bluuebunny/crossref_metadata_2025 huggingface dataset:
TWIST MOVES AND VASSILIEV INVARIANTS
Authors: JEONG MYEONG-JU , KIM EUN-JIN , PARK CHAN-YOUNG
Published: September 2004

The transforms of two oriented parallel strands to a k-half twist of two strands are called tk-move and [Formula: see text]-move respectively depending on the orientations of the two strands. In this paper we give criterions to detect whether a knot K can be transformed to a knot K' by t2k-moves and [Formula: see text]-moves respectively and if so, we give some results on how many moves are needed in these transformations respectively, by using some Vassiliev invariants. Moreover we give a relation between the Δ-move and the t2k-move by considering the coefficient of z2 in the Conway polynomial of a knot, which is a Vassiliev invariant of degree 2.
GRAPHS WITH DISJOINT LINKS IN EVERY SPATIAL EMBEDDING
Authors: CHAN STEPHAN , DOCHTERMANN ANTON , FOISY JOEL , HESPEN JENNIFER , KUNZ EMAN , LALONDE TRENT , LONEY QUINCY , SHARROW KATHERINE , THOMAS NATHAN
Published: September 2004

We exhibit a graph, G12, that in every spatial embedding has a pair of non-splittable 2 component links sharing no vertices or edges. Surprisingly, G12does not contain two disjoint copies of graphs known to have non-splittable links in every embedding. We exhibit other graphs with this property that cannot be obtained from G12by a finite sequence of Δ-Y and/or Y-Δ exchanges. We prove that G12is minor minimal in the sense that every minor of it has a spatial embedding that does not contain a pair of non-splittable 2 component links sharing no vertices or edges.
EDGE-HOMOTOPY CLASSIFICATION OF SPATIAL COMPLETE GRAPHS ON FOUR VERTICES
Authors: NIKKUNI RYO
Published: September 2004

Two spatial embeddings of a graph are said to be edge-homotopic if they are transformed into each other by self-crossing changes and ambient isotopies. We show that two spatial embeddings of the complete graph on four vertices are edge-homotopic if and only if they have the same α-invariant.
Cn-MOVES, BRAID COMMUTATORS AND VASSILIEV KNOT INVARIANTS
Authors: PLACHTA L.
Published: September 2004

We show that for each positive integer n>1 a simple Cn-move on knots, introduced by Habiro, is equivalent to the (non-oriented) insertion in a knot via a tangle map the geometric pure braid n-commutator of the form pn=[pn-1,n,[pn-2,n-1,…, [p1,2,p0,1]…]∈Pn+1, where Pn+1 is the subgroup of pure braids of the braid group Bn+1 on n+1 strands. We relate the insertions of the pure braid commutators in knots to the operations of inverting and mirroring the knots.
Elevated flagellin-specific immunoglobulins in Crohn's disease
Authors: Sitaraman Shanthi V. , Klapproth Jan-Michael , Moore Daniel A. , Landers Carol , Targan Stephan , Williams Ifor R. , Gewirtz Andrew T.
Published: September 2004

Crohn's disease (CD) is driven by seemingly aberrant immune responses directed toward commensal enteric microflora. However, the specific antigens targeted by this immune response remain largely undefined. Herein, we demonstrate that common enteric flagellins are one such target of the CD-associated immune response. Thus flagellin may not only drive acute inflammation via activation of Toll-like receptor 5-mediated gene expression but may also serve as a target of the adaptive immune response that maintains the chronic inflammation characteristic of CD.
Phase-averaged characterization of respiratory sinus arrhythmia pattern
Authors: Gilad O. , Swenne C. A. , Davrath L. R. , Akselrod S.
Published: September 2004

A method for the accurate time-domain characterization of respiratory sinus arrhythmia (RSA) pattern is presented and applied to two groups of healthy subjects to lay the baseline of RSA patterns and to underlay their features: response to standing, stability in successive recordings, and individuality of the shape of RSA pattern. RSA pattern is evaluated by selective averaging of heart rate (HR) changes from multiple respiratory cycles over the respiratory phase and represents the complete modulating function of HR by respiration. The RSA pattern is evaluated with free respiration and even in cases of severe arrhythmia. Estimation error is 6–8% in magnitude, phase resolution is 0.2 rad, and sensitivity margin for respiratory-related HR variability (HRV) components is 1%. RSA magnitude, phase lag, and expiration-to-inspiration time ratio are derived in addition to the entire pattern. In a group of 10 healthy young adults, a phase lag difference of 11.4 ± 8.5% (mean ± SD, P < 0.004) was observed between supine and standing postures, possibly ascribed to breathing mechanics. A second group of 15 healthy young adults at supine rest showed stability of the RSA pattern in successive recordings (several weeks apart) as well as individuality among subjects. This may suggest a nonscalar individual long-term index for cardiorespiratory coupling. The method is complementary to the existing statistical and spectral methods. It allows the complete characterization of the primary RSA components and may provide new insight into the effects of vagal activity and changes in clinical conditions.
Role of cytosolic vs. mitochondrial Ca2+accumulation in burn injury-related myocardial inflammation and function
Authors: Maass David L. , White Jean , Sanders Billy , Horton Jureta W.
Published: September 2004

This study was designed to examine the role of mitochondrial Ca2+homeostasis in burn-related myocardial inflammation. We hypothesized that mitochondrial Ca2+is a primary modulator of cardiomyocyte TNF-α, IL-1β, and IL-6 responses to injury and infection. Ventricular myocytes were prepared by Langendorff perfusion of hearts from adult rats subjected to sham burn or burn injury over 40% of total body surface area to produce enzymatic (collagenase) digestion. Isolated cardiomyocytes were suspended in MEM, cell number was determined, and aliquots of myocytes from each experimental group were loaded with fura 2-AM (2 μg/ml) for 1) 45 min at room temperature to measure total cellular Ca2+, 2) 45 min at 30°C followed by incubation at 37°C for 2 h to eliminate cytosolic fluorescence, and 3) 20 min at 37°C in MnCl2(200 μM)-containing buffer to quench cytosolic fura 2-AM signal. In vitro studies included preparation of myocytes from control hearts and challenge of myocytes with LPS or burn serum (BS), which have been shown to increase cytosolic Ca2+. Additional aliquots of myocytes were challenged with LPS or BS with or without a selective inhibitor of mitochondrial Ca2+, ruthenium red (RR). All cells were examined on a stage-inverted microscope that was interfaced with the InCyt Im2 fluorescence imaging system. Heat treatment or MnCl2challenge eliminated myocyte cytosolic fluorescence, whereas cells maintained at room temperature retained 95% of their initial fluorescence. Compared with Ca2+levels measured in sham myocytes, burn trauma increased cytosolic Ca2+from 90 ± 3 to 293 ± 6 nM ( P < 0.05) and mitochondrial Ca2+from 24 ± 1 to 75 ± 2 nM ( P < 0.05). LPS (25 μg/5 × 104cells) or BS (10% by volume) challenge for 18 h increased cardiomyocyte cytosolic and mitochondrial Ca2+and promoted myocyte secretion of TNF-α, IL-1β, and IL-6. RR pretreatment decreased LPS- and BS-related rise in mitochondrial Ca2+and cytokine secretion but had no effect on cytosolic Ca2+. BS challenge in perfused control hearts impaired myocardial contraction/relaxation, and RR pretreatment of hearts prevented BS-related myocardial contractile dysfunction. Our data suggest that a rise in mitochondrial Ca2+is one modulator of myocardial inflammation and dysfunction in injury states such as sepsis and burn trauma.
Mapping of the functional microcirculation in vital organs using contrast-enhanced in vivo video microscopy
Authors: Varghese Hemanth J. , MacKenzie Lisa T. , Groom Alan C. , Ellis Christopher G. , Chambers Ann F. , MacDonald Ian C.
Published: September 2004

A functional microcirculation is vital to the survival of mammalian tissues. In vivo video microscopy is often used in animal models to assess microvascular function, providing real-time observation of blood flow in normal and diseased tissues. To extend the capabilities of in vivo video microscopy, we have developed a contrast-enhanced system with postprocessing video analysis tools that permit quantitative assessment of microvascular geometry and function in vital organs and tissues. FITC-labeled dextran (250 kDa) was injected intravenously into anesthetized mice to provide intravascular fluorescence contrast with darker red blood cell (RBC) motion. Digitized video images of microcirculation in a variety of internal organs (e.g., lung, liver, ovary, and kidney) were processed using computer-based motion correction to remove background respiratory and cardiac movement. Stabilized videos were analyzed to generate a series of functional images revealing microhemodynamic parameters, such as plasma perfusion, RBC perfusion, and RBC supply rate. Fluorescence contrast revealed characteristic microvascular arrangements within different organs, and images generated from video sequences of liver metastases showed a marked reduction in the proportion of tumor vessels that were functional. Analysis of processed video sequences showed large reductions in vessel volume, length, and branch-point density, with a near doubling in vessel segment length. This study demonstrates that postprocessing of fluorescence contrast video sequences of the microcirculation can provide quantitative images useful for studies in a wide range of model systems.
Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy
Authors: Taylor Paul D. , McConnell Josie , Khan Imran Y. , Holemans Kathleen , Lawrence Kevin M. , Asare-Anane Henry , Persaud Shanta J. , Jones Peter M. , Petrie Linda , Hanson Mark A. , Poston Lucilla
Published: September 2004

We previously reported that prenatal and suckling exposure to a maternal diet rich in animal fat leads to cardiovascular dysfunction in young adult rat offspring with subsequent development of dyslipidemia and hyperglycemia. We have further investigated glucose homeostasis in adult female offspring by euglycemic-hyperinsulinemic clamp and by dynamic assessment of glucose-stimulated insulin secretion in isolated, perifused pancreatic islet cells. Additionally, given the link between reduced mitochondrial DNA (mtDNA) content and the development of type 2 diabetes mellitus, we have measured mtDNA in organs from young adult animals. Sprague-Dawley rats were fed a diet rich in animal fat or normal chow throughout pregnancy and weaning. Infusion of insulin (5 mU·kg−1·min−1) resulted in a higher steady-state plasma insulin concentration in 1-year-old offspring of fat-fed dams (OHF, n = 4) vs. offspring of control dams (OC, n = 4, P < 0.01). Glucose-stimulated insulin secretion in isolated islets from 9-mo-old OHF was significantly reduced compared with OC ( n = 4, P < 0.05). Transmission electron micrography showed altered insulin secretory granule morphology in OHF pancreatic β-cells. Kidney mtDNA was reduced in 3-mo-old OHF [16S-to-18S gene ratio: OC ( n = 10) 1.05 ± 0.19 vs. OHF ( n = 10) 0.66 ± 0.06, P < 0.05]. At 6 mo, gene chip microarray of OHF aorta showed reduced expression of the mitochondrial genome. Prenatal and suckling exposure to a diet rich in animal fat leads to whole body insulin resistance and pancreatic β-cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression.
Nuclear localization of angiotensinogen in astrocytes
Authors: Sherrod Mikhiela , Liu Xuebo , Zhang Xiaoji , Sigmund Curt D.
Published: September 2004

In the brain, angiotensinogen (AGT) is primarily expressed in astrocytes; brain ANG II derived from locally produced AGT has been shown to influence blood pressure. To better understand the molecular basis of AGT expression in the brain, we identified a human astrocytoma cell line, CCF-STTG1, that expresses endogenous AGT mRNA and produces AGT protein. Studies examining CCF-STTG1 cell AGT after N- and O-glycosidase suggest that AGT may not be posttranslationally modified by glycosylation in these cells as it is in plasma. Small amounts of AGT (5% of HepG2) were detected in the culture medium, suggesting a low rate of AGT secretion. Immunocytochemical examination of AGT in CCF-STTG1 cells revealed mainly nuclear localization. Although this has not been previously reported, it is consistent with nuclear localization of other serpin family members. To examine this further, we generated a fusion protein consisting of green fluorescent protein (GFP) and human AGT and examined subcellular localization by confocal microscopy after confirming expression of the fusion protein by Western blot. In CCF-STTG1 cells, a control GFP construct lacking AGT was mainly localized in the cytoplasm, whereas the GFP-AGT fusion protein was primarily localized in the nucleus. To map the location of a potential nuclear localization signal, overlapping 500-bp fragments of human AGT cDNA were fused in frame downstream of GFP. Although four of the fusion proteins exhibited either perinuclear or cytoplasmic localization, one fusion protein encoding the COOH terminus of AGT was localized in the nucleus. Importantly, nuclear localization of human AGT was confirmed in primary cultures of glial cells isolated from transgenic mice expressing the human AGT under the control of its own endogenous promoter. Our results suggest that AGT may have a novel intracellular role in the brain apart from its predicted endocrine function.
Increase in interstitial interleukin-6 of human skeletal muscle with repetitive low-force exercise
Authors: Rosendal Lars , Søgaard Karen , Kjær Michael , Sjøgaard Gisela , Langberg Henning , Kristiansen Jesper
Published: September 2004

Interleukin (IL)-6, which is released from muscle tissue during intense exercise, possesses important metabolic and probably anti-inflammatory properties. To evaluate the IL-6 response to low-intensity exercise, we conducted two studies: 1) a control study with insertion of microdialysis catheters in muscle and determination of interstitial muscle IL-6 response over 2 h of rest and 2) an exercise study to investigate the IL-6 response to 20 min of repetitive low-force exercise. In both studies, a microdialysis catheter (cutoff: 3,000 kDa) was inserted into the upper trapezius muscle of six male subjects, and the catheters were perfused with Ringer-acetate at 5 μl/min. Venous plasma samples were taken in the exercise study. The insertion of microdialysis catheters into muscle resulted in an increase in IL-6 from 8 ± 0 to 359 ± 171 and 484 ± 202 pg/ml after 65 and 110 min, respectively ( P < 0.001). Similarly, in the exercise study, IL-6 increased to 289 ± 128 pg/ml after a 55-min rest ( P < 0.001). During the subsequent repetitive low-force exercise, muscle IL-6 further increased to 1,246 ± 461 pg/ml and reached 2,132 ± 477 pg/ml after a 30-min recovery (all P < 0.001). In contrast to this, plasma IL-6 did not significantly change in response to exercise. We conclude that upper extremity, low-intensity exercise results in a substantial increase in IL-6 in the interstitium of the stabilizing trapezius muscle, whereas no change is seen for plasma IL-6.
Changes in cardiovascular function during the sleep onset period in young adults
Authors: Carrington M. J. , Barbieri R. , Colrain I. M. , Crowley K. E. , Kim Y. , Trinder J.
Published: September 2004

Blood pressure (BP) and heart rate (HR) are influenced by the sleep-wake cycle, with relatively abrupt falls occurring in association with sleep onset (SO). However, the pattern and rate of fall in BP and HR during SO and the processes that contribute to the fall in these variables have not been fully identified. Continuous BP and HR recordings were collected beginning 1 h before lights out (LO) until the end of the first non-rapid eye movement sleep period in 21 young, healthy participants maintained in a supine position. Five consecutive phases were defined: 1) the 30 min of wakefulness before LO; 2) LO to stage 1 sleep; 3) stage 1 to stage 2 sleep; 4) stage 2 sleep to the last microarousal before stable sleep; and 5) the first 30 min of undisturbed stable sleep. The data were analyzed on a beat-by-beat basis and reported as 2-min periods for phases 1 and 5 and 10% epochs for phases 2, 3, and 4 (as participants had variable time periods in these phases). The level of baroreflex (BR) activity was assessed by the sequence technique and an autoregressive multivariate model. Furthermore, during phases 3 and 4, the BP and HR responses to arousal from sleep were determined. There were substantial falls in BP and HR after LO before the initial onset of θ-activity (phase 3) and again after the onset of stable sleep after the cessation of spontaneous arousals. During phases 3 and 4 when there were repeated arousals from sleep, the fall in both variables was retarded. Furthermore, both the rate and magnitude of the fall in BP were negatively associated with the number of arousals during phases 3 and 4. There was a small increase in the sensitivity of the BR and indirect evidence of a substantial fall in its set point.
Brain Activity During Predictable and Unpredictable Weight Changes When Lifting Objects
Authors: Schmitz Christina , Jenmalm Per , Ehrsson H. Henrik , Forssberg Hans
Published: September 2004

When humans repetitively lift the same object, the fingertip forces are targeted to the weight of the object. The anticipatory programming of the forces depends on sensorimotor memory representations that provide information on the object weight. In the present study, we investigate the neural substrates of these sensorimotor memory systems by recording the neural activity during predictable or unpredictable changes in the weight of an object in a lifting task. An unpredictable change in weight leads to erroneous programming of the fingertip forces. This triggers corrective mechanisms and an update of the sensorimotor memories. In the present fMRI study, healthy right-handed subjects repetitively lifted an object between right index finger and thumb. In the constant condition, which served as a control, the weight of the object remained constant (either 230 or 830 g). The weight alternated between 230 and 830 g during the regular condition and was irregularly changed between the two weights during the irregular condition. When we contrasted regular minus constant and irregular minus constant, we found activations in the right inferior frontal gyrus pars opercularis (area 44), the left parietal operculum and the right supramarginal gyrus. Furthermore, irregular was associated with stronger activation in the right inferior frontal cortex as compared with regular. Taken together, these results suggest that the updating of sensorimotor memory representations and the corrective reactions that occur when we manipulate different objects correspond to changes in synaptic activity in these fronto-parietal circuits.
Stochastic Properties of Synaptic Transmission Affect the Shape of Spike Time–Dependent Plasticity Curves
Authors: Shouval Harel Z. , Kalantzis Georgios
Published: September 2004

Theoretical studies have shown that calcium influx through N-methyl-d-aspartate (NMDA) receptors is a sufficient signal to account for various induction protocols of bidirectional synaptic plasticity, including spike time–dependent plasticity (STDP). The STDP curves obtained by these different models exhibits a form of spike time–dependent long-term depression that occurs when a presynaptic spike precedes the postsynaptic spike (pre-post LTD). We have previously proposed that this novel form of LTD can serve as an experimental test for the validity of these models. These calcium based theoretical models assumed deterministic calcium dynamics that reflect average properties of synaptic calcium currents. In this paper, we show that taking into account the stochastic properties of synaptic transmission significantly alters the form of STDP curves and may significantly reduce the magnitude of pre-post LTD.
Neuromodulation by a Cytokine: Interferon-β Differentially Augments Neocortical Neuronal Activity and Excitability
Authors: Hadjilambreva Gergana , Mix Eilhard , Rolfs Arndt , Müller Jana , Strauss Ulf
Published: September 2004

The immunomodulatory cytokine interferon-β (IFN-β) is used in the treatment of autoimmune diseases such as multiple sclerosis. However, the effect of IFN-β on neuronal functions is currently unknown. Intracellular recordings were conducted on somatosensory neurons of neocortical layers 2/3 and 5 exposed to IFN-β. The excitability of neurons was increased by IFN-β (10–10,000 U/ml) in two kinetically distinct, putatively independent manners. First IFN-β reversibly influenced the subthreshold membrane response by raising the membrane resistance RM 2.5-fold and the membrane time constant τ 1.7-fold dose-dependently. The effect required permanent exposure to IFN-β and was reduced in magnitude if the extracellular K+ was lowered. However, the membrane response to IFN-β in the subthreshold range was prevented by ZD7288 (a specific blocker of Ih) but not by Ni2+, carbachol, or bicuculline, pointing to a dependence on an intact Ih. Second, IFN-β enhanced the rate of action potential firing. This effect was observed to develop for >1 h when the cell was exposed to IFN-β for 5 min or >5 min and showed no reversibility (≤210 min). Current-discharge ( F-I) curves revealed a shift (prevented by bicuculline) as well as an increase in slope (prevented by carbachol and Ni2+). Layer specificity was not observed with any of the described effects. In conclusion, IFN-β influences the neuronal excitability in neocortical pyramidal neurons in vitro, especially under conditions of slightly increased extracellular K+. Our blocker experiments indicate that changes in various ionic conductances with different voltage dependencies cause different IFN-β influences on sub- and suprathreshold behavior, suggesting a more general intracellular process induced by IFN-β.
Differentiation of Hepatic Tumors by Color Doppler Imaging: Role of the Maximum Velocity and the Pulsatility Index of the Intratumoral Blood Flow Signal
Authors: Kudo Masatoshi , Tochio Hitoshi , Zhou Pei
Published: September 2004

Doppler spectral analysis using color Doppler ultrasonography (US) was performed in a total of 133 patients with 135 hepatic tumors, including 88 hepatocellular carcinomas (HCCs), 30 metastatic hepatic cancers, 15 hemangiomas and 2 focal nodular hyperplasias (FNHs). Mean ± SD of maximum velocity (Vmax) in hemangiomas (15.0 ± 16.0 cm/s) was significantly lower than in HCCs (34.9 ± 26.7 cm/s) and in metastases (37.9 ± 17.4 cm/s). Mean ± SD of the pulsatility index (PI) in hemangiomas (0.45 ± 0.41) was significantly lower than in HCCs (1.52 ± 0.71) and metastases (1.44 ± 0.43). Mean ± SD of Vmax and PI in FNH was 20.0 ± 11.3 cm/s and 0.90 ± 0.35, respectively. HCC showed a wide spectrum in terms of Vmax and PI; however, 18% of the HCC nodules had relatively high PI (>2.0). Specificity of Vmax more than >60 cm/s and PI more than 2.0 for the diagnosis of HCC were 92 and 94%, respectively. On the other hand, 87% of hemangiomas showed relatively lower Vmax (<30 cm/s) and 87% of hemangiomas showed relatively low PI (<1.0 cm/s). Specificity of Vmax less than 30 cm/s and PI less than 1.0 for the diagnosis of hemangioma were 47 and 78%, respectively. When taking account of both parameters, Vmax and PI, diagnostic efficacy for hemangioma and HCC was greatly improved (sensitivity, specificity, accuracy, positive predictive value and negative predictive value of 80, 86, 85, 41 and 97%, respectively, in hemangioma, and 38, 85, 54, 83 and 58%, respectively, in HCC) as compared with the results with Vmax or PI alone. In conclusion, in addition to the information obtained by Vmax, simultaneous measurement of PI adds valuable information useful in the noninvasive differentiation among hepatic tumors by Doppler spectral analysis at color Doppler US.
Imaging of Early Hepatocellular Carcinoma and Adenomatous Hyperplasia (Dysplastic Nodules) with Dynamic CT and a Combination of CT and Angiography: Experience with Resected Liver Specimens
Authors: Takayasu Kenichi , Muramatsu Yukio , Mizuguchi Yasunori , Moriyama Noriyuki , Ojima Hidenori
Published: September 2004

Early hepatocellular carcinoma (HCC) as defined by the Liver Cancer Study Group of Japan would correspond to high-grade dysplastic nodules with small foci of HCC in the majority of cases, using the classification system proposed by the International Working Party. A large number of early HCCs were revealed to be hypo- or isovascular in the arterial phase of dynamic CT. Only 5% of the lesions evaluated were hypervascular, which contrasted with advanced small HCCs, of which 94% were hypervascular. CT arterial portography (CTAP) showed hypoattenuation in 66% of early HCCs and isoattenuation in 34%. CT hepatic arteriography (CTHA) demonstrated hypoattenuation in 55% of early HCC, isoattenuation in 30% and hyperattenuation in 15%. These findings suggest that most early HCCs receive equal or reduced blood supply from both portal and arterial flow compared with surrounding noncancerous parenchyma. In contrast, 97% of small HCCs are hypoattenuated on CTAP, and 93% are hyperattenuated on CTHA. For nodule-in-nodule type HCC (advanced HCC within early HCC), the CT attenuation of the central and peripheral portions revealed areas of isolated advanced HCC and isolated early HCC, respectively. Adenomatous hyperplasia (low-grade dysplastic nodules) was not readily differentiated using the various imaging modalities, mainly due to the smaller size of these lesions compared to early HCC and/or a portal and arterial blood supply very similar to that of the surrounding parenchyma. Hemodynamic changes in cirrhotic liver were similarly evaluated using CTAP and CTHA, and the treatment of early HCC is briefly discussed herein.
Nodular Lesions Associated with Abnormal Liver Circulation
Authors: Kondo Fukuo , Koshima Youhei , Ebara Masaaki
Published: September 2004

In order to present new findings of imaging studies and pathology, we describe nontypical lesions rather than well-known typical lesions such as focal nodular hyperplasia (FNH), hepatocellular adenoma, nodular regenerative hyperplasia (NRH) and large regenerative nodules in liver with idiopathic portal hypertension (IPH). Nontypical lesions are not definitively diagnosed as any of the above typical well-known lesions. These lesions are not rare, and are clinically important since they must be differentiated from hepatocellular carcinoma. These lesions can be formed by hyperperfusion of either the artery or the portal vein. They are found in either the hilar area or peripheral area. The extranodular liver (background liver) shows various histological findings, being nearly normal in some cases but showing a clearly abnormal vasculature in others. The lesions, therefore, present various patterns in imaging. Pathological examination also shows variation in the size of the lumen of portal veins and arteries. Abnormal arrangement of arteries and portal veins are also demonstrated, while parenchymal nodular liver tissues are uniformly nonneoplastic benign hyperplastic tissues. These nontypical lesions and well-known typical lesions (FNH, NRH and IPH) are explained by a single etiological mechanism of anomaly of the portal tract. They can be collectively called anomalous portal tract syndrome. For their definitive diagnosis, the structure and hemodynamics of the nodules need to be clarified by images. Biopsy is also necessary to confirm that the lesions consist of benign hepatic tissues. Subsequently, these findings should be evaluated comprehensively.
Valosin-Containing Protein (p97) and Ki-67 Expression Is a Useful Marker in Detecting Malignant Behavior of Pancreatic Endocrine Neoplasms
Authors: Yamamoto Shinji , Tomita Yasuhiko , Nakamori Shoji , Hoshida Yoshihiko , Iizuka Norishige , Okami Jiro , Nagano Hiroaki , Dono Keizo , Umeshita Koji , Sakon Masato , Ishikawa Osamu , Ohigashi Hiroaki , Aozasa Katsuyuki , Monden Morito
Published: September 2004

Objective: To determine the prognostic value of valosin-containing protein (VCP) expression and the Ki-67 labeling index (LI) in pancreatic endocrine neoplasms (PENs), the present analysis was employed. Methods: The Ki-67 LI and VCP expression at the mRNA and protein level were evaluated in 32 patients (12 male and 20 female) with PENs aged from 22 to 73 years (median 49 years). VCP staining intensity in tumor cells was categorized as weaker (level 1) or equal to stronger (level 2) compared to nontumorous islet cells. Ki-67 LI was divided into two categories: level 1, Ki-67 LI <5%, and level 2, ≧5%. Results: Five cases (15.6%) showed level 1 and 25 (84.4%) level 2 VCP expression by immunohistochemistry. A significant association was observed between VCP expression and the malignant behavior of PENs (p < 0.01). All level 1 VCP tumors were benign PENs. Quantitative reverse transcription polymerase chain reaction analysis showed higher VCP mRNA expression in malignant PENs (n = 5) than benign cases (n = 5) (p < 0.05). For Ki-67 LI, 28 cases (87.5%) showed level 1 and 4 (12.5%) level 2 expression. All patients with level 2 Ki-67 LI had metastasis. Conclusion: VCP expression analysis and Ki-67 LI are useful prognosticators for PENs.
Effect of Plasmid Copy Number and lac Operator Sequence on Antibiotic-Free Plasmid Selection by Operator-Repressor Titration in Escherichia coli
Authors: Cranenburgh Rocky M. , Lewis Kathryn S. , Hanak Julian A.J.
Published: September 2004

The Escherichia coli strain DH1lacdapD enables plasmid selection and maintenance that is free from antibiotics and selectable marker genes. This is achieved by using only the lac operator sequence as a selectable element. This strain is currently used to generate high copy number plasmids with no antibiotic resistance genes for use as DNA vaccines and for expression of recombinant proteins. Until now these have been limited to pUC-based plasmids containing a high copy number pMB1-derived origin of replication, and the principle lacO1 and auxiliary lacO3 operators. In this study we have shown that this system can also be used to select and maintain pBR322-based plasmids with the lower copy number pMB1 origin of replication, and that lacO1 alone or a palindromic version of lacO1 can provide a sufficient level of repressor titration for plasmid selection. This is advantageous for recombinant protein production, where low copy number plasmids are often used and plasmid maintenance is important. The degree of repressor titration due to these plasmids was measured using the natural lactose operon in E. coli DH1 as a model.
The Complete Genome Sequence of  Bacillus licheniformis DSM13, an Organism with Great Industrial Potential
Authors: Veith Birgit , Herzberg Christina , Steckel Silke , Feesche Jörg , Maurer Karl Heinz , Ehrenreich Petra , Bäumer Sebastian , Henne Anke , Liesegang Heiko , Merkl Rainer , Ehrenreich Armin , Gottschalk Gerhard
Published: September 2004

The genome of Bacillus licheniformis DSM13 consists of a single chromosome that has a size of 4,222,748 base pairs. The average G+C ratio is 46.2%. 4,286 open reading frames, 72 tRNA genes, 7 rRNA operons and 20 transposase genes were identified. The genome shows a marked co-linearity with Bacillus subtilis but contains defined inserted regions that can be identified at the sequence as well as at the functional level. B. licheniformis DSM13 has a well-conserved secretory system, no polyketide biosynthesis, but is able to form the lipopeptide lichenysin. From the further analysis of the genome sequence, we identified conserved regulatory DNA motives, the occurrence of the glyoxylate bypass and the presence of anaerobic ribonucleotide reductase explaining that B. licheniformis is able to grow on acetate and 2,3-butanediol as well as anaerobically on glucose. Many new genes of potential interest for biotechnological applications were found in B. licheniformis; candidates include proteases, pectate lyases, lipases and various polysaccharide degrading enzymes.
Rosacea: A Clinicopathological Approach
Authors: Aroni Kyriaki , Tsagroni Eugenia , Lazaris Andreas C. , Patsouris Efstratios , Agapitos Emmanouil
Published: September 2004

Background: There are few reports of the histological changes in rosacea, and little attempt has been made to correlate such changes with clinical findings. In the present study, we describe in detail the histopathological features of rosacea in a large number of patients and simultaneously investigate the aetiopathogenesis of the disease based on the comparative assessment of epidemiological, clinical and histological findings. Methods: The study included 73 patients with rosacea. A skin biopsy with a 4-mm punch was performed in each case. All biopsy specimens included subcutaneous tissue. In 10 randomly selected patients, facial biopsy specimens were obtained from both involved and uninvolved (non-lesional) skin. Demodex mite presence was estimated semi-quantitatively under light microscopy. Patients with self-reported gastro-intestinal symptoms were submitted to upper gastro-intestinal endoscopy, and a rapid urease test was performed. Serological antibodies, IgG and IgA, against Helicobacter pylori were also detected. Results: The patients had a broad clinical spectrum of lesions. No specific histological features associated with either erythematous-telangiectatic or papulopustular clinical forms were noticed. Histological examination showed that there is no histological pattern unique to rosacea. Three different types of granulomas were observed: small palisaded ones around altered collagen and other granulomas of elastolytic and non-specific epithelioid type, all coexisting in 5 cases. The deep dermis and subcutis were frequently involved. Comparative study in 10 rosacea patients between lesional and non-lesional skin biopsies revealed almost the same histological changes to the latter biopsies, to a lesser degree though. Conclusion: Rosacea seems to be a reaction pattern to which a variety of pathogenetic routes may lead.
Mu-Opiate Receptor and Beta-Endorphin Expression in Nerve Endings and Keratinocytes in Human Skin
Authors: Bigliardi-Qi M. , Sumanovski L.T. , Büchner S. , Rufli T. , Bigliardi P.L.
Published: September 2004

We have previously shown that human epidermal keratinocytes express a functionally active µ-opiate receptor, which adds a new dimension to the recently developed research in neuroimmunodermatology and neurogenic inflammation in skin diseases. Human keratinocytes specifically bind and also produce β-endorphin, the endogenous µ-opiate receptor ligand. Using confocal imaging microscopy, we could now demonstrate that µ-opiate receptors are not only expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in the dermis and epidermis. Some of the peripheral nerve fibers also express the ligand β-endorphin. The keratinocytes positive for β-endorphin staining are clustered around the terminal ends of the unmyelinated nerve fibers. Therefore the opiate receptor system seems to be crucial in the direct communication between nerves and skin. The keratinocytes can influence the unmyelinated nerve fibers in the epidermis directly via secreting β-endorphin. On the other hand, nerve fibers can also secrete β-endorphin and influence the migration, differentiation and probably also the cytokine production pattern of keratinocytes.
Prevalence and Risk Factors for Superficial Fungal Infections among Italian Navy Cadets
Authors: Ingordo Vito , Naldi Luigi , Fracchiolla Stefania , Colecchia Bruno
Published: September 2004

Background: Limited studies on the prevalence and risk factors for superficial mycoses are available. Objective: The aim of this paper was to evaluate the prevalence and risk factors for superficial mycoses (dermatophytes and Candida spp.) in a sample of young Italian people resident at a military school. Methods: A total of 1,024 young cadets from the Italian Navy Petty Officers School in Taranto, including 975 (95.21%) males and 49 (4.79%) females, mean age 22.5 ± 3.0 years (range 18–30), were consecutively examined by the same observer. A complete dermatological examination was performed on all the subjects, and skin scrapings for microscopy and fungal culture were obtained from suspected lesions. All the subjects completed a questionnaire providing information on sports practice, swimming-pool attendance, marching, wearing shower sandals, frequent use of ‘gummed’ shoes, history of severe traumas to the nails, presence of hyperhidrosis and history of superficial mycoses. The affected subjects were also asked if they were aware of their condition. Data were analysed by the Statistical Analysis System, version 8.0. The Fisher exact test and odds ratios were calculated. Results: A total of 33 subjects (3.2%) were found to suffer from a mycologically confirmed fungal infection (3% by dermatophytes and 0.2% by Candida albicans): tinea pedis/Candida intertrigo of the feet was suspected in 126 (12.1%) subjects and confirmed in 30 (2.9%), including 28 cases of tinea pedis and 2 cases of Candida intertrigo; tinea cruris/Candida intertrigo of the groin was suspected in 28 (2.7%) subjects, but confirmed in only 1 case (0.1%); onychomycosis was suspected in 64 (6.1%) subjects and confirmed in 2 cases (0.2%). The organism most frequently responsible in tinea pedis was Trichophyton mentagrophytes var. interdigitale (82.1%). The same species (50%) and T. mentagrophytes var. mentagrophytes (50%) were associated with tinea unguium, Epidermophyton floccosum was the only species detected in tinea cruris. Non-dermatophytic filamentous fungi (Penicillium spp., Fusarium spp., Aspergillus spp. and Paecilomyces spp.), not considered pathogenic, were isolated in 48 samples. None of the risk factors analysed were significantly associated with fungal infection. Only 2 subjects out of the 33 people affected were aware of their condition. They both had tinea pedis. Conclusion: The prevalence of mycoses in sailors living in an Italian military school was lower than rates detected in other military populations. This may be due to the cadets’ lifestyle and environmental conditions. The most frequent infection was tinea pedis, mainly caused by T. interdigitale. None of the investigated risk factors were significantly associated with the disease, and most of the affected individuals were not aware of their condition.
Detection of Human Papillomavirus Type 58 in Polydactylous Bowen’s Disease on the Fingers and Toes of a Woman – Concurrent Occurrence of Invasive Vulval and Cervical Carcinomas
Authors: Hara Hiroyuki , Honda Ayano , Suzuki Hiroyuki , Sata Tetsutaro , Matsukura Toshihiko
Published: September 2004

The group related to human papillomavirus (HPV) type 16 (HPV-16, -31, -33, -35, -52, -58 and -67) is dominantly identified in cervical intraepithelial neoplasia and cervical carcinomas. HPV-16 has also been frequently detected in Bowen’s disease on the hands and feet. We describe herein a case of polydactylous Bowen’s disease on the fingers and toes of a woman who had had radical vulvectomy and hysterectomy for concomitant invasive vulval and cervical carcinomas. All the lesions, except for the lesions on the periungual side of her left index, middle and ring fingers, harbored HPV-58 DNA with more than 100 entire viral genome copies per cell detected by Southern blot hybridization. The histological localization of the viral DNA was confirmed in all the lesions by in situ hybridization. We could also retrospectively demonstrate HPV-58 DNA in her invasive vulval and cervical carcinoma tissues.
Multiple Myofibromas and an Epidermal Verrucous Nevus in a Child with Neurofibromatosis Type 1
Authors: De Schepper Sofie , Janssens Sandra , Messiaen Ludwine , van den Broecke Caroline , Naeyaert Jean-Marie
Published: September 2004

Neurofibromatosis type 1 (NF1) is a common neurocutaneous autosomal dominant genetic disorder affecting primarily tissues derived from the embryonic neural crest. Two hallmark features of NF1 are the wide range of potentially affected tissues and the enormous phenotypic variability of disease traits even among patients from the same family. We present a boy fulfilling the diagnostic criteria for NF1 with two unusual lesions: infantile myofibromatosis and a verrucous epidermal nevus. To our knowledge this association has never been described before.
Hebrew Derived Nouns in Context: A Developmental Perspective
Authors: Seroussi Batia
Published: September 2004

Derived nouns constitute a productive group of abstract nouns in Hebrew, consisting of action nominals as well as other verb-related nouns in other morphological patterns. This study traces the route taken by Hebrew-speaking children, adolescents and adults on a written sentence-construction test. The test consisted of six pairs of derived nouns sharing the same root but having different meanings (analogous to English pairs like process-procedure, destiny-destination) and was administered to 110 native speakers of Hebrew (school-goers in grades VI, VIII, and XI and two groups of adults, younger and older). Results of both quantitative and qualitative analyses point to the influence of various semantic factors on later lexical development on the one hand, and a close semantic-syntactic interdependency, on the other.
Relationship between Speech and Swallowing Disorders in Patients with Neuromuscular Disease
Authors: Nishio Masaki , Niimi Seiji
Published: September 2004

The intelligibility of monosyllabic speech, word speech, and conversational speech was evaluated in 113 dysarthric speakers, and the presence and severity of swallowing disorders were evaluated using videofluoroscopic and bedside examinations. The results revealed a high correlation between swallowing function and all levels of speech intelligibility. Furthermore, the prevalence of concomitant dysphagia in dysarthric patients was quite high regardless of the primary etiology and time elapsed since the onset. However, the relationship between the two functions is more complex than is initially apparent. The prevalence and severity of dysphagia vary markedly according to the type of dysarthria. Patients in the flaccid, spastic, and mixed categories encompass a broad range of severity levels with many individuals being severely impaired, while patients in the ataxic, hypokinetic, and unilateral upper motor neuron categories seldom have severe concomitant swallowing problems. Furthermore, the correlation coefficient between conversational intelligibility and swallowing function varies considerably according to the type of dysarthria. The correlation was not significant in the flaccid, hypokinetic, and UUMN dysarthria groups. Based on these findings, we discuss herein the clinical management of dysarthric patients with dysphagia.
Distinct Phenotypic Presentations of Gastroesophageal Reflux Disease: A New View of the Natural History
Authors: Fass Ronnie
Published: September 2004

For decades the natural history of gastroesophageal reflux disease (GERD) has been approached as spectrum-continuum, emphasizing the potential progress over time of patients along the spectrum. This commonly adopted conceptual framework had a profound impact on the field, affecting our research priorities and current management of GERD patients. A recent new conceptual framework has been proposed, suggesting that in response to factors that promote gastroesophageal reflux, patients may develop 3 distinct phenotypic presentations: non-erosive reflux disease; erosive esophagitis, and Barrett’s esophagus. Most studies thus far, albeit unsatisfactory in their design, have demonstrated a very limited movement in between the 3 phenotypic presentations of GERD, further suggesting that those once determined remain true to form. The new conceptual framework emphasizes the importance of understanding symptom generation in GERD and the need to focus on the etiology and management of each phenotypic presentation of GERD. Additionally, it supports the usage of on-demand or intermittent antireflux treatment in clinical practice and provides better understanding of one of the most important clinical dilemmas – proton pump inhibitor failure.
Review of the Quality of Life and Burden of Illness in Gastroesophageal Reflux Disease
Authors: Wiklund Ingela
Published: September 2004

Gastroesophageal reflux disease (GERD) is associated with a range of symptoms (typically heartburn, acid regurgitation and dysphagia), which may or may not be accompanied by endoscopically evident esophagitis. A number of studies have demonstrated that health-related quality of life (HRQoL) in reflux disease patients is significantly impaired in comparison to the general population, regardless of the endoscopic findings. Furthermore, this impairment is comparable to or greater than that observed in other chronic conditions, such as diabetes, arthritis or congestive heart failure. Impaired HRQoL in GERD patients is a result of features such as disturbed sleep, reduced vitality, generalized body pain, an impaired sex life and anxiety about the underlying cause of the symptoms. Nocturnal symptoms of reflux disease appear to have a particularly marked impact on HRQoL. The burden of illness imposed by reflux disease on HRQoL also has an impact on productivity, both at and outside work. The impact of reflux disease on productivity is significant and comparable to that caused by headache or back pain. Effective treatment is available for reflux disease, and there is evidence that this can quickly restore HRQoL to levels observed in the general population. However, poor communication between physicians and patients is contributing to unacceptable levels of patient dissatisfaction. Understanding patients’ experience of GERD and its treatment through the study of HRQoL is one way to address this problem.
Carditis at the Interface between GERD and Helicobacter pylori Infection
Authors: Peitz U. , Vieth M. , Malfertheiner P.
Published: September 2004

Inflammation of the gastric cardia (‘carditis’) is a histological diagnosis. It seems reasonable to transfer histological criteria of the updated Sydney classification from the distal stomach to the cardia as long as a special classification of inflammation of the esophagogastric junction is lacking. The two best characterized causes of carditis are Helicobacter pylori infection and gastroesophageal reflux disease (GERD). However, the causal contribution and interference of these two factors are highly controversial, as is the clinical relevance of carditis in terms of eliciting symptoms or conferring an increased cancer risk. Variability of studies on carditis is based on conflicting concepts of the normal anatomy of the esophagogastric junction. Cardia-type mucosa (CM) apparently exists at birth as a tiny circular area, and extends to a larger area in adulthood. This implies that cardia-type mucosa is largely metaplastic. Metaplastic CM may evolve in the lower esophagus as a consequence of GERD. It is a general phenomenon that H. pylori-induced gastritis also involves the gastric cardia, irrespective whether the cardia is lined by fundus-type mucosa or CM. The contribution of GERD to inflammation of CM in H. pylori-negative individuals is, however, highly controversial. Prevalence of carditis in GERD patients fluctuates between 10 and 97%. Hence, because of its high frequency and low specificity, carditis can currently not be considered as a clinical entity. The role of carditis for the increasing incidence of cancer of the esophagogastric junction requires careful studies that include accurate description of the area with adequate biopsy protocols.