Needle biopsy of the liver for the diagnosis of nonneoplastic liver diseases

The results of 209 liver biopsy needle washings were compared with the corresponding histologic findings. An effort was made to distinguish major categories of liver disease on the basis of cytologic findings. Pigment identification and fat quantitation were also evaluated. It was found that it was often possible to determine whether a liver needle washing was normal or abnormal; however, it was rarely possible to provide specific diagnoses. Pure fatty change and primary cholestasis could be reliably differentiated from the steatosis and bile plugging seen in other liver disorders. Cirrhosis could be suggested in a limited number of cases, although in most cases the findings were nonspecific. Cytology was found to be less reliable than biopsy in the discrimination between the major pigments. Finally, cytology was an acceptable method for detecting and quantitating fatty change.     

Therapeutic liver repopulation for the treatment of metabolic liver diseases

Orthotopic liver transplantation is the treatment of choice for many inherited and acquired liver diseases. Unfortunately, the supply of donor organs is limiting and therefore many patients cannot benefit from this therapy. In contrast, hepatocyte suspensions can be isolated from a single donor liver can be transplanted into several hosts, and this procedure may help overcome the shortage in donor livers. In classic hepatocyte transplantation, however, only 1% of the liver mass or less can be replaced by donor cells. Recently though, we have used a mouse model of hereditary tyrosinemia to show that > 90% of host hepatocytes can be replaced by a small number of transplanted donor cells in a process we term "therapeutic liver repopulation". This phenomenon is analogous to repopulation of the hematopoietic system after bone marrow transplantation. Liver repopulation occurs when transplanted cells have a growth advantage in the setting of damage to recipient liver cells. Here we will review the current knowledge of this process and discuss the hopeful implications for treatment of liver diseases.     

清肝泄浊法治疗脂肪肝30例临床研究

目的:观察清肝泄浊法治疗脂肪肝的临床疗效.方法:治疗组30例口服自拟清肝泄浊汤,对照组24例口服复方益肝灵,观察肝功能及血脂变化.结果:治疗组30例,有效率90.0%,对照组30例,有效率36.6%.结论:清肝泄浊法治疗脂肪肝的疗效明显,适宜临床推广运用.     

Method for the decellularization of intact rat liver

We have developed a method for the decellularization of whole rat livers by perfusion with increasing concentrations of detergents. This procedure resulted in an intact, decellularized organ with an intact liver capsule. These decellularized organs were analyzed by immunohistochemistry, and retained an appropriate distribution of extracellular matrix components. The laminin basement membranes of the liver vasculature also remain intact. These acellular vessel remnants were strong enough to be cannulated, providing a convenient means for the delivery of cells to areas deep within the decellularized organ. Cannulation of the extrahepatic vessel remnants allow for media to be circulated through the decellularized organ. These decellularized livers provide a natural matrix for research in the fields of bio-artificial livers and liver engineering.     

Methods for the study of liver cell heterogeneity

A large number of histological, histochemical and biochemical techniques are available for studying liver cell heterogeneity. Structural differences are recognized by morphometric analyses of electron micrographs. The zonal heterogeneity of enzyme activities can be demonstrated by histochemistry and more precisely by ultramicrobiochemical assays in microdissected periportal and perivenous tissue. Immunohistochemistry is useful for quantifying and localizing proteins, especially isoenzymes, without depending on their biological activity. The zonal quantification of specific mRNA can be achieved by in situ hybridization. The different structural and enzymic equipment of periportal and perivenous tissue found by these techniques has led to the concept of metabolic zonation. This hypothesis can be confirmed by determination of metabolic rates in perfused liver after selective zonal damage, in separated periportal and perivenous hepatocytes as well as in periportal and perivenous tissue of perfused liver by non-invasive techniques.     

An immortalized human liver endothelial sinusoidal cell line for the study of the pathobiology of the liver endothelium

Background

The endothelium lines blood and lymph vessels and protects underlying tissues against external agents such as viruses, bacteria and parasites. Yet, microbes and particularly viruses have developed sophisticated ways to bypass the endothelium in order to gain access to inner organs. De novo infection of the liver parenchyma by many viruses and notably hepatitis viruses, is thought to occur through recruitment of virions on the sinusoidal endothelial surface and subsequent transfer to the epithelium. Furthermore, the liver endothelium undergoes profound changes with age and in inflammation or infection. However, primary human liver sinusoidal endothelial cells (LSECs) are difficult to obtain due to scarcity of liver resections. Relevant derived cell lines are needed in order to analyze in a standardized fashion the transfer of pathogens across the liver endothelium. By lentiviral transduction with hTERT only, we have immortalized human LSECs isolated from a hereditary hemorrhagic telangiectasia (HHT) patient and established the non-transformed cell line TRP3. TRP3 express mesenchymal, endothelial and liver sinusoidal markers. Functional assessment of TRP3 cells demonstrated a high capacity of endocytosis, tube formation and reactivity to immune stimulation. However, TRP3 displayed few fenestrae and expressed C-type lectins intracellularly. All these findings were confirmed in the original primary LSECs from which TRP3 were derived suggesting that these features were already present in the liver donor. We consider TRP3 as a model to investigate the functionality of the liver endothelium in hepatic inflammation in infection.     

Direct enzymatic procedure for the determination of liver glycogen

A method is proposed to measure glycogen content in liver homogenates without extraction and acid hydrolysis of tissue glycogen. Homogenates were treated with amyloglucosidase, which degrades glycogen to glucose, and the glucose was the determined enzymatically by the use of glucose oxidase and peroxidase. The method was shown to yield nearly complete (99%) recoveries of standard glycogen, while 5 hr of acid hydrolysis of standard glycogen were required to obtain comparable recoveries. When compared to an acid hydrolysis method for liver, amyloglucosidase degradation of rat liver glycogen and subsequent determination of glucose resulted in higher values for glycogen content. The amyloglucosidase, glucose oxidase: peroxidase method has the advantage of rapidity, whereas the traditional method consisting of extraction, precipitation, and acid hydrolysis is not only time consuming, but may also be subject to losses of glycogen in each step.     

Novel methods for segment-specific blood flow simulation for the liver

Abstract

One challenge for hepatic flow simulation is to divide the hepatic vasculature into individual Couinaud segments, and to simulate flow at both segmental and organ levels. We propose to integrate a segment simulation algorithm with the flow solver in a Constructive Constraint Optimisation (CCO) algorithm to address this problem. In this way blood flow simulations can be conducted for large segment-specific vasculatures as relevant to surgical procedures. In this short communication we outline the methods and present some preliminary results.     

Engineered liver for transplantation

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Liposomes for liver scintigraphy

Abstract

Liposomes were prepared by detergent dialysis method and ^99mTc-GHA, a radiopharmaceutical of choice for kidney imaging was entrapped in SUVs of different surface charges. The organ specificity of the agent with and without encapsulation in liposomes was studied in experimental animals. Results obtained show that ^99mTc-GHA entrapped SUV can be targeted to liver. These results were corroborated by scintigraphy studies. The effect of entrapping the agent in SUV on its half-life is discussed.     

Ocular stereometric grid for research on the liver

A new ocular network of the light microscope and the method of its application for histometric investigation of hepatocytes, and microcirculatory bed of the liver lobe based on the morphofunctional peculiarities of peripheral and central lobular zones are described. Histometry of biopsy material from the dog liver has demonstrated that with a smaller volume of sinusoids in normal animals, the nuclear-cytoplasmic hepatocyte ratio was greater in the peripheral than in the central lobular zones.     

Biochemical evidence for the role of alkyl-lysophospholipids on liver sialyltransferase

Antineoplastic alkyl-lysophospholipids were found to exert a strong inhibitory effect on membranous or solubilized asialomucin-sialyltransferase (CMP-N-acetylneuraminate: D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) activity. This inhibitory effect was dependent on the presence of the choline moiety in position 3 of the glycerol molecule, as well as on the presence of long ether-linked aliphatic side chain in position 1 and the absence of any large substituent in position 2. As an example, 1-octadecyl-2-O-methyl-glycero-3-phosphorylcholine acted as a mixed-type inhibitor. Such an inhibitory process on sialyltransferase activity might be an additional factor in the tumor cell destructive effect of alkyl-lysophospholipids.     

A family of models for the elimination of substrate in the liver

A family of models describing the elimination of substrates from the blood by the liver is proposed. It is shown how it contains some previously proposed models for elimination in the liver, diffusion through the capillaries and absorption in the intestine, where the elimination is assumed to follow either first-order or simple Michaelis-Menten kinetics.Applications to allosteric reactions are suggested.