intrahepatic portal-venous anastomoses known to occur in cirrhosis would be demonstrated by contrast medium directly placed in the portal vein, percutaneous transhepatic portograms were analyzed in 82 patients with liver cirrhosis in relation to the estimated degree of shunting. The degree of intrahepatic shunt was measured during transhepatic portography using 99mTc-macroaggregated albumin. Hepatic veins began to opacify at 4 to 10 s after the start of injection of contrast medium during portography in 20 patients with cirrhosis who had intrahepatic shunt indices of 58.5 +/- 18.5%, but it was not visualized in 62 patients with cirrhosis whose shunt indices were 19.9 +/- 14.1%. Anomalous large anastomoses of 1 or 2 mm in size between the right portal vein and the right hepatic vein were clearly visualized during portography in 18 of 20 patients in whom the hepatic vein was opacified. Frequency and time of beginning opacification of the hepatic vein were closely correlated with the degree of intrahepatic shunt. Thus, opacification of the hepatic vein and abnormal anastomoses between the portal and hepatic vein systems in an early phase of portography indicates extensive intrahepatic shunts.     

Experimental portal fibrosis produced by intraportal injection of killed nonpathogenic Escherichia coli in rabbits

An attempt was made to develop an animal model for the study of the etiology of noncirrhotic portal fibrosis or idiopathic portal hypertension based on the assumption that it is related to chronic abdominal infection. Rabbits were given killed nonpathogenic Escherichia coli intraportally or intravenously. The animals to which a mixture of killed E. coli and rabbit antiserum (aggregated E. coli) was given intraportally developed remarkable histologic changes in the liver. The early inflammatory reactions in the portal area and parenchyma were followed by rapid disappearance of inflammation and development of portal fibrosis with bile duct proliferation. Three intraportal challenges with aggregated E. coli were sufficient to produce pronounced portal fibrosis, although there was considerable variation in response among individual animals. This procedure also produced splenomegaly, and in some animals marked portal hypertension. Injection of nonaggregated killed E. coli into the portal vein or aggregated E. coli into the ear vein also caused similar hepatic changes, but they were milder in degree. These histologic changes resemble portal fibrosis seen in idiopathic portal hypertension and, less closely, pericholangitis associated with inflammatory bowel disease in humans.     

Comparison of clinicopathological features of patients with hepatocellular carcinoma seropositive for alpha-fetoprotein alone and those seropositive for des-gamma-carboxy prothrombin alone

BACKGROUND: There has been no comparative study of the clinicopathological features of HCC patients who are seropositive for alpha-fetoprotein (AFP) alone and those who are seropositive for des-gamma-carboxy prothrombin (DCP) alone. The authors, thus, performed this comparative study. METHODS: The clinicopathological features of patients with solitary hepatocellular carcinoma (HCC), who underwent a hepatectomy were compared among the four below groups according to the seropositivity of AFP and DCP: group A, seronegative for both AFP below 20 ng/mL and DCP below 40 mAU/mL; group B, seropositive for AFP above 100 ng/mL and seronegative for DCP; group C, seronegative for AFP and seropositive for DCP above 100 mAU/mL; and group D, seropositive for both AFP and DCP. RESULTS: Group B patients showed a higher incidence of HCC with an indistinct margin, and a somewhat higher incidence of small HCC less than 2 cm in greatest dimension compared with group C patients. By contrast, group C patients had a higher frequency of HCC with a distinct margin compared with that of an indistinct margin, large tumors more than 3 cm compared with that of small tumors less than 2 cm, and a somewhat higher frequency of moderately to poorly differentiated HCC compared with that of well-differentiated HCC. Our HCC cases showed advanced clinicopathological features in the order of group C, group B and group A. Groups C and D patients showed similar characteristics. CONCLUSIONS: Hepatocellular carcinoma patients who were seropositive for AFP alone demonstrated clinicopathological features of less advanced HCC compared with those who were seropositive for DCP alone.     

Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet

OBJECTIVE: Chitin and chitosan are polymers containing more than 5000 acetylglucosamine and glucosamine units, respectively, and their molecular weights are over one million Daltons. The present study assessed the effects of chitin-chitosan on the activity of pancreatic lipase in vitro and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for nine weeks. DESIGN: Mice were fed a high-fat diet and treated with chitin-chitosan for nine weeks. Experiments were also carried out to clarify whether or not chitin-chitosan inhibited pancreatic lipase activity in assay systems using triolein emulsified with lecithin, gum arabic or Triton X-100. RESULTS: Chitin-chitosan prevented the increase of body weight, hyperlipidaemia and fatty liver induced by a high-fat diet. Chitin-chitosan inhibited hydrolysis of triolein, emulsified with phosphatidylcholine, but not that of triolein emulsified with gum arabic and Triton X-100. These results suggest that the site of inhibitory action of chitin-chitosan may not be the enzyme but its substrate. CONCLUSION: The anti-obesity effects of chitin-chitosan in high-fat diet-treated mice might be partly due to the inhibition of intestinal absorption of dietary fat. Consequently, chitin-chitosan might cause improvement of the fatty liver and hyperlipidaemia in mice fed a high fat diet through inhibiting intestinal absorption of dietary fat.