Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 685 records · Page 38Linked to original sources

PubMed1997

Use of an artificial neural network to analyse an ECG with QS complex in V1-2 leads.

A feed-forward neural network with back-propagation algorithm is used to distinguish anterior wall myocardial infarction (AI) and non-infarction based on analysis of computerised electrocardiograms. Data used in the study are from 132 patients diagnosed as having AI by automated electrocardiograph analysis. Their ECGs show an abnormal Q-wave (or QS complex) or small R progression in leads V1 and V2. However, 66 of them are diagnosed as old AI from the history, physical examination, echocardiogram and other laboratory data, whereas the other 66 are not. The network is trained with the data from half of the AI and non-infarction patients; respectively. The diagnostic accuracy rate is then tested with the remaining 66 patients (33 infarction, 33 non-infarction) who have not been exposed to the network. The neural network correctly identifies 90.2% of the patients with AI and 93.3% of the patients without infarction. The neural network is capable of diagnosing anterior wall myocardial infarction better than a computer electrocardiograph.

Decision Trees↗

PubMed1997

Gene expression of transforming growth factor-alpha in human endometrium during decidualization.

PURPOSE: We previously reported the gene expression of epidermal growth factor (EGF) in the process of decidualization in the human endometrium. This study was undertaken to investigate the biological significance of transforming growth factor-alpha (TGF-alpha), which shares a significant sequence homology with EGF, in the regulation of decidualization. METHODS: The gene encoding TGF-alpha was analyzed by Northern blot hybridization in nonpregnant human endometria and decidua from 6 to 8 weeks of gestation as well as in cultured stromal cells with or without medroxyprogesterone acetate. RESULTS: No transcript was detected in proliferative and secretory endometrium, whereas a transcript of 4.8 kb, which was in agreement with the size of human prepro-TGF-alpha mRNA previously reported, was clearly detected in decidua. Transcript of 4.8 kb was also detected in vitro in medroxyprogesterone acetate (MPA)-induced decidual cells, while no TGF-alpha transcript was found in endometrial stromal cells cultured without MPA. CONCLUSIONS: These results suggest that the gene expression of TGF-alpha in uterine stromal cells is enhanced by stimulation from sex steroids and that TGF-alpha, like EGF, functions as one of the regulatory factors for decidualization in the human uterus.

Blotting, Northern↗

PubMed1997

Contents of pollutant and nutrient elements in rice and wheat grown on the neighboring fields.

Because of recent agricultural policy to suppress rice production, a rather rare situation occurred in one prefecture in Japan that rice and winter wheat were grown in fields neighboring each other, rice being grown from May to October, and wheat from November to June of the next year. Grains of such rice and wheat were analyzed for cadmium (Cd) and lead (Pb) by atomic absorption spectrometry, and eight nutrient minerals by inductively coupled plasma emission spectrometry. Concentrations of nutrient minerals were higher in wheat grains than in unpolished rice grains (without husk), and similar trends were observed also for Cd and Pb. Flour obtained by milling of the wheat grains had significantly less Cd and nutrient minerals than the mother grains, and such reduction was also observed by treatment of unpolished rice to polished grain. Pb concentration was also reduced by the polishing of rice. Pb in wheat flour appeared to be higher than that in whole grain. Comparisons between the final edible forms of the two cereals showed that K and Cu were higher in polished rice than in wheat flour and that such may also be the case for Cd, whereas the reverse was the case for Ca and Fe, and possibly for Pb.

Cadmium↗

PubMed1997

Endoscopic follow-up study of development of gastric antral vascular ectasia associated with liver cirrhosis.

Gastric antral vascular ectasia is an important cause of chronic gastrointestinal blood loss. However, its development and progression have not yet been clarified. We investigated its early lesions and progression by reviewing endoscopic films of five patients with gastric antral vascular ectasia followed for liver cirrhosis. In all patients, early findings were prepyloric red spots. In two patients, anemia due to gastrointestinal bleeding was already observed when vascular lesions were confined to the distal antrum. In the other three patients, anemia was observed 1-2 years after they showed a diagnostic pattern of gastric antral vascular ectasia. The vascular lesions gradually thickened and extended throughout the antrum, with the complete picture shown in 1.5-5 years. The pattern of distribution was classified into three types: diffuse spotty, diffuse confluent, and striped. These types could be predicted before the complete formation. Gastric antral vascular ectasia associated with liver cirrhosis started as prepyloric red spots and extended to the proximal antrum in various ways and varying time courses of less than 5 years; this entity may cause hemorrhage even in the early stage.

Aged↗

PubMed1997

Characteristics of palytoxin-induced cation currents and Ca2+ mobilization in smooth muscle cells of rabbit portal vein.

We examined the nature of the palytoxin (PTX)-induced channel and its relevance to the Ca2+ mobilizing effect of the toxin on smooth muscle cells isolated from rabbit portal vein using whole-cell voltage-clamp and microfluorimetric techniques. PTX (1 nM) induced a sustained, irreversible inward current at a holding potential of -40 mV. The PTX-induced current reversed at 0.5 +/- 0.6 mV, and the PTX-induced channel permitted the passage of Na+, K+, Cs+ and, to a lesser extent, Li+, but not choline+ or Ca2+. During the sustained phase of the current, superfusion of Ni2+ (5 mM), La3+ (0.5 mM) or 2,4-dichlorobenzamil (2,4-DCB, 25 microM) reduced the current amplitude and decreased the slope conductance without changing the reversal potential. In 5 of 7 experiments, ouabain transiently increased the PTX-induced inward current and shifted the reversal potential in a positive direction. Subsequently, ouabain inhibited the current in every cell. PTX (10 nM) induced a sustained rise in cytosolic Ca2+ ([Ca2+]i), which was resistant to verapamil but suppressed by omission of extracellular Ca2+. When external Na+ was replaced by choline+, PTX did not increase [Ca2+]i. Pretreatment with 2,4-DCB prevented the elevation of [Ca2+]i due to PTX. These results suggest that PTX does not directly stimulate Ca2+ entry but induces entry through Na(+)-Ca2+ exchange as a consequence of increased cytosolic Na+. Ni2+, La3+, 2,4-DCB and ouabain were shown to act as blockers of the PTX-induced channel. Ouabain may also inhibit Na+ pump current activated by cytosolic Na+.

Acrylamides↗

PubMed1997

Suppression of pentylenetetrazol-induced seizures by carnitine in mice.

When ddY mice were pretreated with L-carnitine (5, 10 or 20 mmol/kg), clonic as well as tonic seizures induced by pentylenetetrazol (PTZ) were dose-dependently suppressed. A time/response study (PTZ was injected 1, 5, 15 or 30 min after L-carnitine) showed that the anticonvulsive effects were apparent when the interval between L-carnitine and PTZ administration was 15-30 min. Saline containing 43% sucrose prolonged the latency to the first clonic seizure but was less effective than 20 mmol/kg L-carnitine and did not suppress clonic or tonic seizures. Alterations in brain energy metabolites caused by PTZ including increase of lactate and decrease of ATP and phosphocreatine were also suppressed by L-carnitine. L-carnitine was more potent than D-carnitine in prolonging the latency to the first clonic seizure and in decreasing the frequency of clonic as well as tonic seizures. The anticonvulsive effects of L-carnitine in PTZ-induced seizures may be unrelated to the transport of long-chain acyl CoA since they were not interfered with by D-carnitine.

Animals↗

PubMed1997

Cooperative inhibition of acetylcholinesterase activities by hexachlorophene in human erythrocytes.

Hexachlorophene (HCP), pentachlorophenol (PCP), 2,4,5-trichlorophenol (2,4,5-TCP) and 2,4,6-trichlorophenol (2,4,6-TCP) all hemolyzed washed human erythrocytes and inhibited acetylcholinesterase (AchE) activities in erythrocyte membrane. HCP was much more potent in either effect than any other compound examined. The inhibition of AchE activities by HCP was reversed on adding albumin. The dose-response curves by HCP and PCP were sigmoidal, indicating cooperative inhibition, while those by 2,4,5-TCP and 2,4,6-TCP were not. Furthermore, the cooperativity of the inhibition by HCP was greater than by PCP. Differing from that by PCP, the cooperativity of inhibition increased depending on the temperature (13, 25, 37 degrees C) and decreased when the membrane was treated with Triton X-100. The cooperativity was also decreased in the presence of albumin. On a Scatchard plot analysis, erythrocyte membranes appeared to have multiple binding sites of different affinities for HCP; binding of HCP to the low affinity site [dissociation constant (Kd) 4.7 x 10(-5) M] seemed to be responsible for the observed cooperative inhibition of AchE activities. Neither neostigmine nor fenitrothion altered the cooperativity. HCP seems to be the most potent cooperative inhibitor of AchE in human erythrocyte membranes known to date. HCP may be useful to examine AchE and milieu in human erythrocyte membranes.

Adult↗

PubMed1997

Diffusive sampling and biological monitoring of 2-bromopropane.

The possibilities to apply personal ambient air monitoring by diffusive sampling and biological exposure monitoring by urinalysis for 2-bromopropane or its metabolites were explored. The abilities of carbon cloth to adsorb 2-bromopropane was examined by experimental vapor exposure followed by solvent extraction and FID-GC. Urine from factory workers and rats exposed to 2-bromopropane were analyzed for 2-bromopropane, acetone and isopropyl alcohol by FID-GC, and for bromide ion by ECD-GC after chemical methylation. Carbon cloth adsorbed 2-bromopropane in a manner linearly related to exposures up to 1500 mg/m3 and to 8 h. The adsorption could quantitatively detect a 15 min peak exposure at 3,000 mg/m3. In rat experiments, analyses of urine samples collected over a 4-h period after termination of a 4-h exposure to 2-bromopropane at 500, 1,000 or 1,500 mg/m3 showed that acetone and bromide ion were excreted dose-dependently. Essentially, no 2-bromopropane or isopropyl alcohol was detected. When the analytical methods were applied to urine samples from 5 male workers exposed to 2-bromopropane at a low level (3 mg/m3 as a geometric mean), acetone and bromide ion levels were within respective normal ranges in four cases, but were higher than the upper limits of the normal ranges in the fifth case of a foreman who probably had the highest exposure. Thus, diffusive sampling is applicable to monitor exposure to 2-bromopropane. Urinalysis for acetone and bromide ion in combination appears to be a promising selective tool for biological monitoring of occupational exposure to 2-bromopropane.

Air Pollutants↗

PubMed1997

In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites.

Interferon-gamma-inducing factor/interleukin-18 is a novel cytokine that reportedly augments natural killer (NK) activity in human and mouse peripheral blood mononuclear cell cultures in vitro and has recently been designated IL-18. In this study, IL-18 exhibited significant antitumor effects in BALB/c mice challenged intraperitoneally (i.p.) with syngeneic Meth A sarcoma when administered i.p. on days 1, 2 and 3 after challenge. Intravenous (i.v.) administration also induced antitumor effects in the tumor-bearing mice; however, subcutaneous (s.c.) administration did not. When mice were twice pretreated with 1 microg IL-18 3 days and 6 h before tumor challenge, all mice survived whereas control mice died within 3 weeks of challenge. Inhibitory effects on Meth A cell growth in vitro were not observed with either IL-18 or interferon gamma. The effects of IL-18 pretreatment were abrogated by abolition of NK activity after mice had been injected with anti-asialo GM1 antibody 48 h before and, 24 h and 72 h after tumor challenge. Mice pretreated with IL-18 and surviving tumor challenge resisted rechallenge with Meth A cells but could not reject Ehrlich ascites carcinoma, and spleen cells from the resistant mice, but not control mice, exhibited cytotoxic activity against Meth A cells in vitro after restimulation with mitomycin C-treated Meth A cells for 5 days. The effector cells in the spleen cell preparations from resistant mice appear to be CD4+ cells because cytolytic activity was significantly inhibited after depletion of this subset by monoclonal antibodies and complement. In conclusion, IL-18 exhibits in vivo immunologically (primarily NK) mediated antitumor effects in mice challenged with syngeneic Meth A sarcoma and induces immunological memory and the generation of cytotoxic CD4+ cells.

Animals↗

PubMed1997

Comparison of the DNA content of megakaryocytes identified immunologically with that identified morphologically.

We devised a new microfluorometric method for determining the ploidy of megakaryocytes identified immunologically in bone marrow smears. The smears were immunostained by incubation with mouse monoclonal anti-glycoproteins (GP) IIb antibodies, followed by fluorescein isothiocyanate-conjugated goat antimouse IgG antibodies. They were then stained with 4',6-diamidino-2-phenylindole (DAPI). Megakaryocytes were identified by their GPIIb immunofluorescence using a microfluorometer and, after the filters were changed, their DNA content was assayed by measuring the intensity of DAPI fluorescence. This intensity was shown to be proportional to the DNA content when the aperture of the objective lens was reduced. We compared these results with those obtained when megakaryocytes were identified morphologically, using DAPI staining after Wright-Giemsa destaining. In all 12 normal controls, the ploidy peaks were shown to be 16N by both methods, and the mean ploidy detected by the immunological method was only reduced 0.961 times relative to the estimate from the morphological method. In contrast, in eight myelodysplastic syndrome (MDS) patients, the ploidy peaks were either 8N or 4N and the mean was reduced by 0.906 times (P = 0.018). Thus we could immunologically identify small megakaryocytes which we could not identify morphologically. Therefore, this method is useful for measuring megakaryocytic ploidy, especially in the pathological megakaryocytes of MDS patients.

Bone Marrow Examination↗

PubMed1997

Monitoring of occupational exposure to 1-butanol by diffusive sampling and urinalysis.

OBJECTIVES: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol. METHODS: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation. RESULTS: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35-40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm. CONCLUSIONS: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm.

1-Butanol↗

PubMed1997

Background exposure of urban populations to lead and cadmium: comparison between China and Japan.

OBJECTIVES: To assess and compare the background exposure of the general population to lead (Pb) and cadmium (Cd) in China and in Japan. METHODS: Food duplicates and peripheral blood samples were collected from nonoccupationally exposed subjects, viz 202 Chinese women in four Chinese cities (Beijing, Shanghai, Nanning, and Tainan) and 72 Japanese women in three Japanese cities (Tokyo, Kyoto, and Sendai) in the years 1993-1995. Wet-ashing and graphite furnace atomic absorption spectrometric methods were used for the determination of Pb and Cd levels in food and blood samples. RESULTS: Geometric mean (GM) dietary Pb intake (25.8 micrograms/day) and the GM Pb concentration in blood (56.7 micrograms/l) in Chinese were significantly higher than in Japanese women (11.6 micrograms/day in food and 32.1 micrograms/l in blood), whereas Cd in food (32.1 micrograms/day) and Cd in blood (1.92 micrograms/l) in Japanese were significantly higher than in Chinese women (9.9 micrograms/day in food and 1.07 micrograms/l in blood). The intake of Pb and Cd via boiled rice accounted for 3.6% and 31.1% of the total dietary burden in Chinese, and 12.1% and 32.7% in Japanese, respectively. The Cd burden was acquired almost exclusively through the dietary route, whereas the Pb burden came from both air and food, especially in the case of the Chinese population. CONCLUSIONS: The background Pb exposure in the Chinese population was higher than that in the Japanese population, whereas Cd exposure was lower in Chinese women than in their Japanese counterparts.

Air Pollutants↗

PubMed1997

The integrity of the liver among people environmentally exposed to cadmium at various levels.

The objective of the present study was to examine if environmental exposure to cadmium (Cd) had any impact on the integrity of the liver among the general Japanese population. A nationwide survey was conducted in the winter seasons of 1991-1995 in 15 prefectures in Japan to collect 24-h food duplicates, peripheral blood samples, and morning spot urine samples from healthy nonsmoking adult women. The samples were analyzed for Cd by automated graphite furnace atomic absorption spectrometry. In total, 371 women offered food duplicate, blood, and urine samples. The dietary Cd intake was 17.3-79.4 micrograms/day, the level of Cd in blood was 1.58-3.82 ng/ml, and the urinary Cd concentration was 1.06-4.74 micrograms/g creatinine as geometric means calculated on a regional group basis. Analyses for correlation with liver function showed no Cd-exposure-related elevation in enzyme levels or reduction in albumin levels' in serum. The distribution of cases with enzyme levels above normal ranges (below normal in the case of albumin) did not show any dose-related bias. The age of the subject, not the exposure to Cd, was the most influential factor in determining serum enzyme levels. Environmental exposure to Cd has not affected the integrity of the liver among the general population in Japan.

Adult↗

PubMed1997

Types of organic solvents used in small- to medium-scale industries in Japan; a nationwide field survey.

OBJECTIVE: The aim of the present survey is to identify organic solvents commonly used in various workplaces in Japan. METHODS: A total of 24 occupational health service institutions (OHSI) distributed nationwide in Japan offered data on types of solvent workplaces, types of solvents used therein, and the solvent concentrations surveyed in a 2-month period between April and May 1996 to form a data base (OHSI data base, consisting of 1597 cases). Separately, Kyoto Industrial Health Association (KIHA) offered information on 948 cases studied during a 1-year period ranging from April 1995 to March 1996 (KIHA data base). The two data bases were treated in parallel to examine the reproducibility of the results. RESULTS: Detection prevalence was very low (0-1%) for almost half of the 47 legally regulated solvents. Among the solvents in use, toluene was most frequently detected, although the prevalence appeared to be reduced as compared with that recorded for the early 1980s. The most frequently observed solvent combinations comprised toluene, xylenes, and ethyl acetate in the OHSI data base and toluene, xylenes, and methanol in the KIHA data base. Contrary to the case in the 1980s, dichloromethane was used more often than trichloroethylene as a degreasing agent in the present survey. No use was detected for carbon tetrachloride, chloroform, 1,2-dichloroethane, 1,2-dichloroethylene, or 1,1,2,2-tetrachloroethane except for research purposes. CONCLUSIONS: Toluene remained the most common solvent and was used in combination with xylenes, ethyl acetate, and methanol. There was an increase in the use of dichloromethane as a degreasing agent.

Acetates↗

PubMed1997

Immunohistochemical and immuno-electron-microscopic detection of interferon-gamma-inducing factor ("interleukin-18") in mouse intestinal epithelial cells.

The novel cytokine interferon-gamma-inducing factor ("interleukin-18") is produced by macrophage-like cells in mice with endotoxin shock and induces the production of interferon-gamma by T cells in vitro. To determine the physiological role for mouse interferon-gamma-inducing factor, we studied its tissue distribution in several organs (intestine, spleen, thymus, kidney, and liver) in healthy mice of different ages, including fetal stages. Activity of the cytokine in the organ extracts of adult mice was measured by enzyme-linked immunosorbent assay, and the cellular distribution of interferon-gamma-inducing factor in organs from fetal and adult mice was determined by immunohistochemistry. Intestinal extracts of adult mice showed the highest concentrations among the organs studied. Other organ extracts of adult mice showed lower concentrations of the cytokine. Immunohistochemical analysis revealed that interferon-gamma-inducing factor was localized in the cytoplasm of intestinal epithelial cells from fetal and adult mice. These results show for the first time that intestinal epithelial cells may be the main producers of interferon-gamma-inducing factor under normal physiological conditions and suggest that its constitutive expression in intestinal epithelial cells may have an important role in the induction of mucosal immunity.

Animals↗

PubMed1997

Effect of low concentration of epinephrine on human platelet aggregation analyzed by particle counting method and confocal microscopy.

The effect of a physiologic concentration of epinephrine (Ep) on platelet activation was studied by using a novel method that simultaneously measures platelet aggregation by changes in light transmission and counts particles of various sizes by using light scattering. Detailed morphologic changes associated with activation process were studied by using confocal laser scanning microscopy (CLSM). A low concentration of Ep (20 nmol/L) corresponding to a high physiologic concentration triggered the formation of small platelet aggregates (diameter 7 to 30 microm) without any change in light transmission. The redistribution of filamentous actin (F-actin) and the expression of activated glycoprotein IIb-IIIa complex (GPIIb-IIIa), detected by PAC-1 binding, were also observed in the platelets comprising the small aggregates. Attempts were then made to detect changes in cytoplasmic ionized Ca2+ ((Ca2+)i) in individual platelets involved in the aggregate formation by CLSM with fluo-3, a Ca2+-indicating dye. Ep caused a weak (Ca2+)i increase in some individual platelets involved in the formation of small aggregates. This (Ca2+)i increase was associated with platelet aggregation, because no (Ca2+)i rise was detected in single platelets. Furthermore, platelets stimulated by Ep in the presence of RGDS or Ro 44-9883, a GPIIb-IIIa antagonist, did not form small aggregates or trigger a (Ca2+)i rise. Prior incubation with low concentrations of Ep (20, 100 nmol/L) enhanced the initial formation of small (diameter 7 to 30 microm), medium (diameter 30 to 50 microm), or large (diameter 50 to 70 microm) aggregates induced by a subthreshold concentration of adenosine diphosphate (0.25 micromol/L) as determined by the particle counting method. However, no apparent synergistic (Ca2+)i increase was observed in platelets involved in aggregate formation. From these observations the following conclusions have been reached. (1) A high physiologic concentration of Ep (20 nmol/L) is capable of triggering the formation of small aggregates, resulting in the redistribution of F-actin and the expression of activated GPIIb-IIIa complex. (2) An increase in (Ca2+)i is observed in platelets comprising the small aggregates. This increase is not related to the binding of Ep to its receptor but most likely is triggered by platelet-platelet association. (3) The characteristic potentiating effect of Ep is not due to the synergistic increase in (Ca2+)i.

Actins↗

PubMed1997

Endothelium inhibits the palytoxin-induced depolarization and Ca2+ mobilization in porcine coronary artery through endothelium-derived hyperpolarizing factor and nitric oxide released by palytoxin.

Palytoxin induced increases in cytosolic Ca2+ and tension, which were dependent on external Ca2+, and depolarized the membrane in endothelium-denuded porcine coronary arteries. When the endothelium was present, however, these effects were greatly inhibited, suggesting that some factors from endothelium inhibited the palytoxin-actions. Pretreatment with 100 microM N omega-nitro-L-arginine partially reversed the inhibitory effect of endothelium on the Ca2+ movement and the contraction but not that on the depolarization. Pretreatment with 10 microM indomethacin did not affect the inhibition. These results suggest that palytoxin released both nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) from the endothelium, both of which counteracted the actions of palytoxin on smooth muscle cells. It is thought that the palytoxin-induced depolarization was attenuated by hyperpolarization due to EDHF.

Acrylamides↗

PubMed1997

Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia-reperfusion injury.

BACKGROUND: The source of reactive oxygen species in the liver remains to be elucidated. The present study was undertaken to determine whether polymorphonuclear neutrophils (PMNs) can contribute to hepatic ischemia-reperfusion injury, and pretreatment with monoclonal antibodies (mAbs) to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function associated antigen-1 (LFA-1), and CD 18 could improve energy metabolism and prolong the viability of the organ. METHODS: Male Wistar rats were used. Rat liver ischemia was induced by clamping blood vessels supplying median and left lateral hepatic lobes. Monoclonal antibodies to ICAM-1, LFA-1, or CD18 were injected intravenously 5 minutes before inducing ischemia. To determine the effect of mAbs on the survival rate, total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct after making a portafemoral shunt. RESULTS: Although ischemia of the liver for 90 minutes did not permit survival of the animals, pretreatment with mAbs to ICAM-1 plus LFA-1 increased the survival rate to 57%. Pretreatment with mAb to ICAM-1 failed to increase the survival rate. The number of PMNs in the liver increased continually up to 24 hours after reperfusion after 90 minutes of ischemia, and the expression of ICAM-1 was enhanced 4 hours after reperfusion. This is accompanied by a low recovery of hepatic adenosine triphosphate and, on the contrary, a marked increase in lipid-peroxide in the reperfused liver. Pretreatment with mAbs suppressed the infiltration of PMNs and the elevation of lipid peroxide and enhanced the recovery of hepatic adenosine triphosphate 6, 12, or 24 hours after reperfusion. Pretreatment with mAbs also prevented the rise in serum alanine aminotransferase level after reperfusion. CONCLUSIONS: These results suggest that PMNs contribute to ischemia-reperfusion injury in the liver 4 hours and more after reperfusion, and pretreatment with mAbs to adhesion molecules is useful for the prevention of ischemic liver cell injury.

Adenine Nucleotides↗