bluuebunny/crossref_metadata_2025 huggingface dataset:
Consequences of transfusion of platelet antibody: a case report and literature review
Authors: Pavenski Katerina , Webert Kathryn E. , Goldman Mindy
Published: June 2008

BACKGROUND: Passive transfer of platelet (PLT) antibody by blood transfusion can lead to severe thrombocytopenia, bleeding, and an acute transfusion reaction.

CASE REPORT: A 49‐year‐old male on warfarin developed thrombocytopenic bleeding within 2 hours of transfusion with a single unit of fresh‐frozen plasma (FFP). The patient's PLT count on admission was 122 × 109 per L. Two hours after transfusion, PLT count has decreased to 5 × 109 per L. The patient's PLT antibody screen by solid‐phase enzyme‐linked immunosorbent assay was negative and his genotype was HPA‐1a/1b. The donor's genotype was HPA‐1b/1b and antibody screen revealed anti‐HPA‐1a. A lookback investigation identified another case of severe thrombocytopenia after FFP infusion 4 years previously.

REVIEW OF LITERATURE: A literature review identified 19 cases of passive transfer of PLT antibody that resulted in thrombocytopenia. The PLT nadir of 7 × 109 per L was reached within 6 hours after transfusion with a median time to PLT recovery of 5 days. Transfusion was accompanied by an acute transfusion reaction in 30 percent of recipients. Approximately 75 percent of recipients developed thrombocytopenic bleeding. All cases involved a female donor with a history of pregnancy. High‐plasma‐volume components accounted for the majority of cases while anti‐HPA‐1a was the most frequently implicated antibody.

CONCLUSION: Unexplained posttransfusion thrombocytopenia should be investigated to rule out passive transfer of PLT antibodies. Implicated donors should be deferred from subsequent donations. Switching to predominantly male plasma for transfusion may lead to reduction in cases of thrombocytopenia due to passive transfer of PLT antibody. Rational use of blood products may further reduce incidence of this complication.
A Leishmania minicircle DNA footprint assay for sensitive detection and rapid speciation of clinical isolates
Authors: Selvapandiyan Angamuthu , Duncan Robert , Mendez Juan , Kumar Rajesh , Salotra Poonam , Cardo Lisa J. , Nakhasi Hira L.
Published: June 2008

BACKGROUND: Diversity in clinical outcome, due to different species of Leishmania, and its presence in asymptomatic blood donors in endemic areas warrant development of methods that are sensitive and can rapidly identify infecting species.

STUDY DESIGN AND METHODS: The kinetoplast minicircle DNA is known to have heterogeneity in sequence and is present in many thousands of copies in Leishmania. Fluorescence‐based polymerase chain reaction (PCR) was used to amplify minicircle DNA from six Leishmania species from different geographic locations. The sequences were then used to construct a phylogenetic tree. Speciation of 46 blinded parasite clinical isolates from various geographic regions was validated using the assay.

RESULTS: Analysis displayed a distinct cluster for each species or strain. Forty‐three of 46 isolates were correctly assigned to the same species identified by isoenzyme electrophoresis. The three untyped isolates were all either new species or samples from a unique geographic region. The minicircles of the three isolates formed new clusters in the tree analysis. Using minicircle DNA as PCR target, the sensitivity of the parasite detection in the spiked blood samples was five parasites per mL.

CONCLUSION: Increased sensitivity and speciation without the need for parasite culture will be useful for diagnosis and treatment in clinical settings.
The clinical impact of platelet refractoriness: correlation with bleeding and survival
Authors: Kerkhoffs Jean‐Louis H. , Eikenboom Jeroen C.J. , Van De Watering Leo M.G. , Van Wordragen‐Vlaswinkel Rinie J. , Wijermans Pierre W. , Brand Anneke
Published: June 2008

BACKGROUND: Despite supportive care with platelet (PLT) transfusions, bleeding complications occur in a substantial number of patients with thrombocytopenia due to cytotoxic therapy. Moreover, refractoriness to PLT transfusions remains a frequently encountered problem. The clinical impact of PLT transfusion failure was investigated in 117 patients, part of a randomized PLT transfusion trial, which excluded patients with HLA and/or HPA alloantibodies.

STUDY DESIGN AND METHODS: Between October 2003 and April 2005, a multicenter randomized controlled trial, testing the clinical efficacy of PLTs stored in plasma compared to PLT additive solution (PAS II), was performed. Using multiple regression analysis of observational data of patients randomized in one of the participating centers, the occurrence of PLT transfusion refractoriness was analyzed for a relation with bleeding complications and patient survival.

RESULTS: PLT transfusion failure occurred at least once in 49.6 percent of the patients. Mild to moderate bleeding complications occurred in 19 percent of the patients. PLT transfusion failure was, independently from thrombocytopenia, positively associated with bleeding complications (odds ratio, 3.4; 95% confidence interval, 1.1‐11). Moreover, patients experiencing one or more 24‐hour PLT transfusion failures had, compared to patients always showing a sufficient 24‐hour increment, a significantly reduced median survival of 491 days (interquartile range [IQR], 156‐858 days) versus 825 days (IQR, 355‐996 days), respectively. In a Cox regression model, the effect on survival was independent of therapy, diagnosis, and age.

CONCLUSION: Our results suggest that PLT transfusion failure might be a sensitive clinical marker for the occurrence of bleeding and impaired patient survival. PLT transfusion failure, bleeding complications, and decreased survival could be manifestations of a more severe degree of endothelial damage.
Fatal group C streptococcal infection due to transfusion of a bacterially contaminated pooled platelet unit despite routine bacterial culture screening
Authors: Lessa Fernanda , Leparc German F. , Benson Kaaron , Sanderson Roger , Van Beneden Chris A. , Shewmaker Patricia L. , Jensen Bette , Arduino Matthew J. , Kuehnert Matthew J.
Published: June 2008

BACKGROUND: An elderly man with chronic myelomonocytic leukemia developed respiratory distress and died less than 48 hours after transfusion of a pool of eight whole blood–derived platelets (PLTs). Blood cultures from the recipient and cultures of remnants from the pooled PLT bag grew group C streptococci (GCS). An investigation was conducted to identify both the infection's source and the reasons for the false‐negative screening result.

STUDY DESIGN AND METHODS: Red blood cell (RBC) units (cocomponent from the eight donations) were traced, quarantined, and cultured. Specimens from the implicated donor were obtained. Isolates were identified and typed by 16S rRNA and pulsed‐field gel electrophoresis (PFGE). The blood center screening method was reviewed.

RESULTS: β‐Hemolytic GCS, cultured from 1 of 8 RBC units, linked the fatal case to a single donor. The donor's throat swab collected 20 days after donation was positive for the presence of GCS, identified as Streptococcus dysgalactiae subsp. equisimilis. Isolates from the recipient, RBC unit, residual PLTs, and donor's throat swab were indistinguishable by PFGE. The donor denied any symptoms of infection before or after donation. PLT bacterial screening at the blood center was performed using a commercially available bacterial detection system (BacT/ALERT, bioMérieux) with a threshold of 15 colony‐forming units per bag.

CONCLUSION: An asymptomatic donor was implicated as the source of GCS‐contaminated PLTs. Current screening methods for PLTs are not sufficient to detect all bacterial contamination. Pooled PLTs are a particular challenge because the small volume of individual units places limits on culturing strategies. Improved detection of bacterial contamination of PLTs is needed.
Leukodepletion of autologous whole blood has no impact on perioperative infection rate and length of hospital stay
Authors: Frietsch Thomas , Karger Ralf , Schöler Michael , Huber Daniela , Bruckner Thomas , Kretschmer Volker , Schmidt Susanne , Leidinger Werner , Weiler‐Lorentz Arnulf
Published: June 2008

BACKGROUND: Several mechanisms have been proposed as possible causes of transfusion‐related immunomodulation (TRIM) after allogeneic transfusion. If one of these mechanisms, the release of mediators of immunity and inflammation (“biologic response modifiers”[BRMs]) from disintegrating blood cells during storage of blood products, really causes TRIM, it should in principle also occur after autologous transfusion. As a consequence, prestorage leukoreduction of autologous blood should be able to prevent the clinical consequences of TRIM after autologous transfusion.

STUDY DESIGN AND METHODS: This hypothesis was investigated in a multicenter, double‐blind, randomized controlled trial. A total of 1089 patients scheduled for total hip arthroplasty and eligible for preoperative autologous blood donation were randomly assigned to receive autologous whole blood (AWB) either unmodified or leukoreduced when transfusion was indicated.

RESULTS: Neither the primary study outcome, that is, the overall postoperative infection rate (17.3% vs. 17.6%, p = 0.59), nor several secondary outcomes like median length of hospital stay (14 days vs. 14 days, p = 0.17) were significantly different between groups, whether analyzed according to the intention‐to‐treat principle or “as treated.”

CONCLUSION: This trial provides strong evidence, from clinically relevant outcome data, that leukoreduction of AWB does not improve postoperative patient outcome and that the release of BRMs from disintegrating blood cells during storage cannot explain the immunomodulatory effect of blood transfusion.
Mixed‐type autoimmune hemolytic anemia: differential diagnosis and a critical review of reported cases
Authors: Mayer Beate , Yürek Salih , Kiesewetter Holger , Salama Abdulgabar
Published: June 2008

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is usually classified as either warm or cold type. During the past few decades, mixed types (Mxs) have also been described in a number of cases (6%‐8% of AIHA), often without serologic data to support the diagnosis. In this study, we demonstrate that the incidence of Mx AIHA in our institution is extremely rare.

STUDY DESIGN AND METHODS: Between August 1998 and August 2007, all in‐ and outpatients with detectable warm autoantibodies (WABs) were included in this study. Serologic testing was performed using standard techniques for the detection of red blood cell antibodies.

RESULTS: From a total of 2194 patients with detectable WABs, only 2 patients (<0.1%) developed both WABs and cold agglutinins (CAs), which in the presence of clinical evidence of hemolytic anemia, satisfies the criteria for Mx AIHA. Only 1 of these patients, however, showed cold and warm hemolysis. Insignificant CAs at temperatures of not more than 24°C were found in 242 patients.

CONCLUSION: There is evidence that the presence of CAs with high thermal amplitude and WABs may lead to confusion and misdiagnosis in some patients with AIHA. This study demonstrates that Mx AIHA is less common than previously reported.
Endothelial permeability is increased by the supernatant of peripheral blood mononuclear cells stimulated with HLA Class II antibody
Authors: Wakamoto Shinobu , Fujihara Mitsuhiro , Sakagawa Hisako , Takahashi Daisuke , Niwa Koichi , Morioka Masanobu , Sato Shinichiro , Kato Toshiaki , Azuma Hiroshi , Ikeda Hisami
Published: June 2008

BACKGROUND: The generation of inflammatory mediators from monocytes activated by HLA Class II antibodies is thought to play important roles in the etiology of nonhemolytic transfusion reactions. Increased permeability of endothelial cells contributes to the pathogenesis of rash, urticaria, angioedema, and pulmonary edema, which are symptoms of transfusion reactions.

STUDY DESIGN AND METHODS: We investigated whether inflammatory mediators released from monocytes upon stimulation by HLA Class II antibodies could increase endothelial permeability. Human endothelial cell monolayers were incubated with cell‐free supernatants of peripheral blood mononuclear cells (PBMNCs) stimulated with HLA Class II antibody–containing plasma (anti‐HLA‐DR plasma), which has been implicated in severe nonhemolytic transfusion reactions. The permeability of endothelial cells to dextran was measured.

RESULTS: The supernatants of PBMNCs stimulated with the anti‐HLA‐DR plasma in corresponding antigen‐antibody combinations were able to increase endothelial permeability. At least 3 hours of exposure of PBMNCs to anti‐HLA‐DR plasma was required to produce a supernatant that could induce a significant increase in permeability. Simultaneous addition of tumor necrosis factor α (TNF‐α) and interleukin 1β (IL‐1β) neutralizing antibodies to the activated PBMNC supernatant significantly reduced the increase in permeability. Treatment of the endothelial cells with an inhibitor of nuclear factor κB (NF‐κB), but not inhibitors of apoptosis, significantly prevented the increase in permeability.

CONCLUSION: Both TNF‐α and IL‐1β, generated from PBMNCs by anti‐HLA‐DR plasma in a corresponding antigen‐antibody–dependent manner, led to an increase in endothelial permeability. The activation of monocytes by the HLA‐DR antibodies and the resultant inflammatory mediators could contribute to the pathogenesis of rash, urticaria, angioedema, and pulmonary edema after transfusion.
A New Vascular Closure Device for the Transradial Approach: The D Stat Radial System
Authors: KORN HUBERTUS V. , OHLOW MARC A. , YU JIANGTAO , HUEGL BURKHARD , SCHULTE WALTER , WAGNER ANDREAS , HABERL KAI , GRUENE STEFAN , LAUER BERNWARD
Published: June 2008

Background:

The transradial approach is associated with low complication rates. The D Stat Radial® vascular closure system offers hemostatic pressure locally at the puncture site with residual venous flow.

Methods:

We prospectively included 113 consecutive patients presenting between August 2006 and December 2006. Diagnostic coronary procedures were performed using 4 Fr or 5 Fr sheaths, while 6 Fr devices were used for PCI. In every case at least 5.000 IU heparin was given. Compression with the retention strap was planned for ∼3 hours before the pad was fixed using a medical strip. All data were entered into a database after a two‐dimensional ultrasound examination study of the puncture site.

Results:

The mean age was 65 years (±SD 10.3), with 62% being male. Patients presenting with acute coronary syndrome amounted to 6.2%, where 5r F sheaths were usually used with these patients (64.6%). PCI was carried out in 21.2% of cases. The system was applied successfully in all patients. The mean duration of compression was 4.6 hours (±SD 1.4). Bleeding after removal of the system occurred in 18.6% of cases, which resulted in prolonged compression in 17.7%. A hematoma >5 cm was seen in 4.4% of the sample. Ultrasound examinations revealed closure of the radial artery in 6.2%.

Conclusions:

We conclude that this new device operates efficiently, but bleeding occurred in 18.6%. Compression time should be extended to 6 hours.
Immunohistochemical determination of the P15INK4b protein expression in cutaneous squamous cell carcinoma
Authors: Moad Ahmed I. , Lan Tan Mei , Kaur Gurjeet , Hashim Hasnah , Mabruk Mohamed J. E. M. F.
Published: June 2008

The tumor suppressor gene p15INK4b is a cyclin‐dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor‐derived cell lines. The precise role of p15INK4b protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15INK4b gene. This study is a continuation of our previous study and aims to determine the possible role of p15INK4b protein expression in the genesis of cutaneous SCC. P15INK4b protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15INK4b was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15INK4b protein expression. The absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC.
Localized lymphedema (elephantiasis): a case series and review of the literature
Authors: Lu Song , Tran Tien Anh , Jones David M. , Meyer Dale R. , Ross Jeffrey S. , Fisher Hugh A. , Carlson John Andrew
Published: June 2008

Background:  Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor.

Objective:  To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema.

Methods:  Case–control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4‐year period.

Results:  We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16–74). Anogenital involvement was most frequent (75%) – mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn’s disease) (8%), and bacterial cellulitis (12%). Eighty‐five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p < 0.05). A history of cellulitis, morbid obesity, lymphoid follicles and follicular cysts predicted recurrent or progressive swelling despite excision (p < 0.05).

Conclusions:  Localized lymphedema should be considered in the etiology of skin tumors when assessing a polyp, plaque, swelling or mass showing dermal edema, fibrosis and dilated lymphatics on biopsy. A combination of lymph stasis promoting factors (trauma, obesity, infection and/or inflammatory disorders) produces localized elephantiasis.
Immunohistochemical differentiation of four benign eccrine tumors
Authors: Missall Tricia A. , Burkemper Nicole M. , Jensen Sarah L. , Hurley Maria Yadira
Published: June 2008

Background:  The histogenesis and differentiation of eccrine tumors, including cylindroma, poroma, spiradenoma and syringoma, remains controversial. This controversy may be because of sporadic and incomplete studies of these neoplasms.

Methods:  Ten examples each of normal eccrine structures and of four benign eccrine tumors are analyzed with antibodies to cytokeratin (CK) 7, CD34, CK6, CK10, smooth muscle actin (SMA) and CD10. These markers represent two different immunohistochemical stains for each part of the eccrine structure; CK7 and CD34 stain the secretory coil, CK6 and CK10 stain the straight duct and SMA and CD10 stain the myoepithelial cells. This redundancy in staining is performed on four benign eccrine tumors to better interpret the existing literature.

Results:  We find that CK7 is a sensitive marker for the secretory coil; both cylindromas and spiradenomas express CK7. We also find that CK6 is a marker for the inner ductal cells, while CK10 is a marker for the middle ductal cells; syringomas express both these markers. SMA appears to be a more specific marker for myoepithelial cells surrounding normal eccrine coils, and none of the studied tumors express SMA or CD10.

Conclusions:  Our studies suggest that syringomas are tumors of the eccrine duct, while cylindromas and spiradenomas are tumors of the secretory coil.
A histopathologic study of arthropod bite reactions in 20 patients highlights relevant adnexal involvement
Authors: Miteva Maria , Elsner Peter , Ziemer Mirjana
Published: June 2008

Background:  Insect bites produce diverse skin reactions. Although quite common, the histopathologic features of arthropod assaults have not ever been studied systemically.

Materials and methods:  Twenty biopsies from cases, clinically diagnosed as arthropod bite reactions between January 2003 and June 2007 were reviewed retrospectively. The aim of the study was to verify as to whether reliable histopathologic criteria could be established based on the frequency of findings observed.

Results:  Epidermal spongiosis (present in 16 of 20 cases), in particular spongiosis of the infundibular epithelium and acrosyringia as well as eosinophilic spongiosis, emerge as relevant diagnostic clues. A moderately dense, superficial and deep infiltrate consisting mainly of lymphocytes and eosinophils was prevalent in the dermis, with eosinophils tending to interstitial and periadnexal distribution. Of note, 19 of 20 (95%) cases revealed periadnexal involvement, whereas 16 of 20 (80%) had the infiltrate extending particularly along the sweat ducts and the coiled glands. In three biopsies, concomitant involvement of sweat glands, hair follicles and sebaceous glands was noted.

Conclusion:  A practical histopathologic algorithm of arthropod bite recognition is proposed. The involvement of the sweat glands in the pattern of arthropod bite reaction is suggested as a new reliable diagnostic clue.
Paraneoplastic pemphigus with negative direct immunofluorescence in epidermis or mucosa but positive findings in adnexal structures
Authors: Barnadas Maria A. , Curell Román , Alomar Agustín , Gelpí Carmen
Published: June 2008

Introduction:  Paraneoplastic pemphigus (PNP) is considered an autoimmune, multiorgan disease caused by antiplakin antibodies. We present three PNP patients who had negative epithelial direct immunofluorescence (DIF) findings in one or more biopsies.

Patients:  An early lip biopsy of uninvolved oral epithelia in patient 1 was negative. A later biopsy from foreskin showed intense intercellular immunoglobulin G (IgG) deposits in the epithelia. In the early phase of the disease in patient 2, the intercellular fluorescence was negative in the epidermis, while intercellular IgG and C3 were observed in the sweat ducts. A later biopsy showed weak intercellular epidermal IgG and C3 fluorescence. Patient 3 showed intercellular IgG and/or C3 in follicular, sebaceous and sweat duct structures in several biopsies. No intercellular IgG or C3 was observed in the epithelia.

Discussion:  The presence of immunoreactants in adnexal structures suggests that desmoplakins can be more strongly expressed in adnexa than in the epidermis, facilitating visualization of antibody deposits.

Conclusions:  Negative DIF findings in epithelia do not rule out the diagnosis of PNP, and the presence of IgG and/or C3 at the intercellular level of adnexal structures can help establish this diagnosis.
Immunohistochemical clues at aging of the skin microvascular unit
Authors: Quatresooz Pascale , Piérard Gérald E.
Published: June 2008

Background:  Skin aging is a multifaceted process influenced by various factors affecting at variable degree at different body sites. This study focused on the aging process affecting dermal dendrocytes and the microvasculature. We also explored the effect of substance P released by capsaicin because this neuropeptide is known to affect the microvasculature environment.

Methods:  The first part of the present study was undertaken in two groups of 35 men who were younger than 30 years and older than 65 years, respectively. A skin biopsy was taken from the intact skin of a thigh during orthopedic surgical intervention after road accident. The second part of the study was performed on 30 men aged 65–68 years. They applied once daily a 0.05% capsaicin gel and the vehicle in a randomized design on the volar forearms. A skin biopsy was taken at inclusion and after a 5‐month treatment phase. Immunohistochemistry was performed using a panel of antibodies. Dermal cells were distinguished according to the presence of factor XIIIa, CD34 or thrombomodulin. Blood and lymphatic vessels were studied by Ulex europaeus agglutinin‐1, human podoplanin, human vascular endothelial growth factor‐C (H‐VEGF‐C) and α‐actin immunoreactivities.

Results:  In the study phase 1, a significant decrease in thrombomodulin‐positive cells and vascularity were evidenced in the aged group. In the study phase 2, capsaicin appeared to boost the factor XIIIa‐positive dendrocytes, the thrombomodulin‐positive cells and the blood vessel network as well.

Conclusions:  Specific subsets of the dermal dendrocyte populations and the blood microvasculature appear affected by aging. Capsaicin may limit these aging effects.
Changing a concept – controversy on the confusing spectrum of the reticulate pigmented disorders of the skin
Authors: Müller Cornelia S. L. , Pföhler Claudia , Tilgen Wolfgang
Published: June 2008

Galli‐Galli disease (GGD) and Dowling‐Degos disease (DDD) are inherited skin diseases with variable progressive course. They are of benign and harmless behaviour but aesthetically annoying. They are subsumed within the group of reticulate pigmented disorders of the skin to which, additionally, Kitamura’s and Haber’s diseases are counted. Clinical appearance is approximately similar, with slight differences in age of onset and associated disorders. Histopathological features are almost similar aside from the unique hallmark of suprabasal acantholysis, which can exclusively be observed in GGD. We report four typical cases of reticulate pigmented disorders, clinically accordable to DDD but histopathologically allocated to GGD. In conclusion, we purpose the idea of a wide spectrum of reticulate pigmented disorders in which Morbus Galli‐Galli should probably be reclassified as a subset of DDD.
Habitat relationships with fish assemblages in minimally disturbed Great Plains regions
Authors: Fischer J. R. , Paukert C. P.
Published: June 2008

Abstract –  Effects of local environmental influences on the structure of fish assemblages were evaluated from 159 sites in two regions of the Great Plains with limited anthropogenic disturbance. These regions offered an opportunity to evaluate the structure and variation of streams and fish assemblages within the Great Plains. We used canonical correspondence analyses to determine the influence of environmental conditions on species abundances, species occurrences and assemblage characteristics. Analysis of regions separately indicated that similar environmental factors structured streams and fish assemblages, despite differences in environmental conditions and species composition between regions. Variance in fish abundance and assemblage characteristics from both regions was best explained by metrics of stream size and associated metrics (width, depth, conductivity and instream cover). Our results provide a framework and reference for conditions and assemblage structure in North American prairie streams.
Effects of fish species richness and assemblage composition on stream ecosystem function
Authors: Hargrave C. W.
Published: June 2008

Abstract –  Biodiversity is declining across aquatic ecosystems because of biological invasions and species extinctions. Because fishes have pervasive effects on ecosystems through species‐specific food web interactions, alterations to species and functional richness, and composition of natural assemblages could have negative effects on aquatic ecosystem function. In this study, I tested the effects of fish species and functional richness, and assemblage composition on primary production (PPR), benthic invertebrate density, and benthic particulate organic matter (BPOM) in a 42‐day experiment in artificial stream mesocosms. I found that fish species richness and assemblage composition were important predictors of PPR in stream mesocosms. However, the effect of species richness on PPR increased with time, suggesting that richness‐related effects might strengthen as the magnitude of community‐level interactions increases in ecosystems. There was no effect of fish species or functional richness or assemblage composition on benthic invertebrate densities or BPOM. These data provide additional support that fishes can be important regulators of ecosystem function in aquatic systems, and suggest that positive effects of fishes on ecosystems can be strengthened by increased species richness and composition of the assemblage. This study broadens the applicability of the biodiversity ecosystem‐function literature to a new suite of taxa, supporting the overall hypothesis that ecosystem functions and services are likely to decline in response to species extinctions.
Significance of thrombomodulin release from gingival epithelial cells in periodontitis patients
Authors: Matsuyama T. , Tokuda M. , Izumi Y.
Published: June 2008

Background and Objective:  Thrombomodulin, a cell transmembrane glycoprotein, binds to thrombin and converts it from a procoagulant protease to an anticoagulant enzyme that activates protein C. Thrombomodulin is very important in regulating the function of thrombin. Elevated soluble thrombomodulin is present in the gingival crevicular fluid of subjects with periodontitis. The objective of the present study was to investigate the mechanisms about the elevated soluble thrombomodulin in gingival crevicular fluid.

Material and methods:  Gingival sections from six patients with chronic periodontitis and from three periodontally healthy subjects were immunostained for thrombomodulin detection. Thrombomodulin levels were investigated in the gingival crevicular fluid of 11 subjects with chronic periodontitis. The effects of neutrophil enzymes on thrombomodulin release and on thrombomodulin in the gingival crevicular fluid were examined by an enzyme‐linked immunosorbent assay or by Western blotting.

Results:  The expression of gingival epithelial thrombomodulin was lost or decrease near infiltrating neutrophils. Thrombomodulin was rapidly released from gingival epithelial cells by neutrophil enzymes, and gingival crevicular fluid with periodontitis included the proteolytic cleavage thrombomodulin using immunoblotting analysis. The thrombomodulin release was not caused by rapid cell damage, on lactate dehydrogenase assay. There were significant differences in thrombomodulin content between gingival crevicular fluid samples from healthy and diseased sites, regardless of the degree of probing depth.

Conclusion:  Neutrophil enzymes induced rapid thrombomodulin release from the membrane surface of gingival epithelial cells. This might explain the thrombomodulin increase in gingival crevicular fluid with local diseased gingiva. Elevation of thrombomodulin in gingival crevicular fluid may be a potential marker of epithelial cell membrane injury.
Cell death and quantitative reduction of rests of Malassez according to age
Authors: Gonçalves J. S. , Sasso‐Cerri E. , Cerri P. S.
Published: June 2008

Background and Objective:  Rests of Malassez are clusters of epithelial cells that remain in the periodontal ligament throughout life. However, it has been reported that the number of these structures decreases with age, and some epithelial cells undergo apoptosis in rests of Malassez of young and adult rats. Therefore, the purpose of the present study was to investigate the incidence of epithelial cell death and the quantitative changes in the rests of Malassez in rat molars of different ages.

Material and Methods:  Fragments containing the upper molars of rats aged 29, 45 and 120 d were fixed, decalcified and embedded for analysis by light microscopy. In the sections stained by hematoxylin and eosin, the number of rests of Malassez and the number of nuclei of these epithelial structures were obtained. Moreover, the nuclei exhibiting typical features of cell death were also counted in each rest of Malassez. The terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) method for detection of cell death was also carried out.

Results:  In all groups examined, some rests of Malassez exhibited epithelial cell nuclei with typical features of apoptosis and some of them were also TUNEL positive. From 29 to 120 d of age in rats, the quantitative analysis showed a significant decrease in the total number of rests of Malassez in the cervical, middle and furcation regions of the periodontal ligament. Moreover, a significant decrease of epithelial cell nuclei was concomitant to an increase in the frequency of cell death in the oldest rats.

Conclusion:  These results suggest that epithelial cell death by apoptosis may be, at least in part, responsible for the reduction in the number of rests of Malassez according to age.
Oral malodorous compound causes apoptosis and genomic DNA damage in human gingival fibroblasts
Authors: Yaegaki K. , Qian W. , Murata T. , Imai T. , Sato T. , Tanaka T. , Kamoda T.
Published: June 2008

Background and Objective:  Volatile sulfur compounds are the main cause of halitosis. Hydrogen sulfide is one of these volatile sulfur compounds and the principal malodorous compound in physiological halitosis. Periodontally pathogenic activities of hydrogen sulfide have been previously reported. Hydrogen sulfide induces apoptotic cell death in aorta smooth muscle cells and in other tissues. Apoptosis plays an important role in the onset and progress of periodontitis. The objective of this study was to determine whether hydrogen sulfide causes apoptosis in human gingival fibroblasts.

Material and methods:  Necrotic cells were detected using a lactate dehydrogenase assay. Apoptosis was ascertained using a histone‐complexed DNA fragment assay and flow cytometry. The level of caspase 3, a key enzyme in apoptotic signaling, was also measured, and the effects of hydrogen sulfide on reactive oxygen species and superoxide dismutase were assessed. DNA damage caused by hydrogen sulfide was examined by means of single‐cell gel electrophoresis.

Results:  After 72 h of incubation with 100 ng/mL of hydrogen sulfide, necrosis was found in less than 10% of human gingival fibroblasts, whereas apoptosis was significantly increased (p < 0.05). Superoxide dismutase activity was strongly inhibited, and reactive oxygen species production was enhanced, after 48 and 72 h of incubation. Caspase 3 activity was also increased after 72 h of incubation (p < 0.01). Tail length, percentage of DNA in tail, and tail moment, measured by single‐cell gel electrophoresis, were also intensified after 72 h of incubation (p < 0.001).

Conclusion:  Hydrogen sulfide caused apoptosis and DNA damage in human gingival fibroblasts. An increased level of reactive oxygen species stimulated by hydrogen sulfide may induce apoptosis and DNA strand breaks.
Inhibition of the formation of oral calcium phosphate precipitates: the possible effects of certain honeybee products
Authors: Hidaka S. , Okamoto Y. , Ishiyama K. , Hashimoto K.
Published: June 2008

Background and Objective:  We studied the effects of honeybee products on the in vitro formation of calcium phosphate precipitates.

Material and Methods:  Screening tests of the in vitro formation of calcium phosphate precipitates using 20 types of honey and four types of propolis were carried out using the pH drop method.

Results:  The inhibitory effect on the rate of amorphous calcium phosphate transformation to hydroxyapatite and on the induction time varied greatly among the 20 types of honey and four types of propolis. We classified them according to their effects on decreasing the rate of amorphous calcium phosphate transformation to hydroxyapatite and/or increasing the induction time. Two of the 20 honeys showed little or no inhibition, either on the rate of amorphous calcium phosphate transformation to hydroxyapatite or on the induction time. Six of the honeys reduced the rate of amorphous calcium phosphate transformation to hydroxyapatite by 12–35% and with a 2.5‐ to 4.4‐fold increase in the induction time. The remaining 12 honeys showed even greater activity. Because four of these 12 honeys had an inhibitory effect on the rate of amorphous calcium phosphate formation, they were excluded as candidates for anticalculus agents. Furthermore, three of the four types of propolis showed an inhibitory effect that was the same as or greater than 1‐hydroxyethylidene‐1,1‐bisphosphonate.

Conclusion:  These results suggest that eight honeys and three types of propolis may have potential as anticalculus agents in toothpastes and mouthwashes.
Platelet‐derived growth factor‐B gene delivery sustains gingival fibroblast signal transduction
Authors: Lin Z. , Sugai J. V. , Jin Q. , Chandler L. A. , Giannobile W. V.
Published: June 2008

Background and Objective:  Platelet‐derived growth factor‐BB is a potent mediator of tooth‐supporting periodontal tissue repair and regeneration. A limitation of the effects of topical platelet‐derived growth factor‐BB application is its short half‐life in vivo. Gene therapy has shown strong promise for the long‐term delivery of platelet‐derived growth factor in both skin ulcer healing and periodontal tissue engineering. However, little is known regarding the extended effects of platelet‐derived growth factor‐B on cell signaling via gene delivery, especially at the level of phosphorylation of intracellular kinases. This study sought to evaluate the effect of gene transfer by Ad‐PDGF‐B on human gingival fibroblasts (HGFs) and the subsequent regulation of genes and cell‐surface proteins associated with cellular signaling.

Material and Methods:  HGFs from human subjects were treated by adenoviral PDGF‐B, PDGF‐1308 (a dominant negative mutant of PDGF) and recombinant human platelet‐derived growth factor‐BB, and then incubated in serum‐free conditions for various time points and harvested at 1, 6, 12, 24, 48, 72 and 96 h. Exogenous PDGF‐B was measured by RT‐PCR and Western blot. Cell proliferation was evaluated by [methyl‐3H]thymidine incorporation assay. We used proteomic arrays to explore phosphorylation patterns of 23 different intracellular kinases after PDGF‐B gene transfer. The expression of α and β PDGFR and Akt were measured by Western blot analysis.

Results:  Sustained in vitro expression of PDGF‐B in HGFs by Ad‐PDGF‐B transduction was seen at both the mRNA and protein levels. Compared to rhPDGF‐BB and Ad‐PDGF‐1308, Ad‐PDGF‐B maintained cell growth in serum‐free conditions, with robust increases in DNA synthesis. Gene delivery of PDGF‐B also prolonged downregulation of the growth arrest specific gene (gas) PDGFαR. Of the 23 intracellular kinases that we tested in proteomic arrays, Akt revealed the most notable long‐term cell signaling effect as a result of the over‐expression of Ad‐PDGF‐B, compared with pulse recombinant human platelet‐derived growth factor BB. Prolonged Akt phosphorylation was induced by treatment with Ad‐PDGF‐B, for at least up to 96 h.

Conclusion:  These findings further demonstrate that gene delivery of PDGF‐B displays sustained signal transduction effects in human gingival fibroblasts that are higher than those conveyed by treatment with recombinant human platelet‐derived growth factor‐BB protein. These data on platelet‐derived growth factor gene delivery contribute to an improved understanding of these pathways that are likely to play a role in the control of clinical outcomes of periodontal regenerative therapy.
CD1a and MHC Class I Follow a Similar Endocytic Recycling Pathway
Authors: Barral Duarte C , Cavallari Marco , McCormick Peter J , Garg Salil , Magee Anthony I , Bonifacino Juan S , De Libero Gennaro , Brenner Michael B
Published: June 2008

CD1 proteins are a family of major histocompatibility complex (MHC) class I‐like antigen‐presenting molecules that present lipids to T cells. The cytoplasmic tails (CTs) of all human CD1 isoforms, with the exception of CD1a, contain tyrosine‐based sorting motifs, responsible for the internalization of proteins by the clathrin‐mediated pathway. The role of the CD1a CT, which does not possess any sorting motifs, as well as its mode of internalization are not known. We investigated the internalization and recycling pathways followed by CD1a and the role of its CT. We found that CD1a can be internalized by a clathrin‐ and dynamin‐independent pathway and that it follows a Rab22a‐ and ADP ribosylation factor (ARF)6‐dependent recycling pathway, similar to other cargo internalized independent of clathrin. We also found that the CD1a CT is S‐acylated. However, this posttranslational modification does not determine the rate of internalization or recycling of the protein or its localization to detergent‐resistant membrane microdomains (DRMs) where we found CD1a to be enriched. We also show that plasma membrane DRMs are essential for efficient CD1a‐mediated antigen presentation. These findings place CD1a closer to MHC class I in its trafficking and potential antigen‐loading compartments among CD1 isoforms. Furthermore, we identify CD1a as a new marker for the clathrin‐ and dynamin‐independent and DRM‐dependent pathway of internalization as well as the Rab22a‐ and ARF6‐dependent recycling pathway.
Two Viral Kinases are Required for Sustained Long Distance Axon Transport of a Neuroinvasive Herpesvirus
Authors: Coller Kelly E. , Smith Gregory A.
Published: June 2008

Axonal transport is essential for the successful establishment of neuroinvasive herpesvirus infections in peripheral ganglia (retrograde transport) and the subsequent spread to exposed body surfaces following reactivation from latency (anterograde transport). We examined two components of pseudorabies virus (US3 and UL13), both of which are protein kinases, as potential regulators of axon transport. Following replication of mutant viruses lacking kinase activity, newly assembled capsids displayed an increase in retrograde motion that prevented efficient delivery of capsids to the distal axon. The aberrant increase in retrograde motion was accompanied by loss of a viral membrane marker from the transported capsids, indicating that the viral kinases allow for efficient anterograde transport by stabilizing membrane–capsid interactions during the long transit from the neuron cell body to the distal axon.
Factors affecting the oral condition of patients with severe motor and intellectual disabilities
Authors: Idaira Y , Nomura Y , Tamaki Y , Katsumura S , Kodama S , Kurata K , Asada Y
Published: June 2008

Background:  Handicapped persons living in nursing homes have special risks for oral diseases.

Objective:  To investigate the specific factors related to the occurrence of dental caries and tooth extraction in patients with severe motor and intellectual disabilities (PSMI) residing in an institution.

Methods:  One hundred eighty‐nine PSMI residing in a single institution in Japan were followed for 3 years. Oral examinations were conducted at baseline and 3 years later. The following items were investigated: age of subject at admission, period of institutionalization, age at baseline oral examination, status of rumination, drooling, type of ward, dietary mode, and etiology of the impairment. Logistic regression analyses were conducted to examine factors associated with new dental caries and tooth extraction occurring during the study period.

Results:  By multivariate analysis, rumination and tube feeding were identified as significant factors associated with new dental caries. On the other hand, infancy or childhood impairment and drooling were identified as significant factors related to tooth extraction.

Conclusion:  Some specific factors in this patient population affect the dental caries and tooth extraction and oral programs targeting these factors may reduce dental degeneration in these patients.
Chronic ulcerative stomatitis
Authors: Solomon LW
Published: June 2008

Chronic ulcerative stomatitis (CUS) is a recently described condition with specific immunopathologic findings. Demographics indicate that white women in their late middle age are more susceptible to this condition. The clinical history of CUS patients is of painful, exacerbating and remitting oral erosions, and ulcerations. The histologic features are non‐specific, with a chronic inflammatory infiltrate, often appearing similar to oral lichen planus (OLP). Diagnosis of CUS requires surgical biopsy with immunofluorescence microscopic examination. Accurate diagnosis is important because the usual treatment option for immunologically mediated diseases, glucocorticoids, is often not effective in treating CUS. However, hydroxychloroquine pharmacotherapy is beneficial in many cases. The lack of awareness of the condition among clinicians and the technical challenges in specimen processing make diagnosis of CUS a challenge, and hence the true prevalence is unknown. Immunofluorescence studies show circulating and tissue‐bound autoantibodies to a protein, ΔNp63α, which is a normal component of stratified epithelia. It is unknown if the antibodies are pathogenic, thus the etiology of CUS is also unknown. Studies are needed to elucidate the pathogenesis of CUS, optimize clinical management, and clarify its relationship to OLP and neoplasia.
The ectomesenchymal chondromyxoid tumor: a review
Authors: Allen CM
Published: June 2008

The ectomesenchymal chondromyxoid tumor is a relatively recently described neoplasm that appears to involve uniquely the oral cavity, particularly the tongue. Thirty well‐accepted cases have been reported since the initial description of this lesion in 1995. While a wide age range (9–78 years) has been documented, most of these tumors are diagnosed from the third to sixth decades of life. No sex predilection is seen. The size of the neoplasm is typically <2 cm, and most affect the anterior dorsal tongue. The duration of the lesion was difficult to gauge, probably due to the asymptomatic nature of the process. Some tumors, however, were well documented to have been present for as long as 10–20 years. Histopathologically, the ectomesenchymal chondromyxoid tumor is characterized by a well circumscribed, but unencapsulated, lobular growth pattern. Varying degrees of cellularity are noted, with the lesional cells often set in a myxoid, chondroid or hyalinized background. Immunohistochemical studies reveal positivity of the lesional cells for antibodies directed against glial fibrillary acidic protein, cytokeratins, S‐100 protein and CD‐57 in the majority of tumors. Treatment consists of conservative surgical excision, and while recurrence is possible, it has been noted in <10% of reported cases.