bluuebunny/crossref_metadata_2025 huggingface dataset:
Antioxidant consumption during exercise in intermittent claudication
Authors: Khaira H S , Maxwell S R J , Shearman C P
Published: March 2007

Twenty male claudicant patients and nine age-matched controls were exercised on a treadmill. Blood and urine samples were taken before and after exercise. Total antioxidant concentration was measured using an enhanced chemiluminescent assay and microalbuminuria determined by radioimmunoassay. Claudicants had increased microalbuminuria after exercise. Mean(s.e.m.) antioxidant concentrations were similar for patients and controls at rest: 479(28) and 438(23) µmol/l respectively. Claudicants showed a significant decrease in antioxidant concentration 1 min after exercise to 428(27) µmol/l; this returned to 470(30) µmol/1 by 10 min. A correlation was found between the decrease in antioxidant concentration and the increase in microalbuminuria (rs = −0.496, P < 0.05). This study supports the concept of ischaemia-reperfusion injury in claudicant patients and has implications for treatment.
Preoperative intra-aortic ultrasonography to determine resectability in advanced oesophageal cancer
Authors: Akiyama S , Kodera Y , Sekiguchi H , Fujiwara M , Sakamoto J , Kondo K , Ito K , Endo T , Takagi H
Published: March 2007

This study was designed to evaluate the effectiveness of intra-aortic ultrasonography in the preoperative diagnosis of aortic wall invasion by oesophageal cancer. Twenty-four patients with advanced oesophageal cancer underwent the procedure, and aortic invasion was found in seven. In three of these seven patients, the invasion was diagnosed to be limited to the aortic adventitia, enabling preoperative prediction of the resectability of the tumour. The contact angle of the tumour in relation to the descending aorta was more than 90° in six patients, and aortic invasion to all layers was visualized in four by intra-aortic ultrasonography. On the other hand, aortic invasion to the adventitia was found in three of 14 patients in whom the contact angle was less than 90°. Intra-aortic ultrasonography provides important information to help determine the resectability of advanced oesophageaf cancer.
Role of the spleen in lipid metabolism
Authors: Fatouros M , Bourantas K , Bairaktari E , Elisaf M , Tsolas O , Cassioumis D
Published: March 2007

The frequency of ischaemic heart disease observed after splenectomy for trauma and the low cholesterol levels found in patients with hypersplenism are observations that suggest a possible role for the spleen in lipid metabolism and in the aetiology of atherosclerosis. The present study was designed to examine this role in experimental animals. Serum levels of total cholesterol, triglyceride and high-density lipoprotein (HDL) cholesterol were determined in 32 rats. The spleen was removed in 16 rats and the remaining 16 were sham operated. Half of the splenectomized and half of the remaining rats were fed on a diet rich in fat and the two other subgroups were fed normal chow. Blood tests were performed before, and 3 and 6 months after operation. A significant increase in serum triglyceride and decrease in serum HDL cholesterol levels was observed after splenectomy in rats fed normal chow compared with sham-operated rats. An increase in serum triglyceride and a decrease in serum HDL cholesterol levels was observed in both groups of rats fed normal chow plus high-fat cheese. However, these changes were more pronounced in splenectomized rats. These findings suggest that the spleen has a role in lipid metabolism in rats and may therefore influence atherosclerosis.
Quality-of-life assessment in patients undergoing treatment for oesophageal carcinoma
Authors: O'Hanlon D M , Harkin M , Karat D , Sergeant T , Hayes N , Griffin S M
Published: March 2007

In a prospective study of 69 patients being treated for oesophageal carcinoma, quality of life was assessed with the Rotterdam Symptom Checklist, a dysphagia score and an activities of daily living questionnaire. Significant correlations were found between the results of the Rotterdam Symptom Checklist, the dysphagia score and most aspects of the activities of daily living questionnaire. Eighteen patients underwent surgery, 43 radiotherapy or intubation, and eight a combination of surgery and other therapy. Patients undergoing surgery were significantly younger and had better scores in all parameters examined before operation, including significantly better scores in ‘knowledge and communication’ and ‘mobility and fatigue’. The dysphagia score fell significantly after intervention both in patients undergoing surgery alone and in those receiving palliative therapy. The activities of daily living questionnaire showed significant improvements in two parameters in the surgical group (‘self-care’ and ‘eating and drinking’) and in none of the parameters assessed in the palliation group in 16 weeks. Quality-of-life assessment is useful in assessing quality of care and patient well-being after the diagnosis and treatment of oesophageal carcinoma.
Number of lymph node metastases is significantly associated with survival in patients with radically resected carcinoma of the ampulla of Vater
Authors: Roder J D , Schneider P M , Stein H J , Siewert J R
Published: March 2007

Between 1983 and 1994, 66 patients with cancer of the ampulla of Vater were studied to identify prognostic factors and determine who might benefit from radical resection. Three patients (4.5 per cent) died after operation. Radical resection including lymphadenectomy resulted in potentially curative (R0) resection in 92 per cent. The rate of nodal positivity increased with tumour diameter. Patients with up to two positive lymph nodes had a more favourable prognosis than other patients (P < 0.001). Median survival time for all patients was 41 months; the 5-year survival rate was 35 per cent. Radical resection and lymphadenectomy should therefore be the treatment of choice for patients with tumours of the ampulla of Vater.
Risk of further ulcer complications after an episode of peptic ulcer bleeding
Authors: Ng E K W , Chung S C S , Lau J T F , Sung J J Y , Leung J W C , Raimes S A , Chan A C W , Li A K C
Published: March 2007

To identify the risk factors for developing recurrent ulcer complications after recovery from an episode of peptic ulcer bleeding 611 patients admitted with peptic ulcer bleeding were studied. Some 557 (91 per cent) were discharged without operation. A total of 22 patients were lost to follow-up and five were excluded as maintenance H2 blockers were required. Of the remaining 530 patients at risk, 169 (32 per cent) developed another complication (166 bleeding, three perforations) over a median follow-up period of 36 months. Patients with duodenal ulcers at the time of bleeding, previous history of peptic ulcer, previous bleeding, history of dyspepsia longer than 3 months, and a short interval between previous ulcer complications and the index bleed were more likely to develop further complications. Sex, age, smoking, coexisting illness, non-steroidal anti-inflammatory drugs intake and time taken to achieve ulcer healing had no predictive value.
Management and follow-up of 78 giant haemangiomas of the liver
Authors: Pietrabissa A , Giulianotti P , Campatelli A , di Candio G , Farina F , Signori S , Mosca F
Published: March 2007

The natural history and appropriate treatment of giant liver haemangioma remain poorly defined. The diagnostic strategy and the results of a longitudinal study of 78 such lesions are described. Sixteen resected patients and 62 with asymptomatic giant haemangiomas were entered into a follow-up programme consisting of clinical assessment and abdominal ultrasonography every 6 months. Resection was considered only for symptomatic patients (14 cases) and rapidly growing lesions (two cases). The mean follow-up was 36 months for the resected patients and 55 months for the observed group. Surgery permanently relieved symptoms. No recurrence of haemangioma was observed. Some 32 of 36 unresected lesions followed up remained stable in size. Minor changes were observed in four of 36. None ruptured or became symptomatic. It is concluded that asymptomatic large haemangiomas can be managed safely by observation. However, the occasional occurrence of rapid growth might represent a further indication for resection and justifies strict imaging follow-up. The pattern of growth, rather than absolute size, of a lesion is suggested for selection of asymptomatic patients who might benefit from preventive surgical excision. When feasible, the authors prefer enucleation to remove giant haemangiomas.
Early localization of necrosis by contrast-enhanced computed tomography can predict outcome in severe acute pancreatitis
Authors: Kemppainen E , Sainio V , Haapiainen R , Kivisaari L , Kivilaakso E , Puolakkainen P
Published: March 2007

A total of 161 primary contrast-enhanced computed tomography (CT) scans of patients with acute necrotizing pancreatitis taken between 1982 and 1994 were analysed retrospectively. The aim was to assess the prognostic significance of the extent and anatomical site of pancreatic tissue necrosis in the first contrast-enhanced CT scan. The scans were obtained a mean of 2·9 days after the onset of symptoms. The pancreatic head was affected in 107 patients, the body in 119 and the tail in 138. Pancreatic tissue necrosis, when divided into four groups according to anatomical site, correlated with overall clinical outcome. The anatomical site of necrosis was clearly better than its crude extent in predicting the risk of complications. For patients with necrosis in the head of the pancreas, the outcome was as severe as when the entire pancreas was affected. In contrast, for patients with necrosis only in the distal part of the pancreas, the outcome was favourable with few complications. The exact site of pancreatic tissue necrosis should be known when early contrast-enhanced CT is used in prognostic scoring.
Prospective analysis of the distal margin of clearance in anterior resection for rectal carcinoma
Authors: Kwok S P Y , Lau W Y , Leung K L , Liew C T , Li A K C
Published: March 2007

The distal resection margin measured in situ at operation, on the fresh specimen and on the fixed specimen was analysed prospectively in 55 consecutive patients undergoing anterior resection for carcinoma of the rectum. There was obvious contraction in length from the operative margin to the specimen margin and to the fixed margin. As measured by contraction coefficients, contraction was greater in more proximal tumours than in distal ones. Eight of 55 patients had microscopic intramural spread in the fixed distal margin and the maximum spread was 12 mm. Taking contraction of the fixed margin into account, the extrapolated microscopic spread in the operative margin ranged from 0 to 47 mm.
Iron status following trauma, excluding burns
Authors: Walsh D S , Pattanapanyasat K , Lamchiagdhase P , Siritongtaworn P , Thavichaigarn P , Jiarakul N , Chuntrasakul C , Komoltri C , Dheeradhada C , Pearce F C , Wiesmann W P , Webster H K
Published: March 2007

Serum concentration of iron, transferrin saturation and total iron binding capacity (TIBC) were measured on days 1, 2, 3, 5, 7, 10 and 13 in 36 Thai patients with trauma (burns excluded) to determine temporal changes in iron metabolism. Throughout the study profound hypo-ferraemia was observed in association with decreased transferrin saturation. TIBC, in contrast, did not differ significantly from that in controls. These findings confirm previous reports which describe altered iron metabolism in association with an adverse event, a response known as ‘stress hypoferraemia’, and extends these observations to non-burned patients with trauma. The degree of hypoferraemia in patients in this study was not related to sepsis, Injury Severity Score, volume of blood transfused or surgery, suggesting that hypoferraemia following trauma is an independent event. The recognition of rapid and prolonged iron sequestration provides insight into the clinical condition of patients with trauma.
Pathological evidence in support of total mesorectal excision in the management of rectal cancer
Authors: Reynolds J V , Joyce W P , Dolan J , Sheahan K , Hyland J M
Published: March 2007

Some 50 total mesorectal excision specimens were examined following rectal excision for cancer. Circumferential margin involvement was rare, but mesorectal tumour deposits were present in 17 of 44 patients with pT3 tumours, and 23 of 44 had mesorectal nodal involvement. No patient with a pT2 tumour had mesorectal involvement. Failure to excise the mesorectum completely has the potential to leave gross or microscopic residual disease that may in theory predispose to local failure. Total mesorectal excision is necessary to avoid incomplete pathological evaluation of the mesorectum and understaging of rectal cancer.
Plasminogen activators in oesophageal carcinoma
Authors: Hewin D F , Savage P B , Alderson D , Vipond M N
Published: March 2007

The expression of components of the plasminogen activator system was investigated in patients with oesophageal carcinoma. Tumour and normal mucosa were obtained from resected oesophageal carcinomas and antigens were measured by enzyme-linked immunosorbent assay. Median levels of urokinase plasminogen activator (uPA) and the uPA receptor were higher in carcinoma than in matched normal mucosa (squamous cell carcinoma: uPA 4·05 versus 0·66 ng antigen per mg protein, uPA receptor 1·95 versus 0·50 ng/mg, n = 10, P < 0·05; adenocarcinoma: uPA 2·16 versus 0·61 ng/mg, uPA receptor 2·01 versus 0·49 ng/mg, n = 8, P < 0·05). Tissue plasminogen activator (tPA) level was lower than control values in squamous cell carcinoma but not in adenocarcinoma (1·97 versus 4·70 ng/mg, P < 0·05). There was no difference in plasminogen activator inhibitor (PAI) 1 level between carcinoma and normal mucosa. The PAI-2 level was lower than that in normals in adenocarcinoma only (6·0 versus 64·77 ng/mg, P < 0·05). These data support the hypothesis that membrane-bound uPA has a role in the breakdown of extracellular matrix in invasive oesophageal carcinoma.
Randomized trial of blunt-tipped versus cutting needles to reduce glove puncture during mass closure of the abdomen
Authors: Hartley J E , Ahmed S , Milkins R , Naylor G , Monson J R T , Lee P W R
Published: March 2007

Eighty-five consecutive patients were randomized to undergo mass closure of the abdomen with no. 1 polydioxanone mounted on either a blunt-tipped (n = 46) or cutting (n = 39) needle. Gloves were changed before closure and tested for perforation afterwards using standard air or water techniques. Fourteen pairs of gloves were punctured when using a cutting needle, and three pairs when a blunt-tipped needle was used. The majority of punctures were to the non-dominant glove. The surgeon was aware of the puncture in eight of the 14 instances involving a sharp needle and in one of the three involving a blunt-tipped needle. Blunt-tipped needles, while not eliminating the risk, significantly reduced the incidence of surgical glove puncture (P < 0·001, Fisher's exact test). The use of cutting needles for abdominal closure should be abandoned.
Localization of the transcriptional coactivator PGC‐1α to GABAergic neurons during maturation of the rat brain
Authors: Cowell Rita Marie , Blake Kathryn Rose , Russell James W.
Published: March 2007

The transcriptional coactivator peroxisome proliferator activated receptor γ coactivator 1α (PGC‐1α) can activate a number of transcription factors to regulate mitochondrial biogenesis and cell‐specific responses to cold, fasting, and exercise. Recent studies indicate that PGC‐1α knockout mice exhibit behavioral abnormalities and progressive vacuolization in various brain regions. To investigate the roles for PGC‐1α in the nervous system, we evaluated the temporal and cell‐specific expression of PGC‐1α in the normal developing rat brain. Western blot of whole brain homogenates with a PGC‐1α‐specific antibody revealed that PGC‐1α protein was most abundant in the embryonic and early postnatal forebrain and cerebellum. Using quantitative reverse‐transcriptase polymerase chain reaction (RT‐PCR), we determined that PGC‐1α mRNA expression increased most markedly between postnatal days 3 (P3) and 14 in the cortex, striatum, and hippocampus. Immunohistochemical and immunofluorescence analyses of brain tissue indicated that while PGC‐1α was found in most neuronal populations from embryonic day 15 to P3, it was specifically concentrated in GABAergic populations from P3 to adulthood. Interestingly, PGC‐1α colocalized with the developmentally regulated chemoattractant reelin in the cortex and hippocampus, and the survival‐promoting transcription factor myocyte enhancing factor 2 was highly concentrated in GABAergic populations in the striatum and cerebellum at times of PGC‐1α expression. These results implicate PGC‐1α as a regulator of metabolism and/or survival in GABAergic neurons during a phase of mitochondrial and synaptic changes in the developing brain and suggest that PGC‐1α may be a good target for increasing metabolism in GABAergic populations in neurodevelopmental and neurodegenerative disorders. J. Comp. Neurol. 502:1–18, 2007. © 2007 Wiley‐Liss, Inc.
Combining visual information from the two eyes: The relationship between isthmotectal cells that project to ipsilateral and to contralateral optic tectum using fluorescent retrograde labels in the frog, Rana pipiens
Authors: Dudkin Elizabeth A. , Sheffield Joel B. , Gruberg Edward R.
Published: March 2007

The frog nucleus isthmi (homolog of the mammalian parabigeminal nucleus) is a visually responsive tegmental structure that is reciprocally connected with the ipsilateral optic tectum; cells in nucleus isthmi also project to the contralateral optic tectum. We investigated the location of the isthmotectal cells that project ipsilaterally and contralaterally using three retrograde fluorescent label solutions: Alexa Fluor 488 10,000 mw dextran conjugate; Rhodamine B isothiocyanate; and Nuclear Yellow. Dye solutions were pressure‐injected into separate sites in the superficial optic tectum. Following a 6‐day survival, brains were fixed, sectioned, and then photographed. Injection of the different labels at separate, discrete locations in the optic tectum result in retrograde filling of singly labeled clusters of cells in both the ipsilateral and contralateral nucleus isthmi. Generally, ipsilaterally projecting cells are dorsal to the contralaterally projecting cells, but there is a slight overlap between the two sets of cells. Nonetheless, when different retrograde labels are injected into opposite tecta, there is no indication that individual cells project to both tecta. The set of cells that project to the ipsilateral tectum and the set of cells that project to the contralateral tectum form a visuotopic map in a roughly vertical, transverse slab. Our results suggest that nucleus isthmi can be separated into two regions with cells in the dorsolateral portion projecting primarily to the ipsilateral optic tectum and cells in the ventrolateral nucleus isthmi projecting primarily to the contralateral optic tectum. J. Comp. Neurol. 502:38–54, 2007. © 2007 Wiley‐Liss, Inc.
Pathology of cytoskeleton of liver cells: Demonstration of mallory bodies (alcoholic hyalin) in murine and human hepatocytes by immunofluorescence microscopy using antibodies to cytokeratin polypeptides from hepatocytes
Authors: Denk Helmut , Franke Werner W. , Dragosics Brigitte , Zeiler Ingrid
Published: March 2007

A cytoskeleton fraction enriched in intermediate-sized filaments and resistant to high and low salt buffer containing Triton X-100 was prepared from dissociated mouse liver cells and mouse liver homogenates. One-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a family of polypeptides in the relative molecular weight (Mr) range from 41,000 to 55,000, with two polypeptides (component A, Mr 55,000; component D, Mr 48,000) as major constituents. Antibodies to isolated cytokeratin components of lower molecular weights (48,000 and 45,000 to 41,000) decorated, in indirect immunofluorescence microscopy, a distinct cytoplasmic filament meshwork in hepatocytes of various species whereas antibodies to higher molecular weight components were less or even not effective. The antibodies also reacted with cytokeratin filaments present in epithelial cells of various other organs and species, confirming the widespread occurrence of immunologically related cytokeratin filaments in epithelial tissues. The antibodies to higher molecular weight components showed a higher affinity to cytokeratin filaments of epidermis, stratified epithelia, and myoepithelial cells compared to epithelial cells of other organs, including small intestinal crypt epithelium and secretory cells of the submandibular gland. These observations further support the biochemical and immunologic heterogeneity in the cytokeratin family.

Mallory bodies (MBs) present in murine and human livers specifically reacted not only with antibodies to lower molecular weight polypeptides, but also even more so with antibodies to higher molecular weight components, indicating (i) the relatedness of MB material to hepatocyte cytokeratin, and (ii) differences of exposed antigenic determinants of cytokeratin(s) during MB development. In polypeptide composition, MB material differed from hepatocyte cytokeratin by polypeptides of molecular weights in the range of 55,000 to 66,000, which is more reminiscent of the pattern of epidermal cytokeratin. The development of MBs was associated with severe derangement of the cytokeratin filament meshwork in the affected hepatocytes, as revealed by immunofluorescence microscopy, indicating that cytoskeletal material progressively coalesced and was incorporated into MBs. The results present the first demonstration of the hepatocyte cytokeratin meshwork and an example of a pathologic change of this structure. The observations suggest that liver disorders associated with MB development can be regarded as cytoskeleton diseases.
Effect of short-term ethanol administration on lorazepam clearance
Authors: Hoyumpa Anasticio M. , Patwardhan Rashmi , Maples Michael , Desmond Paul V. , Johnson Raymond F. , Sinclair Alicia P. , Schenker Steven
Published: March 2007

The disposition of chlordiazepoxide (Librium®) and diazepam (Valium®), compounds which are initially degraded by oxidative processes, differs from that of oxazepam (Serax®) and lorazepam (Ativan®), drugs which are inactivated by conjugation with glucuronic acid. Liver disease and cimetidine impair the elimination of the former agents, but not the latter two benzodiazepines. In addition, ethanol inhibits the metabolism of chlordiazepoxide and diazepam. The present studies were performed to determine the effect of short-term ethanol administration on glucuronidation and elimination of lorazepam in dogs and humans. Because, in dogs, lorazepam has a high extraction ratio (approximately 0.9) with an anticipated large presystemic elimination, the influence of ethanol on the presystemic (first-pass) elimination of lorazepam was determined. Administration of p.o. lorazepam to five healthy dogs 1 hr after i.v. saline or ethanol (3 gm/kg) reduced the presystemic elimination of lorazepam by 52% (p < 0.05). In man, lorazepam has a low (approximately 0.05) extraction ratio and only a small first-pass effect. Short-term administration of ethanol (0.8 gm/kg followed by 0.5 gm/kg p.o. every 5 hr for four doses) reduced i.v. lorazepam clearance by 18% (p < 0.03). In dogs and man, ethanol did not significantly alter lorazepam t½, plasma protein binding, or distribution volume (Vdβ). The results suggest that short-term ethanol administration impairs the conjugation of lorazepam in dogs and man.
Woodchuck hepatitis and hepatocellular carcinoma: Correlation of histologic with virologic observations
Authors: Popper Hans , Shih James W.-K. , Gerin John L. , Wong Doris C. , Hoyer Bill H. , London William T. , Sly David L. , Purcell Robert H.
Published: March 2007

The livers of 33 captive woodchucks were examined histologically in 30 biopsy and 10 autopsy specimens and the findings were correlated with serum determinations for woodchuck hepatitis virus (WHV), surface antigen (WHsAg) and antibody (anti-WHs), and WHV DNA and DNA polymerase. The liver appeared normal in all 3 serum-negative animals, 7 of 16 with indeterminate WHV status, and 1 of 4 with anti-WHs, but not in 10 animals with WHsAg, WHV DNA, and DNA polymerase. Mild hepatic inflammation was found in 7 woodchucks with indeterminate status, 4 with anti-WHs, and 2 with each marker of WHV infection. Significant inflammation was found in 2 of indeterminate status and 4 with every marker, whereas more severe lesions (2 of chronic active type) occurred, almost always in autopsy specimens, in 8 animals with every marker. Eight of 10 animals with all markers had orcein-positive inclusions (Shikata’s technique) and 6 had hepatocellular carcinoma associated with acute and chronic hepatic inflammation and, usually, neoplastic nodules in the noncarcinomatous parenchyma. Features distinguishing the woodchuck lesion from human hepatitis B disease were: association of carcinoma with acute hepatic inflammation (but not with cirrhosis) and DNA polymerase in the serum; transition to carcinoma from neoplastic nodules; conspicuous plasma-cellular reaction of hepatic inflammation, and hematopoietic cells in the tumor. Significant hepatic lesions in the woodchucks were regularly associated with serum WHsAg, WHV DNA, and DNA polymerase. In contrast to man, hepatocellular carcinoma in woodchucks was regularly associated with these markers of active viral replication. The nature of the orcein-positive inclusions requires elucidation, although they may assist in screening for similar viruses in other species. The woodchuck may help in the study of the relation between hepatocellular carcinoma and hepatitis B, including the possibility of cocarcinogenic factors.
Transferrin receptors and the uptake and release of iron by isolated hepatocytes
Authors: Young Stephen P. , Aisen Philip
Published: March 2007

Isolated rat hepatocytes accumulate iron from iron-transferrin by a process which is dependent on the temperature and on the transferrin concentration, and which is diminished by treatment of the cells with a proteolytic enzyme. These observations are consistent with a mechanism for iron uptake into hepatocytes involving the binding of iron-transferrin to a specific cell-surface receptor.

Apotransferrin is also able to bind to the hepatocyte but the apparent binding constant is about 35 times lower than that observed for the binding of iron-transferrin. The binding of apotransferrin to the cells is completely abolished by a low concentration of iron-transferrin. This suggests that the apotransferrin is binding weakly to the same receptor to which iron-transferrin binds and that there are no receptors on the surface of the hepatocyte specific for apotransferrin. In the absence of such specific-binding sites, apotransferrin may act as a passive acceptor of iron released from the hepatocyte.
The δ agent: HBsAg particles with δ antigen and RNA in the serum of an HBV carrier
Authors: Bonino Ferruccio , Hoyer Bill , Ford Eugenie , Shih Wai-Kuo J. , Purcell Robert H. , Gerin John L.
Published: March 2007

The hepatitis B virus-associated delta antigen was detected in the serum of a young female drug addict with acute hepatitis and a previous history of hepatitis B surface antigen carrier. Delta antigen was associated with a 35- to 37-nm subpopulation of hepatitis B surface antigen particles which banded at a density of 1.25 gm per cm3 of CsCl and contained a small RNA of approximately 5.5 × 105 molecular weight. This report demonstrates that delta antigen is associated with a unique subpopulation of hepatitis B surface antigen particles and small RNA in human serum.
Presence of receptors for polymerized albumin in HBsAg-containing hepatocytes and hepatoma cell line
Authors: Thung Swan N. , Gerber Michael A.
Published: March 2007

Recent evidence suggests that hepatitis B virions (HBV) and HBsAg particles contain receptors for polymerized human serum albumin (pHSA). We studied, by immunohistochemical techniques, the relationship between HBsAg and pHSA receptors in liver tissue from eight patients with chronic HBV infection and in a human hepatocellular carcinoma cell line (PLC/PRF/5) producing HBsAg. Both parallel sections and double fluorescent antibody staining of liver tissue demonstrated that only HBsAg-containing hepatocytes expressed pHSA receptors. The receptors could not be demonstrated in eight HBsAg negative livers. Sequential studies of PLC/PRF/5 cells revealed that pHSA and HBsAg emerged simultaneously in the cytoplasm, on the cell surface, and in the supernatant culture media. These findings indicate that pHSA receptors are closely associated with HBsAg during its synthesis and secretion by hepatocytes and suggest that the receptors are HBV-specific.
Bile acid metabolism in cirrhosiso. VII. Evidence for defective feedback control of bile acid synthesis
Authors: Vlahcevic Reno Z. , Goldman Marc , Schwartz Charles C. , Gustafsson Jan , Swell Leon
Published: March 2007

The present report has been directed toward providing additional information on the major defects in the bile acid pathways present in patients with cirrhosis and its relevance to the problem of how bile acid synthesis is regulated in man. An unusual patient with severe liver disease and a completely broken enterohepatic circuit was studied. The synthesis of cholic and chenodeoxycholic acids was examined over a 5-d period. The secretion rates and the incorporation of [3H]7α-hydroxycholesterol and [3H]26-hydroxycholesterol into both primary bile acids in the cirrhotic bile fistula patient was cross compared to earlier data obtained on patients with and without liver disease and an intact enterohepatic circuit and patients with no liver disease and a bile fistula. The daily synthesis rate of cholic acid increased 7-fold and chenodeoxycholic acid 2-fold in the cirrhotic bile fistula patient. The incorporation of [3H]7α-hydroxycholesterol into bile acids in the cirrhotic bile fistula patient was efficient (75%) and equal to bile fistula patients with no cirrhosis (76%); chenodeoxycholic acid synthesis was favored over cholic acid particularly in the cirrhotic patient. [3H]26-hydroxycholesterol was poorly incorporated in patients with no cirrhosis (25%) and the cirrhotic patient (20%); chenodeoxycholic acid was favored by a wide margin. It is concluded from this and previous reports that the profound reduction in bile acid synthesis present in patients with cirrhosis is not caused singly by a failure in the metabolic pathways from 7α-hydroxycholesterol to cholic and chenodeoxycholic acid (i.e., 12α-hydroxylation step), but rather due to a defect in the feedback control regulating bile acid synthesis.
Antiviral treatment of chronic hepatitis B virus infection: Improvement in liver disease with interferon and adenine arabinoside
Authors: Scullard George H. , Andres Ljudevit L. , Greenberg Harry B. , Smith Joseph L. , Sawhney Vinod K. , Neal Andrew E. , Mahal Anmol S. , Popper Hans , Merigan Thomas C. , Robinson William S. , Gregory Peter B.
Published: March 2007

Twelve of 32 patients lost HBeAg and DNA polymerase from their serum after completing antiviral therapy with interferon and/or adenine arabinoside. Three lost serum HBsAg as well. Loss of corresponding viral markers from hepatic tissue was also seen. There was improvement in symptoms, hepatic tests, and histologic findings in the 12 patients whose viral markers disappeared when compared to the 20 whose viral markers persisted despite treatment. These findings provide support for the use of antiviral agents in hepatitis B positive chronic liver disease.
Presence and meaning of anti-HBc IgM as determined by ELISA in patients with acute type B hepatitis and healthy HBsAg carriers
Authors: Kryger Peter , Mathiesen Lars R. , Aldershvile Jan , Nielsen Jens O.
Published: March 2007

To evaluate the clinical implication of IgM antibody against hepatitis B core antigen (anti-HBc IgM), a consecutive series of 87 patients with acute type B hepatitis and 16 healthy carriers of hepatitis B surface antigen (HBsAg) were studied by a newly developed reverse ELISA technique.

Anti-HBc IgM was present for at least 2 months in 81 of the 82 patients with HBsAg at the time of admission. Seroconversion from HBsAg to anti-HBs was observed in 38 patients during the time of observation, and in all patients, anti-HBc IgM was present until clearance of HBsAg. Thirty-three of the 38 patients remained anti-HBc IgM positive, at least until the appearance of anti-HBs. Quantitation of anti-HBc IgM by ratio unit (RU) values revealed that 3 of 8 patients with RU values ≧5 for more than 6 months subsequently developed chronic liver disease, as compared to 1 of 72 patients with anti-HBc IgM above this level for less than 6 months.

Anti-HBc IgM was demonstrated in 3 of 5 patients with total anti-HBc titer above 1:100 despite the presence of anti-HBs. In these patients, anti-HBc IgM steadily decreased after the onset of illness indicating a recent acute hepatitis B infection.

Anti-HBc IgM was present in 12 of 16 healthy HBsAg carriers (75%). However, these 12 carriers had RU values between 2.5 to 5.5, compared with RU values above 5 (mean RU value 11.3) at the onset of illness in 80 of 82 HBsAg-positive patients with acute hepatitis.

Anti-HBc IgM seems to be a specific serological marker for recent or ongoing hepatitis B infection which may be useful in differentiation between hepatitis B infection with or without HBsAg and acute non-A, non-B hepatitis.
δ antigen in hepatitis B: Immunohistology of frozen and paraffin-embedded liver biopsies and relation to HBV infection
Authors: St. Öcklin Elisabeth , Gudat Fred , Krey Gunthild , Dürmüller Ursula , Gasser Markus , Schmid Martin , Stalder Georg , Bianchi Leonardo
Published: March 2007

The finding that the recently described hepatitis B (HB)-associated delta antigen (δ Ag) is preserved in pronase-treated, formalin-fixed paraffin sections allowed a combined prospective and retrospective immunohistological study of its occurrence in 571 liver biopsies.

Among 116 frozen biopsies (69 HBAg seropositive, 47 HBAg seronegative) and 455 paraffin-embedded biopsies (296 HBAg seropositive, 159 HBAg-negative), δ Ag was found in 10 HBAg seropositive patients. With the exception of 1 patient with chronic persistent HB, all had chronic-active HB and none had acute HB; 5 patients were i.v. drug abusers. In follow-up biopsies, the δ Agpersisted with HBsAg for as long as 6 years. The expression of δ Ag showed similarities to the HBcAg system including nuclear localization, mixed nuclear cytoplasmic expression, and coexistence with anti-δ in blood.

The findings are compatible with the hypothesis that δ Ag represents a transmissible, defective viral agent which requires HBV as a helper and may modulate, but not terminate, ongoing HBV infection.
Hepatic lysosomal copper protein in dogs with an inherited copper toxicosis
Authors: Johnson Gerald F. , Morell Anatol G. , Stockert Richard J. , Sternlieb Irmin
Published: March 2007

Hepatic copper overload inherited as an autosomal recessive trait in Bedlington Terriers is characterized by the presence of hepatocellular lysosomal granules of unusually high specific gravity and electron density which contain at least two thirds of the total hepatic copper.

Fractionation of homogenates of liver from such affected Bedlington Terriers yielded a low-speed pellet which contained the lysosomal granules. This fraction was used for isolation of a copper-binding protein by alkaline-reduction, solubilization, fractional acetone precipitation, and gel filtration. The purified protein yielded a single band on polyacrylamide gel electrophoresis and resembled other metallothioneins in containing 15 cysteine residues and 7 to 8 atoms of copper (but no zinc) per 54 amino acid residues. No methionine, histidine, or any aromatic amino acid was present. The accumulation of this lysosomal copper protein appears to be related to the primary genetic defect which underlies the hepatic copper toxicosis of the Bedlington Terrier.
Increase in ascites white blood cell and protein concentrations during diuresis in patients with chronic liver disease
Authors: Hoefs John C.
Published: March 2007

Serum and ascites protein concentration and ascites cell concentration alterations were determined serially during diuresis in 27 patients with uncomplicated liver disease. The total protein concentration in ascites increased from 1.38 ± 0.96 gm% to 2.86 ± 1.28 gm% (p < 0.001); the serum protein concentration from 6.26 ± 0.81 gm% to 7.24 ± 0.93 gm% (p < 0.001), and the ascites to serum ratio of the total protein concentration from 0.21 ± 0.13 to 0.38 ± 0.14 (p < 0.001). The white blood cell (WBC) concentration in ascites increased from 289 ± 179 cells per mm3 to 1,108 ± 924 cells per mm3 (p < 0.001). Despite the increase in WBC concentration, the polymorphonuclear cell concentration remained constant (42 ± 52 cells per mm3 to 68 ± 96 cells per mm3). Protein concentration of the ascitic fluid greater than 3.0 gm% was demonstrated in 12 patients before completion of diuresis and ascitic fluid WBC concentration was greater than 750 cells per mm3 in 17 patients. Ten of 27 patients eventually developed ascites which had a combination of more than 3.0 gm% total protein concentration and greater than 750 cells per mm3. Ascitic fluid protein and WBC concentrations are not „fixed” at a low level in chronic liver disease since each rose during diuresis. Thus, the interpretation of these parameters must be made with caution in patients following significant diuresis.
Phenylbutazone liver injury: A clinical-pathologic survey of 23 cases and review of the literature
Authors: Benjamin Stanley B. , Ishak Kamal G. , Zimmerman Hyman J. , Grushka Amos
Published: March 2007

Phenylbutazone has been reported to produce several forms of hepatic injury. A clinical and histologic review of 23 well-substantiated cases in conjunction with review of 43 case reports in the literature was undertaken. Utilizing the histologic features and available clinical data, the injury was classified as moderate-marked hepatocellular injury, minor hepatocellular injury, and other injury. No sexual differences were noted. Most patients had used the drug for less than 6 weeks. Features of hypersensitivity were common. Granulomas on liver biopsy were seen mainly in association with clinical evidence of hypersensitivity and with minor hepatocellular liver injury. The majority of deaths occurred in cases with significant hepatocellular injury or systemic vasculitis. Analysis of available data suggests that, although hypersensitivity appears to contribute to phenylbutazone-associated hepatic injury, the drug also appears to have intrinsic hepatotoxic potential. Speculation is offered regarding the relative role of these two mechanisms in the several forms of hepatic injury induced by phenylbutazone.
Plasma clearance of intravenous chenodeoxycholic acid in rabbits with varying severity of hepatocellular necrosis
Authors: Mackinnon Malcolm , Hall Pauline
Published: March 2007

The plasma clearance of an i.v. bolus of chenodeoxycholic acid (10 μm per kg) was determined in rabbits with graded degrees of hepatocellular necrosis produced by i.p. injection of carbon tetrachloride. Plasma chenodeoxycholic acid levels were determined by radioimmunoassay, and the volume fraction of necrosis was quantitated by a computerized (Quantimet 720) system. Impaired plasma clearance was observed only when necrosis was extensive, and the volume fraction of necrosis >34%. In contrast, measurement of fasting plasma chenodeoxycholic acid concentration was more sensitive, and elevated levels were associated with a mean volume fraction of necrosis of 12.5%. This study reinforces the conclusion based on clinical studies that measurement of fasting bile acid concentration is a more sensitive discriminant of hepatic dysfunction than is measurement of the plasma clearance of an i.v. bolus of bile acid.
Hepatic and extrahepatic glucuronidation of lorazepam in the dog
Authors: Gerkens John F. , Desmond Paul V. , Schenker Steven , Branch Robert A.
Published: March 2007

The pharmacokinetic disposition of lorazepam was investigated in sham-operated anesthetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham-operated dogs, lorazepam distribution was extensive (100 ± 15.2 liters) and clearance approximated expected liver blood flow (971 ± 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr. Urinary recovery of the conjugate in 5 hr was 45% of administered dose. Hepatic devascularization resulted in 39% reduction in distribution volume, and 89% reduction in clearance; however, there was still 105 ± 88 ml per min of extrahepatic lorazepam clearance. Five-hour urinary recovery of conjugate decreased by 80%. Total splanchnic devascularization resulted in 37% further reduction in extrahepatic clearance, almost complete inhibition of urinary recovery of conjugate, and further reduction in the volume of distribution. It is concluded that the liver is the major site for lorazepam metabolism in dogs; however, appreciable extrahepatic metabolism occurs, partly in nonhepatic components of the splanchnic organs which act as a reservoir during drug distribution.
Vitamin A and zinc therapy in primary biliary cirrhosis
Authors: Herlong Franklin H. , Russell Robert M. , Maddrey Willis C.
Published: March 2007

Eleven patients with primary biliary cirrhosis were surveyed for evidence of vitamin A and zinc deficiencies. Vitamin A deficiency manifested as a low serum vitamin A concentration and abnormal dark adaptation was present in 9 of the 11 patients. A low serum zinc level was present in four patients who were also vitamin A deficient. All seven patients who received p.o. vitamin A therapy with 25,000 to 50,000 units per day for 4 to 12 weeks achieved normal vitamin A levels. Normalization of serum vitamin A was associated with significant improvement in dark adaptation (p < 0.01). In three patients, normalization of serum vitamin A level did not correct the abnormal dark adaptation. These three patients also had decreased serum zinc levels and dark adaptation abnormalities were corrected following p.o. zinc supplementation. These studies suggest high dose and long term p.o. vitamin A and zinc therapy may be required to correct abnormalities in dark adaptation in patients with primary biliary cirrhosis.
Mallory body-like abnormalities in carcinomas induced by cultured transformed rat liver cells
Authors: Borenfreund Ellen , DeHarven Etienne , Garra Lorraine
Published: March 2007

Hepatoma cells isolated from rats after administration of a carcinogen, diethylnitrosamine, and propagated in culture, contained a genetically stable cytoskeletal abnormality resembling Mallory bodies. These juxtanuclear aggregates of intermediate-sized filaments were maintained in carcinomas produced in nude mice after inoculation of uncloned mass cultures and a cloned subculture. Paraffin and frozen sections of these tumors revealed acentric nuclei and a glassy hyalin-type cytoplasmic lesion which stained pink with hematoxylin-eosin and blue with Mallory’s aniline blue stain. The cells in culture and in the tumor sections were strongly positive for γ-glutamyl transpeptidase. Cryostat sections examined by indirect immunofluorescence microscopy with antisera to purified bovine hoof prekeratin, desmosome-associated tonofilaments from bovine muzzle, and murine vimentin, as well as transmission electron microscopy revealed the presence of juxtanuclear aggregates of intermediate-sized filaments. All characteristics previously reported for the tissue culture cell line were stably maintained in the tumor tissue. These results suggest that the Mallory body-containing cells frequently observed in man in alcoholic hepatitis and other degenerative liver diseases could, under appropriate environmental “promoting” conditions, be precursor cells in focal hepatocellular carcinoma formation.
Physiologic cholestasis II: Serum bile acid levels reflect the development of the enterohepatic circulation in rats
Authors: Belknap William M. , Balistreri William F. , Suchy Frederick J. , Miller Philip C.
Published: March 2007

We have shown that serum bile acid concentrations are elevated in human infants reflecting physiologic immaturity of the enterohepatic circulation. To define further the ontogeny of bile acid metabolism in mammals, we examined maturational changes in the serum concentration of total cholate conjugates by radioimmunoassay in fetal, neonatal, suckling, and mature Sprague-Dawley rats. Fetal (21st day) levels were low (1.4 ± 0.23 μM; X̄ ± S.E.), possibly due to minimal enterohepatic cycling in utero. The concentrations in samples obtained minutes after birth, prior to suckling were significantly elevated (12.6 ± 2.37; p < 0.001 vs. fetal); these high values persisted after feeding was initiated (6 hr = 13.5 ± 0.99), but fell at 12 hr (5.2 ± 0.81) and remained unchanged for the duration of the first day. Serum values fluctuated briefly, being 9.6 ± 0.73 on Day 4, and then rose progressively through the suckling period (Day 10 = 7.2 ± 0.57; Day 14 = 10.4 ± 1.70; Day 21 = 16.8 ± 1.93); there was a dramatic peak after weaning (Day 28 = 21.8 ± 1.53). The serum concentration of cholate conjugates then fell (5.6 ± 0.68 on Day 42) to achieve adult levels by 56 days (4.0 ± 0.55), a value substantially different from that of all developing animals (p < 0.025). These data corroborate studies which suggest that a period of physiologic cholestasis occurs in the developing rat. Serum cholate conjugate concentrations likely reflect interrelated morphologic alterations (bile canalicular structure and portal blood flow) and physiologic changes (bile acid synthesis, pool size, and transport) occurring in the enterohepatic circulation during early life.
α-1-antitrypsin phenotypes in hepatocellular carcinoma
Authors: Govindarajan Sugantha , Ashcavai Mary , Peters Robert L.
Published: March 2007

α-1-Antitrypsin deficiency due to homozygous Pi ZZ state is reported to be associated with cirrhosis and hepatocellular carcinoma (HCC); however, the role of heterozygous Pi Z state is not definitively known. In order to investigate the possible association, we studied the phenotypic distribution of α-1-antitrypsin variants (Pi) in 124 cases of HCC. Two thousand ten normal American Red Cross blood donors were studied as controls. Twelve patients with HCC had aberrant pheno-types, an incidence of 9.67% as compared to 8.36% among normal controls. Nine of 12 patients with HCC with aberrant Pi type had cirrhosis; 5 of the 9 had cirrhosis due to hepatitis B virus; 2 of the 9 had alcoholic liver disease with cirrhosis, and 2 had cryptogenic cirrhosis. The three patients with HCC arising in noncirrhotic livers who also had aberrant Pi phenotypes, had a relatively rare variety of HCC called fibrolamellar type. Z gene was found in five patients: all five were MZ. Incidence of MZ phenotype in HCC was similar to that of the normal control population (4.0% in HCC and 2.9% in the controls). However, 3 of 5 MZ were associated with fibrolamellar HCC. Another aberrant phenotype found among the patients with HCC was MF (fast moving) which occurred with an incidence of 2.41% as compared to none in the control group. In conclusion, we found no significant increase in the incidence of Z gene among 124 patients with HCC as compared to the normal population.