bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial Cell Transformation in Primary Biliary Cirrhosis: A Morphological and Biochemical Study
Authors: Babbs Christopher , Haboubi Najib Y. , Mellor Jonathan M. , Smith Alexander , Rowan Brenda P. , Warnes Thomas W. 
Published: March 2007

There is increasing interest in the changes of the endothelial lining of the hepatic sinusoids during the development of chronic liver disease. In this study we looked for evidence of hepatic sinusoidal endothelial cell transformation and basement membrane production in patients with primary biliary cirrhosis.
Morphological transformation to vascular–type endothelial cells, as evidenced by the development of positive immunohistochemical staining for factor VIII–related antigen, was seen at the interface between portal tracts or fibrous septae and hepatic parenchyma; the most marked changes were observed in patients with established cirrhosis. Increased immunohistochemical staining for the basement membrane components type IV collagen and laminin was also found in a similar distribution. Raised serum levels of hyaluronic acid, a glycosaminoglycan metabolized by normal hepatic endothelial cells, were found in most patients and correlated strongly with advancing histological stage. Furthermore, significant positive correlations were found between serum hyaluronic acid and serum levels of laminin and type IV collagen.
The unique structure of the normal endothelial lining of the hepatic sinusoids is important in the maintenance of hepatic function. Our data show that significant changes in endothelial cell structure and function occur in primary biliary cirrhosis and appear to be a contributing factor to the progression of the disease. Further studies are needed to determine the extent and importance of these changes in other forms of chronic liver disease.(HEPATOLOGY 1990; 11:723–729.)
Cholesteryl Ester Storage Disease: Hepatopathology and Effects of Therapy With Lovastatin
Authors: Di Bisceglie Adrian M. , Ishak Kamal G. , Rabin Lionel , Hoeg Jeffrey M. 
Published: March 2007

We describe three patients with cholesteryl ester storage disease. Diagnosis was confirmed by demonstrating a deficiency in lysosomal acid cholesteryl hydrolase activity in cultured skin fibroblasts from each of these patients. All had hepatomegaly, elevated serum aminotransferase activities and hyperlipoproteinemia. Histological examination of liver biopsy specimens before treatment revealed accumulation of fat within hepatocytes, bile duct epithelium and endothelial and Kupffer cells. Cholesterol crystals were recognized by their birefringence in frozen sections. A striking feature was the presence of markedly hypertrophied Kupffer cells and portal macrophages with foamy, tan–colored cytoplasm that stained readily with the periodic acid–Schiff reagent and aldehyde fuchsin. Periportal fibrosis was noted in all cases; incomplete cirrhosis was present in one case. Distinctive and hitherto undescribed lysosomal accumulations of triglyceride and cholesterol crystals were noted.
The patients were treated with lovastatin, a cholesterol–lowering agent, for at least 12 mo. No significant changes were seen in serum lipoprotein concentrations or liver histopathology after therapy. Thus lovastatin did not have an obviously beneficial effect on abnormal lipid metabolism in these patients.(HEPATOLOGY 1990; 11:764–772.)
Higher Blood Alcohol Levels in Women Than in Men: Vive La Petite Diféfrence
Authors: Batey R. , Conn Harold O. 
Published: March 2007

After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant “first–pass metabolism” of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex–related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics.
The first–pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first–pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (r8 = 0.659) between first–pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first–pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first–pass metabolism was virtually abolished.
We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism.
Immunohistochemistry of the Hepatic Extracellular Matrix in Acute Viral Hepatitis
Authors: Inuzuka Sadataka , Ueno Takato , Torimura Takuji , Sata Michio , Abe Hirohiko , Tanikawa Kyuichi 
Published: March 2007

The distribution of several extracellular matrix components in the liver of patients with acute viral hepatitis was studied by light and electron microscopy using indirect immunoperoxidase methods.
Light microscopy revealed type III and type V collagen and fibronectin in the portal tracts and the area of focal necrosis, showing cell infiltration. Type III and type V collagen were more strongly stained in the periphery of focal necrosis. Type IV collagen was seen around the vessels and hepatocytes near the focal necrosis. Electron microscopy showed many transitional Ito cells in the area of focal necrosis and fibroblasts were observed in the portal tracts, showing collagen fiber deposition. Numerous collagen fibrils were observed around fibroblasts, Ito cells and hepatocytes. Using immunoelectron microscopy, type III and type IV collagen and fibronectin were observed in the rough endoplasmic reticulum of Ito cells and hepatocytes localized near the area of focal necrosis or fiber deposition. In addition, type IV collagen was seen in the rough endoplasmic reticulum of endothelial cells forming capillary vessels.
These results suggest that several extracellular matrix components such as types III, IV and V collagen and fibronectin, produced by Ito cells, hepatocytes or endothelial cells, play important roles in the healing of liver damage in acute viral hepatitis. (Hepatology 1990; 12:249-256).
Renal sodium retention complicating alcoholic liver disease: Relation to portosystemic shunting and liver function
Authors: Rector William G. , Lewis Frederick , Robertson Alastair D. , Everson Gregory T. 
Published: March 2007

The aim of this study was to determine whether liver function and portosystemic shunting are related to renal sodium retention in alcoholic liver disease. Twenty-three studies were performed; 10 patients had ascites. Liver function was assessed from the plasma elimination rates of antipyrine, caffeine and stable isotopes of cholic acid, the latter administered both orally [2,2,4,4-2H] and intravenously [24-13C]. Portosystemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid.
Portosystemic shunt fraction was similar in patients with and without ascites (61% ± 16% vs. 64% ± 11%) and unrelated to urinary sodium excretion in patients with ascites (r = −0.145). Patients with ascites had significantly lower elimination rates of all administered compounds as compared with patients without ascites (antipyrine = 0.012 ± 0.007 vs. 0.031 ± 0.016/hr, p < 0.001; caffeine = 0.014 ± 0.013 vs. 0.061 ± 0.041/hr, p < 0.002; intravenous cholic acid = 1.355 ± 0.442 vs. 2.284 ± 0.885/hr, p = 0.005; orally administered cholic acid = 2.178 ± 0.841 vs. 4.056 ± 1.837/hr, p = 0.007). However, urinary sodium excretion in patients with ascites was not related to the elimination constants of these compounds (r = 0.360, 0.319, 0.067, -0.073, respectively).
Ascites complicating alcoholic liver disease is associated with impaired liver function but not the extent of portosystemic shunting. (Hepatology 1990;12:455-459).
Pretranslational and posttranslational regulation of the EGF receptor during the prereplicative phase of liver regeneration
Authors: Johansson Staffan , Andersson Niclas , Andersson Göran 
Published: March 2007

We studied the regulation of the epidermal growth factor receptor mRNA and the number of epidermal growth factor binding sites in subcellular compartments involved in the biosynthesis and endocytosis of the epidermal growth factor receptor during the prereplicative phase of liver regeneration. The epidermal growth factor receptor mRNA, quantified by solution hybridization, decreased after partial hepatectomy, with a nadir of about 35% 18 hr after hepatectomy. An even strongèr decrease in the number of epidermal growth factor binding sites after partial hepatectomy was observed in a Golgi-enriched low-density membrane fraction, reflecting available newly synthesized epidermal growth factor receptors. It is suggested that this decrease in newly synthesized available epidermal growth factor receptors is caused primarily, but not entirely, by decreased epidermal growth factor receptor mRNA levels and the additional downregulation of epidermal growth factor binding sites may involve posttranslational mechanisms such as intracellular occupation by transforming growth factor-α.
The observation that the number of specific epidermal growth factor binding sites after partial hepatectomy was only moderately reduced in prelysosomal endosomes and in lysosomes, compared with the newly synthesized receptors, may indicate that a pool of receptors targeted for lysosomes exists and these receptors are regulated in a different manner than the receptor pool targeted for the cell surface.
Furthermore, at least two separable endocytic subcompartments are involved in the transport of the epidermal growth factor/epidermal growth factor receptor complex in the liver. The complex first enters early endosomes, then enters late, prelysosomal endosomes, where the epidermal growth factor is proteolytically processed, before arriving in the lysosomal compartment. (Hepatology 1990;12:533-541).
Interferon and chronic non-A, non-B hepatitis: Whom are we treating?
Authors: Conn Harold O. , Koretz Ronald L. 
Published: March 2007

Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment.
The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P <0.001) and 28 percent in those treated with 1 million units (P <0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units.
We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.
Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twentyone patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo.
The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment ended, however, serum aminotransferases usually returned to pretreatment levels; 6 to 12 months after the discontinuation of interferon therapy, only two patients (10 percent) still had normal values.
We conclude that interferon alfa therapy is beneficial in reducing disease activity in chronic hepatitis C; however, the beneficial responses are often transient.
Characterization of holmium loaded alginate microspheres for multimodality imaging and therapeutic applications
Authors: Zielhuis S.W. , Seppenwoolde J.H. , Bakker C.J.G. , Jahnz U. , Zonnenberg B.A. , van het Schip A.D. , Hennink W.E. , Nijsen J.F.W. 
Published: March 2007

AbstractIn this paper the preparation and characterization of holmium‐loaded alginate microspheres is described. The rapid development of medical imaging techniques offers new opportunities for the visualisation of (drug‐loaded) microparticles. Therefore, suitable imaging agents have to be incorporated into these particles. For this reason, the element holmium was used in this study in order to utilize its unique imaging characteristics. The paramagnetic behaviour of this element allows visualisation with MRI and holmium can also be neutron‐activated resulting in the emission of gamma‐radiation, allowing visualisation with gamma cameras, and beta‐radiation, suitable for therapeutic applications. Almost monodisperse alginate microspheres were obtained by JetCutter technology where alginate droplets of a uniform size were hardened in an aqueous holmium chloride solution. Ho3+ binds via electrostatic interactions to the carboxylate groups of the alginate polymer and as a result alginate microspheres loaded with holmium were obtained. The microspheres had a mean size of 159 μm and a holmium loading of 1.3 ± 0.1% (w/w) (corresponding with a holmium content based on dry alginate of 18.3 ± 0.3% (w/w)). The binding capacity of the alginate polymer for Ho3+ (expressed in molar amounts) is equal to that for Ca2+, which is commonly used for the hardening of alginate. This indicates that Ho3+ has the same binding affinity as Ca2+. In line herewith, dynamic mechanical analyses demonstrated that alginate gels hardened with Ca2+ or Ho3+ had similar viscoelastic properties. The MRI relaxation properties of the microspheres were determined by a MRI phantom experiment, demonstrating a strong R2* effect of the particles. Alginate microspheres could also be labelled with radioactive holmium by adding holmium‐166 to alginate microspheres, previously hardened with calcium (labelling efficiency 96%). The labelled microspheres had a high radiochemical stability (94% after 48 h incubation in human serum), allowing therapeutic applications for treatment of cancer. The potential in vivo application of the microspheres for a MR‐guided renal embolization procedure was illustrated by selective administration of microspheres to the left kidney of a pig. Anatomic MR‐imaging showed the presence of holmium‐loaded microspheres in the kidney. In conclusion, this study demonstrates that the incorporation of holmium into alginate microspheres allows their visualisation with a gamma camera and MRI. Holmium‐loaded alginate microspheres can be used therapeutically for embolization and, when radioactive, for local radiotherapy of tumours. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Polymers with tunable toxicity: A reference scale for cytotoxicity testing of biomaterial surfaces
Authors: Knetsch Menno L.W. , Olthof Nadine , Koole Leo H. 
Published: March 2007

AbstractA series of copolymers, with varying ratio di‐methylamino‐ethylmethacrylate (DMAEMA) and methyl‐methacrylate (MMA), was designed as a potential scale for cytotoxicity. These copolymers were characterized for toxicity of their surface. The surfaces of washed copolymers display increasing toxicity with increasing DMAEMA content. The toxicity was observed for three different cell‐types, namely mouse fibroblasts, human endothelial cells and human osteoblast‐like cells. With an increasing toxic surface, cell growth was inhibited as was indicated by the proliferation marker Ki‐67. Staining for F‐actin revealed that with increasing DMAEMA, cells adopted a more and more round morphology, resulting in decreased surface‐contact area. Immuno‐staining for phospho‐tyrosine or vinculin demonstrated gradual loss of focal adhesions on increasingly toxic surfaces. Surprisingly loss of focal adhesions coincided with an increase in paxillin and vinculin protein, indicating cells try compensating for loss of adhesion. This series of copolymers may have potential as a cytotoxicity scale. They provoke cellular responses ranging from highly toxic to completely non‐toxic, with some showing intermediate toxicity. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Clinical and serologic effects of live attenuated serum inhibitor‐resistant influenza B vaccine in seronegative adults
Authors: Miller Louis W. , Togo Yasushi , Hornick Richard B. 
Published: March 2007

AbstractThe clinical effects, nasal and serum antibody responses, and virus excretion of a live attenuated serum inhibitor‐resistant influenza B virus vaccine, R75, was evaluated in 43 seronegative healthy adults by a random double‐blind study. Symptom responses were minimal and were not significantly different between vaccine and placebo groups. No fevers, abnormalities in physical examination or laboratory testing developed during 4 weeks of observation.Among vaccinees, 10 (48%) developed serum hemagglutination‐inhibition (HI) antibodies, 16 (76%) developed serum neutralization (N) antibodies and 4(19%) developed nasal N antibodies. The GMT responses from study day 0 to day 28 were 4.0 to 10.4 for serum HI, 1.8 to 9.8 for serum N, and 1.0 to 1.4 for nasal N. There were no significant titer changes in the placebo group. No virus excretion was detected.Although there are some questions concerning the relationship of antibody levels to protection, the low antibody responses in this study are an indication that R75 is not sufficiently immunogenic.
Experimental infection of chimpanzees with the Norwalk agent of epidemic viral gastroenteritis
Authors: Wyatt Richard G. , Greenberg Harry B. , Dalgard Dan W. , Allen William P. , Sly D. Lewis , Thornhill Thomas S. , Chanock Robert M. , Kapikian Albert Z. 
Published: March 2007

AbstractA fecal filtrate of human origin containing the Norwalk agent of epidemic viral gastroenteritis was administered by stomach tube to chimpanzees in an attempt to induce diarrheal disease. Significant postchallenge serum antibody rises against Norwalk viral antigens were demonstrated in all animals using the techniques of immune electron microscopy and radioimmunoassay. In addition, viral antigens were detected in feces from five of nine animals using radioimmunoassay. Clinical illness characterized by diarrhea and/or vomiting did not occur. Infection was transmitted subsequently by feeding four additional chimpanzees a fecal filtrate prepared from one of the previously infected animals. Development of an antibody response in four animals and detection of viral antigen in two animals that received this passage filtrate indicated that viral replication had occurred in the absence of clinical illness. The availability of the chimpanzee as an experimental animal host susceptible to infection with the Norwalk agent should facilitate the study of epidemic viral gastroenteritis.
e‐antigen and age in acute and chronic type B hepatitis
Authors: Villarejos Victor M. , Visona Kirsten Anderson , Eduarte A. Carlos E. 
Published: March 2007

AbstractThe influence of e‐antigen upon the course and outcome of acute type B hepatitis was studied in a series of 202 patients. Of these, 54 (27%) had e‐Ag, detected in the serum at the same time as HBsAg during the incubation period or at onset. In 39 patients (73%) the e‐Ag disappeared within eight weeks after onset, regularly followed by clearance of HBsAg approximately four weeks later; anti‐HBs was detected shortly thereafter in 34 cases. In 15 (28%) of e‐Ag‐positive and in 4 (3%) of e‐Ag‐negative patients, HBsAg persisted for one year or longer; chronic hepatitis developed in 13 of these cases, 12 of which were e‐Ag‐positive. Among e‐Ag‐positives HBsAg persisted only in those cases in which the e‐Ag also persisted; all these were persons under 15 years of age. Transaminase and bilirubin values were equally high in e‐Ag‐positive and e‐Ag‐negative patients with resolving hepatitis, but were low from the start in those who later developed chronic liver conditions, irrespective of the presence or absence of e‐Ag. It is concluded that in e‐Ag‐positive acute type B hepatitis patients the disappearance of this antigen from the serum is a good prognostic sign, whereas its persistence beyond eight weeks, especially in young children with low transaminase and bilirubin response, signals evolution towards chronicity.
Detection of Epstein‐Barr virus antigens and antibodies by peroxidase‐labeled specific immunoglobulins
Authors: Kurstak E. , de Thé G. , van den Hurk J. , Charpentier G. , Kurstak C. , Tijssen P. , Morisset R. 
Published: March 2007

AbstractDetection of the Epstein‐Barr (EBV) antigens, early antigen (EA), viral capsid antigen (VCA), and nuclear antigen (EBNA) by the indirect immunoperoxidase technique was highly sensitive. Antibody titers to EBNA, EA, and VCA were determined in more than 25 sera of patients with Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), or normal persons. A good correlation between the titers of these antigens was obtained by the immunoperoxidase and immunofluorescence methods. The indirect (anti‐IgG) immunoperoxidase technique for the detection of EBNA is, in contrast to the indirect immunofluorescence method, highly sensitive. EBNA was associated with the chromosomes in cells arrested in the metaphase with colchicine.