bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital dermatofibrosarcoma protuberans with fibrosarcomatous and myxoid change
Authors: Gu W , Ogose A , Kawashima H , Umezu H , Kudo N , Hotta T , Endo N
Published: August 2005

This report describes a case of congenital dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous (FS) and myxoid areas. Immunohistochemical results showed that tumour cells in ordinary DFSP areas were diffusely positive for CD34, whereas in the FS and myxoid areas, few tumour cells were positive for this antigen. Ki-67 positive tumour cell numbers were greater in the FS (11.8%) and myxoid areas (19.8%) relative to ordinary DFSP areas (2.2%). Reverse transcription polymerase chain reaction and sequence analysis showed the presence of an identical COL1A1–PDGFB fusion transcript in ordinary DFSP (plaque-like area), FS, and myxoid areas of DFSP. These results indicate that the three components of DFSP have a common histogenesis. This study documents the first application of gene analysis involving the myxoid area of DFSP.
Adenosquamous carcinoma of the pancreas with an acantholytic pattern together with osteoclast-like and pleomorphic giant cells
Authors: Alwaheeb S , Chetty R
Published: August 2005

A 45 year old man presented with abdominal pain, loss of appetite, and significant weight loss over a period of about four weeks. Imaging of the abdomen showed a mass in the region of the head of the pancreas. In view of the size of the mass and the clinical picture, a Whipple’s procedure was performed. Histological evaluation of the pancreatic tumour showed an adenosquamous carcinoma (predominantly composed of squamous carcinoma), which was extensively infiltrative with perineural invasion and involvement of peripancreatic lymph nodes. Areas of pancreatic intraepithelial neoplasia grade III and merging of the squamous and adenocarcinoma components were evident. Unusual histological features that characterised this case included a pronounced acantholytic pattern within the squamous carcinoma component, and the presence of both osteoclastic and pleomorphic giant cells. Giant cells have not been documented previously in association with an adenosquamous carcinoma. Although an acantholytic pattern has been noted in squamous carcinomas in other sites, this is the first report of such a pattern in an adenosquamous carcinoma of the pancreas.
Antistreptokinase antibodies: implications for thrombolysis in a region with endemic streptococcal infection: Table 1
Authors: Blackwell N , Hollins A , Gilmore G , Norton R
Published: August 2005

Aims:To determine antistreptokinase antibody (anti-SK) titres in patients with the acute coronary syndrome from communities with endemic group A streptococcal infection because of the implications for streptokinase (SK) thrombolysis.

Methods:Anti-SK titres were determined using a standard method in 47 consecutive SK naive patients, presenting to the Mt Isa Hospital emergency department, Australia, with an acute coronary syndrome. Both indigenous and non-indigenous subjects were enrolled. Antistreptolysin O (ASOT) and anti-DNAse B (ADB) titres were also determined.

Results:Indigenous patients were more likely to have anti-SK antibodies (p < 0.001) than the non-indigenous cohort. Anti-SK antibody titres also correlated well with ASOT/ADB titres.

Conclusions:Anti-SK antibodies are highly prevalent in SK naive indigenous patients presenting with the acute coronary syndrome. Streptokinase should not be used for thrombolysis in populations with endemic group A streptococcal infection.
Can urine dipstick testing for urinary tract infection at point of care reduce laboratory workload?
Authors: Patel H D , Livsey S A , Swann R A , Bukhari S S
Published: August 2005

Aim:The University Hospitals of Leicester NHS Trust microbiology laboratory receives 150 000 urine samples each year, approximately 80% of which prove to be culture negative. The aim of this study was to reduce the proportion of culture negative urines arriving in the laboratory, by producing local evidence based guidelines for the use of urine dipstick testing at point of care within the trust’s three acute hospitals.

Methods:One thousand and seventy six unborated urine samples were dipstick tested at the point of care using an automatic strip reader. Quantitative results for the four infection associated markers—leucocyte esterase, nitrite, blood, and protein—were compared with the results of conventional laboratory microscopy and culture.

Results:The performance of different marker combinations was calculated against the routine laboratory methods. One hundred and seventy five (16.3%) samples were negative for all four markers. Of these dipstick negative samples, only three (1.7% of all true positives) were positive by culture. The absence of all four infection associated markers was found to have a greater than 98% negative predictive value and a sensitivity and specificity of 98.3% and 19.2%, respectively.

Conclusions:A urinary dipstick testing algorithm for infection associated markers was derived for use in hospital patients to screen out negative urines. Two years after distributing the algorithm and promoting access to reagent strips and strip readers, a reduction in the urine workload has been seen against an otherwise increasing laboratory specimen load.
Myeloid metaplasia in the gall bladder: a case report
Authors: Sahasrabudhe N , Davenport A
Published: August 2005

Idiopathic myelofibrosis is often associated with myeloid metaplasia (extramedullary haemopoiesis) in the spleen and liver. However, the gall bladder is an extremely unusual site for it to occur. A 59 year old man with myelofibrosis, who underwent cholecystectomy for chronic cholecystitis, showed myeloid metaplasia in his gall bladder. Pathologically, this may lead to diagnostic difficulties.
Activation induced cytidine deaminase expression in lymphocyte predominant Hodgkin lymphoma
Authors: Mottok A , Hansmann M-L , Bräuninger A
Published: August 2005

Background:The lymphocytic and histiocytic (L&H) cells of lymphocyte predominant Hodgkin lymphoma (HL) originate from germinal centre B cells and carry mutated V gene rearrangements, usually with intraclonal diversity. It is unclear whether intraclonal V gene diversification by somatic hypermutation, which is strictly dependent on the enzyme activation induced cytidine deaminase (AID), is restricted to the early phase of lymphoma clone expansion and later silenced, or whether it remains active throughout malignant proliferation.

Aims:To analyse whether AID is expressed in L&H cells as an indicator of active somatic hypermutation in the tumour cells.

Methods:L&H cells from lymphocyte predominant HL cases and centroblasts from lymphadenites were micromanipulated and analysed for AID expression by quantitative real time polymerase chain reaction.

Results:The AID transcription level was higher than background in three of the six lymphocyte predominant HL cases, although it was lower than that seen in centroblasts.

Conclusions:Somatic hypermutation may remain active in L&H cells in a considerable proportion of cases, increasing the risk of acquiring further transforming mutations.
High cystine in platelets from patients with nephropathic cystinosis: a chemical, ultrastructural, and functional evaluation
Authors: Olcay L , Erdemli E , Kesimer M , Büyükaşık Y , Okur H , Kalkanoğlu H S , Coşkun T , Altay Ç
Published: August 2005

Aim:To investigate the morphology and function of platelets in nephropathic cystinosis (NC).

Methods:Seven patients (mean age, 6.5 years; SD, 20 months) with NC were investigated. Their platelets were examined by transmission electron microscopy (TEM) and the characteristics of the dense granules (DGs) were determined by mepacrine labelling and the uranaffin reaction. Bleeding time, turbidometric aggregation, and luminescence aggregation were studied and intraplatelet cystine was measured.

Results:Increased intraplatelet cystine, primary and secondary aggregation defects, and the absence of ATP release were demonstrated. TEM revealed DGs of various shapes and sizes and lamellary or amorphous cytoplasmic inclusions. Viscous material had been released into the vacuolar spaces and enlarged open canalicular system. Mepacrine labelling revealed that the numbers of DGs/platelet were comparable between the patients and the controls (mean, 2.9 (SD, 0.22)v3.32 (0.18); p  =  0.34). The uranaffin reaction revealed that the numbers of type 1, 3, and 4 DGs were comparable between the patients and the controls, but that there were fewer type 2 DGs in the patients (mean, 8.5 (SD, 1.95)v17.22 (1.58); p  =  0.01). TEM for platelet aggregation revealed a lack of induction and/or defective execution and/or delayed transmission. The patients’ intraplatelet cystine concentrations were higher than the controls (mean, 1.56 (SD, 0.84)v0.08 (0.01) nmol/mg protein; p  =  0.009).

Conclusions:This is the first report to demonstrate raised intraplatelet cystine, abnormal platelet ultrastructural findings, and defective aggregation in NC.
J/Ψ PRODUCTION IN HIGH ENERGY PARTICLE AND NUCLEAR COLLISIONS: SUPPRESSED, ENHANCED, OR JUST NORMAL?
Authors: GUPTAROY P. , SANYAL GOURI , DE BHASKAR , BHATTACHARYYA S.
Published: August 2005

The oncoming recent data on production of J/Ψ mesons in some high energy particle and nuclear collisions are of special importance in view of the controversies centering around the so-called suppression or enhancement mechanisms for this particle-species. We will try to explain here the features of some of the basic observables on J/Ψ production with the help of an approach which has no direct links with quark–gluon plasma (QGP) considerations, but can interpret a large amount of data related to the proposed physical signatures of QGP. The final outcome, based on the present study, amounts to stating the fact that the J/Ψ production is neither suppressed nor enhanced; rather it exhibits both in our theoretical approach and also in the experimental measurements a behavior which is just as normal as many other secondaries, with only specificities of its own intrinsic quantum numbers and the very massive nature.
NILPOTENT SYMMETRIES FOR MATTER FIELDS IN NON-ABELIAN GAUGE THEORY: AUGMENTED SUPERFIELD FORMALISM
Authors: MALIK R. P.
Published: August 2005

In the framework of superfield approach to Becchi–Rouet–Stora–Tyutin (BRST) formalism, the derivation of the BRST and anti-BRST nilpotent symmetry transformations for the matter fields, present in any arbitrary interacting gauge theory, has been a long-standing problem. In our present investigation, the local, covariant, continuous and off-shell nilpotent (anti-)BRST symmetry transformations for the Dirac fields [Formula: see text] are derived in the framework of the augmented superfield formulation where the four (3 + 1)-dimensional (4D) interacting non-Abelian gauge theory is considered on the six (4 + 2)-dimensional supermanifold parametrized by the four even space–time coordinates xμand a couple of odd elements (θ and [Formula: see text]) of the Grassmann algebra. The requirement of the invariance of the matter (super)currents and the horizontality condition on the (super)manifolds leads to the derivation of the nilpotent symmetries for the matter fields as well as the gauge and the (anti)ghost fields of the theory in the general scheme of augmented superfield formalism.
GIBBS FREE ENERGY OF A SYSTEM OF TWO HIGHLY CHARGED PLATES IMMERSED IN AN ELECTROLYTE
Authors: SHINOHARA TADATOMI , SMALLEY MARTIN V. , SOGAMI IKUO S.
Published: August 2005

The Gibbs free energy of two highly charged plates immersed in an electrolyte solution in a finite container is investigated using mean field theory. Adiabatic potential of the charged plates, which is derived from the Gibbs free energy, has a long-range weak attractive part and medium range strong repulsive part under the Dirichlet boundary condition. From comparison with the Helmholtz adiabatic potential, it is proved that the two adiabatic potentials have qualitatively the same structure of a repulsive component and an attractive component and that the Gibbs adiabatic potential shows the stronger attractive effect.
CONTINUOUS PATH VERIFICATION IN MULTI-AXIS NC-MACHINING
Authors: WEIN RON , ILUSHIN OLEG , ELBER GERSHON , HALPERIN DAN
Published: August 2005

We introduce a new approach to the problem of collision detection between a rotating milling-cutter of an NC-machine and a model of a solid workpiece, as the rotating cutter continuously moves near the workpiece. Having five degrees of motion freedom, this problem is hard to solve exactly and we approximate the motion of the tool by a sequence of sub-paths of pure translations interleaved with pure rotations. The collision-detection problem along each sub-path is then solved by using radial projection of the obstacles (the workpiece and the static parts of the NC-machine) around the tool axis to obtain a collection of critical surface patches in ℝ3, and by examining planar silhouettes of these surface patches. We thus reduce the problem to successive computations of the lower envelope of a set of planar curves, which we intersect with the profile of the tool. Our reduction is exact, and incurs no loss of accuracy. We have implemented our algorithm in the IRIT environment for solid modeling, using an extension package of the CGAL library for computing envelopes. The algorithm, combined with the proper data structures, solves the collision detection problem in a robust manner, yet it yields efficient computation times as our experiments show. Our approach produces exact results in case of purely translational motion, and provides guaranteed (and good) approximation bounds in case the motion includes rotation.
FINDING PLANAR REGIONS IN A TERRAIN – IN PRACTICE AND WITH A GUARANTEE
Authors: FUNKE STEFAN , MALAMATOS THEOCHARIS , RAY RAHUL
Published: August 2005

We consider the problem of computing large connected regions in a triangulated terrain of size n for which the normals of the triangles deviate by at most some small fixed angle. In previous work an exact near-quadratic algorithm was presented, but only a heuristic implementation with no guarantee was practicable. We present a new approximation algorithm for the problem which runs in O(n/∊2) time and—apart from giving a guarantee on the quality of the produced solution—has been implemented and shows good performance on real data sets representing fracture surfaces consisting of around half a million triangles. Further we present a simple approximation algorithm for a related problem: given a set of n points in the plane, determine the placement of the unit disk which contains most points. This algorithm runs in linear time as well.
WHEN THUE-MORSE MEETS KOCH
Authors: MA JUN , HOLDENER JUDY
Published: August 2005

In this paper, we reveal a remarkable connection between the Thue-Morse sequence and the Koch snowflake. Using turtle geometry and polygon maps, we realize the Thue-Morse sequence as the limit of polygonal curves in the plane. We then prove that a sequence of such curves converges to the Koch snowflake in the Hausdorff metric. In the final section we consider generalized Thue-Morse sequences and provide a characterization of those that encode curves converging to the Koch snowflake.
AN ANALYSIS METHOD FOR SAMPLING IN SHIFT-INVARIANT SPACES
Authors: ERICSSON STEFAN , GRIP NIKLAS
Published: August 2005

A subspace V of L2(ℝ) is called shift-invariant if it is the closed linear span of integer-shifted copies of a single function.

As a complement to classical analysis techniques for sampling in such spaces, we propose a method which is based on a simple interpolation estimate of a certain coefficient mapping. Then we use this method to derive both new results and relatively simple proofs of some previously known results. Among these are some results of rather general nature and some more specialized results for B-spline wavelets.

The main problem under study is to find a shift x0 and an upper bound δ such that any function f ∈ V can be reconstructed from a sequence of sample values (f(x0 + k + δk))k∈ℤ, either when all δk = 0 or in the irregular sampling case with an upper bound sup k|δk| < δ.
INTERPOLATING SCALING VECTORS
Authors: KOCH KARSTEN
Published: August 2005

In this paper we construct a one-parameter family of interpolating multigenerators which generalize the scalar generators constructed in Ref. 4 in a natural way. Furthermore we extend this approach to design a family of interpolating orthonormal multigenerators. The construction is based on the factorization techniques introduced in Ref. 27.
BIG CAT GENOMICS
Authors: O'Brien Stephen J. , Johnson Warren E.
Published: August 2005

▪ Abstract  Advances in population and quantitative genomics, aided by the computational algorithms that employ genetic theory and practice, are now being applied to biological questions that surround free-ranging species not traditionally suitable for genetic enquiry. Here we review how applications of molecular genetic tools have been used to describe the natural history, present status, and future disposition of wild cat species. Insight into phylogenetic hierarchy, demographic contractions, geographic population substructure, behavioral ecology, and infectious diseases have revealed strategies for survival and adaptation of these fascinating predators. Conservation, stabilization, and management of the big cats are important areas that derive benefit from the genome resources expanded and applied to highly successful species, imperiled by an expanding human population.
DISEASE GENE DISCOVERY THROUGH INTEGRATIVE GENOMICS
Authors: Giallourakis Cosmas , Henson Charlotte , Reich Michael , Xie Xiaohui , Mootha Vamsi K.
Published: August 2005

▪ Abstract  The availability of complete genome sequences and the wealth of large-scale biological data sets now provide an unprecedented opportunity to elucidate the genetic basis of rare and common human diseases. Here we review some of the emerging genomics technologies and data resources that can be used to infer gene function to prioritize candidate genes. We then describe some computational strategies for integrating these large-scale data sets to provide more faithful descriptions of gene function, and how such approaches have recently been applied to discover genes underlying Mendelian disorders. Finally, we discuss future prospects and challenges for using integrative genomics to systematically discover not only single genes but also entire gene networks that underlie and modify human disease.
NOONAN SYNDROME AND RELATED DISORDERS: Genetics and Pathogenesis
Authors: Tartaglia Marco , Gelb Bruce D.
Published: August 2005

▪ Abstract  Noonan syndrome is a pleiomorphic autosomal dominant disorder with short stature, facial dysmorphia, webbed neck, and heart defects. In the past decade, progress has been made in elucidating the pathogenesis of this disorder using a positional cloning approach. Noonan syndrome is now known to be a genetically heterogeneous disorder with nearly one half of cases caused by gain-of-function mutations in PTPN11, the gene encoding the protein tyrosine phosphatase SHP-2. Similar germ line mutations cause two related genetic disorders, Noonan-like disorder with multiple giant cell lesion syndrome and LEOPARD syndrome, and somatic PTPN11 mutations can underlie certain pediatric hematopoietic malignancies, including juvenile myelomonocytic, acute lymphoblastic, and acute myelogenous leukemias. A mouse model of PTPN11-related Noonan syndrome was recently generated, providing a reagent for studying disease pathogenesis in greater depth as well as experimenting with novel therapeutic strategies.
SILENCING OF THE MAMMALIAN X CHROMOSOME
Authors: Chow Jennifer C. , Yen Ziny , Ziesche Sonia M. , Brown Carolyn J.
Published: August 2005

▪ Abstract  Mammalian X chromosome inactivation is one of the most striking examples of epigenetic gene regulation. Early in development one of the pair of ∼160-Mb X chromosomes is chosen to be silenced, and this silencing is then stably inherited through subsequent somatic cell divisions. Recent advances have revealed many of the chromatin changes that underlie this stable silencing of an entire chromosome. The key initiator of these changes is a functional RNA, XIST, which is transcribed from, and associates with, the inactive X chromosome, although the mechanism of association with the inactive X and recruitment of facultative heterochromatin remain to be elucidated. This review describes the unique evolutionary history and resulting genomic structure of the X chromosome as well as the current understanding of the factors and events involved in silencing an X chromosome in mammals.
Subtractive hybridization unravels a role for the ion cotransporter NKCC1 in the murine intestinal pacemaker
Authors: Wouters Mira , Laet Ann De , Donck Luc Ver , Delpire Eric , van Bogaert Pierre-Paul , Timmermans Jean-Pierre , de Kerchove d'Exaerde Alban , Smans Karine , Vanderwinden Jean-Marie
Published: August 2005

In the small intestine, interstitial cells of Cajal (ICC) surrounding the myenteric plexus generate the pacemaking slow waves that are essential for an efficient intestinal transit. The underlying molecular mechanisms of the slow wave are poorly known. Our aim was to identify ICC-specific genes and their function in the mouse jejunum. Suppression subtractive hybridization using two independent ICC-deficient mouse models identified 56 genes putatively downregulated in the muscularis propria compared with wild-type littermates. Differential expression was confirmed by real-time quantitative PCR for the tyrosine kinase receptor KIT, the established marker for ICC, and for the Na+-K+-2Cl−cotransporter (NKCC1). Immunoreactivity for NKCC1 was detected in myenteric ICC but not in the ICC population located at the deep muscular plexus. NKCC1 was also expressed in enteric neurons and mucosal crypts. Bumetanide, an NKCC1 inhibitor, reversibly affected the shape, amplitude, and frequency of the slow waves. Similar alterations were observed in NKCC1 knockout mice. These data support the hypothesis that NKCC1 expressed in myenteric ICC is involved in the mechanism of slow waves in the murine jejunum.
Inhibitory effect of experimental colitis on fluid absorption in rat jejunum: role of the enteric nervous system, VIP, and nitric oxide
Authors: Mourad Fadi H. , Barada Kassem A. , Bou Rached Nadine A. , Khoury Carmen I. , Saadé Nayef E. , Nassar Camille F.
Published: August 2005

Impairment of small intestinal absorption has been described in patients with ulcerative colitis and in animal models of experimental colitis. The pathophysiology of this dysfunction has not been elucidated. The aim of this study was to investigate the effect of chemical colitis on jejunal fluid absorption and determine the role of the enteric nervous system and some putative neurotransmitters. In a rat model of iodoacetamide-induced colitis, jejunal net fluid absorption was evaluated by the in vivo single-pass perfusion technique. The effects of 1) tetrodotoxin (TTX), 2) benzylalkonium chloride (BAC), 3) capsaicin, 4) vasoactive intestinal polypeptide (VIP) antagonism, 5) nitric oxide (NO) synthase (NOS) inhibition, and 6) 5-hydroxytryptamine type 3 and 4 (5-HT3and 5-HT4) receptor antagonism on the changes in fluid movement were investigated. A significant decrease in jejunal net fluid absorption was found 2 and 4 days after colitis induction: 26 (SD 14) and 28 (SD 19) μl·min−1·g dry intestinal wt−1, respectively [ P < 0.0002 compared with sham rats at 61 (SD 6.5) μl·min−1·g dry intestinal wt−1]. No histological changes were evident in jejunal sections. TTX and BAC reversed this decrease in fluid absorption: 54 (SD 13) and 44 (SD 14) μl·min−1·g dry intestinal wt−1( P = 0.0005 and P = 0.019, respectively, compared with colitis). Ablation of capsaicin-sensitive primary afferent fibers had a partial effect: 45 (SD 5) μl·min−1·g dry intestinal wt−1( P = 0.001 and P = 0.003 compared with colitis and sham, respectively). Constitutive and neuronal NOS inhibition and VIP antagonism returned jejunal net fluid absorption to normal values: 66 (SD 19), 61 (SD 5), and 56 (SD 14) μl·min−1·g dry intestinal wt−1, respectively. 5-HT3and 5-HT4receptor antagonism had no effect. Chemical colitis is associated with a significant decrease in jejunal net fluid absorption. This decrease is neurally mediated and involves VIP- and NO-related mechanisms.
NF-κB-mediated expression of iNOS promotes epithelial defense against infection byCryptosporidium parvumin neonatal piglets
Authors: Gookin Jody L. , Chiang Sophia , Allen Jessica , Armstrong Martha U. , Stauffer Stephen H. , Finnegan Colleen , Murtaugh Michael P.
Published: August 2005

Cryptosporidium sp. parasitizes intestinal epithelium, resulting in enterocyte loss, villous atrophy, and malabsorptive diarrhea. We have shown that mucosal expression of inducible nitric oxide (NO) synthase (iNOS) is increased in infected piglets and that inhibition of iNOS in vitro has no short-term effect on barrier function. NO exerts inhibitory effects on a variety of pathogens; nevertheless, the specific sites of iNOS expression, pathways of iNOS induction, and mechanism of NO action in cryptosporidiosis remain unclear. Using an in vivo model of Cryptosporidium parvum infection, we have examined the location, mechanism of induction, specificity, and consequence of iNOS expression in neonatal piglets. In acute C. parvum infection, iNOS expression predominated in the villous epithelium, was NF-κB dependent, and was not restricted to infected enterocytes. Ongoing treatment of infected piglets with a selective iNOS inhibitor resulted in significant increases in villous epithelial parasitism and oocyst excretion but was not detrimental to maintenance of mucosal barrier function. Intensified parasitism could not be attributed to attenuated fluid loss or changes in epithelial proliferation or replacement rate, inasmuch as iNOS inhibition did not alter severity of diarrhea, piglet hydration, Cl−secretion, or kinetics of bromodeoxyuridine-labeled enterocytes. These findings suggest that induction of iNOS represents a nonspecific response of the epithelium that mediates enterocyte defense against C. parvum infection. iNOS did not contribute to the pathogenic sequelae of C. parvum infection.
The activity of a single muscle sympathetic vasoconstrictor nerve unit is affected by physiological stress in humans
Authors: Murai Hisayoshi , Takata Shigeo , Maruyama Michiro , Nakano Manabu , Kobayashi Daisuke , Otowa Kan-ichi , Takamura Masayuki , Yuasa Toyoshi , Sakagami Satoru , Kaneko Shuichi
Published: August 2005

Recording of neural firing from single-unit muscle sympathetic nerve activity (MSNA) is a new strategy offering information about the frequency of pure sympathetic firing. However, it is uncertain whether and when single-unit MSNA would be more useful than multiunit MSNA for analysis of various physiological stresses in humans. In 15 healthy subjects, we measured single-unit and multiunit MSNA before and during handgrip exercise at 30% of maximum voluntary contraction for 3 min and during the Valsalva maneuver at 40 mmHg expiratory pressure for 15 s. Shapes of individual single-unit MSNA were proved to be consistent and suitable for further evaluation. Single-unit and multiunit MSNA exhibited similar responses during handgrip exercise. However, acceleration of neural firing determined from single-unit MSNA became steeper than multiunit MSNA during the Valsalva maneuver. During the Valsalva maneuver, unlike handgrip exercise, the distribution of multiunit burst between 0, 1, 2, 3, and 4 spikes was significantly shifted toward multiple spikes within a given burst ( P < 0.05). These results indicated that evaluation of single-unit MSNA could provide more detailed and accurate information concerning the role and responses of neuronal discharges induced by various physiological stresses in humans, especially amid intense sympathetic activity.
Initiation of remote microvascular preconditioning requires KATP channel activity
Authors: Mabanta Lauren , Valane Patrick , Borne Jonathan , Frame Mary D.
Published: August 2005

The purpose of this study was to investigate vascular preconditioning of individual microvascular networks. Prior work shows that exposure of downstream arterioles to specific agonists preconditions upstream arterioles so that they exhibit an altered local vasoactive response [remote microvascular preconditioning (RMP)]. We hypothesized that mitochondrial ATP-sensitive K+ (KATP) channels were involved in stimulation of RMP. Arteriolar diameter (∼15 μm) was observed ∼1,000 μm upstream of the remote exposure site in the cheek pouch of pentobarbital sodium-anesthetized (70 mg/kg) male hamsters ( n = 104); all agonists were applied via micropipette. RMP was initiated by application of pinacidil (Pin), diazoxide (DZ), sodium nitroprusside (SNP), or bradykinin (BK) to the downstream vessel. After 15 min, RMP was apparent at the upstream observation site from testing of local vasoactive responses to l-arginine. Pin, DZ, SNP, and BK each stimulated RMP. To evaluate a specific role for mitochondrial KATP channels in this response, 5-hydroxydecanoate was applied (via a 2nd pipette) during downstream stimulation with agonist. 5-Hydroxydecanoate blocked RMP initiated by Pin, DZ, or SNP, suggesting that mitochondrial KATP channels are involved before SNP signal transduction. To verify this, we applied Nω-nitro-l-arginine during DZ or SNP stimulation. RMP was blocked during SNP, but not during DZ, stimulation. Thus stimulation of the RMP response requires mitochondrial KATP channel activity after stimulation by nitric oxide donors.
Angiopoietin-1 decreases plasma leakage by reducing number and size of endothelial gaps in venules
Authors: Baffert Fabienne , Le Tom , Thurston Gavin , McDonald Donald M.
Published: August 2005

Angiopoietin-1 (Ang-1) is essential for remodeling of the primitive vascular plexus and recruitment of mural cells during embryonic development. In the adult vasculature, Ang-1 can reduce plasma leakage in inflammation, but the mechanism of this action is not well understood. In the present study, we determined the magnitude and cellular mechanism of the antileak effect of Ang-1 in the airways of mice. Intravenous injection of bradykinin resulted in leakage of fluorescent microspheres (diameter 25–1,000 nm) from tracheal venules. The leakage peaked in 3–4 min and resolved by 10 min. High-resolution confocal microscopy revealed the presence of focal gaps at intercellular junctions of leaky venules. Genetically engineered Ang-1*, delivered systemically by adenoviral transduction of the liver, reduced leakage of 500-nm microspheres after bradykinin by 69%. The reduction in leakage coincided with a decrease in number and size of endothelial gaps. The proportion of venular surface occupied by endothelial gaps decreased 61%. Microsphere leakage correlated strongly with gap number and size ( r2 = 0.89). Together the results suggest that Ang-1 reduces leakage from inflamed venules by restricting the number and size of gaps that form at endothelial cell junctions through effects on intracellular signaling, cytoskeleton, and junction-related molecules.
Translational regulation of ANG II type 1 receptors in proliferating vascular smooth muscle cells
Authors: Lee Sunghou , Ji Hong , Wu Zheng , Zheng Wei , Hassan Ali , Sandberg Kathryn
Published: August 2005

The current study examined angiotensin receptor (ATR) regulation in proliferating rat aortic vascular smooth muscle cells (VSMCs) in culture. Radioligand competition analysis coupled with RNase protection assays (RPAs) revealed that angiotensin type 1a receptor (AT1aR) densities (Bmax) increased by 30% between 5 and 7 days in culture [Bmax(fmol/mg protein): day 5, 379 ± 8.4 vs. day 7, 481 ± 12, n = 3, P < 0.05] under conditions in which no significant changes in AT1aR mRNA expression occurred [in RPA arbitrary units (AU): day 5, 0.23 ± 0.01 vs. day 7, 0.24 ± 0.04, n = 4] or in mRNA synthesis determined by nuclear run-on assays [AU: day 5, 0.35 ± 0.14 vs. day 7, 0.33 ± 0.11, n = 5]. In contrast, polysome distribution analysis indicated that AT1aR mRNA was more efficiently translated in day 7 cells compared with day 5 [% of AT1aR mRNA in fraction 2 out of total AT1R mRNA recovered from the sucrose gradient: day 5, 20.9 ± 9.9 vs. day 7, 56.8 ± 5.6, n = 3, P < 0.001]. Accompanying the polysome shift was 50% less RNA-protein complex (RPC) formation between VSMC cytosolic RNA binding proteins in day 7 cells compared with 5-day cultures and the 5′ leader sequence (5′LS) of the AT1aR [5′LS RPC (AU): day 5, 0.62 ± 0.15 vs. day 7, 0.23 ± 0.03; n = 4, P < 0.05] and also with exon 2 [Exon 2 RPC (AU): day 5, 35.0 ± 5.7 vs. day 7, 17.2 ± 3.6; n = 4, P < 0.05]. Taken together, these results suggest that AT1aR expression is regulated by translation during VSMC proliferation in part by RNA binding proteins that interact within exon 2 in the 5′LS of the AT1aR mRNA.
Influence of estradiol on micturition thresholds in the rat: involvement of the hypogastric nerve
Authors: Dmitrieva Natalia , Berkley Karen J.
Published: August 2005

Studies have shown that the severity of bladder hyperreflexia induced by acute bladder inflammation varies with the ovarian cycle. These results suggest that the hyperreflexia is modulated by ovarian hormones. Other studies have suggested that such modulation involves the bladder's sympathetic innervation. These hypotheses were tested by assessing the development of bladder hyperreflexia in urethane-anesthetized rats subjected to different hormonal manipulations with or without bilateral hypogastric neurectomy (HYPX). The groups included sham ovariectomy (sham OVX), ovariectomy (OVX), OVX with estradiol replacement (OVX+E), OVX+HYPX, and OVX+HYPX+E. Assessments were performed using repeated cystometrograms (CMGs) to measure micturition thresholds (MT) before and hourly for 3 h after intravesicular treatment with 50% turpentine oil (or olive oil in an OVX+E control group). In the uninflamed bladder, treatment with estradiol increased MTs in the OVX+E group compared with the OVX group. As expected, bladder inflammation induced bladder hyperreflexia in sham OVX rats (studied in estrus). This hyperreflexia was eliminated by OVX and restored by either estradiol replacement or HYPX. Combining estradiol replacement and HYPX (i.e., OVX+E+HYPX) did not increase the severity of bladder hyperreflexia compared with either manipulation alone. These results indicate that the bladder hyperreflexia that is induced by bladder inflammation requires the presence of estradiol and suggest that this hormonal modulation is exerted via the sympathetic control of the bladder, possibly via an increase of β-adrenergic inhibitory actions on the detrusor muscle. Similar mechanisms may contribute to bladder disorders in postmenopausal women.
Mandibular advancement decreases pressures in the tissues surrounding the upper airway in rabbits
Authors: Kairaitis Kristina , Stavrinou Rosie , Parikh Radha , Wheatley John R. , Amis Terence C.
Published: August 2005

The pharyngeal airway can be considered as an airway luminal shape formed by surrounding tissues, contained within a bony enclosure formed by the mandible, skull base, and cervical vertebrae. Mandibular advancement (MA), a therapy for obstructive sleep apnea, is thought to increase the size of this bony enclosure and to decrease the pressure in the upper airway extraluminal tissue space (ETP). We examined the effect of MA on upper airway airflow resistance (Rua) and ETP in a rabbit model. We studied 11 male, supine, anesthetized, spontaneously breathing New Zealand White rabbits in which ETP was measured via pressure transducer-tipped catheters inserted into the tissues surrounding the lateral (ETPlat) and anterior (ETPant) pharyngeal wall. Airflow, measured via surgically inserted pneumotachograph in series with the trachea, and tracheal pressure were recorded while graded MA at 75° and 100° to the horizontal was performed using an external traction device. Data were analyzed using a linear mixed-effects statistical model. We found that MA at 100° increased mouth opening from 4.7 ± 0.4 to 6.6 ± 0.4 (SE) mm ( n = 7; P < 0.004), whereas mouth opening did not change from baseline (4.0 ± 0.2 mm) with MA at 75°. MA at both 75° and 100° decreased mean ETPlat and ETPant by ∼0.1 cmH2O/mm MA ( n = 7–11; all P < 0.0005). However, the fall in Rua (measured at 20 ml/s) with MA was greater for MA at 75° (∼0.03 mmH2O·ml−1·s·mm−1) than at 100° (∼0.01 mmH2O·ml−1·s·mm−1; P < 0.02). From these findings, we conclude that MA decreases ETP and is more effective in reducing Rua without mouth opening.
Surgical Closure of the Left Atrial Appendage – A Beneficial Procedure?
Authors: Schneider Birke , Stöllberger Claudia , Sievers Hans H.
Published: August 2005

Background: Closure of the fibrillating left atrial appendage (LAA) has been recommended during valve surgery to decrease the risk of arterial embolism. However, patients undergoing surgical LAA closure have not systematically been reevaluated for complete LAA obliteration. Methods and Results: During a 12-month period, we studied 6 consecutive patients with paroxysmal (n = 3) or permanent (n = 3) atrial fibrillation who underwent surgical LAA closure at the time of valve surgery. Transesophageal echocardiography (TEE) performed 23–159 days (mean 51) postoperatively demonstrated complete LAA closure in only 1 patient. In 5 patients, incomplete LAA closure was found due to disruption of the closure line. The size of the residual LAA orifice ranged from 3 to 20 mm. There was a high flow velocity at the LAA orifice (0.33–2.2 m/s), whereas flow in the LAA body was low (<0.2 m/s). Spontaneous echocardiographic contrast (SEC) in the LAA had newly developed (n = 3) or was much more intense than preoperatively (n = 2). Despite therapeutic anticoagulation 2 patients showed a LAA thrombus which had not been present on the preoperative TEE, and 1 patient with SEC suffered a stroke 4 weeks after attempted LAA closure. Conclusion: Surgical LAA closure was incomplete in most patients, resulting in blood stagnation and an increased likelihood of clot formation. Incomplete surgical LAA closure, therefore, may promote rather than reduce the risk of stroke. Intraoperative TEE is mandatory to verify complete LAA obliteration.
Dobutamine Stress Echo Is Superior to Exercise Stress Testing in Achieving Target Heart Rate among Patients on Beta Blockers
Authors: Sabbath Adam , Pack Michael , Markiewicz Richard , John Jooby , Gaballa Mohamed , Goldman Steven , Thai Hoang
Published: August 2005

Published guidelines recommend continuing β-adrenergic receptor blockade in patients undergoing stress testing. We evaluated the role of pharmacological versus exercise stress testing in achieving target heart rate (THR) among patients on β-adrenergic blockade. We compared data from 140 patients who underwent dobutamine stress echo (DSE) and 143 patients who underwent exercise treadmill testing (ETT). In both groups, β-adrenergic blocker was continued at the time of stress testing. Overall, patients undergoing DSE achieved THR more frequently than ETT. With β-adrenergic blockade, DSE patients met THR more frequently than ETT patients (p < 0.001). Without β-adrenergic blockade, there was no difference between either modality in achieving THR. In both DSE and ETT patients, absence of β-adrenergic blockade increased the odds of achieving THR [odds ratio (OR): 2.46, p = 0.042 and OR: 7.44, p < 0.001, respectively]. Atropine use with DSE increased the odds of achieving THR (OR: 3.76, p = 0.006). In conclusion, pharmacological stress testing appears to be superior to exercise stress testing in achieving THR among patients on β-adrenergic blockade.
A History of Abuse in Community Subjects with Irritable Bowel Syndrome and Functional Dyspepsia: The Role of Other Psychosocial Variables
Authors: Koloski Natasha A. , Talley Nicholas J. , Boyce Philip M.
Published: August 2005

Background/Aims: Why abuse is associated with irritable bowel syndrome and functional dyspepsia remains unclear but other psychosocial factors may be important. We hypothesized that other psychosocial variables may confound the association. Methods: 207 subjects identified from a previous population survey who also met Rome I criteria for IBS (n = 156) or functional dyspepsia (n = 51) were included in the study. Controls (n = 100) did not report having any abdominal pain in a previous population survey. Sexual, physical, emotional/verbal abuse as a child (≤13 years) and adult (≧14 years) was assessed using validated self-report questions. Other psychological variables were assessed via validated self-report. Results: Adulthood abuse was significantly more common in IBS and/or functional dyspepsia (40%) compared with healthy controls (25%). Abuse was not an independent predictor for IBS or functional dyspepsia when psychological and buffering factors were controlled for in the analyses. Having a diagnosis of depression and using a self-controlling coping style were significantly associated with having a history of abuse. Conclusions: Abuse occurring as an adult was significantly associated with IBS and/or functional dyspepsia, but it was not an important factor when psychosocial factors were controlled for in these disorders.
Usefulness of Progressive Inhomogeneity of Myocardial Perfusion and Chronotropic Incompetence in Detecting Cardiac Allograft Vasculopathy: Evaluation with Dobutamine Thallium-201 Myocardial SPECT
Authors: Wu Yen-Wen , Yen Ruoh-Fang , Lee Chii-Ming , Ho Yi-Lwun , Wang Shoei-Shen , Hsu Ron-Bin , Chou Nai-Kuan , Huang Por-Jau
Published: August 2005

Background: The aim of the study was to investigate the value of longitudinal follow-up of dobutamine thallium-201 single photon emission tomography (201Tl SPECT) in the development of significant cardiac allograft vasculopathy (CAV) after orthotopic heart transplantation. Methods: We studied 38 cardiac recipients (mean age 57 ± 12 years) who underwent at least two follow-up dobutamine 201Tl SPECT since January 1998. All patients had normal coronary angiography and normal left ventricular function initially. Results: After 2.3 ± 1.8 years, 12 patients developed significant CAV and there were 4 cardiac deaths (1 died suddenly). Of the 99 scans retrospectively analyzed, patients with significant CAV had elevated values of inhomogeneity score, lung/heart ratio (LHR) at stress and lower left ventricular ejection fraction (all p < 0.05). The higher values of inhomogeneity were significantly correlated with higher stress LHR (r = 0.301, p = 0.021), and lower ejection fraction (r = –0.379, p < 0.001). Progressive inhomogeneity was noted in all heart recipients, and more rapid, although statistically insignificant, in patients who developed significant CAV. Ten patients had inadequate chronotropic response to dobutamine infusion up to 40 µg/kg/min in the follow-up studies. The late onset of chronotropic incompetence was an independent predictor of CAV development (p = 0.03). Conclusions: Progressive inhomogeneity of myocardial perfusion, higher lung uptake at stress and chronotropic incompetence assessed by dobutamine 201Tl myocardial SPECT provide incremental diagnostic value in detecting significant CAV.
Identification of Clinical Prognostic Factors in Patients with Unknown Primary Tumors Treated with a Platinum-Based Combination
Authors: Piga Andrea , Gesuita Rosaria , Catalano Vincenzo , Nortilli Rolando , Cetto Gianluigi , Cardillo Francesca , Giorgi Francesca , Riva Nada , Porfiri Emilio , Montironi Rodolfo , Carle Flavia , Cellerino Riccardo
Published: August 2005

Objective: The aim of this study was to evaluate patient and tumor characteristics in 102 patients with unknown primary tumors (UPT) prospectively treated with a combination of carboplatin, doxorubicin, and etoposide, to identify clinical variables predictive of response and survival. Patients and Methods: The association between clinical characteristics and outcome was evaluated by univariate and multivariate analysis: χ2 test and logistic regression analysis were used to study variables predictive of response, and survival analysis, comparison of survival curves and Cox multiple regression analysis to study variables predictive of survival. Results: We obtained 26.5% objective responses (95% confidence interval: 18.2–36.1%) and a median survival of 9 months (95% confidence interval: 7–11 months). Several variables were associated with response to treatment and survival at univariate analysis. At multivariate analysis the number of tumor sites, bone/visceral involvement and epithelial tumor markers were significantly predictive of response; presence of pain, serum alkaline phosphatase, carboplatin AUC and response to treatment were significantly associated with survival. Conclusions: The identification of variables that can predict prognosis and response to treatment in patients with UPT may be useful to offer aggressive treatment to sensitive subsets of patients and provide therapeutic alternatives to those with a low probability of benefiting from standard treatment. In our patients the use of carboplatin AUC higher than 6 and response to treatment were the most important factors associated with prognosis, together with presence of pain and serum alkaline phosphatase. However, larger series and identification of new disease markers are necessary to better define predictive and prognostic variables in UPT patients.
p53 Gene Status and Response to Topotecan-Containing Chemotherapy in Advanced Ovarian Carcinoma
Authors: Oggionni M. , Pilotti S. , Suardi S. , Ditto A. , Luoni C. , Mariani L. , Scambia G. , Fanfani F. , Zunino F.
Published: August 2005

Objective: Since the p53 gene has been identified as a determinant of response to chemotherapy in ovarian carcinoma in previous studies, we investigated the significance of the p53 status in response to topotecan as second-line therapy. Methods: Twenty-eight patients with advanced ovarian carcinoma, pretreated with standard platinum/paclitaxel chemotherapy, received topotecan as single-agent second-line therapy. Tumors were investigated by molecular analysis for p53 mutations in tumor samples obtained at primary surgery (i.e. before first-line therapy). Results: Wild-type p53 tumors responsive to first-line therapy maintained substantial responsiveness to topotecan. In contrast, p53 mutation was associated with a low responsiveness to second-line therapy. Conclusions: The better outcome in relapsed patients with wild-type p53 suggests that the presence of a functional wild-type p53 confers stability of the drug-sensitive phenotype. This outcome is consistent with the clinical observation that the efficacy of topotecan in the treatment of relapsed ovarian carcinoma patients is dependent on platinum sensitivity, because platinum-sensitive tumors are expected to carry wild-type p53. Although untreated mutant p53 tumors may be responsive to first-line paclitaxel-containing therapy, it is likely that loss of p53 leads to genomic instability resulting in rapid progression to drug resistance.