bluuebunny/crossref_metadata_2025 huggingface dataset:
Complexes between kinases, mitochondrial porin and adenylate translocator in rat brain resemble the permeability transition pore
Authors: Beutner Gisela , Rück Alexander , Riede Birgit , Welte Wolfram , Brdiczka Dieter
Published: April 2003

In vitro incubation of isolated hexokinase isozyme I or isolated dimer of mitochondrial creatine kinase with the outer mitochondrial membrane pore led to high molecular weight complexes of enzyme oligomers. Similar complexes of hexokinase and mitochondrial creatine kinase could be extracted by 0.5% Triton X‐100 from homogenates of rat brain. Hexokinase and creatine kinase complexes could be separated by subsequent chromatography on DEAE anion exchanger. The molecular weight, as determined by gel‐permeation chromatography, was approximately 400 kDa for both complexes. The M
r suggested tetramers of hexokinase (monomer 100 kDa) and creatine kinase (active enzyme is a dimer of 80 kDa). The composition of the complexes was further characterised by specific antibodies. Besides either hexokinase or creatine kinase molecules the complexes contained porin and adenylate translocator. It was possible to incorporate the complexes into artificial bilayer membranes and to measure conductance in 1 M KCl. The incorporating channels had a high conductance of 6 nS that was asymmetrically voltage dependent. The complexes were also reconstituted in phospholipid vesicles that were loaded with ATP. Complex containing vesicles retained ATP while vesicles reconstituted with pure porin were leaky. The internal ATP could be used by creatine kinase and hexokinase in the complex to phosphorylate external creatine or glucose. This process was inhibited by atractyloside. The hexokinase complex containing vesicles were furthermore loaded with malate or ATP that was gradually released by addition of Ca2+ between 100 and 600 μM. The liberation of malate or ATP by Ca2+ could be inhibited by N‐methylVal‐4‐cyclosporin, suggesting that the porin translocator complex constitutes the permeability transition pore. The results show the physiological existence of kinase porin translocator complexes at the mitochondrial surface. It is assumed that such complexes between inner and outer membrane components are the molecular basis of contact sites observed by electron microscopy. Kinase complex formation may serve three regulatory functions, firstly regulation of the kinase activity, secondly stimulation of oxidative phosphorylation and thirdly regulation of the permeability transition pore.
Metal‐dependent α‐helix formation promoted by the glycine‐rich octapeptide region of prion protein
Authors: Miura Takashi , Hori-i Ayako , Takeuchi Hideo
Published: April 2003

Prion diseases share a common feature in that the normal cellular prion protein (PrPC) converts to a proteaseresistant isoform PrPSc. The α‐helix‐rich C‐terminal half of PrPC is partly converted into β‐sheet in PrPSc. We have examined by Raman spectroscopy the structure of an octapeptide PHGGGWGQ that appears in the N‐terminal region of PrPC and a longer peptide containing the octapeptide region. The peptides do not assume any regular structure without divalent metal ions, whereas Cu(II) binding to the HGGG segment induces formation of α‐helical structure on the C‐terminal side of the peptide chain. The N‐terminal octapeptide of prion protein may be a novel structural motif that acts as a promoter of α‐helix formation.
Physiologic cyclic stretch inhibits apoptosis in vascular endothelium
Authors: Liu Xiao-ming , Ensenat Diana , Wang Hong , Schafer Andrew I , Durante William
Published: April 2003

Since apoptosis of endothelial cells (ECs) plays an important role in the pathogenesis of atherosclerosis, we investigated the effect of cyclic stretch on EC apoptosis. Application of moderate, physiologic levels of cyclic stretch (6–10% at 1 Hz) inhibited EC apoptosis. This anti‐apoptotic effect was dependent on the activation of phosphatidylinositol 3‐kinase and associated with the activation of Akt and the phosphorylation of Bad. Interestingly, a higher potentially pathologic level of cyclic stretch (20% at 1 Hz) stimulated EC apoptosis. The ability of physiologic cyclic stretch to inhibit EC apoptosis may provide a previously unrecognized mechanism by which hemodynamic forces exert an anti‐atherogenic effect.
Intracellular localization of the 90 kDA heat shock protein (HSP90α) determined by expression of a EGFP—HSP90α‐fusion protein in unstressed and heat stressed 3T3 cells
Authors: Langer Thomas , Rosmus Susann , Fasold Hugo
Published: April 2003

Heat shock protein 90 (Hsp90) is an abundant protein and essential for all eukaryotic cells. The expression of Hsp90 is further enhanced after exposure to stress factors, e.g. a heat shock. Many proteins interacting with Hsp90 as well as the various functions for Hsp90 have been described. In this study, an Hsp90α fusion protein along with the enhanced green fluorescence protein (EGFP) was expressed under the control of the human cytomegalovirus immediate early promoter. EGFP—Hsp90α was mainly localized in the cytoplasm, with only minor amounts inside the nuclei. No EGFP—Hsp90α could be detected inside the nucleoli. Following exposure to elevated temperatures, higher amounts of EGFP—Hsp90α are inside the nucleus, but not within the nucleoli. As the most remarkable finding under these conditions, an association of EGFP—Hsp90α with the nuclear membrane became visible.
Does cognitive-behavioural therapy influence the long-term outcome of generalized anxiety disorder? An 8–14 year follow-up of two clinical trials
Authors: DURHAM R. C. , CHAMBERS J. A. , MACDONALD R. R. , POWER K. G. , MAJOR K.
Published: April 2003

Background. Generalized anxiety disorder is a common condition of excessive worry and tension which tends to run a chronic course associated with significant psychiatric and medical problems. Cognitive behaviour therapy (CBT) has been shown to be of clinical value in about 50% of cases with treatment gains maintained over follow-up periods ranging from 6 to 12 months. The potential value of CBT over the longer term has not been subject to rigorous investigation.

Method. Results are reported of 8–14 year follow-up of two randomized controlled trials of cognitive-behaviour therapy for generalized anxiety disorder employing structured interview with an assessor blind to initial treatment condition. Comparison groups included medication and placebo in one study based in primary care, and analytical psychotherapy in the other based in secondary care. Follow-up samples (30% and 55% of trial entrants) were broadly representative of the original cohorts.

Results. Overall, 50% of participants were markedly improved of whom 30–40% were recovered (i.e. free of symptoms). Outcome was significantly worse for the study based in secondary care in which the clinical presentation of participants was more complex and severe. For a minority (30–40%), mainly from the secondary care study, outcome was poor. Treatment with CBT was associated with significantly lower overall severity of symptomatology and less interim treatment, in comparison with non-CBT conditions, but there was no evidence that CBT influenced diagnostic status, probability of recovery or patient perceptions of overall improvement.

Conclusions. Both CBT and the complexity and severity of presenting problems appear to influence the long-term outcome of GAD.
A demonstration of attentional bias, using a novel dual task paradigm, towards clinically salient material in recovering alcohol abuse patients?
Authors: WATERS HELEN , GREEN MICHAEL W.
Published: April 2003

Background. This study examined whether alcohol abuse patients are characterized either by enhanced schematic processing of alcohol related cues or by an attentional bias towards the processing of alcohol cues.

Method. Abstinent alcohol abusers (N=25) and non-clinical control participants (N=24) performed a dual task paradigm in which they had to make an odd/even decision to a centrally presented number while performing a peripherally presented lexical decision task. Stimuli on the lexical decision task comprised alcohol words, neutral words and non-words. In addition, participants completed an incidental recall task for the words presented in the lexical decision task.

Results. It was found that, in the presence of alcohol related words, the performance of patients on the odd/even decision task was poorer than in the presence of other stimului. In addition, patients displayed slower lexical decision times for alcohol related words. Both groups displayed better recall for alcohol words than for other stimuli.

Conclusions. These results are interpreted as supporting neither model of drug cravings. Rather, it is proposed that, in the presence of alcohol stimuli, alcohol abuse patients display a breakdown in the ability to focus attention.
Does ‘errorless learning’ compensate for neurocognitive impairments in the work rehabilitation of persons with schizophrenia?
Authors: KERN R. S. , GREEN M. F. , MINTZ J. , LIBERMAN R. P.
Published: April 2003

Background. Because neurocognitive impairments of schizophrenia appear to be ‘rate limiting’ in the acquisition of skills for community functioning, it is important to develop efficacious rehabilitative interventions that can compensate for these impairments. Procedures based on errorless learning may facilitate work rehabilitation because they effectively automate training of work and other skills, thereby reducing the cognitive burden on persons with schizophrenia.

Method. The present study examined the ability of a training method based on errorless learning to compensate for neurocognitive deficits in teaching two entry-level job tasks (index card filing and toilet-tank assembly) to a sample of 54 unemployed, clinically stable schizophrenic and schizoaffective disorder out-patients. Participants were randomly assigned to one of two training groups, errorless learning v. conventional trial-and-error type instruction. Prior to randomization, all subjects were administered a neurocognitive battery. Job task performance was assessed by percentage accuracy scores immediately after training.

Results. For three of the six inter-relationships among neurocognitive functioning and training condition, the pattern was the same: the errorless learning group scored high in job task performance regardless of neurocognitive impairment, whereas the conventional instruction group showed a close correspondence between job task performance and degree of neurocognitive impairment.

Conclusions. These findings support errorless learning as a technique that can compensate for neurocognitive deficits as they relate to the acquisition of new skills and abilities in the work rehabilitation of persons with schizophrenia.
Effect of neuroticism, response style and information processing on depression severity in a clinically depressed sample
Authors: LAM D. , SMITH N. , CHECKLEY S. , RIJSDIJK F. , SHAM P.
Published: April 2003

Background. It is postulated that individuals who score high on neuroticism would ruminate when faced with stress. A ruminative response style to depression is associated with faulty attribution and higher dysfunctional beliefs, which in turn is associated with a higher level of depression and hopelessness. Distraction is associated with less severe depression. Evidence supporting these hypotheses mainly comes from a non-clinical population. Hence it is not clear if these theories apply to clinical depression.

Method. One hundred and nine out-patients suffering from unipolar major depressive disorder were recruited to test these theories, using model-fitting analysis technique.

Results. Certain rumination responses to depression were associated with higher levels of depression and hopelessness, faulty attribution and dysfunctional attitudes when gender and the level of depression were controlled. Principal component analysis of the Rumination Scale yielded four factors: ‘symptom-based rumination’, ‘isolation/introspection’, ‘self-blame’ and ‘analyse to understand’. Unlike the other factors, ‘analyse to understand’ did not correlate with the level of depression. Model fitting analysis, though not reflecting entirely the true model, captures most of the hypothesized relationships between important variables. Neuroticism was associated with stress. Rumination was associated with an increased level of dysfunctional beliefs and faulty attribution, which in turn was associated with increased severity of depression. Distraction, in contrast, was associated with lower levels of negative mood.

Conclusion. The results of our study support the importance of teaching depressed patients to manage their depressive symptoms by avoiding rumination about their symptoms and engaging in distracting and pleasurable activities.
Cytomegalovirus infection in the brain of liver transplant recipients: Do pathologically occult infections matter clinically?
Authors: Razonable Raymund R. , Paya Carlos V.
Published: April 2003

Cytomegalovirus (CMV) infection remains a highly prevalent systemic complication following orthotopic liver transplantation (LT), accounting for a significant increase in morbidity and affiliated costs. However, unlike other immunosuppressed groups of population, CMV infection of the central nervous system in LT is rarely diagnosed, either clinically or postmortem. Furthermore, in 20% of the LT patients who develop preterminal neurological complications, the etiology remains undetermined. With the hypothesis that at least some of these cases could be related to an occult CMV infection, we examined brain tissue from 83 unselected autopsies of LT patients by morphological, immunohistochemical (IHC), in situ hybridization (ISH), and nested polymerase chain reaction (nested PCR) techniques. Microglial nodules were observed in 17 brains of the LT group (20.4%) but in none of the 36 controls. Isolated positive cells by either IHC, ISH, or both techniques, were identified in 11 LT patients (13.2%) and in 2 controls (5.5%). CMV DNA amplification was obtained from paraffin embedded tissues in 41 of 81 LT cases (50.6%), and in 5 controls (13.8%) (P=0.00017). Viral inclusion bodies, inflammatory infiltrates, or necrotizing changes were not identified in any case. Our findings indicate an increased susceptibility of the brain of LT patients to occult infection by CMV and suggest that a latent or low-grade infection of the central nervous system could operate as a reservoir of the CMV and play a role in some of the unexplained neurological symptoms that appear in the postoperative period.
Prevention of ischemic-type biliary lesions by arterial back-table pressure perfusion
Authors: Moench Christian , Moench Kerstin , Lohse Ansgar W. , Thies Jochen , Otto Gerd
Published: April 2003

Ischemic-type biliary lesions (ITBLs) lead to considerable morbidity after orthotopic liver transplantation (OLT). The exact pathogenesis is unknown. We tested the hypothesis that insufficient perfusion of biliary arterial vessels might be responsible for ITBLs. This could be prevented by improved perfusion techniques. Since February 2000, we performed a controlled study using arterial back-table pressure perfusion (AP) to achieve reliable perfusion of the biliary-tract capillary system, which may be impaired by the high viscosity of University of Wisconsin solution. We retrospectively analyzed 190 OLTs performed between September 1997 and July 2002 with regard to ITBLs. One hundred thirty-one grafts were preserved by in situ standard perfusion (SP), including portal perfusion, whereas in 59 cases, additional AP was performed. Donor-related factors, recipient age, indication for OLT, OLT technique, immunosuppression, and ischemia time were similar in both groups. In the SP group, 21 of 131 patients (16%) developed ITBLs. Only 1 of 59 patients with grafts receiving AP developed ITBLs. This difference was highly significant (P = .004). Peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels within the first 3 days were significantly lower in the AP group (AST, P = .016; ALT, P = .007). Multivariate analysis showed a significant influence of AP (P = .010) and donor age (P = .003) on the development of ITBLs. AP is an easy and reliable method to prevent ITBLs in OLT. It therefore should be used as the standard technique in liver procurement.
Clinical and ethnic differences in candidates listed for liver transplantation with and without potential living donors
Authors: Rudow Dianne LaPointe , Russo Mark W. , Hafliger Sylvia , Emond Jean C. , Brown Robert S.
Published: April 2003

The shortage of cadaver livers and improved outcomes in partial liver transplants has led to an increase in adult living donor liver transplantation (LDLT). Only a fraction of potential liver recipients have donors. The characteristics of candidates who have volunteers for living donation may be different than those without donors. We compared adult patients on the waiting list who had potential living donors with those who did not have living donors. Two-hundred and four consecutive patients were listed for transplantation. During evaluation, all were informed and educated about LDLT. To avoid coercion, we did not solicit a living donor. Sixty (29%) potential recipients had at least one living donor volunteer for evaluation. Twenty-eight (14%) patients from the entire cohort and 46% of the 60 patients who had potential living donors underwent LDLT. Compared with Caucasians, Hispanics were more likely to have living donors (P = .006). No patient with alcoholic liver disease (ALD) had a donor come forward (P = .006). Patients with living donors were twice as likely to have cancer (P = .08). Systematic differences exist between patients who have potential living donors versus those without donors. Candidates with potential donors are more likely to be Hispanic and have cancer and less likely to have ALD compared with cadaveric recipients. Only a minority of patients listed for orthotopic liver transplantation (OLT) will lead to LDLT. Further understanding of the cultural differences and motivating factors for why people volunteer for evaluation and subsequently choose to donate may help improve cadaveric and living donor transplant rates.
Transjugular intrahepatic portosystemic shunts: an update
Authors: Rosado Barbara , Kamath Patrick S.
Published: April 2003

Transjugular intrahepatic portosystemic shunts (TIPS) have been used in the treatment of complications of portal hypertension. TIPS is used for the control of acute variceal bleeding and for the prevention of vericeal rebleeding when pharmacologic therapy and endoscopic therapy have failed. Patients with refractory ascites with adequate hepatic reserve and renal function who fail to respond to large volume paracentesis may be reasonable candidates for TIPS. Promising indications for TIPS are Budd-Chiari syndrome uncontrolled by medical therapy, severe portal hypertensive gastropathy, refractory hepatic hydrothorax, and hepatorenal syndrome. TIPS cannot be recommended for preoperative portal decompression solely to facilitate liver transplantation. Special care should be taken to insure proper placement of the stent to avoid increasing the technical difficulty of the transplantation procedure. The major limiting factors for TIPS success are shunt dysfunction and hepatic encephalopathy. Because shunt stenosis is the most important cause of recurrent complications of portal hypertension, a surveillance program to monitor shunt patency is mandatory. The MELD score may be useful in predicting post-TIPS survival, and also in counseling patients and their families.
Changing management in Scottish birch woodlands: a potential threat to local invertebrate biodiversity
Authors: Woodcock B.A. , Leather S.R. , Watt A.D.
Published: April 2003

The silvicultural management of Scottish birch woodlands for timber production is replacing traditional low intensity management practices, such as domesticated livestock grazing. These new management practices involve thinning of existing woodlands to prescribed densities to maximize biomass and timber quality. Although presently infrequent, the wide scale adoption of this practice could affect invertebrate community diversity. The impact of these changes in management on Staphylinidae and Carabidae (Coleoptera) in 19 woodlands in Aberdeenshire, north-east Scotland was investigated. Grazing and logging practices were important determinants of beetle community structure. Woodland area had no effect on any measure of beetle community structure, although isolation did influence the abundance of one carabid species. Changes towards timber production forestry will influence the structure of invertebrate communities, although the scale at which this occurs will determine its effect.
GEOMETRIC LEAST SQUARES FITTING OF CIRCLE AND ELLIPSE
Authors: AHN SUNG JOON , RAUH WOLFGANG
Published: April 2003

The least squares fitting of geometric features to given points minimizes the squares sum of error-of-fit in predefined measures. By the geometric fitting, the error distances are defined with the orthogonal, or shortest, distances from the given points to the geometric feature to be fitted. For the geometric fitting of circle and ellipse, robust algorithms are proposed which are based on the coordinate descriptions of the corresponding point on the circle/ellipse for the given point, where the connecting line of the two points is the shortest path from the given point to the circle/ellipse.
Toll-like receptor ligand links innate and adaptive immune responses by the production of heat-shock proteins
Authors: Kumaraguru Udayasankar , Pack Christopher D , Rouse Barry T
Published: April 2003

The report shows that CpG can exert additional adjuvant effects by inducing cells that are normally inferior antigen (Ag)-presenting cells to participate in immune induction by cross-priming. Macrophages (Mφ) exposed to protein Ag in the presence of bioactive CpG DNA released material that induced primary CD8+ T cell responses in DC-naïve T cell cultures. This cross-priming event was accompanied by up-regulation of the stress protein response as well as inflammatory cytokine expression in treated Mφ. The material released was indicated to contain inducible heat shock protein-70 and epitope peptide, which in turn, were presented by dendritic cells (DCs) to responder T cells. Such an adjuvant effect by CpG may serve to salvage immunogenic material from otherwise inert depot cellular sites and additionally stimulate DCs to effectively cross-prime. The cross-priming, shown also to occur in vivo, may be particularly useful when Ag doses are low and have minimal opportunity for delivery to DCs for consequent direct priming.
Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration
Authors: de la Rosa Gonzalo , Longo Natividad , Rodríguez-Fernández Jose L , Puig-Kroger Amaya , Pineda Alfonso , Corbí Ángel L , Sánchez-Mateos Paloma
Published: April 2003

Distinct subsets of dendritic cells (DCs) are present in blood, probably “en route” to different tissues. We have investigated the chemokines and adhesion molecules involved in the migration of myeloid (CD11c+) and plasmacytoid (CD123+) human peripheral blood DCs across vascular endothelium. Among blood DCs, the CD11c+ subset vigorously migrated across endothelium in the absence of any chemotactic stimuli, whereas spontaneous migration of CD123+ DCs was limited. In bare cell migration assays, myeloid DCs responded with great potency to several inflammatory and homeostatic chemokines, whereas plasmacytoid DCs responded poorly to all chemokines tested. In contrast, the presence of endothelium greatly favored transmigration of plasmacytoid DCs in response to CXCL12 (stromal cell-derived factor-1) and CCL5 (regulated on activation, normal T expressed and secreted). Myeloid DCs exhibited a very potent transendothelial migration in response to CXCL12, CCL5, and CCL2 (monocyte chemoattractant protein-1). Furthermore, we explored whether blood DCs acutely switch their pattern of migration to the lymph node-derived chemokine CCL21 (secondary lymphoid-tissue chemokine) in response to microbial stimuli [viral double-stranded (ds)RNA or bacterial CpG-DNA]. A synthetic dsRNA rapidly enhanced the response of CD11c+ DCs to CCL21, whereas a longer stimulation with CpG-DNA was needed to trigger CD123+ DCs responsive to CCL21. Use of blocking monoclonal antibodies to adhesion molecules revealed that both DC subsets used platelet endothelial cell adhesion molecule-1 to move across activated endothelium. CD123+ DCs required β2 and β1 integrins to transmigrate, whereas CD11c+ DCs may use integrin-independent mechanisms to migrate across activated endothelium.
Leukocyte uropod formation and membrane/cytoskeleton linkage in immune interactions
Authors: Fais Stefano , Malorni Walter
Published: April 2003

The acquisition of a cell polarity is a crucial requirement for migration, activation, and apoptosis of leukocytes. The polarization of leukocytes involves the formation of two distinct poles: the leading edge—the attachment cell site to the substrate allowing directional movements of the cell—and on the opposite side, the uropod—mostly involved in cell-to-cell interaction and in a variety of leukocyte activities including activation and apoptosis. However, the uropod takes shape in neutrophils, monocytes, and natural killer cells, and the formation of this cell protrusion seems to exert an important role in immune interactions. In fact, the polarization sites of leukocytes are involved in a complex cross-talk between cells and extracellular matrix components, and a number of receptors and counter-receptors crowd in the contact sites to allow efficient cell-to-cell or cell–substrate interaction. The membrane/cytoskeleton interaction plays a crucial role in tuning these activities and in “predisposing” leukocytes to their function through the acquisition of a polarized phenotype. This review is focused on the mechanisms underlying the formation of the leukocyte uropod, the role of cytoskeleton in defining its structure and function, and the involvement of the uropod in the complex interplay between immune cells.
Ion channel gene expression in human lung, skin, and cord blood-derived mast cells
Authors: Bradding Peter , Okayama Yoshimichi , Kambe Naotomo , Saito Hirohisa
Published: April 2003

Immunoglobulin E (IgE)-dependent activation of human mast cells (HMC) is characterized by an influx of extracellular calcium (Ca2+), which is essential for subsequent release of preformed (granule-derived) mediators and newly generated autacoids and cytokines. In addition, flow of ions such as K+ and Cl− is likely to play an important role in mast cell activation, proliferation, and chemotaxis through their effect on membrane potential and thus Ca2+ influx. It is therefore important to identify these critical molecular efectors of HMC function. In this study, we have used high-density oligonucleotide probe arrays to characterize for the first time the profile of ion channel gene expression in human lung, skin, and cord blood-derived mast cells. These cells express mRNA for inwardly rectifying and Ca2+-activated K+ channels, voltage-dependent Na+ and Ca2+ channels, purinergic P2X channels, transient receptor potential channels, and voltage-dependent and intracellular Cl− channels. IgE-dependent activation had little effect on ion channel expression, but distinct differences for some channels were observed between the different mast cell phenotypes, which may contribute to the mechanism of functional mast cell heterogeneity.
Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis
Authors: Graziadei I W , Obermoser G E , Sepp N T , Erhart K H , Vogel W
Published: April 2003

Atorvastatin and other members of the statin family are widely used for the treatment of hypercholesterolaemia in order to reduce the risk of atherosclerosis and cardiovascular disease. Atorvastatin-induced adverse events are mostly mild and only a few cases of lupus-like syndrome or severe acute hepatitis have been documented. In this case report we describe a patient who developed an atorvastatin-induced severe autoimmune hepatitis. In addition, this patient presented with a concomitant systemic lupus-like syndrome which has been already described for statins but not in association with severe liver disease. Although the drug was immediately withdrawn the disease persisted and even deteriorated to a fulminant disease with evidence of acute hepatic failure. The patient failed to respond to conventional immunosuppression with corticosteroids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery of the patient. Interestingly, the patient was HLA DR3- and HLA DR4-positive, which are well-known genetic factors associated with autoimmune diseases. This case is the first report of a drug-induced lupus-like syndrome concomitant with a severe autoimmune hepatitis in a genetically predisposed patient.
Clinical, immunogenetic and outcome features of Hispanic systemic lupus erythematosus patients of different ethnic ancestry
Authors: Calvo-Alén J , Reveille J D , Rodríguez-Valverde V , McGwin G , Baethge B A , Friedman A W , Alarcón G S
Published: April 2003

The aim of this study was to compareand contrastthe clinical, immunogeneticand outcome featuresof two subgroups of Hispanic patients with systemic lupus erythematosus (SLE), one from Northern Spain (Spaniards) and one of from the USA (Hispano-Americans: Hispanics primarily of Mexican ancestry (Amerindian and Spaniard backgrounds). Patients with SLE as per the American College of Rheumatology classification criteria, from two University-affiliated Hospitals (Universidad de Cantabria) and disease of five or less years in duration (n 28) and with four years of follow up constituted the Spaniard subgroup. Fifty-two patients of Hispano-American ancestry from the LUMINA (Lupus in Minority populations: Nature versus Nurture) cohort constituted the Hispano-American subgroup. Patients were studied using a similar protocol. In short, sociodemographic, clinical, immunological, immunogenetic and psychosocial and behavioral features were obtained at enrollmentinto the study(baselinevisit) and yearly thereafter.The relationshipbetweenthesevariables and disease activity at baseline and over time, as measured by the systemic lupus activity measure (SLAM) and disease damage, as measured by the SLICC (Systemic Lupus InternationalCollaborating Clinics) Damage Index(SDI) were determined.Variablesfound to be significant at P 0.10 were then entered into multivariablelinear regression models with disease activity at baselineand over time, and damage as the outcome measures. Patients of Hispano-American and Spaniard ethnicity had comparablesociodemographicfeaturesexceptforhome density, which was higheramong theHispano-Americans.HLA-DRB1*08 was associatedwith SLE among the Hispano-Americansbutnotamong the Spaniards.Hispano-Americanpatientshad more severediseaseas manifestedby more frequentclinical manifestations(renal and neurological), higher SLAM scores at baselineand over time and higher SDI scoresat the year4 visit(thatdespitethefactthat Hispano-Americanpatientshad overallshorterdisease durationthan the Spaniard patients). Hispano-Americanethnicity, youngerage at disease onset and the number of ACR criteria at baseline and over time were consistently associated with disease activity, whereas increasedhome density and the absence of HLA-DRB1*0301 were significant predictors only over time. Disease damagewas associatedwith diseaseactivityover time, the number of ACR criteriaat baseline, increasedhomedensityandthe presenceof HLA-DRB1*08. This is thefirst longitudinalstudy of SLE in two different Hispanic subgroups. Hispanics with a strong Amerindian background have a more seriousdisease than that observedin Spaniards.Genetic and socio-economicdifferencesbetween these two Hispanic subgroups probably account for these findings
A fatal case of systemic lupus erythematosus complicated by acute pancreatitis, invasive aspergillosis and features of thrombotic thrombocytopenic purpura
Authors: Fantini F , Cimaz R
Published: April 2003

We describe the case of a 23-year-oldwoman with a mild form of systemic lupus erythematosus who presented a febrile illness rapidly followed by general worsening, neurologic involvement, renal failure and coma. While hospitalized in the intensive care unit she also suffered from acute pancreatitis, microangiopathic hemolitic anemia, thrombocytopenia and prolongation of clotting times. Despite aggressive treatment the patient died at day 17 of hospitalization in the intensive care unit. At autopsy necrotico-hemorragicpancreatitis, diffuse pneumonia, peritonitis and cerebral edema were present. Most striking was the presence of invasive aspergillosis, which was detected in all organs examined. In this case thrombotic thrombocytopenic purpura, invasive aspergillosis and multiorgan failure including acute pancreatitis were present. The relationship between the three entities is complex, and it is difficult to establish which of the different events took place first and triggered the others.
Atypical cutaneous findings in a patient with systemic lupus erythematosus
Authors: Elkayam O , Gat A , Lidgi M , Segal R , Yaron M , Caspi D
Published: April 2003

A previouslydiagnosed systemic lupus erythematosuspatient presented with arthralgia, skin rash and muscular weakness. When treated with high-dose corticosteroids and methotrexate she improved, except for a persistent lesion in the hand which evolved into a profound ulcer, along with tender subcutaneous nodules in the calf. A skin biopsy disclosed necrotizing vasculitis with giant cell granuloma revealing acid fast positive bacteria on ziels nilsen staining. A chest X-ray disclosed miliary tuberculosis (TB). The patient was diagnosed as miliary TB with prominent cutaneous involvement and treated with four anti-tuberculous drugs with slow resolution of her systemic, pulmonary and skin signs.
The ductile grinding of glass using diamond fibres oriented radially in a grinding wheel
Authors: Smith N P , Smith D J , Pearce T R A , Ashfold M N R
Published: April 2003

Diamond-coated fibres, produced by a hot filament chemical vapour deposition technique and having a high facet density, have been prepared for use as abrasives. Two grinding wheels containing such fibres have been fabricated with the fibres placed in a radial orientation. One wheel contained a single fibre, the other contained multiple fibres. The single diamond fibre wheel was used first to evaluate the potential for ductile grinding of BK7 glass. A ductile-brittle transition was found, occurring at a depth of cut of ∼1 μm over a range of feed rates (5–50 μm/s). The multiple diamond fibre wheel was then used to grind an area, using parameters identified by the single fibre tests. Microstructural analysis revealed that material removal was predominantly in the ductile mode.
DNA Dissolves Single-walled Carbon Nanotubes in Water
Authors: Nakashima Naotoshi , Okuzono Shingo , Murakami Hiroto , Nakai Tonau , Yoshikawa Kenichi
Published: April 2003

Transmission electron microscopy, atomic force microscopy, and UV-vis-NIR absorption spectroscopy have revealed that deoxyribonucleic acid (DNA) molecules dissolve single-walled carbon nanotubes in an aqueous solution.
An Epizootic of Lymphoplasmacytic Gastritis Attributed to Helicobacter pylori Infection in Cynomolgus Monkeys (Macaca fascicularis)
Authors: Reindel J. F. , Fitzgerald A. L. , Breider M. A. , Gough A. W. , Yan C. , Mysore J. V. , Dubois A.
Published: April 2003

An epizootic of subclinical lymphoplasmacytic gastritis occurred in cynomolgus monkeys maintained at our research facility. Gastric pathology data and histologic sections of 63 adolescent monkeys (2.5-3.5 years old) sacrificed during the epizootic were reviewed. Localized to multifocal reddening of the gastric mucosa was noted grossly in 7 of 44 (16%) monkeys harboring Helicobacter pylori, but not in any of 19 monkeys in which these bacteria were not seen. Gastritis, characterized by accentuation of lymphoplasmacytic infiltrates in antral and to a lesser degree cardiac mucosa, occurred in 42 of 63 (67%) monkeys evaluated and in 42 of 44 (93%) monkeys in which H. pylori was observed microscopically. Two monkeys with H. pylori infection had infiltrate scores that overlapped with the upper limit of scores of H. pylori-negative animals. Coincident with accentuated infiltrates were gastric gland epithelial hyperplasia, reduction in mucin content of surface and gland epithelia, and comparatively minor infiltrates of neutrophils in superficial lamina propria and gastric glands. Antral mucosa thickness often exceeded 1.5 to 2 times normal. Antral mucosal erosions occurred in 7 of 44 (16%) monkeys with H. pylori. Argyrophilic bacteria morphologically consistent with H. pylori were present in antral and less commonly cardiac mucosal glands. Intensity of bacterial colonization correlated with lymphoplasmacytic infiltrates ( r = 0.754) and hyperplasia ( r = 0.700), although responses were quite variable. These bacteria were not detected in fundic mucosa except in instances where parietal cells were substantially depleted in glands coincident with localized increases in lamina propria inflammatory cell infiltrates. Helicobacter heilmannii-like organisms (HHLOs) were present in fundic glands of all 63 monkeys; colonization was often pronounced. Scores for fundic mucosal inflammation did not correlate with presence or intensity of colonization with HHLOs ( r = 0.005). Rather, fundic inflammation scores positively correlated with the antral inflammation scores ( r = 0.548). Bacteria morphologically, biochemically, and genetically consistent with H. pylori were cultured from gastric mucosal specimens confirming bacterial identification. These findings demonstrate that adolescent cynomolgus monkeys are susceptible to natural infection with H. pylori and develop many morphologic hallmarks of H. pylori-related gastritis in humans.
Extraskeletal Osteosarcoma of the Mandibular Salivary Gland in a Dog
Authors: Thomsen B. V. , Myers R. K.
Published: April 2003

A 14-year-old spayed female shepherd/collie crossbred dog had a 6 x 4-cm mass excised from below the right ear. The partially encapsulated, neoplastic mass had a necrotic core and was embedded in the mandibular salivary gland. Histologically, the mass was composed of numerous multinucleate giant cells and large, oval, pleomorphic cells that produced osteoid. Neoplastic cells were immunoreactive for vimentin and actin but not for keratin, desmin, or S-100 protein. At postmortem examination 1 month later, an 11-cm spherical mass had recurred at the surgical site, and there were metastatic nodules in the lungs, ipsilateral mandibular lymph nodes, and kidney. The tumor was diagnosed as an osteosarcoma of the mandibular sali vary gland with pulmonary, lymphatic, and renal metastasis. In addition, a 17-year survey of canine salivary-gland neoplasms revealed that most were adenocarcinomas or carcinomas.
Subacute Massive Necrotizing Myocarditis by Canine Parvovirus Type 2 Infection with Diffuse Leukoencephalomalacia in a Puppy
Authors: Agungpriyono D. R. , Uchida K. , Tabaru H. , Yamaguchi R. , Tateyama S.
Published: April 2003

Severe necrotizing myocarditis associated with canine parvovirus type 2 (CPV-2) infection and diffuse leukoencephalomalacia was recognized in a 4-week-old mongrel puppy. The cardiac lesions were characterized by severe diffuse myocardial degeneration and necrosis with occasional massive mineralization and distinct intranuclear inclusion bodies. Immunohistochemical examination revealed the presence of CPV-2 antigens in both the cytoplasm and nuclei of the myocytes. In the white matter of the cerebrum, moderate to severe diffuse necrosis with diffuse infiltration of gitter cells and occasional diffuse mineral deposits were recognized symmetrically and bilaterally. In the meningocortical area of the cerebellum, there was mild focal hemorrhage and accumulation of hemosiderin-laden histiocytes. In addition to the absence of viral antigen (as judged by immunohistochemistry), neither viral inclusions nor other vascular lesions were identified in examined sections of brain. These findings suggest that the brain lesions were not induced by direct CPV-2 infection but were related to severe myocardial lesions producing prolonged hypoxia and/or ischemia.
Expression of Vascular Endothelial Growth Factor in N-butyl-N-(4–hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis
Authors: Wakui S. , Furusato M. , Sasaki S. , Muto T. , Takahashi H. , Masaoka T. , Ushigome S.
Published: April 2003

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are proteins implicated in tumor-associated microvascular angiogenesis. Expressions of VEGF and bFGF in various stages of chemical-induced rat bladder carcinogenesis were immunohistochemically investigated. Thirty-two male 6-week-old Wistar rats were given drinking water containing 0.05% N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN) for 20 weeks. VEGF and bFGF were not detected in the normal bladder epithelium. In simple hyperplasia, intensive expression of VEGF was observed in a few epithelial cells, and the expression of epithelial VEGF became more pronounced in papillary or nodular (PN) hyperplasia and papilloma. In carcinoma, heterogeneous expression of VEGF was observed in focal tumor cells, intensely expressed in the invading tumor cells. Ultrastructurally, carcinoma cells showed VEGF immunoreactivity in the cytoplasmic matrix and some rough endoplasmic reticulum, and VEGF-positive and -negative carcinoma cells were also clearly defined. High levels of VEGF mRNA were observed in the carcinoma. However, bFGF was not detected in the epithelium throughout the carcinogenesis. Increased microvessel counts appeared at simple hyperplasia and became more pronounced in PN hyperplasia, papilloma, and carcinoma ( F-test; P < 0.05). In the carcinoma, the microvessel counts of the VEGF-expressing tumor areas were significantly higher than that of the non-VEGF-expressing tumor areas ( U-test; P < 0.05). The present study suggests that upregulation of epithelial VEGF may begin at a quite early stage in BBN-induced rat bladder carcinogenesis, but bFGF may not be involved.
Overexpression of c-Ras in Hyperplasia and Adenomas of the Feline Thyroid Gland: An Immunohistochemical Analysis of 34 Cases
Authors: Merryman J. I. , Buckles E. L. , Bowers G. , Neilsen N. R.
Published: April 2003

Formalin-fixed, paraffin-embedded thyroid glands from 18 cats diagnosed with hyperthyroidism were evaluated immunohistochemically for overexpression of the products of oncogenes c-ras and bcl2 and the tumor suppressor gene p53. Fourteen thyroid glands from euthyroid cats without histologically detectable thyroid lesions were examined similarly as controls. Results from these investigations showed that all cases of nodular follicular hyperplasia/adenomas stained positively for overexpression of c-Ras protein using a mouse monoclonal anti-human pan-Ras antibody. The most intensely positively staining regions were in luminal cells surrounding abortive follicles. Subjacent thyroid and parathyroid glands from euthyroid cats did not stain immunohistochemically for pan-Ras. There was no detectable staining for either Bcl2 or p53 in any of the cats. These results indicated that overexpression of c-ras was highly associated with areas of nodular follicular hyperplasia/adenomas of feline thyroid glands, and mutations in this oncogene may play a role in the etiopathogenesis of hyperthyroidism in cats.
Salinomycin-induced Polyneuropathy in Cats: Morphologic and Epidemiologic Data
Authors: Van Der Linde-Sipman J. S. , Van Den Ingh T. S. G. A. M. , Van Nes J. J. , Verhagen H. , Kersten J. G. T. M. , Beynen A. C. , Plekkringa R.
Published: April 2003

In April 1996, an outbreak of toxic polyneuropathy in cats occurred in the Netherlands. All cats had been fed one of two brands of dry cat food from one manufacturer. Chemical analyses of these foods, stomach contents, and liver and kidney of affected cats revealed contamination with the ionophor salinomycin. Epidemiologic and clinical data were collected from 823 cats, or about 1% of the cats at risk. In 21 affected cats, postmortem examination was performed. The affected cats had acute onset of lameness and paralysis of the hindlimbs followed by the forelimbs. Clinical and pathologic examination indicated a distal polyneuropathy involving both the sensory and motor nerves.
Lymphangiosarcomas in Cats: A Retrospective Study of 12 Cases
Authors: Hinrichs U. , Puhl S. , Rutteman G. R. , van der Linde-Sipman J. S. , Van Den Ingh T. S. G. A. M.
Published: April 2003

Clinical, macroscopic, and histologic features of 12 lymphangiosarcomas in cats are described. Nine tumors were located in the subcutaneous tissue at the caudoventral abdominal wall (eight cats) or in the neck (one cat). The remaining three cats had lymphangiosarcomas around the cranial mesenteric artery (two cats) or precardial in the mediastinum (one cat). Macroscopically, the tumors were noncircumscribed, white, edematous, and intermixed with fat tissue. Histologic features varied from cleft-forming and cavernous growth to papilliform and solid patterns. Follow-up data were available for seven cats with subcutaneous lymphangiosarcomas. All these cats died or were euthanatized within 6 months after surgery because of poor wound healing, local recurrence, or distant metastases. The cats with abdominal or thoracic masses were either euthanatized at surgery or within 6 months after the first surgery because of recurrent chylothorax, chyloperitoneum, or distant metastases.
Intranasally Inoculated Mycoplasma hyorhinis Causes Eustachitis in Pigs
Authors: Morita T. , Ohiwa S. , Shimada A. , Kazama S. , Yagihashi T. , Umemura T.
Published: April 2003

Specific-pathogen-free pigs were experimentally inoculated with Mycoplasma hyorhinis, Pasteurella multocida, or both bacterial isolates to evaluate the role of these bacteria in the pathogenesis of otitis media. Six pigs were inoculated intranasally with 4.4 × 108 colony-forming units (CFU) of M. hyorhinis. Twenty-one days later, three of these six pigs were inoculated intranasally with 5.0 × 108 CFU of P. multocida. Three additional pigs were also inoculated intranasally at the time with P. multocida alone. Two pigs served as uninoculated controls. Seven days later, all pigs were euthanatized. Histologically, subacute inflammation was found in 10 auditory tubes of six pigs and two tympanic cavities of two pigs inoculated with M. hyorhinis. Immunohistochemically, M. hyorhinis antigens were detected on the luminal surface of eight of 10 inflamed auditory tubes, and ultrastructural examination confirmed mycoplasmal organisms in two pigs. M. hyorhinis was isolated from the inflamed tympanic cavities of two pigs. None of the pigs inoculated only with P. multocida had otitis, and P. multocida was not isolated from the tympanic cavity. These findings indicate that M. hyorhinis can cause eustachitis but rarely otitis media in specific-pathogen-free pigs.