bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐A and anti‐B titers in pooled group O platelets are comparable to apheresis platelets
Authors: Cooling Laura L. , Downs Theresa A. , Butch Suzanne H. , Davenport Robertson D.
Published: July 2008

BACKGROUND: Although uncommon, acute hemolytic transfusion reactions (AHTRs) have been reported after transfusion of group O single‐donor apheresis platelets (SDPs) to group A, B, and AB recipients. Current methods for identifying “high‐titer” SDPs include tube and gel methods. The risk of a high‐titer unit is considered low with group O, poststorage, pooled platelet concentrates (PPLTs); however, data regarding anti‐A and anti‐B titers in PPLTs are lacking.

STUDY DESIGN AND METHODS: Anti‐A and anti‐B titers were determined in 185 PPLTs by direct agglutination using manual gel and tube methods. PPLTs tested included 124 group O PPLTs, 25 group A PPLTs, 26 group B PPLTs, and 10 PPLTs containing a mix of either groups O plus A or groups O plus B (mixed PPLTs). The reciprocal of the highest dilution giving macroscopic agglutination was considered the agglutinin titer.

RESULTS: Mean anti‐A and anti‐B titers in group O PPLTs were, respectively, 16 and 8 by tube and 64 and 32 by gel (p < 0.0001). Gel titers were one to two dilutions higher than tube and sensitive to reagent red cell lots. With the use of at least 64 as a critical titer, 60 percent of group O PPLTs tested by gel would be considered high‐titer. In mixed PPLTs, the addition of one non‐group O PLT significantly decreased or neutralized the corresponding anti‐A or anti‐B (p < 0.0001).

CONCLUSION: Anti‐A and anti‐B titers in group O PPLTs are comparable to those reported in group O SDPs and significantly lower than titers reported in AHTR. A critical direct agglutinin titer of 64 for identifying high‐titer units by gel is too low and should be increased to 128 or higher.
Red blood cell alloantibody frequency, specificity, and properties in a population of male military veterans
Authors: Tormey Christopher A. , Fisk John , Stack Gary
Published: July 2008

BACKGROUND: The prevalence of red blood cell (RBC) alloantibodies among general, hospital‐based patients typically has averaged approximately 1 percent in various studies. The frequency and properties of RBC alloantibodies in military veterans has never been examined.

STUDY DESIGN AND METHODS: Transfusion records of 18,750 military veterans at a Department of Veterans Affairs (VA) medical center were retrospectively reviewed. For patients with RBC alloantibodies, the following were collected: sex, race/ethnicity, decade of birth, transfusion history, alloantibody specificity, reaction phase(s), and whether alloantibodies were detected at the initial type and screen or later.

RESULTS: The RBC alloantibody prevalence was 2.4 percent among predominantly male military veterans. Alloantibody prevalence varied with decade of birth, ranging up to 3.3 percent (1911‐1920). The 10 most frequent alloantibodies in males, as a percentage of total male antibodies, were K (21.9%), E (19.4%), D (9.1%), Lea (7.4%), Fya (5.4%), c (4.8%), C (4.6%), P1 (3.9%), Jka (3.7%), and Leb (3.5%). Investigation of D alloimmunization in men revealed that antibody development occurred before VA care in 80 percent (39/49) of cases. For alloimmunization during VA care, anti‐D was mostly associated with the transfusion of D+ platelets (7/10). The majority of alloantibodies in males reacted at the antiglobulin (AG) phase, even anti‐Lea, ‐Leb, M, ‐Lua, and ‐P1.

CONCLUSION: Military veterans have a relatively high prevalence of RBC alloantibodies, including anti‐D, despite a large male predominance and lack of pregnancy‐related alloimmunization. Alloantibody prevalence was highest in World War II veterans. The majority of male alloantibodies reacted with AG, even those traditionally considered to be clinically insignificant.
Vascular access for hemodialysis: Experience of a team of nephrologists
Authors: STANZIALE Rodolfo , LODI Massimo , D'ANDREA Enrico , D'ANDREA Tonino
Published: July 2008

A survey conducted by Bonucchi et al. underlined the different types of doctors placing arteriovenous fistula (AVF) for hemodialysis in the United States and Europe (in particular Italy). In fact, nephrologists definitely prevail in Italy, where almost 48.8% of nephrologists place an AVF themselves or with the help of a vascular surgeon (26.4%). In Europe, only 35% do so, whereas 89% of AVF are performed by surgeons in the United States. In 98% of the cases occurring at our center, the AVF was placed and reviewed by the nephrologists. This paper reports surgery cases related to the period between January 1983 and September 2006. Over this time, 1386 operations for placing and reviewing vascular access were conducted. Among these, 47 (3.3%) were related to a cuffed central venous catheter (CVC); 1138 (80.2%) related to a distal AVF; 201 (10.6%) related to a proximal AVF; and 51 (3.6%) related to an arteriovenous graft (AVG). In addition, 33 (2.3%) operations performed before January 1983 relating to AV Scribner shunts were included. Arteriovenous fistulas or AVGs were provided to our patients (only 2.6% of them have a CVC), and AVF rescue operations were performed in the shortest possible time with advantages for the patient and his vascular access.
Human platelet antigens polymorphisms and susceptibility of thrombosis in hemodialysis patients
Authors: GORGI Yousr , SFAR Imen , BEN AABDALLAH Taieb , AOUADI Houda , ABDERRAHIM Ezzeddine , BARDI Rafika , JENDOUBI‐AYED Saloua , AYED Khaled
Published: July 2008

To investigate the association between the polymorphisms of human platelet antigen (HPA)‐1,2,3,4,5 and susceptibility to develop thrombosis accident in arteriovenous fistula (AVF), genomic DNA of 112 hemodialysis (HD) patients and 100 healthy blood donors were genotyped by PCR‐SSP. The patients were classified into 2 groups: G1 included 54 HD patients presented at least one thrombotic episode on the level of the AVF, and G2 included 58 HD patients without any episode of thrombosis. The allelic frequencies of HPA‐1, 2, 3, and 5 among patients and controls did not reveal significant differences. However, the HPA‐4b allele was significantly more frequent in G1 than in controls or in G2 patients (23.1% vs. 11.5% and 0.9%, respectively), p<0.01 and p<0.001. The genotype distribution of HPA‐4 polymorphism reveals that the HPA‐4a4b genotype was more frequent in G1 patients (23/54: 42.6%) than in all HD patients (25/112: 22.3%) or in G2 patients (1/58: 1.72%) (p<0.001, odds ratio: 45.6). Among 24 HD patients with HPA‐4a4b genotype, 23 (96%) developed at least 1 or more thrombotic episode on the level of their AVF. However, 30 patients (34.5%) among 87 HD patients with HPA‐4a4a genotype presented thrombotic episode (p<0.001). These results reveal a significant association between HPA‐4a4b and thrombosis, and it is likely that HPA polymorphisms could be useful markers for potential risk of thrombosis in hemodialysis.
Central venous oxygen saturation and thoracic admittance during dialysis: New approaches to hemodynamic monitoring
Authors: CORDTZ Joakim , OLDE Bo , SOLEM Kristian , LADEFOGED Soeren D.
Published: July 2008

Intradialytic hypotension (IDH) is one of the most important short‐term complications to hemodialysis (HD). Inadequate cardiac filling due to a reduction in the central blood volume is believed to be a major etiological factor. The aim of this study was to evaluate whether these pathophysiologic events are reflected in the central venous oxygen saturation (ScO2) and thoracic admittance (TA) during dialysis. Twenty ambulatory HD patients, 11 hypotension prone (HP) and 9 hypotension resistant, with central vascular access, were monitored during 3 HD sessions each. ScO2, TA, finger blood pressure (BP), and relative change in blood volume (ΔBV) were measured and sampled continuously. The relative TA decrease and ΔBV were both largest in the HP group (p<0.05 for both), whereas ScO2 decreased only in HP patients (p<0.001). Baseline TA was lower in the HP group (p<0.01). Changes in ScO2 and TA correlated much closer than did changes in ScO2 and ΔBV (r=0.43 and 0.18, respectively). Our results suggest that an intradialytic decrease in cardiac output, as reflected by a fall in ScO2, is a common feature to HD patients prone to IDH. In patients using a central vascular access, ScO2 and TA measurements may be more specific to the pathophysiologic events preceding IDH than ΔBV—the current standard monitoring method.
Decreased hemodialysis circuit pressures indicating postpump tubing kinks: A retrospective investigation of hemolysis in five patients
Authors: MALINAUSKAS Richard A.
Published: July 2008

The source of hemolysis during hemodialysis must be quickly identified to avoid life‐threatening complications. At a single clinic, over a 10‐day period in which 550 treatments were performed, 5 case‐patients were retrospectively identified for experiencing acute hemolysis (4 deaths) from an unknown origin. The investigation focused on the postpump arterial tubing as the pressure was not monitored in this region, and the segment was shorter than required and could kink if overly stressed at bend points (i.e., tubing support clips, dialyzer inlet). To determine whether the circuit pressures indicated kinked tubing, a relative comparison between each case‐patient's recorded arterial (prepump) and venous circuit pressures throughout their adverse event treatment and their immediately preceding treatment was conducted. Treatment pressure‐time traces showed that sustained, significant decreases (>25 mmHg) in both of the circuit pressures occurred only on the hemolytic event dates. While direct observations of kinked tubing were not reported, the circuit pressure decreases could only be explained by severe postpump tube kinking causing a decrease in the blood flow rate. While postpump obstructions and hemolysis can occur without causing noticeable changes to the prepump arterial and venous blood line pressures (due to the highly occlusive setting of the roller blood pump), recognizing sudden and/or sustained decreases in the circuit pressures during treatment may help to prevent adverse patient events. This analysis reinforces the importance of regularly checking the blood tubing set for kinks and for monitoring the circuit pressures for atypical trends within and between treatments.
Home hemodialysis in Australia and New Zealand: Practical problems and solutions
Authors: AGAR John W. M.
Published: July 2008

Home hemodialysis, as practiced in Australia and New Zealand, offers patients the return of self‐control and self‐esteem. It also allows reconnection with family, friends and (re)employment. Though there are emotional and time‐related “costs” with home hemodialysis, these center on training time, commitment and patient or family stresses and, if carefully managed and properly resourced, can be overcome for most home‐suitable patients. As we believe many center‐based hemodialysis patients are home‐suitable and that home care is severely under‐utilized, assessment techniques to maximize uptake are examined. While patient dropout from home care relates more to staff attitudes than to true home‐failure, dropout is minimized by ensuring the patient and not a carer takes full dialysis responsibility with the carer acting as a supporter and not the facilitator. Installation of home equipment is simple and cheap, the financial costs of home hemodialysis being substantially less than those of facility care where salary and infrastructure costs far exceed training, equipment, installation and maintenance costs at home. Home monitoring is not routinely required especially with longer, more frequent regimens—but effective 24‐hour on‐call nurse and technician cover is essential. Intravenous drug self‐administration at home is safe and effective, reducing the need for hospital visits to a 2–3 monthly minimum. The debilitating effects of facility care cannot be over‐emphasized while the liberating psychology of a well‐supported hemodialysis program is truly satisfying for patient and staff alike.
Short and long nightly hemodialysis in the United States
Authors: LOCKRIDGE Robert S. , PIPKIN Mary
Published: July 2008

When hemodialysis first started in the United States in the 1960s, a large percentage of patients performed their treatments at home. However, because of reimbursement issues, home hemodialysis (HHD) gradually succumbed to an in‐center approach and eventually a mindset. Since the introduction of nightly HHD by Uldall and Pierratos in 1993, there has been a resurgence of interest in HHD. This paper describes the different types of home hemodialysis being performed as of December 31, 2007 in this country. Because neither the United States Renal Data System (USRDS) nor the End Stage Renal Disease (ESRD) Networks break down home dialysis into the different modalities, a provider questionnaire was sent out to 2 major providers, a number of mid‐level providers and other providers known to do HHD. In addition, a questionnaire was sent out to 3 machine providers to obtain the number of patients using their machine for HHD as of December 31, 2007. The results showed that 91.7% of patients are dialyzing in‐center, 7.3% are doing peritoneal dialysis, and 0.7% are doing HHD. Currently about 1% of ESRD patients in the United States are doing home hemodialysis. NxStage, however, has started 1000 patients in the past year on short‐daily home hemodialysis. Patients are beginning to understand that there are better options than 3 times a week in‐center dialysis. And as a result of the “HEMO Study,” nephrologists now believe that longer and more frequent dialysis is a better therapy for ESRD patients. Therefore, promotion of HHD should become a priority for the renal community in the future.
Acute heart inflammation: ultrastructural and functional aspects of macrophages elicited by Trypanosoma cruzi infection
Authors: Melo Rossana C. N.
Published: July 2008

Introduction

Acute T. cruzi infection induces accentuated mobilization/migration of monocytic lineage cells into heart

Heart inflammatory macrophages show a distinct morphology and are actively involved in parasite phagocytosis

Lipid bodies as structural markers of inflammatory macrophages

Macrophages and the resolution of acute inflammation and heart repair

Concluding remarks

The heart is the main target organ of the parasite Trypanosoma cruzi, the causal agent of Chagas' disease, a significant public health issue and still a major cause of morbidity and mortality in Latin America. During the acute disease, tissue damage in the heart is related to the intense myocardium parasitism. To control parasite multiplication, cells of the monocytic lineage are highly mobilized. In response to inflammatory and immune stimulation, an intense migration and extravasation of monocytes occurs from the bloodstream into heart. Monocyte differentiation leads to the formation of tissue phagocytosing macrophages, which are strongly activated and direct host defence. Newly elicited monocyte‐derived macrophages both undergo profound physiological changes and display morphological heterogeneity that greatly differs from originally non‐inflammatory macrophages, and underlie their functional activities as potent inflammatory cells. Thus, activated macrophages play a critical role in the outcome of parasite infection. This review covers functional and ultrastructural aspects of heart inflammatory macrophages triggered by the acute Chagas' disease, including recent discoveries on morphologically distinct, inflammation‐related organelles, termed lipid bodies, which are actively formed in vivo within macrophages in response to T. cruzi infection. These findings are defining a broader role for lipid bodies as key markers of macrophage activation during innate immune responses to infectious diseases and attractive targets for novel anti‐inflammatory therapies. Modulation of macrophage activation may be central in providing therapeutic benefits for Chagas' disease control.
PPARγ2 expression in growth plate chondrocytes is regulated by p38 and GSK‐3
Authors: Stanton Lee‐Anne , Li Jennifer Ruizhe , Beier Frank
Published: July 2008

Although peroxisome proliferator activated receptor (PPAR)γ remains a critical regulator of preadipocyte differentiation, new roles have been discovered in inflammation, bone morphogenesis, endothelial function, cancer, longevity and atherosclerosis. Despite the demonstration of PPARγ expression in chondrocytes, its role and the pathways affecting its expression and activity in chondrocytes remain largely unknown. We investigated the effects of PPARγ activation on chondrocyte differentiation and its participation in chondrocyte lipid metabolism. PPARγ2 expression is highly regulated during chondrocyte differentiation in vivo and in vitro PPARγ activation with troglitazone resulted in increased Indian hedgehog expression and reduced collagen X expression, confirming previously described roles in the inhibition of differentiation. However, the major effect of PPARγ2 in chondrocytes appears to be on lipid metabolism. During differentiation chondrocytes increase expression of the lipid‐associated metabolizing protein, Lpl, which is accompanied by increased gene expression of PPARγ. PPARγ expression is suppressed by p38 activity, but requires GSK‐3 activity. Furthermore, Lpl expression is regulated by p38 and GSK‐3 signalling. This is the first study demonstrating a relationship between PPARγ2 expression and chondrocyte lipid metabolism and its regulation by p38 and GSK‐3 signalling.
Genetic transfer of fusion proteins effectively inhibits VCAM‐1‐mediated cell adhesion and transmigration via inhibition of cytoskeletal anchorage
Authors: Hagemeyer Christoph E. , Ahrens Ingo , Bassler Nicole , Dschachutaschwili Natia , Chen Yung C. , Eisenhardt Steffen U. , Bode Christoph , Peter Karlheinz
Published: July 2008

The adhesion of leukocytes to endothelium plays a central role in the development of atherosclerosis and thus represents an attractive therapeutic target for anti‐atherosclerotic therapies. Vascular cell adhesion molecule‐1 (VCAM‐1) mediates both the initial tethering and the firm adhesion of leukocytes to endothelial cells. Our work evaluates the feasibility of using the cytoskeletal anchorage of VCAM‐1 as a target for gene therapy. As a proof of concept, integrin αIIbβ3‐mediated cell adhesion with clearly defined cytoskeletal anchorage was tested. We constructed fusion proteins containing the intracellular domain of β3 placed at various distances to the cell membrane. Using cell adhesion assays and immunofluorescence, we established fusion constructs with competitive and dominant negative inhibition of cell adhesion. With the goal being the transfer of the dominant negative mechanism towards VCAM‐1 inhibition, we constructed a fusion molecule containing the cytoplasmic domain of VCAM‐1. Indeed, VCAM‐1 mediated leukocyte adhesion can be inhibited via transfection of DNA encoding the designed VCAM‐1 fusion protein. This is demonstrated in adhesion assays under static and flow conditions using CHO cells expressing recombinant VCAM‐1 as well as activated endothelial cells. Thus, we are able to describe a novel approach for dominant negative inhibition of leukocyte adhesion to endothelial cells. This approach warrants further development as a novel gene therapeutic strategy that aims for a locally restricted effect at atherosclerotic areas of the vasculature.
IL‐12 immunotherapy of murine leukaemia: comparison of systemic versus gene modified cell therapy
Authors: Labbe Alain , Nelles Megan , Walia Jagdeep , Jia Lintao , Furlonger Caren , Nonaka Takahiro , Medin Jeffrey A. , Paige Christopher J.
Published: July 2008

The ability of IL‐12 to initiate anti‐leukaemia immune responses has been well established; however clinical outcomes fail to recapitulate the therapeutic benefits observed in the laboratory. To address this, we compared two systems of IL‐12 therapy that elicit protective immune responses against the murine acute lymphoblastic leukaemia (ALL) cell line, 70Z/3. These systems differ in the method of IL‐12 administration and ultimately result in leukaemia clearance by distinct mechanisms, emphasizing the importance of treatment vehicle. Injecting low‐dose IL‐12 was sufficient to elicit long‐term protective immunity against an established leukaemia burden, mediated by both CD4+ and CD8+ T cells. These findings agree with the standard model of IL‐12 activity. We compared this protocol to a cell‐based approach in which a novel lentiviral vector (LV) expressing murine IL‐12 was created, 70Z/3 cells transduced, and clones selected that stably secrete different amounts of IL‐12. We found that only a small proportion (1%) of IL‐12 secreting cells were required for rejection but that the amount of IL‐12 produced per cell was critical for successful therapy. Importantly, the levels of IL‐12 required were found to be higher than the levels reported to date in the human clinical trial literature. We found that the cell‐based approach led to protective immunity that was both long‐term and specific but dependent primarily on a CD4+ cellular subset alone. Our results highlight that the mode of IL‐12 delivery has a distinct impact on the immune response initiated, leading to leukaemia clearance by disparate mechanisms. We also establish a new and critical parameter, IL‐12 production/cell, which may have significant implications for future therapeutic design.
Activation of protease calpain by oxidized and glycated LDL increases the degradation of endothelial nitric oxide synthase
Authors: Dong Yunzhou , Wu Yong , Wu Mingyuan , Wang Shuangxi , Zhang Junhua , Xie Zhonglin , Xu Jian , Song Ping , Wilson Kenneth , Zhao Zhengxing , Lyons Timothy , Zou Ming‐Hui
Published: July 2008

Oxidation and glycation of low‐density lipoprotein (LDL) promote vascular injury in diabetes; however, the mechanisms underlying this effect remain poorly defined. The present study was conducted to determine the effects of ‘heavily oxidized’ glycated LDL (HOG‐LDL) on endothelial nitric oxide synthase (eNOS) function. Exposure of bovine aortic endothelial cells with HOG‐LDL reduced eNOS protein levels in a concentration‐ and time‐dependent manner, without altering eNOS mRNA levels. Reduced eNOS protein levels were accompanied by an increase in intracellular Ca2+, augmented production of reactive oxygen species (ROS) and induction of Ca2+‐dependent calpain activity. Neither eNOS reduction nor any of these other effects were observed in cells exposed to native LDL. Reduction of intracellular Ca2+ levels abolished eNOS reduction by HOG‐LDL, as did pharmacological or genetic through calcium channel blockers or calcium chelator BAPTA or inhibition of NAD(P)H oxidase (with apocynin) or inhibition of calpain (calpain 1‐specific siRNA). Consistent with these results, HOG‐LDL impaired acetylcholine‐induced endothelium‐dependent vasorelaxation of isolated mouse aortas, and pharmacological inhibition of calpain prevented this effect. HOG‐LDL may impair endothelial function by inducing calpain‐mediated eNOS degradation in a ROS‐ and Ca2+‐dependent manner.
Chitosan cooperates with mesenchyme‐derived factors inregulating salivary gland epithelial morphogenesis
Authors: Yang Tsung‐Lin , Young Tai‐Horng
Published: July 2008

Chitosan is a widely used biocompatible biomaterial in the tissue regeneration, but its utility and application in the tissue morphogenesis of salivary gland remains unclear. The study aimed to explore the effects of chitosan on the epithelial morphogenesis of submandibular gland (SMG). With chitosan, the branching morphogenesis of the whole SMG explant was facilitated, and the morphogenetic‐promoting effects of mesenchymal tissue on SMG were further enhanced. Furthermore, chitosan was competent to induce recombined SMG epithelium to form branches in the serum‐free condition independently. In the presence of chitosan, the morphogenetic efficacy of mesenchyme‐derived growth factors responsible for epithelial morphogenesis including fibroblast growth factors 7, fibroblast growth factor 10 and hepatocyte growth factor increased. The specific epithelial phenotype induced by individual growth factor, which was required for the accomplishment of salivary epithelial morphogenesis, was promoted by chitosan. Moreover, the proliferative and the chemotactic properties of these growth factors towards the SMG epithelia were also reinforced by chitosan. Therefore, in orchestrating and intensifying the essential mesenchyme‐derived growth factors, chitosan is versatile in mediating SMG epithelium to form a predetermined phenotype more efficiently and comprehensively. This study suggested that chitosan is a morphogenetic‐regulating biomaterial for salivary tissue, which might be useful for the future salivary gland investigation and regeneration.
5‐year clinical experience with BTI® dental implants: risk factors for implant failure
Authors: Anitua Eduardo , Orive Gorka , Aguirre José Javier , Ardanza Bruno , Andía Isabel
Published: July 2008

Objectives: The aims of this study were to identify with appropriate statistical tests the risk factors associated with implant failure and to evaluate the long‐term survival of dental implants using implant loss as an outcome variable and performing an implant‐, surgery‐ and patient‐based analysis of failures.

Material and Methods: A retrospective cohort study design was used. One thousand sixty patients received 5787 BTI® implants during the years of 2001–2005 in Vitoria, Spain. The potential influence of demographic items, clinical items, surgery‐dependent items and prosthetic variables on implant survival was studied. Implant survival was analysed using a life‐table analysis. Cox proportional hazards regression was used to identify risk factors related to implant failure.

Results: Smoking habits, implant position, implant staging (two‐stage implants) and the implementation of special techniques were statistically correlated with lower implant survival rates. Two risk factors associated with implant failure were detected in this study: implant staging (two‐stage implants) and the use of special techniques. Additionally, the overall survival rates of BTI® implants were 99.2%, 96.4% and 96% for the implant‐, surgery‐ and patient‐based analysis, respectively. Totally, 28 out from 5787 implants (0.48%) were lost during the observation period. Most of the patients with implant failure (69.6%) presented chronic or aggressive periodontitis.

Conclusions: Implant staging and the use of special techniques are risk factors for implant failure.
Clonal stability of Porphyromonas gingivalis in untreated periodontitis
Authors: Van Winkelhoff Arie J. , Rijnsburger Martine C. , Van Der Velden Ubele
Published: July 2008

Objectives: The objective of the present investigation was to study the clonal stability of Porphyromonas gingivalis in a population of Indonesian subjects, deprived of dental care and with varying degrees of periodontitis over a period of 8 years.

Material and Methods: In 1994, 105 subjects and in 2002, 103 subjects were P. gingivalis culture positive. Multiple isolates from each of these subjects were used for amplified fragment length polymorphism (AFLP) typing.

Results: Sixty‐six individuals were P. gingivalis culture positive at both time points. In 31 subjects (47%) an exact identical P. gingivalis genotype distribution was found in 1994 and in 2002. In 26 of these subjects one genotype, in eight subjects two identical genotypes were found at both time points. In 70% of the subjects at least one P. gingivalis genotype was found in 1994 and 2002, whereas other genotypes were either newly detected or were no longer detectable. Identical genotypes were found in 26% of the sibships. Clonal stability in siblings was 39%. Horizontal transmission of P. gingivalis was only found in 2002 and was low (11%). In total, 56 P. gingivalis genotypes were identified in 1994 and 61 in 2002. Twenty‐four appeared unique, whereas other genotypes were found in multiple subjects within as well as without families. One genotype occurred in 11 different subjects.

Conclusions: The clonal stability of P. gingivalis under natural conditions is high. Complete different genotype distribution was found in only 27% of the subjects. Transmission of P. gingivalis occurred frequently among siblings but not among spouses.
Atrophoderma of Pasini and Pierini: a clinical and histopathological study
Authors: Saleh Zenus , Abbas Ossama , Dahdah Maurice J. , Kibbi Abdul G. , Zaynoun Shukrallah , Ghosn Samer
Published: July 2008

Background:  Idiopathic atrophoderma of Pasini and Pierini (IAPP) usually manifests as one or multiple depressed and hyperpigmented patches, with a predilection to the trunk. No diagnostic changes are usually seen on histology. Elastic stains often reveal no abnormalities.

Objective:  To review our cases of IAPP, describe their clinical and histological findings and compare them with the literature.

Methods:  Retrospective review of IAPP cases who presented to our institution between 1994 and 2006.

Results:  From a total of 16 patients, only 19% displayed hyperpigmented lesions, while 81% had either hypopigmented (9/16) or skin‐colored (4/16) lesions. The sites predominantly affected were the lower extremities (62.5%), followed by the upper extremities and trunk. Only in one patient was IAPP co‐existent with morphea. Histology revealed no diagnostic abnormalities; however, elastic stains showed a spectrum of changes ranging from normal to severe diminution and fragmentation of elastic fiber network.

Conclusions:  Our study shows several new aspects of IAPP. Clinically, the lesions were most commonly hypopigmented and involved predominantly the extremities. Histologically, IAPP exhibited a spectrum of alterations in elastic fibers. The most prevalent form of IAPP in our country seems to be unassociated with morphea.
Myocardial infarction in thrombotic thrombocytopenic purpura: a single‐center experience and literature review
Authors: Wahla Ali S. , Ruiz Jimmy , Noureddine Nizar , Upadhya Bharathi , Sane David C. , Owen John
Published: July 2008

Background:  Several case reports and series have described myocardial infarctions (MIs) in patients hospitalized for thrombotic thrombocytopenic purpura (TTP). The exact magnitude and outcome of this complication are unknown.

Methods:  Electronic medical records for patients admitted to Wake Forest University Baptist Medical Center were examined from 1996 to 2005. Those patients having a diagnosis of TTP during the hospitalization period were included in the analysis. Only patients’ initial episodes of TTP were analyzed. Baseline cardiac and TTP risk factors were documented. Outcomes analyzed included MIs, arrhythmias, development of congestive heart failure and death.

Results:  Eighty‐five patients diagnosed with TTP were identified with 13 (15.3%) having MIs, as defined by an elevation of cardiac enzymes. Median troponin I value was 5.9 ng/mL (range 3.7–8.8 ng/mL). Twelve patients had non‐ST segment elevation MIs and one had ST segment elevation. Two of 13 patients who had echocardiographic analysis had documented wall motion abnormalities. There was no difference between non‐MI and MI patients in cardiac risk factors, prior cardiac events, history of thromboembolic disease or heart failure. There was no in‐hospital mortality difference.

Conclusion:  MI is an important complication of TTP, identified in 15.3% of patients in our study. Routine cardiovascular evaluation with cardiac enzymes, electrocardiography, and telemetry is warranted in acute TTP patients. Appropriate intervention is yet to be determined.
Total population density during the first year of life as a major determinant of lifetime body‐length trajectory in marble trout
Authors: Vincenzi S. , Crivelli A. J. , Jesensek D. , De Leo G. A.
Published: July 2008

Abstract – The conditions experienced early in life can strongly influence life‐history trajectories in a variety of animal species. Here, we use data from four isolated populations of the endangered stream‐dwelling salmonid marble trout (Salmo marmoratusCuvier 1817) living in the Soca and Idrijca river basins (Slovenia) to explore the influence of the total density experienced during and after the first year of life by marble trout year‐classes on body length of marble trout through the lifetime. Analyses were performed by pooling together the stream‐specific datasets to cover a wider range of densities. Mean body length of marble trout year‐classes through the lifetime (from age 1+ to 5+) was negatively related to total density of marble trout during the first year of life. The relationship between density during the first growth period and body length through the lifetime was well described by negative power curves. Total population density after the first year of life was not correlated with body length, thus suggesting that body growth trajectories are heavily determined early in life. Given size‐dependent sexual maturity and egg production in marble trout, the relationship between density early in life and lifetime individual growth may have strong implications in terms of population dynamics and regulation of population size.
Char ecology. Natal homing in sympatric populations of anadromous Arctic char Salvelinus alpinus (L.): roles of pheromone recognition
Authors: Nordeng Hans
Published: July 2008

Abstract –  This study revealed that progeny of sympatric Salangen Arctic char, omitted from any kind of imprinting to home water, returned with high precision to the home river and parental locality upon releases in their native marine environments. Fish did not select river randomly, and the homing precision was the same for progeny whether fertilized in home stream or in foreign water. The progeny studied originate from the lake Øvervatnet and the Salangen River population and were hatched and reared at a hatchery at Voss in southern Norway. Experimental material comprised freshwater resident and smolt released from parr directly. The freshwater resident is partly anadromous exhibiting about 74% smolt when released directly into the sea. Char at all stages (resident, transformed resident, and smolt released from parr directly) returned in significant numbers to the home river system and the site of the specific parental population.
IL‐1, IL‐18, and IL‐33 families of cytokines
Authors: Arend William P. , Palmer Gaby , Gabay Cem
Published: July 2008

Summary: The interleukin‐1 (IL‐1), IL‐18, and IL‐33 families of cytokines are related by mechanism of origin, receptor structure, and signal transduction pathways utilized. All three cytokines are synthesized as precursor molecules and cleaved by the enzyme caspase‐1 before or during release from the cell. The NALP‐3 inflammasome is of crucial importance in generating active caspase‐1. The IL‐1 family contains two agonists, IL‐1α and IL‐1β, a specific inhibitor, IL‐1 receptor antagonist (IL‐1Ra), and two receptors, the biologically active type IL‐1R and inactive type II IL‐1R. Both IL‐1RI and IL‐33R utilize the same interacting accessory protein (IL‐1RAcP). The balance between IL‐1 and IL‐1Ra is important in preventing disease in various organs, and excess production of IL‐1 has been implicated in many human diseases. The IL‐18 family also contains a specific inhibitor, the IL‐18‐binding protein (IL‐18BP), which binds IL‐18 in the fluid phase. The IL‐18 receptor is similar to the IL‐1 receptor complex, including a single ligand‐binding chain and a different interacting accessory protein. IL‐18 provides an important link between the innate and adaptive immune responses. Newly described IL‐33 binds to the orphan IL‐1 family receptor T1/ST2 and stimulates T‐helper 2 responses as well as mast cells.
Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics
Authors: Feldmann Marc , Maini Sir Ravinder N.
Published: July 2008

Summary: Advances in cDNA and monoclonal antibody technology in the 1980s fuelled the discovery and characterization of the properties of cytokines. It became apparent that because cytokines were expressed in tissues derived from autoimmune diseases, they were likely to be of fundamental importance in disease pathogenesis and developing a new class of biological therapeutics. In this review, we describe the history of bench to bedside translation of work that led to the identification of tumor necrosis factor (TNF) as a key regulator of the loss of homeostatic immune‐inflammatory responses in rheumatoid arthritis (RA) and a good therapeutic target. First in human clinical trials in collaboration with a biotechnology company, the safety and efficacy of TNF blockade with a chimeric monoclonal antibody was substantiated in patients refractory to standard anti‐rheumatoid drugs. Abnormal immune‐inflammatory responses after therapy showed improvement and remain a focus of ongoing research in many laboratories. Longer term multi‐center studies that followed with several anti‐TNF biologicals have demonstrated the augmented efficacy, including inducing clinical remission, of low dose methotrexate and anti‐TNF therapy co‐therapy, but serious infections and lymphomas in a low frequency have been observed. In the course of the past decades, three ‘blockbuster’ anti‐TNF biologicals are in the clinic. Over a million patients with RA and other immune‐mediated diseases have been successfully treated, and a better perspective on the risk of harm and its management has become part of good clinical practice. This success has encouraged a burgeoning industry of biologicals for chronic diseases.
Development of TLR inhibitors for the treatment of autoimmune diseases
Authors: Barrat Franck J. , Coffman Robert L.
Published: July 2008

Summary The innate immune system is a critical element of protection from invading pathogens. The specific receptors that recognize various components of the pathogens trigger signals that result in the production of proinflammatory cytokines as well as the activation of antigen‐presenting cells, which activate the adaptive immune system. The discovery of the Toll‐like receptors (TLRs) as important components of pathogen recognition has brought new understanding of the key signaling molecules involves in innate immune activation. Interestingly, it appears that most TLRs can recognize self‐ligands as well and that mechanisms are required to discriminate between self and non‐self ligands. One of these mechanisms is the expression of all the nucleic acid‐specific TLR in endosomal compartments and not on the cell surface. Inappropriate activation of TLRs by self‐components can result in sterile inflammation or autoimmunity. For example, TLR7 and TLR9 activation by endogenous RNA and DNA, transported to the endosomes in the form of immune complexes or non‐covalently associated with cationic peptides, could be an important mechanism involved in promoting diseases such as systemic lupus erythematosus and psoriasis. In this review, we discuss the rationale for self‐recognition by TLR7 and TLR9 as an important part of the development of lupus and other autoimmune diseases. We describe novel inhibitors of these receptors and provide evidence to support their use as novel therapeutic agents for autoimmunity.
Strategies for use of IL‐10 or its antagonists in human disease
Authors: O'Garra Anne , Barrat Franck J. , Castro Antonio G. , Vicari Alain , Hawrylowicz Catherine
Published: July 2008

Summary: Interleukin‐10 (IL‐10) is a cytokine with broad anti‐inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen‐presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T‐helper 1 (Th1)‐type and Th2‐type responses. This review discusses the potential use of IL‐10 or agents that induce IL‐10 as potential anti‐inflammatory therapies in inflammatory diseases. Although IL‐10‐deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti‐inflammatory properties of IL‐10, although it should be noted that as discussed below, IL‐10 can also promote B‐cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL‐10 may result in chronic infection. Thus, antagonists of IL‐10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL‐10, which may lead to potential uses of IL‐10 or its antagonists in human disease.
The Luminal Domain of p23 (Tmp21) Plays a Critical Role in p23 Cell Surface Trafficking
Authors: Blum Robert , Lepier Alexandra
Published: July 2008

p23 (Tmp21 or p24δ), a member of the p24 family, is important for maintaining the integrity of the secretory pathway in mammals. It is a type I protein with a receptor‐like luminal domain and a short cytoplasmic tail. This cytoplasmic tail carries an atypical endoplasmic reticulum (ER) retention KKXX motif that binds to coat protein I. The trafficking of p23 has been thought to be restricted to the early secretory pathway. However, recent findings as well as this study demonstrate that p23 is also found in the plasma membrane. By tagging different domains of p23 with green fluorescent protein, it is shown that it is the luminal domain that is primarily responsible for the appearance of p23 in the plasma membrane, despite the presence of a functional KKXX‐ER retention and retrieval motif. When the KKXX motif is abolished, p23 shows an extremely increased trafficking to the plasma membrane. These experiments reveal the presence of two fractions of p23 with distinct trafficking destinations. One fraction cycles through the ER–Golgi pathway using its functional KKXX retrieval motif. The transient appearance of p23 in the plasma membrane is supported by the luminal domain. These results help to explain the functional presence of p23 in plasma membrane protein complexes and post‐Golgi compartments.
Root development of rat tooth germs implanted in the tooth socket and in the subcutaneous tissue
Authors: Ina Y , Sasano Y , Akiba N , Hatori K , Honma T , Sasaki K
Published: July 2008

Objective:  This study was designed to investigate root development of a rat tooth germ implanted in a tooth socket or in a subcutaneous region.

Materials and methods:  Tooth germs of the upper left first molars in 2‐week‐old rats were extracted and implanted in the original tooth socket or in the subcutaneous region of the back. The upper right first molar was used as a control. The rats were fixed in weeks 1, 2, 4, 8 and 12. The root development was examined quantitatively with X‐ray radiographic morphometry. The cellular activity of producing matrix proteins was assessed using in situ hybridization for type I collagen.

Results:  Root development was observed in the implanted teeth in the tooth socket as also in the control teeth. In contrast, roots hardly developed in subcutaneously implanted teeth. Histology showed that periodontal ligaments were arranged around roots of implanted teeth in the tooth socket as around control teeth, but few periodontal ligaments were identified in the subcutaneous implantation. Dentin and cementum formed in both the implanted teeth as also in the control teeth and odontoblasts, cementoblasts and cementocytes expressed type I collagen.

Conclusion:  Tooth sockets may possess specific environments that allow root development of a tooth germ.
MAGNETIC RESONANCE IMAGING FEATURES OF EMPTY SELLA IN DOGS
Authors: KONAR MARTIN , BURGENER IWAN A. , LANG JOHANN
Published: July 2008

In humans, the empty sella is defined as herniation of the subarachnoidal space into the sella turcica with invisible (total empty sella) or reduced (partial empty sella) hypophyseal size. An empty sella can be associated with endocrine disturbances. The purpose of this study was to determine if the empty sella exists in dogs or cats and whether it is associated with endocrinopathy or hydrocephalus. Archived magnetic resonance images of the head of 370 dogs and 77 cats were re‐evaluated specifically for the presence or absence of the pituitary gland. Hypophyseal tissue filling more than 50% of the sella was considered normal, between 30% and 50% was defined as partial empty sella and less than 30% was defined as total empty sella. In patients with an empty sella, and in all other imaged dogs of the affected breeds, the ventricle to brain ratio was measured. In patients with an empty sella, the medical record was searched for evidence of endocrinopathy. No cat had an empty sella but 11 dogs (3%) had a small or missing hypophysis. Seven of these dogs had a ventricle to brain ratio greater than 15%. Only small dogs (mean weight of 6.7 kg) were affected. One dog with an empty sella had signs of central hyperadrenocorticism while the other 10 had no sign of endocrinopathy. We conclude that the empty sella exists in dogs but is not generally associated with endocrinopathy.
CHARACTERIZATION OF NORMAL FELINE RENAL VASCULAR ANATOMY WITH DUAL‐PHASE CT ANGIOGRAPHY
Authors: CÁCERES ANA V. , ZWINGENBERGER ALLISON L. , ARONSON LILLIAN R. , MAI WILFRIED
Published: July 2008

Helical computed tomography angiography was used to evaluate the renal vascular anatomy of potential feline renal donors. One hundred and fourteen computed tomography angiograms were reviewed. The vessels were characterized as single without bifurcation, single with bifurcation, double, or triple. Multiplicity was most commonly seen for the right renal vein (45/114 vs. 3/114 multiple left renal veins, 0/114 multiple right renal arteries, and 8/114 multiple left renal arteries). The right kidney was 13.3 times more likely than the left to have multiple renal veins. Additional vascular variants included double caudal vena cava and an accessory renal artery. For the left kidney, surgery and computed tomography angiography findings were in agreement in 92% of 74 cats. For the right kidney, surgery and computed tomography angiography findings were in agreement in 6/6 cats. Our findings of renal vascular anatomy variations in cats were similar to previous reports in humans. Identifying and recognizing the pattern of distribution of these vessels is important when performing renal transplantation.
QUALITATIVE AND QUANTITATIVE COMPARISON OF RENAL VS. HEPATIC ULTRASONOGRAPHIC INTENSITY IN HEALTHY DOGS
Authors: IVANČIĆ MARINA , MAI WILFRIED
Published: July 2008

A prospective, cross‐sectional study was performed to qualitatively and quantitatively compare the echogenicity of the renal cortex relative to the liver in healthy dogs. Twenty‐five normal adult dogs were examined ultrasonographically. Three standard B‐mode images (8.0 MHz) and three tissue harmonic images of the cranial pole of the right kidney adjacent to the caudate lobe of the liver were obtained. Renal and hepatic echogenicities were qualitatively compared by two observers. Subsequently, regions of interest (ROIs) were drawn in the renal cortex and the adjacent liver parenchyma at equal depths on each image, using two different ROI geometries: deep adjacent half‐annular ROIs centered at the focal zone and small superficial adjacent squares placed in the near field. Renal and hepatic mean pixel intensities were quantified and averaged for individual subjects. Qualitatively, the right renal cortex was more commonly hyperechoic to liver. Quantitatively, the renal cortical mean pixel intensity was significantly higher than that of liver using deep half‐annular ROIs, but not superficial square ROIs, for both standard (P=0.0007) and harmonic (P=0.0107) tissue imaging. These findings suggest that the renal cortex can be slightly hyperechoic to adjacent liver. The framework within which the canine renal cortical parenchyma is routinely evaluated in abdominal ultrasonography should be reconsidered, and mild hyperechogenicity relative to the liver (at 8.0 MHz) interpreted as a normal finding.