bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction between isolated and purified liver cells and small unilamellar liposomes
Authors: Dini L. , Falasca L. , Ruzzittu M. T. , Mossa G. , Finazzi‐Agrò A. , Di Giulio A.
Published: August 2010

ABSTRACT— Aims/Background: The mechanism of interaction and the role played by the vesicle lipid composition for the selective association between liposomes and liver cells were studied, at the ultrastructural level, by investigating both in situ and in vitro the interaction between hepatocytes, Kupffer and endothelial liver cells with egg‐phosphatidylcholine (eggPC) or eggPC/stearylamine (9:1; mol:mol) reverse‐phase evaporation (REV) liposomes. Methods: Liver cells from rats, isolated by enzymatic perfusion and purified by differential centrifugation, were incubated, in a rotating bath at 37°C, with liposomes (2.5 mM final liposomal lipid concentration). Cell aliquots were withdrawn and processed for electron microscope observation at fixed time intervals. Parallel experiments were carried out by in situ liver perfusion with liposome suspensions. Results and Conclusions: Our first conclusions are: 1) lipidic composition affects the rate of liposomes uptake and internalization by hepatocytes; 2) liposome uptake by hepatocytes or Kupffer cells is likely an endocytic process; 3) endothelial cells internalize lipid vesicles as well; 4) liposome uptake was due to a phagocytic activity for all isolated liver cells, while in the in situ observation endothelial cells seem to use another mechanism (fusion); and 5) the rate of internalization is related to the viability of the treated cells. Experimental data seem to indicate that differential behaviour in the internalization of lipid vesicles exists among parenchymal, Kupffer and endothelial liver cells. These differences suggest that clearance of liposomes by these cells involves two mechanisms (i.e., endocytosis or fusion) with different rates of uptake and internalization that facilitate the design of carriers that can deliver drugs preferentially to a specific liver cell type.
Short‐term effects of transjugular intrahepatic portosystemic shunt (TIPS) on functional liver plasma flow in patients with advanced cirrhosis
Authors: Bar Fabrizio , Battista Stefania , Garello Enrico , Grosso Maurizio , Spalluto Francesco , Zanon Eugenio , Torchio Mauro , Molino Gianpaolo
Published: August 2010

ABSTRACT— Aims/Background: TIPS, an effective procedure applied for the treatment of complications of portal hypertension, is potentially followed by worsening of the hyperdynamic circulation of cirrhosis and the impairment of liver function. The aim of the present study was to evaluate short‐term changes of functional liver plasma flow after application of TIPS, using the hepatic (extrarenal) clearance of D‐sorbitol (S‐HCl). Methods: Twenty‐five cirrhotic patients submitted to TIPS for prevention of variceal rebleeding entered the study. At steady‐state, during constant infusion of a solution of D‐sorbitol (25 mg/min), appropriate blood and urine samples were collected in order to calculate S‐HCl before and 120 min after TIPS opening. In addition, the hepatic extraction ratio of D‐sorbitol was directly measured at the level of the right (Er), where TIPS was applied, and of the left (El) hepatic veins; meanwhile the portocaval gradient (PCG) was registered, before and after stent dilation. A comparison of values obtained before and after TIPS application was performed by Student's t‐test for paired data. Results: After application of TIPS, a substantial reduction was observed in PCG (12.1 ± 4.2 vs 24.8 ± 4.3 mmHg; p<0.001) and Er values (20.6 ± 14.8 vs 57.5 ± 22.3%; p<0.001) but not El values (47.4 ± 22.0 vs 53.4 ± 21.4%; p=0.178). S‐HCl measured 120 min after TIPS opening was not statistically different from pre‐TIPS values (389.2 ± 212.1 vs 394.6 ± 152.7 ml/min; p=0.892), although S‐HCl variations in Child‐Pugh class B patients were positively correlated with portal pressure variations (r=0.63, p=0.016). Conclusion: Our results demonstrate that in patients with advanced cirrhosis, TIPS procedure, while effective in reducing portal hypertension, does not lead to alterations in the functional liver plasma flow within the first 2 h.
Diaphragmatic and subcutaneous seeding of hepatocellular carcinoma following fine‐needle aspiration biopsy
Authors: Navarro Francis , Taourel Patrice , Michel Jacques , Perney Pascal , Fabre Jean‐Michel , Blanc François , Domergue Jacques
Published: August 2010

ABSTRACT— Aims/Background: We report the discovery of associated metastatic subcutaneous and metastatic diaphragmatic nodules on the needle track after fine‐needle biopsy aspiration under echography, which has not yet been reported in the literature. Methods: A 35‐year‐old man with non‐replicating hepatitis B virus presented with a tumor that suggested hepatocarcinoma with cirrhosis. A diagnostic needle biopsy was carried out before surgery. Twelve months later, he presented with a series of four continuous metastatic diaphragmatic nodules on the inner wall lining the needle track. Surgery was performed, followed by external radiation (40 Gy). Conclusions: The risk of seeding following fine‐needle biopsy aspiration of hepatocellular carcinoma can no longer be considered negligable. The real risk is probably underestimated. Even for biopsy of lesions localized to the inferior part of the liver, diaphragmatic seeding is possible. This seeding necessitates surgical resection, increasing the therapeutic morbidity of hepatocellular carcinomas. We believe that in cases where investigation of a small hepatic tumor suggests a hepatocellular carcinoma that could be resected, or for candidate patients for liver transplantation, one should not puncture the tumor. If this diagnostic biopsy is essential, then the needle track could be resected upon surgery, after cutaneous external tattooing.
Hepatitis G virus infection in Spanish patients with hepatocellular carcinoma
Authors: Agulló José L. Rodríguez , Suárez Avelina , Ladero José M. , López‐Alonso Gustavo , Picazo Juan J. , Díaz‐Rubio Manuel
Published: August 2010

ABSTRACT— Aims/Background: To establish the rate of infection with a newly discovered Flaviviridae family member – hepatitis G virus (HGV) – in Spanish patients with hepatocellular carcinoma (HCC), chronic alcoholic liver disease (CALD) with cirrhosis, or hepatitis C virus (HCV)‐induced chronic hepatitis (CH). Methods: The presence of HGV‐RNA was assessed in sera of 117 patients divided in three groups: group 1: 40 patients with HCC (35 men, mean age 62.7 years, SD 10.9 years); group 2: 41 patients with chronic alcoholic liver disease (CALD) (36 men, mean age 52.5 years, SD 9.8 years); group 3: 36 patients with HCV‐induced CH (27 men, mean age 35.8 years, SD 8.5 years). Serum samples were tested for HGV‐RNA by specific reverse transcriptase‐polymerase chain reaction (RT‐PCR). Serological markers of hepatitis B virus (HBV) and HCV were investigated in all patients and were negative in CALD patients, as a prerequisite for their inclusion in the study. All patients in group 1 were also tested for HBV‐DNA. Results: Rates of HGV‐RNA positivity were, respectively, 47%, 10% and 28% in groups 1, 2 and 3. Differences were significant between groups 1 and 2 (p=0.00017) and groups 2 and 3 (p=0.042), but not between groups 1 and 3 (p=0.079). Conclusions: HGV infection is common in HCC patients, but usually in association with HCV, indicating that both agents share common routes of infection. HGV was the only hepatitis virus detected in 12% of HCC patients, but its possible role in the pathogenesis of HCC remains unclear.
Replication error frequencies in primary hepatocellular carcinoma: a comparison of solitary primary versus multiple primary cancers
Authors: Takagi Keiko , Esumi Mariko , Takano Seigo , Iwai Shigetomi
Published: August 2010

ABSTRACT— Aims/Background: Replication errors (RERs) at microsatellite loci are associated with the development of not only hereditary non‐polyposis colon cancer but also sporadic cancers. To examine the association between RERs and human hepatocarcinogenesis, we looked for microsatellite instability in solitary and multiple primary hepatocellular carcinomas (HCCs). Methods: DNAs were extracted from 34 solitary primary HCCs and 14 HCCs with multiple primary cancers. Twelve micro‐satellite alleles were amplified by PCR from the DNAs, and RERs were assessed by their mobility shift. Results: RERs were found in only two cases (6%) of solitary HCC and four cases (29%) of HCC with multiple primary cancers. Two of the four HCCs with multiple primary cancers showed RERs at two and three microsatellite loci, respectively. Of 12 microsatellite loci examined, TP53 and D16S476 sensitively detected RERs in HCCs with multiple primary cancers, at a frequency of 23% and 33%, respectively. Conclusions: RERs are rarely associated with carcinogenesis in human primary HCC, and RER‐related genetic alterations may be associated with a part of HCC with multiple primary cancers. If future studies confirm this association, then the two probes TP53 and D16S476 may be useful for the prediction of development of multiple primary cancers with HCC.
Primary liver tumour of intermediate (hepatocyte—bile duct cell) phenotype: a progenitor cell tumour?
Authors: Robrechts C. , De Vos R. , Van den Heuvel M. , Van Cutsem E. , Van Damme B. , Desmet V. , Roskams T.
Published: August 2010

ABSTRACT— A 57‐year‐old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte‐type cytokeratins (cytokeratin 8 and 18) and bile duct‐type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone‐related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.
Secondary structure of the hepatitis C virus 5‘ untranslated region and efficacy of interferon therapy for chronic hepatitis C
Authors: Suzuki Katsunori , Shinzawa Haruhide , Kuboki Makoto , Ishibashi Masamichi , Yoshii Eiichi , Saito Takafumi , Takahashi Tsuneo
Published: August 2010

Abstract: The hepatitis C virus 5′ untranslated region (HCV 5'UTR) contains secondary structures typical of internal ribosome entry site elements leading to translation. Variations of this secondary structure in relation to the efficacy of interferon (IFN) therapy were investigated. Methods: Natural IFN‐alpha was administered to 22 patients with chronic hepatitis C due to HCV subtype 1b and their serum HCV‐RNA levels were examined using the reverse‐transcription polymerase chain reaction (RT‐PCR). The HCV 5'UTR sequence was determined by direct sequencing, and variations of the putative secondary structure were detected by analyzing single‐strand confirmation polymorphisms (SSCP) in the patient's sera. Results: Five of the 22 patients (22%) were complete responders to IFN and eradicated HCV‐RNA from their sera and 17/22 (78%) were nonresponders in whom HCV‐RNA persisted. The SSCP electrophoretic results predicted the efficacy of IFN therapy: the complete responders showed greater pattern diversity than the nonresponders. The serum HCV‐RNA level correlated with the SSCP electrophoretic pattern: patients with the IFN‐resistant SSCP electrophoretic pattern had higher levels than the others (10.1 ± 2.4 vs 1.2 ± 0.4 Meq/ml; p<0.001). Sequencing analysis suggested three one‐point mutations influence alteration of the secondary structure. Conclusions: Analysis of the secondary structure of the HCV 5'UTR contributes to predicting viremia severity and the efficacy of IFN therapy in patients with chronic hepatitis C.
Nm23‐H1 expression in intrahepatic or extrahepatic metastases of hepatocellular carcinoma
Authors: Shimada Mitsuo , Taguchi Ken‐ichi , Hasegawa Hirofumi , Gion Tomonobu , Shirabe Ken , Tsuneyoshi Masazumi , Sugimachi Keizo
Published: August 2010

Abstract: Aims/Background: Decreased expression of nm23, a putative metastasis suppressor gene, has been reported to be related to either intrahepatic metastasis or a poor prognosis in hepatocellular carcinoma (HCC). The aim of this study was to elucidate the true role of nm23‐H1 expression in both intrahepatic and distant metastases of HCC. Methods: Thirteen patients with single‐nodule HCC, seven patients with HCC having satellite nodules and seven patients with HCCs having extrahepatic metastases were included in this study. The expression of nm23‐H1 protein was immunohistochemically examined in both primary and metastatic nodules. Results: Ten of 13 single‐nodule HCCs were found to overexpress nm23‐H1 protein. All main tumors, having satellite nodules, were found to overexpress nm23‐H1 protein, except for two HCCs, which only partially expressed nm23‐H1 protein. Regarding the nm23‐H1 expression in intrahepatic metastases, most nodules overexpressed the protein. The expression of nm23‐H1 was found to be low in only one intrahepatic metastasis specimen, while its primary tumor was also found to show a low expression of nm23‐H1 protein. Microscopic portal vein invasion was found in three of the five patients studied, and all cancer cells in portal invasion overexpressed nm23‐H1 protein. Nm23‐H1 protein was expressed in all distant metastatic tumors and the staining intensity of most metastatic nodules was similar to that of the primary tumors. Conclusions: Our study demonstrated that nm23‐H1 expression did not always decrease but instead tended to increase at both intrahepatic and extrahepatic metastatic sites. Based on these findings, nm23‐H1 expression is not considered to be a reliable indicator of either intrahepatic or distant metastasis in HCC.
Estrogen‐induced hepatic toxicity and hepatic cancer: differences between two closely related hamster species
Authors: Coe J. E. , Ishak K. G. , Ross M. J.
Published: August 2010

Abstract: Aims/Background: Estrogen is known to affect hepatobiliary function; however, it is unusual for high serum levels of estrogen to actually result in clinically detectable hyperbilirubinemia. Women affected by cholestatic jaundice during pregnancy share this genetic susceptibility with two Cricetulus hamsters, the Armenian hamster (Cricetulus migratorius) and the Chinese hamster (Cricetulus griseus). Nevertheless, the pathophysiologic process responsible for this estrogen induced icterus may be different in women and hamsters. The present study compares various facets of estrogen‐induced icterus in these two closely related hamsters. Methods: Hamsters were injected with various estrogens and the acute and chronic effects on liver were monitored by measuring changes in serum constituents and by observing changes in hepatic structure as seen grossly and by light and electron microscopy. Results: In previous studies, hepatic tumors developed in most Armenian hamsters after chronic estrogen treatment, but in the present study, the livers of Chinese hamsters were remarkably free of neoplastic change under similar conditions. Also, when compared with the responses in the Armenian hamsters, signs of hepatic destruction and regeneration were less prevalent in estrogentreated Chinese hamsters, and they were less susceptible to the effects of estrogen (because larger doses of estrogen were required to produce icterus and the bilirubin levels were lower and of shorter duration). In contrast to the findings in Armenian hamsters, bile canaliculi were severely affected in livers of estrogen‐treated Chinese hamsters, and hepatic microvesicular steatosis, indicative of an unusual lipodystrophy caused by estrogen, was prominent. An additional lesion peculiar to the Chinese hamster was striking sinusoidal dilatation, which may be analogous to the oral contraceptive‐induced sinusoidal dilatation in humans. Conclusions: Although these two hamster species are genetically similar, the genes activated by the estrogen receptor show remarkable heterogeneity when their respective livers are examined. Comparisons within these species may provide information about the specific gene activation responsible for particular pathologic events.
Influence of GB virus‐C/hepatitis G virus infection on the long‐term course of chronic hepatitis B
Authors: Fattovich Giovanna , Ribero Maria Lisa , Favarato Susanna , Azzario Franco , Donato Francesco , Giustina Giuliano , Fasola Michele , Pantalena Maurizio , Portera Giuseppe , Tagger Alessandro
Published: August 2010

Abstract: Aims/Background: The clinical significance of GB virus‐C/hepatitis G virus (GBV‐C/HGV) infection in chronic hepatitis B is not well known and its role in the outcome of liver disease was investigated. Methods: HGV‐RNA and antibody to HGV (anti‐E2) were studied in 125 patients with chronic hepatitis B (41 with multiple hepatitis virus exposure), 82 asymptomatic HBsAg carriers and 103 healthy adults. Results: In chronic hepatitis B, HGV‐RNA was more frequent in patients with HDV infection and/or anti‐HCV positivity than in those without (29% vs 6%, p<0.0001), mainly in drug addicts (38%). At diagnosis the overall prevalence of any marker (HGV‐RNA plus anti‐E2) was similar in chronic hepatitis due to HBV alone (17%), in HBsAg carriers (16%) and in healthy adults (17%) and increased to 58% in those exposed to HDV and/or HCV. During 1–11 years of follow‐up, HGV infection persisted in 70% of patients with chronic hepatitis B. About 40% of HGV persistently coinfected patients underwent sustained biochemical remission, whereas continuing disease activity was observed in 80% of patients who cleared HGV‐RNA. Conclusions: In chronic HBV infection the rate of exposure to HGV is similar to that in healthy adults, except for high risk patients. Long lasting HGV coinfection or anti‐E2 seroconversion did not modify the course of chronic hepatitis B.
Plasma‐kallikrein clearance during liver regeneration after partial hepatectomy in the rat
Authors: Braulio Valeria Bender , Kouyoumdjian Maria , Zucoloto Sergio , Figueiredo Florencio , Borges Durval Rosa
Published: August 2010

Abstract: Aims/Background: The liver clears circulating plasma‐kallikrein through a receptor‐mediated endocytosis process: an initial fast phase is followed by a slow exponential phase. Methods: To determine whether the clearance rate of plasma‐kallikrein is affected during liver regeneration, we perfused isolated rat livers with rat plasma‐kallikrein (rPK) at 0, 1, 2, 3 and 7 days after partial hepatectomy or sham operation. Results: Liver regeneration was followed by the expression of the proliferating‐cell nuclear antigen (PCNA) labeling index. The serum concentration of α2‐macroglobulin, an acute phase protein in rats, was measured. At day 1, the fast phase of rPK clearance rate increased in hepatectomized rats when compared with day 0 (4.9±0.4 and 3.7±0.4 mU/g liver · min, p<0.05). However, at day 2, the rPK fast phase clearance rate dropped significantly (2.6±0.2, p<0.05), when compared with day 1. No difference was found among the sham groups at different days of hepatectomy. These changes seem to be independent of the acute phase reaction. The regenerative liver weight increased continuously during the observation period. PCNA expression increased significantly after hepatectomy, with maximal PCNA‐labeling indices at days 1 and 2, declining thereafter. Conclusion: The rPK fast phase clearance rate changes during liver regeneration, with a zenith occurring when PCNA labeling index is maximal (day 1) and a nadir occurring at the mitotic phase (day 2).
Quantitative and functional analysis of core‐specific T‐helper cell and CTL activities in acute and chronic hepatitis B
Authors: Löhr Hanns F. , Krug Sandra , Herr Wolfgang , Weyer Sandra , Schlaak Jörg , Wölfel Thomas , Gerken Guido , zum Büschenfelde Karl‐Hermann Meyer
Published: August 2010

Abstract: Aims/Background: CD4+ T‐helper cell (Th) responses to hepatitis B virus (HBV) core antigen (HBc) are increased during exacerbations in acute and chronic hepatitis B (AHB, CHB) and might influence the induction of CD8+ cytotoxic T lymphocytes (CTL) that are important for viral clearance. Methods: HBc‐specific proliferative responses and cytokine release of blood mononuclear cells (PBMC) were studied in patients with AHB or CHB, as well as responders and non‐responders to interferon‐α treatment (IFN‐R, IFN‐NR), by [3H]‐thymidine‐uptake, enzyme‐linked immunosorbent assay (ELISA) and Elispot assay and were compared to peptide HBc18–27‐specific CTL precursor frequencies among CD8+ T cells derived from HLA‐A2+ patients. Results: HBc‐specific proliferative PBMC responses and Th frequencies were significantly increased in AHB patients compared with untreated CHB patients. PBMC derived from IFN‐R showed stronger cellular responses than IFN‐NR. Stimulated PBMC from all patient groups secreted significantly more IFN‐γ than IL‐4 indicating Th1/Th0 cell responses. Furthermore, in AHB and IFN‐R patients, high peptide HBc18–27‐specific CTL precursor frequencies closely correlated with strong HBc‐specific Th responses, whereas in untreated CHB and IFN‐NR patients lower CTL frequencies were observed without correlation to Th activities. Conclusions: HBV core‐specific Th‐cell responses appeared to support efficient CTL induction in patients with viral clearance, whereas in chronic HBV carriers quantitatively insufficient Th and CTL responses were observed. This observation could be important for future therapeutic strategies.
Power Doppler sonography for hepatocellular carcinoma: factors affecting the power Doppler signals of the tumors
Authors: Imamura Masatoshi , Shiratori Yasushi , Shiina Shuichiro , Sato Sin'pei , Obi Shun'taro , Okudaira Takehito , Teratani Takuma , Kato Naoya , Akahane Masaaki , Ohtomo Kuni , Minami Manabu , Omata Masao
Published: August 2010

Abstract: Aims/Background: A recent advancement in Doppler ultrasonography (US) is power Doppler for detecting low‐velocity blood flow at the microvascular level with angle independence. The present study was performed to characterize the factors contributing to the power Doppler signals of hepatocellular carcinoma (HCC). Method: Correlation of Doppler signals of HCC in 114 patients with 178 HCC nodules was analyzed in relation to the findings of CT and angiography, tumor characteristics (size, echo pattern, and histological differentiation of tumor), viral markers and severity of liver disease. Results: The sensitivity of power Doppler US was superior to that of CT and angiography (each p<0.05; McNemar's test). The detection rate of power Doppler signal was significantly higher in tumors with diameter ≥2 cm (vs <2 cm in diameter), and with low/mixed echo pattern (vs high echo appearance), and with moderately/poorly differentiated HCC (vs well‐differentiated HCC). Univariate analysis revealed that echo pattern, tumor size and histological differentiation of HCC in addition to CT and angiographic findings were significant. Multivariate analysis showed that tumor size and differentiation were significant. Conclusion: These results indicate that tumor characteristics play an important role in power Doppler signals and that these could be assessed by the presence or absence of power Doppler signals.
EPITHELIOID‐CELL GRANULOMAS IN HODGKIN'S DISEASE
Authors: Brincker Hans
Published: August 2010

The relevant literature on the occurrence of epithelioid‐cell granulomas without a demonstrable infectious genesis in malignant systemic diseases—in particular Hodgkin's disease—is briefly reviewed. Six cases of Hodgkin's disease with epithelioid‐cell granulomas are reported and the aetiology discussed. It is concluded that a consistent explanation of the phenomenon is not afforded by the material available up till now.
RENIN LOCATION IN CONTRACTED HUMAN KIDNEYS*
Authors: Faarup P. , Nielsen I. , Jensen G. , Clausen E. , Kemp E.
Published: August 2010

In haemodialysed patients with non‐functioning contracted kidneys – in some of which nearly all glomeruli were found to be hyalinized and the juxtaglomerular apparatus often unidentifiable – a pronounced hyperplasia of epithelioid‐like cells could be demonstrated in the muscular layer of the small cortical arteries. In addition, juxtaglomerular‐like granules could be observed in some of these epithelioid cells. The ultrastructure was found to be similar to that of the epithelioid cells of the juxtaglomerular apparatus. In freeze‐dried tissue sections from kidneys supravitally stained with Neutral Red, vascular fractions comprising the cortical small arteries, including epithelioid cells, were isolated by microdissection. In these fractions a high renin content was found, in contrast to the low renin activity of the surrounding tubular tissue. The total renin content of the kidney tissue was increased and in most patients plasma renin values were elevated before nephrectomy. It is concluded that, in contracted kidneys, significant amounts of renin are formed outside the juxtaglomerular apparatus in epithelioid cells situated in the media of small arteries, morphologically identical to the epithelioid cells in the afferent arteriole of the normal kidney.
REACTIONS OF THE GUINEA PIG'S SKIN AND ADIPOSE TISSUE TO EXPERIMENTAL FROSTBITE
Authors: Laiho K. , Hirvonen J.
Published: August 2010

Vital and postmortal frostbites of various ages in the skin and adipose tissue of guinea pigs were examined by histochemical methods. The microscopic lesions were slight, both in the skin and in the adipose tissue. Nuclear changes were seen in vital as well as postmortal frostbites. Four hours after the freezing, NAD‐diaphorase and lactate dehydrogenase showed decreasing reactions in the epithelial cells and fibroblasts, and later in fat cells of the frozen area, and the reaction had almost entirely disappeared after 24 hours. In two to four hours after freezing, diffuse extracellular staining of naphthyl amidase and esterase appeared in the frozen tissue. Small fat cell necroses were noticed after a reaction time of four hours. Exudation was observed in the sections within one to two hours after vital freezing. No morphological signs of damage to vascular walls were seen. In blood vessels, closely packed red cells filled the lumen, but real thromboses with fibrin and platelets were rare. The inflammatory reaction started in the skin within one hour and in the adipose tissue, within 30 minutes. Mononuclear macrophages appeared within four hours in the skin and within two hours in the adipose tissue. In frostbites of 16 hours' age epidermal blisters filled with fibrinous exudate and inflammatory cells were seen. The blisters were surrounded by a semicircular demarcation zone of polymorphonuclears and macrophages developing within 8–16 hours. In the adipose tissue new fibroblasts appeared within four hours after freezing. In the skin, epithelial proliferation was seen after 36 hours around the blisters. The fastest and most reliable vital sign was the post‐freezing inflammation.
LIPOGRANULOMAS IN HUMAN LIVER BIOPSIES WITH FATTY CHANGE
Authors: Christoffersen Per , Brændstrup Otto , Juhl Erik , Poulsen Hemming
Published: August 2010

The material comprises 67 percutaneous liver biopsies all with fatty change as the chief morphological diagnosis. Among others biopsies with cirrhosis and Mallory bodies have been excluded. Lipogranulomas have been found in 43 out of 67 biopsies. A description of lipogranulomas is given, and three types are described according to size and age. Steatosis is a conditio sine qua non for the development of lipogranulomas. Biopsies with lipogranulomas show higher histologic activity (lytic liver cell necrosis, acidophilic bodies and rnesenchymal reaction) and more parenchymal fibrosis than biopsies without. The patients with lipogranulomas have higher S. G. O. T. values. Whereas lipogranulomas type 1 and 2 can disappear without sequelae there is good reason to believe that lipogranulomas type 3 may give rise to development of connective tissue in the parenchyma.
OCCURRENCE OF AMYLOID DEPOSITS IN THE SKIN IN SECONDARY SYSTEMIC AMYLOIDOSIS
Authors: Westermark Per
Published: August 2010

Among 9 patients with secondary systemic amyloidosis, 8 had amyloid deposits in the skin. Amyloid was found in the deepest part of the dermis around the adnexa and in the subcutaneous tissue in the form of rings around fat cells. The amount of amyloid varied somewhat between different skin areas and, among the parts of the body examined, the scalp and the abdominal skin showed the heaviest infiltration. It is obvious that secondary amyloidosis can be diagnosed by means of skin biopsy in many cases.
QUANTITATIVE STUDIES OF THE RENAL CORPUSCLES II: A METHODOLOGICAL STUDY
Authors: Sorensen F. Hanberg , Ledet T.
Published: August 2010

The camera lucida drawing method with planimetric area measurements was compared with direct microscopy and systematic point count in a quantitative study of glomeruli, the study including differential counts of nuclei and determination of the total and mesangial areas. Good reproducibility was found using both methods, but the camera lucida drawing method was found to be at least three times more time‐consuming than direct microscopy for total and differential counts of nuclei and systematic point count for mesangial area determination. Measurement of total glomerular area was done planimetrically, by point counting and by determination of the area as an ellipse or a circle. The results obtained planimetrically and by point counting did not differ significantly, whereas the difference between the results of the planimeter measurements and the results obtained by applying the formula of an ellipse or a circle on glomerular sections was found to be statistically significant. If central sections were compared with random sections of glomeruli, deviation of results was found to be greater in the random sections, and it was calculated that 10 central and about 30 random sections have approximately the same value in quantitative examination of a renal tissue specimen. Thus, it appears advisable to use direct microscopy for total and differential counts of nuclei, systematic point count for mesangial area determination, planimetric measurement or point counting for total glomerular area determination and to apply this method on central sections of glomeruli.
COMPARATIVE LIGHT AND ELECTRON MICROSCOPICAL STUDIES OF DECAYING THYMIC LYMPHOID CELLS
Authors: Claesson Mogens Helweg , Jørgensen Ole , Olsson Lennart
Published: August 2010

Normal thymic lymphoid cell suspensions were studied in the electron microscope. The suspensions contained cells (6–23 per cent) in various degrees of lytic degeneration with swelling and disintegration of both nucleus and cytoplasm. Only a minority of the degenerating cells showed pyknotic changes and these cells had always a well preserved cytoplasm. The percentage of degenerating cells was compared with the percentage of cells stained in the nigrosin‐dye exclusion test. A close relationship between these two values was found, suggesting that supravital staining primarily affects cells in lytic cell degeneration. It appears that vital stains only affect already degenerating cells with a subsequent increase of a preexisting intracellular edema. This suggestion was corroborated by the finding that addition of nigrosin dye to thymic cell suspensions does not depress aerobic metabolism.
TESTIS WEIGHT AND THE HISTOLOGY OF THE PROSTATE IN ELDERLY MEN
Authors: Harbitz Thorstein B.
Published: August 2010

As part of a study of the pituitary gland, adrenal glands and the testis in men with hyperplasia and neoplasia of the prostate, combined testis weight was analysed in a consecutive autopsy series of 172 men over 40 years of age. None had clinically manifest carcinoma of the prostate or had previously been subjected to prostatic surgery. Testis weight varied widely at all ages and showed no clear association with age. Weights below 20 grams were shown in 21 patients (12.2 per cent) and were associated with wasting disease and low body weight. No relationship between the testis weight per se and prostatic histology could be demonstrated at multiple regression analysis. However, in patients who had benign nodular hyperplasia of the prostate, testis weight showed a significant decrease with increasing age. Four of the 54 patients who had carcinoma of the prostate had testis weight under 20 grams. Twenty‐four patients who had undergone prostatic surgery for benign prostatic hyperplasia showed testis weights which were similar to those in non‐operated cases.
LIVER MORPHOLOGY AND GALLSTONE FORMATION IN HAMSTERS AND MICE TREATED WITH CHENODEOXYCHOLIC ACID
Authors: Bergman F. , Van Der Linden W.
Published: August 2010

Hamsters fed a lithogenic diet showed a significantly stronger tendency to gallstone formation if the diet was supplemented with 0.5 per cent chenodeoxycholic acid. In hamsters and in mice the addition of chenodeoxycholic acid to the diet resulted in a rapid and drastic shift towards this bile acid in the animals' bile. Mice were fed normal chow with supplements of 1 per cent cholesterol, 1 per cent cholesterol plus 0.5 per cent cholic acid and 1 per cent cholesterol plus 0.5 per cent chenodeoxycholic acid respectively. After four months, slight fatty degeneration with occasional cholesterol crystals were observed in the livers of the animals of the first group. In the second group there was marked fatty degeneration with a massive accumulation of cholesterol crystals. In the third group, the liver histology was essentially normal. Gallstones were present in the second group and absent in the other two. In a regression experiment, hamsters were first fed chow supplemented with cholesterol and cholic acid. After one month they were divided into two groups which were fed chow supplemented with 0.5 per cent chenodeoxycholic acid and unsupplemented chow respectively. When the animals were sacrificed 40 days later the massive accumulation of cholesterol crystals, induced by the cholesterol cholic acid containing diet, was still present in all animals fed chow. In the hamsters fed chow supplemented with chenodeoxycholic acid there were far less such crystals. The conclusion is that with chow as the basic diet a chenodeoxycholic acid supplement aids the hamster in freeing itself from excess cholesterol. On the other hand, inflammatory‐ changes of the liver were present in many of the chenodeoxyholic acid treated hamsters while they were missing in the controls. The same experiment was repeated with a gallstone provoking diet as the basic diet during the regression period. With this basic diet, chenodeoxycholic acid did not have any effect on the accumulation of cholesterol crystals in the liver. It did, however, result in the development of inflammatory changes in the liver, comparable to those observed in animals fed lithocholic acid. The results of these experiments perhaps suggest that the basic diet may be an important factor also in the clinical trials with chenodeoxycholic acid which are now carried out. They also stress the importance of careful control of liver function and morphology during these trials.
THE EFFECT OF CYCLIC AMP ON THE ERYTHROPOIESIS IN MICE (NMRI)
Authors: Jakobsen A. , Thoriing E. B.
Published: August 2010

The effect of N6‐2O‐dibutyryl cyclic AMP (db‐cyclic‐AMP) on erythropoiesis in NMRI mice was investigated. This effect was measured by the incorporation of 59Fe into peripheral blood, spleen, and bone marrow. The study included plethoric as well as normal mice. Route of administration and dose schedule were varied. In spite of this, we were unable to demonstrate any stimulating effect of db‐cyclic‐AMP on erythropoiesis.
PULMONARY BONE MARROW EMBOLISM
Authors: HAVIg Ö. , GrÜner O. P. N.
Published: August 2010

Bone marrow embolism (BME) was found in 80 out of 507 consecutive autopsies (15.7 per cent). BME was associated with accident in more than 50 per cent and with cardiac disease in approximately 25 per cent of the cases. Mechanisms for the production of BME other than fracture must be sought since 8 per cent of the cases did not have any bone involvement. BME should not be considered proof of antecedent intravital trauma and pulmonary BME did not appear to have any clinical significance.
MALE BREAST CANCER
Authors: Scheike Ole , Visfeldt Jakob
Published: August 2010

In order to elucidate the question of whether or not gynecomastia is a premalignant state, a Danish series comprising 265 cases of male breast cancer was reviewed with regard to a previous history of gynecomastia and the finding of clinical gynecomastia on admission. Furthermore, preparations from 187 cases of the same series were assessed with a view to the presence of histologically verified gynecomastia. In 10 patients there was a history of gynecomastia; only one patient presented clinical gynecomastia on admission. In 79 cases there was sufficient breast tissue for a histological study; this revealed gynecomastia in 21 cases, 6 of which were of florid type (type I) and 15 of quiescent fibrous type (type II). In 2 cases ducts with severe atypia of the epithelium were found, but in spite of investigations of serial sections no transition into invasive growth was revealed. It is concluded that the following features seem to support the theory that gynecomastia, may be a premalignant state: A, the finding of severe atypia of the epithelium in the ducts in concurrent gynecomastia and breast cancer; B. lower mean age in cases of breast cancer with concurrent gynecomastia; C. the higher ratio of male to female breast cancer and the low mean age of the male patients in an area with a high frequency of gynecomastia; D. heavily increased frequency of breast cancer in patients with the Klinefelter syndrome.
ORAL GIANT CELL GRANULOMAS A Clinical and Histological Study of 129 New Cases
Authors: Andersen Lis , Fejerskov Ole , Philipsen Hans P.
Published: August 2010

Ninety‐seven peripheral and 32 central oral giant cell granulomas have been studied clinically and histologically. The distribution according to age (below and over 15 years of age) is similar in the two types of granulomas. It applies to both lesions that the prevalence usually is higher in females than in males. Both granulomas are most frequently found in the mandible. The central giant cell granuloma occur anterior to the molar region. The recurrence rate of the lesions in this material is high as compared with that observed in earlier studies. The radiographic features are non‐specific. The histopathology of the peripheral and central giant cell granulomas is fundamentally identical, both being composed of 1) a highly vascular and cellular granulation tissue containing, 2) a great number of multi‐nuclear giant cells of foreign body type scattered in the tissue, 3) extravasation by red blood cells and the presence of haemosiderin, 4) occasionally bone formation, and 5) several mitoses in the stromal cells. Comparative statistical analysis of the clinical findings and comparative histomorphological evaluation of the present material suggest that both types of lesions are manifestations of the same pathological condition.
HETEROTOPIC GASTRIC EPITHELIUM IN THE DUODENUM AND ITS CORRELATION TO GASTRIC DISEASE AND ACID LEVEL
Authors: Johansen AA. , Hansen O. Hart
Published: August 2010

The frequency of gastric mucosal heterotopia with parietal cells in the duodenal cuff of 250 gastric resection specimens and in 22 duodenal resection specimens was studied. 22.4 per cent of the gastric specimens disclosed parietal cell heterotopia. The frequency was largest in specimens with prepyloric or duodenal ulcers, and a statistically significant variation with the underlying disease was found. The gastric acid output was estimated in 203 cases. There was a statistically significant correlation between prevalence of the heterotopia and the acid output. This correlation was also evident in the individual gastric diseases. In the duodenal resection specimens, gastric heterotopia was found in 22.7 per cent. The heterotopia was localized in the first part of the duodenum in all cases; in one case it was also found in the second part. The significance of the phenomenon for the endoscopist and the pathologist is mentioned.
FAMILIAL PLASMA LECITHIN: CHOLESTEROL ACYLTRANSFERASE (LCAT) DEFICIENCY
Authors: Hovig Torstein , Gjone Egil
Published: August 2010

Kidney biopsies, plasma, and aspirated spleen specimens from a patient with an inborn error of metabolism, Familial LCAT‐deficiency, have been studied by light and electron microscopy. The kidney lesions were characterized by deposition of phospholipid membranes and membrane‐bound particles in the glomeruli and small arteries and veins. This material was found within the glomerular capillary lumina, in the capillary wall, in the mesangium and in Bowman's capsule. The endothelial cells appeared partly to be detached from the basement membrane which became exposed to blood flow. The lipid material was found in the subendothelial space as well as in the basement membrane (both on the endothelial and epithelial side). Arteries and veins showed a similar pattern of lipid deposition. Foam cells were frequently seen in the glomeruli as well as in the interstitial tissue. It is suggested that the deposition of phospholipid membranes (rich in lecithin and free cholesterol) and lipid particles (possibly with a high content of triglycerides) cause tissue damage and leads to progressive renal failure. The spleen contained numerous lipid‐laden cells which are assumed to be partly responsible for the splenomegaly found in patients with Familial LCAT‐deficiency. Examination of plasma with negative staining technique revealed membranes and membrane‐bound particles indicating that such structures are circulating with the blood and may leak out in the vessels and the perivascular tissue.
THE CALCIFIED CARTILAGE AND THE SUBCHONDRAL BONE UNDER NORMAL AND ABNORMAL CONDITIONS
Authors: Stougård J.
Published: August 2010

The main object was to study the osteocartilaginous junction under normal and abnormal conditions from the femur and patella. To this end the author used samples removed at autopsy from normal knee joints and biopsies from patients with patellar chondromalacia. Slight differences were found between non‐weight‐bearing and weight‐bearing areas of the joint. These differences were accentuated in cases with mild cartilaginous changes, manifesting themselves in increased thickening of the calcified cartilage and the subchondral bone, the junction of the two tissues growing more irregular and the number of bony extensions from the subchondral bone into the calcified cartilage increasing. This indicated increased activity in the skeletal tissue in the presence of cartilaginous changes, as also confirmed by tetracycline labelling.
DISTRIBUTION OF ALKALINE PHOSPHATASE ACTIVITY IN HEALTHY AND DISEASED HUMAN LIVER TISSUE
Authors: Hägerstrand Inga
Published: August 2010

Histochemical demonstration of the alkaline phosphatase activity with an azo‐dye method in human livers showed that the activity, which is normally localized to endothelial cells of portal and central veins as well as of sinusoids around the central veins and to a lesser extent of sinusoids around the portal connective tissue, is increased in various liver diseases. Appreciable canalicular activity is rare, and when it occurs it is most prominent in parenchyma involved by malignant tumours.
PROLIFERATING AND NON‐PROLIFERATING COMPARTMENTS IN CERVICAL DYSPLASIA AND CARCINOMA IN SITU
Authors: Rubio C. A. , Lagerlöf B.
Published: August 2010

The existence of proliferating and non‐proliferating compartments in atypical cervical epithelium is suggested by autoradiographical investigations and studies on the topographical distribution of mitosis performed on human cervical cones and on cervices of mice following carcinogenic treatment.
DIABETOGENIC EFFECTS OF N‐NITROSOMETHYLUREA IN THE CHINESE HAMSTER
Authors: Wilander Erik , Gunnarsson Rolf
Published: August 2010

To evaluate the role of the glucose residue of the diabetogenic substance streptozotocin, the effect of its aglucone derivate N‐nitrosomethylurea was tested in Chinese hamsters. At a dose of 50 mg/kg body weight of N‐nitrosomethylurea a triphasic blood glucose curve was recorded with an initial hyperglycaemic peak after 3 hours followed by a decrease at 6 hours. After 24 hours and during the following days the values were moderately elevated. There was a high mortality in the diabetic animals, about 80 per cent of them dying within one week. The approximate L.D. 50 of N‐nitrosomethylurea injected intraperitoneally in non‐fasting adult animals was about 125 mg/kg body weight at an observation time of 48 hours. On light microscopy, degenerative changes with nuclear pyknosis were seen after 3 hours in the pancreatic islet cells, followed by cellular disintegration. Both β‐, α2‐ and α1‐cells were obviously affected. Pretreatment with 500 mg nicotinamide/kg body weight given intraperitoneally 10 minutes before the injection of N‐nitrosomethylurea inhibited the hyperglycaemia and seemed to prevent the injurious effects of N‐nitrosomethylurea on the islet cells. The results show that the glucose residue of the streptozotocin molecule is not necessary for the induction of diabetes in Chinese hamsters, but it seems to increase the selectivity of the toxic effects for the islet cells. This is a clear advantage in studies of experimental diabetes, especially when longer observation periods are desired.
THE EFFECT OF PORTOCAVAL ANASTOMOSIS ON THE PERMEABILITY TO HORSERADISH PEROXIDASE OF CEREBRAL VESSELS OF THE RAT
Authors: Laursen H. , Schrø H. , Westergaard E.
Published: August 2010

The blood‐brain barrier to horseradish peroxidase (HRP) was tested in rats with hepatic encephalopathy induced by portocaval anastomosis. An increased number of vesicles containing HRP was seen in endothelial cells. Basement membranes of some vessels and the adjacent neuropil were filled with HRP. Astrocytes showed swollen end‐feet. The cytoplasm of astrocytes adjacent to HRP containing basement membranes was evenly filled with HRP. This phenomenon could be caused either by cellular hyperactivity or by leaking membranes due to cell damage.
SPONTANEOUS TOXIC NEPHROPATHY IN POULTRY ASSOCIATED WITH OCHRATOXIN A
Authors: Elling F. , Hald B. , Jacobsen Chr. , Krogh P.
Published: August 2010

At a poultry slaughterhouse 14 birds with macroscopic renal changes were collected, and the kidneys were examined histologically and the muscular tissue was analysed for ochratoxin A residues. Out of 14 birds 5 birds had ochratoxin A residues ranging from 4.3 to 29.2 μg/kg. In 4 of these birds a toxic nephropathy was found characterised by atrophy and degeneration of proximal and distal tubules and interstitial fibrosis. The possibility of birds with ochratoxin A residues being presented for human consumption is discussed.
CONGENITAL GENERALIZED LIPODYSTROPHY:
Authors: Berge Thorbjörn , Brun Arne , Hansing Bengt , Kjellman Bengt
Published: August 2010

Generalized lipodystrophy (Berardinelli‐Seip's syndrome) was diagnosed in a boy at the age of 81/2 months. Ten months later he died because of aspiration of food. Necropsy with special reference to the CNS revealed hypothalamic lesions, probably of a malformative or hamartomatous nature. The findings lend additional support to the view that hypothalamic dysfunction is responsible for the signs and symptoms of generalized lipodystrophy.