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Biomedical subjects

G H Lee

Publications and source records attributed to G H Lee.

At least 37 records · Page 2Linked to original sources
PubMed2001

Stress fracture of the femoral neck in young adult: report of four cases.

Stress fracture of the femoral neck is an uncommon injury. If the diagnosis is missed or delayed and fracture displacement results, serious complications such as avascular necrosis of the femoral head, nonunion or varus deformity may occur. Treatment depends on the type of stress fracture. Compression and tension stress fractures can be successfully treated with conservative management or prophylactic internal fixation using multiple screws. Displaced stress fractures are an orthopedic emergency, requiring prompt surgical intervention. Poor outcomes after fracture displacement have been reported by many authors. We present four cases demonstrating three types of stress fracture of the femoral neck. It is hoped that these case reports will serve to increase practitioner awareness of this injury and emphasize the need for careful diagnosis and treatment of this potentially problematic injury.

Adult↗
PubMed2001

Lymphosarcoma in a brown bear (Ursus arctos).

An example of lymphoblastic lymphosarcoma was found in a 7-year-old male brown bear (Ursus arctos) that died after having a 7-month history of depression, anorexia and watery diarrhea. Grossly the mesenteric lymph nodes were enlarged to approximately 4 to 6 times their normal size and histologically diagnosed as lymphoblastic lymphosarcoma. The small intestinal mucosa was corrugated and had severe mural thickening due to infiltrated neoplastic cells. Hepatic metastasis was also noted. This is the first reported case of lymphosarcoma in Ursidae in Korea. As an incidental finding, endogenous lipid pneumonia was noted in the lung.

Animals↗
PubMed2000

Dissociation of sarcoglycans and the dystrophin carboxyl terminus from the sarcolemma in enteroviral cardiomyopathy.

Enteroviral infection can cause an acquired form of dilated cardiomyopathy. We recently reported that dystrophin is cleaved, functionally impaired, and morphologically disrupted in vitro as well as in vivo during infection with coxsackievirus B3. Genetic dystrophin truncations lead to a marked decrease in dystrophin-associated glycoproteins, whereas expression of only the naturally occurring dystrophin carboxyl terminus, Dp-71, restores the sarcolemmal association of the dystrophin-associated glycoproteins. We sought to determine whether acute cleavage of dystrophin leads to a dissociation of the carboxyl-terminal dystrophin fragment and of the sarcoglycans from the sarcolemma during coxsackievirus B3 infection. We found that in cultured cardiac myocytes and murine hearts infected with coxsackievirus B3, the sarcolemmal localization of the dystrophin carboxyl terminus is lost. The dystrophin-associated glycoproteins alpha-, beta-, gamma-, and delta-sarcoglycan and beta-dystroglycan were markedly decreased in the membrane fraction of infected cells in culture, and the typical sarcolemmal localization for each of these proteins was lost in coxsackievirus-B3-infected cardiomyocytes in vivo. Furthermore, sucrose gradient ultracentrifugation demonstrated that delta-sarcoglycan was physically dissociated from dystrophin within the membrane fraction. In vivo, the sarcolemmal integrity was functionally impaired with Evans blue dye uptake even though there was no generalized disruption of the sarcolemma of infected myocytes evidenced by intact wheat germ agglutinin staining. In analogy to hereditary sarcoglycanopathies, this disintegration of the sarcoglycan complex may, in addition to the dystrophin cleavage, play an important role in the pathogenesis of enterovirus-induced cardiomyopathy. These results imply a potential role for disruption of the sarcoglycans in an acquired form of heart failure.

Animals↗
PubMed2000

Synthesis and structural characterization of configurational isomers of tungsten-palladium complexes with bridging diphenyl(dithioalkoxycarbonyl)phosphine as a ligand and phosphine transfer from tungsten to palladium.

Treatment of the complex [W(CO)5[PPh2(CS2Me)]] (2) with [Pd(PPh3)4] (1) affords binuclear complexes such as anti-[(Ph3P)2Pd[mu-eta 1,eta 2-(CS2Me)PPh2]W(CO)5] (3), syn-[(Ph3P)2Pd[mu-eta 1,eta 2-(CS2Me)PPh2]W(CO)5] (4), and trans-[W(CO)4(PPh3)2] (5). In 3 and 4, respectively, the W and Pd atoms are in anti and syn configurations with respect to the P-CS2 bond of the diphenyl(dithiomethoxycarbonyl)phosphine ligand, PPh2(CS2Me). Complex 3 undergoes extensive rearrangement in CHCl3 at room temperature by transfer of a PPh3 ligand from Pd to W, eliminating [W(CO)5(PPh3)] (7), while the PPh2CS2Me ligand transfers from W to Pd to give [[(Ph3P)Pd[mu-eta 1,eta 2-(CS2Me)PPh2]]2] (6). In complex 6, the [Pd(PPh3)] fragments are held together by two bridging PPh2(CS2Me) ligands. Each PPh2(CS2Me) ligand is pi-bonded to one Pd atom through the C=S linkage and sigma-bonded to the other Pd through the phosphorus atom, resulting in a six-membered ring. Treatment of Pd(PPh3)4 with [W(CO)5[PPh2[CS2(CH2)nCN]]] (n = 1, 8a; n = 2, 8b) in CH2Cl2 affords syn-[(Ph3P)2Pd[mu-eta 1,eta 2-[CS2(CH2)nCN]PPh2]W(CO)5] (n = 1, 9a; n = 2, 9b). Similar configurational products syn-[(Ph3P)2Pd[mu-eta 1,eta 2-(CS2R)PPh2]W(CO)5] (R = C2H5, C3H5, C2H4OH, C3H6CN, 11a-d) are synthesized by the reaction of Pd(PPh3)4 with [W(CO)5[PPh2(CS2R)]] (R = C2H5, C3H5, C2H4OH, C3H6CN, 10a-d). Although complexes 11a-d have the same configuration as 9a,b, the SR group is oriented away from Pd in the former and near Pd in the latter. In these complexes, the diphenyl(dithioalkoxycarbonyl)phosphine ligand is bound to the two metals through the C=S pi-bonding and to phosphorus through the sigma-bonding. All of the complexes are identified by spectroscopic methods, and the structures of complexes 3, 6, 9a, and 11d are determined by single-crystal X-ray diffraction. Complexes 3, 9, and 11d crystallize in the triclinic space group P1 with Z = 2, whereas 6 belongs to the monoclinic space group P2/c with Z = 4. The cell dimensions are as follows: for 3, a = 10.920(3) A, b = 14.707(5) A, c = 16.654(5) A, alpha = 99.98(3) degrees, beta = 93.75(3) degrees, gamma = 99.44(3) degrees; for 6, a = 15.106(3) A, b = 9.848(3) A, c = 20.528(4) A, beta = 104.85(2) degrees; for 9a, a = 11.125(3) A, b = 14.089(4) A, c = 17.947(7) A, alpha = 80.13(3) degrees, beta = 80.39(3) degrees, gamma = 89.76(2) degrees; for 11d, a = 11.692(3) A, b = 13.602(9) A, c = 18.471(10) A, alpha = 81.29(5) degrees, beta = 80.88(3) degrees, gamma = 88.82(1) degrees.

Journal Article↗
PubMed2000

Heterobimetallics of nickel-iron dinitrosyl: electronic control by chelate and diatomic ligands.

Reaction of [PPN][Fe(NO)2(SePh)2] (1) with dimeric [Ni(mu-SCH2CH2SCH2CH2S)]2 in the presence of additional NO2- produced the neutral heterobimetallic [(ON)Ni[(mu-SCH2CH2)2S]Fe(NO)2] complex (2). The X-ray crystal structures of 1 and 2 show distorted tetrahedral iron dinitrosyl groups, assigned according to the Feltham-Enemark notation as [Fe(NO)2]9 The Fe-NO bonds are off linearity by an average of approximately equals 10 degrees for compounds 1 and 2, while a more linear Ni-NO coordination with a Ni-NO distance of 1.644(2) A was found in 2. The v(NO) value of complex 2 is consistent with an assignment for [Ni(NO)]9 of Ni0(NO)+ as is known for analogous phosphine derivatives, P3Ni0(NO)+. EPR signals of g values = 2.02-2.03 confirmed the existence of the odd electron in the chalcogenated [Fe(NO)2]9 compounds. Two [Fe(NO)2]10 complexes coordinated by the nickel(II) dithiolate, (bismercaptoethanediazacyclooctane)nickel(II), (Ni-1), (Ni-1)Fe(CO)(NO)2 and (Ni-1)Fe(NO)2, were prepared for comparison to the Ni0(NO)+ derivative and other monomeric and homodimetallic derivatives of the Fe(NO)2 fragment. While the oxidation level of Fe(NO)2 is the primary determinant of v(NO) values, they are also highly sensitive to ancillary ligands and, thereby, the distal metal influence through the bridging thiolate donor.

Binding Sites↗
PubMed2000

Enteroviral cardiomyopathy: bad news for the dystrophin-glycoprotein complex.

Genetic deficiency of the dystrophin-glycoprotein complex causes hereditary dilated cardiomyopathy. Enteroviruses can also cause cardiomyopathy and we have recently described a potential molecular mechanism for enterovirus-induced dilated cardiomyopathy. The coxsackieviral protease 2A proteolytically cleaves and functionally impairs dystrophin. Additionally, during infection with coxsackievirus B3, the dystrophin-glycoprotein complex becomes disrupted and the sarcolemmal integrity is lost. This review article discusses the importance of the dystrophin cleavage for the development of increased sarcolemmal permeability and potential pathways for mechanisms by which the dystrophin cleavage during coxsackieviral infection may contribute to dilated cardiomyopathy.

Cell Transformation, Viral↗
PubMed2000

Life-threatening intraabdominal arterial embolization after histoacryl injection for bleeding gastric ulcer.

N-butyl-cyanoacrylate (Histoacryl) injection has become the treatment of choice for acutely bleeding esophagogastric varices, and is the only effective option for endoscopic treatment of gastric varices. Recent reports confirm the ability of Histoacryl injection therapy to achieve immediate hemostasis in cases of gastric ulcer bleeding or Dieulafoy ulcer, where conventional endoscopic hemostatic treatment had failed. Although the overall safety record of Histoacryl injection has been relatively good, there have been scattered cases of serious complications. Here, we present two patients showing life-threatening intraabdominal arterial embolization after Histoacryl injection. They had chronic gastric ulcers with active arterial bleeding. In spite of attempts at hemostatic treatment, complete hemostasis was not achieved. We injected Histoacryl, diluted with Lipiodol, into bleeding gastric ulcers, resulting in successful hemostasis. Soon after the procedure, intraabdominal arterial embolization developed in both patients. One patient survived and the other died. Based on these experiences, we would like to warn gastrointestinal endoscopists to be alert to these fatal complications, and we propose that less diluted Histoacryl seems to be preferable in cases of bleeding peptic ulcers.

Celiac Artery↗
PubMed2000

Influence of glutathione S-transferase M1 and T1 genotypes on larynx cancer risk among Korean smokers.

Glutathione S-transferase (GST) isoenzymes are involved in the detoxification of major carcinogens present in tobacco smoke. It is thus conceivable that deficiency in GST activity due to homozygous deletions of the GSTM1 and GSTT1 genes (the null genotypes) may modulate susceptibility to smoking-induced cancers. The influence of the GSTM1 and GSTT1 null genotypes on larynx cancer risk among the Korean population were evaluated using peripheral blood DNA from 82 larynx cancer patients and 63 healthy controls, all of whom were male current smokers. Increased larynx cancer risk was related to the GSTM1 null genotype (odds ratio (OR)=3.53, 95% confidence interval (CI)=1.27-9.83). The OR associated with the GSTT1 null genotype was also increased, but did not reach statistical significance (OR=1.83, 95% CI=0.70-4.79). Individuals lacking both the GSTM1 and GSTT1 genes were at a significantly higher risk for larynx cancer than individuals with both genes present (OR=4.04, 95% CI=1.33-12.30). These data confirm that the GSTM1 null genotype is an important risk modifier for larynx cancer among Korean smokers and combined GSTM1 and GSTT1 null genotypes could be a useful predictor of genetic susceptibility to larynx cancer.

Adult↗
PubMed1999

Induction of tight junctions in human connexin 32 (hCx32)-transfected mouse hepatocytes: connexin 32 interacts with occludin.

Small gap junction plaques are associated with tight junction strands in some cell types including hepatocytes and it is thought that they may be closely related to tight junctions and the establishment of cell polarity. In order to examine roles of gap junctions in regulating expression and structure of tight junctions, we transfected human Cx32 cDNA into immortalized mouse hepatocytes (CHST8 cells) which lack endogenous Cx32 and Cx26. Immunocytochemistry revealed that endogenous integral tight junction protein occludin was strongly localized and was colocalized with Cx32 at cell borders in transfectants, whereas neither was detected in parental cells. In Northern blots, mRNAs encoding occludin and the other integral tight junction proteins, claudin-1 and -2, were induced in the transfectants compared to parental cells. In Western blots, occludin protein was increased in the transfectants compared to parental cells, and binding of occludin to Cx32 protein was demonstrated by immunoprecipitation. In freeze fracture of the transfectants, tight junction strands were more numerous and complex compared to parental cells, and small gap junction plaques appeared within induced tight junction strands. Nevertheless, no change in barrier function of tight junctions was observed. These results indicate that in hepatocytes, gap junction, and tight junction expression are closely coordinated, and that Cx32 may play a role in regulating occludin expression.

Animals↗
PubMed1999

Nitric oxide protects PC12 cells from serum deprivation-induced apoptosis by cGMP-dependent inhibition of caspase signaling.

Although nitric oxide (NO) induces neuronal cell death under some conditions, it also can prevent apoptosis resulting from growth factor withdrawal. We investigated the molecular mechanism by which NO protects undifferentiated and differentiated PC12 cells from trophic factor deprivation-induced apoptosis. PC12 cells underwent apoptotic death in association with increased caspase-3-like activity, DNA fragmentation, poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c release after 24 hr of serum withdrawal. The apoptosis of PC12 cells was inhibited by the addition of NO-generating donor S-nitroso-N-acetylpenicillamine (SNAP) (5-100 microM) and the specific caspase-3-like protease inhibitor Ac-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-cho) but not the YVADase (or caspase-1-like protease) inhibitor N-acetyl-Tyr-Val-Ala-Asp-aldehyde (Ac-YVAD-cho). SNAP and Ac-DEVD-cho prevented the increase in DEVDase (caspase-3-like protease) activity. The SNAP-mediated suppression of DEVDase activity was only minimally reversed by the incubation of cell lysate with dithiothreitol, indicating that NO did not S-nitrosylate caspase-3-like proteases in PC12 cells. Western blot analysis showed that NO inhibited the proteolytic activation of caspase-3. The cGMP analog 8-bromo-cGMP (8-Br-cGMP) blocked apoptotic cell death, caspase-3 activity and activation, and cytochrome c release. The soluble guanylyl cyclase inhibitor 1-H-oxodiazol-[1,2,4]-[4,3-a] quinoxaline-1-one (CODQ) significantly attenuated NO-mediated, but not 8-Br-cGMP-dependent, inhibition of apoptotic cell death, PARP cleavage, cytochrome c release, and DEVDase activity. Furthermore, the protein kinase G inhibitor KT5823 reversed both SNAP- and 8-Br-cGMP-mediated anti-apoptotic events. All these apoptotic phenomena were also suppressed by NO production through neuronal NO synthase gene transfer into PC12 cells. Furthermore, similar findings were observed in differentiated PC12 cells stimulated to undergo apoptosis by NO donors and NGF deprivation. These findings indicate that NO protects against PC12 cell death by inhibiting the activation of caspase proteases through cGMP production and activation of protein kinase G.

Animals↗
PubMed1999

Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy.

Enteroviruses such as Coxsackievirus B3 can cause dilated cardiomyopathy, but the mechanism of this pathology is unknown. Mutations in cytoskeletal proteins such as dystrophin cause hereditary dilated cardiomyopathy, but it is unclear if similar mechanisms underlie acquired forms of heart failure. We demonstrate here that purified Coxsackievirus protease 2A cleaves dystrophin in vitro as predicted by computer analysis. Dystrophin is also cleaved during Coxsackievirus infection of cultured myocytes and in infected mouse hearts, leading to impaired dystrophin function. In vivo, dystrophin and the dystrophin-associated glycoproteins alpha-sarcoglycan and beta-dystroglycan are morphologically disrupted in infected myocytes. We suggest a molecular mechanism through which enteroviral infection contributes to the pathogenesis of acquired forms of dilated cardiomyopathy.

Animals↗
PubMed1999

Near infra-red interactance for nutritional assessment of dialysis patients.

BACKGROUND: Malnutrition is a common problem in dialysis patients and may affect up to one-third of patients. Near-infrared interactance (NIR) is a novel approach to estimate body composition and per cent total body fat. METHODS: We used near-infrared interactance (Futrex 5000) to estimate the body composition including body fat percentage, as well as subjective global assessment (SGA), anthropometric measurements including mid-arm circumference (MAC), triceps and biceps skinfold thickness, calculated mid-arm muscle circumference (MAMC), body mass index (BMI), and laboratory values. NIR score, SGA assessment and anthropometric parameters were measured shortly after the end of a dialysis session. NIR measurement was made by placing a Futrex sensor on the nonaccess upper arm for several seconds. Serum albumin, transferrin (reflected by total iron binding capacity), and total cholesterol concentrations were performed as well. RESULTS: Thirty-four patients (20 men and 14 women) were selected from a pool of 120 haemodialysis patients. Their ages ranged from 26 to 86 years (58+/-14 years). Time on dialysis ranged from 8 months to 19 years (4.5+/-4.6 years). NIR scores were significantly different in three SGA groups: (A) well-nourished, 32.5+/-6.9%; (B) mildly to moderately malnourished, 29.2+/-5.3%; and (C) severely malnourished, 23.2+/-10.2% (P<0.001). Pearson correlation coefficients (r) between the NIR score and nutritionally relevant parameters were significant (P<0.001) for body mass index (r=+0.81), mid-arm circumference (r=+0.74), triceps skin fold (r=+0.54), biceps skin fold (r=+0.55), and mid-arm muscle circumference (r=+0.54). An inverse correlation was also found between NIR and years dialysed (r=-0.49, P=0.004), denoting a lesser body fat percentage according to NIR for patients dialysed longer. NIR was correlated with serum transferrin (r=+0.41, P=0.016) and cholesterol (r=+0.39, P=0.022) and marginally with serum albumin (r=+0.29, P=0.097). CONCLUSIONS: We conclude that NIR, which can be performed within seconds, may serve as an objective indicator of nutritional status in haemodialysis patients. More comparative and longitudinal studies are needed to confirm the validity of NIR measurements in nutritional evaluation of dialysis patients.

Adipose Tissue↗
PubMed1999

A modified quantitative subjective global assessment of nutrition for dialysis patients.

BACKGROUND: Malnutrition, a predictor of increased mortality in dialysis patients, can be estimated using the subjective global assessment (SGA), a semiquantitative scale with three severity levels. This semiquantitative feature restricts the SGA's reliability and precision. METHODS: Using the components of the conventional SGA, we developed a fully quantitative scoring system (the dialysis malnutrition score) consisting of seven variables: weight change, dietary intake, gastrointestinal symptoms, functional capacity, comorbidity, subcutaneous fat and signs of muscle wasting. Each component was assigned a score from 1 (normal) to 5 (very severe). The sum of all seven components in this malnutrition score lies between 7 (normal) and 35 (severely malnourished). To evaluate nutritional status in chronic dialysis patients, anthropometric measurements including mid-arm circumference (MAC), triceps skin-fold thickness, calculated mid-arm muscle circumference (MAMC), body mass index (BMI, ratio of weight to square of height) and laboratory parameters were used. Forty-one patients (20 men and 21 women) were randomly selected from a pool of 120 haemodialysis patients. Patients were aged between 26 and 81 years (mean SD, 57 +/- 12 years) and had undergone haemodialysis for between 7 months and 12 years (mean +/- SD, 3.0 +/- 2.1 years). RESULTS: The malnutrition score of each patient was assessed by a dietitian within 5-20 min (12.0 +/- 3.5 min) with no knowledge of anthropometric findings. Pearson correlation coefficients between the malnutrition score and biceps skin-fold (r= -0.32) MAC (r= -0.55), MAMC (r= -0.66), BMI (r= -0.35), total iron-binding capacity (TIBC, r= -0.77), the serum albumin concentration (r= -0.36) and total protein (r= -0.33) were all significant, whereas the conventional SGA had significant correlation only with TIBC (r= -0.35) and MAMC (r= -0.37). Malnutrition score showed a significant correlation with age (r= +0.34) and years dialysed (r= +0.28). Multiple regression analysis showed a significant correlation between the malnutrition score and the combination of the MAMC, BMI, serum albumin concentration and TIBC (r= 0.81, P<0.001). There was no correlation between the malnutrition score and sex, urea reduction ratio, protein catabolic rate, and the absolute lymphocyte count. CONCLUSIONS: We conclude that our invented malnutrition score, which can be performed in minutes, reliably assesses the nutritional status of haemodialysis patients. We suggest that our malnutrition score may be superior to the SGA. More comparative and longitudinal studies are needed to confirm the validity of this scoring system in nutritional evaluation of dialysis patients.

Adult↗
PubMed1999

Morphology, proliferation and apoptosis of mouse liver epithelial cells cultured as spheroids.

The MLEC10 is an epithelial cell line derived from an untreated, normal C3H/HeN mouse liver. We previously demonstrated that tumorigenic variants from this cell line produced moderately differentiated hepatocellular carcinomas in nude mice. However, it has remained unclear whether the parental MLEC10 cells represent immortalized hepatocytes or so-called oval cells, both of which may serve as precursors for hepatocellular neoplasms. In this study, we performed 3-dimensional, spheroid culture of the MLEC100 cells in order to facilitate histological assessment of their lineage. Spheroidal aggregates were formalin-fixed and embedded in paraffin for routine light-microscopic observation of hematoxylin and eosin-stained sections. Histopathologically, the MLEC10 cells were indistinguishable from immature hepatocytes and distinct from oval cells. At the electron-microscopic level, their hepatocytic nature was evidenced by bile canaliculus structures and glycogen storage. Intriguingly, the spheroids contained fragmentary material reminiscent of Councilman bodies, implying apoptosis of the hepatocytes. Although the cells significantly proliferated during the first three days of culture, apoptotic death then resulted in a 75 % decrease in viable cell number. Thereafter, both apoptosis and cell division appeared silent, the numbers being unchanged. Expression of the p53 tumor suppressor gene became gradually elevated, correlating positively with growth arrest, but negatively with apoptosis, suggesting that the cell death occurred independently of p53. Our results indicate that at least some liver epithelial cell lines derived from untreated murine livers exhibit a hepatocytic morphology in spheroid culture. Also, the present culture system provides a useful tool for investigating biological phenomena, e.g. apoptosis, specifically involving liver cells, under 3-dimensional conditions.

Agar↗
PubMed1999

Screening for hypercholesterolaemia in patients with other risk factors for coronary heart disease.

OBJECTIVE: To determine the prevalence of hypercholesterolaemia in individuals with other major risk factors of coronary heart disease and markers of hypercholesterolaemia. METHODS: A community-based cross-sectional study on a random sample of 261 persons aged between 35 and 69 years residing in the flatted housing estate of West Coast, Singapore, was conducted in 1997. A questionnaire, together with a medical examination and investigation involving the use of Reflotron machine, were used to collect the information required. RESULTS: 43.2% of the population had at least 1 major risk factor, with 18.1% being smokers, 18.1% with hypertension, 6.5% with diabetes mellitus, 5.1% being obese, and 5.0% with a family history of coronary heart disease. Higher percentages of individuals with hypercholesterolaemia were found when each risk factor was present. 9.5% had 2 or more risk factors, of which, 21.1% had high cholesterol levels. A high prevalence of hypercholesterolaemia that was statistically significant was found amongst subjects with corneal arcus below the age of 60. CONCLUSIONS: The risk factors of coronary heart disease remain prevalent in our population. We recommend screening for serum cholesterol only in those with at least 2 major risk factors of coronary heart disease in the general population between 35 and 69 years of age.

Adult↗
PubMed1999

Expression of an IL-1 receptor antagonist during mouse hepatocarcinogenesis demonstrated by differential display analysis.

The differential display technique was applied for identification of genes that have altered expression in mouse hepatocellular carcinomas relative to normal liver. Three genes were identified. The IL-1 receptor antagonist (IL-1ra) was expressed in hepatocellular carcinomas, whereas the major urinary protein (MUP) and cytochrome P-450 naphthalene hydroxylase (cyp2F2) genes were down-regulated. Because IL-1ra is a natural antagonist of IL-1, and because the latter has been reported to suppress the growth of hepatic cells, we also studied the expression of IL-1ra in hepatocarcinogenesis. IL-1ra was immunohistochemically detected in tumor cells in approximately 70% of hepatocellular adenomas and carcinomas, whereas early preneoplastic hepatocytic foci, as well as normal hepatocytes surrounding the lesions, were negative. In addition, 20% of human hepatocellular carcinomas were also partly positive for IL-1ra. RT-PCR analysis demonstrated that mouse hepatic tumors contain both secreted and intracellular forms of IL-1ra. On the other hand, there were no differences in levels of IL-1alpha and IL-1beta between hepatic tumors and normal liver in mice, suggesting that the majority of tumors create a microenvironment that inhibits the actions of IL-1. Furthermore, IL-1ra-positive adenomas contained more proliferating cell nuclear antigen-positive cells than IL-1ra-negative adenomas, indicating a link with high proliferation activity, although this was no longer evident in carcinomas. The observed altered gene expression may be related to biological phenotypes of hepatic tumors, and IL-1ra in particular may positively influence tumor cell growth through its antagonism of IL-1.

Animals↗