Biomedical subjects

Nobuyuki Enomoto

Publications and source records attributed to Nobuyuki Enomoto.

59 records · Page 4Linked to original sources

PubMed2002

A case of primary leiomyoma of the liver in a patient without evidence of immunosuppression.

A 31-year-old Japanese male was admitted to our hospital for investigation of an asymptomatic nodular lesion of the liver detected by abdominal ultrasonography (US) during a routine medical examination. Computed tomography (CT) revealed a single, hypovascular mass 35 mm in diameter, within the left lobe of the liver. The tumor demonstrated hypointensity on T1-weighted, and hyperintensity on T2-weighted magnetic resonance (MR) imaging. Hematological and biochemical investigations were normal. There were no abnormalities of the gastrointestinal or urinary tracts. A left lateral segmentectomy of the liver was performed. Pathological examination of the nodule revealed a primary leiomyoma of the liver, with positive immunohistochemical staining for vimentin and desmin antigens. Primary leiomyoma of the liver is rare, with the majority of cases associated with immunodeficiency disorders. This patient had no evidence of any underlying disease. Primary leiomyoma of the liver should be considered when a nodular lesion is found in a patient without evidence of viral hepatitis.

Journal Article↗

PubMed2002

Thalidomide prevents alcoholic liver injury in rats through suppression of Kupffer cell sensitization and TNF-alpha production.

BACKGROUND & AIMS: Sensitization of Kupffer cells (KCs) to lipopolysaccharide (LPS) and overproduction of tumor necrosis factor (TNF) alpha are critical for progression of alcoholic liver injury. Thalidomide has been shown to suppress TNF-alpha production from macrophages. Accordingly, the purpose of this study was to determine whether thalidomide could prevent alcohol-induced liver injury. METHODS: Rats were given ethanol (5 g/kg body wt) and thalidomide (5 mg/kg) once every 24 hours intragastrically. To assess the sensitization of Kupffer cells, LPS (5 mg/kg intravenously) was administered and liver histology was evaluated 24 hours later. KCs were isolated after 4 weeks of ethanol treatment and intracellular Ca2+ ([Ca2+]i) was measured using fura-2, whereas TNF-alpha was evaluated by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. CD14 was determined by Western and fluorescence staining. RESULTS: Treatment with ethanol for 8 weeks caused marked steatosis, necrosis, and inflammation in the liver. These pathologic parameters were diminished markedly by treatment with thalidomide. In the 4-week ethanol group, the LPS-induced liver damage was aggravated and KCs were sensitized to LPS. Coadministration of thalidomide with ethanol prevented the KC sensitization completely. Furthermore, thalidomide abolished the LPS-induced increase in CD14 expression and [Ca2+]i elevation in KCs. Gut permeability was increased about 10-fold after 4 weeks of ethanol exposure, which was not affected by thalidomide. Moreover, thalidomide reduced the LPS-induced TNF-alpha production by KCs by decreasing TNF-alpha messenger RNA. CONCLUSIONS: These results collectively indicate that thalidomide prevents alcoholic liver injury through suppression of TNF-alpha production and abolishment of KC sensitization.

Animals↗

PubMed2002

Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver.

In this study, we investigated hepatic fibrogenesis caused by long-term thioacetamide (TAA) administration in ob/ob mice, a naturally occurring leptin deficient animal. In the lean littermates, prominent hepatic fibrosis, as well as positive staining for alpha smooth muscle actin (alpha-SMA), was induced by treatment with TAA (200 microg/g, IP, 3 times per week) for 4 to 8 weeks as expected. In sharp contrast, almost no hepatic fibrosis developed in ob/ob mice given the equivalent doses of TAA, where specific staining for alpha-SMA barely was detected. Induction of alpha1(I) procollagen mRNA caused by TAA also was prevented in ob/ob mice almost completely. Further, transforming growth factor beta (TGF-beta) mRNA was increased in the liver after TAA treatment for 4 weeks in lean littermates, which also was prevented in ob/ob mice. Interestingly, fibrotic septa in the hepatic lobules, as well as increases in alpha1(I) procollagen mRNA, was observed in ob/ob mice, when they were injected with recombinant murine leptin (1 microg/g daily) in combination with TAA treatment. Leptin per se did not cause any fibrotic changes in the liver in ob/ob mice. These findings clearly indicated that leptin deficiency is responsible for the resistance to TAA-induced profibrogenic responses in ob/ob mice. In conclusion, leptin appears to promote profibrogenic responses in the liver, in part, by up-regulation of TGF-beta.

Actins↗

PubMed2002

Estriol enhances lipopolysaccharide-induced increases in nitric oxide production by Kupffer cells via mechanisms dependent on endotoxin.

BACKGROUND: Estriol causes sensitization of Kupffer cells to lipopolysaccharide (LPS) via mechanisms dependent on gut-derived LPS. Accordingly, this study examines the effect of estriol treatment on nitric oxide (NO) production from Kupffer cells. METHODS: Rats were given estriol (20 mg/kg body weight) intraperitoneally, and Kupffer cells were isolated 24 hr later. Some rats were treated for 4 days with 150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin to prevent growth of intestinal bacteria, the primary source of endotoxin in the gastrointestinal tract. After addition of LPS, NO production by Kupffer cell was detected using a fluorescence indicator, DAF-2. RESULTS: Twenty-four hours after estriol administration, LPS-induced NO production by Kupffer cells was enhanced as compared with control Kupffer cells. Sterilization of the gut with antibiotics blocked this enhancement. CONCLUSIONS: Estriol treatment in vivo enhances LPS-induced NO production in Kupffer cells.

Animals↗

PubMed2002

Oral contraceptives worsen endotoxin-induced liver injury in rats.

BACKGROUND: Oral contraceptives are widely used; however, these drugs occasionally cause liver injury. Recently, it was reported that estriol worsens alcoholic liver injury by the mechanism involving activation of Kupffer cells as a result of gut-derived endotoxin. However, the relationship between oral contraceptives and endotoxin-induced liver injury has not been elucidated. Here we show that oral contraceptives sensitize Kupffer cells via a mechanism dependent on increased gut permeability to endotoxin. METHODS: Female Wistar rats (200-250 g) were given intraperitoneally a combination of estradiol (35 ng/kg of 17 alpha-Ethynylestradiol) and progesterone (2 microg/kg of Norethindrone), each dose being similar to that contained in oral contraceptives (EP treatment). After 24 hr, a sublethal dose of lipopolysaccharide (LPS; 5 mg/kg) was injected via the tail vein. In some experiments, antibiotics (150 mg/kg/day of polymyxin B and 450 mg/kg/day of neomycin) were administered orally for 4 days before EP treatment. Gut permeability was measured in isolated segments of ileum by translocation of horseradish peroxidase. Kupffer cells were isolated and cultured in RPMI 1640 + 10% fetal bovine serum for 24 hr. After addition of LPS (100 ng/ml) to the culture medium, intracellular calcium concentration ([Ca2+](i) ) was measured with fura-2. RESULTS: Liver histology in rats given EP treatment intraperitoneally followed by an injection of LPS (5 mg/kg) 24 hr later revealed pronounced liver damage with massive necrosis. Whereas mean values of alanine aminotransferase (ALT) in the control, nontreated rats were 30 +/- 6 IU/liter, ALT increased to 75 +/- 21 IU/liter 24 hr after LPS injection. This increase was aggravated 6-fold (483 +/- 118 IU/liter; p< 0.05) by EP treatment. The EP treatment-induced increase in ALT was completely blocked by antibiotics (82 +/- 26 IU/liter; p< 0.05). Gut permeability was increased approximately 10-fold with EP treatment. This increase in gut permeability was not altered by treatment with nonabsorbable antibiotics. In isolated Kupffer cells, LPS increased [Ca2+](i) of Kupffer cells in control rats from basal levels (36 +/- 8 nmol/liter) to 100 +/- 8 nmol/liter. In contrast, the LPS-induced [Ca2+](i) elevation was approximately 3-fold greater in the group given EP treatment before 24 hr (305 +/- 17 nmol/liter; p< 0.05). This increase was also blocked completely by treatment with antibiotics (128 +/- 13 nmol/liter). Similar results were obtained for LPS-induced tumor necrosis factor-alpha production by Kupffer cells from either control or EP treatment group. The increased tumor necrosis factor-alpha production as a result of EP treatment was blocked completely by antibiotics. CONCLUSIONS: These results indicate that EP treatment in vivo sensitizes Kupffer cells to LPS via a mechanism dependent on the portal increase of gut-derived endotoxin. This event suggests that oral contraceptives exacerbate alcoholic liver injury.

Animals↗