Search PubMed⌕ Search

Biomedical subjects

S Ji

Publications and source records attributed to S Ji.

At least 109 records · Page 6Linked to original sources
PubMed1983

Cell surface changes and enzyme release during hypoxia and reoxygenation in the isolated, perfused rat liver.

We examined the effects of hypoxia and reoxygenation in isolated, perfused rat livers. Hypoxia induced by a low rate of perfusion led to near anoxia confined to centrilobular regions of the liver lobule. Periportal regions remained normoxic. Within 15 min, anoxic centrilobular hepatocytes developed surface blebs that projected into sinusoids through endothelial fenestrations. Periportal hepatocytes were unaffected. Both scanning and transmission electron microscopy suggested that blebs developed by transformation of preexisting microvilli. Upon reoxygenation by restoration of a high rate of perfusion, blebs disappeared. Other changes included marked shrinkage of hepatocytes, enlargement of sinusoids, and dilation of sinusoidal fenestrations. There was also an abrupt increase in the release of lactate dehydrogenase and protein after reoxygenation, and cytoplasmic fragments corresponding in size and shape to blebs were recovered by filtration of the effluent perfusate. We also studied phalloidin and cytochalasin D, agents that disrupt the cytoskeleton. Both substances at micromolar concentrations caused rapid and profound alterations of cell surface topography. We conclude that hepatic tissue is quite vulnerable to hypoxic injury. The morphological expression of hypoxic injury seems mediated by changes in the cortical cytoskeleton. Reoxygenation causes disappearance of blebs and paradoxically causes disruption of cellular volume control and release of blebs as cytoplasmic fragments. Such cytoplasmic shedding provides a mechanism for selective release of hepatic enzymes by injured liver tissue.

Animals↗
PubMed1983

Aldehyde dehydrogenase-dependent acetaldehyde metabolism in periportal and pericentral regions of the perfused rat liver.

NADH fluorescence (366 leads to 450 nm) was measured with a large tipped light guide from the surface of rat liver perfused with hemoglobin-free medium without recirculation. A good correlation (r = 0.93) was found between the increase in NADH fluorescence and the rate of oxidation of infused acetaldehyde (0.1-4.0 mM). By using microlight guides placed on either periportal or pericentral areas of the liver, it was found that infusion of acetaldehyde increased NADH fluorescence first in periportal regions and then in pericentral areas. During retrograde perfusions, NADH fluorescence in pericentral areas increased before portal areas. By using the correlation between the increase in NADH fluorescence and the rate of acetaldehyde uptake established with the large light guide, rates of acetaldehyde uptake in pericentral and periportal areas were estimated from the microlight guide measurement of the periportal and pericentral NADH fluorescence increments caused by acetaldehyde infusions. Half-maximal acetaldehyde uptake was observed at about 0.8 mM in both regions. Maximal rates of acetaldehyde uptake were 212 and 197 mumol/g/hr in periportal and pericentral regions, respectively. The results indicate that rates of aldehyde dehydrogenase-dependent acetaldehyde oxidation are similar in periportal and pericentral regions of the liver lobule.

Acetaldehyde↗
PubMed1983

Effect of size on portal circulation of hepatic nodules from carcinogen-treated rats.

The portal circulation of diethylnitrosamine-initiated nodules (0.5 to 7 mm in diameter) was studied in rat livers perfused exclusively via the portal vein. Microlight guides were placed on normal and nodular tissue on the capsular surface of the liver to measure pyridine nucleotide fluorescence (366 leads to 450 nm). When oxygen tension of the inflow perfusate was lowered, fluorescence in both normal tissue and small nodules (less than 2 mm in diameter) increased sharply due to the reduction of pyridine nucleotides, indicating previous normoxia. In contrast, similar manipulations did not increase fluorescence in nodules greater than 2 mm in diameter, demonstrating that nicotinamide adenine dinucleotide was reduced maximally previously; i.e., the nodules were anoxic. Direct measurements of nodule oxygen concentrations with a miniature oxygen electrode confirmed these results. 7-Hydroxycoumarin or fluorescein could be detected with micro-light guides in normal tissue and nodules less than 2 mm in diameter but not in nodules greater than 2 mm in diameter. Furthermore, fluorescent microscopy indicated an absence of fluorescein in nodules greater than 2 mm in diameter. Therefore, with four independent optical and polarographic techniques, we have demonstrated reduced portal circulation in nodules greater than 2 mm in diameter; however, smaller nodules could not be differentiated from normal tissue.

2-Acetylaminofluorene↗
PubMed1982

Periportal and pericentral pyridine nucleotide fluorescence from the surface of the perfused liver: evaluation of the hypothesis that chronic treatment with ethanol produces pericentral hypoxia.

Pyridine nucleotide fluorescence made from the surface of the hemoglobin-free perfused rat liver was measured continuously by using a "micro-light guide" placed on selected periportal and pericentral regions of the liver lobule. From the portal oxygen tension at which pyridine nucleotide reduction first occurred in pericentral regions, the oxygen gradient across the liver lobule was estimated in livers from rats treated chronically with ethanol or sucrose. Chronic treatment with ethanol increased the average lobular oxygen gradient from 275 to 400 torr (1 torr = 133 Pa), primarily due to the increase in the oxygen gradient in pericentral regions. Ethanol treatment also increased hepatic oxygen uptake significantly, from 110 to 144 (mumol/g)/hr. Treatment with the antithyroid drug 6-propyl-2-thiouracil reversed the effect of ethanol on O2 uptake and on the lobular oxygen gradient. The oxygen gradients measured with the micro-light guide were confirmed by direct measurement of tissue oxygen tensions in periportal and pericentral areas by using an oxygen electrode. These data are consistent with the hypothesis that chronic treatment with ethanol causes the pericentral region of the liver lobule to become susceptible to hypoxic cellular injury. This may be responsible, at least in part, for the localized hepatotoxic effects of ethanol.

Animals↗
PubMed1982

Rates of alcohol dehydrogenase-dependent ethanol metabolism in periportal and pericentral regions of the perfused rat liver.

Infusion of ethanol into hemoglobin-free perfused rat liver caused an increase in NADH fluorescence (366 leads to 450 nm) which was measured with a large-tip (2-mm) light guide placed on the surface of the liver. A linear correlation (r = 0.83) was observed between the increase in NADH fluorescence and rate of ethanol uptake in the concentration range 0.05--2.0 mM. When a micro-light guide (tip diameter 170 micrometer) was placed on periportal or pericentral regions of the liver surface, the maximal fluorescence increase due to ethanol (2 mM) was 31.2 +/- 2.0 and 31.9 +/- 1.7% in periportal and pericentral regions, respectively. The infusion of 4-methylpyrazole (80 microM), an inhibitor of alcohol dehydrogenase, completely abolished the fluorescence increase in both regions, indicating that the changes are entirely attributable to perturbation of cofactor levels due to alcohol dehydrogenase-dependent ethanol metabolism. Using the correlation between the NADH fluorescence increase and rate of ethanol uptake, rates of ethanol metabolism in periportal and pericentral regions were calculated. Values for maximal ethanol uptake were identical in periportal and pericentral regions. Half-maximal ethanol uptake was observed at 0.24 and 0.25 mM ethanol in periportal and pericentral regions, respectively. These results indicate that the rates of alcohol dehydrogenase-dependent ethanol metabolism are similar in periportal and pericentral regions of the liver lobule.

Alcohol Dehydrogenase↗
PubMed1981

Centrilobular injury following hypoxia in isolated, perfused rat liver.

Hypoxia was produced in isolated, hemoglobin-free, perfused rat liver by reducing the flow rate of oxygen-carrying fluid entering the organ. The procedure caused anoxia in centrilobular regions. In these anoxic areas, structural derangements developed rapidly, characterized by bleb-like protrusions of hepatocyte plasma membrane through fenestrations in the sinusoidal endothelium. Periportal tissue remained normoxic and was completely spared. Cellular injury resulting from localized anoxia may play an important role in the pathogenesis of centrilobular liver disease.

Animals↗
PubMed1980

Ethanol-induced changes in the intralobular oxygen gradient of perfused rat liver.

A new tissue fluorometric method was developed to estimate the intralobular oxygen gradient in hemoglobin-free perfused rat liver. The method employs a two-branch micro-light guide with a tip diameter of 170 mu. With this light guide, it was possible to measure pyridine nucleotide fluorescence (366 nm leads to 450 nm) from periportal and pericentral regions of the liver lobule. By measuring inflow PO2 values at which pyridine nucleotide fluorescence increased in the pericentral regions of the liver lobule, the mean intralobular oxygen gradient was estimated. The measured gradient was approximately 180 torr in livers from sucrose-treated control rats. Chronic treatment with ethanol increased both the mean intralobular oxygen gradient and the rate of hepatic oxygen uptake by 30%. The antithyroid drug, 6-propyl-2-thiouracil, completely reversed the effects of ethanol on both the intralobular oxygen gradient and the rate of oxygen uptake. These data present direct physical evidence that the increased tissue respiration induced by chronic ethanol treatment indeed accentuates the intralobular oxygen gradient and thus support the hypothesis that selective depletion of oxygen in the pericentral region of the liver lobule may underlie ethanol-induced cellular injury confined to this site.

Animals↗
PubMed1979

Micro-light guides: a new method for measuring tissue fluorescence and reflectance.

Three-way light guides containing one or more strands of 25-micron or 80-micron diameter optical fibers in each channel have been constructed and used to measure the NADH fluorescence and UV reflectance from mitochondrial suspensions, the perfused, hemoglobin-free rat liver, and the perfused beating interventricular septum of the rabbit. The optical changes measured with these so-called micro-light guides, which have channels containing one or several strands of optical fibers less than 100 micron, are comparable in magnitude with those measured using much larger conventional light guides. The effect of light scattering on the fluorescence channel has been determined and an empirical equation for correcting the fluorescence channel for light scattering has been obtained for mitochondrial suspensions. A mathematical equation characterizing the optical behavior of a two-way micro-light guide has been derived and has been shown to account satisfactorily for reflectance and fluorescence measurements of a mat surface in air.

Animals↗
PubMed1978

Action of norepinephrine on microcirculation and PO2 distribution in the isolated perfused rat liver.

The addition of a potent vasoconstrictor, such as norepinephrine, induces an influx of sodium and an efflux of calcium and potassium in the parenchymal cells of the perfused liver. This reaction can be reversed by the addition of dihydroergotoxine mesylate (active substance of Hydergine). The example shows clearly that very distinct biological signals are generated under such conditions at the membrane level of the hepatocytes and presumably of other cells of liver tissue. At present, our investigations cannot clearly answer the question of whether or not swelling the shrinkage of parenchymal cells and of endothelial cells can serve as an additional mechanism for regulating microcirculation.

Animals↗
PubMed1977

Two-dimensional analysis of the redox state of the rat cerebral cortex in vivo by NADH fluorescence photography.

A photographic method for measuring two-dimensional changes in NADH fluorescence and hemoglobin distributions in the rat cerebral cortex in vivo has been developed. Intracellular NADH was excited by UV light peaking at 360 nm and the emission was observed through a window with the maximum transmission at 450 nm. The fluorescence photographs (360 leads to 450 nm) required 20-25 sec exposures at the aperture opening of f/5.6 and the reflectance photographs (360 leads to 360 nm) 10 sec exposures at f/32. The digitization of photographic images was achieved either by a PDP-8-controlled microdensitometer coupled to an A/D converter or by a combination of a manually operated microdensitometer and a computer-controlled digitizer. In the latter case, a photographic negative was scanned with a Joyce-Loebl microdensitometer in parallel lines 170 mum apart, and the densitometric tracings were digitized with a PDP-8-controlled TV digitizer. The digital data were processed by DEC PDP-10 computer and the results were displayed in 3-dimensional surfaces. Nitrogen anoxia caused increases in fluorescence at 450 nm ranging from 10 to 75% fo the normoxic fluorescence intensities (after correcting for the logarithmic characteristics of the photographic films) and decreases in reflectance intensities in the range of 10-30%. The spatial resolution of the present technique is limited to approximately 30 mum X 30 mum on the cortical surface and the time resolution to 10-25 sec. The optical properties of the cerebral cortex in vivo appear to be controlled primarily by blood vessel patterns and hemodynamic factors and secondarily by the redox state of the tissue. Evidence for a heterogeneous redox response of the cerebral cortex toward N2 anoxia was obtained.

Animals↗