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Objective: Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. Methods: Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. Results: Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up‐regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3− Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/β TCR repertoire. Conclusion: We established the presence of a specific Tfh cell signature in both circulating and aorta‐infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Hyperphosphataemia is common in patients with nephrogenic systemic fibrosis (NSF). NSF has been linked to administration of gadolinium (Gd) chelates (GCs) and elevated serum phosphate levels accelerate the release of Gd from linear, non-ionic GCs but not macrocyclic GCs. Hence, we determined whether hyperphosphataemia is a cofactor or risk factor for NSF by investigating the role of hyperphosphataemia in renally impaired rats. EXPERIMENTAL APPROACH Firstly, the clinical, pathological and bioanalytical consequences of hyperphosphataemia were investigated in subtotal nephrectomized (SNx) Wistar rats following i.v. administration of the non-ionic, linear GC gadodiamide (5 × 2.5 mmol·kg−1·day−1). Secondly, the effects of several GCs were compared in these high-phosphate diet fed rats. Total Gd concentration in skin, femur and plasma was measured by inductively coupled plasma mass spectrometry (ICP-MS) and free Gd3+ in plasma by liquid chromatography coupled to ICP-MS. Relaxometry was used to measure dissociated Gd in skin and bone. KEY RESULTS Four out of seven SNx rats fed a high-phosphate diet administered gadodiamide developed macroscopic and microscopic (fibrotic and inflammatory) skin lesions, whereas no skin lesions were observed in SNx rats treated with saline, the other GCs and free ligands or in the normal diet, gadodiamide-treated group. Unlike the other molecules, gadodiamide gradually increased the r1 relaxivity value, consistent with its in vivo dissociation and release of soluble Gd. CONCLUSIONS AND IMPLICATIONS Hyperphosphataemia sensitizes renally impaired rats to the profibrotic effects of gadodiamide. Unlike the other GCs investigated, gadodiamide gradually dissociates in vivo. Our data confirm that hyperphosphataemia is a risk factor for NSF. [ABSTRACT FROM AUTHOR]

Myxoid degeneration of the cardiac valves is a common feature in a heterogeneous group of disorders that includes Marfan syndrome and isolated valvular diseases. Mitral valve prolapse is the most common outcome of these and remains one of the most common indications for valvular surgery. While the etiology of the disease is unknown, recent genetic studies have demonstrated that an X-linked form of familial cardiac valvular dystrophy can be attributed to mutations in the Filamin-A gene. Since these inheritable mutations are present from conception, we hypothesize that filamin-A mutations present at the time of valve morphogenesis lead to dysfunction that progresses postnatally to clinically relevant disease. Therefore, by carefully evaluating genetic factors (such as filamin-A) that play a substantial role in MVP, we can elucidate relevant developmental pathways that contribute to its pathogenesis. In order to understand how developmental expression of a mutant protein can lead to valve disease, the spatio-temporal distribution of filamin-A during cardiac morphogenesis must first be characterized. Although previously thought of as a ubiquitously expressed gene, we demonstrate that filamin-A is robustly expressed in non-myocyte cells throughout cardiac morphogenesis including epicardial and endocardial cells, and mesenchymal cells derived by EMT from these two epithelia, as well as mesenchyme of neural crest origin. In postnatal hearts, expression of filamin-A is significantly decreased in the atrioventricular and outflow tract valve leaflets and their suspensory apparatus. Characterization of the temporal and spatial expression pattern of filamin-A during cardiac morphogenesis is a crucial first step in our understanding of how mutations in filamin-A result in clinically relevant valve disease. Developmental Dynamics 239:2118-2127, 2010 © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether an external magnet field can induce preferential trafficking of magnetically labeled Huh7 hepatoma cells to the liver following liver cell transplantation. Huh7 hepatoma cells were labeled with anionic magnetic nanoparticles (AMNP) and tagged with a fluorescent membrane marker (PKH67). Iron-uptake was measured by magnetophoresis. Twenty C57Bl6 mice received an intrasplenic injection of 2 x 10(6) labeled cells. An external magnet (0.29 T; 25 T/m) was placed over the liver of 13 randomly selected animals (magnet group), while the remaining 7 animals served as controls. MRI (1.5 T) and confocal fluorescence microscopy (CFM) were performed 10 days post-transplantation. The presence and location of labeled cells within the livers were compared in the magnet group and controls, and confronted with histological analysis representing the standard of reference. Mean iron content per cell was 6 pg. Based on histology, labeled cells were more frequently present within recipient livers in the magnet group (p < 0.01) where their distribution was preferentially peri-vascular (p < 0.05). MRI and CFM gave similar results for the overall detection of transplanted cells (kappa = 0.828) and for the identification of peri-vascular cells (kappa = 0.78). Application of an external magnet can modify the trafficking of transplanted cells, especially by promoting the formation of perivascular aggregates. [ABSTRACT FROM AUTHOR]

In a series of 84 head and neck patients, a statistically significant correlation was observed between high serum soluble interleukin (IL)-2 receptor alpha (sIL-2Rα) ( P = 0·034) and metalloproteinase-9 (MMP-9) concentrations ( P = 0·036) at diagnosis and a shorter survival of these patients. As MMP-9 has been shown to mediate cleavage of IL-2Rα (CD25) by preactivated T cells, we looked for a relationship between MMP-9 expression and soluble IL-2Rα serum concentrations in these cancer patients. We did not find any correlation between intratumoral expression of MMP-9 or serum MMP-9 concentrations and serum sIL-2Rα levels. These results led us to reassess the role of MMP-9 in the release of sIL-2Rα. Treatment of Kit225 leukaemic cells with recombinant MMP-9 slightly decreased membrane CD25 expression and was associated with an increased concentration of sIL-2Rα in the supernatants. However, using a selective inhibitor of MMP-9 we did not succeed in specifically inhibiting the release of sIL-2Rα by the Kit225 cell line or by phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells. In addition, in a preclinical mouse model, basal serum sIL-2Rα concentrations and sIL-2Rα production by activated cells were not altered in MMP-9-deficient mice compared to wild-type mice. Interestingly, a broad spectrum metalloproteinase inhibitor inhibited the release of sIL-2Rα by PHA-activated peripheral blood mononuclear cells, suggesting that in contrast with current views concerning the major role of MMP-9 in the cleavage of membrane IL-2Rα, other proteases are involved in the shedding of sIL-2Rα. MMP-9 and sIL-2Rα appear therefore as independent prognostic markers in head and neck cancers. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) enhanced with ultrasmall superparamagnetic particles of iron oxide (USPIO) has previously been evaluated in hyperlipidemic rabbits. The aim of this study was therefore to compare USPIO in ruptured and non-ruptured arteries in an atherosclerotic rabbit model. Methods: Atherosclerotic-like lesions were induced by the combination of endothelial abrasion and high-cholesterol diet in iliac rabbit arteries (n = 16). Rupture of atherosclerotic lesions was realized by oversized balloon angioplasty in one iliac artery, whereas the contralateral artery was used as control. USPIO (ferumoxtran-10: 1 mmol Fe/kg) was administered immediately (n = 10) or 28 days (n = 6) after injury. MRI and histological analysis were performed 7 and 35 days after injury and in control arteries. Results: In vivo MRI analysis showed extended susceptibility artifact with transluminal signal loss in all ruptured arteries 7 days after injury. In contrast, hyposignal was reduced 35 days following injury (i.e. after healing), and absent in non-ruptured arteries. Similarly, histological analysis of iron uptake was significantly increased 7 days after injury compared to healed-ruptured and control arteries. Conclusions: Accumulation ofUSPIO is significantly increased in ruptured as compared to non-ruptured arteries in the atherosclerotic rabbit model. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Selective transporters account for rapid urea transport across plasma membranes of several cell types. UT-B1 urea transporter is widely distributed in rat and human tissues. Because mice exhibit high urea turnover and are the preferred species for gene engineering, we have delineated UT-B1 tissue expression in murine tissues. A cDNA was cloned from BALB/c mouse kidney, encoding a polypeptide that differed from C57BL/6 mouse UT-B1 by one residue (Val-8-Ala). UT-B1 mRNA was detected by RT-PCR in brain, kidney, bladder, testis, lung, spleen, and digestive tract (liver, stomach, jejunum, colon). Northern blotting revealed seven UT-B1 transcripts in mouse tissues. Immunoblots identified a nonglycosylated UT-B1 protein of 29 kDa in most tissues and of 36 and 32 kDa in testis and liver, respectively. UT-B1 protein of gastrointestinal tract did not undergo N-glycosylation. Immunohistochemistry and in situ hybridization localized UT-B1 in urinary tract urothelium (papillary surface, ureter, bladder, and urethra), prominently on plasma membranes and restricted to the basolateral area in umbrella cells. UT-B1 was found in endothelial cells of descending vasa recta in kidney medulla and in astrocyte processes in brain. Dehydration induced by water deprivation for 2 days caused a tissue-specific decrease in UT-B1 abundance in the urinary bladder and the ureter. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The acute-phase proteins, serum amyloid As (SAA), are precursors of amyloid A, involved in the pathogenesis of AA amyloidosis. This work started with the characterisation of systemic AA amyloidosis concurrent with SAA overexpression in the subcutaneous white adipose tissue (sWAT) of an obese patient with a leptin receptor deficiency. In the present study a series of histopathological, cellular and gene expression studies was performed to assess the importance of SAA in common obesity and its possible production by mature adipocytes. Materials and methods: Gene expression profiling was performed in the sWAT of two extremely obese patients with a leptin receptor deficiency. Levels of the mRNAs of the different SAA isoforms were quantified in sWAT cellular fractions from lean subjects and from obese subjects before and after a very-low-calorie diet. These values were subsequently compared with serum levels of SAA in these individuals. In addition, histopathological analyses of sWAT were performed in lean and obese subjects. Results: In sWAT, the expression of SAA is more than 20-fold higher in mature adipocytes than in the cells of the stroma vascular fraction (p<0.01). Levels of SAA mRNA expression and circulating levels of the protein are sixfold (p<0.001) and 3.5-fold (p<0.01) higher in obese subjects than in lean subjects, respectively. In lean subjects, 5% of adipocytes are immunoreactive for SAA, whereas the corresponding value is greater than 20% in obese subjects. Caloric restriction results in decreases of 45-75% in levels of the transcripts for the SAA isoforms and in circulating levels of the protein. Conclusions/interpretation: The results of the present study indicate that SAA is expressed by sWAT, and its production at this site is regulated by nutritional status. If amyloidosis is seen in the context of obesity, it is possible that production of SAA by adipocytes could be a contributory factor. [ABSTRACT FROM AUTHOR]

Exposure to hyperglycemia in utero impairs rat nephrogenesis. The effect of maternal diabetes on insulin-like growth factors and their receptors in the fetal kidney is associated with an increase in both mRNA and protein of the insulin-like growth factor II/mannose 6-phosphate receptor. However, this receptor has never been localized in the fetal kidney. The spatial and temporal distribution of the three insulin-like growth factor receptors (insulin-like growth factor I receptor, insulin-like growth factor II/mannose 6-phosphate receptor and insulin receptor) in rat metanephros during both normal and streptozotocin-induced diabetic renal development was investigated using in situ hybridization and immunohistochemistry. All receptors were found in the fetal kidney from the start of nephrogenesis. Insulin-like growth factor I receptor expression was ubiquitous and continuously present during metanephric development. Insulin receptor expression was developmentally regulated during kidney maturation with an enhanced expression in proximal tubules at the late stages of development. Insulin-like growth factor II/mannose 6-phosphate receptor expression was ubiquitous in the early stages of development and was dramatically decreased at the late stages of normal kidney development. Insulin receptor and insulin-like growth factor I receptor expressions were unchanged in diabetic metanephroi. Although the spatial expression of insulin-like growth factor II/mannose 6-phosphate receptor was unaffected by hyperglycemia, its expression was not downregulated in the mesenchyme of the nephrogenic zone of diabetic fetuses on gestational day 20. This study suggests a crucial role of insulin-like growth factor II/mannose 6-phosphate receptor in the pathogenesis of the impaired nephrogenesis in fetuses of diabetic mothers. [ABSTRACT FROM AUTHOR]

The micturition profile in conscious animals and the urethrovesical coordination in anesthetized conditions were investigated in 6- and 24-mo-old male Sprague-Dawley rats. The in vitro pharmacological responses to KCl, electrical field stimulation (EFS), carbachol, phenylephrine, and isoprenaline were determined in the isolated bladder body, the bladder neck, and urethra. A morphometric and immunohistological study has been included. During conscious cystomanometry, 63% of the aging rats but only 25% of the adult rats showed spontaneous contractions during the bladder-filling phase. In conscious aging rats, basal pressure, threshold pressure, and micturition pressure were also significantly increased. In anesthetized aging rats, a decrease in resting urethral pressure at micturition threshold and the occurrence of a significant delay in urethral relaxation during micturition were associated with an increased residual volume. In all isolated tissues, contractile response to KCl was not modified with aging, whereas age-related decreases in maximal responses to carbachol in the bladder body and to phenylephrine and carbachol in the urethra were observed. In the bladder neck only, we found a significant decrease in the amplitude of neurogenic contractions associated with fibrosis but without decrease in nerve density. These experiments show significant modifications in the voiding pattern of aging rats associated with urethral dysfunction and with regionally specific pharmacological and structural changes of the urinary tract. We propose that aging in rats is characterized by an impairment of the urethrovesical coordination, leading to bladder dysfunctions similar to those induced by bladder outlet obstruction. [ABSTRACT FROM AUTHOR]

Intestinal vasculitis is uncommon and usually accompanies systemic vasculitis. Although intestinal vascular changes including vasculitis have been studied intensively, and are found regularly in Crohn's disease, giant cell arteritis is distinctly unusual. We describe a case of giant cell arteritis localized to the colon of an 18-year-old girl suffering from Crohn's disease. After three years of medical treatment, the patient underwent a proctocolectomy. The medium-sized arteries of the mesocolon demonstrated striking changes characterized by intimal fibrous thickening and an inflammatory infiltrate with giant cells, most predominant at the intima–media junction. Epithelioid cells and sarcoid-like granulomas were not observed. The internal elastic lamina was fragmented. Neither clinical symptoms nor laboratory findings showed evidence of systemic vasculitis. Neither the chest CT scan nor the echo-Doppler of the temporal arteries, supra-aortic and abdominal vessels revealed any abnormality. This case illustrates an extremely rare feature in the spectrum of vascular lesions in Crohn's disease which have to be differentiated from temporal and Takayasu's arteritis. [ABSTRACT FROM AUTHOR]

Reports on a case of a 30-year-old man with intrapericardial lymphangioma with podoplanin immunohistochemical characterization of lymphatic endothelial cells. Patient's medical history; Diagnostic imaging findings; Histological examination findings.

Diabetic glomerulosclerosis is defined by increased glomerular extracellular matrix (ECM) that is mainly synthesized by mesangial cells that underwent an activation mediated by cytokines and growth factors from various cellular origins. In this study, we tested whether macrophages could infiltrate the glomeruli and influence ECM synthesis in experimental diabetes. To test our hypothesis, we initially studied the dynamics of glomerular macrophage recruitment in streptozotocin-induced diabetic rats at days 1, 2, 4, 8, 15, and 30 by using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on isolated glomeruli and immunohistochemistry and morphometry. We then assessed the role of macrophages on the basis of the pharmacological modulation of their recruitment by insulin or ACE inhibitor treatments and by X-irradiation-induced macrophage depletion at days 8 and 30. Macrophages were recruited within the glomeruli at the very early phase of hyperglycemia by using RT-PCR CD14 detection from day 2 and by using ED1 immunohistochemistry from day 8. This glomerular macrophage infiltration was associated with an increase in alpha1-chain type IV collagen mRNA. In parallel, the diabetic glomeruli became hypertrophic with an increase in the mesangial area. Macrophage recruitment was preceded by or associated with an increased glomerular expression of vascular cell adhesion molecule 1, intracellular adhesion molecule 1, and monocyte chemoattractant protein 1, which contributes to monocyte diapedesis. Glomerular interleukin-1beta mRNA synthesis was also enhanced as early as day 1 and could be involved in the increase in ECM and adhesion molecule gene expressions. Insulin treatment and irradiation-induced macrophage depletion completely prevented the glomerular macrophage recruitment and decreased alpha1-chain type IV collagen mRNA and mesangial area in diabetic rats, whereas ACE inhibitor treatment had an incomplete effect. It can be concluded that in the streptozotocin model, hyperglycemia is followed by an early macrophage recruitment that contributes to the molecular and structural events that could lead to glomerulosclerosis. Therefore, besides direct stimulation of mesangial cells by hyperglycemia, macrophages recruited in the glomeruli during the early phase of hyperglycemia could secondarily act on mesangial cells. [ABSTRACT FROM AUTHOR]

The endothelin system is composed of three endothelin isoforms (ET-1, ET-2, and ET-3), the endothelin receptors ETA and ETB, and the endothelin-converting enzyme (ECE). Besides having a major vasoactive role, endothelins have roles in different cell types at a local level. We investigated the presence of the different components of the endothelin system in primate ovaries. Human ovaries and gonadotropin-stimulated monkey ovaries were studied using immunohistochemistry for endothelin, and in situ hybridization with probes for ET-1, ET-2, ET-3, ETA and ETB receptors, and ECE. ET-1 and ETA receptors were detected in endothelial cells and vascular smooth muscle cells, respectively, in stromal vessels adjacent to follicles and corpora lutea. ETB receptors and ET-1 were found in the endothelial cells of capillaries of corpora lutea. ECE was present in internal theca cells of secondary, de Graaf, atretic follicles, and in luteinized granulosa cells of the corpora lutea. The endothelin system components are present in or around the follicles of human and monkey ovaries. Although the components are not expressed in the same cell types, they are synthesized, mainly in follicles, by cells that are in close proximity. Thus, the endothelin system could act in a paracrine manner. ECE expression in steroid-producing cells changes its compartmentalization during follicle maturation. [ABSTRACT FROM AUTHOR]

Transcatheter radiofrequency (RF) ablation of atrial fibrillation or flutter requires the creation of linear lesions. However, conventional catheters are not predictably effective because of poor endocardial contact, and limited lesion size and penetration. The purpose of the study was to assess, in the right atrium, the efficacy and safety of a new catheter designed to create long myocardial tissue lesions using RF energy. The main characteristics of this 8 Fr deflectable RF ablation catheter were: (1) a perpendicularly contacting articulated bilimb electrodes ensuring stable and firm endocardial firm contact; and (2) an irrigated planar interface. Three different electrode prototypes were tested. Fourteen anesthetized sheep weighing 61 ± 7 kg underwent RF ablation in the right atrium using three incremental power levels (25 to 45, 50, 55 to 75 W) with the aim of creating fully transmural (FT) lesions, defined as continuous and complete epicardial and endocardial lesion imprints. The animals were euthanized 1 hour later for macroscopic and histologic examinations. Forty-three of the 80 right atrial lesions created, in smooth us well as in trabeculated areas, were FT. The percentage of FT lesions increased with the applied power from 37% with 25-45 W, to 49% with 50 W, and up to 86% for 55-75 W. in all but two cases, histologic examination showed no discontinuity between FT lesions produced by both limbs resulting in 19 coalescent linear lesi ons with an average size of 25 × 6 × 4 mm (length × width × depth). In situ bipolar electrograms after ablation in the FT group showed split potentials and/or a marked decrease in amplitude from 2.85 ± 1.79 to 0.33 ± 0.14 mV (P = 0.001) accompanied by near complete disappearance of unipolar electrograms. There was no perforation due to RF ablation. In conclusion, continuous and FT lesions can be achieved in various areas of sheep atria, including the trabecular right atrium, with a perpendicularly contacting bilimb electrode catheter. it represents a promising tool for catheter ablation of atrial fibrillation and flutter. [ABSTRACT FROM AUTHOR]

To characterize myocardial lesions induced by Nd-YAG laser in vivo , laser pulses were delivered on the epicardial surface of beating dog hearts. Acute lesions were studied at the optical and ultrastructural levels. The size of the lesions depended on the power of the laser beam. Tissue vaporization could be avoided if total delivered energy did not exceed 350 J. Laser energy induced different types of myocardial necrosis distributed in concentric layers of coagulation necrosis, and contraction band necrosis. Thus, laser energy can produce controlled irreversible lesions without crater formation. These effects may be of use in the treatment of arrhythmias. [ABSTRACT FROM PUBLISHER]

A prototype directional atherectomy catheter (Omnicath) was evaluated in four Yucatan microswines. Atherectomy was performed on iliac or aortic target lesions. After control angiography, the animals were sacrificed and the target arteries were examined histologically. Atherectomy resulted in arterial ruptures in three cases, and the track of the blade was measured to be of an average depth of 0.38 mm. Maneuverability was satisfactory but aspiration was not efficient. Precise localization of the atherectomy window was difficult. We conclude that modification of the catheter seems mandatory before use in humans. [ABSTRACT FROM AUTHOR]

The labeling index of endothelial cells as measured by in vitro autoradiography with H-thymidine and the electron microscopic structure of microvessels were studied in telangiectases. The telangiectases of eight patients with progressive systemic sclerosis (PSS) were compared with the cherry angiomas of six healthy controls subjects. The ultrastructural features of telangiectases were similar in the two groups and were characteristic of capillaries and postcapillary venules of the dermis, with multilayering of the vascular basement membrane. However, a significant difference existed between these two groups in an autoradiographic study: in PSS telangiectases, the average labeling index was 5.9%, whereas in cherry angiomas it was around 0.8%. Thus, the telangiectases in PSS are structures with accelerated endothelial proliferation, as are the other endothelial cells of microvessels anywhere in dermis in this disease. However, the great heterogeneity of the labeling index (varying from 0.5% to 27%) must be emphasized in telangiectases. [ABSTRACT FROM AUTHOR]

Xenotransplantation between discordant species leads to a hyperacute rejection mediated by natural antibodies. both of the IgG and IgM isotypes, activation of complement and endothelial cell activation. The combination of these mechanisms leads to a transplant survival of minutes to a few hours. Polyclonal human irnmunoglobulins for intravenous use ([V]g) from normal donors have proved effective in a number of antibody-mediated disorders, as well as in inflammatory disorders. We demonstrate that administration of [V]g in a guinea pig to rat model of cardiac xenografting can effectively delay hyperacute rejection. This effect is mediated by the F(ab')2 fragments of [V]g. and is correlated to an anti-complementary activity. [ABSTRACT FROM AUTHOR]

In order to investigate the consequences of different types of cardiac hypertrophy on myocardial capillary and fibrosis density in rats we describe here, in the same hearts, the pattern of capillary bed density visualized by fluoresceine isothiocyanate dextran (FITC-dextran) and the pattern of fibrosis density as determined by automated image analysis. Pressure overload was induced by clipping one renal artery in rats (one-clip, two-kidney Goldblatt hypertension, RHV). Volume overload was induced by creation of an arteriovenous shunt between the abdominal aorta and the vena cava (aorto-caval fistula model ACF). Animals were sacrified at 1, 3 and 6 months following surgical procedure. Immediately prior to sacrifice, FITC-dextran (MW 150,000) was injected with the animal under ether anesthesia. Five minutes later, cardiac diastolic arrest was induced by the i.v. injection of potassium chloride. The heart was rapidly excised and placed in a formaldehyde solution. The degree of cardiac hypertrophy was calculated after measurement of cardiac weight. Left ventricular wall thickness and cavity area were measured by microscopic methods. Capillary density and geometry were determined by morphometric methods, under ultraviolet light microscopy, using a graphic tablet connected to a microcomputer. The degree of myocardial fibrosis, visualized with Sirius Red, was estimated by the use of automated image analysis using light microscopy. In renovascular hypertension, cardiac hypertrophy was maximum at one month (36%) and persisted through the six months of the study. This increase in cardiac mass was concentric, due to a significant increase in ventricular wall thickness and was associated with a marked increase in fibrosis and a significant decrease in subendocardial capillary density. These effects existed already one month and did not change with time. In the aorto-caval fistula model, cardiac hypertrophy was also maximum at one month (+56%), but this eccentric increase in cardiac mass was associated with no significant change in left ventricular wall thickness, but rather with a significant increase in the surface area of the left ventricular cavity. This volume overload hypertrophy was associated with a decrease in subendocardial capillary density which was negatively correlated with time. In contrast to concentric hypertrophy there was no increase in the fibrosis density compared to the sham-operated groups. Despite the identical degrees of hypertrophy, pressure and volume cardiac overload differed in a significant manner in both left ventricular wall thickness and cavity surface area. The observed changes in capillary bed and fibrosis density seem to be influenced predominantly by this change in geometry of the left ventricle. [ABSTRACT FROM AUTHOR]

The localization of immunoreactive angiotensin I-converting enzyme (ACE) has been investigated at the optical and ultrastructural level with anti-human ACE antibodies in the human kidney and small intestine. In both tissues ACE was found in blood vessels and in extravascular situation in the absorptive epithelial cells of intestinal mucosa and renal proximal tubules. Ultrastructural immunohistochemistry showed that in intestinal and renal proximal tubular cells ACE was prominent in microvilli and brush borders. In the kidney ACE was also present on the basolateral part of the plasmalemmal membrane, where it may contribute to the regulation of angiotensin II-dependant absorption processes. Intracellular positivities were also observed inside the renal vascular endothelial and proximal tubular cell in endoplasmic reticulum and nuclear envelope reflecting the synthesis and the cellular processing of ACE. The intestinal microvascular endothelium was strongly labeled suggesting that the mesenteric circulation is an important site for the production of angiotensin II. Vascular endothelial ACE was also detected in the peritubular but not glomerular capillaries of the kidney. [ABSTRACT FROM AUTHOR]

Closed chest ablative technique that avoid barotrauma would be attractive for ablation at thin walled cardiac structures, such as the atrial free wall or coronary sinus. Transcatheter radiofrequency (RF) currents produce tissue necrosis the size of which is dependent on the contact between the tissue and the electrode. In order to assess the effects of transvenous RF ablation of atrial free wall using a suction electrode catheter, we delivered in ten dogs, one single unmodulated RF pulse 1.2 MHz, in a unipolar mode, through the distal electrode of a lumen catheter (USCI 8F) (USCI, Billerica, MA, USA) located in the right appendage. During the pulse an 80 KPa vacuum depression was applied to the lumen of the catheter. Each pulse had a 10 seconds duration and the mean delivered power was 4.3 ± 1.4 W. Aortic pressure and electrocardiogram were monitored during the procedure. A right atrial electrophysiological study was performed at the ablated site, at control, after suction application and after RF pulse delivery. The animals were sacrificed after 14 or 22 days. Atrial pacing threshold values decreased after suction application in comparison to control values after the pulse (0.42 ± 0.06 vs 0.60 ± 0.23 mA, P < 0.05) but increased after the pulse delivery (2.60 ± 1.85 mA, P < 0.01). In contrast, the atrial effective refractory period did not significantly change after suction, nor after RF pulse delivery. Aortic pressure remained unchanged throughout the procedure. Complex arrhythmias were not observed during or after RF pulse delivery. One dog died suddenly at the first day after ablation, but this death was most probably unrelated to RF ablation. Anatomic lesions had a length of 8.8 ± 3.3 mm, a width of 4.6 ± 2.5 mm and a depth of 3.6 ± 1.1 mm. They were transmural in nine of the ten dogs but without atrial wall perforation in any case. Lesions suggesting tissue volatilization were present in four dogs. These results demonstrate that low energy RF currents delivered with a suction electrode catheter can produce transmural necrosis of free wall, without risk of perforation. Such ablative technique would be of interest for ablation of right sided accessory pathways or atrial ectopic foci. Further experimental data are required in order to define the optimal energy level required to avoid tissue volatilization. [ABSTRACT FROM AUTHOR]

The endothelium and internal elastic lamina (IEL) appear to be the main barriers to adenovirus-mediated gene transfer to medial smooth muscle cells (SMC). The present randomized study tested whether controlled incubation with elastase enhanced the efficiency of catheter-based gene transfer to medial SMC by adenoviral vectors. After an initial safety dose ranging study, rabbits underwent balloon abrasion of the iliac endothelium followed by local incubation of either elastase (2 × 10-7 IU over 5 min) or saline using a double balloon catheter (DBC). Then, adenoviral vectors (5 × 109 p.f.u.) carrying Cmv-Luc or RSV-βgal reporter genes were instilled for 30 min. Three days later, the number of medial SMC expressing lacZ was increased in the elastase-treated arteries compared with saline-treated arteries (7.2 ± 2.5 versus 2.3 ± 0.9 cells per section, P = 0.003). Likewise, the amount of luciferase protein product was increased (70 ± 32 versus 36 ± 15 pg luciferase/mg tissue, P = 0.03). No vessel enlargement, light or electron microscopic evidence of injury or inflammation was seen in elastase-treated arteries up to 7 weeks. Preincubation with elastase increased transduction efficiency of catheter-based gene delivery of replication-defective adenoviral vectors to rabbit iliac arteries without detectable arterial damage. [ABSTRACT FROM AUTHOR]

In order to determine the respective roles of catheter (Ct) physical properties and of energy levels in myocardial effects of fulguration. we delivered an electrical shock between the tip electrode of a Ct placed at the apex of the right ventricle and a large cutaneous cathodal electrode in 12 dogs. Two energy levels were used: Group A = 25 J (n = 6) and group B 100 5 (n = 6), and three Cts were studied. These Cts had different resistances (R) and active surface electrodes (S): Ct 1 (R = 0.3 Ω, S = 12 mm²), Ct 2 (B = 0.3 Ω, S = 2 mm²), Ct 3 (R = 2 Ω, S = 13 mm²). Complex ventricular arrhythmias were observed in 5/6 cases at 100 J but only in l/6 case at 25 J and were independent of the Ct type. Following the shock, the effective ventricular refractory period (S1 S1 = 300 msec) increased significantly only at 100 J (11%, p = 0.03). Anatomical lesions were wider (10.6 vs, 5.2 mm, p <0.05) and deeper (100 vs. 55%, p < 0.05) in the 100 J group. In contrast, there was no significant difference in the electrophysiological and anatomical changes between the three Cts. In conclusion, (1) arrhythmogenic adverse effects of ventricular Ct fulguration are related to the delivered energy; (2) on the contrary, they seem only slightly dependent on Cf physical properties at these energy levels; (3) a 2 J/kg shock is not only effective but also seems to be safe. [ABSTRACT FROM AUTHOR]

The article presents the case summaries and pathological findings of three cases of isolated tumor cervical lymphadenopathy in patients with no clinically detectable nasopharyngeal tumor. All the three cases displays striking similarities and highlight the difficulty that clinician and pathologists encounter in distinguishing between undifferentiated carcinoma of nasopharyngeal type and aggressive lymphoma in young patients presenting with isolated cervical lymphadenopathy.

A letter to the editor is presented offering a comparision of the frozen section diagnosis and the final histological diagnosis (FD) in the parotid tumours.

The authors describe a case of valvular heart disease in a 48-year-old woman receiving benfluorex (150 mg t.i.d. for 8 years) and leading to surgical mitral valve replacement. Examination showed severe dyspnea with severe mitral regurgitation associated with tricuspid regurgitation. No other common disease known to affect mitral valves nor intake of other drugs (ergot derivatives or appetite suppressant drugs) was found. The paper discusses the imputability of benfluorex, a drug used as an adjuvant in hypercholesterolemia, structurally related to amphetamines. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor concerning CD34 positivity in a thoracic monophasic fibrous synovials sarcoma.