bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate Measurements of Valence Electron Distribution and
Interfacial Lattice Displacement Using Quantitative Electron
Diffraction
Authors: Zhu Yimei , Wu Lijun , Tafto J.
Published: October 2003

We developed a novel electron-diffraction technique by focusing a
small probe above (or below) the sample in an electron microscope to
measure charge density and lattice displacement in technologically
important materials. The method features the simultaneous acquisition
of shadow images within many Bragg reflections, resulting in parallel
recording of dark-field images (PARODI). Because it couples diffraction
with images, it is thus suitable for studying crystals as well as their
defects. We used this technique to accurately locate the
charge-carrying holes in superconducting crystals, and to determine
displacement vectors across planar faults by comparing the experiments
with calculations, and by using fitting and error analyses. Examples
are given for complex YBa2Cu3O7 and
Bi2Sr2CaCu2O8+δ oxides
and the newly discovered MgB2 superconductor.
Laser wavelength selection for Raman spectroscopy of microbial pigments in situ in Antarctic desert ecosystem analogues of former habitats on Mars
Authors: Edwards Howell G.M. , Newton Emma M. , Wynn-Williams David D. , Dickensheets David , Schoen Chris , Crowder Chelle
Published: October 2003

The vital ultraviolet- (UV-) protective and photosynthetic pigments of cyanobacteria and lichens (microbial symbioses) that dominate primary production in Antarctic desert ecosystems auto-fluoresce at short wavelengths. We therefore use a long-wavelength (1064 nm) infrared laser for non-intrusive in situ Raman spectrometry of their ecologically significant compounds (especially pigments). To confirm that the power loss at this longer wavelength is justified to avoid swamping by background fluorescence, we compared Raman spectra obtained with excitation at 1064, 852, 830, 785, 633 and 515 nm. These are typical of lasers used for Raman spectroscopy. We analysed communities of the cyanobacterium Nostoc commune and the highly pigmented lichens Acarospora chlorophana and Caloplaca saxicola. These require screening compounds (e.g. pigments such as scytonemin in cyanobacteria and rhizocarpic acid in the fungal symbiont of lichens). They are augmented by quenching pigments (e.g. carotenoids) to dissipate the energy of free radicals generated by penetrating UV. We also analysed organisms having avoidance strategies (e.g. endolithic communities within translucent rocks, including the common cyanobacterium Chroococcidiopsis). These require accessory pigments for photosynthesis at very low light intensities. Although some organisms gave useable Raman spectra with short-wavelength lasers, 1064 nm was the only excitation that was consistently excellent for all organisms. We conclude that a 1064 nm Raman spectrometer, miniaturized using an InGaAs detector, is the optimal instrument for in situ studies of pigmented microbial communities at the limits of life on Earth. This has practical potential for the quest for biomolecules residual from any former surface life on Mars.
Systematic Research Synthesis to Inform Policy, Practice and Democratic Debate
Authors: Gough David , Elbourne Diana
Published: October 2003

Issues surrounding the role and provision of evidence to inform policy and practice have become topical and problematic. The context of these controversies is discussed, with particular emphasis on systematic approaches to synthesising research evidence. We contrast the ‘positivist’ emphasis with interpretative qualitative synthesis, and suggest that many of the viewpoints have become unnecessarily and unhelpfully polarised. The methods for systematic research syntheses will vary as they depend on the question being asked. The process is transparent, allowing readers to see how conclusions have been reached, and forms the basis of reviews which can be updated to help provide sustainable and relevant evidence.
Is it only ‘What works’ that ‘Counts’ in New Knowledge Economies? Evidence-based Practice, Educational Research and Teacher Education in Australia
Authors: Blackmore Jill
Published: October 2003

Recent texts on globalisation and education policy refer to the rapid flow of education policy texts producing or responding to common trends across nation states with the emergence of new knowledge economies. These educational policies are shaping what counts as research and the dynamics between research, policy, and practice in schools, creating new types of relationships between universities, the public, the professions, government, and industry. The trend to evidence-based policy and practice in Australian schools is used to identify key issues within wider debates about the ‘usefulness’ of educational research and the role of universities and university-based research in education in new knowledge economies.
Consumerism, Health and Social Order
Authors: Shaw Ian , Aldridge Alan
Published: October 2003

The concept of consumerism has multiple meanings, many of which are heavily value-laden; similarly, there are conflicting stereotypes of ‘the consumer’. After exploring the key dimensions of debates about consumerism and the consumer, this paper addresses some paradoxical consequences of the discourse of consumer empowerment in the field of health promotion and specifically in the ‘new public health’ movement.
Systems, Fiddling and Strangers: Young People on the ‘Welfare State’
Authors: McIntosh Ian
Published: October 2003

This paper is concerned with young people's understanding of the welfare state; who and what is it for, and what is their relation to it? It is argued that such qualitative research into these questions is not common. Exploring these issues increases our knowledge of the presence that ideas and discourses about welfare states have in young people's understanding of the social world. Qualitative approaches such as the one adopted in this paper can tap into meanings and perceptions that young people have in relation to the welfare state that can be glossed over with more quantitative concerns with ‘attitudes’.
The effect of immunoglobulin immunoadsorptions on delayed xenograft rejection of human CD55 transgenic pig kidneys in baboons
Authors: Ashton‐Chess Joanna , Roussel Jean‐Christian , Bernard Pierre , Barreau Nathalie , Karam Georges , Dantal Jacques , Moreau Anne , Letessier Eric , Nagasaka Takaharu , Cozzi Emanuele , Minault David , Soulillou Jean‐Paul , Blancho Gilles
Published: October 2003

Abstract:  Delayed xenograft rejection (DXR) remains a major obstacle in discordant xenotransplantation. As strategies of complement inhibition and xenogeneic natural antibody (Ab) removal have been shown to give prolonged xenograft survival, we endeavored to determine whether combining these two strategies would lead to an additive effect in terms of graft survival. The study was initiated with two groups, A and B, where group A received normal kidneys and group B received hCD55 transgenic kidneys. Both groups underwent pre‐transplant (day − 1) total immunoglobulin (Ig) immunoadsorption (IA) and received an immunosuppression of cyclophosphamide, cyclosporine A, mycophenolate mofetil and corticosteroids. Two subsequent groups (C and D) receiving hCD55 transgenic pig kidneys were then performed with an ‘optimized’ immunosuppression (Cyclophosphamide starting 1 day earlier) but only group D recipients were immunoadsorbed. Biopsies taken during the post‐transplantation period were analyzed for Ab deposition, complement activation and cellular infiltration. No hyperacute rejection was observed. In the initial immunoadsorbed groups A and B, all baboons underwent DXR, which started surprisingly early (day 5 in most cases). In the subsequent two groups, the immunoadsorbed group D baboons also underwent DXR, again as early as day 5. In contrast, group C baboons did not show any signs of DXR on their day 6 biopsy or at their time of death. Analysis of graft biopsies from the kidneys undergoing rejection or with stable function showed strong deposition of anti‐Gal IgM in all cases whereas strong complement C5b‐9 deposits were only observed in biopsies at rejection. Cellular infiltration consisted mostly of monocytes/macrophages, was more pronounced in biopsies taken at rejection and was associated with a pro‐inflammatory environment involving interleukins 1α, 6 and 8. Our findings suggest that non‐specific Ig (anti‐Gal and non‐Gal Ig of all isotypes) IA or even incomplete IA in immunosuppressed baboon recipients of transgenic pig kidneys is detrimental to graft survival by being associated with an Ab and complement driven rejection. We speculate that the IA were insufficient in terms of Ig depletion or frequency inducing an Ab rebound or that this total Ig depletion also removed components facilitating graft survival.
Sensitivity to human serum of gammaretroviruses produced from pig endothelial cells transduced with glycosyltransferase genes
Authors: Kurihara Takashi , Miyazawa Takayuki , Miyagawa Shuji , Tomonaga Keizo , Hazama Kenji , Yamada Junko , Shirakura Ryota , Matsuura Yoshiharu
Published: October 2003

Abstract: Reduction of pig cell‐surface α‐galactosyl (Gal) epitope, Galα1, 3Galβ1, 4GlcNAc‐R, by the introduction of glycosyltransferase genes is effective in suppressing hyperacute rejection (HAR) in pig‐ to‐human xenotransplantation. The transmission of porcine endogenous retroviruses (PERVs) has been recognized as a potential risk factor associated with xenotransplantation. In this study, effects of the introduction of glycosyltransferase genes to pig cells on the sensitivity of gammaretroviruses to human serum were investigated. Pig endothelial cells (PEC), PEC transduced with α1,2 fucosyltransferase (FT), α2,3 sialyltransferase (ST) or N‐acetylglucosaminyltransferase III (GnT‐III), and human embryonic kidney (HEK) 293 cells were transduced with the LacZ gene with the packaging signal of murine leukemia virus (MuLV) under the control of the long terminal repeat of MuLV by a pseudotype infection. Then, the cells were further infected with PERV subtype B (PERV‐B) or feline leukemia virus subgroup B (FeLV‐B). Culture supernatants of the infected cells were mixed with human serum (HS) and then inoculated to HEK293 cells. The inoculated cells were histochemically stained and lacZ‐positive blue foci were counted. Glycosyltransferase activity, xenoantigenicity, and α‐Gal epitope density in the cells were measured at the time of the infection experiments. PERV‐B or FeLV‐B particles from the parental PEC were efficiently neutralized by HS, while those from PEC transduced with α1,2FT, α2,3ST or GnT‐III were less sensitive to HS. The transduced PEC exhibited high levels of activity of the introduced glycosyltransferases, and expressed fewer xenoantigens and cell‐surface α‐Gal epitopes. Our results suggest that gammaretroviruses including PERVs produced by transgenic pigs, that are genetically modified to reduce the cell‐surface α‐Gal epitope to overcome the HAR in xenotransplantation, are less sensitive to HS.
Long‐term survival of neonatal porcine Sertoli cells in non‐immunosuppressed rats
Authors: Dufour Jannette M. , Rajotte Ray V. , Seeberger Karen , Kin Tatsuya , Korbutt Gregory S.
Published: October 2003

Abstract: Sertoli cells from the testis contain immunoprotective properties which allow them to survive as allografts and also to protect islets and adrenal chromafin cells from immune rejection without the use of immunosuppressive drugs. Experiments were designed to determine whether xenogeneic neonatal porcine Sertoli cells (NPSCs) survive transplantation in rats without the use of immunosuppression. NPSCs (92.2 ± 5.1%) were isolated, cultured and then transplanted under the kidney capsule of non‐immunosuppressed Lewis rats. To assess survival, grafts were removed after 4, 20, 30, 40, 60, and 90 days post‐transplant and immunostained for the Sertoli cell marker vimentin. Survival was confirmed by polymerase chain reaction (PCR) for the porcine mitochondrial cytochrome oxidase II (COII) subunit gene, a marker for porcine tissue. In both methods, NPSCs were detected in the grafts for at least 90 days. Histologically, NPSCs were clustered in small aggregates or organized in tubule‐like structures. When stained for the presence of proliferating cell nuclear antigen (PCNA), many Sertoli cells stained positive at 20 days post‐transplant, indicating not only cell survival but also Sertoli cell proliferation. The number of PCNA postive cells decreased somewhat by 40 days with almost no positive Sertoli cells at 60 and 90 days. These data demonstrate that NPSCs survive long‐term following xenotransplantation in rats, which to our knowledge is the first report of a discordant xenograft surviving without immunosuppression in a non‐immunoprivileged site. Further study of the mechanism of NPSC xenograft survival may provide clues for promoting a local tolerogenic environment.
CD46 protects pig islets from antibody but not cell‐mediated destruction in the mouse
Authors: McKenzie Ian F. C. , Li Yu Qin , Xing Pei Xiang , Dinatale Irene , Koulmanda Maria , Loveland Bruce E. , Sandrin Mauro S.
Published: October 2003

Abstract:  We have previously reported that islets present in cultured fetal pig pancreas (FPP) are resistant to destruction by Galα(1,3)Gal antibodies and complement, but are susceptible to the ‘secondary’ antibody response which occurs on transplanting pig islet tissue to Galo/o murine recipients. In a model of antibody‐mediated graft rejection, we tested the resistance of porcine islets to antibody. Using FPP from human CD46 transgenic pigs, we now report that the complement regulator, CD46, affords protection from antibody‐mediated rejection when mouse anti‐pig serum (MAPS) was administered to scid mice bearing FPP grafts from either CD46 transgenic or normal pigs. Indeed, whereas normal pig islets were destroyed by an intraperitoneal (i.p.) injection of 0.1 to 0.2 ml of MAPS antibody, destruction of CD46‐expressing transgenic islets required 0.5 ml, i.e. up to five times the amount. In contrast, there was no prolongation of the survival of CD46 transgenic mouse skin or heart major histocompatibility complex‐compatible or ‐incompatible allografts – rejected by predominantly cellular immune mechanisms, as opposed to xenograft rejection. Although complement regulators have been examined for their protective role in hyperacute rejection of vascularized xenografts, it is clear that they also have protective effects in the later, antibody‐mediated responses, but are unlikely to effect the inflammatory response in cell‐mediated rejection.
Oxcarbazepine: clinical experience with hospitalized psychiatric patients
Authors: Centorrino Franca , Albert Matthew J , Berry Judith M , Kelleher James P , Fellman Veronica , Line Gyorgy , Koukopoulos Alexia E , Kidwell Jennifer E , Fogarty Kate V , Baldessarini Ross J
Published: October 2003

Background: Oxcarbazepine (10‐keto‐carbamazepine) appears to be better tolerated and simpler to use than carbamazepine. It has antimanic effects but, as its potential clinical usefulness and tolerability in broad samples of psychiatric patients remain to be tested, we reviewed both the pharmacology of oxcarbazepine and our early experience with this new agent among psychiatric inpatients.

Methods: We reviewed medical records of all inpatients given oxcarbazepine in the first 15 months of its use at McLean Hospital. Data analyzed included dosing, presenting illnesses, other medications, clinical changes, and adverse effects.

Results: Oxcarbazepine was given to 56 inpatients (1.3% of admissions; 31 women, 25 men) presenting with depression (n = 23), mania (n = 19), or psychosis (n = 14). The discharge daily dose for the 43 patients (76%) taking oxcarbazepine was 831 mg/day, 34% higher in men than women, and fell by 9 mg/year‐of‐age. Oxcarbazepine was the only putative mood‐stabilizing agent given at discharge in 19 of 43 cases (44%). It was discontinued in 20% of patients for apparent inefficacy, and 4% for adverse effects. Changes in CGI and GAF scores were similarly high across illnesses, and unrelated to days of use of oxcarbazepine or its dose.

Conclusions: Oxcarbazepine was well tolerated and simpler to use clinically than its precursor carbamazepine. This agent should be studied in controlled trials to test its efficacy in specific types of major psychiatric disorders, and particularly for long‐term maintenance treatment in bipolar disorder.
Testing competing path models linking the biochemical variables in red blood cells from Li+‐treated bipolar patients
Authors: Williams Nicole , Layden Brian T , Suhy Joyce , Metreger Tabitha , Foley Kathleen , Abukhdeir Abde M , Borge George , Crayton John , Bryant Fred B , Mota de Freitas Duarte
Published: October 2003

Objectives: Red blood cells (RBCs) from Li+‐treated bipolar patients have shown abnormalities in intracellular Li+ concentration ([Li+]i), Na+/Li+ exchange rates, and membrane phospholipid levels. Based on Li+‐loaded RBC studies, we hypothesized that Li+‐treated bipolar patients also have varied intracellular free Mg2+ concentrations ([Mg2+]f) as compared with normotensive patients. We addressed how these experimentally determined values are intercorrelated. Assuming that Li+ treatment alters these biochemical parameters, we provide hypothetical pathways based upon structural equation modeling statistics.

Methods: In RBCs from 30 Li+‐treated bipolar patients, we determined [Li+]i, serum [Li+] ([Li+]e), Na+/Li+ exchange parameters, membrane phospholipid levels, [Mg2+]f, and Li+ membrane binding affinities. Comprehensive statistical analyses assessed correlations among the biochemical data. We used path analysis statistics to propose potential pathways in which the data were correlated.

Results: We found significant correlations within the three Na+/Li+ exchange parameters and percentage composition of the membrane phospholipids. Additional correlations existed between [Mg2+]f and Vstd, Km, or phospholipid composition, between [Li+]i and percentage of phosphatidylcholine, and between percentage of phosphatidylserine and Km. Based on these findings, we hypothesized and statistically determined the most probable pathway through which these parameters were intercorrelated.

Conclusions: Significant correlations existed between the biochemical parameters that describe the cell membrane abnormality and the Li+/Mg2+ competition hypotheses. Using path analysis statistics, we identified a biochemical pathway by which Li+ may assert its cellular effects. This study serves as an illustrative example how path analysis is a valuable tool in determining the direction of a certain biochemical pathway.
School achievements and schizophrenia: a case–control study
Authors: Helling I. , Öhman A. , Hultman C. M.
Published: October 2003

Objective: To compare school performance during middle childhood and adolescence among subjects later diagnosed with schizophrenia and their peers.

Method: School records were ascertained from archives in 76 acutely symptomatic schizophrenic patients and 146 controls matched for gender and graded by the same teachers.

Results: At age 9, no differences in yearly graded school subjects were found. At 12, cases had higher marks in drawing/art and a tendency to excel in language and religion. At 15, the proficient performance in drawing/art remained, but cases performed worse than controls in gymnastics. The cases reported high frequency of school adaptation problems. Severity of psychotic symptoms at admission was associated with lower and declining marks.

Conclusion: Schizophrenic patients seem to perform as well as their classmates in most subjects taught in compulsory basic school. Findings indicating specific talents in artistic ability and impairments in motor development need to be further investigated.
Psychotic disorder in a case with Hallervorden–Spatz disease
Authors: Öner Ö. , Öner P. , Deda G. , İçağasioğlu D.
Published: October 2003

Objective: Hallervorden–Spatz disease is a rare autosomal recessive condition, with early onset of predominantly extrapyramidal dysfunction. The symptoms of the disease are dystonia, rigidity, choreoathetosis, pyramidal signs, and intellectual decline. Recent genetic studies mapped the disease to chromosome 20p12.3‐p13, and identified mutations in the pantothenate kinase gene. This report describes a childhood onset case of Hallervorden–Spatz disease with schizophreniform psychotic symptoms. Former reports about the psychiatric comorbidity generally included depressive disorder.

Method: A single case report.

Results: A 14‐year‐old boy with Hallervorden–Spatz disease presented a psychotic episode with prominent auditory hallucinations. Symptoms were relieved after neuroleptic treatment.

Conclusion: To the authors’ knowledge, this is the first published report of the disease with psychotic symptoms. The contribution of basal ganglia, with their wide projections, to the emergence of psychotic symptoms was discussed.
Attempted suicide among young people: risk factors in a prospective register based study of Danish children born in 1966
Authors: Christoffersen M. N. , Poulsen H. D. , Nielsen A.
Published: October 2003

Objective: In order to prevent suicidal behaviour among adolescents and young adults it would be valuable to know if altering the conditions of their upbringing could reduce their suicidal behaviour. The study surveys possible risk factors.

Method: Population‐based registers covering children born in Denmark in 1966 at the age span of 14–27 years and their parents for: health, education, family dissolution, suicidal behaviour, substance abuse, criminality and unemployment. A discrete‐time proportional hazard modelling was used to analyse the longitudinal observations.

Results: First‐time suicide attempts were associated with parental psychiatric disorder, suicidal behaviour, violence, child abuse and neglect. Increased risks were also found among adolescents and young adults who suffered from psychiatric disorder or physical handicap, had been legally imprisoned, were addicted to drugs, or without graduation, vocational training or employment.

Conclusion: Stigmatization, social exclusion, and mental disorders in the adolescents or young adults and parents increased risks for attempted suicide.
A suggested revision of the Ward Atmosphere Scale
Authors: Røssberg J. I. , Friis S.
Published: October 2003

Objective: In a previous study, we have suggested a revision of the Anger/Aggression and the Spontaneity subscales. The main aim of this study was to re‐evaluate the psychometric properties of the other eight subscales of the Ward Atmosphere Scale.

Method: A total of 550 patients and 822 staff members on 54 psychiatric wards for psychotic patients completed the WAS and the Good Milieu Index (GMI). We calculated Cronbach's α, the Corrected Item Total subscale Correlation, subscale intercorrelations and the correlation between subscales and GMI.

Results: By removing a total of 16 items, the psychometric properties improved. The revised subscales had acceptable psychometrics and gave a clearer picture of the relationship between the perceived level of patient satisfaction and the WAS subscale scores.

Conclusion: The revision suggested in this study ‘modernized’ several of the subscales. We suggest that this revision is implemented in the future use of the WAS.
Suicidal feelings run high among mothers in refugee camps: a cross‐sectional survey
Authors: Rahman A. , Hafeez A.
Published: October 2003

Objective: To study levels of mental distress in a sample of Afghan mothers caring for children in two refugee camps in North West Frontier Province (NWFP) of Pakistan.

Method: Cross‐sectional survey of 297 consecutive mothers with young children, attending primary care centres, using a psychiatric screening instrument, the Self‐Reporting Questionnaire (SRQ‐20).

Results: One hundred and six (36%) of women in the sample screened positive for a common mental disorder. Ninety‐six (91%) of those screening positive had had suicidal thoughts in the previous month, and nine (8%) rated suicidal feeling as their topmost concern.

Conclusion: There is a high prevalence and severity of mental distress in Afghan mothers caring for young children in refugee camps. This may have serious long‐term effects on the psychological and physical development of their children.
Rapid development in vitro and in vivo of resistance to ceftazidime in biofilm‐growing Pseudomonas aeruginosa due to chromosomal β‐lactamase
Authors: Bagge NIELS , Ciofu OANA , Skovgaard LENE T. , HØIby NIELS
Published: October 2003

The aim of this study was to examine the development of resistance of biofilm‐growing P. aeruginosa during treatment with ceftazidime. Biofilms were established in vitro using a modified Robbins device (MRD) and in vivo in the rat model of chronic lung infection. Three P. aeruginosa strains isolated from the lungs of cystic fibrosis (CF) patients (MICceftazidime‐basal/induced β‐lactamase activity: PAO 579= 0.8 mg/l‐19/550 milliunits, 19676A=50 mg/l‐38/957 milliunits, 17107B=100 mg/l‐504/947 milliunits) were studied. After 1 or 2 weeks of continuous or intermittent (4 h/day) administration of ceftazidime to biofilms established in MDR, a statistically significant development of resistance to ceftazidime in PAO 579 or 19676A bacterial populations occurred. When ceftazidime was administered 4 h/day (200 mg/1) for 2 weeks, the frequency of resistant 19676A having MIC>25 mg/l was 4.4. 10−1compared to 6.0 · 10−5in the control biofilm. The same trend was observed after continuous administration of ceftazidime. MICceftazidime of the more resistant variants was increased 500‐fold for PAO 579 and 8‐fold for 19676A, and the specific basal β‐lactamase activities from 19 to 1,400 units for PAO 579 and from 38 to 10,000 units for 19676A. Chronic P. aeruginosa lung infection was established with alginate‐embedded PAO 579, 19676A or 17107B in 146 Lewis rats which were treated with ceftazidime 4 g/kg intraperitoneally twice a day for 1 week. A statistically significant development of resistance was observed for all three strains. The MICceftazidime of the more resistant variants was increased 15‐fold for PAO 579, 8‐fold for 19676A, and 4‐fold for 17107B, and the specific basal β‐lactamase activity from 19 to 100 units for PAO 579, from 38 to 1,300 units for 19676A, and from 500 to 1,300 units for 17107B. It was shown that, during treatment with ceftazidime, biofilm‐growing P. aeruginosa had the capacity to develop resistance due to the production of chromosomal β‐lactamase.
Glomerular structure in lithium‐induced chronic renal failure in rats
Authors: Min GUO , Christensen STEN , Marcussen NIELS , ØSterby RUTH
Published: October 2003

The effects of long‐term lithium administration on glomerular structure and intervention with angiotensin converting enzyme inhibitor (ACEI) were studied in rats. Male Wistar rats were fed a lithium‐containing diet (Li) or control diet (C) for 16 weeks postnatally. Litreated rats developed renal failure, hypertension and proteinuria. During the subsequent 24 weeks, subgroups were treated with ACEI. The kidneys were fixed by perfusion, and tissue blocks were serially cut for estimation of glomerular volume and glomerular characteristics by light microscopy. Mesangial and mesangial matrix volume fractions, surface density of capillary walls, basement membrane thickness and foot process width (FPW) were measured by electron microscopy. Glomerular volume was decreased in Lirats, with increased intra‐individual variation. In all Li‐rats, some glomeruli (mean 27%) were abnormal, with severe changes in only three rats. Ultrastructural parameters obtained by systematic sampling of three glomeruli in each rat showed no differences among groups. Among Litreated animals there was a significant correlation between FPW and albumin excretion per unit filtration surface, and between filtration surface per glomerulus and inulin clearance. In conclusion, long‐term lithium administration to newborn rats caused marked changes in glomerular volume which were not associated with measurable changes in structural parameters. No effect of ACEI‐treatment was detectable.
Resident aerobic microbiota of the adult human nasal cavity
Authors: Rasmussen T. TANG , Kirkeby L. P. , Poulsen K. , Reinholdt J. , Kilian M.
Published: October 2003

Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of Gram‐negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal microbiota was dominated by species of the genera Corynebacterium, Aureobacterium, Rho‐dococcus, and Staphylococcus, including S. epidermis, S. capitis, S. hominis, S. haemolyticus, S. lugdu‐nensis and S. warneri. These studies show that the microbiota of the nasal cavity of adults is strikingly different from that of the pharynx, and that the nasal cavity is a primary habitat for several species of diphtheroids recognized as opportunistic pathogens. Under special circumstances, single species, including IgAl protease‐producing bacteria, may become predominant in a restricted area of the nasal mucosa.
Strain differentiation in Bacteroides fragilis by RAPD and Dendron computer‐assisted gel analysis
Authors: Eribe EMENIKE RIBS , Olsen INGAR
Published: October 2003

Bacteroides fragilis is the anaerobe most frequently isolated from human infections. Strains of this species are not easily distinguished by phenotypic tests. It is important to make this distinction because virulence may vary between strains and because B. fragilis seems to be a heterogeneous species. The aim of this study was to assess the utility of randomly amplified polymorphic DNA (RAPD) analysis for differentiation of 46 strains of B. fragilis. Twenty‐seven of the strains belonged to Johnson's DNA homology group I and 8 to group II, while 11 strains had not been assigned to any of these groups (NI group). The primers OPA16 and 18 were chosen among 30 primers tested for optimal RAPD analysis. OPA18 gave best discrimination, revealing a total of 15 genotypes while OPA16 gave 13. The gels obtained after RAPD analysis were evaluated with the Dendron computer‐assisted program. Most strains showed similarity levels (SAB) within 70%. Strain clusters thus established were not always in agreement with DNA homology since strains from both homology groups fell in the same cluster. Similarly, strains of the NI group fell among the group I and II homology strains. RAPD was useful for differentiation of B. fragilis strains and thus probably suitable for epidemiological studies. On the other hand, DNA‐DNA homology, comparing the entire genome of strains rather than a few random priming sites, would be more reliable for taxonomy. Computer‐assisted gel analysis made it possible to objectively evaluate multiple banding patterns, thereby increasing the reliability of the RAPD analysis.
Enhancement of lymphocyte proliferation induced by interleukin‐12 and anti‐interleukin‐10 in HIV‐infected patients during highly active antiretroviral therapy
Authors: Stylianou EVA , Aukrust PÅL , NordØY INGVILD , MÜLler FREDRIK , FrØLand STIG S.
Published: October 2003

Based on the potentially important role of IL‐10 and IL‐12 in the pathogenesis of HIV infection, we have examined the effect of highly active antiretroviral therapy (HAART) on the production of these two cytokines, and whether addition of IL‐12 or anti‐IL‐10 in vitro could improve the proliferative response in peripheral blood mononuclear cells (PBMC) from HIV‐infected patients during such therapy. Our findings are: (i) After initiating HAART there were no significant changes in PHA‐ or MAC‐PPD‐stimulated IL‐10 and IL‐12 levels in PBMC supernatants in the patient group as a whole. (ii) However, while a decline in IL‐10 synthesis was shown in patients with high baseline MAC‐PPD‐ and PHA‐stimulated IL‐10 levels, IL‐10 increased in patients with lower baseline levels. A similar pattern was seen for MAC‐PPD‐stimulated IL‐12 levels. (iii) Exogenously added IL‐12 and anti‐IL‐10 markedly and additively improved MAC‐PPD‐stimulated PBMC proliferation in vitro. Thus, a loss of cell‐mediated immune response exists in HIV‐infected patients also during apparently successful HAART and this can be significantly improved by addition of IL‐12 and anti‐IL‐10, at least in vitro. These results suggest that further exploration of both IL‐10 and IL‐12 as targets for immunomodulating therapy in HIV‐infected patients in addition to HAART might be important.
Complement activation reaches maximum during equilibrium between antigen and antibody in an in vitro model for thrombolysis with streptokinase
Authors: LeinØE EVA , PachaÏ ANDRA , Brandslund IVAN
Published: October 2003

Treatment with streptokinase (SK) of patients with acute myocardial infarction (AMI) is known to activate the complement system. In a previous investigation we found a great variation in the degree of complement activation taking place during infusion of SK in patients with AMI (range: 0–293% increase in pretreatment complement split product 3d (C3d) levels). In this in vitro study we added SK to serum with different concentrations of SK‐antibodies (SK‐Ab) and found that both the relative concentrations and the total concentrations of SK and Ab determined the degree of complement activation elicited by SK. This finding was in accordance with the Kendall‐Heidelberger equation of antigen‐antibody equivalence. Furthermore, we found parallel rises in C3d and C4d, indicating that complement was activated via the classical pathway. A condition for maximal complement activation is antigen‐antibody equivalence.
Endothelial and epithelial expression of sialyl Lewisxin squamous carcinoma of the tongue
Authors: Renkonen JUTTA , HeinÄVaara SIRPA , Sankila RISTO , Paavonen TIMO
Published: October 2003

In this retrospective study we describe the immunohistochemical expression pattern of sLexepitopes in endothelial and epithelial cells of 59 squamous carcinomas of the tongue, and relate this to the relative survival rates of the patients. Endothelial sLexexpression was significantly elevated in malignant lesions compared to normal tissues, but did not have any prognostic value for the relative survival rate. In contrast, epithelial sLexexpression was decreased in carcinomas compared to normal tongue. The patients whose carcinoma showed only moderate epithelial HECA‐452 reactivity had a significantly better relative survival rate than the patients with tumor specimens with neglible or very high HECA‐452 reactivity. The epithelial staining with the two other anti‐sLexantibodies (CSLEX‐1 and 2F3) did not correlate with the survival rates of tongue carcinoma patients.
Giant cell arteritis Epidemiology, etiology and pathogenesis
Authors: Nordborg C. , Nordborg E. , Petursdottir V.
Published: October 2003

Giant cell arteritis (GCA) is a chronic inflammatory disorder targeting large and medium‐sized arteries, which predominantly affects postmenopausal women. Its high incidence in populations with Scandinavian lineage, some familial accumulation, and the association with the HLA‐DR4 haplotype indicate a genetic predisposition. Epidemiological observations, as well as the symptomatology, may indicate an infectious origin, but so far GCA has not been shown to be a truly infectious form of vasculitis. Immunological research indicates an antigen‐driven disease with local T‐cell and macrophage activation in the vessel wall. Morphologically, the inflammatory process appears to be initiated by a foreign‐body giant‐cell attack on calcified internal elastic membrane in arteries and on calcified atrophic parts of the aortic media. The ensuing diffuse chronic inflammation leads to vessel dilatation and extensive intimal thickening. The latter, which relates to the production of promoting factors by the inflammatory cells, causes arterial stenosis and ischemic complications. The possible role of female sex hormones in GCA requires further investigation. Mononuclear and giant cells in GCA display the cytoplasmic accumulation of estrogen receptor (ER) a. Cytoplasmic ER‐oc is also seen in media smooth‐muscle cells in GCA and in non‐GCA controls, but nucleotide sequence analysis of the ER‐a gene revealed no differences between GCA patients and controls. In the future, comprehensive morphological, cell biological and immunological research will be required for a better understanding of the complex etiology and pathogenesis of GCA.
Retesting and follow‐up of first‐catch urines from men yield variable results with three Chlamydia trachomatis nucleic acid amplification tests
Authors: NordbØ SVEIN ARNE , Lund KRISTIN , Skjeldestad FINN EGIL
Published: October 2003

First‐catch urines from 276 asymptomatic male military recruits were screened by polymerase chain reaction for the detection of Chlamydia trachomatis. Eight initially positive specimens were retested by polymerase chain reaction, ligase chain reaction and transcription‐mediated amplification. Urine specimens from six (2.2%) subjects were considered to contain C. trachomatis. However, retesting of serially collected urines from five of these six subjects using different nucleic acid amplification methods showed some discrepancy. This may have a major impact on the efficacy of screening programs for C trachomatis in low prevalence populations.
Buffy coat PCR for diagnosis of experimental pneumococcal pneumonia
Authors: Ng W. , Olsen K. , Lutsar I. , Wubbel L. , Ghaffar F. , Jafri H. , Mccracken G. H. , Friedland I. R.
Published: October 2003

An immunocompetent murine model of pneumococcal pneumonia and bacteremia was used to evaluate a PCR assay based on amplification of the pneumolysin gene. Mice were treated with trovafioxacin to determine the decline in sensitivity of PCR as lung bacterial concentrations decreased and blood cultures became sterile. Forty‐three mice were studied for up to 120 h after start of antibiotic treatment. PCR of buffy coat specimens was more sensitive than PCR of plasma. Only 21% of animals had a positive blood culture, whereas 77% of PCR buffy coat assays were positive. After 48 h of therapy all blood culture specimens were sterile, whereas buffy coat PCR was positive in 57.8% of specimens. PCR of buffy coat specimens was negative in all mice colonized nasally with Streptococcus pneumoniae and in rabbits with Escherichia coli bacteremia. Our results demonstrate that our PCR technique using buffy coat specimens is highly specific for invasive pneumococcal disease and remains positive in the majority of animals for at least 48 h after start of antibiotic therapy.
Comparison of nasal swab culture, quantitative culture of nasal mucosal tissue and PCR in detecting Streptococcus pneumoniae carriage in rats
Authors: Kontiokari TERO , Renko MARJO , Kaijalainen TARJA , Kuisma LEENA , Leinonen MAIJA
Published: October 2003

It is not known how well nasopharyngeal swab culture represents pneumococcal carriage status. We tested this by comparing swab culture to quantitative culture and quantitative PCR of mucosal tissue in a rat model of pneumococcal carriage. Quantitative culture and quantitative PCR identified significantly more carriers compared to swab culture (differences 15% and 33%, 95% CI 1–28% and 16–47%, p=0.04 and 0.001, respectively). The sensitivity and specificity of swab culture was 75/92% and 63/100% compared to quantitative tissue culture and quantitative PCR, respectively. The quantitative estimates of culture and PCR were very similar (Pearson correlation coefficient 0.79, p<0.001). In conclusion, even a well‐controlled swab sampling markedly underestimates pneumococcal carriage rate, and simultaneous use of quantitative culture and PCR increases the number of positive samples by about one third.
Hepatitis C virus genotypes in Estonia
Authors: ŽUsinaite EVA , Krispin TÕNU , Raukas ELVE , Kiiver KAJA , Salupere RIINA , Ott KRISTI , Ustina VALENTINA , Zilmer KAI , Schmidt JELENA , Sizemski LEONID , Jaago KRISTA , Luman MERIKE , Ilmoja MADIS , PrÜKk TIINA , Ustav MART
Published: October 2003

Distribution of hepatitis C virus (HCV) geno(sub)types among 215 Estonian patients hospitalized with acute or chronic hepatitis and with HCV RNA‐positive sera was investigated. For genotyping, both multiplex PCR with subtype‐specific primers of the core region and RFLP analysis of cDNA of the 5′ NCR region were used. These two methods permitted a correct characterization of genotypes, a more truthful characterization of mixed infections, and combined use of single‐tube performances. They revealed, respectively, 200 and 202 (93.0% and 93.9%) HCV‐positive samples of sera, subtype la ‐ 0.9% and 0.9%, lb ‐ 56.3% and 64.2%, 3a ‐ 13.9% and 22.3%, 2a ‐ 6.5% and 5.6%, type 4 ‐0.5% and 0%, mixed infections ‐ 13.5% and 0%, and unidentified ‐ 1.4% and 0.9%. In the majority of cases (84.7%) both methods gave completely or partially concordant results; in mixed infections, as determined by subtype‐specific PCR, only one subtype was revealed by the RFLP method. In the remaining 15.3% of the cases (Ohno ‐ 7.0%, RFLP ‐ 8.3%) only one of the methods was positive. The epidemiological analysis of the dynamics of the subtypes' relative participation may indicate increasing 3a and decreasing lb subtype infection during recent years.
Immunohistochemical localization of inducible and endothelial constitutive nitric oxide synthase in neoplastic and autoimmune thyroid disorders
Authors: Kayser LARS , Francis DORTHE , Broholm HELLE
Published: October 2003

Aim. To investigate the distribution of nitric oxide synthase in tissues derived from patients with autoimmune or neoplastic disorders of the thyroid gland in order to test whether the expression of inducible nitric oxide synthase or endothelial constitutive nitric oxide synthase (two subtypes of EC 1.14.13.39) may be related to the inflammatory activity or degree of neoplasia. Experimental design. The expression of nitric oxide synthases was examined by immunohistochemistry in tissues from patients with either Hashimoto's thyroiditis (n=6), hyperplastic glands (Graves' disease) (n=7), adenomas (n=8), multinodular goitres (n=7), papillary carcinomas (n=4) or follicular carcinomas (n=5). Results. Expression of inducible nitric oxide synthase was found in 22 of the tissues and was not specific for any of the examined thyroid disorders. Expression of endothelial constitutive nitric oxide synthase was found in some of the epithelial cells in all the tissues. There was no correlation between the intensity and distribution of the immunostaining and the thyroid disorders. Conclusion. Demonstration of nitric oxide synthase cannot be used for diagnostic purposes. The expression of endothelial constitutive nitric oxide synthase in all tissues indicates that the enzyme may be of importance for the function or growth of the thyroid epithelial cells.
Lack of endotoxin tolerance with respect to TNFα production in the subarachnoid space
Authors: Steinshamn Sigurd , Waage Anders
Published: October 2003

To study endotoxin tolerance in the subarachnoid space 0.1 mg of endotoxin derived from Neisseria meningitidis was injected intracisternally into rabbits on 2 consecutive days. On day 1 the maximum peak level of TNFα was 7 ng/ml 2 h after injection, whereas on day 2 the highest levels were 3.6 ng/ml and 3.7 ng/ml, respectively, 1 and 2 h after injection. Pretreatment with intravenous endotoxin 5 or 21 h before consecutive intracisternal endotoxin did not affect the cerebrospinal fluid (CSF) levels of TNFα. In contrast, there was a marked endotoxin tolerance with respect to TNFα in the systemic circulation. Cells appearing in the CSF 5, 12 and 20 h after intracisternal injection of endotoxin were harvested, cultured, and then stimulated with 0.1 mg/ml of endotoxin. In 10 experiments a marked TNFα production in the range 10–70 ng/ml was detected in the supernatants, whereas unstimulated cells did not produce TNFα. We conclude that tolerance to endotoxin does not develop in the subarachnoid space as evaluated by the present experimental design. The pattern of TNFα production and endotoxin tolerance is distinctly different in the subarachnoid space and systemic circulation.
Low prevalence of antibodies and other plasma factors binding to CC chemokines and IL‐2 in HIV‐positive patients
Authors: Meyer Christian N. , Svenson Morten , Larsen Carsten Schade , øDum Niels , SkinhøJ Peter , Bendtzen Klaus
Published: October 2003

Neutralizing cytokine antibodies are found in healthy and diseased individuals, including patients treated with recombinant cytokines. Identification of CCR‐5 as co‐receptor for HIV has focused interest on CC chemokines and their potential therapeutic use. Chemokine‐binding components in plasma of HIV‐infected patients were therefore assessed by radioimmunoassay and radioreceptor assay. IgG from 4/505 HIV patients and 9/2000 healthy controls (p>0.05) bound rMIP‐1α and rMIP‐1β, but not rRANTES. No other plasma factors bound the chemokines. The antibodies inhibited receptor binding of both chemokines. There was no association between presence of antibodies and disease stage or HIV progression rate. Three of 11 patients treated with rIL‐2 developed IgG antibodies suppressing cellular binding and growth promotion of rIL‐2. Hence, circulating factors, including antibodies MIP‐1α/MIP‐1β, are uncommon in healthy individuals and HIV patients, and are apparently without prognostic significance. In contrast to earlier reports, IL‐2 antibodies were found only in HIV patients treated with rIL‐2.
The prevalence of gentamicin resistance among clinical isolates of enterobacteria in a Danish region
Authors: SchøNheyder Henrik Carl , Sanden Anne Katrine , SøRensen Henrik Toft
Published: October 2003

The susceptibility of enterobacteria to gentamicin was studied in the County of North Jutland during 1993–1998. A total of 378 patients had a first‐time gentamicin‐resistant isolate. The annual number rose from 34 patients in 1993 to 89 in 1998. The prevalence of resistance per 1000 patients with isolates examined was 13.5 for Escherichia coli, 15.8 for Klebsiella pneumoniae, 26.1 for Klebsiella oxytoca, and 150.4 for Citrobacter freundii. E. coli accounted for 67% of gentamicin‐resistant isolates. K. oxytoca was probably associated with a nosocomial epidemic, whereas a source for C. freundii remained unresolved. An analysis confined to E. coli identified specimens other than urine as risk factors for gentamicin resistance. Likewise, resistance to sulfonamides and to fluoroquinolones were strong risk factors for gentamicin resistance among urinary isolates of E. coli. Thus, it is likely that aminoglycoside resistance may be promoted by other antibiotic groups due to co‐resistance. The therapeutic and prophylactic uses of aminoglycosides have as yet not been undermined, but continuous population‐based surveillance and vigilance are recommended.