bluuebunny/crossref_metadata_2025 huggingface dataset:
Killing curve activity of ciprofloxacin is comparable to synergistic effect of β‐lactam‐tobramycin combinations against Haemophilus species endocarditis strains
Authors: WESTH HENRIK , FRIMODT‐MØLLER NIELS , GUTSCHIK ERNÖ , BANGSBORG JETTE
Published: August 2009

Nine Haemophilus species strains, all β‐lactamase negative, isolated from patients with endocarditis were tested in killing curve experiments. Antibiotics used were penicillin, amoxicillin, aztreonam alone and in combination with tobramycin, as well as ciprofloxacin alone. Synergism between β‐lactams and tobramycin with reduction of colony counts to zero was seen after 24 h for H. influenzae, H. parainfluenzae and H. segnis strains. Ciprofloxacin was as effective as β‐lactam‐tobramycin combinations. The H. aphrophilus strain was not killed as effectively as other strains by any of the antibiotics.
Descriptive epidemiology of infections due to thermotolerantCampylobacterspp. in Norway, 1979–1988
Authors: KAPPERUD GEORG , AASEN SIGMUND
Published: August 2009

This report reviews the first ten years ofCampylobactersurveillance in Norway. During 1979–1988, a total of 3,545 isolates of thermotolerantCampylobacterspp. were reported. The isolation rate increased from 1.8 per 100,000 persons per year in 1979 to 13.1 in 1988. The highest isolation rate for both sexes occurred during the first five years of life (31.0 per 100,000). A smaller second peak was detected in the age group 15–24 years (11.1 per 100,000). The male‐to‐female ratio was 1.52:1 for infants less than five years of age, compared with a ratio of 1.35:1 for all ages combined. Thirty‐eight percent of the infections had most probably been acquired abroad. The isolation rate in urban areas (12.4 per 100,000) was over twice that observed in rural agricultural municipalities (5.5 per 100,000). However, this difference was largely due to a higher proportion of imported cases in urban areas, only small variations in isolation rate were observed when imported cases were excluded. The seasonal distribution ofCampylobacterisolates showed a peak during the warm months of the year. Travel activity during summer holidays did not account for this trend, since the summer peak became even more pronounced when imported cases were excluded. A north‐south gradient in the seasonality was observed; when domestic cases were considered, the summer peak became more accentuated with increasing latitude reaching a maximum in subarctic areas. This might be explained by corresponding variations in occurrence of campylobacters in surface water sources.
Capsular polysaccharide is linked to the outer surface of type 6A pneumococcal cell walls
Authors: SØRENSEN UFFE B. SKOV , BLOM JENS
Published: August 2009

The in situ attachment of capsular polysaccharide of type 6A pneumococci was examined by immunoelectron microscopy using anti‐type 6A monoclonal antibody. The result discloses an asymmetrical cross‐section of pneumococcal cell walls because capsular polysaccharides are located on the outer surface of the walls only, in contrast to the cell wall polysaccharide, which has been shown to be located on both surfaces.
Immunohistochemical evaluation of the cytoarchitecture of benign and malignant breast lesions
Authors: SOINI YLERMI , MIETTINEN MARKKU
Published: August 2009

Fifty‐three breast lesions, which had been fixed in formalin and embedded in paraffin, were immunohistochemically analyzed with monoclonal antibodies to cytokeratin subtypes 1, 5, 10, 14 (34BE12), muscle‐specific actins (HHF35) and antiserum to S100 protein, all of which have been used as markers for myoepithelial cells. With these antibodies, a continuous myoepithelial cell layer could generally be seen around the benign ducts and acini. In in situ carcinomas, such a layer could still be observed, though it was usually discontinuous and sometimes absent. In infiltrating carcinomas, no myoepithelial cell layer could be observed. In intraductal hyperplasias, scattered HHF35, 34BE12 and S100‐positive cells could be seen amongst the proliferating intraductal cells. In in situ and infiltrating carcinomas, however, such cells could also be observed. This was seen especially with antibodies 34BE12 and S100, and to a lesser extent also with HHF35. Morphologically these cells seemed to belong to the malignant cell population. Although myoepithelial cell preservation is an important morphological parameter in the histological evaluation of breast lesions, the results suggest that the myoepithelial cell markers 34BE12, HHF35 and S100 cannot be used in the differential diagnosis between benign and malignant breast lesions in a straightforward manner. This is because in situ carcinomas have a more or less preserved myoepithelial cell layer, and because many infiltrating and in situ carcinomas contain a subpopulation of neoplastic cells expressing these markers, possibly signifying myoepithelial cell differentiation.
Immunohistochemical study of 158 lung carcinomas
Authors: JOHANSSON LEIF , ANDERSSON CHRISTINA , ALBIN MARIA
Published: August 2009

Lung carcinomas were studied immunohistochemically and the results were related to type of tissue sample (bronchoscopic biopsies, surgical specimens, autopsies). All cytokeratins (CAM 5.2, PKK‐1, AE1/AE3) reacted with virtually all adenocarcinomas, most squamous, and 65% of the large cell carcinomas, while CAM 5.2 was most efficient with the small cell carcinomas. CEA stained 33% and 60% of the small and large cell carcinomas, respectively, most adenocarcinomas, and 84% of the squamous cell carcinomas, among which staining decreased with dedifferentiation and was often focal. EMA reacted with 90%, and NSE with 20% of all histological types. There was no staining for NF. All antibodies, except EMA, were more efficient with surgical specimens. Our study implies that the cytokeratins we used work better with surgical material, but are generally comparable to mono‐specific cytokeratin antibodies. Also, EMA is a reliable marker for epithelial differentiation with all types of tissue samples. Moreover, CEA negativity in several poorly differentiated lung carcinomas might have implications in the differential diagnosis against pleural mesothelioma.
16. Malignant tumours of the stomach
Authors: NIKULÄSSON SIGFÄS , HALLGRÍMSSON JÓNAS , TULINIUS HRAFN , SIGVALDASON HELGI , ÓLAFSDÓTTIR GUDRÍDUR
Published: August 2009

Iceland is one of the high‐risk countries for stomach cancer. During the period 1955‐84 the incidence declined from 76 to 28 per 105p.a. for males and from 30 to 12 for females. Tissue material from the primary site in 978 males and 448 females was available for histological typing. By the WHO classification tubular carcinoma was most frequent in both sexes, 66% in males and 63% in females, and signet‐ring carcinoma second, 13% in males and 16% in females. By the Laurén classification in males 78.1% were intestinal and 16.5% diffuse carcinomas, and in females 73.1% were intestinal and 20.7% diffuse carcinomas. The decline in stomach cancer in Icelanders has mostly affected the intestinal type of tumour (Laurén) and the tubular type of tumour (WHO). Diffuse type tumours (Laurén) have declined slightly. This supports the theory that intestinal carcinomas are more influenced by environmental and especially dietary factors, and that diffuse carcinomas are more influenced by other as yet unknown factors. For epidemiological studies both histological classifications have their value, the WHO especially in that it is based on standard histopathological criteria and the Laurén especially in that it only includes two tumour types. The WHO classification can roughly be transcribed to the Laurén classification as tubular, mucinous and papillary carcinomas fall into the group of intestinal tumours, and signet‐ring and more than half of undifferentiated carcinomas into the group of diffuse tumours.
Influence of muramyl dipeptide on renal candidiasis in genetically distinct mice
Authors: MARQUIS GABRIEL A. , BOUSHIRA MICHELE , RUSSO PIERRE , MONTPLAISIR SERGE
Published: August 2009

Susceptible (DBA/2) and resistant (C57BL/6) mice were inoculated intravenously with Candida albicans to evaluate the effect of a four‐day prophylaxis with muramyl dipeptide (MDP) on the renal burden of organisms during the first week after infection. In sham‐treated DBA/2 mice injected with 8 times 104 candida cells, renal CFU (LOG10, ± SEM) on days 1, 4 and 7 after infection were found to average 5.050 ± 0.109, 4.882 ± 0.133 and 5.482 ± 0.245. In sham‐treated C57BL/6 mice injected with 2 times 105 candida cells, renal CFU on days 1, 4 and 7 reached only 3.610 ± 0.118, 3.404 ± 0.107 and 4.176 ± 0.580. MDP‐treated DBA/2 mice achieved significant reduction in CFU of C. albicans on day 1 (1.3 log units) and day 4 (0.6 log unit), while MDP‐treated C57BL/6 mice had significant reduction in CFU of C. albicans only on day 1 (0.6 log unit) after infection. Sham‐treated mice of both strains had a 28.6 to 30% increase in kidney weights on day 4 only, a transient change not seen in MDP‐treated mice. Histopathological examination on days 8, 15 and 21 after infection revealed a higher incidence of renal papillary necrosis in DBA/2 mice than C57BL/6 mice (approximately 70%vs 10%). The incidence of granulomas and of chronic interstitial inflammation was much higher in MDP‐treated mice. We conclude that the genetic makeup of the host influences the potential effectiveness of MDP as a biological response modifier.
Expression of proliferative cell nuclear antigen (PCNA) in urinary bladder carcinoma. Evaluation of antigen retrieval methods
Authors: MALMSTRÖM PER‐UNO , WESTER KENNETH , VASKO JANOS , BUSCH CHRISTER
Published: August 2009

Proliferative cell nuclear antigen (PCNA) expression was analyzed in formalin‐fixed and paraffin‐embedded specimens from patients with urinary bladder cancer using three different anti‐PCNA monoclonal antibodies. In 20 recent cases a positive correlation was found between the extent and intensity of PCNA staining and grade of malignancy. In 95 specimens, three to six years old, extensive positive staining was detected in 15 and 23% of grade 2B and 3–4 tumors, respectively. No equivalent staining was found in the grade 1 and 2A tumors. In material more than six years old, a remarkably weak staining was observed regardless of grade. Similarly, in a test of archival material of tonsils a very weak immuno‐reactivity was found as compared with fresh material. However, antigen retrieval by microwave heating of the tissue sections was possible in the majority of all cases, and the difference in extent and intensity of the staining between low and high grade tumors remained.
Macrophage association of polyomavirus in progressive multifocal leukoencephalopathy: an immunohistochemical and ultrastructural study
Authors: MESQUITA ROBERTO , PARRAVICINI CARLO , BJÖRKHOLM MAGNUS , EKMAN MARIANNE , BIBERFELD PETER
Published: August 2009

Progressive multifocal leukoencephalopathy (PML) in a patient following autologous bone marrow transplantation for a non‐Hodgkin's centroblastic lymphoma was studied by immunohistochemistry and transmission electron microscopy. Our observations indicate that a large amount of polyomavirus, most probably JC virus, is taken up and segregated within vacuoles of macrophages by phagocytosis. A relevant role of macrophages in the pathogenesis of PML is emphasized.
A T‐helper cell epitope overlaps a major B‐cell epitope in human papillomavirus type 18 E2 protein
Authors: LEHTINEN MATTI , STELLATO GIOVANNI , HYÖTY HEIKKI , NIEMINEN PEKKA , VESTERINEN ERVO , PAAVONEN JORMA
Published: August 2009

Cultivated CD4+ T‐helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T‐cell epitopes, and is located at the beginning of an 11‐amino acid‐long A‐helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T‐helper cell epitope and a B‐cell epitope) overlap in the HPV 18 E2.
Expression of cytokeratin and erbB‐2 oncoprotein in Paget's disease of the nipple
Authors: HAERSLEV TORBEN , JACOBSEN CRETE KRAG
Published: August 2009

The occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB‐2 oncoprotein was investigated in twenty‐eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin‐fixed, paraffin‐embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB‐2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB‐2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB‐2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas.
Comparison of the effects of methoxysuccinyl‐Ala‐Ala‐Pro‐Val‐chloromethyl ketone‐inhibited neutrophil elastase with the effects of its naturally occurring mutationally inactivated homologue (HBP) on fibroblasts and monocytes in vitro
Authors: ØSTERGAARD E. , NIELSEN O. F. , FLODGAARD H.
Published: August 2009

The mature neutrophils in the circulation contain, besides the different proteases known for a long time, a recently discovered proteolytically inactive elastase homologue (HBP/CAP37/azurocidin). This homologue, which we have named HBP due to its strong affinity to heparin, is a chemoattractant for monocytes and has been shown to induce reversible detachment and contraction when added to monolayers of endothelial cells or fibroblasts. HBP may therefore play a pivotal role in leukocyte migration in response to inflammation. In this report a comparison of CH3O‐Suc‐Ala‐Ala‐Pro‐Val‐CH2Cl‐inhibited elastase with HBP, its naturally occurring homologue selectively mutated in active serine and histidine, reveals that homotypic aggregation of monocytes and contraction of fibroblasts is specific for HBP. HBP induces thrombospondin secretion from monocytes four times as efficiently as the inhibited elastase, and the same molecule was found unable to compete for a specific saturable binding of HBP to monocytes with an apparent KD of 3 times 10‐8M.
Remnant kidney pathology after five‐sixth nephrectomy in rat
Authors: FARAJ A. H. , MORLEY A. R.
Published: August 2009

In Wistar male rats, hypertension was induced by 5/6 nephrectomy (5/6N). Body weight, blood pressure measurements, morphological and biochemical changes were followed (at four weekly intervals) for 12 weeks after 5/6N. Renal function was assessed by daily total urinary protein (TUP), plasma creatinine concentration [(Cr)p] and creatinine clearance rate. Plasma renin concentration (PRC), aldosterone concentration and erythrocyte content of sodium [Na]E and potassium [K]E were also investigated. Significant increases in systolic blood pressure (SBP), TUP, [(Cr)p] and [Na]E occurred after 4, 8, and 12 weeks of 5/6N. Progressive glomerulosclerosis (GSC), tubular atrophy and interstitial fibrosis were observed. Positive correlations were found between GSC and SBP and TUP. Positive correlations were also found between SBP and [Na]E and [(Cr)P]. PRC was not increased and showed no correlation with SBP. It is concluded that 5/6N produced hypertension associated with a series of morphological and biochemical alterations in kidney structure and function. In this model, mechanisms other than the renin‐angiotensin system may be involved.
Fetal antigen 2: An amniotic protein identified as the aminopropeptide of the α1 chain of human procollagen type I
Authors: TEISNER B. , RASMUSSEN H. BOJE , HØJRUP P. , YDE‐ANDERSEN E. , SKJØDT K.
Published: August 2009

Fetal antigen (FA2) was purified from second trimester human amniotic fluid by immunospecific chromatography, gel filtration and reversed‐phase chromatography. Gel filtration revealed two molecular forms of FA2 eluting at volumes corresponding to an Mr of approximately 100 kDa and 30 kDa. SDS‐PAGE analysis gave an Mr= 27 kDa under reducing and non‐reducing conditions for both forms, whereas the exact Mr determined by mass spectrometry was 14,343±3 Da. FA2 was N‐terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity with the aminopropeptide of the α1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio‐iodination (iodogen and chloramine‐T), FA2 lost its immunoreactivity. An antigen which cross‐reacted with polyclonal rabbit anti‐human FA2 was demonstrated in fetal calf serum. Gel filtration with analysis of fractions by inhibition ELISA showed that the bovine homologue was present in the same molecular forms as those in human amniotic fluid, and immunohistochemical analysis with anti‐human FA2 showed that its distribution in bovine skin was identical to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the α1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans.
In vitro antimicrobial susceptibility testing of rapidly growing mycobacteria using the tablet diffusion method: resistance pattern of Norwegian Mycobacterium fortuitum and Mycobacterium chelonae isolates
Authors: HOEL TERJE , CASALS JOSÉ B. , ENG JAN
Published: August 2009

Thirty‐one Norwegian clinical isolates of rapidly growing mycobacteria classified as Runyon's group IV, including 20 Mycobacterium fortuitum and 11 Mycobacterium chelonae strains, were found resistant to a majority of tuberculostatic agents. Minimal inhibitory concentration (MIC) was determined for twelve other antimicrobial agents: amikacin, tobramycin, streptomycin, cefoxitin, imipenem, norfloxacin, ciprofloxacin, doxycycline, erythromycin, fusidic acid, co‐trimoxazole and capreomycin. The agar plate dilution method was employed and compared with the agar tablet diffusion method. Regression lines were established correlating MIC values and inhibition zones. The agar tablet diffusion method was found to be a simple and useful method for testing antimicrobial susceptibilities of M. fortuitum and M. chelonae, and a good correlation between MIC values and zone sizes with twelve antimicrobial agents was revealed. Correlation coefficients for most of these antimicrobial agents were around ‐0.90. M. chelonae was generally more resistant than M. fortuitum. Four antimicrobial agents, capreomycin, norfloxacin, ciprofloxacin and amikacin, showed differences between M. fortuitum and M. chelonae large enough to allow the zone diameter to be used diagnostically.
Induction of oxidative burst response in human neutrophils by adherent Staphylococci
Authors: RIBER ULLA , ESPERSEN FRANK , SKINHØJ PETER , KHARAZMI ARSALAN
Published: August 2009

The ability of staphylococci adherent to silicone surfaces to induce superoxide anion (O2−) production by polymorphonuclear leukocytes (PMNs) was investigated and compared with the same activity induced by planktonic bacteria. The responses to Staphylococcus aureus strain E 2371 and Staphylococcus epidermidis strain ATCC 14990 were compared. The staphylococci were allowed to adhere to silicone catheters for 2 h at 37°C. After opsonization of adherent bacteria in 30% human AB‐positive serum, the induction of superoxide anion production by PMNs was measured in a cytochrome C reduction assay. Both bacterial strains, when adhered to the surfaces, were able to induce superoxide anion production by PMNs to about the same extent. Comparing adherent and planktonic bacteria with these two bacterial strains, it was found that planktonic S. epidermidis induced one to three times higher superoxide anion production than the adherent bacteria, whereas planktonic S. aureus induced four to seven times higher superoxide anion production than the adherent bacteria. Interstrain variation between the response to adherent and planktonic staphylococci was found. The lower phagocytic response to adherent staphylococci as compared to the response to planktonic organisms may interfere with the killing process and thereby contribute to poor clearance of these bacteria when adherent to foreign bodies such as catheters.
Remnant kidney pathology after five‐sixth nephrectomy in rat
Authors: FARAJ A. H. , MORLEY A. R.
Published: August 2009

In Wistar male rats, hypertension was induced by 5/6 nephrectomy (5/6N). Electron microscopy revealed an increase in the number of epithelial cells on the Bowman's capsule during the early stages (4 weeks). After 8 and 12 weeks, frequent adhesion was observed between the glomerular tuft and Bowman's capsule. The abnormal podocytes showed nuclear irregularities and distortions. Characteristic foot process fusion formed cytoplasmic plates. There was a considerable increase in mesangial matrix and cells. No immune deposits or breaks in the glomerular basement membrane were observed. In the endothelial cells, the fenestration disappeared in sclerosed glomeruli. Some capillary loops were obliterated by fibrin, macrophages and foam cells. These findings combined with our previous light microscopy and immunofluorescent observations suggest a non‐immunogenic glomerular sclerosis.
Hypothyroidism and anti‐endothelial cell antibodies
Authors: WANGEL ANDERS G. , KONTIAINEN SIRKKA , MELAMIES LIISA , WEBER TEDDY
Published: August 2009

Because of our previous demonstration of anti‐endothelial cell antibodies (AECA) in patients with insulin‐dependent diabetes mellitus and their association, in this condition, with thyroid disease, we sought these antibodies in patients with suspected thyroid dysfunction using an enzyme immunoassay with human umbilical vein endothelial cells as the substrate. AECA were found in 5/120 (4.2%) patients with normal and 15/97 (15.4%) with abnormal thyroid function. The increased prevalence in the latter group was due to a highly significant association between the presence of AECA and raised levels of TSH. We conclude that a highly significant correlation exists between the levels of AECA and TSH, but not between those of AECA and fT4. Patients with hypothyroidism as defined by high levels of TSH have AECA significantly more often than patients with low or normal TSH (22.2% versus 2.8% and 5.8%).
Effect of ambient temperature on phenotype and functions of professional phagocytes of athymic nude mice
Authors: VETVICKA V. , HOLUB M. , HOUSTEK J.
Published: August 2009

Cytofluorometric analysis of surface marker expression was performed on myeloid cells isolated from bone marrow, spleen and lymph nodes of nude mice and nu/+ and +/+ mice (haired controls) exposed for various time periods to ambient temperature of 22°C or 28°C. A rise in the proportion of cells bearing macrophage markers (MAC‐1, MAC‐3 and F4/80) in the spleen and of FcR+ cells in all tissues tested was found in 22°C‐exposed nudes with high nonshivering thermogenesis. Numbers of MAC‐1+ macrophages and actively phagocytic cells increased also in peritoneal exudates. There was a conspicuous predominance of large macrophages in the exudates and the specific markers decreased in density on their surface. Ia expression declined in all tissues tested with the length of exposure to cold. In the granulocytic series (BP‐2+ cells), there was a decrease in the bone marrow and lymph nodes and an increase in the spleen and circulation, which suggested an enhanced mobilization and increased production at extramedullary sites in cold‐exposed nude mice. The changes in haired mice were negligible.
Cleavage of tumor necrosis factor‐α by Legionella exoprotease
Authors: HELL W. , ESSIG A. , BOHNET S. , GATERMANN S. , MARRE R.
Published: August 2009

The role of the major secretory protein of Legionella pneumophila, a zinc protease, in Legionella infection is not known. Since an important step of the host reaction in Legionnaires' disease is the production of tumor necrosis factor‐α (TNF‐α) by alveolar macrophages, we studied the interaction of Legionella protease and U‐937 cells with respect to TNF‐α. The Legionella protease was purified by fractionated precipitation, gel filtration and hydrophobic interaction chromatography. The purified enzyme was added to U‐937 cells, a promyelocytic cell line. In the supernatants of PMA‐treated U‐937 cells we found low concentrations of TNF‐α after incubation with protease. Therefore we pursued the hypothesis of direct enzymatic degradation of TNF‐α by Legionella protease. Enzymatic cleavage of TNF‐α was proven by SDS‐PAGE, ELISA and TNF‐α bioassay with L‐929 cells. The degradation of TNF‐α by the Legionella protease was shown in all three systems. Enzymatic degradation of TNF‐α might be important for the pathogenesis of Legionnaires' disease.
Adherence and surface properties of buoyant density subpopulations of group B streptococci, type III
Authors: GRANLUND‐EDSTEDT MARGARETA , SELLIN MATS , HOLM ANDERS , HÅKANSSON STELLAN
Published: August 2009

From clinical isolates of group B streptococci, buoyant density subpopulations with variable amounts of type‐specific polysaccharide can be derived. The ability of these subpopulations to adhere to vaginal epithelial cells and to glass was assessed by using [3H]‐labeled bacteria. Subpopulations with no or minute amounts of capsule showed good adherence capacity and a hydrophobic cell surface. In contrast, a large capsule made the bacteria less adherent and rendered their surface hydrophilic. A negative cell surface charge, judged by determination of the z‐potential, was directly related to the amount of capsule. Proteinase K treatment of less encapsulated variants significantly decreased the cell hydrophobicity. The ability of a GBS strain to express different surface characteristics may be a mechanism for adaptation to environmental changes, and may thereby contribute to the pathogenicity of GBS.
CD4 and CD8 expression of large granular lymphocytes after bone marrow transplantation and its effect on lymphocyte CD4/CD8 ratio
Authors: LESKINEN RITVA
Published: August 2009

Peripheral blood lymphocytes from 33 allogeneic bone marrow transplant recipients were studied. The number of large granular lymphocytes (LGL) in circulation increased rapidly after bone marrow transplantation (BMT). Their proportion of lymphoid cells exceeded 40% during the first month and was highest, 57%, one to three months after BMT. The CD4 and CD8 expression of LGL differed at different times after BMT. The CD4 positivity decreased from the pre‐BMT value of 9.2 ± 3.3% to 2.5 ± 0.3% (p<0.05) at 31–90 days post‐BMT. The expression of CD8, on the other hand, was lowest during the first 30 days, 17.1 ± 1.7%, and increased thereafter to reach its highest level, 49.2 ± 4.3%, after three months. The low CD4 and high CD8 positivity together with a high proportion of LGL in lymphoid cells after the first month post‐BMT inverted the CD4/CD8 ratio of lymphocytes for more than a year after BMT.
Glycosylation of the major human Pneumocystis carinii surface antigen
Authors: LUNDGREN BETTINA , KOCH CLAUS , MATHIESEN LARS , NIELSEN JENS O. , HANSEN JOHN‐ERIK S.
Published: August 2009

It has recently been shown that the major rat P. carinii surface antigen is important for initial host‐organism attachment, possibly through binding to fibronectin, mannose‐binding protein, or surfactant protein A. Since a carbohydrate/lectin interaction may be involved in adhesion, we undertook this study to characterize the glycosylation of the major human P. carinii surface glycoprotein (gp95). We have used purified gp95 as a source of antigen, and in lectin binding and deglycosylation studies it was found that approximately 9% of gp95 consists of N‐linked carbohydrates of mainly high‐mannose and bisected complex‐type glycans. Using a polyclonal antibody raised against purified gp95 and crossed affinoimmunoelectrophoresis and the lectins Con A and WGA, gp95 exhibited carbohydrate‐dependent microheterogeneity. We therefore suggest that gp95 is composed of subtypes which differ in N‐linked glycosylation.
Homology between cryptic plasmid from Neisseria gonorrhoeae and genomic DNA from Neisseria meningitidis
Authors: GRIMHOLT UNNI , OLSAKER INGRID , AALEN REIDUNN , GUNDERSEN WENCHE BLIX
Published: August 2009

The human pathogenic Neisseria species N. gonorrhoeae and N. meningitidis are closely related. In contrast to N. meningitidis, however, almost all clinical isolates of N. gonorrhoeae harbour a pheno‐typically cryptic plasmid. In some gonococcal strains regions of the cryptic plasmid have been found in the gonococcal genome and it has been suggested that large segments of the cryptic plasmid can be integrated into the gonococcal chromosome of both plasmid‐bearing and plasmid‐free strains. Here we report homology between parts of the cryptic gonococcal plasmid and genomic DNA from four different N. meningitidis strains from systemic disease isolates in which no plasmids have been found with the applied methods. Serogroup B strains, causing many of the cases of meningococcal disease in Norway, hybridized strongly to the cryptic plasmid probe, in contrast to serogroup A and C strains. Clones hybridizing to the cryptic plasmid were isolated from a meningococcal genomic Λ EMBL3 DNA library and characterized by restriction mapping. When using one such clone as a probe the parts of the cryptic plasmid showing homology to the genomic meningococcal DNA were confined to two small separate regions of 420 and 88 bp.
Location of plasminogen activator (PA) and PA inhibitor in human colorectal adenocarcinomas
Authors: BUØ LAILA , LYBERG TORSTEIN , JØRGENSEN LARS , JOHANSEN HARALD T. , AASEN ANSGAR O.
Published: August 2009

Both the coagulation and fibrinolytic cascades generate proteolytic enzymes which appear to be essential for tumor invasion. In the present investigation adenocarcinomas and normal colon from 14 patients with colorectal cancer were studied by immunohistochemistry. The most striking observation was an enrichment of plasminogen activator inhibitor in the tumor tissue, whereas no such immunoreactivity was detected in the biopsies of normal colon. The tumor‐host interface was characterized by a massive accumulation of inflammatory cells, macrophages and T lymphocytes. In this area fibrin(ogen) immunoreactivity as a sign of local activation of the coagulation cascade was also seen. The transition zone between the tumor and normal tissue was furthermore characterized by a marked enrichment of urokinase plasminogen activator immunoreactivity. The study strongly indicates that proteases and inhibitors of the fibrinolytic system may be of great importance in tumor invasion.
Epithelium‐mesenchyme interconversion as example of epithelial plasticity
Authors: BOYER BRIGITTE , THIERY JEAN PAUL
Published: August 2009

This review focuses on epithelium‐mesenchymal transitions (EMT), defined as dynamic cell restructurations changing the epithelial state of differentiation into a mesenchymal phenotype. These transitions, known to occur during embryogenesis are also involved during some pathological events of adult life, such as wound repair and metastasis of cancer cells. Numerous studies of embryonic EMTs, found during some morphogenetic processes, have stressed the importance of intercellular and cell‐matrix adhesive interactions as key elements regulating cell dissociation and acquisition of cell motility. On the other hand, in vitro studies indicate that growth factors, growth‐factor related molecules and extracellular matrix components are involved in initiation of EMT. Therefore, the cellular targets of EMT‐inducing molecules are likely to include molecules participating in cell adhesion systems.
Distribution of presumptive pathogenicity factors among beta‐hemolytic streptococci isolated from Ethiopia
Authors: TEWODROS WEZENET , KRONVALL GÖRAN
Published: August 2009

Beta‐hemolytic streptococci are known to bind several mammalian proteins, which are presumed to be important in pathogenicity. The distribution of such binding structures was examined for mouse albumin, human serum IgA, human IgG, human fibrinogen, and human plasminogen. A total of 218 group A beta‐hemolytic streptococci (GAS) were studied: 5 isolates from children with acute rheumatic fever (ARF), 18 from acute post‐streptococcal glomerulonephritis (APSGN), 57 from tonsillitis, 52 from skin infections, and 86 from healthy carriers. Sixty‐eight Streptococcus equisimilis and 20 group G streptococci were also included. Most of the S. equisimilis (60/68) and group G (14/20) were obtained from apparently healthy carriers. The results were evaluated with respect to T type, serum opacity reaction (SOR), site of isolation, and disease type. No direct correlation was detected between the protein‐binding structures studied. There was no apparent correlation between any particular protein‐binding structure and specific T type. Albumin‐binding and IgA‐binding activities were inversely correlated among skin and nephritis GAS isolates. A strong correlation was demonstrated between IgA‐binding activity and SOR production, while albumin‐binding activity correlated with SOR‐negative strains. Albumin‐binding levels in isolates from ARF, APSGN and tonsillitis were significantly higher than in isolates from healthy carriers (P< 0.001). A higher albumin‐binding capacity was shown in skin isolates from APSGN than in isolates from impetigo (P< 0.001).
Experimental Yersinia enterocolitica infection in rodents: A model for human yersiniosis
Authors: HEESEMANN J. , GAEDE K. , AUTENRIETH I. B.
Published: August 2009

Yersinia enterocolitica infection in humans causes a broad spectrum of diseases ranging from acute bowel disease to extraintestinal manifestations such as reactive arthritis, erythema nodosum and uveitis. During the last decade a fascinating part of the molecular biology of the pathogenicity of human pathogenic Yersinia species has been unraveled. Pathogenicity factors such as protein tyrosine phosphatase, protein kinase, thrombin‐ and collagen‐binding factors have been identified and characterized on the molecular level. In contrast to many animal models for human enteropathogenic microorganisms, experimental Y. enterocolitica infection in rodents resembles yersiniosis in humans and thus offers extraordinary opportunities to study the sequential steps of the infectious process. Rabbits are suitable animals in which to study Yersinia‐induced enteritis (enterotoxin‐mediated) and the humoral immune response after oral infection. The role of Peyer's patches (PP) in the entry of enteropathogenic Yersinia species has been elucidated in mice and rabbits. M cells are probably the primary target cells of invading Yersiniae. Surprisingly, after penetration of the mucosal epithelial cell layer Yersinia bacilli were visualized to be exclusively extracellular in PP tissue. Obviously neutrophils within PP were unable to phagocytize the invading microorganisms. Presently, it is not clear how the microorganisms disseminate from PP into lymph nodes, spleen, liver and lung of mice where they form abscesses and granuloma‐like lesions. Immunohistologically the involvement of macrophages and T cells could be demonstrated in Yersinia‐induced lesions of mice. Direct evidence for the role of T cells and cytokine‐activated macrophages in the host defense reaction against a primary Yersinia infection in mice could be obtained from experiments including adoptive transfer of Yersinia‐specific T cells and in vivo neutralization of TNF‐alpha and IFN‐gamma. The experimental rat model turned out to be a suitable model for studying Yersinia‐induced aseptic arthritis. Lewis‐and SHR rats proved to be arthritis‐susceptible. Arthritogenicity of Yersinia for rats appeared to be restricted to Y. enterocolitica of serotype 08 and correlated with the virulence potential of this serotype. Surprisingly, expression of YadA, the collagen‐binding factor, was not necessary for arthritis induction. A close association between both susceptibility to arthritis induction and Yersinia infection could be demonstrated in various rat strains. Depletion of alpha/beta T‐cell receptor (αβ‐TCR)‐positive T cells by treatment with αβ‐TCR‐specific antibody revealed that T cells were required for clearance of the pathogen. However, in contrast to e.g. adjuvant arthritis, Yersinia‐induced arthritis in Lewis rats was not affected by T‐cell depletion. Thus, we expect significant differences between the pathomechanisms of Yersinia‐triggered arthritis and antigen‐induced arthritis in Lewis rats.
Pathological hepatic accumulation of long‐chain n‐alkanes (“paraffin liver”) in cows (Harbitz and Föling, 1940). An overlooked discovery*,**
Authors: HALSE KARL , SOLHEIM EINAR , NORDSTOGA KNUT
Published: August 2009

About 50 years ago crystalline deposits of a substance representing approximately 7 per cent wet tissue weight and believed to be hentriacontane or a mixture of similar long‐chain n‐alkanes (30–34 carbon atoms) were detected in two discoloured and swollen cow livers. Stored purified extracts from these livers were recently reanalysed using gas chromatography and mass spectrometry. They were found to contain about equal amounts of nonacosane and hentriacontane with a small admixture of tritriacontane and other long carbon‐chain alkanes. On the basis of histological findings, five additional cases of “paraffin liver” in cows have been recorded. In the discussion comparison is made with the only known case of a similar disorder in a human, visceral accumulation of the same three alkanes as in the cows, which was recently described in the literature. Concerning the origin of the deposits, importance is given to the fact that the long‐chain alkanes with odd carbon numbers identified both in cattle and man predominate in the cuticular waxes of many dietary plants. The very large quantities of the abnormal substance in the cow livers indicate low toxicity, and evidently accumulation over long periods of time.
The SCID‐ra mouse: Rat T‐cell differentiation in the severe combined immunodeficient mouse
Authors: DE HEER C. , VERLAAN A. P. J. , PENNINKS A. H. , SCHUURMAN H.‐J. , VAN LOVEREN H.
Published: August 2009

The SCID‐hu mouse model offers the possibility to study the human thymus in vivo in an isolated xenogeneic environment. Whilst studying the toxicology of the human thymus using the SCID‐hu model, a “control” model to test for differences in toxicokinetics due to the different localization of the thymus is desirable when SCID‐hu data have to be extrapolated to the normal human situation. For this reason, SCID‐ra mice were constructed by implanting rat fetal or postnatal thymus and liver explants under the renal capsule of severe combined immunodeficient (SCID) mice. Implantation of rat fetal thymus in combination with fetal liver resulted in thymus grafts with a histological appearance that was virtually identical to that of normal age‐matched rat thymus. T cells of rat origin were found in the circulating blood and lymphoid organs of the recipient mice. After implantation of postnatal thymus and liver, the thymus grafts showed a dysplastic morphology. These grafts were devoid of thymocytes and consisted mainly of thymic microenvironmental components and large numbers of thymic macrophages. Some SCID‐ra mice showed signs of graft‐versus‐host (GVH) reactions in the skin. The incidence of GVH reactions was higher with increasing developmental stage of the donor material used for implantation.
Cervical cancers in Greenlandic women diagnosed after negative results on cervical cytology: Perspectives in a high‐risk population
Authors: NIELSEN NILS HØJGAARD , JENSEN HENNING
Published: August 2009

A total of 160 indigenous Greenlandic women had incident cervical cancer diagnosed during 1976–1991, and 41 of these women (27%) had had at least one negative smear reported during the 10 years preceding the diagnosis of cancer. Thirteen patients had previously had abnormalities of the cervix. Of the remaining 28 patients, 17 had so‐called interval cancer diagnosed within three years after a negative smear result. In seven of these cases, representing 4% of all incident cancers during the period, there had previously been two or more negative smears. Suboptimal sampling of negative smears was suggested in roughly one out of two interval cancers. The results suggest that rapid biological development of cervical cancer is infrequent among Greenlandic females and that efforts should be aimed at increasing the smear test's sensitivity and providing a better follow‐up of women with cervical abnormalities rather than shortening the three‐year rescreening interval.
Acute kidney graft rejection
Authors: Andersen CLAUS B. , Ladefoged SØREN D. , Larsen SVEND
Published: August 2009

Serial biopsies from 41 consecutive renal allotransplanted patients were evaluated in order to obtain pretransplant data as well as information on well‐functioning and acutely rejecting grafts. Each patient served as his own control. Thirty‐five patients were followed according to the schedule which included biopsy prior to transplantation, shortly after opening of reanastomosis, at least once postoperatively (days 7–10), and furthermore whenever clinically indicated. The morphological evaluation was in each case combined with immunofluorescence (to detect immunoglobulins and complement fractions) and immunohistochemistry with a wide panel of monoclonal antibodies for T cells (CD2, CD3, CD4, CD8, γφ), B cells (CD20, CD22), macrophages (CD68, MAC387) NK cells (leu‐7, CD 16), activation markers (IL‐2‐R, Ki‐67, transferrin‐R), MHC antigens (HLA‐ABC, HLA‐DR), adhesion molecules (ICAM‐1, VCAM‐1, ELAM‐1, PADGEM, VLA‐4, LFA‐1 α/β), and growth factors (EGF, TGF‐α, EGF‐R). When 132 biopsies and 10 failed allografts were examined, no specific morphological or immunohistological parameter predictive of rejection or graft outcome could be found. Morphology in follow‐up biopsies from non‐rejecting and rejecting patients revealed a continuum of inflammatory changes, and several non‐rejecting cases demonstrated cellular inflammatory infiltrates which could not be discriminated from those seen in acute rejection. Of the patients 44% had acute rejection accompanied by increased infiltration of T cells and macrophages showing enhanced IL‐2‐R expression, increased tubular and endothelial staining for MHC class II, ICAM‐1, and VCAM‐1, and strong leukocytic expression of VLA‐4 and LFA‐1 α/β.
Redistribution of granulocytes in patients after major surgical stress
Authors: Toft P. , TØNnesen E. , Helbo‐Hansen H. S. , Lillevang S. T. , Rasmussen J. W. , Christensen N. J.
Published: August 2009

Major surgery induces a stress response characterized by granulocytosis in peripheral blood, and increased secretion of adrenaline and Cortisol. The purpose of this study was to investigate the redistribution of granulocytes in response to major surgical stress. Granulocytes were isolated from eight surgical patients and eight healthy volunteers, labelled with Indium‐lll‐tropolone, and reinjected. The distribution of granulocytes was imaged with a gamma camera and calculated by an interfaced computer before surgery and at 2, 4 and 6 h after the end of surgery. The volunteers served as a control group. In the hours after surgery the radioactivity of the area around the surgical field increased to 410.7% of initial values, while the radioactivity of the spleen decreased to 77.5%. In conclusion, the spleen constitutes a readily mobilizable source of granulocytes. This in vivo model demonstrates pronounced postoperative efflux of granulocytes to the area around the surgical field within hours.
Intravenous Helicobacter pylori induces low levels of TNF‐α and IL‐1α in a murine model
Authors: WadstrÖM T. , Rydberg J. , Rozalska B. , Lelwala‐Guruge J.
Published: August 2009

A murine model for testing cytokine production stimulated by Helicobacter pylori is described. H. pylori induced significantly lower levels of TNF‐a and IL‐la compared to Escherichia coli or Pseudo‐monas aeruginosa when injected intravenously. The mean TNF‐a concentration in serum during 6 h after stimulation with H. pylori was 0.2 ng/ml, whereas E. coli induced 4.7 ng/ml and P. aeruginosa 6.0 ng/ml. This was not explained by rapid elimination of H. pylori as bacteria were present for at least 3 h in the blood. The difference in cytokine induction may be a reflection of the bacteria's different biological qualities. E. coli and P. aeruginosa are both capable of causing systemic disease, whereas H. pylori causes only a local, often low grade, inflammation in the gastric mucosa.
Serine‐stretch protein (SERP) of Plasmodium falciparum corresponds to the exoantigen Ag2, a target of antibodies associated with protection against malaria
Authors: Jakobsen P. H. , Hundt E. , Hansen M. B. , Knapp B.
Published: August 2009

A mixture of Plasmodium falciparum exoantigens inducing lymphocyte activation and cytokine production was shown to contain the malaria vaccine candidate, the serine‐stretch protein. This protein was shown serologically to correspond to Ag2, an exoantigen recognized by antibodies linked with protection against malaria. The glycophorin‐binding protein, the histidine‐rich protein II, the S‐antigen, the heat shock protein 70, the ring‐infected erythrocyte surface antigen, and the apical membrane antigen‐1 were also shown serologically to be present in the mixture of exoantigens.
The number and size of glomeruli in long‐term lithium‐induced nephropathy in rats
Authors: Nyengaard JENS R. , Bendtsen THOMAS F. , Christensen STEN , Ottosen PETER D.
Published: August 2009

Chronic renal failure was induced in 10 Wistar rats using a lithium‐containing (40 mmol/kg) diet from time of birth until an age of 55–65 weeks. Nine Wistar rats served as controls. The plasma lithium, the plasma urea, and the inulin clearance were measured, and one kidney was fixed by vascular perfusion with glutaraldehyde. The number of glomeruli was estimated stereologically by the fractionator method. The total number of glomeruli per kidney was 23.9 × 103±3.65 × 103 (±SD) in controls and 22.0 × 103±1.48 × 103 in the lithium‐treated group, showing no statistically significant difference. The mean glomerular volume was also estimated using stereological methods. The number‐weighted mean volume was reduced by 42% in the lithium‐treated group, whereas the volume‐weighted mean volume was unchanged. This can be attributed to the occurrence of many small glomeruli and a few very large glomeruli in the lithium‐treated group. The many small glomeruli have in a previous study been shown to be atubular. The present study showed that the glomerular population is quite resistant to the deleterious effect of lithium; thus glomerular atrophy was seen, but no loss of glomeruli occurred.