bluuebunny/crossref_metadata_2025 huggingface dataset:
Established treatments of skin hypermelanoses
Authors: Nikolaou Vasiliki , Stratigos Alexander J , Katsambas Andreas D
Published: December 2006

Cutaneous hypermelanoses are frequently encountered conditions that can have severe adverse psychosocial and emotional effects on affected patients. Melasma, postinflammatory hyperpigmentation, drug‐induced pigmentation, and erythema dischromicum perstans are among the most common cutaneous disorders leading to acquired skin hyperpigmentation. The treatment of these disorders is often challenging and requires a great deal of patience from the patient and a wealth of experience and knowledge from the dermatologist. Current treatments include depigmenting agents, chemical peels, and lasers. The ideal bleaching agent has to fulfill certain pharmacologic criteria. It should have a potent bleaching effect with a rapid time of onset, carry no side effects, and lead to a permanent removal of undesired pigment. We review the established treatment approaches of cutaneous hyperpigmentation based on literature review and our personal experience.
Phorbol 12‐myristate 13‐acetate can transform monocyte‐derived dendritic cells to different cell types similar to those found in dermatofibroma
Authors: Aiba Setsuya , Tagami Hachiro
Published: December 2006

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evidence indicating that factor XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas. However, it is still unknown what stimulation is responsible for trans‐forming DDCs into different cell types, producing different sub‐types of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identical with DDCs in their phenotypic and functional characteristics, from the culture of CD 14+ peripheral blood monocytes to which IL‐4 and GM‐CSF were added. Using these monocyte‐derived DCs, we examined the ability of various cytokines, such as IL‐Iβ, IL‐3, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, TNFα, TGFβ, M‐CSF, IFNα, and IFNγ, and phorbol 12‐myristate 13‐acetate (PMA), to induce different cell types observed in DFs. Among them, only PMA could induce a variety of cell types such as histiocytic cells, fibroblastic spindle‐shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenotypically, all the induced cell types expressed CD1a, CD80, CD86, HLA‐DR, and CD68 in a magnitude similar to that of non‐treated monocyte‐derived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in giant cells.

These data suggest that dermatofibromas are a kind of neoplastic disease which is induced only by the effect of some tumor promoter on DDCs.
The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity
Authors: Magro C. M. , Crowson A. N. , Schapiro B. L.
Published: December 2006

We present 20 patients in whom drug therapy was associated with interstitial histiocytic infiltrates with variable degeneration of collagen and elastic fibers mimicking early lesions of granuloma annulare (GA). Most patients had a reproducible clinical presentation comprising erythematous‐to‐violaceous, nonpruritic plaques, often with an annular pattern, predominantly involving inner aspects of the arms, medial thighs and intertriginous areas. The most frequent clinical differential diagnoses inchided cutaneous T cell lymphoma, erythema annulare centrifigum (EAC), GA, and lupus erythematosus. A drug reaction was suspected in only 3 cases. The implicated drug classes included calcium channel blockers, angiotensin converting enzyme inhibitors, beta‐blockers, lipid‐lowering agents, antihistamines, anticonvoilsants and antidepressants. Patients were often on two or more of these drugs; all have been associated with pseudolymphomatotis infiltrates of the skin, the presumptive basis of which is iatrogenic pertubation of immune function. The defining histomorphology was diffuse infiltration of the interstitium by lymphocytes and histiocytes with piecemeal fragmentation of collagen and elastic fibers in concert with a vacuolar interface dermatitis. Ten cases showed intermediate and transformed lymphocytes with hyperchromatic convoluted nuclei disposed interstitially within the dermis or along the dermoepidermal junction with variable epidermotropism. In the 15 patients who discontinued the implicated drug, lesional resolution occurred. We propose the designations interstitial granulomatous drug reaction for this novel cutaneous reaction pattern.
Ultrastructural localization of cell junctional components (desmoglein, plakoglobin, E‐cadherin, and β‐catenin) in Hailey‐Hailey disease, Darier's disease, and pemphigus vulgaris
Authors: Tada Joji , Hashimoto Ken
Published: December 2006

The distribution of desmoglein, plakoglobin, E‐cadherin, and β‐catenin in the peri‐lesional and lesional skin of Hailey‐Hailey disease, Darier's disease, and pemphigus vulgaris was examined by immunoelectron microscopy. In the peri‐lesional skin, the immunolabeling of these desmosomal components was localized to desmosomes. Adherens junction‐associated E‐cadherin and β‐catenin were at the cell periphery, excluding desmosomes. The labeling pattern was similar among these diseases, but the labeling intensity particularly that of plakoglobin in Hailey‐Hailey disease and Darier's disease, was less than that of normal controls, suggesting that these glycoproteins are quantitatively less concentrated in the normal epidermis of these inherited diseases. In the acantholytic cells of Hailey‐Hailey disease and Darier's disease the immunolabeling of the components of desmosomes was diffusely distributed in the cytoplasms, whereas that of adherens junction was mostly at the cell periphery and partly diffusely in the cytoplasm. In contrast, desmosomes of detaching keratinocytes in pemphigus vulgaris still showed the labeling of desmoglein and plakoglobin. These findings suggest that the inherited acantholytic diseases, i.e., Hailey‐Hailey disease and Darier's disease have a different pathogenesis from that of autoimmune acantholysis in pemphigus vulgaris: The intracellular components of desmosomes may primarily be disrupted in the genetic acantholytic diseases in the initial stages of acantholysis. Several unsolved questions in the previous light microscopic immunofluorescence sttidies using the same antibodies are now answered: 1) the diffusion of desmosomal proteins is not due to the internalization of desmosomes, 2) intracellular components of adherens junction are also finally dissolved, 3) diffuse cytoplasmic immunofluorescence patterns of desmosomal components could be explained by immunoelectron microscopy as those attached to cell membrane and trapped in tonofilament aggregates.
Collodion baby and lamellar ichthyosis
Authors: Sandler Brian , Hashimoto Ken
Published: December 2006

It is important to differentiate the collodion baby from harlequin ichthyosis as the latter rarely survives past the first few days of life. Occasionally, babies share features of both disorders and defy a clinical diagnosis. We recently encountered such a baby who initially presented with harlequin‐like features, but evolved into lamellar ichthyosis once the keratin cast was shed. Since the routine histology of all these ichthyoses is similar, we used electron microscopy to study serial biopsy specimens from the affected infant on days 7, 14, and 150, and compared them to our own other cases of harlequin ichthyosis and lamellar ichthyosis. Electron microscopic studies of our case revealed that the marginal band of cornified cells of the stratum corneum was absent when the baby exhibited collodion/harlequin ichthyosis features. Another biopsy taken when the clinical picture evolved into lamellar‐like ichthyosis, showed a well‐formed marginal band in the cornified cells. In harlequin ichthyosis, the marginal band is present at birth. It is suggested that electron microscopy can differentiate severe collodion baby from harlequin ichthyosis at birth using the absence of the marginal band. Previously reported features of harlequin ichthyosis, such as the presence of giant mitochondria and an abnormal formation of the marginal band in luminal villi of acrosyringeal eccrine duct, were absent in our case.
Atypical decubital fibroplasia: a series of three cases
Authors: Baldassano Marisa F. , Rosenberg Andrew E. , Flotte Thomas J.
Published: December 2006

We report three cases of atypical decubital fibroplasia (ADF), a benign, reactive pathologic process that develops in the skin and subcutaneous tissue of immobilized or debilitated patients. Two patients were immobilized, one wheelchair bound, and one bedridden. The third patient frequently lay over the affected area. Two were male, one female, ages 49, 66, and 89 (mean 68 years old). Each patient presented with a subcutaneous mass, one with focal surface ulceration, present for 5 months, 6 months, and 12 months (mean 7.7 months). The locations included back, lateral thigh (over greater trochanter), and lateral chest wall. No other lesions were present, and none had recurrences. Histologically, atypical decubital fibroplasia is characterized principally by dermal and subcutaneous tissue involvement with fibrinoid necrosis, reactive fibrosis, and focal myxoid change with surrounding more cellular zones of prominent reactive neovascularization including granulation tissue and ectatic vessels with reactive atypical fibroblasts and fat necrosis. Other findings include hyalinization of vessel walls, fibrin thrombi, red blood cell extravasation, hemosiderin deposition, and acute and chronic inflammation. Although the changes are predominantly deep, involving the dermis, subcutaneous tissue and skeletal muscle, the overlying epidermis may ulcerate. Recognition of atypical decubital fibroplasia is of paramount importance, for it may be misinterpreted as a sarcoma, both clinically and histologically.
The lymphocytic infiltrate in acute cutaneous allogeneic graft‐versus‐host reactions lacks evidence for phenotypic restriction in donor‐derived cells
Authors: Horn Thomas D. , Haskell Jennifer
Published: December 2006

The lymphocytic subtypes effecting allogeneic graft‐versus‐host disease (GVHD) are unknown. We studied 35 skin biopsy specimens from 19 women transplanted with bone marrow from men for patterns and time course of infiltration of the skin by Y chromosome‐bearing lymphocytes using in situ hybridization. Immunophenotypic analysis was performed on serial sections. Significant numbers of donor cells were first observed by day 13 after bone marrow transplantation (BMT), although a few cells were noted at earlier time points. The quantity of donor lymphocytes in the dermis correlated with the diagnosis of GVHD. For specimens with grade 1 features, only rare cells bore the Y chromosome, whereas the majority of lymphocytes in grade 2 tissues, whether heavily inflamed or not, contained the Y chromosome. These lymphocytes were predominantly CD4+ with fewer CD8+ and CD56+ cells in the dermis and epidermis. No concentration of a specific subtype in the epidermal compartment was observed. These data do not support the observation that a cutaneous graft‐versus‐host reaction (GVHR) is mediated primarily by CD8+ lymphocytes. Several effector cell populations may mediate a cutaneous GVHR with further variation over time and in BMTs between different individuals.
Sebaceous neoplasm with reticulated and cribriform features: a rare variant of sebaceoma
Authors: Nielsen Timothy A. , Maia‐Cohen Sandra , Hessel Adam B. , Xie Dong‐Lin , Pellegrini Arthur E.
Published: December 2006

Troy and Ackerman defined the term sebaceoma (Am J Dermatopathol 1984: 6: 7‐13) as benign neoplasm of basaloid cells with varying numbers of mature sebocytes. Steffen and Ackerman (Neoplasms with sebaceous differentiation. Philadelphia: Lee and Febiger, 1994: 401‐425) illustrated many examples of sebaceoma, two of which had a reticulated and cribriform pattern. We report a case of sebaceoma from the scalp of a 52‐year‐old white female. Histologically, it displayed reticulated and cribriform basaloid epithelial islands. This is the third reported case of sebaceoma, to our knowledge, with these unusual features.
Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma
Authors: Miracco Clelia , Santopietro Rosa , Biagioli Maurizio , Lazzi Stefano , Nyongo Aggrey , Vatti Rosella , Luzi Pietro
Published: December 2006

Ninety‐six cutaneous melanomas (CMs) were investigated aiming at finding differences, if any, among tbe main four chnicopatho‐logical types, for Bcl‐2. c‐myc and p53 protein expression, and for tumor cell proliferation and death indices. Proliferation was assessed by calculating die mitotic index (MI, number of mitoses) and the MIBl labelling index (M‐LI, number of MIBI+ nuclei), and tumor cell death by calculating tbe apoptotic index (AI, number of apoptoses) among 1000 tumor cells. CMs were subdivided into thin (<1 mm) and intermediate thickness (1‐4 mm) tumors. Bcl‐2 expression did not significantly change among different types, c‐myc Expression decreased expecially in thicker superficial spreading (SSM) and lentigo maligna melanoma (LMM) types. p53 Expression was higher in nodular melanoma (NM) and in acral lentigiuous melanoma(ALM), which also showed the highest degrees of proliferation. AI was significantly higher in thin rather than in intermediate thickness SSMs, LMMs and ALMs (8.4 vs. 2; 6.1 vs. 2.3. and 5.8 vs. 3.6, respectively). AI was low in thin (1.7) and intermediate thickness (1.9) NMs. Which also showed high MI (3.9 and 4.5, respectively), and M‐LI (16.7 and 2.9, respectively). Thin and intermediate thickness ALMs also showed high MI and M‐LI (4.1 vs. 5.2 and 11.3 vs. 14.6, respectively). Bcl‐2 is among genes which inhibit apopiotic death, whereas c‐myc and p‐53 genes promote this process. In CMs. no relation was found between BcI‐2 expression, MI, PI, and AI. All SSMs, LMMs, and ALMs with a high AI showed a high c‐myc expression and were negative for p53. c‐myc, Although highly expressed, did not promote a significant apoptotic death in NM type. Bc12, c‐myc, and p53 were not equally expressed nor equally related to tumor cell turnover in all CMs, suggesting their different influence on the various types and stages, and the role of other factors in CM growth control.
Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases
Authors: Tran Tien Anh , Carlson J. Andrew , Basaca Poelinda Colis , Mihm Martin C.
Published: December 2006

Atypical cellular blue nevus (ACBN) has clinicopathologic features intermediate between typical cellular blue nevus (CBN) and the rare malignant blue nevus (MBN)/malignant melanoma (MM) arising in a CBN. Herein we report 9 cases of ACBN. The patients were caucasian (6 females and 3 males) with a mean and median age of 47/51 years. Two patients complained of recent changes and about half of these tumors were located on the buttocks or scalp, averaging 1.5 cm in diameter. Histologically, they were characterized by architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia (hypercellularity, nuclear pleomorphism, hyperchromasia, mitotic figures, and/or necrosis). Assessment of the expression of 3 tissue markers demonstrated rare solitary cell staining with oncogene product bcl‐2, and a proliferative index of 23±19 and 39±30 cells/10 high power field with antibodies to PCNA and Mib‐1, respectively. No significant differences were detected comparing the above levels of expression to a control group of 15 CBN; however, ACBNs tended to show a higher proliferative index by PCNA and Mib‐1 as well as a significantly higher mitotic rate (1/10 HPF vs. 0; p=0.001). Analysis of DNA content showed DNA anetiploidy in both groups. Follow‐up data on 9 of 9 patients showed 1 patient dead without disease and 8 alive without disease (mean/median follow‐up 42/32 months, range 15‐96 months). No patient during this follow‐up time has experienced either a local recurrence or lymph node or visceral metastasis. These findings highlight the close resemblance of ACBN to the natural history of CBN. Nevertheless, many of the distinguishing histologic features of ACBN are also those of MBN. Because of these intermediate clinicopathologic features, ACBN warrant close scrutiny and long‐term follow‐up.
Dermal infiltrate of enlarged macrophages in patients receiving chemotherapy
Authors: Valks Ruud , Vargas Erich , Muñoz Elia , Fernández‐Herrera Jesus , Garcia‐Diéz Amaro , Fraga Javier
Published: December 2006

A histologically distinct maculopapular eruption has heen associated with the use of recombinant forms of granulocyte and gran‐ulocytte‐inacrophage colony‐stimulating factors (GCSF and GMCSF). One of the most distinctive features was an increase in the number and the size of dermal maerophages, which was proposed as a clue to diagnosis of these cytokine‐induced dermatoses.

We describe 8 patients who received chemotherapy and who developed a maculopapular eruption, of which histological examination showed an increase in the numher and the size of dermal maerophages. Three patients had also received GM‐CSF or G‐CSF, before the onset of rash, but 5 patients had not.

In conclusion, an increase in the number and the size of dermal macrophages is not specific for the reaction to GM‐CSF or G‐CSF, and may also be observed in patients receiving chemotherapy.
A cutaneous case of giant cell angiofibroma occurring with dermatofibrosarcoma protuberans and showing bimodal CD34+ fibroblastic and FXIIIa+ histiocytic immunophenotype
Authors: Silverman Jeffrey S. , Tamsen Ali
Published: December 2006

Dei Tos and colleagues in 1995 reported a series of seven distinctive orbital tumors in adults which they named giant cell angioftbroma (GCA). The morphologic features are intermediate between giant cell fibroblastoma and solitary fibrous tumor with a richly vascularized, patternless spindle cell proliferation forming a collagenous or myxoid stroma with pseudovascular angiectoid spaces. The spindled tumor cells have large, rounded nuclei, sometimes with complex folded shape and pseudoinclusions. There also are multi‐ or mononuclear giant cells, and these tumor cells partly line so‐called angiectoid spaces. Cells express human progenitor cell antigen CD34 and vimentin. One case in the buccinator fascia was also noted by the authors, but similar cutaneous lesions are thus far unknown. We report our experience with a polypoid tumor that ocurred on the thigh of a 49‐year‐old woman that conforms to the description of GCA. The tumor has variegated vessels admixed with patternless spindle and giant cell stroma with angiectoid spaces as well as areas of dermatofibrosarcoma protuberans (DFSP). Most tumor cells express vimentin and CD34, including giant and spindle cells lining angiectoid spaces. Focally up to 40% of the lesional cells express coagulation factor Xllla with histiocytoid to highly dendritic cytosomes. The DFSP component is composed of admixed CD34+ and FXIIIa+ dendritic cells arranged in a storiform pattern. Tumor cells are negative for actin, desmin, S‐100, and cytokeratin. The Ki67 proliferation index is 1 % in GCA areas and 3% in DFSP areas; Ki 67 stains mainly fibroblasts. We conclude that this cutaneous GCA is a fibrohistiocytic tumor closely related to and representing a more organoid angioformative analog of GCF, with both being related histogenetically also to DFSP. These lesions represent part of a greater spectrum of fibrovascular tissue patterns, all probably derived from proliferations of interactive microvascular CD34‐I‐fibroblasts and FXIIIa+histiocytes.
Cutaneous parachordoma
Authors: Imlay Sherwin P. , Argenyi Zsolt B. , Stone Mary Seabury , McCollough Martha L. , Henghold William B.
Published: December 2006

Parachordomas are rare cutaneous tumors that show virtually identical histologic findings to chordomas. Therefore, the major differential diagnosis in a case of parchordoma is metastatic chordoma. Parachordomas are benign neoplasms and most often develop on the extremides adjacent to tendons, synovium or os‐seotis structures, as opposed to chordomas, which are malignant tumors located along the craniospinal axis. While recurrences may occur in cases of parachordoma, metastases have not been reported. In this report, two cases of parachordomas are reported and the literature reviewed. By light microscopy, parachordomas show eosinophilic bands of fibrous tissue separating lobules of cells with variably vacuolated cytoplasm (physaliphorous cells) admixed with more epithelioid cells in a myxoid stroma. Para‐chordomas and chordomas share immunohistochemical and ultrastructiral features. Both stain with S‐100 protein and vimentin, and ultrastrueturally both demonstrate cytoplasmic vacuoles, intermediate filaments, pinocytotic vesicles, cell junctions, and cytoplasmic membranes with microvillous processes. Chordomas more frequently express cytokeratin (98% vs. 66% in parachordomas) and epithelial membrane antigen (90% vs. 20% in para‐chordomas) and chordomas have a larger number of rough endoplasmic reticulum–mitochondrial complexes. Thus, positive staining with epithelial membrane antigen and the identification of a large number of rough endoplasmic reticulum–mitochondrial complexes are suggestive of metastatic chordoma. However, the definitive distinction remains a clinical one after appropriate radiologic studies of the skull and spinal chord.
Oral lesions in HIV‐positive dental patients – one more argument for tobacco smoking cessation
Authors: Sroussi HY , Villines D , Epstein J , Alves MCF , Alves MEAF
Published: December 2006

Objective:  To determine the prevalence of oral lesions associated with human immunodeficiency virus (HIV) in a population of dental patients and analyze its association with psycho‐social variables and biological markers.

Study design:  The dental charts of 415 dental patients consecutively treated between May and July 2005 in a dedicated HIV dental clinic were reviewed. Oral soft tissue examinations, psycho‐social and medical variables were extracted and recorded for each patient. Ethnicity, gender, HIV treatment, peripheral CD4 counts and tobacco usage were analyzed in correlation with oral lesions associated with HIV.

Results:  Fifty‐five percent of all subjects had at least one oral lesion associated with HIV, with oral candidiasis, salivary gland enlargement and oral hairy leukoplakia being the most commonly observed conditions. Gender and ethnicity did not correlate with a higher prevalence in lesions. However, tobacco smoking correlated significantly with a higher prevalence of oral lesions, independent of CD4 counts.

Conclusions:  These findings suggest that oral lesions remain commonly observed morbidities among HIV‐infected dental patients independent of gender and ethnicity and that tobacco usage is a major and often underestimated risk factor for those lesions.
CARDIOVASCULAR AND GASTROINTESTINAL RADIOGRAPHIC CONTRAST STUDIES IN THE HORSESHOE CRAB (LIMULUS POLYPHEMUS)
Authors: SPOTSWOOD TIM , SMITH STEPHEN A.
Published: December 2006

Survey and contrast radiographic studies of the cardiovascular and gastrointestinal systems of the American horseshoe crab (Limulus polyphemus) were undertaken using conventional and flouroscopic techniques. Normal gastrointestinal and cardiovascular structures were difficult to resolve on survey radiographs, but were well visualized with gastrointestinal follow through studies and angiography, respectively. All three contrast agents (iohexol, Gastrografin, and barium sulfate) used for the gastrointestinal studies varied minimally in their radiographic quality and transit times, and all appeared to be safe for use in the horseshoe crab.
IMAGING DIAGNOSIS—INFILTRATIVE LIPOMA CAUSING SPINAL CORD COMPRESSION IN A DOG
Authors: MORGAN LEE W. , TOAL ROBERT , SIEMERING GEORGE , GAVIN PATRICK
Published: December 2006

An 11‐year‐old, 43 kg neutered female Labrador retriever dog developed acute pelvic limb paraparesis. In magnetic resonance images there was a T1‐ and T2‐hyperintense extradural at the fifth thoracic intervertebral space that was causing marked compression of the spinal cord. In short τ inversion recovery and fat suppressed T1‐weighted images the signal from the mass was decreased indicating it was of fatty origin. The mass was removed via a dorsal hemilaminectomy in the thoracic area. Histopathologic analysis confirmed the mass was an infiltrative lipoma. The dog recovered and is fully ambulatory 24 months after surgery. This report provides additional evidence that lipomas in the vertebral canal may be the source of pelvic limb neuropathy and also illustrates the value of magnetic resonance imaging in establishing the fatty nature of some soft tissue masses.
COMPARISON OF TRANSPLENIC MULTIDETECTOR CT PORTOGRAPHY TO MULTIDETECTOR CT‐ANGIOGRAPHY IN NORMAL DOGS
Authors: ECHANDI RITA L. , MORANDI FEDERICA , DANIEL WILLIAM T. , PAQUETTE JANET L. , DANIEL GREGORY B.
Published: December 2006

We evaluated transplenic injection of iodinated contrast medium for computed tomography (CT) assessment of the portal vasculature. Specific aims were to: (1) establish a protocol for transplenic transplenic CT portography using a 40‐row multidetector scanner; (2) compare transplenic CT portography to dual‐phase CT angiography in terms of image quality, opacification of the portal system, and contrast enhancement of the portal vasculature and liver; (3) compare personnel exposure during transplenic CT portography and transplenic portal scintigraphy. Seven juvenile dogs underwent transplenic portal scintigraphy, CT angiography, and transplenic CT portography. Transplenic portal scintigraphy and CT angiography were performed using previously established protocols. For transplenic CT portography, a 20‐ or 22 gauge needle attached to an extension set was placed into the splenic parenchyma using CT guidance. Iodinated contrast medium (175 mg I/ml) was administered, and CT acquisition was started at the time of the injection. Transplenic CT portography was simple, rapid and provided more intense enhancement of the splenic and portal veins, with a lower contrast medium dose (median dose: 525 mg I for transplenic CT portography, 7700 mg I for CT angiography), but caused inconsistent intrahepatic portal branches and parenchymal opacification due to streamlining and streak artifacts. Despite significantly lower attenuation values in the portal vein, CT angiography provided sufficient enhancement for vessel identification and more consistent parenchymal hepatic enhancement. Personnel radiation exposure rate was higher during transplenic CT portography (0.0725 mSv/min) compared with transplenic portal scintigraphy (0.000125 mSv/min). As transplenic CT portography requires an average injection time of 1 min per study; over 6500 studies must be performed before reaching the maximum permissible whole body dose of 0.5 Sv.
ASSESSMENT OF THE REPEATABILITY OF FELINE ECHOCARDIOGRAPHY USING CONVENTIONAL ECHOCARDIOGRAPHY AND SPECTRAL PULSE‐WAVE DOPPLER TISSUE IMAGING TECHNIQUES
Authors: SIMPSON KERRY E. , CRAIG DEVINE B. , GUNN‐MOORE DANIÈLLE A. , FRENCH ANNE T. , DUKES‐McEWAN JOANNA , KOFFAS HARALAMBOS , MORAN CARMEL M. , CORCORAN BRENDAN M.
Published: December 2006

The objective of this study was to determine the intraoperator, intraobserver, and interobserver repeatability in a series of conventional echocardiographic parameters and in some of the newer measurements of diastolic function, including color M‐mode flow propagation velocity, isovolumic relaxation time and pulsed‐wave Doppler tissue imaging velocities. Four healthy cats were each scanned five times over a 3‐day period. The repeatability of these echocardiographic analyses was compared using Bland–Altman analysis (intraoperator repeatability). After a minimum of 5 weeks, one scan was randomly selected from each cat, and was remeasured by the original observer and the results compared using a standard paired Student'st‐test (intraobserver repeatability). One scan from each cat was then randomly selected and two observers, with similar levels of experience, measured each of these scans. The repeatability of these echocardiographic analyses was compared using Bland–Altman analysis (interobserver repeatability). The conventional two‐dimensional (2D), M‐mode and spectral Doppler measurements were repeatable in both their acquisition and measurement by a single investigator; there was a greater degree of variation between the two observers. The predominant (S′, E′, and A′) pulsed‐wave Doppler tissue imaging velocities from the left apical four‐chambered view, generally had a coefficient of variation of approximately 20% (range 9.62–34.08%). However, with pulsed‐wave Doppler tissue imaging, velocities recorded during the isovolumic phases, the velocity of the tricuspid annulus, and the radial fiber velocity within the interventricular septum, frequently had coefficients of variation in excess of 20% and should therefore be interpreted with caution.
DOPPLER ULTRASONOGRAPHIC ESTIMATION OF RENAL AND OCULAR RESISTIVE AND PULSATILITY INDICES IN NORMAL DOGS AND CATS
Authors: NOVELLAS ROSA , ESPADA YVONNE , DE GOPEGUI RAFAEL RUIZ
Published: December 2006

Resistive index (RI) and pulsatility index (PI) are indirect measurements of blood flow resistance that may be used to evaluate vascular changes in renal and ophthalmologic diseases. To our knowledge, no reports are available describing values for renal and ocular PI index in the unsedated dog and ocular RI and PI indices in the unsedated cat. The purpose of this study was to measure normal values for both intrarenal and ocular RI and PI within the same subject in unsedated clinically normal dogs and cats. Twenty‐seven dogs and 10 cats were considered healthy by means of physical examination, CBC, biochemical profile, urinalysis, and ultrasonography. Systolic blood pressure was measured by Doppler ultrasonography. Intrarenal and ocular arteries were scanned by pulsed Doppler ultrasonography to calculate RI and PI. No significant differences were noted between the values obtained for the right vs. the left kidney and eye. The upper values of these indices were calculated as mean+2 standard deviations resulting in 0.72 and 1.52 for dog renal RI and PI; 0.7 and 1.29 for cat renal RI and PI; 0.76 and 1.68 for dog ocular RI and PI; and 0.72 and 1.02 for cat ocular RI and PI.
SONOGRAPHIC APPLICATION IN THE DIAGNOSIS OF PYELONEPHRITIS IN CATTLE
Authors: FLOECK MARTINA
Published: December 2006

Nineteen cattle with pyelonephritis were examined sonographically. A 3.5‐ and 5.0‐MHz convex transducer was used for percutaneous and a 5.5‐MHz linear scanner for transrectal examination. Ultrasonographic changes included enlarged kidneys, echogenic material, and flocculent fluid within a dilated and deformed renal sinus and a poor cortical medullary differentiation. Azotemia was detected in 10 and hematuria and proteinuria in all animals. Microbial culture revealedCorynebacterium renalein eight andEscherichia coliin five cattle. Sonography supplemented the clinical examination and clinicopathological analysis by providing additional information on renal disease in these patients.
Amiodarone Induces Angiotensinogen Gene Expression in Lung Alveolar Epithelial Cells through Activation Protein‐1
Authors: Uhal Bruce D. , Zhang Huiying , Abdul‐Hafez Amal , Shu Ruijie , Li Xiaopeng
Published: December 2006

Abstract:  Previous work from this laboratory has shown that amiodarone induces alveolar epithelial cell apoptosis that was abrogated by antagonists of angiotensin II. In this study, amiodarone up‐regulated angiotensinogen mRNA and protein in primary cultures of rat type II pneumocytes and in the human A549 cell line. The mechanism of amiodarone‐induced angiotensinogen expression was studied in A549 cells with a human angiotensinogen promoter‐luciferase reporter (angiotensinogen/luciferase). Amiodarone (3 µg/ml) induced both angiotensinogen/luciferase and endogenous angiotensinogen mRNA; the latter was completely blocked by actinomycin‐D. Amiodarone did not affect the half‐life of endogenous angiotensinogen mRNA. Deletion analyses of angiotensinogen/luciferase identified at least two amiodarone‐responsive domains in the angiotensinogen promoter between −350 to −260 bp and −203 to −46 bp. DNA/Protein array and electrophoretic mobility shift assays showed that amiodarone increases DNA binding of both activation protein‐1 and STAT‐5 transcription factors. Site‐directed mutagenesis of three IL‐6‐responsive signal transducer activator of transcription (STAT) binding sites within the amiodarone‐response domains had no effect on amiodarone‐induced angiotensinogen/luciferase expression. In contrast, amiodarone‐induced angiotensinogen/luciferase expression was abrogated by a dominant‐negative fos construct and was stimulated over five times by c‐fos and c‐jun expressed together but not separately. Mutagenesis of the activation protein‐1 binding site at −15 to −12 bp completely eliminated the response to amiodarone. These data show that activation protein‐1 family transcription factors mediate amiodarone‐induced angiotensinogen expression in human alveolar epithelial cells and identify an activation protein‐1 site, located between the TATA (DNA sequence) box and the transcription initiation site, that is required for the response.
N,N‐Diacetyl‐l‐cystine Improves Endothelial Function in Atherosclerotic Watanabe Heritable Hyperlipidaemic Rabbits
Authors: Pettersson Knut S. , Eliasson Ulla Brandt , Abrahamsson Tommy , Wågberg Maria , Carrier Martin , Kengatharan Ken M.
Published: December 2006

Abstract:N,N‐diacetyl‐l‐cystine (DiNAC), a novel immunomodulator, stimulates contact sensitivity/delayed type hypersensitivity reactions in mice induced by oxazolone and reduces atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Forty‐week‐old WHHL rabbits were given DiNAC (3 µmol/kg per day) for 8 weeks, and endothelium‐mediated dilatation was investigatedin vivousing pulse wave analysis. A significant improvement in endothelial function was found after 3 weeks of treatment, which was further improved after 8 weeks. For experiments on isolated blood vessels, 40‐week‐old rabbits were treated for 3 weeks. Treatment did not affect plasma lipid levels. At termination, aortic rings from the thoracic and abdominal aorta were contracted with phenylephrinein vitro. Concentration‐effect curves to acetylcholine and the calcium ionophore A 23187 were used to measure endothelium‐mediated vasodilatation, and nitroprusside to elicit endothelium‐independent relaxations. Abdominal aorta relaxations were generally larger than in thoracic aorta. DiNAC improved endothelium‐dependent relaxations in the abdominal but not in the thoracic aorta. This effect was independent of the degree of atherosclerosis. It is concluded that DiNAC improved endothelial function in atherosclerotic rabbit arteriesin vivoandin vitro, and may represent a new treatment modality for atherosclerosis‐related diseases.
Non‐Clinical Pharmacology and Safety Evaluation of TH9507, a Human Growth Hormone‐Releasing Factor Analogue
Authors: Ferdinandi Eckhardt S. , Brazeau Paul , High Kim , Procter Bryan , Fennell Stephen , Dubreuil Pascal
Published: December 2006

Abstract:  TH9507, an analogue of human growth hormone‐releasing factor (hGRF(1–44)NH2) minimally modified by addition of a trans‐3‐hexenoyl moiety to Tyr1 of the amino acid sequence, was found to be resistant to dipeptidyl aminopeptidase‐IV deactivation. Compared to natural hGRF(1–44)NH2, the modification slowed the in vitro degradation of the peptide in rat, dog and human plasma and prolonged the in vivo plasma elimination kinetics of immunoreactive TH9507. Plasma growth hormone and insulin‐like growth factor‐1 (IGF‐1) markedly increased in pigs, rats and dogs after daily repeat intravenous or subcutaneous injections of TH9507 at doses up to 600 µg/kg. Subchronic toxicity studies in rats and dogs with TH9507 treatment for up to 4 months showed a significant, but not dose‐related, increase in body weight gain associated with increased biomarker response. Although TH9507 was well tolerated by both rats and dogs, a more pronounced anabolic effect and more evident (reversible) adverse effects (liver and kidney findings, anaemia, clinical chemistry changes, organ weight effects) were observed in dogs after repeat daily subcutaneous injections, which were attributed to prolonged exposure to supraphysiological levels of growth hormone and/or IGF‐1. In both rats and dogs, toxicokinetic evaluations indicated that exposure to immunoreactive TH9507 was dose related after both routes of administration. The apparent elimination t1/2 in dogs ranged from 21 to 45 min. In conclusion, TH9507 is a modified hGRF peptide having enhanced potency and duration of action. The adverse treatment‐related effects in dogs appear to be associated with sustained exposure to supraphysiological levels of growth hormone and IGF‐1 induced by prolonged TH9507 treatment.
Early Adolescents Perceptions of Health and Health Literacy*
Authors: Brown Stephen L. , Teufel James A. , Birch David A.
Published: December 2006

Background:  Health illiteracy is a societal issue that, if addressed successfully, may help to reduce health disparities. It has been associated with increased rates of hospital admission, health care expenditures, and poor health outcomes. Because of this, much of the research in the United States has focused on adults in the health care system. This study investigated the effect of aspects of health literacy on the motivation to practice health‐enhancing behaviors among early adolescents.

Methods:  Measures were generally based on 3 National Health Education Standards for grades 5‐8. Data were obtained from 1178 9‐ to 13‐year‐old students visiting 11 health education centers in 7 states. Students responded via individual electronic keypads.

Results:  Multivariate logistic regression revealed that, in addition to age, difficulty understanding health information and belief that kids can do little to affect their future health, decreased the likelihood for interest in and desire to follow what they were taught about health. Further, low interest independently decreased motivation to follow what was taught. Girls were more likely to turn to school, parents, and medical personnel for health information. Older students were more likely to turn to school and to the Internet.

Conclusions:  Programs and curricula should be designed to increase student interest in health issues and their self‐efficacy in controlling their own health destinies. Educators should also teach students to more effectively use nonconventional health information sources such as the Internet, parents, and medical professionals.
Regulation of the nuclear export of the transcription factor NFATc1 by protein kinases after slow fibre type electrical stimulation of adult mouse skeletal muscle fibres
Authors: Shen Tiansheng , Cseresnyés Zoltán , Liu Yewei , Randall William R. , Schneider Martin F.
Published: December 2006

The transcription factor nuclear factor of activated T cells (NFAT)c1 has been shown to be involved in turning on slow skeletal muscle fibre gene expression. Previous studies from our laboratory have characterized the stimulation pattern‐dependent nuclear import and resting shuttling of NFATc1–green fluorescent protein (GFP) in flexor digitorum brevis (FDB) muscle fibres from adult mouse. In this study, we use viral expression of the transcription factor NFATc1–GFP fusion protein to investigate the mechanisms underlying the nuclear export of the NFATc1–GFP that accumulated in the nuclei of cultured dissociated adult mouse FDB muscle fibres during slow‐twitch fibre type electrical stimulation. In these studies, we found that inhibition of either glycogen synthase kinase 3β (GSK3β) or casein kinase 1 or 2 (CK1/2) markedly slowed the decay of nuclear NFATc1–GFP after cessation of muscle fibre electrical stimulation, whereas inhibition of casein kinase 1δ, p38 mitogen‐activated protein kinase, c‐Jun N‐terminal kinase and protein kinase A had little effect. Simultaneous inhibition of GSK3β and CK1/2 completely blocked the nuclear export of NFATc1–GFP after muscle activity. We also developed a simplified model of NFATc1 phosphorylation/dephosphorylation and nuclear fluxes, and used this model to simulate the observed time courses of nuclear NFATc1–GFP with and without NFATc1 kinase inhibition. Our results suggest that GSK3β and CK1/2 are the major protein kinases that contribute to the removal of NFATc1 that accumulates in muscle fibre nuclei during muscle activity, and that GSK3β and CK1/2 are responsible for phosphorylating NFATc1 in muscle nuclei in a complementary or synergistic fashion.
Imaging of Germinal Center Selection Events During Affinity Maturation
Authors: Allen Christopher D. C. , Okada Takaharu , Tang H. Lucy , Cyster Jason G.
Published: December 2006

The germinal center (GC) is an important site for the generation and selection of B cells bearing high-affinity antibodies, yet GC cell migration and interaction dynamics have not been directly observed. Using two-photon microscopy of mouse lymph nodes, we revealed that GC B cells are highly motile and extend long cell processes. They transited between GC dark and light zones and divided in both regions, although these B cells resided for only several hours in the light zone where antigen is displayed. GC B cells formed few stable contacts with GC T cells despite frequent encounters, and T cells were seen to carry dead B cell blebs. On the basis of these observations, we propose a model in which competition for T cell help plays a more dominant role in the selection of GC B cells than previously appreciated.
ON PRODUCTION OF MAGNETIC MONOPOLES VIA γγ FUSION AT HIGH ENERGY pp COLLISIONS
Authors: KUROCHKIN YU. , SATSUNKEVICH I. , SHOUKAVY DZ. , RUSAKOVICH N. , KULCHITSKY YU.
Published: December 2006

We consider the production of magnetic monopoles via γγ fusion at high energy pp collisions. In the assumption that the monopole spin is equal 0, 1/2, 1, the monopole–antimonopole pair production cross-section by this mechanism at LHC energies is estimated and analyzed.
INFLUENCE OF LORENTZ- AND CPT-VIOLATING TERMS ON THE DIRAC EQUATION
Authors: FERREIRA MANOEL M. , MOUCHEREK FERNANDO M. O.
Published: December 2006

The influence of Lorentz- and CPT-violating terms (in "vector" and "axial vector" couplings) on the Dirac equation is explicitly analyzed: plane-wave solutions, dispersion relations and eigenenergies are explicitly obtained. The nonrelativistic limit is worked out and the Lorentz-violating Hamiltonian identified in both cases, in full agreement with the results already established in the literature. Finally, the physical implications of this Hamiltonian on the spectrum of hydrogen are evaluated both in the absence and presence of a magnetic external field. It is observed that the fixed background, when considered in a vector coupling, yields no qualitative modification in the hydrogen spectrum, whereas it does provide an effective Zeeman-like splitting of the spectral lines whenever coupled in the axial vector form. It is also argued that the presence of an external fixed field does not imply new modifications on the spectrum.
MORPHOLOGICAL COLOR IMAGE SIMPLIFICATION BY SATURATION-CONTROLLED REGIONAL LEVELINGS
Authors: ANGULO JESÚS
Published: December 2006

This paper deals with color image simplification using levelings. This class of connected filters suppresses details but preserves the contours of the remaining structures or objects. As the notion of "color structure" is not trivial, the formulation of morphological operators for color images involves many open issues. The principle choice of a well-defined color space is crucial and it is proposed to work on a luminance/saturation/hue representation defined by the norm L1. A family of morphological color operators is then introduced using the classical formulation with total orderings by means of lexicographic cascades. In this framework, a methodology for color image simplification is introduced, which takes advantage of a saturation-controlled combination of the chromatic and the achromatic (or the spectral and the spatio-geometric) components. More precisely, it is based on the application of a color leveling to each significant region, specifically adapted to the nature (chromatic/achromatic) of the region and which needs an initial image partition into the homogenous regions. Experimental results illustrate the performance of the new developed algorithms.
INTEGRATING GLOBAL AND LOCAL ANALYSIS OF COLOR, TEXTURE AND GEOMETRICAL INFORMATION FOR CATEGORIZING LARYNGEAL IMAGES
Authors: VERIKAS ANTANAS , GELZINIS ADAS , BACAUSKIENE MARIJA , ULOZA VIRGILIJUS
Published: December 2006

An approach to integrating the global and local kernel-based automated analysis of vocal fold images aiming to categorize laryngeal diseases is presented in this paper. The problem is treated as an image analysis and recognition task. A committee of support vector machines is employed for performing the categorization of vocal fold images into healthy, diffuse and nodular classes. Analysis of image color distribution, Gabor filtering, cooccurrence matrices, analysis of color edges, image segmentation into homogeneous regions from the image color, texture and geometry view point, analysis of the soft membership of the regions in the decision classes, the kernel principal components based feature extraction are the techniques employed for the global and local analysis of laryngeal images. Bearing in mind the high similarity of the decision classes, the correct classification rate of over 94% obtained when testing the system on 785 vocal fold images is rather encouraging.
EXACT SOLUTIONS AND DYNAMICS OF GLOBALLY COUPLED OSCILLATORS
Authors: BONILLA L. L. , PÉREZ VICENTE C. J. , RITORT F. , SOLER J.
Published: December 2006

We analyze mean-field models of synchronization of phase oscillators with singular couplings and subject to external random forces. They are related to the Kuramoto–Sakaguchi model. Their probability densities satisfy local partial differential equations similar to the porous medium, Burgers and extended Burgers systems depending on the degree of singularity of the coupling. We show that porous medium oscillators (the most singularly coupled) do not synchronize and that (transient) synchronization is possible only at zero temperature for Burgers oscillators. The extended Burgers oscillators have a nonlocal coupling first introduced by Daido and they may synchronize at any temperature. Exact expressions for their synchronized phases and for Daido's order function are given in terms of elliptic functions.