bluuebunny/crossref_metadata_2025 huggingface dataset:
The ventilatory responsiveness to CO2 below eupnoea as a determinant of ventilatory stability in sleep
Authors: Dempsey Jerome A. , Smith Curtis A. , Przybylowski Tadeuez , Chenuel Bruno , Xie Ailiang , Nakayama Hideaki , Skatrud James B.
Published: July 2004

Sleep unmasks a highly sensitive hypocapnia‐induced apnoeic threshold, whereby apnoea is initiated by small transient reductions in arterial CO2 pressure (PaCO2) below eupnoea and respiratory rhythm is not restored until PaCO2 has risen significantly above eupnoeic levels. We propose that the ‘CO2 reserve’ (i.e. the difference in PaCO2 between eupnoea and the apnoeic threshold (AT)), when combined with ‘plant gain’ (or the ventilatory increase required for a given reduction in PaCO2) and ‘controller gain’ (ventilatory responsiveness to CO2 above eupnoea) are the key determinants of breathing instability in sleep. The CO2 reserve varies inversely with both plant gain and the slope of the ventilatory response to reduced CO2 below eupnoea; it is highly labile in non‐random eye movement (NREM) sleep. With many types of increases or decreases in background ventilatory drive and PaCO2, the slope of the ventilatory response to reduced PaCO2 below eupnoea remains unchanged from control. Thus, the CO2 reserve varies inversely with plant gain, i.e. it is widened with hyperventilation and narrowed with hypoventilation, regardless of the stimulus and whether it acts primarily at the peripheral or central chemoreceptors. However, there are notable exceptions, such as hypoxia, heart failure, or increased pulmonary vascular pressures, which all increase the slope of the CO2 response below eupnoea and narrow the CO2 reserve despite an accompanying hyperventilation and reduced plant gain. Finally, we review growing evidence that chemoreceptor‐induced instability in respiratory motor output during sleep contributes significantly to the major clinical problem of cyclical obstructive sleep apnoea.
Analysis of Nonlinear Aeroelastic Panel Response Using Proper Orthogonal Decomposition
Authors: Mortara Sean A. , Slater Joseph , Beran Philip
Published: July 2004

The nonlinear panel flutter problem solved by Dowell in 1966 is used to investigate the new application of the proper orthogonal decomposition model reduction technique to aeroelastic analysis. Emphasis is placed on the nonlinear structural dynamic equations with nonconservative forcing modeled assuming a supersonic, inviscid flow. Here the aeroelastic coupled equation is presented in discrete form using a finite difference approach, and subsequently in state space form, to be integrated as a set of first order differential equations. In this paper, a POD approach is developed for generalized second-order differential equations; however, the application of POD to the governing equations in state space form is also discussed. This study compares the results and effectiveness of the model reduction technique for integration of the full set of degrees of freedom. The solution is compared to Dowell’s classic results which forms the base reference for the model reduction study. The reduced order model is then created from the full simulation model. Accuracy of the solution, reduced computational time, limits of stability, and the strengths and weaknesses of the model reduction are investigated.
On a Persistent Misunderstanding of the Role of Hysteretic Damping in Rotordynamics
Authors: Genta Giancarlo
Published: July 2004

Even though the role of damping in rotordynamics has been known for more than half a century, some incorrect statements on the effects of hysteretic damping, particularly in the subcritical range, can be found still in even the most authoritative journals. Although clarified in the 1970s, this issue recently resurfaced with the incorrect statement that hysteretic damping of rotating elements is destabilizing at any speed (even subcritical). The aim of the present paper is to clarify this issue in terms of the practical applications of the theory in an unequivocal way.
Dynamic Analysis of a Multi-Shaft Helical Gear Transmission by Finite Elements: Model and Experiment
Authors: Kubur M. , Kahraman A. , Zini D. M. , Kienzle K.
Published: July 2004

A dynamic model of a multi-shaft helical gear reduction unit formed by N flexible shafts is proposed in this study. The model consists of a finite element model of shaft structures combined with a three-dimensional discrete model of helical gear pairs. Bearing and housing flexibilities are included in the model as well. Eigenvalue solution and the Modal Summation Technique are used to predict the free and forced vibrations of the system. Results of experimental study on a helical gear-shaft-bearing system are also presented for validation of the model. It is demonstrated that the predictions match well with the experimental data in terms of excited modes and the forced response given in the form of the dynamic transmission error. Forced vibrations of an example system formed by three shafts are also studied to demonstrate the influence of some of the key system parameters.
A New Regularization of Coulomb Friction
Authors: Quinn D. Dane
Published: July 2004

We present a new regularization of Coulomb’s law of friction that permits a straight-forward incorporation of frictional forces within existing numerical simulations. Similar to existing regularizations, the proposed modification to Coulomb friction leads to a continuous representation of friction and does not require the identification of transitions between slip and stick. However, unlike more common regularizations, the current reformulation maintains a structure at zero contact velocity that is identical to the classical, discontinuous form of Coulomb friction. The implementation of this regularization is presented through two examples in which slip-stick motion induced by sliding friction is of primary importance. The first is a simple one degree-of-freedom system and illustrates the existence of nontrivial equilibrium states. The second example is a multi-degree-of-freedom system in which the present model provides a computationally efficient scheme for simulating the dissipation arising from sliding friction. For systems in which slip-stick transitions are important the proposed regularization provides a computationally efficient scheme to obtain time-accurate simulations.
Observation of a One-Dimensional Tonks-Girardeau Gas
Authors: Kinoshita Toshiya , Wenger Trevor , Weiss David S.
Published: July 2004

We report the observation of a one-dimensional (1D) Tonks-Girardeau (TG) gas of bosons moving freely in 1D. Although TG gas bosons are strongly interacting, they behave very much like noninteracting fermions. We enter the TG regime with cold rubidium-87 atoms by trapping them with a combination of two light traps. By changing the trap intensities, and hence the atomic interaction strength, the atoms can be made to act either like a Bose-Einstein condensate or like a TG gas. We measure the total 1D energy and the length of the gas. With no free parameters and over a wide range of coupling strengths, our data fit the exact solution for the ground state of a 1D Bose gas.
Argonaute2 Is the Catalytic Engine of Mammalian RNAi
Authors: Liu Jidong , Carmell Michelle A. , Rivas Fabiola V. , Marsden Carolyn G. , Thomson J. Michael , Song Ji-Joon , Hammond Scott M. , Joshua-Tor Leemor , Hannon Gregory J.
Published: July 2004

Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes “Slicer” activity to RISC, providing the catalytic engine for RNAi.
Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity
Authors: Song Ji-Joon , Smith Stephanie K. , Hannon Gregory J. , Joshua-Tor Leemor
Published: July 2004

Argonaute proteins and small interfering RNAs (siRNAs) are the known signature components of the RNA interference effector complex RNA-induced silencing complex (RISC). However, the identity of “Slicer,” the enzyme that cleaves the messenger RNA (mRNA) as directed by the siRNA, has not been resolved. Here, we report the crystal structure of the Argonaute protein from
Pyrococcus furiosus
at 2.25 angstrom resolution. The structure reveals a crescent-shaped base made up of the amino-terminal, middle, and PIWI domains. The Piwi Argonaute Zwille (PAZ) domain is held above the base by a “stalk”-like region. The PIWI domain (named for the protein piwi) is similar to ribonuclease H, with a conserved active site aspartate-aspartate-glutamate motif, strongly implicating Argonaute as “Slicer.” The architecture of the molecule and the placement of the PAZ and PIWI domains define a groove for substrate binding and suggest a mechanism for siRNA-guided mRNA cleavage.
TEMPERATURE DEPENDENCE OF THE CRITICAL CURRENT DENSITY OF SUPERCONDUCTORS IN TWO-BAND GINZBURG–LANDAU THEORY: APPLICATION TO MgB2
Authors: ASKERZADE I. N.
Published: July 2004

Temperature dependence of the critical current density j c (T) for the superconducting magnesium diboride MgB 2 is studied in the vicinity of T c by using a two-band Ginzburg–Landau (G–L) theory. The result is in good agreement with experimental data for a bulk MgB 2. Comparision of obtained results with single-band GL theory are presented.
EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes
Authors: Andl Claudia D. , Mizushima Takaaki , Oyama Kenji , Bowser Mark , Nakagawa Hiroshi , Rustgi Anil K.
Published: July 2004

The epidermal growth factor receptor (EGFR) activates several signaling cascades in response to epidermal growth factor stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT), whereas another involves activation of the phosphatidylinositol 3-OH kinase pathway. Two possibilities for STAT activation exist: a janus kinase (JAK)-dependent and a JAK-independent mechanism. Herein, we demonstrate that EGFR overexpression in primary esophageal keratinocytes activates STAT in a JAK-dependent fashion with the functional consequence of enhanced cell migration, which can be abolished by use of a JAK-specific inhibitor, AG-490. We determined the mechanisms underlying the signal transduction pathway responsible for increased cell migration. Stimulation of EGFR induces Tyr701 phosphorylation of STAT1 and initiates complex formation of STAT1 and STAT3 with JAK1 and JAK2. Thereafter, the STATs translocate to the nucleus within 15 min. In addition, we found that activation of this signaling pathway results in matrix metalloproteinase-1 (MMP-1) activity. By contrast, Akt activation does not impact the EGFR-STATs-JAKs complex formation and nuclear translocation of the STATs with subsequent MMP-1 activity, although Akt activation may contribute to cell migration through an independent mechanism. Taken together, we find that the recruitment of the STAT-JAK complex by EGFR is responsible for keratinocyte migration that, in turn, might be mediated by MMP-1 activation.
Cobalt chloride induces delayed cardiac preconditioning in mice through selective activation of HIF-1α and AP-1 and iNOS signaling
Authors: Xi Lei , Taher Mohiuddin , Yin Chang , Salloum Fadi , Kukreja Rakesh C.
Published: July 2004

Acute systemic hypoxia induces delayed cardioprotection against ischemia (I)-reperfusion (R) injury via inducible nitric oxide synthase (iNOS)-dependent mechanism. Because CoCl2 is known to elicit hypoxia-like responses, we hypothesized that this chemical would mimic the delayed preconditioning effect in the heart. Adult male mice were pretreated with CoCl2 or saline. The hearts were isolated 24 h later and subjected to 20 min of global I and 30 min of R in Langendorff mode. Myocardial infarct size (% of risk area; mean ± SE, n = 6–8/group) was reduced in mice pretreated with 30 mg/kg CoCl2 (16.1 ± 3.1% vs. 27.6 ± 3.3% with saline control; P < 0.05) without compromising postischemic cardiac function. Higher doses of CoCl2 failed to induce similar protection. Electrophoretic mobility gel shift assay demonstrated significant enhancement in DNA binding activity of hypoxia-inducible factor 1α (HIF-1α) and activator protein 1 (AP-1) in nuclear extracts from CoCl2-treated hearts. Activation of HIF-1α and AP-1 was evident at 30 min and sustained for the next 4 h after CoCl2 injection. In contrast, CoCl2-induced protection was independent of NF-κB activation because no DNA binding or p65 translocation was observed in nuclear extracts. Also, CoCl2-induced cardioprotection was preserved in p50 subunit NF-κB-knockout (KO) mice (11.1 ± 3.0% vs. 25.1 ± 5.0% in saline-treated p50-KO mice; P < 0.05). The infarct-limiting effect of CoCl2 was absent in iNOS-KO mice (20.9 ± 3.0%). We conclude that in vivo administration of CoCl2 preconditions the heart against I/R injury. The delayed protective effect of CoCl2 is achieved through a distinctive signaling mechanism involving HIF-1α, AP-1, and iNOS but independent of NF-κB activation.
Rat heart is a site of leptin production and action
Authors: Purdham Daniel M. , Zou Min-Xu , Rajapurohitam Venkatesh , Karmazyn Morris
Published: July 2004

Leptin, the 16-kDa peptide hormone product of the ob gene, is produced primarily by adipocytes and was initially thought to exert its effects exclusively through actions on the hypothalamus via distinct leptin receptors termed OB-R. However, recent data show that leptin is produced elsewhere and that receptors are present in many other tissues. Using real-time PCR, we determined whether leptin and its receptors are present in the rat heart and demonstrated regional distribution patterns and gender differences as well as the effect of ischemia and reperfusion. Gene expression of leptin and its receptors (OB-Ra, OB-Rb, and OB-Re) was identified in myocytes and whole heart homogenates from all regions of the heart of male and female rats, with the highest abundance in left and right atria of male and female rats, respectively. No differences in regional distribution of OB-R were evident in male rat hearts. In female rats, expression was highest in right atria for all three isoforms and was significantly greater than in male rats. Ischemia and reperfusion significantly downregulated leptin and OB-R expression, although this was more pronounced in male rat hearts. Leptin release in the coronary effluent was also detected using ELISA, although this was generally unaffected by global ischemia and reperfusion. Our results demonstrate for the first time the presence of the leptin system, including the peptide and its receptors, in all regions of the rat heart. In view of emerging evidence for cardiac effects of leptin, it is proposed that the heart is a target for leptin action and that the peptide modulates function through a paracrine- or autocrine-dependent manner.
Intracellular-specific colocalization of prostaglandin E2synthases and cyclooxygenases in the brain
Authors: Vazquez-Tello Alejandro , Fan Li , Hou Xin , Joyal Jean-Sébastien , Mancini Joseph A. , Quiniou Christiane , Clyman Ronald I. , Gobeil Fernand , Varma Daya R. , Chemtob Sylvain
Published: July 2004

Prostaglandin E2(PGE2) is the major primary prostaglandin generated by brain cells. However, the coordination and intracellular localization of the cyclooxygenases (COXs) and prostaglandin E synthases (PGESs) that convert arachidonic acid to PGE2in brain tissue are not known. We aimed to determine whether microsomal and cytosolic PGES (mPGES-1 and cPGES) colocalize and coordinate activity with either COX-1 or COX-2 in brain tissue, particularly during development. Importantly, we found that cytosolic PGES also associates with microsomes (cPGES-m) from the cerebrum and cerebral vasculature of the pig and rat as well as microsomes from various cell lines; this seemed dependent on the carboxyl terminal 35-amino acid domain and a cysteine residue (C58) of cPGES. In microsomal membranes from the postnatal brain and cerebral microvessels of mature animals, cPGES-m colocalized with both COX-1 and COX-2, whereas mPGES-1 was undetectable in these microsomes. Accordingly, in this cell compartment, cPGES could coordinate its activity with COX-2 and COX-1 (partly inhibited by NS398); albeit in microsomes of the brain microvasculature from newborns, mPGES-1 was also present. In contrast, in nuclei of brain parenchymal and endothelial cells, mPGES-1 and cPGES colocalized exclusively with COX-2 (determined by immunoblotting and immunohistochemistry); these PGESs contributed to conversion of PGH2into PGE2. Hence, contrary to a previously proposed model of exclusive COX-2/mPGES-1 coordination, COX-2 can coordinate with mPGES-1 and/or cPGES in the brain, depending on the cell compartment and the age group.
FHL5, a novel actin-binding protein, is highly expressed in eel gill pillar cells and responds to wall tension
Authors: Mistry Abinash Chandra , Kato Akira , Tran Yen Ha , Honda Shinji , Tsukada Takehiro , Takei Yoshio , Hirose Shigehisa
Published: July 2004

Supporting evidence for the contractile nature of fish branchial pillar cells was provided by demonstrating the presence of actin fibers and a novel four-and-a-half LIM (FHL) protein in which expression is specific for contractile tissues and sensitive to the tension applied to the pillar cell. When eel gill sections were stained with rhodamine-phalloidin, a selective fluorescent probe for fibrous actin, a strong bundle-like staining was observed around collagen columns in pillar cells, suggesting the presence of abundant actin fibers. A cDNA clone encoding a novel member of the actin-binding FHL family, FHL5, was isolated from a subtracted cDNA library of eel gill. Northern analysis revealed that FHL5 mRNA is highly expressed only in gills, heart, and skeletal muscle. In gills, FHL5 was found to be confined to pillar cells by immunohistochemistry. Confocal fluorescence microscopy showed that FHL5 is present in both cytosol and nucleus; within the cytosol, a large portion of FHL5 is colocalized with the phalloidin-positive actin bundles. Furthermore, transfection of myogenic C2C12 cells with FHL5 cDNA demonstrated, in addition to its interaction with actin stress fibers, a nuclear shuttling activity of FHL5. The mRNA and protein levels were found to be elevated on 1) transfer of eels from seawater to freshwater, 2) volume expansion by infusion of isotonic dextran-saline, and 3) constriction of gill vasculature by bolus injection of endothelin-1. These results suggest contractile nature of pillar cells and a role of FHL5 in maintaining the integrity and regulating the dynamics of pillar cells.
Measuring committed preadipocytes in human adipose tissue from severely obese patients by using adipocyte fatty acid binding protein
Authors: Tchoukalova Yourka D. , Sarr Michael G. , Jensen Michael D.
Published: July 2004

To understand the significance of the reported depot differences in preadipocyte dynamics, we developed a procedure to identify committed preadipocytes in the stromovascular fraction of fresh human adipose tissue. We documented that adipocyte fatty acid binding protein (aP2) is expressed in human preadipocyte clones capable of replication, indicating that can be used as a marker of committed preadipocytes. Because aP2 expression can be induced in macrophages, stromovascular cells were also stained for the macrophage marker CD68. We found aP2+CD68−cells (designated as committed preadipocytes) that did not have lipid droplets (true preadipocytes) and that did have lipid droplets <6.5 μm in diameter (very immature adipocytes). Adipose tissue from subcutaneous, omental, and mesenteric depots was obtained from nine patients undergoing bariatric surgery for measurement of stromovascular cell number, the number of committed preadipocytes (aP2+CD68−), aP2+macrophages (aP2+CD68+), and aP2−macrophages (aP2−CD68+). The number of committed preadipocytes did not differ significantly between depots but varied >20-fold among individuals. Total cell number, stromovascular cell number, and the number of aP2−macrophages was less ( P < 0.05) in subcutaneous than in omental fat (means ± SE, in millions: subcutaneous, 2.3 ± 0.3, 1.4 ± 0.3, and 0.17 ± 0.08; and omental, 4.8 ± 0.7, 3.8 ± 0.5, and 0.34 ± 0.06); mesenteric depot was intermediate. These data indicate that the cellular composition of adipose tissue varies between depots and between individuals. The ability to quantify committed preadipocytes in fresh adipose tissue should facilitate study of adipose tissue biology.
Lingual, splanchnic, and systemic hemodynamic and carbon dioxide tension changes during endotoxic shock and resuscitation
Authors: Guzman Jorge A. , Dikin Mathew S. , Kruse James A.
Published: July 2004

Sublingual and intestinal mucosal blood flow and Pco2 were studied in a canine model of endotoxin-induced circulatory shock and resuscitation. Sublingual Pco2 (PsCO2) was measured by using a novel fluorescent optrode-based technique and compared with lingual measurements obtained by using a Stowe-Severinghaus electrode [lingual Pco2 (PlCO2)]. Endotoxin caused parallel changes in cardiac output, and in portal, intestinal mucosal, and sublingual blood flow (Q̇s). Different blood flow patterns were observed during resuscitation: intestinal mucosal blood flow returned to near baseline levels postfluid resuscitation and decreased by 21% after vasopressor resuscitation, whereas Q̇s rose to twice that of the preshock level and was maintained throughout the resuscitation period. Electrochemical and fluorescent Pco2 measurements showed similar changes throughout the experiments. The shock-induced increases in PsCO2 and PlCO2 were nearly reversed after fluid resuscitation, despite persistent systemic arterial hypotension. Vasopressor administration induced a rebound of PsCO2 and PlCO2 to shock levels, despite higher cardiac output and Q̇s, possibly due to blood flow redistribution and shunting. Changes in PlCO2 and PsCO2 paralleled gastric and intestinal Pco2 changes during shock but not during resuscitation. We found that the lingual, splanchnic, and systemic circulations follow a similar pattern of blood flow variations in response to endotoxin shock, although discrepancies were observed during resuscitation. Restoration of systemic, splanchnic, and lingual perfusion can be accompanied by persistent tissue hypercarbia, mainly lingual and intestinal, more so when a vasopressor agent is used to normalize systemic hemodynamic variables.
Pharmacokinetics of Bupropion and Its Metabolites in Haemodialysis Patients Who Smoke
Authors: Worrall Simon P.R. , Almond Michael K. , Dhillon Soraya
Published: July 2004

To date, no study has investigated the effects of bupropion (BP) in renal-impaired humans. This study aims to identify the pharmacokinetics of BP and metabolites in haemodialysis patients who smoke, determine whether haemodialysis affects BP and metabolite clearance, and suggest the BP dose in haemodialysis. The pharmacokinetics of BP and two of its major metabolites, hydroxybupropion (HB) and threohydrobupropion (TB) were studied in 8 smokers with ESRD receiving haemodialysis. Following a single oral dose of 150 mg bupropion hydrochloride sustained-release, blood samples were taken over 7 days, which were assayed using HPLC-mass spectrometry. Pharmacokinetic analysis was undertaken by non-linear regression using MWPharm. The BP results were similar to those for individuals with normal renal function. The metabolites demonstrated increased areas under the curve, indicating accumulation. Dialysis clearance of HB is unlikely. The results suggest significant accumulation of the metabolites in renal failure. Clarification of the clinical importance of the metabolites and toxic plasma levels is required. The effects of haemodialysis on BP and metabolites require further study. A dose of 150 mg bupropion every 3 days in patients receiving haemodialysis is more appropriate than the current manufacturer’s recommendation (in renal impaired patients) of 150 mg daily. A multi-dose study is required.
Measuring Blood Pressure in Stable Renal Transplant Recipients: What You Measure Depends on What You Use
Authors: Afzali Behdad , Haydar Ali A. , Abbs Ian C. , Goldsmith David J.A.
Published: July 2004

Background: Blood pressure levels have a major impact on cardiovascular and renal transplant outcomes after renal transplantation. But there are significant challenges to accurately measure blood pressure levels in stable healthy renal transplant outpatients. We aimed to test whether there are differences in BP measurements taken using either automated oscillometric machines or a random zero sphygmomanometer. Methods: Blood pressure was recorded twice in a random order with each of three BP measuring devices (DINAMAP BP8800; OMRON HEM 713 and a Random-Zero Hawskley sphygmomanometer). Results were analysed to determine observer bias, cardiovascular artefacts, and intra- and inter-machine BP variation. Results and Conclusions: There was no significant observer bias or cardiovascular artefacts. Intra-machine variability was small. BP measurement using DINAMAP and OMRON could lead to a difference of up to 30 mm Hg higher or 15 mm Hg lower than Hawskley random zero BP readings. Though widely used for ‘convenience’, oscillometric measures of BP in the renal transplant clinic are not optimal.
Proatrial Natriuretic Peptide (1–98), but Not Cystatin C, Is Predictive for Occurrence of Acute Renal Insufficiency in Critically Ill Septic Patients
Authors: Mazul-Sunko B. , Žarković N. , Vrkić N. , Antoljak N. , Bekavac Bešlin M. , Nikolić Heitzler V. , Širanović M. , Krizmanić-Dekanić A. , Klinger R.
Published: July 2004

Introduction: N-terminal prohormone of atrial natriuretic peptide ((proANP(1–98)) has been extensively analyzed in patients with chronic renal failure. It has been found to be closely related to the renal function and to interdialytic hydration status. The clinical relevance of proANP(1–98) and cystatin C, a novel marker of glomerular filtration, has not been investigated in the subgroup of critically ill septic patients with no history of chronic renal impairment. Methods: We measured plasma level ofproANP(1–98) and cystatin C in 29 critically ill septic patients on admittance to the surgical intensive care unit and correlated it with the occurrence of acute renal failure. Results: The proANP(1–98) plasma level was significantly higher in the group of patients who developed renal failure (12,722 ± 12,421 vs. 2,801± 2,023 fmol/ml, p < 0.05). Multiple regression analysis shows that proANP(1–98) on the first day in the intensive care unit has a superior predictive value for the occurrence of renal failure to diuresis, calculated creatinine clearance or cystatin C (r = 0.42, p < 0.039). proANP(1–98) is also higher in non-survivors (9,303.8 ± 11,053 vs. 2,448.5 ± 1,803 fmol/ml, p < 0.018). Conclusion: proANP(1–98) is possibly a better predictor of acute renal failure to calculated creatinine clearance or diuresis among critically ill septic patients. Cystatin C was not correlated with occurrence of acute renal failure in this subgroup of patients.
Elevated ε-(γ-Glutamyl)lysine in Human Diabetic Nephropathy Results from Increased Expression and Cellular Release of Tissue Transglutaminase
Authors: El Nahas A.M. , Abo-Zenah H. , Skill N.J. , Bex S. , Wild G. , Griffin M. , Johnson T.S.
Published: July 2004

Introduction: Diabetic nephropathy (DN) is the leading cause of chronic kidney failure, however the mechanisms underlying the characteristic expansion of the extracellular matrix (ECM) in diabetic kidneys remain controversial and unclear. In non-diabetic kidney scarring the protein crosslinking enzyme tissue transglutaminase (tTg) has been implicated in this process by the formation of increased Ε-(γ-glutamyl)lysine bonds between ECM components in both experimental and human disease. Studies in db+/db+ diabetic mice and in streptozotocin-treated rats have suggested a similar mechanism, although the relevance of this to human disease has not been addressed. Methods: We have undertaken a retrospective analysis of renal biopsies from 16 DN patients with type 2 diabetes mellitus using an immunohistochemical and immunofluorescence approach, with tTg and Ε-(γ-glutamyl)lysine crosslink quantified by confocal microscopy. Results: Immunofluorescent analysis of human biopsies (confocal microscopy) showed increases in levels of tTg (+1,266%, p < 0.001) and Ε-(γ-glutamyl)lysine (+486%, p < 0.001) in kidneys with DN compared to normal. Changes were predominantly in the extracellular periglomerular and peritubular areas. tTg staining correlated with Ε-(γ-glutamyl)lysine (r = 0.615, p < 0.01) and renal scarring (Masson’s trichrome, r = 0.728, p < 0.001). Significant changes in Ε-(γ-glutamyl)lysine were also noted intracellularly in some (≤5%) tubular epithelial cells. This is consistent with cells undergoing a novel transglutaminase-mediated cell death process in response to Ca2+ influx and subsequent activation of intracellular tTg. Conclusion: Changes in tTg and Ε-(γ-glutamyl)lysine occur in human DN. Cellular export of tTg may therefore be a factor in the perpetuation of DN by crosslinking and stabilisation of the ECM, while intracellular activation may lead to cell death contributing towards tubular atrophy.
Renal Functional Reserve Evolution in Children with a Previous Episode of Hemolytic Uremic Syndrome
Authors: Dieguez Stella , Ayuso Sandra , Brindo Mabel , Osinde Eugenia , Cánepa Carlos
Published: July 2004

Introduction: Glomerular filtration rate (GFR) is the most widely used indicator of kidney function in patients with renal disease, although it does not invariably reflect functional status after renal injury. The concept of renal functional reserve (RFR) as the ability of the kidney to increase GFR following a protein load was introduced in the 1980s. In this study we evaluated the RFR test in 26 children who had developed hemolytic-uremic syndrome (HUS) at least 2 years before the first evaluation, then 8 years later. At the beginning of the study they had no signs of proteinuria, hypertension or renal insufficiency. RFR was also evaluated in 15 healthy control children. Methods: Proteinuria and creatinine in serum and urine were tested. Functional reserve index (FRI) was defined in order to evaluate RFR. Patients with FRI level >1.36 were considered as responders (R) and with FRI <1.36 as non-responders (NR). Results: R and NR groups failed to show any significant differences when basal creatinine clearance (CCr) was evaluated. The NR group presented a significant low initial FRI that persisted unchanged at the end of the study. These patients developed proteinuria and a renal protector treatment with protein restriction was indicated. Although the proteinuria diminished, it remained within pathological range. The lack of RFR response in the NR group was significantly related to the presence of oliguria lasting longer than 8 days during the acute phase of disease. Conclusions: Those patients with a previous history of HUS with normal basal CCr should be evaluated by the RFR test to detect those at risk of developing glomerular hyperfiltration.
Expression of Nuclear Pore Complex Oxalate Binding Protein p62 in Experimental Hyperoxaluria
Authors: Sivakamasundari P. , Sakthivel R. , Kalaiselvi P. , Selvam R. , Varalakshmi P.
Published: July 2004

Proteins are thought to play a major role in stone formation. Oxalate binding protein plays a vital role in the transport of oxalate. This study was aimed at determining whether hyperoxaluria induces the expression of nuclear pore complex oxalate binding protein p62 which has the transport function. Hyperoxaluria was induced in male Wistar rats by feeding 0.75% ethylene glycol in water. The oxalate binding activity of the nuclear pore complex protein increased markedly during experimental hyperoxaluria, whereas nuclear lamina had no binding at all. There was an alteration in the elution profile of the nuclear pore complex oxalate binding protein during the hyperoxaluric condition. The protein was purified and had a molecular weight of 62 kDa (data not shown). The purified protein showed cross-reactivity with the monoclonal antibody (MAb 414) and it showed homogeneity. The expression of this protein (p62) during the hyperoxaluric condition was determined by ELISA and a 3-fold increase was observed when compared to control rats. The increased expression is further confirmed by Western blotting and immunohistochemistry. The increase in p62 protein expression may be either due to increased expression of certain genes or degradation of the cell membrane by oxalate-induced cell injury. Thus, the present study suggests that the increased expression of this protein (p62) may be due to the oxalate induction.
Differential Diagnosis of Focal Liver Lesions in Signal-Enhanced Ultrasound Using BR 1, a Second-Generation Ultrasound Signal Enhancer
Authors: Peschl R. , Werle A. , Mathis G.
Published: July 2004

Aim: The aim was to evaluate the diagnostic value of contrast-enhanced ultrasound in the differential diagnosis of focal liver lesions, in a blinded experiment. In clinical routine the examiner can generally be influenced by the patient’s history. Method: 62 patients with focal liver lesions, which could not be clearly differentiated and diagnosed by conventional ultrasound, were examined with contrast-enhanced (BR1, SonoVue®, Bracco) ultrasound and included in a blinded prospective and randomized study. The examinations performed on a Sequoia 512 (Acuson) in a coherent contrast imaging method were recorded by an S-VHS recorder and afterwards analyzed by an examiner who did not know the patient’s history. The basis of the diagnosis was the dynamic appearance and enhancement of the ultrasound contrast enhancer in different phases of liver perfusion. The conformation of the diagnoses was made by corresponding reference methods, as computer tomography, magnetic resonance imaging, biopsy and clinical follow-up. Results: The following diagnoses were confirmed by reference methods: 18 patients with metastases, 4 hepatocellular carcinomas, 19 haemangiomas, 6 focal nodular hyperplasias, 13 patients with focal fatty infiltration and 2 patients with focal fatty sparing. 59 out of 62 patients with one or more liver lesions were correctly diagnosed by contrast-enhanced ultrasound. Conclusion: Second-generation ultrasound contrast enhancers improve the differential diagnosis of benign and malignant liver lesions considerably, especially in a blinded study.
Evaluation of Diagnostic Criteria for Liver Metastases of Adenocarcinomas and Neuroendocrine Tumours at Conventional Ultrasound, Unenhanced Power Doppler Sonography and Echo-Enhanced Ultrasound
Authors: Rickes Steffen , Ocran Kenneth W. , Gerstenhauer Grete , Neye Holger , Wermke Wolfram
Published: July 2004

Purpose: In order to improve the differential diagnosis between liver metastases of neuroendocrine tumours and adenocarcinomas, criteria for the masses at conventional ultrasound, unenhanced power Doppler sonography and echo-enhanced ultrasound were evaluated. Methods: Seventy-three patients with histologically proven liver metastases of a neuroendocrine tumour (n = 26) or an adenocarcinoma (n = 47) were investigated by conventional ultrasound as well as unenhanced power Doppler sonography and echo-enhanced ultrasound focusing on specific properties of the lesions. Results: Liver metastases of neuroendocrine tumours and adenocarcinomas showed a different contrast behaviour with echo-enhanced sonography. A hypervascularisation at the arterial and capillary phase were found in 85% of the neuroendocrine metastases, and in 17% of the masses of adenocarcinomas, respectively (p < 0.05). Conclusions: The successful treatment of liver metastases requires a highly sensitive and specific diagnostic procedure for their differentiation. A hypervascularisation of the lesions during the arterial and capillary phase at echo-enhanced ultrasound may point to a neuroendocrine primary tumour. However, histology is the only standard of reference for the differentiation of liver metastases, and is necessary for optimal therapy.
Reduced Anxiety Level by Therapeutic Interventions and Cell-Mediated Immunity in Panic Disorder Patients
Authors: Koh Kyung Bong , Lee Youngjoon
Published: July 2004

Objective: This study examined the relationship between reduced anxiety level by therapeutic interventions and cell-mediated immunity (CMI) in patients with panic disorder. Methods: The subjects consisted of 42 patients with panic disorder and 42 normal gender- and age-matched controls. Among the patients, 21 were randomly assigned to a combined treatment of cognitive-behavioral therapy and the benzodiazepine antianxiety agent ethyl loflazepate (2 mg daily), and 21 were assigned to the antianxiety agent only. The treatment lasted for 6 weeks. Cell-mediated immune function was measured by the lymphocyte proliferative response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production. The anxiety level was assessed by the Hamilton Rating Scale for Anxiety and the anxiety subscale of the Symptom Checklist-90 Revised. Results: Prior to treatment, the panic disorder patients had significantly lower IL-2 production and blastogenic response to PHA than the normal controls. However, no significant differences in CMI were found between the pretreatment and posttreatment period in either the patient group receiving medication only or the combined treatment group, though after treatment, patients were significantly less anxious than before treatment in both intervention groups. The delta change (posttreatment value minus pretreatment value) in the self-reported anxiety level was significantly associated with the delta change in the blastogenic response in the combined treatment group. Conclusion: These findings suggest that panic disorder may be associated with decreased CMI, and the reduced level of self-reported anxiety in the patients who underwent combined therapeutic intervention is likely to increase the blastogenic response. Further studies are needed to evaluate the long-term effects of treatment on immune function.
Study on Effects of Life Review Activities on the Quality of Life of the Elderly: A Randomized Controlled Trial
Authors: Hanaoka Hideaki , Okamura Hitoshi
Published: July 2004

Background: The objective of this study was to evaluate the mid-term efficacy of life review activities on the quality of life (QOL) of the elderly by conducting a randomized controlled trial, and to identify the factors that should be taken into consideration when conducting life review activities. Methods: Written consent was obtained from 80 of the 97 eligible elderly persons. After randomly assigning them to two groups, an intervention group and a control group, group life review activities were conducted in the intervention group and discussion activities about health were conducted in the control group. In both the intervention group and the control group, life satisfaction, self-esteem, depression, and hopelessness were evaluated using self-rating scales at three points: at baseline, immediately after completion of the 8 weeks of sessions, and 3 months after completion of the intervention. Results: Repeated measures analysis of covariance showed significant differences between the two groups in the changes in scores for depression (p = 0.04) and hopelessness (p = 0.04). Regarding the factors that were associated with depression and hopelessness, 3 months after completion of the intervention, depression and hopelessness of a more severe nature at baseline and having greater unresolved conflicts in the past were extracted by multiple regression analysis. Conclusions: The results suggested that group life review activities have a role in assisting the developmental stage of old age and supporting mental health, and have mid- to long-term effectiveness in maintaining and improving the QOL of the elderly.
Preservation Injury of Jejunal Grafts and Its Modulation by Custodiol and University of Wisconsin Perfusion Solutions in Wistar Rats
Authors: Baláž P. , Matia I. , Jackanin S. , Rybárová Emília , Kron I. , Pomfy M. , Froněk J. , Ryska M.
Published: July 2004

Background: The two preservation solutions most commonly used in human transplantation surgery are University of Wisconsin (UW) and Custodiol (histidine-tryptophan-ketoglutarate; HTK). The aim of our study was to compare the protective effect of UW and HTK solutions on preservation-induced injury of jejunal grafts, as evaluated by the histological changes (semiquantitative method) and small bowel mucosal serotonin levels (as a possible new quantitative method). Methods: Male Wistar rats (n = 50) weighing 316 ± 52 g were divided into two main groups according to which preservation solution was used, i.e. UW (n = 25) or HTK (n = 25), and each of these groups was divided into five subgroups according to cold ischemic time (0, 1, 6, 9 and 12 h). Jejunal mucosa biopsy specimens were obtained to determine the serotonin concentration in mucosa and for standard light histology. To grade histological changes in mucosa, Park’s small bowel injury grading system was used. Results: Histological examination revealed that injury increased with cold ischemic time in the UW as well as in the HTK group, and there were no significant differences in injury between the two groups, except for the 6-hour cold ischemic period (p < 0.05), when HTK-preserved grafts showed a lower degree of injury (0.97 ± 0.41) compared with UW-preserved grafts (1.25 ± 0.39). The mucosal serotonin concentration decreased with cold ischemic time in both groups, and there were significant differences (p < 0.05) in concentrations between the groups after 9 and 12 h of cold ischemia. A significantly higher concentration was measured in grafts preserved in UW solution at these time points. Conclusion: The concentration of mucosal serotonin in rat small bowel grafts preserved for 9 and 12 h in UW preservation solution was significantly higher than that in HTK solution. These findings indicate a better protective effect of UW solution on small bowel injury after 9 h of cold ischemia.
Implantation of Novel Small-Diameter Polyurethane Vascular Prostheses Interposed in Canine Femoral and Carotid Arteries
Authors: Karapınar K. , Ulus A.T. , Tütün U. , Aksöyek A. , Apaydın N. , Pamuk K. , Can Z. , Sarıtaş Z. , Küçükay F. , Arda K. , Katırcıoğlu S.F.
Published: July 2004

Objectives: The performance of small-diameter (3–5-mm) vascular grafts still poses a challenge in the field of vascular surgery. We present here our preliminary experience with implanting unique small-sized polycarbonate urethane vascular grafts in 7 dogs. Material and Methods: Each animal was implanted with 4 interposition grafts, 2 femoral and 2 carotid. No anti-thrombotic medication was administered. Doppler sonography was performed at 3-month intervals to examine for patency and flow characteristics. Animals were sacrificed electively at 3, 6 and 12 months. Results: At 3 months, all grafts were patent. After 6 months, 3 grafts occluded and at 1 year a further 6 grafts occluded. Hence 9 of 28 grafts occluded (67.9% patency). During the study, no correlation could be established between flow velocity or resistance index and occlusion. Histopathology showed intimal hyperplasia to be the cause of occlusion. Conclusions: Compared to literature data on small-diameter grafts in the same position, ADIAM’s Biomechanical grafts performed clearly better. Compliance data suggest a correlation between elastic compliance and patency.
Efficacy of Local Adrenalin Injection during Sacrococcygeal Pilonidal Sinus Excision
Authors: Aysan E. , Basak F. , Kinaci E. , Sevinc M.
Published: July 2004

Background: The most commonly preferred treatment method for sacrococcygeal pilonidal sinus disease is surgery. Peroperative and postoperative hemorrhages may develop frequently because of the increased vascularity of the region. The aim of this study was to evaluate the effects of adrenalin, a potent vasoconstrictor agent, on pilonidal sinus operations in comparison to a control group. Methods: A prospective, randomized, double-blind, clinical study was designed and 51 patients with symptomatic, uncomplicated pilonidal disease were included (44 males and 7 females; mean age 24.5, range 16–44 years). Adrenalin 0.1 mg with 10 ml 0.9% NaCl (1/100,000 dilution) was injected through the incision tracts to all layers and the base of the incision area in group 1 (n = 21). The same process was applied to group 2 (n = 21) with 10 ml physiological serum solution. Then, after removal of the sinus and its tracks, a suction-type drain was placed in the pouch in all cases and the incision was primarily closed. Peroperative and postoperative hemorrhage, and operation time were accepted as the evaluation criteria. Cases were followed for 6 months postoperatively. Results: The amount of peroperative hemorrhage was 6.5 ± 3.5 ml in group 1 and 17.5 ± 9.5 ml in group 2 (p < 0.001). The postoperative hemorrhage was 11 ± 7.5 ml in group 1 and 13.5 ± 6 ml in group 2 (p > 0.05). The operation time was 14 ± 5 min in group 1 and 22 ± 8.5 min in group 2 (p < 0.05). No reactionary hemorrhage, hematoma or recurrence was seen during the follow-up period. Conclusions: Adrenalin injection is quite effective to decrease peroperative bleeding and operation time, but it does not decrease postoperative bleeding and the need for a drain.
Should Major Depression with ‘High Normal’ Thyroid-Stimulating Hormone Be Treated Preferentially with Tricyclics?
Authors: Corruble Emmanuelle , Berlin Ivan , Lemoine Antoinette , Hardy Patrick
Published: July 2004

In a prospective and naturalistic setting, two samples representing 209 depressed inpatients were assessed for thyroid functioning at admission before antidepressant treatment, and for depression before and after 1 month of antidepressant treatment. We hypothesized that serum thyroid-stimulating hormone (TSH) elevation ≧upper 25th percentile of the normal reference range is associated with poorer response to antidepressant therapy and differences between tricyclic antidepressants (TCA) and other antidepressants. Screening for mild thyroid failure defined as serum TSH concentrations ≧upper 25th percentile of the normal range may provide clues to the clinician. Such patients have a more severe form of depression and a slower or impaired response to antidepressant therapy. It is also possible that they would benefit preferentially from TCA rather than other antidepressants.