“
“Dream no small dreams for they have no power to move the hearts of men. Goethe I would like to thank Dr. Lindor and other members of the editorial

board of HEPATOLOGY for honoring me by asking me to contribute to the “Masters of Hepatology” series. My background is very different from that of other renowned hepatologists who have already contributed to this series. For this reason, I will go back to the beginning of my medical career to explain why I left Argentina selleck to continue my medical career in this country and why, once in the United States, I decided to pursue an academic career. I hope that this brief memoir will inspire potential researchers in this generation with the excitement of scientific discovery that has sustained me through my career. FHVP, free hepatic venous pressure; HVPG, hepatic venous pressure gradient; NSBB, nonselective beta blocker; VA, Veterans Administration; WHVP, wedged hepatic venous pressure. I was born in Buenos Aires, Argentina, where my father was a Jewish Hungarian immigrant and my mother was Argentinian of Jewish Hungarian descent. My father arrived in Argentina in the 1920s fleeing an already convulsed Europe. I attended public school and then studied medicine

at the University of Buenos Aires School of Medicine, which was also public and free. At the time, the best schools were public and funded by the government so tuition was free. In order to limit class sizes, NSC 683864 solubility dmso to matriculate at the School of Medicine, it was necessary to pass a rigorous academic exam that excluded many candidates. Nevertheless, the medical students’ classes were very large (approximately

4000 students the first year) and impersonal and did not allow for any close contact between students and professors. The intensely interesting study of medicine in Buenos Aires in the early 1960s took place against a dramatic backdrop of inescapable political unrest and violence in a country that was alternately governed by short-lived democratic government and military PtdIns(3,4)P2 dictators. Dr. Bernardo Houssay, one of three Nobel Prize winners from the University of Buenos Aires, had brought the Department of Physiology at Buenos Aires School of Medicine to its highest prestige. Dr. Houssay and his collaborators had written a seminal textbook of physiology from which we studied at that time and which was also widely used in translation at U.S. medical schools. The tradition in Physiology was to teach through practical demonstrations in classical experimental models. Most experimental demonstrations were performed in a toad (Bufo arenarum Hensel, a species commonly found in Argentina). I found this part of my medical education especially riveting. From these experiences, I developed a great respect for the power of well-designed experimental models to translate science from the realm of ideas to the laboratory bench and from there to the clinical bedside.

“
“Dream no small dreams for they have no power to move the hearts of men. Goethe I would like to thank Dr. Lindor and other members of the editorial

board of HEPATOLOGY for honoring me by asking me to contribute to the “Masters of Hepatology” series. My background is very different from that of other renowned hepatologists who have already contributed to this series. For this reason, I will go back to the beginning of my medical career to explain why I left Argentina Selleck Sotrastaurin to continue my medical career in this country and why, once in the United States, I decided to pursue an academic career. I hope that this brief memoir will inspire potential researchers in this generation with the excitement of scientific discovery that has sustained me through my career. FHVP, free hepatic venous pressure; HVPG, hepatic venous pressure gradient; NSBB, nonselective beta blocker; VA, Veterans Administration; WHVP, wedged hepatic venous pressure. I was born in Buenos Aires, Argentina, where my father was a Jewish Hungarian immigrant and my mother was Argentinian of Jewish Hungarian descent. My father arrived in Argentina in the 1920s fleeing an already convulsed Europe. I attended public school and then studied medicine

at the University of Buenos Aires School of Medicine, which was also public and free. At the time, the best schools were public and funded by the government so tuition was free. In order to limit class sizes, http://www.selleckchem.com/products/hydroxychloroquine-sulfate.html to matriculate at the School of Medicine, it was necessary to pass a rigorous academic exam that excluded many candidates. Nevertheless, the medical students’ classes were very large (approximately

4000 students the first year) and impersonal and did not allow for any close contact between students and professors. The intensely interesting study of medicine in Buenos Aires in the early 1960s took place against a dramatic backdrop of inescapable political unrest and violence in a country that was alternately governed by short-lived democratic government and military new dictators. Dr. Bernardo Houssay, one of three Nobel Prize winners from the University of Buenos Aires, had brought the Department of Physiology at Buenos Aires School of Medicine to its highest prestige. Dr. Houssay and his collaborators had written a seminal textbook of physiology from which we studied at that time and which was also widely used in translation at U.S. medical schools. The tradition in Physiology was to teach through practical demonstrations in classical experimental models. Most experimental demonstrations were performed in a toad (Bufo arenarum Hensel, a species commonly found in Argentina). I found this part of my medical education especially riveting. From these experiences, I developed a great respect for the power of well-designed experimental models to translate science from the realm of ideas to the laboratory bench and from there to the clinical bedside.

“
“Dream no small dreams for they have no power to move the hearts of men. Goethe I would like to thank Dr. Lindor and other members of the editorial

board of HEPATOLOGY for honoring me by asking me to contribute to the “Masters of Hepatology” series. My background is very different from that of other renowned hepatologists who have already contributed to this series. For this reason, I will go back to the beginning of my medical career to explain why I left Argentina click here to continue my medical career in this country and why, once in the United States, I decided to pursue an academic career. I hope that this brief memoir will inspire potential researchers in this generation with the excitement of scientific discovery that has sustained me through my career. FHVP, free hepatic venous pressure; HVPG, hepatic venous pressure gradient; NSBB, nonselective beta blocker; VA, Veterans Administration; WHVP, wedged hepatic venous pressure. I was born in Buenos Aires, Argentina, where my father was a Jewish Hungarian immigrant and my mother was Argentinian of Jewish Hungarian descent. My father arrived in Argentina in the 1920s fleeing an already convulsed Europe. I attended public school and then studied medicine

at the University of Buenos Aires School of Medicine, which was also public and free. At the time, the best schools were public and funded by the government so tuition was free. In order to limit class sizes, Atezolizumab in vitro to matriculate at the School of Medicine, it was necessary to pass a rigorous academic exam that excluded many candidates. Nevertheless, the medical students’ classes were very large (approximately

4000 students the first year) and impersonal and did not allow for any close contact between students and professors. The intensely interesting study of medicine in Buenos Aires in the early 1960s took place against a dramatic backdrop of inescapable political unrest and violence in a country that was alternately governed by short-lived democratic government and military Carnitine dehydrogenase dictators. Dr. Bernardo Houssay, one of three Nobel Prize winners from the University of Buenos Aires, had brought the Department of Physiology at Buenos Aires School of Medicine to its highest prestige. Dr. Houssay and his collaborators had written a seminal textbook of physiology from which we studied at that time and which was also widely used in translation at U.S. medical schools. The tradition in Physiology was to teach through practical demonstrations in classical experimental models. Most experimental demonstrations were performed in a toad (Bufo arenarum Hensel, a species commonly found in Argentina). I found this part of my medical education especially riveting. From these experiences, I developed a great respect for the power of well-designed experimental models to translate science from the realm of ideas to the laboratory bench and from there to the clinical bedside.

Serum glucose levels were increased with HFD/HF feeding, but were Tamoxifen datasheet similar in Xbp1−/− and Xbp1f/f mice. Hepatic triglycerides were also increased with HFD/HF feeding, but were significantly lower in Xbp1−/− compared to Xbp1f/f mice (55±10 vs 21 ±4 mg/g liver, p<0.02). Histology confirmed these findings. In vitro, PA induced expression

of the active spliced form of XBP1 (XBP1s) in Huh7/SCR, but not in Huh7/KD cells. Huh7/KD cells had increased CHOP gene expression compared to Huh7/SCR cells both at baseline and after PA treatment (p<0.05). PA-treated Huh7/KD cells had higher cytotoxicity compared to PA-treated Huh7/ SCR cells as measured by both LDH (p<0.01) and caspase 3/7 activity (p<0.05) assays. Conclusion: Hepatic Xbp1 deficiency increases liver injury in mice fed a HFD/HF diet. Huh7 cells with reduced XBP1 have enhanced injury induced by palmitic acid. We speculate that hepatic XBP1 may be a potential therapeutic target

for patients with NASH. Disclosures: The following people have nothing to disclose: Xiaoying Liu, Anne S. Henkel, Brian E. LeCuyer, Richard Green Background: Genetic modification and dietary challenges FK506 in vivo have been two major approaches to generate animal models of non-alcoholic fatty liver disease and its more severe form non-alcoholic steatohepatitis. However, these animal models rarely develop late stage diseases such as cirrhosis and hepato-cellular carcinoma within months. This study aimed to examine if disease progression is accelerated by combining genetic and diet-induced dyslipidemia in rodents and if the model exhibits more severe conditions compared to other animal models. Methods: Male low-density lipoprotein receptor knockout (LDLR-KO) mice were fed a normal chow or choline-deficient amino acid-defined diet including 1 w/w% cholesterol and 41 kcal% fat, i.e. modified CDAA diet. Separate groups of animals were under the diet for 1, 4, 8, 16, 24 or 31

weeks. Blood biochemistry, hepatic inflammatory and fibrotic gene expression analyses, histopathology, and immunohistochem-istry were conducted. Results: Plasma hepatic transaminase levels increased 1 week after the diet-feeding and showed the highest level in the 4 weeks group, which Cobimetinib nmr gradually decreased thereafter. Microvesicular and macrovesicular steatosis in the liver were observed from 1 week. The macrovesicular steatosis was exacerbated over time and was observed in almost all hepatocytes after 8 weeks. Inflammatory cell infiltration was observed from 1 week, reached the highest level after 4 weeks, and remained throughout the study. The infiltrated cells were mainly composed of F4/80-positive macrophages and MPO-positive neutrophils and monocytes. Desmin-positive hepatic stellate cells and α-SMA-positive activated stellate cells were increased by 8 weeks. Hepatic fibrosis area stained with Sirius red was increased after 4 weeks and spread all over the liver over time.

[2] Alternate techniques of ad libitum ethanol delivery, in which ethanol is incorporated into a liquid diet,[3] partially overcome a rodent’s natural aversion to alcohol and daily ethanol intake is sufficient to produce steatosis. Although liquid diet models are distinct improvements over drinking water models, liver

pathology is still limited predominantly to steatosis.[3] Another means to bypass aversion to ethanol is by enteral feeding by way of a surgically implanted intragastric tube,[4] which allows the researcher to achieve blood alcohol counts (BACs) that are much higher than ad libitum alcohol feeding. The main advantage of enteral feeding is that the pathology is more severe than in ad libitum models and better mimics early ALD in humans.[4] However, the technical demands of this protocol have limited the number of research see more groups that actively employ it. Although hepatic steatosis is generally considered an asymptomatic disease state, it sensitizes the liver to injury caused by a second insult.[5] For example, steatosis caused

by ethanol exposure is well known to enhance liver pathology induced by bolus injection of the bacterial cell wall product, lipopolysaccharide (LPS).[6] However, although circulating LPS levels are BYL719 supplier elevated in both humans and in experimental animals consuming ethanol,[7, 8] these levels are much lower than observed after bolus injection in these models. Therefore, the relevance of the alcohol:LPS “2-hit” model to human ALD has been questioned.[9] LPS is not the only hit for which ethanol exposure enhances hepatotoxicity. Indeed, human studies have suggested that the risk of ALD increases in individuals who engage in binge episodes of drinking

on top of heavy daily consumption.[10] These data suggest that acute high-dose ethanol exposure itself can serve as the second “hit” on the background of chronic consumption. Gao and colleagues have “reverse-translated” these clinical observations into a mouse model of acute bolus ethanol exposure after chronic ad libitum exposure (i.e., the “NIAAA model”[11, 12]). This model employs 10 days ad libitum exposure, followed by an acute bolus gavage (Fig. 1); the latter dose regimen yields BACs of ∼400 mg/dL,[12] which is in the range that “professional” Depsipeptide order drinkers can attain.[13] Whereas neither the chronic nor the acute regimens cause major hepatic changes by themselves, their combination synergistically induces inflammatory liver damage[11, 12]; this model may also therefore represent human acute alcoholic hepatitis (AH). The results of the current study indicate that neutrophil chemoattraction plays a key role in the observed liver damage in this model.[14] Monocytes/macrophages appear to play a more dominant role in most rodent models of AH/ALD, whereas human AH has a strong neutrophil component.[15] Here, the production of neutrophil chemoattractants (e.g.

[2] Alternate techniques of ad libitum ethanol delivery, in which ethanol is incorporated into a liquid diet,[3] partially overcome a rodent’s natural aversion to alcohol and daily ethanol intake is sufficient to produce steatosis. Although liquid diet models are distinct improvements over drinking water models, liver

pathology is still limited predominantly to steatosis.[3] Another means to bypass aversion to ethanol is by enteral feeding by way of a surgically implanted intragastric tube,[4] which allows the researcher to achieve blood alcohol counts (BACs) that are much higher than ad libitum alcohol feeding. The main advantage of enteral feeding is that the pathology is more severe than in ad libitum models and better mimics early ALD in humans.[4] However, the technical demands of this protocol have limited the number of research JNK inhibitor groups that actively employ it. Although hepatic steatosis is generally considered an asymptomatic disease state, it sensitizes the liver to injury caused by a second insult.[5] For example, steatosis caused

by ethanol exposure is well known to enhance liver pathology induced by bolus injection of the bacterial cell wall product, lipopolysaccharide (LPS).[6] However, although circulating LPS levels are Gemcitabine cost elevated in both humans and in experimental animals consuming ethanol,[7, 8] these levels are much lower than observed after bolus injection in these models. Therefore, the relevance of the alcohol:LPS “2-hit” model to human ALD has been questioned.[9] LPS is not the only hit for which ethanol exposure enhances hepatotoxicity. Indeed, human studies have suggested that the risk of ALD increases in individuals who engage in binge episodes of drinking

on top of heavy daily consumption.[10] These data suggest that acute high-dose ethanol exposure itself can serve as the second “hit” on the background of chronic consumption. Gao and colleagues have “reverse-translated” these clinical observations into a mouse model of acute bolus ethanol exposure after chronic ad libitum exposure (i.e., the “NIAAA model”[11, 12]). This model employs 10 days ad libitum exposure, followed by an acute bolus gavage (Fig. 1); the latter dose regimen yields BACs of ∼400 mg/dL,[12] which is in the range that “professional” 5-Fluoracil order drinkers can attain.[13] Whereas neither the chronic nor the acute regimens cause major hepatic changes by themselves, their combination synergistically induces inflammatory liver damage[11, 12]; this model may also therefore represent human acute alcoholic hepatitis (AH). The results of the current study indicate that neutrophil chemoattraction plays a key role in the observed liver damage in this model.[14] Monocytes/macrophages appear to play a more dominant role in most rodent models of AH/ALD, whereas human AH has a strong neutrophil component.[15] Here, the production of neutrophil chemoattractants (e.g.

Oxidative stress markers (4-hydroxy-2-nonenal and 8-hydroxy-2′-deoxyguanosine) were increased in LPS-treated animals; CoPP treatment ablated these alterations. An inhibitor for the opening of mitochondrial permeability transition pore, cyclosporine A, suppressed oxidative

stress as well as liver damage during LPS administration. CoPP promoted autophagy and prevented rats from liver damage during LPS administration. Conclusion:  HO-1 promotes autophagy and elimination of damaged mitochondria thereby repressing oxidative stress in LPS-treated rat liver, revealing a novel mechanism for protection by HO-1 against septic liver damage. SEPSIS IS CAUSED by severe infection and is clinically characterized by a systemic inflammatory response, buy Ipilimumab cardiovascular dysfunction, and a precipitous drop in blood Selisistat research buy pressure that leads to multiple organ failure and eventual death.1,2 Recent progress has

indicated that mitochondrial dysfunction is a crucial event during septic shock.3 In addition, recent reports have also indicated a protective role for heme oxygenase-1 (HO-1).4,5 The cytoprotective roles of HO-1 against oxidative stresses have been demonstrated under various pathological conditions including the infection of hepatocytes by hepatitis C.6 Autophagy is a cellular defense system involved in the recycling of proteins during fasting Baricitinib and in the elimination of damaged organelles under pathological conditions.7–10 Septic shock elicited by lipopolysaccharide (LPS) administration causes oxidative stresses in the liver through reducing endogenous antioxidants11 or other mechanisms. Autophagy is induced by LPS in the cardiomyocytes to reduce oxidative stresses and subsequent cellular injuries,12 but the effect of HO-1 induction on LPS-induced autophagy in the

liver has not been examined. THE ANIMAL EXPERIMENTATION protocols used in this study were approved by the Institutional Animal Care and Use Committee of University of Tokyo. Five-week-old male Sprague–Dawley rats were injected i.p. with 15 mg/kg LPS (from Escherichia coli obtained from Sigma [L-2630; St Louis, MO, USA]) dissolved in 0.5 mL isotonic NaCl, or vehicle (n = 4/group). To determine if mitochondrial damage following LPS administration is attenuated by HO-1, an inducer of this enzyme, cobalt protoporphyrin (CoPP [Sigma], 1.5 mg/kg in 0.5 mL dimethylsulfoxide) was injected s.c. into the rats for 4 days consecutively at 24-h intervals. LPS was injected 24 h after the last round of CoPP injection. The animals in the control group received vehicle injections at the same intervals (n = 4/group). Cyclosporin A (CysA, 5 mg/kg) was injected 2 h before the treatment with LPS.

[108-110] Until recently, the source of anti-HEV seropositivity in rats could not be identified. However, in 2010, Johne et al.[111] identified a novel HEV sequence from rats in Germany, which shared only 53–55% sequence identity with human HEV. Various rat HEV strains have now been identified in Germany, the USA, Vietnam and Indonesia, but not in Japan.[111-114] It remains to be determined if the rat HEV can cross the species

barrier and infect humans or other animal species. Recently, HEV-like viruses, forming novel phylogenetic clades in the family Hepeviridae (Fig. 5) have been identified from ferrets in the Netherlands,[115] from African, Central American and European bats,[116] and from cutthroat trout in the www.selleckchem.com/products/chir-99021-ct99021-hcl.html USA.[99] So far, no clinical disease has been Z-VAD-FMK research buy reported to be associated with these HEV-like viruses in humans and animals. In addition, anti-HEV IgG antibodies have been detected by ELISA using the human

HEV-derived ORF2 protein as antigen probe in various animals including cattle,[117-120] horses,[121, 122] sheep,[118, 123, 124] goats,[120, 123] dogs[117, 121, 125] and cats.[126, 127] However, it remains unknown whether these animals are infected with human-related HEV or animal-specific HEV-like viruses. A HEV-like virus, named avian HEV, has also been identified in chickens with or without hepatitis-splenomegaly syndrome in Australia, European countries, the USA, China and Korea.[128-132] Avian HEV in chickens shares only

approximately 50% nucleotide sequence identity across the full-length genome with human and swine HEV. No data on the circulation of avian HEV in chickens in Japan are available so far. SEVERAL CASES OF post-transfusion clinical or subclinical HEV infection have been reported in Japan,[64, 133, 134] including a case of transfusion-transmitted HEV infection in 1979 which was identified through a retrospective study among hemodialysis patients.[49] Therefore, the potential risk of transfusion-associated Tangeritin hepatitis E is not negligible. As mentioned above, sporadic cases or clusters of zoonotic food-borne HEV infection have been reported from various parts of Japan, particularly from Hokkaido where hepatitis E is endemic. Among 199 domestic hepatitis E cases in Japan, a food source was identified in 94 cases (47%) in total, including 48 cases (74%) in Hokkaido, with the leading cause being the consumption of uncooked or undercooked liver/colon/intestine from pigs (Table 4). It is therefore clear that the main route of HEV transmission is zoonotic food-borne transmission in Japan. Japan-indigenous genotype 3 HEV was detected in two of 32 packages of a bivalves called Yamato-Shijimi (Corbicula japonica) obtained from Japanese rivers, indicating that HEV also contaminates the river water in Japan.

However, it is not yet indicated to eradicate all East-Asian cagA-positive cases, as most H. pylori infections in this region are the East Asian type. For instance, in the authors’ recent study, 94% of H. pylori infections among Korean subjects were of the East-Asian cagA type.57 First-degree relatives

of gastric cancer patients might be at an increased risk of developing gastric cancer, as judged by a significantly higher prevalence of H. pylori, Roxadustat chronic atrophic gastritis, and intestinal metaplasia.58,59 Compared with healthy controls, first-degree relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria, and of gastric atrophy than patients with non-ulcer dyspepsia matched for H. pylori prevalence.60 Notably, among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria is increased only in those with H. pylori infection. Further, it is greater in relatives of patients with familial cancer than among relatives of sporadic

cancer index patients, and increases with age. Eradication of H. pylori resolved the gastric inflammation, hypochlorhydria and atrophy in half of the subjects.60 In subjects with family history of gastric cancer, H. pylori detection and prophylactic eradication of the infection should be offered, especially when the subject is less than 40 years old. Siblings of patients who develop gastric cancer before 40 years of age have a higher H. pylori infection rate and higher prevalence of intestinal CHIR-99021 nmr metaplasia in the body, and show a higher multivariate-adjusted odds ratio (OR) for gastric Selleckchem Belinostat cancer (OR 3.60).61 Because gastric cancer

in patients younger than 40 years old is closely associated with H. pylori infection rather than genetic causes, eradication may be adopted as a strategy for the prevention or early detection of cancer in young subjects.62 To date, it is not well defined whether to treat all H. pylori-positive patients taking a PPI and/or antiplatelet agents. There is evidence in patients taking NSAIDs long term in favor of H. pylori eradication,63 but there is no objective clinical data on cyclooxygenase-2 inhibitors and aspirin. Despite the conflicting opinions, it is reasonable to recommend screening for H. pylori eradication in subjects taking antiplatelet agents since the presence of H. pylori infection aggravates mucosal damage.63 Notably, the opinions and clinical practice patterns for the management of anticoagulation and antiplatelet medications differ significantly between Eastern and Western endoscopists.64 Since there is a tendency among Eastern endoscopists to think that Asians are more prone to bleeding than Caucasians, H. pylori eradication might be considered more seriously in East Asians to prevent drug-induced ulcers. PPI may accelerate the development of atrophic gastritis when H. pylori is present,65 and thus H. pylori may need to be treated before long-term PPI therapy.

Using a published algorithm to find p53 consensus sites,25 we mapped potential, shared

p53 and TA-p73 (p53/p73) binding sites upstream of four TA-p73–bound genes that changed expression during the 24 to 48 hours of liver regeneration: Foxo3, Janus kinase 1 (Jak1), phosphoprotein enriched in astrocytes 15 (Pea15), and tubulin alpha 1 (Tuba1; Supporting Table 4 and Supporting Fig. 3). Binding of p53 and TA-p73 was observed for all examined genes at identified p53REs, and this confirmed that putative targets uncovered by TA-p73 ChIP/chip Nutlin-3 concentration may be bound by both p53 and TA-p73 in the quiescent liver in vivo (Fig. 2). Afp p53RE served as a positive control for p53/p73 binding in the quiescent liver, whereas upstream regions of albumin (Alb) and brain-specific protein 3B (Brn3B) genes served as negative controls for p53 and TA-p73 binding.4, 26 Taken together, these results suggest that p53 and TA-p73 activate or repress target genes in the quiescent liver and that regulatory activities of p53 and TA-p73 change during

liver regeneration. Among the 17 TA-p73 gene targets revealed by ChIP/chip, Foxo3 had the most significant change in expression in response to PH and strong p73 binding (Supporting Table 4). We found a p53 consensus site −3.7 kb upstream Small molecule library of the TSS of Foxo3 as well as several other potential p53 binding sites within the second and third introns (Fig. 3A). We detected binding of both p53 and TA-p73 to the p53RE −3.7 kb upstream of Foxo3 (Fig. 3B). To confirm the specificity of p53/p73 binding to the Foxo3 p53RE, we used primers for a region that contains no p53REs (located −2.0 kb upstream of the Foxo3 TSS) and saw background levels of interaction (nonspecific region; Fig. 3A,B). TA-p73 compensates for a loss of p53 by binding to the Afp p53RE in the absence of p534 and promotes a delayed but significant MTMR9 reduction of Afp expression in the liver by 4 months of age in p53−/− mice.26 We performed ChIP from liver tissue collected from p53−/− mice at 2 months of age and found that TA-p73 binds the p53RE of Foxo3 in the absence of p53 (Fig. 3C). Thus, both p53 and TA-p73 regulate transcription of Foxo3 in the adult mouse liver

at time zero. On the basis of known functions of FoxO3 as a tumor suppressor, we hypothesized that p53 and TA-p73 act as positive regulators of Foxo3 at the level of transcription. We determined levels of Foxo3 messenger RNA (mRNA) isolated from liver tissue collected from p53+/−, p53−/−, and p73+/− mice in comparison with WT littermates, and we observed a significant decrease in Foxo3 expression in p53−/− and p73+/− mice (Fig. 4A). Transcription of Trp73 from multiple promoters, together with alternative mRNA splicing, results in at least 28 isoforms of p73.27 We performed transient transfection of a mouse hepatoma–derived cell line (Hepa1-6)28 with plasmids that expressed transactivating TA-p73 isoforms, HA–TA-p73α and HA–TA-p73β or HA-p53.