bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of Expression of Somatostatin Genes by Sex Steroid Hormones in Goldfish Forebrain
Authors: Canosa Luis Fabián , Lin Xinwei , Peter Richard E.
Published: April 2003

Recently, our laboratory has identified three distinct pre-pro-somatostatin (PSS) genes in goldfish brain: PSS-I encodes for somatostatin (SRIH)-14, PSS-II encodes SRIH-28, which contains [Glu1, Tyr7, Gly10] SRIH-14 at its C-terminus, and PSS-III encodes [Pro2] SRIH-14. In goldfish, increasing levels of the sex steroid estradiol increase the plasma levels of growth hormone (GH). However, whether sex steroids act at the level of the brain to regulate GH release is unclear. In the present study, the effects of sex steroids on the expression of the three PSS genes in goldfish forebrain were examined. The results demonstrate that treatment with estradiol significantly increases the expression of PSS-I and PSS-III genes in both male and female fish. The effects of estradiol were evident after only 2.5 days of treatment. Testosterone treatment increased the expression of PSS-I and PSS-III genes in female but not male fish, and only at the highest dose used. In addition, the effects of testosterone were evident only after treatment for 5 or 10 days and were blocked by an aromatase inhibitor, suggesting that testosterone must be converted to estradiol to exhibit the effect. Neither estradiol nor testosterone treatment had effects on the expression of the PSS-II gene. These results suggest that sex steroids can act either directly or indirectly on the brain to regulate PSS-I and PSS-III gene expression, influencing in turn the regulation of GH secretion.
Superoxide in the Vascular System
Authors: Wolin Michael S. , Gupte Sachin A. , Oeckler Richard A.
Published: April 2003

Oxidant production and regulation is becoming increasingly important in the study of vascular signaling mechanisms, and recent reviews have characterized some of the possible roles for known downstream products of superoxide formation. In this review, we will examine current research in the field, with a special emphasis on the role of the superoxide molecule itself and its place amongst the slightly better understood roles of peroxide and peroxynitrite. The regulatory roles of oxidant species are wide-ranging, and their involvement in processes ranging from intracellular and receptor signaling mechanisms that regulate endothelial mediator release and vascular contractile function to processes that control cellular growth and apoptosis has been implied. Cellular sources of superoxide production and metabolism and the chemical interaction of oxidant species with specific components of cellular signaling mechanisms are considered important factors which determine physiological responses that control vascular function.
Both ICAM-1- and VCAM-1-Integrin Interactions Are Important in Mediating Monocyte Adhesion to Human Saphenous Vein
Authors: Crook Martin F. , Southgate Kay M. , Newby Andrew C.
Published: April 2003

Atherosclerosis underlies late occlusion of human saphenous vein (HSV) coronary artery bypass grafts. Monocyte infiltration is implicated, but its mechanisms are unclear given that HSV normally expresses the ICAM-1 but not the VCAM-1 adhesion molecule. To define the mechanisms underlying monocyte adhesion, samples of HSV taken from coronary artery bypass graft patients were co-cultured with human monocytes and adherent monocytes were quantified by immunocytochemistry for CD68 on transverse sections. Pre-treatment of veins with anti-ICAM-1 antibodies reduced monocyte adhesion (monocytes/mm of section) from 7.2 ± 1.5 to 3.1 ± 0.7 (p < 0.05, n = 6), but the effect of anti-VCAM-1 was not significant (4.1 ± 0.7). Paradoxically, pre-treatment of monocytes with either anti-β2-integrins, the counter-receptor of ICAM-1, or anti-α4 integrins, the counter-receptor of VCAM-1, significantly reduced adhesion (1.8 ± 0.6 and 2.4 ± 0.7, respectively, p < 0.05). These results were clarified by immunocytochemistry, which confirmed that VCAM-1 expression was absent in harvested vein but was induced in the endothelium during co-culture. Consistent with this, when anti-ICAM-1 or anti-VCAM-1 was present throughout co-culture, either of them reduced adhesion (from 4.2 ± 0.9 to 2.3 ± 0.5 and 2.2 ± 0.4, respectively, p < 0.02, n = 8) and there was no further effect of adding both (2.0 ± 0.5). These results demonstrate that both ICAM-1/β2 and VCAM-1/α4 integrin interactions mediate monocyte adhesion to HSV, possibly as part of a common pathway. These experiments imply that either integrin might be targeted to reduce monocyte infiltration into HSV grafts.
Vasculogenesis, Angiogenesis and the Molecular Organisation of Endothelial Junctions in the Early Human Placenta
Authors: Leach Lopa , Babawale Michael O. , Anderson Mark , Lammiman Michael
Published: April 2003

Vasculogenesis and angiogenesis are regulated by the capacity of endothelial cells to adhere to each other and form new tubes. The presence and role of junctional adhesion molecules during physiological vasculogenesis is unknown. Using ultrastructural and immunocytochemical approaches, we compared the junctional phenotype of developing vessels of the first-trimester human placenta with vessels in the last trimester; the latter include newly formed terminal capillaries and the quiescent vascular bed. First-trimester placental vessels contained the adherens junctional molecules, vascular endothelial cadherin and α- and β-catenin but lacked plakoglobin, the component of fully differentiated adherens junctions. Furthermore, these vessels did not contain the transmembrane tight junctional molecules occludin and claudin-1 and -2. This profile reflects the phenotype of terminal capillaries but differs from large vessels of the full-term placenta. Electron microscopic studies revealed that endothelial tight junctions are present in the first-trimester placenta. Thus, occludin and claudin-1 appear to play no part in the formation of endothelial tight junctions, but are a later requirement. In the early placenta, the predominant growth factor appears to be vascular endothelial growth factor (VEGF), whilst at term, angiopoietin-1 was present in large vessels, with intense angiopoietin-2 immunofluorescence (and VEGF) located in terminal villous capillaries. Thus, endothelial junctions in the human placenta possess two distinct molecular phenotypes, i.e. stable or dynamic, dependent on maturity and plasticity. These distinct phenotypes may be influenced by the angiopoietins/VEGF present in the placenta.
Topological Properties and Spatial Organization of Villous Capillaries in Normal and Diabetic Placentas
Authors: Jirkovská Marie , Kubínová Lucie , Janáček Jiří , Moravcová Milena , Krejčí Vratislav , Karen Petr
Published: April 2003

Spatial arrangement and complexity of the capillary bed of placental terminal villi were analyzed in 9 normal and 11 diabetic placentas. Specimens were taken by systematic random sampling, fixed and stained in toto, and embedded in paraffin. Fifteen fields of view were sampled systematically from 120-µm-thick sections of specimens and examined using a confocal laser scanning microscope. Series of thin optical sections of terminal villi and their developmental forms were recorded by the confocal microscope and used as initial data for three-dimensional visualization of the spatial arrangement of villous capillaries. Vascular topology and branching were studied by focusing through the villus, making a schematic drawing of the villous capillary bed and counting redundant capillary connections. It was found that the basic arrangement of villous capillaries is similar in both normal and diabetic placentas. Nevertheless, the proportion of simple forms of the capillary bed without redundant connections is significantly higher in normal placentas and the mean number of redundant connections per villus is significantly higher in diabetic placentas. It is concluded that both the longitudinal growth and branching of capillaries contribute to the increase in the placental capillary bed in late gestation and that the capillary bed of diabetic villi is more complicated due to more intense capillary branching.
Gremlins: Is This What Renal Fibrogenesis Has Come To?
Authors: Murphy Madeline , McMahon Ruth , Lappin David W.P. , Brady Hugh R.
Published: April 2003

Gremlin is a member of the differential screening-selected gene aberrative in the neuroblastoma (DAN) family of bone morphogenetic protein (BMP) antagonists. Gremlin influences diverse processes in growth, differentiation and development. Increased expression of gremlin has recently been demonstrated in several models of diabetic nephropathy. Gremlin arrests the cell cycle in mesangial cells and has also been shown to be upregulated in transdifferentiated renal proximal tubular cells. This review summarizes emerging evidence implicating gremlin in the pathophysiology of glomerulosclerosis and tubulointerstitial fibrosis. Gremlin is a potential novel therapeutic target in progressive renal diseases.
Proximal Tubular Injury Attenuates Outer Medullary Hypoxic Damage: Studies in Perfused Rat Kidneys
Authors: Heyman Samuel N. , Shina Ahuva , Brezis Mayer , Rosen Seymour
Published: April 2003

The straight segment (S3) of the proximal tubule is predominantly damaged during renal ischemia-reflow, whereas medullary thick ascending limbs (mTALs) are principally affected in other models of hypoxic acute tubular necrosis (ATN). Since the latter injury pattern largely depends on the extent of reabsorptive activity during hypoxic stress, we hypothesized that proximal tubular damage might attenuate downstream mTAL injury by means of diminished distal solute delivery for reabsorption. In isolated rat kidneys perfused for 90 min with oxygenated Krebs-Henseleit solution, mTAL necrosis developed in 75 ± 3% of tubules in the mid-inner stripe of the outer medulla. By contrast, S3 segments in the outer stripe were minimally affected, with tubular fragmentation involving some 5 ± 2% of tubules. In kidneys subjected in vivo to proximal tubular injury and subsequently used for isolated perfusion studies, the injury pattern was inverted: following 20 and 30 min ischemia and reflow for 24 h, S3 fragmentation rose to 18 ± 16% and 72 ± 13%, while mTAL damage was reduced to 33 ± 10 and 24 ± 8%, respectively. In kidneys subjected in vivo to D-serine S3 necrosis rose to 100%, while mTAL damage fell to 1 ± 1% (p < 0.001). Substantial S3 tubular collapse (involving approximately 30% of tubules) and inner stripe interstitial hemorrhage were also noted, exclusively in kidneys subjected to ischemia-reflow. Proximal tubular necrosis alone or in combination with collapse inversely correlated with mTAL necrosis (R = –0.51 and –0.72, respectively, p < 0.003). This cogent inverse association might imply that disruption of the proximal nephron attenuates downstream mTAL necrosis by a reduction of distal tubular reabsorptive workload.
Collateral Circulation via the Ophthalmic Artery or Leptomeningeal Vessels Is Associated with Impaired Cerebral Vasoreactivity in Patients with Symptomatic Carotid Artery Occlusion
Authors: Hofmeijer J. , Klijn C.J.M. , Kappelle L.J. , van Huffelen A.C. , van Gijn J.
Published: April 2003

Background and Purpose: In patients with carotid artery occlusion (CAO), collateral flow may reduce the risk of ischemic stroke. Collateral flow via the ophthalmic artery (OphthA) and flow via leptomeningeal vessels have been considered secondary collaterals, which are recruited only if the primary collateral circulation via the circle of Willis is insufficient. The aim of this study was to investigate whether patients with symptomatic CAO who have secondary in addition to primary collaterals have a worse flow state of the brain than those without secondary collaterals, as measured by vascular reactivity testing. Methods: We studied 70 patients with symptomatic CAO who were independent for their daily activities. In all patients, collateral circulation through the circle of Willis was present. Vascular reactivity, measured by means of transcranial Doppler sonography with carbogen inhalation, was compared between patients with and without secondary collaterals. Results: CO2 reactivity was lower in 64 patients with (mean ± standard deviation 8 ± 14%) than in 6 patients without secondary collaterals (33 ± 18%) resulting in a mean difference of 24% (95% confidence interval 12–37%; p < 0.01). Conclusions: Patients with symptomatic CAO with collateral circulation through the OphthA or through leptomeningeal vessels in addition to collaterals via the circle of Willis have a worse hemodynamic status of the brain than those with Willisian collaterals only. Therefore the presence of these collaterals may indicate insufficiency of collateral blood flow via the circle of Willis.
SonoVue® (BR1), a New Long-Acting Echocontrast Agent, Improves Transcranial Colour-Coded Duplex Ultrasonic Imaging
Authors: Droste Dirk Wolfgang , Llull Jean Bernard , Pezzoli Carla , Bogdahn Ulrich , Kaps Manfred
Published: April 2003

Background and Purpose: Visualization of normal or pathological flow in the intracranial arteries using transcranial colour-coded duplex sonography (TCCS) is occasionally obstructed by insufficient temporal bone windows, unfavourable insonation angles, or low flow velocities or volumes. SonoVue® (BR1) is a new, long-acting echocontrast agent, which could be helpful in these instances. Methods: SonoVue was studied in two separate multicentre investigations of patients with insufficient bone windows (BR1-014 with 73 patients and BR1-017 with 40 patients) using an identical protocol. The agent was given intravenously as a bolus in four different doses (0.3, 0.6, 1.2 and 2.4 ml). Evaluation was performed on-site and off-site with video clips. Results: The contrast agent was well tolerated. As compared to the precontrast scans, SonoVue facilitated the visualization of vessel patency, stenosis, occlusion, and collateral flow, decreased the need for additional tests, and had an impact on the patient’s treatment. In 66–74%, a non-diagnostic investigation was converted into a diagnostic investigation. The highest dose (2.4 ml) allowed for a clinically useful signal enhancement of a median 1.9–6.3 min. Conclusions: SonoVue at a single dose of 1.2 or 2.4 ml is effective in increasing the detection of normal or pathological flow in the intracerebral arteries in patients who do not have a fully diagnostic unenhanced TCCS examination.
Hydroxyethyl Starch for Hypervolemic Hemodilution in Patients with Acute Ischemic Stroke: A Randomized, Placebo-Controlled Phase II Safety Study
Authors: Rudolf J.
Published: April 2003

Background: Hypervolemic hemodilution (HH) with hydroxyethyl starch (HES) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. The objective of this study was to investigate the safety of a 10% solution of HES 130/0.4 versus 0.9% saline solution in acute ischemic stroke by the incidence of adverse events (AEs). Methods: In a controlled, double-blind, randomized, multicenter, phase II, parallel-group study, 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a randomization ratio of 2:1 in favor of HES therapy. Results: There were no significant differences between the groups with regard to the incidence of the specific AEs (cardiovascular events, bleeding complications, allergic reactions) assessed over days 1–30, or mortality over days 1–8. In addition, global tests of efficacy showed a trend towards a better functional outcome with HES therapy; however, the study was not designed to prove efficacy. Conclusions:  High-dose HH with HES or NaCl was generally safe and well tolerated. Safety profiles were similar for the two treatment groups, and there was a nonsignificant trend towards a better functional outcome with HES therapy.
In Search of King Solomon’s Ring: Cognitive and Communicative Studies of Grey Parrots (Psittacus erithacus)
Authors: Pepperberg Irene M.
Published: April 2003

During the past 24 years, I have used a modeling technique (M/R procedure) to train Grey parrots to use an allospecific code (English speech) referentially; I then use the code to test their cognitive abilities. The oldest bird, Alex, labels more than 50 different objects, 7 colors, 5 shapes, quantities to 6, 3 categories (color, shape, material) and uses ‘no’, ‘come here’, wanna go X’ and ‘want Y’ (X and Y are appropriate location or item labels). He combines labels to identify, request, comment upon or refuse more than 100 items and to alter his environment. He processes queries to judge category, relative size, quantity, presence or absence of similarity/difference in attributes, and show label comprehension. He semantically separates labeling from requesting. He thus exhibits capacities once presumed limited to humans or nonhuman primates. Studies on this and other Greys show that parrots given training that lacks some aspect of input present in M/R protocols (reference, functionality, social interaction) fail to acquire referential English speech. Examining how input affects the extent to which parrots acquire an allospecific code may elucidate mechanisms of other forms of exceptional learning: learning unlikely in the normal course of development but that can occur under certain conditions.
Behavioral Studies of Learning in the Africanized Honey Bee (Apis mellifera L.)
Authors: Abramson Charles I. , Aquino Italo S.
Published: April 2003

Experiments on basic classical conditioning phenomena in adult and young Africanized honey bees (Apis mellifera L.) are described. Phenomena include conditioning to various stimuli, extinction (both unpaired and CS only), conditioned inhibition, color and odor discrimination. In addition to work on basic phenomena, experiments on practical applications of conditioning methodology are illustrated with studies demonstrating the effects of insecticides on learning and the reaction of bees to consumer products. Electron microscope photos are presented of Africanized workers, drones, and queen bees. Possible sub-species differences between Africanized and European bees are discussed.
Contributions of Monastic Medicine: From Hippocratic School to Salernitan Medical School
Authors: Iorio L. , Avagliano F.
Published: April 2003

Due to the intense relationship between Byzantium and the Abbey of Montecassino, which lasted for about three centuries, some of the Hippocratic Medical Texts were gathered by the Roman Catholic Church during the last years of the Roman Empire. Some texts were transferred directly from the Byzantine Empire to the abbey. Some of the earliest texts which were written in Greek and Latin have been lost; afterwards they were only written in Latin and in Beneventano-Cassinese type. They constituted the basis of medical assistance that was given in the ‘ospitia’ near the monastery to sick monks and pilgrims needing treatment on their way from Rome to Monte Sant’Angelo of Gargano. The Diuresis et pulsis secundum praecepta Dionisi is kept in Cod. Cas. No. 69 (10th century), pp 551–562, in the Montecassino archive. The author of this text tried to perform a urine examination considering the clinical signs, such as high temperature and pulse examination. The text is thought to have been written by Dionysius, a Hippocratic physician and contemporary of Herophilus, who lived around the 4th century BC. This text was read again in the Salernitan Medical School and compared with other texts from Arabic countries also influenced by Hippocrates.
Balkan Nephropathy: A Disorder of Renal Embryogenesis?
Authors: Nenov Vesselin D. , Nenov Dimitar S.
Published: April 2003

There is evidence to suggest that a renal embryogenesis disorder, with an associated deficit of nephrons, may be the cause of nephropathy later in the lives of patients with Balkan endemic nephropathy (BEN). This evidence includes the renal dysplasia or hypoplasia observed in BEN patients, the high incidence of renal pelvic and renal artery aberrations, primitive glomeruli and obstructed tubules on kidney biopsy, and an adult Fanconi-type syndrome of generalized proximal tubular dysfunction with hyperchloremic acidosis, potassium wasting, preserved urinary acidification, tubular proteinuria, aminoaciduria, uricosuria, hypomagnesemia, sodium wasting and normotension, as well as evidence from epidemiological data. The disease has affected no more than 2 generations, most of whom were in their 50s during 1965–1970, when maximal numbers of patients were seen. We are now observing a decreasing prevalence of BEN in Bulgaria and, even though this may have resulted from some prophylactic measures, the disease disappears much as it had appeared, as an epidemic. We speculate that some environmental factor may have had an impact on embryogenesis and resulted in nephropathy in patients with BEN. This could have been famine during the devastating Balkan wars in the beginning of 20th century, but may also have been an infectious or environmental factor, limited to the affected areas around the Danube river, which acted only during a limited period of time.
Nitric Oxide Damage to Colonocytes in Colitis-by-Association: Remote Transfer of Nitric Oxide to the Colon
Authors: Roediger W.E.W.
Published: April 2003

New observations of (1) colitis-by-association, (2) the carriage of nitric oxide by haemoglobin, (3) nitric oxide inactivation of CoA, (4) the damage caused to colonocytes by a combination of nitric oxide/sulphide/hydrogen peroxide and (5) colonic extraction of nitric oxide from the circulation, has led to new views on colonocyte damage in colitis. These observations should assist to define initiating factors that lead to release of damaging agents (nitric oxide/hydrogen peroxide) and to delineate protective mechanisms against colonocyte damage. Overall, the production, release, disposal and inactivation of nitric oxide are related to damage to colonocytes and consequent ulceration in colitis.
Influence of Interleukin 10 and Transforming Growth Factor-β on T Cell Stimulation through Allogeneic Retinal Pigment Epithelium Cells in vitro
Authors: Enzmann Volker , Hollborn Margrit , Kühnhoff Sandra , Wiedemann Peter , Kohen Leon
Published: April 2003

The effect of interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) on the immunological capability of human retinal pigment epithelium (RPE) cells was tested by measuring the proliferation of allogeneic T cells after stimulation through the RPE cells in vitro. For this, human RPE cells were activated with different concentrations of interferon-γ (0, 50, 100 and 250 U/ml) used as stimulator cells. The following T cell proliferation was measured with a tetrazolium-based colorimetric assay over a period of up to 4 days. Our results show that RPE cells are able to stimulate allogeneic T cells in the presence or absence of professional antigen-presenting cells (macrophages). Additionally, the proliferation could be significantly decreased by IL-10 or TGF-β. The maximum of suppression, especially by TGF-β, was found after 48 and 72 h of incubation. This shows that the antigen-presenting properties of human RPE cells can be altered in culture.
Papular Elastorrhexis
Authors: Buechner S.A. , Itin P.
Published: April 2003

Papular elastorrhexis is a rare disorder that occurs predominantly during adolescence. We report 5 patients with asymptomatic white, nonfollicular, firm papules scattered over the trunk and extremities. Histologically, the papules demonstrate focal areas of collagen homogenization with decreased and fragmented elastic fibers. The clinical differential diagnosis includes papular acne scars, dermatofibrosis lenticularis disseminata (Buschke-Ollendorff syndrome), cutaneous collagenoma and nevus anelasticus, but histology clearly separates papular elastorrhexis from the other entities.
A Randomised Controlled Trial of the Efficacy of Supervised Toothbrushing in High-Caries-Risk Children
Authors: Curnow M.M.T. , Pine C.M. , Burnside G. , Nicholson J.A. , Chesters R.K. , Huntington E.
Published: April 2003

Scottish children have one of the highest levels of caries experience in Europe. Only 33% of 5-year-old children in Dundee who developed caries in their first permanent molars by 7 brushed their teeth twice a day. High-caries-risk children should benefit if they brush more often with fluoridated toothpaste. The aim of this clinical trial was to determine the reduction in 2-year caries increment that can be achieved by daily supervised toothbrushing on school-days with a toothpaste containing 1,000 ppm fluoride (as sodium monofluorophosphate) and 0.13% calcium glycerophosphate, combined with recommended daily home use, compared to a control group involving no intervention other than 6-monthly clinical examinations. Five hundred and thirty-four children, mean age 5.3, in schools in deprived areas of Tayside were recruited. Each school had two parallel classes, one randomly selected to be the brushing class and the other, the control. Local mothers were trained as toothbrushing supervisors. Children brushed on school-days and received home supplies. A single examiner undertook 6-monthly examinations recording plaque, caries (D1 level), and used FOTI to supplement the visual caries examination. For children in the brushing classes, the 2-year mean caries increment on first permanent molars was 0.81 at D1 and 0.21 at D3 compared to 1.19 and 0.48 for children in the control classes (significant reductions of 32% at D1 and 56% at D3). In conclusion, high-caries-risk children have been shown to have significantly less caries after participating in a supervised toothbrushing programme with a fluoridated toothpaste.
Chemolitholysis and Lithotripsy of Infectious Urinary Stones – An in vitro Study
Authors: Heimbach D. , Jacobs D. , Müller S.C. , Hesse A.
Published: April 2003

Objectives: This study was performed to look for an improvement of therapeutic strategies with regard to the treatment of infectious urinary stones using artificial stones made of struvite and apatite (‘Bon(n) stones’) which are comparable to their natural counterparts. Materials and Methods: Using an experimental arrangement simulating the physiological conditions in the upper urinary tract, the efficacy of artificial urine (pH 5.7), Suby G solution (pH 3.6), mixtures of artificial urine with Suby G (pH 3.9 and pH 4.1) in dissolving artificial struvite and apatite stones (Bon(n) stones) was investigated. The dissolution of natural infectious urinary stones was also measured. Additionally, investigations on shock-wave lithotripsy (SWL) combined with initial chemolytic treatment of the stones were performed. Results: The efficacy of Suby G solution in dissolving artificial stones was demonstrated. Direct comparison of chemolysis of natural and artificial stones showed no statistical difference between infectious urinary stones and Bon(n) stones of the same material. The investigations on SWL showed a significant improvement on stone comminution, especially of artificial apatite stones after initial chemolytic treatment with Suby G. Conclusion: New basics to improve dissolution of infectious urinary stones have been developed by performing standardized in vitro investigations. Local chemolysis with Suby G is an effective tool in the treatment of infectious stone disease. SWL can be improved by varying the physical properties of infectious stones through initial treatment with Suby G solution.
An Evaluation of Quality of Life in Patients Who Underwent Orthotopic Bladder Replacement after Cystectomy: Comparison of Ileal Neobladder versus Colon Neobladder
Authors: Miyake Hideaki , Nakamura Ichiro , Eto Hiroshi , Gotoh Akinobu , Fujisawa Masato , Okada Hiroshi , Arakawa Soichi , Kamidono Sadao , Hara Isao
Published: April 2003

Objective: The objective of this study was to determine whether the quality of life (QOL) in patients who underwent orthotopic bladder replacement after radical cystectomy was affected by the intestinal segment used for the creation of a neobladder. Materials and Methods: A total of 52 patients who underwent radical cystectomy for bladder cancer were included in this study; i.e., 24 patients with an ileal neobladder and 28 patients with a sigmoid neobladder. QOL was evaluated using the SF-36 health-related QOL survey and a questionnaire designed to evaluate the continent status. Results: The mean follow-up periods for patients with an ileal and a sigmoid neobladder was 40.2 and 43.1 months, respectively. The SF-36 survey revealed that patients with colon neobladder had a significantly higher score for role-emotional functioning than those with ileal neobladder, while there was no significant difference in the remaining seven scores between patients with ileal and colon neobladders; however, general health and social functioning in patients with both types of neobladder appeared to be significantly lower than those in the general population in the United States. The results of the questionnaire analyzing the continent status were also similar between these two groups, including the desire to urinate, the incidence of both day- and nighttime urinary leakage, the frequency of pad exchange, and the concern of urine odor. Conclusions: Six of the eight scales concerning health-related QOL were favorable with both patients with ileal and colon neobladders, and the health-related QOL in orthotopic neobladder patients except for role-emotional functioning was not affected by the segment of the intestine used for neobladder construction. Moreover, no significant differences were observed in the QOL associated with continent status between these two groups. Therefore, patients with both types of orthotopic neobladder were generally satisfied with their health-related as well as disease-specific QOL.
Kinetics of 5-Aminolevulinic Acid-Induced Fluorescence in Organ Cultures of Bronchial Epithelium and Tumor
Authors: Gamarra Fernando , Wagner Simon , Al-Batran Salah , Maier Irmgard , Castro Mirna , Hautmann Hubert , Bergner Albrecht , Baumgartner Reinhold , Huber Rudolf Maria
Published: April 2003

Background: 5-Aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PPIX) fluorescence improves the differentiation of tumor and normal tissue in the bladder, skin and brain. Objective: The kinetics of 5-ALA-induced protoporphyrin IX (PPIX) fluorescence in organ cultures of normal human bronchial epithelium and cocultures of bronchial epithelium and tumor have been studied. Methods: Cultured biopsies of bronchial epithelium were exposed for 5 or 15 min, or continuously to 5-ALA. PPIX fluorescence was quantified for up to 300 min by spectroscopy. Cocultures of normal bronchial epithelium and a non-small-cell lung cancer cell line (EPLC-32M1) were incubated with 5-ALA. Space-resolved fluorescence microscopy was used to quantify PPIX fluorescence kinetics in the tumor and normal epithelium. Results: In cultures of normal epithelium, PPIX fluorescence kinetics were shown to depend on the duration of exposure to 5-ALA. There was a trend to higher fluorescence intensities with longer exposure times. In cocultures of bronchial epithelium and tumor, increases of fluorescence intensity were significantly greater in the tumor. Best tumor/normal tissue fluorescence ratios were found between 110 and 160 min after exposure to 5-ALA. Conclusion: Data obtained in this coculture system of bronchial epithelium and tumor is valuable to optimize modalities of fluorescence bronchoscopy for the diagnosis of early bronchial carcinoma.
Presence on human chromosome 10 of omeprazole-sensitivity gene whose product mediates CYP1A1 induction
Authors: Kikuchi H. , Fukushige S. , Shibazaki M. , Shiratori Y.
Published: April 2003

Previously, we showed that CYP1A1 expression can be induced by omeprazole (OP) in the human cell line HepG2, but not in the mouse cell line Hepa-1. Now we show induction of CYP1A1 by α-naphthoflavone (αNF) in Hepa-1 cells. This induction was inhibited by the tyrosine kinase inhibitor herbimycin A, but not by the aromatic hydrocarbon (Ah)-receptor antagonist PD98059, suggesting the presence of a ligand-independent signal-transduction pathway in the mouse cell line too. We utilized the lack of CYP1A1 induction by OP in Hepa-1 cells to map a putative human gene for OP-respon- siveness in cell hybrids produced by fusion of Hepa-1 and HepG2 cells. OP-induced CYP1A1 expression was detected in four out of the 32 Hepa-1 × HepG2 cell hybrids analyzed. To help identify the gene locus, a radiation-hybrid cell (E11) was constructed. Use of reverse-fluorescence in situ hybridization revealed that these five cell lines commonly retained human chromosome 10p. These results suggest that the human gene for OP-responsiveness is present on chromosome 10p.
Multicolor chromosome banding (MCB) with YAC/BAC-based probes and region-specific microdissection DNA libraries
Authors: Liehr T. , Weise A. , Heller A. , Starke H. , Mrasek K. , Kuechler A. , Weier H.-U.G. , Claussen U.
Published: April 2003

Multicolor chromosome banding (MCB) allows the delineation of chromosomal regions with a resolution of a few megabasepairs, i.e., slightly below the size of most visible chromosome bands. Based on the hybridization of overlapping region-specific probe libraries, chromosomal subregions are hybridized with probes that fluoresce in distinct wavelength intervals, so they can be assigned predefined pseudo-colors during the digital imaging and visualization process. The present study demonstrates how MCB patterns can be produced by region-specific microdissection derived (mcd) libraries as well as collections of yeast or bacterial artificial chromosomes (YACs and BACs, respectively). We compared the efficiency of an mcd library based approach with the hybridization of collections of locus-specific probes (LSP) for fluorescent banding of three rather differently sized human chromosomes, i.e., chromosomes 2, 13, and 22. The LSP sets were comprised of 107 probes specific for chromosome 2, 82 probes for chromosome 13, and 31 probes for chromosome 22. The results demonstrated a more homogeneous coverage of chromosomes and thus, more desirable banding patterns using the microdissection library-based MCB. This may be related to the observation that chromosomes are difficult to cover completely with YAC and/or BAC clones as single-color fluorescence in situ hybridization (FISH) experiments showed. Mcd libraries, on the other hand, provide high complexity probes that work well as region-specific paints, but do not readily allow positioning of breakpoints on genetic or physical maps as required for the positional cloning of genes. Thus, combinations of mcd libraries and locus-specific large insert DNA probes appear to be the most efficient tools for high-resolution cytogenetic analyses.
The genomic structure, chromosomal localization, and analysis of SIL as a candidate gene for holoprosencephaly
Authors: Karkera J.D. , Izraeli S. , Roessler E. , Dutra A. , Kirsch I. , Muenke M.
Published: April 2003

Holoprosencephaly (HPE) is the most common congenital malformation of the brain and face in humans. In this study we report the analysis of SIL (SCL interrupting locus) as a candidate gene for HPE. Fluorescent in situ hybridization (FISH) analysis using a BAC 246e16 confirmed the assignment of SIL to 1p32. Computational analysis of SIL at the protein level revealed a 73% overall identity between the human and murine proteins. Denaturing high performance liquid chromatography (dHPLC) techniques were used to screen for mutations and these studies identified several common polymorphisms but no disease-associated mutations, suggesting that SIL is not a common factor in HPE pathogenesis in humans.
Molecular cloning and characterization of a novel human gene (ANP32E alias LANPL) from human fetal brain
Authors: Jiang M. , Ma Y. , Ni X. , Cao G. , Ji C. , Cheng H. , Tang R. , Xie Y. , Mao Y.
Published: April 2003

Leucine-rich acidic nuclear protein (LANP) is a member of the leucine-rich repeats (LRRs) superfamily. Here we report on a human homologue of LANP, encoded by the gene ANP32E (alias LANPL). The gene was cloned and identified during large-scale sequencing analysis of a human fetal brain cDNA library. The human protein shared 70% amino acid identity with rat LANP. According to bioinformatics analysis, ANP32E is located on chromosome 1q22. RT-PCR analysis indicates that ANP32E was expressed in human peripheral blood leukocytes, colon, small intestine, prostate, thymus, spleen, skeletal muscle, liver and kidney.
Mutagenic transgene insertion into a region of high gene density and multiple linkage disruptions on mouse chromosome 11
Authors: Kleiter N. , Artner I. , Gmachl N. , Ghaffari-Tabrizi N. , Kratochwil K.
Published: April 2003

We have characterized a 185-kb contig surrounding a transgene on distal mouse chromosome 11, the insertion of which has caused a recessive phenotype with skeletal malformations. By cDNA selection and sequencing we have found six genes (Lasp1, Rpl23, Mllt6, Pip5k2b, Psmb3, Zfp144), one truncated gene (Mel13), and one pseudogene (Rps15-ps) within this region. The murine Mllt6 gene is new, it was identified by its high homology (90% identity) with the human homologue MLLT6. Psmb3 and Pip5k2b had not yet been assigned to mouse chromosomes. A comparison with the corresponding region on human chromosome 17q12 revealed several small-scale rearrangements during evolutionary divergence within this cluster of densely packed genes.
Genomic structure and refined chromosomal localization of the mouse Ptch2 gene
Authors: Fröhlich L. , Liu Z. , Beier D.R. , Lanske B.
Published: April 2003

The vertebrate Patched 2 (Ptch2) gene encodes a putative membrane-embedded protein which may have roles in Hedgehog signaling during development and in tumorigenesis. We determined the genomic structure of the mouse Ptch2 gene and show that Ptch2 is composed of 22 exons spanning approximately 18 kb of genomic DNA. The exon-intron boundaries were found to be conserved within the human and mouse Ptch2 genes. Analysis of the 5′ flanking region revealed a CpG island, the putative promoter region and the transcriptional start site while a polyadenylation signal as well as a mRNA destabilizing motif were identified in the 3′ flanking region. Single-strand conformation polymorphism analysis was used to map mouse Ptch2 to chromosome 4 between the microsatellite markers D4Mit20 and D4Mit334.
Characterization and chromosome assignment of the porcine AHCY gene for S-adenosylhomocysteine hydrolase
Authors: Leeb T. , Rohrer G.A.
Published: April 2003

The gene for S-adenosylhomocysteine hydrolase (AHCY) is involved in the regulation of cellular methylation reactions. Here we report the cloning, sequencing, and chromosomal assignment of the porcine AHCY gene. The gene consists of 10 exons spanning approximately 19 kb of genomic DNA. It encodes a protein of 432 amino acids that shows about 96% identity to the orthologous S-adenosylhomocysteine hydrolases from human, rat, and mouse. The porcine AHCY gene is located very close to the agouti signaling protein gene (ASIP) on SSC17q21. The chromosomal localization was subsequently confirmed by RH mapping and the genetic mapping of an intragenic microsatellite that maps to 57 cM on the linkage map of SSC17.
New Trends in the Treatment of Scleroderma Renal Crisis
Authors: Shor R. , Halabe A.
Published: April 2003

The main pathological changes observed in scleroderma kidney are edema and proliferation of intimal cells, glomerular changes with thickening and obliteration of arteries leading to decreased renal perfusion and increased renin release. Angiotensin converting enzyme inhibitors are the cornerstone in the treatment of patients with scleroderma renal crisis. Statins are used in the prevention of primary and secondary cardiovascular events. These drugs control cell proliferation and may prevent the injury observed in scleroderma kidney.
Can Haemodialysis-Induced Hypotension Be Predicted?
Authors: Cai Yan , Zimmerman Andre , Ladefoged Søren , Secher Niels H.
Published: April 2003

Background: During haemodialysis (HD) ultrafiltration may affect the central blood volume to an extent that blood pressure decreases. Thoracic electrical impedance (TI) is applied to monitor the central blood volume and we evaluated if it can be used to predict HD-induced hypotension. Methods: In 12 hypotensive prone (H) and 13 non-hypotensive prone (N) patients, blood pressure and heart rate were recorded during one dialysis session every 30 min, while TI, thoracic intracellular water (ThICW) and total body impedance (TBI) were followed every 10 min. Hypotension was defined as a decrease in systolic blood pressure (SAP) ≧30 mm Hg or a SAP < 90 mm Hg. Results: All 12 H patients developed hypotension after 190 ± 10 min (mean ± SE) as SAP decreased 35 ± 5 mm Hg, while the 13 N patients maintained blood pressure. TBI increased in all patients and the increase was similar (60 ± 5 and 56 ± 6 Ω in H and N patients, respectively). In N patients TI did not change significantly for the first 2 h of HD, while it became elevated by 2.8 ± 0.6 Ω (1.5 kHz) and 2.3 ± 0.7 Ω (100 kHz) by the end of the dialysis. In H patients, the increase in TI took place at the onset of HD to reach higher values (by 7.0 ± 0.5 Ω at 1.5 kHz and 5.9 ± 0.5 Ω at 100 kHz). ThICW was changed only in H patients (decreased by 7.9 ± 2.1 Siemens (S) 10–4, p < 0.05), while HR increased (9 ± 2 beats/min) in 8 of 12 H patients, while it decreased in 1 patient (by 9 beats/min). Conclusions: The results suggest that in HD patients hypotension is elicited by a reduction in the central blood volume that affects heart rate and the distribution of red cells within the body. To prevent HD-induced hypotention, the ultrafiltration rate could be reduced when an increase in thoracic impedance approaches 5 Ω, or when an index of intracellular water decreases by 6 10–4.
Wall Shear Stress Assessment in the Common Carotid Artery of End-Stage Renal Failure Patients
Authors: Samijo S.K. , Barkhuysen R. , Willigers J.M. , Leunissen K.M.L. , Ledoux L.A.F. , Kitslaar P.J.E.H.M. , Hoeks A.P.G.
Published: April 2003

Under physiological circumstances in the common carotid artery (CCA), mean wall shear stress (WSS), defined as mean wall shear rate (WSR) times local whole blood viscosity (WBV), is maintained at approximately 1.5 Pa. In patients with end-stage renal failure (ESRF) whole blood viscosity is low and it is not unlikely that mean WSS is lower in these patients than in control subjects. Moreover, hemodialysis causes an acute increase in blood viscosity with possible effects on WSS. In this study WSS in the CCA was determined with the Shear Rate Estimating System, an apparatus based on ultrasound, in ESRF patients (n = 13) and in presumed healthy age- and sex-matched control subjects (n = 13). Prior to hemodialysis, mean WSS (0.67 ± 0.23 Pa) was significantly lower (p < 0.05) in patients with ESRF, due to both a lower WBV (2.80 ± 0.52 mPa·s) and mean WSR (271 ± 109 s–1), than in the control subjects (mean WSS: 1.24 ± 0.20 Pa; WBV: 3.20 ± 0.29 mPa·s; WSR: 387 ± 51 s–1). Hemodialysis induced an increase in WBV (up to 3.71 ± 1.54 mPa·s, p < 0.01), but mean WSS did not change significantly due to a reciprocal decrease in mean wall shear rate. These findings demonstrate that WSS is lower in hemodialysis patients than in control subjects, and that mean WSS is maintained at this low level despite an acute change in blood viscosity.
Blood Volume Control by Biofeedback and Dialysis-Induced Symptomatology
Authors: Wolkotte Chantalle , Hassell Daxenos R. , Moret Karin , Gerlag Paul G. , Warmold van den Wall Bake A. , van der Sande Frank M. , Kooman Jeroen P.
Published: April 2003

In earlier studies, a reduction in intradialytic procedures was observed in patients with severe intradialytic hypotension symptomatology by the use of blood volume controlled biofeedback systems. However, few data are present on the use of biofeedback-controlled treatments in patients experiencing minor intradialytic symptoms. In the present study, 157 standard and 158 biofeedback-controlled treatments were compared during a 2-month period in 16 hemodialysis patients. Both the percentage of hypotensive episodes (6.3 ± 11.3 vs. 15.8 ± 18.3%; p < 0.05) as well as other intradialytic symptoms (cramps, nausea, headache, abdominal pain) (11.0 ± 12.8 vs. 18.1 ± 16.9%; p < 0.05) were significantly less during biofeedback-controlled treatments compared to standard dialysis treatments, despite a similar decline in relative blood volume (8.8 ± 3.5 vs. 8.3 ± 3.1%; p = n.s.). Interdialytic weight gain and intradialytic rise in plasma sodium levels were comparable. Concluding, in this short-term preliminary study, blood volume controlled biofeedback improved dialysis tolerance also in patients with minor intradialytic symptomatology.
Severe Alloimmune Hemolytic Anemia after Renal Transplantation
Authors: Odabaş Ali Rıza , Tutucu Kutlay Naci , Turkmen Aydın , Keskin Huseyin , Sever Mehmet Sukru
Published: April 2003

Alloimmune hemolytic anemia is a rare complication following allogeneic organ transplantation. Despite that some other drugs have also been reported, in the majority of cases this complication has been associated with cyclosporine therapy. We here present a case of severe alloimmune hemolytic anemia due to ABO minor incompatibility after renal transplantation in a patient treated with tacrolimus.
Acute Interstitial Nephritis due to Nicergoline (Sermion®)
Authors: Kim Mi Jeong , Chang Jae Hyuck , Lee Suk Kyeong , Park Joo Hyun , Choi Yeong Jin , Yang Chul Woo , Kim Yong Soo , Park Sung Hak , Bang Byung Kee
Published: April 2003

We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion®). A 50-year-old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i.e. arthralgia and fever) and laboratory findings (i.e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline-associated AIN.
Increased Circulating Levels of Natriuretic Peptides Predict Future Cardiac Event in Patients with Chronic Hemodialysis
Authors: Goto Takatoshi , Takase Hiroyuki , Toriyama Takayuki , Sugiura Tomonori , Kurita Yutaka , Tsuru Nobuo , Masuda Hiroaki , Hayashi Kunihiko , Ueda Ryuzo , Dohi Yasuaki
Published: April 2003

Background/Aim: Cardiovascular events are the major determinant of the prognosis in patients with chronic hemodialysis. The present study was designed to investigate whether increased plasma levels of atrial or brain natriuretic peptides (ANP or BNP) predict future cardiac events in such patients. Methods: Fifty-three patients undergoing chronic hemodialysis without clinical symptoms suggestive of cardiac disorders were enrolled and their blood was sampled for ANP and BNP measurements. Electrocardiograms demonstrated left ventricular hypertrophy in 28 patients but no other abnormal findings. We followed them up for 11.3 ± 0.2 months. The endpoint was cardiac events. Results: Cardiac events occurred in 13 patients (CE group). Both ANP and BNP levels were higher in CE group than in patients without cardiac events (ANP: 118 ± 21 vs. 56 ± 5 pg/ml, BNP: 769 ± 204 vs. 193 ± 25 pg/ml, respectively). Receiver operating characteristics curve revealed that the cut-off levels of ANP and BNP were 58 and 390 pg/ml, respectively. Using the Kaplan-Meier method, the incidence of cardiac events was significantly greater in patients with higher levels of ANP (50.0 vs. 0.0%) or BNP (72.7 vs. 11.9%) than in those with lower levels of the peptides. Conclusion: Elevated levels of ANP or BNP indicate an increased risk of cardiac events and these peptides are clinically useful to predict cardiac events in patients with hemodialysis.