| 1. |
- Arkadopoulos, N, et al.
(författare)
-
Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats
- 1998
-
Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 28:5, s. 1365-1370
-
Tidskriftsartikel (refereegranskat)abstract
- To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic, Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta 1 (TGF-beta 1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic, Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group I anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta 1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01), Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta 1 levels when compared with sham-transplanted controls, In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta 1 levels in rats rendered anhepatic.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Nishio, Akiyosho, et al.
(författare)
-
Comparative studies of mitochondrial autoantibodies in sera and bile in primary biliary cirrhosis
- 1997
-
Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 25:5, s. 1085-1089
-
Tidskriftsartikel (refereegranskat)abstract
- Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little is known about the presence of AMA in bile. In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients (21.1%) patients. AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient. Immunoglobulin (Ig)A AMA were found in the bile of 9 of 19 patients (47.7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%). Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls. Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites. Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.
|
|
| 9. |
- Ohlson, Lena C. E., et al.
(författare)
-
Inhibition of in vivo rat liver regeneration by 2-acetylaminofluorene affects the regulation of cell cycle-related proteins
- 1998
-
Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 27:3, s. 691-696
-
Tidskriftsartikel (refereegranskat)abstract
- The effects of dietary 2-acetylaminofluorene (2-AAF) on cell cycle-related proteins was studied in regenerating livers from male Wistar rats, The levels of cyclins, cyclin dependent kinases (cdks), and related proteins were studied at different times during the first cell cycle after partial hepatectomy (PH). The frequency of proliferation cell nuclear antigen (PCNA)-positive nuclei, a marker of S phase progression, was almost zero during the first 27 hours after PH in the mitoinhibited 2-AAF-treated rats, while about 50% of the nuclei were labeled 24 hours after PH in control animals. Accordingly, Western blot tests showed markedly elevated PCNA protein levels from 18 hours to the end of S phase in untreated animals but no upregulation in response to 2-AAF. Compared with control animals, animals treated with 2-AAF showed increased levels of cdk 4 and cyclin D-3 from 12 and 15 hours after PH, respectively, and altered cyclicity in cyclin Dg expression. No effects on cyclin E were observed, while the increase in cdk 2 levels in control animals during late G(1)/S (15-27 hours) was abolished by 2-AAF. p53 was induced by 2-AAF treatment during the same period, with a peak at 24 hours. The protein detected with p21 antibodies was highly expressed in unstimulated hepatocytes in control animals, and further increased by 2-AAF. The expression was sustained until 15 hours after PH in control rats while 2-AAF-treated animals lacked detectable protein during this period; however, a transient increase was observed at 21 hours, Thus, 2-AAF affects several parameters of cell cycle regulation of possible relevance for its inhibitory effects on hepatocyte proliferation in vivo.
|
|
| 10. |
|
|
