bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation‐associated angiosarcoma of the small bowel:
Authors: Hansen Steen Holger , Holck Susanne , Flyger Henrik , Tange Ulla Brix
Published: August 2009

Angiosarcoma developing in unusual sites such as the gastrointestinal tract is not uncommonly associated with a known eliciting factor. Thus, among hitherto reported cases of angiosarcoma of the small bowel, five were radiation‐associated. One additional example of ileal angiosarcoma induced by therapeutic irradiation of endometrial carcinoma is herein reported as a reminder of this causal association. DNA analyses of the primary growth as well as the metastatic deposits showed at least four aneuploid cell clones indicating genetic instability. This observation corresponds to the consistently poor prognosis of radiation‐associated angiosarcoma of the small bowel.
Detection of galactomannan and complement activation in the pregnant mouse during experimental systemic aspergillosis
Authors: Jensen H. E. , AalbæK B. , Hau J. , Latge J.‐P.
Published: August 2009

Foeto‐placental infections are obtained when pregnant mice are challenged intravenously with conidial suspensions of Aspergillus fumigatus. This experimental model, which is used without any immunosuppressive pretreatment, can be employed to screen for differences in foeto‐placental infectivity of A. fumigatus strains when the number of colony‐forming units (CFUs) in conidial suspensions used for infection is from 1×105 to 1×106. In the foeto‐placental unit, hyphal growth was initiated at the periphery of the placental disc from which infection spread to the central parts of the placenta, the extrafoetal membranes and the foetus. Complement activation was noticed as a consequence of pregnancy and conidial inoculation, but was neither dose‐dependent nor related to the extent of infection. Galactomannan was present in the plasma of infected mice and, in contrast to the situation in bovine placental aspergillosis, can be used as a good marker of foeto‐placental aspergillosis.
Lectin staining of renal cell tumours with special emphasis on oncocytomas
Authors: Engel Ulla , Breborowicz Danuta , Albrectsen Jens M. , BØG‐Hansen Thorkild C. , Francis Dorthe
Published: August 2009

There are conflicting results respecting the segmental tubular origin of renal oncocytomas, a type of tumour said to be highly differentiated and benign, though metastases have been described. The aim of this study was, by applying different lectins on renal cell carcinomas (n = 50) and oncocytomas (n=12), to search for patterns which could indicate a specific segmental origin of oncocytomas and perhaps elucidate the differentiation of this tumour. The following lectins were applied: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA‐E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). The results show that oncocytomas are positive when jacalin, a Lectin that stains distal tubules and collecting tubules, is used, supporting the view that the tumour derives from distal or collecting tubules. The staining of the oncocytomas is generally polarized as in normal kidney tubules underlining that the tumour is highly differentiated. Two oncocytomas with aggressive behaviour showed areas with a diffuse pattern suggesting lower differentiation.
Cellular and molecular mechanisms of murine autoimmune myocarditis
Authors: PENNINGER JOSEF M. , PUMMERER CHRISTIAN , LIU PETER , NEU NIKOLAUS , BACHMAIER KURT
Published: August 2009

Dilated cardiomyopathy is a prevalent cause of progressive heart disease and sudden death, and most patients with cardiomyopathy have a history of viral myocarditis. Coxsackie B3 (CB3) picornaviruses can be detected in as many as 50% of these patients and CB3 infections have been epidemiologically linked to chronic heart disease. Several clinical and experimental studies suggest that chronic stages of disease are mediated by an autoimmune response against heart muscle myosin. Human heart disease can be mimicked in mice using cardiac myosin as autoantigen. Murine cardiac myosin‐induced myocarditis is an organ‐specific autoimmune disease and mediated by CD4+ T cells that recognize a myosin‐specific peptide in association with MHC class II molecules. Here, the recent discovery of autoimmune epitopes derived from the alpha isoform of cardiac myosin, the functional roles of surface receptor and signal transduction molecules, and the molecular mechanisms of target organ susceptibility will be discussed.
Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co‐cultured agarose beads
Authors: BERGE V. , JOHNSON E. , HØGÅSEN K.
Published: August 2009

Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co‐cultured agarose beads. Clusterin is a multifunctional regulatory protein rendering the terminal complement complex (TCC) soluble and unable to insert into cell membranes. The aim of the present study was to examine whether clusterin was an integral part of serum‐derived TCC bound to agarose beads which activate the alternative pathway of complement. Further, we searched for evidence of clusterin synthesis in human umbilical vein endothelial cells (EC) and whether this synthesis was regulated by various proinflammatory cytokines (IL‐1, IL‐6, and TNF) and IFN‐γ. The clusterin and TCC on co‐incubated beads were measured by radioimmunoassay based on primary anti‐complement antibodies (anti‐C3c, anti‐TCC, anti‐clusterin). We found that clusterin in serum experiments is bound to C9 in agarose bound TCC and not directly to the agarose. Addition of the protein synthesis inhibitor cycloheximide to cultured human umbilical vein cells resulted in a strong reduction (about 70%) of anti‐clusterin binding to co‐cultured beads, which strongly supports de novo synthesis of clusterin in EC. The results indicate that clusterin derived from the EC is linked with the TCC on the co‐incubated beads for the following reasons: First, in serum experiments clusterin like vitronectin, was co‐deposited with C9 in agarose‐bound TCC. Second, cytokine stimulation of the EC with proinflammatory cytokines such as IL‐1, IL‐6 and TNF, known to increase the detection of bound TCC, also increased the amount of clusterin detected on the beads. Third, IFN‐γ, which reduces the concentration of bound TCC, exhibited the same effect on the amount of clusterin detected on such beads. There was a strong and dose‐dependent reduction of anti‐TCC binding from about 45% to about 95% when clusterin (5–40 μg/ml) was added to EC cultures. This effect was also evident (about 40–50% inhibition of bound TCC) using human serum as complement source. These results are probably mainly caused by clusterin binding to C5b‐7, making this complex soluble without the capacity to bind to the agarose surface. This study supports the view that clusterin is a potent regulator of TCC at the levels of C5b‐7 and C9.
Plasminogen activators and inhibitors in peritoneal tissue
Authors: HOLMDAHL LENA , FALKENBERG MÅRTEN , IVARSSON MARIE‐LOUISE , RISBERG BO
Published: August 2009

Serosal trauma elicits an inflammatory response which leads to the deposition of fibrin at injured sites, the residuals of which appear to be essential in excessive tissue repair and formation of intraabdominal adhesions. Local plasminogen activity may modulate this early phase of tissue repair. The present study was undertaken to investigate the distribution and cellular expression of plasminogen activators and their inhibitors in human peritoneal normal and inflamed tissue. Tissue‐type plasminogen activator (t‐PA) was expressed in subserosal capillary walls, and in normal mesothelium, but not in inflammation. Immunoreactivity for the plasminogen activator inhibitor type 1 (PAI‐1) was present in normal mesothelium, and substantially increased in inflammation, where, in addition, immunoreactivity was found throughout the submesothelial tissue. This PAI‐1 was partly co‐localized with macrophages, as was the urokinase plasminogen activator (u‐PA), suggesting an involvement of these cells in peritoneal tissue fibrinolysis. Inflammation or abrasion of the mesothelium during surgery is likely to cause a depletion of the local t‐PA source and expose the potentially PAI‐1‐containing submesothelial tissue, thus promoting persistence of fibrin and formation of adhesions.
Lectin staining of renal tubules in normal kidney
Authors: ENGEL ULLA , BREBOROWICZ DANUTA , BØG‐HANSEN THORKILD , FRANCIS DORTHE
Published: August 2009

Lectins are glycoproteins able to bind carbohydrate structures specifically. In this study we applied six different lectins on normal renal tissue to investigate their specificity for different segments of the renal tubular system. The following lectins were used: jacalin, peanut agglutinin (PNA), wheat germ agglutinin (WGA), phytohemagglutinin E (PHA‐E), concanavalin A (Con A), and Dolichos biflorus agglutinin (DBA). Particular attention was paid to jacalin lectin as its staining properties respecting the renal tubular system were not known. We showed that jacalin lectin strongly stains the luminal border of distal tubules, as well as single cells of the collecting tubules. As regards the other five lectins, PNA stained distal tubules, WGA the whole nephron, PHA‐E proximal tubules, and Con A and DBA a few cells of the loop of Henle.
Bcl‐2 overexpression in basaloid proliferations overlying dermatofibromas and basal cell carcinomas
Authors: ROSSEN KRISTIAN , HAERSLEV TORBEN , HOU‐JENSEN KLAUS , JACOBSEN GRETE KRAG
Published: August 2009

Basaloid proliferations overlying dermatofibromas resembling superficial basal cell carcinomas have been interpreted both as reactive/regressive and frankly malignant. Basal cell carcinoma is a slow‐growing tumour, which so far has been regarded as an actively proliferating lesion with a high apoptotic activity. We examined immunohistochemically 6 dermatofibromas with overlying simple hyperplasia, 12 dermatofibromas with overlying basaloid proliferations, and 24 basal cell carcinomas for expression of Ki‐67 protein and bcl‐2 protein. The Ki‐67 labelling index represents an estimate of proliferative activity. Bcl‐2 protein suppresses apoptosis. The Ki‐67 labelling indexes of basaloid proliferations, basal cell carcinomas, and normal epidermis were similar (11–15%, p<0.05, Mann‐Whitney test). Bcl‐2 protein was expressed in all cells of basaloid proliferations, similar to the expression pattern in basal cell carcinomas. We suggest that basaloid proliferations overlying dermatofibromas might have achieved a phenotype that equals an early stage of BCC carcinogenesis.
A preliminary study on the pathogenicity of Bacillus licheniformis bacteria in immunodepressed mice
Authors: AGERHOLM J. S. , JENSEN N. E. , GIESE S. B. , JENSEN H. E.
Published: August 2009

The pathogenicity of 13 strains of Bacillus licheniformis was studied in immunodepressed mice. The strains had been isolated from cases of bovine abortions (n=5), bovine feedstuffs (n=3), soil (n=1), and grain products (n=2). The origin of two strains was unknown. Groups of 10 mice were inoculated intravenously with B. licheniformis bacteria at doses from <106 to 1010 colony‐forming units. Following 7 days of infection, the animals were euthanized and examined bacteriologically, histologically, and immunohistochemically using a PAP technique based on primary polyclonal rabbit anti‐B. licheniformis antibodies. B. licheniformis bacteria were reisolated from the liver, spleen, or kidneys of mice in all groups. Inflammatory lesions were present in mice of all immunodepressed groups, but only brain and pulmonic lesions were definitely attributed to B. licheniformis infection, as strong immunostaining was found within these lesions. It is concluded that all strains of B. licheniformis examined were pathogenic for immunodepressed mice, and that spontaneous infections may be established by bacterial strains to which susceptible individuals are accidentally exposed.
The influence of mammography screening on the pathological panorama of breast cancer
Authors: LINDGREN A. , HOLMBERG L. , THURFJELL E.
Published: August 2009

The pathologist describes the biological domain of breast cancer in which the clinician works. Over the last 20 years there have been indications that the biological domain has shifted following the introduction of fine‐needle biopsies, clinical mammography, and later screening mammography. The most commonly used parameters for staging, classification and grading of cancer in some respects probably reflect the biological domain. We describe how the pathological panorama of breast cancer has changed with the introduction of population‐based mammography screening. Our experiences are based on a consecutive series of 1961 breast cancers diagnosed from 1977 to 1994 in a region where screening mammography was introduced in 1988. All results, including histological classification and grading were prospectively registered in a computerized data base. There were more comedo than tubuloductal carcinomas and there was a corresponding preponderance of grade III tumours in the youngest and a high incidence of tubuloductal, lobular and colloid cancers in the oldest age group. The proportion of women with comedo carcinoma decreased after 1987. Looking at changes in the grade distribution after 1987, the proportion of women with grade I tumours increased and grade III tumours decreased in women over 50 years of age, but in the youngest women only marginal changes were noted. Very few in situ carcinomas were diagnosed in the prescreening period. About 11% of all tumours were in situ after 1987. The percentage of node‐positive cancer decreased in the screening period in all histological types of cancer regardless of tumour size. The percentage of small tumours ≤20 mm increased with time, though less so for comedo carcinomas. Comedo carcinomas dominate among the largest cancers most frequently detected clinically. From a biological standpoint it is interesting to note that screening seems to entail a larger shift in the biological domain in older as compared to younger women. Furthermore, comedo carcinomas seem to be less well detected by the screening procedure.
The effect of human cytomegalovirus on selected functions of peripheral blood monocytes
Authors: HOLBERG‐PETERSEN M. , ROLLAG H. , BECK S. , DEGRÉ M.
Published: August 2009

The effect of in vitro infection of human cytomegalovirus (HCMV) on various monocyte functions relevant to antimicrobial defence mechanisms has been investigated: the phagocytic activity of monocytes, the release of lysozyme and intracellular concentration of acid phosphatase, and the release of the cytokines interleukin‐1 (IL‐1), IL‐6, and tumour necrosis factor‐α (TNF‐α). HCMV significantly inhibited the release of lysozyme and intracellular concentration of acid phosphatase. Regarding the phagocytic activity and the release of cytokines, there was considerable variation in the HCMV effect among the different blood donors tested. There was no clear tendency in the observed results; both stimulation and inhibition were seen. The HCMV‐specific pp65 was detected in the nucleus of about 1% of the monocytes 3 h after infection and HCMV‐specific IE antigens were found in about 0.1% of the monocytes 2 days postinfection. No E‐ or L‐gene expression was observed and no infectious virus was produced in the monocytes. Our results indicate that HCMV infection may influence monocyte functions in spite of no productive infection of these cells.
Phage‐displayed Fab fragments against anti‐human interleukin‐2 receptor α. Detection of antigen‐bound phages with anti‐cpIII monoclonal antibodies
Authors: RAIVIO EVA , KRONQVIST MALIN , BRODIN THOMAS N. , PERSSON MATS A. A. , LINDQVIST CHRISTER
Published: August 2009

The genes encoding the VHCH1 and VLCL parts of the mouse anti‐human IL‐2Rα antibody 7G7B6 were amplified by PCR and the corresponding antibody fragments displayed on the surface of filamentous phages. The expression of Fab fragments was analysed by immunoblotting using HRP‐labelled goat anti‐mouse Ig antisera. By traditional hybridoma technology, splenocytes from Balb/c mice, immunized with native phage particles, were fused with P3X63‐Ag8.653 myeloma cells in order to yield monoclonal antibodies against filamentous phage proteins. The obtained monoclonal antibody IF8 (μ/k) recognized the minor coat protein III as a 65–70 kDa protein band by immunoblotting, whereas the monoclonal antibody IVC8 (μ/k), in addition to cpIII, recognized a protein with an approximate molecular weight of 38–43 kDa. Both antibodies were employed to determine the binding specificity of the phage‐displayed anti‐human IL‐2Rα Fab fragments in an ELISA using recombinant baculovirus‐expressed human IL‐2Rα proteins as antigens.
Genomic instability and poor prognosis associated with abnormal TP53 in breast carcinomas. Molecular and immunohistochemical analysis
Authors: VALGARDSDOTTIR RUT , TRYGGVADOTTIR LAUFEY , STEINARSDOTTIR MARGRET , OLAFSDOTTIR KRISTRUN , JONASDOTTIR SIGURROS , JONASSON JON G. , ÖGMUNDSDOTTIR HELGA M. , EYFJÖRD JORUNN E.
Published: August 2009

Alterations of theTP53gene were analyzed in samples from 87 primary breast cancer patients, using molecular and immunohistochemical approaches. Mutations were detected in 17% of the samples, using polymerase chain reaction (PCR) and constant denaturant gel electrophoresis (CDGE) on exons 5–8 of theTP53gene, and were confirmed by sequencing. Abnormal TP53 protein staining was found in 55% of the primary samples, using the monoclonal TP53 antibody DO7. A statistically significant association was found betweenTP53mutations and abnormal protein staining (p=0.002). Our results suggest that dysfunction of the TP53 protein is associated with tumor progression, as we found an association between TP53 abnormalities and accumulation of genetic lesions, measured as overall allelic imbalance (AI), homogeneously staining regions (HSR) and strong ERBB2 overexpression. Furthermore, patients withTP53mutation had a highly elevated risk of dying from breast cancer during the study period (p<0.001, RR = 10.68) at a median follow‐up time of 42 months. Abnormal TP53 staining was much more frequent than the mutations, but it was not of prognostic significance, whereas strong staining was an independent prognostic factor. We therefore conclude that loss of functional TP53 leads to genetic instability, resulting in poorer short‐term prognosis, and that only strong staining of TP53, and not abnormal protein staining in general, is of prognostic significance.
Decreased plasma levels of factor II+VII+X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections
Authors: BYGBJERG I. C. , HANSEN M. B. , RØNN A. M. , BENDTZEN K. , JAKOBSEN P. H.
Published: August 2009

The levels of coagulation factors II+VII+X and of blood platelets (thrombocytes) as well as of cytokines and soluble cytokine receptors were studied in patients with malaria or meningococcal infections. The coagulation factors were decreased particularly in the meningococcal patients, while thrombocytes were lowest in the Plasmodium falciparum malaria patients. There was no correlation between factors II+VII+X and thrombocytes, but plasma levels of coagulation factors II+VII+X were found to correlate inversely with levels of soluble interleukin‐2 receptor (sIL‐2R) and soluble tumour necrosis factor‐I (sTNF‐RI) in patients with malaria and meningococcal infections. Elevated sIL‐2R and sTNF‐RI levels and decreased coagulation factors reverted to normal within 3–5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may be used to monitor the course of these common and potentially life‐threatening infections.
Feasibility of Helicobacter pylori identification by a slide agglutination test
Authors: MÆLAND JOHAN A. , PIENE MARIT , MÜLLER LIV I.
Published: August 2009

Culture isolation and identification of Helicobacter pylori represents a considerable work load in clinical microbiology. The aim of this study was to test if antibody‐mediated bacterial agglutination could be used for rapid identification of H. pylori. Rabbit antiserum against H. pylori strain I and against another strain, H. pylori 330, which was very weakly agglutinated (1+) by anti‐H. pylori I serum, were mixed and used in a slide agglutination test. Of 107 consecutive clinical isolates tested, 101 (94%) strains showed 2+ or 3+ reaction using the antiserum mixture, whereas 6 (6%) strains could not be evaluated owing to autoagglutinability. Bacteria of a variety of other species, including Campylobacter spp., showed no agglutination with the antiserum mixture. The results support the notion that reliable identification of the majority of cultured H. pylori strains should be possible in less than 3 min by agglutination testing.
Interferons α/β and their receptors: place in the hierarchy of cytokines
Authors: ZAV'YALOV VLADIMIR P. , ZAV'YALOVA GALINA A.
Published: August 2009

Interferons α/β (IFNs‐α/β) are the first cytokines to be produced by recombinant DNA technology. They regulate growth and differentiation, affecting cellular communication, signal transduction pathways and immunological control. This review focuses on the relationships between the structure and biological activities of IFNs‐α/β induced as a result of specific interactions with different types of polypeptide receptors as well as on the role of glycolipids in the modulation of these activities. The discovery of the primary structure homology of HuIFNs‐α and thymus hormone‐thymosin α‐1 (TMα1), the experimental finding of the competition between IFN‐α and TMα1 for common receptors and the reproduction by reHuIFN‐α2 of TMα1 immunomodulating activities create the basis of reHu‐IFN‐α therapeutics instead of TMα1 and potentiation of vaccines by reHuIFN‐α. The first successful attempt at grafting of the HuIFN‐α2′s TMα1‐like immunomodulating site to the designed de novo protein albeferon is described. This article also aims at reviewing recent data concerning the structure of other cytokines and their receptors. Their reciprocal structure‐function taxonomy is proposed. The place of IFNs‐α/β and their receptors in the hierarchy of cytokines is determined.
A rat model of non‐lethal bacterial infection
Authors: WANDALL DORTE ALNOR , ARPI MAGNUS , WANDALL JOHAN H.
Published: August 2009

The purpose of the study was to develop a small animal model of intraperitoneal infection without mortality and with a catabolic response to the infection, viz. to mimic the clinical situation in man. Intraperitoneal infection was induced in female Wistar rats by deposition of a gelatin capsule containing a mixture of Escherichia coli and Bacteroides fragilis and adjuvant substances. Seven groups of animals were infected with different bacterial inocula (0.2–4.3times106 CPU) to establish reproducible and dose‐dependent changes in mortality, body weight in relation to food intake, blood cultures, peripheral blood leukocyte counts, and abscess formation on autopsy. No mortality was observed in animals with an inoculum below 2.2times106 CFU in spite of positive blood cultures. Initial weight loss was followed by weight gain in all animals except the group infected with the low inoculum (0.2times106 CFU). This group had no mortality, was in a catabolic state for three days, indicated by weight loss in spite of nearly normal food intake, and the infectious state was supported by intraperitoneal dissemination of small abscesses. The low‐grade character of the infection was reflected by changes in peripheral blood lymphocyte and neutrophil ***granulocyte concentrations. In conclusion, this study presents a small animal model with a reproducible dose response to the bacterial challenge, allowing prolonged studies of metabolic changes following infection.
Identification of Afipia felis antigens in culture medium: reaction with human sera
Authors: ENGBÆK KRÆSTEN , UTTENTHAL LARS OTTO , KOCH CLAUS
Published: August 2009

Fourteen protein antigens were identified on SDS‐PAGE of Afipia felis culture supernatant. Immunoblotting against 10 monoclonal antibodies obtained from mice infected with live A. felis showed that 4 antibodies reacted with a 56 kDa band and 3 with both 56 kDa and 62 kDa bands. Compared with A. felis sonicate, the reacting proteins in culture supernatant showed an increase in molecular mass of 2–3 kDa, suggesting that they were more glycosylated. Purified antigen obtained by affinity chromatography of culture supernatant on the seven immobilized antibodies was tested against antibodies reacting with the 56 kDa and 62 kDa bands. All eluates contained both components, suggesting that the antibodies were directed against different epitopes of a double antigen held together during the affinity chromatography but cleaved by reduction and SDS‐PAGE. The molecular size of the uncleaved protein in culture supernatant was determined by size‐exclusion chromatography as >1000 kDa. Testing of pre‐ and post‐infection rabbit sera in immunoblotting against culture supernatant demonstrated that the 56 kDa and 62 kDa components gave the most prominent specific reactions with post‐infection sera. One of fifty human sera submitted for testing for cat‐scratch disease and 1 of 50 sera from healthy blood donors reacted with several bands in A. felis culture supernatant, including the 56 kDa and 62 kDa bands.
Mast cell and mast cell granule phenotypes in normal and Nippostrongylus‐infected rats
Authors: KRÜGER P. G. , HUNTLEY J. F. , MacKELLAR A. , RØLI J. , NEWLANDS G. F. J.
Published: August 2009

In the rat, the individual mast cell secretory granules may be divided into three subpopulations based on the presence of the specific proteases RMCP‐1, RMCP‐2, or a variable combination of these two proteases. Mast cells in the tongue only express RMCP‐1, both in normal and infected animals, whereas in the other tissue locations studied (lung, intestinal mucosa and submucosa, tracheal epithelium and submucosa) the mast cells contain all three granule subtypes in a wide variation of combinations. These studies demonstrate that there is wide heterogeneity in protease expression in rat mast cells, which may be influenced by local stimulation with environmental tissue factors.
TNF blockade in rheumatoid arthritis: Implications for therapy and pathogenesis
Authors: MAINI R. N. , ELLIOTT M. , BRENNAN F. M. , WILLIAMS R. O. , FELDMANN M.
Published: August 2009

The role of the immune response in rheumatoid arthritis (RA) is a subject of debate, although it is widely believed to be a T‐cell‐driven disease. Progress is being hindered by lack of convincing evidence of a defined specific antigen initiating or perpetuating the response. Clinical trials using monoclonal antibodies directed against T‐cell surface molecules such as CD4, CD5, and CD7 have thus far not provided evidence of efficacy. The negative data may reflect inadequate dosing or could suggest that indiscriminate depletion of T cells is insufficient by itself as a therapeutic strategy. Blocking proinflammatory cytokines (e.g. TNFα, IL‐1) or augmenting anti‐inflammatory cytokines (e.g. IL‐10) offers an alternative approach to therapy. Clinical trials using monoclonal anti‐TNFα have been particularly successful in controlling inflammation and markedly reducing acute phase proteins and cellular ingress. However, because disease invariably relapses, repeated therapy is necessary. Preliminary experience suggests that this is possible. Anti‐TNF therapy for RA has defined a molecular target and new approach for treating immuno‐inflammatory disorders.
Distribution of serotypes, IS901 and a 40 kDa protein in Mycobacterium avium complex strains isolated from man and animals in Denmark
Authors: KLAUSEN JOAN , GIESE STEEN B. , FUURSTED KURT , AHRENS PETER
Published: August 2009

The aim of the present study was to characterize all strains of the Mycobacterium avium complex isolated in Denmark in 1993. A total of 141 M. avium complex strains (86 from man, 38 from animals, and 17 from peat) were analysed by serotyping, ELISA specific for a 40 kDa protein, and IS901‐specific PCR. Serotype analysis showed that the most frequent serotypes among human strains were serotype 4 (27%) and serotype 6 (19%), which differs from an earlier survey where serotype 1 was most prevalent. The most frequent serotypes in animals were serotype 2 (53%) and serotype 6 (13%), whereas the most prevalent serotypes among strains isolated from peat were serotype 4 (29%) and serotype 9 (18%). There was a concurrent appearance of IS901 and p40 in all strains. Only M. avium complex strains isolated from animals, and belonging to serotype 1 or serotype 2, contained the IS901/p40 markers. The different distribution of serotypes of M. avium complex strains in animals and man, and the presence of IS901/p40 exclusively in animal strains, suggests that transmission of M. avium from animals to man is not of significance in Denmark.
The determination of neutrophil membrane fluidity in patients with hepatitis B: a fluorescence polarization study
Authors: FAN XUE‐GONG , ZHANG ZHENG
Published: August 2009

Although numerous studies on abnormality of neutrophil function in patients with viral hepatitis have previously been reported, little is known about mechanisms of neutrophil dysfunction. To investigate mechanisms of neutrophil dysfunction in these patients, neutrophil membrane fluidity was measured by fluorescence polarization technique in 76 hepatitis patients. The results showed that membrane fluidity of neutrophils from patients with chronic active hepatitis (CAH) or subfulminant hepatic failure (SFHF) was much lower than that in normal controls (p<0.01), but such a difference could not be found in patients with acute hepatitis (p>0.05). Furthermore, recombinant interleukin‐2 could significantly increase membrane fluidity, while lipopolysaccharide decreased membrane fluidity of neutrophils (p<0.01, p<0.001). The present study indicates that there is abnormal membrane fluidity of neutrophils in patients with CAH and SFHF. Neutrophil dysfunction in hepatitis patients may be partly due to altered membrane fluidity.
Intratumoral heterogeneity in prostate cancer demonstrated by volume‐weighted mean nuclear volume
Authors: FUJIKAWA KEITA , SASAKI MIHARU , AOYAMA TERUYOSHI , ITOH TADAHIRO , YOSHIDA OSAMU
Published: August 2009

This study was conducted to investigate the degree of heterogeneity of the volume‐weighted mean nuclear volume (MNV) calculated from radical prostatectomy specimens, and to evaluate how closely the MNV calculated from transrectal biopsy specimens reflected the overall malignancy. MNV was evaluated using 77 sections of histological specimens from 9 patients who underwent radical prostatectomy at Shizuoka City Hospital between January 1990 and December 1995. The MNV values calculated from radical prostatectomy specimens were compared with those calculated from preoperative transrectal biopsy specimens. MNV was judged to be homogeneous in six cases and heterogeneous in three cases. Of the heterogeneous cases, MNV calculated from the transrectal biopsy specimens was judged to be underestimated in 2 of 3 cases. This study shows that intratumoral heterogeneity of prostate cancer may affect clinical estimates of the grade of malignancy based on the MNV, and indicates the need for a sufficient number of specimens in order to evaluate the MNV by transrectal biopsy.
Control of gene expression during lymphoid development: targeted gene disruption provides new clues
Authors: DOOIJES DENNIS , CLEVERS HANS
Published: August 2009

The expression of structural genes is thought to be regulated by DNA‐binding factors interacting with cis‐acting regulatory elements. These regulatory elements, identified for many lymphopoietic genes, have served in recent years to identify and clone novel transcription factors. The expression of some of these factors is found to be confined to the lymphoid lineage. This regulated expression in both time and space is thought to mediate entry into and progression along the correct developmental differentiation programs. In recent years, many laboratories have tried to assess the functional relevance of these DNA‐binding factors by making use of gene targeting techniques. A review of the results of such knock‐out experiments and the consequences for lymphoid development models appears below.
Chronic cold agglutinin disease of the “idiopathic” type is a premalignant or low‐grade malignant lymphoproliferative disease
Authors: BERENTSEN SIGBJØRN , BØ KRISTINE , SHAMMAS FUAD VICTOR , MYKING ANDREAS O. , ULVESTAD ELLING
Published: August 2009

We investigated the clinical, pathological, and immunological features of “idiopathic” cold agglutinin disease (CAD) in a population‐based study. Fourteen patients were studied, giving a prevalence of about 14 per million with a mean age of 75 years. Haemolysis was present in all cases, but only eight patients had clinical symptoms of peripheral haemagglutination. Serum electrophoresis, immunofixation, morphological bone marrow evaluation, and flow cytometric immunophenotyping were used to detect any monoclonal lymphoproliferative disorder. Flow cytometry seemed to be a sensitive way to demonstrate a clonal B‐cell proliferation. Some evidence of clonality was found in 13 patients, and a clonal lymphoproliferative disease was documented by flow cytometry or biopsy in 10 out of 11 patients. We conclude that CAD is a symptom‐producing monoclonal lymphoproliferative disorder in nearly all patients.
Sclerosing peritonitis in a case of benign cystic ovarian teratoma
Authors: STENRAM U.
Published: August 2009

A 52‐year old woman with regular menstruation presented with ascites and abdominal swelling and pain. Bilateral salpingo‐oophorectomy, hysterectomy and excision of a few peritoneal nodules was performed. The omentum was firm, giving the impression of carcinoma. The ovaries were enlarged, each containing a non‐ruptured cyst with thick yellowish fluid. Microscopy revealed a sclerosing peritonitis in the omentum and nodules. There was a benign cystic teratoma in the left ovary, a corpus luteum in the right ovary. Follow‐up has been uneventful for 26 months. The sclerosing peritonitis is considered to be secondary to the ovarian changes, most probably the teratoma.
Eikenella corrodens‐caused botryomycosis‐type pneumonia in a barbary ape (Macaca sylvanus)
Authors: BRACK M.
Published: August 2009

An 18‐year‐old female barbary ape in a safari park died from a mixed bacterial infection. Staphylococcus aureus was isolated from a purulent necrotic mastitis and from a chronic purulent granulomatous sialoadenitis of the sublingual glands, Eikenella corrodens from a botryomycosis‐type pneumonia. As judged by histopathology, mixed infection of S. aureus and E. corrodens was present in the sialoadenitis, and E. corrodens botryomycosis‐type bacterial colonies were also present in the pancreatic parenchyma, though here no bacteriological isolation was attempted. A generalized amyloidosis, and especially pancreatic islet amyloidosis, probably indicated an altered immunological competence.
Congenital heart block: HLA differences between affected children and healthy siblings in four Finnish families
Authors: SIRÉN MARJA‐KAISA , JULKUNEN HEIKKI , KAAJA RISTO , KOSKIMIES SAIJA
Published: August 2009

Congenital heart block without intracardiac anatomic malformations is a potentially lethal disease affecting children and newborns. The mother often has an autoimmune disorder with autoantibodies against SS‐A/Ro and/or SS‐B/La antigens. However, only a minority of the children of these mothers develop complete heart block. It is believed that the maternal antibodies are pathogenic, but other immunological mechanisms such as cell‐mediated injury cannot be excluded. Maternal cells may recognize fetal antigens adjacent to fetal HLA, and thus some children may be more susceptible to heart block than others, depending on their HLA genetics. The purpose of this study was to evaluate whether there are HLA differences between children with heart block and their healthy siblings. Six affected children in four families and their siblings were studied. MHC class I were typed serologically and class II and some non‐HLA alleles were typed by DNA techniques. DQB1*03/04 were seen more often in the affected children than in the siblings. Some other differences were also seen in the other antigens of the MHC area.
Primary retroperitoneal mucinous tumor of low malignant potential: histogenetic aspects and review of the literature
Authors: PAPADOGIANNAKIS NIKOS , GAD ADEL , EHLIAR BENGT
Published: August 2009

We report an unusual mucinous tumor of low malignant potential, of ovarian‐like type, arising in the retroperitoneum of an otherwise healthy 33‐year‐old woman. This is the fifth described case of such a tumor in the world literature, and the first reported in Scandinavia or Europe. We also discuss aspects of the histogenesis of this type of tumor and review the available literature. The histological heterogeneity and metastatic potential of the tumor warrant careful histopathologic analysis and follow‐up of patients presenting with such lesions.
Tumor growth in a defined microcirculation
Authors: CHRISTOFFERSON R. H. , SKÖLDENBERG E. G. , NILSSON B. O.
Published: August 2009

The fate of human tumor cells deposited in rat uteri was investigated by light microscopy of histological sections, immunohistochemistry, and scanning electron microscopy of microvascular corrosion casts. The human colonic tumor cell line LS 174 T was used as graft since it can be detected by CEA immunohistochemistry, and spayed nude rats (PVG rnu/rnu) were used as hosts, subjected to different hormonal regimens (no exogenous hormones, medroxyprogesterone acetate, 17‐β‐estradiol, or the last two regimens in combination). Intrauterine deposition of a suspension of 2times106 tumor cells resulted in tumor take in 72% (21/29) of the nude rats. Endometrial growth was verified in only three animals (14%, 3/21). Extraendometrial growth, however, was found in all animals with tumor take. These observations suggest that the endometrium is comparatively resistant to growth of xenografted human colonic tumor cells. The tumor microcirculation consisted of new vessels, giving morphological evidence that tumor growth is dependent on angiogenesis and not on invasion of preexisting vessels.
Characteristics of CD14 shedding from human monocytes: Evidence for the competition of soluble CD14 (sCD14) with CD14 receptors for lipopolysaccharide (LPS) binding
Authors: ROKITA E. , MENZEL E. J.
Published: August 2009

The accumulation of sCD14 shed from human monocytes in vivo might correlate with other inflammatory parameters and could be of importance in overcoming a sepsis situation. The development of the sCD14 titer in the supernatant of monocyte‐enriched MNC cultures isolated from healthy volunteers was studied utilizing a commercially available sCD14 ELISA. These culture experiments revealed the prolonged liberation of sCD14 into the supernatant during a period of several days. A medium‐exchange schedule of 2–3 days was found to be superior to a longer incubation period with respect to the sCD14 yield. PMA initially enhanced the CD14 shedding slightly, but after a few hours it strongly repressed the process. Such a reduction was also achieved by protein synthesis inhibitors (cycloheximide, actinomycin D). Additionally, we monitored the concentration of sCD14, CRP, IL‐6 and IL‐8 in human sera from healthy persons or patients suffering from severe burn injuries with or without sepsis. Our results indicate that sCD14 is strongly correlated with IL‐6, but not with IL‐8. sCD14 titers were higher in the group of patients with both burn injuries and sepsis. From experiments with monocyte‐enriched MNC cultures isolated from healthy volunteers and medium supplemented with sera containing sCD14 as well as radiolabeled LPS, we conclude that the enhanced shedding of CD14 in vivo during sepsis is probably not able to reduce the binding of LPS to monocytes.
A population‐based case‐control study of canine mammary tumours and clinical use of medroxyprogesterone acetate
Authors: STØOVRING MERETE , MOE LARS , GLATTRE EYSTEIN
Published: August 2009

We investigated whether or not an association could be found between mammary tumours and prior clinical use of medroxyprogesterone acetate (MPA) in bitches. A population‐based retrospective agematched case‐control study was designed based on interviews with the owners of the bitches. The proportion of bitches with diagnosed mammary tumours (group MT+, n = 98) that had received progestin injections was compared with the proportion in a control group without mammary tumours (group MT‐, n=98). In the case group 39%, and in the control group 21% of the bitches had been treated with MPA. A significantly higher number of bitches with mammary tumours had been exposed to progestins, compared with the control group without mammary tumours (odds ratio = 2.32, Chisquare=7.01, p=0.008). Bitches treated clinically with low doses of MPA to avoid oestrus were at a greater risk of developing mammary tumours, the majority of which were histologically malignant (91%).
An in vitro cellular system for generation of AA‐amyloid
Authors: PALM M. , NIELSEN E. HOLM , SVEHAG S.‐E.
Published: August 2009

Different conditions for establishing a cell culture system for generation of AA‐amyloid were investigated. The most effective system was based on peritoneal macrophages from CBA/J mice that had received repeated injections of Hammersten casein, with subsequent cultivation of the cells at high density, high levels of acute phase serum, and neutral pH. Staining with Congo red, thioflavin T, and anti‐AA revealed amyloid‐like structures associated with macrophage clusters. The structures increased in number and size from day 2 to 6 of cell cultivation. The concentration of apoSAA in the culture medium fell markedly in the amyloid‐producing cell cultures, while the SAP concentration was not reduced. The described cell culture system can be useful in studies of the influence of chaperone molecules and other factors on the formation and degradation of amyloid fibrils.
Effect of oral administration of Lactobacillus casei on alloxan‐induced diabetes in mice
Authors: MATSUZAKI TAKESHI , NAGATA YURIKO , KADO SHOUICHI , UCHIDA KAZUMI , HASHIMOTO SHUSUKE , YOKOKURA TERUO
Published: August 2009

The effects of Lactobacillus casei (LC) on the onset of alloxan (AXN)‐induced diabetes in 7‐week‐old BALB/c mice were examined. It was observed that the mice given a diet containing 0.1% or 0.05% LC or orally administered LC showed significantly decreased incidence of diabetes induced by intravenous injection of AXN and that the plasma glucose level was slightly lower than that in the control group. The body weight in the LC‐treated groups was higher than that in the control group, although the food intake weights were almost the same. Pathological analysis revealed that the AXN‐induced disappearance of insulin‐secreting β‐cells in the islets of Langerhans was strongly inhibited in the LC‐treated groups. It was also shown that the serum nitric oxide level was maintained at a normal level in LC‐treated mice, whereas the level in the control group was increased by AXN administration. Taken together, these findings suggest that oral administration of LC to AXN‐treated BALB/c mice contributed to the reduction of diabetes and the increase in plasma glucose level.
Prevention of onset in an insulin‐dependent diabetes mellitus model, NOD mice, by oral feeding of Lactobacillus casei
Authors: MATSUZAKI TAKESHI , NAGATA YURIKO , KADO SHOUICHI , UCHIDA KAZUMI , KATO IKUO , HASHIMOTO SHUSUKE , YOKOKURA TERUO
Published: August 2009

The effects of Lactobacillus casei (LC) on the onset of diabetes in an insulin‐dependent diabetes mellitus model, nonobese diabetic (NOD) mice, were examined. From the age of 4 weeks, female NOD mice were fed a diet of either standard laboratory chow (n= 12) or the same chow containing 0.05% weight heat‐killed cells of LC (n=12), and the onset of diabetes was thereafter recorded. The incidence of diabetes in the control group (10/12) was significantly higher than that in the LC‐treated group (3/12) (p<0.01). Pathological analysis in the LC‐treated group revealed strong inhibition of the disappearance of insulin‐secreting β cells in Langerhans islets caused by autoimmune disease. The proportion of CD45R+ B‐cells in the spleen was increased and that of CD8+ T‐cells in spleen cells was decreased in the LC‐treated group. Analysis of cytokine production revealed lower interferon‐Λ production in the LC‐treated group compared to the control group, while the interleukin (IL)‐2 production was higher. The levels of IL‐4, IL‐5, IL‐6 and IL‐10 in the LC‐treated group were somewhat higher than in the control group. Taken together, these findings clearly demonstrated that oral feeding of LC to NOD mice effectively inhibited the occurrence of diabetes and regulated the host immune responses.
Modification of mononuclear cell function after incubation with albumin‐bound unsaturated fatty acids or soybean oil emulsion
Authors: BØRSUM KJETIL , AKSNES JON , MÜLLER FREDRIK , HAGVE TOR‐ARNE , KIERULF PETER , ROLLAG HALVOR
Published: August 2009

Administration of total parenteral nutrition (TPN) with soybean oil emulsion leads to a linoleic acid enrichment of the plasma membrane that may explain an in vivo activation of mononuclear cells (MNC) seen in our previous studies. Fatty acids from the lipid emulsion may have been accessible to MNC after endocytosis of lipid particles, or by direct uptake of fatty acids after lipoprotein lipase hydrolyzation of the emulsion triglycerides. To resemble the incorporation of fatty acids in vivo, we have modified MNC membrane lipid composition by incubation with different albumin‐bound unsaturated fatty acids (UFA) or soybean oil emulsion. After incubation with albumin‐bound linoleic and oleic acid, the unstimulated release of superoxide anion was unchanged, while zymosan‐stimulated release was 140% (n.s) and 112% (p<0.05) and phorbol‐myristate‐acetate (PMA)‐stimulated release 148% (p<0.05) and 124 % (p<0.05) of controls, respectively. Incubation with other UFAs or emulsion did not change superoxide anion release. Unstimulated lymphocyte proliferation increased 3 to 13‐fold (p<0.05) after incubation with all UFAs compared to controls, while UFA incubation did not change phytohemagglutinin (PHA) or PMA‐stimulated proliferation. Unstimulated lymphocyte proliferation was decreased after incubation with emulsion, while PHA/PMA‐stimulated proliferation was unchanged. Increase in membrane fluidity was detectable only after incubation with emulsion. The increased reactivity may have been caused by changes in the lipid environment surrounding membrane‐bound enzymes important for signal transduction through the plasma membrane.