bluuebunny/crossref_metadata_2025_split huggingface dataset:
γ‐Aminobutyric acid‐containing sympathetic preganglionic neurons in rat thoracic spinal cord send their axons to the superior cervical ganglion
Authors: Ito Tetsufumi , Hioki Hiroyuki , Nakamura Kouichi , Tanaka Yasuyo , Nakade Hiroyuki , Kaneko Takeshi , Iino Satoshi , Nojyo Yoshiaki 
Published: March 2007

Abstractγ‐Aminobutyric acid (GABA)‐containing fibers have been observed in the rat superior cervical ganglion (SCG) and, to a lesser extent, in the stellate ganglion (STG). The aim of present study is to clarify the source of these fibers. No cell body showed mRNAs for glutamic acid decarboxylases (GADs) or immunoreactivity for GAD of 67 kDa (GAD67) in the cervical sympathetic chain. Thus, GABA‐containing fibers in the ganglia are suggested to be of extraganglionic origin. GAD67‐immunoreactive fibers were found not in the dorsal roots or ganglia, but in the ventral roots, so GABA‐containing fibers in the sympathetic ganglia were considered to originate from the spinal cord. Furthermore, almost all GAD67‐immunoreactive fibers in the sympathetic ganglia showed immunoreactivity for vesicular acetylcholine transporter, suggesting that GABA was utilized by some cholinergic preganglionic neurons. This was confirmed by the following results. 1) After injection of Sindbis/palGFP virus into the intermediolateral nucleus, some anterogradely labeled fibers in the SCG were immunopositive for GAD67. 2) After injection of fluorogold into the SCG, some retrogradely labeled neurons in the thoracic spinal cord were positive for GAD67 mRNA. 3) When the ventral roots of the eighth cervical to the fourth thoracic segments were cut, almost all GAD67‐ and GABA‐immunoreactive fibers disappeared from the ipsilateral SCG and STG, suggesting that the vast majority of GABA‐containing fibers in those ganglia were of spinal origin. Thus, the present findings strongly indicate that some sympathetic preganglionic neurons are not only cholinergic but also GABAegic. J. Comp. Neurol. 502:113–125, 2007. © 2007 Wiley‐Liss, Inc.
Proline trapping in granulomas, the site of collagen biosynthesis in murine schistosomiasis
Authors: Dunn Michael A. , Seifter Sam , Hait Penelope K. 
Published: March 2007

Proline, a critical substrate for collagen synthesis, is increased in liver undergoing fibrosis. In mice with schistosomiasis, the incorporation of proline into collagen occurs within liver granulomas. To study the interaction of liver cells and granulomas in the development of fibrosis, we assayed the enzymes that catalyze the formation and degradation of proline in isolated granulomas and liver.
Two sequential enzymes involved in the formation of proline from arginine are ornithine-δ-aminotransferase and Δ1-pyrroline-5-carboxylate (P5C) reductase. Activities of both these enzymes in granulomas were approximately 10% of those in liver, expressed on the basis of DNA content.
The enzymes involved in degradation of proline are proline oxidase and P5C dehydrogenase; both are present in liver cells. In isolated granulomas, activity of proline oxidase was minimal, and P5C dehydrogenase activity was absent. These findings suggest that the metabolism of proline within granulomas differs greatly from that in liver cells. Earlier studies showed that exogenous proline enters granulomas and is rapidly incorporated into collagen. The combined findings raise the possibility that granulomas serve as a proline trap. Proline can enter this compartment and can be incorporated into collagen; however, proline within granulomas cannot readily be diverted into other pathways by degradation.
In vitro effect of bile salts on rat liver plasma membrane, lipid fluidity, and ATPase activity
Authors: Scharschmidt Bruce F. , Keeffe Emmet B. , Vessey Donald A. , Blankenship Nancy M. , Ockner Robert K. 
Published: March 2007

Considerable evidence suggests that liver plasma membrane (LPM) NaK-ATPase [(Na+ + K+)-dependent adenosinetriphosphatase] and Mg-ATPase (Mg2+-dependent adenosinetriphosphatase) activity and lipid fluidity are important in liver cell functions such as bile formation. However, little is known regarding factors which might alter these membrane properties in vivo. Bile salts are actively concentrated by liver cells under normal conditions and reach even higher tissue concentrations in cholestasis. Since current methodology does not permit investigation of the effect of bile salts on LPM in vivo, we have examined the effects of bile salts in vitro on isolated rat LPM essentially free of organelle contamination and enriched 52.9-, 23.8-, and 27.8-fold in NaK-ATPase, 5′-nucleotidase, and alkaline phosphatase, respectively, compared with homogenate. We found that taurocholate (0.5 to 4.0 mM), taurochenodeoxycholate (0.25 to 4.0 mM), deoxycholate (0.25 to 4.0 mM), but not dehydrocholate (0.25 to 4.0 mM) caused immediate, concentration-dependent inhibition of LPM Mg- and NaK-ATPase which at low bile salt concentration (1.0 mM) was reversible. By contrast, taurocholate (1 to 4 mM) had no effect on LPM 5′-nucleotidase activity. Both 1 mM taurocholate and taurochenodeoxycholate caused a decrease in the apparent Km for ATP of NaK-ATPase, but not of Mg-ATPase, and 1 mM taurochenodeoxycholate caused no significant change in the activation of either Mg- or NaK-ATPase by cations. Finally, LPM lipid fluidity measured by fluorescence polarization using 1,6-diphenyl-1,3,5-hexatriene as a probe was reversibly increased by taurocholate, taurochenodeoxycholate, and deoxycholate, but not dehydrocholate; the effect of taurochenodeoxycholate on lipid fluidity was confirmed by electron spin resonance using 5-(2,2-dimethyl-N-oxyl-oxayalidine)-stearic acid as a probe. However, by both techniques, the effect of low concentrations of these bile salts on ATPase activity was independent of detectable changes in fluidity.
These findings indicate that at concentrations comparable to those reported for liver tissue endogenous, micelle-forming bile salts reversibly inhibit LPM ATPases and reversibly increase LPM lipid fluidity in vitro; these two effects being dissociable at low bile salt concentrations. It is possible that bile salts may have similar effects in vivo, particularly under cholestatic conditions.
Experimental HBV and δ infections of chimpanzees: Occurrence and significance of intrahepatic immune complexes of HBcAg and δ antigen
Authors: Rizzetto Mario , Canese Maria G. , Purcell Robert H. , London William T. , Sly David L. , Gerin John L. 
Published: March 2007

The occurrence and pathogenetic role of intrahepatic deposits of immunoglobulins in experimental viral infection have been evaluated by determining with immunofluorescence their capacity to fix complement in vitro [in vitro complement fixation (VCF)]. Liver biopsies from chimpanzees chronically or acutely infected with hepatitis B virus or the hepatitis B surface antigen (HBsAg)-associated δ agent were used in the study. VCF was observed in each animal expressing hepatitis B core antigen (HBcAg) or δ antigen in the liver and concurrently circulating the homologous antibody in the blood. In acutely infected animals, VCF appeared at the same time that the homologous serum antibody appeared, and the intensity of VCF staining was proportional to the antibody titer in the serum. In animals expressing sequentially the HBcAg/antibody system and then δ antigen and antibody to δ, VCF was first observed in HBcAg-containing nuclei and then in nuclei expressing δ antigen. There was no relationship between VCF and intrahepatic expression of HBsAg or serologic expression of hepatitis B e antigen (HBeAg).
A positive VCF reaction appears related to the formation of intrahepatic immune complexes between HBcAg or δ antigen and the homologous antibody. Although acute hepatitis developed in parallel with the occurrence of VCF in two animals, strong VCF fluorescence was also observed in each of the asymptomatic carriers of HBsAg, and, in one of them, preexisting VCF staining of HBcAg disappeared in parallel with development of acute hepatitis.
In experimentally infected chimpanzees, the finding in liver biopsies of immune complexes detectable by VCF appears to be a common epiphenomenon without pathogenic significance.
Immunosuppressive Treatment of Hbsag–Positive Chronic Liver Disease: Significance of Hbeag
Authors: Tage-Jensen Ulrik , Aldershvile Jan , Schlichting Poul 
Published: March 2007

In a randomized clinical trial in 148 patients of azathioprine vs. prednisone treatment of chronic aggressive hepatitis and/or nonalcoholic cirrhosis, 20 were HBsAg positive on entry. In this subgroup sequential serum samples were investigated for HBs and HBe markers by radioimmunoassay. At the time of evaluation, 13 patients were still alive; their median age was 53 years (25 to 72) and median follow–up time was 46 months (23 to 82).
Of 16 patients with cirrhosis, 5 of 7 with persistence of HBeAg died, compared with 2 of 9 with anti–HBe. In three patients with anti–HBe, HBeAg reappeared several times with simultaneous rise in transaminase values.
The overall survival was 65% after 5 years. The prognosis of HBsAg–positive chronic liver disease seemed to depend on the presence of cirrhosis and HBeAg rather than on improvement in biochemical activity during immunosuppressive treatment.
Plasma Clearance of Intravenously Injected Aspartate Aminotransferase Isozymes: Evidence for Preferential Uptake by Sinusoidal Liver Cells
Authors: Kamimoto Yukio , Horiuchi Seikoh , Tanase Sumio , Morino Yoshimasa 
Published: March 2007

Both cytosolic (c–AAT) and mitochondrial (m–AAT) isozymes of aspartate aminotransferase (EC 2.6.1.1) appear in serum in some diseases including hepatobiliary dysfunction. The present study aimed at elucidation of the mechanism by which AAT isozymes are cleared from blood. Intravenous injection into rats of m–AAT and c–AAT purified from rat liver exhibited a biphasic clearance curve with an overall half–life of 42 min and 4.7 hr, respectively. The tissue distribution of the radioactivity following intravenous administration of 125I–labeled isozymes revealed that the liver is a major organ involved in plasma clearance of these isozymes. This conclusion was also supported by the significant retardation in plasma clearance of m–AAT in hepatectomized as well as CCI4–intoxicated rats. Furthermore, clearance rate of each AAT isozyme in an isolated perfused liver exhibited a single exponential process with the uptake rate for m–AAT being much faster than that for c–AAT.
Separation of hepatocytes and sinusoidal liver cells from the rat intravenously injected with 125I–labeled AAT isozymes revealed that sinusoidal cells were responsible for the plasma clearances. In vitro uptake study showed that both isozymes were exclusively taken up by sinusoidal liver cells. The uptake rate for m–AAT was considerably greater than that for c–AAT. Endocytotic index for uptake by sinusoidal cells was 16 times with c–AAT and 34 times with m–AAT as compared with that for inulin or dextran which are taken up by fluid–phase endocytosis, suggesting involvement of adsorptive endocytosis in the uptake of the isozymes.
Serum Type Iii Procollagen Peptide in Alcoholic Liver Disease and Idiopathic Hemochromatosis: Its Relationship to Hepatic Fibrosis, Activity of the Disease and Iron Overload
Authors: Colombo Massimo , Annoni Giorgio , Donato Maria Francesca , Conte Dario , Martines Dino , Zaramella Maria Grazia , Bianchi Paolo A. , Piperno Alberto , Tiribelli Claudio 
Published: March 2007

To assess the value of type III procollagen peptide (sPIIIP) as a marker of hepatic fibrosis, sera from 73 patients with alcohol–related liver disease and 30 patients with idiopathic hemochromatosis (IHC) were studied by a specific radioimmunoassay. sPIIIP was increased in 87% of 30 patients with cirrhosis, in 16% of 32 with steatofibrosis but in none of 11 with steatosis.
There was a significant correlation with histologic hepatocellular necroinflammation (r = 0.42, p < 0.01), but not with hepatic fibrosis.
sPIIP was increased in 33% of 30 patients with IHC, whether or not they had cirrhosis or fibrosis, and whatever the level of iron overload or the extent of the hepatic deterioration. IHC patients with increased levels of sPIIIP had a higher prevalence of superimposed hepatic damage than did those with normal procollagen levels (p < 0.05).
Our findings, therefore, weaken the diagnostic value of sPIIIP as an index of connective tissue deposition in the liver, and suggest that, at least in alcohol–related liver disease and IHC, hepatocellular necroinflammation influences the results.
Cellular Theories of Aging As Related to the Liver
Authors: Dice Fred J. 
Published: March 2007

The age–associated decjline in function of several organs, including the liver, may be caused by mechanisms operating on the cellular level. Fibroblasts and several other cell types derived from normal individuals have limited lifespans in culture, and several abnormalities described for senescent cultured fibroblasts also apply to hepatocytes and other cell types obtained from aged organisms.
Cellular theories of aging can be divided into two broad and overlapping categories: (a) those that view cell death as an actively programmed developmental process, and (b) those that consider cellular aging to result from a passive accumulation of errors in macromolecules. These theories are not necessarily mutually exclusive, and many of the phenotypic changes in senescent hepatocytes, fibroblasts and other cells are compatible with several different theories. The challenge for the future is to distinguish primary causes from secondary consequences of cellular aging so that rational attempts to intervene in the aging process are possible.
Hereditary Chronic Conjugated Hyperbilirubinemia in Mutant Rats Caused by Defective Hepatic Anion Transport
Authors: Jansen Peter L.M. , Peters Wilbert H. , Lamers Wouter H. 
Published: March 2007

A mutant rat strain is described with autosomal recessive conjugated hyperbilirubinemia. Transport of conjugated bilirubin and tetrabromosulfophthalein from liver to bile is severely impaired whereas uptake of organic anions from plasma to liver is normal. During the first 10 days of life, serum bilirubin levels are 147 ± 11 μmoles per liter with 68.7% diconjugates and 27.9% monoconjugates. In adult rats, serum bilirubin is 33 ± 8 μmoles per liter with 81.8% diconjugates and 12.1% monoconjugates vs. 0.3 ± 0.1 μmole per liter unconjugated bilirubin in normal adult rats. Bile acid metabolism is only mildly affected. In young rats, serum bile acid levels are normal. In adult rats, bile acid levels are elevated to 49 ± 11 μmoles per liter vs. 10 ± 6 μmoles per liter in normal rats. The bile flow in mutant rats is reduced to about 50%. This might be caused by a reduction of the bile acid–independent bile fraction.
Liver marker enzyme activities in mutant rat serum are normal. Liver morphology is also normal. Total urinary coproporphyrin excretion is not elevated but urinary coproporphyrin isomer I excretion is increased, a pattern like that in Dubin–Johnson syndrome in humans. However, unlike Dubin–Johnson syndrome, the mutant rats do not have the characteristic black hepatic pigment. These rats provide a unique model to study mechanisms of bile formation and cholestasis.
Endoscopic Sclerosis and Esophageal Balloon Tamponade in Acute Hemorrhage From Esophagogastric Varices: A Prospective Controlled Randomized Trial
Authors: Paquet Karl-Joseph , Feussner Hubertus 
Published: March 2007

A prospective randomized controlled clinical trial was performed in 43 consecutive histologically proved cirrhotic patients with endoscopically proved actively bleeding esophageal varices. Twenty–two were randomly selected to have esophageal tamponade with the Sengstaken–Blakemore tube, and 21 were selected to have endoscopic sclerosis of the esophageal wall.
The two groups were similar in demographic, clinical and laboratory data. Bleeding was controlled by the Sengstaken–Blakemore tube in 16 of 22 patients (73%) and by endoscopic sclerosis in 20 of 21 (95%). Among those controlled by the Sengstaken–Blakemore tube, seven (44%) rebled and three (43%) were again controlled by the Sengstaken–Blakemore tube; in the endoscopic sclerosis group, four (20%) rebled and three (75%) were controlled. Thus, hemorrhage was definitively controlled in 52% of patients and 66% of bleeding episodes in the Sengstaken–Blakemore tube group and in 90% of patients and 92% of bleeding episodes in the endoscopic sclerosis group. The definite control of hemorrhage was significantly better in the endoscopic sclerosis group (p < 0.01). The Sengstaken–Blakemore tube patients received no definitive therapy after bleeding had been controlled.
Within 30 days, six patients (27%) in the Sengstaken–Blakemore tube group had died compared to 2 (10%) in the endoscopic sclerosis group which is statistically significant (p < 0.01) in favor of endoscopic sclerosis. The frequency of complications was similar in the two groups. Endoscopic sclerosis patients received serial endoscopic sclerosis after bleeding had been stopped during the whole period of follow–up. After 6 months, 11 patients in the Sengstaken–Blakemore tube group had died (55%) compared to three patients (16%) in the endoscopic sclerosis group. Cumulative survival was statistically better in the endoscopic sclerosis group after 6 months (p < 0.01) and after 3 years of follow–up (p < 0.001). Survival was related to Child classification on admission. This investigation shows that endoscopic sclerosis is effective and superior to the Sengstaken–Blakemore tube in stopping active hemorrhage from esophageal varices and highly superior to the Sengstaken–Blakemore tube in reducing short– and long–term mortality.
Changes of Hepatitis B Virus Dna in Liver and Serum Caused by Recombinant Leukocyte Interferon Treatment: Analysis of Intrahepatic Replicative Hepatitis B Virus Dna
Authors: Yokosuka Osamu , Omata Masao , Imazeki Fumio , Okuda Kunio , Summers Jesse 
Published: March 2007

Twenty patients with HBeAg–positive chronic liver disease were given large doses of recombinant leukocyte interferon for 4 weeks. Changes of hepatitis B virus DNA in livers and sera were analyzed by the molecular hybridization technique in paired biopsies obtained before and 2 weeks after treatment. Serum hepatitis B virus DNA was examined before, during and after the treatment until 4 weeks post–interferon.
Analysis of hepatic hepatitis B virus DNA revealed species that appeared to represent various forms of replicative hepatitis B virus DNA, i.e., relaxed circular, linear, supercoiled and single–stranded hepatitis B virus DNA, respectively. No evidence of integration of hepatitis B virus DNA in genomic DNA was obtained. Of 15 cases which were positive for hepatic hepatitis B virus DNA before treatment and in which paired biopsies were obtained, hepatic hepatitis B virus DNA became negative in 4, decreased in 5 and unchanged in 6. Among several types of replicative viral DNA in liver tissue, supercoiled hepatitis B virus DNA tended to remain after other forms were reduced.
A close correlation between hepatic and serum hepatitis B virus DNA was found in 37 liver biopsy samples and corresponding sera.
These results indicate that interferon treatment reduces serum hepatitis B virus levels by inhibiting viral replication in the liver and that persistence or reappearance of hepatitis B virus in serum after interferon is associated with replication.
Analysis of Dna Polymerase Reaction Products for Detecting Hepatitis B Virus in Serum—Comparison With Spot Hybridization Technique
Authors: Imazeki Fumio , Omata Masao , Yokosuka Osamu , Matsuyama Yasuhisa , Ito Yoshimi , Okuda Kunio 
Published: March 2007

An assay for DNA polymerase reaction products using slab gel electrophoresis and autoradiography was compared with the spot hybridization technique for the detection of hepatitis B virus DNA in 317 blood samples. The former could identify the nature and size of DNA on electrophoresis, and reduce potentially false–positive results due to artifacts.
Discordant results between the two methods occurred in 36 of 317 samples; 22 were positive by the spot technique alone, and 14 were positive by the analysis of DNA polymerase reaction products alone. However, the samples positive with the spot test alone showed weak radioactive signals on electrophoresis/autoradiography that were often interpreted as “inconclusive” by blind observations.
Correlation of hepatitis B e antigen/antibody with hepatitis B virus DNA was studied in 91 patients with various chronic liver diseases. Discordant results, i.e., presence of the DNA in antibody positive sera, or its absence in the antigen positive sera, were obtained in 15 (19%) cases. Such patients tended to have advanced liver disease with fluctuating serum aminotransferase levels.
Analysis of DNA polymerase reaction products by slab gel electrophoresis and autoradiography is not only sensitive, but is also as specific as the Southern blot technique in the detection of hepatitis B virus DNA in serum, and may prove useful in selected samples, especially where no cloned hepatitis B virus DNA is available, or in search of new hepatitis B virus–like viruses.
Ultrastructural Immunocytochemical Demonstration of Hla Class I Antigens in Human Pathological Liver Tissue
Authors: De Vos Rita , De Wolf-Peeters Chris , Den Van Oord Joost J. , Desmet Valeer 
Published: March 2007

Major histocompatibility complex products Class I (HLA Class I) antigens are not expressed on the surface of normal human hepatocytes but become so in pathological conditions. The purpose of this study was to specify the ultrastructural topography of HLA Class I antigens expression.
Nine human liver specimens, known from light microscopic investigation to display membranous positivity for HLA Class I antigens, were processed for immunoelectronmicroscopy using monoclonal anti–HLA Class I in an indirect immunoperoxidase procedure.
HLA Class I antigens were detected on the basolateral membrane of hepatocytes and bile duct cells; some cisternae of the endoplasmic reticulum were also positive. The membranes of normal bile canaliculi of hepatocytes and the apical border of bile duct cells were negative. In one case of presumably drug–induced cholestasis, abnormal cholestatic canaliculi displayed HLA Class I antigens.
These results indicate that HLA Class I antigens are synthesized by the hepatocytes and bile duct cells and incorporated into the plasma membrane; the basolateral expression follows the pattern as in other polarized cells. The expression in cholestatic canaliculi suggests a disturbed polarity of the hepatocyte.
On the Pathogenesis of Focal Nodular Hyperplasia of the Liver
Authors: Wanless Ian R. , Mawdsley Carolyn , Adams Ronald 
Published: March 2007

Fifty–one focal nodular hyperplasia lesions from 36 patients were examined histologically. Serial sections and three–dimensional models were studied in selected cases. Lesions were multiple in 19% of patients. Thirty–four patients were female. One case had 11 focal nodular hyperplasia lesions and 7 hemangiomata in the liver. Three had astrocytoma and one had anomalous pulmonary venous drainage. Morphometric analysis revealed that the lesions were supplied by an anomalous artery larger than expected for the locale in the liver. This artery branched to form a spider–like structure and was usually not accompanied by a portal vein or duct. Each terminal arterial branch supplied a separate nodule 1 mm in diameter; adjacent nodules coalesced to form the focal nodular hyperplasia lesion. The arterial blood appeared to drain directly into the sinusoids of the nodule.
We propose that focal nodular hyperplasia is an hyperplastic response of the hepatic parenchyma to a preexisting arterial spider–like malformation. The frequent coexistence of focal nodular hyperplasia with other vascular and neuroendocrine anomalies suggest that the malformations are developmental in origin. The basic requirement for development of hepatic hyperplasia may be greater blood flow to a region compared to the adjacent parenchyma. This requirement appears to be met in the other forms of nodular transformation of the liver, i.e., nodular regenerative hyperplasia and partial nodular transformation.