bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of several sex steroid hormones on the growth rate of three morris hepatoma tumor lines
Authors: Erdstein Julius , Wisebord Steven , Mishkin Shaindel Y. , Mishkin Seymour 
Published: March 2007

Morris hepatoma 44, whose growth is sensitive to thyroid hormones and prolactin, contains specific receptors for these hormones. In the present experiments, male Buffalo rats bearing Morris hepatoma 7787 were studied to determine the effects of several sex steroid hormones. Castration 1 week postimplantation inhibited tumor growth relative to controls (-53%). Replacement with testosterone propionate (1 mg per day s.c. injection) restored tumor growth to control levels, whereas administration of testosterone (2 mg per day s.c. injection) to castrated controls resulted in significant stimulation. Testosterone administered to control animals at a dose of 1 mg per day stimulated tumor growth (62%), whereas 2 mg per day failed to do so. Progesterone (4-pregnon-3,20-dione) at doses of 125 or 250 μg per day (Silastic implants) had no effect on tumor growth, whereas 500 μg per day stimulated tumor growth relative to controls. Estrogen (17β-estradiol) at doses of 6, 12, 04 24 μg per day (Silastic implants) did not influence tumor growth. Cytoplasmic testosterone receptors have been demonstrated in tumors (2.2 ± 0.8 fmoles per mg cytoplasm), although specific cytoplasmic estrogen and progesterone receptors could not be identified in this model. In female rats bearing either Morris hepatoma 44, 7787 or 5123-D, testosterone markedly stimulated tumor growth (226, 328 and 58%, respectively, relative to controls).
In conclusion, although Morris hepatoma 7787 appears to be androgen (testosterone) dependent and contains cytoplastic androgen receptors, it lacks specific cytoplasmic receptors for estrogen and progesterone and is not influenced by these hormones except at very high doses of progesterone.
Impaired sulfoxidation in patients with primary biliary cirrhosis
Authors: Scharschmidt Bruce F. , Lake John R. 
Published: March 2007

An impaired sulfoxidation pathway has been implicated in the pathogenesis of chlorpromazine-induced hepatotoxicity. Since some patients with chronic chlorpromazine-induced cholestasis may have features of primary biliary cirrhosis, we studied the ability to sulfoxidate the amino acid analogue S-carboxymethyl-cysteine in 44 patients with primary biliary cirrhosis and in two control groups—one without liver disease and one with a variety of liver diseases other than primary biliary cirrhosis.
Poor sulfoxidation was observed in 84 percent of the patients with primary biliary cirrhosis, as compared with 24 percent of patients with other liver diseases and 22 percent of normal controls (P < 0.0005 for both comparisons). Poor sulfoxidation did not correlate with the degree of hyperbilirubinemia or histologic severity of liver disease in any of the groups studied. There was an inverse correlation with age only in the patients with primary biliary cirrhosis (r = −0.44, P < 0.001). Liver transplantation was performed in six of the patients and improved sulfoxidation in five; in the four with primary biliary cirrhosis, sulfoxidation improved from poor to good or intermediate.
Targeted therapy for hepatic cancer: Good in theory, problematic in practice
Authors: Wright Teresa L. 
Published: March 2007

We present evidence that normal hepatocytes can be specifically protected from galactosamine toxicity in vitro by targeting an antagonist to these cells via receptor-mediated endocytosis. The strategy is based upon the following principles: 1) galactosamine is a highly selective hepatotoxin that causes a dose-dependent depletion of uridine intermediates; 2) galactosamine toxicity can be antagonized by supplemental administration of uridine; 3) normal hepatocytes possess unique cell-surface receptors that can internalize galactose terminal (asialo-) glycoproteins with subsequent degradation of the glycoprotein ligand.
Based on these facts, we hypothesized that chemical coupling of a galactosamine antagonist to an asialoglycoprotein could result in cell-specific delivery and protection of normal hepatocytes by targeting the antagonist via asialoglycoprotein receptors. Using a model system consisting of freshly isolated rat hepatocytes (receptor(+)) and Morris 7777 rat hepatoma (receptor (−)) cells, sensitivity to galactosamine in vitro was determined and found to be similar for both types of cells. A targetable antagonist was synthesized by coupling uridine monophosphate to asialoorosomucoid in a molar ratio of 5 to 1. Exposure of Morris 7777 cells to the targetable antagonist in the presence of a toxic concentration of galactosamine did not protect these cells as evidenced by a steady decline in the number of viable cells in a fashion identical to cells treated with galactosamine alone. However, normal hepatocytes that received the conjugate in the presence of galactosamine were protected as their viable cell number remained the same as control (untreated) cells. Competition by an excess of asialoglycoprotein inhibited the protective effect of the conjugate, supporting the concept that the asialoglycoprotein component of the conjugate was responsible for the specific delivery of the antagonist to the target cells.
Expression of different members of heat shock protein 70 gene family in liver and hepatomas
Authors: Cairo Gaetano , Schiaffonati Luisa , Rappocciolo Emilia , Tacchini Lorenza , Bernelli-Zazzera Aldo 
Published: March 2007

The levels of expression of some genes of the HSP 70 family have been assessed in rat liver and in a series of transplantable hepatomas with different growth rates, subjected to heat shock in vivo. For this purpose, the mRNAs for the constitutive cognate HSC 73, the heat-inducible HSP 70 and the glucose-regulated GRP 78 have been analyzed by: (i) translation in reticulocyte lysates; (ii) hybrid-selected translation, and (iii) Northern blot analysis. In comparison with the liver, the fastgrowing 3924A hepatoma has an increased constitutive amount of HSC 73 mRNA and a lower induction of HSP 70 mRNA after heat shock. The behavior of the 9618A slow-growing hepatoma is more similar to that of the liver, indicating that the changes detected in the fastgrowing hepatoma are correlated to the high growth rate of the tumor rather than to carcinogenesis. This conclusion is reinforced by the results obtained with Yoshida AH-130 cells, growing at two different rates imposed by the environment in which they develop. When the Yoshida hepatoma grows rapidly in the peritoneal cavity, constitutive expression of HSC 73 mRNA is high and the inducibility of HSP 70 mRNA is poor: the opposite occurs when the tumor grows slowly in the subcutaneous compartment.
The amount of GRP 78 mRNA increases progressively from the liver to the fast-growing hepatoma.
The level of HSC 73 mRNA seems to correlate with the methylation state of the corresponding gene.
Histochemical and biochemical studies on the effect of the prostacyclin derivative iloprost on CCI4-induced lipid peroxidation in rat liver and its significance for hepatoprotection
Authors: Bursch Wilfried , Taper Hendryk S. , Somer Marie P. , Meyer Stefan , Putz Barbara , Schulte-Hermann Rolf 
Published: March 2007

In the present study, it was investigated whether the prostacyclin derivative Iloprost would protect hepatocytes against CCl4-induced liver injury and which mechanism(s) of hepatocellular pathogenesis might be affected by it. Rats were treated with a single oral dose of CC14 (2 ml per kg); Iloprost was infused continuously from 2 to 4 hr before intoxication until killing. The following results were obtained.
The CCl4-induced release of AST, lactate dehydrogenase and alkaline phosphatase into the serum was reduced by 50 to 70% in rats treated with doses of 0.1 and 0.5 μg Iloprost per kg per min. Infusion of 0.02 and 0.004 μg Iloprost per kg per min did not affect the CCl4-induced enzyme release into the blood.
CCl4 induced the occurrence of aldehydes (products of lipid peroxidation), which were detected by histochemical and biochemical means. At 12, 48 and 72 hr after CCI4, the aldehyde-positive liver section area was about 58, 69 and 16% in rats treated with CCl4 alone, but only about 18, 13 and <1% in rats treated additionally with Iloprost. The aldehyde-positive hepatocytes were located predominantly in the centrilobular zone of the liver. At 24 hr the extent of the aldehyde-positive section area was the same in rats with or -without Iloprost treatment (about 90%). Biochemical determination, however, revealed that at this time point the malondialdehyde content after Iloprost in rats was about 70% lower than without Iloprost treatment.
Other histochemical and histological signs of cell damage were also reduced by Iloprost treatment, predominantly in the periportal zone: loss of granular pyroninophilia indicating destruction of ribosomal RNA, fatty degeneration and hepatocellular necrosis visible in hematoxylin and eosin-stained sections.
At 48 and 72 hr after CCI4, the mitotic activity in the liver of rats treated with Iloprost was about one-half and one-quarter of that without Iloprost treatment.
In conclusion, Iloprost partially protects hepatocytes against CCI4-induced cell damage and death; periportal hepatocytes appear to be protected more effectively than centrilobular hepatocytes. The reduced content of lipid peroxidation products indicates that reduction of lipid peroxidation and/or stimulation of aldehyde elimination (repair) is involved in the hepatoprotective action of Iloprost.
Bile acid metabolism in human hyperthyroidism
Authors: Pauletzki Jürgen , Stellaard Frans , Paumgartner Gustav 
Published: March 2007

Decreased levels of serum cholesterol are a well-recognized finding in hyperthyroidism. Since the conversion to bile acids is an important pathway for the elimination of cholesterol, we studied primary bile acid kinetics in seven hyperthyroid patients before and after medical treatment. Pool sizes, fractional turnover and synthesis rates of cholic acid and chenodeoxycholic acid were determined after oral administration of 50 mg [13C]cholic acid and 50 mg [13C]chenodeoxycholic acid. 13C/12C isotope ratios in serum were measured by capillary gas chromatography/electron impact mass spectrometry.
Compared with the euthyroid state, serum cholesterol levels were distinctly lower in hyperthyroidism (150 ± 33 vs. 261 ± 51 mg per dl, p < 0.01). Thyroid hormone excess caused a 34% reduction in cholic acid synthesis (5.8 ± 2.8 vs. 7.9 ± 4.2 μmoles per kg per day, p < 0.02), which was associated with a 47% decrease in cholic acid pool size (11.7 ± 3.4 vs. 22.0 ± 5.2 μmoles per kg, p < 0.01). Chenodeoxycholic acid kinetics exhibited no apparent changes. Thus, total primary bile acid synthesis was diminished by 20% in hyperthyroidism. After normalization of thyroid function, the ratio of cholic acid/chenodeoxycholic acid pool size increased in all patients. This was paralleled by a rise in the ratio of concentrations of cholic acid/chenodeoxycholic acid in serum.
The depression of cholic acid synthesis in the presence of unaltered chenodeoxycholic acid synthesis found in hyperthyroid subjects is compatible with an inhibition of hepatic 12α-hydroxylation by thyroid hormone. Furthermore, evidence is provided that, in man, the low serum cholesterol levels found during hyperthyroidism are not caused by an increased conversion of cholesterol to bile acid.
Characterization of the incorporation of woodchuck hepatitis virus surface antigen into hepatocyte plasma membrane in woodchuck hepatitis and in the virus-induced hepatocellular carcinoma
Authors: Michalak Tomasz I. , Snyder Robert L. , Churchill Norma D. 
Published: March 2007

Interaction between woodchuck hepatitis virus surface antigen and proteins of hepatocyte plasma membranes were examined in the course of woodchuck hepatitis virus infection. Membranes purified from animals with histologically confirmed acute hepatitis, active or persistent chronic hepatitis and the virus-related hepatocellular carcinoma were evaluated for the virus surface antigen contents, treated with agents eluting plasma membrane-bound antigen to test the extent of the antigen-membrane associations and incubated with purified, particulate woodchuck hepatitis virus surface antigen to determine membrane potential for the antigen adsorption.
Hepatocyte plasma membranes originating from woodchucks chronically infected with the virus showed the highest quantities of the incorporated virus surface antigen among membranes studied, the behavior of bound antigen as an integral and a peripheral membrane protein and the resistance to bind an exogenous antigen. Similar properties were expressed by plasma membranes prepared from hepatocytes of nontumor parenchyma displaying chronic active hepatitis of a woodchuck hepatitis virus carrier with hepatoma. Furthermore, plasma membranes originating from animals with active or persistent chronic hepatitis demonstrated identical properties, implicating that histologic activity of the chronic liver inflammatory process is not dependent on the quantity of the virus surface antigen insertion into the membrane. In contrast, hepatocyte plasma membranes from animals with acute hepatitis showed significantly lower antigen quantities, presence of the antigen specificity exclusively behaving as an integral membrane protein and noticeable ability to bind an exogenous surface antigen of the virus. Comparable, but not identical, features were observed for hepatocyte membranes purified from nodules of hepatocellular carcinoma, suggesting that neoplastic transformation of infected hepatocytes is associated with loss of the membrane-bound antigen and with simultaneous, partial recovery of the membrane potential for the antigen binding.
Comparative analysis of the properties on the woodchuck hepatitis virus surface antigen incorporation into hepatocyte plasma membranes in studied cases indicated that sustained infection with woodchuck hepatitis virus leads to an increase in the quantity of the membrane-incorporated antigen and to the appearance of the virus surface antigen specificity behaving as a peripheral membrane protein. In conclusion, this study demonstrated that the extent and the character of the antigen interaction with hepatocyte plasma membranes undergoes significant variations in the natural course of hepadna viral infection in woodchucks and that histologically distinct forms of the virus-induced liver disease express specific properties on the association.
The effects of monensin on the transport of horseradish peroxidase into intracellular lumina in cultured rat hepatocytes
Authors: Hashieh Imad Abou , Rémy Lionel , Mathieu Sylvie , Gérolami André 
Published: March 2007

A kinetic study of horseradish peroxidase transport was carried out on short-term cultured adult rat hepatocytes. After 4 hr of plating, cells were preincubated with monensin (1 μM) for 1 hr before their incubation with horseradish peroxidase for different times. Monensin treatment resulted in the dilatation of the Golgi apparatus and caused the appearance of numerous intracellular lumina lined with microvilli in associated as well as isolated hepatocytes but did not modify newly formed bile canaliculi.
The frequency of their appearance increased to 28% in cells pretreated with monensin compared to 2% in controls. Intracellular lumina membranes had the morphological features of apical membranes and were stained with horseradish peroxidase more frequently than those of newly formed bile canaliculi. This work therefore provides a model for studying bile secretion in cultured hepatocytes. Our results also suggest that the biliary transport of horseradish peroxidase does not involve the Golgi apparatus, since horseradish peroxidase was never observed in the Golgi stacks even after monensin treatment.
The portocardiorenal axis and refractory ascites: The underfilled cup runneth over
Authors: Witte Charles L. , Witte Marlys H. 
Published: March 2007

Plasma immunoreactive alpha-human atrial natriuretic peptide (ANP) was measured in six cirrhotic patients with massive refractory ascites, under strict metabolic conditions, while they were receiving a 20-meq sodium diet, both before and at two-hour intervals for eight hours following peritoneovenous shunting (PVS). The mean preoperative level of ANP was 75±18pg/ml, which was found to be significantly higher than the normal range for this laboratory *8 to 24pg/ml) (p<0.05). This value was also significantly higher than the value of 21±5pg/ml (p<0.05) obtained in six patients with cirrhosis but without ascites. Following shunt insertion, an immediate natriuresis and diuresis were observed in five of the six cirrhotic patients with refractory ascites. In these five, right atrial pressure and ANP rose immediately, followed by a rise in the level of urinary cyclic guanosine monophosphate. The sixth subject had a delayed rise in right atrial pressure, and correspondingly the rise in ANP, the diuresis, and natriuresis were with changes in right atrial pressure (p<0.05), urinary cyclic guanosine monophosphate (p<0.05), urinary sodium excretion (p<0.05), and urine volume (p<0.05). These results suggest that ANP may be important in mediating the acute response to PVS.
Human atrial natriuretic factor (ANF) levels were measured before and after peritoneovenous shunt implantation in 10 cirrhotic patients with ascites in whom sodium retention is a major clinical problem. The mean preoperative plasma level of ANF was 82ng/L (normal range, 5-80ng/L). Peritoneovenous shunting resulted in a significant rise in plasma ANF to 308ng/L (<0.0025) immediately after operation. This was followed by a constant fall until the seventh postoperative day, when mean plasma ANF was still significantly elevated (149ng/L) compared with the preoperative value (p<0.01). Three months after shunt implantation mean plasma ANF had returned to the preoperative level (75ng/L). Mean sodium excretion increased from 2.6mEq/h peoperatively to 10.2mEq/h at the second postoperative day (p<0.025). No direct relationship was noted between changes in plasma ANF level and changes in urinary sodium excretion after shunt implantation. These data demonstrate that intact ANF release response to intravascular volume expansion in cirrhotic patients with ascites, but exclude ANF as the diminished natriuretic factor as proposed by the overflow theory of ascites formation. Sodium excretion and fluid retention seem to be the result of vascular underfill and fluid maldistribution, and hormonal changes are likely to be secondary to them.
The effects of intraduodenal bile acid administration on biliary secretion of ionized calcium and carbonate in man
Authors: Knyrim Klaus , Vakil Nimish , Pfab Rudolf , Classen Meinhard 
Published: March 2007

The importance of calcium in gallstone formation is increasingly recognized. Calcium carbonate is an important constituent of gallbladder stones and may be present in the nidus of cholesterol stones. Secondary deposition of calcium carbonate on the surface of cholesterol gallstones is an important reason for failure of oral bile acid dissolution therapy. We sought to determine the effects of bile acids on the crystallization conditions of calcium carbonate in bile.
We studied 18 patients with choledocholithiasis with a percutaneous or endoscopically placed catheter high in the biliary tree. Samples of bile in the basal state and following replacement of the bile acid pool with cholic acid, chenodeoxycholic acid and ursodeoxycholic acid were analyzed for total calcium, ionized calcium, bicarbonate and carbonate, and the saturation index for calcium carbonate was calculated.
Hepatic bile in the basal state was supersaturated with calcium carbonate. Total calcium concentrations rose linearly with rising bile acid concentrations but ionized calcium was maintained in a relatively narrow range. These data are consistent with an important role for bile acids in binding calcium. Extrapolation of the linear regressions between bile acid concentration and calcium concentrations suggested that in the absence of bile acids, biliary calcium concentrations are in passive equilibrium with plasma. Chenodeoxycholic acid and ursodeoxycholic acid caused a bicarbonate-rich choleresis and significantly augmented the saturation index for calcium carbonate, whereas cholic acid caused no change. In contrast with animal models, the apparent choleretic activity of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid was similar, and no hypercholeresis was observed with ursodeoxycholic acid. Chenodeoxycholic acid and ursodeoxycholic acid therefore increase the thermodynamic possibility for calcium carbonate precipitation.
A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy
Authors: Saracco Giorgio , Mazzella Giuseppe , Rosina Floriano , Cancellieri Claudio , Lattore Valter , Raise Enzo , Rocca Giuseppe , Giorda Laura , Verme Giorgio , Gasbarrini Giovanni , Barbara Luigi , Bonino Ferruccio , Rizzetto Mario , Roda Enrico 
Published: March 2007

Sixty-four heterosexual Italian carriers of HBsAg with chronic HBeAg and hepatitis B virus DNA-positive hepatitis were assigned randomly either to receive human lymphoblastoid interferon (injections of 5 million units per m2 three times per week for 6 months) or to serve as untreated controls. After 18 months of followup evaluation, 26 of the 33 treated patients (79%) had cleared hepatitis B virus DNA, 23 (70%) had lost HBeAg and 20 (61%) had seroconverted to anti-HBe. Fifteen of the 31 controls (48%) had cleared hepatitis B virus DNA (p = 0.01), 12 (39%) had lost HBeAg and nine (29%) had seroconverted to anti-HBe (p = 0.002). Eight treated patients but only one control had lost HBsAg and seroconverted to anti-HBs (24% vs. 3%, p = 0.01). Treated patients cleared hepatitis B virus markers after a mean interval of 4 months, compared with 8 months in the controls.
All responders to interferon cleared intrahepatic HBcAg, and 50% showed histological improvement. The baseline hepatitis B virus DNA levels and the original histology were not predictive of a response to therapy; women appeared to respond better than men. Lymphoblastoid interferon provides an effective therapy in the heterosexual Italian patient with chronic hepatitis B.