Dark liver cell

There is a dark side to receptor-mediated endocyto-sis in that viruses which cause such diseases as hepatitis (affecting liver cells), poliomyelitis (affecting motor neurons), and AIDS (affecting T cells) initiate their damage by this mechanism. Iron toxicity also begins with excessive uptake due to endocytosis. 

Liver cells are then exposed in vitro to the test compound and incubated with tritium-labeled thymidine for about 18 hours. At the end of the incubation, the cells are fixed on slides and prepared for autoradiography. For that the slides are first exposed to liquid photographic emulsion, air-dried and following a 7-day exposure in the dark, exposed to developing solution. 

Figure 22.17. Electron Micrograph of a Peroxisome in a Liver Cell. A crystal of urate oxidase is present inside the organelle, which is bounded by a single bilayer membrane. The dark granular structures outside the peroxisome are glycogen particles. [Courtesy of Dr. George Palade.]...

Fig. 2.18 Nucleus, nucleolus and hyaloplasm of the liver cell (20) cell nucleus (CN), marginal nucleolus (N), electron-dense dark nuclear capsule (DC), undulating nuclear membrane with (partial) fusion of the two membranes (NM), endoplasmic reticulum (ER), mitochondria (M) X 14,600...

Haemochromatosis As a result of the accumulation of iron in the liver cells, the relaxation time T2 is considerably shortened, with a corresponding decrease in signal intensity. This can also be determined quantitatively. Depending on the iron content, the liver appears dark grey to black, (s. fig. 8.8) The success rate is 100% at an iron concentration of 1 mg/g liver tissue. An iron-free node may suggest HCC. Haemosiderosis with iron deposition in the RES is also characterized by similar, yet less marked findings. A fall in signal intensity is discernible when the iron content/g in the liver tissue has almost quadrupled. (58, 64, 78, 91, 94, 113)... 

Chronic congestion leads to an enlarged and plump liver with a dark red (purplish) colour. The central veins are dilated. In continued congestion, stasis paths develop between the central veins, resulting in the formation of confluent stasis areas. Various degrees of fatty changes in the liver cells as well as pigment deposits (lipofuscin, ceroid) appear. In the course of time, fibrosis of sinusoidal reticular fibres takes place fibroses can also be observed... 

An in vitro method using hair follicle cells to investigate unscheduled DNA synthesis (UDS) has been developed. Plucked follicles were exposed to tritiated thymidine and the UDS activities were determined autoradiographically (the number of dark grains in the outer root sheath of nonperipheral cells were used to estimate UDS). Many, but not all chemicals that have been shown to induce UDS in rat liver cells also stimulated UDS in hair follicles. 

Fig. 1.1 Morphological and biochemical studies (a) One biochemical approach to study enzymes is to analyze the activity levels with results plotted on a graph and to include error bars from multiple assays. The morphological approach gives information about where the enzyme is located. Three different types of liver cells are shown here as circular, elongated, and rectangular, (b) The enzyme (dark cells) can be located in all the different types of liver cells, (c) More likely the enzyme is found in only one cell type, the rectangular cells, (d) As a result of disease, the enzyme may be expressed in only a small number of cells in a single cell type, (e) Following an injury, the enzyme may be expressed in multiple cell types located near the injury sites...

It was conclusively shown that deoxychlordiazepoxide (393) had none of the phototoxic properties of the parent drug, at least in the rat [225]. Chlordiazepoxide, demethylchlordiazepoxide, demoxepam and diazepam-4-oxide were all phototoxic to a bacterial cell preparation. There was a close relationship between the phototoxicities of the A-oxides and the toxicity in the dark of their oxaziridines. The reduced forms of the four compounds were not phototoxic [ 228 ]. Kinetic studies demonstrated that the oxaziridine (390) covalently bonds to plasma proteins. The half-life of the oxaziridine in the presence of high concentrations of protein was about 30 min. It therefore has time not only to bind to biomolecules in the skin surface, but also to attack internal organs. This was put forward as the explanation of previously observed kidney and liver damage in the rat [229]. 

Effects reported in humans following dermal exposure to phenol include liver damage, diarrhea, dark urine, and red blood cell destruction. Skin exposure to a relatively small amount of concentrated phenol has resulted in the death of humans. Small amounts of phenol applied to the skin of animals for brief periods can produce blisters and burns on the exposed surface, and spilling dilute phenol solutions on large portions of the body (greater than 25% of the body surface) can result in death. 

In addition to the classical symptoms of zinc deficiency mentioned above, the following unusual conditions have been reported liver and spleen enlargement, abnormal dark adaptation and abnormalities of taste. Several laboratory procedures for diagnosing zinc deficiency are available. Measurement of zinc levels in plasma is useful in certain cases. Levels of zinc in the red cells and hair may be used for assessment of body zinc status. More accurate and useful parameters are neutrophil zinc determination and quantitative assay of alkaline phosphatase activity in neutrophils. Determination of zinc in 24 h urine may help diagnose deficiency if sickle cell disease, chronic renal disease and liver cirrhosis are ruled out. A metabolic balance study may clearly distinguish zinc-deficient subjects. 

The incubation mixture contained in a Anal volume of 100 /iL 400 fiM DL-homocysteine, 500 (iM ( )-L-A/5-methyltetrahydrofolate, 50 fiM cyanocobalamin, 300 fiM 5-adenosylmethionine, 125 mM 2-mercaptoethanol, 20 fiM L-norvaline, 50 mM potassium phosphate buffer (pH 7.4), and 50 /xL of liver or cell extract. The incubation mixture was immediately flushed with nitrogen and overlayered with 50 /tL of bis(3,5,5-trimethylcyclohexyl)-phthalate. The incubation, carried out at 37°C in the dark, was stopped by the addition of 10 / L of 4 TV perchloric acid. The acid was then neutralized by addition of 10 / L of 4 TV KOH containing 3.3 M potassium bicarbonate. After centrifugation, 90 /iL of supernate was mixed with 175 fiL of o-phthaldialdehyde reagent (prepared by mixing 1 mL of 56 mM o-phthaldialdehyde in methanol with 9 mL of 0.1 M sodium borate buffer, pH 9.5, then adding 40 fiL of 2-mercaptoethanol). After 2 minutes at 23°C, 220 /xL of this mixture was used for HPLC analysis. The assay is linear for at least 2 hours. 

A particular hepatotropicity causing severe herpes hepatitis is ascribed to herpesvirus 6 (HHV-6). There have even been reports of a fulminant course with this virus infection. (18, 23, 35) HHV-8 causes Kaposi s sarcoma. The liver is the most common site, with dark reddish-violet tumour nodes. Histological analysis reveals endothelial cell proliferations and growths of spindle-shaped fibroblast-like cells. The bile ducts may be altered. Transaminase levels are elevated, and jaundice occurs. There may be a causal relationship between HHV-8 infection and multicentric Castlemans disease. The latter usually implies the presence of peliosis hepatis, perisi-nusoidal fibrosis and nodular regenerative hyperplasia. 

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